Tag: nevin manimala

Bioinformatics. 2025 Oct 11:btaf561. doi: 10.1093/bioinformatics/btaf561. Online ahead of print.

ABSTRACT

MOTIVATION: Understanding the genetic basis of drug-induced toxicity is crucial for drug development. In-silico analysis of toxicogenomics datasets facilitates early detection of toxicity biomarkers. However, existing tools struggle with the complex interdependencies among hierarchically structured variables, leading to inaccurate biomarker identification. To address this limitation, we developed a Hierarchical Linear Model (HLM) and implemented it in the R package ToxAssay, offering extensive functionality for comprehensive toxicity assessment.

RESULTS: ToxAssay outperforms existing methods by improving biomarker detection and computational efficiency. Applied to glutathione depletion-induced toxicity, it prioritized 71 key genes and identified 26 core genes with high discriminative accuracy (AUC = 0.97) and strong cross-correlation (Pearson’s r = 0.88) with external datasets. Additionally, our advance outcome pathway (AOP) analysis algorithm uncovered disease outcomes linked to glutathione depletion. These findings provide precise insights into the molecular mechanisms driving drug-induced toxicity.

AVAILABILITY: ToxAssay is available as an open-source R package at https://github.com/Fun-Gene/toxassay.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:41075158 | DOI:10.1093/bioinformatics/btaf561

Clin Rheumatol. 2025 Oct 11. doi: 10.1007/s10067-025-07736-x. Online ahead of print.

ABSTRACT

INTRODUCTION/OBJECTIVE: Respiratory muscle function may be impaired in axial spondyloarthritis (axSpA) due to mechanical limitations of the thoracic spine and chest wall. However, the extent of respiratory muscle weakness and its clinical associations remain largely underexplored.

METHODS: This comparative cross-sectional study included 51 patients with radiographic axSpA (r-axSpA) and 52 healthy controls. Maximal inspiratory (PI_max) and expiratory (PE_max) pressures were measured using standardized protocols. Patients with r-axSpA also underwent assessments of pulmonary functions (forced vital capacity (FVC), forced expiratory volume in the first second (FEV₁)), spinal pain, disease activity, spinal mobility, functional status, physical performance, quality of life, anxiety/depression, and fatigue. Subgroup analyses were performed based on the presence of respiratory muscle weakness (< 80% of predicted PI_max and PE_max), and stepwise multiple regression was used to identify clinical predictors of PI_max.

RESULTS: Although the PI_max (mean difference: – 8.6% [95% CI: – 21.7% to 4.6%]) and PE_max (mean difference: – 4.6% [95% CI: – 16.7% to 7.5%]) were lower in the r-axSpA group, the differences were not statistically significant (p > 0.05). Seventeen patients (33.3% of the total sample) with r-axSpA exhibited inspiratory muscle weakness. This subgroup demonstrated significantly poorer FVC, spinal pain at rest, spinal mobility, and quality of life (p < 0.05). Regression analysis revealed that pain at rest (β = – 0.317, p = 0.013) and FVC (β = 0.296, p = 0.022) independently predicted 19.2% of the variance in PI_max.

CONCLUSION: Although respiratory muscle strength was mostly preserved in r-axSpA, a substantial subgroup exhibited inspiratory muscle weakness associated with adverse clinical outcomes. Identifying these patients may guide tailored interventions for optimal care.

KEY POINTS: A substantial proportion of patients with radiographic axSpA demonstrate inspiratory muscle weakness despite preserved average respiratory pressures. Patients with inspiratory muscle weakness exhibit diminished lung volumes, decreased spinal mobility, higher pain levels, and poorer quality of life compared to those without weakness. Inspiratory muscle strength is independently predicted by spinal pain at rest and forced vital capacity.

PMID:41075137 | DOI:10.1007/s10067-025-07736-x

Clin Rheumatol. 2025 Oct 11. doi: 10.1007/s10067-025-07715-2. Online ahead of print.

ABSTRACT

OBJECTIVE: Axial spondyloarthritis (AxSpA) and Behçet’s disease (BD) have clinical and HLA locus overlap and have been grouped under MHC-I-opathy. This study aimed to identify overlapping loci between AxSpA and BD to help elucidate MHC-I-opathy pathogenesis.

METHODS: Association clustering methods, such as OASIS, reduce the multiple-testing burden and are more powerful than single variant analysis for identifying modest genetic effects. Two large publicly available genome-wide association studies (GWAS) of AxSpA (921 cases, 907 controls) and BD (1215 cases and 1278 healthy controls) from Turkiÿe were subjected to OASIS meta-analyses to identify common non-HLA loci. Statistics used to identify significant loci included the novel OASIS locus index (OLI). Expression analysis was performed using GEO datasets, GSE181364 for AxSpA and GSE209567 for BD. STRING network analysis was performed.

RESULTS: GWAS for both diseases had the highest significance at the HLA-I locus. Of the 234 independent modestly significant non-HLA loci, there were 15 loci common to both AxSpA and BD. These included known MHC-I-opathy loci, 1p31.3 for IL23R (P = 5.37 × 10^-6, OLI = 52.7) and 13q14.11 for LACC1 (P = 7.41 × 10^-6, OLI = 65.3). A novel locus identified in this study is 3p21.31 containing CXCR6 (P = 2.46 × 10^-5, OLI = 25.8). The locus 3p22.3 had the highest overall OLI (81.3), and the most significant SNP at this locus (rs2291897; P = 1.82 × 10^-5) is an intronic variant in the gene FBXL2. However, this association was specific for BD only.

CONCLUSION: Several loci containing pathologically relevant genes for MHC-I-opathy were identified here, using a cluster-based approach in AxSpA and BD GWAS, with CXCR6 being a novel target. Key Points • MHC-I-opathy immunopathogenesis is incompletely understood and challenged by risk genes of modest effect. • This meta-analysis identified 15 loci common to both AxSpA and BD that may provide diagnostic and therapeutic targets for MHC-I-opathy. • Major candidate genes for MHC-I-opathy identified here are IL23R, LACC1, and CXCR6. • FBXL2 was associated strongly with BD by OASIS analysis.

PMID:41075136 | DOI:10.1007/s10067-025-07715-2

Med Biol Eng Comput. 2025 Oct 11. doi: 10.1007/s11517-025-03460-5. Online ahead of print.

ABSTRACT

Minimally invasive neurosurgery presents specific challenges due to the limited operative space and complex cranial anatomy, requiring highly precise and safe surgical guidance. Augmented Reality (AR) technology offers the potential to improve surgical accuracy and safety by overlaying critical digital information onto real-world surgical environments. In this study, we present a study that aims to compare four AR visualization methods-2D flat display, smart tablet, head-mounted display (HMD), and 3D autostereoscopic display-in guiding minimally invasive neurosurgical procedures, specifically focusing on ventriculocentesis. The effectiveness of the AR methods was evaluated through comprehensive user studies involving 32 participants (including 11 experienced surgeons), with assessment focused on critical performance metrics including accuracy, completion time, usability, and cognitive workload during simulated surgical procedures. Results demonstrated that 3D visualization methods significantly outperformed traditional 2D approaches in terms of puncture accuracy and angular precision. Specifically, surgeons showed a statistically significant improvement in localization accuracy, with mean error reduced from 2.69 mm to 1.67 mm, and angular deviation from 5.62° to 1.54°. In comparing the two 3D visualization systems, the HMD exhibited superior task completion efficiency, while the 3D autostereoscopic display demonstrated higher usability scores and lower perceived workload ratings. Notably, the 3D systems effectively reduced the performance disparity between novice and experienced practitioners, suggesting their potential to accelerate the learning curve for less experienced users. We conclude that AR holds significant potential to enhance performance and decision-making in minimally invasive neurosurgical guidance.

PMID:41075112 | DOI:10.1007/s11517-025-03460-5

Cancer Causes Control. 2025 Oct 11. doi: 10.1007/s10552-025-02046-8. Online ahead of print.

ABSTRACT

PURPOSE: This study evaluated the feasibility, acceptability, usability, and HPV vaccine completion rate of the Now I Know (NIK) mHealth intervention to promote HPV vaccine completion among minority and low-income young women.

METHODS: This quasi-experimental pilot study recruited 35 women aged 18-26 at two federally supported outpatient clinics in a large city in the Northeastern United States. Participants were allocated to two groups: 24 received the NIK intervention plus usual care and 11 received usual care only. After completing a baseline assessment, intervention group participants launched the NIK mobile app, which entailed HPV vaccine education, self-managed vaccine record & reminder, and Q&A features. Follow-up visits were conducted at 2 and 6 months. Feasibility was assessed through screening, recruitment, fidelity, and retention. Acceptability and usability were evaluated via survey and exit interview. The primary outcome-HPV vaccine 3-dose series completion-was analyzed using descriptive statistics.

RESULTS: This study demonstrated feasibility by reaching the recruitment target (n = 35) and high retention rate (89%). Participants reported the app was acceptable, appreciating reliable information, convenient access, providing a personal touch, and raising awareness. Regarding usability, users found the app easy to navigate, accessible, well organized, and user-friendly. The HPV vaccine completion rate was higher in the intervention group (55%) than in the usual care group (45.5%).

CONCLUSION: Findings showed improved vaccination completion among those using the Now I Know mHealth intervention (compared to usual care), acceptability of the intervention, and feasibility of recruiting, retaining, and delivering the intervention to promote HPV vaccine completion among young women in federally subsidized healthcare settings.

PMID:41075078 | DOI:10.1007/s10552-025-02046-8

J Mater Sci Mater Med. 2025 Oct 11;36(1):78. doi: 10.1007/s10856-025-06938-8.

ABSTRACT

OBJECTIVES: This study evaluated the mechanical and surface characteristics of the transition zone of multilayered translucent zirconia (TZ) after aging and analyzed the correlation between the 4-point bending flexural strength (4PBFS) and biaxial flexural strength (BFS) in each zone.

METHODS: Traditional (3Y-TZP of LT; L, 4Y-TZP of MT; M) and multilayered TZ (5Y-TZP of MT Multi; T, 3Y/5Y-TZP of Prime; P, 4Y/5Y-TZP of Prime esthetic; E) IPS E.max ZirCAD blocks were used to fabricate 525 disk-shaped and 300 bar-shaped specimens. Specimens were separated into three groups, aged in an autoclave at 134 °C under 0.2 MPa for 0 h, 5 h, and 10 h. The mechanical and surface characteristics of the transition zone in multilayered TZ were analyzed, following statistical analyses (α = 0.05).

RESULTS: L showed the highest 4PBFS and BFS, irrespective of aging. Consistent correlations between the 4PBFS and BFS were found in all groups. L showed the highest Weibull characteristic strength under all conditions. T showed the highest nanoindentation hardness and Young’s modulus, and the Vickers hardness of L and P were lower than other groups. Aging led to surface uplifts and microcracks caused by phase transformation, particularly in L and P.

CONCLUSIONS: The flexural strength of 3Y/5Y-TZP and 4Y/5Y-TZP was comparable to that of 3Y-TZP and 4Y, 5Y-TZP respectively, regardless of aging. Surface roughness showed a marked increase after aging in 3Y-TZP and 3Y/5Y-TZP. Furthermore, the interaction between yttria content and aging was evident across all mechanical and surface characteristics, except for flexural strength.

PMID:41075051 | DOI:10.1007/s10856-025-06938-8

Aging Clin Exp Res. 2025 Oct 11;37(1):291. doi: 10.1007/s40520-025-03183-5.

ABSTRACT

Global population aging is increasing the demand for Long-Term Care Facilities to support older adults with complex health needs. The Prescription Day LTCFs project is a national multicenter point-prevalence study, conducted by the Italian Society of Gerontology and Geriatrics in collaboration with the ANASTE Humanitas Foundation, investigated medication prescription patterns and administration practices in 3,400 residents across 82 facilities in Italy. Participants had a mean age of 84.7 years, with a high prevalence of frailty (49.7%) and polypharmacy (84.8% taking five or more medications). Common chronic conditions included hypertension, dementia, and dysphagia. The study highlighted the complexity of pharmacological regimens, emphasizing risks related to potentially inappropriate medications, drug-drug interactions, and frequent modifications of solid oral dosage forms to facilitate administration in residents with swallowing difficulties or cognitive impairment. These complexities contribute to increased nursing workload. Despite advances in deprescribing research, polypharmacy remains highly prevalent, underlining the need for tailored prescribing guidelines. Variability among Long Term Care Facilities reflects differences in organization and regional healthcare frameworks. The findings provide a valuable foundation for developing strategies to optimize medication management, enhance safety, and improve quality of care in Italian Long Term Care Facilities. This study also offers insights to inform healthcare policies and best practices in pharmacological care for older adults in Long Term Care settings. PRE BIO CE n. 0027032 (20/06/2024), National Ethics Committee, Istituto Superiore di Sanità, Rome, Italy.

PMID:41075050 | DOI:10.1007/s40520-025-03183-5

J Robot Surg. 2025 Oct 11;19(1):678. doi: 10.1007/s11701-025-02869-2.

ABSTRACT

The comparative effectiveness of da Vinci robot-assisted versus conventional laparoscopic Nissen fundoplication for gastroesophageal reflux disease remains controversial despite increasing adoption of robotic platforms. Previous meta-analyses have yielded conflicting results regarding patient-centered outcomes and long-term durability. We conducted a systematic review and meta-analysis of randomized controlled trials comparing da Vinci-assisted versus conventional laparoscopic Nissen fundoplication. This review was prospectively registered with PROSPERO (CRD420251139110). We searched MEDLINE, Embase, Cochrane CENTRAL, Web of Science, Scopus, ClinicalTrials.gov, WHO ICTRP, and grey literature sources through August 2025. Primary outcomes included postoperative dysphagia, proton pump inhibitor use, and intraoperative complications. Secondary outcomes encompassed reoperation rates, operative time, length of stay, and conversion to open surgery. Risk ratios and mean differences were calculated using random-effects models. Evidence certainty was assessed using the GRADE methodology. Four randomized controlled trials involving 160 patients (79 robotic, 81 conventional laparoscopic) met the inclusion criteria. No significant differences were observed in early dysphagia (RR 1.05, 95% CI 0.45-2.45), postoperative proton pump inhibitor use (RR 0.97, 95% CI 0.25-3.79), or intraoperative complications (RR 0.43, 95% CI 0.07-2.81). Secondary outcomes showed no differences in reoperation rates (RR 1.65, 95% CI 0.40-6.90), length of hospital stay (MD -0.03 days, 95% CI -0.41 to 0.36), or conversion rates (RR 1.23, 95% CI 0.19-7.99). Operative time demonstrated substantial heterogeneity; sensitivity analysis revealed significantly longer times with robotics when one outlier study was removed (MD 40.28 min, p < 0.00001). Da Vinci robot-assisted and conventional laparoscopic Nissen fundoplication achieve equivalent clinical outcomes with no significant differences in patient-reported outcomes, complications, or long-term effectiveness, while robotic procedures consistently require longer operative times and substantially higher costs without demonstrable clinical benefits. These findings question the routine application of robotic platforms in antireflux surgery until cost-effectiveness and operative efficiency are optimized.

PMID:41075046 | DOI:10.1007/s11701-025-02869-2

J Robot Surg. 2025 Oct 11;19(1):679. doi: 10.1007/s11701-025-02834-z.

ABSTRACT

The da Vinci robotic platform, as the earliest operative platform implemented in routine clinical use, has been employed for various complex surgical conditions owing to its precision in manipulation. However, its prohibitive costs have restricted widespread adoption in certain regions. Consequently, China’s domestically developed KangDuo robotic surgical platform was developed to address this need. Currently, comparative studies on perioperative outcomes between these two platforms for performing robot-assisted radical prostatectomy (RARP) remain scarce. This meta-analysis aims to systematically compare perioperative outcomes among these robotic platforms. A structured search of the literature was undertaken across several principal online databases-such as PubMed, Web of Science, the Cochrane Library, and SpringerLink-to locate prospective investigations comparing K-RARP with D-RARP published before August 1, 2025. The comparative outcomes across the two robotic systems consisted of total operating time, estimated intraoperative blood loss, length of hospitalization, urinary continence recovery, post-operative complications, and positive surgical margin rates. This quantitative synthesis included four comparative studies encompassing an aggregate of 188 participants. The results revealed no significant differences in PSM rates (OR 1.06, 95% CI 0.55-2.04; p = 0.86), estimated intraoperative blood loss (WMD – 1.04 ml, 95% CI – 21.72 to 19.63; p = 0.92), length of hospitalization (WMD – 0.32 days, 95% CI – 1.33 to 0.70; p = 0.54), urinary continence (OR 0.96, 95% CI 0.50-1.83; p = 0.90), when contrasting K-RARP with D-RARP. Moreover, no meaningful differences were detected in the incidence of Clavien-Dindo grade I complications (OR 1.14, 95% CI 0.33-3.89; p = 0.84), grade II complications (OR 1.11, 95% CI 0.39-3.18; p = 0.84), or overall complication incidence (OR 1.28, 95% CI 0.59-2.76; p = 0.53). However, for K-RARP, operative duration was significantly longer (WMD 41.34 min, 95% CI 22.42-60.26; p < 0.05). As the inaugural comparative assessment of perioperative outcomes between KangDuo and da Vinci robotic systems, this study demonstrated that while K-RARP required significantly longer operative times, it achieved comparable outcomes to D-RARP in EBL, positive surgical margin rate, hospital stay, continence, and complication rates. This evidence positions the KangDuo platform as a viable future option for localized prostate cancer management. However, this conclusion remains preliminary and exploratory, and will need to be confirmed through large-scale, multicenter, multi-regional randomized controlled trials combined with long-term follow-up.

PMID:41075042 | DOI:10.1007/s11701-025-02834-z

Aging Clin Exp Res. 2025 Oct 11;37(1):293. doi: 10.1007/s40520-025-03195-1.

ABSTRACT

BACKGROUND: Hand grip measures are promising candidate markers for recovery in geriatric patients.

AIMS: To advance interpretation of these measures, we examined: (1) the associations between grip measures at admission and measures of frailty, daily functioning and fatigue to understand the constructs they measure; (2) alternate operational definitions of grip measures.

METHODS: 181 geriatric inpatients completed twice daily grip measurements using the Eforto^® vigorimeter, including maximum grip strength (GSmax), fatigue resistance (FR), grip work (GW) and capacity to perceived vitality ratio (CPV). Associations with each of these measures and the outcomes frailty index (range 0-100), functional limitations (10-40), and total (4-20) and physical (20-100) fatigue were examined using linear regression. Analyses were repeated for the baseline value, average of first two measurements, within-person standard deviation of all values, and the coefficient of variation of all values for each of the grip measures.

RESULTS: Associations approached statistical significance for baseline GSmax and the outcomes frailty (B=-0.09, 99%CI=–0.21, 0.02), functional limitations (B=-0.10, 99%CI=-0.20, 0) and physical fatigue (B=-0.07, 99%CI=-0.14, 0). Baseline, average and standard deviation values for FR, GW and CPV showed trends towards associations with functional limitations, but not with frailty or fatigue.

CONCLUSIONS: GSmax and CPV constructs overlapped more strongly with the construct of frailty than FR and GW. FR, GW and CPV overlapped with functional limitations, supporting their potential as early markers of recovery. Average values are more reliable than single values and variance measures may add additional information.

PMID:41075041 | DOI:10.1007/s40520-025-03195-1