Nevin Manimala

Front Immunol. 2026 Mar 6;17:1761515. doi: 10.3389/fimmu.2026.1761515. eCollection 2026.

ABSTRACT

BACKGROUND: Long-term antigen-specific data in PMN among Chinese populations remain limited. This study evaluated six target antigens and their clinical significance during extended follow-up.

METHODS: We retrospectively analyzed 132 treatment-naïve PMN patients diagnosed by biopsy (2010-2018) and followed for a median of 62.9 months. Renal tissue expression of PLA2R, THSD7A, NELL-1, PCDH7, EXT1, and EXT2 was assessed by immunohistochemistry, and serum anti-PLA2R antibodies were measured by ELISA. Associations between antigen profiles and 5-year outcomes (remission, renal survival, malignancy) were evaluated.

RESULTS: PLA2R was the predominant antigen (84.1%), followed by THSD7A (5.3%) and NELL-1 (0.76%); no PCDH7, EXT1, or EXT2 positivity was detected. PLA2R-negative patients were more often female (71.4% vs. 36.0%, P = 0.003), with better renal function and more frequent C1q deposition (38.1% vs. 13.5%, P = 0.016). Serum anti-PLA2R antibodies were detected in 55.3% of patients and strongly correlated with tissue PLA2R positivity (AUC = 0.851; optimal cutoff ≥17.47 RU/mL). Baseline antibody titers were not associated with remission (P = 0.573). During 5-years follow-up, 42.4% achieved CR, 36.4% PR, and 21.2% had NR, with an estimated 5-year renal survival rate of 81.95%. No malignancy events were observed among the seven THSD7A-positive patients or the single NELL-1-positive patient in this cohort. Statistical power for rare antigen subgroups was limited.

CONCLUSIONS: This >5-year Chinese PMN cohort provides the first comprehensive analysis of six target antigens. PLA2R remains predominant, while PLA2R-negative patients distinct immunopathologic features yet favorable long-term outcomes. A population-specific anti-PLA2R cutoff showed good diagnostic performance for predicting tissue antigen deposition. Rare antigens were infrequent and their malignancy associations require cautious interpretation. These findings provide long-term antigen-specific data supporting antigen-guided, population-adapted precision management of PMN.

PMID:41869300 | PMC:PMC13002824 | DOI:10.3389/fimmu.2026.1761515

J Am Stat Assoc. 2026 Mar 17. doi: 10.1080/01621459.2026.2637894. Online ahead of print.

ABSTRACT

While deep neural networks (DNNs) are used for prediction, inference on DNN-estimated subject-specific means for categorical or exponential family outcomes remains underexplored. We address this by proposing a DNN estimator under generalized nonparametric regression models (GNRMs) and developing a rigorous inference framework. Unlike existing approaches that assume independence between estimation errors and inputs to establish the error bound, a condition often violated in GNRMs, we allow for dependence and our theoretical analysis demonstrates the feasibility of drawing inference under GNRMs. To implement inference, we consider an Ensemble Subsampling Method (ESM) that leverages U-statistics and the Hoeffding decomposition to construct reliable confidence intervals for DNN estimates. We show that, under GNRM settings, ESM enables model-free variance estimation and accounts for heterogeneity among individuals in the population. Through simulations under nonparametric logistic, Poisson, and binomial regression models, we demonstrate the effectiveness and efficiency of our method. We further apply the method to the electronic Intensive Care Unit (eICU) dataset, a large scale collection of anonymized health records from ICU patients, to predict ICU readmission risk and offer patient-centric insights for clinical decision making.

PMID:41869283 | PMC:PMC13003751 | DOI:10.1080/01621459.2026.2637894

J Am Stat Assoc. 2026 Feb 24. doi: 10.1080/01621459.2025.2587321. Online ahead of print.

ABSTRACT

In the past decade, the increased availability of genome-wide association studies summary data has popularized Mendelian Randomization (MR) for conducting causal inference. MR analyses, incorporating genetic variants as instrumental variables, are known for their robustness against reverse causation bias and unmeasured confounders. Nevertheless, classical MR analyses using summary data may still produce biased causal effect estimates due to the winner’s curse and pleiotropy issues. To address these two issues and establish valid causal conclusions, we propose a unified robust Mendelian Randomization framework with summary data, which systematically removes the winner’s curse and screens out invalid genetic instruments with pleiotropic effects. Unlike existing robust MR literature, our framework delivers valid statistical inference on the causal effect without requiring the genetic pleiotropy effects to follow any parametric distribution or relying on perfect instrument screening property. Under appropriate conditions, we demonstrate that our proposed estimator converges to a normal distribution, and its variance can be well estimated. We demonstrate the performance of our proposed estimator through Monte Carlo simulations and two case studies. The corresponding R package MRcare is available at https://chongwulab.github.io/MRcare/. Supplementary materials for this article are available online, including a standardized description of the materials available for reproducing the work.

PMID:41869282 | PMC:PMC13004071 | DOI:10.1080/01621459.2025.2587321

Environ Epidemiol. 2026 Mar 19;10(2):e467. doi: 10.1097/EE9.0000000000000467. eCollection 2026 Apr.

ABSTRACT

BACKGROUND: Improving air quality requires addressing sector-specific air pollution (SSAP). This study examined the relationship between long-term SSAP and Alzheimer’s disease and dementia mortality in Canada, and whether associations were modified by neighborhood greenness, educational attainment, and material deprivation.

METHODS: We used data from the 2006 Canadian Census Health and Environment Cohort with mortality follow-up through 2019, linked to the Canadian Vital Statistics-Death database. Annual exposures to ambient air pollutants (i.e., PM_2.5, SO₂, NO₂, and O₃) from multiple sectors were estimated using the Global Environmental Multiscale-Modelling Air Quality and Chemistry model (10 km resolution) with sector-specific contributions anchored to 2015 emissions profiles. Quantile g-computation models were used to estimate hazard ratios (HRs) for Alzheimer’s disease and dementia per quartile increase in SSAP.

RESULTS: Alzheimer’s disease mortality was most strongly associated with SSAP from residential fuel combustion (RES: HR = 1.29; 95% CI: 1.16, 1.43), and was also positively associated with emissions from on-road transportation (HR = 1.22; 95% CI: 1.12, 1.32), ore and mineral industries (ORE: HR = 1.17, 95% CI: 1.10, 1.24), air-marine-rail transportation (HR = 1.12; 95% CI: 1.06, 1.18), and manufacturing (MAN: HR = 1.06; 95% CI: 1.01, 1.11), while inverse associations were observed for the oil and gas sector (HR = 0.85; 95% CI: 0.81, 0.88). Dementia mortality was positively associated with oil and gas (HR = 1.06; 95% CI: 1.03, 1.09), and inversely associated with air-marine-rail transportation (HR = 0.88; 95% CI: 0.85, 0.92) and ORE (HR = 0.89; 95% CI: 0.85, 0.92). Associations were generally stronger in lower greenness areas and among individuals with lower educational attainment, although heterogeneity by sector was observed.

CONCLUSION: SSAP mixtures were associated with Alzheimer’s disease and dementia mortality in Canada. The direction and magnitude of associations varied by sector and by environmental and sociodemographic context, supporting the value of targeted, sector-specific mitigation strategies to reduce neurodegenerative mortality risk.

PMID:41869280 | PMC:PMC13004229 | DOI:10.1097/EE9.0000000000000467

Open Res Eur. 2026 Feb 23;6:56. doi: 10.12688/openreseurope.22009.1. eCollection 2026.

ABSTRACT

BACKGROUND: Generative artificial intelligence is spreading rapidly across academic research, yet its role in the development and maintenance of research software remains insufficiently characterized.

METHODS: A six week, institutional review board approved, anonymized online survey of faculty and research staff at a large research intensive university in late 2024 (n = 251). Branching survey questions distinguished general users of research software from those who create or maintain it. Quantitative associations were examined using chi square or Fisher’s exact tests, and free text descriptions of generative AI use in software development were analyzed thematically.

RESULTS: Overall, 29% of respondents reported using generative AI for at least one research task. Within the subsample of active research software developers, 33% reported using generative AI for software development and 51% indicated continued or planned future use. No statistically significant associations were found for age, recency of highest degree, or external funding. Gender was significantly associated with generative AI use for software development, with higher uptake among men than women (41% versus 15%; χ ²(1)=5.03, p=.025). Reported generative AI uses clustered around four practical roles: generating initial code and queries, supporting debugging and testing, transforming data or commands via natural language prompts, and reducing cognitive burden in repetitive or complex tasks.

CONCLUSIONS: At a large research intensive university, generative AI adoption in research software development is already common among active developers and is expected to expand. The observed gender disparity signals a potential equity risk as tool assisted development becomes normalized. These findings provide an empirical baseline for multi institution replication and for evaluating how generative AI may reshape the organization and distribution of research software work.

PMID:41869273 | PMC:PMC13000399 | DOI:10.12688/openreseurope.22009.1

Cureus. 2026 Feb 18;18(2):e103865. doi: 10.7759/cureus.103865. eCollection 2026 Feb.

ABSTRACT

BACKGROUND: Hypokalemic periodic paralysis (HPP) presenting as acute quadriparesis is a neuromuscular emergency. While its etiology is described in general wards, its severe “critical care phenotype” in the intensive care unit (ICU) remains poorly characterized. We aimed to define this phenotype by analyzing the clinical profile, etiological spectrum, and predictors of life-threatening severity.

METHODS: A retrospective study was conducted of 12 patients (nine male, three female; median age: 31.5 years) admitted to a tertiary ICU (2015-2021) with acute quadriparesis and hypokalemia (median potassium: 1.75 mmol/L). We analyzed management and outcomes and compared patients requiring mechanical ventilation (MV+) with those who did not (MV-) using distribution-appropriate statistical methods to identify factors associated with respiratory failure.

RESULTS: All patients presented with acute flaccid quadriparesis and areflexia. Five (41.7%) required invasive mechanical ventilation, defining a severe “critical care phenotype.” A secondary cause was identified in eight patients (66.7%), including thyrotoxicosis (n=2), distal renal tubular acidosis (n=2), primary hyperaldosteronism, sepsis, dengue fever, and gastroenteritis. Critically, the need for mechanical ventilation was not associated with the degree of hypokalemia (MV+ 1.7 mmol/L vs. MV- 1.7 mmol/L, p=0.87) or other baseline characteristics. With potassium supplementation and targeted therapy, 11 patients (91.7%) achieved complete neurological recovery; one death occurred in a patient with sepsis.

CONCLUSION: HPP in the ICU represents a distinct critical care phenotype with a high risk of respiratory failure. As the requirement for mechanical ventilation was not predicted by admission potassium levels, vigilant monitoring for respiratory muscle fatigue is warranted in all cases. Favorable outcomes are achievable with prompt correction and treatment of the underlying cause, reinforcing that HPP is a reversible ICU emergency.

PMID:41869263 | PMC:PMC13004642 | DOI:10.7759/cureus.103865

Cureus. 2026 Feb 17;18(2):e103778. doi: 10.7759/cureus.103778. eCollection 2026 Feb.

ABSTRACT

Background Heart rate variability (HRV) represents beat-to-beat fluctuations in heart rate arising from the dynamic balance between sympathetic and parasympathetic nervous system activity. Altered HRV reflects autonomic dysregulation and has been reported across several psychiatric disorders, including schizophrenia, where it may contribute to cardiovascular risk and cognitive dysfunction. Aim The aim of this study was to compare the time-domain and frequency-domain heart rate variability parameters between patients with schizophrenia and their first-degree relatives and to analyze the correlation between heart rate variability indices and cognitive performance within an endophenotypic framework. Methods This healthcare-based cross-sectional observational study was performed at the Kalinga Institute of Medical Sciences in Bhubaneswar, India, from October 2023 to October 2024. Fifteen clinically stable subjects diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria and fifteen age- and gender-matched first-degree relatives without schizophrenia were included. 5-minute resting HRV was assessed once at a single time point using a standardized three-lead electrocardiogram (ECG) after a 10-minute adaptation period. Time-domain parameters measured overall variability, whereas frequency-domain parameters analyzed sympathetic and parasympathetic modulation. Cognitive functioning was assessed using the Wechsler Abbreviated Scale of Intelligence (WASI). To compare the groups, we used the Mann-Whitney U test, and to look for associations, we used Spearman’s rank correlation. Results Time-domain heart rate variability parameters were comparable between patients with schizophrenia and first-degree relatives (p > 0.05). In the frequency domain, the low frequency (LF) to high frequency (HF) ratio (LF/HF) was significantly higher in patients with schizophrenia than in their relatives (median 1.57 vs. 0.79; p = 0.041), indicating relative sympathetic predominance. Absolute LF, HF, and very-low-frequency (VLF) power values did not differ significantly between groups (p > 0.05). Within the schizophrenia group, the LF/HF ratio showed a significant positive correlation with WASI scores (r = 0.701, p = 0.004). Conclusion Schizophrenia is associated with altered autonomic regulation characterized by an increased LF/HF ratio, suggesting sympathovagal imbalance, while time-domain HRV measures remain comparable to those of first-degree relatives. The observed association between autonomic modulation and cognitive performance supports the relevance of HRV as a potential physiological marker linked to cognitive functioning in schizophrenia. Further longitudinal and genetic studies are required to clarify its role as a potential endophenotypic trait.

PMID:41869260 | PMC:PMC13001836 | DOI:10.7759/cureus.103778

Cureus. 2026 Feb 19;18(2):e103910. doi: 10.7759/cureus.103910. eCollection 2026 Feb.

ABSTRACT

INTRODUCTION: Feedback is fundamental to Emergency Medicine (EM) education; however, residents frequently encounter obstacles when attempting to obtain and implement it. Learner-driven feedback strategies may strengthen feedback culture; however, methods to develop feedback literacy, the ability of learners to understand, value, and effectively use feedback, remain largely underexplored. We developed and evaluated a workshop to prepare EM residents to actively engage in the feedback process.

METHODS: A prospective pre-post survey was conducted at a single academic EM residency. Postgraduate year (PGY) 1-3 residents participated in a 1.5-hour interactive, practice-based workshop that included didactic components and hands-on activities focused on clarifying expectations, goal setting, and receiving feedback. Residents completed pre- and post-surveys using a five-point Likert scale to assess comfort. Knowledge retention was assessed one week later with a 15-question assessment. Pre- and post-surveys were evaluated by paired t-test analysis.

RESULTS: Thirty-one residents completed the pre-survey, and 30 completed both the post-survey and the knowledge assessment. Statistically significant improvements were observed in resident comfort for clarifying expectations (Δ = 0.67; p < 0.001), creating goals (Δ = 0.90; p < 0.001), comfort receiving feedback (Δ = 0.33; p = 0.01), seeking feedback (Δ = 0.40; p = 0.02), creating feedback action plans (Δ = 1.70; p < 0.001), reflecting on and implementing feedback (Δ = 0.40; p < 0.001), and recognizing feedback as the learner’s responsibility (Δ = 0.53; p = 0.002). Perceptions of feedback’s importance and impact on patient care remained high and unchanged. Knowledge retention among residents was high, with 91.1% of items (247/270) answered correctly. The strongest performance was observed in the domains of Expectations (87/90, 96.7%) and Goal Setting (88/90, 97.8%), while the Feedback Action Plan domain showed the lowest scores (73/90, 81.1%). Conclusion: A structured workshop significantly improved EM residents’ comfort, knowledge, and skills in engaging with feedback. Early introduction of learner‑driven strategies may strengthen feedback culture and support professional development. This learner‑centered model represents a meaningful shift from traditional faculty‑directed feedback frameworks by placing primary ownership of the process in the hands of learners. Further research is needed to assess long‑term retention, clinical application, and the role of faculty development.

PMID:41869253 | PMC:PMC13005656 | DOI:10.7759/cureus.103910

Cureus. 2026 Feb 17;18(2):e103803. doi: 10.7759/cureus.103803. eCollection 2026 Feb.

ABSTRACT

BACKGROUND: Managing such fractures is a difficult challenge in developing countries. Many kinds of internal fixation devices, including recently developed plates with screws, have been applied to treat these complex fractures. In this study, dual plating of bicondylar proximal tibia fractures is done to assess the outcome of the patients in terms of knee range of motion, fracture union, and reduction, which dictates the functional outcome.

MATERIALS AND METHODS: A prospective study was carried out to assess the outcomes of proximal tibial fractures in the department of orthopaedics from May 2022 to April 2025. A total of 30 patients with bicondylar proximal tibia fractures were operated on. The patients were monitored for an average of six months. Data were entered into a spreadsheet and analyzed using descriptive statistics. Continuous variables were expressed as mean ± standard deviation, while categorical variables were summarized as frequencies and percentages.

RESULT: Mean time to fracture union was 3.81 ± 0.82 months. The mean range of motion of the knee joint was 134.5 ± 11.09 degrees (range: 0° to 10° for extension and range: 0° to 120°-150° for flexion). At the last follow-up, the mean Rasmussen’s functional grading score was 27.96 ± 2.95. Five (16.67)% patients in the current study experienced complications.

CONCLUSION: Rigid and stable fixation with proper articular reduction, maintaining the soft tissue integrity, is the most important determinant for outcome in the treatment of Schatzker V and VI proximal tibia fractures, which can be achieved with bi-column fixation with locking plates using the dual approach.

PMID:41869248 | PMC:PMC13002921 | DOI:10.7759/cureus.103803

Cureus. 2026 Feb 17;18(2):e103800. doi: 10.7759/cureus.103800. eCollection 2026 Feb.

ABSTRACT

Background Idiopathic inflammatory myositis represents heterogeneous systemic autoimmune disorders characterized by progressive proximal muscle weakness and multisystem manifestations. Traditional corticosteroid therapy precipitates substantial adverse effects during prolonged administration. This prospective, open-label, comparative observational study evaluated clinical outcomes associated with mycophenolate mofetil combination therapy versus corticosteroid monotherapy, examining muscle strength improvements, inflammatory biomarker profiles, pulmonary function parameters, and comparative corticosteroid dose requirements. Methodology This prospective observational study enrolled 40 consecutive participants with a confirmed idiopathic inflammatory myositis diagnosis through non-probability convenience sampling. Group 1 (n=17) received prednisolone monotherapy (mean 17.9±6.71 mg/day); Group 2 (n=23) received mycophenolate mofetil combination therapy (mean 1.19±0.259 g/day) with low-dose corticosteroids. Sample size calculation employed pooled standard deviation σ=16.77 points and minimum clinically significant difference δ=5 points. Participants completed a 24-week observation with assessments at baseline, six, 12, and 24 weeks. The primary outcome measured was Manual Muscle Testing-8 score changes; secondary outcomes encompassed inflammatory biomarkers and pulmonary function parameters. Results Baseline Manual Muscle Testing-8 scores demonstrated significant between-group differences (79.7±6.86 versus 71.3±8.07, p=0.0017). Analysis of covariance adjusting for baseline disease severity demonstrated persistent differences (adjusted mean difference: 4.23 points, 95% CI: 0.97-7.49, p=0.0127). Within-group analysis revealed that mycophenolate mofetil-treated participants achieved mean improvements of 12.5±10.42 points, representing a 17.53±14.61% increase, compared to 3.0±2.84 points, representing a 3.77±3.56% increase in corticosteroid monotherapy (p=0.0004 for percentage comparison). Inflammatory biomarkers demonstrated comparable reductions: creatinine phosphokinase decreased 31.69±13.11% in Group 1 versus 32.85±14.34% in Group 2 (p=0.8022). Pulmonary function assessment in participants with interstitial lung disease (n=11) documented forced vital capacity improvements of 12.26±6.00% versus 11.86±5.58%. Corticosteroid dose reduction of 34.08±19.10% was observed in Group 1 (17.9 to 11.8 mg/day, p<0.0001). Safety surveillance documented no serious adverse events, treatment discontinuations, or deaths, with the composite metabolic adverse event rate significantly lower in mycophenolate combination therapy (8.70% versus 41.18%, p=0.0166). Conclusion This prospective observational study provides preliminary evidence that mycophenolate mofetil combination therapy was associated with statistically significant muscle strength improvements and inflammatory biomarker reductions while being administered with substantially lower cumulative corticosteroid doses compared to prednisolone monotherapy. However, non-randomized treatment allocation with significant baseline disease severity differences introduces confounding by indication, precluding definitive causal inference. These hypothesis-generating observations warrant confirmation through adequately powered, multicenter randomized controlled trials before mycophenolate mofetil can be definitively recommended in evidence-based therapeutic algorithms.

PMID:41869239 | PMC:PMC13002546 | DOI:10.7759/cureus.103800