Category: Statistics

Proc Natl Acad Sci U S A. 2025 Jun 3;122(22):e2500001122. doi: 10.1073/pnas.2500001122. Epub 2025 May 28.

ABSTRACT

NMR-based metabolic biomarkers provide comprehensive insights into human metabolism; however, extracting biologically meaningful patterns from such high-dimensional data remains a significant challenge. In this study, we propose a manifold-fitting-based framework to analyze metabolic heterogeneity within the UK Biobank population, utilizing measurements of 251 NMR biomarkers from 212,853 participants. Initially, our method clusters these biomarkers into seven distinct metabolic categories that reflect the modular organization of human metabolism. Subsequent manifold fitting to each category unveils underlying low-dimensional structures, elucidating fundamental variations from basic energy metabolism to hormone-mediated regulation. Importantly, three of these manifolds clearly stratify the population, identifying subgroups with distinct metabolic profiles and associated disease risks. These subgroups exhibit consistent links with specific diseases, including severe metabolic dysregulation and its complications, as well as cardiovascular and autoimmune conditions, highlighting the intricate relationship between metabolic states and disease susceptibility. Supported by strong correlations with demographic factors, clinical measurements, and lifestyle variables, these findings validate the biological relevance of the identified manifolds. By utilizing a geometrically informed approach to dissect metabolic heterogeneity, our framework enhances the accuracy of population stratification and deepens our understanding of metabolic health, potentially guiding personalized interventions and preventive healthcare strategies.

PMID:40434639 | DOI:10.1073/pnas.2500001122

Hepatol Commun. 2025 May 29;9(6):e0701. doi: 10.1097/HC9.0000000000000701. eCollection 2025 Jun 1.

ABSTRACT

BACKGROUND: Sarcopenia is a syndrome of severe muscle wasting, associated with adverse outcomes related to liver transplantation (LT). There are several approaches used to identify sarcopenia. We aimed to investigate the prevalence of sarcopenia using 3 different criteria and determine how these performed in relation to clinical outcomes.

METHODS: The cohort study included 237 adults with cirrhosis referred for LT. Sarcopenia was identified using (1) CT-defined; and the (2) original and (3) updated European Working Group on Sarcopenia in Older People criteria (EWGSOP1 and 2). Logistic regression was used to estimate OR and 95% CI for the relationships between sarcopenia and receiving an LT, unplanned admissions pre-LT, surgical complications, and length of stay for the LT admission. Fine-Gray competing risk analysis explored the impact of sarcopenia on receiving an LT and unplanned admissions. The AUC determined the predictive utility of the criteria.

RESULTS: The prevalence of CT-defined sarcopenia (52%) was more than twice and 4-fold that of EWGSOP1-defined (22%) and EWGSOP2-defined (11%) sarcopenia, respectively. No criteria demonstrated a significant association with time to LT nor the time to unplanned admissions pre-LT. Similarly, none of the 3 criteria had superior predictive utility for the clinical outcomes for unplanned hospital admissions pre-LT of receiving an LT, with all 3 criteria having identical moderate AUCs for unplanned admissions (0.70) and similar weak AUCs (≤0.55) for the likelihood of receiving an LT.

CONCLUSIONS: Sarcopenia in patients undergoing LT evaluation is prevalent. EWGSOP criteria appear to offer no advantage over CT-only criteria in identifying patients at increased risk of adverse LT outcomes. Bedside measures of muscle function may be of benefit in tracking the effectiveness of interventions targeting sarcopenia.

PMID:40434634 | DOI:10.1097/HC9.0000000000000701

Clin Exp Reprod Med. 2025 May 28. doi: 10.5653/cerm.2024.07304. Online ahead of print.

ABSTRACT

OBJECTIVE: In the application of assisted reproductive technologies (ART), selection of the optimal sperm presents a challenge. This study introduces an innovative microfluidic device that utilizes rheotaxis to efficiently sort sperm, offering superior selection of high-quality sperm compared to conventional methods.

METHODS: We analyzed 30 normal samples from couples undergoing intracytoplasmic sperm injection cycles at the Infertility Center of Fatemieh Hospital in Hamadan, Iran. Each sample was divided into three groups: the initial sample, representing the control group; direct swim-up sperm selection; and sperm selection using rheotaxis. A syringe pump connected to the microfluidic device generated optimal flow conditions. Spermatozoa were evaluated regarding concentration, motility, morphology, mitochondrial membrane potential (MMP), and sperm DNA fragmentation index (DFI). Statistical significance was determined using one-way analysis of variance and the Student t-test.

RESULTS: The concentration (7.46±2.84 million cells/mL vs. 56.67±18.27 million cells/mL, p<0.0001) and DFI (2.93±2.70 vs. 21.13±5.27, p<0.0001) were significantly lower in the sperm selected using the rheotaxis microfluidic device than in the control sperm. Progressive motility (98.10%±2.41% vs. 44.13%±7.06%, p<0.0001), normal morphology (8.36%±1.47% vs. 5.20%±1.15%, p<0.0001), and MMP (99.63%±0.71% vs. 81.13%±9.19%, p<0.0001) were significantly higher with the device than in the control group.

CONCLUSION: The use of a rheotaxis-based microfluidic device appeared effective in selecting high-quality sperm, demonstrating improvements in motility, morphology, and MMP and a reduction in DFI. This advancement has the potential to improve the outcomes of ART.

PMID:40433763 | DOI:10.5653/cerm.2024.07304

Angew Chem Int Ed Engl. 2025 May 28:e202507348. doi: 10.1002/anie.202507348. Online ahead of print.

ABSTRACT

Cross-linking mass spectrometry (XL-MS) has become a powerful tool in structural biology for investigating protein structure, dynamics, and interactomics. However, short-range cross-links, defined as those connecting residues fewer than 20 positions apart, have traditionally been considered less informative and largely overlooked, leaving significant data unexplored in a systematic manner. Here, we present a system-wide analysis of short-range cross-links, demonstrating their intrinsic correlation with protein secondary structure. We introduce the X-SPAN (Cross-link Structural Pattern Analyzer) software, which integrates publicly available XL-MS datasets from system-wide experiments with AlphaFold-predicted protein structures. Our analysis reveals distinct cross-linking patterns that reflect the spatial constraints imposed by secondary structural elements. Specifically, α-helices exhibit periodic cross-linking patterns consistent with their characteristic helical pitch, whereas coils and β-strands display nearly monotonic distributions. A context-dependent protein grammar reinforces short-range cross-link specificity. Short-range cross-links can enhance the statistical inference of secondary structures within integrative modeling workflows. Additionally, our work establishes a framework for benchmarking AlphaFold’s local prediction accuracy and provides novel quality control criteria for XL-MS experiments. We anticipate that X-SPAN and our short-range cross-link database will serve as a valuable resource for exploring local secondary structure rearrangements and their potential roles in protein function and allosteric regulation.

PMID:40433759 | DOI:10.1002/anie.202507348

Curr Eye Res. 2025 May 28:1-8. doi: 10.1080/02713683.2025.2503207. Online ahead of print.

ABSTRACT

PURPOSE: The purpose of this study is to provide an evidence-based protocol for iris measurement from ultrasound biomicroscopy (UBM) images with reproducibility analysis and resulting normative iris thickness dataset of the pediatric human iris by age.

METHODS: Healthy pediatric subjects (14 subjects, 25 eyes, mean age 2.0 ± 1.2 years) were recruited prospectively and underwent UBM imaging. Iris parameters were measured in 4 UBM images per eye in raw image and processed edge detection format. Agreement and variability were evaluated. Regression assessed the association between measurement differences and the variables expected to influence measurement reproducibility (image quality, orientation, and processing). Iris thickness by age was reported.

RESULTS: Intraclass correlation was >0.6 and correlation was >0.7 for all parameters. Coefficient of variation was <30% for iris measurements not involving the ciliary body. Image quality improved reproducibility but was not statistically significant (p = 0.10). Age of subject, edge detection, and image orientation were also not significant. Iris thickness increased with increasing age (r = 0.63, p < 0.0001).

CONCLUSIONS: This study demonstrated reproducible iris measurements using a prospective protocol. We found image features, including image quality and edge detection pre-processing, were not critical to reproducibility. In the future, clinical correlations with iris morphology may be more rigorously studied using a well-defined, reproducible, and quantitative approach as presented in this UBM-based image analysis protocol.

PMID:40433750 | DOI:10.1080/02713683.2025.2503207

Eur Psychiatry. 2025 May 28;68(1):e58. doi: 10.1192/j.eurpsy.2025.2452.

ABSTRACT

BACKGROUND: Exposure to Adverse Childhood Experiences (ACEs) might increase the risk of suicide behaviors in the general adult population, while this association in individuals with affective disorders remains less characterized.

METHODS: A comprehensive search was conducted in MEDLINE, PsycINFO, CINAHL, Web of Science, Scopus, and PubMed up to July 10th, 2024. Observational studies that compared the risk of suicide behaviors in individuals exposed and unexposed to ACEs were included. Pairwise random-effects meta-analyses were conducted, and the certainty of evidence was assessed with validated criteria.

RESULTS: A total of 41 studies from 17 countries, comprising 19,588 participants, were analyzed. The main findings indicated a significant association between ACEs and suicidal behaviors, with an odds ratio (OR) of 1.98 (95% confidence interval [CI] 1.74-2.26), and a “highly suggestive” strength of association. This was consistent across diagnostic subgroups (i.e., Major Depressive Disorders, Bipolar Disorders, and mixed diagnoses). The association was confirmed for any ACE, with sexual abuse being the most frequently reported and showing the highest risk (OR 2.24; 95% CI 1.90-2.64), for suicidal ideation (OR 2.16; 95% CI 1.42-3.29), and for suicide attempts (OR 1.95; 95% CI 1.70-2.25), while death by suicide and non-suicidal self-injury were underreported. Meta-regression analyses did not suggest potential moderators, though underreporting was noted.

CONCLUSIONS: This meta-analysis shows that exposure to ACEs nearly doubles the risk of suicide behaviors in individuals with affective disorders, warranting the targeted clinical, research, and policy measures to timely address this global mental health issue.

PMID:40433733 | DOI:10.1192/j.eurpsy.2025.2452

Echocardiography. 2025 Jun;42(6):e70207. doi: 10.1111/echo.70207.

ABSTRACT

BACKGROUND: Keratoconus (KC) is a multifactorial disease characterized by progressive corneal thinning and structural deformation. Despite being an ophthalmological disorder, KC is proposed to have systemic implications. The aim of this study was to evaluate cardiac functions in KC patients by two-dimensional (2D) speckle-tracking echocardiography (STE) and three-dimensional (3D) echocardiography.

METHODS: The study included 45 consecutive patients with KC (mean age: 37.6 ± 12.6 years, 23 male) and 42 healthy controls (mean age: 38.1 ± 8.6 years, 23 male). All participants underwent standard transthoracic echocardiography, 3D echocardiography, and 2D STE to evaluate cardiac functions.

RESULTS: Although there were no significant differences in the conventional echocardiographic markers regarding left ventricular (LV) and right ventricular (RV) functions except tricuspid annular plane systolic excursion; patients with KC had significantly lower LV global longitudinal strain (GLS) compared to controls (-17.75 ± 2.43% vs. -19.71 ± 1.97%, p < 0.001). They also had lower RV GLS, left and right atrial reservoir, and conduit strains, although the differences were not statistically significant. LV GLS negatively correlated with corneal densitometry in KC patients. Linear regression analysis showed that KC was independently associated with LV GLS when adjusted for age and sex.

CONCLUSION: Patients with KC had significantly lower LV GLS, suggesting the presence of a subclinical LV dysfunction in these patients, which supports that KC may be a component of a systemic disease.

PMID:40433730 | DOI:10.1111/echo.70207

Int J Urol. 2025 May 28. doi: 10.1111/iju.70131. Online ahead of print.

ABSTRACT

INTRODUCTION: Hypospadias is a congenital anomaly of male genitalia that requires surgical correction to achieve normal anatomy and function. Tubularized incised plate urethroplasty (TIP) is a common repair method, but prognostic studies of TIP outcomes are limited by their methodological quality. This systematic review evaluates the methodological rigor of prognostic studies on TIP urethroplasty in hypospadias cases, employing the Quality in Prognosis Studies (QUIPS) Cochrane tool.

METHODS: Following PRISMA guidelines, a systematic review of single-arm prognostic studies of TIP was conducted. Inclusion criteria were primary studies (first attempt of surgery), evaluating prognostic factors and outcomes, with the QUIPS tool used for quality assessment. Review studies and reports without full text were excluded. Inter-rater agreement was then evaluated using Cohen’s kappa analysis.

RESULTS: Among 14 included studies, most exhibited low risk of bias (RoB). Inter-rater agreement varied across domains, being strongest for statistical analysis (κ = 0.89) and weakest for prognostic factor measurement (κ = 0.42). Nevertheless, overall assessment showed minimal agreement (κ = 0.49), indicating poor reliability of the included studies. Our findings highlight biases inherent in existing literature, particularly with respect to outcome measurement domains, underscoring the need for standardized methods and validated patient-reported outcomes. Selection bias and lack of standardized outcome measures pose significant challenges in interpreting study findings.

CONCLUSION: Low inter-rater agreement indicates methodological shortcomings in prognostic studies of TIP in the context of hypospadias. Future research should prioritize methodological rigor to enhance the reliability and generalizability of findings, thus improving clinical practice and future patient outcomes.

PMID:40433712 | DOI:10.1111/iju.70131

J Cosmet Dermatol. 2025 Jun;24(6):e70261. doi: 10.1111/jocd.70261.

ABSTRACT

INTRODUCTION: Wound healing is a complex process encompassing four main stages: hemostasis, inflammation, cell proliferation, maturation, and differentiation. Timolol (TM) may influence these stages, particularly re-epithelialization. This study aims to evaluate the 1-month effects of timolol on acute surgical wounds in post-mammoplasty patients.

OBJECTIVES: To investigate the efficacy of topical timolol in improving postoperative breast scars, aiming to guide future treatment protocols and prescriptions.

METHODS: A total of 12 patients who underwent bilateral mammoplasty were enrolled in this double-blind randomized clinical trial. Treatment commenced 48 h post-surgery; one breast was treated with 0.5% timolol eye drops, while the contralateral breast received distilled water (control). Patients were advised to minimize sun exposure and pressure on the treated area, and no additional oral or topical medications were prescribed. Cleansing with a prescribed cleanser occurred every 3 days. Cosmetic assessments were conducted by a specialist at 10 and 30 days post-surgery using a 10-point Likert scale. Data were analyzed using two-way repeated measures ANOVA.

RESULTS: Timolol significantly reduced erythema over time (Interaction, p < 0.0001; Treatment, p = 0.02), with an average decrease of 5.38 points (95% CI: 4.22-6.55) compared to 4.41 points (95% CI: 3.83-5) for placebo. The difference in reduction was 0.972 points (95% CI: 0.18-1.7). A significant improvement in the aesthetic appearance of the breast was also noted (Interaction, p < 0.0001; Treatment, p = 0.015), with timolol enhancing the aesthetic score by approximately 5.5 points (95% CI: 4.9-6.2) versus 4.58 points (95% CI: 3.4-5.7) for the placebo. Overall, timolol improved the aesthetic score by 0.972 points (95% CI: 0.23-1.7) more than the placebo.

CONCLUSION: Topical application of 0.5% timolol significantly improved the aesthetic appearance and reduced erythema of post-mammoplasty breast scars over a 1-month period. The results demonstrate a measurable clinical benefit, with statistically significant differences favoring timolol over placebo. These findings suggest that early intervention with topical timolol may offer a safe, effective, and non-invasive option for optimizing scar outcomes in surgical patients.

PMID:40433711 | DOI:10.1111/jocd.70261

Health Informatics J. 2025 Apr-Jun;31(2):14604582251347120. doi: 10.1177/14604582251347120. Epub 2025 May 28.

ABSTRACT

Objective: This review systematically synthesizes empirical evidence from past NEHR initiatives to identify critical gaps between knowledge and practice and provide actionable insights for policymakers, health IT leaders, and practitioners.Materials and Methods: A rapid review approach was employed, focusing on qualitative content analysis of empirical studies published between 2010 and 2024. The search covered the Scopus, PubMed, Medline, and CINAHL databases. A total of 24 studies met the eligibility criteria and were analyzed across key dimensions.Results: Our analysis reveals that successful NEHR implementation hinges on three interdependent factors: (1) Stakeholder engagement and governance-meaningful clinician involvement and adaptive leadership strategies are crucial for system adoption; (2) Institutional and cultural alignment-the tension between centralized mandates and local adaptation must be carefully managed; and (3) Technological and process standardization-balancing interoperability with customizability remains a persistent challenge. Notably, rigid top-down implementations often face resistance, whereas hybrid “middle-out” approaches tend to facilitate smoother transitions.Conclusions: NEHR deployments require a nuanced approach that integrates strategic decision-making, continuous stakeholder engagement, and flexible governance models. Policymakers and project leaders should prioritize participatory implementation strategies, adaptive standardization, and mechanisms for iterative learning to enhance the sustainability and effectiveness of these systems.

PMID:40433709 | DOI:10.1177/14604582251347120