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F1000Research

F1000 Research Ltd

Preprints posted in the last 90 days, ranked by how well they match F1000Research's content profile, based on 79 papers previously published here. The average preprint has a 0.14% match score for this journal, so anything above that is already an above-average fit.

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Community needs for FAIR pathogen data

van Geest, G.; Thomas-Lopez, D.; Feitzinger, A. A.; Weissgold, L. A.; Halabi, S.; Cuesta, I.; Hjerde, E.; Gurwitz, K. T.; Arora, N.; Neves, A.; Palagi, P. M.; Williams, J. J.

2026-04-15 scientific communication and education 10.64898/2026.04.14.718420 medRxiv
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BackgroundDatasets related to infectious diseases are essential for public health decision-making, yet their reuse remains limited by persistent barriers to data sharing and integration. Achieving data that are Findable, Accessible, Interoperable, and Reusable (FAIR) is widely recognized as essential for accelerating scientific discovery and enabling coordinated responses to emerging threats, but the needs of the global pathogen data community have not been systematically characterized. AimThis study, conducted by the Pathogen Data Network (PDN), aims to identify infrastructural and educational priorities among stakeholders working with infectious disease-related data in order to guide community-responsive support for data sharing and interoperability. MethodsA cross-sectional stakeholder survey was disseminated to a well-defined expert population within PDN networks and via open professional channels. A total of 136 responses from researchers, healthcare professionals, bioinformaticians, and educators were analyzed descriptively to identify prioritized barriers, training needs, and preferred support mechanisms. ResultsRespondents consistently identified structural constraints as the primary impediments to effective data use, including limited funding (74%), data-aggregation challenges (68%), and a shortage of skilled personnel (52%). Respondents identified bioinformatics for infectious disease research (68%) as the highest priority for training, followed by guidance on using the integrated pathogen data and tools portal provided by the PDN, the Pathogens Portal (51%). The Pathogens Portal was also ranked as the most essential PDN resource (72%). Preferred training formats included virtual short courses (68%) and webinars (66%). Notably, while researchers emphasized technical subjects like machine learning, educators prioritized foundational case studies. ConclusionThese findings provide an evidence-based diagnostic of community needs and suggest that barriers to FAIR pathogen data are predominantly systemic rather than purely technological. The survey framework and openly available dataset offer a reusable template for assessing needs in other communities and regions. By aligning training, infrastructure development, and outreach with empirically identified priorities, organizations supporting infectious disease research can strengthen the interoperability and reuse of data and establish a benchmark for future community-driven improvements.

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Glucocorticoid signaling regulates expression of the EBI3 subunit of IL-27 in neonatal macrophages: Implications for antenatal corticosteroid therapy

Vance, J. K.; Wang, L.; Povroznik, J. M.; Busada, J.; Hu, G.; Robinson, C.

2026-03-26 immunology 10.64898/2026.03.24.713718 medRxiv
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BackgroundHumans and mice display elevated levels of IL-27, an immunosuppressive cytokine shown to increase during neonatal bacterial sepsis and compromise survival. This study explores two hypotheses for regulation of IL-27 expression: 1) decreased DNA methylation in newborns that contributes to increased expression of IL-27 genes; 2) neonatal hormones regulate IL-27 expression through upstream hormone response elements (HREs). MethodsWhole genome methyl-seq analysis of neonatal and adult blood-derived macrophages identified differentially methylated regions (DMRs) at steady-state. Quantitative PCR (qPCR) measured expression of IL-27 genes (IL27p28 and EBI3) in human and murine neonatal macrophages stimulated in vitro with synthetic glucocorticoid or progesterone. Confocal microscopy and chromatin immunoprecipitation (ChIP) of glucocorticoid receptor (GR) assessed translocation into the nucleus and binding to the EBI3 promoter. ResultsThe IL-27p28 promoter contained DMRs that were increased in the neonatal cohort. The analysis did not identify DMRs within the EBI3 promoter. Dexamethasone stimulation increased EBI3 gene expression in human and murine neonatal macrophages. GR localized to the nucleus in response to dexamethasone and was enriched at the EBI3 upstream regulatory region. ConclusionThese data suggest glucocorticoid (GC) signaling increases EBI3 expression. This has importance in the context of antenatal GC administration that may increase IL-27 levels. Impact Statement{blacksquare} Elevated expression of IL-27 in early life impairs the host response to invasive bacterial infection in neonates. {blacksquare}Understanding the regulatory mechanisms contributing to increased IL-27 during the neonatal period is necessary to reduce susceptibility to infection in this vulnerable population. {blacksquare}The methylation status of the IL-27 genes in macrophages from neonatal and adult blood donors does not suggest regulation of differential expression with age. {blacksquare}Glucocorticoids are a signal that can induce EBI3 gene expression in a GR-dependent manner. {blacksquare}Glucocorticoid therapy for premature infants may increase IL-27 expression and promote enhanced susceptibility to infection.

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Adaptation of the Walk 'n Watch intervention for UK Community Stroke Rehabilitation: A Structured Adaptation Process

Ackerley, S.; Peters, S.; Eng, J. J.; Hung, S. H.; Hancock, S.; Smith, C.; Keenan, N.; Woodford, P.; Connell, L. A.

2026-05-03 rehabilitation medicine and physical therapy 10.64898/2026.05.01.26352175 medRxiv
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BackgroundWalk n Watch (WnW) is a structured, progressive walking exercise intervention developed for Canadian inpatient stroke rehabilitation. Although its mechanisms align with UK guidance for intensive walking therapy, stroke rehabilitation in the UK is delivered predominantly in the community. This change in service context has implications for safety, feasibility, and fidelity, necessitating structured pre-implementation intervention adaptation to support delivery. MethodsA prospective adaptation process used ADAPT guidance. A multidisciplinary coalition and learning collaborative (UK clinicians, clinical- academics, people with lived experience, and Canadian WnW developers) participated in stakeholder co-production activities. Informed by ADAPT steps 1-2, co-production focused on rationale, core components, contextual mapping and planning adaptations. Discussions were analysed through rapid deductive mapping using Consolidated Framework for Implementation Research (CFIR) domains. Candidate fidelity-consistent adaptations were refined by the learning collaborative. Conceptual outputs of the process were synthesised. ResultsThree intervention core components were confirmed: 1) prioritised, high-volume, weight-bearing walking-related activities at moderate effort; 2) structured progression of steps based on performance on a walking test (e.g. Six-Minute Walk Test); 3) objective monitoring of steps and cardiovascular intensity. Several contextual determinants across CFIR domains were likely to influence UK community implementation. Fidelity-consistent modifications to the adaptable periphery were specified across four areas: 1) therapy & practice, 2) environment & safety, 3) monitoring & feedback, and 4) workflow & documentation. Adaptations included hybrid supervision, planned out-of-session practice, and monitoring using validated proxies. A WnW Adaptation Model was produced. ConclusionsThis paper provides a transparent pre-implementation adaptation of WnW for delivery within UK community stroke rehabilitation. Anchoring adaptations to intervention mechanisms and principles through co-production and implementation science frameworks, this work establishes a foundation for piloting and hybrid effectiveness-implementation evaluation. The WnW Adaptation Model offers support for future implementation efforts. Discussion positions adaptation as a pragmatic means for applying optimisation principles. PLAIN LANGUAGE TITLEAdapting the Walk n Watch walking exercise programme for home-based stroke rehabilitation in the UK: A structured step-by-step process PLAIN LANGUAGE SUMMARYO_ST_ABSBackgroundC_ST_ABSWalk n Watch (WnW) is a structured exercise programme that helps people improve their walking. It was originally developed for people recovering from stroke in hospital in Canada. While the approach fits well with United Kingdom (UK) recommendations for intensive therapy, stroke rehabilitation in the UK often takes place at home. Because of this difference, WnW needs careful adaptation for safe and effective delivery. MethodsPublished ADAPT guidance was used to adapt WnW. UK therapists, researchers, people with stroke, and Canadian WnW developers undertook adaptation activities. Together, they identified which parts of WnW were essential, explored differences between the Canadian and UK settings, and planned changes. Discussions were reviewed using an established framework to develop adaptations that kept the most important parts of WnW intact (fidelity-consistent adaptations). The adaptation process was summarised. ResultsThree essential intervention parts were confirmed: 1) prioritised, high-volume, weight-bearing walking-related activities at moderate effort; 2) structured progression of steps based on performance on a walking test; 3) objective monitoring of steps and cardiovascular intensity. Several factors were likely to influence delivery in the UK community. Changes focused on four areas: 1) therapy & practice, 2) environment & safety, 3) monitoring & feedback, and 4) workflow & documentation. They included using both in-person and online sessions, planning safe between session practice, and using non-digital monitoring. A WnW Adaptation Model was produced. ConclusionsThis paper clearly describes the steps taken to adapt WnW for delivery in UK community stroke rehabilitation. By working closely with stroke experts and using established research frameworks, the adapted programme keeps the most important parts of WnW while allowing it to fit into real-life. The WnW Adaptation Model offers support for further testing and may assist others looking to adapt WnW. Discussion offers perspective on how adaptation aligns with optimising interventions.

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An optimized protocol for single-brain isolation of sex-defined pure mouse astrocyte cultures

Al-Jaf, S.; Ai, E.-H.; Wilson, J. A.; Abd-Elrahman, K. S.

2026-03-25 pharmacology and toxicology 10.64898/2026.03.23.713747 medRxiv
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BackgroundPrimary astrocyte cultures derived from neonatal rodent cortices provide a controlled system for investigating astrocyte-specific mechanisms. However, mixed glial preparations frequently contain contaminating microglia and oligodendrocyte progenitor cells, and most existing protocols require pooling tissue from multiple mouse pups to obtain sufficient astrocyte yields. This approach is impractical as it obscures sex and genotype, limits investigations of sex dependent astrocyte phenotypes, and precludes studies in certain transgenic models. To address this gap, our protocol achieves a high astrocyte yield from a single neonatal mouse brain, enabling sex- and genotype-specific cultures without the need for pooling. Mechanical removal of oligodendrocyte progenitors combined with pharmacological depletion of microglia using a Colony Stimulating Factor 1 Receptor (CSF1R) inhibitor produces highly enriched astrocytes suitable for functional assays, including those focused on sex-specific biology. MethodsCortical tissue was isolated from a single mouse pup is mechanically dissociated in astrocyte media. Cell suspensions are transferred to poly-D-lysine-coated flasks in astrocyte media. After 10-15 days in culture, OPCs are mechanically removed by horizontal shaking and microglia are selectively depleted by incubating cultures with CSF1R inhibitor PLX5622 for 24, 48, 72 and 96 hours. After PLX treatment, media is replaced and enriched astrocytes were maintained or passaged for experimentation. The sex of the pups is determined by PCR performed on DNA extracted from tail biopsies. ResultsImmunocytochemical analysis for astrocyte and microglia markers (GFAP and Iba1, respectively) showed that 24 hours of PLX5622 treatment did not fully eliminate microglia from mixed glial cultures. Extending treatment to 48 hours effectively depleted microglia while minimizing cytotoxicity and astrocyte loss and produced a pure, high-yield, sex-specific primary astrocyte culture. PCR reliably enabled the sex identification of pups used in culture using DNA extracted from tail biopsies. DiscussionThis protocol provides an efficient and reproducible method for generating high-purity, sex-specific primary astrocyte cultures from a single mouse brain. It improves consistency and purity while eliminating the need to pool tissue, preserving sex and genotype and enabling studies in transgenic mouse lines of both sexes.

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Making Course Structure Visible in a Multi-Instructor Graduate Genomics Course: A Course-Level Evaluation of Standardized Learning Supports

SAITOU, M.; Diblasi, C.

2026-05-08 scientific communication and education 10.64898/2026.05.06.723173 medRxiv
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Graduate-level genomics courses require students to integrate dense material across subfields, concepts and methods. In modular, multi-instructor courses, students may struggle because the coherence between lectures can be difficult to navigate, while the course structure may be visible to instructors. We evaluated a 2025 navigation redesign of BIO322, a graduate genomics course at the Norwegian University of Life Sciences, while preserving course content, multi-instructor teaching, modular organization and assessment framework. The redesign includes introducing a standardized self-learning guide, expanded syllabus, enriched online quiz feedback, and added support for a final group research proposal. Using anonymized course evaluation scores from 2021-2025 and aggregated learning management system access data from 2023-2025, we examined student experience and resource use. In 2025, five of six course evaluation items reached their highest observed BIO322 scores, while one, lecture-specific score remained within the previous range. The consolidated self-learning guide was accessed by nearly all students, whereas access to optional readings declined across the course sequence, despite comparatively stable page views per accessing student. These course-level findings are consistent with improved perceived navigability following the introduction of standardized learning support. However, some students continued to report difficulty identifying priorities and connections among course components, indicating that challenges in perceived course coherence remained for part of the cohort despite the redesign. Practitioner PointsO_LIMaking course structure explicit may improve students perceived navigability in multi-instructor graduate genomics courses. C_LIO_LIA centralized self-learning guide can broaden access to preparatory guidance without changing core course content or assessment. C_LIO_LIOptional learning supports may be used unevenly, so resource availability should not be assumed to translate into uniform resource access. C_LI

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Cortical activity during narrative discourse production in individuals with post-stroke aphasia and controls measured via functional near-infrared spectroscopy

Braun, E. J.; Carpenter, E. A.; Gao, Y.; Yucel, M. A.; Boas, D. A.; Kiran, S.

2026-06-10 rehabilitation medicine and physical therapy 10.64898/2026.06.05.26354921 medRxiv
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Introduction: Aphasia is an acquired language disorder with a significant negative functional impact. Much of the research on aphasia has focused on word-level language comprehension and production. Further evaluation of discourse-level tasks, both at behavioral and neural levels, will allow for an ecologically valid understanding of the functional implications of language impairment in this population. Method: This study evaluated bilateral frontal, temporal, and parietal cortical activity during computer-based narrative production in 14 young neurotypical individuals, 17 individuals with post-stroke aphasia, and 15 age-matched neurotypical participants using functional near-infrared spectroscopy (fNIRS). Oxygenated hemoglobin (HbO) was measured during narrative production following short video clips and compared to HbO during counting aloud. In addition, behavioral measures quantifying in-task performance were correlated with averaged HbO values. Results: Young neurotypical individuals showed greater cortical activity in bilateral language regions for narrative production compared to counting aloud. In contrast, people with aphasia showed positive condition-related effects in the right frontal ROI and the age-matched group showed positive condition-related effects in the left frontal and right precentral ROIs. Each group showed different patterns in relationships between cortical activity and discourse performance measures. Conclusion: Overall, young participants showing more consistent condition-related effects for narrative discourse production than individuals with aphasia and age-matched controls. This study shows the potential for fNIRS to evaluate cortical activity for ecologically valid language tasks in individuals with post-stroke aphasia.

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Paclitaxel sensitizes TRAIL (tumor necrosis factor-related apoptosis-inducing ligand)-resistant breast cancer cells towards TRAIL-mediated apoptosis

Ghosal, N.; Biswas, D.; Chaudhuri, D.; Sarkar, M.; Giri, K.; PAL, R.

2026-03-20 cancer biology 10.64898/2026.03.18.712553 medRxiv
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BackgroundThe ability of TRAIL to specifically induce apoptosis in cancer cells makes it a promising candidate to be an effective chemotherapeutic drug. But resistance to TRAIL treatment is a major obstacle. Finding combinatorial therapies that make resistant tumors more susceptible to TRAIL is an effective preclinical approach. In this work, we investigated the possibility that pre-treatment of paclitaxel may promote apoptosis in TRAIL-resistant breast cancer cells. MethodsIn silico analysis was done to investigate the binding affinity between TRAIL receptors (DR5 and DCR2) and paclitaxel via docking and MD simulation. To check whether any non-lethal dose of paclitaxel can modulate the expression of TRAIL receptors, qPCR was done in paclitaxel treated breast cancer cells. Next, paclitaxel was pre-administered to TRAIL-resistant MCF7 and MDA-MB-453 human breast cancer cells followed by rhTRAIL treatment. Cell viability and survival was evaluated using the MTT assay and colony formation assay, respectively. Immunoblot for caspase-3 was performed to study apoptosis. The expression level changes of DR5 and DCR2 were analyzed post-treatment using qPCR and immunoblot assay. ResultsIn silico analysis showed that paclitaxel can bind with higher stability to DCR2 in comparison to DR5 thereby changing the preference of TRAIL molecules towards DR5. Next, in cell line experiments we observed that administering a non-lethal dose of paclitaxel to MDA-MB-231 and MCF7 breast cancer cells resulted in no significant cell death but led to an increase in DR5 and a decrease in DCR2 expression at both the transcript and protein levels. Furthermore, in TRAIL-resistant MCF7 and MDA-MB-453 cells, pre-treatment with paclitaxel followed by rhTRAIL administration induced significant cell death due to paclitaxel induced increase in DR5 as well as decrease in DCR2 expression at both the transcript and protein levels. Moreover, long term survival of MDA-MB-453 cells was significantly lower when pretreated with paclitaxel and exposed to rhTRAIL compared to control, paclitaxel alone or rhTRAIL alone group. ConclusionThus, our study uncovers a novel therapeutic strategy to overcome TRAIL resistance underscoring the clinical potential of using a non-lethal dose of paclitaxel to modulate TRAIL receptor dynamics. Future research should be aimed at exploring the potentiality of using paclitaxel-based combinatorial approaches in crafting effective TRAIL therapies.

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Adherence to CDC Antimicrobial Stewardship Core Elements and Barriers to stewardship practices among Healthcare Workers at a Tertiary Care Hospital Uttarakhand, India

K, K.; K, M.; Kumari, K.; Meena, K.; Pilania, M.; Kashyap, M.; Mahala, K.; Bhakar, M.; Kataria, N.; Singh, V.; Panda, P. K.; Sharma, M.

2026-03-28 pharmacology and therapeutics 10.64898/2026.03.26.26349469 medRxiv
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Background: Antimicrobial resistance (AMR) is a growing global health concern driven largely by inappropriate antimicrobial use. Antimicrobial stewardship programs (ASPs), guided by the Centers for Disease Control and Prevention (CDC) core elements, are essential for optimizing antimicrobial use. However, adherence to these practices and the barriers faced by healthcare workers remain inadequately explored, particularly in resource-limited settings. Objective To assess adherence to the CDC antimicrobial stewardship checklist and identify barriers affecting stewardship practices among healthcare workers at a tertiary care hospital in Uttarakhand, India. Methods A quantitative cross sectional descriptive study was conducted among 355 healthcare workers, including nursing officers and physicians. Data were collected using a sociodemographic questionnaire, the CDC antimicrobial stewardship checklist, and a self-structured barrier assessment tool (test retest reliability r = 0.78). Descriptive and inferential statistics were applied using SPSS version 23.0, with a significance level set at p < 0.05. Results The overall adherence to the CDC antimicrobial stewardship checklist was 52.3%, indicating moderate compliance. Higher adherence was observed in action-oriented interventions, while lower adherence was noted in domains such as accountability, pharmacy expertise, reporting, and education. Major barriers identified included lack of antimicrobial supply (89.0%), shortage of key personnel (88.5%), delays in laboratory reports (85.1%), lack of training (83.9%), and inadequate administrative support (79.2%). Significant associations were found between perceived barriers and factors such as working area, designation, qualification, and work experience (p < 0.05), whereas age and gender showed no significant association. Conclusion Adherence to antimicrobial stewardship practices was moderate, with notable gaps in organizational and educational components. Multiple systemic, resource-related, and behavioral barriers hinder effective implementation. Targeted interventions focusing on strengthening infrastructure, workforce capacity, training, and administrative support are essential to improve stewardship practices in tertiary care settings. Keywords: Antimicrobial resistance, Antimicrobial stewardship program, Barriers, CDC Checklist

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Altered cerebrovascular response to breath holding in thoracolumbar spinal cord injury measured using functional near-infrared spectroscopy

Karunakaran, K. D.; Chen, D. Y.; Chiaravalloti, N. D.; Biswal, B. B.

2026-03-13 rehabilitation medicine and physical therapy 10.64898/2026.03.12.26348285 medRxiv
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Spinal cord injury (SCI) is associated with cardiovascular deficits that affect cerebral blood flow, cerebral perfusion, and cerebrovascular control. While several studies use neuroimaging techniques such as functional magnetic resonance imaging (fMRI) to understand neuroplasticity following SCI, more work needs to be done to evaluate the cerebrovascular changes following SCI. Understanding these effects using neuroimaging is essential as these deficits also affect neurovascular coupling and how we interpret neuroplasticity measured based on neuroimaging. Hence, we conducted a pilot study in twelve healthy males and thirteen males with thoracolumbar SCI using functional near-infrared spectroscopy (fNIRS) to understand the effects of breath-holding induced hypercapnia on the hemodynamics of the sensorimotor cortex and prefrontal cortex (PFC) after SCI. Participants performed 30 seconds of regular breathing alternated by 15 seconds of breath-holding for 5 minutes. Compared to controls, the SCI group presented with a greater initial decrease in oxy-hemoglobin concentration change and a delayed subsequent increase in oxy-hemoglobin concentration change in response to hypercapnia at p<. Additionally, the net increase in oxy-hemoglobin concentration change following BH in the PFC was negatively correlated with the level of injury at p=0.005, where higher levels of injury were associated with a smaller increase in oxy-hemoglobin concentration following hypercapnia. These findings confirm that a) SCI, including lower levels of injury (below T6) are associated with cerebrovascular changes that are quantifiable using fNIRS, and b) fNIRS could be a robust tool to understand the neuroplastic and cerebrovascular changes in people with SCI.

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Overground suspension walkers elicit more and higher quality stepping than treadmills: A longitudinal study of pre-walking infants with Down syndrome

Hospodar, C. M.; Enriques, F. A.; Paez, A. I.; Feldner, H. A.; Looper, J. E.; Kretch, K. S.

2026-05-12 rehabilitation medicine and physical therapy 10.64898/2026.05.05.26352150 medRxiv
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ImportanceChildren with Down syndrome (DS), a genetic condition associated with neuromotor impairments, walk [~]1 year later than typically developing peers. Treadmill training is the most successful known intervention for accelerating walking onset in DS. Overground stepping with mobility devices better mimics critical properties of real-world walking, but it is unknown how overground stepping develops in pre-walking infants with DS. ObjectiveWe aimed to characterize the developmental trajectory of stepping quantity and quality in supported overground stepping compared to supported treadmill stepping. We also measured infants ability to self-propel in the walker. Finally, we assessed caregivers perspectives on both devices. DesignWe tested infants at 10, 13, 16, and/or 19 months of age. SettingThis study occurred in a university laboratory in the United States. ParticipantsWe tested 31 pre-walking infants with Down syndrome across 69 sessions. ExposureAt each session, infants completed four trials per task (treadmill and walker) and a test of self-propulsion in the walker. Main Outcomes and MeasuresWe measured step quantity (overall step rate and alternating step rate), step quality (percentage of steps that were alternating, forward, and flat-landing), the ability to self-propel the walker, and caregiver perspectives on both devices. ResultsStep quantity increased with age and varied by task--infants took more steps per minute in the walker compared to the treadmill. Moreover, steps were of equal or higher quality in the walker. By 16 months, about half of infants could self-propel. Caregivers viewed both devices favorably, though the majority preferred the walker for home and/or community use. ConclusionsOverground walkers promote more stepping than a treadmill in pre-walking infants with DS, with stepping of similar or higher quality. Caregivers feel positively about overground walkers. RelevanceOverground stepping using a suspension walker shows promise as an intervention for pre-walking infants with Down syndrome.

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Predicting Phage Host Interactions Across Taxonomic Levels: A Systematic Review and Meta-Analysis for Microbial Ecology

Romero-Calle, D. X.; Yucra Rojas, M.; Middelboe, M.

2026-04-30 microbiology 10.64898/2026.04.28.721508 medRxiv
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The prediction of phage-host interactions is key for several applications in biotechnology, medicine, and microbial ecology. Wide studies in machine learning tools have allowed the exploration of these interactions across multiple taxonomic levels. A systematic review and meta-analysis were conducted on 570 records retrieved from PubMed, Scopus, and Web of Science. Eleven studies were selected for the meta-analysis, encompassing 61 datasets. Precision across taxonomic levels (Domain, Phylum, Class, Order, Family, Genus, Species) was evaluated for several prediction tools. Statistical tests, including the Shapiro-Wilk and ANOVA tests, were used. A mixed-effects meta-regression model was used to examine the impact of taxonomic subgroups on the prediction of the proportion of Correctly Predicted PHIs. The results indicated significant variability in the performance of prediction tools across taxonomic levels. Domain-level predictions exhibited near-perfect Proportion of Correctly Predicted PHIs (0.99), whereas finer resolutions (Family and Order) showed considerable variability, with average precision values of 0.682 and 0.775, respectively. The mixed-effects meta-regression analysis revealed that Family and Species taxonomic subgroups were associated with significant reductions in the prediction Proportion of Correctly Predicted PHIs with effect sizes of -0.1464 and -0.1944, respectively. Residual heterogeneity was negligible, indicating that the moderators adequately explained the variability in prediction precision. This study highlights the importance of selecting the appropriate prediction tool based on the desired taxonomic resolution. The findings emphasize the need for further refinement of prediction algorithms, particularly at the Family and Species levels, where tools exhibit the most variability. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=136 SRC="FIGDIR/small/721508v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@4105bforg.highwire.dtl.DTLVardef@e07c46org.highwire.dtl.DTLVardef@1ff139corg.highwire.dtl.DTLVardef@1608690_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical Abstract.C_FLOATNO Overview of the systematic review and meta-analysis framework evaluating ML-based phage-host interaction prediction tools across taxonomic levels. C_FIG

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Healthy Heart Actions Right Time (HHART): Co-design priorities to connect Aboriginal and Torres Strait Islander community and clinic activities for healthy hearts

Wyber, R.; Zagler, J.; Liu, C.; Yadav, U. N.; O'Dwyer, Z.; Hart, K.; Chapman, K.; McGrady, L.; Kohn, A.; Winterfield, N.; Williams, D.; Watson, N.; Morey, K.; Pearson, O.

2026-06-10 primary care research 10.64898/2026.06.05.26354870 medRxiv
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Aim: Healthy Heart Actions Right Time (HHART) is a multi-phased research project that seeks to identify, implement and evaluate strategies to connect community and clinical activities to reduce the burden of heart disease for Aboriginal and Torres Strait Islander people. The aim in Phase One was to identify priority activities for two participating services. Background: The ongoing effects of colonisation drive a disproportionate burden of heart disease for Aboriginal and Torres Strait Islander people. Clinical and community groups both have established strengths in reducing the risk of heart disease, but these are not always well connected. Methods: Using a case study methodology in two locations we partnered in a 12-month co-design process to identify priority activities to connect clinical and community activities. Findings: Three priorities emerged from the Phase One co-design process: (i) community-led gardening as a strategy to promote heart health through connection and healthy lifestyles; (ii) community days to increase engagement in heart checks and strengthen community-clinic relationship; and (iii) clinic-led development of culturally relevant education resources to promote clinician confidence and community heart health knowledge.

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Clinical Predictors of Emergence Delirium in Children: A Prospective Cohort Study

Myasnikova, V. V.; Mausheva, S. K.; Aksenova, L. E.

2026-06-03 anesthesia 10.64898/2026.06.01.26354640 medRxiv
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Abstract Objective. To determine the incidence and identify independent clinical predictors of emergence delirium (ED) in children aged 2-12 years. Material and methods. A prospective observational study included 56 children aged 2-12 years undergoing elective surgery under general anaesthesia. Preoperative anxiety (m-YPAS), induction behaviour (4 point scale), anaesthesia duration, opioid use, and postoperative pain (FLACC) were assessed. ED was diagnosed when the maximum PAED score was [&ge;]12. Results. The incidence of ED was 55.4% (31/56). Univariate analysis with false discovery rate (FDR) correction identified significant associations with ED for anaesthesia duration (q=0.002), induction behaviour (q=0.007), and surgery type (q=0.027). Multivariable logistic regression revealed three independent predictors: induction behaviour (category 3 vs 1) - odds ratio (OR) 14.2 (95% CI 2.6-78.1); anaesthesia duration (per minute) - OR 1.07 (95% CI 1.02-1.13); opioid use - OR 12.1 (95% CI 1.3-113.0). The model showed good discriminatory ability: area under the ROC curve (AUC) = 0.83 (95% CI 0.72-0.94). Conclusion. Emergence delirium in children aged 2-12 years without pharmacological premedication occurs in 55.4% of cases. The strongest independent predictors are adverse induction behaviour, longer anaesthesia duration, and intraoperative opioid use. The derived model can be used for personalised risk stratification of ED. Keywords: emergence delirium; children; risk factors; PAED; prediction model.

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Influences on Preventive Health Behaviors After Stroke with Telemonitoring: Patient Perceptions and Practices

Naqvi, I. A.; Fisher, K.; Strobino, K.; Arcia, A.; Bassile, C. C.; Patel, S. R.; Cheung, K.; Stein, J.; Williams, O. A.; Elkind, M. S. V.; Kronish, I. M.; Quinn, L.

2026-05-04 neurology 10.64898/2026.04.28.26352004 medRxiv
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BackgroundAlthough Blood Pressure (BP) self-management and physical activity (PA) are secondary stroke preventive behaviors, adherence gaps exist. This study explored factors influencing these behaviors after telemonitoring experience among patients in an underserved urban community. MethodsWe conducted semi-structured interviews with purposive sampling of patients discharged home after mild stroke who had hypertension and participated in the Telehealth After Stroke Care (TASC) trial. Self-reported short form (SF) surveys included Patient Reported Outcomes Measurement Information System-Physical Function-SF, International Physical Activity Questionnaire-SF, and University of Rhode Island Change Assessment. The first interview assessed knowledge of BP and PA guidelines with perceived barriers, facilitators and BP telemonitoring experience, while the second was after PA monitoring for one month. We performed open (inductive) and social cognitive theory-based (deductive) coding. ResultsWe included 14 participants: mean age 59 {+/-} 9.6 years; 7 women (50%); 57% Black, 29% Hispanic; 29% [&le;] high school education, 43% Medicaid or no insurance. Mean daily step count was 5147 {+/-} 2534. Three themes interpreted included: 1) positive outcome expectations; 2) self-efficacy; and 3) agency. Participants associated BP control with reduced recurrence risk and PA to functional recovery (1) but lacked knowledge of specific targets (2). High self-efficacy individuals (2) used action planning to navigate environmental constraints. Both BP and PA monitoring with feedback facilitated self-regulation, goal setting and problem solving (3). ConclusionGaps between knowledge of and participation in health behaviors after stroke persist. Targeting outcome expectations, self-efficacy, and agency through educated training, tailored support, and telemonitored feedback may promote sustained positive health behaviors.

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Patients' Ideas, Concerns, Expectations in Physiotherapy: A Questionnaire Study

Dani, R.; Dave, D.

2026-04-06 rehabilitation medicine and physical therapy 10.64898/2026.04.06.26350229 medRxiv
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Global healthcare is targeting patient-centred care, as it leads to better health outcomes and higher level of patient satisfaction. Patient-centred communication, is an important part of patient-centred care because it focuses on involving patients in their care. Recent surveys both nationally and globally have shown that patients are not involved enough in their own healthcare decisions. This problem is especially common among the elderly with chronic conditions. This study aimed to describe patient-healthcare professional interactions, expectations, and satisfaction in physiotherapy within an understudied context, thereby providing important, specific data on ICE dynamics and satisfaction in the specific setting. Cross-sectional study of participants in scheduled consultations was conducted. Two government physiotherapy centres, seven private physiotherapy centres and two trust centres with physiotherapy facilities in Gujarat, India. 232 patients (from various public and private physiotherapy clinics) participated in the study. Patients' ideas, concerns, expectations (ICE) and satisfaction were explored. Almost 88% of patients reported their thoughts and explanations about their symptoms during the consultation. Most patients described not having any concerns about the diagnosis/treatment, and more than two-third of patients consulting PTs expected explanation for their symptoms. Almost 90% patients were satisfied with the consultation. The study revealed that while most patients conveyed their thoughts during consultations, very few expressed their concerns. Overall, patients were satisfied with their consultations.

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Impact of high-fat Western diet on chronic lymphocytic leukemia disease progression and gut microbiome profile in Eμ-TCL1 mice

Skupa, S. A.; Hernandez, J. B.; Smith, A. L.; Drengler, E. M.; Seth, A. K.; Rai, S. N.; Clayton, J. B.; D'Angelo, C. R.; El-Gamal, D.

2026-04-01 cancer biology 10.64898/2026.03.30.715124 medRxiv
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BackgroundThe composition and function of the gut microbiome have been shown to contribute to both health and disease. One of the most powerful modulators of microbial composition and function is diet. Materials & MethodsUsing the E{micro}-TCL1 murine model of B-cell chronic lymphocytic leukemia (CLL), we assigned male and female mice to a high-fat, high-carbohydrate Western diet (HF) or standard chow (CH) diet. ResultsMice consuming a HF diet had significantly shorter survival than those consuming a CH diet, irrespective of sex, with female mice exhibiting particularly poor outcomes. We also observed a significant increase in splenic involvement by CLL in the HF diet-fed mice at time of sacrifice. Mice receiving the HF diet demonstrated immediate and profound effects on the gut microbiome, marked by reduced alpha diversity and significantly different community composition as measured by beta diversity. Notably, there was a sustained increase in Akkermansia muciniphila and Bacteroidetes thetaiotaomicron in HF diet-fed mice, coupled with a corresponding increase in microbiome functional pathways related to arginine and histidine biosynthesis, chitin degradation, and nucleotide biosynthesis. DiscussionCollectively our data provides evidence of the profound and sustained impact of a high-fat Western diet upon the gut microbiome community and CLL pathogenesis in the E{micro}-TCL1 murine model of CLL.

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Epidemiology and Associated Risk Factors of Diabetic Retinopathy in Patients with Diabetes Mellitus Attending a Tertiary-care Hospital in Hargeisa, Somaliland

Woredekal, A. T.

2026-03-31 ophthalmology 10.64898/2026.03.29.26349614 medRxiv
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Purpose Diabetic retinopathy (DR) is one of the most important complications of diabetes mellitus (DM), representing the leading cause of blindness among working age adults in developed countries. This study was aimed to investigate the epidemiology and risk factors of DR in patients with diabetes mellitus in a hospital setting in Somalia. Methods The study was an observational, descriptive cross-sectional and hospital-based study and data were collected from January 2023 to May 2023. A structured questionnaire was used to collect relevant demographic and clinical data. Both univariate and bivariate tables were used for analysis. Data analysis included frequency distribution, cross-tabulation, co-relation and association, and statistically significant tests between variables (X2, p-value, and CI). Results A total of 384 DM patients were studied and 76% (n=293) of them had type 2 DM. The average duration of diabetes mellitus was 9.7 SD 6.9 years and the mean age was 47.24 SD 19.36 years (range 18 -100 years old). A majority 66% (n=253) were female, about a third of them had normal body mass index (BMI) (n=172, 44.8%) and 170 (44.3%) had concomitant hypertension. About 51% of the patients (n=197) had DR out of which 17% had non-proliferative diabetic retinopathy (NPDR) (n=67) and 26% had Macular oedema (n=98). Age above 40 years (p=0.020), marital status (P=0.010), employment status (P=0.002) and literacy status (P=0.020) were significantly associated with the presence of DR. Patients aged below 40 had 37% lesser risk of having diabetic retinopathy than patients aged above 40 years. Longer duration of diabetes (p=0.001) and the presence of concomitant cardiac illness (p=0.001) were strongly associated with the presence of diabetic retinopathy. Patients with duration of diabetes more than 10 years had approximately 2 times higher chance of developing DR than those with duration less than 10 years. Conclusion: The very high prevalence of DR (51%) among our patients implies the needs for a good health policy to manage DM and DR patients in Somalia. Effective regular eye screening and treatment for all diabetes patients should get priority.

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Participant engagement and feedback in microbiome projects: a case of AWI-Gen 2

Nkera-Gutabara, C.; Olubayo, L. A. I.; Oduaran, O. H.; Kisiangani, I.; Khoza, S.; Gama, K.; Maritze, M.; Mabunda, C.; Keya, D.; Adetunji, K. E.; Tollman, S.; Micklesfield, L. K.; Mohamed, S. F.; Gomez-Olive, F. X.; Tluway, F.; Ramsay, M.; Bhatt, A. S.; Hazelhurst, S.; Maghini, D. G.; AWI-Gen Collaborative Centre, ; MADIVA Research Hub,

2026-04-22 scientific communication and education 10.64898/2026.04.20.718838 medRxiv
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Returning individualized microbiome results in ways that are ethical, comprehensible, and useful remains under-explored in African settings. We nested a multi-site, mixed-methods study within the AWI-Gen Wave 2 gut microbiome sub-study of 1,801 women aged 42 - 86 years to engage the participants and provide feedback. All (1,001) participants from Agincourt and Soweto (South Africa) and Nairobi (Kenya) were invited to feedback meetings: 496 from Agincourt, 87 from Soweto, and 195 from Nairobi responded. Engagement strategies were tailored by site (small-group and home-based sessions, visual metaphors, Foldscopes, and local-language delivery). Using semi-structured discussions and structured observations analysed thematically in MAXQDA under COREQ, five cross-cutting themes emerged: (1) understanding of microbiome reports, (2) emotional responses to feedback, (3) perceived health relevance, (4) trust in research institutions, and (5) suggestions for improving engagement. Culturally grounded explanations and local-language facilitation enhanced comprehension and perceived relevance; English-heavy sessions were associated with more confusion. Most participants expressed satisfaction and described planned or enacted dietary and lifestyle changes, while frustration centred on long delays between sampling and feedback. Trust increased with transparency and individualized return of results but was often conditional on minimizing burdensome procedures such as repeat blood sampling (phlebotomy) and ensuring timely feedback. Engagement was feasible and low-cost (approximately USD 29-59 per participant) with site-specific resource needs. Limitations included constrained generalizability beyond the three study sites. Returning individualized microbiome findings in community settings in Africa is acceptable, feasible, and can motivate health-promoting behaviours when delivered promptly and in culturally and linguistically appropriate ways. IMPORTANCEMicrobiome studies rarely return individualized results in low-resource settings due to concerns about appropriate feedback and associated costs. This gap risks eroding trust and diminishing research impact. In three African communities, tailored feedback on gut microbiome profiles was provided to 778 women. By documenting a costed, multi-site engagement model and the themes influencing acceptance and actionability, this work offers a practical framework for ethically returning complex -omics results at scale in underrepresented populations - advancing scientific equity and strengthening community trust in microbiome research.

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Long-term impact of Training the Trainers program on Primary Eye Care networks in Malawi using the Arclight Project package

Windle, T.; Maliko, F.; Burgiss-Kasthala, S.; Blaikie, A.

2026-04-02 ophthalmology 10.64898/2026.03.31.26349901 medRxiv
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Background The World Health Organisation (WHO) advocates integrating primary eye care (PEC) within community health systems, supported by task-shifting and frugal technologies. While low-cost tools such as the Arclight device and Wilson anterior segment loupe have demonstrated training and diagnostic value, their long-term impact on community health worker (CHW) roles and professional networks remain poorly understood. Methods We conducted a qualitative follow-up study 3 years after implementation of an Arclight Project enabled cascade training of the trainers (ToT) PEC programme in central Malawi. Ophthalmic Clinical Officers (OCOs) trained using the Arclight training and diagnostic package subsequently cascaded PEC training to Health Surveillance Assistants (HSAs). Semi-structured interviews were undertaken 3 years later with OCOs and HSAs to explore device use, evolving professional roles, training diffusion, and communication patterns. Data were analysed thematically, informed by concepts from social network analysis to examine changes in advice-seeking, mentorship and peer collaboration. Results Frugal eye-care technologies functioned not only as diagnostic tools but as mechanisms of professional repositioning. HSAs equipped with low-cost diagnostic devices became recognised as community eye focal persons, receiving referrals from colleagues and community members. OCOs who delivered training emerged as central hubs for clinical advice and ongoing training, creating strong vertical networks between district and community levels. However, horizontal peer-to-peer networks among HSAs remained weak and largely informal. Communication relied heavily on ad-hoc phone calls and WhatsApp messaging, with limited structured communities of practice. Despite sustained use of devices and retention of key skills, network activity often declined over time without active reinforcement. Conclusions Frugal eye-care technologies act as social as well as clinical interventions, reshaping CHW networks and professional hierarchies. Designing PEC programmes with explicit attention to strengthening and sustaining professional networks, rather than focusing solely on skills transfer, may further enhance alignment with WHO Integrated People-Centred Eye Care and improve long-term programme sustainability and impact.

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Pre-analytical delay of blood cultures: poor compliance with the recommended standard is linked to laboratory centralisation.

Noone, M. r.

2026-03-22 pathology 10.64898/2026.03.19.26348778 medRxiv
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BackgroundUnited Kingdom Standards for Microbiology Investigations limits the pre-analytical delay of blood cultures to a maximum of four-hours between collection and incubation. Compliance with this delay standard is a measure of the ability of a microbiology service to support the management of sepsis which is a life-threatening complication of infection. A positive blood culture confirms the infection and an early result is critical to the effective management of the condition. Delayed results lead to the prolongation of empiric broad spectrum antimicrobial therapy which is considered a causal factor in the emergence of antimicrobial resistance. This retrospective observational study documents compliance with the standard by microbiology services in England in 2022/23. The impact of laboratory centralisation on the ability of microbiology services to comply with this standard is examined. MethodsFreedom of Information requests were submitted to 116 National Health Service Trusts/administrative units in England requesting retrospective audit data showing compliance with the recommended pre-analytical delay standard. Data relating to service configuration and cost were also requested. ResultsResponses were received from 89 Trusts (76.7%) managing 146 hospitals. Overall, the rate of compliance was low, with only four hospitals (2.7%) showing full compliance and 31.5% showing >80% compliance. ConclusionsPoor rates of compliance with the PAD standard are a concern as prompt attention to blood cultures improves patient outcomes from sepsis and supports antimicrobial stewardship. Laboratory centralisation has resulted in withdrawal of staff and facilities from some hospitals with insufficient investment in others, leading to a demonstrable inability of many hospitals to comply with this standard. Compliance will require investment in microbiology services. The financial implications of the improvements proposed should be evaluated in the context of overall health care and community benefits.