Tag: nevin manimala

JAMA Netw Open. 2025 Sep 2;8(9):e2530972. doi: 10.1001/jamanetworkopen.2025.30972.

ABSTRACT

IMPORTANCE: Predialysis nephrology care is associated with the likelihood of having a mature, usable arteriovenous access for starting hemodialysis (ie, incident vascular access), a key care quality metric for patients with kidney failure. However, the magnitude of this association has not been quantified to date.

OBJECTIVE: To quantify the attributable association between lack of access to predialysis nephrology care and incident vascular access outcomes among Hispanic patients.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study is a retrospective analysis of the 2021 US Renal Database System. Participants were all adult Medicare recipients initiating hemodialysis between 2010 and 2019; primary analysis was restricted to those with at least 6 months of predialysis Medicare status. Data analysis was performed from June 2022 to November 2024.

EXPOSURE: Self-reported race and ethnicity, with the non-Hispanic White category serving as the reference and Hispanic ethnicity as the primary comparator. Any predialysis nephrology care was the primary mediator, and at least 6 months of nephrology care and predialysis kidney disease education were the mediators for sensitivity analyses.

MAIN OUTCOMES AND MEASURES: The attributable association between predialysis nephrology care and incident vascular access (ie, the composite of arteriovenous fistula [AVF] or arteriovenous graft [AVG]) disparity was the primary outcome, and its attributable association between remaining incident access types, including central venous catheter (CVC) with maturing in-situ AVF or AVG, and CVC without any other access (CVC only) disparity, were the secondary outcomes. Causal mediation analysis with logistic regression was used to determine the unadjusted and adjusted associations.

RESULTS: Among 427 340 eligible patients undergoing incident hemodialysis (mean [SD] age, 72.65 [10.68] years; 241 420 male [56.5%]), 92 887 (21.7%) were Black, 46 146 (10.8%) were Hispanic, 269 697 (63.1%) were White, and 18 610 (4.35%) were other races and ethnicities. AVF was used in 62 075 patients (14.5%), AVG in 13 163 patients (3.1%), and CVC in 351 315 patients (82.2%). Compared with White patients, Hispanic patients had adjusted odds ratios (aORs) of 0.70 (95% CI, 0.68-0.72) for receiving predialysis nephrology care and 0.77 (95% CI, 0.75-0.80) for receiving incident vascular access, for a 23% lower rate. A lack of nephrology care accounted for 32.59% of incident vascular access and 62.00% of maturing vascular access underuse. Sensitivity analyses enhancing the predialysis care disparities strengthened incident vascular access disparity and the attributable association. Secondary analyses revealed that compared with White patients, Hispanic individuals with CVC and a maturing AVF or AVG had 38% (aOR, 1.38; 95% CI, 1.23-1.53) higher odds and those with CVC only had 30% (aOR, 1.30; 95% CI, 1.25-1.35) higher odds of conversion to a functional AVF or AVG within the first year of dialysis, with predialysis care negatively mediating these outcomes.

CONCLUSIONS AND RELEVANCE: This retrospective cohort study of incident hemodialysis patients found that system-based disparities in predialysis access to nephrology care contribute to approximately one-third of incident vascular access disparities among Hispanic individuals. Targeted system-based remedies and policies are needed to improve timely identification and nephrology referrals among Hispanic individuals, for equitable improvements in incident kidney failure outcomes.

PMID:40911306 | DOI:10.1001/jamanetworkopen.2025.30972

JAMA Netw Open. 2025 Sep 2;8(9):e2531038. doi: 10.1001/jamanetworkopen.2025.31038.

ABSTRACT

IMPORTANCE: Subjective cognitive decline (SCD) may be an early indicator of Alzheimer disease and related dementias (ADRD), yet its association with plasma biomarkers remains unclear among middle-aged and older adults (aged 50-86 years).

OBJECTIVE: To examine associations between plasma biomarkers of amyloid, tau, neuroaxonal damage, and glial activation with SCD in a heterogeneous cohort of Hispanic and/or Latino adults.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used survey-weighted data from the Study of Latinos-Investigation of Neurocognitive Aging, an ancillary study of the Hispanic Community Health Study/Study of Latinos. Participants were aged 50 to 86 years and resided in 4 major US cities. Data were collected from 2016 to 2018 and analyzed between December 2024 and June 2025.

EXPOSURE: Plasma biomarkers included amyloid-beta (Aβ42/40), phosphorylated tau-181 (ptau-181), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP), quantified using Simoa (Quanterix HD-X) and log-transformed (ln) to reduce skewness.

MAIN OUTCOMES AND MEASURES: SCD was assessed using the short-form Everyday Cognition Scale (ECog-12), evaluating global-, executive-, and memory-related SCD, and a single-item cognitive concerns question. Survey-weighted linear and logistic regression models tested associations between biomarkers and SCD, adjusting for demographic, cardiovascular, kidney, and APOE genotype covariates.

RESULTS: Among 5712 adults (mean [SD] age, 63.47 (8.15) years; unweighted 3663 [53.92%] female), higher ln(ptau-181) was associated with ECog-12 memory (unstandardized β = 0.088; 95% CI, 0.005-0.170). Higher ln(NfL) levels were associated with greater ECog-12 global (unstandardized β = 0.169; 95% CI, 0.074-0.265), executive (unstandardized β = 0.182; 95% CI, 0.087-0.277), and memory (unstandardized β = 0.156; 95% CI, 0.065-0.248) domains. Higher ln(GFAP) levels were associated with greater ECog-12 global (unstandardized β = 0.109; 95% CI, 0.019-0.198) and executive (unstandardized β = 0.121; 95% CI, 0.031-0.211) domains. Ln(Aβ42/40) was not associated with SCD domains. Cognitive concerns significantly modified the associations between ln(NfL) and ECog-12 domains, with more pronounced associations among those reporting cognitive concerns. No biomarkers were associated with the single-item cognitive concerns score.

CONCLUSIONS AND RELEVANCE: In this study of middle-aged and older Hispanic and/or Latino adults, plasma biomarkers of p-tau181, NfL, and GFAP, but not Aβ42/40, were associated with greater SCD. These findings underscore their potential utility in early ADRD detection strategies.

PMID:40911305 | DOI:10.1001/jamanetworkopen.2025.31038

Evolution. 2025 Sep 5:qpaf177. doi: 10.1093/evolut/qpaf177. Online ahead of print.

ABSTRACT

Intraspecific phenotypic variation provides the basic substrate upon which the evolutionary processes that give rise to morphological innovation, such as adaptation, operate. Work in living clades has shown standing population-level variation fuels ecological speciation and gives rise to adaptive radiations. Despite its importance in evolutionary biology, the role of intraspecific variation in shaping phylogenetic and macroevolutionary patterns and processes has remained underexplored. I introduce a model of morphological evolution that accommodates polymorphism. The model describes the stochastic gain and loss of phenotypic character states within taxa, i.e., anagenesis, and the sorting of ancestral polymorphic variation during speciation, i.e., cladogenesis. I explore the behaviour of the model using simulations, then deploy it to reconstruct evolutionary relationships between the highly variable species belonging to the Cretaceous echinoid genus Micraster. The analysis revealed strong statistical support for several contentious relationships. The clade depicts a pattern where morphological variation accumulates within a small number of ancestral lineages and then is sorted into descendants without being fully replenished by anagenetic gains. This disproportionate maintenance of variation within early taxa and loss among later taxa could provide a link between the population processes that maintain intraspecific variation and the radiation and decline of clades.

PMID:40911295 | DOI:10.1093/evolut/qpaf177

Syst Biol. 2025 Sep 5:syaf061. doi: 10.1093/sysbio/syaf061. Online ahead of print.

ABSTRACT

For many questions in ecology and evolution, the most relevant data to consider are attributes of lineage pairs. Comparative tests for causal relationships among traits like ‘diet niche overlap’, ‘divergence time’, and ‘strength of reproductive isolation (RI)’ – measured for pairwise combinations of related species or populations – have led to several groundbreaking insights, but the correct statistical approach for these analyses has never been clear. Lineage-pair traits are non-independent, but unlike the expected covariance among species’ traits, which is captured by a phylogenetic covariance matrix arising from a given model, the expected covariance among lineage-pair traits has not been explicitly formulated. Analyses of pairwise-defined data have thus employed untested workarounds for non-independence rather than direct models of lineage-pair covariance, with consequences that are unexplored. Here, we consider how evolutionary relatedness among taxa translates into non-independence among taxonomic pairs. We develop models by which phylogenetic signal in an underlying character generates covariance among pairs in a lineage-pair trait. We incorporate the resulting lineage-pair covariance matrices into modified versions of phylogenetic generalized least squares and a new phylogenetic beta regression for bounded response variables. Both outperform previous approaches in simulation tests. We find that a common heuristic method, node averaging, imparts a greater cost to model performance than does the non-independence it was designed to correct. We re-analyze two empirical datasets to find dramatic improvements in model fit and, in the case of avian hybridization data, an even stronger relationship between pair age and RI than is revealed from uncorrected analysis. We finally present a new tool, the R package phylopairs, that allows empiricists to test relationships among pairwise-defined variables in a way that is statistically robust and more straightforward to implement.

PMID:40911284 | DOI:10.1093/sysbio/syaf061

MSMR. 2025 Aug 20;32(8):9-17.

ABSTRACT

Arboviruses pose a significant health threat to U.S. military personnel deployed in the U.S. Indo-Pacific Command (INDOPACOM) region. In 2023 we conducted a sero-epidemiological study to determine the arboviruses circulating in 185 Papua New Guinea military personnel (PNGMP), using the neutralizing antibody (NAb) assay. Overall, sero-positivity rates among the 185 PNGMP tested were: anti-Zika virus (ZIKV), 87% (n=161); anti-Japanese encephalitis virus (JEV), 62.2% (n=115); anti-Ross River virus (RRV), 44.3% (n=82); anti-Murray Valley encephalitis virus (MVEV), 39.5% (n=73); anti-chikungunya virus (CHIKV), 33.5% (n=62); anti-Barmah Forest virus (BFV), 10.8% (n=20); and anti-West Nile virus (WNV), 5.9% (n=11). The monotypic NAb sero-positivity rates for dengue virus (DENV) serotypes were: anti-DENV-1 94.6% (n=175), anti-DENV-2 93% (n=172), anti-DENV-3 95.1% (n=176), and anti-DENV-4 31.4% (n=57). These findings indicate that the majority of PNGMP had prior exposure to DENV and ZIKV, with a notable proportion exposed to CHIKV, RRV, JEV, and MVEV, and lower levels of exposure to BFV and WNV. Low or moderate prior exposure may leave individual PNGMP immunologically naïve and more susceptible to infection and disease upon first exposure. Furthermore, secondary DENV infections with a different serotype can increase risk of severe disease due to immune enhancement mechanisms such as antibody-dependent enhancement. Understanding these exposure patterns is crucial for assessing population risk and informing surveillance and prevention strategies. U.S. soldiers exercising or deploying to Papua New Guinea should adhere to strict preventive measures for minimizing mosquito bites and reducing their risk of arboviral infections. To our knowledge, this study provides the first comprehensive examination of arbovirus sero-positivity rates in Papua New Guinea military personnel (PNGMP) following the COVID-19 pandemic. After examining sero-positivity of 11 arboviruses, we found a majority of PNGMP with neutralizing antibodies (NAb) to dengue and Zika viruses, with some NAb to chikungunya, Japanese encephalitis, Ross River, and Murray Valley encephalitis viruses. Sero-prevalence to Barmah Forest and West Nile viruses was less common.

PMID:40911282

Fam Cancer. 2025 Sep 5;24(4):70. doi: 10.1007/s10689-025-00494-4.

ABSTRACT

This study compares three hereditary colorectal cancer (CRC) registries-the Iranian Hereditary Colorectal Cancer Registry (IHCCR), the Singapore Polyposis Registry (SPR), and the University of Cape Town Familial CRC Registry-to illuminate diverse approaches to identification, management, and research across different healthcare systems. Each registry, while emphasizing patient diversity, employed unique strategies reflecting available resources and epidemiological contexts. The IHCCR, leveraging WES, revealed considerable genetic heterogeneity, including novel mutations. The SPR, a nationalized service, focused on structured surveillance and management of FAP and other polyposis syndromes, highlighting the challenges of cultural conservatism and limited public awareness. The UCT registry, initially concentrating on Lynch syndrome, expanded to encompass other hereditary CRC syndromes, revealing a high prevalence of these conditions within the South African population. All three registries encountered challenges related to access to genetic testing and early diagnosis. The registries’ combined experiences underscore the critical need for integrated, culturally sensitive strategies combining genetic testing, enhanced surveillance, and family-based management to improve outcomes for individuals and families affected by hereditary CRC. Future efforts should focus on addressing disparities in access to care and expanding research to improve understanding and management of this complex disease.

PMID:40911264 | DOI:10.1007/s10689-025-00494-4

Pharmacol Rep. 2025 Sep 5. doi: 10.1007/s43440-025-00784-9. Online ahead of print.

ABSTRACT

BACKGROUND: The isobolographic analysis is a gold standard in the assessment of interactions between drugs in experimental studies. Although some isobolographic approaches are available, the most popular methods to characterize drug-drug interactions are the log-probit method accompanied with statistical analysis of interactions (by Tallarida) and the method based on mass-action law using CompuSyn software (elaborated by Chou-Talalay-Martin). The aim of this study was to compare the results from these two isobolographic approaches.

METHODS: Two isobolographic methods (log-probit associated with Tallarida statistics and Chou-Talalay-Martin) were applied to analyze the interaction between two antiseizure medications – clonazepam and lamotrigine in the mouse maximal electroshock-induced seizure model.

RESULTS: Both isobolographic approaches confirmed that the combination of clonazepam with lamotrigine produced synergistic interaction and allowed for detailed characteristics of the interaction at various effect levels for the two-drug mixture. Calculation of the combination index values (at various effect levels) confirmed that synergy slightly decreased when the antiseizure effect increased (combination index values increased from 0.44 for 16% to 0.65 for 84%).

CONCLUSIONS: The log-probit method with statistical analysis of data (by Tallarida) was more subtle and precise in the assessment of the synergistic interaction, whereas the isobolographic analysis by Chou-Talalay-Martin offered more automatic options facilitating visualization of the interaction.

PMID:40911251 | DOI:10.1007/s43440-025-00784-9

J Mol Model. 2025 Sep 5;31(10):264. doi: 10.1007/s00894-025-06486-6.

ABSTRACT

CONTEXT: This study systematically investigates the growth mechanism of nitrogen-doped graphene in a plasma environment, with a particular focus on the effects of temperature and hydrogen radicals on its structural evolution. The results reveal that, at 3000 K, the formation of nitrogen-doped graphene proceeds through three stages: carbon chain elongation, cyclization, and subsequent condensation into planar structures. During this process, nitrogen atoms are gradually incorporated into the carbon network, forming various doping configurations such as pyridinic-N, pyrrolic-N, and graphitic-N. An increase in temperature accelerates the reaction kinetics and cluster growth, but concurrently reduces the stability of nitrogen incorporation. Hydrogen radicals play a dual role: they help maintain the planar structure and suppress the curling of carbon clusters; however, excessive hydrogen radicals compete for edge-active sites, thereby inhibiting nitrogen doping efficiency. This work provides deeper insight into the growth mechanism of nitrogen-doped graphene and offers theoretical guidance for its efficient and controllable synthesis.

METHODS: In this study, we employed molecular dynamics (MD) simulations using the LAMMPS software package combined with the ReaxFF reactive force field to systematically investigate the growth mechanism of nitrogen-doped graphene in a plasma environment, as well as the effects of temperature and hydrogen radicals on its structural evolution. All simulations were performed in the NVT ensemble with a time step of 0.1 fs and a total simulation duration of 15,000 ps. To reduce variability and enhance the reliability of the results, each simulation was carefully repeated three times under identical conditions for subsequent statistical analysis.

PMID:40911219 | DOI:10.1007/s00894-025-06486-6

Bull Math Biol. 2025 Sep 5;87(10):145. doi: 10.1007/s11538-025-01522-1.

ABSTRACT

Tree balance plays an important role in various research areas in phylogenetics and computer science. Typically, it is measured with the help of a balance index or imbalance index. There are more than 25 such indices available, recently surveyed in a book by Fischer et al. They are used to rank rooted binary trees on a scale from the most balanced to the least balanced. We show that a wide range of subtree-size based measures satisfying concavity and monotonicity conditions are minimized by the complete or greedy from the bottom (GFB) tree and maximized by the caterpillar tree, yielding an infinitely large family of distinct new imbalance indices. Answering an open question from the literature, we show that one such established measure, the $\hat{s}$ -shape statistic, has the GFB tree as its unique minimizer. We also provide an alternative characterization of GFB trees, showing that they are equivalent to complete trees, which arise in different contexts. We give asymptotic bounds on the expected $\hat{s}$ -shape statistic under the uniform and Yule-Harding distributions of trees, and answer questions for the related Q-shape statistic as well.

PMID:40911217 | DOI:10.1007/s11538-025-01522-1

J Math Biol. 2025 Sep 5;91(3):33. doi: 10.1007/s00285-025-02254-5.

ABSTRACT

Human movement plays a key role in spreading vector-borne diseases globally. Various spatial models of vector-borne diseases have been proposed and analyzed, mainly focusing on disease dynamics. In this paper, based on a multi-patch Ross-Macdonald model, we study the impact of host migration on the local and global host disease prevalences. Specifically, we find that the local disease prevalence of any patch is bounded by the minimum and maximum disease prevalences of all disconnected patches and establish a weak order-preserving property. For global disease prevalence, we derive its formula at both zero and infinite dispersal rates and compare them under certain conditions, and calculate the right derivative at no dispersal. In the case of two patches, we give two complete classifications of the model parameter space: one is to compare the host disease prevalences with and without host dispersal, and the other is to determine the monotonicity of host disease prevalence with respect to host dispersal rate. Numerical simulations confirm inconsistence between disease persistence and host disease prevalence, as well as between host prevalence and vector prevalence in response to host movement. In general, a more uneven distribution of hosts and vectors in a homogeneous environment leads to lower host prevalence but higher vector prevalence and stronger disease persistence.

PMID:40911201 | DOI:10.1007/s00285-025-02254-5