Category: Nevin Manimala

Basic Clin Pharmacol Toxicol. 2026 Jun;138(6):e70249. doi: 10.1111/bcpt.70249.

ABSTRACT

A French signal detection study identified an association between sulfonamide diuretics use, particularly furosemide, and lower Parkinson’s disease (PD) risk. Our aim was to confirm this association in a Finnish nationwide nested case-control study (FINPARK), primarily in an indication-restricted case-control study of persons with heart or renal failure. Altogether 19 568 PD cases diagnosed in 1999-2015 and 130 156 age, sex and region-matched controls were included. The case-control study restricted to those with heart or renal failure included 1222 PD cases and 4766 matched controls. Furosemide use was identified from Prescription Register (1995-2015). The main analysis considered exposure at least 3 years before the matching date (3-year lag). Additional analyses with no lag, 5- and 8-year lags were conducted. Furosemide was not associated with PD risk (adjusted OR, 95% CI 1.00, 0.87-1.15 for user-non-user comparison with 3-year lag). A statistically significant borderline association between higher exposure levels and lower PD risk was observed in comparing risk across categories of cumulative furosemide exposure (adjusted OR, 95% CI 0.80, 0.64-1.00 with 3-year lag). Our nationwide indication-restricted case-control study of persons with PD found no robust evidence on the association between furosemide use and PD risk. However, there was suggestive evidence of reduced risk for participants in the highest exposure category.

PMID:42168783 | DOI:10.1111/bcpt.70249

Med Vet Entomol. 2026 May 21. doi: 10.1111/mve.70086. Online ahead of print.

ABSTRACT

Sand flies are arthropod vectors responsible for transmitting Leishmania parasites to humans. Among them, Phlebotomus (P.) major, P. syriacus and P. neglectus are closely related sister species that play an important role in disease transmission in Türkiye. This study aimed to statistically analyse the morphological measurements of these three species and to identify reliable diagnostic characters. Seven morphometric traits were measured in both female and male specimens. Statistical analyses, including analysis of variance (ANOVA), discriminant function analysis (DFA) and principal component analysis (PCA), were performed to determine significant variables contributing to species differentiation. A total of 1729 sand flies were collected, comprising P. tobbi (44.58%), P. papatasi (21.26%), P. similis (20.30%), P. neglectus (8.50%), P. major (2.88%), P. syriacus (2.19%) and Sergentomyia (S.) fallax (0.27%). The female-to-male ratio was 1.42. ANOVA revealed significant interspecific differences (p < 0.001) in antennal, pharyngeal and genital characters. In females, P. neglectus exhibited shorter antennal segments A3 and A4 + A5, P. syriacus had the shortest pharynx (PHX), and P. major showed the longest epipharynx (EPI). In males, P. major had the longest coxite (CX), whereas P. neglectus displayed the shortest second style segment (S2) (p < 0.05). DFA confirmed clear species separation, with antennal and pharyngeal traits primarily driving differentiation in females, and genital characters being most informative in males. PCA explained 78.37% and 90.24% of the total morphometric variation in females and males, respectively, highlighting sex-specific patterns of morphological variation. Overall, these statistically supported morphometric differences provide robust diagnostic features that can complement molecular approaches, improving species identification and enhancing taxonomic resolution in sand fly vector studies.

PMID:42168762 | DOI:10.1111/mve.70086

J Ophthalmic Inflamm Infect. 2026 May 21. doi: 10.1186/s12348-026-00578-x. Online ahead of print.

ABSTRACT

BACKGROUND: Ocular toxoplasmosis is a leading cause of vision impairment and is burdened by the risk of recurrence. This study, conducted at the University Hospital of Verona, aimed to identify potential risk factors associated with disease recurrence.

MAIN BODY: A total of 86 patients were treated for ocular toxoplasmosis between 1996 and 2023, with 43 completing treatment and follow-up of at least 18 months after treatment. Patients were treated with one of two therapeutic options: either trimethoprim-sulfamethoxazole or pyrimethamine-sulfametopyrazine. Over the study period, 21 patients experienced at least one recurrence, with a median time for the first recurrence of approximately six years. The average follow-up duration was eight years, and the probability of recurrence after seven years was 58%. Sleep duration emerged as a significant risk factor, as patients who slept between six and eight hours per night had a lower likelihood of recurrence. No significant associations were found with other factors, including gender, ethnicity, country of birth, education level, smoking, alcohol consumption, age at diagnosis, autoimmune diseases, vitamin deficiencies, vaccinations, cat ownership, consumption of raw or undercooked meat, place of residence, occupational soil exposure, primary infection (IgM positive), or the affected eye’s laterality. Moderate evidence suggested a potential link between recurrences and psychological factors, such as stressful life events, lesion location, and pregnancy following the first diagnosis. Notably, women who experienced pregnancy after diagnosis had a threefold increased risk of recurrence. Regarding visual outcomes, there was modest evidence indicating that patients treated with trimethoprim-sulfamethoxazole achieved better final visual acuity compared to those treated with pyrimethamine. However, this difference was not statistically significant, and the underlying mechanism remains unclear.

CONCLUSION: The findings highlight the potential role of sleep duration in reducing recurrence risk and suggest a possible association between psychological stress, post-diagnosis pregnancy, and recurrence. Additionally, trimethoprim-sulfamethoxazole treatment may contribute to better long-term visual acuity, although further research is needed to confirm these observations.

PMID:42168755 | DOI:10.1186/s12348-026-00578-x

Geroscience. 2026 May 21. doi: 10.1007/s11357-026-02324-6. Online ahead of print.

ABSTRACT

INTRODUCTION: Physical activity may enhance cognition in older adults, yet evidence from randomized controlled trials (RCTs) on mechanistic pathways remains inconclusive.

METHODS: This single-blinded RCT examined the effects of an 8-week, online-guided, multicomponent physical activity intervention on cognitive function, resting-state functional brain connectivity (rsFC), and the gut microbiome in 92 healthy older adults (M age = 66.35). Participants were randomized to a physical activity group performing moderate-to-vigorous-intensity aerobic, coordination, and balance exercises, or to an active control group engaging in progressive muscle relaxation and listening to aging-related podcasts. The primary outcome was change in visual processing speed (items/s) from pre- to post-assessment. Secondary outcomes included changes in additional cognitive measures, rsFC, cardiorespiratory fitness (CRF), and the gut microbiome.

RESULTS: The primary outcome showed no significant between-group differences. However, exploratory analyses revealed potential improvements in inhibition (η2 = 0.061; p = 0.025) and visual memory (η2 = 0.047; p = 0.040) in the physical activity group. This group also showed a potential increase in rsFC between visual and dorsal attention networks (η2 = 0.101; p = 0.009). Visual memory gains correlated with improvements in rsFC (p = 0.013). No between-group differences were observed in CRF or gut microbiome composition.

DISCUSSION: While the primary outcome (visual processing speed) and predefined mechanistic pathways (e.g., gut microbiome composition) remained unaffected, this may partly reflect the sample’s high baseline fitness, which likely limited observable improvements. Exploratory findings suggest potential cognitive and associated rsFC benefits in memory and attention-related networks. The online format enabled a structured, scalable intervention while minimizing potential confounding from social interaction.

TRIAL REGISTRATION: https://drks.de/search/de/trial/DRKS00028022 (date of registration: 14.02.2022).

PMID:42168724 | DOI:10.1007/s11357-026-02324-6

Geroscience. 2026 May 21. doi: 10.1007/s11357-026-02280-1. Online ahead of print.

ABSTRACT

Identifying physiological sweet spots (optimal ranges for homeostasis) is essential for precision medicine. However, traditional statistical methods often rely on globally linear or locally jagged models that struggle to capture the smooth, non-linear nature of biological regulation in high-dimensional data. We present the Quantile Feature Selection Network (Q‑FSNet), a neural network-based framework that integrates quantile regression, feature selection, and uncertainty estimation to identify biomarkers with sweet spots. Unlike traditional methods, Q-FSNet learns continuous response curves without requiring a pre-specified number of change points. We further introduce Quantile Dirichlet Network (Q-DirichNet), a fully Bayesian extension that utilizes Dirichlet priors to automate feature shrinkage. Using data from the Canadian Longitudinal Study on Aging, we identified 25 metabolites with distinct homeostatic ranges for which biological age acceleration is minimized. The metabolites with sweet spots for biological aging include some derived from diet or produced by the gut microbiome; this highlights their potential for knowledge translation and public health impact. Our results, corroborated by existing literature, demonstrate that these sparse neural network-based methods offer a scalable and interpretable tool for discovering metabolic signatures of healthy aging vs. dysregulation in large-scale omics research.

PMID:42168723 | DOI:10.1007/s11357-026-02280-1

Sci Rep. 2026 May 22. doi: 10.1038/s41598-026-54428-w. Online ahead of print.

ABSTRACT

To address the shortcomings of the Grey Wolf Optimizer (GWO) in solution accuracy, convergence speed, and search capability, this paper proposes a Dynamic Multi-Strategy Grey Wolf Optimizer (DMSGWO). Based on GWO, DMSGWO introduces four improvement strategies. First, a nonlinear convergence factor strategy is adopted to better balance global exploration and local exploitation. Second, a population dynamic grouping strategy is employed to dynamically adjust the population sizes of exploration and exploitation groups during the iteration process. Third, a random position update strategy is applied to the exploration group to enhance the global exploration capability. Finally, an adaptive perturbation position update strategy is applied to the exploitation group to improve the local exploitation capability. To comprehensively evaluate the performance of DMSGWO, it is compared with GWO, four other swarm intelligence optimization algorithms, and four other improved GWO algorithms on 23 benchmark test functions and the CEC2022 test suite. The comparative results demonstrate that DMSGWO exhibits excellent solution accuracy, stability, and convergence speed. Further validation through Friedman ranking tests and Wilcoxon signed-rank tests confirms that DMSGWO ranks first in overall performance. The test results show statistically significant performance differences from the other algorithms on most test functions, and further verify the superior performance of DMSGWO. To validate the practical application value of DMSGWO, it is applied to two typical engineering design optimization problems and WSN coverage optimization problem alongside the comparative algorithms. The results show that DMSGWO can effectively handle constraints and achieve the best objective values. Thus, these results demonstrates the effectiveness and practicality of DMSGWO in solving real-world complex application problems.

PMID:42168712 | DOI:10.1038/s41598-026-54428-w

AIDS Behav. 2026 May 22. doi: 10.1007/s10461-026-05177-4. Online ahead of print.

ABSTRACT

Housing instability and homelessness remain pervasive structural determinants of poor HIV outcomes in the United States. People living with HIV (PLWH) who experience homelessness face intersecting barriers, including stigma, behavioral comorbidities, and fragmented care systems, that undermine antiretroviral therapy adherence and viral suppression (VS). To quantify the impact of homelessness on viral suppression, we conducted a systematic review and meta-analysis of U.S.-based studies published from 2014 to 2024. Following PRISMA 2020 guidelines, PubMed, SCOPUS, and Web of Science were searched using controlled vocabulary and keywords related to HIV, viral suppression, and homelessness. Eligible studies included quantitative and/or qualitative analyses of PLWH reporting associations between housing instability or homelessness and VS outcomes. Study suitability was assessed using an adapted GRACE checklist, and random-effects meta-analysis was conducted in STATA v19 to pool adjusted odds ratios (aORs), with heterogeneity assessed via Q and I² statistics. Of 603 identified studies, 43 met inclusion criteria and 21 contributed to the meta-analysis (total n = 46,291). Individuals experiencing homelessness had significantly lower odds of VS compared with housed counterparts (pooled OR = 0.38, 95% CI 0.33-0.45), with moderate to high heterogeneity (I² = 74.2%) but consistent directionality across definitions of housing instability and analytic adjustments. No evidence of publication bias was detected (Egger’s p = 0.125). Thematic synthesis identified five primary pathways linking homelessness to reduced VS: disrupted ART adherence and retention; psychosocial stressors such as stigma and depression; syndemic interactions with substance use and mental illness; stress-related immune dysregulation; and broader structural inequities including poverty, criminalization, and neighborhood disadvantage. Overall, findings demonstrate a robust and persistent association between homelessness and lower odds of HIV viral suppression, underscoring housing as a fundamental social determinant of health. Integrated, low-barrier housing interventions paired with behavioral health and case management services show the greatest promise for improving viral suppression and advancing equity. Addressing housing instability of any severity is essential to achieving the goals of the Ending the HIV Epidemic initiative and sustaining Undetectable = Untransmittable (U = U) outcomes.

PMID:42168709 | DOI:10.1007/s10461-026-05177-4

Commun Med (Lond). 2026 May 21;6(1):298. doi: 10.1038/s43856-026-01612-8.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors have transformed melanoma therapy, yet only a subset of patients achieve durable responses. Gut microbes have been linked to response, but reported biomarkers vary across studies. We aim to identify reproducible microbial features and test their generalizability across cohorts and treatment settings.

METHODS: We reprocessed stool metagenomic sequencing data from 15 melanoma cohorts (763 samples from 484 individuals), including 12 cohorts treated with immune checkpoint inhibitors alone and 3 trials combining immune checkpoint inhibitors with fecal microbiota transplantation. Using a unified analysis pipeline, we profiled microbial species, metabolic pathways, and biosynthetic gene clusters, and analyzed their associations with treatment response using Tweedie regression, random-effects meta-analysis, and multimodal integration with leave-one-dataset-out validation.

RESULTS: Here, we show that responders in immune checkpoint inhibitor-only cohorts are enriched for several short-chain fatty acid-producing commensals, whereas non-responders show higher abundance of taxa associated with disrupted gut communities. In fecal microbiota transplantation plus immune checkpoint inhibitor trials, response associates with distinct communities and shifts in amino-acid, nucleotide and cofactor metabolism. Across cohorts, multiview prediction models repeatedly select gene clusters linked to antimicrobial peptides and surface polysaccharides, but cross-study discrimination remains modest.

CONCLUSIONS: Microbiome signatures of response are treatment-context dependent and are not captured by a single universal species. These harmonized findings prioritize microbial taxa and functions for mechanistic studies and future microbiome-informed interventions.

PMID:42168704 | DOI:10.1038/s43856-026-01612-8

Obes Surg. 2026 May 21. doi: 10.1007/s11695-026-08717-y. Online ahead of print.

ABSTRACT

INTRODUCTION: Single-anastomosis duodenoileal bypass with sleeve gastrectomy (SADI-S) was developed as a simplified alternative to biliopancreatic diversion with duodenal switch but remains technically demanding. Ligation of the right gastric artery (RGA) may facilitate duodenal mobilization and reduce anastomotic tension; however, concerns persist regarding anastomotic perfusion and vagal fiber disruption. This study aimed to assess the safety and physiological effects of RGA ligation, including its potential impact on vagal function, using pancreatic polypeptide (PP) as an indirect marker, as well as gastric and gallbladder emptying.

METHODS: In this prospective double-blind randomized exploratory trial conducted at a single public bariatric center, patients undergoing SADI-S were randomized to RGA ligation (n = 10) or no ligation (n = 9). Participants underwent clinical evaluation, liquid mixed-meal tolerance tests to assess glucose and PP dynamics, gastric emptying scintigraphy, and hepatobiliary scintigraphy before and 12 months after surgery.

RESULTS: Clinical outcomes were comparable between groups, with no differences in postoperative morbidity or mortality. After surgery, both groups exhibited similar rates of symptoms consistent with dumping syndrome during the mixed meal test, along with reduced PP secretion. No correlation was observed between dumping symptoms and PP levels. Gastric emptying and hepatobiliary scintigraphy revealed no significant differences between groups before or after surgery. No symptoms suggestive of biliary reflux were reported.

CONCLUSION: In this prospective randomized study, no significant differences were observed between groups across the evaluated outcomes. RGA ligation was not associated with adverse clinical or physiological effects compared to no ligation within the limitations of this cohort. However, the small sample size limits statistical power and the ability to exclude clinically meaningful differences; therefore, these findings should be considered exploratory and require confirmation in larger studies.

PMID:42168687 | DOI:10.1007/s11695-026-08717-y

Sci Rep. 2026 May 21. doi: 10.1038/s41598-026-53315-8. Online ahead of print.

ABSTRACT

Hybrid electric vehicle (HEV) powertrain systems exhibit complex dynamic and nonlinear characteristics due to the coupling effects among mechanical, electrical, and thermal subsystems. Traditional multivariate statistical process monitoring (MSPM) methods based on the time lag shift method (TLSM) may suffer from redundant information problems where historical data not used for prediction can contaminate the extracted features and reduce fault detection sensitivity. To address this limitation, this paper proposes a kernel dynamic orthonormal subspace analysis (KDOSA) method for monitoring HEV powertrain faults. The proposed method extends the OSA framework to the kernel feature space using Gaussian kernel functions, aiming to capture nonlinear dependencies while maintaining orthogonal separation between dynamic and static components. By decomposing real-time data into dynamic and static subspaces in the reproducing kernel Hilbert space, KDOSA is designed to mitigate the redundant information problem inherent in TLSM-based kernel methods such as dynamic kernel PCA. A comprehensive monitoring framework is developed with [Formula: see text] indices for both dynamic and static subspaces, providing fault detection capability and diagnostic information about fault origins. The effectiveness of the proposed method is examined through numerical simulations and real-world HEV powertrain experiments. Experimental results demonstrate that KDOSA achieves favorable fault detection performance with performance index (PI) values exceeding 95% across all test scenarios without triggering false alarms in the tested cases, showing improved performance compared with existing OSA-based nonlinear dynamic methods.

PMID:42168681 | DOI:10.1038/s41598-026-53315-8