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Nondominant Hand Training in Laparoscopy for Surgical Interns: Feasibility and Impact.

OBJECTIVE: Laparoscopy requires bimanual proficiency, yet early trainees demonstrate underdeveloped nondominant hand (NDH) performance. Although deliberate practice of NDH skill contributes to overall performance, NDH training is rarely incorporated into residency simulation curricula and has not been formally evaluated in surgical trainees. We assessed feasibility and impact of integrating structured NDH training with established laparoscopic curriculum for surgery interns. DESIGN: Prospective, single-institution randomized pilot study. Interns were assigned the standard 4-week curriculum of laparoscopic dominant hand and bimanual tasks (Control) or completed assigned NDH tasks in addition to the standard curriculum (Intervention). Feasibility was determined by assigned task completion, daily standard and NDH-specific self-reported practice time, and improvement in bimanual task performance. Performance was video recorded weekly and assessed by blinded evaluators using MISTELS and GOALS scoring. Cognitive workload during laparoscopic tasks was measured via NASA-TLX. Exploratory analyses were conducted within a Bayesian framework. SETTING: A single academic institution with a surgical simulation training program. PARTICIPANTS: General surgery interns on their 4-week simulation rotation. RESULTS: Eleven general surgery interns (6 intervention, 5 controls; all right-hand dominant) completed the study with 100% task completion and practice log compliance. Both groups improved in bimanual performance and perceived cognitive load. Reduction in cognitive workload during bimanual task performance was greater in the NDH group. Time spent on NDH practice over 4 weeks was associated with improved bimanual performance, independent of time spent on standard curriculum tasks. CONCLUSIONS: Structured NDH training is feasible to implement within an existing curriculum and reduces perceived cognitive workload during bimanual laparoscopic tasks. NDH practice demonstrates a beneficial dose-response relationship with performance, supporting its integration into early laparoscopic training.

Laparoscopy

The effect of hip abductor or external rotator strength on dynamic knee valgus in healthy subjects-a systematic review with partial meta-analysis.

BACKGROUND: Weak hip abductors and external rotators (ER) have long been suggested to cause increased dynamic knee valgus. Patients are often prescribed strengthening of these muscles with the expectation that it will reduce their risk of pain and injury. The validity of this claim remains unclear. METHOD: We conducted a systematic review and partial meta-analysis assessing the association between hip strength and knee valgus in healthy subjects. An online search was conducted in May 2026. Databases included Medline, EMBASE, CINAHL and Google Scholar. INCLUSION CRITERIA: English language, asymptomatic subjects, dynamometric hip strength, single or multi-camera kinematic analysis, and statistical tests of difference or correlations between hip abductor or ER strength and dynamic valgus. Data were extracted concerning study design, subject characteristics, relevant outcome measures and statistics. RESULTS: 22 papers qualified for inclusion. Hip abductor correlations: 12 papers found no significant correlation, 2 supported the hypothesis and 2 found evidence contrary. Hip ER correlations: 8 papers found no significant correlation, 2 supported the hypothesis and 2 were contrary. Group differences for hip abduction strength: 3 papers found no difference, 2 found significant differences in support of the hypothesis, 1 found significant difference to contrary. Group differences for ER strength: 1 paper found no significant difference. None of the partial meta-analyses achieved statistical significance. CONCLUSION: Weakness in hip abductors or external rotators may not result in increased dynamic knee valgus in healthy subjects. While continued research may further illuminate our understanding, we discuss alternative explanations.

Humans

Multiplexed CRISPR/Cas9 mediated knockdown of BCH gene in potato enhances beta-carotene to combat vitamin A deficiency.

The inadequate amounts of provitamin A carotenoids in crops contribute to the widespread vitamin A deficiency, leading to malnutrition and blindness in humans. Suppression of the β-carotene hydroxylase (BCH) increases β-carotene levels. In the current study, we utilized the multiplexed CRISPR/Cas9 approach by designing three targets against the BCH gene in a local potato cultivar. Transformation efficiency was recorded as 15%, the successful integration of the CRISPR/Cas9-BCH multiplex construct in potatoes was confirmed through PCR. When analysed using TIDE software, Sanger sequencing revealed the highest indel efficacy of 92.1% in plant 7 and 26.6% in plant 1. qRT-PCR (quantitative real-time PCR) analysis indicated a significant 89-fold reduction in BCH transcript levels in genome-edited potato lines compared to control plants. Spectrophotometry demonstrated a notable increase in beta-carotene levels in genome-edited potato plants, ranging from 0.831 µg/mL FW to 4.236 µg/mL FW, compared to the control plant with the lowest beta-carotene concentration (0.344 µg/mL FW). HPLC analysis further confirmed increased beta-carotene levels in genome-edited potato plants, ranging from 0.11 mg/mL FW to 0.36 mg/mL FW, compared to the unmodified control plant with a minimum beta-carotene value of 0.09 mg/mL. Our results revealed that the multiplexed CRISPR-Cas9 approach targeting the BCH gene results in enhanced beta-carotene contents in potato tubers.

Solanum tuberosum

Updated adjunctive minocycline for schizophrenia: A systematic review and meta-analysis of clinical and cognitive outcomes.

BACKGROUND: Minocycline has been proposed as an adjunctive treatment for schizophrenia due to its anti-inflammatory and neuroprotective properties. However, evidence regarding its efficacy across clinical and cognitive outcomes remains inconsistent. METHODS: A systematic review and meta-analysis of double-blind RCTs was conducted following PRISMA guidelines. PubMed, Web of Science, Embase, Ovid MEDLINE, and the Cochrane Library were searched from January 2000 to August 2025. Eligible studies included patients with schizophrenia receiving adjunctive minocycline plus stable antipsychotics. Primary outcomes were PANSS total and subscale scores and overall cognitive performance. Secondary outcomes included SANS, CDS, CGI, GAF, and seven cognitive domains. Standardized mean differences (SMDs) with 95% CIs were calculated. RESULTS: Ten RCTs involving 895 participants were included. Adjunctive minocycline was associated with improvements in negative symptoms (PANSS negative: SMD = -0.55, 95% CI: -0.96 to -0.13; SANS: SMD = -0.75, 95% CI: -1.00 to -0.49) and overall psychopathology (PANSS total: SMD = -0.49, 95% CI: -0.80 to -0.18). Cognitive benefits were limited to a modest improvement in working memory (SMD = 0.24, 95% CI: 0.08 to 0.39), with no significant effects in other cognitive domains. Subgroup analyses suggested that illness stage, antipsychotic regimen, treatment duration, sample size, and geographic region may contribute to variability in treatment effects. Adverse event rates were comparable between groups. CONCLUSIONS: Adjunctive minocycline may improve negative symptoms and provide modest working memory benefits in schizophrenia. However, the evidence is limited by substantial heterogeneity, potential small-study effects, and inconsistent findings. Although short- to medium-term tolerability appeared comparable to placebo, larger, longer-term RCTs are needed to confirm its efficacy and safety.

Humans

Phytolacca acinosa Roxb. induces intestinal toxicity through the histamine-MLCK-tight junction axis: Integrated evidence from proteomics, metabolomics, intestinal organoids and epithelial barrier validation.

Phytolacca acinosa Roxb. (PR) is a saponin-rich medicinal plant associated with gastrointestinal toxicity, but the mechanisms underlying PR-induced intestinal barrier injury remain unclear. In this study, raw PR extract was analytically characterized by UPLC-ZenoTOF-MS/MS, confirming triterpenoid saponins as the predominant constituents. C57BL/6 J mice were orally exposed to characterized PR extract (1.20 or 12.0 g/kg for 5 h), and Caco-2 cells and mouse intestinal organoids were used to assess epithelial toxicity and barrier disruption. Histopathology, ELISA, FITC-dextran permeability assays, immunofluorescence, CCK-8, LDH release, western blotting, DIA-based proteomics and untargeted metabolomics were integrated to define toxicological mechanisms. PR induced dose-dependent intestinal inflammation and barrier dysfunction, with the ileum as the most sensitive target. PR increased serum DAO and D-lactate and intestinal TNF-α and IL-1β, disrupted organoid morphology, enhanced epithelial permeability, and reduced ZO-1 expression. Proteomics revealed changes in inflammatory, lipid-metabolic, cytoskeletal and tight-junction pathways, including upregulation of MLCK3 and phospholipase-related proteins and downregulation of ZO-1 and ZO-2. Metabolomics identified histidine metabolism disturbance and histamine accumulation. Integrated multi-omics and pharmacological validation indicated that histamine activated the PLC/IP₃/Ca²⁺/CaM/MLCK cascade, promoting MLC phosphorylation, tight-junction disassembly and epithelial leakiness. MLCK inhibition partially restored ZO-1/ZO-2 expression and attenuated PR-induced epithelial injury. These findings identify the histamine-MLCK-tight junction axis as a key mechanism of PR-induced intestinal toxicity and support hazard identification of saponin-rich PR exposure.

Animals

Statistical test to compare the linkage model and the admixture model based on central limit results.

In the Admixture Model, the probability that an individual carries a certain allele at a specific marker depends on the allele frequencies in K ancestral populations and the proportion of the individual's genome originating from these populations. The markers are assumed to be independent. The Linkage Model is a Hidden Markov Model that extends the Admixture Model by incorporating linkage between neighboring loci. We prove consistency and asymptotic normality of maximum likelihood estimators for the ancestry of individuals in the Linkage Model, complementing earlier results by (Pfaff et al., 2004; Pfaffelhuber and Rohde, 2022; Heinzel, 2025) for the Admixture Model. These results are used to prove that a statistical test that allows for model selection between the Admixture Model and the Linkage Model is an asymptotic level-α-test. Finally, we demonstrate the practical relevance of our results by applying the test to real-world data from The 1000 Genomes Project Consortium (2015).

Genetic Linkage

Uce-based phylogeny and classification of Megachilini.

The generic-level classification of the bee tribe Megachilini (Megachilidae) has remained controversial due to poor phylogenetic resolution at the base of the group, particularly among the brood parasitic genera and the numerous dauber ("Chalicodoma s. l.") lineages. We present a phylogenomic analysis of Megachilini based on ultraconserved elements (UCEs), sampling 52 ingroup taxa with emphasis on the dauber lineages. We also present a combined UCE + six-gene analysis to improve taxon coverage, resulting in a dataset with 127 ingroup taxa. Maximum likelihood, coalescent, and Bayesian analyses of multiple UCE matrices recover largely congruent topologies with substantially improved support relative to previous studies. Our results strongly support the monophyly of Megachilini, the early divergence of Noteriades and Gronoceras, and a single origin of brood parasitism. All remaining non-parasitic Megachilini form a moderately supported clade sister to the brood parasitic lineage. The leafcutter bees are monophyletic and nested within dauber lineages. Several major dauber clades are consistently recovered, including an exclusively Australian clade corresponding to the Hackeriapis group of subgenera, while several recognized subgenera are paraphyletic. The lineage known as Morphella, previously placed in synonymy with the subgenus Callomegachile, was not closely related to that subgenus and is here treated as a valid subgenus. Divergence-time analyses place the crown age of Megachilini in the late Eocene to early Oligocene, with major extant lineages diversifying during the Miocene. Limited morphological diagnosability of several clades indicates that splitting non-parasitic lineages into numerous genera would result in an impractical classification that would widen the gap between taxonomists and non-specialists and exacerbate the taxonomic impediment in bees. We therefore advocate retaining a single genus Megachile for non-parasitic Megachilini (excluding Noteriades and Gronoceras), as the classification best supported by phylogenomic evidence and most robust to future taxon sampling.

Animals

Cytonuclear conflict and reticulate evolution in the Morelloid clade (Solanum, Solanaceae): Insights from genome skimming and network Phylogenomics.

The Morelloid clade (black nightshades) is one of the most strongly supported clades within the megadiverse Solanum genus. It comprises 76 globally distributed, non-spiny herbaceous and suffrutescent species. While often erroneously considered poisonous weeds, several species are economically important as orphan crops. The clade is closely related to tomato and potato but, due to a lack of focused breeding efforts, remains a putative reservoir of genetic diversity for crop improvement. Despite this potential, we lack fundamental knowledge on the evolution of the Morelloid clade. The group includes polyploid species with unknown parental origins-likely reflecting reticulate processes such as hybridization, introgression, and associated backcrossing events. Prior analyses have been unable to disentangle these processes, leaving the mechanisms underlying reticulate evolution in the Morelloid clade poorly understood. Here, we use genome skimming to produce a well-supported maximum likelihood plastid phylogeny from complete circularized plastomes and a coalescent-based species tree from combined Angiosperms353 and conserved ortholog set nuclear markers. Our dataset, composed of previously published data and deep genome skimming from herbarium samples, spans 26 Morelloid species. To investigate phylogenetic discordance, we used a nuclear phylogenetic network, multispecies coalescent simulations, a fused rooted nuclear chloroplast tree, and quantification of nuclear gene tree concordance. We show that incongruence between nuclear and plastid trees is pervasive and cannot be explained by incomplete lineage sorting alone. Instead, our results demonstrate that events consistent with repeated chloroplast capture have shaped the reticulate evolutionary history of the clade, especially among African polyploid and Pan-American diploid lineages.

Phylogeny

Sex Differences in Postoperative Recovery and Mortality After High-Risk Cardiac Surgery: A Propensity Score-Matched Post Hoc Analysis of the SUSTAIN-CSX Trial.

BACKGROUND: Sex-related differences after cardiac surgery remain controversial because women often present with higher baseline risk and complexity than men. We performed a post hoc propensity score-matched analysis of the SUSTAIN-CSX (Sodium Selenite Administration in Cardiac Surgery) trial to evaluate sex differences in mortality, postoperative complications, and recovery after high-risk cardiac surgery. METHODS: Of 1394 trial participants, 1386 had complete data. Women were matched 1:1 to men using nearest-neighbor propensity score matching based on age and European System for Cardiac Operative Risk Evaluation II (EuroSCORE II), with exact matching on surgical category, yielding 327 female-male pairs. Prespecified sensitivity analyses adjusted for frailty, baseline hemoglobin, renal disease, left ventricular ejection fraction, previous myocardial infarction, preoperative medications, and baseline creatinine. RESULTS: In the primary matched analysis, 180-day survival did not differ between women and men (log-rank P=0.086; unadjusted hazard ratio, 1.80 [95% CI, 0.91-3.55]; P=0.091). In descriptive matched comparisons, women had numerically longer intensive care unit stay (median, 3 days [quartile 1, quartile 3 (Q1, Q3)=1, 6 days] versus 2 days [Q1, Q3=1, 5 days]) and hospital stay (median, 10 days [Q1, Q3=7, 18 days] versus 9 days [Q1, Q3=6, 16 days]; P=0.292), whereas major postoperative complications were similar. In adjusted sensitivity analyses accounting for the matched design and residual imbalance, female sex remained associated with longer intensive care unit stay (adjusted incidence rate ratio [IRR], 1.8 [95% CI, 1.2-2.9]; P=0.009) and hospital stay (adjusted IRR, 1.4 [95% CI, 1.0-1.9]; P=0.031). Mortality sensitivity analyses were model-dependent. CONCLUSIONS: In this propensity score-matched cohort of high-risk cardiac surgery patients, women showed a longer postoperative recovery trajectory in adjusted analyses, whereas mortality findings were sensitive to model specification and should be interpreted cautiously. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02002247.

Aged

Thyroid-joint crosstalk: a systematic review and meta-analysis of thyroid autoimmunity and dysfunction in juvenile idiopathic arthritis.

BACKGROUND: Recent observational studies outlined the concomitant presence of autoimmune diseases in children with juvenile idiopathic arthritis (JIA), including endocrine autoimmunity. Despite the growing evidence of thyroid involvement in JIA, available data are heterogeneous and fragmented. We aimed to systematically review the available evidence on the prevalence of thyroid autoantibody positivity and thyroid dysfunction in patients with JIA. METHODS: PubMed/Medline, Cochrane, and Scopus databases were approached to identify studies reporting data on thyroid autoantibody positivity and dysfunction in children with JIA. RESULTS: A total of 15 studies were included in the final analysis, encompassing 19 015 children with JIA (13 225 females, 69.6%) with a weighted mean age of 8.0 years (range 1.8-21 years). The pooled prevalence estimates of antithyroid antibody positivity and thyroid dysfunction were 0.04 (95% CI: 0.03-0.05) and 0.04 (95% CI: 0.03-0.08), respectively. The risk difference for thyroid autoantibody positivity between children with JIA and controls was 0.08 (95% CI: 0.02-0.14). Possible risk factors were analyzed: the presence of family history for thyroid autoimmune disease (odds ratio - OR 3.91, 95% CI 1.86-8.25), concurrent Antinuclear Antibodies (ANA) positivity (OR 1.62, 95% CI 1.13-2.31), and older age (MD 2.10 years, 95% CI 1.32-2.89) were associated with thyroid autoantibody positivity and/or thyroid dysfunction in children with JIA. No significant difference emerged for the specific JIA form. CONCLUSION: Thyroid dysfunction may be detected in children with JIA, with a significant risk difference in comparison to healthy controls. Specific clinical characteristics, such as family history, ANA positivity, and older age at JIA onset, may suggest which patients should benefit from thyroid autoantibody screening.

Humans

Bedtime tetrahydrocannabinol ingestion reduces morning orthostatic cardiovascular reactivity in adults: An exploratory study.

Acute cannabis use and its primary psychoactive constituent tetrahydrocannabinol (THC) can induce postural dizziness, indicating increased risk of orthostatic instability. However, it is unknown if vulnerabilities persist the morning after bedtime THC consumption. This study investigated the influence of bedtime THC consumption on cardiovascular variables during an orthostatic challenge. Nine individuals with no cannabis use and eight individuals who regularly use cannabis participated in a tilt table test associated with a 3-day in-laboratory stay. Participants underwent an acclimatization day, followed by a placebo dosing day, and a 10 mg THC dosing day. Placebo and THC pills were given 1 h before a participant's habitual bedtime, and the tilt table test was performed ~1 h upon awakening. Participants were instrumented with an electrocardiogram and an automated sphygmomanometer. Fluid intake and output were measured throughout the study. The morning after THC administration, individuals with no cannabis use reported a higher frequency of dizziness and exhibited a significant reduction in both diastolic blood pressure and heart rate reactivity to tilt (reactivity = tilt - baseline) compared to the morning after placebo. Our results indicate a potential increased risk for orthostatic instability the morning after cannabis consumption in individuals with no cannabis use history.

Humans

Could the preoperative urethral curve be used to predict immediate urinary continence following Retzius-sparing robot-assisted radical prostatectomy? A retrospective multi-center study.

PURPOSE: Immediate urinary continence (UC) recovery following Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) remains highly variable, highlighting the need for reliable preoperative prediction. We aimed to develop and validate models to identify patients likely to achieve immediate UC recovery following RS-RARP. MATERIALS AND METHODS: A total of 580 prostate cancer patients who underwent RS-RARP from four medical centers were assigned to a training set (n=348), an internal validation set (n=103) and an external validation set (n=129). Independent predictors were identified through univariate analysis and LASSO regression. A nomogram was constructed using multivariate logistic regression. Its performance was evaluated with receiver operating characteristic (ROC) curve, calibration curves, and decision curve analysis. RESULTS: Immediate UC recovery was observed in 84.5% (294/348) of patients in the training cohort, 80.6% (83/103) in the internal validation cohort, and 81.4% (105/129) in the external validation cohort, respectively. Multivariate analysis identified membranous urethral length (MUL) (OR=1.23, P=0.029) and urethral curvature (OR=2.84, P<0.001) as independent predictors, while prostate volume (PV) (OR=0.84, P <0.001) as a protective factor. The nomogram integrating MUL, PV, and urethral curvature demonstrated superior predictive accuracy, with an AUC of 0.87 (95% CI, 0.83-0.91) in the training cohort. The bootstrap-corrected calibration slope was 0.96, and the Brier score was 0.08.&#xa0;Calibration curves and decision curve analysis confirmed the predictive accuracy and clinical utility of the nomogram. CONCLUSIONS: Our study introduces a novel quantitative method for assessing urethral curvature. The mpMRI-based model, integrating urethral curvature and prostate spatial configuration, offers enhanced predictive accuracy for postoperative immediate UC recovery.

Humans

A Web-Based, Pedometer-Mediated Intervention Increases Amount and Intensity of Physical Activity in COPD: A Randomized Controlled Trial.

INTRODUCTION: Ground-based walking training is an aerobic exercise used in supervised pulmonary rehabilitation (PR). Physical activity (PA) interventions typically promote step counts, but it is unclear whether community-based walking intensity can be targeted as aerobic exercise. This randomized controlled trial evaluated a web-based, pedometer-mediated PA intervention designed to increase walking amount and intensity. MATERIAL AND METHODS: Participants with COPD who had never enrolled in PR were randomized 1:1 to control or intervention. The intervention included individualized step-count goals, iterative feedback, educational content, and an online community forum. The Fitbit Inspire Heart Rate objectively monitored daily step counts. Participants were instructed to achieve step-count goals with as many steps of moderate-intensity as possible guided by a modified Borg rating of 4-5 for dyspnea. The primary outcome was change in PA measured as average daily step count at 12&#xa0;weeks. Aerobic intensity was assessed by the Rapid Assessment of PA Questionnaire which uses self-reported moderate or vigorous PA to categorize responders as underactive or active. Linear mixed-effects models (PROC MIXED, SAS v9.4), adjusting for group, time, group*time, FEV1%predicted, enrollment season, and study modality (eg, in-person, virtual, hybrid), assessed between-group change. RESULTS: Participants (57 intervention, 52 control) were 97% male, mean age 73&#xb1;7 years, and baseline FEV1 73&#xb1;23% predicted. Baseline daily steps were 4,222&#xb1;1,929 (intervention) and 4,851&#xb1;2,637 (control). Intervention participants increased average daily steps by 1,410 steps/day more than controls (p=0.005). The intervention group showed greater transitions from underactive to active intensity (between-group: p=0.025), with 20 (41%) moving to active status (within-group: p=0.001). CONCLUSION: Technology-mediated community-based walking increased PA amount and intensity. These findings support further evaluation of this intervention as a potential option for ground-based walking training with objective measurement of exercise intensity.

Humans