Conectar
by Wenshu Li, Jeffrey A. Leibowitz, Shuoguo Wang, Louisa Walker, Chang Xu, Kuei-Ting Chen, Alexa B. Schrock, Jason Hughes, Nimesh Patel, Julia A. Elvin, Lauren L. Ritterhouse, Ethan Sokol, Garrett Frampton, Lucas Dennis, Bahar Yilmazel, Brennan Decker
Homologous recombination repair (HRR) is a cellular pathway for high-fidelity double strand DNA break repair that uses the sister chromatid as a guide to ensure chromosomal integrity and cell viability. Deficiency in the HRR pathway (HRD) can sensitize tumors to poly (ADP-ribose) polymerase inhibitors (PARPi) and platinum-based chemotherapy, offering an avenue to identify patients who may benefit from targeted therapies. HRD signature (HRDsig) is a pan-solid-tumor biomarker on the FoundationOne®CDx (F1CDx®) assay that employs a DNA scar-based approach to calculate a score based on copy number features (e.g., segment size, oscillation patterns, and breakpoints per chromosome arm) and does not rely on HRR gene alterations, enabling detection of genomic and epigenetic mechanisms of HRD. After finalizing the HRDsig algorithm, analytical validation was conducted in a CAP-accredited, CLIA-certified laboratory on 278 solid tumor and normal tissue specimens. HRDsig results were compared with an independent HRD biomarker, defined by the presence of a reversion mutation restoring HRR gene function. In this evaluation, 100 HRD-positive and 126 HRD-negative samples showed a positive percent agreement of 90.00% and a negative percent agreement of 94.44%. The limit of detection (LoD) was estimated at 23.04% tumor purity, with the limit of blank (LoB) confirmed as zero in 60 normal tissue replicates. Reproducibility testing on 11 positive and 11 negative samples across multiple labs, reagent lots, and sequencers yielded agreement in 99.49% of positive and 99.73% of negative replicates. HRDsig status remained consistent in the presence of interfering substances, demonstrating 100% concordance in spiked samples. These validation results underscore the high analytical concordance, low false-positive rate, and overall robustness of HRDsig for reliable assessment of homologous recombination deficiency.Community health workers (CHWs) are critical to healthcare delivery in low-resource settings but often lack formal clinical training, limiting their decision-making. Large language models (LLMs) could provide real-time, context-specific support to improve referrals and management plans. This study aims to evaluate the potential utility of LLMs in assisting CHW decision-making in Rwanda.
This is a prospective, observational study conducted in Nyabihu and Musanze districts, Rwanda. Audio recordings of CHW-patient consultations will be transcribed and analysed by an LLM to generate referral decisions, differential diagnoses and management plans. These outputs, alongside CHW decisions, will be evaluated against a clinical expert panel’s consensus. The primary outcome is the appropriateness of referral decisions. Secondary outcomes include diagnostic accuracy, management plan quality, and patient and user perceptions to ambient recording of consultations. Sample size is set at 800 consultations (400 per district), powered to detect a 15–20 percentage point improvement in referral appropriateness.
Ethical approval has been obtained from the Rwandan National Ethics Committee (RNEC) (Ref number: RNEC 853/2025) in June 2025, recruitment started in July 2025 and results are expected in late 2025. Results will be disseminated via stakeholder meetings, academic conferences and peer-reviewed publication.
PACTR202504601308784.
A novel advanced synthetic bioactive glass matrix was studied in patients with non-healing diabetic foot ulcers (DFUs). Bioactive glasses can be constructed to be biocompatible, with water-soluble materials in multiple geometries including fibre scaffolds that mimic the 3D architecture of a fibrin clot. In this trial, chronic, Wagner Grade 1 DFUs were randomised to receive borate-based bioactive glass Fibre Matrix (BBGFM) plus standard of care (SOC) therapy for 12 weeks or SOC alone. The primary study endpoint was the proportion of subjects that obtained complete wound closure at 12 weeks. Secondary endpoints included time to achieve complete wound closure at 12 weeks. In the modified intent-to-treat (mITT) analysis, 48% (32/67) treated with BBGFM plus SOC healed at 12 weeks compared to 24% (16/66) with SOC alone (p = 0.007). In the per protocol (PP) population, 73% (32/44) of subjects treated with BBGFM plus SOC healed versus 42% (16/38) in the SOC group (p = 0.007). Based on the success of this trial, BBGFM demonstrates faster healing of DFUs compared to SOC and should be considered in the treatment armamentarium for Wagner Grade 1 DFUs. Future trials should investigate the use of BBGFM for healing deeper chronic DFUs, other wound aetiologies, or complex surgical wounds.
To investigate whether quantitative retinal markers, derived from multimodal retinal imaging, are associated with increased risk of mortality among individuals with proliferative diabetic retinopathy (PDR), the most severe form of diabetic retinopathy.
Longitudinal retrospective cohort analysis.
This study was nested within the AlzEye cohort, which links longitudinal multimodal retinal imaging data routinely collected from a large tertiary ophthalmic institution in London, UK, with nationally held hospital admissions data across England.
A total of 675 individuals (1129 eyes) with PDR were included from the AlzEye cohort. Participants were aged ≥40 years (mean age 57.3 years, SD 10.3), and 410 (60.7%) were male.
The primary outcome was all-cause mortality. Quantitative retinal markers were derived from fundus photographs and optical coherence tomography using AutoMorph and Topcon Advanced Boundary Segmentation, respectively. We used unadjusted and adjusted Cox-proportional hazards models to estimate hazard ratios (HR) for the association between retinal features and time to death.
After adjusting for sociodemographic factors, each 1-SD decrease in arterial fractal dimension (HR: 1.54, 95% CI: 1.18 to 2.04), arterial vessel density (HR: 1.59, 95% CI: 1.15 to 2.17), arterial average width (HR: 1.35, 95% CI: 1.02 to 1.79), central retinal arteriolar equivalent (HR: 1.39, 95% CI: 1.05 to 1.82) and ganglion cell-inner plexiform layer (GC-IPL) thickness (HR: 1.61, 95% CI: 1.03 to 2.50) was associated with increased mortality risk. When also adjusting for hypertension, arterial fractal dimension (HR: 1.45, 95% CI: 1.08 to 1.92), arterial vessel density (HR: 1.47, 95% CI: 1.05 to 2.08) and GC-IPL thickness (HR: 1.56, 95% CI: 1.03 to 2.38) remained significantly associated with mortality.
Several quantitative retinal markers, relating to both microvascular morphology and retinal neural thickness, are associated with increased mortality among individuals with PDR. The role of retinal imaging in identifying those individuals with PDR most at risk of imminent life-threatening sequelae warrants further investigation.
Increasing physical activity and effectively managing stress can positively impact immunity and may reduce the duration of respiratory tract infections (RTIs). As part of a larger trial, participants accessed a digital behavioural change intervention that encouraged physical activity and stress management to reduce RTIs. We aimed to understand the barriers and facilitators to engaging in physical activity and stress reduction.
A qualitative process analysis from semistructured interviews of the behavioural intervention in a randomised control trial.
Primary care in the UK.
34 participants (aged 18–82 years) in the behavioural intervention arm.
The larger trial involved four interventions: a gel-based antiviral nasal spray; a saline water-based nasal spray; a behavioural intervention; usual care. In this study, we focused on participants allocated to the behavioural intervention. The behavioural intervention included two components: one to increase physical activity (getting active) and another for stress management techniques (healthy paths) to reduce RTIs.
We analysed the interviews using thematic analysis with a critical realist perspective (focusing on). We developed five themes: digital intervention engagement, views on intervention allocation, the role of getting active, the role of healthy paths and benefits reinforcing behaviour. Participants’ views on the relevance and benefit of the behavioural intervention shaped their engagement with the intervention website and behaviour. Facilitators of intervention engagement included awareness of inactivity, goal setting, increasing immunity, positive outcome expectations and benefits from changing behaviour. Barriers to engagement included negative outcome expectations, such as around efficacy of the behaviours.
Overall, the results highlighted the importance of positive expectations for a digital intervention promoting physical activity and stress management for RTI reduction. Future interventions should consider how to clearly communicate a broad range of perceived benefits to users.
The trial was prospectively registered with International Standard Randomized Controlled Trial Number (ISRCTN) registry (17936080).
The characteristics, application, and effectiveness of chatbots in improving the mental health of young people have yet to be confirmed through systematic review and meta-analysis.
This systematic review aims to evaluate the effectiveness of chatbot-delivered interventions for improving mental health among young people, identify factors influencing effectiveness, and examine feasibility and acceptability.
To identify eligible interventional studies, we systematically searched 11 databases and search engines covering a publication period of January 2014 to September 2024. Meta-analyses and subgroup analyses were performed on randomized controlled trials to investigate the effectiveness of chatbot-delivered interventions and potential influencing factors. Narrative syntheses were conducted to summarize the feasibility and acceptability of these interventions in all the included studies.
We identified 29 eligible interventional studies, 13 of which were randomized controlled trials. The meta-analysis indicated that chatbot-delivered interventions significantly reduced distress (Hedge's g = −0.28, 95% CI [−0.46, −0.10]), but did not have a significant effect on psychological well-being (Hedge's g = 0.13, 95% CI [−0.16, 0.41]). The observed treatment effects were influenced by factors including sample type, delivery platform, interaction mode, and response generation approach. Overall, this review demonstrates that chatbot-delivered interventions were feasible and acceptable.
This review demonstrated that chatbot-delivered interventions had positive effects on psychological distress among young people. Chatbot-delivered interventions have the potential to supplement existing mental health services provided by multidisciplinary healthcare professionals. Future recommendations include using instant messenger platforms for delivery, enhancing chatbots with multiple communication methods to improve interaction quality, and refining language processing, accuracy, privacy, and security measures.
To synthesize approaches used to evaluate nurse-led clinics (NLCs) and student-led clinics (SLCs) delivering community-based primary healthcare.
A scoping review based on Joanna Briggs Institute (JBI) guidelines.
This review included articles evaluating the impact of NLCs and SLCs, published between 2013 and 2023. The Quadruple Aim Framework for health systems quality improvement was a reference point for thematic analysis.
CINAHL Complete, ProQuest Nursing & Allied Health, PubMed, Scopus, Health Systems Evidence, Ovid Emcare and grey literature repositories were searched in March–June 2023.
Our search yielded a total of 891 articles and 43 articles were included in this scoping review. Diverse quantitative and qualitative methods and concepts of interest were evident in the evaluations of NLCs (n = 15), medical SLCs (n = 15) and interprofessional SLCs (n = 13). Extracted data spoke to the evaluation of either client experience, health of communities, systems of care delivery or provider experience, with systems of care delivery being the most consistently evaluated domain across all clinic types.
Traditional and non-traditional evaluation measures spanning the Quadruple Aim Framework were used to study community-based NLCs and SLCs. Opportunities remain for broadening the range of indicators and methods used to capture clinic impact on health equity.
Numerous transferable research approaches are available to students and clinical professionals for supporting the design and iterative improvement of innovative primary healthcare clinics.
The results highlight ways in which NLCs and SLCs may be evaluated for their concurrent impact on healthcare service delivery and clinical education systems.
PRISMA-ScR.
Feedback amassed during presentations to nursing audiences informed the enclosed discussion points.
Review protocol was published with the Open Science Framework under ID 10.17605/OSF.IO/FP6S4
To investigate the incidence and the factors associated with paternal postpartum depression amongst new fathers in Singapore.
A prospective repeated measures study was conducted from September 2023 to March 2024.
A total of 200 fathers aged 21 years and above who had a neonate born at full term and no serious health events for both mother and neonate were recruited from a local hospital via convenience sampling. Fathers completed questionnaires at the third trimester of pregnancy (baseline) and 1 month postpartum. Multiple regression analyses were used to identify significant factors associated with postpartum depression in fathers.
The incidence of paternal postpartum depression was 5.26% at 1 month post-childbirth, using the Edinburgh Postpartum Depression Scale (EPDS). Using the Gotland Male Depression Scale (GMDS), 7% of the fathers were identified with high risk of depression and 14.3% of the fathers had moderate depressive symptoms. Paternal postpartum depression at 1 month post-childbirth could be predicted by paternal postpartum depression scores at baseline measured by EPDS and GMDS, as well as by baseline perceived social support and parental self-efficacy at 1 month post-childbirth.
This study found that a considerable number of fathers in Singapore are at risk of postpartum depression. There is an urgent need for the development of more comprehensive tools to measure postpartum depression in fathers that are culturally adapted to the local context.
Early screening during antenatal visits enables timely intervention and access to support, benefiting the entire family. Nurses could help fathers to be more involved by extending patient education and teaching infant care skills to both parents. When counselling patients, the involvement of extended family members and navigating new roles as caregivers of a new baby and breadwinners are important considerations for new parents.
This study is the first of its kind to measure the incidence of postpartum depression amongst new fathers in an urban multicultural Asian setting, like Singapore. The study found that the incidence of postpartum depression in fathers were 5.26% when measured using EPDS and 14.3% when measured using GMDS at 1 month postpartum. These findings could inform future family-centred and father-specific interventions to improve the mental health outcomes of new parents.
This study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
No patient or public contribution.
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