Tag: nevin manimala

Nat Med. 2026 Feb 2. doi: 10.1038/s41591-025-04156-x. Online ahead of print.

ABSTRACT

Routine adolescent health check-ups can support healthy development and well-being, but evidence on the feasibility, acceptability and effectiveness of contextually relevant comprehensive check-ups in low- and middle-income settings is limited. We conducted a hybrid implementation-effectiveness study incorporating a mixed-methods pre-post design of Y-Check, a comprehensive health check-up intervention in Zimbabwe, as part of a multicountry study developed and coordinated by the World Health Organization. Eligible participants were 10-19-year-old adolescents attending school or community venues. We used self-administered digital questionnaires, provider-led clinical tests and nurse reviews to screen for 25 conditions/behaviors. We provided health promotion, on-site care and referral to relevant providers. From October 2022 to September 2023, 2,097 adolescents were enrolled, of whom 1,843 (87.9%) were seen at 6 months. The primary outcome of appropriate care and/or referral(s) for all identified issues was achieved for 70.8% (95% confidence interval: 68.7-72.9%) of 1,865 participants with at least one issue. At follow-up, there were improvements in nutrition, health-related quality of life, self-esteem, behaviors and educational outcomes. The intervention was feasible and largely acceptable. Uptake of referral services varied by issue. Y-Check cost US$47 per participant. Through Y-Check, we identified untreated conditions and risk behaviors and successfully treated and linked adolescents to services. Here we provide evidence on the potential of the intervention to positively impact health and well-being.

PMID:41629426 | DOI:10.1038/s41591-025-04156-x

Nat Med. 2026 Feb 2. doi: 10.1038/s41591-025-04181-w. Online ahead of print.

ABSTRACT

Retrospective studies suggest that early time-of-day (ToD) infusions of immunochemotherapy may improve efficacy. However, prospective randomized controlled trials are needed to validate it. In this randomized phase 3 LungTIME-C01 trial, 210 patients with treatment naive stage IIIC-IV nonsmall cell lung cancer (NSCLC) lacking driver mutations were randomly assigned in a 1:1 ratio to either an early or late ToD group, defined by the administration of the first four cycles of an anti-PD-1 agent before or after 15:00 h. The primary endpoint was progression-free survival (PFS), while secondary endpoints included overall survival (OS) and objective response rate (ORR). After a median follow-up of 28.7 months, the median PFS was 11.3 months (95% confidence interval (CI) = 9.2-13.4) in the early ToD group and 5.7 months (95% CI = 5.2-6.2) in the late ToD group, corresponding to a hazard ratio (HR) for earlier disease progression of 0.40 (95% CI = 0.29-0.55; P < 0.001). The median OS was 28.0 months (95% CI = not estimable (NE)-NE) in the early ToD group and 16.8 months (95% CI = 13.7-19.9) in the late ToD group, corresponding to an HR of an earlier death of 0.42 (95% CI = 0.29-0.60; P < 0.001). Treatment-related adverse events were consistent with the established safety profile, with no new safety signals observed. No significant differences in immune-related adverse events were observed between the two groups. Over the first four cycles, morning circulating CD8⁺ T cells increased in the early ToD group, whereas they declined in the late ToD group (P < 0.001). Furthermore, the ratio of activated (CD38⁺ HLA-DR⁺) versus exhausted (TIM-3⁺PD-1⁺) CD8⁺ T cells was higher in the early ToD group (P < 0.001) compared with the late ToD group (P < 0.001). In summary, our study indicates that early ToD immunochemotherapy substantially improves PFS and OS and is associated with enhanced antitumor CD8⁺ T cell characteristics compared with late ToD treatment. ClinicalTrials.gov registration: NCT05549037 .

PMID:41629425 | DOI:10.1038/s41591-025-04181-w

Sci Rep. 2026 Feb 2. doi: 10.1038/s41598-026-38210-6. Online ahead of print.

ABSTRACT

Residual cholesterol (RC) is associated with an increased risk of atherosclerosis. High levels of RC have been shown to be associated with unstable plaque in healthy populations. However, the association between RC and unstable carotid plaque in specific populations with carotid stenosis has not been investigated. In this study, the association between RC and unstable carotid plaque in patients with carotid stenosis was investigated. Carotid ultrasound was used to determine the stability of carotid plaque. The relationship between RC levels and unstable carotid plaque was analyzed using logistic regression. The relationship between RC levels and unstable carotid plaque was assessed according to the degree of carotid stenosis. In addition, the predictive efficacy of RC levels for unstable plaques was determined by receiver operating characteristic (ROC) curves. A total of 507 patients with carotid stenosis were included in the study. 271 with stable carotid plaque and 236 with unstable carotid plaque. Multiple logistic regression analysis revealed that RC (OR, 1.44 [95% CI 1.09-1.91]) remained a risk factor for carotid artery unstable plaque after adjusting for statistically significant variables identified via LASSO regression. The OR was significantly greater for severe stenosis (OR, 2.16 [95% CI 1.49-3.15]) than for mild-moderate stenosis (OR, 1.03 [95% CI 1.00-1.07]). The area under the curve (AUC) of the RC in patients with unstable carotid plaque was 0.694. The cutoff value of the RC was 0.435 mmol/L. RC levels were significantly associated with unstable carotid plaque in patients with carotid stenosis. The association was stronger in severe stenosis than in mild-moderate stenosis, and patients with carotid stenosis whose RC level was greater than 0.435 mmol/L had an increased risk of developing unstable plaque.

PMID:41629388 | DOI:10.1038/s41598-026-38210-6

Sci Rep. 2026 Feb 2. doi: 10.1038/s41598-025-33630-2. Online ahead of print.

ABSTRACT

Vulvar Lichen Sclerosus (VLS) is a chronic inflammatory dermatosis of unknown etiology affecting the external genitalia. In pediatric patients, it can lead to significant discomfort and progressive structural changes in tissues. In recent years, there has been increasing interest in the participation of immune checkpoints and inflammatory mediators in the pathogenesis of chronic diseases, including VLS. Immune checkpoints, such as PD-1, PD-L1, CTLA-4, CD200, and CD200R, play a crucial role in modulating the immune response and may serve as potential diagnostic markers and therapeutic targets. This study aimed to evaluate the expression of PD-1, PD-L1, CTLA-4, CD200, and CD200R molecules on CD4+ T cells, CD8+ T cells, and CD19+ B lymphocytes in prepubertal girls diagnosed with VLS. Additionally, the concentrations of their soluble forms and the levels of proinflammatory cytokines, including IL-2, IL-6, and TNF-α, in serum were determined to assess their potential as diagnostic biomarkers. The study included patients with VLS (study group) and healthy children (control group). The expression of checkpoints was analyzed using flow cytometry, while the concentrations of soluble forms and cytokines were determined using the enzyme-linked immunosorbent assay (ELISA) technique. Statistical significance tests and Spearman’s rank correlation analysis were used. Patients with VLS showed markedly higher serum C-reactive protein (CRP) levels compared with healthy controls (49.99 ± 6.09 mg/L vs. 2.70 ± 0.96 mg/L, p < 0.001). A significant increase in checkpoint expression was observed on lymphocyte subsets, including CD4+ T cells expressing PD-1 (4.90 ± 1.67% vs. 0.85 ± 0.56%, p < 0.001) and CTLA-4 (11.58 ± 4.70% vs. 0.96 ± 0.48%, p < 0.001), as well as CD8+ T cells expressing PD-1 (17.31 ± 4.81% vs. 0.76 ± 0.67%, p < 0.001) and CD19+ B cells expressing PD-L1 (16.10 ± 9.50% vs. 1.41 ± 0.45%, p < 0.001). Soluble checkpoint molecules were consistently elevated, for example, sPD-1 (26.69 ± 3.88 pg/mL vs. 4.40 ± 0.75 pg/mL, p < 0.001) and sCTLA-4 (43.96 ± 3.77 pg/mL vs. 5.09 ± 1.09 pg/mL, p < 0.001). Similarly, cytokine levels were significantly increased in VLS patients, including interleukin-2 (28.80 ± 6.36 pg/mL vs. 4.32 ± 1.33 pg/mL, p < 0.001), interleukin-6 (25.35 ± 7.52 pg/mL vs. 2.35 ± 0.78 pg/mL, p < 0.001), and tumor necrosis factor alpha (31.26 ± 3.10 pg/mL vs. 12.80 ± 1.30 pg/mL, p < 0.001). Correlation analyses confirmed significant positive associations between cytokine concentrations and checkpoint expression, highlighting their interdependence in VLS immunopathogenesis. The obtained results confirm an increased immunoactivation profile in children with VLS, characterized by elevated checkpoint expression and increased levels of proinflammatory cytokines. The studied parameters show potential as diagnostic and prognostic biomarkers, which may constitute the basis for the development of new diagnostic tools and targeted therapeutic strategies in VLS in pediatric patients.

PMID:41629379 | DOI:10.1038/s41598-025-33630-2

Sci Rep. 2026 Feb 2. doi: 10.1038/s41598-025-33191-4. Online ahead of print.

ABSTRACT

The development of environmentally friendly analytical methods is important in the current scientific landscape. This study presents an investigation into several green spectrophotometric methods for the determination of amlodipine besylate and hydrochlorothiazide in both their pure binary mixtures and pharmaceutical formulations. A spectrophotometric method is proposed for the selective determination of amlodipine besylate in the presence of hydrochlorothiazide at 366 nm, where no interference from hydrochlorothiazide was observed. Additionally, a novel five different spectrophotometric approaches were applied for the determination of hydrochlorothiazide: the dual wavelength method, first derivative method, ratio difference method, and ratio derivative method, as well as Fourier Self-Deconvolution method. Amlodipine besylate’s linearity range was 5-30 µg/mL, whereas hydrochlorothiazide’s was 3-18 µg/mL reaching limits of detection of 1.238, 0.906, 0.825, 0.540, 0.779 and 0.805 µg/mL, respectively for all the proposed methods. The proposed methods were validated in accordance with ICH international guidelines, including full statistical analysis and comprehensive environmental evaluation using multiple assessment tools as The Analytical GREEnness Calculator, the Modified Green Analytic Procedure Index, spider diagram, and green analytical selection tool.

PMID:41629378 | DOI:10.1038/s41598-025-33191-4

NPJ Aging. 2026 Feb 2. doi: 10.1038/s41514-026-00338-0. Online ahead of print.

ABSTRACT

Aging is accompanied by low-grade intestinal inflammation, shifts in gut microbiota, and impaired oxidative balance. Probiotic supplementation has been proposed to mitigate these processes, yet evidence in elderly populations remains limited. In this pilot trial, older adults received oral Lactiplantibacillus plantarum OL3246 or placebo, with assessments including fecal calprotectin and zonulin as markers of intestinal inflammation, systemic oxidative stress parameters, self-reported quality of life and mood, and gut microbiome composition analyzed by sequencing and functional profiling. L. plantarum OL3246 supplementation was well tolerated and associated with consistent improvements across clinical, biochemical, and microbial measures. Participants reported enhanced quality of life and mood, while fecal calprotectin levels declined, indicating reduced intestinal inflammation. Moreover, oxidative stress markers improved with lower AOPP, stabilization of SOD, and restoration of redox balance. Microbiome analyses showed greater diversity and enrichment of health-associated taxa. These findings indicate that Lactiplantibacillus plantarum OL3246 may support healthy aging.

PMID:41629309 | DOI:10.1038/s41514-026-00338-0

J Esthet Restor Dent. 2026 Feb 2. doi: 10.1111/jerd.70114. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the influence of various bonding protocols on the fracture resistance and failure mode of CAD/CAM-milled hybrid resin composite occlusal overlays.

MATERIALS AND METHODS: Fifty sound human premolars (n = 50) were sectioned to expose superficial dentin surrounded by enamel. Each specimen was digitally scanned and restored with a CAD/CAM-milled hybrid resin composite overlay designed in Exocad DentalCAD. The restorations were assigned to five groups (n = 10) based on the luting protocol: Group I, Calibra Ceram; Group II, SDR Flow; Group III, heated Grandio; Group IV, Panavia F2 (self-etch), and Group V, Calibra Universal (self-adhesive). All specimens underwent thermomechanical aging simulating 1 year of clinical service, followed by compressive load testing at 1 mm/min until fracture. Failure modes were examined under magnification. Statistical significance was set at p < 0.05.

RESULTS: Group III (heated Grandio) exhibited the highest mean fracture load (1728.28 ± 156.64 N), whereas Group II (SDR Flow) showed the lowest (835.49 ± 151.69 N). Groups I, IV, and V demonstrated intermediate, statistically comparable values (p > 0.05). Tukey’s HSD confirmed significant differences between Groups II and all others (p < 0.001) and between Group III and Groups IV-V (p < 0.001).

CONCLUSIONS: Bonding strategy significantly affects the mechanical performance of hybrid resin composite overlays. All tested protocols achieved clinically acceptable strength based on ISO DIS 6872, confirming milled hybrid resin overlays as a conservative and durable restorative option.

CLINICAL SIGNIFICANCE: Selecting an optimal bonding strategy, particularly using heated resin composites, can enhance the durability and fracture resistance of conservative CAD/CAM hybrid resin overlays, offering a viable minimally invasive alternative to full-coverage crowns.

PMID:41623109 | DOI:10.1111/jerd.70114

Technol Cult. 2026;67(1):173-199. doi: 10.1353/tech.2026.a980969.

ABSTRACT

Technical monitoring-the routine assessment of radio signal quality-gained unexpected significance during the Cold War. In an era marked by unreliable sources and propaganda, quantifiable technical data became especially valuable. Radio Free Europe/Radio Liberty, a major Western broadcaster subject to deliberate interference by communist states, regularly measured the audibility of its jammed signal. These recordings went beyond technical concerns: acoustic categories became tools for studying closed societies during political crises. Meanwhile, technicians across the Iron Curtain provided party officials with statistics indicating who was winning the radio war. Acoustic data thus crossed geographical, ideological, and professional boundaries. This article examines how such technical monitoring transformed sound into data, bridging engineering, intelligence, and political communication. It also situates these practices within the wider history of Cold War media and the origins of datafication, inviting parallels to today’s surveillance regimes.

PMID:41623105 | DOI:10.1353/tech.2026.a980969

Circ Cardiovasc Interv. 2026 Feb 2:e016255. doi: 10.1161/CIRCINTERVENTIONS.125.016255. Online ahead of print.

ABSTRACT

BACKGROUND: Data comparing valve systems in the valve-in-valve transcatheter aortic valve replacement field have been obtained from retrospective studies. This prespecified secondary analysis of the LYTEN randomized trial (Comparison of the Balloon-Expandable Edwards Valve and Self-Expandable CoreValve Evolut R or Evolut PRO System for the Treatment of Small, Severely Dysfunctional Surgical Aortic Bioprostheses) aims to compare the 3-year hemodynamic performance and clinical outcomes between balloon-expandable valves (BEV) SAPIEN 3/ULTRA (Edwards Lifesciences) and self-expanding valves (SEV) Evolut R/PRO/PRO+ (Medtronic) in valve-in-valve transcatheter aortic valve replacement.

METHODS: Patients with a failed small (≤23 mm) surgical valve undergoing valve-in-valve transcatheter aortic valve replacement were randomized to receive a SEV or a BEV. Patients had a clinical and valve hemodynamic (Doppler echocardiography) evaluation at 3-year follow-up. Study outcomes were defined according to VARC (Valve Academic Research Consortium)-2/VARC-3 criteria. Intended performance of the valve was defined as mean gradient <20 mm Hg, peak velocity <3 m/s, Doppler velocity index ≥0.25, and less than moderate AR.

RESULTS: Ninety-eight patients underwent transcatheter aortic valve replacement (46 BEV-SAPIEN 3/ULTRA-, 52 SEV-Evolut R-PRO-PRO+). At 3 years, patients receiving a SEV had a higher rate of intended valve performance (BEV: 27.6% versus SEV: 82.4%; P<0.001), with lower mean gradients (BEV: 20.40±9.12 versus SEV: 13.12±8.56 mm Hg; P=0.002), and larger indexed effective orifice area (BEV: 0.69±0.27 versus SEV: 0.93±0.32 cm²/m²; P=0.002). The rate of moderate aortic regurgitation was 0% in the BEV group versus 2.9% in the SEV group (P=0.582). Functional status and quality of life improved similarly in both groups. No differences were observed in the composite end point of death, stroke, or heart failure-related hospitalization (BEV: 32.6% versus SEV: 25.5%; P=0.489). Mortality was also not statistically different between groups (BEV: 23.3% versus SEV: 15.7%; P=0.375). No significant differences were observed in other adverse events.

CONCLUSIONS: In patients undergoing valve-in-valve transcatheter aortic valve replacement for failed small aortic bioprostheses, SEV demonstrated a superior valve hemodynamic performance at 3-year follow-up, with similar clinical outcomes and functional improvement compared with BEV.

REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03520101.

PMID:41623058 | DOI:10.1161/CIRCINTERVENTIONS.125.016255

Glob Health Action. 2026 Dec 31;19(1):2611646. doi: 10.1080/16549716.2025.2611646. Epub 2026 Feb 2.

ABSTRACT

BACKGROUND: Bangladesh faces substantial inequalities in water, sanitation, and hygiene (WASH), with disparities across sociodemographic groups and between urban and rural populations. Evidence on temporal changes in household WASH access and its determinants remains limited.

OBJECTIVE: To assess changes in household WASH and examine the influence of sociodemographic factors on access, using data from two national hygiene surveys at national and urban-rural levels.

METHODS: In this repeated cross-sectional study, differences in WASH outcomes between the 2014 National Hygiene Baseline Survey and the 2018 National Hygiene Survey were assessed using prevalence differences (PD), and associations with sociodemographic factors were examined using generalized estimating equations (GEE).

RESULTS: From 2014 to 2018, rural households maintained near-universal basic drinking water, while urban households showed a slight decline. Basic sanitation increased substantially in rural areas (PD = 27.8), driving national gains (PD = 25); urban changes were nonsignificant. Basic hygiene improved minimally across all levels. Higher socio-economic status was linked to better WASH outcomes, while larger households had poorer status. Rental housing was associated with unimproved drinking water (Coef.: 1.9) and lower basic sanitation (Coef.: -0.9) but better overall hygiene than self-owned homes. Urban households had lower access to basic drinking water and sanitation, yet better basic hygiene facilities than rural households.

CONCLUSION: Household WASH improved substantially, especially in rural sanitation and hygiene, while urban areas showed stagnation. Socio-economic status, household size, and housing tenure are key determinants, highlighting the need for targeted interventions to ensure equitable, universal WASH coverage.

PMID:41623016 | DOI:10.1080/16549716.2025.2611646