The study of whether acquired Mendelian diseases are the origin of Alzheimer’s disease from viral respiratory diseases.

The study of whether acquired Mendelian diseases are the origin of Alzheimer’s disease from viral respiratory diseases. | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article The study of whether acquired Mendelian diseases are the origin of Alzheimer’s disease from viral respiratory diseases. Jong hoon Lee This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3238261/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract We must study viral RNA infection, sustained interferon response, acetylcholine excess, and developing Alzheimer’s disease (AD). We analyzed viral respiratory disease (VRD) (+)/(−) and dapsone (DDS) (+)/(−) groups. ANOVA calculator, logistic regression analysis, and Mann-Whitney U Test Calculator were used to examine the association of VRDs, COPD, and anti-AD drugs (AADs) with AD. A total of 107 subjects from 2005 to 2021 developed COPD. The DDS (+) AAD (-) and DDS (-) AAD (+) groups were strongly positively correlated with all COPD subjects. COPD develops into AD without dapsone, and AAD exacerbates AD through COPD. Ten AD among ninety-three non-COPD patients occurred in 2010 since the endemic. Viral infections set a direct pathway into AD directly without COPD. The endemic causes bronchitis, COPD, and AD. Acquired Mendelian up-regulation might set a direct pathway into AD as an origin. Biological sciences/Cell biology/Cell death Biological sciences/Cell biology/Post translational modifications Biological sciences/Cell biology/Senescence Health sciences/Diseases/Immunological disorders/Inflammatory diseases/Autoinflammatory syndrome Health sciences/Diseases/Neurological disorders/Dementia/Alzheimers disease Alzheimer’s disease Anti-Alzheimer’s disease drugs COPD Interferonopathies Mendelian up-regulation Viral respiratory disease Figures Figure 1 Figure 2 Plain language summary Can Alzheimer’s disease (AD) develop after viral infections? Leprosy patients have a low prevalence of VRDs with dapsone. After the endemic, viral infection induces AD directly. In a previous study, the bronchitis/COPD group strongly correlated with acetylcholine excess, and in this study, COPD developed AD, and AAD exacerbated AD in COPD patients. The endemic causes bronchitis, COPD, and AD. Viral interferonopathy sets a direct pathway into AD as an origin. Introduction Sorokdo National Hospital, dedicated to treating leprosy patients, separated the group taking dapsone from those not taking dapsone among Alzheimer’s disease (AD) patients from January 2005 to June 2020. This study demonstrates that the effects of dapsone are mixed with the viral interferonopathy in the Japanese sanatoria autopsy series 1 2 3 . AD patients increased in the DDS (-) group for fifteen years. As a result, data for Sanatoria in 1991 and Sorok Island for 2005-2006 are similar 4 5 6 . Based on the AD prevalence in patients, dapsone had a preventive effect against AD 4 . Their observations were scientific. This study was conducted on the potential clinical impact of continuing AD and related medicines (anti-AD drug, AAD) on elderly care in a real-life setting. The Dementia Management Act (DMA) in South Korea was enacted in August 2011 after declaring the "Warning against Dementia in 2008". From 2012 to 2019, Donepezil, rivastigmine, risperidone and quertiapine increased the number of deaths based on R 2 > 0.75 7 . Acetylation and excess acetylcholine (ACh) affect viral respiratory diseases (VRDs), bronchitis, and chronic obstructive pulmonary disease (COPD) 1 . ACh excess might inhibit ACh receptors for interferon (IFN) production against virus invasion. Some AADs exacerbate viral respiratory inflammatory diseases, but acetylation drugs treat VRDs 8 9 10 . The downstream IFN-stimulated cascade should attenuate the overactive immune-mediated respiratory inflammatory response in the onset stages 9 10 11 12 13 . In a randomized controlled trial (RCT) study of the acetylation effect of dapsone in antihistamine refractory chronic idiopathic urticaria, viral respiratory infections occurred less in the trial group than in the placebo group 14 . We have observed progressive dementia as a complication of VRDs but have remained ambiguous 15 . Choline esterase inhibitors (ChEIs) have frequent side effects, such as pharyngitis, pneumonia, increased cough, and bronchitis 16 ; Anti-psychotic drug uses increase mortality in dementia patients 7 17 . Mendelian disorders demonstrated key up-regulation of IFN or IFN stimulating gene (ISG) expression 18 . The constitutive involvement of IFN is an attractive thesis to the acquired interfernopathies by VRDs or COVID-19. We analyzed the effects of dapsone to decide whether the Mendelian upregulation should induce AD or not from 2005 to 2019 in the Sorok Island cohort. Methods All methods were carried out in accordance with relevant guidelines and regulations. All experimental protocols were approved by the Korea National Institute for Bioethics Policy (KoNIBP) as the institutional and/or licensing committee. The KoNIBP approved this study for the Management of Life-sustaining Treatment and certified that this study was managed properly (approval number P01-202007-22-006). Informed consent was obtained from all subjects and/or their legal guardians. STUDY STRATEGY Influenza A virus (IAV) and SARS-CoV dysregulate human innate immune responses. Severe influenza exhibits distinct cytokine patterns similar to SARS-CoV-2’s ability to suppress immune responses 19 . We analyzed diverse relationships with immune-mediated VRDs, pneumonia, COPD, and AD through national health electronic data interchange (EDI) systems. The Korean government has established compulsory long-term care insurance, and the 'War against Dementia' was announced in 2008. It accelerates the socialization of dementia care services at a national level 20 21 . Due to the DMA, psychiatrists - neurologists diagnosed and treated patients under the Medical Service Act 22 . As randomized by DMA, they bolstered dementia management and administered AADs as therapeutics to mild cognitive impairment (MCI) or AD patients 23 24 . DMA randomized the dapsone-prescribing (+) group from the dapsone-non-prescribing (-) group due to mental psychiatric examinations 7 25 . Medical staff prescribed AADs to treat MCI or AD. The War Against Dementia and DMA encouraged the prescription of AAD. It randomized the EDI code-based cohort studies, tested the cohort in a completely blinded state, and provided definite causality 7 . ELIGIBILITY CRITERIA According to the Infectious Disease Control and Prevention Act, all Hansen subjects on Sorok Island have been registered at Sorokdo National Hospital. The cohort consisted of leprosy patients, dapsone, respiratory diseases, and AD in all Hansen subjects, according to the data received from Sorokdo National Hospital by South Korea's Official Information Disclosure Act. Therefore, we searched all medical records of the Sorokdo National Hospital with ICD-10 codes. (Table S1, S2, S3) DDS(+):VRD(+) group (T1), DDS(-):VRD(+) group (T2), DDS(+):VRD(-) group (T3), and DDS(-):VRD(-) group (T4) were arranged. The T1:T3, T1:T4, T2:T3, and T2:T4 tests indicate that in approximately 2010, the group with dapsone and without dapsone were separated, and the group taking dapsone was less susceptible to VRD infection. The relationship between VRD and DDS each year was analyzed using the chi-square test. The p value was insignificant from 2006 to 2009 or 2011 to 2013 when the p value was considered significant at < 0.05. Thus, we separated two DDS (+/-) groups and classified VRD (+) patients with ICD-10 codes from 2012 to 2019. According to the One-way ANOVA Calculator, the f-ratio value is 116.07984. The p value is <.00001. The result is significant at p <.05. Tukey's honestly significant difference (HSD) procedure facilitates pairwise comparisons within T1:T2, T1:T3, T1:T4, T2:T3, and T2:T4. (Table S4, S5) DATA COLLECTION Medical data on the correlation between DDS and VRDs were analyzed by the International Classification of Diseases (ICD)-10 codes of viral respiratory infectious diseases. We archived data from January 2005 to June 2019 with the ICD codes of respiratory diseases (RDs). (Table S6, S7) According to the ICD-10 codes for AD: F00, F01, F02, F03, F04, F05, F06, F07, F08, F09, and G30 (Table S1), AD drugs for symptomatic relief are donepezil, rivastigmine, galantamine, and memantine. The AD drugs for psychological symptoms are haloperidol, Risperidone, Quetiapine, Olanzapine, Aripiprazole, Oxcarbazepine, fluvoxamine, Escitalopram, Trazodone, Sertraline, Escitalopram, and Fluoxetine. We used the object-oriented database management system (ORDBMS) and Google spreadsheet for R 2 analysis, linear equations, and SPSS. We again applied the linear equation and R 2 . DEMOGRAPHY HD patients would spend their whole lives on Sorok Island. According to the request to disclose health checkup information from 2005 to 2020 on October 27, 2020, 2186 people (1152 males, 1034 females) resided. The average age was 83.7 years (median (M) 84, interquartile range (IQR) 76.8–91.2, standard deviation (SD) 10.8, 95% confidence interval (CI): 0.45, 83.6–84.5). STUDY SELECTION Study Setting for the ICD Code of Korean Diseases and Medicines For VRD Acute nasopharyngitis [common cold] J00, acute pharyngitis J02, acute pharyngitis unspecified J02.9, acute tonsillitis J03, acute tonsillitis unspecified J03.9, acute laryngitis J04.0, acute laryngopharyngitis J06.0, acute upper respiratory infection unspecified J06.9, influenza due to identified zoonotic or pandemic influenza virus J09, influenza with other manifestations seasonal influenza virus identified J10.8, viral pneumonia unspecified J12.9, acute bronchitis unspecified J20.9. (Table S6) For Respiratory Diseases Immune-related: Asthma J45, Predominantly allergic asthma J45.0, Nonallergic asthma J45.1, Asthma unspecified J45.9, Status asthmaticus J46, Vasomotor rhinitis J30.0, Allergic rhinitis, unspecified J30.4, Chronic rhinitis J31.0, Chronic sinusitis J32, Chronic maxillary sinusitis J32.0, Chronic pansinusitis J32.4, Other chronic sinusitis J32.8, Chronic sinusitis, unspecified J32.9, Chronic laryngitis J37.0, Chronic nasopharyngitis J31.1, Chronic pharyngitis J31.2, Abscess furuncle and carbuncle of nose J34.0, Deviated nasal septum J34.2, Other specified disorders of nose and nasal sinuses J34.8, Chronic tonsillitis J35.0, Peritonsillar abscess J36, Retropharyngeal and parapharyngeal abscess J39.0 Bronchitis: Acute Bronchitis unspecified J20.9, Bronchitis, not specified as acute or chronic J40, Unspecified chronic bronchitis J42, Pneumonia: Bacterial Pneumonia NEC J15, Other bacterial pneumonia J15.8, Bacterial Pneumonia unspecified J15.9, Pneumonia in bacterial diseases classified elsewhere J17.0, Other Pneumonia organism unspecified J18.8, Pneumonia unspecified J18.9, COPD: Pneumonitis due to food and vomit J69.0, Other chronic obstructive pulmonary disease J44, Chronic obstructive pulmonary disease, unspecified J44.9, Bronchiectasis J47 End stage: Pulmonary edema J81, Abscess of lung with pneumonia J85.1, Pleural effusion NEC J90, Pneumothorax J93, Hemothorax J94.2, Chronic pulmonary insufficiency following surgery J95.3, Acute respiratory failure J96.0, Pulmonary collapse J98.1, Other specified respiratory disorders J98.8, Respiratory disorder, unspecified J98.9. (Table S7) RISK OF BIAS ASSESSMENT The Korean National Assembly unanimously passed the DMA in 2012 and diagnosed and treated all Hansen subjects without exception 26 . Medical staff treated patients with VRD, while no one knew dapsone's ability to compete with inflammasomes. All were in complete-blinded states. Randomization was unrestricted (no blocking or stratification), and the study's data team analyzed the ICD codes in the EMR databases of Sorokdo National Hospital. (Complete Blinded Study & Randomization) DMA made all medical staff of Sorokdo National Hospital investigate dementia for all HD patients. AAD was prescribed for Hansen subjects, and dapsone was not for inactive HD patients. DMA administered dapsone to the trial group beginning in 2012. Therefore, we classified dapsone-unprescribed subjects as the control group. STATISTICAL ANALYSIS Significance was evaluated based on a p value of 0.05 from 2005 to 2021. We used the software programs Object-Relational DBMS and Google spreadsheet with SPSS, ANOVA calculator, and post hoc Tukey HSP (honestly significant difference) test. In addition, a t test was performed among T1, T2, T3, T4, or T5. Results We investigated 93 subjects who survived non-COPD patients with AD in 2022. There were 62 females, the average age was 83.5 years, hypertension was present in 66 patients, no obesity or cancer was present, diabetes was present in 21 patients, and dapsone was taken in 38 patients. AD occurred in six patients (Number 10. 19, 45, 51, 62, 87) in 2007, four (Number 12, 31, 59, 76) in 2008, 1 (Number 88) in 2009, and ten (Number 33, 53, 54, 55, 57, 63, 69, 77, 84, 89) in 2010 since the endemic. AD patients increase without COPD. (Table S8, S9) Ten in 2010 is evidence that the endemic could directly induce AD. Immune-related viral respiratory diseases, COPD, and Alzheimer’s disease COPD increased slowly from 2008 to 2011, rapidly increased in 2012 and 2013, and decreased 1 . Acute bronchitis quickly rose from 2012 to 2014 and then dropped 1 . Pneumonia increased sharply in 2013 compared to previous years 1 . The longitudinal analysis of all COPD subjects presents vital results. A total of 107 subjects from 2005 to 2021 developed COPD. There were 71 males and 36 females. The population's average age was 87.6 years (M 88.1, IQR 80-93.9, SD 9.55, 95% CI: 0.19, 87.4-87.8). The minimum age was 55.6 years, and the highest was 106.8 years. There were 44 patients with hypertension, no obesity patients, 4 patients with cancer, 17 patients with diabetes mellitus, 26 patients with dapsone, and 31 patients with dementia. We analyzed the DDS (+)/(−) group, dementia diagnosed (+)/undiagnosed (-) group, and COPD group from 2005 to 2021 with the ANOVA calculator. The f-ratio value is 7.94. The p value is.000019. (Significant at p<.05) (Table S10) We investigated 24 subjects who survived COPD in 2022. Twenty subjects took dapsone, four of which had AD, and sixteen patients did not. The other four subjects did not take dapsone, of which three patients had AD and one patient did not have AD: DDS (+) 20, AD (+) 4, AD (-) 16/DDS (-) 4, AD (+) 3, and AD (-) 1. Dapsone-non-taking COPD survivors were more likely to suffer from AD than dapsone-taking COPD survivors, X 2 (1, N = 24) = 4.9, p =.027. (Table S11) COPD has exacerbated AD. The number of AD patients in the COPD patient group was 1 in 2005, 0 in 2006, 3 in 2007, 0 in 2008, 0 in 2009, 0 in 2010, 1 in 2011, 3 in 2012, 4 in 2013, 0 in 2014, 1 in 2015, 2 in 2016, 5 in 2017, 0 in 2018, 0 in 2019, 2 in 2020, 2 in 2021, 0 in 2022. (Table S12) Dapsone was proposed as a treatment for MCI and AD 4 6 16 27 . The post hoc Tukey HSD (honestly significant difference) procedure indicated pairwise comparisons of the DDS (+) AAD (+) group (T1) with the COPD group (T5), DDS (+) AAD (-) (T2) with T5, and DDS (-) AAD (+) (T3) with T5. (Calculator S1) Supplement Calculator (C) 1: T1 and T5 were moderately correlated, r(17) =.72, p =.0012. C2: T1 association would be considered statistically significant. (Calculator S2) C1: T2 and T5 were strongly positively correlated, r(17) =.75, p = 0.00052. C2: T2 association was considered statistically significant. (Calculator S3) C1: T3 and T5 were strongly positively correlated, r(17) =.91, p <.00001. C2: T3 association would be considered statistically significant. (Calculator S4) T1 is data of AD treated by dapsone and evolving AD. T1 has a modest correlation with T5. The modest correlation could explain why COPD would induce AD against dapsone. T2 explains the strong correlation with T5 between the prevalence of AD treated by dapsone from exacerbated AD in the COPD group. T3 correlates highest with T5. COPD without dapsone developed into AD, and AAD exacerbated COPD during medication for AD. This study elucidates the correlation between COPD and AD and paradoxically reports that ACh excess positively affects the clinical prevalence of exacerbated AD in treating COPD. Dapsone treats and prevents AD, but COPD worsens AD despite dapsone treatment. DMA enrolled a total of 9649 participants in the completely blinded state. 4772 subjects were randomized from 2012 to 2020 on Sorok Island. (Fig. S1) VRD (+) subjects (sum (S) = 4156, M = 519.50, SD = 61.98; 95% CI, 517.62–521.38) consisted of T1: VRD (+) DDS (+) (S = 1702, M = 212.75, SD = 36.76) and T2: VRD (+) DDS (−) (S =2454, M = 306.75, SD = 88.70). VRD (−) subjects (S = 616, M = 41.07, SD = 55.46) consisted of T3 VRD (-) DDS (+) (S = 170, M = 21.2, SD = 33.2) and T4 VRD (-) DDS (−) groups (S = 446, M = 55.7, SD = 24.3). The values of f and p were calculated using an ANOVA calculator. Four groups were defined for the T test: T 1: VRD (+) DDS (+), T 2: VRD (+) DDS (−), T 3: VRD (−) DDS (+), and T 4: VRD (−) DDS (−). The f-ratio value in the one-way ANOVA calculator for dependent measures is 116.08, and the p value is <.00001. The result is significant at p < 0.05. The comparisons (T1:T2, T1:T3, T1:T4, T2:T3, and T2:T4) were applicable except for T3:T4. (Table S5) The T1: T2 graph shows that patients with dapsone have a relatively low prevalence among patients with VRD. (Fig. S2) By Mann-Whitney U Test Calculator, the z-score is -2.88808. The p-value is .00386. The result is significant at p < .05. The T1:T3 graph shows that patients with dapsone have a decreased prevalence of VRD. (Fig. S3) By Mann-Whitney U Test Calculator, the z-score is 3.30816. The p-value is .00094. The result is significant at p < .05. T1:T4 demonstrate that the VRD (+) DDS (+) group has conversely shown almost the décalcomnie pattern with the VRD (-) DDS (-) group. This proves that this study is scientific. (Fig. S4) By Mann-Whitney U Test Calculator, the z-score is 3.30816. The p-value is .00094. The result is significant at p < .05. The T2:T3 graph shows that patients with dapsone have a very low prevalence of VRD. (Fig. S5) By Mann-Whitney U Test Calculator, the z-score is 3.30816. The p-value is .00094. The result is significant at p < .05. T2:T4 demonstrated that the VRD (+) and VRD (-) groups without dapsone had a constant prevalence, and dapsone was the decisive factor in preventing most VRD exacerbations. (Fig. S6) By Mann-Whitney U Test Calculator, the z-score is 3.30816. The p-value is .00094. The result is significant at p < .05. SUMMARY OF FINDINGS AND RECOMMENDATIONS The endemic in 2008 caused bronchitis, COPD, and AD. Viral infection induces AD directly. AAD exacerbates VRDs and leads to the development of COPD in the previous study 1 . COPD developed into AD. VRDs and COPD positively cause AD and AAD indirectly contributes to AD’s development in treating COPD. Safety All leprosy patients have lived there with national medical support. Limitations This study included only leprosy patients. Discussion The risk of COPD exacerbation may increase in the first 90 days of ChEI therapy in patients with dementia 28 . Viral infection and interferon treatment decrease muscarinic (M)2 receptor gene expression on parasympathetic nerve endings by causing the release of IFN-gamma, which inhibits M2 receptor gene expression. VRDs and IFN treatment decreased M2 receptor gene expression by causing the release of IFN-gamma. IFN-gamma inhibits M2 receptor gene expression on parasympathetic nerve endings 29 . ACh excess inhibits ACh receptors for IFN production against virus invasion because the genesis of the ACh receptor requires IFN 30 . The muscarinic and nicotinic receptors play critical roles in controlling immune function 31 . A previous study revealed the correlation between donepezil and ACh with VRDs. The ACh excess by AAD might negatively affect ACh receptor gene expression 1 . Chemo genetic concerns predict drugs modulating microglial functions. Tau protein induces substantial changes in microglial-immune signaling and early interferon-driven immune suppression. 32 . This clinical approach clearly defines the origin of AD as another origin from amyloidosis or tau accumulation 33 . Ion Gresser et al. reported in 1980 that the possibility that indecent exposure to IFN-1 might be harmful to the mammalian system and IFN excess should cause adverse reactions in the host. Human diseases were associated with IFN up-regulation. Mendelian up-regulation is inborn human interferonopathies. Systemic lupus erythematosus (SLE) and Aicardi–Goutières syndrome (AGS) are innate Mendelian up-regulation diseases 34 . COPD was associated with incident nonamnestic MCI, and the danger of COPD exacerbation in patients with AD and COPD may increase in the first 90 days of ChEI therapy 35 28 . VRDs and IFN treatment decreased M2 receptor gene expression by causing the release of IFN-gamma. IFN-gamma inhibits M2 receptor gene expression on parasympathetic nerve endings 29 . ACh excess inhibits ACh receptors for IFN production against virus invasion because the genesis of the ACh receptor requires IFN 30 . The muscarinic and nicotinic receptors play critical roles in controlling immune function 31 . A previous study revealed the correlation between donepezil and ACh with VRDs. The ACh excess by AAD might negatively affect ACh receptor gene expression 1 . Neuropilin 1 (NRP1) is a receptor that connects essential pattern recognition receptors and the immune response. It is engaged in developing the heart, vasculature, and neuronal system and establishes primarily a cellular receptor for various molecules 36 . The brain with AIDS has direct dementia effects from the retrovirus 37 . SARS-CoV-2 uses it as a coreceptor with ACE2 38 39 . NRP1 serves as the principal receptor mediating astrocyte entry of SARS-CoV-2 40 . It plays a complex role in the secondary CD8 T-cell response to control VRDs and tumors 41 . NRP1 maintains protein complexes at cell-to-cell junctions in endothelial cells. The NRP1 deficiency was associated with larger plaque sizes in mice 42 . Group 3 innate lymphoid cells (ILC3s) are present in patients with COPD. ILC3s with NRP1 (NRP1 + ILC3s) show higher levels of cytokines than NRP1 - ILC3s, and NRP1 + ILC3s play a potential role in inflammation 43 44 . We define this up-regulation as acquired Mendelian up-regulation. NRP1 + ILC3s constitute the inflammatory cascade pathway with IFN1 or cGAS-STING through acetylation-deacetylation 9 . The cGAS-STING-IFN-I axis in AD pathogenesis by VRDs The factor in the AA equation consisted of the dapsone-taking group and the AAD-taking AD group 7 . Through its acetylation capacity, dapsone inhibits the activation of both IFN-1 and NF-κB by targeting cyclic GMP-AMP synthase (cGAS) 45 . The cGAS-stimulator of interferon genes (STING) and RNA sensing pathway has triggered innate immune responses such as COVID-19 46 47 . COVID-19 has a broad spectrum of diseases and has resulted in unprecedented rates of pneumonia, acute respiratory distress syndrome (ARDS), and death 48 . The IFN-1 system drives excessive inflammation and immunopathology 49 50 . The cGAS-STING-IFN-I axis promotes the clearance of aberrant DNA and RNA viruses from the gut microbiota found in circulation 51 52 . The interferonopathy of VRDs induces bronchitis, COPD, and AD. The endemic in 2008 might induce innate immune responses 1 . Pandemic patients who required intensive care had higher risks of persistent symptoms and higher COPD assessment test scores 53 . SARS-CoV-2 can target granular neurons 54 . Immune-to-brain communication occurs as glia, microglia, and astrocytes interpret and propagate inflammatory signals, influencing physiological and behavioral changes 55 56 . In addition, activating the peripheral immune system affects physiological and clinical responses by the immunological memory engram pathway 9 . Jacqueline et al . reported a relatively high incidence of cognitive impairment in processing speed, category fluency, executive functioning, memory encoding, and recall several months after hospitalization in COVID-19 patients. This dysexecutive syndrome after COVID-19 has considerable implications for occupational, psychological, and functional outcomes 57 . These findings are generally consistent with other viruses' alterations in cognitive and emotional behaviors (e.g., influenza A). VRDs cause AD even if it is not from COPD 58 . Dapsone as a baseline treatment for exacerbated Mendelian diseases Acetylation inhibits cGAS-mediated interferon production 59 . The acetylation of dapsone showed genetic polymorphism and reproducible individual characteristics. Acetylation of dapsone and deacetylation of monoacetyl dapsone occurred concurrently. Plasma ratios acetylated to the parent drug reached constant states but were characteristic for the individual 60 . Dapsone is used to treat an IFN-1 overproduction for SLE, lupus erythematosus profundus, cutaneous lupus erythematosus, and familial Mediterranean fever 61 62 63 64 65 . AGS is also related to upregulated IFN-1 production with slight differences across numerous triggering endogenous nucleotide sensors 66 67 . Based on the relative prevalence in leprosy patients, dapsone had a preventive effect against AD 4 . Therefore, it is necessary to set a prospective cohort for the leprosy patients of Sorok Island after stopping prescribing the AAD. Moreover, RCT studies are needed around the world. (Fig. S7) The endemic causes bronchitis, COPD, and AD. Viral interferonopathy might set a direct pathway into AD as an origin. Declarations Acknowledgments This study was not supported by any institute. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author. Conflict Of Interest Statement The authors have no conflicts of interest to disclose. Funding None Author contributions Conceptualization, J.H.L. ; methodology, J.H.L. ; investigation, J.H.L. ; resources, J.H.L. ; data curation, J.H.L. ; writing—original draft, J.H.L. ; editing, J.H.L. : review, all; supervision, J.H.L. ; project administration, J.H.L. All authors have read and agreed to the published version of the manuscript. Data and materials availability "All data are available in the main text or the supplementary materials." Additional data supporting this study's findings are available from the corresponding author upon reasonable request. In addition, the complete detailed survey is provided as a separate file. LEE, JONG HOON (2023): Data on Viral Respiratory Diseases and Alzheimer's Diseases on Sorok Island in South Korea. figshare. Journal contribution. https://doi.org/10.6084/m9.figshare.22817060.v1 References Lee, J. H. et al. Bronchitis, COPD, and pneumonia after viral endemic of patients with leprosy on Sorok Island in South Korea. Naunyn-Schmiedeberg's Archives of Pharmacology , doi:10.1007/s00210-023-02407-7 (2023). Namba, Y., Kawatsu, K., Izumi, S., Ueki, A. & Ikeda, K. Neurofibrillary tangles and senile plaques in brain of elderly leprosy patients. Lancet 340 , 978, doi:10.1016/0140-6736(92)92870-l (1992). Kimura, T. & Goto, M. Existence of senile plaques in the brains of elderly leprosy patients. Lancet 342 , 1364, doi:10.1016/0140-6736(93)92274-w (1993). Lee, J. H., Kanwar, B., Lee, C. J., Sergi, C. & Coleman, M. D. Dapsone is an anticatalysis for Alzheimer’s disease exacerbation. iScience , doi:10.1016/j.isci.2022.104274 (2022). Mcgeer, P. L., Harada, N., Kimura, H., Mcgeer, E. G. & Schulzer, M. (Google Patents, 1993). McGeer, P. L., Harada, N., Kimura, H., McGeer, E. G. & Schulzer, M. Prevalence of dementia amongst elderly Japanese with leprosy: apparent effect of chronic drug therapy. Dement. Geriatr. Cogn. Disord. 3 , 146-149 (1992). Lee, J. H. The listed, delisted, and sustainability of therapeutic medicines for dementia patients: the study is specific to South Korea. Naunyn Schmiedebergs Arch Pharmacol 395 , 535-546, doi:10.1007/s00210-022-02209-3 (2022). Secnik, J. et al. Dementia and psychotropic medications are associated with significantly higher mortality in geriatric patients hospitalized with COVID-19: data from the StockholmGeroCovid project. Alzheimer's Research & Therapy 15 , 5, doi:10.1186/s13195-022-01154-w (2023). Lee, J. H. et al. COVID-19 Molecular Pathophysiology: Acetylation of Repurposing Drugs. International Journal of Molecular Sciences 23 , 13260 (2022). Lee, J. h. Treatment mechanism of immune triad from the repurposing drug against COVID-19. Translational Medicine of Aging 7 , 33-45, doi:https://doi.org/10.1016/j.tma.2023.06.005 (2023). Lee, J.-h., An, H. K., Sohn, M.-G., Kivela, P. & Oh, S. 4,4′-Diaminodiphenyl Sulfone (DDS) as an Inflammasome Competitor. International Journal of Molecular Sciences 21 , 5953 (2020). Kanwar, B., Lee, C. J. & Lee, J.-H. Specific Treatment Exists for SARS-CoV-2 ARDS. Vaccines 9 , 635 (2021). Kanwar, B. A., Khattak, A., Balentine, J., Lee, J. H. & Kast, R. E. Benefits of Using Dapsone in Patients Hospitalized with COVID-19. Vaccines 10 , 195 (2022). Morgan, M., Cooke, A., Rogers, L., Adams-Huet, B. & Khan, D. A. Double-Blind Placebo-Controlled Trial of Dapsone in Antihistamine Refractory Chronic Idiopathic Urticaria. The Journal of Allergy and Clinical Immunology: In Practice 2 , 601-606, doi:10.1016/j.jaip.2014.06.004 (2014). Sipilä, P. N. et al. Hospital-treated infectious diseases and the risk of dementia: a large, multicohort, observational study with a replication cohort. The Lancet Infectious Diseases 21 , 1557-1567, doi:https://doi.org/10.1016/S1473-3099(21)00144-4 (2021). Lee, J. H., Choi, S. H., Lee, C. J. & Oh, S. S. Recovery of Dementia Syndrome following Treatment of Brain Inflammation. Dement Geriatr Cogn Dis Extra 10 , 1-12, doi:10.1159/000504880 (2020). Stone, M. Mortality and antipsychotic drug use in dementia-related behavioral disorders. US Department of Health and Human Services. Food and Drug Administration, Center for Drug Evaluation and Research 3 , 1-26 (2005). Marié, I. J., Chang, H.-M. & Levy, D. E. HDAC stimulates gene expression through BRD4 availability in response to IFN and in interferonopathies. Journal of Experimental Medicine 215 , 3194-3212, doi:10.1084/jem.20180520 (2018). Liu, G. & Gack, M. U. Insights into pandemic respiratory viruses: manipulation of the antiviral interferon response by SARS-CoV-2 and influenza A virus. Current Opinion in Immunology 78 , 102252, doi:https://doi.org/10.1016/j.coi.2022.102252 (2022). Chon, Y. The expansion of the Korean welfare state and its results@ focusing on lon‡ term care insurance for the elderly. Soc. Policy Adm. 48 , 704-720 (2014). Lee, S. B. The community dementia reassurance center (chime ansim center) in South Korea. Ann Geriatr Med Res 23 , 43-44, doi:10.4235/agmr.19.0024 (2019). Youn, H. & Jeong, H.-G. Pharmacotherapy for dementia. Journal of the Korean Medical Association 61 , 758-764, doi:10.5124/jkma.2018.61.12.758 (2018). Lee, D. W., Huh, Y. S. & Kim, K. W. Evidence-Based Treatment of Alzheimer's Disease. Journal of the Korean Medical Association 52 , 417-425, doi:10.5124/jkma.2009.52.4.417 (2009). Ahn, S. H. et al. Drug persistency of cholinesterase inhibitors for patients with dementia of Alzheimer type in Korea. Arch Pharm Res 38 , 1255-1262, doi:10.1007/s12272-014-0500-8 (2015). Seong Yun Jeong, Y. S. L. Epidemiological study of depression among patients with Hansen Disease at the national sorokdo hospital. Korean Leprosy Bulletin 44 , 63-69 (2011). Han, J. W. et al. Overview of the Korean Longitudinal Study on Cognitive Aging and Dementia. Psychiatry Investig 15 , 767-774, doi:10.30773/pi.2018.06.02 (2018). Lee, J. H., Lee, C. J., Park, J., Lee, S. J. & Choi, S. H. The Neuroinflammasome in Alzheimer's Disease and Cerebral Stroke. Dement Geriatr Cogn Dis Extra 11 , 159-167, doi:10.1159/000516074 (2021). Mahan, R. J. & Blaszczyk, A. T. COPD Exacerbation and Cholinesterase Therapy in Dementia Patients. The Consultant Pharmacist 31 , 221-225, doi:10.4140/TCP.n.2016.221 (2016). Jacoby, D. B., Xiao, H. Q., Lee, N. H., Chan-Li, Y. & Fryer, A. D. Virus- and interferon-induced loss of inhibitory M2 muscarinic receptor function and gene expression in cultured airway parasympathetic neurons. The Journal of Clinical Investigation 102 , 242-248, doi:10.1172/JCI1114 (1998). Balasa, B. et al. Interferon γ (IFN-γ) Is Necessary for the Genesis of Acetylcholine Receptor–induced Clinical Experimental Autoimmune Myasthenia gravis in Mice. Journal of Experimental Medicine 186 , 385-391, doi:10.1084/jem.186.3.385 (1997). Kawashima, K., Fujii, T., Moriwaki, Y. & Misawa, H. Critical roles of acetylcholine and the muscarinic and nicotinic acetylcholine receptors in the regulation of immune function. Life Sciences 91 , 1027-1032, doi:https://doi.org/10.1016/j.lfs.2012.05.006 (2012). Rexach, J. E. et al. Tau Pathology Drives Dementia Risk-Associated Gene Networks toward Chronic Inflammatory States and Immunosuppression. Cell Reports 33 , 108398, doi:https://doi.org/10.1016/j.celrep.2020.108398 (2020). Udeochu, J. C. et al. Tau activation of microglial cGAS–IFN reduces MEF2C-mediated cognitive resilience. Nature Neuroscience 26 , 737-750, doi:10.1038/s41593-023-01315-6 (2023). Crow, Y. J. Type I interferonopathies: Mendelian type I interferon up-regulation. Current Opinion in Immunology 32 , 7-12, doi:https://doi.org/10.1016/j.coi.2014.10.005 (2015). Singh, B. et al. A prospective study of chronic obstructive pulmonary disease and the risk for mild cognitive impairment. JAMA neurology 71 , 581-588 (2014). Jiang, S. X. et al. Neuropilin 1 Directly Interacts with Fer Kinase to Mediate Semaphorin 3A-induced Death of Cortical Neurons * . Journal of Biological Chemistry 285 , 9908-9918, doi:10.1074/jbc.M109.080689 (2010). Price, R. W. et al. The Brain in AIDS: Central Nervous System HIV-1 Infection and AIDS Dementia Complex. Science 239 , 586-592, doi:doi:10.1126/science.3277272 (1988). Daly, J. L. et al. Neuropilin-1 is a host factor for SARS-CoV-2 infection. Science 370 , 861-865, doi:10.1126/science.abd3072 (2020). Pal, D., De, K., Yates, T. B., Kolape, J. & Muchero, W. Mutating novel interaction sites in NRP1 reduces SARS-CoV-2 spike protein internalization. iScience 26 , doi:10.1016/j.isci.2023.106274 (2023). Kong, W. et al. Neuropilin-1 Mediates SARS-CoV-2 Infection of Astrocytes in Brain Organoids, Inducing Inflammation Leading to Dysfunction and Death of Neurons. mBio 13 , e02308-02322, doi:doi:10.1128/mbio.02308-22 (2022). Hwang, J. Y., Sun, Y., Carroll, C. R., Usherwood, E. J. & D'Orazio, S. E. F. Neuropilin-1 Regulates the Secondary CD8 T Cell Response to Virus Infection. mSphere 4 , e00221-00219, doi:doi:10.1128/mSphere.00221-19 (2019). Bosseboeuf, E. et al. Neuropilin-1 interacts with VE-cadherin and TGFBR2 to stabilize adherens junctions and prevent activation of endothelium under flow. Science Signaling 16 , eabo4863, doi:doi:10.1126/scisignal.abo4863 (2023). Shikhagaie, M. M. et al. Neuropilin-1 Is Expressed on Lymphoid Tissue Residing LTi-like Group 3 Innate Lymphoid Cells and Associated with Ectopic Lymphoid Aggregates. Cell Reports 18 , 1761-1773, doi:https://doi.org/10.1016/j.celrep.2017.01.063 (2017). Meininger, I. et al. Tissue-Specific Features of Innate Lymphoid Cells. Trends in Immunology 41 , 902-917, doi:https://doi.org/10.1016/j.it.2020.08.009 (2020). Ellard, G., Gammon, P. T., Helmy, H. & Rees, R. Dapsone acetylation and the treatment of leprosy. Nature 239 , 159-160 (1972). Neufeldt, C. J. et al. SARS-CoV-2 infection induces a pro-inflammatory cytokine response through cGAS-STING and NF-κB. Communications biology 5 , 1-15 (2022). Crow, Y. J. & Stetson, D. B. The type I interferonopathies: 10 years on. Nature Reviews Immunology 22 , 471-483, doi:10.1038/s41577-021-00633-9 (2022). Casanova, J. L. & Anderson, M. S. Unlocking life-threatening COVID-19 through two types of inborn errors of type I IFNs. J Clin Invest 133 , doi:10.1172/jci166283 (2023). Domizio, J. D. et al. The cGAS–STING pathway drives type I IFN immunopathology in COVID-19. Nature 603 , 145-151 (2022). Roy, E. R. et al. Type I interferon response drives neuroinflammation and synapse loss in Alzheimer disease. J Clin Invest 130 , 1912-1930, doi:10.1172/JCI133737 (2020). Erttmann, S. F. et al. The gut microbiota prime systemic antiviral immunity via the cGAS-STING-IFN-I axis. Immunity 55 , 847-861.e810, doi:10.1016/j.immuni.2022.04.006 (2022). Roy, E. R. et al. Concerted type I interferon signaling in microglia and neural cells promotes memory impairment associated with amyloid β plaques. Immunity 55 , 879-894.e876, doi:10.1016/j.immuni.2022.03.018 (2022). Yang, X. et al. Two-Year Health Outcomes in Hospitalized COVID-19 Survivors in China. JAMA Network Open 5 , e2231790-e2231790, doi:10.1001/jamanetworkopen.2022.31790 (2022). Ferren, M. et al. Hamster organotypic modeling of SARS-CoV-2 lung and brainstem infection. Nature Communications 12 , 5809, doi:10.1038/s41467-021-26096-z (2021). Paul, B. D., Snyder, S. H. & Bohr, V. A. Signaling by cGAS–STING in Neurodegeneration, Neuroinflammation, and Aging. Trends in Neurosciences 44 , 83-96, doi:https://doi.org/10.1016/j.tins.2020.10.008 (2021). Norden, D. M., Trojanowski, P. J., Villanueva, E., Navarro, E. & Godbout, J. P. Sequential activation of microglia and astrocyte cytokine expression precedes increased iba-1 or GFAP immunoreactivity following systemic immune challenge. Glia 64 , 300-316, doi:https://doi.org/10.1002/glia.22930 (2016). Becker, J. H. et al. Assessment of Cognitive Function in Patients After COVID-19 Infection. JAMA Network Open 4 , e2130645-e2130645, doi:10.1001/jamanetworkopen.2021.30645 (2021). Beraki, S., Aronsson, F., Karlsson, H., Ögren, S. O. & Kristensson, K. Influenza A virus infection causes alterations in expression of synaptic regulatory genes combined with changes in cognitive and emotional behaviors in mice. Molecular Psychiatry 10 , 299-308, doi:10.1038/sj.mp.4001545 (2005). Dai, J. et al. Acetylation Blocks cGAS Activity and Inhibits Self-DNA-Induced Autoimmunity. Cell 176 , 1447-1460.e1414, doi:https://doi.org/10.1016/j.cell.2019.01.016 (2019). Gelber, R., Peters, J. H., Gordon, G. R., Glazko, A. J. & Levy, L. The polymorphic acetylation of dapsone in man. Clinical Pharmacology & Therapeutics 12 , 225-238, doi:https://doi.org/10.1002/cpt1971122part1225 (1971). RUZICKA, T. & GOERZ, G. Dapsone in the treatment of lupus erythematosus. British Journal of Dermatology 104 , 53-57 (1981). HALL, R. P., LAWLEY, T. J., SMITH, H. R. & KATZ, S. I. Bullous eruption of systemic lupus erythematosus: dramatic response to dapsone therapy. Annals of Internal Medicine 97 , 165-170 (1982). Ujiie, H., Shimizu, T., Ito, M., Arita, K. & Shimizu, H. Lupus erythematosus profundus successfully treated with dapsone: review of the literature. Archives of dermatology 142 , 393-403 (2006). Salehzadeh, F., Jahangiri, S. & Mohammadi, E. Dapsone as an alternative therapy in children with familial Mediterranean fever. Iranian Journal of Pediatrics 22 , 23 (2012). Klebes, M., Wutte, N. & Aberer, E. Dapsone as second-line treatment for cutaneous lupus erythematosus? A retrospective analysis of 34 patients and a review of the literature. Dermatology 232 , 91-96 (2016). Aicardi, J. & Goutières, F. A progressive familial encephalopathy in infancy with calcifications of the basal ganglia and chronic cerebrospinal fluid lymphocytosis. Ann Neurol 15 , 49-54, doi:10.1002/ana.410150109 (1984). Crow, Y. J. et al. Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1. Am J Med Genet A 167a , 296-312, doi:10.1002/ajmg.a.36887 (2015). Tables Table 1. Sanatoria data in Japan in 1991 and Sorok Island data in South Korea from 2005 to 2020 Year *Treated Total AD % *Untreated Total AD % ** 1991 2031 71 0.035 1761 110 0.062 *** 2005 308 18 0.058 436 19 0.044 *** 2006 322 20 0.062 400 37 0.093 *** 2007 339 22 0.065 383 51 0.133 *** 2008 332 22 0.066 370 58 0.157 *** 2009 319 19 0.060 349 66 0.189 *** 2010 295 25 0.085 368 82 0.223 *** 2011 290 35 0.121 366 98 0.268 *** 2012 277 39 0.141 376 135 0.359 *** 2013 229 34 0.148 420 172 0.410 *** 2014 197 25 0.127 426 190 0.446 *** 2015 193 26 0.135 410 242 0.590 *** 2016 187 33 0.176 404 255 0.631 *** 2017 180 37 0.206 383 268 0.700 *** 2018 177 45 0.254 379 292 0.770 *** 2019 160 46 0.288 374 334 0.893 *** 2020 141 32 0.227 356 352 0.989 *For five years, dapsone-treated or -untreated **Japanese Sanatoria data, Intermitteently treated data (Table S14) was summed up as treated data for comparison with Korean data 5 6 ***The AD data among a summed number of dapsone users of Sorok Island in South Korea (Table S15) 4 Table 2. All COPD patients from 2005 to 2021. year COPD patients Non-COPD patients * T1:DDS (+) AD (+) T2:DDS (+) AD (-) T3:DDS (-) AD (+) T4:DDS (-) AD (-) T5:All AD (+) 2005 1 2 4 10 17 35 2006 0 0 0 0 0 2 2007 0 2 1 3 6 6 2008 0 0 0 4 4 4 2009 0 1 2 1 4 1 2010 0 0 0 2 2 10 2011 0 1 2 7 10 1 2012 1 2 7 10 20 2 2013 2 3 3 7 15 3 2014 0 3 0 4 7 4 2015 0 1 0 1 2 1 2016 0 1 0 1 2 4 2017 1 3 6 4 14 4 2018 0 0 0 0 0 5 2019 0 0 0 0 0 5 2020 1 0 0 1 2 3 2021 0 1 0 1 2 1 *Four groups (T1, T2, T3, and T4) were classified: DDS-prescribed (+) subjects, DDS-unprescribed (-) subjects, dementia-diagnosed (+) subjects, and dementia-undiagnosed (-) subjects. Table 3. T1:T2:T3:T4 study of the prevalence of viral respiratory diseases (VRDs) on Sorok Island of South Korea. year VRD (+) T1 * T2 * VRD (-) T3 * T4 * Sum Mean SD f 95% CI g [CI g CI g ] 2012 448 237 211 205 103 102 653 163.25 70.95 10.97 152.28 234.20 2013 618 269 349 31 8 23 649 162.25 172.68 26.79 135.46 334.93 2014 585 236 349 38 6 32 623 155.75 164.85 26.16 129.59 320.60 2015 552 227 325 51 7 44 603 150.75 150.82 24.33 126.42 301.57 2016 526 207 319 65 4 61 591 147.75 142.63 23.25 124.50 290.38 2017 494 193 301 69 14 55 563 140.75 131.44 21.96 118.79 272.19 2018 481 178 303 75 15 60 556 139 129.14 21.66 117.34 268.14 2019 452 155 297 82 13 69 534 133.5 123.66 21.21 112.29 257.16 Sum 4156 1702 2454 616 170 446 Mean 519.50 212.75 306.75 41.07 21.25 55.75 SD 61.98 36.76 43.69 55.46 33.28 24.31 95% CI 1.88 1.75 1.73 4.39 5.04 2.26 517.62 211.00 305.02 36.68 16.21 53.49 521.38 214.50 308.48 45.46 26.29 58.01 * Four groups were classified: T1 group is DDS-prescribed (+) with VRD-diagnosed (+) subjects, T2 group is DDS-unprescribed (-) with VRD-diagnosed (+) subjects, T3 group is DDS-prescribed (+) with VRD-undiagnosed (-) subjects, and T4 group is DDS-unprescribed (-) with VRD-undiagnosed (-) subjects. VRD: Viral Respiratory Disease ** chi-square, e indicates a p value < 0.05, f Standard deviation (SD), g Confidence interval (CI). Additional Declarations No competing interests reported. Supplementary Files OnlineSupplementaryMaterialsTables.docx OnlineSupplementaryMaterialsFigures.docx GA.jpg Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3238261","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":226150214,"identity":"479eddc3-b068-4104-90a5-8bdfe4368111","order_by":0,"name":"Jong hoon Lee","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6ElEQVRIiWNgGAWjYFACxgYQKQfjJiDECGgxJkULBCTCFBHWIt9+uPFxQY1N+vb29ocPfu6xy2OQPnyAceYe3FoMziQ2G884lpY758wZY8OeZ8nFDHxpCYwbnuHRIsHYJs3bcDh3hkQOmwTPgQOJDTw8BowPDuBx2AzG9t+8Df/TJeSfP//5B6yF/wNeLQw3GNuYeRsOJEhIMJgxQ21hYNyARwvIL9I8x5INZ/DkGEvLHEhObONhMzg4A5/D2o8//MxTYycvwX784cc3B+wS+3mYHz7swecwDMAGxCRpGAWjYBSMglGACQAt2VFShmRu5wAAAABJRU5ErkJggg==","orcid":"","institution":"Seoul National University College of Medicine","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Jong","middleName":"hoon","lastName":"Lee","suffix":""}],"badges":[],"createdAt":"2023-08-06 01:14:04","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3238261/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3238261/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":44205539,"identity":"f25b7d7c-17be-400b-a047-bbace6efcd3c","added_by":"auto","created_at":"2023-10-06 20:16:50","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":856238,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRespiratory diseases and Alzheimer’s disease in leprosy patients on Sorok Island\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis is useful for comparing disease trends that are worsening and being treated. i. explain \u003cstrong\u003eAlzheimer’s disease\u003c/strong\u003e (AD) prevalence in 2010 without COPD after the Endemic, and ii. is the cumulative prevalence of AD. iii. explain the prevalence of AD by COPD and iv. is the cumulative prevalence of AD in COPD patients. v) Viral inflammatory diseases showed a sharp increase from 2008, followed by COPD and bronchitis, increasing in 2012 and decreasing from 2014. Pneumonia rose sharply in 2013 compared to previous years. This is useful for comparing disease trends. These are the prevalence of viral respiratory disease (VRDs), COPD, bronchitis, and Alzheimer’s disease (AD). ChEIs have frequent side effects, such as pharyngitis, pneumonia, increased cough, and bronchitis\u003csup\u003e*\u003c/sup\u003e. AD prevalence has increased. vi) The T1: Dapsone-prescribed AD patient group was modestly correlated with the T5 COPD patient group, and the T2 (dapsone-prescribed and AD-free patient group) was highly associated with the T5 COPD patient group. The T3 (dapsone-unprescribed AD patient group) was highly associated with the T5. The T2:T5 and T3:T5 explain the prevalence of COPD with AD. Dapsone prevents AD \u003csup\u003e4\u003c/sup\u003e, and COPD without dapsone provokes AD. In brief, COPD causes AD. (* The association between bronchitis, COPD, and the AA equation variables was considered statistically significant, and bacteria-origin pneumonia was not substantial. Dapsone treats VRDs and not pneumonia, but VRDs can provoke pneumonia \u003csup\u003e1\u003c/sup\u003e. We formulated the relationship as the acetylation by dapsone and Acetylcholine (AA) equation: ㅣ sum Dapsone taking group (+) – sum anti-AD drug-taking group (+) ㅣ \u003csup\u003e1\u003c/sup\u003e.)\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3238261/v1/3c3d5c5309c4e33555b1fe38.jpg"},{"id":44205540,"identity":"9a4a20b3-1134-4f6a-967f-e32309f9ce1b","added_by":"auto","created_at":"2023-10-06 20:16:50","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":923133,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eChanges in the prevalence of viral respiratory diseases (VRDs) after the legislation of the Dementia Management Act (DMA)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe T1 group was DDS-prescribed (+) with VRD-diagnosed subjects, the T2 group was DDS-unprescribed (-) with VRD-diagnosed (+) subjects, the T3 group was DDS (+)with VRD-undiagnosed (-) subjects, and the T4 group was DDS (-) with VRD (-) subjects. After the Dementia Management Act (DMA) was enacted in 2012, it became clear whether DDS was prescribed because patients should visit Sorokdo National Hospital. The column chart for the T test - Changes started in 2012, and the VRD patterns are apparent in T1, T2, T3, and T4. The T1:T2 graph shows that patients with dapsone have a relatively low prevalence among patients with VRD. The T2:T3 ratio shows that patients with dapsone have a very low risk. The T1:T3 chart shows that patients with dapsone have a decreased prevalence of VRD. T1:T4 demonstrate that VRD (+/-) groups with DDS (+/-) are décalcomanie, and this study should be scientific. T2:T4 indicated that the VRD (+) and VRD (-) groups without dapsone had a constant prevalence, and dapsone was the decisive variable for most VRD.\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3238261/v1/ad68d02b672d221ea8addb0c.jpg"},{"id":48432126,"identity":"c80f6d11-19fb-447d-a1e5-b31357359585","added_by":"auto","created_at":"2023-12-19 06:07:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":554308,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3238261/v1/f6165492-ea1f-4d18-912e-897aae047bf4.pdf"},{"id":44205541,"identity":"18dcff0c-b7b3-4b1f-873e-b422e360f9ca","added_by":"auto","created_at":"2023-10-06 20:16:50","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":196042,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineSupplementaryMaterialsTables.docx","url":"https://assets-eu.researchsquare.com/files/rs-3238261/v1/d8a0ee27b88605c7b8a90080.docx"},{"id":44205542,"identity":"e9a4e090-73da-4bb1-8018-9864aa1edd98","added_by":"auto","created_at":"2023-10-06 20:16:50","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":1397999,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineSupplementaryMaterialsFigures.docx","url":"https://assets-eu.researchsquare.com/files/rs-3238261/v1/13c3a34217ecf6d2a73ca9bc.docx"},{"id":44207261,"identity":"9a819d87-7990-4303-b3dd-7d779cec9fcf","added_by":"auto","created_at":"2023-10-06 20:24:50","extension":"jpg","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":236362,"visible":true,"origin":"","legend":"","description":"","filename":"GA.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3238261/v1/eafdae116e60b18921dc5e4e.jpg"}],"financialInterests":"No competing interests reported.","formattedTitle":"The study of whether acquired Mendelian diseases are the origin of Alzheimer’s disease from viral respiratory diseases.","fulltext":[{"header":"Plain language summary","content":"\u003cp\u003eCan Alzheimer\u0026rsquo;s disease (AD) develop after viral infections? Leprosy patients have a low prevalence of VRDs with dapsone. After the endemic, viral infection induces AD directly. In a previous study, the bronchitis/COPD group strongly correlated with acetylcholine excess, and in this study, COPD developed AD, and AAD exacerbated AD in COPD patients. The endemic causes bronchitis, COPD, and AD. Viral interferonopathy sets a direct pathway into AD as an origin.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eSorokdo National Hospital, dedicated to treating leprosy patients, separated the group taking dapsone from those not taking dapsone among Alzheimer\u0026rsquo;s disease (AD) patients from January 2005 to June 2020. This study demonstrates that the effects of dapsone are mixed with the viral interferonopathy in the Japanese sanatoria autopsy series \u003csup\u003e1\u003c/sup\u003e \u003csup\u003e2\u003c/sup\u003e \u003csup\u003e3\u003c/sup\u003e. AD patients increased in the DDS (-) group for fifteen years. As a result, data for Sanatoria in 1991 and Sorok Island for 2005-2006 are similar \u003csup\u003e4\u003c/sup\u003e \u003csup\u003e5\u003c/sup\u003e \u003csup\u003e6\u003c/sup\u003e. Based on the AD prevalence in patients, dapsone had a preventive effect against AD \u003csup\u003e4\u003c/sup\u003e. Their observations were scientific.\u003c/p\u003e\n\u003cp\u003eThis study was conducted on the potential clinical impact of continuing AD and related medicines (anti-AD drug, AAD) on elderly care in a real-life setting. The Dementia Management Act (DMA) in South Korea was enacted in August 2011 after declaring the \u0026quot;Warning against Dementia in 2008\u0026quot;. From 2012 to 2019, Donepezil, rivastigmine, risperidone and quertiapine increased the number of deaths based on \u003cem\u003eR\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.75 \u003csup\u003e7\u003c/sup\u003e. Acetylation and excess acetylcholine (ACh) affect viral respiratory diseases (VRDs), bronchitis, and chronic obstructive pulmonary disease (COPD) \u003csup\u003e1\u003c/sup\u003e. ACh excess might inhibit ACh receptors for interferon (IFN) production against virus invasion. Some AADs exacerbate viral respiratory inflammatory diseases, but acetylation drugs treat VRDs \u003csup\u003e8\u003c/sup\u003e \u003csup\u003e9\u003c/sup\u003e \u003csup\u003e10\u003c/sup\u003e. The downstream IFN-stimulated cascade should attenuate the overactive immune-mediated respiratory inflammatory response in the onset stages \u003csup\u003e9\u003c/sup\u003e \u003csup\u003e10\u003c/sup\u003e \u003csup\u003e11\u003c/sup\u003e \u003csup\u003e12\u003c/sup\u003e \u003csup\u003e13\u003c/sup\u003e. In a randomized controlled trial (RCT) study of the acetylation effect of dapsone in antihistamine refractory chronic idiopathic urticaria, viral respiratory infections occurred less in the trial group than in the placebo group \u003csup\u003e14\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eWe have observed progressive dementia as a complication of VRDs but have remained ambiguous \u003csup\u003e15\u003c/sup\u003e. Choline esterase inhibitors (ChEIs) have frequent side effects, such as pharyngitis, pneumonia, increased cough, and bronchitis \u003csup\u003e16\u003c/sup\u003e; Anti-psychotic drug uses increase mortality in dementia patients \u003csup\u003e7\u003c/sup\u003e \u003csup\u003e17\u003c/sup\u003e. Mendelian disorders demonstrated key up-regulation of IFN or IFN stimulating gene (ISG) expression \u003csup\u003e18\u003c/sup\u003e. The constitutive involvement of IFN is an attractive thesis to the acquired interfernopathies by VRDs or COVID-19. We analyzed the effects of dapsone to decide whether the Mendelian upregulation should induce AD or not from 2005 to 2019 in the Sorok Island cohort.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eAll methods were carried out in accordance with relevant guidelines and regulations. All experimental protocols were approved by the Korea National Institute for Bioethics Policy (KoNIBP) as the institutional and/or licensing committee. The KoNIBP approved this study for the Management of Life-sustaining Treatment and certified that this study was managed properly (approval number P01-202007-22-006). Informed consent was obtained from all subjects and/or their legal guardians.\u003c/p\u003e\n\u003cp\u003eSTUDY STRATEGY\u003c/p\u003e\n\u003cp\u003eInfluenza A virus (IAV) and SARS-CoV dysregulate human innate immune responses. Severe influenza exhibits distinct cytokine patterns similar to SARS-CoV-2\u0026rsquo;s ability to suppress immune responses \u003csup\u003e19\u003c/sup\u003e. We analyzed diverse relationships with immune-mediated VRDs, pneumonia, COPD, and AD through national health electronic data interchange (EDI) systems. The Korean government has established compulsory long-term care insurance, and the 'War against Dementia' was announced in 2008. It accelerates the socialization of dementia care services at a national level \u003csup\u003e20\u003c/sup\u003e \u003csup\u003e21\u003c/sup\u003e. Due to the DMA, psychiatrists - neurologists diagnosed and treated patients under the Medical Service Act \u003csup\u003e22\u003c/sup\u003e. As randomized by DMA, they bolstered dementia management and administered AADs as therapeutics to mild cognitive impairment (MCI) or AD patients \u003csup\u003e23\u003c/sup\u003e \u003csup\u003e24\u003c/sup\u003e. DMA randomized the dapsone-prescribing (+) group from the dapsone-non-prescribing (-) group due to mental psychiatric examinations \u003csup\u003e7\u003c/sup\u003e \u003csup\u003e25\u003c/sup\u003e. Medical staff prescribed AADs to treat MCI or AD. The War Against Dementia and DMA encouraged the prescription of AAD. It randomized the EDI code-based cohort studies, tested the cohort in a completely blinded state, and provided definite causality \u003csup\u003e7\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eELIGIBILITY CRITERIA\u003c/p\u003e\n\u003cp\u003eAccording to the Infectious Disease Control and Prevention Act, all Hansen subjects on Sorok Island have been registered at Sorokdo National Hospital. The cohort consisted of leprosy patients, dapsone, respiratory diseases, and AD in all Hansen subjects, according to the data received from Sorokdo National Hospital by South Korea's Official Information Disclosure Act. Therefore, we searched all medical records of the Sorokdo National Hospital with ICD-10 codes. (Table S1, S2, S3)\u003c/p\u003e\n\u003cp\u003eDDS(+):VRD(+) group (T1), DDS(-):VRD(+) group (T2), DDS(+):VRD(-) group (T3), and DDS(-):VRD(-) group (T4) were arranged. The T1:T3, T1:T4, T2:T3, and T2:T4 tests indicate that in approximately 2010, the group with dapsone and without dapsone were separated, and the group taking dapsone was less susceptible to VRD infection. The relationship between VRD and DDS each year was analyzed using the chi-square test. The p value was insignificant from 2006 to 2009 or 2011 to 2013 when the p value was considered significant at \u0026lt; 0.05. Thus, we separated two DDS (+/-) groups and classified VRD (+) patients with ICD-10 codes from 2012 to 2019. According to the One-way ANOVA Calculator, the f-ratio value is 116.07984. The p value is \u0026lt;.00001. The result is significant at p \u0026lt;.05. Tukey's honestly significant difference (HSD) procedure facilitates pairwise comparisons within T1:T2, T1:T3, T1:T4, T2:T3, and T2:T4. (Table S4, S5)\u003c/p\u003e\n\u003cp\u003eDATA COLLECTION\u003c/p\u003e\n\u003cp\u003eMedical data on the correlation between DDS and VRDs were analyzed by the International Classification of Diseases (ICD)-10 codes of viral respiratory infectious diseases. We archived data from January 2005 to June 2019 with the ICD codes of respiratory diseases (RDs). (Table S6, S7)\u003c/p\u003e\n\u003cp\u003eAccording to the ICD-10 codes for AD: F00, F01, F02, F03, F04, F05, F06, F07, F08, F09, and G30 (Table S1), AD drugs for symptomatic relief are donepezil, rivastigmine, galantamine, and memantine. The AD drugs for psychological symptoms are haloperidol, Risperidone, Quetiapine, Olanzapine, Aripiprazole, Oxcarbazepine, fluvoxamine, Escitalopram, Trazodone, Sertraline, Escitalopram, and Fluoxetine. We used the object-oriented database management system (ORDBMS) and Google spreadsheet for \u003cem\u003eR\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e analysis, linear equations, and SPSS. We again applied the linear equation and R\u003csup\u003e2\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eDEMOGRAPHY\u003c/p\u003e\n\u003cp\u003eHD patients would spend their whole lives on Sorok Island. According to the request to disclose health checkup information from 2005 to 2020 on October 27, 2020, 2186 people (1152 males, 1034 females) resided. The average age was 83.7 years (median (M) 84, interquartile range (IQR) 76.8\u0026ndash;91.2, standard deviation (SD) 10.8, 95% confidence interval (CI): 0.45, 83.6\u0026ndash;84.5).\u003c/p\u003e\n\u003cp\u003eSTUDY SELECTION\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Setting for the \u003c/strong\u003eICD Code of Korean Diseases and Medicines\u003c/p\u003e\n\u003cp\u003eFor VRD\u003c/p\u003e\n\u003cp\u003eAcute nasopharyngitis [common cold] J00, acute pharyngitis J02, acute pharyngitis unspecified J02.9, acute tonsillitis J03, acute tonsillitis unspecified J03.9, acute laryngitis J04.0, acute laryngopharyngitis J06.0, acute upper respiratory infection unspecified J06.9, influenza due to identified zoonotic or pandemic influenza virus J09, influenza with other manifestations seasonal influenza virus identified J10.8, viral pneumonia unspecified J12.9, acute bronchitis unspecified J20.9. (Table S6)\u003c/p\u003e\n\u003cp\u003eFor Respiratory Diseases\u003c/p\u003e\n\u003cul class=\"decimal_type\"\u003e\n\u003cli\u003e\n\u003cp\u003eImmune-related: Asthma J45, Predominantly allergic asthma J45.0, Nonallergic asthma J45.1, Asthma unspecified J45.9, Status asthmaticus J46, Vasomotor rhinitis J30.0, Allergic rhinitis, unspecified J30.4, Chronic rhinitis J31.0, Chronic sinusitis J32, Chronic maxillary sinusitis J32.0, Chronic pansinusitis J32.4, Other chronic sinusitis J32.8, Chronic sinusitis, unspecified J32.9, Chronic laryngitis J37.0, Chronic nasopharyngitis J31.1, Chronic pharyngitis J31.2, Abscess furuncle and carbuncle of nose J34.0, Deviated nasal septum J34.2, Other specified disorders of nose and nasal sinuses J34.8, Chronic tonsillitis J35.0, Peritonsillar abscess J36, Retropharyngeal and parapharyngeal abscess J39.0\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eBronchitis: Acute Bronchitis unspecified J20.9, Bronchitis, not specified as acute or chronic J40, Unspecified chronic bronchitis J42,\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003ePneumonia: Bacterial Pneumonia NEC J15, Other bacterial pneumonia J15.8, Bacterial Pneumonia unspecified J15.9, Pneumonia in bacterial diseases classified elsewhere J17.0, Other Pneumonia organism unspecified J18.8, Pneumonia unspecified J18.9,\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eCOPD: Pneumonitis due to food and vomit J69.0, Other chronic obstructive pulmonary disease J44, Chronic obstructive pulmonary disease, unspecified J44.9, Bronchiectasis J47\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eEnd stage: Pulmonary edema J81, Abscess of lung with pneumonia J85.1, Pleural effusion NEC J90, Pneumothorax J93, Hemothorax J94.2, Chronic pulmonary insufficiency following surgery J95.3, Acute respiratory failure J96.0, Pulmonary collapse J98.1, Other specified respiratory disorders J98.8, Respiratory disorder, unspecified J98.9. (Table S7)\u003c/p\u003e\n\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eRISK OF BIAS ASSESSMENT\u003c/p\u003e\n\u003cp\u003eThe Korean National Assembly unanimously passed the DMA in 2012 and diagnosed and treated all Hansen subjects without exception \u003csup\u003e26\u003c/sup\u003e. Medical staff treated patients with VRD, while no one knew dapsone's ability to compete with inflammasomes. All were in complete-blinded states. Randomization was unrestricted (no blocking or stratification), and the study's data team analyzed the ICD codes in the EMR databases of Sorokdo National Hospital. (Complete Blinded Study \u0026amp; Randomization)\u003c/p\u003e\n\u003cp\u003eDMA made all medical staff of Sorokdo National Hospital investigate dementia for all HD patients. AAD was prescribed for Hansen subjects, and dapsone was not for inactive HD patients. DMA administered dapsone to the trial group beginning in 2012. Therefore, we classified dapsone-unprescribed subjects as the control group.\u003c/p\u003e\n\u003cp\u003eSTATISTICAL ANALYSIS\u003c/p\u003e\n\u003cp\u003eSignificance was evaluated based on a p value of 0.05 from 2005 to 2021. We used the software programs Object-Relational DBMS and Google spreadsheet with SPSS, ANOVA calculator, and post hoc Tukey HSP (honestly significant difference) test. In addition, a t test was performed among T1, T2, T3, T4, or T5.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eWe investigated 93 subjects who survived non-COPD patients with AD in 2022. There were 62 females, the average age was 83.5 years, hypertension was present in 66 patients, no obesity or cancer was present, diabetes was present in 21 patients, and dapsone was taken in 38 patients. AD occurred in six patients (Number 10. 19, 45, 51, 62, 87) in 2007, four (Number 12, 31, 59, 76) in 2008, 1 (Number 88) in 2009, and ten (Number 33, 53, 54, 55, 57, 63, 69, 77, 84, 89) in 2010 since the endemic. AD patients increase without COPD. (Table S8, S9) Ten in 2010 is evidence that the endemic could directly induce AD.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eImmune-related viral respiratory diseases, COPD, and Alzheimer\u0026rsquo;s disease\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCOPD increased slowly from 2008 to 2011, rapidly increased in 2012 and 2013, and decreased \u003csup\u003e1\u003c/sup\u003e. Acute bronchitis quickly rose from 2012 to 2014 and then dropped \u003csup\u003e1\u003c/sup\u003e. Pneumonia increased sharply in 2013 compared to previous years \u003csup\u003e1\u003c/sup\u003e. The longitudinal analysis of all COPD subjects presents vital results. A total of 107 subjects from 2005 to 2021 developed COPD. There were 71 males and 36 females. The population\u0026apos;s average age was 87.6 years (M 88.1, IQR 80-93.9, SD 9.55, 95% CI: 0.19, 87.4-87.8). The minimum age was 55.6 years, and the highest was 106.8 years. There were 44 patients with hypertension, no obesity patients, 4 patients with cancer, 17 patients with diabetes mellitus, 26 patients with dapsone, and 31 patients with dementia. We analyzed the DDS (+)/(\u0026minus;) group, dementia diagnosed (+)/undiagnosed (-) group, and COPD group from 2005 to 2021 with the ANOVA calculator. The f-ratio value is 7.94. The p value is.000019. (Significant at p\u0026lt;.05) (Table S10)\u003c/p\u003e\n\u003cp\u003eWe investigated 24 subjects who survived COPD in 2022. Twenty subjects took dapsone, four of which had AD, and sixteen patients did not. The other four subjects did not take dapsone, of which three patients had AD and one patient did not have AD: DDS (+) 20, AD (+) 4, AD (-) 16/DDS (-) 4, AD (+) 3, and AD (-) 1. Dapsone-non-taking COPD survivors were more likely to suffer from AD than dapsone-taking COPD survivors, \u003cem\u003eX\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e (1, \u003cem\u003eN\u003c/em\u003e = 24) = 4.9, \u003cem\u003ep\u003c/em\u003e =.027. (Table S11)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCOPD has exacerbated AD.\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe number of AD patients in the COPD patient group was 1 in 2005, 0 in 2006, 3 in 2007, 0 in 2008, 0 in 2009, 0 in 2010, 1 in 2011, 3 in 2012, 4 in 2013, 0 in 2014, 1 in 2015, 2 in 2016, 5 in 2017, 0 in 2018, 0 in 2019, 2 in 2020, 2 in 2021, 0 in 2022. (Table S12)\u003c/p\u003e\n\u003cp\u003eDapsone was proposed as a treatment for MCI and AD \u003csup\u003e4\u003c/sup\u003e \u003csup\u003e6\u003c/sup\u003e \u003csup\u003e16\u003c/sup\u003e \u003csup\u003e27\u003c/sup\u003e. The post hoc Tukey HSD (honestly significant difference) procedure indicated pairwise comparisons of the DDS (+) AAD (+) group (T1) with the COPD group (T5), DDS (+) AAD (-) (T2) with T5, and DDS (-) AAD (+) (T3) with T5. (Calculator S1)\u003c/p\u003e\n\u003cp\u003eSupplement Calculator (C) 1: T1 and T5 were moderately correlated, \u003cem\u003er(17)\u003c/em\u003e =.72, \u003cem\u003ep\u003c/em\u003e =.0012.\u003c/p\u003e\n\u003cp\u003eC2: T1 association would be considered statistically significant. (Calculator S2)\u003c/p\u003e\n\u003cp\u003eC1: T2 and T5 were strongly positively correlated, \u003cem\u003er(17)\u003c/em\u003e =.75, \u003cem\u003ep\u003c/em\u003e = 0.00052.\u003c/p\u003e\n\u003cp\u003eC2: T2 association was considered statistically significant. (Calculator S3)\u003c/p\u003e\n\u003cp\u003eC1: T3 and T5 were strongly positively correlated, \u003cem\u003er(17)\u003c/em\u003e =.91, \u003cem\u003ep\u003c/em\u003e \u0026lt;.00001.\u003c/p\u003e\n\u003cp\u003eC2: T3 association would be considered statistically significant. (Calculator S4)\u003c/p\u003e\n\u003cp\u003eT1 is data of AD treated by dapsone and evolving AD. T1 has a modest correlation with T5. The modest correlation could explain why COPD would induce AD against dapsone. T2 explains the strong correlation with T5 between the prevalence of AD treated by dapsone from exacerbated AD in the COPD group. T3 correlates highest with T5. COPD without dapsone developed into AD, and AAD exacerbated COPD during medication for AD.\u003c/p\u003e\n\u003cp\u003eThis study elucidates the correlation between COPD and AD and paradoxically reports that ACh excess positively affects the clinical prevalence of exacerbated AD in treating COPD. Dapsone treats and prevents AD, but COPD worsens AD despite dapsone treatment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eDMA enrolled a total of 9649 participants in the completely blinded state.\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e4772 subjects were randomized from 2012 to 2020 on Sorok Island. (Fig. S1)\u003c/p\u003e\n\u003cp\u003eVRD (+) subjects (sum (S) = 4156, M = 519.50, SD = 61.98; 95% CI, 517.62\u0026ndash;521.38) consisted of T1: VRD (+) DDS (+) (S = 1702, M = 212.75, SD = 36.76) and T2: VRD (+) DDS (\u0026minus;) (S =2454, M = 306.75, SD = 88.70).\u003c/p\u003e\n\u003cp\u003eVRD (\u0026minus;) subjects (S = 616, M = 41.07, SD = 55.46) consisted of T3 VRD (-) DDS (+) (S = 170, M = 21.2, SD = 33.2) and T4 VRD (-) DDS (\u0026minus;) groups (S = 446, M = 55.7, SD = 24.3).\u003c/p\u003e\n\u003cp\u003eThe values of f and p were calculated using an ANOVA calculator. Four groups were defined for the T test: T 1: VRD (+) DDS (+), T 2: VRD (+) DDS (\u0026minus;), T 3: VRD (\u0026minus;) DDS (+), and T 4: VRD (\u0026minus;) DDS (\u0026minus;). The f-ratio value in the one-way ANOVA calculator for dependent measures is 116.08, and the p value is \u0026lt;.00001. The result is significant at p \u0026lt; 0.05. The comparisons (T1:T2, T1:T3, T1:T4, T2:T3, and T2:T4) were applicable except for T3:T4. (Table S5)\u003c/p\u003e\n\u003cp\u003eThe T1: T2 graph shows that patients with dapsone have a relatively low prevalence among patients with VRD. (Fig. S2) By Mann-Whitney U Test Calculator, the z-score is -2.88808. The p-value is .00386. The result is significant at p \u0026lt; .05.\u003c/p\u003e\n\u003cp\u003eThe T1:T3 graph shows that patients with dapsone have a decreased prevalence of VRD. (Fig. S3) By Mann-Whitney U Test Calculator, the z-score is 3.30816. The p-value is .00094. The result is significant at p \u0026lt; .05.\u003c/p\u003e\n\u003cp\u003eT1:T4 demonstrate that the VRD (+) DDS (+) group has conversely shown almost the d\u0026eacute;calcomnie pattern with the VRD (-) DDS (-) group. This proves that this study is scientific. (Fig. S4) By Mann-Whitney U Test Calculator, the z-score is 3.30816. The p-value is .00094. The result is significant at p \u0026lt; .05.\u003c/p\u003e\n\u003cp\u003eThe T2:T3 graph shows that patients with dapsone have a very low prevalence of VRD. (Fig. S5) By Mann-Whitney U Test Calculator, the z-score is 3.30816. The p-value is .00094. The result is significant at p \u0026lt; .05.\u003c/p\u003e\n\u003cp\u003eT2:T4 demonstrated that the VRD (+) and VRD (-) groups without dapsone had a constant prevalence, and dapsone was the decisive factor in preventing most VRD exacerbations. (Fig. S6) By Mann-Whitney U Test Calculator, the z-score is 3.30816. The p-value is .00094. The result is significant at p \u0026lt; .05.\u003c/p\u003e\n\u003cp\u003eSUMMARY OF FINDINGS AND RECOMMENDATIONS\u003c/p\u003e\n\u003cp\u003eThe endemic in 2008 caused bronchitis, COPD, and AD. Viral infection induces AD directly. AAD exacerbates VRDs and leads to the development of COPD in the previous study \u003csup\u003e1\u003c/sup\u003e. COPD developed into AD. VRDs and COPD positively cause AD and AAD indirectly contributes to AD\u0026rsquo;s development in treating COPD.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSafety\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll leprosy patients have lived there with national medical support.\u003c/p\u003e"},{"header":"Limitations","content":"\u003cp\u003eThis study included only leprosy patients.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe risk of COPD exacerbation may increase in the first 90 days of ChEI therapy in patients with dementia \u003csup\u003e28\u003c/sup\u003e. Viral infection and interferon treatment decrease muscarinic (M)2 receptor gene expression on parasympathetic nerve endings by causing the release of IFN-gamma, which inhibits M2 receptor gene expression. VRDs and IFN treatment decreased M2 receptor gene expression by causing the release of IFN-gamma. IFN-gamma inhibits M2 receptor gene expression on parasympathetic nerve endings \u003csup\u003e29\u003c/sup\u003e. ACh excess inhibits ACh receptors for IFN production against virus invasion because the genesis of the ACh receptor requires IFN \u003csup\u003e30\u003c/sup\u003e. The muscarinic and nicotinic receptors play critical roles in controlling immune function \u003csup\u003e31\u003c/sup\u003e. A previous study revealed the correlation between donepezil and ACh with VRDs. The ACh excess by AAD might negatively affect ACh receptor gene expression \u003csup\u003e1\u003c/sup\u003e. Chemo genetic concerns predict drugs modulating microglial functions. Tau protein induces substantial changes in microglial-immune signaling and early interferon-driven immune suppression. \u003csup\u003e32\u003c/sup\u003e. This clinical approach clearly defines the origin of AD as another origin from amyloidosis or tau accumulation \u003csup\u003e33\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eIon Gresser et al. reported in 1980 that the possibility that indecent exposure to IFN-1 might be harmful to the mammalian system and IFN excess should cause adverse reactions in the host. Human diseases were associated with IFN up-regulation. Mendelian up-regulation is inborn human interferonopathies. Systemic lupus erythematosus (SLE) and Aicardi\u0026ndash;Gouti\u0026egrave;res syndrome (AGS) are innate Mendelian up-regulation diseases \u003csup\u003e34\u003c/sup\u003e. COPD was associated with incident nonamnestic MCI, and the danger of COPD exacerbation in patients with AD and COPD may increase in the first 90 days of ChEI therapy \u003csup\u003e35\u003c/sup\u003e \u003csup\u003e28\u003c/sup\u003e. VRDs and IFN treatment decreased M2 receptor gene expression by causing the release of IFN-gamma. IFN-gamma inhibits M2 receptor gene expression on parasympathetic nerve endings \u003csup\u003e29\u003c/sup\u003e. ACh excess inhibits ACh receptors for IFN production against virus invasion because the genesis of the ACh receptor requires IFN \u003csup\u003e30\u003c/sup\u003e. The muscarinic and nicotinic receptors play critical roles in controlling immune function \u003csup\u003e31\u003c/sup\u003e. A previous study revealed the correlation between donepezil and ACh with VRDs. The ACh excess by AAD might negatively affect ACh receptor gene expression \u003csup\u003e1\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eNeuropilin 1 (NRP1) is a receptor that connects essential pattern recognition receptors and the immune response. It is engaged in developing the heart, vasculature, and neuronal system and establishes primarily a cellular receptor for various molecules \u003csup\u003e36\u003c/sup\u003e. The brain with AIDS has direct dementia effects from the retrovirus \u003csup\u003e37\u003c/sup\u003e. SARS-CoV-2 uses it as a coreceptor with ACE2 \u003csup\u003e38\u003c/sup\u003e \u003csup\u003e39\u003c/sup\u003e. NRP1 serves as the principal receptor mediating astrocyte entry of SARS-CoV-2 \u003csup\u003e40\u003c/sup\u003e. It plays a complex role in the secondary CD8 T-cell response to control VRDs and tumors \u003csup\u003e41\u003c/sup\u003e. NRP1 maintains protein complexes at cell-to-cell junctions in endothelial cells. The NRP1 deficiency was associated with larger plaque sizes in mice \u003csup\u003e42\u003c/sup\u003e. Group 3 innate lymphoid cells (ILC3s) are present in patients with COPD. ILC3s with NRP1 (NRP1\u003csup\u003e+\u003c/sup\u003e ILC3s) show higher levels of cytokines than NRP1\u003csup\u003e-\u003c/sup\u003e ILC3s, and NRP1\u003csup\u003e+\u003c/sup\u003e ILC3s play a potential role in inflammation \u003csup\u003e43\u003c/sup\u003e \u003csup\u003e44\u003c/sup\u003e. We define this up-regulation as acquired Mendelian up-regulation. NRP1\u003csup\u003e+\u003c/sup\u003e ILC3s constitute the inflammatory cascade pathway with IFN1 or cGAS-STING through acetylation-deacetylation \u003csup\u003e9\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eThe cGAS-STING-IFN-I axis in AD pathogenesis by VRDs\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe factor in the AA equation consisted of the dapsone-taking group and the AAD-taking AD group \u003csup\u003e7\u003c/sup\u003e. Through its acetylation capacity, dapsone inhibits the activation of both IFN-1 and NF-\u0026kappa;B by targeting cyclic GMP-AMP synthase (cGAS) \u003csup\u003e45\u003c/sup\u003e. The cGAS-stimulator of interferon genes (STING) and RNA sensing pathway has triggered innate immune responses such as COVID-19 \u003csup\u003e46\u003c/sup\u003e \u003csup\u003e47\u003c/sup\u003e. COVID-19 has a broad spectrum of diseases and has resulted in unprecedented rates of pneumonia, acute respiratory distress syndrome (ARDS), and death \u003csup\u003e48\u003c/sup\u003e. The IFN-1 system drives excessive inflammation and immunopathology \u003csup\u003e49\u003c/sup\u003e \u003csup\u003e50\u003c/sup\u003e. The cGAS-STING-IFN-I axis promotes the clearance of aberrant DNA and RNA viruses from the gut microbiota found in circulation \u003csup\u003e51\u003c/sup\u003e \u003csup\u003e52\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eThe interferonopathy of VRDs induces bronchitis, COPD, and AD.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe endemic in 2008 might induce innate immune responses \u003csup\u003e1\u003c/sup\u003e. Pandemic patients who required intensive care had higher risks of persistent symptoms and higher COPD assessment test scores \u003csup\u003e53\u003c/sup\u003e. SARS-CoV-2 can target granular neurons \u003csup\u003e54\u003c/sup\u003e. Immune-to-brain communication occurs as glia, microglia, and astrocytes interpret and propagate inflammatory signals, influencing physiological and behavioral changes \u003csup\u003e55\u003c/sup\u003e \u003csup\u003e56\u003c/sup\u003e. In addition, activating the peripheral immune system affects physiological and clinical responses by the immunological memory engram pathway \u003csup\u003e9\u003c/sup\u003e. Jacqueline \u003cem\u003eet al\u003c/em\u003e. reported a relatively high incidence of cognitive impairment in processing speed, category fluency, executive functioning, memory encoding, and recall several months after hospitalization in COVID-19 patients. This dysexecutive syndrome after COVID-19 has considerable implications for occupational, psychological, and functional outcomes \u003csup\u003e57\u003c/sup\u003e. These findings are generally consistent with other viruses\u0026apos; alterations in cognitive and emotional behaviors (e.g., influenza A). VRDs cause AD even if it is not from COPD \u003csup\u003e58\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eDapsone as a baseline treatment for exacerbated Mendelian diseases\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAcetylation inhibits cGAS-mediated interferon production \u003csup\u003e59\u003c/sup\u003e. The acetylation of dapsone showed genetic polymorphism and reproducible individual characteristics. Acetylation of dapsone and deacetylation of monoacetyl dapsone occurred concurrently. Plasma ratios acetylated to the parent drug reached constant states but were characteristic for the individual \u003csup\u003e60\u003c/sup\u003e. Dapsone is used to treat an IFN-1 overproduction for SLE, lupus erythematosus profundus, cutaneous lupus erythematosus, and familial Mediterranean fever \u003csup\u003e61\u003c/sup\u003e \u003csup\u003e62\u003c/sup\u003e \u003csup\u003e63\u003c/sup\u003e \u003csup\u003e64\u003c/sup\u003e \u003csup\u003e65\u003c/sup\u003e. AGS is also related to upregulated IFN-1 production with slight differences across numerous triggering endogenous nucleotide sensors \u003csup\u003e66\u003c/sup\u003e \u003csup\u003e67\u003c/sup\u003e. Based on the relative prevalence in leprosy patients, dapsone had a preventive effect against AD \u003csup\u003e4\u003c/sup\u003e. Therefore, it is necessary to set a prospective cohort for the leprosy patients of Sorok Island after stopping prescribing the AAD. Moreover, RCT studies are needed around the world. (Fig. S7)\u003c/p\u003e\n\u003cp\u003eThe endemic causes bronchitis, COPD, and AD. Viral interferonopathy might set a direct pathway into AD as an origin.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was not supported by any institute. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict Of Interest Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no conflicts of interest to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization, J.H.L. ; methodology, J.H.L. ; investigation, J.H.L. ; resources, J.H.L. ; data curation, J.H.L. ; writing\u0026mdash;original draft, J.H.L. ; editing, J.H.L. : review, all; supervision, J.H.L. ; project administration, J.H.L. All authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData and materials availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026quot;All data are available in the main text or the supplementary materials.\u0026quot; Additional data supporting this study\u0026apos;s findings are available from the corresponding author upon reasonable request. In addition, the complete detailed survey is provided as a separate file. LEE, JONG HOON (2023): Data on Viral Respiratory Diseases and Alzheimer\u0026apos;s Diseases on Sorok Island in South Korea. figshare. Journal contribution. https://doi.org/10.6084/m9.figshare.22817060.v1\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLee, J. H.\u003cem\u003e et al.\u003c/em\u003e Bronchitis, COPD, and pneumonia after viral endemic of patients with leprosy on Sorok Island in South Korea. \u003cem\u003eNaunyn-Schmiedeberg\u0026apos;s Archives of Pharmacology\u003c/em\u003e, doi:10.1007/s00210-023-02407-7 (2023).\u003c/li\u003e\n\u003cli\u003eNamba, Y., Kawatsu, K., Izumi, S., Ueki, A. \u0026amp; Ikeda, K. Neurofibrillary tangles and senile plaques in brain of elderly leprosy patients. \u003cem\u003eLancet\u003c/em\u003e \u003cstrong\u003e340\u003c/strong\u003e, 978, doi:10.1016/0140-6736(92)92870-l (1992).\u003c/li\u003e\n\u003cli\u003eKimura, T. \u0026amp; Goto, M. Existence of senile plaques in the brains of elderly leprosy patients. \u003cem\u003eLancet\u003c/em\u003e \u003cstrong\u003e342\u003c/strong\u003e, 1364, doi:10.1016/0140-6736(93)92274-w (1993).\u003c/li\u003e\n\u003cli\u003eLee, J. H., Kanwar, B., Lee, C. J., Sergi, C. \u0026amp; Coleman, M. D. Dapsone is an anticatalysis for Alzheimer\u0026rsquo;s disease exacerbation. \u003cem\u003eiScience\u003c/em\u003e, doi:10.1016/j.isci.2022.104274 (2022).\u003c/li\u003e\n\u003cli\u003eMcgeer, P. L., Harada, N., Kimura, H., Mcgeer, E. G. \u0026amp; Schulzer, M. (Google Patents, 1993).\u003c/li\u003e\n\u003cli\u003eMcGeer, P. L., Harada, N., Kimura, H., McGeer, E. G. \u0026amp; Schulzer, M. Prevalence of dementia amongst elderly Japanese with leprosy: apparent effect of chronic drug therapy. \u003cem\u003eDement. Geriatr. Cogn. Disord.\u003c/em\u003e \u003cstrong\u003e3\u003c/strong\u003e, 146-149 (1992).\u003c/li\u003e\n\u003cli\u003eLee, J. H. The listed, delisted, and sustainability of therapeutic medicines for dementia patients: the study is specific to South Korea. \u003cem\u003eNaunyn Schmiedebergs Arch Pharmacol\u003c/em\u003e \u003cstrong\u003e395\u003c/strong\u003e, 535-546, doi:10.1007/s00210-022-02209-3 (2022).\u003c/li\u003e\n\u003cli\u003eSecnik, J.\u003cem\u003e et al.\u003c/em\u003e Dementia and psychotropic medications are associated with significantly higher mortality in geriatric patients hospitalized with COVID-19: data from the StockholmGeroCovid project. \u003cem\u003eAlzheimer\u0026apos;s Research \u0026amp; Therapy\u003c/em\u003e \u003cstrong\u003e15\u003c/strong\u003e, 5, doi:10.1186/s13195-022-01154-w (2023).\u003c/li\u003e\n\u003cli\u003eLee, J. H.\u003cem\u003e et al.\u003c/em\u003e COVID-19 Molecular Pathophysiology: Acetylation of Repurposing Drugs. \u003cem\u003eInternational Journal of Molecular Sciences\u003c/em\u003e \u003cstrong\u003e23\u003c/strong\u003e, 13260 (2022).\u003c/li\u003e\n\u003cli\u003eLee, J. h. Treatment mechanism of immune triad from the repurposing drug against COVID-19. \u003cem\u003eTranslational Medicine of Aging\u003c/em\u003e \u003cstrong\u003e7\u003c/strong\u003e, 33-45, doi:https://doi.org/10.1016/j.tma.2023.06.005 (2023).\u003c/li\u003e\n\u003cli\u003eLee, J.-h., An, H. K., Sohn, M.-G., Kivela, P. \u0026amp; Oh, S. 4,4\u0026prime;-Diaminodiphenyl Sulfone (DDS) as an Inflammasome Competitor. \u003cem\u003eInternational Journal of Molecular Sciences\u003c/em\u003e \u003cstrong\u003e21\u003c/strong\u003e, 5953 (2020).\u003c/li\u003e\n\u003cli\u003eKanwar, B., Lee, C. J. \u0026amp; Lee, J.-H. Specific Treatment Exists for SARS-CoV-2 ARDS. \u003cem\u003eVaccines\u003c/em\u003e \u003cstrong\u003e9\u003c/strong\u003e, 635 (2021).\u003c/li\u003e\n\u003cli\u003eKanwar, B. A., Khattak, A., Balentine, J., Lee, J. H. \u0026amp; Kast, R. E. Benefits of Using Dapsone in Patients Hospitalized with COVID-19. \u003cem\u003eVaccines\u003c/em\u003e \u003cstrong\u003e10\u003c/strong\u003e, 195 (2022).\u003c/li\u003e\n\u003cli\u003eMorgan, M., Cooke, A., Rogers, L., Adams-Huet, B. \u0026amp; Khan, D. A. Double-Blind Placebo-Controlled Trial of Dapsone in Antihistamine Refractory Chronic Idiopathic Urticaria. \u003cem\u003eThe Journal of Allergy and Clinical Immunology: In Practice\u003c/em\u003e \u003cstrong\u003e2\u003c/strong\u003e, 601-606, doi:10.1016/j.jaip.2014.06.004 (2014).\u003c/li\u003e\n\u003cli\u003eSipil\u0026auml;, P. N.\u003cem\u003e et al.\u003c/em\u003e Hospital-treated infectious diseases and the risk of dementia: a large, multicohort, observational study with a replication cohort. \u003cem\u003eThe Lancet Infectious Diseases\u003c/em\u003e \u003cstrong\u003e21\u003c/strong\u003e, 1557-1567, doi:https://doi.org/10.1016/S1473-3099(21)00144-4 (2021).\u003c/li\u003e\n\u003cli\u003eLee, J. H., Choi, S. H., Lee, C. J. \u0026amp; Oh, S. S. Recovery of Dementia Syndrome following Treatment of Brain Inflammation. \u003cem\u003eDement Geriatr Cogn Dis Extra\u003c/em\u003e \u003cstrong\u003e10\u003c/strong\u003e, 1-12, doi:10.1159/000504880 (2020).\u003c/li\u003e\n\u003cli\u003eStone, M. Mortality and antipsychotic drug use in dementia-related behavioral disorders. US Department of Health and Human Services. \u003cem\u003eFood and Drug Administration, Center for Drug Evaluation and Research\u003c/em\u003e \u003cstrong\u003e3\u003c/strong\u003e, 1-26 (2005).\u003c/li\u003e\n\u003cli\u003eMari\u0026eacute;, I. J., Chang, H.-M. \u0026amp; Levy, D. E. HDAC stimulates gene expression through BRD4 availability in response to IFN and in interferonopathies. \u003cem\u003eJournal of Experimental Medicine\u003c/em\u003e \u003cstrong\u003e215\u003c/strong\u003e, 3194-3212, doi:10.1084/jem.20180520 (2018).\u003c/li\u003e\n\u003cli\u003eLiu, G. \u0026amp; Gack, M. U. Insights into pandemic respiratory viruses: manipulation of the antiviral interferon response by SARS-CoV-2 and influenza A virus. \u003cem\u003eCurrent Opinion in Immunology\u003c/em\u003e \u003cstrong\u003e78\u003c/strong\u003e, 102252, doi:https://doi.org/10.1016/j.coi.2022.102252 (2022).\u003c/li\u003e\n\u003cli\u003eChon, Y. The expansion of the Korean welfare state and its results@ focusing on lon\u0026Dagger; term care insurance for the elderly. \u003cem\u003eSoc. Policy Adm.\u003c/em\u003e \u003cstrong\u003e48\u003c/strong\u003e, 704-720 (2014).\u003c/li\u003e\n\u003cli\u003eLee, S. B. The community dementia reassurance center (chime ansim center) in South Korea. \u003cem\u003eAnn Geriatr Med Res\u003c/em\u003e \u003cstrong\u003e23\u003c/strong\u003e, 43-44, doi:10.4235/agmr.19.0024 (2019).\u003c/li\u003e\n\u003cli\u003eYoun, H. \u0026amp; Jeong, H.-G. Pharmacotherapy for dementia. \u003cem\u003eJournal of the Korean Medical Association\u003c/em\u003e \u003cstrong\u003e61\u003c/strong\u003e, 758-764, doi:10.5124/jkma.2018.61.12.758 (2018).\u003c/li\u003e\n\u003cli\u003eLee, D. W., Huh, Y. S. \u0026amp; Kim, K. W. Evidence-Based Treatment of Alzheimer\u0026apos;s Disease. \u003cem\u003eJournal of the Korean Medical Association\u003c/em\u003e \u003cstrong\u003e52\u003c/strong\u003e, 417-425, doi:10.5124/jkma.2009.52.4.417 (2009).\u003c/li\u003e\n\u003cli\u003eAhn, S. H.\u003cem\u003e et al.\u003c/em\u003e Drug persistency of cholinesterase inhibitors for patients with dementia of Alzheimer type in Korea. \u003cem\u003eArch Pharm Res\u003c/em\u003e \u003cstrong\u003e38\u003c/strong\u003e, 1255-1262, doi:10.1007/s12272-014-0500-8 (2015).\u003c/li\u003e\n\u003cli\u003eSeong Yun Jeong, Y. S. L. Epidemiological study of depression among patients with Hansen Disease at the national sorokdo hospital. \u003cem\u003eKorean Leprosy Bulletin\u003c/em\u003e \u003cstrong\u003e44\u003c/strong\u003e, 63-69 (2011).\u003c/li\u003e\n\u003cli\u003eHan, J. W.\u003cem\u003e et al.\u003c/em\u003e Overview of the Korean Longitudinal Study on Cognitive Aging and Dementia. \u003cem\u003ePsychiatry Investig\u003c/em\u003e \u003cstrong\u003e15\u003c/strong\u003e, 767-774, doi:10.30773/pi.2018.06.02 (2018).\u003c/li\u003e\n\u003cli\u003eLee, J. H., Lee, C. J., Park, J., Lee, S. J. \u0026amp; Choi, S. H. The Neuroinflammasome in Alzheimer\u0026apos;s Disease and Cerebral Stroke. \u003cem\u003eDement Geriatr Cogn Dis Extra\u003c/em\u003e \u003cstrong\u003e11\u003c/strong\u003e, 159-167, doi:10.1159/000516074 (2021).\u003c/li\u003e\n\u003cli\u003eMahan, R. J. \u0026amp; Blaszczyk, A. T. COPD Exacerbation and Cholinesterase Therapy in Dementia Patients. \u003cem\u003eThe Consultant Pharmacist\u003c/em\u003e \u003cstrong\u003e31\u003c/strong\u003e, 221-225, doi:10.4140/TCP.n.2016.221 (2016).\u003c/li\u003e\n\u003cli\u003eJacoby, D. B., Xiao, H. Q., Lee, N. H., Chan-Li, Y. \u0026amp; Fryer, A. D. Virus- and interferon-induced loss of inhibitory M2 muscarinic receptor function and gene expression in cultured airway parasympathetic neurons. \u003cem\u003eThe Journal of Clinical Investigation\u003c/em\u003e \u003cstrong\u003e102\u003c/strong\u003e, 242-248, doi:10.1172/JCI1114 (1998).\u003c/li\u003e\n\u003cli\u003eBalasa, B.\u003cem\u003e et al.\u003c/em\u003e Interferon \u0026gamma; (IFN-\u0026gamma;) Is Necessary for the Genesis of Acetylcholine Receptor\u0026ndash;induced Clinical Experimental Autoimmune Myasthenia gravis in Mice. \u003cem\u003eJournal of Experimental Medicine\u003c/em\u003e \u003cstrong\u003e186\u003c/strong\u003e, 385-391, doi:10.1084/jem.186.3.385 (1997).\u003c/li\u003e\n\u003cli\u003eKawashima, K., Fujii, T., Moriwaki, Y. \u0026amp; Misawa, H. Critical roles of acetylcholine and the muscarinic and nicotinic acetylcholine receptors in the regulation of immune function. \u003cem\u003eLife Sciences\u003c/em\u003e \u003cstrong\u003e91\u003c/strong\u003e, 1027-1032, doi:https://doi.org/10.1016/j.lfs.2012.05.006 (2012).\u003c/li\u003e\n\u003cli\u003eRexach, J. E.\u003cem\u003e et al.\u003c/em\u003e Tau Pathology Drives Dementia Risk-Associated Gene Networks toward Chronic Inflammatory States and Immunosuppression. \u003cem\u003eCell Reports\u003c/em\u003e \u003cstrong\u003e33\u003c/strong\u003e, 108398, doi:https://doi.org/10.1016/j.celrep.2020.108398 (2020).\u003c/li\u003e\n\u003cli\u003eUdeochu, J. C.\u003cem\u003e et al.\u003c/em\u003e Tau activation of microglial cGAS\u0026ndash;IFN reduces MEF2C-mediated cognitive resilience. \u003cem\u003eNature Neuroscience\u003c/em\u003e \u003cstrong\u003e26\u003c/strong\u003e, 737-750, doi:10.1038/s41593-023-01315-6 (2023).\u003c/li\u003e\n\u003cli\u003eCrow, Y. J. Type I interferonopathies: Mendelian type I interferon up-regulation. \u003cem\u003eCurrent Opinion in Immunology\u003c/em\u003e \u003cstrong\u003e32\u003c/strong\u003e, 7-12, doi:https://doi.org/10.1016/j.coi.2014.10.005 (2015).\u003c/li\u003e\n\u003cli\u003eSingh, B.\u003cem\u003e et al.\u003c/em\u003e A prospective study of chronic obstructive pulmonary disease and the risk for mild cognitive impairment. \u003cem\u003eJAMA neurology\u003c/em\u003e \u003cstrong\u003e71\u003c/strong\u003e, 581-588 (2014).\u003c/li\u003e\n\u003cli\u003eJiang, S. X.\u003cem\u003e et al.\u003c/em\u003e Neuropilin 1 Directly Interacts with Fer Kinase to Mediate Semaphorin 3A-induced Death of Cortical Neurons *\u0026lt;sup\u0026gt; \u0026lt;/sup\u0026gt;. \u003cem\u003eJournal of Biological Chemistry\u003c/em\u003e \u003cstrong\u003e285\u003c/strong\u003e, 9908-9918, doi:10.1074/jbc.M109.080689 (2010).\u003c/li\u003e\n\u003cli\u003ePrice, R. W.\u003cem\u003e et al.\u003c/em\u003e The Brain in AIDS: Central Nervous System HIV-1 Infection and AIDS Dementia Complex. \u003cem\u003eScience\u003c/em\u003e \u003cstrong\u003e239\u003c/strong\u003e, 586-592, doi:doi:10.1126/science.3277272 (1988).\u003c/li\u003e\n\u003cli\u003eDaly, J. L.\u003cem\u003e et al.\u003c/em\u003e Neuropilin-1 is a host factor for SARS-CoV-2 infection. \u003cem\u003eScience\u003c/em\u003e \u003cstrong\u003e370\u003c/strong\u003e, 861-865, doi:10.1126/science.abd3072 (2020).\u003c/li\u003e\n\u003cli\u003ePal, D., De, K., Yates, T. B., Kolape, J. \u0026amp; Muchero, W. Mutating novel interaction sites in NRP1 reduces SARS-CoV-2 spike protein internalization. \u003cem\u003eiScience\u003c/em\u003e \u003cstrong\u003e26\u003c/strong\u003e, doi:10.1016/j.isci.2023.106274 (2023).\u003c/li\u003e\n\u003cli\u003eKong, W.\u003cem\u003e et al.\u003c/em\u003e Neuropilin-1 Mediates SARS-CoV-2 Infection of Astrocytes in Brain Organoids, Inducing Inflammation Leading to Dysfunction and Death of Neurons. \u003cem\u003emBio\u003c/em\u003e \u003cstrong\u003e13\u003c/strong\u003e, e02308-02322, doi:doi:10.1128/mbio.02308-22 (2022).\u003c/li\u003e\n\u003cli\u003eHwang, J. Y., Sun, Y., Carroll, C. R., Usherwood, E. J. \u0026amp; D\u0026apos;Orazio, S. E. F. Neuropilin-1 Regulates the Secondary CD8 T Cell Response to Virus Infection. \u003cem\u003emSphere\u003c/em\u003e \u003cstrong\u003e4\u003c/strong\u003e, e00221-00219, doi:doi:10.1128/mSphere.00221-19 (2019).\u003c/li\u003e\n\u003cli\u003eBosseboeuf, E.\u003cem\u003e et al.\u003c/em\u003e Neuropilin-1 interacts with VE-cadherin and TGFBR2 to stabilize adherens junctions and prevent activation of endothelium under flow. \u003cem\u003eScience Signaling\u003c/em\u003e \u003cstrong\u003e16\u003c/strong\u003e, eabo4863, doi:doi:10.1126/scisignal.abo4863 (2023).\u003c/li\u003e\n\u003cli\u003eShikhagaie, M. M.\u003cem\u003e et al.\u003c/em\u003e Neuropilin-1 Is Expressed on Lymphoid Tissue Residing LTi-like Group 3 Innate Lymphoid Cells and Associated with Ectopic Lymphoid Aggregates. \u003cem\u003eCell Reports\u003c/em\u003e \u003cstrong\u003e18\u003c/strong\u003e, 1761-1773, doi:https://doi.org/10.1016/j.celrep.2017.01.063 (2017).\u003c/li\u003e\n\u003cli\u003eMeininger, I.\u003cem\u003e et al.\u003c/em\u003e Tissue-Specific Features of Innate Lymphoid Cells. \u003cem\u003eTrends in Immunology\u003c/em\u003e \u003cstrong\u003e41\u003c/strong\u003e, 902-917, doi:https://doi.org/10.1016/j.it.2020.08.009 (2020).\u003c/li\u003e\n\u003cli\u003eEllard, G., Gammon, P. T., Helmy, H. \u0026amp; Rees, R. Dapsone acetylation and the treatment of leprosy. \u003cem\u003eNature\u003c/em\u003e \u003cstrong\u003e239\u003c/strong\u003e, 159-160 (1972).\u003c/li\u003e\n\u003cli\u003eNeufeldt, C. J.\u003cem\u003e et al.\u003c/em\u003e SARS-CoV-2 infection induces a pro-inflammatory cytokine response through cGAS-STING and NF-\u0026kappa;B. \u003cem\u003eCommunications biology\u003c/em\u003e \u003cstrong\u003e5\u003c/strong\u003e, 1-15 (2022).\u003c/li\u003e\n\u003cli\u003eCrow, Y. J. \u0026amp; Stetson, D. B. The type I interferonopathies: 10 years on. \u003cem\u003eNature Reviews Immunology\u003c/em\u003e \u003cstrong\u003e22\u003c/strong\u003e, 471-483, doi:10.1038/s41577-021-00633-9 (2022).\u003c/li\u003e\n\u003cli\u003eCasanova, J. L. \u0026amp; Anderson, M. S. Unlocking life-threatening COVID-19 through two types of inborn errors of type I IFNs. \u003cem\u003eJ Clin Invest\u003c/em\u003e \u003cstrong\u003e133\u003c/strong\u003e, doi:10.1172/jci166283 (2023).\u003c/li\u003e\n\u003cli\u003eDomizio, J. D.\u003cem\u003e et al.\u003c/em\u003e The cGAS\u0026ndash;STING pathway drives type I IFN immunopathology in COVID-19. \u003cem\u003eNature\u003c/em\u003e \u003cstrong\u003e603\u003c/strong\u003e, 145-151 (2022).\u003c/li\u003e\n\u003cli\u003eRoy, E. R.\u003cem\u003e et al.\u003c/em\u003e Type I interferon response drives neuroinflammation and synapse loss in Alzheimer disease. \u003cem\u003eJ Clin Invest\u003c/em\u003e \u003cstrong\u003e130\u003c/strong\u003e, 1912-1930, doi:10.1172/JCI133737 (2020).\u003c/li\u003e\n\u003cli\u003eErttmann, S. F.\u003cem\u003e et al.\u003c/em\u003e The gut microbiota prime systemic antiviral immunity via the cGAS-STING-IFN-I axis. \u003cem\u003eImmunity\u003c/em\u003e \u003cstrong\u003e55\u003c/strong\u003e, 847-861.e810, doi:10.1016/j.immuni.2022.04.006 (2022).\u003c/li\u003e\n\u003cli\u003eRoy, E. R.\u003cem\u003e et al.\u003c/em\u003e Concerted type I interferon signaling in microglia and neural cells promotes memory impairment associated with amyloid \u0026amp;#x3b2; plaques. \u003cem\u003eImmunity\u003c/em\u003e \u003cstrong\u003e55\u003c/strong\u003e, 879-894.e876, doi:10.1016/j.immuni.2022.03.018 (2022).\u003c/li\u003e\n\u003cli\u003eYang, X.\u003cem\u003e et al.\u003c/em\u003e Two-Year Health Outcomes in Hospitalized COVID-19 Survivors in China. \u003cem\u003eJAMA Network Open\u003c/em\u003e \u003cstrong\u003e5\u003c/strong\u003e, e2231790-e2231790, doi:10.1001/jamanetworkopen.2022.31790 (2022).\u003c/li\u003e\n\u003cli\u003eFerren, M.\u003cem\u003e et al.\u003c/em\u003e Hamster organotypic modeling of SARS-CoV-2 lung and brainstem infection. \u003cem\u003eNature Communications\u003c/em\u003e \u003cstrong\u003e12\u003c/strong\u003e, 5809, doi:10.1038/s41467-021-26096-z (2021).\u003c/li\u003e\n\u003cli\u003ePaul, B. D., Snyder, S. H. \u0026amp; Bohr, V. A. Signaling by cGAS\u0026ndash;STING in Neurodegeneration, Neuroinflammation, and Aging. \u003cem\u003eTrends in Neurosciences\u003c/em\u003e \u003cstrong\u003e44\u003c/strong\u003e, 83-96, doi:https://doi.org/10.1016/j.tins.2020.10.008 (2021).\u003c/li\u003e\n\u003cli\u003eNorden, D. M., Trojanowski, P. J., Villanueva, E., Navarro, E. \u0026amp; Godbout, J. P. Sequential activation of microglia and astrocyte cytokine expression precedes increased iba-1 or GFAP immunoreactivity following systemic immune challenge. \u003cem\u003eGlia\u003c/em\u003e \u003cstrong\u003e64\u003c/strong\u003e, 300-316, doi:https://doi.org/10.1002/glia.22930 (2016).\u003c/li\u003e\n\u003cli\u003eBecker, J. H.\u003cem\u003e et al.\u003c/em\u003e Assessment of Cognitive Function in Patients After COVID-19 Infection. \u003cem\u003eJAMA Network Open\u003c/em\u003e \u003cstrong\u003e4\u003c/strong\u003e, e2130645-e2130645, doi:10.1001/jamanetworkopen.2021.30645 (2021).\u003c/li\u003e\n\u003cli\u003eBeraki, S., Aronsson, F., Karlsson, H., \u0026Ouml;gren, S. O. \u0026amp; Kristensson, K. Influenza A virus infection causes alterations in expression of synaptic regulatory genes combined with changes in cognitive and emotional behaviors in mice. \u003cem\u003eMolecular Psychiatry\u003c/em\u003e \u003cstrong\u003e10\u003c/strong\u003e, 299-308, doi:10.1038/sj.mp.4001545 (2005).\u003c/li\u003e\n\u003cli\u003eDai, J.\u003cem\u003e et al.\u003c/em\u003e Acetylation Blocks cGAS Activity and Inhibits Self-DNA-Induced Autoimmunity. \u003cem\u003eCell\u003c/em\u003e \u003cstrong\u003e176\u003c/strong\u003e, 1447-1460.e1414, doi:https://doi.org/10.1016/j.cell.2019.01.016 (2019).\u003c/li\u003e\n\u003cli\u003eGelber, R., Peters, J. H., Gordon, G. R., Glazko, A. J. \u0026amp; Levy, L. The polymorphic acetylation of dapsone in man. \u003cem\u003eClinical Pharmacology \u0026amp; Therapeutics\u003c/em\u003e \u003cstrong\u003e12\u003c/strong\u003e, 225-238, doi:https://doi.org/10.1002/cpt1971122part1225 (1971).\u003c/li\u003e\n\u003cli\u003eRUZICKA, T. \u0026amp; GOERZ, G. Dapsone in the treatment of lupus erythematosus. \u003cem\u003eBritish Journal of Dermatology\u003c/em\u003e \u003cstrong\u003e104\u003c/strong\u003e, 53-57 (1981).\u003c/li\u003e\n\u003cli\u003eHALL, R. P., LAWLEY, T. J., SMITH, H. R. \u0026amp; KATZ, S. I. Bullous eruption of systemic lupus erythematosus: dramatic response to dapsone therapy. \u003cem\u003eAnnals of Internal Medicine\u003c/em\u003e \u003cstrong\u003e97\u003c/strong\u003e, 165-170 (1982).\u003c/li\u003e\n\u003cli\u003eUjiie, H., Shimizu, T., Ito, M., Arita, K. \u0026amp; Shimizu, H. Lupus erythematosus profundus successfully treated with dapsone: review of the literature. \u003cem\u003eArchives of dermatology\u003c/em\u003e \u003cstrong\u003e142\u003c/strong\u003e, 393-403 (2006).\u003c/li\u003e\n\u003cli\u003eSalehzadeh, F., Jahangiri, S. \u0026amp; Mohammadi, E. Dapsone as an alternative therapy in children with familial Mediterranean fever. \u003cem\u003eIranian Journal of Pediatrics\u003c/em\u003e \u003cstrong\u003e22\u003c/strong\u003e, 23 (2012).\u003c/li\u003e\n\u003cli\u003eKlebes, M., Wutte, N. \u0026amp; Aberer, E. Dapsone as second-line treatment for cutaneous lupus erythematosus? A retrospective analysis of 34 patients and a review of the literature. \u003cem\u003eDermatology\u003c/em\u003e \u003cstrong\u003e232\u003c/strong\u003e, 91-96 (2016).\u003c/li\u003e\n\u003cli\u003eAicardi, J. \u0026amp; Gouti\u0026egrave;res, F. A progressive familial encephalopathy in infancy with calcifications of the basal ganglia and chronic cerebrospinal fluid lymphocytosis. \u003cem\u003eAnn Neurol\u003c/em\u003e \u003cstrong\u003e15\u003c/strong\u003e, 49-54, doi:10.1002/ana.410150109 (1984).\u003c/li\u003e\n\u003cli\u003eCrow, Y. J.\u003cem\u003e et al.\u003c/em\u003e Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1. \u003cem\u003eAm J Med Genet A\u003c/em\u003e \u003cstrong\u003e167a\u003c/strong\u003e, 296-312, doi:10.1002/ajmg.a.36887 (2015).\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1. \u003c/strong\u003eSanatoria data in Japan in 1991 and Sorok Island data in South Korea from 2005 to 2020\u003c/p\u003e\n\u003ctable style=\"border: none; width: 100.0%; border-collapse: collapse;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.28%; border: 1pt solid black; background: white; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: top;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cstrong\u003eYear\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.74%; border-top: 1pt solid #bfbfbf; border-right: 1pt solid #bfbfbf; border-bottom: 1pt solid #bfbfbf; border-image: initial; border-left: none; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: top;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cstrong\u003e\u003cem\u003e*Treated Total\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.98%; border-top: 1pt solid #bfbfbf; border-right: 1pt solid #bfbfbf; border-bottom: 1pt solid #bfbfbf; border-image: initial; border-left: none; background: #f2f2f2; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: top;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"color: black;\"\u003eAD\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.02%; border-top: 1pt solid #bfbfbf; border-right: 1pt solid #bfbfbf; border-bottom: 1pt solid #bfbfbf; border-image: initial; border-left: none; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: top;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cstrong\u003e\u003cem\u003e%\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.64%; border-top: 1pt solid #bfbfbf; border-right: 1pt solid #bfbfbf; border-bottom: 1pt solid #bfbfbf; border-image: initial; border-left: none; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: top;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cstrong\u003e\u003cem\u003e*Untreated Total\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.34%; border-top: 1pt solid #bfbfbf; border-right: 1pt solid #bfbfbf; border-bottom: 1pt solid #bfbfbf; border-image: initial; border-left: none; background: #f2f2f2; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: top;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"color: black;\"\u003eAD\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13%; border-top: 1pt solid #bfbfbf; border-right: 1pt solid #bfbfbf; border-bottom: 1pt solid #bfbfbf; border-image: initial; border-left: none; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: top;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cstrong\u003e\u003cem\u003e%\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.28%; border-right: 1pt solid black; border-bottom: 1pt solid black; border-left: 1pt solid black; border-image: initial; border-top: none; background: #92d050; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: top;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cstrong\u003e\u003cem\u003e\u003csup\u003e\u003cspan style=\"color: black;\"\u003e**\u003c/span\u003e\u003c/sup\u003e\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"color: black;\"\u003e1991\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.74%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #92d050; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cem\u003e\u003cspan style=\"color: black;\"\u003e2031\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.98%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #92d050; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cem\u003e\u003cspan style=\"color: black;\"\u003e71\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.02%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #92d050; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cem\u003e\u003cspan style=\"color: black;\"\u003e0.035\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.64%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #92d050; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cem\u003e\u003cspan style=\"color: black;\"\u003e1761\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.34%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #92d050; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cem\u003e\u003cspan style=\"color: black;\"\u003e110\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #92d050; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cem\u003e\u003cspan style=\"color: black;\"\u003e0.062\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.28%; border-top: none; border-left: 1pt solid black; border-bottom: 1pt solid #cccccc; border-right: 1pt solid black; background: #00b050; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: top;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cstrong\u003e\u003csup\u003e\u003cspan style=\"color: black;\"\u003e***\u003c/span\u003e\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style=\"color: black;\"\u003e2005\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.74%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #00b050; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e308\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.98%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #00b050; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e18\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.02%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #00b050; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e0.058\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.64%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #00b050; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e436\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.34%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #00b050; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e19\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #00b050; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e0.044\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.28%; border-top: none; border-left: 1pt solid black; border-bottom: 1pt solid #cccccc; border-right: 1pt solid black; background: #00b050; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: top;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cstrong\u003e\u003csup\u003e\u003cspan style=\"color: black;\"\u003e***\u003c/span\u003e\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style=\"color: black;\"\u003e2006\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.74%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #00b050; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e322\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.98%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #00b050; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e20\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.02%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #00b050; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e0.062\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.64%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #00b050; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e400\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.34%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #00b050; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e37\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #00b050; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e0.093\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n 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style=\"color: black;\"\u003e339\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.98%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e22\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.02%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e0.065\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.64%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e383\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.34%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e51\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e0.133\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.28%; border-top: none; border-left: 1pt solid black; border-bottom: 1pt solid #cccccc; border-right: 1pt solid black; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: top;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cstrong\u003e\u003csup\u003e\u003cspan style=\"color: black;\"\u003e***\u003c/span\u003e\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style=\"color: black;\"\u003e2008\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.74%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e332\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.98%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e22\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.02%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e0.066\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.64%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e370\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.34%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e58\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e0.157\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.28%; border-top: none; border-left: 1pt solid black; border-bottom: 1pt solid #cccccc; border-right: 1pt solid black; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: top;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cstrong\u003e\u003csup\u003e\u003cspan style=\"color: black;\"\u003e***\u003c/span\u003e\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style=\"color: black;\"\u003e2009\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.74%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e319\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.98%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e19\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.02%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e0.060\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.64%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e349\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.34%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e66\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e0.189\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.28%; border-top: none; border-left: 1pt solid black; border-bottom: 1pt solid #cccccc; border-right: 1pt solid black; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: top;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cstrong\u003e\u003csup\u003e\u003cspan style=\"color: black;\"\u003e***\u003c/span\u003e\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style=\"color: black;\"\u003e2010\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.74%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e295\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.98%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e25\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.02%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e0.085\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.64%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e368\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.34%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e82\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e0.223\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.28%; border-top: none; border-left: 1pt solid black; border-bottom: 1pt solid #cccccc; border-right: 1pt solid black; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: top;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cstrong\u003e\u003csup\u003e\u003cspan style=\"color: black;\"\u003e***\u003c/span\u003e\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style=\"color: black;\"\u003e2011\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.74%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n 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style=\"color: black;\"\u003e0.121\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.64%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e366\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.34%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e98\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e0.268\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.28%; border-top: none; border-left: 1pt solid black; border-bottom: 1pt solid #cccccc; border-right: 1pt solid black; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: top;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cstrong\u003e\u003csup\u003e\u003cspan style=\"color: black;\"\u003e***\u003c/span\u003e\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style=\"color: black;\"\u003e2012\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.74%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e277\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.98%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e39\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.02%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e0.141\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.64%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e376\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.34%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e135\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e0.359\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.28%; border-top: none; border-left: 1pt solid black; border-bottom: 1pt solid #cccccc; border-right: 1pt solid black; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: top;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cstrong\u003e\u003csup\u003e\u003cspan style=\"color: black;\"\u003e***\u003c/span\u003e\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style=\"color: black;\"\u003e2013\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.74%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e229\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.98%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e34\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.02%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e0.148\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.64%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e420\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.34%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e172\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e0.410\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.28%; border-top: none; border-left: 1pt solid black; border-bottom: 1pt solid #cccccc; border-right: 1pt solid black; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: top;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cstrong\u003e\u003csup\u003e\u003cspan style=\"color: black;\"\u003e***\u003c/span\u003e\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style=\"color: black;\"\u003e2014\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.74%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e197\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.98%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e25\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.02%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e0.127\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.64%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e426\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.34%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e190\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e0.446\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.28%; border-top: none; border-left: 1pt solid black; border-bottom: 1pt solid #cccccc; border-right: 1pt solid black; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: top;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cstrong\u003e\u003csup\u003e\u003cspan style=\"color: black;\"\u003e***\u003c/span\u003e\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style=\"color: black;\"\u003e2015\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.74%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e193\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.98%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e26\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.02%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e0.135\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.64%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e410\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.34%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e242\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e0.590\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.28%; border-top: none; border-left: 1pt solid black; border-bottom: 1pt solid #cccccc; border-right: 1pt solid black; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: top;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cstrong\u003e\u003csup\u003e\u003cspan style=\"color: black;\"\u003e***\u003c/span\u003e\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style=\"color: black;\"\u003e2016\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.74%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e187\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.98%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e33\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.02%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e0.176\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.64%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e404\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.34%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e255\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e0.631\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.28%; border-top: none; border-left: 1pt solid black; border-bottom: 1pt solid #cccccc; border-right: 1pt solid black; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: top;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cstrong\u003e\u003csup\u003e\u003cspan style=\"color: black;\"\u003e***\u003c/span\u003e\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style=\"color: black;\"\u003e2017\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.74%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e180\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.98%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e37\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.02%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e0.206\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.64%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e383\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.34%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e268\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e0.700\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.28%; border-top: none; border-left: 1pt solid black; border-bottom: 1pt solid #cccccc; border-right: 1pt solid black; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: top;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cstrong\u003e\u003csup\u003e\u003cspan style=\"color: black;\"\u003e***\u003c/span\u003e\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style=\"color: black;\"\u003e2018\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.74%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e177\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.98%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e45\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.02%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e0.254\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.64%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e379\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.34%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e292\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e0.770\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.28%; border-top: none; border-left: 1pt solid black; border-bottom: 1pt solid #cccccc; border-right: 1pt solid black; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: top;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cstrong\u003e\u003csup\u003e\u003cspan style=\"color: black;\"\u003e***\u003c/span\u003e\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style=\"color: black;\"\u003e2019\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.74%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e160\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.98%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e46\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.02%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e0.288\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.64%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e374\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.34%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e334\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e0.893\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11.28%; border-right: 1pt solid black; border-bottom: 1pt solid black; border-left: 1pt solid black; border-image: initial; border-top: none; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: top;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cstrong\u003e\u003csup\u003e\u003cspan style=\"color: black;\"\u003e***\u003c/span\u003e\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style=\"color: black;\"\u003e2020\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.74%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e141\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.98%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e32\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.02%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e0.227\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.64%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e356\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.34%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e352\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13%; border-top: none; border-left: none; border-bottom: 1pt solid #cccccc; border-right: 1pt solid #cccccc; background: #ccc0d9; padding: 1.5pt 2.25pt; height: 15.75pt; vertical-align: bottom;\"\u003e\n \u003cp style=\"margin: 0in; font-size: 13px; font-family: 'Times New Roman',serif; text-align: center;\"\u003e\u003cspan style=\"color: black;\"\u003e0.989\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*For five years, dapsone-treated or -untreated **Japanese Sanatoria data, Intermitteently treated data (Table S14) was summed up as treated data for comparison with Korean data \u003csup\u003e5\u003c/sup\u003e \u003csup\u003e6\u003c/sup\u003e ***The AD data among a summed number of dapsone users of Sorok Island in South Korea (Table S15) \u003csup\u003e4\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. \u003c/strong\u003eAll COPD patients from 2005 to 2021.\u003c/p\u003e\n\u003ctable border=\"1\" width=\"100%\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.1010101010101%\"\u003e\n \u003cp\u003eyear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\" width=\"71.71717171717172%\"\u003e\n \u003cp\u003eCOPD patients\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003eNon-COPD patients\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003eT1:DDS (+) AD (+)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003eT2:DDS (+) AD (-)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003eT3:DDS (-) AD (+)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003eT4:DDS (-) AD (-)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003eT5:All\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003eAD (+)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e2005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e2006\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e2007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e2008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e2009\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e2010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e2011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e2012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e2013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e2014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e2015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e2016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.306122448979592%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.204081632653061%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.367346938775512%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*Four groups (T1, T2, T3, and T4) were classified: DDS-prescribed (+) subjects, DDS-unprescribed (-) subjects,\u0026nbsp;dementia-diagnosed (+) subjects, and\u0026nbsp;dementia-undiagnosed (-) subjects.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3.\u003c/strong\u003e T1:T2:T3:T4 study of the prevalence of viral respiratory diseases (VRDs) on Sorok Island of South Korea.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003eyear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003eVRD (+)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003eT1\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003eT2\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003eVRD (-)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003eT3\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003eT4\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003eSum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003eSD\u003csup\u003ef\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e95% CI\u003csup\u003eg\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e[CI\u003csup\u003eg\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003eCI\u003csup\u003eg\u003c/sup\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e2012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e448\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e237\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e211\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e205\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e103\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e102\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e653\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e163.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e70.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e10.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e152.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e234.20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e2013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e618\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e269\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e349\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e649\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e162.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e172.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e26.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e135.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e334.93\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e2014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e585\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e236\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e349\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e623\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e155.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e164.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e26.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e129.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e320.60\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e2015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e552\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e227\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e325\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e603\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e150.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e150.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e24.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e126.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e301.57\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e2016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e526\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e207\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e319\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e591\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e147.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e142.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e23.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e124.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e290.38\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e494\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e193\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e301\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e563\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e140.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e131.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e21.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e118.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e272.19\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e481\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e178\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n 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width=\"7.6923076923076925%\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e517.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e211.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e305.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e36.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e16.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e53.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e521.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e214.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e308.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e45.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e26.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e58.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003e*\u003c/sup\u003eFour groups were classified: T1 group is DDS-prescribed (+) with VRD-diagnosed (+) subjects, T2 group is DDS-unprescribed (-) with VRD-diagnosed (+) subjects, T3 group is DDS-prescribed (+) with VRD-undiagnosed (-) subjects, and T4 group is DDS-unprescribed (-) with VRD-undiagnosed (-) subjects. VRD: Viral Respiratory Disease \u003csup\u003e**\u0026nbsp;\u003c/sup\u003echi-square, e indicates a p value \u0026lt; 0.05, f Standard deviation (SD), g Confidence interval (CI).\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Alzheimer’s disease, Anti-Alzheimer’s disease drugs, COPD, Interferonopathies, Mendelian up-regulation, Viral respiratory disease","lastPublishedDoi":"10.21203/rs.3.rs-3238261/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3238261/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"We must study viral RNA infection, sustained interferon response, acetylcholine excess, and developing Alzheimer’s disease (AD). We analyzed viral respiratory disease (VRD) (+)/(−) and dapsone (DDS) (+)/(−) groups. ANOVA calculator, logistic regression analysis, and Mann-Whitney U Test Calculator were used to examine the association of VRDs, COPD, and anti-AD drugs (AADs) with AD. A total of 107 subjects from 2005 to 2021 developed COPD. The DDS (+) AAD (-) and DDS (-) AAD (+) groups were strongly positively correlated with all COPD subjects. COPD develops into AD without dapsone, and AAD exacerbates AD through COPD. Ten AD among ninety-three non-COPD patients occurred in 2010 since the endemic. Viral infections set a direct pathway into AD directly without COPD. The endemic causes bronchitis, COPD, and AD. Acquired Mendelian up-regulation might set a direct pathway into AD as an origin.","manuscriptTitle":"The study of whether acquired Mendelian diseases are the origin of Alzheimer’s disease from viral respiratory diseases.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-10-06 20:16:45","doi":"10.21203/rs.3.rs-3238261/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c9a53663-0779-45cd-817c-f4229242a50c","owner":[],"postedDate":"October 6th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":24014873,"name":"Biological sciences/Cell biology/Cell death"},{"id":24014874,"name":"Biological sciences/Cell biology/Post translational modifications"},{"id":24014875,"name":"Biological sciences/Cell biology/Senescence"},{"id":24014876,"name":"Health sciences/Diseases/Immunological disorders/Inflammatory diseases/Autoinflammatory syndrome"},{"id":24014877,"name":"Health sciences/Diseases/Neurological disorders/Dementia/Alzheimers disease"}],"tags":[],"updatedAt":"2023-12-19T05:59:23+00:00","versionOfRecord":[],"versionCreatedAt":"2023-10-06 20:16:45","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3238261","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3238261","identity":"rs-3238261","version":["v1"]},"buildId":"ApUGefWb6u5IBVtyqm6d5","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}