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Paramedian supracerebellar transtentorial approach for Yaşargil T2 tentorial incisura meningiomas.

OBJECTIVE: Tentorial incisura meningiomas, particularly those arising from the middle incisural region (Yaşargil T2), are surgically challenging because of their deep location and compression of critical neurovascular structures. These lesions typically have supratentorial or infratentorial extension but can also extend across both compartments. Although approach selection is often guided by the dominant compartment of tumor extension, for lesions with supratentorial-dominant extension, the optimal approach remains controversial, and a standardized strategy has not been established. Authors of this study evaluated the feasibility and outcomes of the paramedian supracerebellar transtentorial (PST) approach for Yaşargil T2 tentorial incisura meningiomas with a supratentorial-dominant or combined extension. METHODS: The authors retrospectively reviewed data from consecutive patients with radiographic and intraoperative findings consistent with a Yaşargil T2 tentorial incisura lesion treated via the PST approach from September 2005 through December 2025. Patients were placed in a semisitting position whenever feasible and in a semilateral position when semisitting was contraindicated. Collected data included demographics, tumor extension patterns, extent of resection on postoperative MRI, neurological outcomes, histopathology, rate of recurrence, and follow-up. RESULTS: Six patients, 1 male and 5 female, with an overall mean age of 43 years, underwent resection via the PST approach. Four lesions had predominantly supratentorial extension, and 2 had combined supra- and infratentorial growth, with no cases of isolated infratentorial extension. Five patients had been placed in the semisitting position and 1 in a semilateral position because of a cardiac contraindication to the semisitting position. No new permanent neurological deficits were observed. Postoperative MRI showed Simpson grade I resection in all 6 patients. The mean follow-up was 8.6 years. Histopathological analysis revealed 3 WHO grade 1 meningiomas, 1 WHO grade 2 meningioma (clear cell), and 2 solitary fibrous tumors (meningioma mimics). These diagnoses were evaluated according to the 2021 WHO classification. CONCLUSIONS: In this consecutive series, the PST approach was a viable single-corridor strategy for Yaşargil T2 tentorial incisura lesions, including supratentorial-dominant tumors, achieving Simpson grade I resection with no permanent neurological deficits. By providing early devascularization at the tentorial attachment and a gravity-assisted, retractorless working corridor with favorable deep venous visualization, the PST approach challenges compartment dominance as the primary determinant of approach selection.

Humans

Effects of positive psychotherapy on anxiety and quality of life in chronic Urticaria.

INTRODUCTION: Individual, social, and economic consequences including anxiety and poor quality of life are recognised to result from allergic disorders. A positive, realistic viewpoint that emphasises balance and the body is provided by positive psychotherapy. The purpose of this randomized, controlled intervention study was to investigate how counseling based on positive psychotherapy affected anxiety and quality of life. METHODS: Patients in the intervention group had eight sessions of individual counseling based on positive psychotherapy in addition to standard treatment. Other than standard care, the members of the control group received no interventions. The Dermatological Quality of Life Scale (DYQS), Urticaria Activity Score, State-Trait Anxiety Scale, and Personal Information Form were employed as data collection instruments. The study had 66 patients with Chronic Spontaneous Urticaria (CSU), 32 of whom were in the intervention group and 34 of whom were in the control group. RESULTS: The mean scores of the intervention group decreased significantly from pre-test to post-test for urticaria activity (UAS7: 28.22&#xa0;&#xb1;&#xa0;11.17 to 4.22&#xa0;&#xb1;&#xa0;4.30, p&#xa0;<&#xa0;0.001), dermatological quality of life (DLQI: 38.63&#xa0;&#xb1;&#xa0;7.61 to 5.09&#xa0;&#xb1;&#xa0;6.19, p&#xa0;<&#xa0;0.001), situational anxiety (61.63&#xa0;&#xb1;&#xa0;7.73 to 26.03&#xa0;&#xb1;&#xa0;4.71, p&#xa0;<&#xa0;0.001), and trait anxiety (61.56&#xa0;&#xb1;&#xa0;7.90 to 25.13&#xa0;&#xb1;&#xa0;3.66, p&#xa0;<&#xa0;0.001). Furthermore, post-test scores between the intervention and control groups showed statistically significant differences in favor of the intervention group in all primary outcomes, including the total UAS7 score (intervention: 4.22&#xa0;&#xb1;&#xa0;4.30 vs. control: 21.56&#xa0;&#xb1;&#xa0;11.81, p&#xa0;<&#xa0;0.001) and the total dermatological quality of life score (intervention:5.09&#xa0;&#xb1;&#xa0;6.19 vs. control:30.85&#xa0;&#xb1;&#xa0;10.17, p&#xa0;<&#xa0;0.001). CONCLUSIONS: Counseling based on positive psychotherapy has been shown to improve people's quality of life while lowering anxiety and urticaria symptoms. This study demonstrates how these treatments can enhance the quality of life for patients with chronic urticaria by lowering their anxiety and illness symptoms.

Humans

The Impact of Chatbot Type and Normative Messaging on Chatbot Usage Intention Based on the Health Technology Acceptance Model: Randomized Controlled Trial.

BACKGROUND: Digital health tools, such as health chatbots, may improve access to scalable health support, but adoption remains inconsistent. Existing models do not fully integrate technology acceptance factors with health motivation factors relevant to digital health use. OBJECTIVE: This study proposed and tested the health technology acceptance model and examined whether normative message framing and chatbot type were associated with health motivation, technology acceptance, and intention to use a health chatbot. METHODS: In October 2025, we conducted a 4 &#xd7; 2 between-participants online experiment with 1000 US adults recruited from a nationally representative YouGov panel. Participants were randomized to 1 of 8 conditions varying norm message type (self-oriented, peer-oriented, expert-oriented, or family-oriented) and chatbot type (AI-powered or rule-based) in a cancer prevention and genetic risk information scenario. Outcomes included descriptive norms, injunctive norms, perceived susceptibility, perceived severity, perceived benefits, self-efficacy, perceived ease of use, trust, privacy concerns, and usage intention. Data were analyzed using a multivariate ANOVA with Bonferroni-adjusted post hoc tests and multiple linear regression. RESULTS: Peer-oriented and family-oriented messages produced higher usage intention than expert-oriented messages, and peer-oriented messages also increased descriptive norms, injunctive norms, self-efficacy, and trust. AI-powered chatbots were associated with higher usage intention (P=.02) and greater trust (P=.008) than rule-based chatbots. In regression analyses, the model explained 50.8% of the variance in usage intention. Usage intention was positively associated with descriptive norms (&#x3b2;=0.087; P=.003), injunctive norms (&#x3b2;=0.078; P=.009), perceived susceptibility (&#x3b2;=0.051; P=.03), perceived benefits (&#x3b2;=0.253; P<.001), and trust (&#x3b2;=0.33; P<.001), and negatively associated with perceived severity (&#x3b2;=-0.047; P=.049) and privacy concerns (&#x3b2;=-0.11; P<.001). Perceived ease of use and self-efficacy were not significant predictors. CONCLUSIONS: The health technology acceptance model was a useful framework for explaining the intention to use a health chatbot by combining technology acceptance and health motivation constructs. Both social design features and chatbot design features shaped adoption-related beliefs, with peer-oriented and family-oriented framing and AI-powered chatbots showing particular promise. Trust and privacy concerns remained central determinants of intended use.

Humans

Pairwise Comparative Safety and Effectiveness of Anti-TNF Blockers, Vedolizumab, and Ustekinumab During Pregnancy: A Systematic Review and Meta-Analysis.

PURPOSE: Biologic therapies, including tumor necrosis factor (TNF) blockers, vedolizumab (VDZ), and ustekinumab (UST), are generally considered safe during pregnancy in patients with inflammatory bowel disease (IBD), though comparative data remain limited. This meta-analysis examines their safety and effectiveness. METHODS: A systematic search of MEDLINE, EMBASE, CINAHL, Cochrane, and Web of Science was conducted through July 2025. Eligible studies reported maternal or neonatal outcomes in pregnant IBD patients treated with biologics. Studies were pooled using a random-effects model to calculate risk ratios (RRs) with 95% confidence intervals. Heterogeneity was assessed using I2. Primary outcomes were preterm birth and disease activity; secondary outcomes included pregnancy and neonatal outcomes. RESULTS: Nine observational studies (n&#x2009;=&#x2009;6,054) were included. Compared to TNF blockers, VDZ was associated with a higher risk of preterm delivery (RR&#x2009;=&#x2009;1.35, 95% CI 1.04-1.75, I2&#x2009;=&#x2009;0%) and active disease (RR&#x2009;=&#x2009;1.55, 95% CI 1.01-2.40, I2&#x2009;=&#x2009;50%). UST was associated with a higher risk of active disease (RR&#x2009;=&#x2009;1.30, 95% CI 1.06-1.60, I2&#x2009;=&#x2009;0%) and congenital anomalies (RR&#x2009;=&#x2009;2.08, 95% CI 1.30-3.32, I2&#x2009;=&#x2009;0%) compared to TNF blockers. Compared to UST, VDZ was linked to increased risks of preterm birth (RR&#x2009;=&#x2009;2.60, 95% CI 1.03-6.57, I2&#x2009;=&#x2009;0%) and low birth weight (RR&#x2009;=&#x2009;2.38, 95% CI 1.01-5.60, I2&#x2009;=&#x2009;0%). No significant differences were observed for live births, abortions, hospitalizations, or neonatal infections. CONCLUSION: TNF blockers showed a favorable safety and effectiveness profile, VDZ and UST performed broadly similar, and all three biological classes appeared compatible with safe use in pregnancy to maintain effective disease control. Observed differences reflect that VDZ and UST cohorts likely had longer disease duration, prior biologic exposure, and more active disease. The results of this meta-analysis support the continuation of biologic therapy for disease control in pregnant patients with IBD. Treatment decisions should be individualized and tailored to each patient's clinical context.

Female

Impact of Commercial Artificial Intelligence on Radiologist Reading Time for Pulmonary Nodule Evaluation at Chest CT.

Background Chest CT is a primary method for identifying pulmonary nodules, yet interpreting scans remains time-intensive and demanding. Currently, artificial intelligence (AI) is expected to reduce reading times, but the effect of AI on reporting times in this setting is unknown. Purpose To evaluate the impact of a commercial AI software on radiologists' reading time for pulmonary nodule assessment on chest CT scans within a real-world clinical setting. Materials and Methods This retrospective study included patients who underwent chest CT examinations at a tertiary medical center between September 2021 and May 2024. The study period was divided into pre- and post-AI phases. The primary outcome was radiology reporting time. The association between AI implementation and reporting time was evaluated using a multivariable parametric Weibull shared frailty survival model adjusted for reader function, examination type, patient location, and requesting specialty, with clustering at the radiologist level. Interaction analyses assessed heterogeneity across prespecified subgroups. An exploratory extrapolation estimated projected workforce and financial impact. Results This study included 19&#x2009;433 patients (mean age, 62 years &#xb1; 14.2 [SD]; 21&#x2009;814 men; 39&#x2009;323 chest CT examinations, 19&#x2009;190 pre-AI, and 20&#x2009;133 post-AI). AI implementation was associated with faster report completion (adjusted hazard ratio, 1.17; 95% CI: 1.14, 1.21; P < .001). The adjusted median reporting time decreased from 21.3 minutes pre-AI to 18.2 minutes post-AI (14.6% reduction; P < .001). Heterogeneity was observed across reader function (P < .001), examination type (P = .048), and requesting specialty (P = .03). The largest relative reductions were observed for CT thorax electrocardiogram-gated examinations (-41.1%; P < .001) and thoracic radiologists (-25.0%; P < .001), whereas emergency department examinations showed increased median reporting time (7.1%; P < .001). At institutional scan volumes (approximately 20&#x2009;000-22&#x2009;000 chest CT examinations annually), exploratory modeling suggested an approximate reduction of 0.5 full-time equivalent radiologist workload. Conclusion Implementation of commercial AI-assisted pulmonary nodule assessment on chest CT scans reduced radiologist reporting time in a real-world clinical setting. &#xa9; The Author(s) 2026. Published by the Radiological Society of North America under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Iwasawa in this issue.

Humans

Colchicine to prevent cardiovascular events in thoracic surgery patients with or without coronary artery disease: a secondary analysis.

OBJECTIVES: This exploratory post hoc secondary analysis of the Colchicine for the Prevention of Perioperative Atrial Fibrillation (COP-AF) randomised controlled trial evaluated the association between coronary artery disease (CAD) and postoperative ischaemic outcomes after non-cardiac thoracic surgery and assessed whether colchicine had differential effects by CAD status. METHODS: Patients were randomised to colchicine 0.5&#x2009;mg or placebo two times per day for 10 days. Follow-up was 14 days. The primary outcome was myocardial injury after non-cardiac surgery (MINS). A key secondary outcome was the composite of death, MINS and stroke. Cox proportional hazards models assessed the association between CAD and outcomes, with interaction terms to explore whether colchicine had differential effects by CAD status. RESULTS: Of 3209 patients enrolled, 331 (10.3%) had CAD. MINS occurred in 29.3% (n=97) and 18.2% (n=523) of patients with and without CAD, adjusted HR (aHR) 1.53 (95% CI 1.22 to 1.92; p<0.001). For colchicine versus placebo, the HR for MINS was 0.82 (95% CI 0.55 to 1.22) in CAD versus 0.91 (95% CI 0.77 to 1.08) in non-CAD patients (p for interaction=0.61). Death, stroke or MINS occurred in 30.2% (n=100) vs 18.6% (n=535), respectively (aHR 1.53, 95% CI 1.22 to 1.91; p<0.001). Colchicine HRs were 0.77 (95% CI 0.52 to 1.14)&#x2009;vs 0.91 (95% CI 0.76 to 1.07; p for interaction=0.45). CONCLUSIONS: Patients with CAD undergoing thoracic surgery had a higher risk of MINS and other ischaemic outcomes than non-CAD patients. There was no evidence that the effect of colchicine differed between patients with and without CAD; however, these analyses were limited by sample size and do not exclude modest differences between subgroups.

Humans

Psychological interventions for children with chronic physical conditions: a systematic review assessing the role of coping, emotional and cognitive processes.

OBJECTIVES: Coping, emotional and cognitive processes are crucial in child development, particularly in children with pediatric chronic physical conditions (CPC). No systematic review in pediatric psychology has investigated the effectiveness of interventions on these processes concurrently. This review addresses this gap by focusing on the effectiveness of psychological interventions on coping, emotional and cognitive processes in children with CPCs. METHODS: Five electronic databases were searched for studies assessing at least one of these processes. Only randomized-controlled trials with children (8-12&#x2009;years) with a CPC (e.g. diabetes, asthma), which implemented a psychological intervention were included. This study is registered in (CRD42021233505). RESULTS: Ten intervention studies were identified. While cognitive interventions (Cogmed) showed some improvements in working memory, the effects varied across studies despite similar methodologies. Coping interventions (e.g. Coping Skills Training) showed little effect on coping strategies or psychological health variables and were no more beneficial than control groups. No study trained coping, emotional processes and cognitive processes together. CONCLUSION: This review shows current limitations in evaluating psychological interventions targeting coping, cognitive or emotional processes in children with CPCs, limiting a comprehensive understanding of the interventions' action mechanisms. Systematically including underlying processes in intervention studies could help to better adjust those interventions.

Humans

Selective and sensitive colorimetric sensing of carbosulfan based on BiO2-x/Bi2O2.75 nanosheets with excellent haloperoxidase-like activity.

The development of colorimetric methods based on directly inhibiting nanozyme activity for pesticide detection has attracted considerable attention. In this study, we report a novel colorimetric sensing strategy utilizing BiO2-x/Bi2O2.75 nanosheets (BiO2-x/Bi2O2.75 NSs) with haloperoxidase (HPO)-like activity for the rapid and sensitive detection of carbosulfan (CBS) in foods. Oxygen-vacancy-rich BiO2-x/Bi2O2.75 NSs with HPO-like activity were rationally constructed. Kinetic studies revealed a remarkable Michaelis-Menten constant (Km) of 0.014&#xa0;mM for I-, indicating a higher affinity for iodide ions than other reported HPO-like nanozymes, as evidenced by its lower Km. Under acidic conditions, CBS tends to be hydrolyzed to produce reductive sulfide species, which directly inhibit the iodoperoxidase-like activity of BiO2-x/Bi2O2.75 NSs, enabling selective detection with a limit of detection (LOD) of 0.18&#xa0;&#x3bc;g/mL and a linear range of 0.20-100&#xa0;&#x3bc;g/mL. When the concentration of interfering pesticides and substances was 5 times that of CBS, the sensor remained unaffected, exhibiting excellent stability and specificity. This work contributes to the detection of CBS in complex food matrices, bridging the application gap of HPO-like nanozymes in pesticide detection and providing a promising method for food safety detection.

Colorimetry

Diagnostic performance of intraoperative in vivo hyperspectral imaging for meningioma grading and molecular alterations: results from a prospective feasibility study.

OBJECTIVE: Hyperspectral imaging (HSI) is an emerging intraoperative, noninvasive, contrast agent-free imaging modality that enables quantitative assessment of tissue composition. The present study aimed to investigate whether HSI-derived tissue parameters correlate with WHO grade and molecular markers of aggressiveness in cranial meningiomas. METHODS: In this prospective study, intraoperative in vivo HSI was performed using the TIVITA tissue system, capturing spectral signatures between 500 and 1000 nm. Quantitative tissue parameters included tissue oxygen saturation (StO2), near-infrared perfusion index, organ hemoglobin index (OHI), and tissue water index (TWI). HSI parameters were correlated with histopathological WHO grade and molecular alterations, including CDKN2A/B deletion, TERT promoter mutation, and 1p/22q loss. Group differences were analyzed using one-way ANOVA, and diagnostic performance was assessed using receiver operating characteristic (ROC) analysis. RESULTS: Forty-six meningiomas were included, comprising WHO grade 1 (n = 35) and WHO grade 2-3 (n = 11) tumors. TWI was significantly higher in WHO grade 2-3 meningiomas compared with WHO grade 1 tumors (mean 0.49 [SD 0.12] vs 0.38 [SD 0.17], p = 0.048). ROC analysis demonstrated an area under the ROC curve (AUC) of 0.71 (95% CI 0.56-0.86, p = 0.036) for TWI in discriminating higher-grade disease. A TWI cutoff &#x2265; 0.367 identified all WHO grade 2-3 meningiomas with 100% sensitivity and 100% negative predictive value. In a molecular subgroup (n = 15), OHI appeared higher in tumors with homozygous CDKN2A/B deletion than in nondeleted tumors (mean 0.77 [SD 0.04] vs 0.62 [SD 0.10]). However, only 3 CDKN2A/B-deleted cases were available, and these findings should be considered descriptive. ROC analysis yielded an AUC of 0.89 (95% CI 0.71-1.00). An OHI cutoff &#x2265; 0.712 identified all three CDKN2A/B-deleted tumors (100% sensitivity), with 83.3% specificity and 86.7% accuracy. CONCLUSIONS: The present investigation demonstrated that HSI-derived tissue water and hemoglobin metrics provide biologically meaningful information in meningiomas. Low tissue water content appeared to rule out higher-grade diseases in this first subset cohort, while elevated hemoglobin showed a potential association with CDKN2A/B deletion in a small exploratory subgroup. These findings support the potential of HSI as a real-time noninvasive tool for intraoperative risk stratification and should be evaluated in large-scale studies. German Clinical Trials Register no. DRKS00036771 (www.drks.de).

Humans

Light regulates capsaicinoid biosynthesis via the CaHY5-CaBBX2-CaACS8 module in pepper.

Capsaicinoids are a class of unique alkaloids that confer the pungent taste to pepper fruits. However, it remains largely unknown how light regulates the biosynthesis of capsaicinoids. We conducted a metabolic analysis on light- and dark-adapted pepper fruits. The results showed that dark-adapted pepper fruits had lower capsaicinoid contents and correspondingly downregulated transcription of capsaicinoid biosynthetic genes (CBGs), indicating that light plays a crucial role in capsaicinoid biosynthesis. Furthermore, silencing of CaHY5, a pivotal transcription factor gene in the light signaling pathway, decreased the content of capsaicinoid and suppressed the expression of CBGs, whereas transient overexpression of CaHY5 generated exactly opposite results. CaHY5 can bind to the G-box motif in the promoters of CaBBX2 and CaACS8, thereby enhancing their transcriptional levels. The activated CaBBX2 then binds to the T/G-box in the CaACS8 promoter to stimulate its expression. CaBBX2 or CaACS8 silencing led to decreased levels of capsaicinoids, while their transient overexpression produced increased capsaicinoid contents. Collectively, our results indicated that the light-activated CaHY5-CaBBX2-CaACS8 regulatory module plays a pivotal role in capsaicinoid biosynthesis. These findings provide new insights into the influence of light on capsaicinoid biosynthesis and potential targets for activation of this biosynthetic pathway in pepper.

Capsicum

Transcriptomic insights into exogenous fatty acid-enhanced halotolerance in Zygosaccharomyces rouxii.

BACKGROUND: High salinity restricts microbial growth during brine-based food fermentation. Although exogenous unsaturated fatty acids improve the salt tolerance of Zygosaccharomyces rouxii, the associated transcriptional mechanisms remain unclear. This study investigated the transcriptomic response of Z. rouxii CGMCC 3791 to palmitoleic acid (C16:1) under high salt conditions. RESULTS: Cells were cultured in yeast extract peptone dextrose (YPD) containing 120&#x2009;g&#x2009;L-1 NaCl, with or without 20&#x2009;&#x3bc;g&#x2009;mL-1 C16:1. They were analyzed by RNA sequencing. Principal component analysis clearly separated the two treatments. Using q&#x2009;<&#x2009;0.05 and |log2 fold change|&#x2009;>&#x2009;1, 23 differentially expressed genes were identified - three upregulated and 20 downregulated. INO1, MLS1, POX1, MEP2, and SOD5 were among the major responsive genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that peroxisome-associated functions, lipid metabolism, oxidative stress responses, nitrogen utilization, and mitogen-activated protein kinase (MAPK) signaling were the principal C16:1-responsive processes. CONCLUSION: Exogenous C16:1 elicited a focused transcriptional adjustment rather than broad transcriptome-wide reprogramming in salt-stressed Z. rouxii. The results indicated that peroxisome-linked lipid processes and redox regulation were candidate mechanisms underlying fatty-acid-associated halotolerance and provided targets for improving the robustness of high-salt food fermentation. &#xa9; 2026 Society of Chemical Industry.

Zygosaccharomyces rouxii

The asymmetry of working memory training transfer: A systematic review and meta-analysis.

Working memory (WM) training is widely used to enhance cognitive performance; however, its transfer to untrained tasks remains controversial. Traditional theories emphasize task similarity as the primary determinant of training transfer, but they cannot fully explain emerging evidence of asymmetric transfer across tasks. Two directional transfer hypotheses are proposed here to explain this asymmetry: the resource-based transfer advantage hypothesis predicts stronger transfer from more to less cognitively demanding tasks, whereas the ability-based transfer advantage hypothesis predicts stronger transfer from tasks engaging broader task-general abilities to tasks engaging task-specific narrower abilities. The contrast between span and updating paradigms provides an informative framework for distinguishing these accounts, because updating tasks are generally more cognitively demanding, whereas span tasks involve broader abilities. Accordingly, we conducted a three-level meta-analysis of 55 studies (208 effect sizes; N = 3,492). The results showed that updating training transferred reliably to span tasks (g = 0.176, p < .001), whereas span training did not reliably transfer to updating tasks (g = 0.048, p = .453), supporting the resource-based account. This advantage of updating training also extended to non-WM outcomes and was more pronounced at lower training doses, in non-adult samples, and with verbal stimuli. Together, these findings extend WM transfer theory beyond task similarity by highlighting the importance of cognitive demand and offer guidance for WM training design.

Humans

Prophylactic Surgical Left Atrial Appendage Closure in Bioprosthetic Aortic Valve Replacement: Short-Term Outcomes of Randomized Controlled LAA-CLOSURE Trial.

BACKGROUND: Surgical closure of the left atrial appendage (LAA) reduces stroke risk in patients with atrial fibrillation (AF) undergoing cardiac surgery. We evaluated the safety and efficacy of prophylactic LAA closure during bioprosthetic surgical aortic valve replacement in patients without prior AF. METHODS: In this investigator-initiated, academic, randomized, open-label, multicenter LAA-CLOSURE (Left Atrial Appendage CLOSURE for the Prevention of Thromboembolisms in Patients Undergoing Aortic Bioprosthesis Surgery) trial, 921 patients without prior AF undergoing bioprosthetic surgical aortic valve replacement with or without concomitant surgery were randomized and 904 patients included in the modified intention-to-treat analysis (prophylactic LAA closure, n=445; or usual care, n=459). Median age was 73&#x2009;years (interquartile range, 69-76), 34.8% were women, and 49% had concomitant coronary artery disease. The primary end point was a composite of cardiovascular death, stroke, or systemic embolism at 30&#x2009;days. RESULTS: The primary end point occurred in 10 of 434 (2.2%) patients in the LAA closure group and 14 of 452 (3.1%) patients in the control group; however, the treatment effect changed direction at &#x2248;7&#x2009;days. In the time-split Cox regression model, hazard ratios were 2.4 (95% CI, 0.62-9.4; P=0.20) between 0 and 7&#x2009;days and 0.29 (95% CI, 0.080-1.0; P=0.056) between 7 and 30&#x2009;days. No closure-related serious complications or differences in bleeding were observed. Postoperative AF occurred in 205 of 445 (46.1%) versus 184 of 459 (40.1%) patients (relative risk, 1.1 [95% CI, 0.99-1.3]; P=0.07), and AF at discharge in 40 of 445 (9.2%) versus 34 of 459 (7.7%) patients (relative risk, 1.2 [95% CI, 0.77-1.8]; P=0.44), in the closure and control groups, respectively. CONCLUSIONS: Prophylactic LAA closure during bioprosthetic surgical aortic valve replacement was safe and did not increase bleeding. REGISTRATION: URL: clinicaltrials.gov; Unique Identifier: NCT02321137.

Aged

Navigating Social Media: Balancing Connectivity With Media Literacy to Combat Misinformation and Protect Mental Well-Being.

BACKGROUND: The pervasive use of social media has created a complex digital ecosystem where high connectivity coexists with significant challenges, including the rapid spread of misinformation, particularly regarding mental health, and documented negative impacts on psychological well-being. Platform architectures designed for engagement maximization have been identified as central factors in both issues. OBJECTIVE: This paper critically analyzes the interconnected relationships between social media use, misinformation dissemination, and mental health impacts, with particular attention to psychiatric misinformation across diagnostic categories (e.g., depression, anxiety, ADHD). A primary objective is to evaluate the potential of advanced critical digital literacy frameworks to serve as protective mechanisms against these dual threats. METHODS: A systematic search was conducted following PRISMA 2020 guidelines across APA PsycInfo, PubMed, JSTOR, and Google Scholar for literature published between January 2018 and March 2026 (updated from the original 2023 search). The search yielded 2672 records. After removing 624 duplicates, 2048 records underwent title and abstract screening, with 1802 excluded. The remaining 246 full-text articles were assessed for eligibility, resulting in 86 studies included in the final qualitative synthesis. Inter-rater reliability was established (Cohen's &#x3ba;&#x2009;=&#x2009;0.82). Quality assessment was conducted using the Joanna Briggs Institute Checklist, AXIS, and CASP tools, with findings weighted by methodological quality. A thematic analysis was undertaken to synthesize findings. RESULTS: The analysis reveals that core architectural features of social media platforms, algorithmic curation and engagement-based metrics, simultaneously foster environments ripe for misinformation spread and contribute to psychological distress, including anxiety, depression, and harmful social comparison. Psychiatric misinformation specifically (e.g., inaccurate claims about treatment effectiveness, diagnostic criteria, and medication side effects) represents a growing concern, particularly on image- and video-based platforms. The findings indicate that conventional media literacy approaches focused solely on fact-checking are insufficient. Instead, a critical digital literacy framework encompassing algorithmic awareness, data literacy, and emotional awareness is essential for building user resilience, with evidence from high-quality systematic reviews supporting this approach. CONCLUSIONS: Navigating the complexities of modern social media requires an integrated approach combining "pedagogies of play" for experiential skill development with advocacy for structural change (e.g., algorithmic transparency, well being by design principles). This dual strategy empowers individual users to critically engage with digital content while advocating for ethical platform design, thereby safeguarding both mental well-being and democratic discourse. Implications for educators, mental health professionals (including competencies for addressing patient encounters with psychiatric misinformation), policymakers, and platform designers are discussed.

Humans

[Optical genome mapping analysis of a Chinese pedigree with a complex balanced translocation involving four chromosomes].

OBJECTIVE: To explore the genetic characteristics of a complex balanced translocation involving four non-homologous chromosomes in a Chinese pedigree using optical genomic mapping (OGM). METHODS: A woman with primary infertility and her family members who presented at the Prenatal Diagnosis Center of the Sixth Affiliated Hospital of Sun Yat-sen University in October 2021 were selected as study subjects. Comprehensive analysis and verification of chromosomal abnormalities were conducted through conventional G-band karyotyping analysis, single nucleotide polymorphism microarray (SNP array) and OGM. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: E2022210). RESULTS: G-band karyotyping analysis indicated that the proband, her father, and younger brother have all carried a complex translocation involving four chromosomes. SNP array analysis revealed a duplication of approximately 21.63 Mb in the 9p24.1-p21.1 region in the proband's younger brother, while no abnormality was detected in other family members. OGM confirmed that the complex balanced translocation has involved chromosomes 5, 8, 9, and 10. CONCLUSION: The proband has harbored a complex balanced translocation. OGM has demonstrated certain advantages in characterization of complex chromosomal structural abnormalities.

Humans

Public health, public protest: The role of health burdens and healthcare access in protest mobilisation.

Health and politics are intertwined, yet few studies have examined the association between health and protest. This study examined whether population health burdens were associated with protest incidence and whether healthcare access modified these associations. Analysis was based on an unbalanced 2004-2023 country-year panel, combining protest counts from ACLED with rates for 22 GBD causes. Mixed-effects negative-binomial models estimated incidence-rate ratios (IRRs) with interactions for healthcare access (&#xb1;1 SD). Two-way fixed-effects Poisson models were estimated as a benchmark to distinguish cross-national associations from within-country dynamics. Health burdens were systematically, but heterogeneously, associated with protest. Rates for several non-communicable burdens were associated with protest, notably musculoskeletal disorders (IRR 1.72, 95% CI 1.37-2.15), neoplasms (1.24, 1.06-1.44), substance-use disorders (1.32, 1.12-1.56) and HIV/AIDS and other STIs (1.24, 1.12-1.38). Higher healthcare access generally attenuated health-protest associations. Fixed-effects models confirmed several associations (e.g. HIV/AIDS, neoplasms) but revealed that others (e.g. maternal/neonatal disorders, enteric infections) were driven primarily by cross-national differences. Population health burdens were associated with cross-national variation in protest mobilisation. Chronic, non-communicable burdens were associated with heightened protest, whereas poverty-linked and early-life burdens were associated with lower mobilisation. Healthcare access was associated with attenuation of these relationships.

Humans

Care Navigation for Methamphetamine Use Disorder: A Randomized Clinical Trial.

IMPORTANCE: Stimulant-involved deaths continue to increase in the US, and methamphetamine use remains a weighty public health concern. Treating methamphetamine use disorders is complicated. Contingency management has demonstrated the best effectiveness but is not widely implemented. OBJECTIVE: To examine the effectiveness of dedicated care navigation in linking patients to treatment. DESIGN, SETTING, AND PARTICIPANTS: This prospective randomized clinical trial was conducted at an integrated safety-net health system in Denver, Colorado, between April 10, 2023, and December 31, 2024. Eligible participants were 18 years or older who had a methamphetamine-related encounter in an acute care setting; those with involuntary treatment holds, substance treatment in past 90 days or actively seeking treatment, and inability to provide consent were excluded. Participants completed baseline, 30-day, and 90-day study visits. INTERVENTION: Dedicated care navigation, incorporating contingency management principles, with a focus on addressing health-related social needs. MAIN OUTCOMES AND MEASURES: Linkage to treatment within 30 and 90 days of enrollment defined as a composite measure of at least 1 of the following: electronic health record data indicating a visit at the health system's substance treatment clinic, a behavioral health encounter at an outpatient clinic, temporary residential treatment, or self-reported treatment on the 30- and/or 90-day follow-up survey. RESULTS: Of 192 participants enrolled in the Beginning Early and Assertive Treatment for Methamphetamine Use trial, 156 (81.3%) were male, and the median age was 39 (IQR, 31-47) years. Most participants were unstably housed (163 [84.9%]), not currently employed (158 [82.3%]), and without regular access to a working phone (94 [49.0%]). Of the 96 participants randomized to the intervention, 60 (62.5%) engaged in 2 or more navigation sessions, 45 (46.9%) completed the 30-day study visit, and 47 (49.0%) completed the 90-day study visit compared with 44 (46.3%) and 37 (38.5%), respectively, of the 96 randomized to the control arm. No statistically significant differences in treatment linkage were observed at 30 days (24 participants [25.0%] in both arms; risk ratio, 1.00 [95% CI, 0.61-1.63]) or 90 days post enrollment, (32 [33.3%] in intervention vs 24 [25.0%] in control arms; risk ratio, 1.33 [95% CI, 0.85-2.09]). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, integrating principles of contingency management into the intervention may have increased engagement with a dedicated care navigator but did not increase likelihood of linkage to treatment for methamphetamine use disorder. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06033365.

Humans

Adeno-Associated Virus Gene Therapy Translation: Lessons from Early Regulatory Meetings.

The Platform Vector-Gene Therapy (PaVe-GT) program is a National Institutes of Health (NIH) initiative that aims to develop adeno-associated virus (AAV) gene therapies for four monogenic rare diseases, two organic acidemias and two congenital myasthenic syndromes. PaVe-GT's platform-based approach identifies and diminishes redundancies and applies efficiencies in preclinical, clinical, and regulatory activities. The program's hypothesis is that implementing these efficiencies can accelerate clinical trial initiation. Based on its platform-centric experience and public-serving mission, the PaVe-GT program actively shares its scientific and regulatory learnings with the public to benefit the development of similar gene therapy products for rare diseases. PaVe-GT's first investigational AAV gene therapy candidate is AAV serotype 9 human propionyl-CoA carboxylase alpha subunit (AAV9-hPCCA) for propionic acidemia caused by PCCA deficiency, which received initial feedback from the Food and Drug Administration (FDA) in an INitial Targeted Engagement for Regulatory Advice on CBER/Center for Drug Evaluation and Research (CDER) ProducTs (INTERACT) meeting. Upon further product development that took into consideration the FDA's initial advice, the program obtained the Agency's feedback in pre-investigational new drug (IND) (Type B) and Type C meetings. Here, we share our experience from these meetings, including strategy, preparation, pre- and post-meeting feedback from the FDA, and lessons learned during the AAV9-hPCCA regulatory process, which the program plans to apply across the PaVe-GT platform. Topics discussed in the regulatory meetings included animal model and efficacy studies, toxicology study plans, manufacturing of the investigational AAV product, and clinical trial design. The main lessons learned from the pre-IND and Type C meetings for AAV9-hPCCA are: (1) Pharmacology/Toxicology studies in a single rodent species are sufficient for filing an initial IND; (2) FDA feedback guides product quality improvements and early development of a quantitative potency assay; (3) use of biomarkers as potential surrogate endpoints in a future efficacy trial benefits from collection of data in the natural history study and the first-in-human Phase 1/2 study; and (4) evidence from the Phase 1/2 clinical trial could be leveraged to support a license application. Lightly redacted regulatory documents and comprehensive templates developed by the PaVe-GT team are available on the PaVe-GT website.

Dependovirus