Tag: nevin manimala

Alzheimers Res Ther. 2025 Nov 14;17(1):247. doi: 10.1186/s13195-025-01898-1.

ABSTRACT

BACKGROUND: Alzheimer’s Disease Spectrum (ADS) progresses from preclinical stages to dementia, with dynamic functional connectivity (dFC) changes emerging early. This study aimed to investigate the dynamic changes in brain networks across different stages of ADS and their underlying molecular mechanisms.

METHODS: This cross-sectional study included 239 participants: 69 Healthy Controls (HC), 83 with Subjective Cognitive Decline (SCD), 56 with Mild Cognitive Impairment (MCI), and 31 with Alzheimer’s disease (AD). All participants underwent neuropsychological testing and resting-state functional magnetic resonance imaging (rs-fMRI). Leading Eigenvector Dynamics Analysis (LEiDA), a data-driven method that captures time-resolved whole-brain dFC, was applied to identify transient brain states and calculated their occupancy rate, dwell time, and transition probabilities. Group differences in these dynamic metrics were assessed using a General Linear Model (GLM), and their correlations with cognitive performance were examined. To explore the molecular basis of significant dFC alterations, we performed gene-category enrichment analysis. This analysis integrated the spatial maps of altered brain states with regional gene expression data from the Allen Human Brain Atlas (AHBA), using spin permutations to ensure statistical robustness.

RESULTS: We identified ten recurring brain states and characterized how their transition patterns, stability, and frequency differed as a function of disease severity. Specifically, early disruptions appeared as altered transition probabilities between states, while later stages showed pronounced changes in the dwell time and occurrence rates of specific states, closely associated with cognitive decline. Notably, one brain state marked by synchronized activity in attention, salience, and default mode networks emerged as a critical hub linked to both cognitive deterioration and excitatory-inhibitory imbalance. Genes associated with this state were enriched in glycine-mediated synaptic pathways and expressed in both excitatory and inhibitory neurons, showing spatial and temporal patterns that extended from early development into late disease stages.

CONCLUSIONS: Our study uncovered the stage-dependent dFC changes and their molecular underpinnings of brain network dysfunction across the ADS.

PMID:41239516 | DOI:10.1186/s13195-025-01898-1

Lipids Health Dis. 2025 Nov 14;24(1):364. doi: 10.1186/s12944-025-02689-1.

ABSTRACT

BACKGROUND: Self-harm is a significant public health concern, with increasing prevalence globally. Omega-3 fatty acids (FAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are known for their health benefits, including potential mental health improvements. This study explores the association between omega-3 FAs and self-harm behaviors using data from the UK Biobank (UKBB).

OBJECTIVES: To investigate the relationship between plasma levels of omega-3 FAs and various measures of self-harm, including passive suicidal ideation and deliberate self-harm, within a large cohort study.

METHODS: This observational study analyzed data from a random subset of 258,012 participants with plasma omega-3 FA levels, covariate data, and self-harm records. Omega-3 levels were measured using Nuclear Magnetic Resonance (NMR) and are expressed as a percent of total FAs. Self-harm outcomes were assessed through self-reported questionnaires and medical records. Covariates included demographic, health, and lifestyle factors. Statistical analyses involved logistic regression and Cox proportional hazards models, adjusting for relevant covariates. Adjusted odds ratios (aORs) are presented and 95% confidence intervals.

RESULTS: Higher levels of DHA, non-DHA (ALA+EPA+DPA) and total omega-3 were generally inversely associated with passive suicidal ideation, history of self-harm, and future self-harm, with both DHA and non-DHA showing some of the strongest associations. Participants in the highest quintile of non-DHA had a 14% lower risk of passive suicidal ideation in the last year (aOR = 0.86; 95% CI 0.75, 0.99), and the highest DHA levels were associated with a 33% lower odds of history of self-harm (aOR = 0.67; 95% CI 0.55, 0.83). These associations were generally stronger for medical record-based outcomes than for self-reported data.

CONCLUSIONS: This study provides evidence that higher omega-3 FA levels, both DHA and non-DHA, are associated with reduced risks of self-harm and suicidal ideation. These findings suggest that omega-3 FAs may play a protective role in mental health, highlighting the potential of dietary interventions to mitigate self-harm behaviors.

PMID:41239514 | DOI:10.1186/s12944-025-02689-1

Mil Med Res. 2025 Nov 14;12(1):79. doi: 10.1186/s40779-025-00670-8.

ABSTRACT

BACKGROUND: The global increase in the incidence of early-onset cancers (defined as cancers diagnosed at 20-49 years old) is a serious public health problem. We investigated 1) whether the incidence trend of early-onset cancers differs from that of later-onset cancers and 2) whether both the incidence and mortality of early-onset cancers have increased concurrently.

METHODS: We utilized age-standardized incidence and mortality rates for early-onset and later-onset cancers diagnosed between 2000 and 2017 from the Cancer Incidence in Five Continents and World Health Organization (WHO) mortality databases. The national obesity prevalence among adults aged 20-49 years was obtained from the National Clinical Database. Using joinpoint regression models, we calculated average annual percentage changes (AAPCs) for cancer incidence and mortality by cancer types and countries. We additionally conducted human development index (HDI)-stratified analyses and assessed the correlation between the obesity prevalence in younger populations and early-onset cancer incidence by country. To investigate the more recent trend of early-onset cancer mortality, we extended our mortality analysis after 2017 for cancer types and countries with statistically significant positive AAPCs in both incidence and mortality of early-onset cancers between 2000 and 2017.

RESULTS: Our analysis showed that 10 early-onset cancer types (thyroid cancer, breast cancer, melanoma, uterine cancer, colorectal cancer, kidney cancer, cervical cancer, pancreatic cancer, multiple myeloma, Hodgkin lymphoma) in females and 7 early-onset cancer types (thyroid cancer, kidney cancer, testis cancer, prostate cancer, colorectal cancer, melanoma, leukemia) in males had statistically significant positive AAPCs in at least 10 countries. Among these, the following early-onset cancer types had significantly higher AAPCs than later-onset cancer types in females: colorectal cancer (6 countries; AAPC range: 1.8-3.8%), cervical cancer (6 countries; AAPC range: 1.2-3.3%), pancreatic cancer (5 countries; AAPC range: 2.3-13.0%), and multiple myeloma (5 countries; AAPC range: 3.1-9.8%); in males: prostate cancer (12 countries; AAPC range: 3.9-18.4%), colorectal cancer (8 countries; AAPC range: 1.8-3.2%), and kidney cancer (6 countries; AAPC range: 2.0-6.0%). We observed statistically significant positive AAPCs in both the incidence and mortality of the following early-onset cancer types: uterine cancer (5 countries) and colorectal cancer (3 countries in females and 5 countries in males). The steeper increases in early-onset cancers compared with later-onset cancers were mainly observed in the very high-HDI country group, including early-onset colorectal cancer (AAPC = 2.4%, 95% CI 2.1-2.6 in females; AAPC = 2.0%, 95% CI 1.7-2.4 in males) to later-onset colorectal cancer (AAPC = -0.1%, 95% CI -0.2 to 0 in females; AAPC = -0.2%, 95% CI -0.3 to 0 in males). We observed strong positive correlations between the increasing obesity prevalence and the rising incidence of early-onset obesity-related cancers in several countries, including Australia (7 cancer types), United Kingdom (7 cancer types), Canada (7 cancer types), Republic of Korea (7 cancer types), and USA (6 cancer types) in females and United Kingdom (7 cancer types), Canada (6 cancer types), Australia (5 cancer types), Sweden (5 cancer types), and Republic of Korea (4 cancer types) in males. Although we did not observe an apparent spike after 2017 in many countries, we observed continued increases in the mortality of certain cancer types, such as uterine cancer (Japan, Republic of Korea, United Kingdom, USA, and Ecuador) in females and colorectal cancer (Argentina, Canada, United Kingdom, and USA) in males.

CONCLUSIONS: The increase in many early-onset cancer types was significantly higher than that of later-onset cancers, and the incidence and mortality of certain early-onset cancer types (such as colorectal cancer) increased simultaneously. Our study highlights global differences in cancer incidence and mortality trends of early-onset and later-onset cancers.

PMID:41239501 | DOI:10.1186/s40779-025-00670-8

Malar J. 2025 Nov 14;24(1):398. doi: 10.1186/s12936-025-05536-x.

ABSTRACT

BACKGROUND: Malaria is a major cause of illness and death in Liberia. Given the high burden of disease and limited resources, Liberia implemented a subnational tailoring (SNT) approach. This approach involved stakeholder engagement, data review, and advanced analytics to update transmission risk assessment, optimize intervention targeting, and revise the national operational plan.

METHODS: An SNT team was established to determine intervention targeting criteria, compile and analyse relevant data sources, and stratify malaria risk and its determinants to inform geographical targeting of interventions. The analysis was performed at the district level. Data collected and reviewed included routine malaria data from health facilities, the national survey on malaria indicators, entomological data, demographic and health surveys, and modelled malaria burden metrics.

RESULTS: Epidemiological stratification was conducted based on modelled parasite prevalence (PfPR), incorporating results from the 2022 Malaria Indicator Survey, to inform intervention strategies. Additional indicators relevant for decision-making, such as insecticide resistance, historical malaria interventions, and access to healthcare, were also stratified. The median PfPR across the 98 health districts was 29% (SD = 4.8%), ranging from 17 to 37%. The stratification identified 84 districts as moderate transmission and 14 as high transmission, with no districts classified as low transmission. Appropriate malaria control interventions were proposed based on these strata. Findings from the SNT analysis informed the revision of the national operational plan and facilitate resource mobilization for the scale-up of dual-active nets and expanding vaccination.

CONCLUSION: This NMCP-led subnational malaria stratification for Liberia effectively informed the targeting of eight key interventions and highlighted data gaps for future refinement. This work not only provides a framework for monitoring progress and accelerating malaria burden reduction through tailored approaches but also sets the stage for continuously data-driven decision-making, emphasizing future prioritization based on projected impact, cost, and resource availability.

PMID:41239496 | DOI:10.1186/s12936-025-05536-x

Behav Brain Funct. 2025 Nov 14;21(1):38. doi: 10.1186/s12993-025-00308-8.

ABSTRACT

BACKGROUND: Depression involves abnormal neural oscillations. Photobiomodulation (PBM) modulates such oscillations but lacks behavioral electrophysiological mechanistic studies. We explored PBM’s effects on hippocampal CA1 oscillations and phase-amplitude coupling (PAC) in a depression model.

METHODS: Male C57BL/6J mice were randomly divided into saline, LPS (2 mg/kg i.p.), and LPS + PBM groups (n = 10/group for behavioral tests, n = 8/group for electrophysiology). LPS groups received lipopolysaccharide to induce neuroinflammation. The LPS + PBM group underwent 810 nm PBM (20 mW/cm², 12 min/day × 4 days) starting day 4 post-injection. Anxiety- and depression-like behaviors were assessed via open field, elevated plus-maze, and tail suspension tests. Wireless electrophysiology recorded CA1 local field potentials (LFP) during rest and behaviors. Oscillations and PAC were analyzed. Data are presented as mean ± SD; group differences were evaluated by one-way ANOVA with Bonferroni post-hoc correction and ɳ² effect sizes, with two-tailed p < 0.05 taken as statistically significant.

RESULTS: PBM (20 mW/cm²) alleviated LPS-induced anxiety and depressive behaviors. Electrophysiologically, PBM restored resting-state δ power (LPS + PBM: 0.0499 ± 0.0282, LPS: 0.1491 ± 0.0887; p < 0.01) and enhanced δ-γ coupling (LPS + PBM: 2.049 ± 0.447, LPS: 0.230 ± 0.298; p < 0.05). During anxiety tasks, PBM suppressed γ power (LPS + PBM: 0.3709 ± 0.1569, LPS: 0.5165 ± 0.06896; p < 0.05) and strengthened δ-γ PAC (LPS + PBM: 0.741 ± 0.508 vs. LPS: 0.217 ± 0.218, p < 0.05). In depression tests, PBM normalized δ power (LPS + PBM: 0.0261 ± 0.0182, LPS: 0.1315 ± 0.0619; p < 0.001) and reduced γ power (LPS + PBM: 0.2848 ± 0.0921, LPS: 0.4067 ± 0.0892; p < 0.05). No significant PAC changes was observed during depression tasks.

CONCLUSION: PBM therapy ameliorates LPS-induced depression and anxiety behaviors while normalizing hippocampal CA1 oscillations and cross-frequency coupling. Its effects are state-dependent, modulating distinct frequency bands and PAC across rest and behavioral contexts, revealing potential electrophysiological therapeutic mechanisms.

PMID:41239492 | DOI:10.1186/s12993-025-00308-8

Malar J. 2025 Nov 14;24(1):400. doi: 10.1186/s12936-025-05642-w.

ABSTRACT

BACKGROUND: The antirelapse efficacy of primaquine is related to the total dose administered, whereas the risks of haemolysis and gastrointestinal intolerance are associated with the daily dose administered. National Malaria Control Programmes require local information on efficacy, tolerability and safety to optimize antimalarial treatment policies for Plasmodium vivax malaria control and elimination efforts.

METHODS: A living systematic review identified efficacy studies of uncomplicated P. vivax malaria including patients treated with daily primaquine regimens, published since January 1, 2000. Available data were pooled and an R Shiny app was developed to integrate statistical analyses performed using R and Stata that assessed the impact of primaquine mg/kg dose on efficacy, hematological safety and gastrointestinal tolerability.

RESULTS: As of January 16, 2025, a total of 9,270 individual patient data records from 41 studies have been collated into the standardized repository. Open-access automated reports were generated for user-selected countries or regions to investigate location specific effects of primaquine dose on efficacy, safety and tolerability. The reports include visual and tabular displays of the outcomes.

CONCLUSIONS: These automated reports leverage a large database to provide accessible data for national and regional policy makers and researchers to assess the clinical consequences of different primaquine regimens in different endemic settings. The reports will inform local and regional policy decisions and research priorities in vivax-endemic areas.

PMID:41239453 | DOI:10.1186/s12936-025-05642-w

BMC Endocr Disord. 2025 Nov 14;25(1):264. doi: 10.1186/s12902-025-02087-9.

ABSTRACT

BACKGROUND: As type 2 diabetes mellitus (T2DM) has emerged as a global health challenge, various treatment strategies, such as the use of metformin and dipeptidyl peptidase-4 (DPP-4) inhibitors, have been widely adopted. However, evidence on the effectiveness of their combination therapy remains limited, particularly in studies utilizing target trial emulation approaches within the South Korean population.

METHODS: This emulated target trial included 68,372 patients with T2DM identified between 2001 and 2024 from four university hospitals in South Korea. After applying exclusion criteria, patients were classified into two groups: metformin monotherapy and metformin plus alogliptin dual therapy. A 1:2 propensity score matching approach was used to balance baseline covariates between groups. The outcome of this analysis was the achievement of glycemic control, defined as haemoglobin A1c (HbA1c) < 6.5% during the follow-up period. Clinical parameters, including glycemic indices, were assessed over 24 weeks from the initiation of therapy using unpaired t-tests. Cox proportional hazards models were employed to estimate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) to evaluate the likelihood of achieving glycemic control.

RESULTS: After applying exclusion criteria and performing 1:2 propensity score matching, 1230 patients were included in the final analysis (371 in the dual therapy group and 662 in the monotherapy group). Over the 24-week follow-up period, the dual therapy group showed greater reductions in HbA1c and fasting plasma glucose, with the greatest improvement observed at 8 weeks. No significant differences were found between groups in changes across other clinical parameters. Although the reduction in HbA1c during 24-week follow-up period was greater in the dual therapy group, the difference did not reach statistical significance. However, over the extended follow-up period, patients receiving dual therapy exhibited a higher likelihood of achieving glycemic control (HbA1c < 6.5%) compared to those on monotherapy (aHR, 2.41; 95% CI, 1.64-3.55).

CONCLUSION: By emulating a target trial, this study showed that dual therapy with metformin and alogliptin improved glycemic control in patients with T2DM in South Korea. Given the growing number of available treatment regimens, future research should incorporate a wider range of antidiabetic agents and explore the effectiveness of various therapeutic combinations.

CLINICAL TRIAL NUMBER: Not applicable.

PMID:41239448 | DOI:10.1186/s12902-025-02087-9

Arch Public Health. 2025 Nov 14;83(1):277. doi: 10.1186/s13690-025-01751-9.

NO ABSTRACT

PMID:41239445 | DOI:10.1186/s13690-025-01751-9

Clin Epigenetics. 2025 Nov 14;17(1):190. doi: 10.1186/s13148-025-02007-7.

ABSTRACT

BACKGROUND: Polypharmacy, defined as taking ≥ 5 different daily medications, is common in older adults and has been linked with neuropsychiatric/neurological and other health conditions. To clarify the potential molecular implications, we tested the hypothesis that polypharmacy may influence DNA methylation (DNAm) patterns in aging, in a longitudinal Italian cohort (N = 1,098; mean (SD) age at recruitment: 58.8 (5.6) years, 51.3% women; median (IQR) follow-up 12.6 (1.1) years).

RESULTS: We tested associations of polypharmacy with several DNAm aging clocks (Hannum, Horvath, GrimAge, DNAmPhenoAge, DunedinPACE), through linear mixed models incrementally adjusted for age, sex, education, prevalent health conditions and lifestyles, leukocyte counts and residual batch effects. This revealed significant positive associations of GrimAge acceleration and DunedinPACE with the switch to polypharmacy status during follow-up (Beta (SE): 0.024 (0.008) and0.0012 (0.0004)). While the association of GrimAge was driven by a DNAm-based surrogate of tissue inhibitor metalloproteinase 1 (TIMP-1), no significant association was detected for component CpGs of DunedinPACE. When we tested associations of polypharmacy with 668,413 CpGs epigenome-wide, we observed no statistically significant findings (top hit: cg07675998; chr11q13.1; Beta (SE) = 0.009 (0.002); p = 1.5 × 10^-6). However, these showed significant enrichments of several biological functions and pathways related to renal tissue, lipoproteins, inflammatory and immune response.

CONCLUSIONS: These findings suggest an influence of polypharmacy on accelerated epigenetic aging and on altered methylation patterns in the genome, suggesting a potential implication of pathways related to renal tissue development, lipoproteins and cholesterol homeostasis, inflammatory and immune response, in line with previous proteomic analyses of polypharmacy mouse models. These observations also suggest potential targets for mitigating disruptive effects of polypharmacy on elderly health.

PMID:41239444 | DOI:10.1186/s13148-025-02007-7

Malar J. 2025 Nov 14;24(1):399. doi: 10.1186/s12936-025-05645-7.

ABSTRACT

BACKGROUND: Ghana still faces prevailing malaria cases despite the progress made in reducing its incidence. The formal private drug retail sector most at times tends to be the first source of healthcare for people with fever. However, there is limited information from this sector with regards to the documentation and reporting of malaria cases and other diseases. This study examined malaria documentation and reporting practices among formal drug retail shops in the Hohoe Municipality as part of efforts to enhance tracking of malaria.

METHODS: A concurrent mixed-methods approach was employed, comprising a cross-sectional study of 57 formal drug retail facilities (9 from Community Pharmacies and 48 from Over-the-Counter Medicine Sellers [OTCMS]) and an exploration study of 7 of them. Quantitative data was collected via semi-structured questionnaires and analysed using Stata. The quantitative data was analysed using descriptive (frequencies and proportions) and bivariate (fishers’ exact test) analysis. Statistical significance was measured at a p-value of 0.05. Qualitative data from 7 in-depth interviews were thematically analysed using ATLAS.ti to identify key themes.

RESULTS: The median age of the participants was 26 years (IQR = 24-42), with 40 (70.2%) qualified as Counter Medicine Assistants, and 38 (66.7%) having 1-5 years of work experience. Of the 57 shops, 51 (89.5%) lacked documentation and reporting tools; only 5 (10.5%) used paper-based methods with significant differences observed between community pharmacies and OTCMS (p = 0.004). Digital reporting was favoured by 35 (61.4%) of attendants, prioritizing a user-friendly interface, data security, and real-time data submission. Participants highlighted barriers like stress and resource constraints but suggested solutions such as improved staffing, training, and digital infrastructure.

CONCLUSIONS: Malaria documentation and reporting were low, with few facilities relying on paper-based methods. Digital reporting was preferred but faces challenges like resource constraints and inadequate training. Addressing these barriers through infrastructure investments and comprehensive training with collaborations between the National Malaria Elimination Programme (NMEP) and the Ghana Pharmaceuticals Council (GPC) will improve data accuracy and reporting, even in low-connectivity areas.

PMID:41239439 | DOI:10.1186/s12936-025-05645-7