Groundwater is the primary source of domestic and agricultural use in Chinnalapatti Firka, Dindigul district, Tamil Nadu, India. This study assesses the suitability of groundwater for drinking and irrigation. A total of 120 samples were collected and analysed for physicochemical parameters during the pre-monsoon (PRM) and post-monsoon (POM) seasons, and the contaminants were mapped using GIS-based interpolation. The potential of hydrogen, electrical conductivity, total dissolved solids, total hardness, calcium, magnesium, sodium, potassium, chloride, sulphate, bicarbonate, and fluoride exceed the most desirable limit in both seasons. The Piper diagram indicates that the PRM water type is Mixed HCO₃--Cl--SO₄2-, whereas in POM, the water type is Na+-K+-SO42--Cl-. Gibbs indicates that rock-water interaction is the primary mechanism controlling the groundwater chemistry in both seasons. The Pearson correlation highlights seasonal shifts in groundwater chemistry, revealing natural processes in PRM and potential anthropogenic influences during the POM season. The groundwater quality index indicates 53% poor and 47% good water in the PRM season, whereas in POM, 70% good and 30% poor water, indicating improved water quality during POM. Wilcox and other irrigation indices indicate improved groundwater suitability for irrigation during the POM season, with reduced sodium and chloride hazards. In contrast, a slight sulphate-related risk arises from increased filtration and oxidation. Overall, weathering, rock-water interactions, and anthropogenic activities are significant factors that affect groundwater chemistry in the study area.
This study focuses on the vessel normalization window of anlotinib to preliminarily explore the optimal intervention timing for combining anlotinib with whole brain radiotherapy (WBRT) in treating brain metastases from non-small cell lung cancer (NSCLC). We aimed to explore the feasibility of combining anlotinib with WBRT based on the hypothesized vascular normalization window, and to investigate potential associations with intracranial tumor control, iPFS, and quality of life in patients with NSCLC brain metastases. This study was designed as a prospective, non-randomized, single-center cohort study. From Feb 8, 2024, to Sep 30, 2025, a total of 38 patients with NSCLC brain metastases diagnosed by the Department of Oncology, the Fifth Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, were prospectively recruited. Anlotinib was used as the intervention measure in this study. According to whether the patients received anlotinib or not, they were divided into the experimental group (anlotinib combined with WBRT) and the control group (sole WBRT), with 19 patients in each group. In the experimental group, the vascular normalization time window of anlotinib, which is 5 to 7 days, was precisely utilized. The specific medication regimen was to start taking 8 mg of anlotinib 5 days before the initiation of WBRT and continue the medication until the end of WBRT. In contrast, the control group received only WBRT. The primary and secondary endpoint indicators of the patients in both groups were followed up regularly. The primary endpoint indicators included the intracranial objective response rate (iORR) and iPFS, while the secondary endpoint indicators included the intracranial disease control rate (iDCR), quality of life, and adverse reactions. The Kaplan-Meier method was used to draw the survival curve.Meanwhile, the clinical characteristics of the patients in both groups, such as gender, age, primary tumor site, T stage, N stage, and the number of brain metastases, were collected. Univariate analysis was used to screen out the prognostic factors that might affect iPFS. Then, the factors with statistical differences (P < 0.10) in the univariate analysis were taken as independent variables, and further Cox multivariate regression analysis was carried out to explore the independent prognostic factors affecting iPFS. The test standard P value was < 0.05. From Feb 8, 2024, to Sep 30, 2025, a total of 38 patients diagnosed with brain metastases from NSCLC by the Oncology Department of the Fifth Affiliated Hospital of Chengdu University of Traditional Chinese Medicine were prospectively recruited and included in the statistical analysis. The median follow-up time was 15.2 months (95% CI: 9.02-21.37). The results showed that the experimental group had better iORR (57.90% vs. 15.79%, P = 0.017) and iDCR (100% vs. 73.68%, P = 0.046) compared to the control group, with statistically differences. Compared with the control group, the experimental group showed a advantage in iPFS (6.7 months vs. 4.27 months, P = 0.038), and the median iPFS was extended by an additional 2.43 months. The results of subgroup analysis showed that the iPFS of patients with ≥ 3 brain metastases and patients with < 3 brain metastases were 6.3 months and 6.7 months, respectively, and there was no significant difference between the two groups (P = 0.723). The iPFS was longer in patients with less than 3 metastases than those with more than 3 metastases (11.73 months vs. 3.17 months, P = 0.035). After WBRT, the iPFS of NSCLC patients with brain metastases who received anti-tumor therapy was improved compared with those who did not receive anti-tumor therapy (8.67 months vs. 3.80 months, P = 0.040). In terms of quality of life, the experimental group showed better outcomes in functional status, symptom domains, and overall health compared to the control group over time. Regarding adverse reactions, the main ones included decreased appetite, fatigue, nausea and vomiting, hypertension, Myelosuppression, dizziness, headache, and abnormal liver function indicators. Grade ≥ 3 adverse reactions primarily included anemia, agranulocytosis, leukopenia, thrombocytopenia, cognitive impairment and abnormal liver function indicators, most of which were tolerable after symptomatic treatment. Univariate regression analysis of the overall population indicated that antitumor therapy after WBRT (P = 0.078) and the number of organ metastases (P = 0.038) were clinically relevant factors affecting iPFS. Further multivariate Cox regression analysis revealed that antitumor therapy after WBRT (P = 0.047) and the number of organ metastases (P = 0.028) were independent prognostic factors influencing iPFS. In this exploratory cohort, low-dose (8 mg) anlotinib administered 5-7 days prior to WBRT was associated with higher iORR, iDCR, and longer iPFS relative to WBRT alone in patients with NSCLC brain metastases. This combination regimen showed a manageable safety profile and trends toward improved quality of life. Subgroup analyses suggested that patients with < 3 organ metastases or those receiving post-WBRT antitumor therapy tended to have prolonged iPFS. Multivariate Cox regression identified post-WBRT antitumor therapy and number of organ metastases as potential independent prognostic factors for iPFS in this cohort. These findings are hypothesis-generating and require validation in larger randomized controlled trials.
Artificial Intelligence (AI), particularly ChatGPT-4, offers promising applications in medical education, including multiple-choice question (MCQ) development. This study aimed to evaluate and compare the quality of 36 MCQs created by medical faculty with their versions reviewed by ChatGPT-4. A cross-sectional, quantitative approach was used. Ten external health education specialists and four study authors (internal evaluators) assessed the questions based on 38 criteria. While external evaluators found no statistically significant difference in criteria met between versions (p = 0.325), the study authors, who underwent standardization meetings, identified a statistically significant increase in the number of criteria met by ChatGPT-4-reviewed MCQs (p < 0.001). Descriptive statistics, Wilcoxon Signed-Rank Test, and Non-Metric Multidimensional Scaling were employed. The results showed that ChatGPT-4 demonstrated proficiency in modifying questions to reflect greater structural clarity and adherence to basic item-writing principles, resulting in questions with increased clarity and objectivity. However, it struggled to incorporate clinical reasoning and higher-order thinking when these were lacking, particularly given the non-optimized prompt used. Despite these limitations, AI's revisions were aligned with faculty quality standards, demonstrating its potential to complement faculty efforts, emphasizing the critical role of calibrated human expertise and effective prompt engineering, rather than replacement.
Damp and mould compromise indoor air quality (IAQ) in millions of European homes. Epidemiological evidence links damp and mould exposure to increased risk of respiratory diseases and symptoms in children. However, longitudinal evidence from the UK remains limited, despite its older housing stock and wet, humid climate. We investigated associations between damp and mould and respiratory health in the Born in Bradford birth cohort (Bradford, UK) among 2594 children aged 3-5, with follow-up for new disease development age 7-11 (n = 1543). We report descriptive analyses of damp and/or mould by household factors and deprivation levels. Unadjusted and adjusted odds ratios (OR) and incidence-rate ratios (IRR, longitudinal analyses only) were estimated for multiple damp and mould indicators in relation to asthma, hay fever (indicator of allergies), wheeze, and secondary outcomes reflecting symptom severity using Logistic and Poisson Regression. Models controlled for individual, household, and neighbourhood confounders, including socioeconomic status and air pollution. Additional analyses were conducted amongst children who did not move house between survey years. A quarter (23%) of children lived with damp and/or mould in early childhood and 3% had mould in their bedrooms. In cross-sectional analyses, mould in the bedroom was significantly associated with a higher adjusted OR of wheeze in early childhood (age 3-5). Early-life exposure to all damp and mould indicators was significantly associated with an increased adjusted-IRR of new reported hay fever in later childhood (age 7-11) (range of IRRs: 1.42 - 1.96 for children who did not move house). Adjusted-IRRs for incident asthma indicated a positive association with damp/mould, but were not statistically significant, likely due to limited sample size reducing statistical power. Our findings are consistent with the broader literature highlighting that damp, and particularly mould, is a risk factor for respiratory illness and allergy in children. Housing and public health interventions aimed at reducing exposures, particularly in bedrooms, may enhance child health and wellbeing.
The extraction of the third molar is a frequent surgical procedure often associated with postoperative sequelae such as pain, oedema, and trismus, which can negatively impact patients' quality of life. This randomized, double-blind, placebo-controlled clinical trial aimed to evaluate the efficacy of low-level light-emitting diode (LED) photobiomodulation (660 nm, continuous wave) in reducing these sequelae after mandibular third molar surgery. Forty-two patients were allocated to an active LED group (n = 21) or a placebo group (n = 21). Pain (visual analogue scale), oedema (linear facial measurements), trismus (maximal mouth opening), analgesic consumption, and quality of life were assessed preoperatively and on postoperative days 2, 4, and 7. No statistically significant differences were observed between groups in facial oedema or quality of life. The LED group showed statistically significant improvements in mouth opening (day 2: P = 0.001; day 4: P = 0.01), pain scores (day 2: P = 0.001; day 4: P = 0.01), and analgesic consumption (day 2: P = 0.001; day 4: P = 0.01) compared with the placebo group. No significant differences were found on day 7 for any variable. LED photobiomodulation provided significant early benefits (days 2 and 4) in mouth opening, pain reduction, and decreased analgesic use after third molar surgery, without affecting oedema or quality of life. These findings support its use as a non-invasive adjuvant therapy for the management of acute postoperative symptoms.
IgG4-related disease (IgG4-RD) is a chronic immune-mediated disease characterised by mass-forming lesions. The smouldering tempo and often asymptomatic nature of IgG4-RD pose challenges in the monitoring of disease activity. The goal of this study is to identify novel biomarkers capable of distinguishing active disease from remission. Ninety-two inflammation-associated proteins were measured across 67 patients with IgG4-RD, 49 healthy donors (HDs), and 21 patients with sarcoidosis. Statistical analyses were adjusted for age, sex, race, and false discovery rate. Biomarkers that distinguished IgG4-RD were studied by unsupervised hierarchical clustering, receiver operator characteristic curves, and statistical analyses. Quantitative enzyme-linked immunosorbent assay (ELISA) was used to validate findings in a cohort of 80 patients with IgG4-RD, including 28 patients with paired longitudinal samples, and 80 age, sex, and race-matched HDs. Twelve inflammation-associated proteins distinguished IgG4-RD. Although most markers correlated with one another, CCL19, CCL2, and CCL13 were the most distinguishing of IgG4-RD. Among these, only CCL19 decreased during treatment-induced remission relative to active IgG4-RD. CCL19 correlated with clinical and laboratory parameters of disease activity and severity. Quantitative ELISA validated the systemic elevation of CCL19 in patients with IgG4-RD. CCL19 performed similarly to IgG4 in dynamically declining in response to treatment and increasing with subsequent relapse. Importantly, CCL19 and IgG4 supplemented one another in distinguishing active disease from remission. CCL19 is a novel and promising biomarker for the longitudinal monitoring of disease activity in patients with IgG4-RD and may provide supplemental value to IgG4 in identifying relapsing disease.
The optimal timing of anticoagulation initiation in patients with large hemispheric infarction (LHI) remains uncertain, particularly the trade-off between thromboembolism and hemorrhagic transformation risk. This study aimed to compare clinical outcomes between early and late anticoagulation (AC) initiation in patients with LHI. We performed an analysis in a retrospective cohort of 264 consecutive patients with LHI (early AC ≤ 7 days; late AC > 7 days). Propensity score matching (PSM) was performed to balance baseline characteristics between early and late groups (43 patients per group). We assessed the efficacy and safety outcomes of anticoagulation at 1 year and 3 months after stroke onset. Primary efficacy outcome was composite of ischemic stroke recurrence or systemic embolism. Cox proportional hazards regression was performed to obtain adjusted hazard ratios (HRs). Secondary efficacy outcomes included favorable functional outcome (modified Rankin Scale [mRS] 0-2) and all-cause mortality. Safety outcomes included symptomatic intracranial hemorrhage, major hemorrhage. Subgroup analyses assessed primary efficacy outcomes across prespecified variables. Before PSM, the early AC group demonstrated a significantly lower rate of stroke recurrence or systemic embolism compared to the late AC group (8.3% vs. 27.7%; HR = 0.55, 95% CI 0.33-0.92; log-rank P < 0.001), which persisted after PSM (9.3% vs. 27.9%; log-rank P = 0.024). On multivariate Cox regression, early AC was independently associated with a markedly reduced risk of stroke recurrence before PSM (adjusted HR = 0.307, 95% CI 0.144-0.655; P = 0.004), however with the reduced sample size and limited outcome events, there was no statistical significance after PSM (HR = 0.443, 95% CI 0.179-1.099; P = 0.158). Good functional outcome (mRS 0-2) favored early AC in the overall cohort (45.3% vs. 18.1%; OR = 3.75, 95% CI 2.00-7.06; P < 0.001), though this difference was attenuated after matching (39.5% vs. 27.9%; P = 0.362). Rates of symptomatic hemorrhage (6.6% vs. 9.6%; P = 0.389), major hemorrhage (8.3% vs. 13.3%; P = 0.204), and all-cause mortality (8.8% vs. 10.8%; P = 0.615) did not differ significantly between groups, a pattern that was maintained in the matched cohort. Subgroup analyses showed statistically significant differences in stroke recurrence or systemic embolism among patients with moderate stroke severity (HR = 0.21, 95% CI 0.03-1.50, P = 0.007), absence of malignant MCA infarction (HR = 0.43, 95% CI 0.14-1.34, P = 0.028), no prior stroke or TIA (HR = 0.42, 95% CI 0.14-1.31, P = 0.022), and below 75 years old (HR = 0.28, 95% CI 0.04-1.97, P = 0.048). Early anticoagulation initiation after large hemispheric infarction was independently associated with a substantially reduced risk of stroke recurrence and systemic embolism without a significant increase in hemorrhagic complications or mortality. These findings support the clinical benefit of early anticoagulation and provide further evidence for LHI patients.
Nigeria faces a significant energy deficit (61.2% electricity access), hindering progress toward SDG 7 (Affordable and Clean Energy) and SDG 13 (Climate Action). Despite geothermal potential, comprehensive assessments of low-enthalpy resources (that is, subsurface temperatures below 100 ℃) in transitional geological environments (TGEs) - basement-sedimentary contact zones with mixed conductive-advective heat transfer - remain underexplored. This study uses high-resolution aeromagnetic data interpretation with statistical modeling to delineate geothermal potential within the Egbako-Share axis of North-Central, Nigeria. Spectral analysis adopting centroid depth technique from 40 overlapping blocks was employed to estimate Curie Point Depths (CPD), geothermal gradients (GTG), and heat flow (HF). Statistical modeling - including correlation analysis, multiple regression, PCA, and spatial autocorrelation (Moran's I, Getis-Ord Gi*) - provided a robust framework for resource assessment and risk evaluation. The analysis revealed significant geothermal resources with CPD ranging from 26 to 46 km (mean: 38 ± 6 km), GTG of 13-23 °C/km (mean: 16 ± 2 °C/km), and HF values of 31-57 mW/m² (mean: 39 ± 6 mW/m²). Strong negative correlations between CPD and both GTG (r = -0.892, p < 0.001) and HF (r = -0.891, p < 0.001) were established, with the regression model explaining 79.5% of HF variance. PCA identified 12 high-potential geothermal zones for low-enthalpy development. Under a conceptual scenario assuming full development of all 12 zones, modelled capacity could range from approximately 15 to 25 MW, with scenario-based annual CO2 emission reductions of 85,000-140,000 t/year (subject to confirmatory drilling and feasibility studies), supporting Nigeria's SDG 7, SDG 13, and related development targets.
Accurate representation of CO over India remains challenging because of large uncertainties in emissions, atmospheric transport, and sparse in‑situ measurements. This study examines the impact of assimilating MOPITT total column CO retrievals into the Weather Research and Forecasting model coupled with Chemistry (WRF‑Chem) using the Gridpoint Statistical Interpolation (GSI) system for October-December 2019, a period strongly influenced by post‑monsoon crop‑residue burning and stagnant meteorology over northern India. Model performance is evaluated against independent TROPOMI CO columns and MOPITT vertical profiles. The control simulation (WRF‑CNTL) shows a persistent positive bias, overestimating TROPOMI CO by about 0.4-0.6 × 10¹⁸ molecules cm⁻² across the Indo‑Gangetic Plain. Assimilation (WRF‑DA) markedly reduces these biases and better captures observed spatial and temporal variability. Normalized mean bias decreases from 33.5% to 14.4%, while the index of agreement increases from 0.45 in the control to 0.72 in the data assimilation run. Comparisons with MOPITT profiles indicate that assimilation lowers near‑surface CO by 40-100 ppbv and reduces profile errors by 40-60% in the lower troposphere. These results show that MOPITT CO assimilation effectively constrains regional CO distributions and substantially enhances WRF‑Chem performance over India.
To evaluate the expression of hypoxia-inducible factor 1 alpha (HIF-1α), NOTCH-1, ADAM-12, and heparin-binding epidermal growth factor (HB-EGF) in adenoid cystic carcinoma (ACC), mucoepidermoid carcinoma (MEC), and normal salivary glands (SG), exploring hypoxia-related stromal and parenchymal adaptations with potential implications for tumor stratification and therapeutic targeting. Forty-six formalin-fixed, paraffin-embedded samples were analyzed: 17 ACC, 19 MEC, and 10 SG controls. Immunohistochemistry was performed for all markers. Protein expression was quantified as percentage of positive labeling area in both parenchymal and stromal compartments. Statistical comparisons were conducted using the Kruskal-Wallis test followed by Dunn's posthoc test with Holm correction (P < .05). All proteins demonstrated significantly higher parenchymal expression in ACC and MEC compared with SG (all P ≤ .002), without significant differences between tumor types. In the stromal compartment, HB-EGF expression was higher in MEC than ACC (P < .0001), whereas HIF-1α expression was higher in ACC than MEC (P < .0001). ADAM-12 and NOTCH-1 were increased in tumor stroma relative to SG but did not differ between ACC and MEC. Hypoxia-related proteins exhibit compartment-specific patterns that distinguish ACC from MEC at the stromal level, supporting molecular stratification and potential targeted approaches in SG carcinomas.
Standard treatment for locoregional (stages I-III) Merkel cell carcinoma (MCC) includes wide local excision (WLE) with lymph node management. However, the optimal surgical approach remains debated, especially in the head and neck, where extensive excision may impair function and aesthetics, affecting patients' health-related quality of life (HR-QoL), and delay postoperative radiotherapy (RT). This systematic review aimed to evaluate the impact of surgical excision modalities - including surgical margins, Mohs micrographic surgery (MMS), and histological resection status - on recurrence and survival outcomes in head and neck MCC (HN-MCC). Secondary objectives included assessing morbidity and HR-QoL. A systematic search of Medline, Embase, and Web of Science identified studies on HN-MCC surgical treatments. Studies were categorized into a narrative review and an individual descriptive analysis of cases. Two independent reviewers performed study selection, data extraction, and risk-of-bias assessment. A total of 43 studies were included: 9 cohort studies, 10 case series, and 24 case reports. No randomized clinical trials were found. No superior technique was identified between MMS and WLE. No studies showed a statistical link between surgical margin categories or histological resection status and local control or survival outcomes. None of the cohort and case series studies reported data on HR-QoL in patients with HN-MCC. Significant heterogeneity in available data limits definitive recommendations on surgical approaches for HN-MCC.
This study presents the largest regional-scale stable isotope investigation of human and faunal remains spanning the Bronze and Iron Ages (c. 2400-100 BCE) in the Eastern Adriatic to date. New δ13C and δ15N data from 51 individuals were integrated with previously published results (n = 233) to explore long-term and region-specific dietary trends, with a focus on the emergence of millet as a dietary component. Results reveal an inland-coastal contrast: while coastal populations predominantly consumed C3-based diets, inland groups show consistently higher δ13C values indicative of direct millet intake from the Middle/Late Bronze Age onwards. Statistical analyses confirm strong effects of both period and location on δ13C values, with most inland populations exhibiting more positive signatures particularly during the Middle/Late Bronze Age transition and again in the Iron Age. A probabilistic two-endmember mixing model estimates millet contributions reaching up to ~ 40% of dietary protein in these inland groups, suggesting episodic but significant integration of C4 crops into subsistence systems. In contrast, faunal baselines reflect purely C3 diets, indicating that the C4 signal in humans derives from direct millet consumption. These findings help refine the chronology of millet adoption in the eastern Adriatic, pushing its significant dietary incorporation back to the Middle/Late Bronze Age transition, and highlight fluctuating patterns of C4 plant consumption through the Bronze and Iron Ages, likely shaped by ecological conditions and local adaptive strategies rather than uniform cultural change.
Effective log assessment is a cornerstone for ensuring the reliability and smooth functioning of large-scale, cloud-based infrastructures. As these environments continuously grow in scope and intricacy, traditional monitoring approaches often struggle to keep up, leading to unnecessary computational strain and diminished system performance. To address these challenges, this research introduces a hybrid framework that integrates natural language processing (NLP) with an optimized LightGBM classifier, tailored for anomaly detection in cloud-generated system logs. Central to the design is a thorough preprocessing pipeline that filters irrelevant information and minimizes bias, thereby sharpening anomaly detection accuracy. The experimental setup explored multiple NLP-based preprocessing strategies, including TF-IDF, BERT, and Word2Vec implementations (employing spaCy and Gensim). Classification relied on the LightGBM model, whose hyperparameters were refined using a customized particle swarm optimization (PSO) metaheuristic. This modified optimization routine boosted both predictive accuracy and model robustness. Results from the study reveal that the combined system significantly enhanced both the identification and classification of anomalies in cloud logs. The most effective configuration achieved up to 100% accuracy under the evaluated experimental conditions, highlighting the framework's potential to strengthen security within cloud ecosystems. To ensure statistical soundness, extensive comparative evaluations were conducted across all configurations. Additionally, model interpretability was improved through SHapley Additive exPlanations (SHAP), which provided transparent insights into the role of individual features in shaping classification outcomes.
Administrative boundaries in the United States frequently shift due to population growth and redistricting, complicating longitudinal analyses of census-based socio-economic data. In California, the number and configuration of census tracts and block groups have changed substantially between 1990 and 2020, often resulting in misaligned or missing historical data-especially for variables such as housing value. This study presents a geospatial methodology for reconstructing historical housing data using Kriging interpolation and zonal statistics. Kriging, a geostatistical method that accounts for spatial autocorrelation, was applied to estimate missing median house values across decades. The interpolated surfaces were then aggregated to consistent 2020 census block group geographic units via zonal statistics, enabling cross-temporal comparison on a uniform spatial basis. Using California as a case study, this work offers a reproducible framework for reconstructing historical datasets across evolving administrative boundaries, supporting more accurate spatial and socio-economic research.
Over 50% of persons with unresectable stage III non-small cell lung cancer (NSCLC) treated with standard-of-care concurrent chemoradiotherapy (CCRT) and durvalumab consolidation progress or die within 18 months. Here adults with untreated, unresectable stage III NSCLC were randomized to nivolumab plus CCRT followed by consolidation with nivolumab plus ipilimumab (arm A) or nivolumab alone (arm B) or CCRT followed by consolidation with durvalumab (arm C). The primary endpoint was progression-free survival (PFS) in arm A versus arm C and secondary endpoints included overall survival (OS), PFS in arm B versus arm C, response rates and safety. At a median follow-up of 30.5 months, there was no statistically significant difference in the primary endpoint of PFS in the nivolumab plus ipilimumab arm versus durvalumab arm (hazard ratio (HR): 0.95, 96% confidence interval (CI): 0.77-1.19; P = 0.65). Descriptive OS analysis showed no improvement (HR: 1.12, 95% CI: 0.87-1.43). Nivolumab alone did not improve PFS or OS versus durvalumab (PFS, HR: 0.84, 95% CI: 0.69-1.04; OS, HR: 0.97, 95% CI: 0.76-1.24). Nivolumab plus ipilimumab and nivolumab alone plus CCRT resulted in increased pneumonitis. These results emphasize the need for novel efficacious treatments for these individuals. (ClinicalTrials.gov: NCT04026412 ).
To investigate the relationship between polyunsaturated fatty acids and biochemical hypogonadism in aging males with a cross-sectional NHANES data. A total of 1165 men aged ≥ 65 years old, who had complete data on total testosterone levels and erythrocyte membrane fatty acid composition measurements, were included from the National Health and Nutrition Examination Survey (NHANES) 2021-2023 dataset. Biochemical hypogonadism was defined as total testosterone ≤ 300 ng/dL. Age, body mass index (BMI), waist circumference, diabetes mellitus (DM), fatty acid enzyme activities, HDL, LDL, triglycerides, and total cholesterol were also recorded. A total of 1,165 men were analyzed, of whom 859 had complete total testosterone data. In multivariate logistic regression analysis using continuous variables, higher arachidonic acid levels were independently associated with lower odds of biochemical hypogonadism (OR 0.80, 95% CI 0.66-0.97, p = 0.026). Triglyceride levels (OR 1.005, 95% CI 1.001-1.009, p = 0.006) and waist circumference (OR 1.037, 95% CI 1.019-1.056, p < 0.001) were positively associated with biochemical hypogonadism. Diabetes mellitus showed a borderline association with hypogonadism but did not reach statistical significance after adjustment (OR 1.54, 95% CI 0.93-2.56, p = 0.09). HDL cholesterol, palmitoleic acid, docosahexaenoic acid, and linoleic acid were associated with biochemical hypogonadism in univariate analysis but did not remain significant after multivariate adjustment. Arachidonic acid (AA), a component of the omega-6 fatty acid pathway, levels were independently associated with lower odds of biochemical hypogonadism. whereas waist circumference, diabetes mellitus and triglycerides were associated with biochemical hypogonadism.
Pediatric intracranial aneurysms (PIAs) are rare and present with distinct clinical and morphological features compared to adult cases. They are often associated with congenital anomalies, larger size, and unusual locations. Despite advancements in diagnosis and treatment, data about PIAs remain scarce. This study presents a 20-year single center experience in the management of PIAs, alongside a comprehensive literature review. A retrospective review of pediatric patients diagnosed with intracranial aneurysms at a tertiary center between January 2005 and January 2025. Demographic, clinical, radiological, and treatment data were collected. Functional outcomes were assessed using the Glasgow Outcome Scale (GOS). Descriptive statistics, chi-square tests were used for analysis. A narrative literature review was also performed. 38 patients with 61 aneurysms were included (63.2% male; mean age 12.3 years). Index aneurysm for each patient was included in the analysis of location and size. Most aneurysms were located in the anterior circulation, particularly the ICA bifurcation (34.2%) and MCA (23.7%). Ruptured aneurysms seen in 73.7% of cases, 44.7% presenting with Fisher grade 4 hemorrhage. Treatment microsurgical clipping (50%), endovascular therapy (36.8%), and conservative management (7.9%). There was no statistically significant association between treatment modality and outcome (p = 0.153). Good functional recovery (GOS 5) achieved in 60.5% of patients; with a mortality rate of 13.2%. PIAs frequently present with rupture and require individualized, multidisciplinary management. Both surgical and endovascular approaches are effective in selected patients, with comparable outcomes. Our findings align with global literature and reinforce the need for early diagnosis, tailored intervention, and long-term follow-up in this unique population.
This study compared two widely used biomechanical models-Plug-in Gait (PiG) and Conventional Gait Model 2.3 (CGM2.3)-during overground walking (WALK) and single-leg squats (SLS) in 24 healthy adults. Data was collected using a 20-camera Vicon system and force plates. Static trials were analyzed with medial knee and ankle markers to align joint axes across models. Kinematic and kinetic outputs were compared using root mean square differences (RMSD) and statistical parametric mapping (SPM) paired t-tests. During WALK, PiG produced greater internal rotation at the knee (RMSD 17.8°, p < 0.001) and hip (RMSD 5.0°, p < 0.001), and smaller sagittal-plane flexion angles (RMSD 2.6° knee, 2.3° hip) compared with CGM2.3. In single-leg squats, these discrepancies increased to 29.1° and 9.0°, respectively, with sagittal-plane differences of 4.4° at the knee and 5.1° at the hip. CGM2.3 yielded higher knee flexion moments (31% in WALK, 104% in SLS), while PiG produced higher frontal-plane knee moments (28% and 89%). The differences were most pronounced at deeper flexion angles. These results demonstrate that biomechanical outcomes differ systematically between models, emphasizing the impact of model selection on joint kinematics and kinetics in human movement analysis.
Botulinum toxin type A (BoNT-A) is widely used in aesthetic medicine to treat dynamic facial rhytides. Despite its well-established safety and efficacy, BoNT-A injections often induce discomfort and anxiety owing to injection-related pain, especially in sensitive facial areas. Although topical anesthetic creams are commonly employed to alleviate pain, they have limitations, such as delayed onset and local side effects. Mechanical analgesic devices, based on the gate control theory of pain, have emerged as promising non-pharmacological alternatives. In this prospective, single-center, split-face study, 80 adult patients undergoing upper-facial BoNT-A injections between May 2024 and August 2025 were enrolled. Each participant received a topical anesthetic cream on one side of the face and a Shot Blocker-like mechanical analgesic device on the contralateral side. All injections were administered by a single experienced physician. Pain levels were assessed immediately post-injection using a visual analog scale (VAS, 0-10) by a blinded evaluator. Statistical analyses included paired t-tests, Wilcoxon signed-rank tests, Spearman correlation, and Mann-Whitney U tests. Effect sizes were reported using Cohen's dz and Cliff's Δ. Mean VAS scores were significantly lower with the mechanical device (3.19 ± 1.08) than with the topical cream (4.14 ± 1.30) (p < 0.001). The intra-individual mean difference (0.95 ± 1.41) favored the mechanical device. Spearman's correlation indicated that higher pain scores with the cream correlated with greater relative benefit from the device (ρ = 0.664, p < 0.001). Patients with higher baseline pain (VAS ≥ 4 on the cream side) experienced significantly greater pain reduction (p < 0.001). A shot blocker-like mechanical analgesic device is more effective than a topical anesthetic cream in minimizing pain during BoNT-A injection into the upper face. Its immediate analgesic effect, absence of pharmacologic side effects, and ease of use make it a valuable adjunct in aesthetic practice, particularly for patients with pain sensitivity. Further studies are warranted to validate these findings in broader populations and different anatomical regions. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors.
High predictive accuracy is frequently misinterpreted as evidence of causal understanding or population-level signal. Models can exploit spurious correlations, confounding, or protocol-induced artefacts, while post-hoc explanations may faithfully describe model behaviour yet remain misleading about the underlying phenomenon. We propose a framework that separates three layers of evidence: (i) causal relations in the phenomenon, (ii) population-level statistical dependence, and (iii) finite-sample, protocol-dependent predictive effects. This separation clarifies why predictive success and feature attributions do not license mechanistic interpretations without additional assumptions. Under log-loss and Bayes-risk-consistent protocols, the population predictive value of adding a feature equals the conditional mutual information, providing a principled reference for "true signal". Using controlled simulations, we illustrate that bootstrap resampling can induce persistent false positives by amplifying chance correlations, and that SHAP can assign high importance to confounded variables while remaining faithful to the fitted model. These results suggest that "feature importance" is best treated as protocol-bounded evidence, and that interpretation benefits from reporting the protocol, robustness checks, and the intended inferential scope.