Cytoplasmic changes in bone marrow cells as indicators of postmortem interval.

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Traditional external markers are limited by environmental and individual variability. Bone marrow, owing to its protected anatomical location and slower decomposition rate, offers a potential histological substrate for PMI estimation. Aim This study aimed to evaluate cytoplasmic changes in sternal bone marrow cells and assess their correlation with Postmortem interval (PMI). Methods A descriptive cross-sectional study of 43 medico-legal autopsies with documented time of death. Sternal bone marrow aspirates were stained with Leishman stain and examined microscopically. Cytoplasmic changes were scored from 0 to 4 (intact morphology to complete dissolution) using a system adapted from Biradar G et al. Data were analyzed using ANOVA (p < 0.05). Results Mild cytoplasmic alterations (S1) were most frequent (51.1%), followed by moderate changes (S2, 25.6%) and severe dissolution (S4, 14%). Only 9.3% of cases showed no observable changes (S0). Mean PMI increased with the severity of cytoplasmic changes (S0: 8.5 h; S1: 14.1 h; S2: 10.5 h; S4: 15.0 h), although some overlap was seen, especially at S2, likely reflecting biological and environmental variability. The overall correlation was not statistically significant (p > 0.05). Conclusion Cytoplasmic autolysis in bone marrow follows a sequential pattern, from early vacuolation to complete dissolution with increasing PMI. Although not statistically significant, observed trends suggest cytoplasmic scoring may aid early PMI estimation when combined with other markers. 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F1000Research 2025, 14 :964 ( https://doi.org/10.12688/f1000research.169755.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Research Article Cytoplasmic changes in bone marrow cells as indicators of postmortem interval. [version 1; peer review: 1 approved, 1 approved with reservations] Mahabalesh Shetty 1 , Vinoth Guru https://orcid.org/0009-0004-1133-4222 2 , Kishan Prasad HL 3 , Suraj S Shetty 4 Mahabalesh Shetty 1 , Vinoth Guru https://orcid.org/0009-0004-1133-4222 2 , Kishan Prasad HL 3 , Suraj S Shetty 4 PUBLISHED 22 Sep 2025 Author details Author details 1 Professor, Nitte (Deemed to be University), KS Hegde Medical Academy (KSHEMA), Department of Forensic Medicine and Toxicology, Mangalore, India 2 Resident, Nitte (Deemed to be University), KS Hegde Medical Academy (KSHEMA), Department of Forensic Medicine and Toxicology, Mangalore, India 3 Professor, Nitte (Deemed to be University), KS Hegde Medical Academy (KSHEMA), Department of Pathology, Mangalore, India 4 Professor and Head, Nitte (Deemed to be University), KS Hegde Medical Academy (KSHEMA), Department of Forensic Medicine and Toxicology, Mangalore, India Mahabalesh Shetty Roles: Conceptualization, Formal Analysis, Project Administration, Resources, Supervision, Validation, Visualization, Writing – Review & Editing Vinoth Guru Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Kishan Prasad HL Roles: Conceptualization, Formal Analysis, Methodology, Supervision, Validation, Visualization, Writing – Review & Editing Suraj S Shetty Roles: Conceptualization, Formal Analysis, Methodology, Software, Supervision, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Health Services gateway. Abstract Background Accurate estimation of the postmortem interval (PMI) remains one of the central challenges in forensic medicine. Traditional external markers are limited by environmental and individual variability. Bone marrow, owing to its protected anatomical location and slower decomposition rate, offers a potential histological substrate for PMI estimation. Aim This study aimed to evaluate cytoplasmic changes in sternal bone marrow cells and assess their correlation with Postmortem interval (PMI). Methods A descriptive cross-sectional study of 43 medico-legal autopsies with documented time of death. Sternal bone marrow aspirates were stained with Leishman stain and examined microscopically. Cytoplasmic changes were scored from 0 to 4 (intact morphology to complete dissolution) using a system adapted from Biradar G et al. Data were analyzed using ANOVA (p < 0.05). Results Mild cytoplasmic alterations (S1) were most frequent (51.1%), followed by moderate changes (S2, 25.6%) and severe dissolution (S4, 14%). Only 9.3% of cases showed no observable changes (S0). Mean PMI increased with the severity of cytoplasmic changes (S0: 8.5 h; S1: 14.1 h; S2: 10.5 h; S4: 15.0 h), although some overlap was seen, especially at S2, likely reflecting biological and environmental variability. The overall correlation was not statistically significant (p > 0.05). Conclusion Cytoplasmic autolysis in bone marrow follows a sequential pattern, from early vacuolation to complete dissolution with increasing PMI. Although not statistically significant, observed trends suggest cytoplasmic scoring may aid early PMI estimation when combined with other markers. READ ALL READ LESS Keywords Bone Marrow Cytology, Forensic Pathology, Postmortem Interval (PMI) Corresponding Author(s) Mahabalesh Shetty ( [email protected] ) Close Corresponding author: Mahabalesh Shetty Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2025 Shetty M et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Shetty M, Guru V, HL KP and S Shetty S. Cytoplasmic changes in bone marrow cells as indicators of postmortem interval. [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2025, 14 :964 ( https://doi.org/10.12688/f1000research.169755.1 ) First published: 22 Sep 2025, 14 :964 ( https://doi.org/10.12688/f1000research.169755.1 ) Latest published: 26 Dec 2025, 14 :964 ( https://doi.org/10.12688/f1000research.169755.2 )  There is a newer version of this article available. Suppress this message for one day. Introduction Thanatology, derived from the Greek word thanatos (meaning “death”), refers to the scientific study of death and its processes. It represents an interdisciplinary field encompassing significant elements of Anthropology, Pathology, Biochemistry, and Entomology. 1 A forensic autopsy is a vital process that helps shed light on the circumstances of deaths that are suspicious, sudden, or legally disputed. It plays a crucial role in uncovering the truth and providing answers for families, investigators, and the judicial system. For forensic pathologists, the primary goals include establishing the identity of the deceased, determining the cause of death, and, importantly, estimating the post-mortem interval (PMI), often referred to as Time Since Death (TSD). 2 Traditionally, Time since death (TSD) is calculated by looking at external physical changes such as body cooling (algor mortis), settling of blood (livor mortis), stiffening of muscles (rigor mortis), and the process of decomposition (putrefaction). Although these methods have been widely used, they are susceptible to numerous external influences, which complicates the precise determination of the time of death. 3 Owing to these limitations, forensic practitioners have shifted attention to histological examination and blood-based biochemical assays, which often yield more reliable estimates of the TSD than external findings alone. 4 Bone marrow has some unique advantages when it comes to postmortem studies, due to its protected anatomical location and slower rate of decomposition compared to soft tissues. This protected setting helps preserve the blood-forming (hematopoietic) cells inside, making bone marrow a valuable resource for understanding what happened after death. 5 After death, the cells in the bone marrow start to break down in a predictable way, offering important clues for estimating the time since death. Once life stops, natural self-digesting (autolytic) processes start, disrupting the delicate balance of cellular homeostasis. The cytoplasm starts to undergo series of progressive morphological alterations, from early vacuolization to eventual dissolution, providing a sequential framework that can be correlated with elapsed time since death. 6 Understanding the morphological changes of cytoplasmic degeneration in bone marrow cells allows forensic experts to approximate PMI with improved accuracy, especially in the early postmortem period. This study aims to examine these cytoplasmic changes in bone marrow after death and assess their value as reliable biological markers for determining the time since death. Materials and methodology This observational study was designed as a descriptive, cross-sectional investigation conducted from June 2023 to November 2024 in the Department of Forensic Medicine at a tertiary care hospital in Mangalore, India. Based on a previous study by Biradar G et al. (2016), 7 which reported a standard deviation (σ) of 75.66, and using an acceptable margin of error (d) of 13.5 with a 99% confidence interval (Z = 2.58), the minimum calculated sample size was determined to be 43. The inclusion criteria for this study were cases with a documented time of death based on inquest or hospital records, bodies stored in cold chambers prior to autopsy, no history of hepatological malignancies or bone marrow disorders, and cases where informed consent and to publish clinical details and images was obtained from the legal next of kin of the deceased individuals. The exclusion criteria included cases with a history of hypothermia, those involving burns, neoplasms, or malnutrition, fractures of the sternum, significant pre-mortem blood loss, unknown or disputed time of death, exposure to extreme environmental conditions such as immersion, extreme heat, or freezing temperatures and individuals who had undergone chemotherapy, radiotherapy, or bone marrow transplantation before death. Sample collection was carried out by first making an I-shaped incision according to standard medico-legal autopsy protocols, carefully exposing the sternum to avoid injury to major vessels. Bone marrow was then aspirated from the junction of the first and second parts of the sternum using a Salah bone marrow aspiration needle attached to either a 10 ml or 50 ml syringe, depending on the resistance ( Figure 1 ). The aspirated samples were promptly transferred into EDTA tubes to prevent clotting. For smear preparation and staining, the samples were placed on frosted slides using a sterile pipette and spread evenly to create uniform smears. Multiple smears were prepared for thorough analysis. These slides were air-dried at room temperature, fixed with absolute alcohol, and subsequently stained using Leishman stain (Romanowsky technique) to demonstrate cytoplasmic details. During microscopic examination, the stained slides were evaluated under an electronic compound microscope, with particular attention given to cytoplasmic changes such as membrane breaks, vacuolation, and eventual dissolution. Table 1. Scoring system for cytoplasmic changes. 7 Score Cytoplasmic changes 0 No observable changes in the cytoplasmic membrane. 1 Breaks or discontinuities in the membrane. 2 Small cytoplasmic vacuoles present. 3 Large vacuoles indicating advanced degeneration. 4 Complete loss of cytoplasmic structure. Figure 1. Aspiration procedure - aspirated using a Salah bone marrow aspiration needle. The scoring system used to assess cellular changes in the bone marrow was adopted from the study by Biradar G, SatishBabu BS, Bakkannavar S, Pradeep Kumar G, Shaila B. Estimation of time since death from cytoplasm changes of bone marrow cells (2016)”. 7 Ethical consideration This study was conducted after obtaining approval from the Institutional Ethics Committee, K. S. Hegde Medical Academy, Nitte (Deemed to be University), Mangalore (Approval No: INST.EC/EC/131/2023, REG. NO: EC/NEW/INST/2022/KA/0174, dated 15th May 2023). Consent to publish: Written informed consent to publish clinical details and images was obtained from the legal next of kin of the deceased individuals who are included in this study. Consent was granted to the authors by the next of kin, and all efforts were made to anonymize data and images. Data collection The time of death issued by the treating physician was collected from the hospital file. Data entry and coding were done in Microsoft Excel. Data analysis Descriptive analysis such as frequencies, percentages, mean and standard deviation was done. Statistical analysis was performed using SPSS version 25. The Analysis of Variance (ANOVA) test was conducted to determine whether there were statistically significant differences among the means of multiple groups. p<0.05 considered as statistically significant. Results A total of 43 cases were included in this study, with a clear predominance of males (79.1%) compared to females (20.9%) ( Table 2 ). Table 2. Gender wise distribution of the participants (N=43). Gender N % Female 9 20.9 Male 34 79.1 Total 43 100.0 The mean age of the cases was 45.67 years with a standard deviation of 16.21. The mean time difference was 12.74 with a standard deviation of 6.02 ( Table 3 ). Table 3. Descriptive statistics for age and time difference. N Minimum Maximum Mean Std. Deviation Age 43 17.0 77.0 45.674 16.2095 Time difference 43 3 26 12.74 6.022 Overall, road traffic accidents (51.2%) were the most common cause of death among the cases, followed by fall from height (20.90%), poisoning(14%) and the least common was sudden death (13.90%). Among the 43 cases studied, cytoplasmic alterations in the bone marrow cells were graded based on the established scoring system. As shown in Table 4 . The majority of cases (51.1%) exhibited mild cytoplasmic changes (S1) ( Figure 3 ). A smaller proportion (25.6%) demonstrated moderate changes (S2) ( Figure 4 ), while extensive cytoplasmic dissolution (S4) ( Figure 5 ) was observed in 14.0% of the cases. Notably, 9.3% of the cases (4 out of 43) showed no observable cytoplasmic alterations (S0) ( Figure 2 ). No cases demonstrated large vacuolation (S3 stage), hence this category is not represented in the figures. Table 4. Distribution of cytoplasmic changes observed among the cases (N=43). Cytoplasm changes Frequency Percent S0 4 9.3 S1 22 51.1 S2 11 25.6 S4 6 14.0 Total 43 100.0 Figure 2. S0 - No change in the cytoplasmic membrane. Figure 3. S1 - Break in the cytoplasmic membrane. Figure 4. S2 - Small vacuoles in cytoplasm. Figure 5. S4 - Complete loss of cytoplasm. An analysis was performed to examine the relationship between the degree of cytoplasmic changes and the time difference (used as an estimate of PMI), as presented in Table 5 . • The four cases classified under S0 (no cytoplasmic changes) had the shortest mean time difference, averaging 8.50 ± 6.56 hours, with a range from 3 to 18 hours. • The 21 cases with mild cytoplasmic changes (S1) had a mean time difference of 14.09 ± 6.34 hours, ranging from 6 to 26 hours. • The 11 cases showing moderate changes (S2) displayed a mean of 10.48 ± 4.31 hours, spanning 5 to 17 hours. • The 6 cases with extensive cytoplasmic changes (S4) had the longest mean time difference, recorded at 14.97 ± 5.84 hours, with values ranging from 7 to 22 hours. Table 5. Relationship between time difference and cytoplasmic changes. (p<0.05 ** ). Cytoplasmic changes N Mean Std. Deviation (p) Minimum Maximum S0 4 8.50 6.557 3 18 S1 22 14.09 6.344 6 26 S2 11 10.48 4.307 5 17 S4 6 14.97 5.849 7 22 Total 43 12.74 6.022 3 26 ** Statistically significant. While a trend suggesting increasing cytoplasmic changes with longer post-mortem intervals was noted, variability was observed across categories, and no statistically significant correlation was found between time difference and cytoplasm changes (p>0.05). Discussion The estimation of the post-mortem interval (PMI) remains a cornerstone of forensic practice, guiding both legal and investigative processes. While traditional markers such as rigor mortis, hypostasis, and core body temperature are routinely employed, their reliability diminishes under certain circumstances, including when bodies have been refrigerated or environmental conditions vary significantly. In this context, microscopic evaluation of internal tissues, particularly bone marrow, the primary hematopoietic site, is relatively protected and decomposes more slowly than most soft tissues, so its cytoplasmic and nuclear autolytic changes provide a sequential, biologically plausible framework for PMI estimation. 8 Tattoli et al. (2014) emphasised the slower autolysis of bone marrow compared to other tissues, highlighting its potential utility in PMI estimation, especially in the early post-mortem period when traditional markers may yield equivocal results. Although our study did not find a statistically significant correlation, the observable pattern of progressive cytoplasmic changes supports this notion, reinforcing the potential role of bone marrow cytology as a complementary tool in forensic time since death estimation. 9 Biradar et al. (2016) observed the onset of cytoplasmic vacuolation at 5–7 hours postmortem, with advanced lysis beyond 16 hours. 7 Our study aligns with this timeline, showing mild cytoplasmic changes (S1) in over half the cases (51.1%) and extensive dissolution (S4) most commonly beyond 14–15 hours. Similarly, Babu et al. (2015) documented progressive vacuolation and cytoplasmic breakdown with increasing PMI, findings echoed in the present work. 10 More recently, Sakr et al. (2024) described minimal cytoplasmic changes at 6 hours, with substantial loss of cellular detail by 10–12 hours and necrosis beyond 18 hours. 11 The present results concur, showing that while early PMI cases exhibited intact or mildly altered cytoplasm, progressive vacuolation and dissolution became evident after 12 hours. Michalova et al. (2011) further demonstrated that hematopoietic stem cells remained viable for 2–12 hours within the intact femur, with marrow cell suspensions preserving viability for up to two days at 37°C and four days at 4°C. 12 Although our study did not examine stem cell–specific survival, the general cytoplasmic changes we observed beginning at 6–12 hours and advancing by 20 hours are consistent with these findings. Taken together, this highlights the influence of storage conditions, particularly refrigeration, in delaying marrow cell autolysis and thereby extending the preservation window for cytoplasmic morphology. Although a general trend of increasing cytoplasmic alteration with longer PMIs was observed, statistical correlation was not significant. This variability is likely attributable to confounding factors such as environmental conditions, cold storage, cause of death, and individual biological differences, all of which influence the rate of cytoplasmic autolysis. Nevertheless, the consistency of trends across multiple studies reinforces the potential of cytoplasmic changes as supportive markers for PMI estimation, particularly in the early postmortem period when external indicators are unreliable. Conclusion This study demonstrates a gradual progression of cytoplasmic autolysis in sternal bone marrow cells with increasing post-mortem intervals, from early vacuolation to complete dissolution. Although no statistically significant correlation with PMI was established, likely due to biological variability, environmental influences, and a modest sample size, the observed trends highlight bone marrow cytology as a useful adjunct for PMI estimation. Its simplicity, cost-effectiveness, and relative resistance of bone marrow to decomposition, cytoplasmic evaluation can strengthen forensic assessments when interpreted alongside other morphological, biochemical, and circumstantial evidence to strengthen accuracy and medico-legal reliability. Limitations The study was limited by a small sample size, a single-centre setting, and restriction to sternal marrow, which may limit generalizability. Variability in refrigeration, environmental factors, and individual biological differences also influenced cytoplasmic autolysis. Additionally, interobserver subjectivity in smear interpretation may have introduced variability. Recommendations Future studies should adopt standardised scoring systems, larger and multicentric samples, and comparative analyses with other organs. Incorporating molecular tests, enzyme assays, and immunohistochemistry may improve sensitivity and precision. Such refinements could enhance the reliability of bone marrow cytology as a supportive tool for postmortem interval estimation. Data availability Underlying data BioStudies: Cytoplasmic changes in bone marrow cells as indicators of postmortem interval. S-BSST2159 https://www.ebi.ac.uk/biostudies/studies/S-BSST2159 . DOI: 10.6019/S-BSST2159 . 13 This project contains the following underlying data: • CYTOPLASM DATA SHEET.xlsx (raw case-wise data including demographic details, cause of death, refrigeration status, Sample collection date and time, postmortem interval, and graded cytoplasmic changes). Data are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication). Reporting guidelines Cytoplasmic changes in bone marrow cells as indicators of postmortem interval. BioStudies, S-BSST2159. Retrieved from https://www.ebi.ac.uk/biostudies/studies/S-BSST2159 . 13 Software availability No specialized software was required beyond Microsoft Excel (2021) for dataset compilation. Data analysis was conducted using SPSS (version 25). Acknowledgments • Department of Forensic Medicine and Toxicology and Department of Pathology, K S Hegde Medical Academy, Nitte (DU), Mangalore, Karnataka, India. References 1. Reddy KSN, Murty OP: The Essentials of Forensic Medicine and Toxicology. 35th ed.Hyderabad: K. Suguna Devi; 2016; p. 122. 2. Madea B: Handbook of forensic medicine. 1st ed.Chichester: Wiley-Blackwell; 2014; p. 81. 3. Saukko P, Knight B: Knight’s forensic pathology. 3rd ed.London: Arnold; 2004; pp. 52–92. 4. Abdel Salam HF, Shaat EA, Abdel Aziz MH, et al. : Estimation of postmortem interval using thanatochemistry and postmortem changes. Alexandria J. Med. 2012; 48 (4): 335–344. Publisher Full Text 5. Cartiser N, Bévalot F, Fanton L, et al. : State-of-the-art of bone marrow analysis in forensic toxicology: a review. Int. J. Legal Med. 2011 Mar; 125 (2): pp. 181–198. PubMed Abstract | Publisher Full Text 6. Kumar V, Abbas AK, Aster JC: Robbins basic pathology. 10th ed.Philadelphia: Elsevier; 2017; pp. 935–936. 7. Biradar G, SatishBabu BS, Bakkannavar S, et al. : Estimation of time since death from cytoplasm changes of bone marrow cells. J. South India Med. Assoc. 2016 Sept 1; 8 (2): 85–89. 8. Bardale JS: Forensic pathology and medicine. 1st ed.New Delhi: Elsevier; 2011; pp. 105–106. 9. Tattoli L, Tsokos M, Sautter J, et al. : Postmortem bone marrow analysis in forensic science: the study of 73 cases and review of the literature. Forensic Sci. Int. 2014; 234 : 72–78. PubMed Abstract | Publisher Full Text 10. Babu SB, Bakkannavar SM, Kumar GP, et al. : Estimation of time since death from nuclei changes of bone marrow cells. Indian J. Forensic Commun. Med. 2015; 2 (4): 198–202. Publisher Full Text 11. Sakr MF, El-Khalek AMA, Mohammad NS, et al. : Estimation of postmortem interval using histological and oxidative biomarkers in human bone marrow. Forensic Sci. Med. Pathol. 2024 Sep; 20 (3): 910–919. Epub 2023 Nov 21. PubMed Abstract | Publisher Full Text 12. Michalova J, Savvulidi F, Sefc L, et al. : Cadaveric bone marrow as potential source of hematopoietic stem cells for transplantation. Chimerism. 2011; 2 (3): 86–87. PubMed Abstract | Publisher Full Text | Free Full Text 13. Vinoth G, Shetty DM, Kishan Prasad HL, et al. : Cytoplasmic changes in bone marrow cells as indicators of postmortem interval. BioStudies. 2025; S-BSST2159 . Reference Source Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 22 Sep 2025 ADD YOUR COMMENT Comment Author details Author details 1 Professor, Nitte (Deemed to be University), KS Hegde Medical Academy (KSHEMA), Department of Forensic Medicine and Toxicology, Mangalore, India 2 Resident, Nitte (Deemed to be University), KS Hegde Medical Academy (KSHEMA), Department of Forensic Medicine and Toxicology, Mangalore, India 3 Professor, Nitte (Deemed to be University), KS Hegde Medical Academy (KSHEMA), Department of Pathology, Mangalore, India 4 Professor and Head, Nitte (Deemed to be University), KS Hegde Medical Academy (KSHEMA), Department of Forensic Medicine and Toxicology, Mangalore, India Mahabalesh Shetty Roles: Conceptualization, Formal Analysis, Project Administration, Resources, Supervision, Validation, Visualization, Writing – Review & Editing Vinoth Guru Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Kishan Prasad HL Roles: Conceptualization, Formal Analysis, Methodology, Supervision, Validation, Visualization, Writing – Review & Editing Suraj S Shetty Roles: Conceptualization, Formal Analysis, Methodology, Software, Supervision, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (2) version 2 Revised Published: 26 Dec 2025, 14:964 https://doi.org/10.12688/f1000research.169755.2 version 1 Published: 22 Sep 2025, 14:964 https://doi.org/10.12688/f1000research.169755.1 Copyright © 2025 Shetty M et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Shetty M, Guru V, HL KP and S Shetty S. Cytoplasmic changes in bone marrow cells as indicators of postmortem interval. [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2025, 14 :964 ( https://doi.org/10.12688/f1000research.169755.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 22 Sep 2025 Views 0 Cite How to cite this report: Bakkannavar S. Reviewer Report For: Cytoplasmic changes in bone marrow cells as indicators of postmortem interval. [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2025, 14 :964 ( https://doi.org/10.5256/f1000research.187128.r425571 ) The direct URL for this report is: https://f1000research.com/articles/14-964/v1#referee-response-425571 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 12 Nov 2025 Shankar Bakkannavar , Kasturba Medical College Hospital, Manipal Academy of Higher Education, Manipal, India Approved VIEWS 0 https://doi.org/10.5256/f1000research.187128.r425571 Overall comments: The manuscript is well written addresses an important and less explored area of forensic pathology wherein bone marrow cytology is used for postmortem interval (PMI) estimation. It demonstrates clear structure, methodological transparency, and responsible scientific reporting. ... Continue reading READ ALL Overall comments: The manuscript is well written addresses an important and less explored area of forensic pathology wherein bone marrow cytology is used for postmortem interval (PMI) estimation. It demonstrates clear structure, methodological transparency, and responsible scientific reporting. Improvements in methodological detail, data interpretation, and contextual framing are necessary to enhance its scientific impact and clarity. The title is concise, informative, and well-aligned with the content. The abstract presents the aim, methods, and key findings clearly. However, the conclusion in the abstract should better reflect the non-significant statistical findings. Consider including confidence intervals or p-values in the abstract for transparency. The introduction provides a logical flow from traditional PMI estimation techniques to the rationale for bone marrow analysis. Integrate recent molecular and biochemical PMI estimation studies (e.g., protein degradation, mRNA decay, oxidative biomarkers). Add a brief paragraph clarifying why cytoplasmic changes , as opposed to nuclear or biochemical ones, may have practical forensic utility. Methodology is detailed, especially regarding sampling and staining procedures. Ethical considerations and inclusion/exclusion criteria are well described. However, specify storage temperature and duration for each case, as this significantly affects autolysis. State whether scoring was performed by a single or multiple blinded observers Though ANOVA is used here, regression or correlation analysis might be more appropriate for continuous PMI data. Tables and figures are clear and appropriately labelled. Discussion is well written which compares findings with multiple previous studies Biological reasoning (autolytic sequence, environmental effects) is well explained. Expand on the possible reasons for statistical non-significance (small sample, wide variance, temperature confounding). Incorporate the recent reviews and systematic studies Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: Forensic Pathology, Identification of human beings, Toxicology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Bakkannavar S. Reviewer Report For: Cytoplasmic changes in bone marrow cells as indicators of postmortem interval. [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2025, 14 :964 ( https://doi.org/10.5256/f1000research.187128.r425571 ) The direct URL for this report is: https://f1000research.com/articles/14-964/v1#referee-response-425571 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Sulis S and Vorobeľová L. Reviewer Report For: Cytoplasmic changes in bone marrow cells as indicators of postmortem interval. [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2025, 14 :964 ( https://doi.org/10.5256/f1000research.187128.r420291 ) The direct URL for this report is: https://f1000research.com/articles/14-964/v1#referee-response-420291 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 28 Oct 2025 Simona Sulis , Department of Anthropology, Comenius University Bratislava, Bratislava, Slovakia Lenka Vorobeľová , Department of Anthropology, Comenius University Bratislava, Bratislava, Slovakia Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.187128.r420291 This descriptive cross-sectional study investigates the relationship between cytoplasmic autolytic changes in sternal bone marrow cells and postmortem interval estimation. The authors analysed 43 medico-legal autopsy cases with recorded times of death, scoring cytoplasmic changes from 0 (intact morphology) to ... Continue reading READ ALL This descriptive cross-sectional study investigates the relationship between cytoplasmic autolytic changes in sternal bone marrow cells and postmortem interval estimation. The authors analysed 43 medico-legal autopsy cases with recorded times of death, scoring cytoplasmic changes from 0 (intact morphology) to 4 (complete dissolution) using Leishman-stained bone marrow aspirates. Results showed a predominance of mild cytoplasmic alterations (51.1%), with mean PMI values ranging from 8.5 hours (S0) to 15.0 hours (S4). However, the correlation between cytoplasmic score and PMI did not reach statistical significance, and the progression showed inconsistencies, notably with Score 2 displaying a lower mean PMI than Score 1. The manuscript displays good structure and clarity. The introduction provides a solid rationale by addressing the limitations of traditional PMI markers and highlighting bone marrow as a promising alternative substrate because of its protected anatomical position. The literature review suitably references recent studies. However, the discussion could be enhanced by broader contextualisation within current forensic methods, especially molecular and biochemical markers for PMI estimation. Including more references that compare histological techniques with larger sample sizes and advanced statistical methods would better position the manuscript within the existing research landscape. Some suggested references: [(Sakr, et al., 2024) - ref 1] [(Franceschetti, et al., 2023) - ref 2] [(Weisensee, et al., 2024) - ref 3] [(Zissler, et al., 2020) - ref 4] The inclusion and exclusion criteria are clearly defined, appropriately excluding confounding factors such as burns, malnutrition, chemotherapy, and extreme environmental exposure. However, several limitations in the design need attention. The single-centre approach limits generalisability, and the manuscript would benefit from a discussion of how regional factors (climate, storage protocols) might influence the results. While the methodology section provides adequate detail on specimen collection, staining procedures, and the scoring system, some gaps undermine reproducibility. Most notably, the manuscript acknowledges refrigeration of bodies prior to autopsy but fails to systematically record the temperature and duration of cold storage for individual cases. This is a confounding variable, as refrigeration significantly slows autolytic processes. The unusual observation that Scores 2 has a lower mean post-mortem interval than Score 1 may directly stem from varying refrigeration conditions. Additional methodological details needing clarification include, for example, whether scoring was performed by a single observer or multiple blinded reviewers, and whether inter-observer or intra-observer reliability testing was carried out. In the discussion, the authors should address the non-linear pattern and its implications more thoroughly, expand the discussion of refrigeration's confounding effects with potential stratified analysis, compare findings more critically with cited studies, and broaden the contextualisation within contemporary forensic approaches, including molecular and biochemical markers. The conclusions need significant adjustment to match the statistical results. The authors describe cytoplasmic scoring as a "useful adjunct" and state that "cytoplasmic autolysis in bone marrow follows a sequential pattern," but the data do not support these claims. The lack of statistical significance, along with the unusual S1/S2 inversion, questions the validity of claims about a clear sequential progression. Without proven predictive value or validation in an independent sample, statements about practical usefulness are premature. The authors rightly acknowledge the non-significant results and overlap between categories, and the limitations section honestly discusses sample size, single-centre design, and environmental confounders. However, the conclusions should better reflect the exploratory nature of this study. A more cautious statement would note that although trends warrant further investigation, the current evidence does not yet statistically confirm the method's reliability or standalone application. The considerable biological variability and methodological limitations that hindered the detection of significant associations should be given greater emphasis. Overall, this study tackles an important question in forensic pathology by examining a relatively unexplored tissue with potential benefits for PMI estimation. The research question is valid, the methodology is mainly sound, and the authors show scientific integrity through transparent reporting and open data sharing. However, the manuscript needs revision to address statistical issues, methodological gaps (especially concerning refrigeration documentation and controls), and conclusions that potentially exaggerate the findings. With specific revisions to address these points, this work could offer a strong basis for future research and contribute significantly to the forensic literature on postmortem interval estimation. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly References 1. Sakr M, El-Khalek A, Mohammad N, Abouhashem N, et al.: Estimation of postmortem interval using histological and oxidative biomarkers in human bone marrow. Forensic Science, Medicine and Pathology . 2023; 20 (3): 910-919 Publisher Full Text 2. Franceschetti L, Amadasi A, Bugelli V, Bolsi G, et al.: Estimation of Late Postmortem Interval: Where Do We Stand? A Literature Review. Biology . 2023; 12 (6). Publisher Full Text 3. Weisensee K, Atwell M: Human Decomposition and Time Since Death: Persistent Challenges and Future Directions of Postmortem Interval Estimation in Forensic Anthropology. American Journal of Biological Anthropology . 2024; 186 (S78). Publisher Full Text 4. Zissler A, Stoiber W, Steinbacher P, Geissenberger J, et al.: Postmortem Protein Degradation as a Tool to Estimate the PMI: A Systematic Review. Diagnostics . 2020; 10 (12). Publisher Full Text Competing Interests: No competing interests were disclosed. Reviewer Expertise: Forensic anthropology, biomedical anthropology We confirm that we have read this submission and believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however we have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Sulis S and Vorobeľová L. Reviewer Report For: Cytoplasmic changes in bone marrow cells as indicators of postmortem interval. [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2025, 14 :964 ( https://doi.org/10.5256/f1000research.187128.r420291 ) The direct URL for this report is: https://f1000research.com/articles/14-964/v1#referee-response-420291 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 17 Nov 2025 Vinoth Guru , Resident, Nitte (Deemed to be University), KS Hegde Medical Academy (KSHEMA), Department of Forensic Medicine and Toxicology, Mangalore, India 17 Nov 2025 Author Response Author Response We thank the reviewers for their constructive feedback and valuable observations. This study was specifically designed to examine histopathological (cytoplasmic) changes in bone marrow cells in relation to ... Continue reading Author Response We thank the reviewers for their constructive feedback and valuable observations. This study was specifically designed to examine histopathological (cytoplasmic) changes in bone marrow cells in relation to postmortem interval, as stated in the title and objectives. Therefore, molecular and biochemical methods were beyond the intended scope of this work. All bone marrow smears were examined and scored by a single observer to maintain uniformity and reduce inter-observer bias. Inter- and intra-observer variation testing was not performed. All bodies were kept in the mortuary cold chamber maintained at approximately 4°C, which is standard in Indian mortuary facilities. The dataset includes documented times of death, placement in cold storage, and sample collection for each case; however, the specific duration of refrigeration was not analysed separately, which has been acknowledged as a limitation. The possible confounding effect of refrigeration on autolysis has been recognised in the Limitations section. The minor inversion between Scores 1 and 2 likely reflects refrigeration variability, sample size constraints, and biological variation, and is interpreted as a methodological variation rather than a biological reversal. The ANOVA results showed no statistically significant correlation (p > 0.05) between cytoplasmic score and postmortem interval. The significance threshold (p < 0.05) was indicated in Table 5, and results were reported as non-significant. As the analysis was primarily descriptive, exact F-values and degrees of freedom were not included but can be provided if required. The findings are preliminary and exploratory, not confirmatory. The terms “appears,” “suggests,” and “may serve” were intentionally used to indicate trends rather than established relationships. The study emphasises the potential value of bone marrow cytoplasmic changes as a supportive parameter for postmortem interval estimation while acknowledging biological, environmental, and methodological limitations. In conclusion, the current version of the manuscript presents an exploratory interpretation, offering preliminary evidence that warrants further validation through larger, multicentric, and molecular correlation studies. Author Response We thank the reviewers for their constructive feedback and valuable observations. This study was specifically designed to examine histopathological (cytoplasmic) changes in bone marrow cells in relation to postmortem interval, as stated in the title and objectives. Therefore, molecular and biochemical methods were beyond the intended scope of this work. All bone marrow smears were examined and scored by a single observer to maintain uniformity and reduce inter-observer bias. Inter- and intra-observer variation testing was not performed. All bodies were kept in the mortuary cold chamber maintained at approximately 4°C, which is standard in Indian mortuary facilities. The dataset includes documented times of death, placement in cold storage, and sample collection for each case; however, the specific duration of refrigeration was not analysed separately, which has been acknowledged as a limitation. The possible confounding effect of refrigeration on autolysis has been recognised in the Limitations section. The minor inversion between Scores 1 and 2 likely reflects refrigeration variability, sample size constraints, and biological variation, and is interpreted as a methodological variation rather than a biological reversal. The ANOVA results showed no statistically significant correlation (p > 0.05) between cytoplasmic score and postmortem interval. The significance threshold (p < 0.05) was indicated in Table 5, and results were reported as non-significant. As the analysis was primarily descriptive, exact F-values and degrees of freedom were not included but can be provided if required. The findings are preliminary and exploratory, not confirmatory. The terms “appears,” “suggests,” and “may serve” were intentionally used to indicate trends rather than established relationships. The study emphasises the potential value of bone marrow cytoplasmic changes as a supportive parameter for postmortem interval estimation while acknowledging biological, environmental, and methodological limitations. In conclusion, the current version of the manuscript presents an exploratory interpretation, offering preliminary evidence that warrants further validation through larger, multicentric, and molecular correlation studies. Competing Interests: None declared. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 17 Nov 2025 Vinoth Guru , Resident, Nitte (Deemed to be University), KS Hegde Medical Academy (KSHEMA), Department of Forensic Medicine and Toxicology, Mangalore, India 17 Nov 2025 Author Response Author Response We thank the reviewers for their constructive feedback and valuable observations. This study was specifically designed to examine histopathological (cytoplasmic) changes in bone marrow cells in relation to ... Continue reading Author Response We thank the reviewers for their constructive feedback and valuable observations. This study was specifically designed to examine histopathological (cytoplasmic) changes in bone marrow cells in relation to postmortem interval, as stated in the title and objectives. Therefore, molecular and biochemical methods were beyond the intended scope of this work. All bone marrow smears were examined and scored by a single observer to maintain uniformity and reduce inter-observer bias. Inter- and intra-observer variation testing was not performed. All bodies were kept in the mortuary cold chamber maintained at approximately 4°C, which is standard in Indian mortuary facilities. The dataset includes documented times of death, placement in cold storage, and sample collection for each case; however, the specific duration of refrigeration was not analysed separately, which has been acknowledged as a limitation. The possible confounding effect of refrigeration on autolysis has been recognised in the Limitations section. The minor inversion between Scores 1 and 2 likely reflects refrigeration variability, sample size constraints, and biological variation, and is interpreted as a methodological variation rather than a biological reversal. The ANOVA results showed no statistically significant correlation (p > 0.05) between cytoplasmic score and postmortem interval. The significance threshold (p < 0.05) was indicated in Table 5, and results were reported as non-significant. As the analysis was primarily descriptive, exact F-values and degrees of freedom were not included but can be provided if required. The findings are preliminary and exploratory, not confirmatory. The terms “appears,” “suggests,” and “may serve” were intentionally used to indicate trends rather than established relationships. The study emphasises the potential value of bone marrow cytoplasmic changes as a supportive parameter for postmortem interval estimation while acknowledging biological, environmental, and methodological limitations. In conclusion, the current version of the manuscript presents an exploratory interpretation, offering preliminary evidence that warrants further validation through larger, multicentric, and molecular correlation studies. Author Response We thank the reviewers for their constructive feedback and valuable observations. This study was specifically designed to examine histopathological (cytoplasmic) changes in bone marrow cells in relation to postmortem interval, as stated in the title and objectives. Therefore, molecular and biochemical methods were beyond the intended scope of this work. All bone marrow smears were examined and scored by a single observer to maintain uniformity and reduce inter-observer bias. Inter- and intra-observer variation testing was not performed. All bodies were kept in the mortuary cold chamber maintained at approximately 4°C, which is standard in Indian mortuary facilities. The dataset includes documented times of death, placement in cold storage, and sample collection for each case; however, the specific duration of refrigeration was not analysed separately, which has been acknowledged as a limitation. The possible confounding effect of refrigeration on autolysis has been recognised in the Limitations section. The minor inversion between Scores 1 and 2 likely reflects refrigeration variability, sample size constraints, and biological variation, and is interpreted as a methodological variation rather than a biological reversal. The ANOVA results showed no statistically significant correlation (p > 0.05) between cytoplasmic score and postmortem interval. The significance threshold (p < 0.05) was indicated in Table 5, and results were reported as non-significant. As the analysis was primarily descriptive, exact F-values and degrees of freedom were not included but can be provided if required. The findings are preliminary and exploratory, not confirmatory. The terms “appears,” “suggests,” and “may serve” were intentionally used to indicate trends rather than established relationships. The study emphasises the potential value of bone marrow cytoplasmic changes as a supportive parameter for postmortem interval estimation while acknowledging biological, environmental, and methodological limitations. In conclusion, the current version of the manuscript presents an exploratory interpretation, offering preliminary evidence that warrants further validation through larger, multicentric, and molecular correlation studies. Competing Interests: None declared. Close Report a concern COMMENT ON THIS REPORT Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 22 Sep 2025 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 3 Version 2 (revision) 26 Dec 25 read Version 1 22 Sep 25 read read Simona Sulis , Comenius University Bratislava, Bratislava, Slovakia Lenka Vorobeľová , Comenius University Bratislava, Bratislava, Slovakia Shankar Bakkannavar , Kasturba Medical College Hospital, Manipal Academy of Higher Education, Manipal, India Matteo Nioi , University of Cagliari, Cagliari, Italy Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Nioi M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 29 Jan 2026 | for Version 2 Matteo Nioi , University of Cagliari, Cagliari, Italy 0 Views copyright © 2026 Nioi M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This manuscript presents a descriptive, cross-sectional forensic pathology study investigating cytoplasmic autolytic changes in sternal bone marrow cells as a potential correlate of the postmortem interval (PMI). The authors analyzed 43 medico-legal autopsy cases with documented times of death, applying a predefined cytoplasmic scoring system (0–4) on Leishman-stained bone marrow aspirates. The study addresses an important and underexplored topic in PMI estimation, namely the use of bone marrow cytology, a tissue that is anatomically protected and potentially less susceptible to early postmortem degradation compared to external tissues. The methodology is clearly described, ethical aspects are appropriately handled, and all underlying data are openly available. The revised version adopts a more cautious and appropriate interpretative tone, explicitly acknowledging the lack of statistical significance and the exploratory nature of the findings. Overall, the work represents a hypothesis-generating investigation rather than a validated forensic method. To further improve scientific clarity, robustness, and alignment between data and interpretation, the authors are encouraged to address the following points: 1) explicitly classify the study throughout the manuscript (title, abstract, discussion, and conclusions) as a proof-of-concept / exploratory study , clearly stating that it is intended for hypothesis generation and not for validation or prediction of PMI; 2) ensure that the absence of statistical significance (p > 0.05) is consistently emphasised in the abstract and conclusions, avoiding any wording that may imply sequential reliability or standalone forensic applicability; 3) expand and clarify the discussion of refrigeration as a major confounding variable, explicitly stating that individual cold-storage duration was not stratified or analysed and explaining how this limitation may have influenced autolytic progression and score distribution; 4) interpret the observed non-linear pattern, including the inversion between intermediate cytoplasmic scores, as a methodological and environmental artefact rather than as a biological phenomenon; 5) acknowledge more explicitly the limitations related to single-observer scoring and the absence of inter- and intra-observer reliability assessment, and recommend blinded multi-observer evaluation in future studies to improve reproducibility; 6) frame the statistical analysis strictly as descriptive, clarifying that the study was not powered for inferential modelling, and suggest that future investigations adopt a priori power calculations and regression-based or mixed-effects approaches incorporating relevant confounders; 7) reinforce in the final conclusions that the principal contribution of the study lies in demonstrating feasibility and biological plausibility of bone marrow cytoplasmic assessment, rather than in proposing a validated forensic tool, and outline concrete directions for future multicentric and methodologically controlled research. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise Forensic pathology and legal medicine, with expertise in postmortem interval assessment, postmortem imaging, and determination of cause of death. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Nioi M. Peer Review Report For: Cytoplasmic changes in bone marrow cells as indicators of postmortem interval. [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2025, 14 :964 ( https://doi.org/10.5256/f1000research.194256.r445335) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-964/v2#referee-response-445335 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Bakkannavar S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 12 Nov 2025 | for Version 1 Shankar Bakkannavar , Kasturba Medical College Hospital, Manipal Academy of Higher Education, Manipal, India 0 Views copyright © 2025 Bakkannavar S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Overall comments: The manuscript is well written addresses an important and less explored area of forensic pathology wherein bone marrow cytology is used for postmortem interval (PMI) estimation. It demonstrates clear structure, methodological transparency, and responsible scientific reporting. Improvements in methodological detail, data interpretation, and contextual framing are necessary to enhance its scientific impact and clarity. The title is concise, informative, and well-aligned with the content. The abstract presents the aim, methods, and key findings clearly. However, the conclusion in the abstract should better reflect the non-significant statistical findings. Consider including confidence intervals or p-values in the abstract for transparency. The introduction provides a logical flow from traditional PMI estimation techniques to the rationale for bone marrow analysis. Integrate recent molecular and biochemical PMI estimation studies (e.g., protein degradation, mRNA decay, oxidative biomarkers). Add a brief paragraph clarifying why cytoplasmic changes , as opposed to nuclear or biochemical ones, may have practical forensic utility. Methodology is detailed, especially regarding sampling and staining procedures. Ethical considerations and inclusion/exclusion criteria are well described. However, specify storage temperature and duration for each case, as this significantly affects autolysis. State whether scoring was performed by a single or multiple blinded observers Though ANOVA is used here, regression or correlation analysis might be more appropriate for continuous PMI data. Tables and figures are clear and appropriately labelled. Discussion is well written which compares findings with multiple previous studies Biological reasoning (autolytic sequence, environmental effects) is well explained. Expand on the possible reasons for statistical non-significance (small sample, wide variance, temperature confounding). Incorporate the recent reviews and systematic studies Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise Forensic Pathology, Identification of human beings, Toxicology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Bakkannavar S. Peer Review Report For: Cytoplasmic changes in bone marrow cells as indicators of postmortem interval. [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2025, 14 :964 ( https://doi.org/10.5256/f1000research.187128.r425571) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-964/v1#referee-response-425571 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Sulis S et al. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 28 Oct 2025 | for Version 1 Simona Sulis , Department of Anthropology, Comenius University Bratislava, Bratislava, Slovakia Lenka Vorobeľová , Department of Anthropology, Comenius University Bratislava, Bratislava, Slovakia 0 Views copyright © 2025 Sulis S et al. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This descriptive cross-sectional study investigates the relationship between cytoplasmic autolytic changes in sternal bone marrow cells and postmortem interval estimation. The authors analysed 43 medico-legal autopsy cases with recorded times of death, scoring cytoplasmic changes from 0 (intact morphology) to 4 (complete dissolution) using Leishman-stained bone marrow aspirates. Results showed a predominance of mild cytoplasmic alterations (51.1%), with mean PMI values ranging from 8.5 hours (S0) to 15.0 hours (S4). However, the correlation between cytoplasmic score and PMI did not reach statistical significance, and the progression showed inconsistencies, notably with Score 2 displaying a lower mean PMI than Score 1. The manuscript displays good structure and clarity. The introduction provides a solid rationale by addressing the limitations of traditional PMI markers and highlighting bone marrow as a promising alternative substrate because of its protected anatomical position. The literature review suitably references recent studies. However, the discussion could be enhanced by broader contextualisation within current forensic methods, especially molecular and biochemical markers for PMI estimation. Including more references that compare histological techniques with larger sample sizes and advanced statistical methods would better position the manuscript within the existing research landscape. Some suggested references: [(Sakr, et al., 2024) - ref 1] [(Franceschetti, et al., 2023) - ref 2] [(Weisensee, et al., 2024) - ref 3] [(Zissler, et al., 2020) - ref 4] The inclusion and exclusion criteria are clearly defined, appropriately excluding confounding factors such as burns, malnutrition, chemotherapy, and extreme environmental exposure. However, several limitations in the design need attention. The single-centre approach limits generalisability, and the manuscript would benefit from a discussion of how regional factors (climate, storage protocols) might influence the results. While the methodology section provides adequate detail on specimen collection, staining procedures, and the scoring system, some gaps undermine reproducibility. Most notably, the manuscript acknowledges refrigeration of bodies prior to autopsy but fails to systematically record the temperature and duration of cold storage for individual cases. This is a confounding variable, as refrigeration significantly slows autolytic processes. The unusual observation that Scores 2 has a lower mean post-mortem interval than Score 1 may directly stem from varying refrigeration conditions. Additional methodological details needing clarification include, for example, whether scoring was performed by a single observer or multiple blinded reviewers, and whether inter-observer or intra-observer reliability testing was carried out. In the discussion, the authors should address the non-linear pattern and its implications more thoroughly, expand the discussion of refrigeration's confounding effects with potential stratified analysis, compare findings more critically with cited studies, and broaden the contextualisation within contemporary forensic approaches, including molecular and biochemical markers. The conclusions need significant adjustment to match the statistical results. The authors describe cytoplasmic scoring as a "useful adjunct" and state that "cytoplasmic autolysis in bone marrow follows a sequential pattern," but the data do not support these claims. The lack of statistical significance, along with the unusual S1/S2 inversion, questions the validity of claims about a clear sequential progression. Without proven predictive value or validation in an independent sample, statements about practical usefulness are premature. The authors rightly acknowledge the non-significant results and overlap between categories, and the limitations section honestly discusses sample size, single-centre design, and environmental confounders. However, the conclusions should better reflect the exploratory nature of this study. A more cautious statement would note that although trends warrant further investigation, the current evidence does not yet statistically confirm the method's reliability or standalone application. The considerable biological variability and methodological limitations that hindered the detection of significant associations should be given greater emphasis. Overall, this study tackles an important question in forensic pathology by examining a relatively unexplored tissue with potential benefits for PMI estimation. The research question is valid, the methodology is mainly sound, and the authors show scientific integrity through transparent reporting and open data sharing. However, the manuscript needs revision to address statistical issues, methodological gaps (especially concerning refrigeration documentation and controls), and conclusions that potentially exaggerate the findings. With specific revisions to address these points, this work could offer a strong basis for future research and contribute significantly to the forensic literature on postmortem interval estimation. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly References 1. Sakr M, El-Khalek A, Mohammad N, Abouhashem N, et al.: Estimation of postmortem interval using histological and oxidative biomarkers in human bone marrow. Forensic Science, Medicine and Pathology . 2023; 20 (3): 910-919 Publisher Full Text 2. Franceschetti L, Amadasi A, Bugelli V, Bolsi G, et al.: Estimation of Late Postmortem Interval: Where Do We Stand? A Literature Review. Biology . 2023; 12 (6). Publisher Full Text 3. Weisensee K, Atwell M: Human Decomposition and Time Since Death: Persistent Challenges and Future Directions of Postmortem Interval Estimation in Forensic Anthropology. American Journal of Biological Anthropology . 2024; 186 (S78). Publisher Full Text 4. Zissler A, Stoiber W, Steinbacher P, Geissenberger J, et al.: Postmortem Protein Degradation as a Tool to Estimate the PMI: A Systematic Review. Diagnostics . 2020; 10 (12). Publisher Full Text Competing Interests No competing interests were disclosed. Reviewer Expertise Forensic anthropology, biomedical anthropology We confirm that we have read this submission and believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however we have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 17 Nov 2025 Vinoth Guru, Resident, Nitte (Deemed to be University), KS Hegde Medical Academy (KSHEMA), Department of Forensic Medicine and Toxicology, Mangalore, India Author Response We thank the reviewers for their constructive feedback and valuable observations. This study was specifically designed to examine histopathological (cytoplasmic) changes in bone marrow cells in relation to postmortem interval, as stated in the title and objectives. Therefore, molecular and biochemical methods were beyond the intended scope of this work. All bone marrow smears were examined and scored by a single observer to maintain uniformity and reduce inter-observer bias. Inter- and intra-observer variation testing was not performed. All bodies were kept in the mortuary cold chamber maintained at approximately 4°C, which is standard in Indian mortuary facilities. The dataset includes documented times of death, placement in cold storage, and sample collection for each case; however, the specific duration of refrigeration was not analysed separately, which has been acknowledged as a limitation. The possible confounding effect of refrigeration on autolysis has been recognised in the Limitations section. The minor inversion between Scores 1 and 2 likely reflects refrigeration variability, sample size constraints, and biological variation, and is interpreted as a methodological variation rather than a biological reversal. The ANOVA results showed no statistically significant correlation (p > 0.05) between cytoplasmic score and postmortem interval. The significance threshold (p < 0.05) was indicated in Table 5, and results were reported as non-significant. As the analysis was primarily descriptive, exact F-values and degrees of freedom were not included but can be provided if required. The findings are preliminary and exploratory, not confirmatory. The terms “appears,” “suggests,” and “may serve” were intentionally used to indicate trends rather than established relationships. The study emphasises the potential value of bone marrow cytoplasmic changes as a supportive parameter for postmortem interval estimation while acknowledging biological, environmental, and methodological limitations. In conclusion, the current version of the manuscript presents an exploratory interpretation, offering preliminary evidence that warrants further validation through larger, multicentric, and molecular correlation studies. View more View less Competing Interests None declared. reply Respond Report a concern Sulis S and Vorobeľová L. Peer Review Report For: Cytoplasmic changes in bone marrow cells as indicators of postmortem interval. [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2025, 14 :964 ( https://doi.org/10.5256/f1000research.187128.r420291) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. 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