Mental health is now recognised as a major global concern affecting people from diverse backgrounds. There is growing evidence that the gut microbiota plays a crucial role by producing metabolites that significantly influence a person’s mood and behaviour. Despite its importance, there is a significant gap in the profiling and understanding of the gut microbiota’s influence on mental health among Malaysians. Therefore, this study aims to determine gut microbiome profiles among patients with major depressive disorders (MDD) of different treatment groups attending psychiatric clinics in the state hospitals and compare them to healthy individuals in the community of Klang Valley, Malaysia.

This cross-sectional study will be carried out in Klang Valley, Malaysia. Eligibility of the patients will be assessed by the psychiatrists prior to recruitment of patients. Patients with MDD will be categorised into monotherapy and polypharmacy while healthy individuals will be used as a comparison group. Demographic data will be recorded. Stool samples will be subjected to DNA extraction and 16S rRNA gene-sequencing analysis to determine the microbial compositions of the gut microbiome.

This study will be conducted following the procedure set by the National Medical Research Register Malaysia. The Medical Research Ethics Committee (MREC), Ministry of Health Malaysia, has ratified this study and granted ethical approval to conduct this study (NMRR ID-22-00893-JVW). All the participants will be given an information sheet and will sign a consent form to participate. Participants have the right to withdraw from the study at any time without an explanation. All information gathered will be used for research purposes only and treated as confidential. The results will be submitted to peer-reviewed journals for publication as well as presented at national and international conferences. Informing policy makers at all levels is a crucial aspect of the dissemination and will be done from local to international levels.

This study was registered under National Medical Research Register Malaysia (NMRR ID-22-00893-JVW), a mandatory procedure of the Ministry of Health Malaysia before the start of a research.

The global prevalence of heart failure continues to increase, particularly in ageing populations. Many older patients receiving home-based medical care have limited access to standard diagnostic tools, such as chest radiography and echocardiography, which can delay the detection of disease progression. AMI-SSS01, an artificial intelligence (AI)-based portable phonocardiography device, enables rapid and reproducible analysis of heart sounds, potentially allowing earlier identification of heart failure exacerbations in home-based medical settings. This trial aims to evaluate the feasibility and safety of implementing the AMI-SSS01 phonocardiography system in patients receiving home-based medical care.

This two-arm, parallel-group, randomised controlled feasibility trial is being conducted at two primary care clinics affiliated with the Research Organisation for Education and Network in Primary Care-Based Research Network in Nagasaki, Japan. Participants aged ≥65 years with symptomatic heart failure receiving home-based medical care are eligible for study inclusion. Participants are randomised in a 1:1 ratio to either the intervention group, in which AI-assisted phonocardiography using the AMI-SSS01 device is performed during physician home visits, or the control group receiving conventional home-based medical care without phonocardiography. Feasibility outcomes include recruitment rate, overall data completeness and completion and protocol-concordant completion rates for phonocardiography examinations. Safety outcomes include adverse events related to device use. The registered primary clinical outcome, collected as an exploratory clinical outcome, is the time from randomisation to hospitalisation for heart failure or cardiovascular death during the 24-week follow-up period. The registered secondary clinical outcome is the number of heart failure exacerbation events.

Ethical approval was obtained from the Nagasaki University Hospital Clinical Research Ethics Committee (CRB24-028). The findings will be disseminated through peer-reviewed publications and scientific conferences.

Japan Registry of Clinical Trials (jRCT1072240118).

Iron-folic acid (IFA) supplementation in pregnancy is recommended by the WHO, with a dose of 60 mg of iron in contexts where anaemia remains a severe public health problem. Iron-containing supplements may cause side effects that affect acceptability and adherence in a dose-response manner. Maternal multiple micronutrient supplements (MMS), which include iron and folic acid plus additional micronutrients, are also recommended in the context of rigorous research, and programmes are considering transitioning from IFA to MMS containing 30 mg of iron. We will evaluate the effect of iron dose in MMS on maternal acceptability, side effects, adherence and preferences.

The Multiple Micronutrient Supplementation (MMS) Iron Dose Acceptability Crossover Trial is an individually randomised, quadruple-blind, non-inferiority crossover trial of daily antenatal MMS supplementation formulations that contain 60 mg, 45 mg and 30 mg elemental iron among pregnant women in Dar es Salaam, Tanzania. A total of 156 pregnant participants will be randomised to a sequence in which they receive each of the three MMS formulations for 1 month. Participants, investigators, outcome assessors and data analysts will be blinded to the treatment sequence. The primary trial outcome is participant-reported acceptability of each MMS formulation, measured on a Likert scale. Secondary and tertiary outcomes include preferred and least preferred formulation, identification of MMS formulation, reported side effects and adherence assessed by pill count. Regression analyses will be used to assess differences between formulations and will account for sequence and period effects of the crossover trial design. Qualitative in-depth interviews from a subsample of participants will be conducted to understand women’s perceptions and experiences taking the different MMS formulations.

The trial protocol was approved by Harvard T. H. Chan School of Public Health Institutional Review Board (IRB), the Ifakara Health Institute IRB, the Muhimbili University of Health and Allied Sciences IRB, the National Health Research Ethics Sub-Committee and the Tanzania Medicine and Medical Device Authority. Results will be shared through publications and presentations at the local, regional and international levels.

ClinicalTrials.gov Identifier: NCT06069869.

To update the rurality index for Japan (RIJ) using the most recent national data and to test and evaluate the updated RIJ variants that incorporate alternative distance metrics and a modified classification of remote islands, thereby providing methodological guidance for their use in research and health policy.

Nationwide methodological study.

Japan.

All postal code areas in Japan; analyses were aggregated into municipalities and secondary medical care areas for evaluation.

Six RIJ variants (‘RIJ family’) constructed by combining three distance metrics (direct distance, road-based distance and travel time by car) and two island classifications (original RIJ and modified RIJ), standardised to a continuous 0–100 scale using percentile ranks.

Concordance among RIJ variants was assessed using Spearman’s rank correlation coefficients, quintile reclassification matrices and rank-difference analyses; convergent validity was evaluated using the national physician distribution index. Criterion-related validity was assessed using municipal-level life expectancy for men and women.

All RIJ variants had extremely high concordance (Spearman’s ≥0.99 across all pairwise comparisons). Compared with the previous RIJ classification, >98% of the geographic units remained in the same rurality quintile and

Despite differences in distance metrics and island classification, all RIJ variants captured highly similar underlying dimensions of rurality and demonstrated comparable validity. These findings indicate that rurality measurement in Japan is stable regardless of methodological refinements, allowing RIJ variants to be flexibly selected according to specific research or policy purposes without materially affecting conclusions.

Research has yielded contradictory results regarding differences in physical fitness and cardiometabolic risk between children and adolescents living in rural and urban areas.

The present study aimed to analyse the moderating role of area of residence on the association of physical fitness and anthropometric parameters in Chilean adolescents.

Cross-sectional analysis of a nationally representative school-based sample from Chile.

A total of 7,833 adolescents with an average age of 15.8±0.7 years participated in both rural (n=759) and urban (n=7,074) settings. Physical fitness tests were evaluated using the Assessing Levels of Physical Activity and Fitness (ALPHA-Fitness) battery and anthropometric variables such as body mass index (BMI), waist circumference (WC) and waist-to-height ratio (WHtR). Generalised linear models with Gaussian distributions were constructed to estimate moderation models, with anthropometric-related variables as dependent variables, physical fitness variables as independent variables and area of residence as a moderator. Moderation analyses were conducted to examine whether the area of residence influences the association between physical fitness and anthropometric indicators (WC, WHtR and BMI).

In all models, place of residence did not moderate the potential associations between physical fitness and anthropometric indicators; for example, cardiorespiratory fitness with WC (B=0.13, 95% CI 0.05 to 0.31; 0=0.160), WHtR (B=0.08, 95% CI –0.03 to 0.20; p=0.143) or BMI (B=0.08, 95% CI –0.03 to 0.20; p=0.207).

These findings suggest the associations between physical fitness and anthropometric outcomes do not differ significantly between rural and urban adolescents.

Addition of bevacizumab and paclitaxel as induction therapy prior to standard atezolizumab and nab-paclitaxel in patients with programmed death-ligand 1 (PD-L1)-positive metastatic triple-negative breast cancer (mTNBC) may help to overcome vascular endothelial growth factor-associated resistance mechanisms that limit the immune-mediated antitumour efficacy of atezolizumab and nab-paclitaxel.

The Induction Therapy of PTX+BV Followed by Atezolizumab+Nab-PTX for PD-L1+TNBC (INDUCE) study is a multicentre, randomised, open-label, phase II trial designed to evaluate the efficacy and safety of two cycles of induction therapy with bevacizumab and paclitaxel followed by atezolizumab and nab-paclitaxel compared with standard atezolizumab and nab-paclitaxel in patients with PD-L1-positive mTNBC. The primary outcome of the study is progression-free survival (PFS) per Response Evaluation Criteria In Solid Tumours, V.1.1. We have estimated that 89 PFS events are needed to allow a power of 80% to detect a difference between treatment groups at a one-sided significance level of 10% in this study. The target sample size is set to 106 patients to account for dropouts.

The study protocol and informed consent form have been approved by the Certified Research Review Board at the Nagoya University Graduate School of Medicine, Nagoya, Japan. Study results will be presented at international conferences and published in a peer-reviewed journal.

jRCTs041240039 NCT06793553.

Diabetic foot is an infection, ulceration or destruction of the tissue of the foot of a person diagnosed with diabetes mellitus (DM). Diabetic foot ulcer (DFU) is a major and preventable complication of DM. Adequate knowledge and foot self-care practices are crucial to reduce the risk of DFU complications, particularly in resource-limited healthcare settings.

To assess the knowledge and practices related to foot self-care and associated factors among individuals diagnosed with diabetes attending diabetic clinics at all base hospitals in Colombo District, Sri Lanka.

An analytical cross-sectional study was conducted among 423 individuals diagnosed with diabetes attending the diabetic clinic at all three base hospitals in Colombo district, from January 2023 to March 2024 (study period). Participants were selected by using a systematic random sampling. Data were collected using a validated and pre-tested interviewer-administered questionnaire. Descriptive and inferential analyses were performed using Statistical Packages for Social Sciences V.26 software. Associations were examined using ² tests, independent sample t-tests and one-way ANOVA (Analysis of Variance), with a p value

The majority of the participants were females (71.2%). Among the participants, 33.8% of them had a poor level of knowledge regarding foot self-care. Knowledge level was significantly associated with the participants’ family history of diabetes and the hospital where they attended the clinic (p

Nearly one-third of participants demonstrated poor knowledge of foot self-care, despite over half exhibiting satisfactory foot-care practices. This gap highlights the need for targeted education to boost awareness and promote consistent foot care, which is a key step in preventing diabetic foot complications and improving long-term outcomes for individuals diagnosed with diabetes.

Non-communicable diseases (NCDs) are rapidly escalating in developing countries and social factors such as the dynamics of the family play an important part in the lifestyle choices that lead to the onset and maintenance of chronic illness. There remains a gap in Malaysia as the majority of the studies were focused on the normal population rather than directly towards persons having NCDs. This study aimed to examine emerging risk factors such as family functionality and its association with NCD.

A cross-sectional survey was conducted using a multistage random sampling method.

Urban residential areas in Selangor, Malaysia.

A total of 2542 adults residing in urban areas of Selangor were recruited.

Family functionality was measured using the APGAR (Adaptation, Participation, Gain or Growth, Affection and Resources) scale and multiple logistic regression was performed to measure the association between emerging risk factors and NCD.

The prevalence of diabetes mellitus and hypertension was 10.8% and 6.1%, respectively. Widowed/separated status (adjusted OR (AOR) 41.53, 95% CI 19.06 to 90.48, p value=0.001) was reported to be a predictor of diabetes. As for hypertension, familial functionality (AOR 4.2, 95% CI 1.11 to 14.50, p value

There is a growing concern that family functionality is an emerging risk factor for NCDs. Future family-centred health promotion programmes should be incorporated to improve self-management behaviours and health outcomes.

Chemotherapy-induced nausea and vomiting (CINV) is a common symptom in cancer, and it is one of the distressing symptoms in patients with cancer receiving chemotherapy. Information about side effects may exacerbate CINV due to the nocebo effect. This study aims to examine the efficacy of pharmacist-led enhanced support for coping with side effects during medication counselling, which includes providing information about side effects, with the goal of mitigating the nocebo effect and reducing CINV.

This multicentre exploratory open-label randomised controlled trial will examine the efficacy of pharmacist-led enhanced support for coping with the side effects of treatments during medication counselling in patients with advanced lung cancer. The control group will receive medication counselling as usual. The study population will consist of patients with advanced lung cancer who have not received chemotherapy and are receiving highly emetogenic chemotherapy or equivalent chemotherapy. The primary endpoint is the prevention of nausea, and the secondary endpoints include complete response (no vomiting event and no rescue medication), stress (objectively assessed using the salivary cortisol and immunoglobulin A), coping strategies and quality of life.

This study received approval from the medical ethics committee of Kansai Medical University. The results will be submitted for publication in an international peer-reviewed journal, and the findings will be presented at international scientific conferences.

1.0, 18 Mar 2025

Registration number: UMIN000056068.

A growing number of national diagnostic reference levels based on clinical indications (NDRL_ci) in CT have been implemented worldwide since the International Commission on Radiological Protection’s 2017 recommendation. This study aims to compare NDRL_ci practices, identify influencing factors and propose evidence-based recommendations for NDRL_ci development, based on the literature published between 1996 and 2025.

Systematic review.

A systematic literature search was conducted in PubMed, Web of Science and Scopus from 1996 to 24 august 2025. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis framework was followed to report the study selection process in this review. Joanna Briggs Institute’s critical appraisal tools were used to evaluate the articles critically.

Adult patients undergoing CT scans for various clinical indications.

Clinical indication-based CT protocols with reported NDRL_ci values as CT dose index volume and dose length product (DLP).

The primary outcomes were NDRL_ci values reported for various clinical indications. The secondary outcomes were CT technology, protocol parameters and patient characteristics influencing NDRL_ci.

A total of 4146 articles were identified. 410 full texts were examined and 11 studies were included in the systematic review. 25 clinical indications across seven anatomical regions were identified across 11 included studies. The NDRL_ci for urinary stones and cerebrovascular accident had the highest number of references, while flank pain and occlusion had the lowest number. The highest NDRL_ci in DLP was found for total body CT in severe trauma (3830 mGy cm) and the lowest for sinusitis (70 mGy cm).

Several factors contribute to dose discrepancies for the same clinical indications in CT imaging, including kilovolt peak and milliampere-second, scan length, number of phases, patient size, reconstruction algorithm, CT scanner age and specifications, underscoring the need for standardised and optimised CT protocols. This review highlighted several challenges, which emphasise the importance of international organisations to standardise the development of NDRL_ci to improve comparability across countries.

CRD42024603574.

Maternal and child mortality has markedly decreased worldwide over the past few decades. Despite this success, the decline remains unequal across countries and is overall insufficient to meet the Sustainable Development Goals. South Asia and sub-Saharan Africa bear most of the burden of maternal and child morbidity and mortality. Major gaps persist in our understanding of the causes, timing, diagnostic thresholds and risk factors for adverse outcomes in these regions. Addressing these gaps requires new ways to prevent and treat disease, from novel diagnostics to precision public health strategies, all of which rely on high-quality clinical data from diverse populations. The Pregnancy Risk, Infant Surveillance, and Measurement Alliance (PRISMA) Maternal and Newborn Health Study aims to estimate population-level prevalence of morbidities and mortality and to assess biological, clinical and sociodemographic risk among mother–infant pairs in India, Pakistan, Kenya, Ghana and Zambia.

This study is a prospective, open cohort study with a planned recruitment of about 6000 women annually across six research sites in five countries. Participants are pregnant women enrolled less than 20 weeks gestation, as determined by ultrasound, identified through active house-to-house and facility-based surveillance. Robust clinical data will be collected at 12 scheduled study visits during antenatal care, labour and delivery, and through 1 year postpartum. A total of 34 outcomes will be captured. The primary analysis will estimate the burden of adverse outcomes and examine associated risk factors to inform future intervention strategies. Data will also be used to develop normative values for pregnant and postpartum women, as well as predictive models to assess pregnancy risk.

PRISMA received institutional and national ethical approvals. Findings will be published in peer-reviewed open-access journals and disseminated at national and international forums to inform clinical guidelines and public health practice.

NCT05904145.