Search Results (6,495)

The GLA IVS4+919G>A founder variant causes a late-onset, cardiac-predominant form of Fabry disease, yet the severity of cardiac remodeling varies markedly among affected men. We studied 167 unrelated male carriers. Genome-wide association analyses included 81 men aged ≥50 years for left ventricular hypertrophy (LVH; left ventricular mass index [LVMI] ≥ 51 g/m^2.7) and septal hypertrophy (interventricular septal thickness at end-diastole [IVSd] ≥ 1.2 cm), and 149 men with plasma globotriaosylsphingosine (lyso-Gb3) measurements. Genotyping was performed with the Axiom Genome-Wide TPM 2.0 Array. Mean LVMI increased from 34.6 ± 11.3 g/m^2.7 at 20–39 years to 75.1 ± 34.0 g/m^2.7 at ≥60 years, although substantial variability persisted within each age stratum. rs1435166 and rs2572260, located in the adjacent EGLN1/SPRTN region, showed identical associations with LVH (both p = 4.14 × 10⁻⁸) and concordant genotypes in all 81 participants (dosage r² = 1.00; D′ = 1.00), indicating a single regional association signal. The association remained evident in exact testing, Firth logistic regression, and an age-adjusted continuous-LVMI analysis yielded concordant results. In the age-adjusted analysis, each rs1435166 T allele was associated with a 12.8 g/m^2.7 lower LVMI. Two intergenic variants met the exploratory threshold for septal hypertrophy, whereas no variant reached genome-wide significance for lyso-Gb3. These findings support the hypothesis that inherited genetic background contributes to variation in cardiac remodeling severity among carriers of the same pathogenic GLA variant. Independent replication, regional fine-mapping, and functional validation are required. Full article

Background: Work-related fatigue is a preventable occupational health concern in high-intensity manufacturing environments. However, supervisors and occupational health services often lack transparent criteria to support the preventive review of overtime practices. This study developed and internally validated an explainable human-in-the-loop concurrent screening model to identify employees with currently elevated work-related fatigue using routinely collected working-hour records and occupational health examination data. Materials and Methods: De-identified administrative and occupational health data from 314 full-time manufacturing employees were linked with standardized fatigue assessment data. Currently elevated work-related fatigue was defined using the top quartile of the standardized work-related fatigue subscale. To reduce information leakage, the work-related fatigue score used to define the outcome was excluded from the predictor sets. Multivariable logistic regression and XGBoost were compared using nested stratified five-fold cross-validation, with aggregated out-of-fold predictions from the outer folds used for the performance evaluation. Model performance was assessed using discrimination, probabilistic accuracy, calibration, and classification metrics at provisional, study-specific thresholds. Results: XGBoost demonstrated greater discrimination and better overall probabilistic accuracy than logistic regression, with an AUC of 0.77 versus 0.68 and a Brier score of 0.14 versus 0.17, respectively. At the provisional study-specific threshold of τ1 = 0.28, XGBoost achieved a sensitivity of 0.78 and a specificity of 0.70. Using τ1 = 0.28 and τ2 = 0.55, 58.0%, 27.1%, and 15.0% of employees were classified into provisional low-, moderate-, and high-priority tiers, respectively. The observed prevalence of currently elevated work-related fatigue increased across these tiers from 9.3% to 28.2% and 78.7%, respectively. Calibration assessment indicated systematic miscalibration for both XGBoost (intercept α = 0.78, slope β = 1.64) and logistic regression (α = −0.49, β = 0.56). Because τ1 and τ2 were selected and evaluated using aggregated out-of-fold predictions generated from the same single-organization development dataset, their stability and transportability are unknown. Medium-term cumulative overtime, particularly during months −2 to −6, together with routinely measured indicators of vulnerability and recovery, contributed substantially to the model-estimated probability of currently elevated fatigue. Conclusions: Routinely collected working-hour and occupational health examination data may support explainable concurrent screening for currently elevated work-related fatigue and illustrate a potential framework for differentiated preventive reviews. However, the proposed thresholds and review-priority tiers are provisional and study-specific and should not be interpreted as implementation-ready decision rules for occupational health practices. Prospective temporal validation, external validation in independent organizations, and local recalibration are required before threshold-based implementation. Full article

Background: Sarcopenia is a multidimensional musculoskeletal-aging phenotype defined by reduced muscle quantity together with weakness and impaired performance, but public genetic resources rarely capture sarcopenia as a single uniformly labeled phenotype. Methods: Official National Human Genome Research Institute-European Bioinformatics Institute (NHGRI-EBI) genome-wide association studies (GWAS) Catalog association files archived locally on 15 April 2026 were grouped into muscle-quantity and function-frailty domains. Exact shared rsIDs were identified, assigned to catalog representative/mapped genes, evaluated against exploratory skeletal-muscle transcriptomic context, benchmarked with trait-grouping sensitivity analyses, and ranked with a secondary multi-criteria evidence-integration framework. Results: The muscle-quantity domain contained 1580 unique single-nucleotide polymorphisms (SNPs) and the function-frailty domain contained 383 unique SNPs, with 14 exact rsIDs shared between domains. A trait-file permutation benchmark did not show that this overlap exceeded a catalog-level null expectation (empirical p = 0.514), so the shared set is interpreted as a descriptive, high-specificity candidate intersection rather than statistically enriched sharing. Sensitivity analyses showed that the 14-rsID set was retained after excluding falling/fall and chronic obstructive pulmonary disease (COPD)-related proxy traits, indicating that the primary shared set was driven mainly by grip/low-grip function traits. Exploratory transcriptomic context and evidence integration organized candidates for follow-up but did not validate causal or linkage disequilibrium (LD)-level sharing. Conclusions: This framework generates candidate hypotheses for sarcopenia-related musculoskeletal aging but does not establish causal, fine-mapped, or statistically enriched genetic sharing. Full article

Extracellular vesicle RNAs (EV-RNAs) possess important biological functions and strong therapeutic potential. Their composition, however, is not yet fully understood. To obtain a comprehensive insight of the composition for healthy individuals, we adopted RNA-based T oligo-primed PCR (RNA TOP-PCR) to amplify all EV-RNA species for three healthy males. The constituent sequences were then sequenced and analyzed. The results showed that rRNAs constitute the major species (31.1–43.6%) of EV-RNAs, followed by ncRNAs (including lncRNAs, 4.3–7.9%, and sncRNAs, 0.4–1.2%), Y RNAs (3.9–9.3%), mRNAs (0.7–1.7%), and tRNAs (~0.1%), together with small amounts of mitochondrial tRNA, pseudogenes, and miRNAs (<0.004% over mappable reads). Noticeably, ~40% of the EV-RNAs remain unannotated, while the annotated EV-mRNAs seem to bear a major mission focusing on signal transduction and oxidative phosphorylation. Motif sequences for lncRNA vesicle localization highly agree with previous reports. Among Y RNAs, RNY3 and RNY4 are the major isoforms. Interestingly, many sequences overlap with precursor miRNAs but do not overlap with mature miRNAs. Taken together, RNA TOP-PCR is a robust method suitable for the study of EV-RNAs complexity, and EV-RNAs-mediated intercellular regulation seems to be much more complicated than previously thought. Full article

Accurate conductor-to-pad alignment is essential in PCB wire welding because misalignment increases rework, lowers yield, and affects product quality. In manufacturing images, precise conductor localization is challenging because the target structures are small, the boundaries are subtle, and the conductors often resemble nearby PCB pads. This study proposes an integrated vision pipeline for precision wire welding under deployment-oriented runtime requirements. The framework combines YOLOv9-Tiny for rapid conductor localization with EfficientViT-SAM for box-prompted mask refinement, enabling accurate conductor segmentation while maintaining practical inference speed. A total least squares (TLS)-based geometric method is introduced to generate x-axis correction offsets from predicted masks for alignment support. The models were validated on data from a 4-conductor system collected under production-like conditions. For box-prompted segmentation, EfficientViT-SAM-L2 achieved an mIoU of 95.9% with a mean inference time of 2.264 s, satisfying the target requirement of high segmentation accuracy and inference time below 3 s. Compared with heavier SAM variants and a transformer-based benchmark, the selected model provided a more practical balance between mask quality and computational efficiency. These results support the feasibility of mask-based offset generation for precision wire welding. Full article

Background: Patients with end-stage renal disease (ESRD) undergoing radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) represent a uniquely high-risk population. While prior studies have demonstrated worse postoperative outcomes among dialysis-dependent patients, no study has systematically compared oncological outcomes between peritoneal dialysis (PD) and hemodialysis (HD) modalities following RNU. This multicenter study evaluates whether dialysis modality (peritoneal dialysis versus hemodialysis) acts as an independent prognostic factor following radical nephroureterectomy. Methods: Using the Taiwan UTUC Collaboration Group Registry—a multicenter, nationwide database comprising 21 tertiary and regional medical centers —we identified 350 ESRD patients who underwent RNU for UTUC between September 1988 and December 2023. Patients were categorized by dialysis modality at the time of surgery: 310 on HD and 40 on PD. Propensity score overlap weighting was applied to account for baseline differences. Multivariate Cox proportional hazards and Fine-Gray competing risk regression models were utilized to evaluate overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), and non-UTUC mortality. Results: After overlap weighting, PD was independently associated with significantly worse OS (HR = 2.34, 95% CI 1.29–4.25, p = 0.005) and PFS (HR = 2.06, 95% CI 1.16–3.66, p = 0.013) compared to HD and exhibited a trend toward worse CSS in univariate analysis (log-rank p = 0.094). Survival curve divergence between PD and HD was most pronounced from 12 to 24 months post-surgery onward. Notably, this survival disadvantage persisted despite PD patients being significantly younger (mean age 58.8 vs. 65.1 years) and receiving adjuvant chemotherapy more frequently (20.0% vs. 6.5%). PD was also independently associated with higher non-UTUC mortality on multivariate competing risk analysis (sHR = 2.17, 95% CI 1.22–3.88, p = 0.009). Conclusions: In this first multicenter systematic comparison of PD versus HD patients undergoing RNU for UTUC, PD modality was independently associated with worse OS and PFS and exhibited a trend toward worse CSS in univariate analysis, compared to HD. This survival disadvantage persists despite favorable baseline characteristics and higher rates of adjuvant chemotherapy. We hypothesize these outcomes may be driven by a dual vulnerability: impaired systemic tumor control and elevated non-cancer mortality following surgical disruption of the peritoneal environment. To mitigate these risks, prioritizing minimally invasive or retroperitoneal surgical approaches to preserve peritoneal integrity, combined with modality-specific multidisciplinary surveillance, is recommended. Full article

Background: Depressive symptoms are highly prevalent among patients with thymoma-associated myasthenia gravis (MG) and are associated with poorer clinical status and quality of life. However, their relationship with psychological counseling outcomes remains insufficiently investigated. Objectives: This study aimed to examine the association between baseline depressive tendency, baseline clinical status, and post-counseling clinical outcomes in patients with thymoma-associated MG. Methods: This single-group pre-post exploratory pilot study enrolled 17 patients with thymoma-associated MG who received eight sessions of Gestalt-oriented psychological counseling. A depressive tendency was defined as a baseline Patient Health Questionnaire-9 (PHQ-9) score ≥10 (n = 6, 35.3%). Clinical outcomes, including the Myasthenia Gravis Activities of Daily Living scale (MG-ADL), Myasthenia Gravis Quality of Life 15-item scale (MG-QoL15), mental BMI (mBMI), and PHQ-9 scores, were assessed before and after the intervention. Multivariable linear regression analyses were performed using baseline depressive tendency as the primary predictor of each post-counseling outcome. The models were sequentially adjusted for the corresponding baseline outcome score and subsequently for age and sex. Results: Following the counseling intervention, statistically significant pre–post changes were observed in MG-ADL (p = 0.044), mBMI (p = 0.018), and PHQ-9 (p = 0.002) scores. After adjustment for the corresponding baseline outcome score, age, and sex, baseline depressive tendency was associated with less favorable post-counseling mBMI (β = −3.52, robust 95% CI −6.19 to −0.86, p = 0.014) and MG-ADL scores (β = 1.70, robust 95% CI 0.51 to 2.89, p = 0.009). Conclusions: Baseline depressive tendency was associated with poorer baseline functional and disease-specific quality-of-life status and with less favorable adjusted post-counseling MG-ADL and mBMI scores. These associations met the Benjamini–Hochberg threshold but not the more conservative Benjamini–Yekutieli threshold. Given the small sample and uncontrolled pilot design, the findings should not be regarded as evidence of counseling effectiveness and require confirmation in prospective controlled studies. Full article

Right ventricular global longitudinal strain (RVGLS) and right ventricular free-wall longitudinal strain (RVFWLS) are both used to assess right ventricular involvement, but they include different myocardial components. We examined their cross-sectional correlates and longitudinal changes associated with enzyme replacement therapy (ERT) in 100 patients with genetically confirmed Fabry disease, including 69 with serial echocardiography. RVGLS was independently associated with left ventricular global longitudinal strain (LVGLS; standardized β = 0.466, p < 0.001) and interventricular septal thickness (standardized β = 0.257, p = 0.027), whereas RVFWLS was independently associated with right atrial reservoir strain (standardized β = −0.542, p < 0.001). RVGLS and RVFWLS were not significantly correlated (r = 0.053, p = 0.654). In the paired RV strain subgroup, longitudinal RVGLS change differed between untreated and ERT-treated patients (+2.06 ± 3.94% vs. −1.28 ± 3.64%, p = 0.017), whereas RVFWLS change did not (p = 0.838). In a sensitivity model adjusted for age, sex, genotype, and baseline RVGLS, ERT remained associated with ΔRVGLS (β = −3.28 percentage points, 95% CI −5.25 to −1.32; p = 0.001). These findings identify different correlates of septal-inclusive and free-wall RV strain and require prospective validation. Full article

Background: Advanced varus ankle osteoarthritis is challenging because correction of malalignment must be balanced against preservation of the native ankle joint. This study evaluated the clinical and radiographic outcomes of distal tibial oblique osteotomy (DTOO) with structural strut allografting, which permits individualized correction and provides mechanical support to the osteotomy gap. Methods: This retrospective case series included 20 patients and 20 operated ankles with Takakura stage IIIa (n = 13) or IIIb (n = 7) varus ankle osteoarthritis who underwent DTOO with structural strut allografting between 2012 and 2024. Clinical outcomes included Manchester–Oxford Foot Questionnaire (MOXFQ), American Orthopaedic Foot & Ankle Society (AOFAS), 12-Item Short-Form Survey (SF-12), and Visual Analog Scale (VAS) pain scores. Radiographic parameters included tibial articular surface angle (TAS), tibial lateral surface angle (TLS), medial malleolar angle (MMA), talar tilt angle (TTA), and tibiotalar surface angle (TTS). Results: Significant improvements were observed at final follow-up. MOXFQ scores decreased from 57.66 ± 22.01 to 10.63 ± 9.72 (p < 0.001), AOFAS scores increased from 63.75 ± 15.17 to 85.45 ± 8.37 (p < 0.001), and VAS pain scores decreased from 4.30 ± 1.75 to 1.00 ± 1.30 (p < 0.001). The SF-12 PCS increased from 45.23 ± 8.48 to 47.96 ± 7.93 (p = 0.258), and the MCS increased from 53.51 ± 9.85 to 55.60 ± 4.75 (p = 0.377); neither change was statistically significant. Significant correction was achieved in TAS (p < 0.001), TLS (p < 0.001), MMA (p = 0.019), and TTS (p < 0.001), with no significant change in TTA (p = 0.336). All achieved radiographic union within 3 months postoperatively. Conclusions: DTOO with strut bone allografting enables alignment correction in advanced varus ankle osteoarthritis, including Takakura stage III, while preserving the ankle joint. This technique is an effective joint-preserving option for severe deformities. Full article

Background: Pleural pigtail catheters are widely used in intensive care units (ICUs), but factors associated with unplanned removal remain incompletely characterized. Methods: We conducted a single-center retrospective cohort study of adult ICU catheter-placement episodes from December 2020 to March 2025. Effusions were grouped as complex (exudative, empyema, malignant, or malignancy-related) or simple (transudative or hemothorax). The primary outcome was unplanned removal for a catheter-related complication or escalation to surgery. Associations were evaluated using Firth penalized logistic regression. Results: Among 175 screened episodes, 140 were analyzed; unplanned removal occurred in 12 (8.6%). Complex effusions (adjusted odds ratio [aOR] 6.50, 95% confidence interval [CI] 1.59–26.55) and ultrasound-assisted insertion (aOR 10.72, 95% CI 1.92–59.94) were associated with higher odds of unplanned removal. Reclassifying hemothorax as complex attenuated but did not reverse the phenotype association (aOR 4.84, 95% CI 1.17–19.93). The ultrasound association may reflect case selection, operator workflow, or procedural complexity rather than causality. Because 33 death-related episodes were excluded, the 8.6% rate applies to episodes with classifiable non-death endpoints, not all screened episodes. Conclusions: These findings are hypothesis-generating and insufficient to change clinical practice without prospective multicenter validation. Full article

Integrated Sensing and Communication (ISAC) has emerged as a key enabling technology for future sixth-generation (6G) wireless networks by enabling sensing and communication functionalities to share spectrum, hardware resources, and signal processing infrastructure. However, practical ISAC systems are affected by self-interference, mutual interference between sensing and communication signals, and environmental clutter, which jointly degrade communication reliability and sensing performance. To address these challenges, this paper proposes a novel three-slot interference mitigation framework for downlink ISAC systems. Unlike conventional ISAC approaches that perform joint sensing and communication within a single transmission stage, the proposed framework separates directional sensing, parameter acquisition, and interference-aware joint transmission into three coordinated slots, enabling transmit-side pre-cancellation of sensing-induced mutual interference using estimated interference parameters. Furthermore, joint convex optimization-based beamforming is employed to mitigate self-interference through sidelobe minimization and suppress environmental clutter through spatial null steering while maintaining the desired sensing and communication links. Simulation results demonstrate beam steering, parameter recovery, communication performance after interference cancellation, and target range, velocity, and angle estimation using Range-Doppler and Multiple Signal Classification (MUSIC) processing. The proposed framework presents an interference-aware ISAC architecture that combines a three-slot transmission protocol for mitigating sensing-induced mutual interference with joint beamforming for suppressing self-interference and environmental clutter while supporting simultaneous sensing and communication. Full article

Background/Objectives: Chronic traumatic posterior lens dislocation may cause ocular hypertension through overlapping lens-induced and traumatic mechanisms. We report a delayed presentation with a dislocated hypermature lens, a phacolytic phenotype, an incomplete capsule, and severe pressure elevation persisting after lens removal. Case Presentation: A 47-year-old man presented 5 years after blunt trauma with pain, redness, and blurred vision. Visual acuity was hand motion at 10 cm, and intraocular pressure (IOP) was 44.1 mmHg. Slit-lamp examination showed corneal edema, milky material in a deep anterior chamber, and the cataractous lens behind the iris. Ultrasonography localized the lens but could not assess capsular integrity or angle anatomy. Mixed lens-induced glaucoma with possible phacolytic, lens-particle, and traumatic components was diagnosed. Two days after 25-gauge pars plana vitrectomy and lensectomy, IOP remained 45.3 mmHg despite intensive therapy, prompting trabeculectomy with mitomycin C. At 6 months, IOP was 20.1 mmHg on three agents (qualified success), and vision remained hand motion at 30 cm with persistent corneal edema, aphakia, and suspected optic-nerve damage. Conclusions: Persistent IOP elevation after the removal of visible lens material suggested established trabecular or traumatic outflow dysfunction. Incomplete characterization of the capsule and angle precluded the assignment of a single mechanism. Full article

Chronic kidney disease (CKD) may reduce physiologic reserve among patients with esophageal cancer, but evidence beyond postoperative cohorts is limited. Using the TriNetX Global Collaborative Network, we studied adults with esophageal cancer diagnosed during 2010–2023. CKD stages 3–5 were defined by diagnostic codes plus estimated glomerular filtration rate < 60 mL/min/1.73 m² within 6 months before or on the index date; dialysis-dependent patients were excluded. Non-CKD patients served as comparators. Prespecified outcomes from day 1 to up to 3 years included all-cause mortality, subsequent recorded metastatic diagnosis, pneumonia, sepsis, blood transfusion, and major adverse cardiovascular events. Propensity score matching produced 832 pairs. All-cause mortality was not significantly higher in the overall cohort with CKD stages 3–5 than in the non-CKD cohort (HR, 1.13; 95% CI, 0.98–1.31; p = 0.099), whereas CKD stages 4–5 were associated with higher mortality in the stage-specific analysis (HR, 1.46; 95% CI, 1.03–2.06; p = 0.031). CKD stages 3–5 were also associated with higher risks of blood transfusion (HR, 1.45; 95% CI, 1.04–2.01; p = 0.025) and MACEs (HR, 1.22; 95% CI, 1.02–1.47; p = 0.027), and with a lower risk of subsequent recorded metastatic diagnosis (HR, 0.80; 95% CI, 0.65–0.99; p = 0.036). These findings suggest that the associations of CKD with post-diagnostic outcomes varied by outcome type, with higher mortality observed in the separate CKD stages 4–5 analysis. Full article

Background: The global spread of antimicrobial resistance in Escherichia coli (E. coli) from food-producing animals is a critical concern within the One Health framework, particularly because of the potential transmission of clinically relevant resistance determinants across the animal–environment–human interface. Although extended-spectrum β-lactamase (ESBL)-producing E. coli strains have been widely characterized, the genomic mechanisms underlying resistance to the last-resort and critically important antimicrobials colistin and fluoroquinolones remain incompletely understood in animal-associated populations. This study characterized these resistance mechanisms in multidrug-resistant (MDR) E. coli from diseased food-producing animals. Methods: We used whole-genome sequencing (WGS) to characterize 77 MDR E. coli isolates from diseased livestock and poultry in Taiwan and analyzed the underlying resistance mechanisms and their co-occurrence. Results: Plasmid-mediated colistin resistance genes, including mcr-1.1, mcr-3.1, and mcr-3.5, were identified alongside chromosomal mutations, such as pmrB substitutions, indicating multiple evolutionary pathways to colistin resistance. Fluoroquinolone resistance was driven by both chromosomal mutations in quinolone resistance-determining regions and plasmid-mediated quinolone resistance genes, including qnr variants and aac(6′)-Ib-cr. Notably, the frequent co-occurrence of resistance determinants targeting multiple antimicrobial classes suggests the presence of mobile genetic elements facilitating horizontal gene transfer. Conclusions: Although a subset of isolates overlapped with those reported in our previous ESBL-focused study, the present work presents a comprehensive genomic dissection of resistance mechanisms beyond β-lactamases. The convergence of colistin, fluoroquinolone, and ESBL-associated resistance determinants within individual isolates highlights the potential role of food-producing animals as reservoirs of multidrug resistance, with potential implications for cross-sectoral transmission. These findings underscore the importance of integrated surveillance strategies addressing potential zoonotic transmission under the One Health framework. Full article

Background: Postoperative bleeding and prolonged drainage after head and neck surgery may delay drainage tube removal and hospital discharge, increasing complication risk and resource utilization. Optimizing intra and postoperative hemostasis is essential to facilitate early recovery and support enhanced recovery after surgery (ERAS) pathways. This study aimed to identify factors associated with postoperative drainage and length of hospital stay, with particular focus on energy-based device and fibrin sealant use. Methods: Adult patients who underwent neck surgery under general anesthesia with inpatient admission at a tertiary medical center between January 2024 and December 2025 were retrospectively analyzed. Surgical procedures included thyroidectomy (n = 99), parotidectomy (n = 43), submandibular gland excision (n = 25), neck dissection (n = 27) and other procedures (n = 22). Clinical variables, surgical factors, use of energy-based device, hemostatic agents, postoperative drainage volume, and length of hospital stay were collected. Logistic regression analysis was performed to evaluate predictors of early discharge (defined as discharge on postoperative day 1). Results: A total of 216 patients were included. Surgical procedure type was strongly associated with operative duration, postoperative day 1 drainage volume, and length of hospital stay. Neck dissection and total thyroidectomy were associated with increased drainage and prolonged hospitalization. The use of fibrin sealants was independently associated with lower postoperative drainage volume, shorter hospital stay, and a significantly higher likelihood of early discharge (adjusted odds ratio: 4.43, 95% CI 1.92–10.23, p < 0.001). Energy-based device use and patient-controlled analgesia were not associated with early discharge. Conclusions: Incorporating fibrin sealant into perioperative management may facilitate safer and earlier discharge, improve patient turnover, and optimize resource utilization within ERAS-based care pathways. Full article