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Animal-assisted therapy in pediatric urodynamics.

INTRODUCTION/BACKGROUND: Urodynamics (UDS) is associated with high levels of patient anxiety/discomfort. Children are often unable to complete UDS, with anesthesia needed to place catheters. Animal-assisted therapy (AAT) has been used in a variety of settings, but it has not been studied for UDS before. OBJECTIVE: To determine if AAT can increase success of completing UDS testing without anesthesia in children who were previously unable to perform UDS, along with decreasing distress levels. STUDY DESIGN: We performed a pilot case series of 7 patients (2 female, 5 male) aged 4-16 (mean 9.7) years who previously were unable to complete UDS awake, with AAT prior to and during the UDS procedure. A visual analog scale (VAS) was used to measure patient stress levels before and after AAT. RESULTS: We were able to successfully complete UDS testing with AAT in 6 of the 7 patients (85.7%) without the need for anesthesia. VAS scores decreased from before to after AAT (5.4-3.6, p = 0.020) but with discrepancy when compared to UDS success. DISCUSSION: Our study was the first to describe AAT during UDS. Our preliminary data found AAT to be feasible in UDS. Subjective distress may not correlate with procedural success. AAT in UDS may be more beneficial in certain populations, such as anxious children who previously were unable to tolerate UDS, and not in others such as severe neurodevelopmental conditions. Our study was limited by the small sample size, a single provider, single center, single therapy dog, inclusion of a specific population of patients, and no control group due to this being a pilot study. CONCLUSION: AAT for certain children undergoing UDS testing could help improve the ability to complete the testing without anesthesia. Further studies are needed to fully demonstrate its usefulness in UDS.

Humans

Maternal prior pregnancy outcome subtype and offspring cryptorchidism: A retrospective case-control study.

OBJECTIVE: To determine whether maternal prior pregnancy outcome subtype and frequency are associated with cryptorchidism in male offspring, and whether first-trimester exogenous progesterone exposure mediates any observed association. MATERIALS AND METHODS: We conducted a hospital-based retrospective case-control study of 1220 mother-son pairs (610 cryptorchidism cases; 610 controls). Maternal prior pregnancy outcome subtype was defined using a prespecified proximal-event approach based on the most recent qualifying pregnancy event before the index pregnancy: no prior pregnancy loss or termination, miscarriage, or pregnancy termination. Subtype-specific frequency was categorized as 0, 1, or ≥2. Adjusted odds ratios (aORs) were estimated using multivariable logistic regression; robustness was examined using 1:1 propensity score matching with conditional logistic regression. Exploratory mediation analysis estimated indirect effects through first-trimester exogenous progesterone exposure. RESULTS: In fully adjusted models, miscarriage was associated with higher odds of cryptorchidism compared with no prior pregnancy loss or termination (aOR 1.97; 95% CI 1.26-3.09), whereas pregnancy termination was not (aOR 1.14; 95% CI 0.86-1.52). In joint subtype-frequency analyses, odds increased with the number of miscarriages (one: aOR 1.74; 95% CI 1.07-2.83; two or more: aOR 3.77; 95% CI 1.22-11.66) and were higher for two or more pregnancy terminations (aOR 1.77; 95% CI 1.10-2.84). Matched analyses were directionally consistent. Mediation analyses suggested a modest indirect effect through first-trimester progesterone exposure for the miscarriage association. CONCLUSIONS: Maternal prior miscarriage was associated with cryptorchidism in male offspring, whereas pregnancy termination showed higher odds only among women with two or more prior procedures. First-trimester exogenous progesterone exposure may account for a modest proportion of the miscarriage-cryptorchidism association.

Humans

Retinal microstructural alterations as early phenotypes of depression in radiogenomics analysis.

BACKGROUND: With the increasing prevalence of depression, there is an urgent clinical need for early screening in depression. The retina offers a promising window for early screening in depression due to its rapid, non-invasive, objective, eye-brain correlated characteristics, but previous research has yielded conflicting alterations in retinal microstructure in depression. METHODS: We screened retinal optical coherence tomography and brain magnetic resonance imaging data in the UK Biobank to enroll 23,225 participants for retinal study of depression occurrence, and 1475 participants for the eye-brain association study. We also used genetic data (ID: ebi-a-GCST90014267 and ukb-d-20,448) from the Integrative Epidemiology Unit Open Genome-Wide Association Study for Mendelian randomization analysis. We used Cox regression to assess the association between retinal microstructure and depression risk, Mendelian randomization to infer causality, and mediation analysis to explore retina-brain pathway association. RESULTS: The Cox regression analysis showed that retinal ganglion cell-inner plexiform layer (GCIPL) thickness remained a significant predictor of depression. The Mendelian randomization analysis indicated a positive statistical association between GCIPL thickness and depression. Moreover, there was a significant positive correlation (all p&#xa0;<&#xa0;0.001) between the volume of specific depression-related brain regions and the GCIPL thickness. Adjusting for age, sex, and head size, the mediation analysis provided preliminary evidence for a potential anatomical pathway linking retinal GCIPL thickness to depression-related brain regions through primary visual cortex and secondary visual cortex volumes. CONCLUSION: Thickened retinal GCIPL is a potential early phenotype of depression and has a potential association pathway with depression-related brain regions using a radiogenomics approach.

Humans

Obstructive sleep apnea and idiopathic intracranial hypertension: a systematic review and meta-analysis.

OBJECTIVE: To determine the pooled prevalence of obstructive sleep apnea (OSA) among adults with idiopathic intracranial hypertension (IIH) using polysomnography (PSG) and the Berlin Questionnaire screening. NATURE: IIH is a vision-threatening disorder characterized by elevated intracranial pressure. OSA shares overlapping risk factors and pathophysiological mechanisms with IIH, including nocturnal hypoxia and hypercapnia. Clarifying OSA prevalence in IIH is clinically important for diagnosis and management. METHODS: For this prospectively registered systematic review and meta-analysis (PROSPERO: CRD420251132794), we searched MEDLINE, Embase, and CENTRAL from inception to August 23, 2025, for studies reporting PSG-confirmed OSA or Berlin Questionnaire positivity in adults with IIH. Risk of bias was assessed using ROBINS-I and RoB-2, and certainty of evidence was checked using the Grading of Recommendations, Assessment, Development and Evaluation tool. Random-effects meta-analyses of proportions generated pooled prevalence estimates. Subgroup analyses excluded high-risk studies, leave-one-out analyses assessed robustness, and funnel plots evaluated publication bias. RESULTS: Eleven studies met the inclusion criteria. Across 9 PSG-based studies (n&#x202f;=&#x202f;299), the pooled prevalence of OSA in IIH was 0.44 (95% CI: 0.26-0.63; I&#xb2;&#x202f;=&#x202f;90.5%). Leave-one-out analyses showed stable results (39%-50%). Excluding high-risk studies (4 studies; n&#x202f;=&#x202f;132) yielded a pooled prevalence of 0.53 (95% CI: 0.32-0.74). Four Berlin Questionnaire studies (n&#x202f;=&#x202f;154) showed a pooled prevalence of 0.65 (95% CI: 0.54-0.74; I&#xb2;&#x202f;=&#x202f;0%). Funnel plot asymmetry suggested publication bias, and certainty of evidence was very low. CONCLUSIONS: OSA is common among patients with IIH, supporting routine objective sleep evaluation. Prospective studies are needed to clarify this association.

Humans

Role of nicotine metabolite ratio in pharmacological interventions on smoking cessation: A systematic review and meta-analyses of randomized controlled trials.

BACKGROUND AND OBJECTIVES: Emerging evidence suggests that the nicotine metabolite ratio (NMR) may influence the efficacy of smoking cessation, yet its role across pharmacotherapies remains unclear. This study aims to investigate how NMR affects cessation outcomes under different medications to guide personalized treatment. METHODS: We searched PubMed, Medline, EMBASE, and the Cochrane Central Register of Controlled Trials (inception to September 30, 2024) for randomized controlled trials on pharmacotherapy for smoking cessation with NMR data. Data were synthesized using random-effects models, with heterogeneity assessment. The primary outcome was verified smoking cessation rate at the end of treatment or the closest time-point. RESULTS: Eleven RCTs with accessible full text were included in the qualitative analyses and nine were included in the quantitative synthesis. For non-titratable nicotine replacement therapy (NRT), normal/fast metabolizers demonstrated lower odds of smoking cessation than slow metabolizers (Odds Ratio, OR=0.81, 95% confidence interval, CI=0.68-0.96; 5 studies, I&#xb2;=62.5%). No significant associations were shown between normal/fast and slow metabolizers using titratable NRT (OR=1.04, 95% CI=0.95-1.14; 2 studies, I&#xb2;=0%), bupropion (OR=0.67, 95% CI=0.38-1.16; 2 studies, I&#xb2;=51.4%), or varenicline (OR=1.17, 95% CI=0.79-1.74; 4 studies, I&#xb2;=59.8%). CONCLUSION: Current evidence demonstrates that NMR moderates' treatment efficacy among those who smoke using non-titratable NRT, with slow metabolizers achieving significantly better cessation outcomes than normal/fast metabolizers. Substantial further research is needed to determine optimal medication hierarchies across metabolic profiles.

Humans

The utility of 18F-fluorodeoxyglucose PET/computed tomography in relapsing polychondritis: a systematic review and meta-analysis.

Relapsing polychondritis is a rare chronic autoimmune inflammation of the cartilage associated with life-threatening respiratory complications. Currently, no clear role of imaging modalities such as 18F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) is defined in the literature. This systematic review and meta-analysis provide current evidence on the PET-positivity rate and utility in relapsing polychondritis. Prospective or retrospective studies with more than five patients of suspected relapsing polychondritis who underwent 18F-FDG PET/CT during their management and reported a PET-positivity rate were included. Low-sample-size studies describing chondritis due to other aetiologies or utilizing PET-based radiopharmaceuticals other than FDG were excluded. A systematic search using relevant keywords was conducted across four databases (PubMed, Embase, Scopus and Web of Science) to include studies up to 25 April 2025. The Joanna Briggs Institute critical appraisal tools were used for risk-of-bias analysis. Data were analysed using the R software package (v4.3.1; 2023). Out of 962 articles, three with a total of 97 patients were included. With a pooled PET-positivity rate of 94% [95% confidence interval (CI): 73-99%, I2&#x2005;=&#x2005;0%, P&#x2005;=&#x2005;0.76] and a pooled baseline SUVmax of 4.0 (95% CI: 3.5-4.6, I2&#x2005;=&#x2005;32%, P&#x2005;=&#x2005;0.23), 18F-FDG PET identified asymptomatic cartilage involvement in more than 25% patients and PET parameters correlated well with inflammatory markers. It had a higher positivity rate for inaccessible sites, such as peripheral airways, and was crucial in treatment monitoring. The pooled PET-positivity rate of 18F-FDG PET in relapsing polychondritis is high but requires prospective large-sample-size studies to explore the diagnostic accuracy and prognostic implications of 18F-FDG PET in relapsing polychondritis.

Polychondritis, Relapsing

Development of a core descriptor set for studies assessing interventions for diabetes-related foot ulceration.

AIMS/HYPOTHESIS: Foot ulceration is a common complication of diabetes and is associated with high mortality and costs. The quality of evidence to inform clinical practice is limited, partly because clinical studies do not consistently report baseline participant characteristics. This study aimed to develop a core descriptor set (CDS), a minimum set of descriptors to be measured in all studies evaluating interventions for people with diabetes-related foot ulceration. METHODS: A longlist of descriptors was generated through a systematic review of studies assessing interventions for diabetes-related foot ulcers, pre-registered with PROSPERO (CRD42019128250). The identified descriptors were then ranked based on perceived importance by healthcare professionals from different fields and geographical locations using a nine-point Likert scale in the first round of a Delphi survey. Using standardised criteria, descriptors without consensus were re-ranked in round two. Critical descriptors and those without consensus after the Delphi process were discussed in the consensus meeting to finalise the CDS. RESULTS: The systematic review yielded 95 candidate descriptors. The two Delphi rounds were completed by 102 and 69 healthcare professionals, respectively. The Delphi process identified 34 critically important descriptors and 13 descriptors without consensus, which were discussed in the consensus meeting. The ratified CDS included 28 descriptors across nine domains: demographic variables; individual factors; ulcer characteristics; limb characteristics; ongoing medical interventions; previous surgical interventions; medication history; biochemical measurements; and quality of life/function/symptoms. CONCLUSIONS/INTERPRETATION: This CDS reflects characteristics important to health professionals and researchers when reporting clinical studies on diabetes-related foot ulceration. Its use will aid the reporting of future studies.

Humans

Beyond multidimensionality: a systematic review of recurrent frailty archetypes in community-dwelling older adults.

BACKGROUND: Frailty is a clinically heterogeneous geriatric syndrome commonly summarised using physical or multidomain severity scores. Whether person-centred analyses identify recurring within-frailty configurations has not been systematically examined in community-dwelling older adults. METHODS: We searched PubMed, Embase, MEDLINE, and CINAHL (January 2000-November 2025) for cross-sectional studies using latent class, latent profile, or analogous clustering methods to derive frailty subgroups. Quality was assessed using the AHRQ checklist and a purpose-built appraisal of person-centred model reporting. Study-derived classes were mapped in duplicate to a structured archetype framework developed through comparison of class-defining features across studies. RESULTS: Fourteen reports representing 12 independent datasets from eight countries were included. Six configurations were identified: minimally impaired reference, mobility-physical, nutritional-metabolic, cognitive-predominant, combined cognitive-physical, and psychosocial/mood-predominant. Convergence was measurement-dependent. The reference and mobility-physical configurations recurred across physical-only and multidomain indicator sets, while the combined cognitive-physical configuration appeared across several multidomain frameworks but required cognition to be measured. The remaining configurations emerged only when their defining domains were included. Evidence of prognostic value beyond aggregate frailty severity came from one deficit-index study. Collapsing shared-provenance reports and excluding the boundary-eligible study did not alter recurrence; excluding the Croatian dataset left five configurations recurrent, with the cognitive-predominant configuration supported by one independent dataset. CONCLUSIONS: Person-centred analyses identify recurring within-frailty configurations, but their apparent stability is partly measurement-dependent. A five-configuration core persisted after exclusion of the Croatian dataset, whereas the cognitive-predominant configuration remained weakly replicated. Harmonised indicators and rigorous external validation are needed before clinical application.

Humans

Adjunctive middle meningeal artery embolization for chronic subdural hematoma: A systematic review and meta-analysis of eight randomized trials.

BACKGROUND: Randomized trials suggest that adjunctive middle meningeal artery embolization (MMAE) may reduce recurrence in chronic subdural hematoma (CSDH), but potential sources of variability in treatment effects across studies remain poorly understood. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of MMAE and to explore potential study-level sources of between-study heterogeneity. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials comparing MMAE plus surgery versus surgery alone, following PRISMA guidelines. Trial sequential analysis (TSA) was prespecified to assess the robustness of pooled findings. Exploratory mixed-effects meta-regression was performed to examine whether aggregate study-level mean age and anticoagulation use were associated with variability in recurrence outcomes. RESULTS: Eight trials including 1961 patients were analyzed. MMAE plus surgery was associated with a reduction in recurrence compared with surgery alone (RR 0.63, 95% CI 0.46-0.85; I&#xb2; = 0%), and TSA supported this finding. Although conventional meta-analysis suggested a reduction in reoperation, the TSA findings were more sensitive to analytical assumptions and less robust. Exploratory study-level meta-regression analyses suggested possible associations between recurrence outcomes and mean age or anticoagulation use, although these findings should be interpreted as hypothesis-generating only. Safety outcomes were comparable between groups. CONCLUSIONS: Adjunctive MMAE was associated with reduced recurrence in CSDH. Exploratory analyses evaluating aggregate study-level characteristics were limited by the small number of included trials and the use of aggregate-level data, and should be considered hypothesis-generating only. Further prospective studies are needed to better understand variability in treatment effects.

Humans

The potential of clustering methods for pre-test triage in sleep medicine: A systematic review.

Sleep disorders exhibit substantial heterogeneity, and traditional classifications may not fully capture clinically relevant subtypes. Clustering techniques can identify patient subgroups that improve phenotypic characterization and may support personalized management. This systematic review evaluated the application of clustering in sleep medicine, with particular focus on its potential use as a pre-test triage tool prior to formal sleep testing. PubMed/MEDLINE, Embase, Web of Science, and Scopus were searched to February 2025. Eligible studies applied clustering to classify sleep disorders in adults. Two reviewers independently conducted screening, data extraction, and risk-of-bias assessment using QUADAS-2. The protocol was registered on PROSPERO. Fifty-one studies (1983-2025) were included, predominantly focused on obstructive sleep apnea (OSA) (n&#x202f;=&#x202f;38, 74%). Hierarchical clustering (n&#x202f;=&#x202f;20) and K-means clustering (n&#x202f;=&#x202f;14) were the most frequently used techniques. Internal validation was reported in only 18% of studies, and external validation was reported in only 1 study. Seven studies relied exclusively on baseline clinical, demographic, or questionnaire data, representing pre-test scenarios, whereas most incorporated polysomnography-derived variables, limiting their applicability to early clinical stratification. Hierarchical clustering was the most commonly applied method; however, the overall lack of validation limits confidence in the robustness and clinical applicability of identified phenotypes. The potential role of clustering as a pre-test triage strategy remains largely unexplored, as most studies focused on post-diagnostic phenotyping and were affected by incorporation bias. Future research should prioritize pre-test clinical variables, rigorously validate internally and externally, and adopt standardized methodological and reporting practices to facilitate clinical translation.

Humans

Genetic determinants of gestational diabetes mellitus in thai pregnant women: role of GCKR, CDKAL1, TCF7L2, NEDD1, and CMIP variants.

BACKGROUND: Gestational diabetes mellitus (GDM) has a high global prevalence and arises from complex interactions between genetic predisposition and environmental factors. GDM is associated with metabolic disturbances and chronic low-grade inflammation, both of which contribute to its pathogenesis. This study aimed to investigate the association between GDM and 135 single-nucleotide polymorphisms (SNPs) across 20 genes related to metabolic traits. METHODS: In this case-control study, 152 pregnant women with GDM and 684 pregnant women with normal glucose tolerance (NGT) who underwent antenatal examination at Siriraj Hospital, Bangkok, were enrolled. Clinical data and blood samples were collected from all participants. Genomic DNA was isolated and subjected to whole-genome sequencing using the DNBSEQ-T7RS high-throughput sequencing platform. Genotype analyses were performed using R software, and haplotype analyses were conducted using the online SNPStats software. RESULTS: After adjusting for maternal age and pre-pregnancy body mass index, polymorphisms in TCF7L2 (rs34872471, rs7901695, rs4506565, rs7903146, rs12243326, and rs12255372), NEDD1 (rs10431408, rs11830756, rs249579, rs249585, and rs4762339), CMIP (rs2306115 and rs201681534), CDKAL1 (rs4710942), GCKR (rs2293572 and rs2293571), and GCK (rs5883890) were significantly associated with the risk of GDM. Haplotype analysis demonstrated that the TCF7L2 rs12243326-rs12255372 CA haplotype was associated with a decreased risk of GDM (OR = 0.44, 95% CI: 0.23-0.81), while the NEDD1 rs249579-rs249585-rs4762339 GGT haplotype was associated with an increased risk of GDM (OR = 1.40, 95% CI: 1.08-1.82). CONCLUSIONS: These findings suggest that genetic variations in TCF7L2, NEDD1, CMIP, CDKAL1, GCK, and GCKR contribute to GDM susceptibility in the Thai population.

Humans

Metabolomic Responses to Oral Glucose Tolerance Test and Hyperinsulinemic-euglycemic Clamp in CKD.

BACKGROUND: The oral glucose tolerance test (OGTT) captures integrated physiological responses involving intestinal glucose absorption, incretin signaling, and endogenous insulin secretion, whereas the hyperinsulinemic-euglycemic clamp (clamp) isolates insulin-mediated glucose uptake. Comparing plasma metabolomic responses to these two challenges may identify processes specific to intestinal nutrient delivery and how they vary in CKD. METHODS: Targeted plasma metabolomics was performed in 59 adults without diabetes (39 with CKD [eGFR <60 mL/min/1.73 m2] and 20 controls) from the Study of Glucose and Insulin in Renal Disease (SUGAR). Each participant underwent a 75-g OGTT and clamp approximately one week apart. Eighty-eight plasma metabolites were quantified at fasting and during each challenge. Metabolite levels were log-transformed and normalized using Systematic Error Removal Using Random Forest (SERRF). Metabolites were classified using adjusted regression slopes relating OGTT and clamp responses. RESULTS: The mean (SD) age and eGFR were 64 (13) years and 54 (26) mL/min/1.73 m2, respectively, and 41% were female. In the overall cohort, OGTT and clamp induced broad plasma metabolic changes, with 63 (72%) and 76 (86%) metabolites significantly altered from fasting, respectively. Seventy-three metabolites (83%) demonstrated a significant relationship between OGTT and clamp responses. Of these, 22 (25%) exhibited true concordance and 51 (58%) demonstrated similar directional changes but differed in magnitude. A total of 15 (17%) metabolites were discordant or non-corresponding, of which only three were discordant. The non-corresponding metabolites were enriched in amino acid metabolism. Eleven metabolites (13%) demonstrated differential responses between OGTT and clamp by CKD status, involving amino acid and glucose metabolism pathways. CONCLUSIONS: Metabolomic responses to OGTT and clamp were largely directionally concordant but differed in magnitude, with attenuation during OGTT. Discordant metabolites were rare, while non-corresponding metabolites were confined to amino acid pathways. CKD modified OGTT-clamp correspondence for metabolites involved in amino acid and glycolytic metabolism.

Journal Article

Quo vadis, BGA? A collaborative EDNAP exercise on the challenges and progress in forensic biogeographical ancestry inference.

There is a broad consensus that forensic tests for the prediction of externally visible characteristics (EVC) and analysis of biogeographic ancestry (BGA) of an individual are technically reliable. However, interpretation of the results and population-specific genotype distribution patterns remains challenging. EVC and BGA analyses provide valuable information for population genetics studies and as investigative leads for criminal cases, as well as for historical and contemporary identification tests. However, inaccurate or incorrect predictions, for example, from subjective bias in the interpretations made, have the potential to misdirect police investigations. The legal situation regarding EVC and BGA testing varies by country: ranging from countries where it is explicitly prohibited, to those without specific regulations on biogeographic ancestry prediction, and others that have already enacted laws governing its use. The reluctance to utilize these analyses is not only due to legal restrictions and data protection concerns, but also to initial limited sets of sufficiently comprehensive forensic DNA assays. Forensic BGA marker panels typically contain up to &#x223c;300 SNPs. This relatively small number of genetic markers, along with limited reference population data, complicates the interpretation of results from donors of unknown origin. This paper presents the results of a collaborative EDNAP study, which, for the first time, evaluated the approach to reporting EVC and BGA data between international laboratories. For the study, DNA from nine individuals with self-reported ancestry was collected and analysed using various forensic panels differing in the number and composition of ancestry-informative markers genotyped, comprising: the Precision ID mtDNA Whole Genome Panel, the VISAGE Basic Tool and the VISAGE Enhanced Tool for Appearance and Ancestry Prediction, and the Ion AmpliSeq&#x2122; PhenoTrivium Panel. To ensure full data protection, all SNP genotypes and uniparental marker haplotypes obtained were not shared with third parties. Instead, the genetic data were analysed using a range of commonly used population analysis software packages. These analysis outcomes were then distributed to twelve European forensic laboratories (both academic and law enforcement institutions), who were asked to prepare reports based on their interpretation of the phenotypes and ancestry they inferred from the analysis data. A questionnaire sent alongside the genetic information, aimed to evaluate which difficulties were encountered by the participants in processing the BGA analysis data they were given.

Humans

A Qualitative Analysis of Cancer Survivors' Experience in a Time-Restricted Eating vs Control Clinical Trial to Address Cancer-Related Fatigue.

PURPOSE: To describe cancer survivors' lived experiences in a clinical trial that tested an individualized nutrition counseling with or without time-restricted eating to address cancer-related fatigue. METHODS: The Fatigue REDuction After cancer study was a two-arm, randomized controlled trial. Participants were adult cancer survivors who were 2 months to 2 years post-treatment. All participants received individualized nutrition counseling; those in the time-restricted eating group self-selected a consistent 10-hour eating window for 12 weeks. After the study, semi-structured exit interviews were conducted to gauge participants' experiences in the trial. Interviews were transcribed and two independent coders thematically analyzed the interviews using inductive and deductive coding. NVivo software was used for data organization and analysis. RESULTS: Participants (n&#x202f;=&#x202f;24; TRE&#x202f;=&#x202f;11; Control&#x202f;=&#x202f;13) were 55 &#xb1; 13 years old, 75% were female, and they had a variety of cancer types. The majority of participants found that being in the study helped them to set and achieve lifestyle goals and would therefore recommend the study to others. Participants in the time-restricted eating group noted that time-restricted eating helped them set a better routine, providing a positive sense of control. However, some noted difficulty switching to a 14-hour fasting schedule, as it can interfere with their regular routine or employment schedules. Many participants noted they were happy that cancer-related fatigue was gaining more attention, hoping to find solutions for persistent cancer-related fatigue. CONCLUSION: The majority of participants found the study useful and, regardless of their group assignment or the intervention's impact on their fatigue, found the study helped them to gain better control of their dietary habits.

Humans

The impact of artificial intelligence on critical thinking and clinical reasoning in health professions education: A systematic review and meta-analysis.

BACKGROUND: Critical thinking and clinical reasoning underpin healthcare professionals' ability to navigate uncertainties and deliver safe and effective care. With artificial intelligence (AI) advancement and growing adoption, AI-based educational tools are increasingly used to support these cognitive competencies' development. OBJECTIVE: To synthesize randomised and controlled clinical trials on AI-based educational tools in health professions education and examine their effects on critical thinking and clinical reasoning among health professions students. METHODS: Six electronic databases were searched from January 1, 2014 to July 28, 2025 was reviewed: PubMed, Cochrane Central Register of Controlled Trials, CINAHL, Scopus, Embase and Web of Science. Two independent reviewers performed data extraction and quality assessment using standardized JBI checklists. The GRADE approach was used to assess the certainty of evidence. Studies were pooled via random-effects meta-analyses or narrative syntheses. RESULTS: Fourteen randomised controlled trials and seven controlled clinical trials were included (n&#xa0;=&#xa0;21). Meta-analyses revealed small to medium effect sizes for the surrogate clinical reasoning outcomes of performance-based assessment scores (SMD 0.68; 95% CI [0.38, 0.98], p-value&#xa0;=&#xa0;0.00; I2&#xa0;=&#xa0;38%) and knowledge test scores (SMD 0.39; 95% CI [0.09, 0.69], p-value&#xa0;=&#xa0;0.01; I2&#xa0;=&#xa0;79%). Critical thinking and clinical reasoning skills and dispositions were narratively synthesized, with majority of included studies favouring AI-based interventions but the evidence had low to very low certainty. CONCLUSION: AI-based educational interventions may improve critical thinking and clinical reasoning among health profession students, but the evidence is very uncertain. This review offers preliminary insights but does not allow identification of optimal interventions or discipline-specific recommendations due to small sample sizes and substantial intervention heterogeneity. Further research is required to draw definitive conclusions. PROTOCOL REGISTRATION: CRD42025634074.

Humans

Whole genome sequencing of unusual Hepatitis C virus subtypes and drug resistance analysis during direct-acting antiviral therapy in India.

INTRODUCTION AND OBJECTIVES: Pangenotypic direct-acting antivirals (DAA) are effective against highly prevalent Hepatitis C virus (HCV) subtypes, but have been clinically validated almost exclusively in high-income countries. Unusual HCV subtypes may carry natural polymorphisms, potentially impacting DAA susceptibility. We conducted full-genome characterization and resistance analysis of unusual HCV subtypes in patients receiving DAA treatment. PATIENTS AND METHODS: In this prospective hospital-based study, eligible patients were screened for anti-HCV antibodies and active infection was confirmed by diagnostic 5'NCR-based HCV RNA detection. Genotyping was performed by core region sequencing, and viral load quantified by real-time PCR. For whole genome sequencing, multiplex primers were designed using alignments of global reference sequences. Sequencing was carried out using the Oxford Nanopore Technology platform. Phylogenetic analysis used multiple sequence alignment and the HCV-GLUE resource for resistance-associated substitution (RAS) analysis. RESULTS: Predominant genotype was genotype 3 in 64.3% (n = 45); genotype 6 in 21.4% (n = 15); and genotype 1 in 14.2% (n = 10). Unusual HCV subtype 6xa was detected in two patients and showed no NS5A resistance mutations. One genotype 3b patient relapsed at 24 weeks post-DAA treatment completion and carried NS5A resistance-associated substitutions 30 K and 31 M both at baseline and at relapse, conferring high-level resistance to NS5A inhibitors. CONCLUSION: This is the first report from India of whole genome sequencing of HCV subtype 6xa. The identification of NS5A resistance mutations in the 3b relapse case underscores challenges for global HCV elimination strategies.

Humans

Smart crutch tipsTM real-time feedback improves adherence to partial weight-bearing protocols following lower extremity fracture surgery: a pilot study.

PURPOSE: To evaluate the effectiveness of Smart Crutch Tips&#x2122; in promoting adherence to prescribed early partial weight-bearing (PWB) protocols and to assess patient experience with real-time weight-bearing feedback during home rehabilitation. METHODS: Twenty patients with lower extremity fractures prescribed partial weight-bearing (PWB) were randomized into two groups utilizing real-time feedback crutch tips (RFC). The Intervention group (n&#x2009;=&#x2009;10) used Smart Crutch Tips&#x2122; (ComeBack Mobility Inc., Kiev, Ukraine), which provided real-time feedback on weight-bearing compliance. The Control group (n&#x2009;=&#x2009;10) also used crutches equipped with Smart Crutch Tips&#x2122;, but notifications were disabled, allowing passive data collection without patient feedback. Weight-bearing compliance was defined as the percentage of steps within &#xb1;&#x2009;10% of the prescribed target. Secondary outcomes included patient satisfaction and device usability assessed using the System Usability Scale (SUS) throughout the home rehabilitation period. RESULTS: The Intervention group demonstrated significantly greater PWB compliance compared with the Control group (73.6% vs. 21.1%, p&#x2009;<&#x2009;0.01). The Intervention group reported a mean SUS score of 84.25, indicating excellent usability. No device-related complications or adverse events were observed. Patient satisfaction, assessed through video interviews, was high, with participants in the Intervention group expressing a strong willingness to recommend the device to others with similar injuries and rating it 10 out of 10. CONCLUSION: Smart Crutch Tips&#x2122; significantly improved adherence to prescribed partial weight-bearing protocols following lower extremity fracture surgery. The RFC device demonstrated high usability, excellent patient satisfaction, and no device-related complications during home rehabilitation throughout the study period.

Humans

Plasma proteomics reveal SERPINA1 and CD59 as candidate biomarkers for COVID-19 severity stratification and prognosis prediction.

BACKGROUND: COVID-19 has been closely associated with coagulation abnormalities. However, existing biomarkers, including D-dimer and fibrin degradation products (FDP), exhibit limited accuracy in stratifying disease severity and predicting long-term clinical outcomes. OBJECTIVES: This study aimed to use proteomic analysis to identify plasma biomarkers associated with COVID-19 severity and prognosis, and validate their predictive utility for mortality and thromboembolic complications. METHODS: Plasma proteomic profiles were analyzed across three COVID-19 severity classes. Differential expression analysis and functional analysis were performed. Clustering analysis was used to identify proteins correlated with disease severity. Candidate biomarkers were validated in an independent cohort. Predictive performance of the biomarkers for mortality, sepsis and venous thromboembolism was evaluated using bootstrap-corrected ROC analyses and multivariable regression analyses. RESULTS: Proteomic analysis revealed progressive involvement of the coagulation and complement pathway with increasing disease severity. SERPINA1 and CD59 were identified as candidate biomarkers and exhibited significantly higher plasma levels in severe cases. Bootstrap-corrected ROC analyses demonstrated strong predictive performance: SERPINA1 achieved AUCs of 0.775 and 0.924 for 30-day and 12-month mortality, and CD59 achieved AUCs of 0.720 for sepsis; the combined model further improved prediction of 12-month mortality (AUC 0.946) and sepsis (AUC 0.904), outperforming D-dimer and FDP. Multivariable regression confirmed their independent prognostic value. CONCLUSION: This exploratory study identifies SERPINA1 and CD59 as candidate prognostic biomarkers in COVID-19, highlighting the role of coagulation and complement-related pathways in disease severity and warranting further prospective validation.

Humans