Category: Nevin Manimala

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

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

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

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

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

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

Eur J Obstet Gynecol Reprod Biol. 2026 Mar 2;321:115050. doi: 10.1016/j.ejogrb.2026.115050. Online ahead of print.

ABSTRACT

INTRO: Uterine fibroids are the most common benign genital tract tumours in women, causing a variety of symptoms including lower urinary tract symptoms (LUTS). The relationship between fibroid size and location, and LUTs is not well established. In this study we aim to understand the relationship between uterine volume and fibroid volume and location, with LUTs as self-reported using the King’s Health Questionnaire (KHQ).

MATERIAL AND METHODS: Women recruited to this study underwent Magnetic Resonance Imaging (MRI) performed with T2-weighted tri-planar MR images. The total uterine volume (TUV) and volume of the largest fibroid (VolFib) were calculated by Reportcard© software. Participants completed the KHQ, a validated questionnaire for LUTs and quality of life.

RESULTS: Linear regression analysis and ANOVA demonstrated that both TUV and VolFib have statistically significant relationships with multiple score domains of the KHQ. Mann Whitney U test showed that an anterior location of VolFib only had a statistically significant relationship with domain 8- sleep/energy score. However anterior fibroids > 500 cm³ showed a statistically significant relationship to the symptom severity score (p = 0.014).

CONCLUSIONS: Increasing uterine volume and fibroid volume was associated with worsening urinary symptom severity and a negative impact on quality of life. Our data demonstrated that the volume of the largest fibroid had the greatest impact on LUTs severity and quality of life. We found that anteriorly located dominant fibroids only had a statistically significant impact on symptom severity if they were > 500 cm³ in volume.

PMID:41795480 | DOI:10.1016/j.ejogrb.2026.115050

Cognition. 2026 Mar 6;272:106512. doi: 10.1016/j.cognition.2026.106512. Online ahead of print.

ABSTRACT

Statistical learning (SL), the ability to extract recurrent patterns from sensory input, plays an important role in a range of cognitive functions. While much research has studied SL in stable artificial environments, natural inputs are rarely fixed: regularities are often probabilistic and continuously changing. A key question, therefore, is how SL unfolds under such conditions and to what extent it is shaped by learners’ previous experiences. In the present study, we asked how trajectories of predictability ranging from highly structured to noisy sequences impact SL performance, and how learning in such conditions affects subsequent learning. To do so, we created a “Whack-a-Mole” game in which mole locations partially predicted subsequent mole locations, while the extent of predictability differed between blocks. In Experiment 1, predictability of mole locations increased across blocks in the first session and decreased in the second session, or vice versa. In Experiment 2, predictability followed the same trajectory in both sessions (either decreasing or increasing). Learning performance was measured using both reaction times and predictive eye movements toward target locations. Across studies, our findings reveal that learning in the second session was shaped by prior experience in the first session. Starting the second session with high predictability facilitated learning, whereas starting with low predictability hindered it, even when predictability later increased. These results suggest that learners are not passive absorbers of regularities but active information seekers, whose expectations about environmental structure impact learning. We discuss the implications of these findings for theories of SL in dynamic environments.

PMID:41795474 | DOI:10.1016/j.cognition.2026.106512

Am J Hum Genet. 2026 Mar 5;113(3):483-493. doi: 10.1016/j.ajhg.2026.02.002.

ABSTRACT

Mendelian randomization (MR) is a statistical method for estimating causal effects using genetic variants as instrumental variables. In two-sample MR (2SMR), different study samples are used to estimate genetic associations with the exposure and outcome. For valid inference, these studies must include individuals from the same population. Using studies from different populations may bias the MR estimate due to differences in variant-exposure associations resulting from differences in linkage disequilibrium or genetic effects on the exposure trait. We show that violation of the same-population assumption leads to bias in the causal estimate toward zero on average and does not increase the rate of false positives when using the most common MR study design. We verify this result in a broad survey of MR estimates, comparing estimates made with matching and mismatching populations across 546 trait pairs measured in 2-7 ancestries. We find that most population-mismatched estimates are attenuated toward zero compared to their corresponding population-matched estimates and that increasing genetic distance between study populations is associated with greater shrinkage. We observe bias even when mismatched populations have the same continental ancestry. However, we also find that, in some cases, using a larger exposure study with mismatching ancestry can improve power by dramatically increasing precision. These results show that even intra-continental population mismatch can bias MR estimates but also suggest that there is potential to improve the power of MR in understudied populations by properly leveraging larger, mismatching study populations.

PMID:41795470 | DOI:10.1016/j.ajhg.2026.02.002

Am J Hum Genet. 2026 Mar 5;113(3):472-482. doi: 10.1016/j.ajhg.2026.02.004.

ABSTRACT

The advent of efficient and accurate imputation for low-coverage sequencing offers an unbiased alternative to SNP array imputation, increasing the accuracy of rare variant imputation across all populations. Since imputation accuracy generally increases with larger reference panels and closer ancestry match between target and reference samples, leveraging imputation from multiple reference panels improves imputation accuracy; however, individual reference panel genotypes are often privacy protected. Meta-imputation bypasses individual-level data by combining single-panel imputed genotypes through estimating panel- and marker-specific weights. We present a meta-imputation method, MetaGLIMPSE, that combines estimates from multiple reference panels for low-coverage sequencing imputation. Across all our scenarios, for both modern and ancient DNA samples, MetaGLIMPSE consistently outperforms the best single-panel imputation for coverages of 0.1×-8× and across all minor-allele frequencies, equaling the combined panel imputation for some parameters. Finally, MetaGLIMPSE is computationally efficient, meta-imputing 500 whole genomes in 16% of the time of GLIMPSE2.

PMID:41795469 | DOI:10.1016/j.ajhg.2026.02.004