Nevin Manimala

JAMA Netw Open. 2025 Sep 2;8(9):e2530677. doi: 10.1001/jamanetworkopen.2025.30677.

ABSTRACT

IMPORTANCE: The association of cardiopulmonary point-of-care ultrasonography (POCUS) with length of stay (LOS) and hospitalization costs for patients admitted to internal medicine wards remains uncertain.

OBJECTIVE: To evaluate a collaborative implementation model involving hospitalists, sonographers, and a remote cardiologist for integrating cardiopulmonary POCUS into the assessment of adult patients (≥18 years) hospitalized with undifferentiated dyspnea, and to assess its association with LOS and hospitalization costs.

DESIGN, SETTING, AND PARTICIPANTS: This quality improvement study employed a type 1 effectiveness-implementation hybrid design using a 6-month stepped-wedge cluster randomized approach, conducted at a tertiary care hospital in the US between December 7, 2023, and July 2, 2024, to compare the standard-of-care (control) with the intervention group. Patients were eligible for inclusion if they were older than 18 years, admitted to 1 of the 5 internal medicine teaching hospitalist teams, and presented with undifferentiated dyspnea.

EXPOSURE: Structured cardiopulmonary POCUS examinations performed by hospitalists and/or sonographers, integrated into routine assessment of dyspnea.

MAIN OUTCOMES AND MEASURES: Study outcomes (LOS and hospitalization costs) were presented using the reach, effectiveness, adoption, and implementation (RE-AIM) framework.

RESULTS: The study reached 208 patients (median [IQR] age, 71 [59-80] years; 121 female [58%]), including 107 in the control group and 101 in the POCUS group. The implementation of cardiopulmonary POCUS was associated with a 30.3% (95% CI, 5.5%-48.9%) reduction in expected LOS (mean [SD] LOS, 8.3 [5.2] days for the POCUS group vs 11.9 [7.5] days in the control group). Based on cumulative assessments, POCUS use was associated with a total reduction of 246 hospital bed-days and direct cost savings of $751 537, with an incremental cost-effectiveness ratio of $3055 per hospital bed-day saved. POCUS altered medical decisions in 30 patients (35%). Adoption and implementation of POCUS by hospitalists remained limited despite comprehensive training, with only 20% of POCUS evaluations (17 patients) being performed independently, while the majority relied on sonographers.

CONCLUSIONS AND RELEVANCE: In this quality improvement study, cardiopulmonary POCUS implementation was associated with a significant reduction in LOS and hospitalization costs, highlighting its clinical utility and potential for improved hospital efficiency; however, limited adoption by hospitalists underscores the need for ongoing training, support, and professional incentives to strengthen competency and motivation. Multicenter studies are needed to evaluate tailored educational models and sustainable support systems to optimize long-term integration of POCUS into routine practice.

PMID:40911308 | DOI:10.1001/jamanetworkopen.2025.30677

JAMA Netw Open. 2025 Sep 2;8(9):e2530691. doi: 10.1001/jamanetworkopen.2025.30691.

ABSTRACT

IMPORTANCE: In the US, children in food-insecure households are at risk for adverse psychological outcomes despite being shielded from hunger and malnutrition by their caregivers and school- and community-based programs. Parenting stress may be an important mechanism through which food insecurity is associated with negative outcomes for child mental health.

OBJECTIVE: To investigate associations of household food insecurity with child mental health, parenting stress, and family functioning.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used a daily-diary design in a community-based sample to examine associations between daily fluctuations in food insecurity and child and family functioning. The study was conducted remotely during the COVID-19 pandemic in the rural (defined by the Health Resource Services Administration) Northeastern US. Caregivers of school-aged children were enrolled during the 2021 school year and completed a baseline visit followed by mobile surveys for 30 days. Participants were adult, legal caregivers of children ages 6 to 12 years who experienced food insecurity within the past month. Participants were required to have English proficiency and access to a device with internet and texting capabilities. Prospective participants completed an online questionnaire to determine eligibility. A total of 553 respondents were screened, of which 327 respondents (59.1%) met all inclusion criteria. The most common reason for ineligibility was not having a child in the study age range. Data analyses were performed between May 2022 and April 2023.

EXPOSURE: Household food insecurity.

MAIN OUTCOMES AND MEASURES: The primary outcomes were caregiver hunger, negative affect, executive functioning, and parent-child interactions (measured via a daily self-report survey) and child mental health problems (measured via the Child Behavior Checklist [CBCL]).

RESULTS: Among 61 caregivers (mean [SD] age, 36.1 [5.9] years; 51 women [83.6%]; 2 American Indian or Alaska Native [3.3%], 1 Black [1.6%], and 55 non-Hispanic White [90.2%]), greater day-to-day fluctuations in household and child food insecurity were associated with more severe child internalizing problems (CBCL Internalizing Problems scale: β = 0.40; P = .003 for household and β = 0.49; P < .001 for child food insecurity) and total mental health problems (CBCL Total Problems scale: β = 0.34; P = .01 for household and β = 0.35; P = .01 for child food insecurity). Additionally, the daily association between food insecurity and parent-child conflict was fully mediated via 2 sequential pathways of caregiver hunger and negative affect (b = .02; P = .001) and caregiver hunger and attention and impulse control (b = 0.01; P = .04). This model explained 17% of variability in daily parent-child conflict (R2 = 0.17).

CONCLUSIONS AND RELEVANCE: This study’s findings suggest that caregiver stress and household instability may be key mechanisms by which food insecurity is negatively associated with child mental health.

PMID:40911307 | DOI:10.1001/jamanetworkopen.2025.30691

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