SEARCH · Search PubMed

Results for “Military-to-civilian transition”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

2,889 records · Page 16Linked to original sources

PubMed2026

Gut microbial diversity at baseline conditions the clinical, microbiome, and metabolic response to paraprobiotic Lactiplantibacillus plantarum LRCC5282 in overweight adults.

The gut microbiota is increasingly recognized as a target for obesity management; however, whether baseline gut microbial diversity conditions responsiveness to microbiota-targeted interventions remains unclear. We aimed to investigate whether baseline gut microbial diversity is associated with responsiveness to a paraprobiotic derived from Lactiplantibacillus plantarum LRCC5282 (LP5282-P) in overweight adults. In a 12-week, randomized, double-blind, placebo-controlled, multicenter trial of 120 overweight adults, LP5282-P produced no significant between-group differences in any clinical outcome across the overall per-protocol population. However, in the low-diversity subgroup, LP5282-P was associated with significant reductions in body weight, body mass index, and circulating leptin levels. These clinical changes were accompanied by compositional shifts in the gut microbiota, including higher relative abundances of Christensenellaceae, Faecalibacterium, and Alistipes. Fecal metabolite profiles showed elevated acetate and butyrate concentrations and altered bile acid composition. Within the low-diversity subgroup, changes in the relative abundances of Akkermansia and Eubacterium were inversely correlated with changes in body weight, body fat mass, and leptin levels. In contrast, the high-diversity subgroup exhibited no consistent response across the outcome domains examined. Overall, baseline gut microbial diversity was associated with differential responsiveness to LP5282-P, supporting its potential use as a stratification variable in future microbiota-targeted intervention trials. Further studies integrating direct measures of microbial activity and host response are warranted to elucidate the biological pathways underlying this diversity-dependent responsiveness. Trial registration: Clinical Research Information Service (CRIS), KCT0008119.

Humans↗

PubMed2026

Pharmacological therapies for the prevention of fractures in men.

RATIONALE: Pharmacological therapies for fracture prevention usually target osteoporosis, a skeletal disorder characterised by compromised bone mass or quality (or both). As most participants in osteoporosis trials are women, a review of pharmacological therapies for fracture prevention in men was warranted. OBJECTIVES: To determine the benefits and harms of bisphosphonates, parathyroid (PTH) or parathyroid-related protein (PTHrP) analogues, denosumab, and romosozumab therapy for the prevention of fractures in men. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trial registries (ClinicalTrials.gov and WHO ICTRP) until 14 October 2025, with no restrictions on date or language of publication. ELIGIBILITY CRITERIA: We included randomised controlled trials that compared bisphosphonates, PTH or PTHrP analogues, denosumab, or romosozumab (alone or with calcium or vitamin D, or both) with placebo, other drugs, or non-pharmacological therapies in men aged 50 years or older. Our primary comparison was bisphosphonates versus placebo. OUTCOMES: Critical outcomes were incidence of hip fractures, symptomatic vertebral fractures, other (not hip or vertebral) fractures, disability, participants with adverse events, study withdrawals due to adverse events, and participants with serious adverse events. Our primary time point was the final time point reported in the trials. RISK OF BIAS: We used Cochrane's RoB 2 tool to assess risk of bias. SYNTHESIS METHODS: We used a random-effects model for meta-analysis employing the Mantel-Haenszel approach, and the DerSimonian and Laird method to estimate between-trial variance. We assessed the certainty of evidence using GRADE. INCLUDED STUDIES: Seventeen trials (4132 participants) met our inclusion criteria. The average age of participants ranged from 52 to 73 years. Twelve trials used a placebo comparator versus bisphosphonate (7 trials, 2548 participants), PTH or PTHrP analogues (4 trials, 569 participants), denosumab (1 trial, 240 participants), and romosozumab (1 trial, 244 participants). For the other planned comparisons, a bisphosphonate was compared to vitamin D/vitamin D analogues (2 trials, 434 participants), to calcitonin (1 trial, 32 participants), to PTH or PTHrP analogues (1 trial, 19 participants), or to another bisphosphonate (1 trial, 301 participants), and one trial compared a bisphosphonate plus calcium to calcium tablets alone (46 participants). SYNTHESIS OF RESULTS: Placebo-controlled trials were largely susceptible to bias in selection of the reported result (83%), while most trials without a placebo control were also susceptible to bias arising from the randomisation process (100%) and in measurement of the outcome (80%). We are very uncertain about the effect of bisphosphonates on the incidence of hip fractures, symptomatic vertebral fractures, or other (non-hip non-vertebral) fractures compared to placebo at the final follow-up (up to two years). We downgraded the certainty of evidence once for risk of bias, twice for imprecision (very low event rates), and once for suspected publication bias. The certainty of evidence for incidence of other fractures was further downgraded for indirectness, as it was unclear if hip fractures were also included in the outcome. At up to two years, 2/875 participants (2 per 1000) in the bisphosphonate group reported hip fractures compared with 2/760 (3 per 1000) in the placebo group (risk ratio (RR) 0.73, 95% confidence interval (CI) 0.06 to 8.51; I² = 36%; 4 trials, 1635 participants); 5/1021 (4/1000) participants in the bisphosphonate group had a symptomatic vertebral fracture compared to 7/855 (8/1000) participants in the placebo group (RR 0.49, 95% CI 0.14 to 1.74; I² = 0%; 5 trials, 1876 participants); 25/1130 participants (16/1000) in the bisphosphonate group reported other (non-hip non-vertebral) fractures compared to 19/913 participants (21/1000) in the placebo group (RR 0.78, 95% CI 0.42 to 1.45; I² = 0%; 6 trials, 2043 participants). Bisphosphonates probably do not increase the risk of adverse events: 1024/1374 participants (746/1000) receiving bisphosphonates reported adverse events compared to 826/1174 participants (704/1000) receiving placebo (RR 1.06, 95% CI 0.93 to 1.19; I² = 75%; 7 trials, 2548 participants; moderate-certainty evidence) or serious adverse events: 329/1329 participants (272/1000) receiving bisphosphonate reported serious adverse events compared to 323/1128 participants (286/1000) receiving placebo (RR 0.95, 95% CI 0.84 to 1.08; I² = 0%; 6 trials, 2457 participants; moderate-certainty evidence). We downgraded the certainty of evidence once due to potential bias for adverse events and serious adverse events. We are very uncertain if bisphosphonates result in more withdrawals due to adverse events: 41/1374 participants (25/1000) in the bisphosphonate group withdrew due to adverse events compared with 43/1174 participants (37/1000) in the placebo group (RR 0.68, 95% CI 0.39 to 1.18; I² = 37%; 7 trials, 2548 participants; very low-certainty evidence). We downgraded the certainty of evidence once for risk of bias, once for indirectness, and once for imprecision. No trial reported disability. We are very uncertain about the effects of PTH or PTHrP analogues, denosumab, or romosozumab compared to placebo on fracture outcomes. We are very uncertain about the effects of PTH/PTHrP analogues on total adverse events, withdrawals due to adverse events, and serious adverse events. Denosumab may not increase the risk of adverse events or serious adverse events compared to placebo, while the evidence for withdrawals due to adverse events is very uncertain. Romosozumab probably does not increase the risk of adverse events and may not increase the risk of serious adverse events or result in more withdrawals due to adverse events. AUTHORS' CONCLUSIONS: We are very uncertain about the effects of bisphosphonates compared to placebo on the incidence of hip fractures, symptomatic vertebral fractures, or other (non-hip non-vertebral) fractures in men at up to two years of use. Bisphosphonates probably do not increase the risk of adverse events or serious adverse events, and we are very uncertain if they result in more withdrawals due to adverse events. We downgraded the certainty of evidence for indirectness, imprecision (low event rate), and serious risk of bias in selection of the reported result, as it was unclear if all studies fully reported every fracture. We found similar results for PTH or PTHrP analogues, denosumab, or romosozumab versus placebo. Larger, longer placebo-controlled studies are needed to determine whether pharmacological therapies are beneficial for reducing fractures in men. FUNDING: This Cochrane review had no dedicated funding. REGISTRATION: Protocol (2021): https://doi.org/10.1002/14651858.CD014707.

Humans↗

PubMed2026

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™ 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 = 10) used Smart Crutch Tips™ (ComeBack Mobility Inc., Kiev, Ukraine), which provided real-time feedback on weight-bearing compliance. The Control group (n = 10) also used crutches equipped with Smart Crutch Tips™, but notifications were disabled, allowing passive data collection without patient feedback. Weight-bearing compliance was defined as the percentage of steps within ± 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 < 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™ 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↗

PubMed2026

A systematic literature review of cultural concepts taught by pharmacist preceptors during pharmacy student experiential placements.

BACKGROUND: Cultural concepts such as cultural intelligence, awareness, competency and safety are essential in guiding culturally responsive care in health professional practice. Pharmacist preceptors play a pivotal role in sharing both clinical and cultural safe practice with pharmacy students. Culturally responsive care can contribute to achieving health equity, which is especially important for Indigenous communities. AIM: To review literature on cultural concepts in pharmacist preceptorship practices, and how these concepts are taught and communicated to pharmacy students during experiential learning. METHOD: The systematic review followed the PRISMA 2020 guideline. Scopus, PubMed, and Google Scholar were used to identify articles specific to pharmacist preceptors and pharmacy students published between 2015 and 2025, and available in English. RESULTS: Three full-text articles met the inclusion criteria. Major themes and subthemes were identified; pharmacist preceptors lacked preparedness to teach cultural concepts, resulting in variability in preceptors' understanding of cultural concepts and confidence in fulfilling preceptor responsibilities, underutilised structured frameworks to guide students' learning, challenges with preceptorship due to limited resources and support, and the influence of preceptorship on student learning, which impacted students' learning and competency. CONCLUSION: Pharmacy students had minimal exposure to culturally informed pharmacist preceptorship. It is likely that pharmacist preceptors require country-specific educational resources to support culturally safe preceptorship. Future research is required to substantiate these findings, and to guide culturally responsive practice and promote equitable health outcomes in diverse populations.

Humans↗

PubMed2026

Cross-kingdom dynamics of the subgingival bacteriome and mycobiome: A pilot study on the effects of a novel HA-H₂O₂-Glycine formulation to treat periodontitis.

OBJECTIVES: Traditional periodontal therapy primarily focuses on bacterial biofilm control; however, recent evidence also suggests a critical role for the oral mycobiome. This study evaluated the clinical and ecological impact of a novel mouthwash formulation containing hyaluronic acid (HA), hydrogen peroxide (H2O2), and glycine on periodontal patients METHODS: This prospective, randomized split-mouth trial included 13 adult participants with periodontitis treated with HA-H2O2-glycine formula (BMG0703A) used twice a day for seven days. Subgingival plaque samples were collected from periodontal pocket and healthy control sites at baseline (T0) and one-week post-treatment (T1). Microbial and fungal communities were characterized using Next-Generation Sequencing (NGS) of the 16S rRNA and ITS2 regions. Linear Mixed Models (LMM) and Spearman correlation were used to assess taxonomic shifts and cross-kingdom relationships. RESULTS: Sequencing revealed a promising ecological shift: the bacteriome shifted from anaerobic dominance (Olsenella, Peptostreptococcus) toward a health-associated aerobic profile, with Rothia near-doubling (11.91% to 22.68%). The mycobiome underwent a "normalization" effect: Candida abundance decreased significantly (22.8% to 9.1%), while fungal Shannon diversity in pockets returned to healthy-site levels. Inter-kingdom analysis identified antagonistic relationships between expanding commensal bacteria and opportunistic fungi, suggesting that the intervention may help re-establish a protective bacterial niche. CONCLUSIONS: The HA-H2O2-glycine formulation seems to facilitate a rapid, cross-kingdom modulation of the subgingival niche. By reducing anaerobic pathogens and normalizing the mycobiome it appear to induce short-term changes, suggesting potential as adjunctive strategy in periodontal management. CLINICAL SIGNIFICANCE: The present work underlines the possible cross-Kingdom effects of a novel compound.

Humans↗

PubMed2026

Left ventricular hypertrophy in hypertension: a systematic review and meta-analysis of echocardiographic studies published from 2011 to 2025.

AIM: An updated meta-analysis targeting the prevalence of left ventricular hypertrophy (LVH), a cardinal marker of hypertensive heart disease (HHD), over the last 15 years is lacking. Thus, we analyzed the literature in order to provide a comprehensive information on LVH prevalence, as assessed by echocardiography, in the hypertensive setting. METHODS: The PubMed, OVID-MEDLINE, and Cochrane Library databases were analyzed to search English-language articles published from 1 January 2011 up to 31 December 2025. Studies were identified by using MeSH terms and crossing the following search items: 'left ventricular hypertrophy', 'left ventricular mass', 'hypertensive heart disease', 'echocardiography', 'hypertension', and 'subclinical cardiac damage'. RESULTS: A total of 51 studies including 74 632 hypertensive patients were considered. Overall, the prevalence of LVH in the pooled cohort, defined according to criteria recommended by echocardiographic guidelines, was 36.6% (95% CI: 33.4-40%). Data provided by 18 studies ( n  = 40 108 patients) showed that the probability of having LVH was lower in men than in women (OR = 0.62, CI: 0.48-0.80, P  < 0.0001). Among patients with LVH (17 studies), the risk of concentric LVH was almost twice as high as eccentric (OR = 1.94, CI: 1.52-2.49, P  < 0.0001). CONCLUSION: Our meta-analysis suggests that the high contemporary prevalence of LVH reflects the failure of therapeutic strategies worldwide in the prevention and treatment of HHD. From a clinical perspective, these data imply the need for a more aggressive treatment of hypertension and related cardiovascular risk factors leading to LVH, especially in women.

Humans↗

PubMed2026

An Integrated Proteomics and Genomics Approach to Identify Essential Protein Kinases During Human Trophoblast Development.

In the developing human placenta, three subtypes of trophoblast cells, cytotrophoblasts (CTBs), extravillous trophoblasts (EVTs), and syncytiotrophoblasts (STBs), mediate critical functions essential for a successful pregnancy. CTBs constitute the stem/progenitor compartment and differentiate into STBs and EVTs within the floating and anchoring villi, respectively. STBs establish the maternal-fetal exchange interface and secrete human chorionic gonadotropin (hCG), a hormone vital for the maintenance of early pregnancy. EVTs anchor the maternal endometrium and invade the uterine tissue to remodel maternal cells, supporting implantation and progression of pregnancy. In this study, we used human trophoblast stem cells (hTSCs) as a model system and performed quantitative, label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) to profile the proteome and phosphoproteome in TSC stem state (analogous to undifferentiated CTBs) and following their differentiation to STBs and EVTs. Through a multiomics approach, we integrated our proteomics data with global gene expression profiles to correlate cell-type specific gene and protein expression during human trophoblast development. We also identified global phosphoproteome and analyzed kinases that are specifically active in hTSC stem state, as well as in differentiated STBs and EVTs. We experimentally validated specific kinases, such as BUB1B, PAK6, PKYMT1, and TNIK, that are essential for maintaining the hTSC stem-state. Additionally, atypical protein kinase C isoforms PKCζ are essential for STB development, whereas PTK2B, SRC, TRIO, and LYN are important for EVT development. Our findings highlight key kinases uniquely required for specific stages of trophoblast development during human placentation and suggest that pharmacological inhibition of these kinases could negatively impact the placentation process during pregnancy.

Humans↗

PubMed2026

AI-enabled viral genomics: from virus discovery to host prediction and emerging variant forecasting.

The rapid expansion of metagenomic sequencing has generated vast repositories of viral sequence data that far outpace our capacity to interpret them using conventional approaches. Highly divergent sequences, sparse functional annotation, and taxonomically uneven sampling present fundamental challenges for reference-dependent methods, which lose sensitivity precisely for novel and understudied viruses with high public health relevance. Artificial intelligence (AI) provides a new avenue to address these challenges by enabling predictive inference from viral genomes and proteins while reducing dependence on sequence similarity. In this Review, we discuss representative advances in AI for virus discovery, taxonomic classification and functional annotation, prediction of host range and zoonotic potential, and efforts toward forecasting emerging variants. These advances are transforming viral genomics from a largely descriptive discipline into one with increasing predictive capability. We also critically assess the major challenges that constrain current approaches, including the availability of high-quality and representative datasets, rigorous model evaluation, biological interpretability and responsible governance for increasingly capable AI models.

Artificial Intelligence↗

PubMed2026

How the Social Context and Peer Helping Contribute to Better Alcohol Outcomes Among Sober Living House Residents: Mediation Analyses.

BACKGROUND: Sober Living Houses (SLHs) adopt a social model approach, which emphasizes peer helping. Although SLHs appear to be effective, little is known regarding why. This longitudinal study examined whether higher SLH social model adherence produces better resident outcomes by increasing resident helping. METHODS: Baselines were conducted with 205 residents entering 28 SLHs, with follow-ups through 6 months. Measures included 1-month perceived SLH social model adherence; 2-month help given to and received from SLH residents; and 6-month alcohol use and severity. Analyses were lagged, multivariate mediation models accounting for clustering within SLH. Separate models examined help given and received for each outcome, yielding four model tests. RESULTS: The hypothesized model was unsupported, with all four tests showing nonsignificant indirect effects. However, exploratory post-hoc tests showed significant indirect effects between higher 1-month resident helping and better 6-month alcohol outcomes via higher 1-month SLH social model adherence. Effects held across three of four model tests. CONCLUSIONS: Results suggest that residences adhering to social model principles do not achieve better outcomes by stimulating helping, but rather that more resident helping may foster a supportive SLH social environment, which itself drives better outcomes. Thus, residences might emphasize both resident helping and social model principles.

Sober living↗

PubMed2026

A systematic review and meta-analysis to estimate the global prevalence of leptospirosis in sheep.

Leptospirosis in sheep is a zoonotic concern considering sheep may act as potential reservoirs for Leptospira spp. infection to humans. This study aimed to estimate the pooled prevalence of leptospirosis in sheep worldwide. A comprehensive literature search was conducted across databases following PRISMA guidelines. Meta-analyses were performed using a random effect model in R software (version 4.3.1) to calculate pooled prevalence with 95% confidence intervals (CI). Subgroup analyses were performed based on prevalence types, diagnostic methods and continental regions to explore sources of heterogeneity. A total of 138 studies comprising 54,174 samples and 10,299 positive detections were included in this study. The global pooled prevalence of leptospirosis in sheep was 15.69% (95% CI: 12.69-19.25) with overall heterogeneity (I2) 98%. The prediction interval ranged from 1.09% to 75.91%, indicating wide inter-study variability. The seroprevalence was 16.16% (95% CI: 12.91-20.04) and infection prevalence was 12.98% (95% CI: 8.07-20.22), showing no significant difference (P = 0.40). In addition, the prevalence of leptospirosis in sheep differed significantly across diagnostic methods and continents (P < 0.01), indicating substantial variation influenced by both methodological and geographical factors. The funnel plot revealed marked asymmetry, suggesting potential publication bias which was confirmed by Egger's regression test (P < 0.01). In conclusion, leptospirosis is widely prevalent in sheep globally, with marked geographical and methodological heterogeneity. These findings highlight the epidemiological importance of sheep in leptospirosis transmission and underscore the need for improved surveillance, standardized diagnostic approaches, and targeted control strategies within a One Health framework.

Animals↗

PubMed2026

Long-term outcomes of non-operative compared to operative management of acute uncomplicated appendicitis - a systematic review and meta-analysis.

BACKGROUND: We evaluated long-term outcomes of non-operative management (NOM) versus surgical management of acute uncomplicated appendicitis. METHODS: Systematic review of studies comparing NOM versus surgery with ≥2 years follow-up. Primary outcome was long-term failure rate. RESULTS: 9/1635 studies were included (3 RCTs; 6 non-RCT studies), involving 3883 patients; 5 were in pediatric populations. Median follow-up was 33.6 (range 24-312) months. NOM pooled long-term failure rate was 38.9% (95% CI: 31.1%-46.7%), increasing to 44.4% (95% CI: 41.4%-47.4%) in RCTs. Pooled appendectomy rate after NOM was 36.3% (95% CI: 28.9%-43.7%). Incidence of appendiceal neoplasms was approximately 0.3%. Non-operative management had cost savings of €1535 (95% CI: -€1892 to -€1178) versus surgery. CONCLUSIONS: NOM of acute uncomplicated appendicitis was associated with high long-term failure rates and significant risk of subsequent appendectomy.

Humans↗

PubMed2026

Long-term safety and efficacy of ponesimod, an oral S1P1 receptor modulator, in relapsing-remitting multiple sclerosis (RRMS): Results from randomized phase 2b core and extension studies spanning up to 13 years.

BACKGROUND: Ponesimod demonstrated efficacy and safety in relapsing-remitting multiple sclerosis (RRMS) in 24-week phase-2 core study, further confirmed by an interim combined analysis of the core and open-label long-term extension (LTE) studies (NCT01093326; up to 8 years). Current study evaluated safety and efficacy of ponesimod using combined core and LTE studies data for up to 13 years. METHODS: Of 393 participants completing the core study, 353 (90%) entered LTE, having 3 treatment periods (TP). In TP1 (∼1.85 years), participants continued core treatment (ponesimod: 10, 20, or 40 mg QD) whereas placebo-treated participants were re-randomized (1:1:1) to respective ponesimod doses. In TP2 (TP2 and TP3 combined duration: ∼10.4 years), participants on 40 mg were re-randomized (1:1) to 10/20 mg, while others continued same dose; in TP3 all participants received 20 mg. Study outcomes included safety and efficacy (ARR, time-to 24-week confirmed-disability-accumulation [24-week CDA], total T1-weighted Gadolinium-enhanced (T1 Gd+) lesions, new/enlarging T2 lesions and Combined Unique Active Lesions [CUALs]). RESULTS: For 20 mg dose, total 92.4% participants experienced ≥1 TEAEs (73.1% mild/moderate severity) and 19 (13%) participants discontinued study. Mean (95% CI) ARR=0.14 (0.10-0.20); Kaplan-Meier estimate (95% CI) of confirmed relapse and 24-week CDA=52.5% (42.3-63.5) and 31.3% (22.6-42.3). Mean [SD] T1 Gd+ lesions decreased from ponesimod baseline (2.62 [7.06]) to 12.4 years (0.26 [1.48]), mean (95% CI) CUALs per participant/year=3.97 (2.75-5.73). CONCLUSION: Ponesimod treatment for up to 13 years was not associated with new safety concerns. Participants continued to experience low levels of disease activity consistently across clinical and MRI outcomes.

Humans↗

PubMed2026

Transvalvular Flow Rate is Associated With Mortality Rate and Lifetime Loss in Aortic Valve Stenosis: A Meta-Analysis of Reconstructed Time-to-Event Data.

Low-flow states are associated with adverse outcomes in aortic stenosis (AS), but the prognostic value of transvalvular flow rate (TFR) has not been consistently established across studies. This study is a systematic review and meta-analysis of reconstructed time-to-event data was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses. PubMed/MEDLINE, EMBASE, and Cochrane Library were searched for studies (published by November 14, 2025) comparing low versus normal TFR in AS. Data were collected from Kaplan-Meier curves. The primary endpoint was all-cause mortality. Survival was assessed using pooled Kaplan-Meier curves, Cox regression, flexible parametric survival models, and restricted mean survival time (RMST) analysis. A total of 9 studies including 6,494 patients were analyzed; 2,575 (39.7%) had low TFR. At 8 years of follow-up, estimated survival was 34.1% (95% confidence interval [CI] 24.7% to 47%) in the low-TFR group and 63% (95% CI 58.9% to 67.4%) in the normal-TFR group. Low TFR was associated with higher all-cause mortality (hazard ratio 1.59, 95% CI 1.45 to 1.74, p < 0.001). We observed a progressively greater hazard over time, with the hazard ratio approaching 1.9 by 8 years. At 8 years, RMST in the normal-TFR group was 7.37 years (95% CI 7.21 to 7.53 years) versus 5.07 years (95% CI 4.91 to 5.23 years) in the low-TFR group, representing a lifetime loss of 2.3 years in the low-TFR group (ΔRMST -2.30 years, 95% CI -2.53 to -2.07 years, p < 0.001). In patients with AS, low TFR is associated with significantly higher mortality and lifetime loss. These findings support TFR as a clinically meaningful marker for risk stratification in AS.

Aortic Valve Stenosis↗

PubMed2026

Effects of H-coil TMS on suicidality in major depression: A secondary analysis of data from a multisite randomized trial comparing accelerated to once-a-day stimulation.

Suicide is the 10th leading cause of death in US adults. Standard once-daily repetitive transcranial magnetic stimulation (rTMS) can reduce suicidal ideation. Yet, antidepressant and anti-suicidal effects often take several weeks to emerge, while rapid improvement is often required. Accelerated TMS has been proposed as a strategy to hasten therapeutic response. A recent FDA-regulated multicenter trial evaluated accelerated intermittent theta burst Deep TMS with the H1-coil versus standard high-frequency Deep TMS in MDD. Both groups demonstrated high remission and response rates for depression, with the accelerated protocol showing non-inferiority and a shorter time to remission. The goal of this exploratory secondary analysis was to evaluate the impact of these two H-coil TMS dosing paradigms on suicidal ideation. The Scale for Suicide Ideation (SSI), as well as suicidality items of HDRS, MADRS and CUDOS were collected and analyzed. On all scales, both accelerated and standard Deep TMS protocols were associated with meaningful reductions in suicidality. The accelerated protocol achieved a faster onset of improvement. Comparison between the timeline of improvement in suicidality and in overall depressive symptoms found a trend for faster improvement in suicidality, especially with the accelerated protocol. These findings highlight the importance of treatment frequency in determining time to clinical benefit and support the use of scalable accelerated protocols for patients requiring more rapid symptom relief.

Humans↗

PubMed2026

Durability and Safety of Imeglimin as an Add-On to DPP-4 Inhibitors in Japanese Type 2 Diabetes: The 104-Week FAMILIAR Trial.

AIMS: To evaluate the long-term efficacy and safety of imeglimin added to dipeptidyl peptidase-4 (DPP-4) inhibitors in Japanese patients with type 2 diabetes, focusing on glycemic durability and safety in elderly patients over 104 weeks. MATERIALS AND METHODS: This multicenter, randomized, placebo-controlled trial comprised a 24-week double-blind phase (imeglimin 1000 mg or placebo twice daily) followed by an 80-week open-label extension in which all patients received imeglimin. Eligible patients had inadequate glycemic control despite DPP-4 inhibitor monotherapy. The main assessment measured HbA1c changes from baseline to week 104. Secondary assessments included meal tolerance tests (MTT) for evaluating physiological changes in β-cell function and insulin resistance and safety monitoring. RESULTS: Of 117 randomized patients, 81 completed 104 weeks. In the early-start group that received imeglimin from week 0, the significant HbA1c reduction observed at week 24 (-0.65%) was maintained through week 104 (-0.55%; p < 0.001 vs. baseline). The delayed-start group that switched to imeglimin at week 24 achieved similar glycemic control thereafter. Elderly patients (≥ 65 years) in the early-start group maintained stable HbA1c reduction (-0.58%) without hypoglycemic events over 2 years. MTT analysis in the early-start group showed sustained improvements in glucose AUC and insulin sensitivity without unnecessary insulin secretion over time. CONCLUSIONS: Imeglimin added to DPP-4 inhibitors appeared to improve glycemic control for 104 weeks, without clear attenuation. The combination was well-tolerated with a low risk of hypoglycemia even in elderly patients. The long-term effect may be associated with improvements in insulin sensitivity. TRIAL REGISTRATION: jRCTs061210082.

Humans↗

PubMed2026

Critical insights on the application of the theory of planned behaviour to food handlers' food safety practices.

Foodborne diseases remain a significant public health concern, often linked to unsafe food-handling practices. The Theory of Planned Behaviour (TPB) is widely used to predict and explain food safety behaviours, yet its application in this field has not been systematically and in-depth evaluated. This review evaluated how the TPB has been applied to study food handlers' behaviour, focusing on methodological approaches, use of the TACT (Target, Action, Context, and Time) framework, validity, elicitation studies, and reliability. Seventeen studies were included following a systematic search of four databases (Scopus, Web of Science, Wiley Online Library, and Taylor & Francis Online). Data were extracted on behaviour definition, aim of study, main findings, use of indirect and direct TPB measures, use of elicitation studies, internal consistency, content validation, analytical methods used, and any extensions to the original TPB framework. Key elements related to adherence to core TPB principles and measurement practices were extracted using a Checklist. Most studies used direct measures of TPB constructs, and only a few reported procedures for content validation. Considerable variability was found in the reporting of key measurement and psychometric practices. Five studies fully applied the TACT framework, while nine incorporated additional factors such as knowledge and moral norms. Elicitation studies were conducted in five cases where indirect measures were employed. Analytical approaches were mainly based on multiple linear regression, with limited use of more advanced techniques such as structural equation modeling. Twelve studies reported internal consistency results. Overall, the review highlights opportunities to strengthen methodological practices in future TPB research on food safety. Greater attention to conducting and reporting content validation, full application of the TACT framework, reporting of internal consistency, and consistent inclusion of elicitation studies when using indirect measures may enhance transparency, reinforcing the credibility and trustworthiness of research findings. A major methodological limitation of this review was that screening and data extraction were conducted by a single reviewer and no formal quality or risk-of-bias assessment of the included studies was performed. Despite these limitations, the findings provide practical guidance for the development and validation of TPB-based questionnaires and may support more robust food safety research, interventions, and policy initiatives aimed at improving food handlers' practices.

Humans↗

PubMed2026

The RrWRKY75-mediated activation of ascorbate synthesis in Rosa roxburghii Tratt contributes to salt stress tolerance.

L-Ascorbic acid (AsA) is a key antioxidant that alleviates oxidative stress in plants. Previous yeast one-hybrid (Y1H) screening identified RrWRKY75 as a transcription factor capable of binding to the promoter of RrGGP2 (GDP-L-galactose pyrophosphatase 2), a key structural gene responsible for massive AsA accumulation in Rosa roxburghii fruit. The function of RrWRKY75 in plant stress responses remains unclear. Here, RrWRKY75 is verified to specifically bind to the RrGGP2 promoter and activate its transcription. This positive regulatory effect on RrGGP2 transcript levels and AsA accumulation is further confirmed through overexpression or silencing of RrWRKY75 in R. roxburghii fruit or callus. Among various abiotic stress conditions, RrWRKY75 expression is significantly induced by salt stress. Upon its overexpression in callus or Arabidopsis thaliana, elevated AsA levels and antioxidant capacity are observed, thereby enhancing salt tolerance. Interestingly, RrWRKY75 also binds to the promoter of RrUNE12, a salt-responsive factor in R. roxburghii, and activates its expression. Moreover, yeast two-hybrid and bimolecular fluorescence complementation (BiFC) assays confirm the physical interaction between RrWRKY75 and RrUNE12, which jointly upregulates RrGGP2 expression and AsA production. Collectively, RrWRKY75 boosts AsA biosynthesis and salt tolerance both by directly trans-activating RrGGP2 and by synergizing with RrUNE12 through transcriptional activation and protein complex formation. These findings provide insights into the regulatory role of RrWRKY75 in abiotic stress tolerance and offer valuable genetic resources for R. roxburghii germplasm improvement.

Rosa↗

PubMed2026

Pictographs: feasibility and acceptability of a novel method of newborn identification to reduce wrong-patient errors in the NICU.

Wrong-patient errors cause serious harm in newborns. These errors involve ordering and administering tests, procedures, medications, and breast milk to an unintended patient. Newborns receiving care in neonatal intensive care units (NICUs) are at particularly high risk. Although more distinct newborn naming conventions as recommended by the Joint Commission significantly reduce wrong-patient orders, name similarities among multiple-birth infants and truncation of differentiating information in some electronic health record (EHR) systems contribute to this persistent increased risk. Accordingly, novel newborn identifiers are urgently needed. We propose Pictographs - images that are appealing, recognizable, and appropriate - to serve as visual identifiers for newborns in NICUs. Pictographs are selected by caregivers, uploaded into the EHR, and displayed at bedside. As part of a multicenter randomized controlled trial assessing effectiveness of Pictographs to prevent wrong-patient order errors, we initially evaluated feasibility and acceptability of Pictographs at two study sites. Pictographs as novel visual identifiers for newborns in the NICU were generally well received by caregivers and clinicians, and the vast majority of caregivers selected a Pictograph for their infant(s), which was posted at the bedside and uploaded into the EHR. Ordering clinicians - the primary target of the intervention to prevent wrong-patient errors - recognized the potential for Pictographs to provide a visual cue when placing orders, particularly for multiple-birth infants. Here, we describe the rationale, implementation, framework, feasibility, usefulness, and acceptability of Pictographs among key stakeholders. If found effective for preventing wrong-patient errors, Pictographs could be adopted as a patient safety solution in hospitals worldwide.

Female↗