Tag: pubmed

Med Phys. 2026 Mar;53(3):e70344. doi: 10.1002/mp.70344.

ABSTRACT

BACKGROUND: Micrometer-scale evaluation of energy deposition is important for radiation protection and therapy as well as for advancing knowledge of responses to radiation in materials and biological systems. Due to the stochastic nature of radiation interactions, there is significant variation in energy deposition in micrometer-sized targets, especially at low doses. This variability underscores the need for a framework for microdosimetry, particularly in low-dose scenarios.

PURPOSE: The goal of this work is to develop a novel system for micron-scale characterization of energy deposition and response to radiation that is applicable at low doses, using a combination of Monte Carlo (MC) simulations and experimental techniques.

METHODS: EBT3 radiochromic film samples are irradiated to absorbed doses of 0.003-0.5 Gy using the 6-MV beam from a clinical linear accelerator. To quantify energy deposition, MC simulations of the experimental irradiations are conducted to evaluate specific energy deposited within micron-scale voxels in the active layer of the film. To investigate the dose response of the film, the following two methods are employed: (i) flatbed scanner measurement of changes in optical density (OD) of the film, and (ii) Raman spectroscopy (RS) to measure response intensity across doses with micron-scale resolution. Experimental film responses are compared to predictions from the microdosimetric one-hit model.

RESULTS: Specific energy distributions obtained from MC simulations show large variation in energy deposition at low doses and within small targets; the “microdosimetric spread” (relative standard deviation) is significantly higher ( $>$ 10 times) at 0.003 Gy than at 0.5 Gy, and is observed to decrease with increases in dose and target size. Both RS and OD measurements exhibit a near linear dose-response relationship, reflecting the film’s sensitivity across micro- and macroscopic spatial scales. Overall, the OD and RS values determined using the one-hit model with MC-obtained specific energy distributions fit well to experimental measurements, with percentage differences up to 15 and 9.8%, respectively. An initial comparison of the relative standard deviation of RS and OD measurements (corrected for offset signal) shows qualitative agreement with the trends observed for MC-determined microdosimetric spread.

CONCLUSION: This study provides first results of a system that combines simulations with experimental techniques to investigate radiation response in micron-scale targets, with a focus on low-dose radiation exposure. The system shows promise in enabling future investigations of energy deposition within small volumes at low doses, where biological responses may be heterogeneous as some cells may receive high energy deposits and incur damage, while others may experience minimal or no deposition.

PMID:41757432 | DOI:10.1002/mp.70344

J Comp Eff Res. 2026 Feb 27:e250183. doi: 10.57264/cer-2025-0183. Online ahead of print.

ABSTRACT

Aim: Real-world evidence (RWE) – defined here as clinical evidence derived from the analysis of real-world data (RWD) on patient health status and healthcare delivery – has become a cornerstone of regulatory and health technology assessment (HTA) decision making. However, despite broad consensus on its value, policy frameworks governing RWE generation and evaluation remain heterogeneous across jurisdictions. Importantly, this heterogeneity partly reflects the distinct purposes for which RWE is used, including regulatory safety assessment, effectiveness evaluation, health-economic modeling and natural-history research. These functional differences are not inherently problematic; however, fragmented operational requirements can create duplication, inefficiency and delays in patient access. Materials & methods: This study employed a narrative comparative policy review of RWE guidance issued by twelve major regulatory and HTA agencies, including the Medicines and Healthcare products Regulatory Agency (MHRA), the EMA, the US FDA and the Canadian Agency for Drugs and Technologies in Health (CADTH). Frameworks were compared across four domains: data quality, statistical methods, registry governance and transparency. Harmonization is defined as alignment across these domains sufficient to enable consistent planning, analysis and interpretation of RWE across jurisdictions, rather than uniformity of decision making. Results: The analysis identified convergence in high-level principles but persistent divergence in operational expectations. The MHRA emphasizes flexibility and scientific dialogue; the EMA prioritizes consistency and structured governance; and the FDA provides comprehensive but resource-intensive guidance, reflecting detailed documentation requirements, prespecified analytic expectations and extensive methodological review. HTA bodies apply additional evidentiary criteria related to comparative effectiveness and value, sustaining functional fragmentation even within the same healthcare systems. Conclusion: RWE fragmentation reflects both legitimate functional differences and avoidable operational misalignment. Progress toward harmonization therefore requires shared minimum standards and transparency mechanisms rather than additional guidance documents. The UK’s post-Brexit autonomy positions it as a test environment for collaborative pilots with the European Medicines Agency, the International Council for Harmonization (ICH) and the International Coalition of Medicines Regulatory Authorities (ICMRA). Six strategic actions are proposed to support pragmatic alignment while preserving contextual flexibility.

PMID:41757419 | DOI:10.57264/cer-2025-0183

J Comp Eff Res. 2026 Feb 27:e250174. doi: 10.57264/cer-2025-0174. Online ahead of print.

ABSTRACT

Aim: Treatment options for late-onset Pompe disease (LOPD) include enzyme replacement therapy (ERT) with alglucosidase alfa (alg), cipaglucosidase alfa plus miglustat (cipa + mig) and avalglucosidase alfa. However, only one randomized controlled trial (RCT) directly compared cipa + mig and alg and had relatively few ERT-naive patients. A multilevel network meta-regression (ML-NMR) integrated individual patient data and aggregate data into indirect treatment comparisons, with relative effects adjusted to any target population, to compare the efficacy of cipa + mig and alg. Materials & methods: A Bayesian ML-NMR was conducted to compare the efficacy of cipa + mig and alg for 6-minute walk distance (6MWD, meters) and percent predicted forced vital capacity (ppFVC) across any target population, using patient-level and aggregate data from RCTs (PROPEL, COMET, LOTS) and phase I/II and open-label extension (OLE) trials (PROPEL OLE, LOTS OLE, COMET OLE, ATB200-02, NEO-1/NEO-EXT), adjusting for baseline covariates. Relative effect estimates were obtained for 6MWD and ppFVC change from baseline to week 52. Two networks were analyzed: network A (RCTs only) and network B (RCTs and single-arm OLE and phase I/II studies matched to comparator arms). To assess the impact of prior ERT exposure, simulations were conducted by only varying ERT duration among included covariates. Results: For cipa + mig compared with alg, both networks were associated with relative increases in 6MWD (mean difference [95% credible interval], Bayesian probability for network A: 13.48 m [6.79, 19.85], >99.9%; network B: 12.59 m [7.89, 17.45], >99.9%) and ppFVC (network A: 1.63% [0.71, 2.60], >99.9%; network B: 3.17% [2.53, 3.81], >99.9%). Network B suggested cipa + mig was favorable (>99.9%) in all groups for both end points and appeared more favorable with increasing ERT duration. Conclusion: Cipa + mig was associated with an improvement in 6MWD and ppFVC relative to alg independent of prior ERT exposure, which appeared more favorable when all available evidence was used. These data could inform decision-making in treating ERT-naive and ERT-experienced patients with LOPD.

PMID:41757410 | DOI:10.57264/cer-2025-0174

Child Dev. 2026 Feb 27;97(1):168-181. doi: 10.1093/chidev/aacaf014.

ABSTRACT

The present study investigated the role of visual statistical learning in how developing readers learn to identify morphemes within words. A total of 121 children (55 girls, aged 6-11 years, M = 8.82, SD = 1.30) were recruited in Trieste, Italy, between January and June 2019. They were familiarized with pseudo-letter strings containing affix-like chunks, which could be identified only by their statistical properties. After passively observing the stimuli, children were more likely to attribute previously unseen strings to the familiarization lexicon if they contained a chunk, regardless of its position within the string. Results indicate that children can acquire morpho-orthographic knowledge through visual regularities from printed input. This ability was not modulated by age nor reading fluency, suggesting an early-maturing learning mechanism. The findings emphasize the importance of incorporating this fundamental, language-agnostic mechanism into morphology and reading acquisition theories.

PMID:41757407 | DOI:10.1093/chidev/aacaf014

J Diabetes Metab Disord. 2026 Feb 24;25(1):78. doi: 10.1007/s40200-026-01898-4. eCollection 2026 Jun.

ABSTRACT

​PURPOSE: Diabetes distress (DD) represents significant emotional burden that hinders self-management in individuals with Type 2 Diabetes Mellitus (T2DM). In Pakistan, where T2DM is rapidly increasing, evidence on the magnitude and determinants of DD remains limited and fragmented. This systematic review aimed to estimate the pooled prevalence of DD and identify its associated factors among adults with T2DM in Pakistan.

METHODS: Seven electronic databases: PubMed, EMBASE, Scopus, Web of Science, PsycInfo, PakMediNet, and Google Scholar were systematically searched. Studies reporting DD prevalence using validated tools such as Diabetes Distress Scale (DDS) or Problem Areas in Diabetes (PAID) were included. Two reviewers independently extracted data and appraised quality using the Joanna Briggs Institute checklist. A random-effects model estimated pooled prevalence, with heterogeneity assessed using I² and Q statistics.

RESULTS: Seven studies, published between 2013 and 2024, involving 1560 adults with T2DM were included. The pooled prevalence of DD was 66.8% (95% CI: 52.3%-79.8%), with substantial heterogeneity (I² = 96.96%), likely due to variations in the study settings and sample characteristics. Funnel plot showed slight asymmetry; however, Egger’s test (p = 0.21) and trim-and-fill analysis indicated no publication bias. Narrative synthesis highlighted key factors, including suboptimal glycemic control, longer disease duration, complications, female gender, low education, low income, limited social support, low self-efficacy and inadequate self-care.

​CONCLUSION: About two-thirds of adults with T2DM in Pakistan experience DD, influenced by clinical, psychosocial, and behavioral factors. Integrating psychosocial screening, culturally tailored education, and support into T2DM care can enhance emotional well-being and adherence.​.

PMID:41757382 | PMC:PMC12932764 | DOI:10.1007/s40200-026-01898-4

Front Microbiol. 2026 Feb 11;16:1722229. doi: 10.3389/fmicb.2025.1722229. eCollection 2025.

ABSTRACT

INTRODUCTION: Rapid and scalable surveillance of antimicrobial resistance (AMR) is urgently needed in resource-constrained countries where routine monitoring is limited. Wastewater-based metagenomics offers a potential solution for early detection and geographic mapping of AMR.

METHODS: We conducted a retrospective DNA shotgun metagenomic analysis of untreated wastewater collected across Nagpur, India (February-April 2021). A total of 422 grab samples were pooled into 138 composite samples from 10 urban zones and rural catchments. The bacterial microbiota and resistome were profiled, and urban-rural patterns were compared using diversity metrics and correlation analyses.

RESULTS: Across all samples, 871 bacterial genera were detected, dominated by Proteobacteria, with frequent presence of Pseudomonas, Acinetobacter, Aeromonas, Acidovorax and Bacteroides. Beta diversity revealed statistically significant but subtle urban-rural compositional shifts. Of 33 globally important pathogens examined, 13 were detected at generally low relative abundance (<1%). Vibrio cholerae appeared in one sample, while Aeromonas spp. were most prevalent. Seven pathogens occurred in ≥10% of samples, with Aeromonas, Citrobacter, and Enterobacter differing significantly between locations (p < 0.05). The resistome comprised 606 unique antimicrobial resistance genes (ARGs), dominated by drug/biocide efflux determinants, followed by macrolide-lincosamide-streptogramin B genes driven largely by 23S rRNA mutations. Carbapenemases (blaNDM, blaKPC) and colistin resistance (mcr) were detected at lower abundance. Correlation analyses linked Pseudomonas with mexEF/emhABC efflux and copBCDRS copper resistance operon, Acinetobacter with oxa and dfrA, and Aeromonas with ctx, tetA, sul1, dfrB/F, and gyrA/parC.

DISCUSSION: These findings show that wastewater metagenomics sensitively resolved clinically relevant pathogens and ARGs in an Indian urban-rural setting, capturing nuanced geographic structure. Integrating routine DNA metagenomics into One Health environmental surveillance could strengthen AMR early warning and guide interventions in resource-constrained contexts.

PMID:41757357 | PMC:PMC12932555 | DOI:10.3389/fmicb.2025.1722229

Front Microbiol. 2026 Feb 11;16:1742406. doi: 10.3389/fmicb.2025.1742406. eCollection 2025.

ABSTRACT

BACKGROUND: Helicobacter pylori infects more than half of the world’s population and is the main risk factor for gastric cancer, although only a small percentage of those infected develop the disease. This disparity suggests the influence of bacterial, environmental, and host susceptibility factors. In Colombia, the department of Nariño presents a unique scenario: in both the Andean region and the Pacific coast, the prevalence of infection reaches 90%, but gastric cancer rates differ markedly (150/100,000 and 6/100,000 inhabitants, respectively), a phenomenon known as the “Colombian enigma.”

METHODS: This study analyzed gastric cancer mortality in 64 municipalities in Nariño, Colombia, using official epidemiological data and genome-based Helicobacter pylori cagA and vacA evolution and virulence.

RESULTS: The results showed a positive correlation between altitude and gastric cancer mortality. Phylogenomically, two local subpopulations were identified: hspColombia_Andes, predominant in high-risk areas and hspColombia_PacificCoast, associated with low risk. These populations showed genetic overlap, reflecting flow between nearby regions.

CONCLUSIONS: Our findings show that the genetic diversity of Helicobacter pylori, particularly the hspColombia_Andes and hspColombia_PacificCoast subpopulations, is associated with regional differences in gastric cancer mortality. Furthermore, the influence of environmental factors such as altitude and the association of the vacA and cagA oncogenes with gastric lesions reinforce their role in pathogenesis and in the possible prediction of cancer risk.

PMID:41757356 | PMC:PMC12932587 | DOI:10.3389/fmicb.2025.1742406

Front Dent Med. 2026 Feb 11;7:1645170. doi: 10.3389/fdmed.2026.1645170. eCollection 2026.

ABSTRACT

INTRODUCTION: In alignment with Saudi Vision 2030, dental colleges are increasingly required to enhance research productivity and international academic standing. This study aimed to identify research training priorities among oral healthcare professionals at Prince Sattam Bin Abdulaziz University, Saudi Arabia.

METHODS: A validated questionnaire was distributed to faculty members and comprised four sections: demographics, prior research training, self-rated performance vs. perceived importance of research competencies, and preferred training delivery methods. Descriptive statistics were used to summarize responses.

RESULTS: A total of 45 out of 61 faculty members completed the survey (response rate: 73.8%). Participants’ evaluations of prior research training ranged from poor or fair to excellent, with the majority reporting training levels between good and very good. Research training priorities varied by academic rank, with assistant professors identifying a broader range of high-priority areas compared to associate professors and full professors.

CONCLUSIONS: The findings support the development of targeted faculty development programs aligned with rank-specific research training priorities to strengthen research competencies and enhance institutional research capacity.

PMID:41757353 | PMC:PMC12932486 | DOI:10.3389/fdmed.2026.1645170

ESMO Real World Data Digit Oncol. 2026 Feb 19;11:100677. doi: 10.1016/j.esmorw.2025.100677. eCollection 2026 Mar.

ABSTRACT

BACKGROUND: Androgen receptor pathway inhibitors (ARPIs) are commonly used in older patients with metastatic castration-resistant prostate cancer (mCRPC). Treatment selection is informed by considering adverse event (AE) profiles, given that there are no previous randomised phase III comparison trials.

MATERIALS AND METHODS: This prospective registry-based randomised trial utilised the electronic Prostate Cancer Australian Database to collect clinical data. Patients aged ≥75 years who were suitable to receive abiraterone or enzalutamide for mCRPC were randomised to receive either ARPI treatment, stratified by prior docetaxel use. Telephone assessments were conducted at baseline and 12 weeks, including the Blessed Orientation-Memory-Concentration (BOMC) tool, Geriatric Depression Scale (GDS), and Falls Risk Questionnaire (FRQ). Descriptive statistics and mixed-effects linear regression were used to compare groups, including changes in assessment scores from baseline. Cox proportional hazards modelling was used to analyse effects of variables on time to treatment failure (TTF) and overall survival (OS).

RESULTS: We enrolled 76 men between June 2019 and September 2023, but closed due to slow accrual in December 2023. Nineteen (25%) had prior docetaxel. The median age was 81 years (interquartile range 77-85 years). The mean score change at 12 weeks trended higher in those receiving enzalutamide for each of BOMC (+0.64 versus -0.51, P = 0.46), GDS (+0.70 versus +0.06, P = 0.06), and FRQ (+1.4 versus -0.12, P = 0.06). A higher baseline GDS score was associated with shorter TTF [hazard ratio (HR) 1.3, 95% confidence interval (CI) 1.05-1.6, P = 0.014], as was higher baseline FRQ score (HR 1.12, 95% CI 1.09-1.22, P = 0.012). There were no differences in TTF, OS, prostate-specific antigen response, or AE rates between treatment groups.

CONCLUSIONS: Our results highlight the importance of individualised assessment of cognition, depression, and falls risk in older patients commencing ARPI treatment.

PMID:41757352 | PMC:PMC12934321 | DOI:10.1016/j.esmorw.2025.100677

Front Cell Neurosci. 2026 Feb 11;20:1757304. doi: 10.3389/fncel.2026.1757304. eCollection 2026.

ABSTRACT

BACKGROUND: Makorin-2 (MKRN2) is an E3 ubiquitin ligase involved in multiple biological processes, yet its role in neurological disorders remains poorly understood. This study aims to elucidate how MKRN2 regulates the RNA-binding protein CSDE1-a molecule linked to autism-related genes-and to explore the functional implications of this interaction in neurodevelopment.

METHODS: Using mass-spectrometry screening, we identified CSDE1 as a direct substrate of MKRN2. Ubiquitination sites were validated through mutagenesis of conserved lysine residues. Liquid-liquid phase separation (LLPS) assays were performed in HEK293 and SH-SY5Y cells, and behavioral phenotypes were assessed in Mkrn2-knockout mice. Statistical analyses included appropriate tests for comparing ubiquitination levels, condensate formation, and social behavior outcomes.

RESULTS: MKRN2 mediates CSDE1 ubiquitination at four lysine residues (K81, K91, K208, K727). Deletion of MKRN2 or mutation of these sites abolished ubiquitination. MKRN2 and CSDE1 formed co-localized condensates via LLPS, which was disrupted by functional impairment of either protein. Mkrn2-knockout mice exhibited sex-specific social abnormalities-increased sociability in males and social withdrawal in females-recapitulating autism-spectrum disorder (ASD) heterogeneity. We further identified MARK1 and HNRNPUL2, ASD-associated mRNAs, as ubiquitination-dependent targets of CSDE1, linking aberrant condensate dynamics to synaptic plasticity deficits.

CONCLUSION: Our study reveals an LLPS-coupled ubiquitination mechanism by which MKRN2 regulates CSDE1, providing a novel molecular pathway underlying neurodevelopmental disorders. These findings offer new insights for understanding and treating neurological diseases such as ASD.

PMID:41757349 | PMC:PMC12932526 | DOI:10.3389/fncel.2026.1757304