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Journal of Infection and Chemotherapy

Elsevier BV

Preprints posted in the last 7 days, ranked by how well they match Journal of Infection and Chemotherapy's content profile, based on 16 papers previously published here. The average preprint has a 0.01% match score for this journal, so anything above that is already an above-average fit.

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Greater intergroup bias in vaccination attitudes among physicians than the general public

Murakami, M.; Ohtake, F.

2026-04-25 infectious diseases 10.64898/2026.04.23.26351641 medRxiv
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While vaccination conflicts have become apparent, physicians' attitudes toward those with differing views remain unclear. Through an online survey of 492 physicians and 5,252 members of the general public in Japan in February 2026, we investigated attitudes toward four vaccines (influenza, measles, HPV, and COVID-19). Intergroup bias was assessed as ingroup minus outgroup attitudes using a feeling thermometer. Multilevel regression examined associations with agreement group and physician status. Intergroup bias was significantly positive in both agreement and disagreement groups across all vaccine types, and was higher in the agreement group. Physicians exhibited higher intergroup bias than the general public. These findings indicate that vaccination conflict is bidirectional: physicians, often viewed as targets of hostility from vaccine-hesitant individuals, themselves exhibit greater intergroup bias toward those with opposing views. Interventions to raise physicians' awareness of their own bias, alongside communication strategies for vaccine-hesitant individuals, are needed.

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ICU admission and mortality in adult patients with influenza A/H1N1-related pneumonia in Vietnam since the 2009 H1N1 pandemic: a 10-year cohort study

Ho, M. Q.; Duong, T. B.; Nguyen, T. L. N.; Tri, N. S.; Bui, T.; Thai, T. T.; Muscatello, D. J.; Sunjaya, A. J.; Chen, S.; Nguyen, N. T.; Nguyen, T. M.; Nguyen, A. T. K.; Duong, C. M.

2026-04-20 infectious diseases 10.64898/2026.04.18.26351156 medRxiv
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The A(H1N1)pdm09 virus remains a major global health threat. This study examined the burden of ICU admission, mortality, and associated predictors among patients with A(H1N1)pdm09 pneumonia in a leading center for infectious diseases in Vietnam. Information on demographic, clinical, and laboratory characteristics, and outcomes was retrieved from medical records of adults admitted with influenza A(H1N1)pdm09 during 2009-2019. Among 729 cases, 21.7% (158/729) developed pneumonia. Among 158 pneumonia cases, 36.7% (58/158) developed moderate-to-severe acute respiratory distress syndrome (ARDS), and 15.2% (24/158) received invasive ventilation. ICU admission and mortality rates were 48.7% (77/158, 95%CI 41.1-56.5%) and 8.2% (13/158, 95%CI 4.9-13.6%), respectively. Predictors of ICU admission included being >60 years old (adjusted OR [AOR] 13.864, 95%CI 2.185-87.956, P=0.005), comorbidities (AOR 6.527, 95%CI 1.710-24.915, P=0.006), AST (AOR 1.013, 95%CI 1.001-1.025, P=0.029), and moderate-to-severe ARDS (AOR 14.027, 95%CI 4.220-46.627, P<0.001). Predictors of mortality were invasive ventilation (AOR 55.355, 95%CI 1.486-2062.375, P=0.030) and double-dose oseltamivir or combination therapy (AOR 32.625, 95%CI 1.594-667.661, P=0.024). In conclusion, mortality is not rare in A(H1N1)pdm09 infection. Monitoring of older patients and those with comorbidities, liver enzyme elevation, or moderate-to-severe ARDS is essential for the timely detection of complications requiring intensive care.

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Chinese Herbal Medicine as a complementary therapy for the management of Colorectal Cancer: Study protocol for a Delphi Expert Consensus survey

Ng, C. Y.; Liu, M.; Ai, D.; Yao, L.; Yang, M.; Zhong, L. L.

2026-04-22 oncology 10.64898/2026.04.21.26350990 medRxiv
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IntroductionColorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality worldwide, despite advances in conventional oncological therapies. In recent years, various studies have made advances in integrative oncology, such as investigating the use of Chinese Herbal Medicine (CHM) as a complementary therapy alongside conventional oncological therapies to alleviate treatment-related adverse effects, improve quality of life, and potentially enhance therapeutic outcomes. Despite this, clinical practice in this area remains highly heterogeneous, with limited standardized guidelines on key areas of concern such as (1) optimal intervention, (2) recommended stage and duration of intervention, (3) safety considerations, and (4) possible herb-drug interactions. Hence, this study aims to establish expert consensus on the usage of CHM as a complementary therapy in the management of CRC, to support safe, consistent, and evidence-informed clinical practice. Methods and AnalysisWe will employ a modified Delphi technique to achieve consensus amongst a panel of international experts in various fields related to integrative oncology. Prior to the study, a list of questionnaire items was developed based on a systematic review of existing clinical practice guidelines on CRC. An international panel will be invited based on established international profile in integrative oncology research and clinical practice, and by peer referral. Two rounds of Delphi will be conducted using anonymous online questionnaires. Consensus will be considered reached if at least 50% of the panel strongly agree/disagree that an item should be included or excluded while strong consensus will be set at 76%. Items which achieve strong consensus after Round 1 will be removed, before being sent out for Round 2 with a summary of Round 1 responses for a final consensus. Ethics and DisseminationEthics approval has been obtained from the Institutional Review Board of Nanyang Technological University (IRB-2025-1222). Our findings will be disseminated through peer-reviewed publications and conference presentations. Strengths and limitations of this studyO_LIThis study will develop an expert consensus which aims to guide future integration of Chinese Herbal Medicine (CHM) as a complementary therapy into colorectal cancer (CRC) management. C_LIO_LIKey concerns in areas such as determining the (1) optimal intervention, (2) recommended stage and duration of intervention, (3) safety considerations, and (4) possible herb-drug interactions, thereby laying the groundwork for potential future incorporation of CHM into CRC treatment protocols alongside conventional oncology approaches has been identified, thus limiting implementation in clinical practice. C_LIO_LIDesigning a study e-guide, followed by the consensus rounds study online will facilitate participants responses and the dissemination of information from previous rounds. C_LI

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Influenza vaccine effectiveness against influenza-associated hospitalizations and emergency department or urgent care encounters among children and adults - United States, 2024-25 season

DeCuir, J.; Reeves, E. L.; Weber, Z. A.; Yang, D.-H.; Irving, S. A.; Tartof, S. Y.; Klein, N. P.; Grannis, S. J.; Ong, T. C.; Ball, S. W.; DeSilva, M. B.; Dascomb, K.; Naleway, A. L.; Koppolu, P.; Salas, S. B.; Sy, L. S.; Lewin, B.; Contreras, R.; Zerbo, O.; Hansen, J. R.; Block, L.; Jacobson, K. B.; Dixon, B. E.; Rogerson, C.; Duszynski, T.; Fadel, W. F.; Barron, M. A.; Mayer, D.; Chavez, C.; Yates, A.; Kirshner, L.; McEvoy, C. E.; Akinsete, O. O.; Essien, I. J.; Sheffield, T.; Bride, D.; Arndorfer, J.; Van Otterloo, J.; Natarajan, K.; Ray, C. S.; Payne, A. B.; Adams, K.; Flannery, B.; Garg,

2026-04-24 public and global health 10.64898/2026.04.22.26350853 medRxiv
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Background: The 2024-25 influenza season was the most severe in the United States (US) since 2017-18, with co-circulation of both influenza A virus subtypes (H1N1 and H3N2). Influenza vaccine effectiveness (VE) has varied by season, setting, and patient characteristics. Methods: Using electronic healthcare encounter data from eight US states, we evaluated influenza vaccine effectiveness (VE) against influenza-associated hospitalizations and emergency department or urgent care (ED/UC) encounters from October 2024-April 2025 among children aged 6 months-17 years and adults aged 18+ years. Using a test-negative, case-control design, we compared the odds of influenza vaccination between acute respiratory illness (ARI) encounters with a positive (cases) versus negative (controls) test for influenza by molecular assay, adjusting for confounders. Results: Analyses included 108,618 encounters (5,764 hospitalizations and 102,854 ED/UC encounters) among children and 309,483 encounters (76,072 hospitalizations and 233,411 ED/UC encounters) among adults. Among children across care settings, 17.0% (6,097/35,765) of cases versus 29.4% (21,449/72,853) of controls were vaccinated. Among adults, 28.2% (21,832/77,477) of cases versus 44.2% (102,560/232,006) of controls were vaccinated. VE was 51% (95% confidence interval [95% CI]: 41-60%) against influenza-associated hospitalizations and 54% (95% CI: 52-55%) against influenza-associated ED/UC encounters among children. VE was 43% (95% CI: 41-46%) against influenza-associated hospitalizations and 49% (95% CI: 47-50%) against influenza-associated ED/UC encounters among adults. Conclusions: Influenza vaccination provided protection against influenza-associated hospitalizations and ED/UC encounters among children and adults in the US during the severe 2024-25 influenza season. These findings support influenza vaccination as an important tool to reduce influenza-associated disease.

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Identifying SARS-CoV-2 Lineages that Share the Same Relative Effective Reproduction Numbers

Musonda, R.; Ito, K.; Omori, R.; Ito, K.

2026-04-24 infectious diseases 10.64898/2026.04.22.26351531 medRxiv
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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continuously evolved since its emergence in the human population in 2019. As of 1st August 2025, more than 1,700 Omicron subvariants have been designated by the Pango nomenclature system. The Pango nomenclature system designates a new lineage based on genetic and epidemiological information of SARS-CoV-2 strains. However, there is a possibility that strains that have similar genetic backgrounds and the same phenotype are given different Pango lineage names. In this paper, we propose a new algorithm, called FindPart-w, which can identify groups of viral lineages that share the same relative effective reproduction numbers. We introduced a new lineage replacement model, called the constrained RelRe model, which constrains groups of lineages to have the same relative effective reproduction numbers. The FindPart-w algorithm searches the equality constraints that minimise the Akaike Information Criterion of constrained RelRe models. Using hypothetical observation count data created by simulation, we found that the FindPart-w algorithm can identify groups of lineages having the same relative effective reproduction number in a practical computational time. Applying FindPart-w to actual real-world data of time-stamped lineage counts from the United States, we found that the Pango lineage nomenclature system may have given different lineage names to SARS-CoV-2 strains even if they have the same relative effective reproduction number and similar genetic backgrounds. In conclusion, this study showed that viruses that had the same relative effective reproduction number were identifiable from temporal count data of viral sequences. These findings will contribute to the future development of lineage designation systems that consider both genetic backgrounds and transmissibilities of lineages.

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Epidemiology and Predictors of Fluoroquinolone Resistance in ESBL-Producing Escherichia coli: Implications for Empirical Therapy in Mexico

Gallardo Mejia, A.; Almeida, J.

2026-04-22 infectious diseases 10.64898/2026.04.21.26351439 medRxiv
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Urinary tract infections (UTIs) are among the most common infectious diseases worldwide, with Escherichia coli being the predominant uropathogen. The increasing prevalence of extended-spectrum beta-lactamase (ESBL)-producing strains and their association with fluoroquinolone resistance pose a significant challenge to empirical therapy, particularly in community settings. The aim of this study was to determine the epidemiology and predictive factors associated with ESBL-producing E. coli and its concomitant fluoroquinolone resistance in community-acquired clinical isolates. A retrospective cross-sectional study was conducted analyzing 244 clinical E. coli isolates. Demographic and microbiological data were collected, including age, sex, sample type, and antibiotic susceptibility. Associations between variables and ESBL production were assessed using Pearsons chi-squared test, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Of the isolates, 165 (68%) were ESBL-producing. A significant association was observed between age group and ESBL production (p < 0.001), with the highest frequency in the 20-39 age group. Most ESBL-positive isolates were obtained from women (73%), although odds ratio (OR) analysis suggested a non-significant trend toward a higher probability in men (OR = 1.29; 95% CI: 0.72-2.31). High rates of fluoroquinolone resistance were identified among the ESBL-producing isolates, with 30% resistance to levofloxacin and 35% to ciprofloxacin (p < 0.001). Urine samples showed the highest concentration of ESBL-positive isolates, with a significant association between sample type and resistance (p < 0.001). The high prevalence of ESBL-producing E. coli and its concomitant resistance to fluoroquinolones highlight a critical challenge for the empirical treatment of urinary tract infections in Mexico, underscoring the need to strengthen antimicrobial use management and local surveillance strategies.

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Clinical outcomes and prognostic factors of low-grade serous ovarian cancer: A single-centre observational retrospective study

Prakash, R.; Khan, A.; Shahbazian, L.; Arthur, A.; Levin, G.; Gilbert, L.; Telleria, C. M.

2026-04-20 oncology 10.64898/2026.04.17.26351112 medRxiv
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ObjectiveThe purpose of the present study is to describe the survival outcomes of patients with low-grade serous ovarian cancer (LGSOC) in the post-operative setting from a tertiary gynecologic oncology referral centre in Quebec, including evaluation of patient characteristics, clinical outcomes and prognostic factors. MethodsThe study included 25 patients: 1) with a post-surgical histopathologic diagnosis of a low-grade serous tumour of the ovary, 2) underwent primary cytoreductive surgery prior to adjuvant therapy, and 3) for whom clinical data was available. Clinical and demographic features were characterized by descriptive statistics. Clinical endpoints of progression-free survival (PFS) and overall survival (OS) were assessed, utilizing the Kaplan-Meier method for estimating survival probabilities. ResultsThe median age of this cohort was 61 years (range, 26-81). Median OS was 140.6 months in patients with no residual disease (R0), 71 months in patients with microscopic residual disease (R1), and 27.7 months in patients with macroscopic residual disease (R2) (p=.001). Residual disease was also found to significantly impact PFS (p=.008). Administration of adjuvant chemotherapy failed to improve survival outcomes altogether (PFS, p = .270; OS, p = .300). ConclusionsThis study supports the shifting consensus that optimal cytoreductive surgery, where feasible, is paramount for successful treatment of LGSOC. Furthermore, treatment with adjuvant chemotherapy may lead to worse survival outcomes.

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Genetic diversity and antimicrobial susceptibility pattern of Shiga toxin-producing Escherichia coli and Campylobacter spp. isolated from healthy goats in southern Thailand

Wiriyaprom, R.; Ngasaman, R.; Kaewnoi, D.; Prachantasena, S.

2026-04-20 microbiology 10.64898/2026.04.18.719346 medRxiv
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Foodborne illness is a significant public health concern worldwide. Shiga toxin-producing Escherichia coli and Campylobacter species are recognized as important zoonotic bacterial pathogens contributing to human infections through the food chain, particularly via foods of animal origin. Although goat meat is in high demand in the southern region of Thailand, studies on foodborne pathogens in this livestock species remain limited. The current study aimed to (i) determine the antimicrobial susceptibility of Campylobacter spp. and STEC isolated from goats, and (ii) analyze the genetic relationships among Campylobacter spp. And E. coli O157 isolates obtained from different sources. Campylobacter jejuni and C. coli isolates were characterized based on sequences of seven housekeeping genes using the Achtman multilocus sequence typing scheme. For E. coli O157:H7, core genome multilocus sequence typing analysis was performed using whole-genome sequencing data. Genetic diversity was observed among C. jejuni, whereas a clonal population structure was detected in C. coli and E. coli O157:H7. Overlapping genetic characteristics were observed between C. jejuni isolates from goats and those previously reported in livestock and humans in Thailand. Among Campylobacter species, resistance to fluoroquinolones, including ciprofloxacin and nalidixic acid, was observed, whereas resistance to fosfomycin was most frequently detected in Shiga toxin-producing E. coli. Tetracycline-resistant isolates were identified in both Campylobacter species and Shiga toxin-producing E. coli at moderate levels. A multidrug-resistant pattern was observed only in C. coli, whereas no multidrug-resistant C. jejuni or Shiga toxin-producing E. coli isolates were detected. These findings indicate that healthy goats may serve as potential reservoirs of zoonotic pathogens and antimicrobial resistance in southern Thailand, where goat meat is frequently consumed.

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Tongue swab Xpert MTB/RIF Ultra testing for tuberculosis in adolescents: a cross-sectional study of diagnostic accuracy and acceptability

MacLean, E. L.; Ma, T. T.; Chuong, L. H.; Minh, K. H.; Hoddinott, G.; Pham, Y. N.; Tiep, H. T.; Nguyen, T.-A.; Fox, G.; Nguyen, N. T.

2026-04-25 infectious diseases 10.64898/2026.04.17.26351119 medRxiv
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Introduction Improved diagnostics are needed for people at risk of tuberculosis, especially adolescents. Tongue swab (TS) molecular testing has emerged as a promising strategy for tuberculosis diagnosis. We evaluated diagnostic accuracy and acceptability of Xpert MTB/RIF Ultra (Xpert) using TS samples for tuberculosis detection among adolescents. Methods We conducted a cross-sectional diagnostic accuracy study with consecutive recruitment in Vietnam. Adolescents aged 10-19 who were recommended to undergo investigation for tuberculosis and had not received tuberculosis treatment in the past years were eligible. Participants provided TS and sputum samples and completed a structured survey regarding sampling experiences. TS was tested on Xpert, with sputum tested on Xpert and liquid culture. We utilised a composite reference standard of a positive result on sputum Xpert or sputum culture to define disease status. Sensitivity, specificity, and diagnostic yield were calculated for TS Xpert. Results From July to December 2025, we enrolled 225 adolescents from Can Tho and An Giang provinces in southern Vietnam. Fewer than half (96/225, 43%) the participants exhibited a tuberculosis -like symptom, and the majority (157/225, 70%) were close contacts of a person recently diagnosed with tuberculosis. TS were collected from all adolescents, while 116 (52%) could provide mucopurulent sputum. Tuberculosis prevalence was relatively low (12/225, 5.3%). TS Xpert sensitivity (90% CI) and specificity (90% CI) were 58.3% (35.6, 78.0) and 99.5% (97.9, 99.9), respectively. Diagnostic yield among all diagnosed was 58.3% (7/12). TS sampling was highly acceptable to adolescents; the short time and simplicity of collecting TS were considered favourably. Conclusions The sensitivity and diagnostic yield of TS Xpert was relatively low among adolescents recommended for tuberculosis investigation, which includes asymptomatic individuals who may not provide high quality sputum. Specificity was excellent, and everyone could provide a TS. TS high acceptability indicates it remains a promising sample for diagnostic algorithms.

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Multimodal prediction of visual improvement in diabetic macular edema using real-world electronic health records and optical coherence tomography images

Sun, S.; Cai, C. X.; Fan, R.; You, S.; Tran, D.; Rao, P. K.; Suchard, M. A.; Wang, Y.; Lee, C. S.; Lee, A. Y.; Zhang, L.

2026-04-24 health informatics 10.64898/2026.04.23.26351616 medRxiv
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Multimodal learning has the potential to improve clinical prediction by integrating complementary data sources, but the incremental value of imaging beyond structured electronic health record (EHR) data remains unclear in real-world settings. We developed a multimodal survival modeling framework integrating optical coherence tomography (OCT) and EHR data to predict time to visual improvement in patients with diabetic macular edema (DME), and evaluated how different ophthalmic foundation model representations contribute to prognostic performance. In a retrospective cohort of 973 patients (1,450 eyes) receiving anti-vascular endothelial growth factor therapy, we compared multimodal models combining 22,227 EHR variables with 196,402 OCT images, with OCT embeddings derived from three ophthalmic foundation models (RETFound, EyeCLIP, and VisionFM). The EHR-only model showed minimal prognostic discrimination (C-index 0.50 [95% CI, 0.45-0.55]). Incorporating OCT improved performance, with the magnitude of improvement depending on the representation. EHR+RETFound achieved the strongest performance (C-index 0.59 [0.54-0.65]), followed by EHR+EyeCLIP (0.57 [0.52-0.62]) and EHR+VisionFM (0.56 [0.51-0.61]). Multimodal models, particularly EHR+RETFound, demonstrated improved risk stratification with clearer separation of Kaplan-Meier curves. Partial information decomposition revealed that prognostic information was dominated by modality-specific contributions, with OCT and EHR providing largely distinct signals and minimal shared information. The magnitude of OCT-specific contribution varied across foundation models and aligned with observed performance differences. These findings indicate that OCT provides complementary prognostic value beyond structured clinical data, but gains are modest and depend strongly on representation choice. Our results highlight both the promise of multimodal modeling for personalized prognosis and the need for rigorous, context-specific evaluation of foundation models in real-world clinical settings.

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From GWAS to drug: A framework for drug candidate prioritisation using a gene expression signature matching approach

Chauquet, S.; Jiang, J.-C.; Barker, L. F.; Hunter, Z. L.; Singh, G.; Wray, N. R.; McRae, A. F.; Shah, S.

2026-04-24 genetic and genomic medicine 10.64898/2026.04.22.26349470 medRxiv
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Drug targets supported by human genetic evidence have significantly higher approval rates, making genome-wide association studies a valuable resource for drug candidate prioritisation. Transcriptome-wide association study signature-matching is an emerging in silico approach that integrates GWAS data with expression quantitative trait loci to generate a disease gene expression signature, which is then compared against drug perturbation databases such as the Connectivity Map. Despite recent adoption, there is no consensus on optimal methodology. Here, we systematically benchmark key parameters, including TWAS method, eQTL tissue model, similarity metric, gene set size, and CMap cell line, using LDL cholesterol, familial combined hyperlipidemia, and asthma as proof-of-concept traits. We demonstrate that while TWAS signature-matching can successfully prioritise known first-line treatments, performance is highly sensitive to parameter choice; for instance, the selection of the cell line used for drug signatures alone can dramatically alter drug prioritisation. Based on these findings, we propose a best-practice framework for robust, genetically-informed drug prioritisation using TWAS signature-matching.

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Comprehensive Exome Sequencing in Swedish Patients with Spontaneous Coronary Artery Dissection

Gunnarsson, C.; Ellegard, R.; Ahsberg, J.; huda, s.; Andersson, J.; Dworeck, C. F.; Glaser, N.; Erlinge, D.; Loghman, H.; Johnston, N.; Mannila, M.; Pagonis, C.; Ravn-Fischer, A.; Rydberg, E.; Welen Schef, K.; Tornvall, P.; Sederholm Lawesson, S.; Swahn, E. E.

2026-04-24 genetic and genomic medicine 10.64898/2026.04.22.26351535 medRxiv
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Abstract Background Spontaneous coronary artery dissection (SCAD) is a well-recognised cause of acute coronary syndrome particularly among women without conventional cardiovascular risk factors. Increasing evidence indicates a genetic contribution; however, the underlying genetic architecture of SCAD remains insufficiently understood. Objective The aim of this study was to assess the prevalence of rare variants in previously reported SCAD associated genes and to explore the potential presence of novel genetic alterations in well-characterised Swedish patients with SCAD. Methods The study comprised 201 patients enrolled in SweSCAD, a national project examining the clinical characteristics, aetiology, and outcomes of SCAD. All individuals had a confirmed diagnosis based on invasive coronary angiography. Comprehensive exome sequencing was performed to identify rare variants contributing to disease susceptibility. Results Genetic variants that have been associated with SCAD according to current clinical genetics practice for variant reporting were identified in approximately 4 % of patients. In addition, rare potentially relevant variants were detected in almost 60 % of patients in genes associated with vascular integrity and vascular remodelling. Conclusion This study supports SCAD as a genetically complex arteriopathy, driven by rare high?impact variants together with broader polygenic susceptibility. Variants in collagen, vascular extracellular matrix, and oestrogen?responsive pathways provide biologically plausible links to female?predominant disease. Although the diagnostic yield of clearly actionable variants is modest, these findings support broader genomic evaluation beyond overt syndromic presentations and highlight the need for larger integrative genomic and functional studies to refine risk stratification and management.

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Histology-Derived Signatures Predict Recurrence Risk and Chemotherapy Benefit in Randomized Trials of Early Breast Cancer

Howard, F. M.; Li, A.; Kochanny, S.; Sullivan, M.; Flores, E. M.; Dolezal, J.; Khramtsova, G.; Hassan, S.; Medenwald, R.; Saha, P.; Fan, C.; McCart, L.; Watson, M.; Teras, L. R.; Bodelon, C.; Patel, A. V.; Symmans, W. F.; Partridge, A.; Carey, L.; Olopade, O. I.; Stover, D.; Perou, C.; Yao, K.; Pearson, A. T.; Huo, D.

2026-04-24 oncology 10.64898/2026.04.23.26351499 medRxiv
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Purpose: To test whether histology-derived gene-expression signatures from routine hematoxylin and eosin slides are prognostic for recurrence and predictive of chemotherapy benefit in early breast cancer. Methods: We conducted a multi-cohort study including CALGB 9344 (anthracycline +/- paclitaxel), CALGB 9741 (standard vs dose-dense chemotherapy), a pooled Chicago real-world cohort, and the American Cancer Society (ACS) Cancer Prevention Studies-II and -3. Whole-slide images were processed with a previously described pipeline to generate 61 histology-derived signatures per patient. The primary endpoint was distant recurrence-free interval (DRFI), except in ACS, where breast cancer-specific survival was used. Secondary endpoints include distant recurrence-free survival (DRFS) and overall survival. The most prognostic signature in CALGB 9344, selected by Harrell's C-index, was evaluated in additional cohorts. Signature-treatment interaction was assessed by likelihood-ratio tests. Multivariable Cox models incorporating age, tumor size, nodal status, estrogen/progesterone receptor status, and signature were fit in CALGB 9344 to improve risk stratification. Results: A total of 7,170 patients were included across four cohorts. The top histology-derived signature in CALGB 9344 showed strong prognostic performance for 5-year DRFI (C-index 0.63) and performed well across validation cohorts (C-index 0.60, 0.70, and 0.62 in CALGB 9741, Chicago, and ACS, respectively). The strongest predictive signal for treatment benefit was observed for DRFS. High-risk cases identified by the signature demonstrated greater benefit from taxane in CALGB 9344 (adjusted hazard ratio [aHR] 0.76 for DRFS, 95% CI 0.66-0.88; interaction p=0.028), from dose-dense chemotherapy in CALGB 9741 (aHR 0.69, 95% CI 0.56-0.85; interaction p=0.039), and differential chemotherapy benefit in the Chicago cohort (aHR 0.84, 95% CI 0.59-1.21; interaction p=0.009). Combined clinical-histology models improved risk stratification and identified low-risk groups with a 2%-10% risk of distant recurrence or breast cancer death. Conclusion: Histology-derived signatures from H&E images are broadly prognostic and, unlike clinical factors, may predict chemotherapy benefit.

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Plasma proteomics link menopause timing to brain aging and dementia risk

Wood Alexander, M.; Wood, B.; Oh, H. S.-H.; Bot, V. A.; Borger, J.; Galbiati, F.; Walker, K. A.; Resnick, S. M.; Ochs-Balcom, H. M.; Wyss-Coray, T.; Kooperberg, C.; Reiner, A. P.; Jacobs, E. G.; Rabin, J. S.; Casaletto, K. B.; Saloner, R.

2026-04-24 neurology 10.64898/2026.04.23.26351500 medRxiv
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Earlier menopause is a risk factor for several age-related diseases, including dementia. The biological pathways linking menopause timing to later-life brain aging are not understood. Leveraging large-scale plasma proteomics in postmenopausal women from the UK Biobank (N=15,012), earlier menopause was associated with upregulation of pro-inflammatory and extracellular matrix degradation pathways, plus accelerated aging across proteomic clocks of organ and cellular aging, including brain and oligodendrocyte aging. Elevated GDF15, a canonical aging marker, was the top protein correlate of earlier menopause. We observed robust replication of menopause timing proteomic shifts in the Women's Health Initiative Long Life Study (N=1,210). In UKB, proteins associated with earlier menopause, including GDF15, exhibited concordant associations with incident dementia risk and brain atrophy, cerebral small vessel disease burden, and white matter microstructural integrity. Collectively, our findings identify proteomic signatures linking ovarian aging to brain aging, providing a framework to inform interventions to reduce dementia risk.

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Impact of chlamydia and gonorrhea point-of-care testing on antibiotic prescribing in routine HIV care in rural Uganda

Abal, A.; Apako, J.; Hurberd, Y.; Flipse, J.; Bastiaens, G.; Schaftenaar, E.

2026-04-23 sexual and reproductive health 10.64898/2026.04.22.26351517 medRxiv
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Objectives: To evaluate whether on-site molecular point-of-care testing (POCT) for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) is associated with reduced antibiotic overtreatment for presumed sexually transmitted infections (STIs) among adults living with HIV in rural Uganda. Methods: We conducted a single-site quasi-experimental pre-post intervention study at Kumi Hospital, comparing syndromic management (April-August 2024) with CT/NG POCT-guided management (September 2024-January 2025). Adults living with HIV presenting with symptoms suggestive of an STI were included. Overtreatment in the pre-intervention phase was estimated by comparing antibiotic prescribing with the expected number of CT/NG infections based on positivity observed during the intervention phase. Results: A total of 404 participants were included (203 pre-intervention, 201 intervention). During the intervention phase, CT and/or NG were detected in 14 individuals (7.0%). Median test turnaround time was 95 minutes, enabling same-day treatment in 93% of positive cases. Antibiotic prescribing decreased from 99.0% to 11.4% following POCT implementation (P < 0.001), corresponding to an absolute reduction of 87.6 percentage points. Estimated overtreatment declined from 30.0% to 5.0% for NG and from 74.9% to 6.0% for CT (both P < 0.001). Conclusions: Implementation of CT/NG POCT in routine HIV care was associated with a marked reduction in antibiotic prescribing and estimated overtreatment for presumed STIs. These findings support the potential of POCT-guided, aetiology-based STI management to reduce unnecessary antimicrobial exposure in settings where syndromic management remains standard practice.

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Generalizing intensive care AI across time scales in resource-limited settings

Devadiga, A.; Singh, P.; Sankar, J.; Lodha, R.; Sethi, T.

2026-04-24 health informatics 10.64898/2026.04.23.26351588 medRxiv
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Temporal resolution of physiological monitoring in intensive care varies widely across healthcare systems. Artificial intelligence models assume a uniform and fixed frequency of sampling, thus limiting the generalizability of models, especially to resource-limited settings. Here, we propose a novel resolution-transfer task for physiological time series and ask whether models trained on high-resolution data can generalize to a low data-density setting without the need to retrain them. SafeICU, a novel longitudinal pediatric intensive care dataset spanning ten years from a tertiary care hospital in India, was used to test this hypothesis. Self-supervised transformer models were trained on 144,271 patient-hours of high-resolution physiological signals from 984 pediatric ICU stays to learn representations of heart rate, respiratory rate, oxygen saturation, and arterial blood pressure. Transfer of this model to low-resolution data established robust performance in clinically relevant lower-frequency intervals, consistently outperforming models trained directly at coarser resolutions. Further, these representations generalized across patient populations, maintaining performance when evaluated on adult intensive care cohorts from the MIMIC-III and eICU databases without retraining. In a downstream task of early shock prediction, models achieved strong discrimination in the pediatric cohort (area under the receiver operating characteristic curve (AUROC) 0.87; area under the precision-recall curve (AUPRC) 0.92) and retained stable performance across monitoring intervals from 10 to 60 minutes (AUROC 0.78-0.88). Together, these results demonstrate that physiological representations learned from high-resolution data enable time-scale-robust and transferable AI for intensive care. The publicly released SafeICU dataset, comprising longitudinal vital signs, laboratory measurements, treatment records, microbiology, and admission and discharge, provides a foundation for developing and deploying generalizable clinical AI in resource-limited settings.

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Association of sexual orientation outness and recent homophobic violence with not being on antiretroviral treatment: Analysis of a Latin American Survey in men who have sex with men living with HIV

ENCISO DURAND, J. C.; Silva-Santisteban, A. A.; Reyes-Diaz, M.; Huicho, L.; Caceres, C. F.; LAMIS-2018,

2026-04-23 public and global health 10.64898/2026.04.22.26351515 medRxiv
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Objectives: In Latin America, up-to-date information to monitor UNAIDS 95-95-95 HIV targets in key populations, such as men who have sex with men, is limited. Elsewhere, structural homophobia restricts access to ART. Conceptual frameworks suggest that intersecting forms of violence and discrimination may negatively influence HIV care outcomes through psychosocial and structural pathways, although empirical evidence remains limited. The study aimed to assess whether sexual orientation outness and recent homophobic violence are associated with not being on ART among Latin American MSM living with HIV. Methods: This cross-sectional study is a secondary analysis of data from LAMIS-2018, including 7,609 MSM aged 18+ with an HIV diagnosis [&ge;]1 year prior from 18 Latin American countries. Participants self-reported ART status, sociodemographic characteristics, homophobic violence, and sexual orientation outness. Bivariate and multivariate logistic regressions identified those factors associated with not being on ART. Results: Nine percent of MSM with HIV were not on ART, 18% reported low sexual orientation outness, and 27% experienced homophobic violence, especially in Andean and Central American countries. Not being on ART was associated with recent homophobic violence (aPR=1.25), low outness (aPR=1.22), unemployment (aPR=1.27), and residence in the Andean subregion (aPR=1.87), Mexico (aPR=1.28), or the Southern Cone (aPR=1.45) versus Brazil. Protective factors included being older (25-39: aPR=0.72; >39: aPR=0.49), living in large cities (aPR=0.72), having a stable partner (aPR=0.78), and university education (aPR=0.74). Conclusions: Recent homophobic violence and low sexual orientation outness were associated with not being on ART among MSM in Latin America. While access varies across countries, structural factors such as stigma and violence may limit engagement in care. Addressing these barriers alongside strengthening health systems may be key to improving ART uptake and advancing progress toward the 95-95-95 targets.

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The impact of cognitive processes associated with image recognition on visuo-vestibular interaction

Malara, P.; Tosin, A. G.; Castellucci, A.; Martellucci, S.; Musumano, L. B.; Mandala, M.

2026-04-23 otolaryngology 10.64898/2026.04.22.26351361 medRxiv
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An increasing number of studies highlight the role of saccadic remodulation in compensatory mechanisms following vestibular injury, and the reappearance of SHIMP saccades correlates with symptom improvement measured by the Dizziness Handicap Inventory (DHI). To investigate the influence of attentional processes and working memory on visuo-vestibular interaction, three independent but interrelated experiments were conducted. In the first two experiments, healthy subjects and patients with unilateral or bilateral vestibular deficits underwent vHIT in SHIMP mode and the Functional Head Impulse Test (fHIT), performed first separately and subsequently simultaneously. Mean latency and clustering of SHIMP saccades, together with Landolt C recognition rates, were analyzed. Differences between separate and combined protocols were assessed, and, in patients, correlated with symptom severity measured by the DHI, to determine whether the near-simultaneous execution of tasks mediated by shared parietal cortical substrates influenced performance. In the third experiment, vHIT in HIMP mode and fHIT were performed using separate and combined protocols to evaluate whether recognition-related cognitive load affected recovery saccade latency and clustering. Results suggest that visual recognition modulates visuo-vestibular interaction, supporting integrated dual-task protocols for ecological balance assessment and helping explain clinical discrepancies.

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A Cross-Cohort Validated Plasma Lipid Biomarker Assay for Early Breast Cancer Detection Using Machine Learning

Huang, T.; Koch, F. C.; Peake, D. A.; Adam, K.-P.; David, M.; Li, D.; Heffernan, K.; Lim, A.; Hurrell, J. G.; Preston, S.; Baterseh, A.; Vafaee, F.

2026-04-23 oncology 10.64898/2026.04.23.26351564 medRxiv
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Early detection of breast cancer remains essential for improving clinical outcomes, and complementary non-invasive approaches are needed to support existing screening methods, particularly for women with dense breast tissue. We have previously reported plasma lipid biomarker discovery using untargeted high-resolution liquid chromatography tandem mass spectrometry (LC-MS/MS). In this study, we performed biomarker confirmation and developed machine-learning models applied to targeted plasma lipid measurements for the non-invasive detection of early-stage breast cancer across international cohorts with independent external validation. Targeted LC-MS/MS was used to quantify candidate lipid panels in plasma samples from European discovery cohorts (n = 554) and an independent Australian cohort (n = 266) used for external validation. Data-driven feature selection identified a 15-lipid panel with strong performance in European cohorts (AUC >= 0.94). External validation prior to confidence stratification yielded 76% sensitivity, 64% specificity, and an AUC of 0.81 in the Australian validation cohort. Clinical assay development requires iterative panel and model testing to support translational feasibility and performance in the intended-use population. An analytically viable panel, excluding lipids requiring complex and costly synthesis, achieved comparable accuracy with improved assay robustness. Confidence-based analysis showed enhanced performance for predictions made with moderate to high confidence, with sensitivity up to 89% and AUC up to 0.85, suggesting that ongoing research should focus on strategies to enhance diagnostic model confidence. Importantly, model predictions were independent of breast density, tumour size, grade, subtype, and morphology, indicating biological specificity of the lipid signature. These results demonstrate that calibrated machine-learning models applied to plasma lipid biomarkers can support non-invasive breast cancer detection. Expanding training datasets to include greater diversity will further improve performance in the ongoing development of this lipid-based detection approach.

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Latent Class Analysis Identifies Pulmonary Function Trajectory Phenotypes in Lung Transplant Recipients with Chronic Allograft Dysfunction

Neely, M.; Wojdyla, D. M.; Hong, H.; Wang, P.; Anderson, M. R.; Arroyo, K.; Belperio, J.; Benvenuto, L.; Budev, M.; Combs, M.; Dhillon, G.; Hsu, J. Y.; Kalman, L.; Martinu, T.; McDyer, J.; Oyster, M.; Pandya, K.; Reynolds, J. M.; Rim, J. G.; Roe, D. W.; Shah, P. D.; Singer, J. P.; Singer, L.; Snyder, L. P.; Tsuang, W.; Weigt, S. S.; Christie, J. D.; Palmer, S. M.; Todd, J.

2026-04-23 transplantation 10.64898/2026.04.22.26351501 medRxiv
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Background: We aimed to identify data-driven FEV1 trajectory phenotypes post-chronic lung allograft dysfunction (CLAD), relate these phenotypes to patient factors and future graft loss, and develop a classification approach for prospective patients. Methods: We studied adult first lung recipients with probable CLAD from two prospective multicenter cohorts: CTOT-20 (n=206) and LTOG (n=1418). FEV1 trajectories over the first nine months post-CLAD were characterized using joint latent class mixed models, jointly modelling time-to-graft loss to account for informative censoring. Models were fit independently in both cohorts and also only among LTOG bilateral recipients. A classification and regression tree (CART) model was derived in LTOG bilateral recipients and applied to CTOT-20 bilateral recipients. Findings: Four distinct early FEV1 trajectory classes were identified in CTOT-20, with large differences in nine month graft loss (72.3%, 31.1%, 2.2%, 0%). In LTOG, similar trajectory patterns were reproduced, with an additional class demonstrating early post-CLAD FEV1 improvement. Among bilateral recipients, trajectory classes showed a clear risk gradient, including a high-risk class with 100% graft loss and a low-risk class with no early graft loss. A CART model incorporating clinical and spirometric variables demonstrated good discrimination in LTOG bilateral recipients (multiclass AUC 0.85) and consistent class assignment and trajectory patterns when applied to CTOT-20. Interpretation: We identified reproducible, clinically meaningful early post-CLAD FEV1 trajectory phenotypes with differential graft loss risk. These phenotypes and a pragmatic classification tool may support risk stratification, trial enrichment, and improved prognostication for patients and clinicians.