Nevin Manimala

Endocr Relat Cancer. 2026 Jul 20:ERC-26-0207. doi: 10.1530/ERC-26-0207. Online ahead of print.

ABSTRACT

Patients with pancreatic neuroendocrine tumours (PNETs) often have similar baseline clinical characteristics, including grade and molecular imaging phenotype, yet have highly variable responses to peptide receptor radionuclide therapy (PRRT). To identify genomic alterations and mutational patterns associated with PRRT treatment response as well as acquired somatic changes following PRRT exposure, whole genome or exome sequencing was applied to 40 PNET samples from 32 patients, including eight paired pre- or post-PRRT samples. The genomic profile of tumours reflected the known mutational landscape of PNET with MEN1 (34%), ATRX/DAXX (47%) alterations and a recurrent pattern of aneuploidy (38%) detected. A recurrent PSIP1::TBL1X fusion of unknown function was also identified in four tumours. The disease control rate following PRRT using RECIST1.1 and molecular imaging criteria was 88% (28/32). No mutational features were found to be statistically associated with progression-free survival. There was no significant increase in tumour mutational burden in the post-PRRT tumours, nor recurrent emergent mutational changes in cancer driver genes to explain progression to higher grade disease, when observed. However, a small indel signature (ID8) previously associated with DNA damage repair by non-homologous end joining (NHEJ), was higher in PRRT-exposed compared with PRRT-naïve samples (23.8% vs 4.8% respectively; p<0.001). Thus, comprehensive DNA analysis of pancreatic NETs did not identify biomarkers predictive of PRRT response nor evidence for high-level PRRT-induced genomic instability or hypermutation, yet mutation signature analysis supports NHEJ as being important for DNA repair and survival of neuroendocrine cells following exposure to beta-particle radiation.

PMID:42473856 | DOI:10.1530/ERC-26-0207

Langmuir. 2026 Jul 20. doi: 10.1021/acs.langmuir.6c01718. Online ahead of print.

ABSTRACT

Unraveling the subtle role of molecular interactions controlling the rheological and thermomechanical responses of graphene-reinforced asphalt binders using molecular dynamics (MD) simulations is a cornerstone problem in statistical thermodynamics because of its chemical heterogeneity, nonergodicity, and sluggish dynamics associated with viscoelastic relaxation. Herein, we emphasize devising generalized models of asphalt binders, resolving finite size effects and phase separation during thermodynamic equilibration of large-scale models, and quantitatively assessing diverse structural and dynamical properties including density, solubility parameter, diffusivity, viscosity, mechanical, and thermophysical properties of pristine asphalt and graphene-modified binders. This study provides a molecular framework for optimizing the thermodynamic compatibility between asphalt components and graphene nanofiller and enhancing thermomechanical properties by tailoring filler percentages. The uniaxial deformation simulations performed at different strain rates demonstrate that the yield stress and postyield softening can be improved just by adding 2 wt. % of graphene filler. The increased toughness in graphene-modified binders strongly correlates with the predicted higher noncovalent intermolecular forces, lower diffusivity of asphalt components, and increased zero-shear equilibrium viscosity compared to the pristine asphalt. The glass transition temperature of asphalt is enhanced by about 26 K for the 2 wt. % graphene-reinforced asphalt composite. Density functional theory (DFT), natural energy decomposition analysis (NEDA), noncovalent interaction (NCI) analysis, and steered molecular dynamics (SMD) simulations were employed to probe the molecular mechanisms governing graphene-asphalt interactions. The multiscale simulations reveal that the strong interfacial interactions between graphene and polar asphalt components, dominated by π-π stacking and dispersion forces, are responsible for the mechanical reinforcement of the asphalt matrix. The resemblance of predicted data with experimental results in many cases further substantiates the applicability of a theoretical framework for the rational design of graphene-modified asphalt binders with desired physicochemical properties.

PMID:42473850 | DOI:10.1021/acs.langmuir.6c01718

Int J Health Plann Manage. 2026 Jul 20. doi: 10.1002/hpm.70101. Online ahead of print.

ABSTRACT

Rising out-of-pocket (OOP) health expenditures in the Eastern Caribbean Currency Union (ECCU) underscore persistent gaps in health insurance coverage. This paper develops a Health Insurance Policy Simulation Model (HIPSM) to assess the potential impact of employer health insurance mandates and health insurance tax credits (HITCs) across five small island developing states (SIDS): Antigua and Barbuda, Dominica, Grenada, St. Lucia, and St. Vincent and the Grenadines (SVG). Using social security and insurance data, the model estimates coverage gains, fiscal costs, and labour market effects under varying thresholds and tax credit levels. Results show that employer mandates and HITCs can reduce coverage gaps and OOP expenditure in these countries but are highly sensitive to design characteristics. The findings offer important guidance for SIDS exploring scalable pathways towards universal health coverage through private insurance mechanisms, particularly in the absence of comprehensive public healthcare financing systems.

PMID:42473832 | DOI:10.1002/hpm.70101

Pediatr Pulmonol. 2026 Jul;61(7):e71740. doi: 10.1002/ppul.71740.

ABSTRACT

BACKGROUND: Advanced cystic fibrosis lung disease (ACFLD) remains a major cause of morbidity, particularly in individuals requiring lung transplantation. Gastrointestinal-related aspiration (GRASP), including reflux and motility disorders, may contribute to adverse respiratory outcomes, yet diagnostic and management strategies vary across specialties.

OBJECTIVE: To evaluate practice patterns in foregut testing and pharmacologic management of GRASP among pulmonologists and gastroenterologists caring for individuals with ACFLD, with and without transplantation.

METHODS: A cross-sectional survey of clinicians at cystic fibrosis centers was distributed via a national listserv. Respondents involved in ACFLD care were included. Descriptive statistics were generated, and comparisons by specialty were performed using Fisher’s exact and Mann-Whitney U tests (α = 0.05).

RESULTS: Forty-five complete responses were analyzed (82% pulmonologists, 18% gastroenterologists). Eighty percent reported access to gastrointestinal motility testing. Overall use of reflux, motility, and gastric emptying testing was similar between specialties; however, modality selection differed. Gastroenterologists favored pH multichannel intraluminal impedance (75%) and BRAVO capsule testing (25%), while pulmonologists demonstrated heterogeneous practices and frequently deferred testing (37.8%). High-resolution manometry was universally preferred by gastroenterologists but variably used by pulmonologists. Acid suppression was widely utilized, with proton pump inhibitors most common, though pulmonologists showed greater variability, particularly post-transplant.

CONCLUSIONS: Substantial variability exists in GRASP evaluation and management in ACFLD. Standardized, multidisciplinary approaches may improve diagnostic consistency and optimize outcomes, especially in the transplant population.

PMID:42473831 | DOI:10.1002/ppul.71740

Public Health Nutr. 2026 Jul 20:1-23. doi: 10.1017/S1368980026103218. Online ahead of print.

ABSTRACT

OBJECTIVE: The environments where individuals live can shape their dietary patterns, but research using intersectionality as a context-informed analytic tool to assess associations between neighbourhood deprivation and diet quality is lacking. We therefore examined whether four dimensions of neighbourhood deprivation were independently and/or jointly associated with diet quality among adults in Canada.

DESIGN: We used 24-hour dietary recall data to calculate Healthy Eating Index (HEI-2015) scores to assess diet quality and the 2016 Canadian Marginalization Index (CAN-Marg) to assess four dimensions of neighbourhood deprivation (material resources, immigration/visible minority, age/labour force, and households/dwellings). Weighted linear regression models were used to examine whether these CAN-Marg dimensions were independently and/or jointly associated with diet quality, adjusting for individual, household, and area characteristics.

SETTING: The ten Canadian provinces.

PARTICIPANTS: Adults (≥18 years) who participated in the 2015 Canadian Community Health Survey-Nutrition.

RESULTS: The material resources (β=-0.955, 95% CI=-1.438, -0.471) and immigration/visible minority (β=0.768, 95% CI=0.268, 1.268) dimensions were independently associated with HEI-2015 scores. Significant interactions suggest the associations between living in a neighbourhood with less material resources and lower HEI-2015 scores was stronger in areas with a smaller proportion of recent immigrants/visible minorities (β=0.521, 95% CI=0.174, 0.868) and non-working individuals (β=-0.643, 95% CI=-1.052, -0.234).

CONCLUSION: Neighbourhood material deprivation was not uniformly associated with poor diet quality. This suggests that associations between neighbourhood deprivation and diet quality are not universal, and vary across neighbourhoods with differing immigrant, visible minority, age, and labour force compositions.

PMID:42473825 | DOI:10.1017/S1368980026103218

J Proteome Res. 2026 Jul 20. doi: 10.1021/acs.jproteome.6c00186. Online ahead of print.

ABSTRACT

Mass spectrometry offers numerous ways to analyze the composition, function, and interactions of complex proteomes. Unfortunately, it suffers from the variation introduced by technological artifacts, which reduces the reproducibility and reliability of the results. In order to detect and minimize deviations from optimal performance, researchers monitor standard mixtures of proteins or peptides and various associated metrics using statistical summaries. Although this approach to monitoring multiple analytes and metrics is often beneficial, most of these methods do not scale well to multivariate situations. In this paper, we present MSstatsQC-ML, a machine learning approach to quality control that optimizes decision-making from standard mixtures with many analytes and metrics. MSstatsQC-ML combines machine learning classifiers with experimental design strategies to simulate possible suboptimal MS runs that have not yet been observed. For training the classifiers, the proposed approach incorporates informative features from metrics. Analysis of longitudinal values of each feature allows us to interpret the root causes of suboptimal performance and helps to design preventive actions. In evaluations on quality control data from discovery and targeted proteomic experiments, MSstatsQC-ML reduced error rates of detecting suboptimal performance and outperformed traditional approaches. MSstatsQC-ML is available as part of the open-source MSstatsQC R/Bioconductor package.

PMID:42473820 | DOI:10.1021/acs.jproteome.6c00186

Cytometry A. 2026 Jul 20. doi: 10.1002/cyto.a.70053. Online ahead of print.

ABSTRACT

Flow cytometers, based on an optical measurement principle, are widely used for cell characterization in a variety of medical applications. Especially in hematology, high counting accuracy is crucial. Therefore, it is essential to develop accurate but also fast coincidence correction methods. We developed a procedure for post-processing the time-dependent signals (pulses) captured by the detectors during the transition of particles or cells through the flow cytometer’s laser beam. These pulses are characterized by their area, maximum intensity, standard deviation, and skewness. By using standard deviation versus area, we are able to detect significantly more coincidences in monodisperse suspensions than by using the common method of area or width versus height. This demonstrates the superior sensitivity and accuracy of our approach for coincidence detection. In polydisperse suspensions and whole blood, we successfully identify and distinguish coincidences between differently sized particles (e.g., 1 and 5 μm) and particles of the same size, as well as between thrombocytes and erythrocytes based on pulse skewness and standard deviation. Unlike the current state-of-the-art method for coincidence correction in cell concentration measurements, which relies on statistical evaluation through dilution series, the developed procedure identifies a specific number of coincidences for individual measurements.

PMID:42473817 | DOI:10.1002/cyto.a.70053

Can Respir J. 2026;2026(1):e2606203. doi: 10.1155/carj/2606203.

ABSTRACT

BACKGROUND: Bronchiolitis obliterans (BO) is a rare chronic pulmonary condition in pediatric patients, characterized by irreversible fibrotic constriction of the small airways. This study aims to analyze the risk factors for BO caused by severe adenovirus pneumonia (SAP) and to develop a nomogram model for personalized prediction.

METHODS: We retrospectively analyzed 251 children with SAP admitted to the Children’s Hospital of Nanjing Medical University between January 2017 and March 2024. Among them, 77 were classified into the BO group and 174 into the non-BO group. A predictive nomogram was developed based on independent risk factors identified through univariate analysis, least absolute shrinkage and selection operator (LASSO) regression, and multivariate logistic regression.

RESULTS: Multivariable analysis identified the following independent risk factors for BO: wheezing (odds ratio [OR] = 4.78; 95% confidence interval [CI], (2.00∼11.40); p < 0.001), large lobar consolidation (OR = 8.53; 95% CI, 3.63∼20.02; p < 0.001), length of hospital stay (OR = 1.20; 95% CI, 1.08-1.33; p < 0.001), and duration of fever (OR = 1.20; 95% CI, 1.09-1.32; p < 0.001). Mechanical ventilation showed a trend toward increased risk but did not reach statistical significance (OR = 5.35; 95% CI, 0.74-38.56; p = 0.096). The nomogram demonstrated excellent discriminative ability, with an area under the curve of 0.90 (95% CI: 0.85-0.94). Calibration curves indicated good agreement between predicted and observed outcomes. Decision curve analysis showed a net clinical benefit within a clinically relevant threshold probability range of 0.10-0.70.

CONCLUSIONS: A nomogram incorporating five independent risk factors-wheezing, duration of fever, length of hospital stay, mechanical ventilation, and large lobar consolidation-was developed to predict BO risk in children with SAP.

PMID:42473815 | DOI:10.1155/carj/2606203

Span J Psychol. 2026 Jul 20;29:e27. doi: 10.1017/SJP.2026.10043.

ABSTRACT

Loneliness is a growing concern in contemporary societies, particularly in urban environments, where social dynamics are rapidly evolving. Existing measures may not fully capture the complexity of loneliness in the context of ongoing technological and social changes. This study introduces the Madrid Loneliness Questionnaire (MLQ), a new instrument designed to assess loneliness in adults within modern sociocultural contexts. A sample of 1,526 adults (77.1% women; 18-87 years) participated in the study. The sample was randomly divided for structural validation: one subsample underwent exploratory factor analysis (EFA, n = 623) and the other confirmatory factor analysis (CFA, n = 903). Measurement invariance across gender and age was examined using multigroup CFA. Convergent validity was assessed through correlations with self-esteem and perceived stress. Internal consistency was evaluated using Cronbach’s alpha and McDonald’s omega. EFA and CFA supported a three-factor structure with excellent fit indices (Comparative Fit Index = 0.998; Tucker-Lewis Index = 0.997; RMSEA = 0.019; SRMR = 0.05): Social Skills, Partner Relationships, and Emotional Isolation. Multigroup CFA confirmed scalar invariance across gender and age. Significant gender differences were found in Social Skills (higher in men) and Partner Relationships (higher in women). The oldest age group (>65 years) scored higher on Partner Relationships than younger groups. The MLQ and its subscales showed moderate to strong negative correlations with self-esteem (rho = -.36 to -.63) and positive correlations with perceived stress (rho = .25 to .49). The scale demonstrated excellent internal consistency (α = .93, ω = .92). The MLQ is a psychometrically sound instrument for assessing loneliness in adults, enabling tailored interventions by serving as a basis for public health policies.

PMID:42473808 | DOI:10.1017/SJP.2026.10043

J Basic Clin Physiol Pharmacol. 2026 Jul 21. doi: 10.1515/jbcpp-2026-0101. Online ahead of print.

ABSTRACT

OBJECTIVES: Conventional semen analysis often fails to detect hidden functional defects contributing to male infertility. Factors such as sperm DNA-integrity, oxidative stress, MMP, and acrosome integrity are critical for fertilization and early embryonic development. This study aimed to evaluate sperm function defects in normozoospermic infertile men and highlight limitations of routine semen parameters in infertility assessment.

METHODS: Semen samples underwent standard semen analysis. Sperm DNA damage was assessed using Acridine Orange staining, acrosome integrity by FITC-PSA staining, and ROS levels along with MMP were measured using flow cytometry. Appropriate statistical analyses were performed to compare infertile men and fertile controls and determine correlations among functional parameters.

RESULTS: Among clinically screened infertile patients, 23 % were normozoospermic according to WHO 2010 criteria. Sperm function parameters were evaluated in normozoospermic infertile men (n=45) and fertile controls (n=17). Infertile men exhibited significantly higher ROS levels and DNA damage (p<0.001), alongside reduced acrosome integrity and MMP (p<0.001) compared to controls. ROS showed a positive correlation with DNA damage and acrosome-reacted sperm, and a negative correlation with MMP.

CONCLUSIONS: Functional sperm defects may underlie infertility in a substantial proportion of normozoospermic men. Incorporating sperm function tests as second-line investigations may improve diagnosis and management of unexplained male infertility.

PMID:42473807 | DOI:10.1515/jbcpp-2026-0101