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BMC Research Notes

○ Springer Science and Business Media LLC

Preprints posted in the last 30 days, ranked by how well they match BMC Research Notes's content profile, based on 33 papers previously published here. The average preprint has a 0.04% match score for this journal, so anything above that is already an above-average fit.

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Cardiovascular Risk Stratification Among University Employees in India: Comparison of WHO/ISH, ASCVD and Framingham Risk Models

Jagtap, A. H.; Ingole Patil, A. S.; Kudale, A. M.

2026-10-14 occupational and environmental health 10.64898/2026.10.12.26365229 medRxiv
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Background Cardiovascular disease (CVD) risk prediction is an important component of primary prevention, particularly in populations with increasing cardiometabolic risk. Several risk prediction models are available, but their estimates may differ because of differences in derivation populations, predictors, calibration, and cardiovascular outcomes. Evidence comparing these models within Indian occupational populations remains limited. This study compared 10-year CVD risk estimates generated by the World Health Organization/International Society of Hypertension (WHO/ISH) cardiovascular risk charts, the American College of Cardiology/American Heart Association (ACC/AHA) Pooled Cohort Equation (ASCVD-PCE), and the Framingham general cardiovascular disease risk equation among university employees in India. Methods A comparative observational study was conducted using standardized health assessment data from 266 university employees. Participants aged 40-74 years were selected to provide a common analytical age range across the three risk prediction approaches. Of 127 employees within this age range, three with documented previous ischemic heart disease were excluded because the analysis focused on primary prevention. The final analytical cohort comprised 124 participants. Blood pressure was assessed using a standardized protocol involving three readings at five-minute intervals, with repeat assessments during three subsequent weekly visits for employees with elevated initial readings. Ten-year cardiovascular risk was estimated using the 2019 WHO/ISH laboratory-based risk charts for the South Asian region, the ASCVD-PCE, and the 2008 Framingham general CVD equation. Agreement between risk categories was assessed using Cohen's kappa and linear weighted kappa. Agreement was also examined at [≥]10% and [≥]20% thresholds. Results The mean age of the 124 participants was 47.63 {+/-} 6.45 years, and 86.3% were male. Diabetes was present in 25.8%, smoking/tobacco use in 19.4%, and 29.0% were receiving antihypertensive treatment. Mean estimated risk was 5.94% for WHO/ISH, 5.95% for ASCVD-PCE, and 12.86% for Framingham. High risk ([≥]20%) was identified in 2.4%, 4.8%, and 20.2% of participants by WHO/ISH, ASCVD-PCE, and Framingham, respectively. Exact four-category agreement was 70.2% between WHO/ISH and ASCVD-PCE, compared with 31.5% between WHO/ISH and Framingham and 26.6% between ASCVD-PCE and Framingham. Cohen's kappa was 0.502 for WHO/ISH versus ASCVD-PCE, 0.079 for WHO/ISH versus Framingham, and 0.047 for ASCVD-PCE versus Framingham. Weighted kappa values were 0.639, 0.323, and 0.342, respectively. Conclusion WHO/ISH and ASCVD-PCE produced closely similar mean risk estimates and substantially greater categorical agreement than either model showed with the Framingham equation. Framingham generated considerably higher 10-year CVD risk estimates and classified a larger proportion of participants into higher-risk categories. These findings highlight the importance of model selection when cardiovascular risk assessment is undertaken in Indian occupational populations and support cautious interpretation of risk estimates derived from models developed in different populations and for different cardiovascular endpoints. Keywords: cardiovascular disease; risk prediction; WHO/ISH; ASCVD; Pooled Cohort Equation; Framingham; India; occupational health; university employees; risk classification

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Knowledge Of Metabolic Syndrome, Lifestyle Risk Behaviours And Preventive Practices Among Women Attending Kasoa Polyclinic, Ghana: A Cross-Sectional Study.

Aitee, G. D.-G.; Owusu, E.; Cann, A. N.; Borkor, E. T.; Siddiq, A. I.; Kwakye, A. P.; Ampong, E. A. K.

2026-10-15 medical education 10.64898/2026.10.14.26365545 medRxiv
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Background. Metabolic syndrome is a cluster of cardiometabolic risk factors that may increase the risk of cardiovascular disease and type 2 diabetes, and African studies report a higher prevalence in women than in men. Prevention may depend, in part, on whether women recognise the condition and its modifiable risk factors. Relatively little appears to be known about this among women using primary-level health facilities in fast-growing peri-urban areas of Ghana. Objective. To assess knowledge of metabolic syndrome, describe lifestyle risk behaviours, self-reported cardiometabolic conditions and preventive practices, and examine selected lifestyle correlates of self-reported diabetes and hypertension among women attending Kasoa Polyclinic, Ghana. Methods. A descriptive cross-sectional survey was conducted in June and July 2024 among 174 women aged 18-45 years recruited by convenience sampling. A structured, interviewer-assisted questionnaire covered knowledge, lifestyle behaviours, self-reported diagnoses and preventive practices. Data were summarised as frequencies and percentages, and associations were examined with Pearson's chi-square test. Results. Only 37 women (21.3%) described metabolic syndrome as a condition that raises the risk of heart disease and type 2 diabetes, 40 (23.0%) identified central (apple-shaped) fat as the high-risk pattern and 31 (17.8%) knew that dietary recommendations exist. Most reported no weekly physical activity (116; 66.7%), daily sugary drinks (109; 62.6%), daily processed or fast food (100; 57.5%), high stress (103; 59.2%), and less than six hours' sleep (94; 54.0%). Self-reported diagnoses were hypertension in 60 (34.5%) and type 2 diabetes in 49 (28.2%). Fifty-nine (33.9%) had never received advice on prevention and 105 (60.3%) did not monitor their weight or waist. Self-reported diabetes was associated with short sleep (36.2% among those sleeping under six hours; p = 0.035) and with stress level (p = 0.028), being most frequent among women reporting low stress. Self-reported hypertension was more common with high stress (42.7%; p = 0.022) and with some physical activity (p = 0.005). Conclusion. Women attending this polyclinic appeared to have limited understanding of metabolic syndrome and a high burden of modifiable risk behaviours. Routine counselling on diet, activity, sleep, and weight monitoring at the polyclinic may be warranted. The bivariate, self-reported associations should be interpreted cautiously.

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A vulnerable space: Health professions education scholars' reflections on AI-use disclosure

Lingard, L. A.; Maggio, L. A.; Ans, M.; Driessen, E.

2026-10-02 medical education 10.64898/2026.10.01.26364502 medRxiv
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Background AI use is growing by HPE scholars, and disclosure of that use is required by scientific ethics and journal policy. In spite of growing unease about the meaning, and meaningfulness, of AI-use disclosures in published manuscripts, little is known about how authors represent their AI use in published disclosure statements. Without such understanding, we are ill-equipped to redirect disclosure practices for increased sufficiency and sincerity, undermining efforts towards transparency in the era of AI-supported scholarship Methods In this descriptive qualitative study, 18 HPE researchers with experience disclosing generative AI use in publications from 2025-2026 were interviewed using Zoom. Data collection and thematic analysis proceeded iteratively, exploring participant experiences with AI use, their disclosure decisions, and evolving disclosure practices. Results Participants reported a wide range of experience writing AI-use disclosures (from 1-16 disclosures/participant); in total 31 published disclosures were shared by participants and discussed during the interviews. Our analysis identified four themes: A spectrum of AI uses; Multi-factorial disclosure decisions; Discrepancies between actual and disclosed use; and Emotions around disclosure. Discussion AI-disclosure takes place at the intersection of shared ethical principles and situated pragmatic concerns. Disclosure is both an intellectual and an emotional practice, changing over time as AI use evolves and journal expectations develop. More generative uses may provoke divisive responses and are related to uncertainty about how to disclose, concern about disclosure penalties, and periodic use-disclosure discrepancies. Understanding how researchers are navigating these complexities may help the HPE community articulate clearer guidance for transparent and meaningful disclosure of AI-use in scholarly work. Reflective methodologies can help bring these issues to the surface of ongoing conversations about AI use.

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Doctors experiences of interruptions in UK secondary care outpatient clinics: a cross-sectional survey of prevalence, consequences and management strategies

Boustani, S.; Staras, C.; Rich, A.; Griffin, A.

2026-10-08 medical education 10.64898/2026.10.07.26364858 medRxiv
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Objectives To examine the prevalence of interruptions during UK secondary care outpatient consultations, their association with clinician mental workload, and the strategies clinicians use to manage them. Design Nationwide cross-sectional online survey. Setting Secondary care outpatient clinics, United Kingdom. Participants A sample of 465 UK secondary care doctors across a range of grades and specialties, recruited through a medical defence organisation's network. Primary and secondary outcome measures Mental workload (NASA Task Load Index, Raw-TLX); interruption frequency; perceived cognitive impact of interruptions; task resumption difficulty; perceived social effects on colleague interactions and team cohesion; and interruption-management strategy use. Results 61.1% of clinicians reported being interrupted often or very often, and mean overall workload was high (Raw-TLX 66.2, SD 11.5). Interruption frequency, patient complexity and perceived cognitive impact were each associated with higher workload across multiple NASA-TLX subscales. In fully adjusted models, interruption frequency retained independent associations with overall workload (beta = 1.79, p = 0.004) and temporal demand (beta = 0.94, p < 0.001). Task resumption difficulty was associated with worse perceived performance (beta = -0.59, p = 0.014), while perceiving interruptions as socially positive was associated with better performance (beta = 0.75, p = 0.003) and lower frustration (beta = -1.16, p < 0.001). Years of experience showed only small effects, and self-reported strategy use (38.7%) was not consistently associated with lower workload. Exploratory natural language processing of open-text descriptions identified three strategy clusters; cognitive offloading, anticipating and preparing, and blunt responses, with distinct emotional profiles. Conclusions Interruptions were commonly reported during UK secondary care outpatient consultations and were associated with measurable cognitive and temporal burden. The perceived social framing of interruptions was independently associated with frustration and self-rated performance. Binary strategy use showed no consistent workload association, indicating a need for system-level approaches addressing interruption frequency, task resumption support and the social context of interruptions rather than reliance on individual coping.

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Multimorbidity and cardiometabolic clustering among university employees: findings from a comprehensive health assessment program in India

Jagtap, A. H.; Ingole Patil, A. S.; Kudale, A. M.

2026-10-20 occupational and environmental health 10.64898/2026.10.20.26365860 medRxiv
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Abstract Objective To estimate the burden and patterns of multimorbidity and cardiometabolic multimorbidity among university employees undergoing a comprehensive health assessment programme, and to examine demographic and behavioural factors associated with multimorbidity. Design Cross-sectional study. Setting A public university in Maharashtra, India. Participants A total of 266 university employees who underwent a comprehensive health assessment were included. Main outcome measures Multimorbidity was defined as the presence of two or more of nine chronic conditions: hypertension, diabetes mellitus, dyslipidaemia, ischaemic heart disease, chronic kidney disease, thyroid disease, stroke, chronic obstructive pulmonary disease and cancer. Cardiometabolic multimorbidity was defined as the presence of two or more of hypertension, diabetes mellitus, dyslipidaemia, ischaemic heart disease and chronic kidney disease. Results Hypertension was identified in 119 participants (44.7%), comprising 50 participants with pre-existing hypertension and 69 newly identified during the assessment. Dyslipidaemia was present in 189 (71.1%) and diabetes mellitus in 45 (16.9%). Overall, 108 participants (40.6%) had multimorbidity and 103 (38.7%) had cardiometabolic multimorbidity. The prevalence of multimorbidity increased progressively with age, from 17.5% among participants aged <30 years to 83.3% among those aged [&ge;]60 years. The predominant exact multimorbidity patterns were hypertension with dyslipidaemia alone (49 participants) and hypertension, diabetes mellitus and dyslipidaemia (27 participants). Overall, 173 participants (65.0%) had at least one newly identified hypertension, diabetes mellitus or dyslipidaemia diagnosis. In multivariable logistic regression, age (adjusted OR [aOR] 1.058 per year, 95% CI 1.027 to 1.091), BMI (aOR 1.163 per kg/m2, 95% CI 1.076 to 1.257) and tobacco use (aOR 3.296, 95% CI 1.377 to 7.888) were independently associated with multimorbidity. The model had an area under the receiver operating characteristic curve of 0.731. Conclusion Multimorbidity affected approximately two in five university employees, with cardiometabolic conditions accounting for most of the observed disease clustering. Comprehensive health assessment identified a substantial burden of previously unrecognised chronic disease. Integrating institutional or occupational health assessment with longitudinal primary care follow-up may provide an opportunity for earlier detection, risk-factor modification and coordinated management of multimorbidity. Keywords: Multimorbidity; cardiovascular diseases; hypertension; diabetes mellitus; dyslipidaemia; occupational health; university employees; India

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Back to work MD - Experiences of internal medicine physicians returning to work after parental leave

Hasan, S.; Tang, G. H.; Van Bakel, T.; Fralick, M.; Sholzberg, M.

2026-10-08 medical education 10.64898/2026.10.06.26364854 medRxiv
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Background: Parenthood in medicine is an experience fraught with challenges that begin in the pre-conception phase and persist as physician-parents navigate their dual role. Methods: This study aims to understand the experiences of physician-parents (both childbearing and non-childbearing) returning to work after parental leave. Physicians, including residents, affiliated with the University of Toronto Department of Medicine internal medicine division who had a child within the last ten years were invited to participate in a self-administered electronic survey from June2022 to 30June 2023. Data were summarized using descriptive statistics. Results: Twenty-nine respondents took part in the survey; 79% were staff physicians while the remaining were trainees at the time of the survey. At the time their first child was born, 48% were staff members and 52% were trainees. The median duration of parental leave was 5 months (range 1-12 months). Among those for whom lactation was applicable, 76% reported that they continued their lactation efforts on returning to work, while 24% chose not to. Thirty five percent (35%, n=6/17) of respondents cited that they were not provided with duty hour modifications when required. Many respondents (46%) felt guilty about burdening their co-workers for requesting accommodations for childcare. When requested to rate their experiences of balancing their personal and professional lives on a scale of 1-10 (1 being impossible to maintain and 10 being extremely easy to maintain), most respondents (66%) chose a rating of 5 or less. Conclusion: This study supports previous findings that physician-parents face a myriad of challenges integrating their roles in medicine and parenthood. A change in culture is required to support and normalize parenthood for physicians and foster sustainability and productivity in academic medicine.

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Dental Anxiety in Oral-Systemic Health: Empirical Evaluation of a Published Conceptual Model

Kajita, M.; Yada, A.; Ylostalo, P.; Pohjola, V.; Sipila, K.; Humphris, G.; Auvinen, J.; Lahti, S.

2026-09-28 dentistry and oral medicine 10.64898/2026.09.25.26364045 medRxiv
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Objectives: A previously published conceptual mapping review integrated fragmented evidence on dental anxiety (DA) into a broader conceptual model of potential causes and consequences. This study focused on consequences, extending from oral health-related behaviours through oral disease to systemic health, and empirically evaluated these hypothesized relationships on the population level. Methods: Cross-sectional data from the 46-year follow-up of the Northern Finland Birth Cohort 1966 (n = 1,859) were analysed using structural equation modelling. DA was modelled as a latent construct; delayed/problem-oriented dental attendance and home oral care as behavioural proxies; periodontal disease burden as the percentage of sites with probing pocket depth >=4 mm; and cardiovascular risk as a Framingham-based risk score. Generalized anxiety, sex, and education were covariates. Smoking-stratified multigroup analyses assessed model robustness. Results: The prespecified associations were observed across behavioural, periodontal, and systemic-risk domains. Higher DA was associated with more delayed/problem-oriented attendance and poorer home care; both were associated with greater periodontal disease burden, which in turn was associated with higher cardiovascular risk. Model fit was good (chi-square(119) = 529.98, CFI = 0.962, TLI = 0.951, RMSEA = 0.043, SRMR = 0.051). The overall association between DA and cardiovascular risk was small (beta = 0.066, p = .004), with a small decomposed indirect association (beta = 0.013, p = .006) and a remaining direct association (beta = 0.053, p = .022). Smoking-stratified multigroup comparisons found no differences in the structural associations by smoking status. Conclusions: This population-based evaluation provides preliminary empirical support for the conceptual model. Findings extend the relevance of DA beyond dental attendance and oral health outcomes to a broader oral-systemic public-health context. Cross-sectional data cannot establish temporal or causal ordering; longitudinal replication is needed.

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Documented Dental Disease in Patients With Staphylococcus aureus Bacteremia

Ssentongo, P.; Peacock, W. F.; Durieux, J. C.; Colovos, C.

2026-10-20 dentistry and oral medicine 10.64898/2026.10.18.26365833 medRxiv
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Importance: Clinicians often look for a dental source in Staphylococcus aureus bacteremia (SAB), but how often dental disease is found, compared with other bacteremias, is unclear. Objective: To compare documented dental disease in adults with SAB, Escherichia coli bacteremia, and a general population cohort. Design, Setting, and Participants: Retrospective cohort study in the Protege database of 48 975 adults with bacteremia from January 1, 2015, through December 31, 2023, assigned by earliest in-window organism, and 81 945 general population adults. Exposures: SAB, with E coli bacteremia as the primary comparator and the general population as the secondary comparator. Main Outcomes and Measures: Documented dental disease from 7 days before through 30 days after index, defined by a qualifying dental procedure or disease-specific note text and adjusted for age, sex, race, and documentation intensity. Results: Dental disease occurred in 528 of 16 435 patients with SAB (3.21%) and 179 of 24 942 patients with E coli bacteremia (0.72%). The adjusted odds ratio was 3.86 (95% CI, 3.23 to 4.63). By the pathology-only definition, disease occurred in 517 patients with SAB (3.15%) and 399 general population patients (0.49%). The adjusted odds ratio was 3.71 (95% CI, 3.08 to 4.46). Within SAB, rates were highest with prior infective endocarditis (9.8%), opioid use disorder (6.2%), injection drug use (5.3%), and prosthetic valve (5.0%). Prevalence ranged from 0.49% in the general population to 7.98% in other streptococcal bacteremia. Of 437 patients with SAB and an assignable first finding date, 333 (76.2%) had the finding after the index date. Conclusions and Relevance: Dental disease was documented more often in SAB than in E coli bacteremia after adjustment. Most findings were first recorded after bacteremia was recognized, during SAB evaluation. These data do not show that dental disease caused the bacteremia.

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Who carries the cost of interruptions? A qualitative study of doctors in UK hospital outpatient departments

Boustani, S.; Staras, C.; Rich, A.; Griffin, A.

2026-10-13 medical education 10.64898/2026.10.11.26365196 medRxiv
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Background Hospital outpatient departments (OPDs) deliver specialist care at scale, under close scrutiny over waiting times. Interruptions are common in this setting and are linked to error. Little is known about how they cause harm, for whom, and under what conditions. Methods Qualitative study using focus groups and interviews with 42 doctors working in UK National Health Service OPDs (19 sessions, September to November 2025). Participants were purposively sampled by clinical experience and self-reported patient complexity. Data were analysed using the Framework Method, informed by Cognitive Load Theory and Social Identity Theory, with independent double coding of 10% of transcripts (kappa = 0.97) and participant validation. Results We developed four themes. (1) Interruptions as a structural and increasingly ambiguous feature of clinical work. Interruptions were a normal part of clinical coordination, but new communication channels lacked shared norms about urgency, so each doctor had to judge what mattered. (2) The hidden cognitive cost of interruptions. The main cost came from returning to the interrupted task. This cost grew with complexity and was only partly offset by experience. (3) The social fabric of interruption burden. Transient teams weakened the norms that regulate interrupting, and approachability and hierarchy concentrated the burden on particular doctors. (4) The social amplification of cognitive burden. Understaffing multiplied cognitive costs. Doctors used familiarity and track record to decide which requests deserved attention, so concerns from junior or unfamiliar colleagues risked being discounted. Conclusions Interruptions are structural, and their impact depends on cognitive and social conditions. Reducing interruption frequency alone may miss the main risk. Interventions should support task resumption, protect capacity at busy times, rebuild shared communication norms and take account of the receiver's capacity when designing escalation.

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Can LLMs Succeed in National Dental Examinations? A Comprehensive Analysis of Performance, Strengths, and Limitations

Xu, Y.; Peng, Y.; Dan, L.; Mei, L.; Han, X.; Duan, P.

2026-10-05 medical education 10.64898/2026.09.30.26364385 medRxiv
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Abstract Background: Large language models (LLMs) are increasingly explored as adjunct tools in graduate medical education, but their reliability for answering discipline-specific certification examinations remains incompletely characterized. In dentistry in China, the national dental examination serves as a milestone for stomatology trainees. Prior studies predominantly rely on single metric, limiting reproducibility and granularity. Objective: To systematically evaluate the performance of five LLMs in answering the national standardized training examination for dental residents. Method: A total of 1,318 questions covering the six dentistry disciplines were selected. Five LLMs (DeepSeek-V3, DeepSeek-R1, Qwen3-32B, Claude 3.5, and GPT-4o) were evaluated via a single-response protocol on the Dify-based Chatflow framework. Performance combined human verification with automated scoring using the Retrieval-Augmented Generation Systems (RAGAS) framework across seven dimensions. Tasks involving question classification, key-point categorization, and instructional requirement summarization were designed to enable a horizontal comparison of models' cognitive capabilities, assessed using inter-model consistency scores. Results: DeepSeek-R1 achieved the highest correct choice rate (80.90%, p < 0.001) and answer correctness score (0.853, p < 0.001), significantly outperforming the others. All models exhibited limitations, including information insufficiency, redundancy, and hallucination-related issues (lowest 44.20% in DeepSeek-R1). In classification and summarization tasks, Claude 3.5 showed higher consistency scores (186/181) than Qwen3-32B (152/151). Conclusion: Evaluated LLMs demonstrated good performance on dental examination questions and in executing tasks. DeepSeek-R1 consistently outperformed the others. While LLMs showed potential as supportive tools in dental education, further refinement and validation are needed before formal adoption in graduate medical educational and clinical training settings.

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Continuous Integration and Software Quality in Scientific Software: A Large-Scale Empirical Analysis of GitHub Repositories

Compton Mellon, W. J.; Sy, M.; Gangrade, N.; Jakobi, T.

2026-10-08 bioinformatics 10.64898/2026.10.01.755028 medRxiv
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Bioinformatics software plays a central role in biological research, yet many academic projects lack robust testing and continuous integration (CI) practices. This absence can compromise reproducibility, accessibility, and long-term maintainability. In this study, we conduct an empirical analysis of GitHub repositories spanning bioinformatics and other scientific software domains to examine the relationship between CI, software testing, and software quality. Repository discovery was performed using domain-specific search terms via GitHub's Application Programming Interface (API). This was followed by a layered data extraction pipeline, which included a Large Language Model (LLM) validation step, that connected repositories to published works, institutions, authors, funding, and citation counts. By integrating repository activity, community engagement, and backlog health into a composite Repository Quality Index (RQI), we find that the presence of CI and software tests is significantly associated with higher repository quality. Additionally, repositories with higher academic citation counts tend to cluster in higher RQI tiers, suggesting that software quality, which is driven by proper testing and integration, is associated with academic impact and funding status. These results demonstrate that adopting industry-standard development practices, such as CI and software testing, is a tractable path toward more sustainable and impactful academic software and funding opportunities.

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Change in the neutrophil-to-lymphocyte ratio after a 3-day orbital flight: A preregistered secondary analysis of NASA open data from the Inspiration4 civilian crew

GODINEZ VAZQUEZ, V. J.

2026-10-19 occupational and environmental health 10.64898/2026.10.16.26365757 medRxiv
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Background: Commercial spaceflight now carries civilians on short missions, yet their stress-axis physiology is poorly described. Earlier shuttle data suggest that sympathetic responses predominate after short flights and glucocorticoid responses after long ones. The neutrophil-to-lymphocyte ratio (NLR) is a low-cost readout of both. Methods: Preregistered secondary analysis of open clinical laboratory data (NASA Open Science Data Repository OSD-569 and OSD-575) from the four Inspiration4 crew members, each sampled seven times: three draws before launch, one the day after return (R+1) and three during recovery (R+45 to R+194). Log-transformed NLR was modelled with a linear mixed model with a random intercept per crew member and Kenward-Roger inference. Lymphocyte and eosinophil counts and C-reactive protein were secondary outcomes with false discovery rate correction. Results: All 28 draws were analysed. NLR at R+1 did not differ from pre-flight (fold change 1.04; 95% CI 0.81 to 1.34; p = 0.73); two crew members increased (+25% and +46%) and two decreased (-27% and -11%). During recovery NLR was 23% lower than pre-flight (fold change 0.77; 95% CI 0.64 to 0.92; p = 0.005). No secondary outcome changed after correction; lymphocytes were 18% lower at R+1 (95% CI -35% to +4%; q = 0.31). Between-person differences explained 58% of the variance. An ordinary regression ignoring repeated measures missed the recovery effect (p = 0.08). Conclusions: A 3-day orbital flight produced no consistent leukocyte stress signature one day after return. The lower NLR during recovery suggests that pre-flight values, not recovery values, deviate from the resting state, which has implications for how baselines are defined in short-duration spaceflight studies.

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Postnatal Development Shapes the Cardiac Response to Milrinone

Salameh, S.; Boozell, E.; Rajtboriraks, M.; Mesfin, F.; Haski, A.; Swift, L. M.; Posnack, N.

2026-09-23 pharmacology and toxicology 10.64898/2026.09.17.750727 medRxiv
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Background: Milrinone, a phosphodiesterase-3 (PDE-3) inhibitor, is widely used to improve cardiac output in pediatric and adult patients. Yet, developmental differences in myocardial responsiveness to milrinone remain incompletely understood. In this study, we examined the impact of postnatal maturation on the acute cardiac effects of milrinone using an intact guinea pig heart model. Methods: Neonatal (0-2 days), juvenile (4-10 days), and adult (> 6 months) guinea pig hearts were excised, Langendorff-perfused, and cardiac metrics were evaluated under basal conditions and in response to acute milrinone treatment (15 minutes, 10 and 100 M sequential concentrations). Pseudo-electrocardiograms were recorded continuously and left ventricular pressure measurements were performed under sinus rhythm and in response to external pacing. Post-rest potentiation was used to assess contractile reserve, and optical action potentials and calcium transients were recorded. Results: Baseline left ventricular developed pressure (LVDP), action potential duration (APD), and calcium transient duration (CaD) increased with postnatal maturation, consistent with developmental cardiomyocyte remodeling and refinement of excitation-contraction coupling. Milrinone increased heart rate in all age groups, with the greatest chronotropic response at 100 M. Milrinone also increased ventricular contractility and relaxation across developmental stages, but the magnitude of the response varied with age and was attenuated during high frequency pacing. Adult hearts had the greatest increase in LVDP during sinus rhythm and robust post-rest potentiation, which were less pronounced in neonatal hearts. APD and CaD were shortened in neonatal and adult hearts, but were minimally affected in juveniles, indicating a non-linear developmental pattern. Conclusions: Milrinone exerts positive chronotropic, inotropic, and lusitropic effects throughout development, but the magnitude and frequency dependence of these responses vary with age. These findings suggest that postnatal maturation influences the cardiac response to PDE3 inhibition. These developmental differences highlight the importance of considering age as a biological factor in pediatric drug selection and dosing.

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Real-time situational assessment of respiratory virus epidemics in Australia over winter 2025 and an out-of-season influenza A H3N2 epidemic

Eales, O.; Young, A. R.; Senior, K. L.; Tobin, R.; Amin, J.; Archer, B. N.; Armstrong, P.; Ellis, S.; Robinson, E. J.; Strachan, J.; Shrestha, A. C.; Veitch, M.; Wood, J.; McCaw, J. M.; Shearer, F. M.

2026-10-02 infectious diseases 10.64898/2026.09.30.26364449 medRxiv
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Introduction: In temperate regions, influenza and respiratory syncytial virus (RSV) typically exhibit seasonal epidemics during the winter months, often concurrently with SARS-CoV-2 epidemics. Monitoring past and real-time trends in infection dynamics is important for informing public health situational awareness, including identifying and characterising unusual epidemic activity. However, data used to monitor these trends can exhibit substantial noise including strong day-of-the-week variation in reporting. In addition, case data for influenza can obscure distinct trends in influenza subtypes if not combined with virological data. Aim: By quantifying trends in respiratory virus activity using statistical methods, the Australia-Aotearoa Consortium for Epidemic Forecasting and Analytics (ACEFA) aims to provide government partners with comprehensive epidemic intelligence. Methods: Analyses were performed on daily case time series data for SARS-CoV-2, RSV and influenza across Australia's eight jurisdictions. Past and real-time trends were inferred for each pathogen and each influenza subtype using Bayesian p-spline models. Results: The 2025 Winter Situational Assessment Program provided weekly reports throughout the winter season and during the out-of-season influenza A H3N2 epidemic, driven by the emergence of the novel influenza subclade ('subclade K'). Despite limited subtyping data, our analysis provided an early signal of increasing influenza A H3N2 during a period in which overall influenza cases were decreasing; increases in influenza A H3N2 activity were first detected in July, and by mid-August, increasing H3N2 activity was estimated across all jurisdictions. Discussion: Our analysis highlights the benefits of incorporating statistical methods into real-time epidemic situational assessment and in consolidating reporting across jurisdictions.

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Birth Spacing And Under-Five Child Survival In Ghana: Evidence From The 2022 Demographic And Health Survey.

Siddiq, A. I.; Akuffo, J. A.; Oppong, A. G.; Ditchfield, A.-M. X.; Agyarko Duah, S.; Lamptey, G. L.

2026-10-15 medical education 10.64898/2026.10.14.26365524 medRxiv
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Background: Short birth intervals are a well-documented, modifiable risk factor for child death in low- and middle-income countries, yet nationally representative evidence from Ghana's most recent Demographic and Health Survey has not been fully examined. This study assessed the association between the preceding birth interval and under-five mortality using the 2022 Ghana Demographic and Health Survey. Methods: The analysis used the complete birth history reported by women aged 15-49 years. The cohort comprised births occurring 60-119 completed months (5-10 years) before the survey, which allowed a complete five-year observation window for under-five survival (n = 8,418; 397 deaths). Spacing models were restricted to second-or-higher-order births with a defined preceding interval (n = 6,340; 282 deaths), categorised as under 18, 18-23, 24-35 (reference), 36-47, and 48 or more months. Crude and adjusted odds ratios were estimated using survey-weighted, Taylor-linearised logistic regression, adjusting for birth order, child sex, plurality, maternal age, residence, region, maternal education, wealth quintile, and marital status. Results: Weighted under-five mortality in the cohort was 45.4 per 1,000 live births (4.54%). Among second-or-higher-order births, weighted mortality fell from 9.3% after intervals of under 18 months and 8.0% after 18-23 months to 4.2%, 3.2%, and 3.5% after 24-35, 36-47, and 48 or more months, respectively. Relative to 24-35 months, the adjusted odds of death were higher after intervals of under 18 months (adjusted odds ratio [AOR] 2.58, 95% confidence interval [CI] 1.48-4.49, p < 0.001) and 18-23 months (AOR 2.09, 95% CI 1.33-3.29, p = 0.001); longer intervals did not differ from the reference. Multiple birth (AOR 2.48, 95% CI 1.33-4.63) and having a mother who was never in union (AOR 3.25, 95% CI 1.29-8.17) were also associated with higher odds of death, and marked regional variation persisted after adjustment. Conclusion: A short preceding birth interval, particularly one of under 18 months, was independently associated with an approximately two- to two-and-a-half-fold increase in the odds of under-five death in this nationally representative sample. The findings support continued investment in postpartum family planning to help women space births at least 24 months apart, alongside closer attention to multiple births, unmarried mothers, and the regions carrying the greatest burden.

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A tetracycline-inducible promoter for gene expression in Gram-negative bacteria including Acinetobacter baumannii

Stella, N. A.; Ginde, R. K.; Ginde, R. K.; Calvario, R. C.; Doi, Y.; Shanks, R. M. Q.

2026-10-10 microbiology 10.64898/2026.10.09.758105 medRxiv
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Carbohydrate inducible promoters on expression plasmids are widely used for biotechnology and basic science research. However, using carbohydrates for inducers has drawbacks including influencing bacterial metabolism, the inducer being used as a carbon source by the bacteria, high background expression, and only a subset of cells experiencing promoter activation. Furthermore, some bacteria including the pathogen Acinetobacter baumannii currently lack good carbohydrate-inducible promoters. To address this issue, a tetracycline-inducible promoter, PtetB, isolated from A. baumannii was cloned and evaluated in a number of important bacteria: Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Pseudomonas fluorescens, and Serratia marcescens. A highly sensitive luxCDABE reporter was used to evaluate promoter activity. S. marcescens strains with elevated and reduced cyclic-AMP levels were used to evaluate the impact of cAMP on PtetB function. The PtetB promoter was induced over 800-fold in A. baumannii and 10-750-fold inducible in the other tested species. Background expression was lower from PtetB in the pseudomonads than previously described carbohydrate inducible promoters. Data indicated that the PtetB promoter system may be a useful tool for future basic science research with the tested bacteria.

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Lipid lowering effects of Fucus vesiculosus and Phytolacca berry extracts: An alternative approach of treating hypertriglyceridemia

Hasan, N.; Ahsan, N.; Ahmed, T. B.; Akhand, A. A.

2026-09-24 pharmacology and toxicology 10.64898/2026.09.18.752646 medRxiv
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Hypertriglyceridemia is commonly managed with lipid-lowering drugs such as statins; however, adverse effects, dose intolerance, and financial barriers may limit their use. Therefore, affordable and potentially safer plant-derived alternatives warrant investigation. This study evaluated the lipid-lowering effects of ethanol extracts of Fucus vesiculosus and Phytolacca berry, administered individually or in combination, in mice fed a butter-enriched diet for 12 weeks. Forty-eight mice were randomly assigned to six groups: normal control (Group 1), butter control (Group 2), statin control (Group 3), Fucus vesiculosus extract (Ext-1; Group 4), Phytolacca berry extract (Ext-2; Group 5), and the combined extracts (Group 6). Body weight, organ-to-body-weight ratios, serum lipid parameters, and histopathological changes were assessed. Group 3 showed the lowest final body weight, while Group 6 demonstrated a comparable body-weight trajectory. Organ-to-body-weight ratios varied among groups, with Group 3 generally showing the highest values and Group 6 comparatively lower ratios for several organs. Group 5 had the lowest total cholesterol concentration, followed by Group 3, whereas Group 6 showed cholesterol levels comparable to the normal control and statin groups. Notably, Group 6 exhibited the lowest serum triglyceride concentration (129.9 mg/dL). Histopathological examination revealed relatively mild hepatic alterations and limited vascular plaque formation in Group 6. The combined extracts demonstrated favorable effects on body-weight gain and serum lipid profiles, particularly triglycerides, with comparatively mild histopathological changes. Further mechanistic, dose-response, toxicity, and long-term studies are warranted before clinical application can be considered.

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Knowledge and practices toward occupational health and environmental sustainability among farmers in Pabna District, Bangladesh: a cross-sectional study

Parvin, S.; Rashid, M. O.; Rahman, M. M.; Zaber, A. A.; Hossain, M. B.; Begum, R.; Haque, M. A.

2026-10-07 occupational and environmental health 10.64898/2026.10.04.26364727 medRxiv
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Bangladesh's agricultural sector remains heavily dependent on pesticides and chemical inputs, yet limited attention has been paid to how farmers' knowledge of occupational health and environmental sustainability translates into actual practice across the full agricultural value chain. This study aimed to assess the knowledge and practices of farmers in Pabna District, Bangladesh, regarding occupational health, pesticide handling, environmentally sustainable farming, and market sanitation. A cross-sectional survey was conducted among 301 farmers in 2024 using a structured questionnaire covering socio-demographic characteristics, sustainable farming knowledge and adoption, soil testing and organic farming practices, pesticide handling and occupational health and safety behaviours, post-harvest waste management, and market sanitation conditions. Data were analysed using descriptive statistics. The majority of respondents were male (87.04%) and had no formal education (63.46%). Although most farmers reported knowledge of environmentally sustainable farming practices (97.70%) and pesticide label instructions (98.00%), corresponding safety practices were poor: only 10.63% reported wearing any personal protective equipment and 1.33% reported using a mask during pesticide application. Eye irritation was the most commonly self-reported health symptom following pesticide exposure (92.69%). Market sanitation infrastructure was similarly inadequate, with 89.00% of respondents reporting an absence of sanitary toilets. These findings indicate a consistent gap between farmers' knowledge and their actual practices across multiple domains of the agri-food system. Strengthening extension services, delivering practical hands-on occupational safety training, and investing in market sanitation infrastructure are recommended to close this gap and support safer, more sustainable farming practices in Bangladesh.

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A Practical Assay for Assessing Mean Red Blood Cell Age Using the Protein 4.1a/4.1b Ratio

Makhro, A.; Seiler, E.; Bender, N.; Eppenberger, P.; Hobbs-Ray, C.; Baerlocher, G.

2026-10-09 biochemistry 10.64898/2026.10.08.757720 medRxiv
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BACKGROUND: The protein 4.1a/4.1b ratio is an intrinsic molecular marker of mean red blood cell (RBC) age resulting from progressive deamidation of protein 4.1b during RBC circulation. Despite its potential for estimating mean RBC age from a single blood sample, its application has been limited by labor-intensive RBC membrane preparation, and its interindividual variability has not been characterized in a large human population. METHODS: We developed a low-volume method for direct RBC membrane isolation from whole blood using saponin permeabilization and differential centrifugation without prior RBC washing. Membrane proteins were separated by SDS-PAGE, and protein 4.1a/4.1b ratios were determined by densitometric analysis with Gaussian peak fitting. Assay conditions, sample-volume requirements, membrane protein recovery, and analytical reproducibility were evaluated. The method was subsequently applied to 114 anonymized residual samples from routine diagnostic testing selected for complete blood count parameters within the corresponding laboratory reference intervals. RESULTS: The optimized procedure used 50 uL of whole blood, 0.06% saponin, and centrifugation at 9000 g, although protein 4.1a/4.1b remained measurable from starting volumes as low as 5 uL. Mean within-subject CVs were 3.90% for electrophoretic/densitometric determination and 5.39% for membrane protein recovery; whole-procedure CVs in 3 subjects were 1.40% to 3.50%. In the population analysis, the mean protein 4.1a/4.1b ratio was 1.428 (SD 0.146), with an observed range of 1.052 to1.799 and a central 95% interval of 1.151 to 1.695. Ratios did not differ significantly between females and males (P=0.246) or among females aged 18 to 50 years, females aged >50 years, and males (P=0.151). The ratio showed modest positive correlations with chronological age in females (Spearman p=0.26, P=0.047) and males (p=0.33, P=0.015), while substantial interindividual variability remained across the age range. CONCLUSIONS: Direct isolation of RBC membranes from small volumes of whole blood enables reproducible determination of the protein 4.1a/4.1b ratio using a simplified workflow. Application of the assay to a comparatively large human population revealed substantial interindividual variation in this molecular marker of mean RBC age that was not explained by sex or chronological age alone. The method provides a practical approach for investigating biological variation in mean RBC age and its potential contribution to laboratory measurements influenced by RBC survival.

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From APTs to advanced persistent biological threats (APBTs): a taxonomy and large-scale metadata audit of genomic surveillance infrastructure

Anjum, N.; Kiran, M.; Alfraihi, H. A.; Kanta, A.; ul-Hassan, M.; Weihs, B. J.

2026-10-11 genomics 10.64898/2026.10.09.757979 medRxiv
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Open genomic repositories have become critical infrastructure for pathogen surveillance, variant tracking, outbreak reconstruction, and public health decision making. However, many of these repositories were designed to support rapid scientific data sharing rather than adversarial verification, creating potential security gaps. This paper introduces Advanced Persistent Biological Threats (APBTs), as a framework for understanding how malicious cyber biological actors can gradually disrupt genomic surveillance without entering a laboratory or releasing a biological agent. Instead of altering biological material, an attacker targets the sequence data, metadata, reference datasets, and analytical models used by surveillance systems. We present, to our knowledge, the first integrated multilayer taxonomy of APBTs, structured around a four phase lifecycle, and investigate whether the metadata weaknesses identified by this framework are present in an operational genomic repository. To assess this, we audited 100,000 SARS-CoV-2 BioSample records obtained from the NCBI. A framework of 23 checks was applied across five metadata layers: temporal, geographic, host and specimen, provenance, and technical metadata. Every record triggered at least one APBT relevant metadata vulnerability indicator, with a mean of 7.34 indicators per record (SD = 1.34). Overall, 97.3% of records were classified in the High or Critical severity categories. Every record also contained at least one indicator in both the provenance and technical metadata layers. These results largely reflect the optional status of several fields in the current BioSample submission model rather than isolated errors by individual data contributors. Temporal and geographic information was comparatively complete, while fields needed for provenance reconstruction, chain of custody assessment, technical validation, and analytical interpretation were frequently missing. These findings do not indicate deliberate manipulation. However, the structural incompleteness of BioSample metadata creates vulnerabilities that an adversary can exploit to introduce poisoned, misleading, or weakly traceable metadata into genomic repositories. As a result, maliciously altered metadata can appear plausible, remain undetected, and influence downstream genomic analysis and surveillance. The findings therefore show that widely used pathogen genomic repositories already contain structural weaknesses that can support metadata poisoning as part of an APBT operation.