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Life

MDPI AG

Preprints posted in the last 7 days, ranked by how well they match Life's content profile, based on 27 papers previously published here. The average preprint has a 0.03% match score for this journal, so anything above that is already an above-average fit.

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Comparative LUSZ Therapeutic Study (LUSZ_AVIST) of Antiviral, Antiretroviral, and Immunosuppressive Treatments in Hospitalized COVID-19 Patients with High-Risk Factors, Biomarkers, and Disease Progression.

Makdissy, N.; Makdessi, E. W.; Fenianos, F.; Nasreddine, N.; Daher, W.; El Hamoui, S.

2026-04-13 respiratory medicine 10.64898/2026.04.10.26350587 medRxiv
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COVID-19 has spread rapidly and caused a global pandemic making it one of the deadliest in history. Early identification of patients with coronavirus disease 2019 who may develop critical illness is of immense importance. Therefore, novel biomarkers were needed to identify patients who will suffer rapid disease progression to severe complications and death. Many treatments were adopted including the antiviral Remdesivir, the antiretroviral Lopinavir /Ritonavir and Tocilizumab. Our study aimed not only to specify high-risk factors and biomarkers of fatal outcome in hospitalized subjects with coronavirus but also to compare the efficacy of the three considered treatments to help clinicians better choose a therapeutic strategy and reduce mortality. We divided the population (n=711) into four main groups based according to the WHO ordinal severity scale. The percentage of mortality, in and out the hospital, the length of stay in the hospital, the pulmonary inflammatory lesion and its distribution, the SARS-CoV-2 IgM and IgG variations at admission, the inflammatory markers, the complete blood count, the coagulation factors and enzymes, proteins and electrolytes profile, glucose and lipid profile, and other relevant markers were measured. The significance of the observed variation was assessed by multivariate and ANOVA analyses. We succeeded to establish a novel predictive scoring model of disease progression based on a cohort of Lebanese hospitalized patients relying on the pulmonary inflammatory lesions, inflammation biomarkers such as LDH, D-Dimer, CRP, IL-6 and the lymphocyte count, the number of comorbidities and the age of the patient which all were significantly correlated with the illness severity showing best outcomes with immunomodulatory and anticoagulant treatments by the results. As top tier, Tocilizumab was more efficient than the two other treatments in non-severe cases but none of the used treatments was insanely effective alone to reduce mortality in severe cases.

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Ventilator triggering control with an LSTM-Based Model

Liu, J.; Fan, J.; Deng, Z.; Tang, X.; Zhang, H.; Sharma, A.; Li, Q.; Liang, C.; Wang, A. Y.; Liu, L.; Luo, K.; Liu, H.; Qiu, H.

2026-04-11 respiratory medicine 10.64898/2026.04.10.26350573 medRxiv
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Background: Patient-ventilator synchrony, an essential prerequisite for non-invasive mechanical ventilation, requires an accurate matching of every phase of the respiration between patient and the ventilator. Methods: We developed a long short-term memory (LSTM)-based model that can predict the inspiratory and expiratory time of the patient. This model consisted of two hidden layers, each with eight LSTM units, and was trained using a dataset of approximately 27000 of 500-ms-long flow signals that captured both inspiratory and expiratory events. Results: The LSTM model achieved 97% accuracy and F1 score in the test data, and the average trigger error was less than 2.20%. In the first trial, 10 volunteers were enrolled. In "Compliance" mode, 78.6% of the triggering by the LSTM model was compatible with neuronal respiration, which was higher than Auto-Trak model (74.2%). Auto-Trak model performed marginally better in the modes of pressure support = 5 and 10 cmH2O. Considering the success in the first clinical trial, we further tested the models by including five patients with acute respiratory distress syndrome (ARDS). The LSTM model exhibited 60.6% of the triggering in the 33%-box, which is better than 49.0% of Auto-Trak model. And the PVI index of the LSTM model was significantly less than Auto-Trak model (36.5% vs 52.9%). Conclusions: Overall, the LSTM model performed comparable to, or even better than, Auto-Trak model in both latency and PVI index. While other mathematical models have been developed, our model was effectively embedded in the chip to control the triggering of ventilator. Trial registration: Approval Number: 2023ZDSYLL348-P01; Approval Date: 28/09/2023. Clinical Trial Registration Number: ChiCTR2500097446; Registration Date: 19/02/2025.

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Attitudes and Perceptions of Generative Artificial Intelligence Chatbots in the Scientific Process of Traditional, Complementary, and Integrative Medicine Research: A Large-Scale, International Cross-Sectional Survey

Ng, J. Y.; Tan, J.; Syed, N.; Adapa, K.; Gupta, P. K.; Li, S.; Mehta, D.; Ring, M.; Shridhar, M.; Souza, J. P.; Yoshino, T.; Lee, M. S.; Cramer, H.

2026-04-15 health informatics 10.64898/2026.04.13.26350612 medRxiv
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Background: Generative artificial intelligence (GenAI) chatbots have shown utility in assisting with various research tasks. Traditional, complementary, and integrative medicine (TCIM) is a patient-centric approach that emphasizes holistic well-being. The integration of TCIM and GenAI presents numerous key opportunities. However, TCIM researchers' attitudes toward GenAI tools remain less understood. This large-scale, international cross-sectional survey aimed to elucidate the attitudes and perceptions of TCIM researchers regarding the use of GenAI chatbots in the scientific process. Methods: A search strategy in Ovid MEDLINE identified corresponding authors who were TCIM researchers. Eligible authors were invited to complete an anonymous online survey administered via SurveyMonkey. The survey included questions on socio-demographic characteristics, familiarity with GenAI chatbots, and perceived benefits and challenges of using GenAI chatbots. Results were analysed using descriptive statistics and thematic content analysis. Results: The survey received 716 responses. Most respondents reported familiarity with GenAI chatbots (58.08%) and viewed them as very important to the future of scientific research (54.37%). The most acknowledged benefits included workload reduction (74.07%) and increased efficiency in data analysis/experimentation (71.14%). The most frequently reported challenges involved bias, errors, and limitations. More than half of the respondents (57.02%) expressed a need for training to use GenAI chatbots in the scientific process, alongside an interest in receiving training (72.07%). However, 43.67% indicated that their institutions did not offer these programs. Discussion: By developing a deeper understanding of TCIM researchers' perspectives, future AI applications in this field can be more informed, and guide future policies and collaboration among researchers.

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The impact of non-invasive prehabilitation before surgery on emotional well-being in neuro-oncology patients: Insights from the Prehabilita project

Brault-Boixader, N.; Roca-Ventura, A.; Delgado-Gallen, S.; Buloz-Osorio, E.; Perellon-Alfonso, R.; Hung Au, C.; Bartres-Faz, D.; Pascual-Leone, A.; Tormos Munoz, J. M.; Abellaneda-Perez, K.; Prehabilita Working Group,

2026-04-12 oncology 10.64898/2026.04.08.26350382 medRxiv
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Prehabilitation (PRH) is a preoperative process aimed at optimizing patients functional capacity to improve surgical outcomes and overall well-being. While its physical and cognitive benefits are increasingly documented, its emotional impact, particularly in neuro-oncology patients, remains less explored. This study assessed the psychological effects of a PRH program on 29 brain tumor patients. The primary outcome, emotional well-being, was measured using quality of life and emotional distress metrices. Secondary outcomes included perceived stress levels and control attitudes. Additionally, qualitative data from structured interviews provided further insights into the psychological effects of the intervention. The results indicated significant improvements in quality of life and reductions in emotional distress, particularly among women. While perceived stress levels remained stable, control attitudes showed an increase. Qualitative analysis further highlighted the positive changes in the control sense and identified additional factors, such as the importance of social support sources during the PRH process. Overall, these findings suggest that PRH interventions play a significant role in enhancing emotional well-being among neuro-oncological patients in the preoperative phase. These results underscore the importance of implementing comprehensive and personalized PRH approaches to optimize clinical status both before and after surgery, thereby promoting sustained psychological benefits in this population. This study is based on data collected at Institut Guttmann in Barcelona in the context of the Prehabilita project (ClinicalTrials.gov identifier: NCT05844605; registration date: 06/05/2023).

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Leveraging State-of-the-Art LLMs for the De-identification of Sensitive Health Information in Clinical Speech

Dai, H.-J.; Mir, T. H.; Fang, L.-C.; Chen, C.-T.; Feng, H.-H.; Lai, J.-R.; Hsu, H.-C.; Nandy, P.; Panchal, O.; Liao, W.-H.; Tien, Y.-Z.; Chen, P.-Z.; Lin, Y.-R.; Jonnagaddala, J.

2026-04-17 health informatics 10.64898/2026.04.13.26349911 medRxiv
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Accurate recognition and deidentification of sensitive health information (SHI) in spoken dialogues requires multimodal algorithms that can understand medical language and contextual nuance. However, the recognition and deidentification risks expose sensitive health information (SHI). Additionally, the variability and complexity of medical terminology, along with the inherent biases in medical datasets, further complicate this task. This study introduces the SREDH/AI-Cup 2025 Medical Speech Sensitive Information Recognition Challenge, which focuses on two tasks: Task-1: Speech transcription systems must accurately transcribe speech into text; and Task-2: Medical speech de-identification to detect and appropriately classify mentions of SHI. The competition attracted 246 teams; top-performing systems achieved a mixed error rate (MER) of 0.1147 and a macro F1-score of 0.7103, with average MER and macro F1-score of 0.3539 and 0.2696, respectively. Results were presented at the IW-DMRN workshop in 2025. Notably, the results reveal that LLMs were prevalent across both tasks: 97.5% of teams adopted LLMs for Task 1 and 100% for Task 2. Highlighting their growing role in healthcare. Furthermore, we finetuned six models, demonstrating strong precision ([~]0.885-0.889) with slightly lower recall ([~]0.830-0.847), resulting in F1-scores of 0.857-0.867.

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A case report on gendered biases in a Finnish healthcare AI assistant

Luisto, R.; Snell, K.; Vartiainen, V.; Sanmark, E.; Äyrämö, S.

2026-04-14 health informatics 10.64898/2026.04.09.26350383 medRxiv
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In this study, we investigate gender bias in a Retrieval-Augmented Generation (RAG) based AI assistant developed for Finnish wellbeing services counties. We tested the system using 36 clinically relevant queries, each rendered in three gendered variants (male, female, gender-neutral), and evaluated responses using both an LLM-as-a-judge approach and a human expert panel consisting of a physician and a sociologist specializing in ethics. We observed substantial and clinically significant differences across gendered variants, including differential treatment urgency, inappropriate symptom associations, and misidentification of clinical context. Female variants disproportionately framed responses around childcare and reproductive health regardless of clinical relevance, reflecting societal stereotypes rather than medical reasoning. Bias manifested both at the LLM generation stage and the RAG retrieval stage, in several cases causing the model to hallucinate responses entirely. Some bias patterns were persistent across repeated runs, while others appeared inconsistently, highlighting the challenge of distinguishing systematic bias from stochastic variation.

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Cross-cultural adaptation and psychometric validation of the ISBAR Structured Handover Observation Tool in ICU-to-ward patient transfer

Ni, N.; Zhao, B.; Wang, Y.; Wang, Q.; Ding, J.; Liu, T.

2026-04-14 nursing 10.64898/2026.04.10.26350669 medRxiv
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Abstract The ISBAR framework is used to standardize clinical handovers and enhance patient safety. Observational tools based on ISBAR have been developed to assess the completeness of information transfer. However, these instruments have primarily been developed in non-Chinese contexts, and validated Chinese-language observational tools suitable for clinical practice remain limited. In this study, a cross-cultural adaptation and psychometric validation of the ISBAR Structured Handover Observation Tool was conducted, examining its reliability and discriminant validity in Chinese clinical settings. The study was conducted in two phases: cross-cultural adaptation and psychometric evaluation in real-world clinical settings. Content validity was assessed using the Content Validity Index (CVI), and inter-rater reliability was evaluated using the Intraclass Correlation Coefficient (ICC) based on a two-way mixed-effects model with absolute agreement. Discriminant validity was examined using the Mann-Whitney U test to compare scores across nurses with varying levels of clinical experience. A total of 233 handover cases involving patient transfers from the intensive care unit (ICU) to general wards were collected, involving 84 nurses. The scale demonstrated good content validity, with item-level content validity indices (CVI) ranging from 0.88 to 1.00 and a scale-level CVI/Ave of 0.98. The inter-rater reliability, assessed using fifty randomly selected cases, was high, with an intraclass correlation coefficient (ICC) of 0.885 for single-rater assessments and 0.939 for average-rater assessments. Discriminant validity analysis showed that nurses with more clinical experience had significantly higher total scores than those with less experience (Z = -4.772, p < 0.001). The Chinese version of the ISBAR Structured Handover Observation Tool demonstrates good content validity, high inter-rater reliability, and acceptable discriminant validity. This tool provides a standardized and practical method for assessing the completeness of information transfer and is expected to support quality improvement in patient handover from the ICU to general wards in Chinese clinical settings.

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Pleuroparenchymal fibroelastosis in monogenic DGUOK-associated mitochondriopathy

von Hardenberg, S.; Maier, P.; Christian, L.; Das, A. M.; Neubert, L.; Ruwisch, J.; Peters, K.; Schramm, D.; Griese, M.; Skawran, B.; Eilers, M.; Jonigk, D.; Junge, N.; Haghikia, A.; Hegelmaier, T.; Hofmann, W.; Seeliger, B.; Renz, D. M.; Stalke, A.; Hartmayer, L.; Duscha, A.; Schulze, M.; DiDonato, N.; Prokisch, H.; Auber, B.; Knudsen, L.; Schupp, J. C.; Schwerk, N.

2026-04-11 respiratory medicine 10.64898/2026.04.08.26349275 medRxiv
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BackgroundPleuroparenchymal fibroelastosis (PPFE) is a rare, fibrotic lung disease with poor prognosis, usually affecting adults which most commonly occurs idiopathically. Biallelic pathogenic variants in DGUOK cause mitochondrial DNA (mtDNA) depletion syndrome, predominantly affecting infants with severe hepatic and neurological symptoms. Detailed description of pulmonary manifestations with late-onset presentation have not been reported. MethodsWe describe nine patients with PPFE and DGUOK-associated mitochondriopathy. Clinical, radiological, histopathological, and genetic data were systematically collected from all patients. Functional studies, single nucleus RNA sequencing (snRNAseq), immunofluorescence staining, transmission electron microscopy and respiratory chain enzyme activity assays were conducted on patient-derived fibroblasts, muscle or lung tissues. mtDNA content quantification was performed on whole genome sequencing (WGS) data. ResultsAll patients (ages 5-36) presented with progressive dyspnea, weight loss and some with spontaneous pneumothoraces. Chest computed tomography and lung biopsies showed features of PPFE. Biallelic pathogenic DGUOK variants were identified in all patients, seven of them carry an unreported intronic variant leading to mtDNA depletion. snRNAseq of lung tissue from four pediatric patients identified Aberrant Basaloid cells and intermediate cells as their precursor localized at the fibrotic edge. Mitochondrial alterations were identified by electron microscopy. ConclusionPPFE in children and young adults is associated with DGUOK-related mitochondriopathy. For the first time, we demonstrate Aberrant Basaloid cells in pediatric fibrotic lung tissue. Since pulmonary involvement may be underrecognized or misinterpreted and the clinical presentation may not always be typical of a mitochondriopathy, we recommend genetic testing in all patients with PPFE of unknown origin.

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Cross-cultural adaptation and validation of the Japanese Charite Alarm Fatigue Questionnaire (CAFQa) among ICU nurses and physicians: a multicenter study

Sato, T.; Ishiseki, M.; Kataoka, Y.; Someko, H.; Sato, H.; Minami, K.; Kaneko, T.; Takeda, H.; Crosby, A.

2026-04-11 intensive care and critical care medicine 10.64898/2026.04.07.26350292 medRxiv
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ObjectivesAlarm fatigue is a patient safety concern in ICUs, yet no validated instrument exists to assess alarm fatigue among healthcare professionals in non-Western settings. This study aimed to cross-culturally adapt the Charite Alarm Fatigue Questionnaire (CAFQa) into Japanese and evaluate its reliability and validity among ICU nurses and physicians. MethodsThe Japanese CAFQa was cross-culturally adapted following the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines, including forward translation, back-translation, expert panel review, and cognitive interviews. A multicenter cross-sectional validation study was performed across eight ICUs at five hospitals in Japan. A total of 129 participants (103 nurses and 26 physicians) completed the Japanese CAFQa, the NIOSH Brief Job Stress Questionnaire, and the Insomnia Severity Index (ISI). Structural validity, internal consistency, test-retest reliability (n = 102), convergent validity, and known-groups validity were assessed. ResultsCFA confirmed the two-factor structure with acceptable fit (CFI = 0.922, RMSEA = 0.041, SRMR = 0.076), with standardized factor loadings ranging from 0.33 to 0.82. The two factors were not correlated (r = 0.05). Cronbachs alpha was 0.688 for the overall scale, 0.805 for Alarm Stress, and 0.649 for Alarm Coping. Test-retest ICCs ranged from 0.616 to 0.753. The CAFQa total score correlated with the NIOSH total (r = 0.261) and the ISI total (r = 0.338). Healthcare professionals with [&ge;]4 years of ICU experience had higher Alarm Coping scores than those with 1-3 years (median 7.0 vs 6.5), and physicians scored higher on Alarm Coping than nurses (median 8.0 vs 7.0). ConclusionsThe Japanese CAFQa demonstrated acceptable structural validity, reliability, and convergent and known-groups validity, providing the first validated tool for quantitatively measuring alarm fatigue in Japan. Implications for Clinical PracticeThe Japanese CAFQa enables ICU managers to quantify alarm fatigue at individual and unit levels, identify high-risk staff, and evaluate the effectiveness of alarm management interventions.

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Evaluating the impact of school-based interventions on youth loneliness: A systematic review and meta-analysis

Sticpewich, L.; Stuttard, H.; Bu, F.; Fancourt, D.; Hayes, D.

2026-04-16 public and global health 10.64898/2026.04.15.26349177 medRxiv
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Aims: Youth loneliness is a prevalent global health concern with lifelong health ramifications. Schools, as children's primary peer environments, are promising settings for loneliness interventions. However, school-based interventions are highly heterogeneous and no review to date has evaluated their effect on loneliness specifically. Methods: A systematic review was conducted to identify studies of school-based interventions measuring loneliness as an outcome in children and young people aged up to 18. Meta-analyses were conducted using a random-effects model to pool effect sizes and examine the significance of intervention characteristics and study design. Reported implementation factors were extracted and narratively synthesised. Results: Thirty-eight studies were included in meta-analysis, of which 19 were randomized controlled trials, ten were non-randomized controlled, and nine were single group studies. A small-to-moderate effect estimate was found, Hedges' g = -0.42 [95% CI: -0.71, -0.13], p = .006, and sub-group analyses indicated that differences in study design and quality did not result in significantly different effect estimates. Psychological interventions, followed by social and emotional skills training, produced significantly higher effects estimates compared with other intervention types. Conclusions: Findings indicate that school-based interventions are effective in reducing youth loneliness. However, study heterogeneity, reporting inconsistencies, and a wide prediction interval indicates this finding should be interpreted with caution. Future research may benefit from improved measurement and reporting of implementation factors, particularly dosage and fidelity.

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Can NLP Detect Loneliness in Electronic Health Records? A Proof-of-Concept Study

Park, T.; Habibi, S.; Lowers, J.; Sarker, A.; Bozkurt, S.

2026-04-11 health informatics 10.64898/2026.04.08.26350462 medRxiv
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Loneliness is clinically important but under-documented in electronic health records (EHRs), posing challenges for secondary use and computational phenotyping. This study evaluated whether natural language processing (NLP) methods can detect and classify loneliness severity from clinical notes. Patients with a loneliness survey (mild, moderate, severe) were identified, and notes within six months prior to the survey were retrieved. An expert-expanded lexicon was applied, and transformer models (RoBERTa, ClinicalBERT, Longformer) were fine-tuned for loneliness severity classification. Large language model-based summarization of social and psychiatric history was also tested as an alternative input representation. Performance was evaluated using accuracy, weighted-F1, and per-class F1. All models achieved modest accuracy (0.3 to 0.7), and struggled to identify severe loneliness, reflecting sparse and inconsistent documentation even among surveyed patients. While summarization marginally improved accuracy, gains primarily reflected mild predictions. Manual review of 100 social worker notes from severely lonely patients found explicit mentions of loneliness in only two cases, confirming that relevant documentation is exceedingly rare. These findings demonstrate that model performance is constrained by the sparse and inconsistent documentation of loneliness in EHRs, rather than by deficiencies in the modeling approach itself.

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A Tale of Two Countries: Comparison of Rectal Cancer Characteristics Between Pakistani Americans and Native Pakistanis

Sherwani, M.; Azhar, M. K.; Khan, S.; Ali, D.; Husain, S.; Khan, A.

2026-04-11 surgery 10.64898/2026.04.07.26350364 medRxiv
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IntroductionComparison of rectal cancer characteristics in Pakistani Americans and native Pakistanis remains poorly investigated, as migrant studies have predominantly concentrated on East and Southeast Asian groups. This research aims to compare clinicopathological characteristics between the two groups. We hypothesize that significant differences will exist between these cohorts, mediated by gene-environment interactions. MethodsThis was a retrospective cohort study utilizing two multi-institutional databases to identify adult patients with rectal cancer: the National Cancer Database in the U.S (2018-2022) and the Rectal Cancer Surgery and Epidemiology Study in Pakistan (2020-2021). Non-Hispanic Whites (NHWs) were included as a reference population for comparative analysis. Clinicopathological characteristics were compared using Wilcoxon rank-sum and chi-square tests. ResultsA total of 523 Pakistani Americans and 608 native Pakistanis were included in the study. The median age at diagnosis was 57 years in Pakistani Americans (IQR 48-68), 42 years (IQR 33-54) in native Pakistanis and 63 years in NHWs (IQR 54-73) (p < 0.001). Native Pakistanis presented with early-stage disease less often than Pakistani Americans and NHWs (5.3%, 25.1%, and 20.5%, respectively; p < 0.001) and had markedly higher rates of signet cell carcinoma (20.1%, 0.6%, and 0.4%, respectively; p < 0.001) and poorly differentiated tumors (29.0%, 10.4%, and 11.4%, respectively; p < 0.001). ConclusionsThis study found that Native Pakistanis with rectal cancer presented at a younger age and with more aggressive tumor characteristics compared to both Pakistani Americans and NHWs. Notably, Pakistani Americans displayed a distinct clinical profile, intermediate between both groups.

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Risk of Post-acute Symptoms and Conditions After SARS-CoV-2 Compared to Other Respiratory Viral Infections: A Systematic Review and Meta-Analysis

Pinto, T. F.; Santoro, A.; Oliveira, A. L. G.; Tavares, T. S.; Almeida, A.; Incardona, F.; Marchetti, G.; Cozzi-Lepri, A.; Pinto, J.; Caporali, J. F. M.

2026-04-13 infectious diseases 10.64898/2026.04.11.26350682 medRxiv
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Background: How post-COVID-19 condition (PCC) differs from post-acute infection syndromes (PAIS) caused by other respiratory viruses remains uncertain. Comparing these conditions may clarify whether post-acute symptoms reflect specific consequences of SARS-CoV-2 infection or broader post-viral mechanisms. Methods: We conducted a systematic review and meta-analysis of cohort studies comparing persistent symptoms or conditions in adults after SARS-CoV-2 infection with those following other acute respiratory viral infections. PubMed, Embase, and Scopus were searched. Random-effects models were used to estimate pooled risks. Results: Among 9,371 records screened, 22 studies were included and 14 contributed to the meta-analysis. Increased risk after SARS-CoV-2 infection was observed for pulmonary embolism, abnormal breathing, fatigue, hemorrhagic stroke, memory loss/brain fog, and palpitations; heart rate abnormalities showed borderline significance. For most other outcomes pooled estimates were inconclusive. Conclusions: Only a subset of outcomes appears more frequent after SARS-CoV-2 infection, suggesting many symptoms attributed to PCC may reflect broader post-viral syndromes.

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Validated Synthetic Data Generation from a Multicenter Spine Surgery Registry: Methodology and Benchmark

Challier, V.; Jacquemin, C.; Diebo, B.; Dehouche, N.; Denisov, A.; Cristini, J.; Campana, M.; Castelain, J.-E.; Lonjon, G.; Lafage, V.; Ghailane, S.; SpineDAO Collaborative Group,

2026-04-11 health informatics 10.64898/2026.04.07.26350316 medRxiv
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BackgroundSynthetic data have emerged as a complementary strategy for secondary use of clinical registries, enabling data sharing without patient-level exposure. In spine surgery, multicenter data sharing is constrained by institutional governance and patient privacy regulations. Validated synthetic data generation may enable broader access to surgical outcomes data for artificial intelligence development without compromising patient confidentiality. ObjectiveTo describe and benchmark a three-domain validated synthetic data pipeline applied to a multicenter, tokenized spine surgery registry (SpineBase), and to establish a reproducible certification framework for synthetic spine surgery datasets. MethodsWe extracted 125 sacroiliac joint fusion cases from the SpineBase registry (SIBONE study, IRB-SOFCOT approval Ref. 14-2025; CNIL MR-004 Ref. 2234503 v 0). A GaussianCopula generative model was trained on 52 structured variables spanning demographics, preoperative assessments, operative details, and longitudinal outcomes at 3, 6, 12, and 24 months. Synthetic datasets of 100, 1,000, and 10,000 patients were generated. Validation followed a three-domain framework: (1) fidelity, assessed by Kolmogorov-Smirnov tests and Jensen-Shannon divergence; (2) utility, assessed by train-on-synthetic, test-on-real (TSTR) methodology; and (3) privacy, assessed by nearest-neighbor distance ratio (NNDR), membership inference attack, and k-anonymity proxy. ResultsAll three validation gates passed. Fidelity: mean KS p-value 0.52 (threshold >0.05). Privacy: NNDR >1.0 in 98.9% of synthetic records; membership inference AUROC 0.57. Utility: 12-month Oswestry Disability Index prediction yielded Pearson r = 0.29, consistent with expected attenuation at N = 125. A SHA-256 cryptographic hash of each certified dataset was anchored on the Solana blockchain for immutable provenance. ConclusionsA validated, blockchain-anchored synthetic data pipeline for spine surgery registries is technically feasible and meets current publication-standard criteria for fidelity and privacy. Utility metrics scale with registry size, creating a direct incentive for multicenter data contribution. This framework provides a reproducible methodology for synthetic data certification in spine surgery research, and establishes certified synthetic datasets as a privacy-native substrate for expert-annotation pipelines -- as demonstrated in the companion Spine Reviews study.

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The single item physical activity (SIPA) measure: a major role for global surveillance and community program evaluation

Bauman, A.; Owen, K.; Messing, S.; Macdonald, H.; Nettlefold, L.; Richards, J.; Vandelanotte, C.; Chen, I.-H.; Cullen, B.; van Buskirk, J.; van Itallie, A.; Coletta, G.; O'Halloran, P.; Randle, E.; Nicholson, M.; Staley, K.; McKay, H. A.

2026-04-16 public and global health 10.64898/2026.04.14.26350895 medRxiv
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Military aviation training noise remains understudied despite its widespread impacts across urban, rural, and wilderness areas. The predominance of low-frequency noise and repetitive training can create pervasive noise pollution, yet past research often fails to capture the full range of health and quality-of-life effects. This study analyzed two complaint datasets related to Whidbey Island Naval Air Station noise: U.S. Navy records (2017-2020) and Quiet Skies Over San Juan County data (2021-2023). We analyzed and mapped sentiment intensity from noise complaints relative to modeled annual noise exposure, developed a typology to classify impacts, and modeled the environmental and operational factors influencing complaints. Findings revealed widespread negative sentiment and anger, often beyond the bounds of estimated noise contours, suggesting that annual cumulative noise models inadequately estimate community impacts. Complaints consistently highlighted sleep disturbance, hearing and health concerns, and compromised home environments due to shaking, vibration, and disruption of daily life. Residents also reported significant social, recreational, and work disruptions, along with feelings of fear, helplessness, and concern for children's well-being. The number of complaints were strongly associated with training schedules, with late-night sessions being the strongest predictor. A delayed response pattern suggests residents reach a frustration threshold before filing complaints. Overall, our findings demonstrate persistent negative sentiment and diverse impacts from military aviation noise. Results highlight the need for improved noise metrics, modeling and operational adjustments to mitigate the most disruptive effects.

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Democratizing Scientific Publishing: A Local, Multi-Agent LLM Framework for Objective Manuscript Editing

Bhansali, R.; Gorenshtein, A.; Westover, B.; Goldenholz, D. M.

2026-04-17 health informatics 10.64898/2026.04.13.26350761 medRxiv
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Manuscript preparation is a critical bottleneck in scientific publishing, yet existing AI writing tools require cloud transmission of sensitive content, creating data-confidentiality barriers for clinical researchers. We introduce the Paper Analysis Tool (PAT), a free, multi-agent framework that deploys 31 specialized agents powered by small language models (SLMs) to audit manuscripts across multiple quality dimensions without external data transmission. Applied to three published clinical neurological papers, PAT generated 540 evaluable suggestions. Validation by two expert reviewers (R.B., A.G.) confirmed 391 actionable, high-value revisions (90% agreement), achieving a 72.4% overall usefulness accuracy spanning methodological, statistical, and visual domains. Furthermore, deterministic re-evaluation of 126 agent-suggested rewrite pairs using Phase 0 metrics confirmed text improvement: total word count decreased by 25%, passive voice prevalence dropped sharply from 35% to 5%, average sentence length decreased by 24%, long-sentence fraction fell by 67%, and the Flesch-Kincaid grade improved by 17% . Our validation confirms that systematic, agent-driven pre-submission review drives measurable improvements, successfully converting manuscript optimization from an opaque, manual endeavor into a transparent and rigorous scientific process. Manuscript preparation is a critical bottleneck in scientific publishing, yet existing AI writing tools require cloud transmission of sensitive content, creating data-confidentiality barriers for clinical researchers. We introduce the Paper Analysis Tool (PAT), a free, multi-agent framework that deploys 31 specialized agents powered by small language models (SLMs) to audit manuscripts across multiple quality dimensions without external data transmission. Applied to three published clinical neurological papers, PAT generated 540 evaluable suggestions. Independent validation by two expert reviewers (R.B., A.G.) confirmed 391 actionable, high-value revisions (90% agreement), achieving a 72.4% overall usefulness accuracy spanning methodological, statistical, and visual domains. Furthermore, deterministic re-evaluation of 126 suggested Phase 0 rewrite pairs confirmed text improvement: total word count decreased by 25%, passive voice prevalence dropped sharply from 35% to 5%, average sentence length decreased by 24%, and long-sentence fraction fell by 67%, and the Flesch-Kincaid grade improved modestly. Our validation confirms that systematic, agent-driven pre-submission review drives measurable improvements, successfully converting manuscript optimization from an opaque, manual endeavor into a transparent and rigorous scientific process.

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The association between household use of unclean cooking fuels and depression symptoms among older adults in India: a cross-sectional study.

Mohsini, K.; Gore-Langton, G. R.; Rathod, S. D.; Mansfield, K. E.; Warren-Gash, C.

2026-04-14 public and global health 10.64898/2026.04.13.26350749 medRxiv
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Aims Indoor air pollution resulting from combustion of unclean cooking fuels has been linked to adverse health outcomes, but evidence regarding its association with mental health in low- and middle-income countries remains limited. We investigated the association between household use of unclean cooking fuels, as a proxy for indoor air pollution, and depression symptoms among adults aged 45 years and older in India, and assessed effect modification by age, sex, caste, and rural/urban residence. Methods We conducted a cross-sectional analysis of the first wave (2017-2018) of data from the Longitudinal Aging Study in India (LASI), a nationally representative survey of adults aged [&ge;]45 years. Cooking fuel type was classified as clean or unclean, and depression symptoms were assessed using the 10-item Centre for Epidemiologic Studies Depression (CES-D-10) scale. We used logistic regression to estimate odds ratios for depression symptoms, and linear regression to compare mean CES-D-10 scores by cooking fuel type, adjusting for sociodemographic and housing characteristics. Results We included 62,650 respondents. Median age was 57 years (IQR: 50-65), 46.7% were women, 47.6% reported using unclean cooking fuels, and 27.6% screened positive on the CES-D-10. After adjusting for sociodemographic and housing characteristics, use of unclean cooking fuels was associated with higher odds of screening positive on the CES-D-10 (aOR: 1.08; 95% CI: 1.02, 1.15), and higher mean CES-D-10 scores (adjusted mean difference: 0.34; 95% CI: 0.24, 0.44). The association was more pronounced among individuals living in urban areas (aOR: 1.36; 95% CI: 1.21, 1.53). Conclusion Use of unclean cooking fuels was associated with depression symptoms among older adults in India, and especially among those living in urban areas.

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A clinicoradiological model for preoperative prediction of lateral lymph node metastasis in rectal cancer

Shen, Q.; Wang, G.; Fu, M.; Yao, K.; Yang, Y.; Zeng, Q.; Guo, Y.

2026-04-15 gastroenterology 10.64898/2026.04.13.26350816 medRxiv
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Background: Lateral lymph node metastasis (LLNM) is associated with poor prognosis in patients with rectal cancer and may influence the indication for lateral lymph node dissection. Accurate preoperative identification of LLNM remains challenging. This study aimed to develop and internally validate a clinicoradiological model for preoperative prediction of LLNM in rectal cancer. Methods A retrospective cohort of 64 patients undergoing lateral lymph node dissection (LLND) for rectal cancer was analysed; 21 (32.8%) had pathological lateral lymph node metastasis (LLNM). A prespecified preoperative clinicoradiological model was fitted using penalised logistic regression with L2 regularisation (ridge), incorporating MRI-measured lateral lymph node short-axis diameter (LLN-SAD), dichotomised clinical T stage (T3-4 vs T1-2), dichotomised clinical N stage (N+ vs N0), and log(CA19-9+1). Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), calibration analysis, and bootstrap internal validation. Results The model showed good discrimination (AUC 0.914), with an optimism-corrected AUC of 0.887 on bootstrap validation. Calibration remained acceptable after optimism correction (calibration intercept -0.127; slope 1.045). Decision curve analysis suggested net benefit across clinically relevant threshold probabilities, particularly between 0.10 and 0.30. The model was implemented as a web-based calculator to facilitate clinical use. Conclusion This clinicoradiological model showed good discrimination, acceptable calibration, and potential clinical utility for preoperative assessment of LLNM risk in rectal cancer. It may assist individualized risk stratification and treatment planning, although external validation is required before routine clinical implementation.

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Years Lived without Chronic Diseases after Statutory Retirement - A Register Linkage Follow-up Study in Finland 2000-2021

Pietilainen, O.; Salonsalmi, A.; Rahkonen, O.; Lahelma, E.; Lallukka, T.

2026-04-13 public and global health 10.64898/2026.04.12.26348889 medRxiv
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Objectives: Longer lifespans lead to longer time on retirement, despite the efforts to raise the retirement age. Therefore, it is important to study how the retirement years can be spent without diseases. This study examined socioeconomic and sociodemographic differences in healthy years spent on retirement. Methods: We followed a cohort of retired Finnish municipal employees (N=4231, average follow-up 15.4 years) on national administrative registers for major chronic diseases: cancer, coronary heart disease, cerebrovascular disease, diabetes, asthma or chronic obstructive pulmonary disease, dementia, mental disorders, and alcohol-related disorders. Median healthy years on retirement and age at first occurrence of illness (ICD-10 and ATC-based) in each combination of sex, occupational class, and age of retirement were predicted using Royston-Parmar models. Prevalence rates for each diagnostic group were calculated. Results: Most healthy years on retirement were spent by women having worked in semi-professional jobs who retired at age 60-62 (median predicted healthy years 11.6, 95% CI 10.4-12.7). The least healthy years on retirement were spent by men having worked in routine non-manual jobs who retired after age 62 (median predicted healthy years 6.5, 95% CI 4.4-9.5). Diabetes was slightly more common among lower occupational class women, and dementia among manual working women having retired at age 60-62. Discussion: Healthy years on retirement are not enjoyed equally by women and men and those who retire early or later. Policies aiming to increase the retirement age should consider the effects of these gaps on retirees and the equitability of those effects.

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Assessment of Bedside-Adaptable Models to Predict Molecular Sepsis Subtypes in a Resource-Limited Setting: A Multicenter Analysis from Uganda

Bakamutumaho, B.; Lutwama, J. J.; Owor, N.; Lu, X.; Eliku, P. J.; Namulondo, J.; Kayiwa, J.; Ross, J. E.; Nsereko, C.; Nsubuga, J. B.; Shinyale, J.; Asasira, I.; Kiyingi, T.; Reynolds, S. J.; Nie, K.; Kim-Schulze, S.; Cummings, M. J.

2026-04-11 public and global health 10.64898/2026.04.08.26350396 medRxiv
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ObjectiveBiologically defined sepsis subtypes have been identified in low- and middle-income countries (LMICs), but limited access to molecular diagnostics challenges broader evaluation and implementation in resource-limited settings. We assessed whether models including bedside clinical and rapid microbiologic data could accurately stratify Ugandan adults with sepsis by molecular subtype. DesignSecondary analysis of two prospective observational sepsis cohorts, testing bedside-adaptable classifier models against transcriptomic and proteomic subtype assignments. SettingEntebbe Regional Referral Hospital (urban) and Tororo General Hospital (rural), Uganda. PatientsAdults ([&ge;]18 years) hospitalized with sepsis, with available transcriptomic (N=355) and/or proteomic (N=495) profiling enabling subtype assignment. InterventionsNone. Measurements and Main ResultsUsing data from two prospective cohorts (RESERVE-U-2-TOR and RESERVE-U-1-EBB), we evaluated bedside-adaptable models against Uganda-derived molecular sepsis subtypes, and, secondarily, against molecular subtypes and axes derived in high-income countries. In RESERVE-U-2-TOR, clinical models including demographics and bedside physiological variables demonstrated moderate discrimination for transcriptomic and proteomic subtype assignment (AUROC 0.75 [95% CI, 0.69-0.81] and 0.73 [0.66-0.80], respectively) with strong calibration (Integrated Calibration Index [Eavg] [&le;]0.015 for both models). Adding rapid diagnostic results for HIV, malaria, and tuberculosis produced similar performance (AUROC 0.76 and 0.74; Eavg [&le;]0.016). In RESERVE-U-1-EBB, discrimination for clinical and clinico-microbiological models was more variable (AUROC range 0.63-0.75) while calibration remained acceptable (Eavg [&le;]0.053). Performance was similar when models were evaluated against molecular sepsis frameworks derived in high-income countries, with acceptable calibration and moderate discrimination. ConclusionsBedside-adaptable clinical models, with or without rapid microbiologic testing, demonstrated acceptable calibration but only modest discrimination for molecular sepsis subtype assignment in Uganda. Expanding laboratory capacity and access to scalable, low-cost molecular biomarker assays will be necessary to advance precision sepsis care in LMIC settings. Key PointsO_ST_ABSQuestionC_ST_ABSAmong adults hospitalized with sepsis in a resource-limited setting, can bedside clinical variables, alone or combined with rapid pathogen diagnostics, accurately stratify molecular sepsis subtype assignments? FindingsIn two prospective Ugandan sepsis cohorts, bedside clinical and clinico-microbiologic models showed robust calibration but only modest discrimination for classifying Uganda-derived transcriptomic and proteomic subtypes. Models also achieved moderate performance for stratifying high-income-country-derived transcriptomic subtypes and immune dysfunction axes, suggesting bedside variables reflect illness severity but incompletely capture underlying molecular signatures. MeaningBedside-adaptable models can support reasonably calibrated risk estimation for molecular sepsis stratification in resource-limited settings but lack sufficient discriminatory power to serve as stand-alone tools. These findings support efforts to improve acute-care laboratory capacity and access to scalable molecular biomarker panels, with the goal of enabling precision sepsis care in low- and middle-income countries.