Tag: nevin manimala

Biogerontology. 2025 Nov 15;27(1):2. doi: 10.1007/s10522-025-10354-4.

ABSTRACT

While immune system involvement in aging is increasingly recognized, causal relationships between specific immune cell populations and biological aging indicators remain unclear. We aimed to identify immune targets influencing aging trajectories to inform future immunomodulatory interventions. We conducted two-sample Mendelian randomization (MR) analysis using immunophenotype GWAS data (3,757 Sardinian participants) and aging phenotype statistics (PhenoAgeAccel: n = 107,460; BioAgeAccel: n = 98,446). Analysis employed IVW methodology with sensitivity analyses including weighted median estimation, MR-Egger regression, MR-PRESSO, and Cochran’s Q statistic. Significance was determined using False Discovery Rate (FDR) correction (P_FDR < 0.05). After FDR correction, seventeen immune cell phenotypes showed significant associations with PhenoAgeAccel: two cDCs, one monocyte subtype, ten myeloid cells, three TBNK cells, and one Treg population. Key findings included protective effects of FSC-A on granulocyte (β = -0.24, 95% CI:-0.37 to -0.10, P_FDR = 1.81 × 10^-2) and risk associations of CD14⁺ CD16^– monocyte (β = 0.41, 95% CI:0.24-0.58, P_FDR = 6.84 × 10^-4). Among TBNK cells, CD8⁺ T cell (β = 0.32, 95% CI: 0.16-0.47, P_FDR = 6.44 × 10^-3) and CD28^– CD8⁺ T cell (β = 0.40, 95% CI: 0.23-0.58, P_FDR = 8.14 × 10^-4) emerged as risk factors. For BioAgeAccel, four phenotypes showed suggestive relationships, with Unswitched Memory B Cell showing the strongest protective effect (β = – 0.32, 95% CI:-0.52 to-0.12, p = 1.75 × 10^-3). Our study revealed causal relationships between specific immune cell phenotypes and biological aging acceleration, identifying potential therapeutic targets for age-modulation and suggesting immune signatures as crucial regulators in aging-related processes.

PMID:41240153 | DOI:10.1007/s10522-025-10354-4

Environ Monit Assess. 2025 Nov 15;197(12):1340. doi: 10.1007/s10661-025-14779-9.

ABSTRACT

Groundwater potential mapping is essential for sustainable water resource management, particularly in tropical lateritic terrains where communities depend heavily on groundwater for domestic and agricultural needs. This study delineates groundwater potential zones (GWPZs) in the Ithikkara River Basin, South Kerala, India, through an integrated geospatial and machine learning framework that combines self-organizing maps (SOM), K-means clustering, and random forest (RF) feature importance analysis. Eight hydro-environmental parameters-land use/land cover (LULC), geomorphology, geology, slope, relative relief, lineament density, drainage density, and mean depth to water table (MDTW)-were normalized and processed in a GIS environment. SOM was trained and optimally clustered into five groundwater potential classes, as supported by a Davies-Bouldin Index (DBI). The clusters were reclassified into very low, low, moderate, high, and very high groundwater potential. RF analysis identified LULC, geomorphology, and geology as the dominant controls on groundwater occurrence. Validation using observed well yield and water table depth confirmed strong agreement, with high-potential zones coinciding with high-yield wells and shallow aquifers in the southwestern and central alluvial-fractured zones. The results provide practical insights for groundwater exploration, artificial recharge planning, and sustainable extraction in hydrogeologically complex terrains of the Western Ghats. Beyond regional applications, the proposed methodology is scalable and interpretable, offering a transferable framework for groundwater potential mapping in other tropical river basins. Future research should incorporate long-term hydroclimatic variability, socio-economic drivers, and climate change projections to further strengthen sustainable groundwater management strategies.

PMID:41240127 | DOI:10.1007/s10661-025-14779-9

Lasers Med Sci. 2025 Nov 15;40(1):481. doi: 10.1007/s10103-025-04730-2.

ABSTRACT

Low-energy semiconductor percutaneous laser disc decompression (LS-PLDD) is a minimally invasive technique that employs laser energy to treat lumbar disc herniation (LDH). To date, no clinical studies have evaluated its efficacy in adolescent patients. This study aimed to assess the safety and effectiveness of LS-PLDD compared with percutaneous endoscopic lumbar discectomy (PELD) in the management of adolescent LDH. Collected data on 30 adolescent LDH patients who underwent LS-PLDD, and 60 adolescent LDH patients who underwent PELD, matched for age and sex. Lumbar ODI scores and back pain VAS scores were recorded preoperatively and at 1 week, 1 month, 3 months, and 6 months postoperatively to evaluate clinical outcomes in the two groups. In addition, lumbar MRI scans obtained preoperatively and at 3 months postoperatively were compared to assess disc changes. The preoperative back VAS scores were (7.0 ± 0.91) and (7 ± 0.8) in the LS-PLDD group and PELD group respectively, with no significant statistical difference (P = 0.779). The VAS scores of both groups had improvement after surgery. At the last follow-up, the VAS scores of both groups were (2.0 ± 1.3) and (1.0 ± 0.8) respectively ( P < 0.01). The VAS scores of patients in PELD group improved most significantly in the first week after surgery and then gradually stabilized, while that in LS-PLDD group improved more gradually during 6 months after surgery. The preoperative ODI scores of the LS-PLDD group and PELD group were (71.1 ± 7.9)% and (68.0 ± 7.3)% (P = 0.061), at the last follow-up, the ODI scores were (28.0 ± 13.1)% and (19.0 ± 8.4)% (P < 0.01). The preoperative canal cross-sectional areas in the LS-PLDD group and PELD group were (1373.0 ± 376.6) and (1457 ± 415.9) respectively, with no significant difference between the two groups (P = 0.157), at the last follow-up, the canal cross-sectional area of the surgical segments were (1373 ± 476.6) and (1457 ± 579.1) (P = 0.227)respectively. This study shows that low energy semiconductor laser LS-PLDD is a safe and effective treatment method for adolescent LDH. It can achieve sustained retraction of the herniated disc and retain the intact structure of the disc.

PMID:41240123 | DOI:10.1007/s10103-025-04730-2

Clin Oral Investig. 2025 Nov 15;29(12):570. doi: 10.1007/s00784-025-06638-1.

ABSTRACT

OBJECTIVES: Obesity is a risk factor for periodontal disease and is associated with socioeconomic status (SES). However, it remains unclear whether SES modifies the relationship between obesity and periodontal disease. This study investigated the influence of SES on the association between obesity and periodontal disease.

MATERIALS AND METHODS: We used multilevel Poisson regression, after adjusting for potential confounding factors including population-level SES, to analyze the body mass index (BMI) and periodontal parameters of 962 participants (mean age 58.3 years; SD: 13.8).

RESULTS: A significant association was observed between obesity and the proportion of teeth with probing pocket depth (PPD) ≥ 4 mm (ratio of means [RM]: 1.25, 95% confidence interval [CI]: 1.14, 1.37; p < 0.001), whereas the high-income group exhibited a significantly lower proportion of teeth with PPD ≥ 4 mm (RM: 0.84, 95% CI: 0.71, 0.998; p = 0.047). Interaction analysis also revealed a significant interaction between obesity and the high-income group regarding the proportion of teeth with PPD ≥ 4 mm (p = 0.020). The subgroup analysis demonstrated that the RM of obesity for the proportion of teeth with PPD ≥ 4 mm was higher in females than in males.

CONCLUSIONS: Income-related inequalities are associated with the relationship between obesity and periodontal disease. Among obese adults, those with low- and middle-income levels may have a higher risk of periodontal disease than those with high income.

CLINICAL RELEVANCE: Comprehensive care and oral health education may be enhanced for obese individuals in low-income populations to mitigate their elevated risk of periodontal disease.

PMID:41240121 | DOI:10.1007/s00784-025-06638-1

Eur J Pediatr. 2025 Nov 15;184(12):763. doi: 10.1007/s00431-025-06568-w.

ABSTRACT

Prognostic scores such as the Pediatric Index of Mortality (PIM-3) are widely used to estimate mortality risk in PICUs, yet their performance in low- and middle-income countries (LMICs) remains uncertain. We aimed to evaluate the predictive performance of PIM-3 in a Moroccan PICU; associations with ICU length of stay (LOS) and duration of mechanical ventilation (MV) were secondary exploratory outcomes. We conducted a prospective cohort study in the Mother-Child PICU at Hassan II University Hospital (Fez, Morocco) from June 1 to September 30, 2024, including all children aged 1 month to 16 years. PIM-3 variables were collected at admission. The primary focus was model performance: discrimination (AUROC, AUPRC), calibration (Hosmer-Lemeshow), and standardized mortality ratio (SMR). Univariable and multivariable regressions were used for the secondary exploratory analyses (mortality correlates, LOS, and MV duration). Among 122 patients, observed mortality was 28.7%, exceeding PIM-3 predictions (SMR = 7.7; p < 0.001). PIM-3 showed good discrimination (AUROC = 0.86; AUPRC = 0.65) but poor calibration. In secondary exploratory analyses, higher PIM-3 scores, lower GCS, multiple organ failures, and need for MV were associated with mortality. MV increased ICU stay duration and organ failures prolonged ventilation duration.

CONCLUSION: In this Moroccan PICU, PIM-3 showed good discrimination but poor calibration and thus underestimated mortality. These findings support considering local recalibration in future work, and exploration of machine-learning-based adaptation for LMIC settings. Clinical trial number: Not applicable.

WHAT IS KNOWN: • PIM-3 is widely used to estimate PICU mortality risk. It was developed and calibrated largely in high-resource settings. • External validations often show good discrimination but variable calibration, with under- or over-estimation in LMICs due to differences in case-mix, care processes, and resources.

WHAT IS NEW: • In a prospective Moroccan PICU cohort (n=122), PIM-3 showed good discrimination (AUROC 0.86; AUPRC 0.65) but markedly underestimated mortality (SMR 7.7). • Higher PIM-3 risk, lower Glasgow Coma Scale, multiple organ failures, and mechanical ventilation were associated with death, underscoring the need for local recalibration and exploration of machine learning-based adaptations for LMICs.

PMID:41240119 | DOI:10.1007/s00431-025-06568-w

World J Urol. 2025 Nov 15;43(1):699. doi: 10.1007/s00345-025-06078-2.

ABSTRACT

PURPOSE: To provide the first randomized study assessing the impact of an Enhanced Recovery after Surgery (ERAS) program on the outcomes of robot-assisted radical prostatectomy (RARP).

METHODS: 129 consecutive patients affected by prostate cancer were randomly assigned to standard-of-care (SoC, 61 patients) or ERAS perioperative protocol (68 patients) during hospitalization for RARP. The differences between the SoC and the ERAS groups were based on preoperative fasting, premedication, anesthesia, analgesia, hydration, and nutrition. The primary endpoint of the study was to compare the length of postoperative hospitalization after RARP surgery between the two groups. Secondary endpoints were the time to autonomous mobilization, the rate of postoperative comorbidities, and patients’ quality of life (QoL) as assessed by a validated questionnaire. The trial was registered on 21/12/2021 on ClinicalTrials.gov (NCT05172986).

RESULTS: Time to autonomous mobilization after surgery was significantly shorter in the ERAS group than in the SoC group (11.9 ± 5.7 h for ERAS and 17.2 ± 5.0 h for SoC, p < 0.001). However, there was no statistically significant difference in the length of postoperative hospitalization (43.1 ± 10.4 vs. 43.7 ± 18.1 h for the SoC and ERAS group, respectively, p = 0.81), time to oral nutrition, complication rate within 30 days from surgery, and QoL domains.

CONCLUSION: Prehabilitation, surgical expertise, and optimized SoC may limit further benefits from ERAS in contemporary RARP. When these three conditions were satisfied, ERAS did not further reduce the length of postoperative hospitalization, time to oral nutrition, postoperative complications, and the impact of surgery on the main domains of the patient’s QoL.

PMID:41240114 | DOI:10.1007/s00345-025-06078-2

Genet Med. 2025 Nov 11:101635. doi: 10.1016/j.gim.2025.101635. Online ahead of print.

ABSTRACT

PURPOSE: This report analyzes Medical Genetics and Genomics (MGG) training trends from 2015 to 2024. Understanding such trends is vital for developing targeted recruitment and workforce development initiatives.

METHODS: Matriculation data from the American Board of Medical Genetics and Genomics (ABMGG) and publicly available data from the National Resident Matching Program (NRMP) Main Residency and Specialty Matches were reviewed. Descriptive statistics and linear regression analysis were used to compare growth among MGG training pathways and to analyze trends.

RESULTS: From 2015 to 2024, there has been a small, but not statistically significant, increase in the total number of individuals who have matched into categorical MGG, combined Pediatrics (Peds)-MGG, and combined Internal Medicine (IM)-MGG residency programs as a whole. This has been driven by an increase in the number of matches to combined Peds-MGG programs. Matriculation into training programs has exceeded the number of matches in categorical MGG as some positions have been filled outside of the NRMP Match. The average match rate for all applicants in categorical MGG (87%) has been higher than that for Peds-MGG (52%).

CONCLUSION: Growth in applicants to combined programs and matriculation into residency programs after the NRMP Match has been promising; however, these increases are not enough to fulfill growing workforce demands.

PMID:41239884 | DOI:10.1016/j.gim.2025.101635

Health Technol Assess. 2025 Nov;29(60):1-29. doi: 10.3310/ANDK1124.

ABSTRACT

BACKGROUND: Patients with symptoms of pain and restricted function related to knee osteoarthritis are typically offered a knee replacement. However, a proportion remain dissatisfied with their outcomes, and the failure risk is disproportionately higher in the young. Knee joint distraction may be an intervention to postpone the time to knee replacement in this patient population.

OBJECTIVE AND MAIN OUTCOME MEASURE: The primary objective of the Knee Arthroplasty versus Joint Distraction Study for Osteoarthritis (KARDS) was to evaluate the effectiveness of knee joint distraction compared to knee replacement based on patient-reported pain 12 months post surgery using the Knee Injury and Osteoarthritis Outcomes Score pain score as the primary outcome.

DESIGN AND METHODS: KARDS was an open-label, two-arm individually randomised controlled non-inferiority trial with an embedded 12-month internal pilot phase and process evaluation to evaluate recruitment feasibility. A hybrid expertise design was used to account for surgeon expertise and potential lack of individual equipoise. The trial was closed to recruitment early following cessation of elective orthopaedic surgery secondary to COVID-19 pandemic. Descriptive statistics are reported.

SETTING: United Kingdom National Health Service Trusts.

PARTICIPANTS: Adult patients aged < 65 years with symptoms severe enough to warrant knee replacement, in the opinion of the treating clinician.

INTERVENTIONS: Participants were randomised to receive either knee joint distraction (static distraction of 5 mm, using external fixator for 6 weeks) or knee replacement.

RESULTS: Twenty-four participants were randomised from a single centre between March 2021 and October 2022 with minimum 3-month safety follow-up post surgery. Eleven participants were randomised to knee joint distraction and 13 to knee replacement. Seventeen patients were male (71%), median age 60 (47-65) years. One patient withdrew due to being medically unfit for surgery and two received a different treatment than which they were randomised (one crossover from each arm). The median Knee Injury and Osteoarthritis Outcomes Score pain score in the knee joint distraction group improved from 38.9 (22-50) at baseline to 55.6 (0-100) at 12 months, corresponding scores in the knee replacement improved from 30.6 (6-36) to 75.0 (50-100). Adverse events were more common with knee joint distraction, pin site infection being the commonest complications (n = 4, 58%). As part of process evaluation, we conducted semistructured qualitative interviews with staff in secondary care and with study participants. Data were analysed using thematic content analysis. One overarching theme emerged: ‘An unexpected journey’, which encapsulates staff and participants’ experiences.

CONCLUSION: Reduced research capacity and the suspension of elective surgery following the COVID-19 pandemic caused significant recruitment barriers. Despite early termination, KARDS demonstrated that patients were willing to be recruited to a trial investigating a novel treatment for knee osteoarthritis and the trial was feasible and implementable. The limited results indicated that the technique is safe with no safety concerns. Clinical and cost-effectiveness of knee joint distraction remains uncertain. The embedded KARDS process evaluation has provided helpful insights.

LIMITATIONS: Reduced research capacity at sites and suspension of elective surgery services within the United Kingdom following COVID-19 caused significant recruitment barriers to KARDS. All the recruited patients in both arms of the study were White.

FUTURE WORK: As a commissioned piece of research with delivery significantly impacted by the National Health Service environment post-COVID and the impact on National Health Service surgical services, the research question remains highly relevant. Any future research in this field can be helped by the pilot data published here along with the lessons learnt.

FUNDING: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 17/122/06.

PMID:41239860 | DOI:10.3310/ANDK1124

Orthod Craniofac Res. 2025 Nov 15. doi: 10.1111/ocr.70061. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to evaluate the association between upper airway obstruction sites and the morphology of lip and perioral soft tissues in paediatric patients.

MATERIALS AND METHODS: Upper airway obstruction sites were classified into four categories using Fujioka and Baroni’s methodology: nasopharyngeal obstruction (NO), oropharyngeal obstruction (OO), combined nasopharyngeal-oropharyngeal obstruction (NO + OO) and a control group (CG). Primary outcomes focused on quantifying upper and lower lip thickness, while secondary outcomes evaluated perioral soft tissue morphology and maxillary skeletal parameters. Statistical comparisons were performed using one-way ANOVA, Kruskal-Wallis H test and chi-square tests. A multinomial logistic regression (reference = CG) examined adjusted associations, including ANB and SN-MP as covariates.

RESULTS: A total of 256 paediatric patients with pre-treatment lateral cephalograms were included, 64 in each group. Comparative analysis revealed the NO group demonstrated significantly greater upper lip thickness (p < 0.001) and eversion (p = 0.012) compared to the CG. Additionally, the NO group displayed a greater distance between the incisal edge of the lower anterior teeth and the uppermost point of the lower lip than the OO and CG groups. Regression analyses confirmed upper lip thickness was positively associated with all obstruction types, whereas upper lip length was inversely related to NO and NO + OO.

CONCLUSIONS: Nasopharyngeal obstruction was associated with upper lip thickening and eversion, while oropharyngeal obstruction corresponded to lower lip protrusion. These findings suggest that distinct obstruction sites are linked to specific perioral and maxillary morphological patterns, emphasising the importance of airway evaluation in orthodontic diagnosis and treatment planning.

PMID:41239851 | DOI:10.1111/ocr.70061

Int J Gynaecol Obstet. 2025 Nov 15. doi: 10.1002/ijgo.70650. Online ahead of print.

ABSTRACT

OBJECTIVE: This study develops and validates a sex-informed transcriptomic prognostic score derived from sex-stratified survival analyses, with a focus on gynecologic malignancies.

METHODS: This retrospective, computational multi-cohort study analyzed transcriptomic and clinical data from The Cancer Genome Atlas (TCGA; n ≈ 5000) and CPTAC-3 (n = 2191). A 10-gene score was constructed using sex-stratified Cox models and LASSO regression across 20 TCGA tumor types. Prognostic performance was evaluated using hazard ratios and time-dependent AUCs at 1, 3, and 5 years. Analyses followed a four-phase design: discovery in TCGA, internal cross-cancer validation, external validation in independent cohorts (MSK-IMPACT, CPTAC-3, and LIHC-FR), and biological validation using single-cell and spatial transcriptomic data from formalin-fixed paraffin-embedded tissues. Patients were stratified into high- and low-risk groups based on the median gene-expression score, with optimal cutpoints determined using maximally selected rank statistics where indicated. While the discovery analyses were sex-stratified, the final 10-gene score is sex-agnostic and applicable to both sexes.

RESULTS: The score showed strong prognostic discrimination (hazard ratio = 2.15; 95% confidence interval 1.60-2.88; P < 0.001), with areas under the curve ranging from 0.69 to 0.72 across timepoints. It remained robust across datasets and analytic platforms. In gynecologic tumors, high-score regions colocalized with fibroblast-rich, immune-depleted areas, reflecting transcriptional programs of stromal remodeling and immune exclusion linked to immunotherapy resistance.

CONCLUSION: This sex-informed, spatially validated score provides a reproducible and biologically interpretable framework for transcriptomic risk stratification in gynecologic cancers. By capturing immune-evasive and aggressive tumor states, it might inform biomarker-guided clinical trials and support context-appropriate implementation of precision oncology strategies.

PMID:41239842 | DOI:10.1002/ijgo.70650