Tag: pubmed

HGG Adv. 2025 Jul 18:100482. doi: 10.1016/j.xhgg.2025.100482. Online ahead of print.

ABSTRACT

Genome-wide association studies (GWAS) from multiple ancestral populations are increasingly available, offering opportunities to improve the accuracy and equity of polygenic scores (PGS). Several methods now aim to leverage multiple GWAS sources, but predictive performance and computational efficiency remain unclear, particularly when individual-level tuning data are unavailable. This study evaluates a comprehensive set of PGS methods across African (AFR), East Asian (EAS), and European (EUR) ancestries for 10 complex traits, using summary statistics from the Ugandan Genome Resource, Biobank Japan, UK Biobank, and the Million Veteran Program. Single-source PGS were derived using methods including DBSLMM, lassosum, LDpred2, MegaPRS, pT+clump, PRS-CS, QuickPRS, and SBayesRC. Multi-source approaches included PRS-CSx, TL-PRS, X-Wing, and combinations of independently optimised single-source scores. All methods were restricted to HapMap3 variants and used linkage disequilibrium reference panels matching the GWAS super population. A key contribution is a novel application of the LEOPARD method to estimate optimal linear combinations of population-specific PGS using only summary statistics. Analyses were implemented using the open-source GenoPred pipeline. In AFR and EAS populations, PGS combining ancestry-aligned and European GWAS outperformed single-source models. Linear combinations of independently optimised scores consistently outperformed current jointly optimised multi-source methods, while being substantially more computationally efficient. The LEOPARD extension offered a practical solution for tuning these combinations when only summary statistics were available, achieving performance comparable to tuning with individual-level data. These findings highlight a flexible and generalisable framework for multi-source PGS construction. The GenoPred pipeline supports more equitable, accurate, and accessible polygenic prediction.

PMID:40684263 | DOI:10.1016/j.xhgg.2025.100482

Postgrad Med J. 2025 Jul 20:qgaf107. doi: 10.1093/postmj/qgaf107. Online ahead of print.

NO ABSTRACT

PMID:40684261 | DOI:10.1093/postmj/qgaf107

Alzheimers Dement. 2025 Jul;21(7):e70485. doi: 10.1002/alz.70485.

ABSTRACT

INTRODUCTION: Cognitive impairment is common but often overlooked due to motor symptoms in progressive supranuclear palsy-Richardson syndrome (PSP-RS). This study investigates whether cognitive deficits predict disease progression in PSP-RS.

METHODS: A total of 146 PSP-RS from the Tilavonemab trial were evaluated at baseline and over 52 weeks using the PSP-Rating Scale (PSPRS), the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and the Unified Parkinson’s Disease Rating Scale Part-II (UPDRS-II). Multiple linear regression analyses were performed between the RBANS, UPDRS-II, and the PSPRS change. Clinical scores, gray matter volumes, and neurofilament-light chain (NfL) were compared using analyses of covariance (ANCOVAs) and linear mixed models between language score-groups.

RESULTS: Lower RBANS-language at baseline predicted greater PSPRS worsening over time. The low language-score group showed poorer cognitive performance, elevated NfL, and reduced gray matter volume in language-related areas.

DISCUSSION: Speech/language deficits predict worse prognosis in PSP-RS, emphasizing the value of including language scores in clinical trials.

HIGHLIGHTS: Speech and language deficits predict a worse prognosis in progressive supranuclear palsy-Richardson syndrome (PSP-RS). Lower language scores are associated with worse cognitive performance over time. Lower language scores related to higher neurofilament-light chain (NfL) at baseline. The low language-score group presented greater atrophy in language-related brain areas. Stratifying PSP-RS cases using language scores may improve clinical trials.

PMID:40684253 | DOI:10.1002/alz.70485

J Health Popul Nutr. 2025 Jul 19;44(1):261. doi: 10.1186/s41043-025-01019-6.

ABSTRACT

One of the most significant global public health concerns for women of reproductive age is the unmet need for modern contraceptives. The goal of increasing the use of modern contraceptives is to lower mother and child mortality and morbidity. Since East African nations are part of sub-Saharan Africa, a region primarily composed of low-income countries, they face significant challenges in accessing modern contraceptives due to limited healthcare infrastructure, economic constraints, and socio-cultural barriers. The objective of this study was to investigate the prevalence and factors associated with modern contraception utilization among reproductive-age East African women.

METHODS: The data was taken from the individual records (IR) of the ten East African countries’ Demographic and Health Surveys. The study included 112,810 women of reproductive age. The primary outcome was modern contraceptive utilization, defined as a binary variable (yes = use of modern methods; no = use of traditional/folkloric or no methods). Key predictors included age, place of residence, marital status, sex of household head, wealth index, exposure to media (newspaper, radio, television), pregnancy termination history, and number of living children. Bivariate analysis was utilized to select the variables for multivariable analysis. At last, 95% CIs for the odds ratio and percentage were presented.

RESULTS: Among women of reproductive age, 33.81% of them used modern contraceptives, with a 95% CI of [33.53-34.09]. Individuals aged 20-24, 25-29, 30-34, and 35-39 demonstrate the following statistically adjusted odds ratios (AOR) and confidence intervals (CI): AOR = 1.68, 95% CI (1.68, 1.79); P = 0.0001; AOR = 1.56, 95% CI (1.46, 2.65); P = 0.0001; AOR = 1.43, 95% CI (1.33, 1.54); P = 0.0001; and AOR = 1.34, 95% CI (1.24, 1.44); P = 0.0001, respectively. urban residence is associated with an AOR of 1.06, 95% CI (0.91, 0.97); P = 0.001; being married [AOR: 1.20, 95% CI (1.13, 1.28); P = 0.0001]; belonging to the highest wealth quantile [AOR: 1.34, 95% CI (1.27, 1.43); P = 0.0001]; reading magazines at least once a week [AOR: 1.07 (1.00, 1.14); P = 0.032]; listening to the radio almost daily [AOR: 1.91 (1.69, 2.17); P = 0.0001]; watching television daily [AOR: 1.62 (1.45, 1.82); P = 0.0001]; and having 3-4 children [AOR: 11.68, 95% CI (10.78, 12.66); P = 0.0001] were found positively associated with modern contraceptive utilization. Conversely, having a history of pregnancy termination [AOR: 0.83 (0.80, 0.87); P = 0.0001] and belonging to a household headed by a woman [AOR: 0.95 (0.92, 0.99); P = 0.037] were found to be inversely associated with modern contraceptive utilization.

CONCLUSION AND RECOMMENDATION: This study identified key factors influencing modern contraceptive use among women in East Africa. Higher utilization was associated with being aged 20-39, urban residence, being married, higher wealth status, media exposure, and having more children. In contrast, lower use was observed among women living in female-headed households and those with a history of pregnancy termination. Despite these influencing factors, modern contraceptive use in East Africa remains below the 2030 Sustainable Development Goal (SDG) target. Therefore, to improve uptake among women of reproductive age, healthcare providers and policymakers should design and implement targeted interventions focusing on adolescents, rural residents, women with a history of pregnancy termination, and socioeconomically disadvantaged groups to enhance contraceptive use and reproductive health outcomes in the region.

PMID:40684244 | DOI:10.1186/s41043-025-01019-6

J Orthop Surg Res. 2025 Jul 19;20(1):683. doi: 10.1186/s13018-025-06086-3.

ABSTRACT

BACKGROUND: Screw placement in lateral plating of calcaneal fractures presents a challenge due to the proximity of medial neurovascular structures. This study aims to identify high-risk zones, determine appropriate screw lengths, and define optimal fluoroscopic angles to enhance intraoperative visualisation and improve surgical safety.

METHODS: Thirty-three fresh-frozen cadaveric specimens were used. Following a lateral extensile approach, locking screws were inserted through an anatomical plate into seven predefined zones using sleeve-guided drilling, without plate bending or freehand angulation. For each screw, the appropriate length was initially measured, but to facilitate identification during subsequent medial dissection, longer screws were intentionally inserted. Following screw insertion, medial dissection was performed to expose neurovascular and tendinous structures. Distances from each screw were measured at two points: (1) the actual exit point on the medial cortex, and (2) the projected trajectory of the screw. Based on these measurements, risk scores were assigned using a validated scoring system. In a separate step, fluoroscopic angle measurements were conducted. K-wires were placed into the posterior facet and the sustentacular sulcus, and the required cranial and medial angulations of the C-arm relative to the plantar referenced axis were determined for the optimal visualisation of the joint and medial cortex.

RESULTS: Zone 4 (subchondral zone) demonstrated the highest risk, with medial plantar vessels, medial plantar nerve, lateral plantar vessels, and flexor hallucis longus at significant risk, particularly at the projection point. In contrast, Zone 2 inferior and Zones 3 had lower risk scores. The anticipated screw lengths ranged from 35.49 mm to 38.73 mm across different zones. Nearly all distances between screw exit points and projections showed statistically significant differences (p < 0.05), highlighting the importance of screw length. Inter- and intra-observer reliability was good to excellent across all measurements (ICC > 0.75). Fluoroscopic analysis revealed that rotating the C-arm cranially by 34.7° relative to a plantar reference axis optimised posterior facet visualisation, while a combination of 26.09° cranial and 17.79° medial angulation provided the best imaging of the medial cortex at the sustentacular sulcus.

CONCLUSIONS: This study identifies Zone 4 (subchondral zone) as the highest-risk area for neurovascular injury in lateral calcaneal plating and highlights the importance of screw length selection, particularly reconsidering screws exceeding 40 mm, and optimal fluoroscopic visualisation of medial high-risk zones. These findings are crucial for enhancing intraoperative safety in calcaneal fracture fixation.

PMID:40684243 | DOI:10.1186/s13018-025-06086-3

BMC Psychol. 2025 Jul 19;13(1):808. doi: 10.1186/s40359-025-03067-3.

ABSTRACT

BACKGROUND: Entrepreneurial learning is widely recognized as a critical factor in enhancing entrepreneurial performance. However, the specific impact of entrepreneurial learning on the performance of female entrepreneurs and the underlying mechanisms involved remain underexplored. The main purpose of this study is to explore the impact mechanism of entrepreneurial learning on entrepreneurial performance among female entrepreneurs and to reveal the mediating roles of psychological capital and opportunity recognition and development in this relationship.

METHOD: This study employs a quantitative research approach, conducting empirical analysis using survey data from 558 Chinese female entrepreneurs. Utilizing AMOS statistical software, we construct structural equation models to examine the relationship between entrepreneurial learning and business performance among female entrepreneurs.

RESULTS: The findings reveal that: (1) Entrepreneurial learning among female entrepreneurs has a direct and positive impact on entrepreneurial performance, and (2) Psychological capital and opportunity recognition and development serve as key mediators in this relationship.

CONCLUSIONS: Grounded in entrepreneurial learning theory, this study proposes a pathway model that illustrates how female entrepreneurs can leverage entrepreneurial learning to improve their performance. By shedding light on the mechanisms through which entrepreneurial learning influences performance, this study extends the application of entrepreneurial learning theory within the context of female entrepreneurship and provides practical insights for enhancing the entrepreneurial success of female entrepreneurs.

CLINICAL TRIAL REGISTRATION: Not applicable.

PMID:40684238 | DOI:10.1186/s40359-025-03067-3

J Exp Clin Cancer Res. 2025 Jul 19;44(1):214. doi: 10.1186/s13046-025-03473-w.

ABSTRACT

BACKGROUND: Glioblastoma (GBM), the most common and aggressive type of primary brain tumor, engages multiple survival mechanisms, including autophagy. GBM exploits both degradative and secretory autophagy pathways to support tumor growth and limit the efficacy of standard-of-care treatments. We have previously shown that lucanthone, a blood-brain barrier permeable autophagy inhibitor, reduces tumor burden. However, although lucanthone-treated tumors are significantly smaller in size, they are not completely obliterated, suggesting compensatory survival mechanisms. A critical factor for GBM survival is communication with the tumor microenvironment (TME), which can be programmed by glioma cells to support growth and immunosuppression. Plasminogen activator inhibitor-1 (PAI-1), a secreted serine protease inhibitor, has been implicated in the progression of several cancers, including GBM, and has been shown to be modulated by autophagy in other cancers. The role of PAI-1 in GBM, namely its relationship with intracellular autophagy dysregulation and extracellular TME as a mechanism of tumor survival, remains incompletely understood.

METHODS: Murine glioma models were established using intracranial injection of GL261 cells in C57BL/6 mice, followed by autophagy inhibition with intraperitoneal lucanthone and/or PAI-1 inhibition with MDI-2268 chow, and tumors were assessed by immunohistochemistry. In culture, glioma cell lines were challenged with MDI-2268, lucanthone, mitoxantrone, or siRNA-LNPs targeting PAI-1, and assessed by MTT assay, q-RT-PCR, ELISA, invasion assay, immunoblot, and immunocytochemistry. Lysosomal markers and transient transfection with fluorescent vesicular proteins were utilized to evaluate PAI-1 intracellular localization via confocal microscopy. Synergy was analyzed using the HSA model in Combenefit, and statistical analyses included t-tests, ANOVA, and log-rank tests for survival.

RESULTS: Lucanthone treatment increased intracellular PAI-1 and autophagy markers while reducing active extracellular PAI-1. PAI-1 colocalized with lysosomal markers, suggesting impaired secretory autophagy. PAI-1 inhibition reduced glioma cell viability and invasion. Combination therapy with lucanthone and MDI-2268 drastically decreased tumor volume, prolonged survival, and promoted a pro-inflammatory state in the tumor microenvironment.

CONCLUSIONS: Our findings suggest that PAI-1 may be a compensatory survival mechanism in GBM after autophagy inhibition, and that dual targeting of autophagy and PAI-1 disrupts tumor progression and enhances anti-tumor immunity, providing promising evidence for targeting this axis.

PMID:40684232 | DOI:10.1186/s13046-025-03473-w

J Orthop Surg Res. 2025 Jul 19;20(1):679. doi: 10.1186/s13018-025-06074-7.

ABSTRACT

BACKGROUND: Ankylosing spondylitis (AS) often leads to severe thoracolumbar kyphotic deformity, requiring surgical correction. Pedicle subtraction osteotomy (PSO) is the gold standard but carries risks of significant blood loss and neurological complications. Posterior trans-intervertebral osteotomy (PTIO) has emerged as a less invasive alternative, but its comparative efficacy and safety remain unclear. This study aimed to compare radiographic outcomes, surgical parameters, and complications between PTIO and PSO in AS-related kyphosis.

METHODS: A single-center retrospective cohort study included 45 AS patients with thoracolumbar kyphosis (19 PTIO, 26 PSO) who underwent posterior spinal correction. Radiographic parameters (global kyphosis GK, sagittal vertical axis SVA, etc.), surgical data (operative time, blood loss), health-related quality of life (SRS-22), and complications were analyzed. Statistical comparisons were performed using independent t-tests or Mann-Whitney U tests for continuous variables and chi-square/Fisher’s tests for categorical variables.

RESULTS: Both groups achieved significant kyphosis correction, with no differences in postoperative GK (PTIO: 51.4° ± 13.3° vs. PSO: 47.4° ± 13.0°, P > 0.05) or SVA (PTIO: 59.1 ± 50.3 mm vs. PSO: 49.0 ± 47.1 mm, P > 0.05). PTIO showed lower intraoperative blood loss (600.9 ± 264.6 mL vs. 1088.7 ± 287.9 mL, P = 0.009) and fewer neurological complications (5.3% vs. 15.4%, P = 0.003). Health-related quality of life improved similarly in both groups (P > 0.05).

CONCLUSION: PTIO provides comparable radiographic correction to PSO while reducing blood loss and neurological risks. It represents a viable, less invasive alternative for AS-related kyphosis, particularly when anterior column support is achievable. Further studies with long-term follow-up are warranted to validate these findings.

PMID:40684231 | DOI:10.1186/s13018-025-06074-7

Am J Hum Biol. 2025 Jul;37(7):e70096. doi: 10.1002/ajhb.70096.

ABSTRACT

This article considers how to approach sporting injury from the perspective of gender/sex entanglement. Taking the case of anterior cruciate ligament (ACL) injuries, I explore how the gender differences and inequalities that fundamentally shape many sporting environments may contribute to injury in women athletes. I look to Australian Rules football (Aussie Rules)-a male-dominated, high-contact, highly skilled running game and Australia’s largest commercial sport-where, following the launch of a women’s professional league in 2017, a marked gender disparity in ACL injury has been reported. Rather than attribute this reported disparity to essential biological differences between women and men, I consider how gendered practices and disparities may accumulate across the life course of athletes with consequences for the embodied experiences of women and girls. Building on the concept of structural sexism as a key determinant of health, I document gender-related differences and inequalities at the early childhood, youth, and elite levels of Aussie Rules football. Via this case, I contribute to calls for a dynamic, developmental, and fundamentally gendered approach to studies of injury both in and beyond sport.

PMID:40682458 | DOI:10.1002/ajhb.70096

Euro Surveill. 2025 Jul;30(28). doi: 10.2807/1560-7917.ES.2025.30.28.2400723.

ABSTRACT

BACKGROUNDGermany lacks comprehensive studies on the relationship between socioeconomic position (SEP) and antimicrobial resistance (AMR).AIMWe assessed the association between area-level SEP and AMR infection and colonisation in Germany.METHODSIn an ecological study design, we analysed statutory notifications of invasive meticillin-resistant Staphylococcus aureus (MRSA, n = 34,440) in 2010-2019, and colonisations and infections with carbapenem-resistant Acinetobacter spp. (CRA, n = 1,979) and Enterobacterales (CRE, n = 10,825) in 2017-2019. Area-level SEP was measured by the German index of socioeconomic deprivation (GISD), incorporating education, employment and income data. A multilevel Poisson regression analysis estimated the association between AMR incidence and GISD at district level, adjusting for age, sex, notification year and urbanisation degree.RESULTSMedian ages of patients with carbapenem-resistant bacteria were between 66 (CRA colonisation) and 69 years (CRE infection). For MRSA infections, the median age was 74 years. Across each pathogen, approximately two thirds of patients were male. Estimated MRSA incidence was almost five times higher in districts with lowest vs highest area-level SEP (incidence rate ratio, IRR: 4.8; 95% CI: 2.8-8.2). This association was strongest in large cities (IRR: 9.1; 95% CI: 2.7-30.9), and sparsely populated rural districts (IRR: 6.5; 95% CI: 2.8-15.0). Associations of CRA (IRR: 0.6; 95% CI: 0.3-1.2) and CRE (IRR: 0.9; 95% CI: 0.6-1.4) infections with SEP were not statistically significant.CONCLUSIONLower area-level SEP and degree of urbanisation were associated with MRSA incidence, however, no associations were uncovered between SEP and CRA or CRE infections. Further individual-level research could explore if health behaviours, living/working conditions or healthcare access explain the findings. Socioeconomic conditions should be considered for AMR prevention and control.

PMID:40682454 | DOI:10.2807/1560-7917.ES.2025.30.28.2400723