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Nevin Manimala Statistics

Improved segmentation of cardiac structures in echocardiograms for diastolic function evaluation

Med Phys. 2026 Mar;53(3):e70373. doi: 10.1002/mp.70373.

ABSTRACT

BACKGROUND: Noninvasive assessment of diastolic dysfunction relies on multiple echocardiographic indicators, including measurements from both standard B-mode images and Doppler, obtained at various cardiac locations such as the mitral annulus, tricuspid annulus, left ventricle, and left atrium. The diagnostic process is complex and subject to interobserver variability, making accurate and rapid evaluation challenging. Automated semantic segmentation of key cardiac structures, such as the left atrium, left ventricle, and mitral valve annulus, offers a potential solution by capturing temporal changes throughout the cardiac cycle.

PURPOSE: This study aims to improve the accuracy of segmenting the left atrium, left ventricle, and mitral valve annulus in echocardiographic images and to leverage the resulting temporal segmentation features for more reliable identification of diastolic dysfunction.

METHODS: This study presents Diff-TransUNet, a novel segmentation model incorporating a noise-robust Differential Transformer module. Evaluations on private (1137 training images, 135 validation images, and 88 test images), CAMUS (1400 training images, 200 validation images, and 200 test images), and EchoNet-Dynamic (5000 training images, 2546 validation images, and 2528 test images) datasets demonstrate improved performance over state-of-the-art methods, assessed by Dice coefficient (Dice), Intersection-over-Union (IoU), and 95th percentile Hausdorff Distance (HD95) metrics. Statistical analysis was performed to compare Diff-TransUNet with baseline methods across evaluation metrics. To control for errors arising from multiple comparisons, p-values were adjusted using the Benjamini-Hochberg false discovery rate (FDR) correction. Statistical significance was assessed at a 95% confidence level. In addition to p-values, Cohen’s d effect size was computed to quantify the practical significance of performance differences.

RESULTS: The proposed Diff-TransUNet achieved a Dice of 87.49%, IoU of 79.07%, and HD95 of 1.48 on the private dataset. Compared with state-of-the-art models, Dice improved by 1.35%-4.30% (p < 0.05, Cohen’s d = 0.32-0.90), IoU by 1.97%-5.67% (p < 0.05, Cohen’s d = 0.37-1.03), and HD95 by 0.16-0.83 (p < 0.05, Cohen’s d = 0.21-0.90). On the CAMUS dataset, the model achieved a Dice of 88.74%, IoU of 80.58%, and HD95 of 2.83, showing improvements of 1.07%-4.96% (p < 0.05, Cohen’s d = 0.18-0.63) in Dice, 1.55%-6.89% (p < 0.05, Cohen’s d = 0.19-0.71) in IoU, and 0.41-2.85 (p < 0.05, Cohen’s d = 0.12-0.46) in HD95 compared to advanced models. On the EchoNet-Dynamic dataset, the model obtained a Dice of 92.25%, IoU of 85.87%, and HD95 of 1.65, outperforming other methods by 0.42%-2.00% (p < 0.05, Cohen’s d = 0.10-0.40) in Dice, 0.69%-3.21% (p < 0.05, Cohen’s d = 0.10-0.43) in IoU, and 0.21-1.12 (p < 0.05, Cohen’s d = 0.09-0.34) in HD95. Furthermore, by extracting volumetric segmentation features, the proposed method achieved an accuracy of 88.95% (95 % CI 87.15% to 90.08%) in identifying diastolic dysfunction.

CONCLUSIONS: The proposed Diff-TransUNet model achieves significant improvements in ultrasound segmentation. Features extracted from the left ventricle, left atrium, and mitral annulus segmented by Diff-TransUNet can be effectively used for the identification of diastolic dysfunction.

PMID:41795688 | DOI:10.1002/mp.70373

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Nevin Manimala Statistics

Effects of Intracellular Force Localization on Cancer Cell Invasion: Revealing Mechanical Trade-offs through Experimentally Validated Computational Models

ACS Biomater Sci Eng. 2026 Mar 8. doi: 10.1021/acsbiomaterials.6c00194. Online ahead of print.

ABSTRACT

Metastasis, leading to 90% of cancer-related deaths, is driven by invasive forces exerted by cancer cells on their microenvironment. While actin is central to force generation and motility, the effects of intracellular force-localization during invasion remain largely unexplored. We previously demonstrated, in a clinically relevant assay, invasive cancer cells indenting soft, elastic gels to cell-scale depths, and developed corresponding experimentally validated finite element models. Here, we applied those models to investigate how the force-application location, above (top) or below (bottom) the nucleus, affects invasion efficiency. Under low force-levels (≤100 nN), top-applied forces produce 35-42% deeper indentations than bottom-applied forces, with modest increases in intracellular stress, indicating potentially increased invasiveness. However, with top-applied forces, ∼10% less stress is transmitted to the gel, suggesting less effective microenvironmental mechanical interaction. In contrast, under higher forces (≥150 nN), bottom-applied forces become more effective, transmitting >15% more stress to the gel, with indentation depths becoming comparable between top- and bottom-applied configurations, and significantly (>250%) less nuclear stress generated, thereby supporting invasion. These trends are particularly evident when the cytoplasm is softer than the nucleus, as is typical of (invasive cancer) cells. Thus, top-applied forces may support shallow invasion into soft environments, whereas bottom-applied forces mimicking actin-rich, stiff, leading-edge protrusions, optimize deep, forceful invasion with reduced cell-integrity risk. We demonstrate that intracellular force-localization critically influences the mechanical trade-offs between invasion efficiency and cellular stability, potentially offering targets for antimetastatic strategies.

PMID:41795681 | DOI:10.1021/acsbiomaterials.6c00194

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Nevin Manimala Statistics

Television and computer use and dementia risk in older adults with limited leisure or social activities: A prospective cohort study

Alzheimers Dement. 2026 Mar;22(3):e71259. doi: 10.1002/alz.71259.

ABSTRACT

INTRODUCTION: Associations between television/computer use and dementia in socially inactive older adults remain unclear, and optimal limits are unknown.

METHODS: We followed 89,671 dementia-free, socially inactive adults aged ≥55 from UK Biobank for a mean of 12.2 years. Adjusted Cox models assessed associations with incident all-cause dementia and subtypes.

RESULTS: Computer use ≤2.4 h/day was associated with lower all-cause dementia risk (hazard ratio [HR] 0.88; 95% confidence interval [CI] 0.82-0.94), whereas higher use increased risk (HR 1.19, 95% CI 1.05-1.34); patterns were similar for Alzheimer’s and vascular dementia. Television viewing showed no association below 2.06 h/day but higher risk thereafter (HR 1.17; 95% CI 1.03-1.32), with a roughly linear increase for vascular dementia. Heavy computer use in apolipoprotein E (APOE) -ε4 homozygotes and higher television viewing in adults < 65 were more harmful.

DISCUSSION: In socially inactive older adults, moderate computer use may be protective, whereas higher computer use and television viewing are linked to increased dementia risk.

PMID:41795676 | DOI:10.1002/alz.71259

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Nevin Manimala Statistics

Alzheimer’s disease and related dementias among transfeminine adults: A cohort study

Alzheimers Dement. 2026 Mar;22(3):e71277. doi: 10.1002/alz.71277.

ABSTRACT

INTRODUCTION: We investigated whether Alzheimer’s disease and related dementias (ADRD) are more common among transfeminine (TF) adults than among demographically similar cisgender people enrolled in the same health system.

METHODS: We analyzed electronic health records of 856 TF adults aged 65+ and matched cisgender men (CM) and cisgender women (CW) and compared ADRD prevalence across groups by calculating enrollment-adjusted odds ratios (aOR) and 95% confidence intervals (CI).

RESULTS: The aOR of ADRD among TF adults were 1.39 (95% CI: 0.99-1.97) relative to CM and 1.29 (95% CI: 0.92-1.82) relative to CW referents. For TF adults with evidence of receiving gender-affirming hormone therapy (GAHT) receipt, the associations were slightly stronger: 1.75 (1.13-2.69) and 1.70 (1.11-2.60). Results restricted to minoritized ethnoracial groups appeared smaller, but imprecise.

DISCUSSION: These findings suggest that ADRD diagnosis and management may represent a priority in the healthcare of older TF people, particularly those with a history of GAHT.

PMID:41795672 | DOI:10.1002/alz.71277

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Nevin Manimala Statistics

Neuropsychiatric symptoms in preclinical and clinically manifest dementia: clusters and their health determinants

Alzheimers Dement. 2026 Mar;22(3):e71255. doi: 10.1002/alz.71255.

ABSTRACT

INTRODUCTION: Neuropsychiatric symptoms (NPSs) are common in dementia, but their patterns in preclinical stages remain unclear. This study identified NPS clusters and associated health factors in a geriatric clinical population.

METHODS: We analyzed 1234 participants from the Italian GERIatric COgnitive evaluation memory clinic cohort with Neuropsychiatric Inventory data. Clusters were derived using machine learning (K-means, Elbow method) separately for dementia and dementia-free groups. Associations were assessed via multinomial logistic regression.

RESULTS: In the overall cohort, four NPS clusters emerged: minimal NPS, depression-anxiety-apathy, depression-anxiety, and delusions-agitation-irritability. Cluster profiles differed between the dementia and dementia-free groups. Specific clinical and metabolic factors – lipid abnormalities, glycemic control, thyroid dysfunction, and underweight status – were differentially associated with NPS clusters.

DISCUSSION: Distinct NPS patterns exist across the dementia continuum. These clusters differ in demographic, cognitive, functional, and metabolic profiles, suggesting NPS may precede cognitive decline and represent syndromic entities with diagnostic relevance. Multidimensional, personalized approaches are needed.

PMID:41795663 | DOI:10.1002/alz.71255

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Nevin Manimala Statistics

Characterizing the Reach of Teledermatology to Underserved Pediatric Populations in Oregon and Washington Compared to Pre- and Post-COVID In-Person Visits

Pediatr Dermatol. 2026 Mar 8. doi: 10.1111/pde.70183. Online ahead of print.

ABSTRACT

BACKGROUND/OBJECTIVES: Patients have limited access to pediatric dermatologists. Telehealth has been touted to increase access to underserved areas; however, previous research has shown underutilization in rural communities. This study aimed to characterize the impact of teledermatology on the reach of pediatric dermatologists to geographically underserved populations in the Pacific Northwest during the COVID-19 pandemic.

METHODS: A single institution retrospective cohort study was performed, analyzing distance-from-home-zip-code (DHZC) from clinic, payer mix, and language preference of new virtual visits during 4/2020-3/2021 compared to new in-person visits in 1/2019-12/2019 and 4/2020-3/2021.

RESULTS: The mean distance from clinic (DHZC) was significantly greater for virtual visits than in-person (51.8 vs. 36.8 miles; difference: 15.0 miles, 95% CI: 9.8 to 20.1; p < 0.001). The proportion of patients living > 20 miles from clinic was slightly higher in the virtual group (45.9% vs. 42.6%; difference: 3.3 percentage points, 95% CI: -0.5 to 7.1; p = 0.095), though it was not statistically significant. The proportion of patients insured by Medicaid was significantly lower in the virtual group (36.7% vs. 44.1%; difference: -7.5 percentage points, 95% CI: -11.2 to -3.7; p < 0.001). The proportion of English-speaking patients was higher in the virtual group (97.0% vs. 88.3%; difference: 8.7 percentage points, 95% CI: 7.1 to 10.3; p < 0.001).

CONCLUSIONS: Teledermatology may increase the reach of care provided by pediatric dermatologists to geographically underserved areas in Oregon and Washington. However, patients with Medicaid insurance or non-English primary languages may face additional barriers, limiting their participation in virtual visits.

PMID:41795658 | DOI:10.1111/pde.70183

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Nevin Manimala Statistics

scDIAGRAM: detecting chromatin compartments from individual single-cell Hi-C matrix without imputation or reference features

Brief Bioinform. 2026 Mar 1;27(2):bbag096. doi: 10.1093/bib/bbag096.

ABSTRACT

Single-cell Hi-C (scHi-C) provides unprecedented insight into 3D genome organization, but its sparse and noisy data pose challenges in accurately detecting A/B compartments, which are crucial for understanding chromatin structure and gene regulation. We presented scDIAGRAM, a data-driven method for annotating A/B compartments in single cells using direct statistical modeling and graph community detection. Unlike existing approaches, scDIAGRAM infers chromatin compartments directly from individual scHi-C matrix without imputation or external reference features, and subsequently assigns A/B labels using conventional genomic annotations. Accuracy and robustness of scDIAGRAM were illustrated through simulated scHi-C datasets and a human cell line. We applied scDIAGRAM to real scHi-C datasets from the mouse brain cortex, mouse embryonic development, and human acute myeloid leukemia, demonstrating its ability to capture compartmental shifts associated with transcriptional variation. This robust framework offers new insights into the functional roles of chromatin compartments at single-cell resolution across various biological contexts.

PMID:41795655 | DOI:10.1093/bib/bbag096

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Finding Significant Hits in Networks: a network-based tool for analyzing gene-level P-values to identify significant genes missed by standard methods

Brief Bioinform. 2026 Mar 1;27(2):bbag061. doi: 10.1093/bib/bbag061.

ABSTRACT

Finding Significant Hits in Networks (FISHNET) uses prior biological knowledge, represented as gene interaction networks and gene function annotations, to identify genes that do not meet the genome-wide significance threshold but replicate, nonetheless. Its input is gene-level P-values from any source, including omicsWAS, aggregation of genome-wide association studies P-values, CRISPR screens, or differential expression analysis. It is based on the idea that genes whose P-values are low purely by chance are distributed randomly across networks and functions, so genes with suggestive P-values that cluster in densely connected subnetworks and share common functions are less likely to reflect chance and more likely to replicate. FISHNET combines network and function analysis with permutation-based P-value thresholds to identify a small set of exceptional genes that we call FISHNET genes. Applied to 11 cardiovascular risk traits, FISHNET identified 19 gene-trait relationships that missed genome-wide significance thresholds but, nonetheless, replicated in an independent cohort. The replication rate of FISHNET genes matched that of genes with lower P-values. FISHNET identified a novel association between RUNX1 expression and HDL that is supported by experimental evidence that RUNX1 promotes white fat browning, which increases HDL cholesterol levels. FISHNET also identified an association between LTB expression and BMI that is supported by experimental evidence that higher LTB expression increases BMI via activation of the LTβR pathway. Both associations failed genome-wide significance thresholds, highlighting FISHNET’s ability to uncover meaningful relationships missed by traditional methods. FISHNET software is freely available at https://brentlab.github.io/fishnet/.

PMID:41795654 | DOI:10.1093/bib/bbag061

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Nevin Manimala Statistics

Patterns and Predictors of Health and Wellness Coaching Use Among Patients With Chronic Obstructive Pulmonary Disease Receiving Care From the United States Veterans Health Administration

Am J Health Promot. 2026 Mar 8:8901171261432422. doi: 10.1177/08901171261432422. Online ahead of print.

ABSTRACT

PurposeHealth & Wellness Coaching is a promising health promotion intervention for patients with complex clinical needs. This study aimed to explore patterns and predictors of coaching use among patients with chronic obstructive pulmonary disease (COPD) receiving care from the U.S. Veterans Health Administration (VA).DesignRetrospective cohort study using VA’s electronic health records (EHR).Sample400 829 patients with COPD receiving VA care during 2021-2023.MeasuresGeographic, demographic, and clinical characteristics associated with coaching use.AnalysisMixed effects logistic regression models to examine predictors of coaching use.ResultsNationally, 4.4% of VA patients with COPD used coaching at least once during the study period. Use of coaching was highly concentrated at select sites, with half of all coaching users receiving care at only 13 VA Medical Centers. Intensive coaching use was limited, with less than 6% of users receiving the recommended 8+ sessions (median = 4.4 sessions). The demographic characteristic most strongly associated with coaching use was being female (OR = 1.64; 95% CI:1.54-1.74). Other demographics significantly associated with coaching use were being Black, Hispanic/Latino, and not married. Being older and living in a rural area were inversely associated with coaching use. Polypharmacy was the clinical characteristic most strongly associated with coaching use (OR = 1.73, 95% CI: 1.62-1.84). Other statistically significant associations with coaching use were obesity, chronic pain, mental health diagnoses, substance use disorders, and smoking were. Prior COPD-related hospitalizations were not significantly associated with using Coaching.ConclusionAn array of geographic, socio-demographic, and clinical characteristics and patterns associated with coaching use among VA patients with COPD may indicate opportunities for improving coaching implementation. VA and other health systems may consider identifying, strengthening, and diversifying pathways through which patients with complex chronic conditions get connected to coaching.

PMID:41795630 | DOI:10.1177/08901171261432422

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Nevin Manimala Statistics

Inflated Denominators, Selection In Utero, and the Black Male Neonatal Death Paradox

Paediatr Perinat Epidemiol. 2026 Mar 8. doi: 10.1111/ppe.70127. Online ahead of print.

ABSTRACT

BACKGROUND: Epidemiologists speculate that comparatively high rates of fetal death among males conceived by non-Hispanic Black (NHB) women in the United States (USA) could explain the unexpectedly low neonatal death rate among extremely preterm (ePTB) NHB males. Consistent with this ‘selection in utero’ argument, conception cohorts exhibiting high sex ratios (M:F) of NHB stillbirths reportedly exhibit greater NHB advantages in ePTB male neonatal death rates. Sceptics, however, attribute this association to an artefact that spuriously inflates the denominators of neonatal death rates in highly stressed populations.

OBJECTIVE: To determine whether the positive association over conception cohorts between the NHB male neonatal death advantage and the sex ratio of NHB stillbirths survives correction for inflated denominators.

METHODS: We retrieved vital statistics for NHB and non-Hispanic white (NHW) singleton ePTB infants born in the USA from 1995 through 2018. We aggregated these data into 282 monthly conception cohorts. We avoided the inflated denominator problem by substituting a ‘NHB share of burden’ variable for the difference between NHB and NHW neonatal death rates. We specify this variable as the NHB proportion of neonatal deaths among NHB and NHW ePTB males born from each conception cohort. We determined, using Box-Jenkins methods, whether cohorts exhibiting unusually high sex ratios of NHB stillbirths also exhibited unusually low NHB shares of the burden of ePTB male neonatal death.

RESULTS: Consistent with the selection in utero argument, the NHB share of neonatal deaths among ePTB males fell 7% below expected among the cohorts exhibiting unusually high sex ratios of NH Black stillbirths.

CONCLUSIONS: Stillbirth affects the composition of birth cohorts by selecting against less fit males in conception cohorts. Although clinical manifestations of this bias remain largely unexplored, they likely include the Black male neonatal death paradox.

PMID:41795615 | DOI:10.1111/ppe.70127