Category: Nevin Manimala

J Prev Alzheimers Dis. 2026 Jan 1:100452. doi: 10.1016/j.tjpad.2025.100452. Online ahead of print.

ABSTRACT

BACKGROUND: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by widespread gray matter volume (GMV) reductions. Emerging evidence links glucose and lipid metabolic dysregulation to AD pathophysiology. However, the extent to which AD-related GMV alterations and metabolic traits share a common genetic basis remains poorly understood.

OBJECTIVES: To explore the shared genetic architecture between GMV alterations in AD and metabolites related to glucose and lipid metabolism, aiming to provide biological insights into the prevention and treatment of AD.

DESIGN: This is a multimodal, cross-disciplinary study combining neuroimaging meta-analysis, transcriptome-neuroimaging association analysis, conjunctional false discovery rate (conjFDR) analysis, and functional enrichment analysis to identify the shared genetic architecture between AD-related brain structural alterations and metabolic traits.

SETTING: Public databases and European populations.

PARTICIPANTS: The meta-analysis included 49 studies (1945 CE patients and 2598 controls). The largest genome-wide association study (GWAS) summary statistics were used for AD (N_case = 39,918; N_control =358,140), two glycemic traits-glucose (GLU, N = 459,772) and glycated hemoglobin (HbA1c, N = 146,864), and three lipid traits (N = 1320,016)-high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG).

MEASUREMENTS: We conducted a voxel-based morphometric meta-analysis of GMV in AD by systematically reviewing 49 neuroimaging studies, identified through a literature search in PubMed and Web of Science using a predefined search strategy. Building upon these neuroanatomical findings, we performed a transcriptome-neuroimaging association analysis using data from the Allen Human Brain Atlas to identify genes spatially correlated with GMV alterations. To further explore the shared genetic architecture, we integrated GWAS summary statistics for AD and five metabolic markers using conjFDR analysis. Finally, functional enrichment analyses were performed to elucidate the biological relevance of the identified genes through this integrative framework.

RESULTS: Consistent GMV reductions in AD were observed in the bilateral middle temporal gyrus, right superior temporal gyrus, and other key subcortical regions. The conjFDR analysis identified 20, 17, 78, 87, and 82 genes shared between AD-related GMV reductions and GLU, HbA1c, HDL-C, LDL-C, and TG, respectively. Notably, 6 genes were shared across all five metabolic markers. Enrichment analysis implicated these genes in biological processes related to Aβ aggregation and phosphatidylinositol metabolism.

CONCLUSIONS: This study reveals a convergent genetic architecture underlying AD-related GMV atrophy and metabolic dysfunction. These findings may offer novel insights into the molecular interplay between systemic metabolism and neurodegeneration in AD and highlight potential targets for therapeutic strategies.

PMID:41478820 | DOI:10.1016/j.tjpad.2025.100452

J Prev Alzheimers Dis. 2026 Jan 1:100450. doi: 10.1016/j.tjpad.2025.100450. Online ahead of print.

ABSTRACT

BACKGROUND: The magnitude of cognitive change before and after incident heart failure (HF) is unclear. We investigated whether incident HF is associated with changes in cognitive function at the time of diagnosis and accelerated trajectory in cognitive decline in the subsequent years.

METHODS: We used data from the Health and Retirement Study, a nationally representative survey of US adults aged 50 years or older. Participants underwent a cognitive assessment at baseline (wave 5, 2000), and at least 1 other time point (from wave 6 [2002] to wave 15 [2020]). The outcomes were change in global cognition, memory, and executive function. Outcomes were standardized into Z-scores, with higher scores indicating better cognitive performance. Linear mixed-effects models estimated changes in cognition at the time of HF (change in the intercept) and the rate of cognitive change over the years after HF (change in the slope), after adjusting for pre-HF cognitive trajectories and potential confounders.

RESULTS: We included 12 850 adults (mean [SD] age, 66.1 [9.4] years; 61.8 % women). Over a median follow-up of 16 years (interquartile range: 8 to 20 years), 1457 participants had incident HF. The annual rate of cognitive decline before HF diagnosis among individuals with incident HF was similar to that of participants who remained HF-free throughout follow-up. However, incident HF was associated with subsequent decreases in global cognition (-0.073 SD [95 % CI -0.109 to -0.038]), memory (-0.070 SD [95 % CI -0.108 to -0.032]), and executive function (-0.054 SD [95 % CI -0.092 to -0.016]) around the time of the HF diagnosis. Moreover, individuals with incident HF vs those without HF demonstrated faster and long-term declines in global cognition (-0.011 SD/year [95 % CI -0.018 to -0.004]) and executive function (-0.008 SD/year [95 % CI -0.015 to -0.001]), but not in memory (-0.006 SD/year [95 % CI -0.013 to 0.001]) over the years after HF compared with pre-HF slopes.

CONCLUSIONS: Incident HF was associated with subsequent decreases in cognitive function at the time of diagnosis and accelerated cognitive decline over the following years.

PMID:41478819 | DOI:10.1016/j.tjpad.2025.100450

Acad Radiol. 2025 Dec 31:S1076-6332(25)01159-6. doi: 10.1016/j.acra.2025.12.024. Online ahead of print.

ABSTRACT

BACKGROUND: Evidence regarding the long-term outcomes of patients with mild large vessel occlusion (LVO) stroke remains limited. This study aimed to compare 12-month outcomes between acute ischemic stroke (AIS) patients treated with endovascular therapy (EVT) versus best medical management (BMM).

METHODS: A multicenter, retrospective study across three centers was conducted, including AIS patients with LVO and National Institutes of Health Stroke Scale score (NIHSS) <6 between January 2019 and December 2023. Patients were categorized into EVT or BMM groups according to initial treatment strategy. The primary outcome was functional independence (modified Rankin Scale score of 0-2) at 12 months. Inverse probability of treatment weighting (IPTW) based on propensity scores was used to adjust for potential confounders.

RESULTS: A total of 976 patients with LVO were screened, and 285 with NIHSS <6 were enrolled. After IPTW adjustment (195 EVT vs. 201 BMM), functional independence was achieved in 78.5% of EVT and 74.1% of BMM patients (adjusted odds ratio [aOR] 1.25, 95% confidence interval [CI] 0.70-2.20) at 12 months. Hemorrhagic transformation was more frequent in the EVT group (13.3% vs. 5.5%; aOR 2.63, 95% CI 1.20-5.85), whereas symptomatic intracranial hemorrhage rates were similar between groups. Notably, stroke recurrence within 12 months was significantly lower in the EVT group compared to the BMM group (4.6% vs. 12.9%; aOR 0.33, 95% CI 0.15-0.70).

CONCLUSION: In patients with mild LVO, no statistically significant difference in long-term functional outcomes was observed between EVT and BMM, although EVT was associated with a lower risk of stroke recurrence.

PMID:41478806 | DOI:10.1016/j.acra.2025.12.024

Dent Mater. 2025 Dec 31:S0109-5641(25)00856-5. doi: 10.1016/j.dental.2025.12.012. Online ahead of print.

ABSTRACT

OBJECTIVES: The high occurrence of fractures, cracking and chipping of zirconia pre-sintered blanks and blocks during machining decreases their yield and can transfer lifetime-limiting cracks to the final sintered restoration. This study has the objective of characterizing the mechanical and fracture properties of two zirconia compositions while varying temperature and time of pre-sintering, in order to assess the space for possible improvement.

METHODS: We selected two typical granular powders with 3 mol% (3YSZ, Zpex®, Tosoh) or 5 mol% (5YSZ, Zpex Smile®, Tosoh) yttria-stabilized zirconia and two pre-sintered commercial analogs (IPS e.max® ZirCAD MO, Ivoclar and Katana™ STML, Kuraray). The debinding and pre-sintering stages of the experimental powders were characterized using thermal analyses (differential scanning calorimetry and thermogravimetry), and the crystal phase composition was quantified using X-ray diffraction (XRD). Physical and mechanical properties such as density, hardness, flexural modulus, biaxial flexural strength and fracture toughness were measured for two pre-sintering temperatures (1000 °C, 1100 °C) and increasing holding times at those temperatures (2 h, 4 h, 6 h). The chipping resistance for those conditions was quantified using the edge chipping test using a Vickers diamond indenter.

RESULTS: Thermal analyses revealed that both powders show comparable debinding behavior and contained approx. 3.8 mass % organic binder, which burns-out completely between 300 and 400 °C. The crystallographic phase changes occurring during the 2-6 h at 1000 °C and 1100 °C was not detectable in the DSC signal, but quantifiable by XRD. Namely, a major content of monoclinic phase in both powders transforms completely into the two tetragonal phases, starting below 1000 °C and concluding above 1100 °C. All physical and mechanical properties increased with holding time for both temperatures, though more steeply for pre-sintering at 1100°C. Edge chipping resistance response was well aligned with other fracture properties, with a more marked improvement for 3YSZ pre-sintered at 1100 °C. For all properties, the 3YSZ zirconia showed statistically-higher values for the same temperature-time conditions, in agreement with the values obtained for the commercial materials as well.

SIGNIFICANCE: The results demonstrate the weakness of pre-sintered zirconia products concerning fracture properties, but also the potential for improvement as related to type of zirconia and pre-sintering conditions. This study outlines the use of a set of mechanical tests that can characterize chipping resistance and guide future research engaging in optimizing the machining resistance of pre-sintered zirconia products.

PMID:41478804 | DOI:10.1016/j.dental.2025.12.012

Oral Surg Oral Med Oral Pathol Oral Radiol. 2025 Nov 26:S2212-4403(25)01321-5. doi: 10.1016/j.oooo.2025.11.010. Online ahead of print.

ABSTRACT

OBJECTIVE: Inherited cancer predisposition syndromes (ICPS) are rare genetic disorders associated with an elevated cancer risk. This study evaluates oral squamous cell carcinoma (OSCC) prevalence across selected ICPS, including Fanconi anemia (FA), Plummer-Vinson syndrome, Cowden syndrome, Li-Fraumeni syndrome, dyskeratosis congenita, and xeroderma pigmentosum, quantifies risk magnitude, examines age at diagnosis, and assesses tobacco’s modifying effect on OSCC risk in these populations.

STUDY DESIGN: We conducted a retrospective cohort study using the TriNetX Research Network, including patients with or without ICPS identified by ICD‑10 codes over a 20‑year period. OSCC cases were matched 1:1 by age and sex to controls. The analyses assessed prevalence, odds ratios, age at diagnosis, and the impact of tobacco use. Statistical significance was set at P < .05.

RESULTS: The prevalence of OSCC among ICPS patients ranged from 0.11% to 4.66%, with the highest in patients with FA. Among ICPS, only FA showed a markedly increased OSCC risk (OR = 40.63, P < .01), while Plummer-Vinson syndrome and dyskeratosis congenita were inversely associated. Patients with ICPS developed OSCC at younger ages (P < .0001). Smoking increased OSCC risk within ICPS (OR = 1.47), whereas nonsmokers with ICPS had a reduced risk (OR = 0.78).

CONCLUSIONS: FA is strongly associated with OSCC; OSCC also occurs in Li-Fraumeni syndrome and Cowden syndrome. Patients with ICPS present with OSCC at a younger age, supporting targeted screening for high‑risk ICPS populations.

PMID:41478787 | DOI:10.1016/j.oooo.2025.11.010

Eur Urol. 2025 Dec 31:S0302-2838(25)04877-8. doi: 10.1016/j.eururo.2025.12.022. Online ahead of print.

ABSTRACT

Intravesical bacillus Calmette-Guérin (BCG) therapy remains the cornerstone for high-risk non-muscle-invasive bladder cancer (NMIBC), but up to 40% of patients experience disease recurrence or progression within 2 yr. We conducted a systematic review and meta-analysis of three phase 3 randomized trials POTOMAC, CREST, and ALBAN; n = 2590) in BCG-naïve high-risk NMIBC disease treated with a combination of BCG and an immune checkpoint inhibitor (ICI). Overall risk of bias was low for all studies. Combination therapy with BCG maintenance was associated with better event-free survival (EFS) in comparison to BCG alone (pooled hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.60-0.99; Q = 3.29, p = 0.2). Using the HR for high-grade recurrence from ALBAN, the pooled estimate was directionally consistent, but not statistically significant (HR 0.78, 95% CI 0.58-1.04; Q = 3.94, p = 0.1). Overall survival was comparable between groups (HR 0.92, 95% CI 0.67-1.26). Grade ≥3 treatment-related adverse events were more frequent with combination therapy (risk ratio [RR] 3.66, 95% CI 2.56-5.24 for BCG induction only; RR 3.97, 95% CI 2.54-6.21 for BCG induction + maintenance). There was a moderate decline in patient-reported quality of life in the ICI + BCG maintenance arms. These findings are supported by moderate-certainty evidence for EFS. BCG monotherapy remains the benchmark for BCG-naïve high-risk NMIBC. ICI addition improves EFS but increases high-grade toxicity, which should prompt cautious and individualized adoption pending mature survival data.

PMID:41478774 | DOI:10.1016/j.eururo.2025.12.022

Br J Oral Maxillofac Surg. 2025 Dec 9:S0266-4356(25)00903-9. doi: 10.1016/j.bjoms.2025.11.015. Online ahead of print.

ABSTRACT

This study aims to provide an overview of patient characteristics, treatment modalities, and associated complications following microvascular free flap reconstructions in maxillofacial surgery, based on data from a large national tertiary care centre. Adult patients who received a microvascular free flap between April 2017 and December 2024 were analysed in this descriptive retrospective single-centre study. Follow up was recorded until February 2025. Fibular (FFF), scapular (SFF), deep circumflex artery (DCIA), radial forearm (RFF), anterolateral thigh (ALT) and latissimus dorsi (LDF) free flaps were included. Variables were stratified by flap type and the N-1 χ²-test used to test for statistical significance of complication rates across years. A total of 1373 cases met the inclusion criteria. DCIA flaps suffered the highest rates of early flap loss (8.7%; x¯ = 3.6%) and wound infection (39.1%; x¯ = 13.5%). SFFs had the highest rate of anastomotic revision (25.0%; x¯ = 6.9%) and longest mean (SD) surgery duration: 715 ± 181 min. Donor site complications were most common among RFFs (36.0%) and FFFs (34.5%). Overall, wound infection rates were higher among bony rather than soft tissue flaps (23.0% vs. 7.8%). FFFs were associated with fewer recipient-site complications than SFFs and DCIA flaps, but donor site complications were higher. Among soft tissue flaps, complication rates did not differ significantly. Overall, complications at the recipient site were more frequent among bony compared to soft tissue flaps.

PMID:41478764 | DOI:10.1016/j.bjoms.2025.11.015

Mol Biol (Mosk). 2025 Nov-Dec;59(6):1002-1021. doi: 10.7868/S3034555325060104.

ABSTRACT

The emergence of new data on the association between the composition of the intestinal microbiota and various human diseases has generated increasing interest in microbiome research. In this context, selection of the DNA extraction method represents a critical stage in the design of the experiment, significantly affecting the reliability and reproducibility of results. This study presents a comparative analysis of 12 DNA extraction methods, including nine commercial kits and three laboratory protocols. We evaluated the taxonomic representation, including Gram-positive (Lactobacillaceae, Coprococcus spp., Streptococcus sp., Clostridium leptum) and Gram-negative bacteria (Enterobacteriaceae, Akkermansia muciniphila, Fusobacterium nucleatum, Bacteroides fragilis). The extraction efficiency was assessed by the DNA yield, expressed in GE/pL of eluate or in GE/-µL of feces, as well as by the frequency of low-abundance taxa loss. Clustering of the methods according to the type of lysis was demonstrated: mechanical lysis provided stable and high DNA yields, particularly for Gram-positive bacteria, while chemical and enzymatic methods showed lower efficiency. We determined that the lysis type and pre-processing of intact fecal samples are the key factors affecting the DNA extraction efficiency and preservation of the native taxonomic profile. The best results were demonstrated by the QIAamp® PowerFecal® Pro DNA Kit (Qiagen) and the combination of AmpliTest UniProb + AmpliTest RIBO-prep kits (Center for Strategic Planning, Federal Medical-Biological Agency, Russia), both of which outperformed other methods in terms of DNA yield. The QIAamp® Fast DNA Stool Mini Kit (Qiagen) showed minimal losses of low-abundance taxa. These findings can be used for the standardization of gut microbiota DNA extraction methodologies and the development of domestic protocols.

PMID:41477720 | DOI:10.7868/S3034555325060104

Mol Biol (Mosk). 2025 Nov-Dec;59(6):979-987. doi: 10.7868/S3034555325060086.

ABSTRACT

Ovarian cancer remains one of the most lethal malignancies with a five-year survival rate around 20% at III-IV stages, which determines the urgent need to develop new therapeutic approaches. Newcastle disease virus (NDV) has demonstrated considerable promise as an oncolytic agent, capable of selectively lysing tumor cells, suppressing the metastatic potential and stimulating anti-tumor immunity. Despite the established therapeutic potential, studies that investigate oncolytic properties of this virus within the context of ovarian cancer remain limited. In this work, we evaluated oncolytic activity of the NDV vaccine strain H in SC-OV-3, TOV-21G and OV-90 ovarian cancer cell lines. Such parameters as ability to support viral replication and cell viability after infection were investigated. As a result, all three lines were permissive to NDV-H infection. Therapeutic efficacy in vivo was assessed using a model of TOV-21G subcutaneous xenografts in BALB/c nude mice. Upon intravenous administration of the virus, a statistically significant reduction in tumor volume was observed compared to the control group. Based on these results, NDV-H strain can be considered as a potential oncolytic agent for the treatment of ovarian cancer.

PMID:41477718 | DOI:10.7868/S3034555325060086

Mol Biol (Mosk). 2025 Nov-Dec;59(6):971-978. doi: 10.7868/S3034555325060076.

ABSTRACT

Although the role of NADPH oxidase 2 (NOX2) in the development of Alzheimer’s disease (AD) is widely recognized, its contribution to the initial stages of amyloid-induced pathology remains unclear. Intraventricular administration of β-amyloid (Aβ) causes acute amyloid toxicity, leading to neurodegenerative changes similar to AD. The acute phase, lasting several days, is a critical time window for studying early pathological mechanisms. In this work, we assessed the level of oxidative stress in the brain of BALB/c mice at the early stages of amyloid toxicity and the role of NOX2 in these processes. Analysis of key markers of oxidative stress in various fractions of brain homogenate on day 4 after Aβ administration showed that individual parameters demonstrated only a tendency to change, without reaching statistical significance. However, principal component analysis (PCA) revealed a clear separation between the Aβ-treated and control groups, indicating the need for a comprehensive rather than isolated analysis of biochemical changes at early stages of pathology. It is noteworthy that the centroids of the groups in PCA were located along the same straight line, and the group receiving Aβ together with the NOX2 inhibitor occupied an intermediate position between the control and Aβ groups. This indicates partial suppression of oxidative stress through NOX2. At the same time, the NOX2 inhibitor completely prevented Aβ-induced microgliosis in the hippocampus, confirming that the concentration used was sufficient to suppress NOX2-dependent microglial activation. The in vivo data demonstrate that oxidative stress induced by Aβ administration may not be entirely mediated by NOX2, although this mechanism plays an important role in the initiation of the pathological process in AD.

PMID:41477717 | DOI:10.7868/S3034555325060076