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Open Research Europe

F1000 Research Ltd

Preprints posted in the last 7 days, ranked by how well they match Open Research Europe's content profile, based on 14 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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Knowledge, attitudes, and practices related to ocular safety among maintenance workers in a Ghanaian university: A cross-sectional study

Kwarteng, C.; Brew, F. M.; Owusu, E.

2026-09-03 occupational and environmental health 10.64898/2026.09.01.26361906 medRxiv
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Occupational ocular injuries are a preventable yet neglected public health problem, particularly in low- and middle-income countries. Maintenance workers are exposed to diverse ocular hazards daily, yet compliance with protective measures is consistently poor. A descriptive cross-sectional study was conducted among 85 maintenance workers at the Maintenance and Essential Services Organization (MESO) of Kwame Nkrumah University of Science and Technology (KNUST), Ghana, recruited through stratified convenience sampling across seven occupational sections. A structured questionnaire assessed knowledge of ocular hazards and protective equipment, attitudes toward ocular safety, and safety practices. Data were analyzed using IBM SPSS version 26 (IBM Corp., Armonk, NY, USA); chi-square and Fishers exact tests assessed associations (p < 0.05). Participants were predominantly male (84/85, 98.8%), with a mean age of 44.5 {+/-} 10.4 years. Overall knowledge was good (mean 9.40 {+/-} 1.59 out of 11), but attitude and practice scores were average (2.78 {+/-} 0.92 and 3.27 {+/-} 0.93, respectively). Most workers correctly identified goggles and face shields as protective, but only about half recognized that ordinary sunglasses and spectacles offer inadequate protection. Although 97.6% (83/85) recognized the need for ocular protection, only 7.1% (6/85) reported consistent protective eyewear use, and fewer than half (45.9%, 39/85) had received formal ocular safety training. Routine general protective equipment use was significantly associated with ocular protection use (Fishers exact test, p = 0.011). Sand and dust particles were the leading causes of injury and only 25% (5/20) of injured workers sought formal care. Workers demonstrated good knowledge but poor attitudes and practices toward ocular safety, suggesting that knowledge alone does not translate into protective behaviour even within a relatively well-resourced institutional setting. Findings suggest that limited access to task-appropriate protective eyewear may represent an important institutional barrier. Institutional PPE supply and section-specific safety training are essential to bridge this knowledge-practice gap.

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Understanding urgent blood-donor mobilisability: a cross-sectional online survey of digitally reachable adults in Ghana

Shen, H.; Agorinya, I. A.; Ayanore, M. A.; Brede, M.; Chapman, A.; Head, M.

2026-08-31 public and global health 10.64898/2026.08.27.26361538 medRxiv
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Introduction Safe and timely blood availability remains a major global health challenge, especially in low- and middle-income countries. Digital tools may accelerate donor contact, but digital reachability alone does not ensure that people will notice, trust and act on urgent requests to support blood donation efforts. We examined factors associated with anticipated engagement in digitally coordinated urgent blood-donor mobilisation among digitally reachable adults in Ghana. Methods We conducted a cross-sectional online survey from September 2025 to January 2026 across Ghana's 16 regions. Participants were recruited via Facebook advertising and snowball sampling. Factors associated with urgent blood-donor mobilisability were assessed under four criteria: high future-donation willingness; high willingness to install a trusted donation app; high willingness to respond to a trusted urgent-request; and high practical flexibility to leave current activities. Descriptive analyses and multivariable logistic regression examined prevalence and associated factors. Results Among 1,067 participants, 577 (54.1%) met all four criteria. Future-donation willingness (91.8%), trusted-app installation willingness (83.2%) and trusted-request response willingness (82.7%) were common, whereas practical flexibility was lower (66.6%). In the adjusted model, high formal health-system trust (adjusted OR (AOR) 3.95, 95% CI 2.08-7.50), high digital-response readiness (AOR 2.26, 1.66-3.08), previous donation (AOR 1.47, 1.08-2.01), high donation knowledge (AOR 1.42, 1.03-1.97) and willingness to donate to strangers were positively associated with high mobilisability. Women (AOR 0.60, 0.43-0.83), participants reporting a work-schedule barrier (AOR 0.43, 0.29-0.66) and those travelling over 30 min to the nearest healthcare facility at night (AOR 0.66, 0.45-0.96) had lower adjusted odds. Conclusions Digital reachability and stated donation willingness may overestimate the population pool available for emergency donation. Digital blood-donor solutions should consider verifiable health-system requests, account for response readiness and current availability, and connect willing individuals with accessible collection options and transport support where needed.

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Comparative Transcriptional Responses of Human Blood to Neutron and Photon Irradiation

Salah, A.; Wollschlaeger, D.; Giesen, U.; Schmidberger, H.; Marini, F.; Zahnreich, S.

2026-09-01 biophysics 10.64898/2026.08.28.747800 medRxiv
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Despite the well-known health risks of neutron exposures, key gaps remain in understanding neutron-induced molecular responses and identifying reliable biodosimetric markers that distinguish neutrons from photon exposure. We provide the first genome-wide analysis of the human blood transcriptional response to an accelerator-derived fission-like spectrum of neutrons versus photons, evaluating transcriptomic relative biological effectiveness (RBE) and radiation quality-discriminating gene signatures. Whole blood from healthy donors was irradiated ex vivo with X-rays (140 kV, 0-4 Gy, n = 3) or neutrons (0.1-8 MeV, 0-1 Gy, n = 2), incubated for 6 h or 24 h, and processed for RNA sequencing from peripheral blood mononuclear cells (PBMCs). Neutrons were markedly more potent than X-rays at inducing differentially expressed genes (DEGs) at equal doses, showing a peak response 6 h post-irradiation followed by a decline. In contrast, X-rays caused a continuous increase in DEGs up to 24 h (neutrons vs. X-rays at 1 Gy: 1,449 vs. 121 DEGs at 6 h; 996 vs. 621 DEGs at 24 h). A universal p53-centered 34-gene signature, including FDXR, EDA2R, GADD45A, and ZMAT3, showed highly monotonic dose responses (Spearman correlation coefficient {approx} 1) across donors, radiation qualities, and timepoints. Additionally, difference-in-differences analysis identified radiation quality-discriminating genes only at 6 h, with transcriptional convergence observed by 24 h, suggesting a very narrow time window for biodosimetric differentiation. We identified a neutron-specific gene signature driven by cGAS-STING-NF-{kappa}B signaling (RELB, NFKB1, C3, MALAT1) and suppression of B-cell and myeloid identity genes (IGHD, TCL1A, CLEC7A, TLR2), defining a biologically coherent neutron quality index with distinct immunomodulatory effects. For the first time, we assessed neutron RBEs at the gene, pathway, and global transcriptomic levels in a human blood model, reporting a global transcriptomic neutron RBE of 1.30 (95% CI: 1.14-1.49) at 6 h and 1.21 (95% CI: 1.14-1.28) at 24 h, providing a valuable basis for biodosimetry in mixed-field exposure scenarios. Our findings advance the mechanistic understanding of neutron radiation responses and support the development of biodosimetric approaches for mixed-field exposure scenarios.

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Spatiotemporal Mapping of Point-of-Care Diagnostic Accessibility: A Data-Driven Pipeline for Point-of-Care Distribution Analysis in Western Uganda

Bergman, D.; Nyehangane, D.; Besancon, L.; Podkorytova, M.; Tsoumari, V.; Staikoglou, D.; Kimuli, A. N.; Richard, M. R.; Ogwok, P.; Nankoma, C.; Alfven, T.; Mwanga-Amumpaire, J.; Gaudenzi, G.

2026-09-01 public and global health 10.64898/2026.08.28.26361594 medRxiv
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All primary healthcare centers owned by the Ugandan government in the Western Region of Uganda were submitted to a questionnaire concerning current availability of POCT from the Essential diagnostic List 2 part 1a and 1b, and the African laboratory inventory done by African Society of Laboratory Medicine and AfricaCDC. The data from the questionnaire was then linked to open source geodata provided by TomTom, and population data to calculate and visualize the accessibility of captured POCT. Findings: Availability of POCT Malaria is almost 100%, HIV 68-90%, and >30% for a majority of the POCT in the EDL-2 panel. 90% of the population in Western Region live within 1 hour by car from most of the essential POCT. Figures in the complementary web-based application visualize the accessibility of POCT for Western Uganda. Diagnostic deserts are visualized. Interpretation: Access to POCT at primary health care facilities in western Uganda has expanded substantially over the past decades. The geo-mapping tool presented here could inform policy decisions on strengthening diagnostic capacity at the national, regional, and provincial level. Funding: Swedish Research Council and Infravis All supplementary materials and a preprint of this submission are available on our OSF repository https://osf.io/j7puk/.

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Patterns of Post-Traumatic Stress Disorder and Associated Cognitive Factors Among Flood Victims in Hanang District, Tanzania

Mwana, E. M.; Katalambula, L.; Emidi, B.; Nyundo, A.

2026-09-03 public and global health 10.64898/2026.09.01.26361894 medRxiv
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Background Floods are among the most devastating natural disasters worldwide and are increasingly associated with adverse mental health outcomes, particularly Post-Traumatic Stress Disorder (PTSD). In December 2023, Hanang District in northern Tanzania experienced catastrophic mud floods that resulted in extensive loss of life, destruction of property, displacement of households, and disruption of livelihoods. While emergency humanitarian responses focused primarily on physical needs, limited evidence exists regarding the long-term psychological consequences among survivors. Therefore, this study aimed to determine the patterns of PTSD manifestations and assess cognitive factors associated with PTSD symptoms among flood victims in Hanang District, Tanzania. Methods A community-based cross-sectional study was conducted among 360 flood victims one year after the disaster. PTSD symptoms were assessed using the PTSD Checklist for DSM-5 (PCL-5). Descriptive statistics summarized PTSD severity, while chi-square tests and regression analyses examined associations between socio-demographic characteristics and PTSD manifestations. Cognitive factors were assessed based on participants' exposure to traumatic experiences and perceptions of traumatic events. Results The mean PCL-5 score was 39.2 (SD = 20.6), indicating a high burden of psychological distress. Approximately 45% of respondents had severe PTSD symptoms (PCL-5 [&ge;]45), while another substantial proportion demonstrated moderate symptom severity. PTSD manifestations varied significantly by geographical location (p < 0.001), household income (p = 0.011), and marital status (p = 0.002). Age positively predicted PTSD severity ({beta} = 0.019, p = 0.001), whereas household income negatively predicted symptom severity ({beta} = -0.297, p = 0.001). Exposure to natural disasters constituted the predominant cognitive factor, with 45% directly experiencing the flood and 38.3% witnessing the event. Exposure to secondary traumatic experiences through witnessing or learning about violent events was also common. Cognitive trauma exposure demonstrated a significant association with PTSD symptoms ({chi}2, p < 0.001). Conclusion PTSD remains highly prevalent among flood survivors in Hanang district. Both direct and indirect trauma exposure significantly contributed to PTSD manifestations. Comprehensive disaster recovery programmes should integrate trauma-focused psychological services, cognitive behavioural interventions, routine PTSD screening, and community-based psychosocial support alongside socioeconomic recovery initiatives.

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Defining use cases for biomarkers and tests across tuberculosis infection, disease and treatment: An international consensus and prioritisation exercise

Wright, S.; Fama, F.; de Wilton, A.; Steward, E.; Saluzzo, F.; Sepulcri, C.; Greenan-Barrett, J.; Mar Aung, K.; Nguyen, T. M.; Engel, N.; Yerlikaya, S.; Esmail, H.; Charalambous, S.; Miller, C.; Nathavitharana, R.; Vo, L. N. Q.; Kohli, M.; Goletti, D.; Cirillo, D.; Noursadeghi, M.; Denkinger, C. M.; MacLean, E. L.-H.; Gupta, R. K.; Gupta-Wright, A.

2026-09-04 public and global health 10.64898/2026.09.01.26361598 medRxiv
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Background Translation of tuberculosis (TB) biomarker and diagnostic research into tools that improve patient and public health outcomes has been slow, partly because no internationally agreed framework exists defining the use cases that new biomarkers and tests should address. We aimed to identify, validate, and prioritise use cases for TB biomarkers and tests across Mycobacterium tuberculosis (Mtb) infection, TB disease, TB treatment, and post-TB care, through an international consensus process. Methods and Findings We conducted a scoping review of the literature, guidelines, and target product profiles (24 documents; 69 candidate use cases consolidated to 13), followed by a hybrid RAND/UCLA modified Delphi consensus process involving 185 identified interest-holders, including clinicians, researchers, diagnostic developers, industry, funders, civil society, national TB programmes, and policymakers (including WHO representatives). Interest-holders completed an online survey rating agreement with each use case, and attended a consensus meeting to discuss use cases with less than 80% agreement, followed by a further validation meeting. Eleven use cases were retained across four TB care pathway stages: three for Mtb infection, four for disease detection, three for treatment optimisation, and one for post-TB care. Highest-priority use cases were detection of drug-resistant TB, prediction of progression from infection to disease, identification of current Mtb infection, and improved diagnosis of active TB disease. Conclusions This consensus exercise provides the first comprehensive, prioritised framework of use cases for TB biomarkers and tests, spanning the full care pathway. These eleven priority use cases can guide investment, focus biomarker discovery, and inform future target product profiles, funding calls, and policy development. Applying the framework to the current biomarker pipeline is a key next step to address gaps between innovation and priority needs.

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Development and Validation of a Point-of-Care Triage Scorecard to Enhance Tuberculosis Case Detection During Active Community Screening in Yogyakarta, Indonesia

Catrianiningsih, D.; Felisia, F.; Abdalla, A. S.; Puspitasari, S.; Dwihardiani, B.; Mulia, H. N.; Hidayat, A.; Triasih, R.

2026-08-31 infectious diseases 10.64898/2026.08.27.26361569 medRxiv
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In primary healthcare centers lacking advanced imaging, community-based active tuberculosis (TB) case finding often relies on basic symptom screening. This approach often misses cases and leads to the inefficient allocation of rapid molecular testing (RMT). We aimed to develop and internally validate a simple clinical triage scorecard to improve TB detection and guide RMT use in resource-constrained settings. We conducted a retrospective cross-sectional study of 15,137 adults ([&ge;]18 years) evaluated within the Zero TB Yogyakarta program (2020-2025). Participants with complete clinical assessments and confirmatory GeneXpert results were included. Using multivariable logistic regression, we identified independent clinical predictors, which were subsequently transformed into an integer-based point scorecard. Model performance was evaluated via discrimination and calibration, utilizing bootstrap resampling (1,000 iterations) for internal validation. Among the 15,137 participants, 251 (1.7%) were GeneXpert-positive. The final multivariable model identified eight independent predictors: age, male sex, body mass index, prolonged cough, hemoptysis, unexplained weight loss, TB contact history, and diabetes mellitus. The model demonstrated strong predictive accuracy, with an optimism-adjusted AUROC of 0.836 and good calibration. When translated to the integer scorecard and compared directly to standard national symptom screening, the scorecard performed (AUROC 0.81 vs. 0.73; p<0.001). At a high sensitivity cut off score of [&ge;] 0, the tool achieved 93.63% sensitivity and 41.33% specificity. This point-of-care clinical scorecard provides higher diagnostic accuracy than standard symptom screening algorithms. By offering flexible operational thresholds, it empowers local health programs to dynamically balance the urgency of case detection with available diagnostic capacity, optimizing GeneXpert allocation where advanced radiological imaging is unavailable.

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Red and blue light cues drive contrasting remodeling of lipophilic metabolites and photophysiology in natural benthic diatom biofilms

Desparmet, A.; Lavaud, J.; Jesus, B.; Medico, A.; Hubas, C.

2026-09-01 cell biology 10.64898/2026.08.30.748109 medRxiv
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Intertidal mudflats are low hydrodynamic energy environments hosting microphytobenthic communities that experience strong spatiotemporal variability in light regimes, including changes in spectral quality and light intensity that can lead to cellular photooxidative stress. To cope with these fluctuations, autotrophs exhibit diverse and highly plastic adaptations that are often species-dependent and shaped by their ecological niches. This study investigates photophysiological responses and metabolic remodeling in a diatom assemblage originating from a natural winter microphytobenthic biofilm under contrasting red and blue light intensities. To this end, photosynthetic parameters were monitored alongside changes in lipophilic metabolites, including untargeted lipids and lipophilic pigments. While few metabolites showed temporal remodeling, rapid and contrasting changes were observed within 30 minutes in response to both spectral quality and light intensity. Red light treatments induced broader remodeling of lipophilic metabolites than blue light, whereas blue light appeared to have a greater impact on photosynthetic parameters. Moreover, red light induced xanthophyll-cycle responses comparable to those observed under blue light at equivalent incident intensity. We discuss these metabolic responses in relation to diatom photoadaptive strategies, placing these findings within the intertidal environmental framework. This work further underlines the importance of understanding rapid metabolic plasticity in coping with light fluctuations, providing new insights into the photoregulatory strategies of natural microphytobenthic communities.

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Sleep Quality and Its Association with Life Satisfaction Among Employees in the United Arab Emirates: A Cross-Sectional Study

Ali, S. I.; Varatharajan, V.; Chacko, S. T.; Hazari, A.; Varghese, S. M.

2026-08-31 public and global health 10.64898/2026.08.28.26361603 medRxiv
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Objectives This study aimed to assess sleep patterns and life satisfaction among employees of a private company in Dubai, United Arab Emirates, and to examine the relationships among sleep quality, life satisfaction, and selected demographic variables. A quantitative descriptive cross-sectional survey design was adopted. Methods A convenience sample of 110 male employees participated in the study. Data were collected using the Sleep Disorder Assessment Scale (16 items; Cronbachs = 0.89) and the Life Satisfaction Scale (5 items). Statistical analysis was performed using SPSS version 29, including descriptive statistics, chi-square tests, and Pearson correlation analysis. Results Most participants (66.4%) were aged 20-30 years, and 82.7% experienced moderate sleep-related problems. Mobile phone use before bedtime was common, with 60.9% reporting occasional use and 35.5% reporting regular use. Overall, 41.8% reported neutral life satisfaction, while 25.5% and 24.6% were slightly and extremely satisfied, respectively. A significant negative correlation was found between poor sleep patterns and life satisfaction (r = -0.389, p < 0.001). Mobile phone use before bedtime and shift work were significantly associated with sleep patterns (p = 0.048). Conclusion Poor sleep quality, particularly among shift workers and frequent bedtime mobile phone users, is associated with lower life satisfaction. Workplace interventions promoting sleep hygiene may enhance employee well-being.

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Location-allocation modeling identifies strategic health facilities to expand access to snakebite antivenom in the Brazilian Amazon

Garcia Campos, M. A.; Rocha, T. A. H.; Perez de Souza, J. V.; Murase, L. S.; Murta, F.; Sartim, M. A.; Sachett, J.; Seabra de Farias, A.; Azevedo Machado, V.; Wen, F. H.; Staton, C. A.; Monteiro, W. M.; Gerardo, C. J.; Nickenig Vissoci, J. R.

2026-08-31 public and global health 10.64898/2026.08.28.26360696 medRxiv
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Background: Snakebite envenoming is a major cause of preventable death and disability in the Brazilian Amazon, where long distances, sparse roads, and dependence on river transport delay access to antivenom. We developed location-allocation models to identify community health centers that could strategically expand access to antivenom in Amazonas State, Brazil. Methodology/Principal Findings: We conducted an ecological geospatial study using a 2025 WorldPop population surface, locations of existing and candidate health facilities, and a multimodal road-and-river transportation network derived from OpenStreetMap and HydroSHEDS. Population demand was represented by 7,065 populated centroids, including 1,586 within Indigenous territories. We applied a maximize-coverage algorithm with a six-hour travel-time threshold. Two models were developed: one for Amazonas excluding Manaus and one for populations living in Indigenous territories. Both models began with 77 facilities already providing antivenom and progressively added candidate community health centers until coverage gains plateaued. The plateau occurred at 110 facilities, corresponding to 33 additional centers. In the model excluding Manaus, this configuration covered 1,118,831 people, or 75.11% of the target population; 87.61% of those covered could reach care within three hours. In Indigenous territories, coverage increased from 50.55% to 69.50%, reaching 50,434 people, of whom 81.39% were within three hours of care. Validation used 3,595 snakebite notifications from the 30 highest-burden municipalities in the Brazilian Notifiable Diseases Information System during 2023-2025. The median proportion reaching care within six hours was 40.81% in observed data and 72.17% in model estimates. Conclusions/Significance: Strategically equipping 33 additional existing community health centers could substantially expand timely access to antivenom, particularly in rural and Indigenous areas. Location-allocation modeling that incorporates river transportation can support evidence-based decentralization of time-sensitive health services in geographically complex settings.

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The Role Of Liquid Crystal Ordering In The Structural Organization Of DNA In Bacteria.

Krupyanskii, Y. F.; Kovalenko, V.; Loiko, N.; Generalova, A.; Tereshkin, E.; Tereshkina, K.; Sokolova, O.; Peters, G.

2026-09-01 biophysics 10.64898/2026.08.31.748243 medRxiv
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This paper presents and critically reviews the results of original and some literature based experimental studies conducted by the authors last years on the structural organization of DNA in dormant (starvation stress), anabiotic dormant (4 HR treatment) E. coli cells, as well as the K12 {Delta}dps strain, which lacks the Dps protein (Dps null E. coli). The experimental data includes small-angle synchrotron radiation diffraction (SAXS) and transmission electron microscopy (TEM) data. Synchrotron radiation diffraction experiments on K12{Delta}dps cells allowed us to conclude that peaks at 44.3, 22.1, and 14.8 angstrom resolutions are associated exclusively with ordered DNA organization. Peaks at 44.3, 22.1, and 14.8 angstrom resolutions are also observed for samples of dormant (starvation stress) cells and anabiotically dormant cells. Therefore, this ordered DNA organization also applies to samples of dormant and anabiotically dormant cells. A model is proposed that considers the ordered DNA organization in the cell as a cholesteric liquid crystal. The powder diffraction pattern calculated based on this model is compared with experimental small angle X ray scattering (SAXS) data obtained on Dps-null cell samples. The model completely reproduces the key features of the experimental diffraction pattern from Dps-null cell samples. Accordingly, the cholesteric liquid crystal model corresponds to DNA packaging in dormant and anabiotically dormant cells. Cholesteric liquid crystal ordering should be further considered in all models of cellular DNA packaging. To address the question of which structural organization of DNA predominates in the cell: the cholesteric liquid crystal or nanocrystalline or whether they coexist and fully manifest themselves under different external conditions, it is necessary to utilize the latest methodological advances in structural analysis.

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Best Practice Manufacturing and Quality Standards for Bacteriophage Therapy Products: Australian Consensus Statements

Watts, K.; Lin, R. C.; Lynch, S.; Warning, J.; Barr, J. J.; Ben Zakour, N.; Campbell, A.; Chan, J.; Collie, L.; Hedges, M.; Hudson, B.; Irwin, A.; Khatami, A.; Kicic, A.; Laucirica, D.; Lauter, C.; Ling, K.-m.; Ng, R.; Pavuk, N.; Rahmatullah, R.; Sinclair, H.; Tucker, E.; Vreugde, S.; Warner, M.; Velickovic, Z.; iredell, j.

2026-08-31 public and global health 10.64898/2026.08.26.26361487 medRxiv
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Objective As antimicrobial resistance (AMR) continues to threaten global public health, bacteriophage therapy products (BTPs) offer a promising alternative to conventional antimicrobials. However, translation into routine clinical practice requires best practice standards for manufacturing and quality control to ensure the consistent safety, quality, and reliability of personalised BTPs produced for individual patients or small cohorts. Design A modified Delphi methodology was used to develop consensus statements, engaging experts from Australia's National Bacteriophage Therapy Regulatory Working Group across the fields of clinical microbiology, phage biology, good manufacturing practice (GMP), regulatory science, and government. The process comprised three iterative phases: (1) structured statement development, (2) an anonymous REDCap survey, and (3) a hybrid consensus meeting. The strength of evidence and recommendations was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework. Results Consensus was reached on 35 statements to provide best practice manufacture and quality control guidance for BTPs. These statements address requirements for phage identification and characterisation; define the point at which GMP-aligned processes commence for ubiquitous phages; outline quality control expectations for phage active pharmaceutical ingredient (pAPI) production and maintenance of BTP and host cell repositories. Additional guidance covers quality management systems, including documentation, traceability, and governance. Conclusion These consensus statements provide comprehensive best practice recommendations for the manufacture and quality control of BTPs in Australia. By promoting consistent, safe, and quality-assured approaches to personalised BTPs, they aim to facilitate clinical implementation while remaining aligned with existing international pharmacopoeial standards and regulatory frameworks.

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Female contraceptive cover duration for miltefosine-containing regimens for the treatment of women with leishmaniasis

Chu, W.-Y.; Alves, F.; Dorlo, T. P. C.

2026-09-02 infectious diseases 10.64898/2026.08.31.26360682 medRxiv
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Introduction Miltefosine is the only approved oral antileishmanial agent, but its use in women of childbearing potential (WOCBP) is restricted due to preclinical teratogenicity. Current labeling recommends contraception during treatment and for at least five months thereafter, based solely on its long terminal elimination half-life. This study re-evaluated the required contraceptive duration using an exposure margin-based approach. Methods Virtual populations were generated from anthropometric data of 382 Indian, 4,462 Eastern African, and 4,019 Brazilian WOCBP with leishmaniasis. Published population pharmacokinetic models were used to simulate miltefosine exposure following 14-42-day regimens for visceral leishmaniasis (VL), post-kala-azar dermal leishmaniasis (PKDL), and cutaneous leishmaniasis (CL). A developmental safety exposure threshold was derived from the rat no-observed-adverse-effect level (0.6 mg/kg/day for 10 days) and adjusted using a 10-fold safety margin. Contraceptive durations resulting in median residual post-contraception exposure (AUCEOC-{infty}) below this threshold were considered supportive of contraceptive discontinuation. Results The developmental safety exposure threshold was estimated at 2.5 mg{middle dot}day/L. Despite pharmacokinetic differences across geographical regions and disease manifestations, required minimum contraceptive durations were consistent: three months from treatment initiation for the 14-day regimen, four months for 21- and 28-day regimens, and five months for the 42-day regimen. For the 14-day regimen, a single dose of a long-acting injectable contraceptive administered at treatment initiation would provide sufficient coverage. Conclusion An exposure margin-based approach supports shorter contraceptive durations than current recommendations. For the 14-day VL regimen, three months of contraception may provide a practical alternative to current labeling.

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Rapid phase resetting of Aedes aegypti circadian rhythms by transient alterations in light exposure

Dessart, M.; Luff, S.; Smith, L.; Sunman, H.; Vinauger, C.

2026-09-01 animal behavior and cognition 10.64898/2026.08.27.747523 medRxiv
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Circadian clocks enable mosquitoes to anticipate recurring environmental variations and coordinate behaviors critical for survival and disease transmission, such as locomotion, reproduction, host-seeking, and blood-feeding, with times of day when performance is maximal. In Aedes aegypti, locomotor activity follows a robust diurnal rhythm shaped by endogenous circadian clocks and environmental cues, among which light has been shown to be the primary source of temporal information. While early studies established the role of light in regulating locomotor activity, behavior, oviposition and pupation, it remains unclear which features of a light cycle drive changes in circadian rhythms. This question is increasingly relevant as Ae. aegypti is frequently exposed to artificial and dynamic lighting conditions in urban environments. Here, we investigated how transient changes in light schedules influence circadian rhythms in locomotor activity by systematically manipulating the timing, duration, and direction of light exposure. Using a high-throughput assay, we tested over 1900 individuals, including wild-type and timeless knockout mutants, and showed that a single day of al tered lighting is sufficient to induce robust phase shifts, with no evidence of masking effects. A 6-hour light pulse was sufficient to re-entrain mosquitoes regardless of the timing of the pulse, and phase shifts were primarily driven by the offset time of the light pulse, indicating that light-offset acts as a major zeitgeber. Together, these findings challenge conventional assumptions about the timescale of circadian synchronization and highlight the remarkable plasticity of mosquito behavior in response to anthropogenic light. Eventually, these effects could explain the rapid adaptation of the species to urban environments and have potential consequences for disease transmission dynamics.

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Identification of genetic variants in Pfs25 and functional evaluation in mosquito infection

Orfano, A.; Cisse, A.; Guo, Y.; Han, L.; Fikadu, N.; Thiam, L. G.; Ba, A.; Li, R.; Pouye, M. N.; Mangou, K.; Moore, A. J.; Sene, S. D.; Diallo, F.; Ngom, E. M.; Sadio, B.; Mbengue, A.; Membi, C.; Ngasala, B.; Bazie, T.; Some, F. A.; Olson, N.; Patel, S. D.; Shapiro, L.; Parikh, S.; Foy, B. D.; Cappello, M.; Vigan-Womas, I.; Premji, Z.; Dabire, R. K.; Ouedraogo, J.-B.; Sheng, Z.; Bei, A. K.

2026-08-31 infectious diseases 10.64898/2026.08.25.26361130 medRxiv
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Transmission-blocking vaccines (TBVs) are a promising strategy to reduce malaria transmission by targeting parasite stages within the mosquito. However, parasite genetic diversity may limit vaccine efficacy. We used next-generation amplicon deep sequencing to identify non-synonymous single nucleotide polymorphisms (SNPs) in Pfs25 from 184 Plasmodium falciparum isolates from Senegal, Tanzania, Ghana, and Burkina Faso. Prioritized SNPs were introduced into P. falciparum via CRISPR-Cas9. For the G116C variant, gametocyte development was evaluated by microscopy and qPCR, and mosquito infectivity was assessed by SMFAs. We identified 26 SNPs, including 24 novel variants. Functional assays showed that the Pfs25 G116C mutation did not affect gametocyte development or exflagellation. SMFA showed no significant differences in oocyst prevalence or intensity between mutant and WT parasites. These findings highlight the importance of integrating genetic surveillance with functional validation to guide the development of effective transmission blocking interventions

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Impact of Detection-Isolation-Leakage on the 2026 DRC Bundibugyo Ebolavirus Outbreak

Oraby, T.; Falay, D.; Ndeffo-Mbah, M. L.

2026-08-31 public and global health 10.64898/2026.08.25.26361360 medRxiv
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The 17th Ebola outbreak in the Democratic Republic of the Congo, announced on 15 May 2026, was attributed to Bundibugyo ebolavirus (BDBV). Although case isolation is the main control strategy, its effectiveness is compromised when patients escape isolation facilities before recovery. Between 14 May and 17 June 2026, 175 individuals reportedly left isolation facilities without formal discharge across Ituri Province. We assessed how this "isolation leakage" affects community transmission. We refined the SEIHFR framework to distinguish undetected community infections, detected but not-yet-isolated cases, isolated individuals, leakage, funeral-associated transmission, and removals. Using Bayesian inference, we fitted the model to daily Ituri surveillance data, escapee counts, and isolation census records. We estimated the leakage rate, reporting and detection probabilities, and the transmission rate, while fixing other parameters based on the BDBV literature. The model reproduced confirmed cases, deaths, discharges, and escapees. We estimated R_0=3.67 (95% HDI: 2.0-5.7), a leakage rate of {rho} {approx} 0.034 day^-1 (0.022-0.051), and high contact-tracing-driven detection (p_d {approx} 0.91-0.99). Leakage increased the detection-dependent reproduction number [R](p_d) from approximately 3.2 to above 5. Eliminating leakage reduced cumulative infections by about one-third, from 1,120 to 764, while the minimum detection level required for control increased from p_d [&ge;] 0.73 without leakage to p_d [&ge;] 0.87 at the fitted leakage rate. Shortening time to isolation prevented the most infections (73.4%; 59-84), followed by reducing leakage (29.7%; 14-52) and re-isolating escapees (12.6%; 6-24). Delaying leakage reduction until week 4 reduced its benefit from about 27% to below 2%. Isolation leakage represents a major transmission pathway that has until now gone largely unmeasured. While rapid initiation of isolation is highly beneficial, it cannot compensate for permeable isolation; therefore, early, community-driven efforts to control leakage, embedded within a multilayered response, are critical.

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Rclade: automated taxonomic collapsing and geological-timescale annotation of time-calibrated phylogenetic trees in R

Zeng, Z.; Wang, Y.

2026-09-01 bioinformatics 10.64898/2026.08.27.747462 medRxiv
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Background: Reproducible taxonomic collapsing and geological-timescale annotation of time-calibrated phylogenetic trees in R often require coordination among several packages and repeated code for label parsing, clade validation, plotting, and export. Workflow-managed analyses additionally benefit from non-interactive configuration, predictable diagnostics, and machine-readable exit status. Results: We present Rclade, an R package that consolidates the multi-package coordination required for taxonomic collapsing into a streamlined, single-function interface. Rclade provides (1) custom ggproto objects (GeomPolygonStraight/GeomSegmentStraight) that bypass coord_munch() interpolation to achieve straight-edge rendering of collapsed triangles in circular layouts; (2) automatic detection and parsing of four taxonomic-label formats (GTDB, Silva, NCBI, embedded) plus user-supplied custom regex, with explicit input-validation contracts and parsing-accuracy evaluation on real and derived test sets; and (3) workflow embeddability through YAML configuration, library-mode APIs, and standard Unix exit codes. Benchmarks on synthetic and real datasets (200-10,000 synthetic tips and real reference trees up to 10,122 tips; 5 replicates at every scale under a unified fully rendered measurement protocol) show that the full-pipeline overhead is modest for interactive use (median {approx}0.87 s in-session rendering and {approx}8.4 s process-level wall-clock at 10,000 tips). Conclusions: Rclade is a convenience layer over the ggtree/deeptime ecosystem that reduces boilerplate while adding targeted technical improvements for circular-layout rendering and format heterogeneity management.

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Population-based urinary pesticide biomonitoring in rural Wisconsin: Longitudinal patterns and determinants of glyphosate, AMPA, and 2,4-D, and other modern use pesticides

Schultz, A. A.; Lange, M.; Shelton, B.; Meinholz, E.; Esselman, D.; Paulsen, E.; Haban, A.; Kesner, V.; Rowe, M.; Burke, R.; Tisler, C.; Tomasallo, C.

2026-08-31 public and global health 10.64898/2026.08.26.26361410 medRxiv
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Background: Population-based biomonitoring of contemporary-use pesticides remains limited in the United States, particularly in rural agricultural regions, and few studies have repeated measurements within the same individuals over time. Methods: We analyzed 28 urinary pesticide-related biomarkers among 600 adults from the population-based Survey of the Health of Wisconsin with archived urine collected during 2008-2016; 296 participants provided repeat urine and updated exposure information in 2025. Detection frequencies, co-detection, and within-person detection patterns were characterized. Generalized estimating equations were used for stacked, repeated-measures analyses of factors associated with detection of aminomethylphosphonic acid (AMPA), glyphosate, 2,4-dichlorophenoxyacetic acid (2,4-D), and any of these three. Prospective-only analyses evaluated more detailed agricultural and recent exposure measures. Results: Glyphosate, AMPA, and 2,4-D were detected in 7.7%, 6.2%, and 4.3% of retrospective specimens and 5.4%, 3.1%, and 4.1% of prospective specimens, respectively. Co-detection and persistent detection across the 9 to 17-year interval was rare. In repeated-measures models, greater fruit and vegetable intake, older age, and male sex were associated with higher 2,4-D detection. Lower household income was associated with lower AMPA detection, while afternoon/evening collection was associated with higher AMPA detection. In prospective analyses, working on field-crop agricultural land showed the strongest agricultural associations, particularly for 2,4-D and detection of any of the three pesticides. Associations were not seen with self-reported conventional versus organic produce consumption. Conclusions: Urinary pesticide detections were generally infrequent in this Wisconsin population. Diet and direct agricultural activities may be more informative exposure pathways than residing near cropland or private well drinking-water characteristics.

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INTerrupting prolifERation of Carbapenem resistance in Indonesia: clinical and genomic Evaluation of Pathways of Transmission (INTERCEPT) : a Study Protocol

Farida, H.; Hapsari, R.; Lestari, E. S.; Farhanah, N.; Roberts, A. P.; Graf, F. E.; Dacombe, R. E.; Moore, M. E.; Lewis, J. M.

2026-08-31 infectious diseases 10.64898/2026.08.28.26361608 medRxiv
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Background Carbapenem-resistant bacteria are a major global public health threat, classified as critical priority pathogens by the WHO. In Indonesia, despite a national antimicrobial resistance control programme established by the Ministry of Health in 2015, resistance rates continue to rise, including increasing carbapenem resistance among clinically important bacteria. Strengthening approaches to directly interrupt transmission is essential, yet transmission pathways remain poorly understood with limited research and policy guidance within the Indonesian context. Methods and analysis The INTERCEPT study is a UK-Indonesia multidisciplinary collaboration aiming to identify transmission routes of carbapenem-resistant bacteria across healthcare and community settings, and the mechanisms of resistance gene transfer between bacteria and mobile genetic elementss. We will conduct genomic surveillance of hospital inpatients, healthcare workers, hospital environments, and surrounding communities, including wastewater systems, combined with genomic analyses and mathematical transmission modelling. A cohort of patients with bloodstream infections will be recruited to evaluate resistant bacteria, treatment practices, and clinical outcomes. Qualitative research will explore behavioural and system-level factors influencing transmission and intervention implementation. Findings will inform stakeholder workshops to co-design context-specific interventions, with pilot intervention over 9 months with pre- and post-intervention assessment to guide scalable strategies to reduce AMR transmission. Discussion The INTERCEPT study addresses carbapenem resistance in Indonesia using an integrated approach combining microbiological surveillance, genomics, modelling, and qualitative methods. Strengths include cross-sectoral analysis (patients, workers, environment) and participatory intervention design. Limitations include geographic scope restricted to Central Java, Indonesia.

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Conditional willingness to care for patients with Ebola virus disease: a qualitative study of risk-benefit perceptions and support needs of clinical students at a Ugandan medical school

Nakabuubi, B. C.; Nabunya, R.; Ngabirano, T. D.; Nankumbi, J.; Kabiri, L.; Kigozi, E.; Christine, A.; Musindi, D.; Alinda, I.; Kyokwijuka, A. M.; Muwanguzi, P.

2026-09-03 public and global health 10.64898/2026.08.29.26361701 medRxiv
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Introduction: Clinical students are a future health workforce, yet their roles during outbreaks of highly infectious diseases remain uncertain because of safety, training, supervision and welfare concerns. Ugandas 2022 outbreak of Ebola disease caused by Sudan ebolavirus highlighted the need to understand how clinical students perceive outbreak-related care. Aim: This study explored willingness to care for patients with Ebola virus disease among clinical students at a Ugandan medical school and examined how perceived risks, perceived benefits and support needs shaped that willingness. Methods: An exploratory descriptive qualitative study was conducted among clinical students of Makerere University in Kampala, Uganda. Fifteen undergraduate medical and nursing students in the later years of training were purposively selected. Data were collected through in-depth interviews, audio-recorded with consent, transcribed verbatim, de-identified and analysed using latent content analysis. The Health Belief Model sensitised interpretation, and reporting was strengthened using the COREQ guidance. Results: Five interrelated themes emerged, showing that willingness to care was conditional rather than simply present or absent. Students described an initial willingness grounded in professional duty, devotion to patients and the desire to save life. This willingness was restrained by perceived risks of contracting Ebola virus disease, dying, transmitting infection to family members or colleagues, emotional distress, lack of epidemic-readiness in the curriculum, inadequate preparedness and weak welfare support. Perceived benefits, including patient survival, professional learning, outbreak experience and personal fulfilment, strengthened willingness but did not override safety concerns. Students identified reliable personal protective equipment, epidemic-ready curricula, practical infection-prevention and control training, simulation, clear protocols, close supervision, psychosocial support, insurance and fair compensation as cues to action that could convert willingness into safe participation. Conclusions: Clinical students in this Ugandan teaching hospital expressed a strong sense of professional responsibility, but their willingness to participate in Ebola care was conditional upon preparedness, protection, epidemic-ready education and institutional trust. Professional duty and learning opportunities promoted participation, whereas perceived risks and inadequate support limited it. Medical education programmes and outbreak-response systems should develop ethical, supervised, competency-based student roles supported by practical curricula, reliable protective equipment and psychosocial and welfare safeguards.