Nevin Manimala

AIDS Res Ther. 2025 Jun 10;22(1):61. doi: 10.1186/s12981-025-00756-2.

ABSTRACT

BACKGROUND: People with HIV (PWH) are at risk of co-infections, such as latent tuberculosis (LTBI), hepatitis B (HBV), hepatitis C (HCV), and syphilis; hence, routine screening is critical. However, evaluation of routine screening is not being fully implemented in Ghana. This study assessed the prevalence of these co-infections among PWH in Accra, Ghana.

METHODS: The HIV Cure Research Infrastructure Study (H-CRIS) followed 390 PWH from three HIV treatment centres in Accra. A cross-sectional study was conducted within this cohort, and participants were screened for LTBI, hepatitis B, hepatitis C, and syphilis using standardized assays. LTBI was detected using the QuantiFERON-TB Gold Plus assay. Syphilis testing included treponemal and non-treponemal assays. HBV and HCV were tested using rapid test kits. Data was collected on demographics, viral load, CD4 count, ART regimen, and therapy duration. Descriptive statistics used frequency and proportion, while inferential analysis employed chi-square tests, t-tests, and odds ratios (OR) to assess associations.

RESULTS: Among 390 participants, median age: 45 years (IQR: 39-52 years), 69% (269/390) were virologically suppressed, and 80% (312/390) had CD4 counts above 350 cells/µL. The prevalence of co-infections was 12% (48/390) for HBV, 10.8% (42/390) for LTBI, 12.5% (40/320) for syphilis, and 1% (4/390) for HCV, with 2% (8/390) having more than two co-infections. LTBI was associated with age (> 60 years; OR = 3.5) and years of HIV diagnosis (> 10 years; OR = 2.2).

CONCLUSION: The significant burden of co-infections among PWH in Ghana highlights the urgent need to integrate routine screening into HIV care.

PMID:40495197 | DOI:10.1186/s12981-025-00756-2

J Ovarian Res. 2025 Jun 10;18(1):127. doi: 10.1186/s13048-025-01696-1.

ABSTRACT

BACKGROUND: Early diagnosis and early delivery are the main strategies for the treatment of premature ovarian insufficiency (POI). However, POI warning markers, especially those that can be detected through noninvasive methods, are very limited; therefore, the identification of noninvasive markers for POI is urgent.

METHODS: We acquired POI GWAS summary statistics from the FinnGen database. The metabolome, circulating plasma proteins, gut microbiota, immunophenotypes, circulating microRNAs (miRNAs), and two proteomes were obtained for two-sample Mendelian randomization (MR). Specifically, we employed inverse variance weighted (IVW) as the main method to calculate the MR effect estimates. eQTL data (from the eQTLGen Consortium) were employed for SMR. Hub genes were identified using the String database and Cytoscape software. Potential mechanisms of POI were identified via pathway enrichment analysis of the identified genes and miRNAs.

RESULTS: Three metabolites (sphinganine-1-phosphate levels, X-23636 levels, 4-methyl-2-oxopentanoate levels), two circulating plasma proteins (fibroblast growth factor 23 levels, neurotrophin-3 levels), one gut microbiota (faecalibacterium abundance), one immunophenotype (HVEM on naive CD8 + T cells), 23 miRNAs (miR-500a-3p, miR-555, miR-584-5p, miR-642a-5p, miR-671-3p, miR-1324, miR-6870-3p, miR-1468-5p, miR-146a-3p, miR-221-3p, miR-3121-5p, miR-3184-3p, miR-3185, miR-335-5p, miR-4302, miR-4506, miR-6808-5p, miR-6894-5p, miR-145-5p, miR-149-3p, miR-23a-3p, miR-3141, and miR-374b-5p), and three hub genes (ESR1, ERBB2, and GART) serve as warning markers for POI. Enrichment analysis indicated that pathways such as glutathione metabolism and the PI3 kinase pathway may be involved in mechanisms regulating POI.

CONCLUSION: Our results are the first to identify noninvasive predictors for POI via MR, providing contributions for early warning and fertility guidance for clinical POI patients.

PMID:40495196 | DOI:10.1186/s13048-025-01696-1

J Transl Med. 2025 Jun 10;23(1):639. doi: 10.1186/s12967-025-06560-w.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is a rapidly progressing disease, frequently caused by hepatitis C virus (HCV) infection and a higher prevalence in males than females. Over 60% of HCCs harbour frequent activating mutations in the telomerase reverse transcriptase promoter (TERTp). However, the relationship between TERTp status, sex, and expression of specific genes remains poorly understood.

METHODS: We conducted a literature search to identify genes that were significantly upregulated in HCV-related HCC, compared to the respective peri-tumour tissues, in at least two independent studies. We identified 90 genes and validated their expression in 59 matched HCV-related HCC and peri-tumour tissues using a custom multiplex array qPCR. HCV-related HCC patients were stratified by TERTp mutations and sex. Statistical analysis was performed to identify relationships between different variables.

RESULTS: Overall, validation analysis confirmed the upregulation of 39 out of 90 genes. Expression levels of 24 genes differed significantly between HCV-related HCC with mutant and wild type TERTp. The expression of FASTK and FLVCR1 genes correlated with TNM and tumour size (p < 0.05). High expression of NUCKS1 was associated with mortality, particularly in male patients. Overall, the expression of 57 genes was sex-linked, with 26 and 48 genes significantly overexpressed in males and in females, respectively, some of which were also associated with mutant TERTp status.

CONCLUSIONS: We identified unique molecular signatures in TERTp mutant HCC associated with the activation of specific genes. Such results suggest that TERTp mutant HCC might represent a distinct clinical entity. Furthermore, the up-regulation of several genes in HCV-related HCC is sex-linked. These results are crucial for understanding the mechanisms underlying TERTp mutations in tumour progression and sex-related HCC risk and for developing more effective diagnostic and prognostic biomarkers.

PMID:40495193 | DOI:10.1186/s12967-025-06560-w

J Transl Med. 2025 Jun 10;23(1):636. doi: 10.1186/s12967-025-06664-3.

ABSTRACT

Cancer is one of the major diseases threatening human health in the world. According to the latest global cancer statistics from the International Agency for Research on Cancer (IARC), there were approximately 20 million new cancer cases and 10 million cancer deaths worldwide. Amidst this global health concern, branched chain amino acids have emerged as key players, playing an important role in the occurrence and development of cancer. In certain malignancies like colorectal cancer, the average level of BCAA in tumor tissues is twice that in normal tissues. BCAA metabolism is intricately associated with the progression of multiple tumors and is modulated by diverse enzymes, including BCAT, BCKDH, and BCKDK. The metabolism of BCAA involves multiple enzymes and biochemical processes via signaling pathways such as PI3K/AKT/mTOR and AMPK/mTOR, etc. In addition, mTOR inhibitors show potential value in cancer treatment by regulating the metabolism and signaling pathways of tumor cells, which provides a new direction for anticancer efforts. Simultaneously, BCAAs are closely associated with tumor immunity, including NK cells, CD4⁺ T cells, and CD8⁺ T cells. At present, the research on BCAA metabolism and related enzymes and signaling pathways is still in progress, aiming at identifying new targets and ideas for cancer therapy, and combined therapy will become an important trend in the future. In this review, we discuss the role and mechanisms of BCAA metabolism in human cancer.

PMID:40495192 | DOI:10.1186/s12967-025-06664-3

J Orthop Surg Res. 2025 Jun 10;20(1):581. doi: 10.1186/s13018-025-05992-w.

ABSTRACT

A clear surgical field of view is one of the key factors for a smooth operation. Whether a new modified oblique retractor can improve the field of view during oblique lumbar interbody fusion (OLIF) surgery and thus shorten the surgical time and reduce blood loss needs to be evaluated. A total of 64 patients who were diagnosed with L4‒5 segment lumbar spondylolisthesis, lumbar spinal stenosis, or lumbar disc herniation and who underwent OLIF surgery in our hospital between January 2023 and December 2023 were retrospectively enrolled. They were divided into two groups on the basis of whether the new modified oblique retractor was used: 32 cases with the new modified oblique retractor and 32 cases with a traditional right-angle retractor. Clinical efficacy was compared between the two groups using the visual analogue scale (VAS) for lower limb pain and the Oswestry Disability Index (ODI). The safety in the perioperative period was compared between the two groups using indicators such as surgical time, intraoperative blood loss, the vertebral canal area, and complications. No statistically significant differences were found in the baseline data (age, sex, or BMI) between the two groups (P > 0.05). There were no significant differences in the postoperative VAS score, postoperative ODI, postoperative vertebral canal area, or incidence of complications between the two groups (P > 0.05). There was a statistically significant difference in surgical time and intraoperative blood loss (P < 0.05) between the two groups. Compared with traditional right-angle retractors, the newly improved oblique retractor is more suitable for the surgeon’s field of view, thereby shortening the surgical time to some extent and reducing blood loss. By reducing traction on the psoas major muscle, the possibility of psoas muscle weakness can be decreased. Although there are differences in overall efficacy between the two groups of patients, these differences are small. The newly improved oblique retractor is better in terms of the appropriate surgical field of view angle and provides easier assistant cooperation, thus it is worth promoting and applying in clinical practice.

PMID:40495186 | DOI:10.1186/s13018-025-05992-w

Diabetol Metab Syndr. 2025 Jun 11;17(1):206. doi: 10.1186/s13098-025-01775-9.

ABSTRACT

BACKGROUND: Despite the association between the triglyceride-glucose (TyG) index and major adverse cardiovascular events (MACE) has been reported, a notable research gap persists regarding its predictive value in patients with acute coronary syndrome (ACS) and chronic kidney disease (CKD). This study endeavors to bridge this gap by investigating the relationship between the TyG index and outcomes among this unique patient cohort.

METHODS: Patients having ACS with CKD were recruited from January 2013 to December 2021. Outcomes included all-cause mortality and MACE. The potential linear relationship was visualized by the restricted cubic spline (RCS) curve. Cox proportional hazards models were employed to rigorously examine the association between the TyG index and study outcomes. Furthermore, to assess the incremental value of the TyG index, we conducted analyses using C-statistics, the continuous net reclassification index (cNRI), and the integrated discrimination index (IDI).

RESULTS: A total of 1094 patients were included in the final analysis. Over a median follow-up period of 30.1 months (IQR: 16.5 to 40.0 months), we recorded 167 (15.3%) all-cause mortality events and 285 (26.1%) MACE. Additionally, each 1-unit increase of it was significantly associated with a 61% elevation in the risk of all-cause mortality (95% CI: 1.28-2.03, P < 0.001) and a 72% increase in the risk of MACE (95% CI: 1.45-2.05, P < 0.001). These associations between TyG index (as quantitative or categorical variables) and endpoints remained robust even after multivariable adjustment. RCS analysis showed linear relationships between TyG and endpoints (all P for non-linear > 0.05). Moreover, subgroup analysis revealed significant interactions of dialysis and renal function (P for interaction = 0.008 and 0.011, respectively) with all-cause mortality. Lastly, combining with the established risk score significantly enhanced the discrimination and reclassification performance of TyG, as evidenced by the C-statistic, cNRI, and IDI values (all P < 0.05).

CONCLUSION: For patients with both ACS and CKD, TyG index is associated with both MACE and all-cause death. Prognostic classification is enhanced by the TyG index. The results collectively suggest that the TyG index serves as a reliable predictor of outcomes among patients with ACS and CKD, offering a novel metabolic perspective.

PMID:40495184 | DOI:10.1186/s13098-025-01775-9

Diabetol Metab Syndr. 2025 Jun 11;17(1):205. doi: 10.1186/s13098-025-01764-y.

ABSTRACT

OBJECTIVE: This study aimed to utilize Mendelian randomization (MR) techniques to determine causal relationships between the plasma lipidome and the occurrence and progression of chronic kidney disease (CKD).

METHODS: Summary statistics for 179 lipid species and six CKD-related phenotypes were retrieved from published large-scale genome-wide association studies. A bidirectional two-sample MR analysis was performed using the inverse-variance weighting (IVW) as the primary MR method. Cochrane’s Q test, the MR‒Egger intercept analysis, and the MR-PRESSO were employed to evaluate heterogeneity and horizontal pleiotropy. The leave-one-out test was applied to ensure the stability of the MR findings, and Benjamini‒Hochberg (BH) correction was utilized to assess the robustness of causal links.

RESULTS: This study unveiled significant associations between 33 plasma lipid levels and various CKD-related outcomes by combining insights from both MR and sensitivity analyses. Various plasma lipid species were identified as having either positive or negative causal connections with kidney conditions, demonstrated by specific ranges of IVW-OR values (all P < 0.05). Following the BH correction, elevated sterol ester (27:1/18:2) levels (OR: 1.012 ~ 1.037, P < 0.05) and reduced phosphatidylcholine (16:1_20:4) levels (OR: 0.954 ~ 0.985, P < 0.05) consistently showed a strong causal relationship with increased urine albumin-creatinine ratio. These findings were robust across all sensitivity analyses.

CONCLUSION: This study revealed potential causal associations between specific types of lipidome other than conventional lipids and the occurrence and progression of CKD. These insights pave the way for the development of early diagnostic and prophylactic CKD interventions.

PMID:40495181 | DOI:10.1186/s13098-025-01764-y

Biomed Eng Online. 2025 Jun 10;24(1):72. doi: 10.1186/s12938-025-01403-7.

ABSTRACT

BACKGROUND: Despite therapeutic advances, acute leukemia (AL) continues to impose a substantial global health burden, with persistently high incidence and mortality rates. Notably, the prediction is that the number of incidence and mortality of acute myeloid leukemia (AML) cases will continue to increase to 184,287.88 and 165,537.59, respectively, by 2040. Using Global Burden of Disease Study (GBD) 2021 data, we assessed the worldwide AL burden from 1990 to 2021, analyzing trends by sex to inform public health strategies.

METHODS: To delineate the burden of AL, we reported incidence, prevalence, mortality, and disability-adjusted life year (DALY) rates at global, regional, and national levels, with these estimates including age-standardized rates (ASRs) per 100,000 population and average annual percentage changes (AAPCs) from 1990 to 2021 which were stratified by age, sex, and socio-demographic index (SDI), and computed ASRs and AAPCs using linear regression. Temporal trends were analyzed using an age-period-cohort (APC) model with intrinsic estimation (principal component regression). Risk factor attribution quantified contributions of 21 behavioral, environmental, and metabolic exposures to AL-related DALYs. For inequality assessment, we applied the Slope Index of Inequality and Concentration Index to evaluate absolute and relative disparities in AL burden across regions and countries. Future projections (2040) were modeled via a Bayesian APC framework with Integrated Nested Laplace Approximation. All statistical analyses were performed using R software (version R 4.4.1). The GATHER (Guidelines for Accurate and Transparent Health Estimates Reporting) statement provides a framework to ensure the transparency, reproducibility, and quality of health estimates reporting.

RESULTS: Between 1990 and 2021, global ASRs of AL declined, except for acute lymphoblastic leukemia (ALL) age-standardized prevalence rates (ASPR) (AAPC 0.84, 95% CI 0.59-1.10). Case numbers rose overall, though ALL mortality and DALYs decreased. AML burden correlated positively with SDI (ρ > 0, P < 0.001), with the highest number of incident and mortality cases in Western Europe. For ALL, SDI showed positive associations with ASIR and ASPR (ρ > 0, P < 0.001) but negative correlations with ASMR and ASDALR (ρ < 0, P < 0.001), with East Asia being the most severely affected region. High body mass index (BMI), smoking, and benzene/formaldehyde exposure were key AL DALY risk factors. High BMI and smoking predominate in developed countries, and the proportion of DALYs decreases progressively as SDI decreases. Occupational exposures prevailed in developing countries. Population growth drove most absolute increases. Males bore a greater AL burden. AML risk rose with age, whereas ALL displayed bimodal peaks (< 5 and > 40 years). Notably, while ASRs in AL are projected to decline slightly and the number of ALL to decrease by 2040, the number of AML is expected to increase, with the number of incidence and mortality cases increasing by 41.56% and 27.16%, respectively.

CONCLUSION: As a major public health concern, despite declining ALL-related mortality and DALYs (1990-2021), AL remains a growing global health challenge, with AML cases projected to rise significantly by 2040. Region-specific intervention strategies are required: high-SDI nations should prioritize smoking cessation and metabolic control to address smoking and high BMI-related AML risks while preparing for aging populations, whereas low/middle-SDI countries urgently need enhanced pediatric ALL diagnosis, treatment capacity, and occupational safety measures. Effective mitigation demands evidence-based health planning, including resource allocation guided by projected AL burden trends and targeted policy interventions to reduce healthcare disparities.

PMID:40495176 | DOI:10.1186/s12938-025-01403-7

J Physiol Anthropol. 2025 Jun 10;44(1):17. doi: 10.1186/s40101-025-00397-4.

ABSTRACT

BACKGROUND: Sleep deprivation and irregular sleep patterns can adversely affect physical and mental health. The COVID-19 pandemic presented a naturalistic opportunity to examine how reduced social time restrictions influence sleep behavior. This study aimed to investigate both group-level and individual-level changes in sleep patterns among Japanese university students before and during the pandemic and to explore how individual characteristics may contribute to these changes.

METHODS: Twenty-two female university students wore waist-worn actigraphy devices for approximately 16 weeks in both 2019 and 2020. Objective sleep data were collected alongside questionnaire assessments of chronotype, personality traits, and subjective sleep feeling.

RESULTS: In total, 4,432 valid days of actigraphy data were analyzed. Compared with the pre-pandemic year, sleep timing was delayed by approximately 20 min for bed-in time and 40 min for bed-out time in 2020. Time in bed (TIB) increased by about 20 min, while total sleep time (TST) remained largely unchanged. Sleep efficiency declined, but subjective sleep feeling remained stable. Individual-level analyses revealed substantial variability: 9 of 22 participants showed significant changes in TST, with both increases and decreases observed. Increased TIB was associated with later bed-out time, shorter baseline sleep duration, and lower neuroticism. A later bed-in time was associated with reduced TST.

CONCLUSIONS: These findings suggest that while social time restrictions can influence sleep timing and duration, the effects vary considerably across individuals. Earlier bedtimes may be more effective than simply extending TIB in promoting adequate sleep. Furthermore, individual characteristics such as personality traits may play a role in sleep adaptation under changing social contexts. Given the diversity of responses observed, both group- and individual-level perspectives are essential for understanding sleep behavior in real-world settings.

PMID:40495174 | DOI:10.1186/s40101-025-00397-4

BMC Public Health. 2025 Jun 10;25(1):2146. doi: 10.1186/s12889-025-23427-3.

ABSTRACT

BACKGROUND: Diphtheria remains a significant public health concern in Nigeria, with over 20,000 suspected cases and more than 500 deaths reported during the 2022-2023 outbreak period, particularly concentrated in the northern regions. Understanding public perceptions and behavior regarding diphtheria, including symptoms, transmission, and vaccination across different seasons, is vital for developing effective interventions. This study aimed to evaluate seasonal variations in public awareness of diphtheria, including knowledge of its symptoms and information sources. Additionally, it sought to assess the perceived at-risk groups and attitudes toward diphtheria vaccination in the country.

METHODS: A cross-sectional survey was conducted among residents aged 18 years and older in Kano, Katsina, Bauchi, Yobe, Borno, Kaduna, Jigawa, Kebbi, and the Federal Capital Territory (FCT). Data were collected by trained fieldworkers over 12 months via structured questionnaires divided into four sections: demographics, public awareness, perceived risk, and vaccination attitudes. Ethical approval was obtained, and verbal informed consent was secured from all participants. Data analysis involved descriptive statistics and statistical tests to examine associations between variables.

RESULTS: A total of 3,070 respondents participated in the study. Public awareness of common diphtheria symptoms such as fever (68.0%) and sore throat (60.5%) was high, whereas awareness of conjunctivitis (23.9%) was lower. Children under 5 years of age were consistently perceived as the most at-risk group (80.5%). The willingness to vaccinate against diphtheria remained high at 94.4%, with no significant seasonal variation (p-value 0.894; Chi-square test). Radio (53.1%) was identified as the primary information source, especially during the rainy season (54.6%). Seasonal variations in preventive and vaccination practices were minimal, indicating consistent public health behaviors throughout the year.

CONCLUSION: This study highlights the importance of maintaining robust public health education campaigns, leveraging both traditional and digital media to sustain high awareness and vaccination rates for public health interventions. Based on our findings, we recommend implementing targeted school-based health education programs and strengthening partnerships with community health workers to enhance diphtheria awareness, especially among caregivers of young children. Understanding sociodemographic and seasonal contexts is crucial for effective public health interventions, ensuring that at-risk groups are adequately protected.

PMID:40495171 | DOI:10.1186/s12889-025-23427-3