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Immunohistochemical evaluation of Ki-67 and GLI1 in sporadic and nevoid basal cell carcinoma syndrome-associated odontogenic keratocysts.

INTRODUCTION: Odontogenic keratocyst (OKC) is a developmental odontogenic cyst that may occur sporadically (OKCsp) or in association with nevoid basal cell carcinoma syndrome (NBCCS) (OKC-sy). NBCCS is an autosomal dominant disorder characterised by morphological abnormalities and an increased predisposition to several neoplasms, including basal cell carcinomas. Mutations in the tumour suppressor gene PTCH1 have been reported in patients with OKC and NBCCS. PTCH1 participates in a signalling cascade that culminates in the translocation of GLI transcription factors to the nucleus, thereby activating target genes involved in cell proliferation. Aberrant GLI1 expression has been associated with increased proliferation in lung adenocarcinoma and other cancers. OBJECTIVE: To compare GLI1 and Ki-67 protein expression in OKCs associated with NBCCS versus sporadic OKCs. MATERIALS AND METHODS: We included 13 OKCsp and 9 OKCsy from a children's hospital and university ... Immunohistochemistry was performed using anti-GLI1 and anti-Ki-67 to assess GLI1 expression and cell proliferation. RESULTS: No significant differences were observed in GLI1 or Ki-67 expression in the epithelial component of OKCsy versus OKCsp. A positive correlation between GLI1 and Ki-67 expression was detected in the total sample (r = 0.71, p < 0.05). CONCLUSION: The positive correlation between GLI1 and Ki-67 expression in OKCs suggests an association between SHH pathway activity and cell proliferation in both sporadic and syndromic lesions.

GLI1

Efficacy and Safety of Celecoxib Combined With Jintiange Capsules for the Treatment of Knee Osteoarthritis: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

BACKGROUND Knee osteoarthritis (KOA) poses a substantial global health burden, and conventional nonsteroidal anti-inflammatory drug (NSAID) therapy with celecoxib is hindered by adverse effects. This study evaluated the efficacy and safety of combining celecoxib with Jintiange capsules, a synthetic tiger bone formulation used in traditional Chinese medicine (TCM), to manage symptomatic KOA. MATERIAL AND METHODS This 12-week, randomized, double-blind, placebo-controlled trial enrolled 120 patients with KOA (age &#xf0b3;40 years; visual analog scale [VAS] score 4-7). Participants received celecoxib (200 mg/day tapered to 100 mg/day) combined with either Jintiange capsules (3.6 g/day) or placebo. The primary outcome was the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score. Secondary outcomes included WOMAC subscale scores (pain, function, and stiffness), VAS scores, and adverse drug reaction reports. RESULTS The experimental group demonstrated a 23.5-point (37.8%) reduction in WOMAC total score from baseline (P<0.001); the control group showed a 13.2-point (21.6%) reduction (P<0.001). The experimental group achieved 51.6% improvement in the WOMAC pain subscale (P<0.001), whereas the control group showed 33.3% improvement (P<0.001). Relative to the control group, the experimental group demonstrated a greater reduction in VAS score (P<0.001). Combined TCM-NSAID therapy produced significantly greater pain relief and functional improvement than NSAID monotherapy. CONCLUSIONS Celecoxib combined with Jintiange capsules provided clinically meaningful improvements in pain relief and functional outcomes relative to celecoxib monotherapy in patients with KOA. These findings support integration of TCM with conventional pharmacotherapy for osteoarthritis management.

Humans

ATF4-histone 2-hydroxyisobutyrylation feedback loop drives sepsis-induced inflammation.

BACKGROUND AND PURPOSE: The role and mechanisms of lysine 2-hydroxyisobutyrylation (Khib) in the acute inflammatory phase of sepsis remain unclear. We investigated the function and underlying mechanisms of histone H4 lysine 5 2-hydroxyisobutyrylation (H4K5-hib) in sepsis-induced inflammation in vivo and in vitro. EXPERIMENTAL APPROACH: Acute sepsis was induced by caecal ligation and puncture (CLP) in mice, and inflammatory responses were modelled in lipopolysaccharide (LPS)-stimulated macrophages. CUT&Tag-seq was used to identify genomic targets associated with H4K5-hib and activating transcription factor 4 (ATF4). Immunofluorescence, Western blotting, qPCR, dual-luciferase assays, and ELISA were performed to investigate the underlying mechanisms. KEY RESULTS: H4K5-hib levels were increased in macrophages during the acute inflammatory phase of sepsis. LPS stimulation enhanced H4K5-hib enrichment at the ATF4 promoter, thereby promoting ATF4 transcription. Inhibition of EP300-mediated 2-hydroxyisobutyrylation or mutation of H4K5 abolished ATF4 activation. Increased H4K5-hib activated the ATF4/NLRP3 signalling axis, promoting inflammasome assembly and amplifying inflammatory responses. ATF4 directly bound to the EP300 promoter and enhanced its transcription, forming a positive feedback loop that further increased H4K5-hib levels. In CLP-induced sepsis, pharmacological inhibition of EP300 or ATF4 reduced H4K5-hib levels and suppressed NLRP3 inflammasome activation. CONCLUSION AND IMPLICATIONS: These findings reveal a previously unrecognized epigenetic mechanism underlying sepsis-induced inflammation and identify the EP300/ATF4/H4K5-hib positive feedback loop as a potential therapeutic target for sepsis.

Animals

From fear to empowerment: the&#xa0;impact of employees AI awareness on workplace well-being - a new insight from the JD-R model.

PURPOSE: The primary purpose of the study was to explore the impact of health workers' awareness of artificial intelligence (AI) on their workplace well-being, addressing a critical gap in the literature. By examining this relationship through the lens of the Job demands-resources (JD-R) model, the study aimed to provide insights into how health workers' perceptions of AI integration in their jobs and careers could influence their informal learning behaviour and, consequently, their overall well-being in the workplace. The study's findings could inform strategies for supporting healthcare workers during technological transformations. DESIGN/METHODOLOGY/APPROACH: The study employed a quantitative research design using a survey methodology to collect data from 420 health workers across 10 hospitals in Ghana that have adopted AI technologies. The study was analysed using OLS and structural equation modelling. FINDINGS: The study findings revealed that health workers' AI awareness positively impacts their informal learning behaviour at the workplace. Again, informal learning behaviour positively impacts health workers' workplace well-being. Moreover, informal learning behaviour mediates the relationship between health workers' AI awareness and workplace wellbeing. Furthermore, employee learning orientation was found to strengthen the effect of AI awareness on informal learning behaviour. RESEARCH LIMITATIONS/IMPLICATIONS: While the study provides valuable insights, it is important to acknowledge its limitations. The study was conducted in a specific context (Ghanaian hospitals adopting AI), which may limit the generalizability of the findings to other healthcare settings or industries. Self-reported data from the questionnaires may be subject to response biases, and the study did not account for potential confounding factors that could influence the relationships between the variables. PRACTICAL IMPLICATIONS: The study offers practical implications for healthcare organizations navigating the digital transformation era. By understanding the positive impact of health workers' AI awareness on their informal learning behaviour and well-being, organizations can prioritize initiatives that foster a learning-oriented culture and provide opportunities for informal learning. This could include implementing mentorship programs, encouraging knowledge-sharing among employees and offering training and development resources to help workers adapt to AI-driven changes. Additionally, the findings highlight the importance of promoting employee learning orientation, which can enhance the effectiveness of such initiatives. ORIGINALITY/VALUE: The study contributes to the existing literature by addressing a relatively unexplored area - the impact of AI awareness on healthcare workers' well-being. While previous research has focused on the potential job displacement effects of AI, this study takes a unique perspective by examining how health workers' perceptions of AI integration can shape their informal learning behaviour and, subsequently, their workplace well-being. By drawing on the JD-R model and incorporating employee learning orientation as a moderator, the study offers a novel theoretical framework for understanding the implications of AI adoption in healthcare organizations.

Humans

Association of hydroxyurea use and sickle cell retinopathy: A systematic review and meta-analysis.

Hydroxyurea (HU) is prescribed to reduce systemic complications of sickle cell disease; however, its association with sickle cell retinopathy (SCR) remains unclear. This meta-analysis (PROSPERO: CRD420251079006) evaluates the pooled association between HU use and SCR. In the primary analysis, HU use was not associated with a statistically significant reduction in SCR (OR = 0.90, 95% CI [0.41, 1.97], p&#x202f;=&#x202f;0.79; I&#xb2; = 77%). In a prespecified leave-one-out analysis, exclusion of the outlier study did not produce a statistically significant association, although the estimate shifted toward a stronger protective effect with reduced heterogeneity (OR = 0.70, 95% CI [0.39, 1.27], p&#x202f;=&#x202f;0.25; I&#xb2; = 67%). In a subgroup analysis excluding high-risk-of-bias studies, HU use was also not associated with a statistically significant reduction in SCR (OR = 0.84, 95% CI [0.39, 1.82], p&#x202f;=&#x202f;0.66; I&#xb2; = 77%). In post hoc analyses, HU use was not associated with a statistically significant reduction in SCR in non-adult populations (OR = 1.14, 95% CI [0.43, 3.05], p&#x202f;=&#x202f;0.79; I&#xb2; = 81%) or genotype-restricted analyses (OR = 1.22, 95% CI [0.81, 1.84], p&#x202f;=&#x202f;0.35; I&#xb2; = 0%). In post hoc analyses restricting studies to retinopathy phenotype, however, HU was associated with statistically significant lower odds of non-proliferative SCR (OR = 0.73, 95% CI [0.54, 0.98], p&#x202f;=&#x202f;0.04; I&#xb2; = 0%) and proliferative SCR (OR = 0.24, 95% CI [0.09, 0.60], p&#x202f;=&#x202f;0.002; I&#xb2; = 12%). Very low-certainty evidence suggests mixed associations between HU and SCR. Prospective studies are needed to clarify its role in SCR prevention.

Humans

Efficacy and safety of once-weekly semaglutide 2&#xb7;4 mg in Chinese adults with overweight or obesity (STEP 12): a randomised, double-blind, placebo-controlled, multicentre, phase 3b trial.

BACKGROUND: Semaglutide 2&#xb7;4 mg is a GLP-1 receptor agonist that reduces bodyweight, and provides other cardiometabolic benefits, among people with a BMI at least 30 kg/m2 or at least 27 kg/m2 and with weight-related comorbidities. This trial aimed to evaluate the efficacy, tolerability, and safety of semaglutide 2&#xb7;4 mg in adults from mainland China and Taiwan with overweight or obesity according to locally defined, BMI thresholds. METHODS: This completed randomised, double-blind, placebo-controlled, multicentre, two-armed, parallel-group, phase 3b trial (STEP 12) was conducted at 19 sites across mainland China and Taiwan. Adults with a BMI of 24-<28 kg/m2 and at least one weight-related comorbidity, or a BMI of 28-<30 kg/m2, with or without type 2 diabetes, were randomly assigned (2:1) to once-weekly subcutaneous semaglutide 2&#xb7;4 mg or placebo, plus lifestyle intervention, for 44 weeks. Randomisation was performed by the study sponsor using the Randomisation Trial Supplies Management System. Coprimary endpoints were percentage change in bodyweight and the proportion of participants achieving at least 5% bodyweight reduction. Safety was analysed descriptively in all participants who received the trial intervention. Missing data at week 44 were imputed with washout multiple imputation. This study is registered with ClinicalTrials.gov, NCT06041217, and is completed. FINDINGS: Between Sept 15, 2023, and May 7, 2025, of 254 screened participants, 161 (66&#xb7;5%) of 242 participants were randomly assigned to semaglutide 2&#xb7;4 mg and 81 (33&#xb7;5%) to placebo; 121 (50&#xb7;0%) participants were female, and 47 (19&#xb7;4%) participants had type 2 diabetes. Bodyweight reduction was greater with semaglutide versus placebo (-12&#xb7;1% [SE 0&#xb7;6] vs -2&#xb7;2% [0&#xb7;8]; estimated treatment difference -9&#xb7;9 percentage points [95% CI -11&#xb7;8 to -8&#xb7;0]; p<0&#xb7;0001), with a greater proportion of participants achieving at least 5% bodyweight reduction (80&#xb7;5% vs 24&#xb7;4%; odds ratio [OR] 14&#xb7;8 [95% CI 7&#xb7;4 to 29&#xb7;6]; p<0&#xb7;0001). Adverse events were reported in 141 (87&#xb7;6%) of 161 participants in the semaglutide 2&#xb7;4 mg group and 61 (75&#xb7;3%) of 81 participants in the placebo group, with gastrointestinal disorders being the most common. INTERPRETATION: Semaglutide 2&#xb7;4 mg provided a superior reduction in bodyweight versus placebo in Chinese adults with overweight or obesity. The safety profile was consistent with the known profile of semaglutide. FUNDING: Novo Nordisk A/S. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.

Adult

Effects of rumen fluid transplantation on longissimus dorsi muscle development in Xizang sheep: An association analysis based on transcriptomic and serum metabolomic profiles.

This study aimed to investigate the effects of rumen fluid transplantation (RFT) on the growth and development of the longissimus dorsi muscle in female Xizang sheep. After RFT, muscle lightness differed significantly between the two groups, with the LDC group showing significantly higher lightness than the LDT group. In contrast, no significant differences were observed between groups in other muscle phenotypic traits, including drip loss, pH, cooking loss, shear force, redness, and yellowness. Antioxidant-related indices (SOD, GSH-PX, MDA, CAT, and T-AOC) also showed no significant differences between groups. Histological analysis revealed that muscle fiber length, width, and density were significantly greater in the experimental group than in the control group. Transcriptomic analysis identified 515 differentially expressed genes (DEGs), of which 419 were downregulated. KEGG analysis indicated that genes involved in muscle development-related pathways, such as cell adhesion and the PI3K-Akt signaling pathway, were predominantly downregulated. Key serum metabolites (L-kynurenine, IPA, allantoin, and propionylcarnitine) showed highly significant positive correlations with muscle fiber growth indices. In contrast, metabolites such as l-carnitine, acetylcarnitine, and citrulline were negatively correlated with muscle fiber growth, but positively correlated with the expression of muscle structure-related genes (COL11A1 and EFNA5) and with meat lightness. Overall, this study provides new insights into the potential molecular basis by which RFT influences muscle growth and development. However, the mechanisms by which RFT affects muscle development and meat quality-related traits remain unclear and warrant further investigation.

Animals

Determinants of private health insurance uptake and its association with healthcare utilization in Gulf Cooperation Council countries: a systematic review.

All Gulf Cooperation Council (GCC) countries have a multi-payer healthcare system that comprises governmental health coverage (GHC), funded by the government, and private health insurance (PHI), mainly sponsored by employers and purchased by individuals. Both are expected to influence healthcare utilization and contribute to system efficiency and patient well-being. This systematic review explored the determinants of PHI uptake and its association with healthcare service utilization in the presence of GHC in GCC countries. We systematically searched CINAHL, PubMed, Scopus, Web of Science, and Cochrane Library for peer-reviewed studies published between January 2012 and October 2022. Study quality was assessed using the Critical Appraisal Skills Programme (CASP) checklists for both quantitative and qualitative studies, following PRISMA guidelines. Twenty-six studies met the inclusion criteria. Determinants of PHI uptake were mapped to Andersen's Behavioral Model of Health Services Use (BMHSU) and categorized into (1) predisposing factors (sex, age, marital status, and education), (2) enabling factors (employment/income and health system-related factors such as access and perceived service quality), and (3) need factors (health status, including chronic noncommunicable diseases). PHI uptake was positively associated with being male, married, highly educated, employed with a high income, and having chronic diseases. PHI was positively associated with healthcare utilization, particularly routine check-ups, preventive services, and the use of prescribed medicines. In GCC countries, PHI uptake is influenced by sociodemographic and socioeconomic characteristics, health status, and perceived service quality. PHI is also associated with higher healthcare utilization, underlining the need for evidence-informed policies that enhance equity and expand coverage.

Humans

Incidence of retropharyngeal lymph node involvement in oropharyngeal squamous cell carcinoma: a systematic review and meta-analysis.

BACKGROUND: Retropharyngeal lymph node (RPN) involvement in oropharyngeal squamous cell carcinoma (OPSCC) may influence prognosis, staging, radiotherapy target volumes, and treatment strategy. However, its true prevalence and association with clinicopathological factors remain incompletely defined. METHODS: A systematic review and meta-analysis was performed in accordance with the PRISMA 2020 statement. MEDLINE, EMBASE, EMCARE, PubMed, Web of Science, Scopus, and the Cochrane Library were searched from database inception to 15 June 2026. Studies reporting radiological or pathological assessment of retropharyngeal lymph node (RPN) involvement in oropharyngeal squamous cell carcinoma (OPSCC) were included. Pooled prevalence estimates were calculated using a random-effects model, with subgroup analyses according to tumour stage, nodal status, HPV status, and primary tumour subsite. RESULTS: Fourteen studies comprising 8,887 patients were included. The pooled prevalence of RPN involvement was (95% CI 11-16%; 95% PI 6-24%), with substantial heterogeneity. HPV-negative tumours demonstrated higher prevalence than HPV-positive tumours (21% vs 11%). Prevalence increased with advancing T stage, from 2% in T1 to 18% in T4 disease, and was higher in node-positive than node-negative disease (16% vs 1%). Tonsillar primaries showed higher prevalence than base of tongue tumours (14% vs 8%). Among patients with RPN involvement, the pooled distant metastasis rate was 16%. CONCLUSION: RPN metastases were identified in approximately one in eight patients with OPSCC and were more frequent in HPV-negative disease, advanced stage, and tonsillar primaries. These findings support careful evaluation of the retropharyngeal space during staging and may assist risk stratification in selected higher-risk patients.

Humans

Extender-dependent effects of reduced glutathione on post-thaw boar sperm quality: A systematic review and meta-analysis.

Supplementation of reduced glutathione (GSH) in freezing media has been proposed to improve post-thaw boar sperm quality, although reported findings remain inconsistent. This study aimed to quantitatively evaluate the effects of reduced glutathione on post-thaw sperm quality through a systematic review and meta-analysis. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Scopus, PubMed, CAB Direct, EBSCOhost, and Google Scholar were systematically searched. Based on predefined inclusion and exclusion criteria, 15 in vitro studies comprising 19 experiments were included. Four outcomes were analyzed: total motility, progressive motility, viability, and acrosome integrity. Standardized mean differences (SMD) were calculated using random-effects models. Heterogeneity was assessed using Cochran's Q test, and the I2 statistic. Publication bias was evaluated using funnel plots, Egger's test, and trim-and-fill analysis, while sensitivity analyses were performed using Baujat plots and leave-one-out analysis. Reduced glutathione was positively associated with total motility (SMD = 0.74; 95% CI: 0.42-1.05; P<0.001), progressive motility (SMD = 0.90; 95% CI: 0.21-1.58; P=0.014), viability (SMD = 0.67; 95% CI: 0.11-1.23; P=0.022), and acrosome integrity (SMD = 0.72; 95% CI: 0.32-1.12; P=0.002). Low to high heterogeneity was observed across outcomes, indicating variability in the estimated effects across studies. Significant subgroup differences were identified according to GSH concentration, freezing media, and thawing media. Overall, the available evidence suggests a possible positive association between GSH supplementation and several post-thaw sperm quality parameters, although these subgroup findings are exploratory and require confirmation in well-standardized experimental studies.

Animals

Aflibercept With Versus Without Reduced-Fluence Photodynamic Therapy for Polypoidal Choroidal Vasculopathy: Optical Coherence Tomography Angiographic Changes From a Randomized Clinical Trial.

OBJECTIVES: To report the longitudinal optical coherence tomography angiography (OCTA) changes in polypoidal choroidal vasculopathy (PCV) treated with intravitreal aflibercept monotherapy or in combination with reduced-fluence PDT. DESIGN: Image analysis of a double-masked, sham-controlled, randomized clinical trial. SUBJECTS: 55 eyes of 55 treatment-na&#xef;ve participants with symptomatic macular PCV completing 52 weeks of follow-up. METHODS: Participants underwent protocolized, multimodal imaging, including OCT, OCTA, fluorescein angiography, and indocyanine green angiography at baseline, week 12, and week 52. Quantitative OCTA parameters included total lesion area, branching neovascular network (BNN) area, and BNN vessel density (VD). Qualitative features included trunk vessel presence and OCTA signal within the polypoidal lesion (PL). Eyes were categorized by treatment arm and PL closure at week 52. MAIN OUTCOME MEASURES: Longitudinal OCTA changes and predictors of PL closure at week 52. RESULTS: We included 55 eyes (28 combination therapy and 27 monotherapy). Total lesion area decreased at week 12 but returned toward baseline at week 52 (combination: 3.72 &#xb1; 3.01mm2 at baseline, 2.86 &#xb1; 2.50mm2 at week 12, 3.59 &#xb1; 3.26mm2 at week 52; monotherapy: 3.77 &#xb1; 2.23mm2 at baseline, 3.27 &#xb1; 2.36mm2 at week 12, and 3.47 &#xb1; 2.58mm2 at week 52). BNN area decreased at week 12 and remained reduced at week 52 in both treatment arms (combination: 2.29 &#xb1; 2.08 mm2 at baseline, 1.46 &#xb1; 1.36mm2 at week 12, and 1.53 &#xb1; 1.32mm2 at week 52; monotherapy: 2.39 &#xb1; 1.85mm2 at baseline, 1.87 &#xb1; 1.68mm2 at week 12, and 1.82 &#xb1; 1.38mm2 at week 52). BNN VD reduction was greater in the combination arm at week 12 (-10 &#xb1; 15% vs - 3 &#xb1; 12%, P = .02). The proportion of eyes with trunk vessels increased over time in both arms (combination: 35.7% at baseline, 59.3% at week 12, and 67.8% at week 52; monotherapy: 25.9% at baseline, 44.4% at week 12, and 71.4% at week 52). In multivariable analysis, baseline BCVA predicted BCVA change at week 52 (&#x3b2;=-0.96 [-1.21 to -0.72], P < .01), and baseline CST predicted CST change (&#x3b2;=0.93 [0.75 to 1.10], P < .01). Greater reduction in BNN VD at week 12 was independently associated with PL closure at week 52 (OR 0.62 [0.39 to 0.97], P = .03). CONCLUSIONS: Early reduction in BNN vessel density, rather than reduction in lesion size, was associated with subsequent PL closure. OCTA-derived vascular changes may serve as noninvasive biomarkers for predicting treatment response in PCV.

Humans

First identification and molecular subtyping of Blastocystis spp. in donkeys in Aksaray province, T&#xfc;rkiye.

Blastocystis is a common intestinal protist worldwide that can infect humans and animals. Although its molecular epidemiology in T&#xfc;rkiye is mostly focused primarily on humans and livestock, equids have received limited attention despite their traditional roles and frequent contact with humans and other animals in rural environments. This study aimed to determine the molecular prevalence and subtype (ST) distribution of Blastocystis spp. in donkeys in Aksaray Province, providing the first molecular data on donkeys in T&#xfc;rkiye. A total of 182 fresh fecal samples were collected from donkeys in nine villages within Aksaray province. Genomic DNA was extracted, and the small subunit ribosomal RNA (SSU rRNA) gene fragment of Blastocystis spp. was amplified via PCR analysis. Positive isolates were sequenced bidirectionally for identification and subsequent phylogenetic analysis of Blastocystis in donkeys. The overall molecular prevalence of Blastocystis spp. in donkeys was 4.4% (8/182). The infection rate was higher in young donkeys (under 3&#xa0;years old; 8.33%) than in adults (3&#xa0;years or older; 2.46%). However, this difference was not statistically significant. Sequence analysis of the positive PCR products revealed the presence of one known livestock-specific subtype, ST10. Phylogenetic analysis showed that the ST10 isolates characterized in this study clustered with isolates identified from different hosts. This study provides the first molecular data on Blastocystis presence in donkeys in T&#xfc;rkiye. The exclusive detection of ST10 suggests potential cross-species transmission, likely facilitated by the traditional practice of co-housing donkeys with other animals in confined barns. These findings indicate that donkeys may contribute to Blastocystis transmission, underscoring the importance of a "One Health" approach in future epidemiological surveillance.

Animals

Clinical and psychological characteristics of adolescents at risk of mood disorders compared with adolescents with suicidal behavior.

Suicide is one of the leading causes of death among adolescents, yet little is understood about the biopsychosocial factors related to suicidality. The demographic, clinical, and biological characteristics of adolescents with and without psychiatric histories may help inform mechanistic approaches to treatment of mood disorders and suicidality. The 'characterizing the inflammatory profile and suicidal behavior in adolescents' and 'RAD arm of the Texas Resilience Against Depression' studies aimed to characterize the clinical and biological profiles of youth with suicidal behavior and youth at risk for mood disorders, compared to healthy adolescents (n&#xa0;=&#xa0;75 in each group). Here, we report the descriptive baseline clinical and psychological characteristics of adolescents at risk of mood disorders and those with suicidal behavior. The adolescents with suicidal behavior reported 3.53 lifetime suicidal events on average, predominantly reported moderate to very severe depression (34.7%, 24%, to 9.3%), moderate to severe anxiety (58.6%), low optimism (91.9%), and mild (39.2%) to moderate (28.4%) degree of hopelessness. The at-risk adolescents predominantly reported no depression (60%) or anxiety (68.9%), moderate optimism (50%), and a positive outlook (85.7%). Healthy adolescents predominantly reported no depression (88.3%) or anxiety (93.2%), moderate optimism (59%), and a positive outlook (87%). The adolescents with suicidal behavior and those at risk of mood disorders exhibited significantly higher irritability and borderline personality disorder features (uncorrected p&#xa0;=&#xa0;0.02 to p&#xa0;<&#xa0;0.001) and lower resilience compared to healthy adolescents. Ongoing investigations using the longitudinal clinical and biological data will help identify the immune biosignatures of suicidality in youth.

Humans

Illicium verum polysaccharide targets fimbriae and flagella to disrupt biofilm and inhibit multidrug-resistant Escherichia coli proliferation.

The widespread dissemination of multidrug-resistant (MDR) E. coli has led to a decrease in the efficacy of antibiotics, posing severe challenges to clinical anti-infective therapy. Owing to their safety, multitarget activities, and low risk of inducing drug resistance, plant polysaccharides represent a promising alternative strategy. In this study, an acidic polysaccharide (IVP-3) was isolated and purified from the medicinal and edible plant Illicium verum, and it was found to inhibit MDR E. coli colonization by disrupting its biofilm. The Mw of IVP-3 was determined to be 35.566&#xa0;kDa. Its backbone consists of &#x2192;4)-&#x3b1;-D-GalpA-6-OMe-(1&#x2192;, &#x2192;4)-&#x3b1;-D-GalpA-(1&#x2192;, &#x2192;4)-&#x3b2;-D-Galp-(1&#x2192;, and &#x2192;3,4)-&#x3b1;-D-GalpA-(1&#xa0;&#x2192;&#xa0;residues, whereas the branched chain is composed of &#x3b1;-L-Araf-(1&#xa0;&#x2192;&#xa0;5)-&#x3b1;-L-Araf-(1&#xa0;&#x2192;&#xa0;attached to the O-5 position of &#x2192;2,5)-&#x3b1;-L-Araf-(1&#x2192;, which is further linked to the O-3 position of the backbone. Mechanistically, IVP-3 disrupts the structure of fimbriae and flagella, inhibits bacterial motility, effectively prevents initial biofilm adhesion, and eradicates preformed mature biofilms. Additionally, IVP-3 damages cell membrane integrity, disrupts the proton motive force, and induces energy metabolism disorder, efflux pump inhibition, and oxidative stress, ultimately leading to bacterial lysis. This study provides a theoretical basis for the development of natural antibacterial agents targeting MDR E. coli biofilms and for the high-value utilization of Illicium verum.

Biofilms

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

Randomized Trial of Intensive Nurse-Led Follow&#x2011;Up Versus Standard Care in Inflammatory Bowel Disease.

BACKGROUND: &#xa0;Nurses play a key role in inflammatory bowel disease (IBD) management. This randomized controlled trial evaluated intensive nurse-led program in patients with IBD starting advanced therapy. METHODS: &#xa0;Patients were randomized (1:1) to intensive nurse follow&#x2011;up (Arm&#xa0;A) or standard care (Arm&#xa0;B). Both arms received baseline nurse education; Arm A additionally had scheduled nurse calls and visits. Primary outcome was reduction in IBD&#x2011;Disk score in W12. Secondary outcomes were W52 reduction, robust response (>&#x2009;20-point improvement), and IBD-Disk remission (score&#x2009;<&#x2009;40). RESULTS: Overall, 98 patients were randomized (Arm&#xa0;A:&#xa0;n&#x2009;=&#x2009;50; Arm&#xa0;B:&#xa0;n&#x2009;=&#x2009;48) with similar baseline characteristics. Mean baseline IBD&#x2011;Disk scores were 49.2&#x2009;&#xb1;&#x2009;20.7 in Arm&#xa0;A and 42.0&#x2009;&#xb1;&#x2009;19.8 in Arm&#xa0;B (p&#x2009;=&#x2009;0.07). At W12, both groups improved, with greater IBD-Disk reductions in Arm A (16.1&#x2009;&#xb1;&#x2009;22.9 vs. 10.1&#x2009;&#xb1;&#x2009;20.1, p&#x2009;=&#x2009;0.09). At W52, improvement was greater in Arm&#xa0;A (18.4&#x2009;&#xb1;&#x2009;20.7 vs 9.4&#x2009;&#xb1;&#x2009;17.8; p&#x2009;=&#x2009;0.08). More patients achieved robust response in Arm A (49% vs 21%, p&#x2009;=&#x2009;0.013) at W12. By W52, IBD-Disk remission was achieved by 22/25 (88%) patients in Arm A vs 18/28 (64%) in Arm B (p&#x2009;=&#x2009;0.045). CONCLUSIONS: &#xa0;In this pilot randomized trial, intensive nurse-led follow-up did not significantly improve IBD-Disk at week 12, yet favorable trends of functional outcomes were observed. Intensive nurse&#x2011;led follow&#x2011;up program may improve quality of life in patients with IBD. These findings support the integration of specialist IBD nurses to improve patient&#x2011;centered outcomes.

Humans

Targeting depression before it starts: An updated systematic review and meta-analysis of preventive interventions in young adults from randomized controlled trials.

INTRODUCTION: Young adulthood is a high-risk period for major depressive disorder (MDD) onset yet is underrepresented in prevention research. This systematic review and meta-analysis examined the effectiveness of psychosocial preventive interventions in adults aged 18-25&#xa0;years, focusing on symptom reduction, medium- and long-term effects, and MDD onset. METHODS: We conducted a PRISMA-compliant systematic review and meta-analysis (PROSPERO: CRD42024625481) of randomized controlled trials (RCTs) of psychosocial preventive interventions for depression in young adults (18-25) published up to April 15, 2025. Between-group symptom reduction was quantified using Hedges' g and pooled with random-effects models. Outcomes were analyzed at post-intervention, 6-, and 12-month follow-up. Effects on MDD onset were assessed via risk ratio (RR). Risk of bias was assessed with the RoB-2 tool. RESULTS: We included 65 interventions from 58 RCTs (N&#xa0;=&#xa0;11,333; mean age 20.4; 61.6% female), with 92.8% rated high risk of bias. Interventions at post-test reduced depressive symptoms vs. controls (k&#xa0;=&#xa0;65; g&#xa0;=&#xa0;-0.52; 95%CI:-0.70;-0.33; p&#xa0;<&#xa0;0.01), with significant heterogeneity (I2&#xa0;=&#xa0;93.0%). Indicated, guided, and face-to-face interventions outperformed universal, selective, self-guided, and online interventions. Effects on symptomatology were highly heterogeneous and non-significant at 6- (k&#xa0;=&#xa0;8) and 12-month (k&#xa0;=&#xa0;4) follow-up. Four RCTs were identified evaluating MDD onset risk; pooled effects suggested a reduction in MDD onset (RR&#xa0;=&#xa0;0.77; 95%CI:0.61;0.97; p&#xa0;<&#xa0;0.01) though risk of bias was high and samples were highly selective. INTERPRETATION: Psychosocial preventive interventions modestly reduce depressive symptoms at post-test and may lower onset risk in highly selective populations. However, findings remain limited by high risk of bias, scarce data on the long-term sustainability of effects, and unclear mechanisms.

Adolescent

Evaluating the persistence of semen under controlled environmental conditions.

When semen is deposited at a crime scene, it may be exposed to harmful environmental conditions. It is important to understand to what extent the different components of semen, specifically acid phosphatase (AP), prostate specific antigens (PSA), sperm and DNA, may become less detectable after exposure to high temperatures and varying levels of humidity. In this study, semen (50&#xa0;&#x3bc;L) was deposited onto squares of black cotton and exposed to 45&#xa0;&#xb0;C and a relative humidity (RH) of 10 or 80% for 0, 7, 14, 21 or 28&#xa0;days (n&#xa0;=&#xa0;5 per day, per climate condition). Source testing included AP test reagent, ABAcard&#xae; p30 immunoassay kits, and hematoxylin and eosin staining. DNA was extracted using the DNA IQ&#x2122; System (Promega, Australia) and quantified using Quantfiler Trio&#x2122; (Thermo Fisher Scientific, Australia). Over the 28-day period under both RH conditions, the time taken for a positive AP test to develop increased significantly (p&#xa0;<&#xa0;0.01) and the number of sperm observed decreased significantly (p&#xa0;<&#xa0;0.01). All ABAcard&#xae; p30 tests were positive regardless of exposure time or conditions. No impact on the quantity of DNA recovered was observed when semen was exposed to 45&#xa0;&#xb0;C and 10% RH, with a higher median quantity of DNA recovered at day 28 compared to day 0. In contrast, when the RH was raised to 80%, the median quantity of DNA recovered was substantially less at day 28 (81.5&#xa0;ng, IQR: 87.5&#xa0;ng) compared to day 0 (181.5&#xa0;ng, IQR: 1172.4&#xa0;ng). This study highlights the impact that temperature and RH may have on the persistence of AP, PSA, sperm and DNA over time.

Humans