AlphaMissense versus laboratory-based pathogenicity prediction of 13 novel missense CPA1 variants from pancreatitis cases

We have read with great interest the study by Wang et al1 in which the authors evaluated the utility of the AlphaMissense prediction programme2 (https://alphamissense.hegelab.org) in the classification of missense CPA1 variants with respect to pathogenicity in chronic pancreatitis. While the AI-driven prediction performed relatively well, the authors highlighted potential shortcomings that can limit its value in clinical practice. Defining the pathogenic potential of CPA1 variants detected in pancreatitis cases can be challenging because the mechanistic basis of disease risk is unrelated to loss of CPA1 function and seems to be determined by mutation-induced misfolding and the ensuing endoplasmic reticulum (ER) stress.3–5 Recently, we used transiently transfected HEK 293T cells to measure the secretion efficiency and induction of BiP mRNA expression, a marker of ER stress, for 50 missense CPA1 variants from pancreatitis cases and healthy controls.

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Factors associated with sleep quality among medical students in Vietnam: a national cross-sectional study

Objective
This study explored factors associated with sleep quality among medical students in Vietnam.

Design
Cross-sectional study.

Setting
The study was conducted from December 2019 to February 2020 among medical students in Vietnam.

Participants
Medical students were defined as those enrolled in undergraduate medical programmes. 1284 medical students who met the inclusion criteria participated in this study.

Outcome measures
The Pittsburgh Sleep Quality Index (PSQI) was used to measure participants’ sleep quality, with a score of 5 or higher indicating poor sleep quality. Multivariable logistic and linear regression models were employed to identify the factors associated with poor sleep quality.

Results
36.6% of the study participants had poor sleep quality. There were statistically significant differences in the percentage of poor sleep quality across genders, health-related quality of life, morbidity status and depression (p

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Randomised controlled trial of LGBTQ-affirmative cognitive-behavioural therapy for sexual minority womens minority stress, mental health and hazardous drinking: Project EQuIP protocol

Introduction
Sexual minority women represent one of the highest-risk groups for hazardous drinking and comorbid mental health problems (eg, depression, anxiety). Research has identified cognitive (eg, expectations of rejection), affective (eg, emotion dysregulation) and behavioural (eg, avoidant coping) pathways through which minority stress (eg, stigma) places sexual minority women at disproportionate risk of hazardous drinking and comorbid depression/anxiety; yet no evidence-based interventions have been tested to address these pathways in this population. This article describes the design of Project EQuIP (Empowering Queer Identities in Psychotherapy), a randomised controlled trial of a transdiagnostic lesbian, gay, bisexual, transgender, queer (LGBTQ)-affirmative cognitive-behavioural therapy intervention (CBT) designed to improve minority stress coping and reduce sexual minority women’s hazardous drinking and mental health comorbidities.

Methods and analysis
This two-arm randomised controlled trial, funded by the National Institute on Alcohol Abuse and Alcoholism, has two objectives: (1) test the efficacy of 10 sessions of LGBTQ-affirmative CBT compared with 10 sessions of supportive counselling for sexual minority women in the community (anticipated n=450) who report hazardous alcohol use and meet criteria for a Diagnostic and Statistical Manual of Mental Disorders – 5 diagnosis of a depression or anxiety disorder and (2) examine psychosocial mechanisms and demographic factors as potential mediators and moderators, respectively, of the treatment-outcome relationship. This study’s primary outcome is change in the proportion of heavy drinking days. Secondary outcomes are changes in depressive and anxious symptoms.

Ethics and dissemination
The Yale University Human Subjects Committee reviewed and approved the research protocol. Results of this study will be disseminated to researchers and practitioners through peer-review publications and conference presentations, and directly to study participants.

Trial registration number
Registered on 17 August 2022 (ClinicalTrials.gov identifier: NCT05509166).

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Effects of household concrete floors on maternal and child health: the CRADLE trial – a randomised controlled trial protocol

Introduction
Early life soil-transmitted helminth (STH) infection and diarrhoea are associated with growth faltering, anaemia, impaired child development and mortality. Exposure to faecally contaminated soil inside the home may be a key contributor to enteric infections, and a large fraction of rural homes in low-income countries have soil floors. The objective of this study is to measure the effect of installing concrete floors in homes with soil floors on child STH infection and other maternal and child health outcomes in rural Bangladesh.

Methods and analysis
The Cement-based flooRs AnD chiLd hEalth trial is an individually randomised trial in Sirajganj and Tangail districts, Bangladesh. Households with a pregnant woman, a soil floor, walls that are not made of mud and no plan to relocate for 3 years will be eligible. We will randomise 800 households to intervention or control (1:1) within geographical blocks of 10 households to account for strong geographical clustering of enteric infection. Laboratory staff and data analysts will be blinded; participants will be unblinded. We will instal concrete floors when the birth cohort is in utero and measure outcomes at child ages 3, 6, 12, 18 and 24 months. The primary outcome is prevalence of any STH infection (Ascaris lumbricoides, Necator americanus or Trichuris trichiura) detected by quantitative PCR at 6, 12, 18 or 24 months follow-up in the birth cohort. Secondary outcomes include household floor and child hand contamination with Escherichia coli, extended-spectrum beta-lactamase producing E. coli and STH DNA; child diarrhoea, growth and cognitive development; and maternal stress and depression.

Ethics and dissemination
Study protocols have been approved by institutional review boards at Stanford University and the International Centre for Diarrheal Disease Research, Bangladesh. We will report findings on ClinicalTrials.gov, in peer-reviewed publications and in stakeholder workshops in Bangladesh.

Trial registration number
NCT05372068.

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From Tragedy to Action—How to Collectively Move Forward

As physicians, most of us are aware of the high prevalence of burnout and depression among medical students, residents, our colleagues, and at times, ourselves. Existing data suggest that, overall, we start our professional journey in medicine with similar or better mental health and lower levels of burnout than other college graduates. However, once we are in medical school and postgraduate education, many of us experience high levels of chronic stress that contribute to depression, burnout, and other forms of distress; these conditions are experienced, on average, at levels higher than in other professions.

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Exploring the impact of COVID-19 hard lockdown on service provision for survivors of violence against women in South Africa: a qualitative study

Objective
To explore the impact of South Africa’s COVID-19 hard lockdown on the provision of services to survivors of violence against women (VAW).

Design
We conducted a qualitative study using semistructured interviews. Data was analysed thematically. We conducted 18 semistructured interviews (10 face-to-face and 8 online or by phone) with service providers and key informants (KIs).

Setting
The study was conducted across healthcare facilities, social services, national helplines and shelters in Gauteng province, South Africa. Data was collected between September 2022 and October 2023.

Participants
The sample included 18 participants, purposively selected, comprising 13 frontline service providers (nurses, social workers and managers) and 5 KIs. Participants shared their experiences of delivering VAW services during the lockdown.

Results
The findings highlight five key themes affecting VAW service provision during COVID-19. (1) Confusion and uncertainty: initial uncertainty about whether VAW services were essential led to temporary closures and reduced availability. (2) Decreased demand for services: fear of mobility restrictions and reporting barriers reduced access, particularly in the first lockdown month. (3) Adaptations by providers: services shifted to remote counselling, while shelters paused new intakes. (4) Challenges in service provision: staff shortages, resource constraints (eg, personal protective equipment shortages) and disrupted referral systems hindered service delivery. (5) Emotional impact on frontline workers: health and helpline workers faced stress, fear of infection, social stigma and burnout, affecting their well-being and capacity to respond effectively.

Conclusions
The study highlights how South Africa’s COVID-19 hard lockdown disrupted essential VAW services, emphasising the need for resilient service delivery models during crises. Strengthening staffing, resources and improving referral pathways are critical for mitigating the emotional and operational challenges faced by service providers and for ensuring sustained support for survivors.

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Efficacy of synovectomy in the treatment of femoral head osteonecrosis with vascularised fibular grafting in Shanghai: a protocol for SYNERGY-VGF trial

Background
Osteonecrosis of the femoral head (ONFH) is characterised by progressive bone death, leading to joint incongruity and eventual osteoarthritis. Various interventions have been explored to forestall disease progression and delay total hip arthroplasty (THA). Free vascularised fibula grafting (FVFG) has shown promise, particularly in the precollapse stages of ONFH. However, the potential benefits of combining synovectomy with FVFG to address synovitis in ONFH have not been systematically studied. This trial seeks to compare outcomes between patients undergoing FVFG with and without synovectomy.

Methods and analysis
The trial is a randomised, single-centre, parallel-group trial comparing FVFG with synovectomy versus FVFG alone in patients with ONFH and synovitis. 90 participants will be randomised into two groups: synovectomy (n=45) and non-synovectomy (n=45). The primary outcome is the Harris Hip Score (HHS) change at 12 months post surgery. Secondary outcomes include HHS, Numeric Rating Scale (NRS) for pain, Depression Anxiety Stress Scales-21 (DASS-21), and EQ-5D scale assessments at intervals up to 12 months post randomisation.

Ethics and dissemination
This trial was approved by the Human Research Ethics Committee of Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine prior to patient recruitment (approval number: 2023-076). Results from this trial will be published in peer-reviewed journals. Results will also be presented at international conferences.

Trial registration number
Chinese Clinical Trial Registry (ChiCTR) Identifier: ChiCTR2300073385. Prospectively registered on 10 July 2023.

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What are the lived experiences of patients with cancer and their families in northern Ghana? A qualitative study using narrative interview and creative task approach

Objectives
Cancer poses a major burden in Ghana that is exacerbated by poor engagement with biomedical treatment. The reasons for this are not well understood for most cancers and in northern Ghana.

Design
This research took combined narrative interviews with a creative task that was analysed through reflexive thematic analysis.

Setting
A tertiary treatment centre in northern Ghana.

Participants
15 adult ( >18 years) patients or their relatives who had been diagnosed and/or treated for cancer within the last 2 years.

Results
The thematic analysis highlighted the psychological burden of cancer and ways participants cope and find meaning, including through religion, trust in biomedical treatment, and occupation and social support. The findings stress the negative impact of the financial burden, shame, worry and the spiralling poverty this causes.
The creative task was found to be resonant, emotive and more humanising, which is anticipated to be more effective when communicating with policy-makers and community members. The findings provide rich contextual insights to understand patients’ and relatives’ perspectives and frame their experiences within what was important to them.

Conclusions
Together the research has identified a critical need for policy to consider the psychosocial, occupational, spiritual and financial needs of patients with cancer in northern Ghana. It has demonstrated narrative interviews with graphical elicitation as an effective approach to discuss sensitive topics for findings that can engage stakeholders and inform holistic cancer service design.

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Health workers conceptualisationand experiences of common mental symptoms and work-related psychosocial stressors in Central and Southern Ethiopian regions: a qualitative study

Objectives
Despite the growing recognition of mental health challenges among health workers, limited information regarding their self-identification of common mental symptoms (CMSs) and their perceptions of causal pathways to work-related psychosocial stressors exists. This study aimed to explore how health workers recognise CMSs, perceive their exposure to work-related psychosocial stressors, conceptualise causal pathways, evaluate the impact of these stressors on the professional quality of life (PQoL), employ coping strategies and encounter barriers to mitigating stressors and seeking support.

Design and settings
Our study employed an interpretive and descriptive phenomenological approach, informed by theoretical frameworks. We conducted focus group discussions (FGDs) and in-depth interviews (IDIs) with purposely selected health workers between January and February 2023. Interviews were audio recorded, transcribed and translated into English. Data was processed and analysed using MAXQDA 2020 software, with thematic findings supported by illustrative participants’ quotations.

Participants
The study included 34 health workers who participated in 10 IDIs and three FGDs.

Results
Five themes emerged from the study, guided by combined theoretical frameworks: (1) conceptualisation of occupational stress, anxiety and depression symptoms; (2) exposure to work-related stressors; (3) perceived impact of work-related stressors on PQoL; (4) experiences with coping strategies; and (5) barriers to mitigating stressors and seeking support. Accordingly, our findings revealed a low self-identification with CMSs (SICMSs), an increased perception to link work-related stressors with CMSs and their negative impact on PQoL, limited use of adaptive coping strategies and the presence of multiple barriers to effective coping and support-seeking practices among health workers across the respective themes.

Conclusions
The findings of this study highlight the need for targeted interventions, including updated training on CMSs, addressing resource-related stressors, improving workplace communication and conflict resolution, enacting policy reforms to ensure equitable compensation and promoting adaptive coping strategies to enhance health workers’ mental well-being and their PQoL. Furthermore, we advocate for a more robust exploration of the perceived causal link supported by lived experiences of health workers with chronic occupational stress, occupational depression and occupational anxiety to provide stronger evidence using longitudinal qualitative and quantitative studies.

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Design and methods of the research unit 5187 PREACT (towards precision psychotherapy for non-respondent patients: from signatures to predictions to clinical utility) – a study protocol for a multicentre observational study in outpatient clinics

Introduction
Cognitive–behavioural therapy (CBT) works—but not equally well for all patients. Less than 50% of patients with internalising disorders achieve clinically meaningful improvement, with negative consequences for patients and healthcare systems. The research unit (RU) 5187 seeks to improve this situation by an in-depth investigation of the phenomenon of treatment non-response (TNR) to CBT. We aim to identify bio-behavioural signatures associated with TNR, develop predictive models applicable to individual patients and enhance the utility of predictive analytics by collecting a naturalistic cohort with high ecological validity for the outpatient sector.

Methods and analysis
The RU is composed of nine subprojects (SPs), spanning from clinical, machine learning and neuroimaging science and service projects to particular research questions on psychological, electrophysiological/autonomic, digital and neural signatures of TNR. The clinical study SP 1 comprises a four-centre, prospective-longitudinal observational trial where we recruit a cohort of 585 patients with a wide range of internalising disorders (specific phobia, social anxiety disorder, panic disorder, agoraphobia, generalised anxiety disorder, obsessive–compulsive disorder, post-traumatic stress disorder, and unipolar depressive disorders) using minimal exclusion criteria. Our experimental focus lies on emotion (dys)-regulation as a putative key mechanism of CBT and TNR. We use state-of-the-art machine learning methods to achieve single-patient predictions, incorporating pretrained convolutional neural networks for high-dimensional neuroimaging data and multiple kernel learning to integrate information from various modalities. The RU aims to advance precision psychotherapy by identifying emotion regulation-based biobehavioural markers of TNR, setting up a multilevel assessment for optimal predictors and using an ecologically valid sample to apply findings in diverse clinical settings, thereby addressing the needs of vulnerable patients.

Ethics and dissemination
The study has received ethical approval from the Institutional Ethics Committee of the Department of Psychology at Humboldt-Universität zu Berlin (approval no. 2021-01) and the Ethics Committee of Charité-Universitätsmedizin Berlin (approval no. EA1/186/22).
Results will be disseminated through peer-reviewed journals and presentations at national and international conferences. Deidentified data and analysis scripts will be made available to researchers within the RU via a secure server, in line with ethical guidelines and participant consent. In compliance with European and German data protection regulations, patient data will not be publicly available through open science frameworks but may be shared with external researchers on reasonable request and under appropriate data protection agreements.

Trial registration number
DRKS00030915.

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