Tag: nevin manimala

DNA Cell Biol. 2026 Mar 11:10445498261421790. doi: 10.1177/10445498261421790. Online ahead of print.

ABSTRACT

Breast cancer is the most diagnosed cancer in women and the second leading cause of cancer-related mortality worldwide. Advances in genetic technology have highlighted the heterogeneity of breast cancer, composed of various biological subtypes, with genetic profiling playing a crucial role in predicting chemotherapy response. This underscores the importance of identifying sensitive diagnostic and prognostic markers for early detection and developing more efficient targeted therapies. Among these, survivin, a protein linked to apoptosis inhibition and cell cycle regulation, is strongly expressed in various cancers, including breast cancer, where its overexpression is associated with poor prognosis and reduced survival rates. To analyze the effects of survivin gene inhibition in a triple-negative breast cancer (TNBC) model. The MDA-MB-231 cell line was stably transfected with short hairpin RNA targeting survivin, and the inhibition was validated via RT-qPCR and Western blot. Morphological evaluation, proliferation and migration assays, and a differential gene expression analysis using the GeneChip™ Human Gene 2.0 ST Array were performed. Statistical analyses were conducted with GraphPad Prism version 8 and Transcriptome Analysis Console. Survivin-inhibited MDA-MB-231-KD cells exhibited evident morphological changes, reduced migration capacity, and altered expression of genes such as BCL2, COX1, COX2, VGF, BIR2, and CDC20, involved in key cancer signaling pathways. Inhibition of survivin in this TNBC model induces critical cellular changes and significantly alters gene expression associated with tumor progression, highlighting its potential as a therapeutic target.

PMID:41813598 | DOI:10.1177/10445498261421790

Int J Cancer. 2026 Mar 11. doi: 10.1002/ijc.70427. Online ahead of print.

ABSTRACT

Monoclonal gammopathy of undetermined significance (MGUS) is a necessary precursor condition to multiple myeloma (MM). Given the role of autophagy in modulating MM risk, we investigated whether genetic variation in autophagy-related genes influences susceptibility to MGUS. We analyzed the association of 34,042 common autophagy-related single nucleotide polymorphisms (SNPs) with MGUS across six independent cohorts, five from Europe and one from North America, comprising 2317 MGUS cases and 282,358 controls. We also assessed their impact on immune parameters, including absolute counts of 91 blood-derived immune cell subsets and 103 circulating immunological proteins. Meta-analysis revealed a genome-wide significant association between the ULK4_rs6599175C allele and increased MGUS risk (p = 3.35 × 10^-8). Carriers of this allele showed reduced counts of memory B cell subsets (IgM+CD38+CD27+ and IgD+IgM+CD27+; p = .0038 and p = .0056, respectively) and natural effector B cells (CD24+CD38+IgD+IgM+ cells; p = .0060). Although these associations were not statistically significant after multiple testing correction, they suggest a role of ULK4 in early B-cell differentiation. Additionally, the CDKN2A_rs2811710 variant showed a suggestive association with MGUS risk (p = 2.17 × 10^-4), affecting transcription factor binding involved in B-cell proliferation and differentiation, although it lacked association with immune markers. In conclusion, we confirm a genome-wide significant association of the ULK4 locus and MGUS risk, supporting its role in early B-cell differentiation, and identify CDKN2A as a candidate susceptibility locus warranting further investigation.

PMID:41813586 | DOI:10.1002/ijc.70427

Trop Med Int Health. 2026 Mar 11. doi: 10.1111/tmi.70114. Online ahead of print.

ABSTRACT

INTRODUCTION: In 1999, the prevalence of female genital mutilation (FGM) was 5% in the Democratic Republic of the Congo (DRC). This study aims to assess FGM prevalence and types, describe its demographic and sociocultural characteristics, and evaluate its long-term impact on pelvic floor and sexual function.

METHODS: A cross-sectional study was conducted from 2021 to 2023 among 519 adult women living in six provinces of the DRC, selected to represent the country’s ethnolinguistic diversity. Pregnant women, those within 6 months of childbirth, survivors of sexual violence, and those with war mutilations were excluded. A questionnaire was designed to collect data, supplemented by a vulvar assessment. The variables were compared using appropriate statistical tests (p < 0.05).

RESULTS: The prevalence of FGM was 15.2% (95% CI: 12.2%-18.6%). The prevalence of FGM Types I-II and inner labia elongation (ILE) was 1.7% (95% CI: 0.8%-3.3%) and 13.5% (95% CI: 10.7%-16.7%), respectively. ILE was on average performed at the age of 13.8 years, mainly by women themselves (88.6%), while the circumstances of FGM I-II practice were unknown. ILE was practiced among the Swahili (65.7%) and the Baluba (27.1%), while FGM I-II were practiced among the Bangala (100%). Women with ILE were at higher risk of urinary incontinence (OR: 2.02; 95% CI: 1.17-3.45), dyspareunia (OR: 2.07; 95% CI: 1.08-3.99), and sexual satisfaction disorders (OR: 2.75; 95% CI: 1.34-5.52) than women without FGM.

CONCLUSION: FGM is practiced in specific ethnic groups in the DRC, with ILE secondarily leading to long-term effects on pelvic floor and sexual function.

PMID:41813581 | DOI:10.1111/tmi.70114

JMIRx Med. 2026 Feb 27;6:e90221. doi: 10.2196/90221.

NO ABSTRACT

PMID:41813577 | DOI:10.2196/90221

JMIR Pediatr Parent. 2026 Mar 2;9:e80129. doi: 10.2196/80129.

ABSTRACT

BACKGROUND: Physical activity (PA) is essential for the healthy development of children. However, the pervasive presence of digital technologies has made digital gaming (DG) a prominent part of children’s everyday lives. As children grow up immersed in these digital environments, concerns about reduced PA have intensified. Given that adults, particularly parents and guardians, play a central role in guiding children’s behavior, their understanding of children’s motivational drivers for both PA and DG is of particular relevance.

OBJECTIVE: This study aimed to explore the motivational differences underlying children’s engagement in either PA or DG. Specifically, the study investigated five distinct motivational scales (recreation, social interaction, coping, competition, and skill) to determine which motives primarily drive behavior in each context. Also, it assessed whether adults accurately perceive these motives in children.

METHODS: Data were collected during events using an on-site questionnaire based on the Videogaming Motives Questionnaire. Both children and their accompanying adults completed parallel assessments regarding motives for PA and DG. The final sample included 94 participants forming 49 parent-child pairs. A 3-way mixed ANOVA with group as a between-subjects factor and activity and motive as within-subjects factors was conducted to examine group, activity, and motive effects and their interactions. To further explore these effects, a series of 2 × 5 repeated measures ANOVAs were conducted to examine the interaction between activity type and motivational dimension across groups, followed by separate multivariate tests per motive.

RESULTS: A significant interaction effect between activity type and motivational dimension emerged in the children’s data (F4,45=3.93, P=.008, partial η²=.259). Further analyses showed that motive competition was rated significantly higher for DG than for PA (F1,48=4.38, P=.04, partial η²=.084). Among adults, separate multivariate tests for each motivational dimension revealed the largest difference in perceived motive coping (F1,48=4.72, P=.01, partial η²=.123), with PA rated higher than DG. Additionally, a significant difference emerged for motive competition (F1,48=4.10, P=.05, partial η²=.079), indicating higher ratings for DG compared to PA.

CONCLUSIONS: The findings emphasize the complexity of children’s motivational profiles, suggesting that engagement in DG is not necessarily a sign of diminished interest in PA but rather reflects alternative, equally compelling motivations. This nuanced understanding challenges simplistic dichotomies and supports the need for balanced perspectives on children’s activity preferences. Importantly, no statistically significant differences were detected between children’s self-reported motives and adults’ perceptions of their children’s motives, suggesting a general tendency toward similar ratings rather than clear evidence of alignment. These insights can inform the development of more tailored strategies for promoting both physical and digital engagement in a healthy and complementary manner.

PMID:41813574 | DOI:10.2196/80129

JMIRx Med. 2026 Feb 27;7:e88830. doi: 10.2196/88830.

NO ABSTRACT

PMID:41813573 | DOI:10.2196/88830

Heart Lung Circ. 2026 Mar 10:S1443-9506(25)01698-1. doi: 10.1016/j.hlc.2025.09.016. Online ahead of print.

ABSTRACT

BACKGROUND: Effective management of volume overload is essential for improving the prognosis of heart failure (HF), which is often complicated by exacerbations and rehospitalisations. Psychosocial and behavioural factors significantly influence volume status. However, studies directly linking these factors to volume overload in patients with HF remain limited.

AIM: This study aimed to model the direct and indirect influences of social support, cognition, self-efficacy, consideration of future outcomes, and self-care on volume overload in patients with HF to guide volume management interventions.

METHOD: A cross-sectional study was conducted among 233 consecutively hospitalised patients with HF from a tertiary hospital in Chongqing, China (January-July 2023). Bioelectrical impedance analysis measured volume status, and psychosocial and behavioural variables were assessed using validated scales, including the Lubben Social Network Scale, Mini-Cog, General Self-Efficacy Scale, Consideration of Future Consequences Scale, and Self-Care of Heart Failure Index, Version 6.2 Behaviour Scale. Data were analysed using IBM SPSS Statistics, Version 26.0 and AMOS 24.0.

RESULTS: Among the patients (mean age=66.49±12.49 years; 43.35% women; 61.8% New York Heart Association stage III), 71% experienced volume overload. Path analysis showed that volume overload (oedema index) was directly and negatively associated with self-care maintenance (β=-0.263; p<0.001), cognition (β=-0.202; p<0.001), and self-efficacy (β=-0.199; p<0.01). Indirect negative effects were observed for social support (β=-0.203; p<0.001), self-care confidence (β=-0.090; p<0.001), and consideration of future outcomes (β=-0.057; p<0.001).

CONCLUSIONS: Factors such as social support, cognitive functioning, self-efficacy, future considerations, and self-care are significant contributors to the vulnerability of patients with HF to volume overload. This underscores the necessity for multifaceted interventions aimed at improving the prognosis of patients with HF.

PMID:41813559 | DOI:10.1016/j.hlc.2025.09.016

Eur Urol Oncol. 2026 Mar 10:S2588-9311(26)00040-4. doi: 10.1016/j.euo.2026.02.003. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Multiparametric magnetic resonance imaging (mpMRI) with targeted biopsies improves detection of clinically significant prostate cancer (csPC), commonly defined as Gleason grade group (GG) ≥2. Current practice combines targeted and systematic biopsies, which increases csPC detection but also increases detection of insignificant PC (GG 1), which contributes to overdiagnosis. Perilesional sampling around MRI-visible lesions has been proposed as a strategy to mitigate targeting imprecision while limiting sampling outside the MRI lesion area and GG 1 detection. The primary objective is to determine the diagnostic performance of the experimental targeted + perilesional biopsy scheme for detection of csPC in comparison to the standard targeted + systematic biopsy scheme.

CLINICAL TRIAL DESIGN AND TIMEFRAME: TARGET is a prospective, multicentre, open-label, comparative clinical trial. Each patient acts as their own control, as each patient will undergo all three types of biopsy (targeted, perilesional, and systematic). The inclusion period will last for 21 mo, and the participation duration for each patient is 3 mo.

ENDPOINTS: The primary endpoint is the sensitivity and specificity of the targeted + perilesional scheme for csPC detection in comparison to the targeted + systematic scheme. Secondary endpoints include differences in the detection rate for insignificant PC (GG 1) and aggressive PC (GG ≥3) between the experimental and standard biopsy schemes.

DATA SOURCES AND STATISTICAL ANALYSIS PLAN: The data collected will include patient demographics and laboratory, radiology, and pathology reports. Analyses will be performed with SAS version 9.4 using a locked database.

STRENGTHS AND LIMITATIONS: Strengths include the prospective and multicentre design. The main limitation is the open-label design.

FUNDING: TARGET is funded by Ramsay Générale de Santé (Paris, France), and supported by the Prostate Cancer Committee of Association Française d’Uologie.

ETHICS AND TRIAL REGISTRATION: The trial was assessed by the CPP Ouest VI ethics committee and is registered on ClinicalTrials.gov as NCT07296042.

PATIENT SUMMARY: Our multicentre trial is comparing two different approaches for prostate biopsy to determine if sampling the area around lesions seen on an MRI (magnetic resonance imaging) scan can maintain the detection rate for clinically significant prostate cancer while reducing detection of low-risk disease.

PMID:41813528 | DOI:10.1016/j.euo.2026.02.003

Lancet Digit Health. 2026 Mar 10:100963. doi: 10.1016/j.landig.2025.100963. Online ahead of print.

ABSTRACT

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with a life expectancy of only 3-5 years and few approved treatments. To identify drug repurposing candidates for the treatment of ALS, we analysed the electronic health records (EHRs) of a large cohort of military veterans with ALS.

METHODS: We analysed the EHRs of individuals in the US Veterans Health Administration (VHA) database who were diagnosed with ALS between Jan 1, 2009 and Dec 31, 2019 to assess medication effects. Individuals without recorded prescriptions after the date of diagnosis were excluded. Two sets of criteria were applied to ascertain exposure. Exposure criteria A were met if the dispense date or the end date of the medication was within 12 months of ALS diagnosis and the end date was at least 6 months after the dispense date. Exposure criteria B were met if there were at least two dispenses within 6 months before diagnosis and 12 months after diagnosis. Propensity score-matched control groups were generated on the basis of confounders included in the EHR, with methodology of potential outcomes used to infer treatment effects. The primary outcome was death. A standard Cox proportional hazards analysis was done to assess association with survival. Survival was defined as the time from diagnosis date recorded in the EHR to death reported in the Department for Veterans Affairs Vital Status File. Follow-up survival time was censored on Dec 31, 2020, for those alive on this date. Downstream protein targets of drugs with clinically significant effects were analysed using the protein-protein interaction networks-based algorithm PathFX.

FINDINGS: The EHRs of 11 003 individuals with ALS in the VHA database were appropriate for analysis. 162 medications with treatment groups of 30 or more individuals were identified. Among these 162 medications, 27 were associated with statistically significant changes (≥0·1) in the hazard ratio (HR) for death. 18 of the medications were associated with a reduced HR for death (prolonged survival), and nine were associated with an increased HR for death (reduced survival). Drugs associated with reduced HR included HMG-CoA reductase inhibitors (simvastatin, pravastatin, lovastatin, and atorvastatin), PDE5 inhibitors (vardenafil and sildenafil), and α-adrenergic antagonists (tamsulosin and terazosin). The medications associated with an increased HR were drugs used either in the management of clinical features of ALS associated with poor outcomes or in end-of-life care. PathFx analysis identified a complex of proteins interacting with several of the identified drugs.

INTERPRETATION: To our knowledge, this analysis is the largest EHR-based study for identifying drug repurposing candidates for ALS. We identified several drugs that warrant further assessment as therapeutic options in ALS, as well as a protein network complex that might serve as a therapeutic target for ALS.

FUNDING: Congressionally Directed Medical Research Programs, US Department of Defense.

PMID:41813498 | DOI:10.1016/j.landig.2025.100963

JMIRx Med. 2026 Mar 3;7:e73211. doi: 10.2196/73211.

ABSTRACT

BACKGROUND: The IT sector is growing and encompasses all professions, from leisure and recreation to hospitals and emergency response groups. IT professionals are experiencing increased threats (eg, ransomware attacks), but little is known about the relationship between these IT profession-specific stressors and the professionals’ mental health.

OBJECTIVE: This study aimed to (1) estimate the associations between IT profession-specific stressors and anxiety, depression, and stress, and (2) examine the role of mental health literacy (MHL) as a mediator of the relationship between depression, anxiety, stress, and help-seeking.

METHODS: Between February and May 2023, IT professionals working in the United States were surveyed online. Participants (n=357) reported demographic characteristics, MHL, mental health symptoms, and help-seeking intentions with the following scales: Mental Health Literacy in the Workplace (MHL-W), Center for Epidemiological Studies Depression-10 (CESD-10), Generalized Anxiety Disorder-7 (GAD-7), Perceived Stress Scale-10 (PSS-10), and the Mental Help Seeking Intention Scale (MHSIS). Descriptive statistics, regression models, and mediation analyses were conducted for CESD-10, GAD-7, and PSS-10.

RESULTS: Respondents who had experienced ransomware attacks in the past year reported significantly higher symptoms of depression (odds ratio [OR] 1.85, 95% CI 1.07-3.22; P=.03). Past-year exposure to balancing security and usability was associated with lower odds of reported anxiety (OR 0.48, 95% CI 0.28-0.82; P=.008). Having made critical technology decisions with limited information in the past year was associated with higher perceived stress by 2.02 points on the PSS-10 scale (SE 0.84, 95% CI 0.37-3.66; P=.02), and working with limited resources in the past year increased perceived stress by 1.70 points (SE 0.84, 95% CI 0.04-3.35; P=.04) after adjusting for the covariates. MHL was found to partially mediate the relationship between depression and help-seeking, but not between anxiety or stress and help-seeking.

CONCLUSIONS: These findings provide insight into the workplace stressors that pose a greater psychological health risk for IT professionals. These results emphasize the important role of MHL in helping facilitate the connection between depressive symptoms and help-seeking.

PMID:41813447 | DOI:10.2196/73211