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Nevin Manimala Statistics

Potential role of tirbanibulin in the management of superficial basal cell carcinoma

J Eur Acad Dermatol Venereol. 2026 Jul 20. doi: 10.1111/jdv.70619. Online ahead of print.

NO ABSTRACT

PMID:42473713 | DOI:10.1111/jdv.70619

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Role of Mitochondrial tRNALeu 12320 A>G Mutation on Heart Rate Variability and Blood Pressure at Low-Altitude and in a High-Altitude Hypoxic Environment

High Alt Med Biol. 2026 Sep;27(3):152-158. doi: 10.1177/15578682251411931. Epub 2026 Jan 9.

ABSTRACT

Pan, Cuiping, Qunyuan Wang, Minglei Zhang, Ruizhe Li, Yining Liu, and Zongbin Li. Role of mitochondrial tRNALeu 12320 A>G mutation on heart rate variability and blood pressure at low altitude and in a high-altitude hypoxic environment. High Alt Med Biol. 27:152-158, 2026.

INTRODUCTION: Mutations-gene mutations-can exert dual, environment-dependent effects on cardiovascular disease.

MATERIALS AND METHODS: We analyzed clinical data and mitochondrial DNA from 84 young Han Chinese men ascending from low-altitude to high-altitude regions (>4,000 m).

RESULTS: Nine subjects harbored the mitochondrial tRNA A12320G mutation. Notably, none of these 9 mutation carriers developed acute mountain sickness (AMS), whereas 34 (40.5%) of the 84 volunteers in the cohort were diagnosed with AMS, indicating a significant protective association (p = 0.009). In the low-altitude environment, time domain parameters of heart rate variability (HRV) in the mutant volunteers were significantly lower than those in the unmutated volunteers (SDNN: 141.76 ± 30.75 ms vs.169.08 ± 32.83 ms, p = 0.020; RMSSD: 29.70 ms vs. 41.35 ms, p = 0.022; HRV triangular index: 41.8% vs. 52.4%, p = 0.024; SDSD: 37.4 ms vs. 50.5 ms, p = 0.016; PNN50: 3.1% vs 7.6%, p = 0.008); 24-hour mean systolic blood pressure (118.63 ± 9.54 vs. 113.39 ± 6.30 mmHg, p = 0.029), nocturnal mean diastolic blood pressure (67.37 ± 7.91 vs. 61.11 ± 7.08 mmHg, p = 0.015) were also higher; HRV and blood pressure were not statistically different between the mutant and nonmutant groups in the high-altitude environment. Hematological analysis revealed mutants at high altitude had significantly lower plateletcrit (0.23% vs. 0.26%, p = 0.019) and total protein (72.78 ± 3.84 g/L vs.75 .65 ± 3.0 g/L, p = 0.008).

CONCLUSION: The A12320G mutation acts as a cardiovascular risk factor (reduced HRV, increased blood pressure) at low altitude, whereas at high altitude it was associated with a reduced incidence of AMS, possibly through metabolic adaptive mechanisms, reflecting the environmentally dependent dual roles of this gene effect.

PMID:42473712 | DOI:10.1177/15578682251411931

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Ten Years of Lumbar Transforaminal Epidural Steroid Injections in a Tertiary Referral Center: Trends in Clinical Indications and Outcomes

Pain Pract. 2026 Sep;26(7):e70191. doi: 10.1111/papr.70191.

ABSTRACT

INTRODUCTION: Transforaminal epidural steroid injection (TFESI) is commonly applied for lumbar radicular pain. High-level evidence supports the use in disc-related radiculopathy, while evidence for TFESI in neuroforaminal stenosis remains consensus-based.

METHODS: A retrospective repeated cross-sectional study was conducted covering January 2013-December 2022. The dataset comprised 11,208 unique patients reimbursed for TFESI. Trends in clinical indications were analyzed using automated keyword-based text recognition. Representative cohorts from 2014 (n = 266) and 2022 (n = 299) were randomly selected for clinical and radiologic reviews. Imaging was reassessed according to established grading systems. Pain intensity and global perceived effect were evaluated approximately 6 weeks post-injection. Parametric and non-parametric statistics, linear regression, and ordinal logistic regression were applied. A two-sided p < 0.05 was considered statistically significant.

RESULTS: Mean patient age and the proportion of stenosis-related indications both increased steadily between 2013 and 2022 (p < 0.001). In the studied cohorts, short-term pain decreased significantly after TFESI across all phenotypical subcategories, except for moderate-to-severe central canal compression in 2014. Neuroforaminal stenosis predicted greater pain improvement regardless of its nature in 2014 (p = 0.006), whereas disco-osteophyte abnormalities and chronic or recurrent symptoms were associated with less pain reduction in 2022 (p < 0.05). Female patients showed less short-term improvement than males. At one-year follow-up, central canal stenosis predicted a lower likelihood of being pain-free (OR = 0.63, p = 0.022).

CONCLUSIONS: This retrospective study found an upward trend in patient age and a growing proportion of non-discogenic neuroforaminal stenosis as indications for TFESI. While modest short-term pain reduction was observed, outcomes were slightly negatively influenced by central compression, disco-osteophyte abnormalities, chronic symptoms, and female sex.

PMID:42473702 | DOI:10.1111/papr.70191

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Complementary structure of statistical significance and predictive relevance in explainable machine learning-based transcriptomic tissue classification of Hanwoo cattle

Front Genet. 2026 Jul 6;17:1818099. doi: 10.3389/fgene.2026.1818099. eCollection 2026.

ABSTRACT

Understanding tissue-specific transcriptomic structures in livestock is essential for elucidating the molecular basis of economically important traits. Conventional differential gene expression analysis efficiently identifies genes with large average expression differences but does not fully capture multivariate expression structures and gene-gene interaction patterns that define tissue identity. In this study, we developed an explainable machine learning framework to classify seven Hanwoo cattle tissues using RNA sequencing data and to systematically compare the relative contributions of statistical and model-derived signals. A Random Forest-based one-versus-rest classification model was trained on 130 Hanwoo transcriptomes and externally validated using 231 independent Bos taurus samples derived from heterogeneous public datasets following reference-based batch correction. Repeated balanced validation demonstrated stable generalization performance, achieving a mean accuracy of 0.907 and a macro-average area under the receiver operating characteristic curve of 0.963. A comparative analysis of gene sets selected by differential expression analysis, genes prioritized by model-based feature attribution, their union, and randomly selected genes within the same classification framework revealed that strongly differentially expressed genes form the primary discriminatory structure for tissue classification. In contrast, integration of model-prioritized genes enhanced classification performance, particularly for biologically related tissues, whereas randomly selected genes produced reduced and unstable predictive performance. Model interpretation further revealed that highly contributory genes were consistent with known tissue-specific biological functions and exhibited non-linear, expression-dependent contribution patterns shaped by coordinated multigene contexts. These findings indicate that tissue identity is supported by a hierarchical transcriptional structure in which dominant differential signals establish primary class boundaries and multivariate interaction patterns refine decision surfaces. The proposed framework provides an interpretable strategy for distinguishing statistical significance from predictive relevance in high-dimensional transcriptomic data and offers practical implications for molecular marker development in livestock genomics and breeding programs.

PMID:42473676 | PMC:PMC13381022 | DOI:10.3389/fgene.2026.1818099

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Nevin Manimala Statistics

Challenges and Misinterpretations of Cohen’s Kappa in Agreement Studies in Ophthalmology

Vet Ophthalmol. 2026 Sep;29(5):e70208. doi: 10.1111/vop.70208.

ABSTRACT

OBJECTIVE: Cohen’s kappa is widely used to measure rater agreement on binary outcomes and performs well when outcome prevalence is relatively balanced. This paper aims to explain the challenges encountered with Cohen’s kappa, and to provide guidance to veterinary ophthalmologists on the usage and interpretation of kappa values.

ANIMALS STUDIED: Article based on an existing dataset in which two examiners graded iridocorneal angle abnormalities in 60 client-owned dogs during pre-breeding examinations.

PROCEDURE: Following the 2022 ECVO-HED (European College of Veterinary Ophthalmology-Hereditary Eye Diseases) gonioscopy grading scheme and its general recommendations, eyes were classified into two categories-“breeding-YES” (not affected, mildly or moderately affected) or “breeding-NO” (severely affected). Inter-examiner agreement was separately assessed for real (60 left and 58 right eyes) and simulated data (manually balanced left eye dataset with unchanged agreement between examiners).

RESULTS: While the two examiners classified 52/60 left and 51/58 right eyes into the “breeding-YES” category, they disagreed on 7/60 left and 1/58 right eyes, with resulting kappa values of 0.18 and 0.91 for the left and right eyes, respectively. After balancing the data, with both examiners classifying 27/60 left eyes into the “breeding-yes” category, but still disagreeing on 7/60 eyes, the kappa value increased to 0.77.

CONCLUSIONS: Readers should be cautious when comparing kappa values across studies with different underlying prevalence and bias. Under non-ideal data distribution, additional statistical indices like prevalence- and bias index, prevalence-and-bias-adjusted kappa (PABAK), and maxKappa, do not replace Cohen’s kappa, but assist in interpreting it.

PMID:42473033 | DOI:10.1111/vop.70208

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Electroacupuncture Treatment on Sarcopenia in Patients Undergoing Maintenance Haemodialysis: An Effective Therapy

J Cachexia Sarcopenia Muscle. 2026 Aug;17(4):e70345. doi: 10.1002/jcsm.70345.

ABSTRACT

BACKGROUND: Electroacupuncture (EA) treatment has been utilized for recovery from neuromuscular-related diseases and may play a significant role in the treatment of sarcopenia. This interventional, randomized controlled clinical study aims to explore the efficacy of EA treatment in maintenance haemodialysis (MHD) patients with sarcopenia.

METHODS: Thirty-six participants with sarcopenia undergoing MHD were randomly divided into the control group and the EA group. The participants in the EA group received a total of 24 treatments, each lasting 30 min, and were administered three times per week. Participants in the control group were instructed to continue their current lifestyle and treatment plans. The assessments were conducted at baseline and after 8 weeks. Statistical analysis was performed using two-way analysis of covariance (ANCOVA) adjusted according to gender and baseline values. Repeated measures analysis of variance (ANOVA) was used to assess EA effects, reporting main effects and the time × group interaction with partial eta squared (η2p) effect sizes. The primary outcome was 6-m gait speed; the secondary outcomes were skeletal muscle mass index (SMI) and handgrip strength. Fasting blood samples were collected, and serum metabolomics using the liquid chromatography-mass spectrometry method was employed to reveal metabolic changes.

RESULTS: One participant from the EA group dropped out, and 35 participants were included in the analysis, aged (59.06 ± 11.69) years, including 22 men and 13 women. After intervention, the 6-m gait speed of the EA group increased (Δ = 0.10 ± 0.08; p < 0.001), whereas that of the control group decreased (Δ = -0.06 ± 0.09; p = 0.018). The handgrip strength of the EA group increased (Δ = 0.68 ± 0.98; p = 0.011), whereas that of the control group decreased (Δ = -0.76 ± 1.19; p = 0.015). The SMI in the EA group increased (Δ = 0.19 ± 0.22; p = 0.003), although there was no significant difference in the control group. No serious adverse events were observed during the EA treatment. The results of serum metabolomics indicated that a total of 127 differentially expressed metabolites were identified (p < 0.05, VIP > 1), including 35 up-regulated metabolites and 92 down-regulated metabolites. KEGG pathway enrichment analysis showed that glycerophospholipid metabolism, linoleic acid metabolism and other pathways related to lipid metabolism were significantly changed.

CONCLUSIONS: EA treatment was an effective therapy for sarcopenia in patients undergoing MHD. Its therapeutic effect may be related to the positive regulation of systemic metabolism (including amino acid and lipid profiles).

PMID:42473028 | DOI:10.1002/jcsm.70345

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Frailty mediates the association between sleep duration and physical, psychological, and cognitive multimorbidity in Chinese middle-aged and older adults

Sci Rep. 2026 Jul 19. doi: 10.1038/s41598-026-63040-x. Online ahead of print.

ABSTRACT

The association between sleep duration and physical, psychological and cognitive multimorbidity (PPC-MM) remains unclear. This study explores whether frailty accounts for part of this association using both cross-sectional and longitudinal analyses. This study utilized data from the China Health and Retirement Longitudinal Study (CHARLS) collected between 2011 and 2018, involving 7,193 participants for cross-sectional and 5,380 for longitudinal analysis. Multivariate logistic regression and Cox proportional hazards models evaluated the association between sleep duration, frailty, and PPC-MM risk. Nonlinear dose-response relationships were assessed with restricted cubic spline (RCS) analysis, and subgroup analyses examined demographic differences. Bootstrap resampling with 1,000 iterations was used to estimate the indirect pathways. In the cross-sectional path analysis, logistic regression analysis showed that sleep duration was negatively associated with PPC-MM (OR = 0.84, 95% CI: 0.80-0.89, P < 0.001). Frailty showed a positive association with PPC-MM (OR = 4.80, 95%CI: 3.92-5.88, P < 0.001). Frailty accounted for 31.61% of the statistical association between sleep duration and PPC-MM. In the longitudinal exploratory mediation analysis, Cox models showed that longer sleep duration was associated with a lower risk of incident PPC-MM (HR = 0.85, 95% CI: 0.80-0.89, P < 0.001). Frailty was positively associated with PPC-MM risk (HR = 5.89, 95% CI: 4.81-7.21, P < 0.001). Exploratory mediation analysis further indicated that the indirect pathway via frailty accounted for 26.99% of the total prospective association between sleep duration and incident PPC-MM. Sleep duration was negatively associated with PPC-MM, while frailty was positively associated with PPC-MM. Exploratory analyses suggested that frailty may serve as a partial intermediary in this association.

PMID:42473003 | DOI:10.1038/s41598-026-63040-x

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A probabilistic state assessment framework for damaged heavy-haul railway bridges using vehicle-bridge collaborative monitoring

Sci Rep. 2026 Jul 19. doi: 10.1038/s41598-026-60777-3. Online ahead of print.

ABSTRACT

In-service heavy-haul railway bridges often operate under damaged conditions, requiring continuous health monitoring to ensure operational safety and facilitate intelligent maintenance. However, conventional assessment methods based on ground monitoring, limited by sparse sensor deployment, cannot fully capture the global bridge state and its evolution, and neglect stochastic track irregularities that induce significant response variability, thereby decreasing assessment reliability. To address these issues, a distribution-driven probabilistic bridge state assessment framework is proposed based on vehicle-bridge collaborative monitoring. The extreme-value distributions of vibration responses from the bogie, wheelset, and key span sections under stochastic track irregularities and varying bridge damage conditions are characterized using the probability density evolution method, revealing a mapping between damage-induced variations in bridge states and the corresponding distribution shifts. Based on this mapping, baseline thresholds for extreme responses are statistically determined under undamaged conditions to define six distinct bridge health levels. The probability for each level is estimated via a weight-adaptive hierarchical probabilistic evaluation model, which fuses probabilities derived from the extreme-value distributions of multi-source vibration response indicators, with weights allocated according to indicator sensitivity to damage. The bridge state is assessed as the one with the highest probability among the six levels. Case studies on scenarios with different damage locations and severities demonstrate that the proposed framework effectively distinguishes the effects of damage on bridge states and traces state evolution as damage progresses, providing reliable and interpretable assessments for bridge maintenance decision-making.

PMID:42472990 | DOI:10.1038/s41598-026-60777-3

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Predictive value of systemic inflammatory indices in metabolic syndrome and non-alcoholic fatty liver disease in Iran

Sci Rep. 2026 Jul 19. doi: 10.1038/s41598-026-63141-7. Online ahead of print.

ABSTRACT

The prevalence of metabolic syndrome has increased significantly, and visceral obesity is closely associated with non-alcoholic fatty liver disease. This study aimed to investigate the association between inflammatory indices derived from blood cell counts and to investigate the association between inflammatory indices, metabolic syndrome, and NAFLD in Sabzevar, Iran, in 2025. This case-control study used data from a large adult cohort. A total of 1500 participants with metabolic syndrome were selected as the case group, and for each case, one control without metabolic syndrome was randomly selected from the same cohort. All participants were subsequently evaluated for the presence or absence of non-alcoholic fatty liver disease and, additionally, for liver fibrosis using the Fibrosis-4 (FIB-4) index. Data were analyzed using SPSS version 16, and a p-value < 0.05 was considered statistically significant. In this study, the mean age was 51.01 ± 8.3 years in the metabolic syndrome group and 46.9 ± 8.2 years in the healthy group. In the metabolic syndrome group, 621 participants were male and 879 were female. Overall, no significant associations were observed between metabolic syndrome and inflammatory indices, including the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, systemic immune-inflammation index, systemic inflammatory response index, hemoglobin level, or liver fibrosis classification based on the Fibrosis-4 (FIB-4) index. In contrast, metabolic syndrome was significantly associated with demographic factors, anthropometric measures, metabolic parameters, non-alcoholic fatty liver disease, and the monocyte-to-high-density lipoprotein cholesterol ratio. Non-alcoholic fatty liver disease showed no significant association with the neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, hemoglobin level, or systemic inflammatory response index. Still, it was significantly associated with demographic characteristics, anthropometric indices, metabolic factors, the platelet-to-lymphocyte ratio, systemic immune-inflammation index. Liver fibrosis classification based on the FIB-4 index was not significantly associated with several metabolic and inflammatory variables; however, it showed significant associations with age, sex, anthropometric measures, selected inflammatory indices, and hemoglobin level. Given that imaging methods are costly and not readily accessible for all patients, the findings of this study may provide a basis for identifying more cost-effective and easily accessible approaches for the diagnosis of this disease.

PMID:42472984 | DOI:10.1038/s41598-026-63141-7

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Radiological mass effect and neurological status are associated with mortality after burr-hole drainage for chronic subdural hematoma: a 10-year cohort study

Neurosurg Rev. 2026 Jul 20;49(1):484. doi: 10.1007/s10143-026-04405-8.

ABSTRACT

Chronic subdural hematoma (CSDH) is increasingly common in older adults and in patients receiving antithrombotic therapy. Although burr-hole drainage is generally safe and effective, perioperative mortality remains a concern, and reliable preoperative predictors are incompletely defined. We aimed to identify independent preoperative predictors of in-hospital mortality after burr-hole drainage for CSDH, with explicit characterization of causes of death, comorbidity burden, and the discriminative performance of candidate predictors. This single-center retrospective cohort study included 121 consecutive adult patients surgically treated for CSDH between January 2015 and December 2024. Preoperative variables included demographics, Glasgow Coma Scale (GCS) score, hematoma thickness, midline shift (MLS), cerebral edema on CT, antithrombotic use, and a comprehensive set of comorbidities (chronic kidney disease, chronic obstructive pulmonary disease, congestive heart failure, coronary artery disease, atrial fibrillation, diabetes mellitus, dementia, malignancy). Intensive care unit admission and postoperative complications were also recorded. The primary outcome was in-hospital mortality. Causes of death were systematically categorized. Associations were evaluated using Firth penalized logistic regression. Discriminative performance was assessed using receiver operating characteristic (ROC) analysis with bootstrap confidence intervals. A prespecified exploratory interaction analysis between cerebral edema and significant midline shift was performed. In-hospital mortality was 12.4% (15/121). The principal cause of death was cerebral herniation (9/15, 60.0%); extracranial complications (respiratory, septic, cardiac) accounted for 6/15 (40.0%). In the original multivariable Firth model, GCS ≤ 13 (adjusted OR 11.71, 95% CI 2.82-48.61, p < 0.001) and cerebral edema (adjusted OR 8.90, 95% CI 1.93-40.98, p = 0.005) were independently associated with mortality. In an extended model incorporating comorbidities, chronic kidney disease (OR 23.78, p = 0.025) and congestive heart failure (OR 42.39, p = 0.043) emerged as additional independent predictors, while cerebral edema (OR 61.89, p = 0.008) and GCS ≤ 13 (OR 5.80, p = 0.032) retained their associations. Combined model discrimination was excellent (Model 1: AUC 0.920; Model 2 with comorbidities: AUC 0.958). Subgroup analysis demonstrated a marked mortality gradient: 0% in patients with neither cerebral edema nor significant midline shift (n = 59), versus 72.2% in patients with both findings (n = 18). The exploratory interaction term (cerebral edema × midline shift ≥ 5 mm) was directionally consistent with synergy but did not reach statistical significance (OR 39.19, 95% CI 0.26-∞, p = 0.152), reflecting limited statistical power. Preoperative neurological impairment and cerebral edema are independently associated with in-hospital mortality after burr-hole drainage for CSDH. The coexistence of cerebral edema and significant midline shift identifies a clinically recognizable high-risk phenotype that may warrant heightened perioperative attention. Renal and cardiac comorbidities further contribute to mortality risk. These findings are hypothesis-generating and require validation in larger, prospective cohorts before incorporation into clinical risk stratification.Clinical trial number: not applicable.

PMID:42472980 | DOI:10.1007/s10143-026-04405-8