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Incidence and Severity of Nurse‐Sensitive Adverse Events in Older Adults After Physical Trauma: A Medical Record Review

ABSTRACT

Aim

This study aimed to investigate the incidence and characteristics of nursing-sensitive adverse events (NSAEs) in older adults (≥ 65 years) hospitalised with traumatic injuries, and to explore associations with frailty, demographic factors, injury characteristics and hospital-related factors.

Design

NSAEs were identified through a retrospective medical record review of a prospectively collected cohort.

Methods

Patients ≥ 65 years admitted with physical trauma to a Swedish level I trauma centre between 2020 and 2024 were included. NSAEs were identified using a modified trigger tool chart review. Descriptive statistics were used to determine the incidence and characteristics of NSAEs in the whole cohort. Group differences, associations and predictors were examined using exact, non-parametric, or logistic regression methods.

Results

A total of 270 trauma patients ≥ 65 years were included, of whom 25.6% had experienced at least one NSAE. The overall incidence was 38.2 events per 100 admissions, with hospital-acquired infections being the most common type of NSAE (16.7%), followed by overdistended bladder (6.3%) and pressure injuries (5.6%). Frailty and length of hospital stay were associated with an increased likelihood of NSAEs, with hospital length of stay emerging as the strongest predictor in multivariable analysis.

Conclusion

NSAEs are common among older trauma patients and are associated with frailty, injury characteristics and length of stay. Improving early risk identification and ensuring timely preventive nursing care may enhance patient safety in this vulnerable population.

Implications for the Profession and/or Patient Care

The findings highlight the important role of nursing in the care of older trauma patients and the need for consistent delivery of fundamental nursing care. Strengthening clinical practices that support early identification of high-risk patients and the timely implementation of preventive interventions may improve patient safety and outcomes in this vulnerable population.

Impact

This study addresses the knowledge gap regarding NSAEs in older trauma patients, a population with increased vulnerability to adverse outcomes. The findings provide insights into the occurrence and risk factors of NSAEs in this group and highlight the importance of translating risk assessment into effective clinical action. These results may inform clinical practice and support the development of strategies to improve patient safety in trauma care for older adults.

Reporting Method

This study was informed by the Standard Elements in Studies of Adverse Events and Medical Error (SESAME). The completed SESAME checklist is provided in the Supporting Information S1.

Patient or Public Contributions

No patient or public contributions.

Bioinformatic identification of CD8+ T cell activation mediated by key genes in fecal microbiota transplantation for irritable bowel syndrome

by Ying Fei, Ming-Yi Gao, Nan Qiao, Jia Hu, Ling He, Jiao-Li Zhou, Ning-Ning Zheng, Ting-Ting Liu

Background

The effect of fecal microbiota transplantation (FMT) in treating irritable bowel syndrome (IBS) may be attributed to the modulation of CD8 + T cells. This study aims to identify FMT-mediated key genes to explore the underlying mechanism.

Methods

Transcriptomic datasets GSE138297 (colonic biopsies from 8 IBS patients pre- and post-FMT) and GSE134649 (single-cell data from 3 healthy colon tissues) were obtained from GEO during December 2023–December 2024. Key genes were identified by intersecting differentially expressed genes (DEGs) and the most relevant co-expression module derived from weighted correlation network analysis. Functional enrichment, gene set enrichment analysis, immune infiltration profiling via TIMER 2.0, single-cell annotation using PanglaoDB and Seurat, and drug–gene interaction screening from DrugBank were conducted to decipher the regulatory mechanisms.

Results

Ten key genes were identified through integration of DEGs and the MEgreen module. Functional analyses revealed significant involvement in the positive regulation of CD8 + T cells activation. Immune infiltration assessment demonstrated a marked increase in CD8 + T cells abundance post-FMT. Single-cell data indicated predominant expression of LILRB1, P2RY13, CLEC10A, and CLEC12A in dendritic cells, and LILRB1, PIPOX, and CLEC11A were annotated within CD8 + T cells clusters in healthy colonic tissue. Nine (database-derived and speculative) drugs targeting seven key genes were identified, most implicated in the management of IBS symptoms or immunomodulation.

Conclusion

An association between key gene regulation and CD8 + T cell-related immunoregulation is correlated with the therapeutic effect of FMT in IBS.

Preparation and in vitro evaluation of photodynamic-responsive nanoliposome loaded PL-5

by Wen Lin, Qiong-zhi Shi, Xiang-ru Liao, Yuan Zeng, Xiang-yang Xie, Gang-jian Ji, Yin-ke Li

Burn wound infections are frequently complicated by biofilm-forming and multidrug-resistant pathogens, particularly methicillin-resistant Staphylococcus aureus (MRSA), posing major therapeutic challenges. Antimicrobial peptides (AMPs) such as PL-5 (peceleganan) exhibit broad-spectrum activity but are limited by instability, poor biofilm penetration, and reduced efficacy in complex wound environments. Here, a red-light-responsive, porphyrin-phospholipid (PoP)-containing cationic liposomal system for PL-5, aiming to enhance its antibacterial and antibiofilm performance was developed. Optimized liposomes achieved high encapsulation efficiency (~73%), uniform nanoscale size (~50 nm), narrow polydispersity, and positive surface charge. They demonstrated good storage stability and controlled peptide release under red-light irradiation (635 nm). In vitro, red-light activation significantly enhanced antimicrobial activity against MRSA and methicillin-susceptible S. aureus (MSSA), reducing minimum inhibitory concentration (MIC) values fourfold and accelerating bactericidal kinetics compared with free PL-5 and non-irradiated liposomes. Additionally, red-light-activated liposomes markedly inhibited biofilm formation. These results indicate that light-responsive liposomal delivery enables spatiotemporally controlled release of PL-5, significantly potentiating its antibacterial and antibiofilm efficacy. This approach offers a promising localized treatment strategy for biofilm-associated burn wound infections and a foundation for future translational studies.

Perceptions of healthcare professionals and community members on acute febrile illness management in Maputo and Quelimane City: a qualitative study

Por: Monteiro · V. D. C. O. · Nhassengo · P. · Muamine · E. · Alho · P. · Manganhe · Y. · Zandamela · A. · Cambe · M. I. · Gudo · E. S. · Craveiro · I.
Introduction

Acute febrile illness is a major cause of morbidity and healthcare seeking in sub-Saharan Africa, including Mozambique. However, few studies have explored the perceptions and practices related to clinical management of acute febrile illness. Our aim was to understand the perceptions, knowledge and practices of healthcare professionals and community members regarding the management of acute febrile illness.

Methods

A qualitative study was conducted using a thematic analysis approach. Eight focus group discussions (FGDs) and three in-depth interviews (IDIs) were conducted in two Mozambican provinces across four healthcare facilities. Purposive sampling was used to select participants, comprising both healthcare professionals and community members. Data were analysed thematically through manual coding, applying inductive and deductive approaches, in line with established qualitative analytical frameworks.

Results

The study included a total of 60 participants, 28 healthcare professionals who participated in FGDs (25) and IDIs (3) and 32 community members who participated in FGDs. Major causes of fever, according to healthcare professionals, were upper and lower respiratory infections, malaria, diarrhoeal diseases and COVID-19. The diagnostic approach for febrile patients primarily included screening, malaria testing and other non-specific investigations depending on availability at health facilities. Antibiotics and antipyretics were the most commonly prescribed treatments. The healthcare professionals reported a decrease in prescribing antimalarials due to extensive training on malaria case management. In contrast, community members reported relying primarily on home-based and traditional practices to treat acute febrile illness before seeking care at health facilities. These practices are related to sociocultural habits, such as the use of traditional medicine and self-medication. The main barriers to seeking care at health facilities were the perception of poor quality of care, long waiting times, cultural beliefs and lack of medicines.

Conclusion

Proper management of non-malarial febrile illness remains a major challenge for both healthcare professionals and communities. Training, adherence to case management protocols and efforts to change behaviours to mitigate harmful sociocultural practices are urgently necessary to improve febrile illness management.

Dialogic reading at age 2 is linked to frontal activation related to executive function at age 5: An fNIRS study

by Ming Yean Sia, Chia-Feng Lu, Ovid J. L. Tzeng, Shinmin Wang

This study investigates the relationship between children’s dialogic reading (DR) experiences with parents at age 2 and their frontal neural responses related to executive function (EF) at age 5. To assess how the intensity of DR influences brain development, we quantitatively measured parental engagement in DR when children are at 2 years of age. Neural activations in frontal regions associated with EF were evaluated using functional near-infrared spectroscopy when children reached age 5. Our results reveal a significant positive correlation between parental dialogic interaction during shared book reading at age 2 and the activation of key brain regions related to EF – the bilateral dorsolateral prefrontal cortex and the bilateral inferior frontal gyrus – during a Dimensional Change Card Sort (DCCS) task at age 5. This correlation persisted even after controlling for maternal education and children’s expressive vocabulary, indicating a robust relationship between early DR experiences and subsequent neural correlates of EF. The results suggest that early DR may help cultivate the neural infrastructure necessary for EF development. By focusing on DR at a young age and assessing neural activity during a classic EF task, the DCCS, our findings contribute additional evidence regarding the role of DR in shaping neural development associated with EF. These results highlight the importance of encouraging interactive DR practices in early childhood, as they not only support language development but also strengthen the neural pathways crucial for cognitive skills essential for academic success.

The safety window of blood magnesium in pulmonary complications of non-pulmonary sepsis: A U-shaped risk and prognostic analysis based on MIMIC-IV

by Taotao Peng, Yu Li, Yukun Ren, Mi Yang, Zonghong Long, Dukun Zuo, Lu Huang, Huawei Liu, Zhenxin Duan, Hong Li

Pulmonary complications in non-pulmonary sepsis (PC-NPS) are the leading cause of morbidity and mortality in the intensive care unit. Early prevention and monitoring are paramount since the prevention strategies remain limited yet. Magnesium, an essential electrolyte involved in inflammation and vascular regulation, may influence the development of such complications. This retrospective cohort study used data from the MIMIC-IV database to explore the relationship between baseline serum magnesium levels and PC-NPS among 4,836 patients with non-pulmonary sepsis. Survival analysis demonstrated that patients who developed PC-NPS had significantly higher 90-day mortality compared with those without lung injury. When stratified by baseline serum magnesium quartiles, patients in the highest quartile (>2.1 mg/dL) showed the poorest survival. Multivariable logistic regression confirmed that elevated magnesium was independently associated with increased risk of PC-NPS, and restricted cubic spline modeling revealed a U-shaped, nonlinear association between baseline magnesium concentration and PC-NPS risk. Inflection points at 1.26 and 1.91 mg/dL identified a range of relatively lower risk. These findings suggest that baseline serum magnesium levels exhibit a U-shaped relationship with the risk of PC-NPS. Evaluating these levels may aid in clinical prognostication and the exploration of underlying mechanisms.

A scoping review of computational models of the diabetic foot

by Yufeng Li, Athia Haron, Chaofan Lin, Yuan Tang, Andrew Weightman, Glen Cooper

The prevalence of diabetes is expected to be 650 million people by 2030, and diabetic foot ulceration (DFU) is one of its most severe complications. It poses a significant challenge to global health and brings substantial social and economic burdens. Although many studies have explored the mechanisms of DFU development, they are still not fully understood. Due to the high cost of the experimental research, many recent studies have employed the computational modelling approaches to simulate the effects of diabetes on foot tissues from mechanical, thermal, fluid, and cellular perspectives. This study aims to provide a comprehensive review of computational modelling approaches used to investigate various factors influencing DFU, discuss current knowledge gaps and limitations, and outline future research directions. A systematic search was conducted in Web of Science, Scopus, and PubMed databases, identifying a total of N = 1631 records up to March 2025, 31 of which studies met the inclusion criteria and were analysed in this study. Results showed that DFU-related computational models can be categorized into five types: mechanical stress models, thermal models, vascular and nerve system models, multiphysics models, and cellular-based models. These models explore the formation mechanisms of DFU from different perspectives, including biomechanics, temperature, fluid dynamics, HHμm neural signalling, and cellular responses. However, except for mechanical stress models, the other approaches remain in the early stages of development, and the single physics modelling strategies are unable to provide understanding on the coupled processes with the foot and their effect on DFU. Future research should further develop modelling approaches and couple these together to develop comprehensive understanding of DFU pathogenesis.

Multidisciplinary Offloading for Healed Diabetic Foot Ulcers: A Prospective Study on Functional Outcomes and Predictors of Recurrence, Amputation, and Mortality

ABSTRACT

To evaluate the effectiveness of multidisciplinary offloading versus standard care on one-year diabetic foot ulcer recurrence, amputation, mortality, and functional recovery. In this prospective cohort study, 232 patients with healed diabetic foot ulcers were stratified into a control group (76 patients) or an intervention group (156 patients) receiving offloading modalities ranging from felt padding to custom-made therapeutic footwear. Assignment was based on shared decision-making considering biomechanical needs and economic feasibility. Primary outcomes included recurrence, amputation, and mortality. Secondary outcomes assessed quality of life, working ability, and ankle function. The intervention group demonstrated significantly lower recurrence (10.9% vs. 25.0%; p = 0.007) and mortality (3.2% vs. 14.5%; p = 0.004). Multivariable analysis identified offloading as independently protective against recurrence (odds ratio 0.35) and mortality (odds ratio 0.24). Amputation rates did not differ significantly after adjustment. Functionally, the intervention group achieved superior recovery in quality of life, working ability, and ankle scores (p < 0.001). Subgroup analysis indicated that customized therapeutic footwear yielded the lowest complication rates and highest patient satisfaction. Multidisciplinary offloading significantly reduces recurrence and mortality while restoring physical function. Although financial barriers influence device selection, customized therapeutic footwear offers the optimal balance of biomechanical protection and functional outcomes.

Minocycline hydrochloride ointment-assisted periodontal treatment of stage III/IV periodontitis associated with type 2 diabetes mellitus targeting Chinese people: study protocol for a randomised controlled trial

Por: Zhao · H. · Lin · S. · He · L. · Zhen · M. · Yang · G. · Wang · X. · Cao · J. · Li · Y. · Hou · J. · Xu · L. · Meng · H. · Liu · K.
Introduction

Scaling and root planing (SRP) combined with adjunctive antibiotic therapy is widely adopted in the management of periodontitis in patients with type 2 diabetes mellitus (T2DM), with the aims of ameliorating glycaemic control, alleviating local inflammation and facilitating periodontal tissue regeneration. As a topically administered adjunctive antibiotic for periodontal treatment, minocycline hydrochloride (MH) ointment has shown favourable clinical efficacy in systemically healthy patients with periodontitis. However, robust evidence supporting its clinical efficacy and potential glycaemic-improving effects in patients with periodontitis complicated by T2DM remains limited. The present study is designed to test the null hypothesis that no significant differences in clinical outcomes exist between SRP combined with MH and SRP alone in the management of periodontitis among patients with T2DM, with its primary objective to investigate whether MH as an SRP adjunct confers superior clinical benefits to SRP alone.

Methods and analysis

We will conduct a randomised, single-blind, placebo-controlled clinical trial. 56 patients with T2DM-associated stage III/IV periodontitis will be recruited from the Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing, China. Eligible participants will be randomised into two groups: the experimental group will undergo SRP combined with topically administered MH ointment and the control group will undergo SRP with a matched placebo. The primary outcomes will include probing depth (PD) changes at periodontal pocket sites with a baseline PD ≥6 mm at 6 months post-baseline, with a specific focus on the percentage of such sites with PD reduced to ≤5 mm. The secondary outcomes will comprise PD changes at pocket sites with a baseline PD ≥5 mm at 6 months post-baseline, as well as clinical attachment loss, the plaque index, bleeding index, the levels of IL-1β, IL-17, calprotectin and insulin levels in gingival crevicular fluid and serum, complete blood count, blood biochemistry, including glycated haemoglobin levels, and the composition of subgingival plaques at baseline, and 2 and 6 months post-baseline.

Ethics and dissemination

This study was approved by the Ethics Committee of Peking University School and Hospital of Stomatology (PKUSSIRB-2024102139b). Results will be published in a peer-reviewed scientific journal.

Trial registration number

ChiCTR2400092305.

Protocol version

V.3.1 (date: 6 January 2026).

Use of clips to prevent delayed post-polypectomy bleeding in non-pedunculated colorectal lesions: protocol for a systematic review and meta-analysis

Por: Wei · Y. · Zhang · S. · Mabenga · H. S. · Ngowi · B. J. · Jin · Z.
Introduction

Delayed post-polypectomy bleeding (DPPB) remains a significant complication of endoscopic resection, contributing to morbidity and increased healthcare costs. Although prophylactic clipping is widely practised to mitigate this risk, evidence from recent randomised controlled trials (RCTs) regarding its efficacy is inconsistent. This protocol outlines a systematic review and meta-analysis to evaluate the effectiveness of prophylactic clips following thermal resection.

Methods and analysis

We will conduct a comprehensive search of MEDLINE, EMBASE and the Cochrane Library from inception to 10 February 2026, to identify RCTs comparing prophylactic clips vs no clips in patients undergoing thermal endoscopic resection of non-pedunculated polyps. The primary outcome is DPPB within 30 days, defined as overt bleeding requiring medical intervention or a haemoglobin decrease ≥2 g/dL. Secondary outcomes include DPPB in proximal large (≥20 mm) lesions, perforation, post-polypectomy syndrome and procedure time. Data synthesis will use a random-effects model. Methodological quality will be assessed using the Cochrane Risk of Bias 2 tool. Publication bias will be visualised using funnel plots. We will quantify the effect of potential effect modifiers by meta-regression if appropriate. The quality of evidence will be evaluated according to the Grading of Recommendations Assessment, Development and Evaluation framework.

Ethics and dissemination

This study will not use primary data, and therefore formal ethical approval is not required. The findings will be disseminated through peer-reviewed journals and committee conferences.

PROSPERO registration number

CRD420251246840.

The association of triglyceride-glucose index with acute myocardial infarction and all-cause mortality in patients with coronary artery disease stratified by acute myocardial infarction status: a large-scale retrospective cohort study from South China

Por: Wang · Y. · Zeng · C. · Huang · Y.-L. · Fang · Y. · Rahmati · A. · Zhou · Z. · Chen · S.
Objectives

This study aimed to investigate the association of the triglyceride-glucose (TyG) index with the risk of acute myocardial infarction (AMI) and all-cause mortality in patients with coronary artery disease (CAD), and to inspect whether AMI mediates the relationship between TyG index and mortality.

Design

A large-scale, retrospective cohort study.

Setting

This single-centre study was conducted at a tertiary academic hospital in South China. The association between the TyG index and AMI was assessed using multivariable logistic regression, with progressive adjustment for demographic and clinical covariates. Cox proportional hazards models were used to estimate the HRs for all-cause mortality associated with TyG index. Restricted cubic splines and mediation analysis were employed to examine non-linear relationships and the mediating role of AMI.

Participants

A total of 20 125 patients diagnosed with CAD during hospitalisation between January 2020 and February 2025 were initially enrolled. After applying exclusion criteria (insufficient data), 18 245 participants were included in the final analysis.

Outcome measures

We examined the association of the TyG index with the risk of AMI, as well as its association with all-cause mortality across different CAD subgroups.

Results

The association between the TyG index and all-cause mortality was significantly modified by AMI status (P for interaction

Conclusions

An elevated TyG index independently predicts the risk of AMI in patients with CAD. Its prognostic value for mortality, however, is critically dependent on the presence of AMI: while a higher TyG index is associated with increased mortality in patients with AMI, moderately elevated TyG levels (Q2–Q3) are associated with lower mortality, whereas the highest quartile shows no significant association. Mediation analysis further reveals that AMI significantly mediates the association between TyG index and mortality, highlighting the importance of AMI prevention in mitigating the adverse prognostic impact of insulin resistance in the CAD population. These findings warrant validation in prospective studies.

Development and validation of the Good Limb Position Management Scale for Stroke Patients with Hemiplegia by Nurses: a cross-sectional study

Por: Leng · M. · Dong · Y. · Liu · B. · Zhang · X. · Ji · X. · Sun · F. · Li · M. · Yang · L. · Chen · X.
Background

A good limb position (GLP) plays an important role in the rehabilitation process of patients who have had a stroke with hemiplegia. However, there remains a lack of effective assessment tools for clinical nurses to evaluate their GLP management practices.

Objective

This study aimed to develop and test the psychometric properties of the Good Limb Position Management Scale for Stroke Patients with Hemiplegia by Nurses (GLPMSSPHN).

Design

A quantitative and cross-sectional design.

Setting

89 hospitals in 16 cities of China.

Participants

A total of 516 participants completed the questionnaire and were finally used for the analyses.

Main outcome measures

An initial scale was developed based on the Capability, Opportunity and Motivation-Behaviour model combined with a comprehensive literature review, semi-structured interviews, Delphi expert consultations and a pilot test. A field survey was then performed using the initial scale to test the reliability and validity of the scale. Reliability analysis was conducted by calculating Cronbach’s α coefficients and test–retest reliability. The results of exploratory factor analysis and confirmatory factor analysis were used as the validity index to further verify the model structure of the scale and develop a formal scale.

Results

The GLPMSSPHN was formulated with 4 dimensions and 35 items. Exploratory factor analysis extracted four factors, with a cumulative variance contribution rate of 81.842%, and confirmatory factor analysis indicated that the scale had good construct validity. The Cronbach’s α coefficient of the scale was 0.978, and the test–retest reliability was 0.863.

Conclusions

The GLPMSSPHN has ideal reliability and validity and provides a valid and reliable tool for clinical nurses to identify and assess the management level of GLP in patients who have had a stroke with hemiplegia.

Comparative efficacy and acceptability of treatment options for depressive disorders in children and adolescents: protocol of a network meta-analysis

Por: Guo · J. · Lu · Z. · Zhang · Y. · Sun · Y. · Kang · Z. · Sun · J. · Zhao · G. · Feng · X. · Yuan · R. · Zhu · Y. · Yu · T. · Yang · Y. · Chen · H. · Yue · W.
Introduction

The incidence of depression among children and adolescents has been increasing in recent years, posing significant challenges to public health and clinical care. A variety of treatments, including pharmacotherapy, psychotherapy and physical interventions, are widely used in clinical practice. However, a comprehensive synthesis of the evidence on the efficacy and acceptability of all these treatment modalities is currently lacking. This study aims to use network meta-analysis (NMA) to compare the efficacy and acceptability of all available treatments for depression in children and adolescents, offering valuable insights to inform clinical decision-making and guide future research in this critical area.

Methods and analysis

We will include randomised controlled trials evaluating active interventions for depressive disorders in children and adolescents. Seven electronic databases (PubMed, Embase, the Cochrane Library, Web of Science, PsycINFO, Scopus and ClinicalTrials.gov) were searched from inception to 2 July 2024 and updated on 2 November 2025. Two of four investigators will independently screen studies, extract data from eligible articles and assess the risk of bias using the Cochrane Risk of Bias 2.0 tool. The primary outcome will be the change in depressive symptoms. Secondary outcomes will include acceptability (all-cause discontinuation), response rate, remission rate and overall functioning. Pairwise and Bayesian NMA will be conducted. Small-study effects and publication bias will be assessed. The certainty of the evidence will be evaluated according to the Confidence in Network Meta-Analysis approach.

Ethics and dissemination

As this review involves secondary analysis of previously published studies, ethical approval is not required. The findings will be disseminated through publication in peer-reviewed journals.

PROSPERO registration number

PROSPERO-ID CRD42024557384.

Continuation of first-line therapy with radiotherapy for oligoprogression versus early switch to second-line therapy in oligoprogressive hepatocellular carcinoma (CROSS): study protocol of a multicentre, randomised, controlled, open-label, phase III trial

Por: Wang · H. · Shi · F. · Zhang · X. · Zhu · K. · Jiang · S. · Feng · R. · Dou · X. · Xu · L. · Yue · J.
Introduction

Treatment options remain limited for patients with advanced hepatocellular carcinoma (HCC) who experience oligoprogression during first-line systemic therapy (FLST), especially given the modest efficacy and restricted availability of second-line systemic therapy (SLST). This trial aims to evaluate whether continuing FLST combined with radiotherapy (RT) to oligoprogressive lesions can improve progression-free survival (PFS) compared with an early switch to SLST in patients with oligoprogressive HCC while maintaining an acceptable safety profile.

Methods and analysis

The continuation of first-line therapy with radiotherapy for oligoprogression versus early switch to second-line therapy in oligoprogressive hepatocellular carcinoma trial is a prospective, multicentre, randomised phase III study that will enrol 132 patients with advanced HCC who experience their first oligoprogression during FLST. Oligoprogression is defined as one to five progressive lesions involving no more than one to three organs. Participants will be randomised (1:1) to either continuation of FLST combined with RT to all oligoprogressive lesions or discontinuation of FLST followed by initiation of SLST. RT will be delivered with a biologically effective dose (linear–quadratic model, α/β=10) of at least 60 Gy whenever feasible. The primary endpoint is PFS. Secondary endpoints include overall survival, objective response rate, disease control rate, duration of response and quality of life. Predefined exploratory analyses include circulating tumour DNA profiling, optional paired tumour biopsies, functional imaging with fibroblast activation protein inhibitor positron emission tomography-CT and longitudinal immune profiling.

Ethics and dissemination

This study has been approved by the Ethics Committee of the Affiliated Cancer Hospital of Shandong First Medical University (number: SDZLEC2025-025-02) and has been registered in ClinicalTrials. gov (NCT06841172). Final study results will be disseminated through peer-reviewed journals.

Trial registration number

NCT06841172.

Uridine diphosphate glucuronosyltransferase 1A1 gene polymorphisms and treatment outcomes in HIV and MTB coinfection in sub-Saharan Africa: a scoping review protocol

Por: Vhanda · D. · Musarurwa · C. · Chikwati · R. P. · Muziringa · M. · Dandara · C. · Manasa · J. · Chirenda · J. · Mavenyengwa · R. T.
Introduction

Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) is closely associated with the management of HIV and tuberculosis (TB) coinfection because it modulates the metabolism of antiretroviral (ARV) drugs. The frequency of UGT1A1 polymorphisms varies widely among sub-Saharan Africans. However, studies examining the frequency of UGT1A1 polymorphisms and their impact on drug response profiles, accounting for environmental factors, drug–drug and gene–drug interactions and non-compliance remain sparse. Given that HIV and TB treatments often involve complex drug regimens with a high risk of interactions, understanding the role of UGT1A1 polymorphisms in these contexts is crucial. Therefore, this scoping review aims to map existing evidence, synthesise findings on how genetic polymorphisms in the UGT1A1 gene affect the metabolism of ARVs and antituberculosis drugs, and identify gaps in literature regarding their impacts on drug efficacy, toxicity and treatment outcomes in sub-Saharan Africa (SSA).

Methods and analysis

The methodology for this scoping review will follow the guidelines outlined in the Joanna Briggs Institute Methodology Manual. Using the keywords, UGT1A1 polymorphism, HIV and TB coinfection, treatment outcomes and SSA, we will search for articles on PubMed/Medline, Cochrane Library, Embase, Web of Science and Scopus to obtain relevant articles published from January 2010 to April 2026. Two independent reviewers will screen and assess quality of titles and abstracts against the predefined inclusion and exclusion criteria and manage the data using Microsoft Excel. Conflicts will be resolved through discussion and where necessary a third reviewer will be consulted. Findings will be narratively synthesised across polymorphisms and treatment outcomes. The reviewers will meet and discuss the themes that will arise as well as the interpretation of the themes to minimise bias in the findings.

Ethics and dissemination

The scoping review relies on publicly available published resources, exempting it from ethical review board oversight. The review findings will be shared in a peer-reviewed journal.

Values and preferences of patients with severe mental illness regarding smoking cessation interventions: a systematic review with best-fit framework synthesis

Por: Coteur · K. · Tops · L. · Bekkering · G. E. · de Almeida Ferreira Fonseca · L. · van den Brand · F. · Cloetens · H. · Zeng · L. · Aertgeerts · B. · Delvaux · N. · Agarwal · A. · Agoritsas · T. · Vermandere · M.
Objective

To identify values and preferences regarding smoking cessation interventions among adults with severe mental illness

Design

Systematic review with best-fit framework synthesis

Data sources

MEDLINE, EMBASE, Web of Science, CINAHL and Scopus from inception to 14 November 2025.

Study selection

Studies with any design, in any clinical and geographical setting, reporting on adult (18+) current or past smokers with a diagnosis of schizophrenia, bipolar or mood disorder, including major depressive disorder or post-traumatic stress disorder. We selected all quantitative and qualitative findings regarding patients’ values and preferences, including beliefs, attitudes, behaviours and perceived barriers and facilitators, in relation to smoking cessation interventions.

Data extraction and synthesis

Two reviewers independently screened studies. After a pilot to increase accuracy, data were extracted by one reviewer and verified by another. Risk of bias was assessed using the Mixed Methods Appraisal Tool. We used the best-fit framework synthesis methodology to synthesise the data.

Results

Of 14 970 identified articles, 65 were included. Most studies were of moderate to high quality. Financial costs posed a significant barrier, while education and social support emerged as important facilitators. Patients preferred personal interactions with healthcare providers. Their motivation for cessation varied and was influenced by habits and perceived nicotine dependence. Health concerns and financial savings were primary drivers for reflective motivation. Beliefs regarding treatment varied. Although commonly used, scepticism about nicotine replacement therapy and concerns about the long-term safety of electronic delivery systems were reported. Overall, patients preferred personalised, flexible programmes and emphasised the need for tailored approaches. Digital interventions, especially mobile apps, that provide support, motivational content and relevant information, were perceived as appealing and helpful when sufficiently considering accessibility and usability aspects. Patients commonly perceived smoking as a coping mechanism for negative emotions. Developing new coping strategies and creating smoke-free environments were deemed to contribute to successful cessation.

Conclusions

Patient-centred care for people with severe mental illness should leverage behavioural and pharmacological strategies for smoking cessation. Flexibility, accessibility and ongoing support appeared important for addressing stress, withdrawal symptom interpretation and relapse vulnerability in this population.

PROSPERO registration number

CRD42022337933.

Identification of candidate sex hormone-associated genes and immune infiltration characteristics in osteoarthritis based on bioinformatics analysis and machine learning

by Yishu Wang, Ling Zhu, Shuna Jin, Yuhan Wang, Zhaoxiang Zeng, Yunzhou Zuo, Xingliang Xiang, Xugui Li, Rongzeng Huang, Chengwu Song

Background

Sex hormones play critical roles in the pathogenesis and progression of osteoarthritis (OA), yet the hormone-related molecular networks remain poorly defined. This study aimed to identify candidate sex hormone-associated genes in OA and to explore their potential functional enrichment and immune-related characteristics using bioinformatics analysis.

Methods

OA gene expression data were obtained from the GEO database and integrated with candidate sex hormone-associated genes retrieved from GeneCards. The R package “limma” was then used to identify differentially expressed genes (DEGs) and sex hormone-associated DEGs (SADEGs). OA-associated SADEGs, termed OA-SADEGs, were selected using weighted gene co-expression network analysis (WGCNA), and their potential biological functions and pathways were explored by GO and KEGG enrichment analyses. Hub genes were identified using three machine learning models. xCell analysis was used to estimate immune infiltration and its associations with hub genes, and hub gene expression was further evaluated in external datasets and peripheral blood samples.

Results

We identified 32 sex hormone-associated genes in OA, enriched in extracellular matrix remodeling, receptor signaling, and antigen presentation pathways. Three candidate hub genes (LOXL1, HLA-DRA, and CYBB) were consistently upregulated in OA and showed significant correlations with immune infiltration scores. xCell analysis identified 13 differentially enriched immune cell types, of which three were associated with hub genes. External dataset analysis and peripheral blood qRT-PCR showed upregulation of LOXL1, HLA-DRA, and CYBB in OA samples.

Conclusion

This study integrated bioinformatics and immune analyses to identify candidate sex hormone-associated genes in OA. These findings provide associative bioinformatics evidence for sex hormone-associated molecular features in OA.

Drug-induced gastric motility disorders: A disproportionality analysis from the FAERS and CVARD databases

by Zhiheng Qian, Ni Jiang

Background

Delayed gastric emptying and gastroesophageal reflux represent critical yet frequently underrecognized complications in hospitalized patients, particularly in the context of polypharmacy. While multiple medication classes have been implicated in disrupting gastrointestinal motility, the comprehensive risk spectrum of individual drugs remains poorly characterized. This study aimed to conduct a comprehensive disproportionality analysis to identify drugs associated with delayed gastric emptying and reflux using large-scale pharmacovigilance data.

Methods

We analyzed adverse event reports from the FDA Adverse Event Reporting System (FAERS; 2004–2025; n > 58 million) and validated findings against the Canada Vigilance Adverse Reaction Online Database (CVARD). Disproportionality analysis was performed using Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Bayesian Confidence Propagation Neural Network (BCPNN). Weibull time-to-onset analysis was conducted to characterize temporal patterns of adverse event onset.

Results

Among the top 50 drugs screened, 20 demonstrated positive signals across all three algorithms. Glucagon-like peptide-1 (GLP-1) receptor agonists exhibited the strongest associations with gastric motility disorders, with semaglutide showing the highest ROR for impaired gastric emptying (ROR: 80.27; 95% CI: 76.39–84.34), validated in CVARD (ROR: 54.17). Insulin formulations, particularly insulin degludec (ROR: 18.90), bisphosphonates, angiotensin receptor blockers, and trofinetide also demonstrated significant signals. Weibull analysis revealed divergent temporal patterns, ranging from early-onset (trofinetide: median 6.6 days) to late-onset (immunoglobulin G: median 535.1 days).

Conclusion

This study identifies a broad spectrum of drug-associated gastric motility disorders with distinct temporal profiles. These findings provide evidence-based priorities for enhanced pharmacovigilance and inform clinical decision-making to mitigate this preventable cause of morbidity.

THSD7B promotes tumor progression and is associated with prognosis in gastric adenocarcinoma

by Xinying Quan, Wei Cheng, Yao Pu, Hong Deng

THSD7B (thrombospondin type-1 domain-containing 7B) has been implicated in several malignancies; however, its role in gastric adenocarcinoma remains unclear. This study aimed to investigate the expression pattern, clinical significance, and biological function of THSD7B in gastric adenocarcinoma. Public datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed to evaluate THSD7B expression and its association with clinical outcomes. Functional enrichment analysis was performed to explore potential biological processes. In vitro assays, including cell proliferation, colony formation, wound healing, and Transwell invasion, were conducted following THSD7B knockdown or overexpression in gastric cancer cell lines. In addition, a xenograft model was established to assess tumor growth in vivo. THSD7B expression was significantly elevated in gastric adenocarcinoma tissues compared with normal controls and was associated with patient survival. Functional analyses suggested that THSD7B-related genes were mainly enriched in cell adhesion and cytoskeleton-associated processes. In vitro experiments showed that THSD7B knockdown suppressed cell proliferation, migration, and invasion, whereas overexpression produced the opposite effects. Consistent with these findings, THSD7B modulation was accompanied by alterations in adhesion-related signaling molecules and phenotype-associated protein expression. In vivo, THSD7B promoted tumor growth in xenograft models. In conclusion, THSD7B is associated with tumor progression and clinical outcomes in gastric adenocarcinoma and may be involved in the regulation of cell motility-related processes. These findings suggest that THSD7B may serve as a potential biomarker in gastric cancer.

Delays in diagnosis and treatment of depressive disorder among young adults: A national online survey-based cross-sectional study

by Rena Xu, David Pletta, Caitlynn Feng, Cassandra Morrow, Maya C. Clark, Badar Omar, Alex S. Keuroghlian, Sari L. Reisner

Background

Depression is highly prevalent among U.S. young adults and associated with long-term functional impairment and increased suicide risk. While delays in diagnosis and treatment of depression are well documented among older adults, the magnitude and predictors of such delays in the younger population are poorly understood.

Objective

To characterize the time to diagnosis and treatment of depressive disorder and predictors of diagnostic and treatment delay among young adults.

Methods

This cross-sectional study used a self-reported survey conducted via the online research platform Prolific in May 2025. Eligible participants were U.S. adults aged 18–35 years with a history of at least one depressive episode. Sociodemographic, clinical, and psychosocial characteristics, including age of depressive symptom onset, degree of social support, and frequency of social group engagement, were assessed. Primary outcomes were probability of not receiving a depressive disorder diagnosis despite symptoms, time from symptom onset to diagnosis, probability of not seeking treatment, and time from symptom onset to treatment. Secondary outcomes were perceived treatment effectiveness and current symptom control.

Results

In total, 871 respondents met inclusion criteria. Of those with one or more lifetime depressive episodes, 46.2% reported never receiving a depressive disorder diagnosis. Median time from symptom onset to diagnosis was 3 years (IQR: 0–7). Over a quarter (27.4%) never sought treatment; among those who did, 93.5% received care, but 31.4% experienced a delay of 1–4 years, and 28.8% experienced a delay of 5 + years. Symptom onset in childhood (ages 0–12) or adolescence (ages 13–17) was associated with longer time to diagnosis and treatment and lower perceived treatment effectiveness. Greater social support was associated with shorter time to diagnosis; lower probability of never receiving a diagnosis, never seeking treatment, or experiencing prolonged treatment delay; and higher perceived treatment effectiveness and current symptom control. Frequent engagement in social groups was also associated with greater perceived treatment effectiveness.

Conclusions

Among U.S. young adults, prolonged delays in depression diagnosis and treatment are common. Early symptom onset is associated with longer delays and worse outcomes, whereas greater social support is associated with shorter delays and more favorable outcomes. These findings highlight the need for further research to clarify causal mechanisms and for interventions to promote timely diagnosis and treatment among young adults at risk for depression.

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