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Nevin Manimala Statistics

Retrograde transduction of dopaminergic cells in substantia nigra of the rhesus monkey

Sci Rep. 2026 Jun 16. doi: 10.1038/s41598-026-55097-5. Online ahead of print.

ABSTRACT

Recent advances in molecular tools have changed how researchers approach selective neural modulation, especially in rodent models where germline modifications and viral vector delivery are readily optimized. However, these tools have not advanced as rapidly for nonhuman primates, despite critical need for translational gene therapy models. A key barrier is targeting specific neuronal populations in the larger primate brain with cell-type and circuit specificity. Dopaminergic neurons pose a particular challenge due to their inaccessible ventral midbrain location, where local injection non-selectively targets all dopaminergic neurons. This work provides NHP researchers with a comparison of retrograde viral vectors, highlighting one which achieves efficient dopaminergic neuron transduction, establishing a foundation for combining vectors with cell-type-specific enhancers for basic and translational applications.

PMID:42304030 | DOI:10.1038/s41598-026-55097-5

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Nevin Manimala Statistics

Causal multi-fidelity surrogate forward and inverse models for ICF implosions

Sci Rep. 2026 Jun 16. doi: 10.1038/s41598-026-57115-y. Online ahead of print.

ABSTRACT

Continued progress in inertial confinement fusion (ICF) requires solving inverse problems relating experimental observations to simulation input parameters, followed by design optimization. However, such high-dimensional dynamic PDE-constrained optimization problems are extremely challenging or even intractable. It has been recently shown that inverse problems can be solved by only considering certain robust features. Here we consider the ICF capsule’s deuterium-tritium (DT) interface, and construct a causal, dynamic, multifidelity reduced-order surrogate that maps from a time-dependent radiation temperature drive to the interface’s radius and velocity dynamics. The surrogate targets an ODE embedding of DT interface dynamics, and is constructed by learning a controller for a base analytical model using low- and high-fidelity simulation training data with respect to radiation energy group structure. After demonstrating excellent accuracy of the surrogate interface model, we use machine learning (ML) models with surrogate-generated data to solve inverse problems optimizing radiation temperature drive to reproduce observed interface dynamics. For sparse snapshots in time, the ML model further characterizes the most informative times at which to sample dynamics. Altogether we demonstrate how operator learning, causal architectures, and physical inductive bias can be integrated to accelerate discovery, design, and diagnostics in high-energy-density systems.

PMID:42304029 | DOI:10.1038/s41598-026-57115-y

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Nevin Manimala Statistics

Determinants of attendant satisfaction with oncology service quality in Tamil Nadu, India: a cross-sectional study

Sci Rep. 2026 Jun 16. doi: 10.1038/s41598-026-58350-z. Online ahead of print.

ABSTRACT

Attendants are continuously involved in coordinating and supporting cancer care, yet their service quality perceptions are rarely modelled as determinants of satisfaction. This study investigates the association between demographic factors and service quality dimensions related to attendants’ satisfaction in oncology hospitals. A cross-sectional survey using a structured questionnaire was conducted among 480 attendants (accompanying patients) across oncology hospitals in Tamil Nadu, India. Service quality was assessed using six dimensions: tangibility, responsiveness, empathy, assurance, service reliability, and process reliability. Differences across demographic groups were evaluated using non-parametric statistical tests. Partial Least Squares Structural Equation Modeling (PLS-SEM) was applied to examine the relationships between service quality dimensions and attendant satisfaction, followed by Importance-Performance Map Analysis (IPMA) to prioritize improvement areas. Significant differences in service quality perceptions were observed across gender, age, education, residential status, financing category, and hospital visit frequency, while income and occupation did not show meaningful effects. Tangibility (β = 0.374), responsiveness (β = 0.313), and empathy (β = 0.196) demonstrated significant positive associations with satisfaction, collectively explaining 80.9% of its variance (R2 = 0.809), whereas assurance, service reliability, and process reliability were not significantly associated with satisfaction. IPMA result indicate that empathy represents a key area for refinement, while tangibility and responsiveness demonstrate high importance alongside strong performance, suggesting areas to be maintained. Overall, the findings provide insights into factors associated with attendant satisfaction, improving patient-centered oncology services.

PMID:42304028 | DOI:10.1038/s41598-026-58350-z

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Nevin Manimala Statistics

A reinforcement learning-enhanced fuzzy multi-objective equilibrium optimization framework for multiple sequence alignment

Sci Rep. 2026 Jun 16. doi: 10.1038/s41598-026-57298-4. Online ahead of print.

ABSTRACT

Multiple sequence alignment (MSA) is a fundamental task in bioinformatics, underpinning comparative genomics, structural analysis, and evolutionary inference. However, MSA remains a challenging multi-objective optimization problem due to the need to simultaneously maximize alignment accuracy, preserve conserved regions, and control gap proliferation, particularly in large and heterogeneous sequence collections. In this work, we propose MOFSACEO-MSA, a novel hybrid optimization framework for multiple sequence alignment that integrates a fuzzy multi-objective evaluation scheme with the Equilibrium Optimizer (EO) and a Soft Actor-Critic (SAC)-based adaptive control mechanism. The proposed framework formulates MSA as a dynamic multi-objective optimization problem, in which alignment quality is assessed using complementary residue-level and column-level criteria, including Sum-of-Pairs score, column conservation, entropy, and gap statistics. Fuzzy membership functions are employed to harmonize competing objectives into a unified optimization landscape, while EO provides robust global exploration. To further enhance adaptability, SAC dynamically regulates key EO parameters during the search process, enabling an effective balance between exploration and exploitation across datasets of varying size and heterogeneity. Extensive experiments werew conducted on diverse biological sequence datasets, with a primary focus on RNA benchmarks, including structured families from Rfam, large-scale repositories from RNAcentral and GenBank, and organism-specific tRNA datasets from GtRNAdb. Comparative evaluations against classical alignment tools (ClustalW, MAFFT, MUSCLE, PRANK, KAlign, and T-Coffee), metaheuristic methods (SAGA, Sequoya and EAFSA), and a reinforcement learning-based approach (RLALIGN) demonstrate that MOFSACEO-MSA consistently achieves competitive or superior Sum-of-Pairs scores while significantly reducing gap proportions and maintaining compact alignment lengths. Notably, the proposed framework exhibits improved robustness on large and highly heterogeneous datasets, where existing methods often suffer from excessive gap insertion or unstable convergence. Overall, MOFSACEO-MSA provides a flexible and extensible optimization paradigm that effectively bridges evolutionary search and reinforcement learning for high-quality multiple sequence alignment, with demonstrated effectiveness on challenging RNA alignment tasks.

PMID:42304027 | DOI:10.1038/s41598-026-57298-4

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Nevin Manimala Statistics

Development and validation of a risk-stratified prediction model for post-stroke vascular dementia: Clinical management value analysis

Clin Neurol Neurosurg. 2026 Jun 10;269:109534. doi: 10.1016/j.clineuro.2026.109534. Online ahead of print.

ABSTRACT

BACKGROUND: Post-stroke vascular dementia (VaD) affects 20-30% of ischemic stroke survivors within the first year, yet existing prediction models lack comprehensive integration of novel blood biomarkers and validated risk stratification strategies. This study aimed to develop and temporally validate a risk-stratified prediction model incorporating clinical, neuroimaging, and serum biomarker variables.

METHODS: This retrospective cohort study comprised a development cohort (n = 998, 2020-2022) and temporal validation cohort (n = 249, 2023-2024). Consecutive acute ischemic stroke patients aged ≥ 18 years with available baseline magnetic resonance imaging (MRI) and 12-month follow-up were included. Candidate predictors encompassed 25 variables: demographics, vascular risk factors, stroke severity assessed by the National Institutes of Health Stroke Scale (NIHSS), neuroimaging markers (Fazekas white matter hyperintensity score, brain atrophy index [BAI]), and serum biomarkers including neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP) measured by single-molecule array (Simoa). The primary outcome was incident VaD diagnosed by NINDS-AIREN criteria at 12 months.

RESULTS: Of 1247 included patients, 354 (28.4%) developed VaD. Least absolute shrinkage and selection operator (LASSO) selected 8 predictors: age, education level, NIHSS score, Fazekas score ≥ 2, BAI, previous stroke, plasma NFL, and plasma GFAP. In the development cohort, the model demonstrated excellent discrimination (C-statistic 0.89, 95% CI 0.86-0.92) and good calibration. Bootstrap validation yielded optimism-corrected C-statistic 0.88. In temporal validation, performance remained robust (C-statistic 0.85, 95% CI 0.81-0.89). Risk stratification revealed distinct cognitive trajectories: high-risk patients (25% of cohort) exhibited 67.3% VaD incidence and steep cognitive decline (mean Montreal Cognitive Assessment [MoCA] change -6.8 points), capturing 59.3% of all VaD cases.

CONCLUSIONS: This biomarker-enhanced prediction model demonstrates excellent discrimination and calibration for post-stroke VaD. Risk stratification effectively identifies high-risk patients for targeted interventions, providing a practical tool for precision-based clinical management.

PMID:42302346 | DOI:10.1016/j.clineuro.2026.109534

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Nevin Manimala Statistics

Real-world burden of cardiovascular events following immune checkpoint inhibitor therapy: impact on mortality and treatment resumption in 29,503 patients

Lung Cancer. 2026 Jun 14;218:109499. doi: 10.1016/j.lungcan.2026.109499. Online ahead of print.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) have transformed cancer therapy but can cause rare, severe cardiotoxicity. The real-world incidence and impact of a broader spectrum of cardiovascular events remains poorly defined. This study aims to evaluate the real-world incidence of cardiovascular events following ICI therapy, explore predictive biomarkers, and assess the impact of treatment interruptions.

METHODS: A retrospective observational study using Optum’s de-identified Market Clarity Data was conducted in 29,503 patients receiving ICI therapy for any cancer type with a minimum follow-up of 6 months. Cardiovascular events including myocarditis, arrhythmias, and reduced left ventricular ejection fraction (LVEF < 50%), were analyzed. Kaplan-Meier survival curves were used to evaluate the timing of these events. Biomarkers such as NT-proBNP and troponin were evaluated for their predictive value.

RESULTS: Out of 29,503 ICI-treated patients, 27.6% experienced a cardiac event during the follow-up period (2 years). Patients with pre-existing cardiovascular conditions who were receiving cardioprotective treatment prior to ICI therapy had an increased risk of cardiovascular events (35% vs 20%, p < 0.001). Patients who experienced a cardiac event had a significantly higher mortality rate (39% vs 25.4%, p < 0.001). Elevated troponin and NT-proBNP levels were associated with increased mortality (p < 0.001).

CONCLUSIONS: Cardiovascular events are frequent in ICI-treated patients, particularly in those with pre-existing cardiac conditions. Elevated troponin and NT-proBNP levels may serve as useful biomarkers for predicting post-ICI cardiovascular events. These findings demonstrate that these events significantly interrupt ICI therapy and increase mortality. They support biomarker-guided risk stratification and prompt collaboration between oncologists and cardio-oncologists to preserve treatment integrity.

PMID:42302339 | DOI:10.1016/j.lungcan.2026.109499

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Nevin Manimala Statistics

Patient reported outcome measures following group and individual therapy in a multidisciplinary functional/dissociative seizure program

Epilepsy Behav. 2026 Jun 16;183:111164. doi: 10.1016/j.yebeh.2026.111164. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Functional/dissociative seizures (FDS) are frequently treated with one-to-one therapeutic interventions. However, data describing patient-reported outcome measures (PROMs) following group-based therapy remain limited. This study evaluated changes in PROMs among a large cohort of individuals receiving virtual, group and individual therapy within a multidisciplinary FDS treatment program.

METHODS: We conducted a retrospective cohort study of 823 individuals referred to a specialty FDS program between April 2020 and January 2025. Baseline PROMs were completed by 436 patients and assessed quality of life (QoL), PTSD, anxiety, depression, and dissociative experiences. Follow up PROMs were available for 165 individuals who participated in one of three treatment pathways: 6-Week psychoeducational group therapy only, 6-Week and 12-Week psychodynamic group therapies combined, or individualized therapy. Mixed-effects linear regression examined changes in PROMs between baseline and follow-up, adjusting for relevant characteristics.

RESULTS: Across all cohorts, significant improvements were observed in depression (PHQ-9: -1.32, p < 0.01), quality of life (QOLIE-10P: -2.20, p < 0.01), and PTSD symptoms (SPRINT: -2.14, p < 0.01). Within-cohort analyses showed significant reductions in PHQ-9 (-2.16, p < 0.01) and SPRINT (-3.14, p < 0.01) for the 6-Week and 12-Week group therapies combined and improved QOLIE-10P (-3.37, p < 0.01) for the 6-Week group only. No significant changes were observed in anxiety or dissociation, and between-cohort differences were not statistically significant.

DISCUSSION: Analyses identified significant improvements in PROMs across treatment cohorts suggesting that group-based and individual interventions can enhance outcomes for individuals with FDS, though absence of a control group limits causal interpretation. This finding is important given limited treatment availability and opportunity for group therapy to increase FDS access.

PMID:42302323 | DOI:10.1016/j.yebeh.2026.111164

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Nevin Manimala Statistics

A Comparative Analysis of Tolerance to Induced Astigmatism Across Various Categories of Intraocular Lenses

J Cataract Refract Surg. 2026 Jun 16. doi: 10.1097/j.jcrs.0000000000002005. Online ahead of print.

ABSTRACT

PURPOSE: To compare tolerance to induced astigmatism (TIA) across four intraocular lenses (IOLs).

SETTING: Medical University of South Carolina, Charleston, South Carolina, USA.

DESIGN: Prospective observational study.

METHODS: Patients underwent cataract surgery with a standard monofocal (ZCB00), enhanced monofocal (DIB00), diffractive violet light filter (VLF) extended depth of field (DOFi) (ZXR00V), or VLF full DOFi (DRN00V) IOL. At 1-3 months postoperatively, astigmatic defocus (0.5-2.0 D) was simulated in WTR, oblique, and ATR orientations.

RESULTS: 100 patients were included. DCIVA was statistically significantly better with VLF extended DOFi compared with the monofocal (P≤0.001) and enhanced monofocal IOLs (P=0.002). DCNVA was significantly better with VLF Full-DOFi IOL than with all other groups (P<0.001). No statistically significant differences were observed among the four IOL groups with induction of WTR astigmatism ≤1.0 D. At 0.5D oblique, the enhanced monofocal group outperformed the extended DOFi group (P=0.014), and at 2.0 D induced oblique astigmatism, it surpassed all other IOL groups. The enhanced monofocal IOL group showed the greatest tolerance to induced ATR astigmatism across all magnitudes. The VLF Full-DOFi IOL group maintained astigmatic tolerance like standard monofocal, enhanced monofocal, and extended DOFi IOLs up to 2.0 D in WTR and ATR, and 1.5 D in oblique orientations.

CONCLUSION: TIA was not statistically significantly different among the standard monofocal, enhanced monofocal, VLF extended DOFi, and VLF Full-DOFi IOL groups with low to moderate induced WTR astigmatism. The enhanced monofocal IOL provided the greatest tolerance to induced astigmatism, especially under oblique and ATR astigmatic defocus.

PMID:42302314 | DOI:10.1097/j.jcrs.0000000000002005

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Nevin Manimala Statistics

Using Social Media Listening to Understand the Pressure Injury Experience: A Qualitative Descriptive Study

JMIR Nurs. 2026 Jun 16;9:e76682. doi: 10.2196/76682.

ABSTRACT

BACKGROUND: Pressure injuries (PIs) are a common complication in people with reduced mobility or sensation and can be burdensome for individuals with PIs and their caregivers. Valuable insights and real-world challenges faced by individuals living with PIs can be captured through candid accounts posted on social media. Social media listening (SML) is a tool that can enhance the understanding of those with lived experience by offering firsthand accounts that are irreproducible from controlled studies.

OBJECTIVE: This study aims to capture the candid experiences of individuals with PIs and caregivers through social media.

METHODS: A noninterventional qualitative descriptive analysis was conducted using SML. Social media posts made on X (formerly Twitter), Reddit, and YouTube between January and December 2022 were compiled using SML tools X Pro (formerly TweetDeck) and Awario, and using Boolean search terms. Posts were manually screened for relevance, and duplicates were removed. Relevant posts were hand-coded by two independent reviewers. Inductive content analysis was used to analyze the posts.

RESULTS: The search yielded 666 relevant posts from 498 unique social media users. Most posts were made in the United States (170/666, 25.5%), the United Kingdom (150/666, 22.5%), and Canada (62/666, 9.3%). Social media users provided detailed descriptions of the PIs, including the setting in which the PI occurred, the cause of the PI, and how the PI was managed. The majority of PIs (197/666, 29.6%) were reported to have occurred in the hospital setting due to a perceived lack of care from care providers, and local wound care was often cited (99/666, 14.9%) as a PI management strategy. Three key themes were developed regarding living with or caring for someone with a PI: (1) challenges experienced when living with or caring for a PI, (2) needs related to PI prevention and management, and (3) emotions experienced when living with or caring for a PI. Social media users frequently discussed challenges associated with living with a PI, including negative personal impacts and poor perceived treatment quality. Users also described a critical need for health care, education, and social support. Finally, users often expressed anger and/or sadness related to living with or caring for a PI.

CONCLUSIONS: SML captured candid insights into the experiences, challenges, and needs of individuals living with PIs and their caregivers globally that may not be gleaned from controlled studies. Individuals with lived experience and their caregivers often struggled with negative personal impacts regarding their physical health and daily functioning related to PIs, further highlighting the urgent need to address barriers to appropriate PI care. Clinicians and policymakers should consider practices and policies that optimize the delivery of person-centered PI care in order to overcome challenges and needs identified in this study.

PMID:42302309 | DOI:10.2196/76682

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Nevin Manimala Statistics

Implementation of Emotional Connection Training in Pediatric Primary Care: Mixed Methods Study

JMIR Med Educ. 2026 Jun 16;12:e81250. doi: 10.2196/81250.

ABSTRACT

BACKGROUND: In 2021, the American Academy of Pediatrics released a policy statement spotlighting the health-promoting and stress-buffering effects of early relational health (ERH) and calling for universal ERH promotion in pediatric primary care. However, little educational content for the observation and promotion of ERH is available, highlighting the need for scalable ERH training modules.

OBJECTIVE: This study aims to investigate the acceptability, feasibility, and impact of the “Lens of Emotional Connection,” a self-paced, asynchronous, ~45-minute ERH training module codeveloped by Reach Out and Read and the Center for Early Relational Health at Columbia University. The module introduces practitioners to emotional connection, an observable component of ERH, through written and video didactic content and experiential rating of emotional connection in videos of parent-child dyads interacting face-to-face.

METHODS: The evaluation was conducted by the Carolinas Collaborative. Pediatric providers across 8 clinical sites were invited to participate and responded to embedded pre-post surveys. Focus groups conducted with participants further examined the educational experience.

RESULTS: Of 653 invited clinicians, 207 (31.7%) participated in the module. Individual survey responses were available for 44-75 participants, depending on the question. Of responders, 64 out of 69 (93%) reported the module was a good way to learn about emotional connection, and 63 out of 69 (91%) felt the module provided valuable knowledge. Overall, 60 out of 69 respondents (87%) reported satisfaction with the module length, and 36 out of 44 respondents (82%) reported they would recommend this training to other clinicians. Focus groups echoed these findings. Comparison of pre-post data showed the greatest changes were in familiarity with emotional connection (n=75, pre mean 54.20, SD 18.59; post mean 73.99, SD 14.73; Cohen d=1.14; P<.001) and confidence in observing the quality of the parent- or caregiver-infant relationship during well-child visits (n=75, pre mean 55.36, SD 18.49; post mean 74.20, SD 14.07; Cohen d=1.28; P<.001). Suggested areas for improvement included more thorough explanations of specific components of emotional connection identified in parent-child interaction videos, a desire for synchronous live training, and additional content addressing what to do if low emotional connection is identified.

CONCLUSIONS: In this evaluation of a training module designed to introduce pediatric practitioners to ERH and emotional connection, acceptability among participants was found to be high, with most responders reporting it as valuable and reporting they would recommend it. Statistically significant impact was noted in both perceptions of the importance of information about emotional connection and perceived knowledge acquisition. Feasibility of widespread implementation with voluntary participation, as here, was relatively low, with only a minority completing the module. Critically, Reach Out and Read’s commitment to iterative creation, validation, and eventual delivery of ERH training creates a scalable avenue for wide-scale implementation, given the organization’s presence in >6500 clinics across the 50 states.

PMID:42302308 | DOI:10.2196/81250