Category: Nevin Manimala

Methods Mol Biol. 2026;2981:275-290. doi: 10.1007/978-1-0716-4836-0_15.

ABSTRACT

Phylogenetic tree construction from homologous sequences is a fundamental approach for studying evolutionary relationships. However, in cases where sequence similarity is too low to generate reliable alignments, comparison of protein structure provides an alternative means for inferring deep evolutionary relationships. MD-phylogeny is a method that integrates structural comparison with molecular dynamics (MD) simulations to generate robust phylogenies for protein datasets within the twilight zone of sequence similarity. This approach uses well-established structural superposition methods for building trees from structure, with a method for generating structural variants using MD simulations, from which confidence scores analogous to bootstrapping can be derived.This protocol provides a step-by-step guide to performing MD-phylogeny, covering dataset selection, structural comparisons, tree construction, and the generation of statistical support through MD simulations.

PMID:42056699 | DOI:10.1007/978-1-0716-4836-0_15

Methods Mol Biol. 2026;2981:1-12. doi: 10.1007/978-1-0716-4836-0_1.

ABSTRACT

I begin with an intuitively plausible principle: if proposition H retrodicts or predicts that proposition D is true, then Pr(D|H) > ½. I then consider the difference between forward-directed and backward-directed conditional probabilities. Until the 1980s, population genetics theory was dominated by the former; the situation changed with the appearance of coalescent theory, which deploys the latter. A forward-directed probability model cannot retrodict, and a backward-directed model cannot predict. A Bayesian model will do both if it deploys both types of conditional probability. I then describe ideas from model selection theory in statistics that throw doubt on the idea that true models of a process will always be more accurate predictors or retrodictors than false models of that process. I then discuss theorems in information theory that show how the passage of time degrades information in a causal chain. The rate of information loss can be reduced and even cancelled by the branching process in phylogenetic trees. The separation of within-lineage from across-lineage assessments of information loss is an instance of Simpson’s paradox.

PMID:42056685 | DOI:10.1007/978-1-0716-4836-0_1

Mol Cell Pediatr. 2026 Apr 30;13(1):24. doi: 10.1186/s40348-026-00236-1.

ABSTRACT

BACKGROUND: Although 22q11.2 deletion syndrome (22q11.2DS) is one of the most common microdeletion syndromes, a substantial proportion of patients with clinically suspected 22q11.2DS (clin22q11.2) remain without a definitive diagnosis. While CNVs other than the typical 22q11.2 deletion have been identified in patients with clin22q11.2 (defined here as phenocopies of 22q11.2DS, or phen22q11.2), SNVs associated with phen22q11.2 are less well defined.

RESULTS: We aimed to investigate genetic variants associated with phen22q11.2 to achieve definitive diagnoses and improve clinical management in the clin22q11.2 cohort, while also comparing the phenotypic features of 22q11.2DS and phen22q11.2 to guide optimal diagnostic approaches. We assessed 336 consecutive pediatric patients from three centers presenting with clin22q11.2 according to Tobias criteria. Diagnostic testing included fluorescence in situ hybridization or multiplex ligation-dependent probe amplification in all patients. In subsets of patients, additional investigations were performed as clinically indicated, including but not limited to karyotyping, chromosomal microarray analysis, and/or exome sequencing (ES) with CNV detection. To identify phenotypic differences, Fisher’s exact test and Chi-squared test were performed. Genetic abnormalities were identified in 127 patients, including 88 patients diagnosed with 22q11.2DS. Phen22q11.2 was identified in 39 patients, including de novo variants in 12 patients. Several SNVs were detected, including variants in recurrently affected genes, such as CHD7 (n = 4), TBX1 (n = 2), JAG1 (n = 2), as well as variants in genes implicated in rare and ultra-rare diseases. We also described several rare and previously unreported clinical features associated with variants linked to phen22q11.2. No statistically significant phenotypic differences were observed between patients with phen22q11.2 and those with 22q11.2DS.

CONCLUSIONS: Phen22q11.2 is genetically and phenotypically heterogeneous. The results support the use of ES with CNV analysis as a first-tier, high-throughput diagnostic approach in clin22q11.2, as comprehensive genomic testing is essential for improving diagnostic accuracy and optimizing both genetic counseling and clinical management in this population.

PMID:42056684 | DOI:10.1186/s40348-026-00236-1

Behav Res Methods. 2026 Apr 29;58(6):146. doi: 10.3758/s13428-026-03003-2.

ABSTRACT

Effect sizes are useful for understanding the magnitude of study results and for planning new studies via power analysis. However, despite their wide usage, effect sizes are often misinterpreted. This is mostly due to an over-reliance on general effect size benchmarks that were not intended for broad application across diverse research fields. Inaccurate effect size interpretations can lead to incorrect conclusions about the magnitude of study results and incorrect sample size estimates, thereby increasing the likelihood of false-positive results. This article introduces the ESDist R package, which is designed to calculate empirically derived effect-size benchmarks or a range of reliably detectable empirical effect sizes for a specific research question or field of interest by computing effect size distributions (ESDs). This package can be used on data that can be easily extracted from pre-existing meta-analyses to help researchers more accurately plan new studies or to better understand how an individual study might relate to other studies in their field. ESDist includes a set of features that make it easy to use in a priori power analysis. Moreover, the package includes a feature for estimating effect size benchmarks that account for publication bias and are weighted by effect sizes’ variances, which addresses existing limitations of using ESDs for study planning or interpretation.

PMID:42056646 | DOI:10.3758/s13428-026-03003-2

AIDS Behav. 2026 Apr 30. doi: 10.1007/s10461-026-05148-9. Online ahead of print.

ABSTRACT

A childhood sexual abuse (CSA) history is more prevalent among people living with HIV and may have lingering effects among older adults living with HIV (OALH). However, studies examining the impact of trauma-informed interventions among OALH are scant. The aim of the study was to determine the preliminary effect of the Coping with Childhood Sexual Abuse, HIV, and Aging (CoSHA) intervention on depressive symptoms, coping and ART adherence among OALH. Data were obtained from 28 OALH recruited from an immunology clinic and an AIDS service organization in South Carolina. Generalized estimating equation (GEE) models were used to determine the preliminary effect of the intervention on depressive symptoms, coping and ART adherence among OALH from baseline to 6-week, 3- and 6- month follow-up using intention-to-treat analysis. The intervention reduced depressive symptoms over the 6-month period (B=-9.13, 95% CI: -10.3, -8.00). There were also positive changes in planning coping (B = 0.73, 95% CI: -0.08, -1.54) and religious coping (B = 1.13, 95% CI: -0.08, 2.34), and ART adherence (B = 15.2, 95% CI: -0.95, 31.3) but these were borderline statistically significant. Future research should determine the impact of the CoSHA intervention in a full randomized controlled trial.

PMID:42056642 | DOI:10.1007/s10461-026-05148-9

Alzheimers Dement. 2026 May;22(5):e71395. doi: 10.1002/alz.71395.

ABSTRACT

INTRODUCTION: Dementia is increasing rapidly in Latin America and the Caribbean (LAC), but research output remains limited. Tracking publication trends, themes, and collaborations is key to guiding regional research and policy.

METHODS: Bibliometric analysis was conducted on dementia-related publications from 21 LAC countries (1990 to 2024) using Scopus. Thirteen keywords identified relevant articles, classified into themes through artificial intelligence (AI)-assisted and manual review. Bibliometrix and VOSviewer assessed publication trends, country and institutional output, and collaboration networks.

RESULTS: Of 201,939 worldwide publications, 6003 (3%) included at least one LAC-affiliated author. Brazil produced 49.9% of all dementia publications, followed by Argentina and Mexico. Clinical scenarios (15%) and basic science (14%) dominated thematic output. Mexico, Argentina, and Chile led regional collaboration efforts.

DISCUSSION: Despite growth, dementia research in LAC remains concentrated in a few countries, with major thematic gaps and uneven collaboration. Strengthening cross-country partnerships, broadening research themes, and increasing investment in applied and policy-focused studies are essential.

PMID:42056639 | DOI:10.1002/alz.71395

Environ Geochem Health. 2026 Apr 29;48(7):324. doi: 10.1007/s10653-026-03207-7.

ABSTRACT

Rainfall plays a key role in the removal of atmospheric pollutants (both particulate matter and gaseous pollutants) through wet scavenging and thus, the interaction between rain and atmospheric pollutants significantly influences the chemical composition of rainwater. Therefore, in this study, PM_2.5 and rainwater samples were collected from an urban site in the middle Indo-Gangetic Plain, Varanasi (25.28° N, 82.96° E), India during January-December 2022. The water-soluble inorganic ions (WSIIs), as well as carbonaceous and nitrogenous species in PM_2.5 and rainwater samples were analysed to understand their sources, seasonal variability, scavenging processes, and deposition fluxes. PM_2.5 mass concentrations ranged from 15.5 to 279.3 µg m^⁻3, with an annual mean of 91.6 ± 50.5 µg m^⁻3, significantly exceeding the Indian NAAQS annual limit of 40 µg m^⁻3. The total WSIIs (sum of concentrations of measured anions and cations) was 29.6 µg m^⁻3 accounted for ~ 33% of the total PM_2.5 mass and was dominated (66%) by secondary inorganic aerosols ( ${\text{SO}}_4^{2–}$ , ${\text{NO}}_3^{–}$ and ${\text{NH}}_4^{+}$ ), indicating strong anthropogenic influence. In rainwater, Ca²⁺, ${\text{NH}}_4^{+}$ , and ${\text{SO}}_4^{2–}$ were the major ions, contributing over 76% of total ionic content, with near-neutral pH (mean 6.6 ± 0.5) indicating effective neutralization by alkaline species. Seasonal variation showed higher ionic, dissolved organic carbon, and nitrogen concentrations during non-monsoon period, indicating pollutant accumulation under dry conditions whereas dilution during the monsoon. Wet deposition fluxes were consistently higher than dry deposition fluxes for all major ionic species. Relatively, high scavenging ratios, particularly for ${\text{NO}}_3^{–}$ and Ca²⁺, indicate efficient washout of both anthropogenic and crustal components, with below-cloud scavenging identified as the dominant mechanism. The relatively low ${\text{NO}}_3^{–}$ / ${\text{SO}}_4^{2–}$ ratios in both rainwater (0.54) and PM_2.5 (0.33) indicate predominant influence of stationary emission sources (e.g., coal/biomass burning and industrial emissions). Statistical analysis and diagnostic ratios further indicate contributions from biomass burning and anthropogenic activities (agriculture, vehicular emissions, and construction) for both rainwater and PM_2.5 samples. Moreover, back-trajectory analysis supports the combined influence of local emissions and regional transport. Overall, our study demonstrates a strong coupling between PM_2.5 composition and rainwater chemistry over the IGP and highlights the importance of wet deposition in controlling the overall deposition pattern over Varanasi.

PMID:42056635 | DOI:10.1007/s10653-026-03207-7

Curr Opin Neurobiol. 2026 Apr 28;99:103206. doi: 10.1016/j.conb.2026.103206. Online ahead of print.

ABSTRACT

Cephalopod camouflage presents a longstanding paradox: many species appear to match the color of their surroundings, yet anatomical and behavioral evidence suggests they lack conventional color vision. Here I discuss behavioral, anatomical, optical, molecular, and ecological evidence bearing on this problem. I evaluate a range of proposed mechanisms that could reconcile color matching with monochromatic vision, including passive skin reflectance, chromatic aberration-based spectral inference, polarization vision, and extraocular photoreception. Each is found to be either insufficient or weakly supported by current data. I then consider the null hypothesis that cephalopods achieve effective color matching without color perception, drawing an analogy with machine vision systems that infer color from grayscale statistics. Cephalopod camouflage may rely on predictive mappings from luminance-based visual input to colored skin output, rather than on true color vision.

PMID:42054709 | DOI:10.1016/j.conb.2026.103206

JMIR Res Protoc. 2026 Apr 29;15:e83629. doi: 10.2196/83629.

ABSTRACT

BACKGROUND: Veterans have an increased risk of developing Alzheimer disease and related dementia (ADRD) due to military exposures such as traumatic brain injury. There is a lack of information on home- and community-based services (HCBS) use among Veterans who served in the post-9/11 era and their caregivers.

OBJECTIVE: This study aims to (1) quantify HCBS use among post-9/11 Veterans with or at higher risk of ADRD, (2) identify facilitators, barriers, and preferences for HCBS among Veterans and family caregivers, and (3) prioritize HCBS interventions with input from Veterans and family caregivers.

METHODS: This study will include post-9/11 Veterans aged 65 years or younger with early-onset Alzheimer disease or frontotemporal dementia (current ADRD), and Veterans at elevated ADRD risk due to traumatic brain injury or cognitive dysfunction. Veterans’ family caregivers will also be recruited. Secondary data will come from the Department of Veterans Affairs (VA), the Department of Defense, and a previous neurotrauma study. Using VA data augmented with Centers for Medicare and Medicaid Services data, we will characterize HCBS utilization. To address aim 1, we will calculate the crude and adjusted cumulative frequency of HCBS use and the proportion of Veterans using a service among Veterans with ADRD, and those at higher and lower risk for ADRD. We will compare groups using t tests for continuous measures (number of services) and chi-square tests for categorical measures (any service use). To address aim 2, we will interview Veterans and caregivers to identify facilitators and barriers to HCBS use. We will use descriptive content analysis, including rich descriptions, coding, and theme identification. Finally, to address aim 3, we will use a modified Delphi approach to identify and rank HCBS modifications that would increase use. Using the ranking data, we will consider items to have consensus on high importance if 70% or more respond “important” or “very important.” Participants for primary data collection will be recruited from prior studies, VA health systems data, VA clinics, and Veteran- and caregiver-serving organizations.

RESULTS: This study was reviewed by the institutional review boards of the University of Utah, Salt Lake City Veterans Affairs, and UT Health at San Antonio and classified as exempt. The 46,053 Veterans in the preliminary aim 1 cohort (903 with early-onset Alzheimer disease/frontotemporal dementia and 45,150 at-risk Veterans matched on age and index year) averaged 55 years old at the index date and were mostly male (38,842/46,053, 84%) and non-Hispanic White (28,016/46,053, 61%).

CONCLUSIONS: This study will quantify current HCBS use and identify barriers and needs of Veterans with or at higher risk of ADRD and their caregivers. It will identify HCBS modifications that have consensus for needed changes, which will be shared with health system leaders.

PMID:42054703 | DOI:10.2196/83629

Global Spine J. 2026 Apr 29:21925682261447888. doi: 10.1177/21925682261447888. Online ahead of print.

ABSTRACT

Study DesignNetwork Meta-Analysis.ObjectiveTo compare the efficacy and safety of osteobiologics used in posterior lumbar spinal fusion (LSF) for degenerative lumbar disorders, setting autologous iliac crest bone graft (AICBG) as the reference standard.MethodsA systematic search of randomized controlled trials (RCTs) evaluating osteobiologics in adult patients undergoing posterior LSF was performed. Primary outcomes were radiologic fusion and osteobiologic-related complications. Secondary outcomes included disability, low back pain, operative time, blood loss, and length of stay (LOS). A frequentist random-effects network meta-analysis (NMA) was performed. Meta-regression was employed to assess the influence of surgical technique on primary outcomes. Risk of bias was evaluated using the Cochrane RoB-2 tool, and certainty of evidence was assessed with the GRADE framework.ResultsThirty-five RCTs including 2298 patients were analyzed. Compared with AICBG, recombinant human bone morphogenetic protein-2 (rhBMP-2) showed significantly higher fusion rates (OR 3.86; 95% CI 2.60-5.74; P < 0.0001) and lower complication risk (OR 0.50; 95% CI 0.34-0.73; P = 0.0004). Disability and pain outcomes were comparable across treatments. rhBMP-2 (MD -21.8 minutes; 95% CI -28.0 to -15.7; P < 0.0001), autologous local bone (MD -12.0 minutes; 95% CI -21.5 to -2.5; P = 0.0133), and ABM/P-15 (MD -17.0 minutes; 95% CI -32.6 to -1.5; P = 0.0322) were associated with shorter operative time. Only rhBMP-2 significantly decreased blood loss (MD -72.6 mL; 95% CI -118.9 to -26.4; P = 0.002), while no treatment reduced LOS.ConclusionsAmong evaluated osteobiologics, rhBMP-2 demonstrated superior efficacy and safety compared to AICBG in posterior LSF. Other agents showed favourable trends without statistical significance, reflecting persistent uncertainty rather than confirmed equivalence.

PMID:42054700 | DOI:10.1177/21925682261447888