F1000Research

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.

Research using model organisms to tackle questions in life sciences and biomedical sciences has been in the spotlight of scientific literature for the better part of the twentieth century. This attention has perceptibly faded over the last twenty years, at least. We set to document this process by examining the publication trends of 48 journals encompassing a broad range of topics and impact factors for eight classic model organisms. We found that the representation of model-organism research has been in continuous decline in the last three decades, with a significant acceleration since 2010. We investigated the origin of the change, from the size of research communities to the shifts in topics and in use of model organisms. While model organism communities appear stable, model organism papers are outpaced by the rest of scientific literature. Also, among papers using model organisms, we note a progressive shift toward applied research, with differences between different model organism species. The mouse, in particular, logically remains the preferred system to study diseases, while non-mouse model organisms continue to be used predominantly to dissect mechanisms of life. We reflect on the consequences of the fading representation that we measured for the future of life sciences. Fundamentally, model organisms afford a direct access to causality in life sciences and their fading from the picture may impact life sciences as a whole. More pragmatically, it will also affect funding, and thereby jeopardizes the maintenance of model organism resources such as repositories built over decades.

PurposeThis study aimed to compare the reliability of myopia-related information from AI chatbots using a set of commonly asked questions by parents and patients on myopia, which is an emerging disease of the 21st-century. DesignProspective comparative reliability study MethodsThe study used ChatGPT(OpenAI(2025)GPT-5), Gemini(Gemini 2.0,Google,2025) and DeepSeek (DeepSeek-R1). Twenty myopia-related questions were framed from the perspective of parents and patients, covering general questions, prevention and control, and complications of myopia. Based on their experience in the field of myopia, two senior clinicians, one junior clinician and one researcher(all[≥]3 years of experience in myopia) rated the responses generated by AI chatbots on a 5-point Likert scale(1:very poor, 2:poor, 3: acceptable, 4:good and 5:very good). ResultsOverall, combined rating for tested chatbots had median score of 4("good"). Gemini received significantly lower ratings than other two chatbots (p[≤]0.001), with a median rating of 3("acceptable"). ChatGPT and DeepSeek had median score of 4("good") and there was no significant difference in ratings (p=0.48). Both ChatGPT(66.0%) and DeepSeek(67.5%) had high proportions of "good" and "very good" ratings, compared to Gemini(40.0%). Combined "poor" and "very poor" ratings were highest for Gemini(7.5%), followed by ChatGPT(5.0%) and DeepSeek(4.0%). For general questions on myopia, ChatGPT and DeepSeek were rated "good"; for complications of myopia, ChatGPT was rated as "good", while others were rated "acceptable". ConclusionsChatGPT and DeepSeek demonstrated consistently high-quality responses, while ratings for Gemini were slightly lower but remained adequate. These findings suggest AI chatbots can support patients or parents in understanding myopia.

Age related macular degeneration is known to be one of the major causes of irreversible blindness among the older generation. We present a mathematical model of partial differential equations for the therapy of this disease, which is based on the intravitreal injection of a drug into the vitreous body. For the treatment to work, the drug has to travel past the inner-limiting membrane into the retina and reduce the free vascular endothelial growth factor (VEGF) concentration by binding to at least one of the two binding sites of the VEGF molecule. Therefore, our model consists of two compartments, the vitreous and the retina. In the vitreous we employ four coupled convection-diffusion-reaction equations with an additional coupling to the underlying aqueous humor flow and four coupled diffusion-reaction equations in the retina. The resulting PDE system is solved numerically in a realistic 3D eye geometry. Temporal discretization is based on one-step theta schemes and spatial discretization is done using the Finite Element method. The numerical results are used to demonstrate the therapy concept and to analyze the drug efficacy of aflibercept and ranibizumab. The results show, among other things, that only about 20 % of the drug reaches the retina through the inner-limiting membrane and that 50 % of the VEGF concentration has been rebuilt in the retina after 38.19 days for a single ranibizumab injection.

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.

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.

ObjectivesTo investigate how nutrition readiness to change influences implementation of dietary behavior changes and to compare the gut microbiomes and document gut microbiome composition changes over time in individuals with early Alzheimers disease dementia (eAD), mild cognitive impairment (MCI), and healthy controls (HC) Overall, this study aims to add to the emerging field of how the gut microbiome influences the nervous system. MethodsThis is a sub-study of a multi-prong proof-of-concept, observational study mapping the gut microbiome: 15 HC, 15 MCI, 15 eAD (n=45). At 0-, 3-, and 6-months, participants are provided lifestyle recommendations tailored to their gut microbiome. Participants may choose to implement this or not and are observed throughout (observational intervention study). In this sub-study, a survey is developed and implemented in conjunction with dietary assessment (DietID) to evaluate the role of Readiness to Change in implementation of dietary recommendations. ResultsThis is the sub-study protocol from an ongoing parent study. DiscussionThis protocol presents a novel intervention to assess the gut microbiome, individual dietary patterns, and readiness to make lifestyle change related to diet. Trial RegistrationNCT06039267

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.

ObjectiveMore people than ever before are living with cancer. Patient education is a core component of cancer care, and patients are increasingly using large language models (LLMs), such as ChatGPT, for advice. The objectives of this study were to evaluate the ability of ChatGPT to explain specialist cancer care records (multidisciplinary team (MDT) meeting reports) to patients and to understand key stakeholders views and opinions about the technology. MethodsSix simulated MDT meeting reports were created by cancer clinicians. MDT reports and 184 realistic patient-centred queries were input into ChatGPT4.0 web version. We conducted a mixed-methods study combining qualitative analysis with exploratory quantitative components to evaluate ChatGPTs responses. The study consisted of three stages: (1) Clinician sense-checking, (2) Clinical and non-clinical annotation, (3) focus groups (including cancer patients, caregivers, computer scientists, and clinicians). ResultsChatGPT was able to summarise complex oncology information into simpler language, to provide definitions of complex terms and to answer questions about clinical care. However, clinician sense-checking identified problems with accuracy, language and content. In clinician annotation, 92.6% of ChatGPTs responses were judged problematic. Across all evaluation methods, six recurring themes were identified: accuracy, language, trust, content, personalisation and integration challenges. Patients and clinicians found the summaries and definitions useful; however, the responses were not tailored to the individual patient or to what the report might mean for them. ConclusionThis study highlights current challenges in using LLMs to explain complex cancer diagnoses and treatment records, including inaccurate information, inappropriate language, limited personalisation, AI distrust and challenges in integrating LLMs into clinical workflow. Understanding of the limitations is crucial for clinicians, patients, computer scientists and policy makers. The issues should be addressed before deploying LLMs in clinical settings.

PurposeRobotic walkers are a new and novel technology with growing evidence of benefits for children living with mobility impairments. However, little is known about how using these devices at home impacts families. This study aims to explore parents perceptions of home-based robotic walking and the impacts on their family and their child living with a mobility impairment. Materials and MethodsQualitative interviews were conducted with seven parents who have a child who used a robotic walker in their home for at least six months. Thematic analysis was used to analyze all interviews. Themes were then mapped to the F-words for child development. ResultsUsing a robotic walker at home led to family bonding and created new ways for parents and siblings to interact with the child living with a mobility impairment. Many children enjoyed using the robotic walker. This, combined with being able to direct its use in their own environments, contributed to less parental stress than was associated with other rehabilitation interventions. However, some parents discussed an increase in parental stress due to certain logistical aspects, getting their child in and out and transporting the robotic walker. Finally, parents discussed that obtaining the device was a financial burden for them. ConclusionRobotic walking in the home environment impacts family relationships and parental stress. Understanding families experiences can inform decision-making by families and practitioners around the appropriateness of robotic walker use for a child living with a disability.

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

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.

AimsPrimary objective: To determine the minimum inhibitory concentration (MIC) of key antifungal drugs (natamycin, amphotericin B, voriconazole and econazole) against fungal isolates cultured from fungal keratitis patients in South India. Secondary objective: to ascertain correlations between antifungal resistance and patient outcome. MethodsIn this prospective observational study, MIC values were determined for fungal isolates cultured from 153 patients, with samples collected between May - August 2025. Clinical characteristics were collected at baseline, one-week and one-month following enrolment to the study. Mean antifungal MIC per fungi genera were compared. Statistical differences in MIC and patient characteristics were determined via multiple logistic or linear regression. Significance for participant outcome against resistant/non-resistant fungi were determined by Fishers exact test. ResultsResistance of Fusarium spp. isolates to: natamycin: 38.3%; amphotericin B: 93.8%; voriconazole: 97.5% and econazole: 76.5%. Resistance of Aspergillus spp. isolates to: natamycin: 66.7%; amphotericin B: 87.9%; voriconazole: 6.1%; and none were resistant to econazole. Natamycin MIC correlated with worse baseline (P[&le;]0.01) and one-week (P[&le;]0.05) visual acuity and ulcer severity. Poor patient outcomes (non-healing or therapeutic keratoplasty) were elevated 6.5x where the infection was caused by natamycin resistant Aspergillus, compared to sensitive Aspergillus strains (P[&le;]0.05). ConclusionThe majority of fungal isolates were resistant to multiple antifungals, none of the Fusarium isolates were sensitive to all four drugs, and 15% were resistant to all four drugs. Aspergillus isolates had high levels of resistance to the polyenes, but remained largely susceptible to the azoles. Overall, worse patient outcomes were associated with increased natamycin MIC. Key MessagesO_ST_ABSWhat is already known on this topicC_ST_ABSFungal keratitis is a major cause of blindness worldwide, disproportionately affecting those across the tropics, with incidence increasing across temperate climates. The majority of cases are caused by the filamentous fungi Fusarium spp. and Aspergillus spp.. Antifungal resistance is poorly characterised in fungal keratitis. What this study addsWe report the fungal aetiology and the minimum inhibitory concentration (MIC) against natamycin, amphotericin B, voriconazole and econazole of isolates cultured from 153 patient corneal scrape samples between May - August 2025 at a South Indian hospital. We found high levels of fungal resistance, with Fusarium isolates having high levels of resistance to both polyenes and azoles. Aspergillus isolates showed good azole sensitivity, but high levels of resistance to polyenes. Aspergillus resistance to natamycin correlated with worse clinical outcomes at one-month. Natamycin resistance contributed to worse visual acuity and ulcer severity at baseline and one-week follow-up across all fungi. How this study might affect research, practice or policyOur study confirmed that natamycin was best available first-line treatment for Fusarium. Aspergillus isolates were mostly resistant to natamycin and amphotericin B, and this impacted patient outcomes. SynopsisWe identified high incidence of multi-drug resistant fungi, and that patients were more likely to have a poor clinical outcome if the fungal isolate was resistant to natamycin. This was most pronounced for Aspergillus isolates.

Metastatic breast cancer is responsible for around 11,500 deaths a year in the UK. The primary tumour likely plays a major role in priming the distant site for metastasis and crosstalk between primary and metastatic sites may be essential for secondary tumour growth. We have developed a novel in vitro model in which we can further study these interactions; evaluating niche priming and cancer cell conditioning as well as assessing their influence on cell homing and colonisation. In this paper we describe a model that we believe adds to the array of in vitro tools available to study various stages of the metastatic cascade, offering a unique opportunity to assess bidirectional, primary to niche interactions in vitro. We show that proliferation, migration and chemotaxis, and stem cell activity are altered in both cancer cell lines and in lung epithelial cells following linked, fluidic culture. Changes in cell homing and colonisation can be modelled in cell lines and within viable lung tissue explants taken from mice, with breast cancer cells settling and growing within the lung epithelial cells and tissue explants over 7 days. The colonisation/growth of cells injected into the system closely represents that seen following tail vein injection and cancer cells can be seen to settle and grow within the lung epithelial cells.

BackgroundDespite recommendations in clinical guidelines, clinical experience indicates that engagement with splints and orthotics varies amongst people after stroke. ObjectivesThe aim of the study was to understand the factors that influence engagement with splints and orthotics in people after stroke. MethodsPeople after stroke who had been wearing a splint or orthotic (also known as devices) for at least 2 months under the care of one Community Neurosciences Team in the UKs National Health Service were included. Semi structured interviews based on the constructs of Banduras Social Cognitive Theory (SCT) were used to gather participants views, and a framework analysis applying the constructs of SCT was completed using NVIVO software. ResultsFour key themes were identified: 1. Self-Regulation; difficulties applying the device and aesthetic acceptability. 2. Self-Efficacy; increased confidence when wearing the device and reduced motivation to wear the device. 3. Outcomes Expectation; reduced falls risk, improved gait, improved balance, maintaining range of movement, and negative effects such as discomfort, pain, itching. 4. Social Support; support needed to apply the device and the burden on family members/carers to apply the device correctly. ConclusionsThe findings of this study highlight key factors that influence engagement with orthotics and splints. These include difficulty applying the device after stroke, device aesthetics, comfort, and the importance of continued support from carers. Manufacturers should consider how people after stroke can independently don and doff devices. Education of carers and family members also appears key to support their engagement.

IntroductionIndigenous groups across the world have been underrepresented in the ongoing efforts to map human microbiome diversity. This study investigates the gut microbiome and resistome diversities of three indigenous Malaysian (Orang Asli, OA) communities with different lifestyles and degree of urbanisation. We included an urban Malay group as a comparison. MethodsHealthy participants over 18 years old gave were recruited from three indigenous communities, namely Temuan (urban, n=12), Temiar (semi-urban, n=9) and Jahai (rural, hunter-gatherer, n=12), and Malay (urban, non-indigenous, n=9). Stools were collected on dry ice and sequenced using shotgun metagenomics. ResultsApproximately 65% of the reads were classified across the dataset. Microbial alpha diversity (Shannon) decreased but antibiotic resistance genes (ARGs) diversity increased as the degree of urbanisation in the groups increased (P < 0.05). The groups contributed to 13% of the variation observed in the microbial composition (PERMANOVA, P = 0.001), and 14.5% in resistome composition (PERMANOVA, P = 0.001). Romboutsia timonensis was significantly depleted in Jahai compared to Malay (FDR = 0.04). Shared ARGs conferring resistance to beta-lactams (cfxA), tetracyclines (tet), and macrolides (erm) were observed across all groups, irrespective of geographical location, ethnicity and lifestyle. ConclusionThis study provides initial characterisation of the gut microbiome and resistome of three underrepresented indigenous OA communities in Malaysia. Our findings offer foundational evidence of antimicrobial resistance patterns and underscores the need for broader inclusion of underrepresented populations in national surveillance and stewardship efforts.

Digital health technologies are powerful-enhancing data collection, participant engagement, and personalized health interventions-yet their rapid proliferation has outpaced guidance for research participant protection. Current practice assists researchers in identifying risks but provides limited support for comprehensive risk management. To address this gap, we developed the Digital Health Checklist-Risk Management (DHC-RM) Tool, which integrates the established Digital Health Checklist with approaches from safety risk management. We conducted a study (n=40) comparing the DHC-RM Tool with current practice using a randomized experimental difference-in-differences design. Primary outcomes were the quantity, variety, and novelty of risks identified; secondary outcomes were the same constructs applied to risk control development. Compared with current practice, use of the DHC-RM Tool resulted in dramatically improved performance across all primary outcomes. Users identified on average 14.7 additional risks (compared to baseline) versus 0.26 in the control group and a higher number of risks in each of six pre-identified risk domains. Half of all distinct risks identified in the comparison phase were identified exclusively using the tool. The tool also improved risk control design, producing 9.63 additional risk control strategies per participant compared with 0.15 for current practice and yielding substantially greater novelty and variety. User feedback was also positive: 75% of participants reported they would use the tool again, citing its structured workflow, just-in-time examples, improved insight into risks, and its value for IRB communication. Suggestions for refinement focused primarily on expanding training examples and providing additional support for risk control development. The DHC-RM Tool significantly improves risk management practice in digital health research. By embedding structured, ethics-informed risk management into digital health research design, the DHC-RM Tool has the potential to improve participant protection while also streamlining ethics approval. Author SummaryDigital health research can put participants (and others) at risk in ways that dont always occur to the researchers who are designing a study. Researchers also face challenges in prioritizing risks and coming up with ideas to reduce those risks. We developed a new approach, the Digital Health Checklist - Risk Management Tool (DHC-RM Tool), to give researchers the support they need to identify, assess, and address research participant risks in this fast-moving field. Our experimental study found that use of the DHC-RM Tool led to a very large improvement in how well researchers managed the risks of digital health research studies. Using the toolkit, they were able to identify more risks than they identified using current practice-including risks they would not otherwise have considered. They were also able to come up with more changes to reduce the risks associated with digital health research studies, including changes they would not otherwise have considered. Those who used the toolkit found it beneficial and easy to use. The DHC-RM Tool fills an important gap in the science and practice of participant protection in digital health research.

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.

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.

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.