Category: Statistics

J Assist Reprod Genet. 2025 Nov 27. doi: 10.1007/s10815-025-03731-y. Online ahead of print.

ABSTRACT

PURPOSE: Sperm mature as they transit through the epididymis, during which they gain progressive motility and the capability to fertilize oocytes. Autophagy plays a significant role in the regulation of testicular spermiogenesis. Autophagy-related gene 5 (Atg5) is recognized as a crucial regulator of autophagy progression. However, the role of Atg5 in regulating epididymal sperm maturation has yet to be elucidated.

METHODS: To investigate the function of Atg5 in regulating epididymal sperm maturation, Atg5 conditional knockout mice were generated using Cre/LoxP technology, and sperm quality and fertility were assessed. Comprehensive quantitative analyses and bioinformatics evaluations of the proteome in segments 4-5 of the caput epididymis and sperm from the cauda epididymis were conducted.

RESULTS: Atg5 deletion reduced autophagy in the caput epididymis but did not significantly affect sperm motility. Quantitative proteomics via data-independent acquisition (DIA) and subsequent bioinformatics analysis revealed significant alterations in the expression of several sperm proteins. Among these, the upregulated proteins were strongly associated with Atg5-independent surrogate autophagy, while the downregulated proteins were linked to sperm maturation. Additionally, qRT-PCR assays demonstrated that seven genes closely related to autophagy and sperm quality were differentially expressed in the 4-5 segments of the caput epididymis.

CONCLUSIONS: Atg5 affects protein expression and abundance in both the caput epididymis (segments 4-5) and cauda epididymal sperm, without statistically significant effects on sperm motility or male fertility. However, the potential impact of autophagy inhibition on sperm maturation may arise under challenging survival conditions by influencing the expression of sperm proteins.

PMID:41307852 | DOI:10.1007/s10815-025-03731-y

Discov Oncol. 2025 Nov 27. doi: 10.1007/s12672-025-04173-9. Online ahead of print.

ABSTRACT

BACKGROUND: Inflammatory bowel disease (IBD), comprising Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic inflammatory condition with increasing evidence of comorbidity with breast cancer (BRCA). While epidemiological studies suggest an association, the underlying genetic mechanisms remain largely unexplored.

METHODS: We conducted a comprehensive genome-wide investigation to explore the shared genetic basis between IBD (including CD and UC) and breast cancer. Summary statistics from large-scale GWAS were analyzed using linkage disequilibrium score regression (LDSC), GNOVA, stratified LDSC (S-LDSC), MAGMA, PLACO, and summary-data-based Mendelian randomization (SMR). Tissue-specific enrichment was evaluated using GTEx data, and functional annotation was performed using FUMA.

RESULTS: We identified significant genetic correlations between IBD and breast cancer at the genome-wide level. Subsequent pleiotropy analyses detected 83 genome-wide significant pleiotropic SNPs and 24 shared risk loci, including 9p24.1 and 10q21.2, involving key immune-regulatory genes such as JAK2, CD274, and ZNF365. MAGMA and FUMA revealed enrichment of shared genes in immune pathways such as cytokine signaling, JAK-STAT signaling, and antigen presentation. Tissue-specific analyses indicated significant expression of pleiotropic genes in the colon, terminal ileum, and breast. SMR analysis further supported the transcriptional regulatory role of genes like P4HA2, ZNF365, SLC22A4, and SLC22A5 in both diseases.

CONCLUSION: This study presents the first systematic genetic evidence of a shared immunogenetic basis between IBD and breast cancer. The identification of pleiotropic loci and candidate drug targets provides novel insights into inflammation-associated tumorigenesis and lays the groundwork for future cross-disease prevention and therapeutic strategies.

PMID:41307839 | DOI:10.1007/s12672-025-04173-9

Discov Ment Health. 2025 Nov 27;5(1):189. doi: 10.1007/s44192-025-00324-0.

ABSTRACT

BACKGROUND: Psoriasis is a chronic inflammatory skin disorder that imposes significant physical, psychological, and social burdens on patients and their family caregivers. Family caregivers play a crucial role in patient care, but often experience substantial caregiving burden and psychological distress. Telenursing, as an emerging approach in healthcare, offers an accessible and cost-effective method for providing education and support to caregivers. This study aims to evaluate the effectiveness of telenursing in care education for family caregivers of patients with psoriasis.

METHODS: A single-site, open-label randomized clinical trial with two parallel groups (intervention and control) will be conducted at the dermatology clinic of Razi Hospital, Tehran University of Medical Sciences, between June 2025 and November 2025. Seventy family caregivers of patients with psoriasis who meet the inclusion criteria will be recruited and randomly assigned (38 per group) to either a telenursing-based care education program (intervention) or usual education (control). The intervention will last six weeks, including four weeks of structured online education via WhatsApp and Skyroom, followed by two weeks of follow-up. Primary outcomes (psychological well-being and caregiving burden) and the secondary outcome (caregiver self-efficacy) will be assessed at baseline and post-intervention using validated questionnaires. Statistical analyses will be conducted using SPSS software V.23, with a significance level of p < 0.05.

DISCUSSION AND CONCLUSION: This trial will evaluate whether a structured telenursing program can improve psychological well-being and caregiver self-efficacy while reducing caregiving burden among family caregivers of patients with psoriasis. The findings may inform scalable nurse-led telehealth strategies to support caregivers in chronic dermatological conditions. Trial registration IRCT20240319061338N2, registered on 17 January 2025 in the Iranian Registry of Clinical Trials (IRCT) ( http://www.irct.ir/ ).

PMID:41307833 | DOI:10.1007/s44192-025-00324-0

Drug Saf. 2025 Nov 27. doi: 10.1007/s40264-025-01629-3. Online ahead of print.

ABSTRACT

BACKGROUND: Sulfonylureas (SU) are widely used for diabetes management in older adults but can cause hypoglycemia, which may be worsened by drug interactions. We applied high-throughput data mining to identify medications that could increase hypoglycemia risk when taken with SU.

METHODS: Using Medicare, MarketScan, and Optum Clinformatics (2003-2022), we identified patients aged ≥ 65 years who experienced a severe hypoglycemic event after at least 90 days on SU. We evaluated all medications dispensed in the 90 days before the event using a case-crossover (CCO) design. We adjusted for time-varying confounding and direct effect of the evaluated medications (precipitant) using a case-case time-control (CCTC) approach and metformin as control. We computed odds ratios (ORs) for its association with hypoglycemia. The false discovery rate (FDR) was controlled at 0.05 to adjust for multiple testing. To reduce confounding from other diabetes medications, we analyzed non-diabetes and diabetes medications separately.

RESULTS: Among 1607 candidate drugs received before experiencing hypoglycemia, 86 non-diabetes medications showed a CCO OR ≥ 1.00. With metformin as control, sulfamethoxazole/trimethoprim (CCTC OR 1.76, p < 0.01, FDR q < 0.01) and metronidazole (CCTC OR 2.17, p < 0.01, FDR q = 0.04) were associated with severe hypoglycemia. Among 10 diabetes medications, insulin showed increased association (CCO OR 1.22, p < 0.01); however, once adjusted for the drug’s direct effects, CCTC OR was 1.03 (p = 0.47, FDR q = 0.47).

CONCLUSIONS: Using a high-throughput data mining approach, we identified two antibiotics (sulfamethoxazole/trimethoprim and metronidazole) that may increase hypoglycemia risk in older adults on sulfonylureas. Given the exploratory nature of this study, these findings warrant further investigation.

PMID:41307830 | DOI:10.1007/s40264-025-01629-3

Arch Osteoporos. 2025 Nov 27;20(1):148. doi: 10.1007/s11657-025-01623-3.

ABSTRACT

In 744 adults from Pune (Western India) and nearby villages, osteoporosis prevalence was higher in rural women than urban (43% vs 18%). Advancing age, location, height, tobacco use and sunlight were key determinants. These findings emphasize urgent need for preventive and management strategies in rural population to reduce osteoporosis burden.

BACKGROUND: About 150 million older adults (age > 60y) live in India presently, representing ~ 14% of the global older population. The population is expected to reach 324 million by 2050, leading to higher healthcare burden from conditions like osteoporosis. However, there is limited knowledge about bone health and its determinants in middle-aged rural and urban Indian adults.

METHODS: This study included 744 adults (398 women) aged > 40y from urban and rural areas of Pune, India. We assessed areal bone mineral density (aBMD) at lumbar spine and femur using dual energy x-ray absorptiometry and volumetric bone parameters by peripheral quantitative computed tomography. Socio-economic-status and lifestyle factors (diet, physical activity, tobacco use, sunlight) were evaluated. Differences in bone parameters were analysed and multiple linear regression was used to identify predictors of bone health.

RESULTS: Significant differences observed in anthropometry and lifestyle factors in urban and rural population. Rural men and women had lower aBMD than urban, with osteoporosis more common in rural women (43%) than urban (18%), and in women compared to men (31% vs 8%). In both sexes, bone outcomes were influenced by anthropometric, residential, and lifestyle factors. Height and rural residence predicted bone density and geometry in men, while in women, age, height, rural residence, tobacco intake, and sunlight exposure were key determinants CONCLUSION: Rural population showed poor bone health. Bone health in both sexes was influence by age, height, rural residence, lifestyle factors like tobacco use and sunlight exposure. Strategies targeting lifestyle modification may help improving bone health among Indians.

PMID:41307825 | DOI:10.1007/s11657-025-01623-3

J Thromb Thrombolysis. 2025 Nov 27. doi: 10.1007/s11239-025-03215-x. Online ahead of print.

ABSTRACT

Several risk assessment models (RAMs) guide standardized prophylaxis to prevent venous thromboembolism (VTE) in trauma patients. The Caprini, Trauma Embolic Scoring System (TESS), and Greenfield Risk Assessment Profile (RAP) have been validated individually, but their predictive powers have not been directly compared in the general trauma population. This study evaluated the discriminatory ability of these three RAMs in trauma patients at an ACS-verified Level I Trauma Center. A retrospective review was performed of adult trauma patients in a single institution over one year. Demographic and clinical data were used to calculate Caprini, TESS, and RAP scores. The primary outcome was inpatient VTE. Logistic regression models – both combined and separate – generated receiver operating characteristic (ROC) curves for each score. Caprini served as the reference for comparing discriminatory ability. Among 1,276 patients, 33 (2.6%) developed inpatient VTE. Caprini, TESS, and RAP scores predicted VTE with odds ratios of 1.07 (95% CI 1.04-1.10), 1.39 (95% CI 1.23-1.56), and 1.20 (95% CI 1.12-1.29), respectively. ROC c-statistics were similar: Caprini 0.75 (95% CI 0.68-0.82), TESS 0.73 (95% CI 0.64-0.83), and RAP 0.70 (95% CI 0.60-0.79). Caprini, TESS, and RAP RAMs showed comparable moderate discriminatory ability (c-statistic > 0.70) in predicting inpatient VTE among trauma patients. No model was superior, suggesting any of these RAMs may guide standardized VTE prophylaxis in this population.

PMID:41307791 | DOI:10.1007/s11239-025-03215-x

Neuroinformatics. 2025 Nov 27;23(4):57. doi: 10.1007/s12021-025-09756-z.

ABSTRACT

Modelling real-world networks allows investigating the structure and the dynamics of such networks, which led to significant developments in various scientific fields. One of the most used models in these investigations is the Watts-Strogatz, with a structure composed of high clustering and short path lengths known as small-world networks. This model proposes an interesting gradient between regular and random networks, but its generating process, which relies on a single rewiring probability parameter, is hard to access and to manipulate. In order to study the mechanics of the Watts-Strogatz model, the present work proposes a new method based on deep neural networks that could estimate its probability p. To illustrate its applicability, neuroimaging and phenotypic resting-state fMRI data were used from patients with ADHD and typical development children, obtained from the ADHD-200 database. The neural network efficiently estimated the probability parameter, resulting in small-world graphs for functional brain connectivity with a mean ± s.e.m. p distribution of 0.804 ± 0.003. Despite no difference was found considering the gender or diagnosis of participants, the generalized linear model revealed age as a significant predictor of p (mean ± s.e.m.: 4.410 ± 0.877; p < 0.001), indicating a great effect of neurodevelopment on the brain network’s structure. The proposed approach is promising in estimating the probability of the Watts-Strogatz model, and its application has the potential to improve investigations of network connectivity with a relatively efficient and simple framework.

PMID:41307783 | DOI:10.1007/s12021-025-09756-z

Arch Osteoporos. 2025 Nov 27;20(1):147. doi: 10.1007/s11657-025-01636-y.

ABSTRACT

Hip fracture poses a major public health burden in aging populations. The relationship between long-term air pollution exposure and hip fracture risk remains unclear. In our study, long-term exposure to PM_2.5, PM₁₀, and NO₂ was associated with increased hip fracture risk, while ozone exposure showed a protective effect.

PURPOSE: This study aimed to evaluate the associations between major air pollutants and incident hip fracture in a nationwide Chinese cohort.

METHODS: We included 14,101 participants aged ≥ 45 years from the China Health and Retirement Longitudinal Study (2011-2020). Annual concentrations of PM_2.5, PM₁₀, O₃, and NO₂ were estimated using the CHAP dataset. Log-binomial regression models were applied to calculate relative risks (RRs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed to assess the robustness and consistency of the findings.

RESULTS: During a 9-year follow-up, 474 participants (3.37%) experienced hip fracture. Each 10 µg/m³ increase in PM_2.5 and PM₁₀ concentrations was associated with a higher risk of hip fracture (PM_2.5: RR 1.129, 95% CI 1.071-1.191; PM₁₀: RR 1.052, 95% CI 1.024-1.081). In contrast, ozone exposure showed an inverse association (RR 0.518, 95% CI 0.458-0.585). No overall association was found for NO₂, although an elevated risk was observed in the third exposure quartile (RR 1.302, 95% CI 1.012-1.675). Subgroup analyses indicated stronger PM_2.5-related risks among participants with higher education levels, a more pronounced inverse association with ozone in adults aged < 60 years and current smokers, and greater NO₂-related risk among non-smokers.

CONCLUSIONS: Long-term exposure to PM_2.5 and PM₁₀ increased hip fracture risk, while ozone exposure appeared protective. Moderate NO₂ exposure may also affect bone fragility. These results highlight the need for pollutant-specific prevention strategies.

PMID:41307780 | DOI:10.1007/s11657-025-01636-y

Arch Osteoporos. 2025 Nov 27;20(1):146. doi: 10.1007/s11657-025-01637-x.

ABSTRACT

Over 14 years, hip fracture patients grew older, with shorter hospital stays. Femoral neck fractures were more common than intertrochanteric fractures, but the latter had worse functional outcomes and higher complications. Surgery was standard, with nailing for intertrochanteric and arthroplasty for femoral neck fractures. Older age increased adverse outcomes.

AIM: We aimed to investigate trends in patient characteristics and outcomes in patients after hip fractures.

METHODS: We analyzed data from hip fracture patients treated at our trauma center between January 2009 and December 2022. Variables included fracture type, sex, age, BMI, admission/discharge times, anesthesia type, ASA classification, treatment methods, surgery duration, discharge activities of daily living, and complications.

RESULTS: This retrospective study of 2965 hip fracture patients revealed a predominance of femoral neck fractures (56.6%) over intertrochanteric fractures (43.4%), with females comprising two-thirds of cases. Mean patient age increased significantly over time, particularly for intertrochanteric fractures (79.4 vs. 75.0 years for femoral neck). Hospital stays markedly decreased (25.5 to 9.1 days for intertrochanteric; 20.2 to 8.9 days for femoral neck). Intertrochanteric fractures were associated with worse functional outcomes (discharge ADL, 38.5 vs. 42.2, P = 0.009) and higher ICU admission (11.4% vs. 6.0%, P < 0.001). Surgical management dominated (92.3%), with intramedullary nailing for intertrochanteric fractures (86.3%) and arthroplasty for femoral neck fractures (73.7%). ASA classification indicated poorer physiological status in intertrochanteric fracture patients (P < 0.001). In-hospital mortality escalated with age and prolonged injury-to-admission time (P < 0.001).

CONCLUSION: During 2009-2022, the mean age of hip fracture patients increased significantly, while hospital stays decreased. Intertrochanteric fractures were associated with poorer functional outcomes and higher complication rates compared to femoral neck fractures. Surgical management, particularly intramedullary nailing and arthroplasty, predominated. Older adults exhibited the higher burden of adverse outcomes, with mortality and complications rising with age.

PMID:41307770 | DOI:10.1007/s11657-025-01637-x

Clin Exp Med. 2025 Nov 27. doi: 10.1007/s10238-025-01964-w. Online ahead of print.

ABSTRACT

Till now, the management of autoimmune thyroid diseases (AITD) depends on symptomatic treatment and replacement or anti-thyroid therapy. Uncovering the pathophysiologic mechanisms of autoimmunity provides hope for new insights into management. These new treatments aim to modulate the immune reaction and stop the autoimmune process. T regulatory cells (Tregs) are central in antagonising autoimmunity. This study aimed to compare the number of CD4/CD25/FOXP3 T regulatory cells in the different forms of autoimmune thyroid diseases and in the normal population, and to compare the number of CD4 + CD25 + FOXP3 + T regulatory cells between the different forms of AITD, HT, and GD. Also, to investigate the difference in the number of CD4/CD25/FOXP3 T regulatory cells in AITD associated with allergic disorders on one hand and autoimmune thyroid diseases not associated with allergic disorders on the other hand. This study included 18 patients suffering from Hashimoto’s thyroiditis (HT), 15 patients suffering from Graves’ disease (GD); and, for comparison, the Tregs level was measured in 15 healthy control patients. A statistically significant decrease was found regarding CD4/CD25, CD25/FOXP3 percentages and CD4/CD25/FOXP3 absolute number between patients of AITD and the normal population. The absolute number of CD4/CD25/FOXP3 was lower in the GD group than in HT group. Allergic comorbidities do not influence Tregs percentage or their CD4/CD25/FOXP3 absolute number in any of the AITD forms. Tregs may be a potential therapeutic target for AITD.

PMID:41307767 | DOI:10.1007/s10238-025-01964-w