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Health impacts of climate change on children and adolescents: A protocol for review of reviews.
Yahaya R, Alhassan SS, Ayebi-Arthur RS … +2 more , Berchie RB, Ansah EW
PLoS One · 2026 · PMID 42391250 · Full text
INTRODUCTION: Climate change is a contemporary phenomenon of grave concern to global public health. Climate change events such as droughts, wildfires, tornadoes, heatwaves, floods, sea level rise, hurricanes, tropical cy...
INTRODUCTION: Climate change is a contemporary phenomenon of grave concern to global public health. Climate change events such as droughts, wildfires, tornadoes, heatwaves, floods, sea level rise, hurricanes, tropical cyclones, landslides, extreme rainfall, typhoons, dust storms, and desertification significantly affect local, regional, and global living conditions. In Sub-Saharan Africa, the most disturbing of these are desertification, droughts, and floods, which directly threaten water supplies, food security, and the livelihoods of millions of people. The climate crisis affects the health of older people, adults, children, and adolescents. However, climate-related events are gravely affecting the current and future health and well-being of children and adolescents. Although evidence exists, its integration is vital for policy and practice to protect children and adolescents in the ever-changing climate. Therefore, this review aims to map the existing reviews of the impact of climate change on the health and well-being of children and adolescents. METHOD: This review will be conducted according to Arksey and O'Malley's [36] recommendations and will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR). Scopus, JSTOR, Web of Science, PubMed, Embase and Cochrane Library will be searched to identify relevant records for inclusion in this review. Additional searches will be conducted in Google Scholar and Google for other relevant articles. The review protocol is registered at Open Science Framework: (https://doi.org/10.17605/OSF.IO/A7DEQ). ANALYSIS: Extracted data will be analysed using thematic content analysis, where data are summarised and qualitatively synthesized according to the recommendations of PRISMA-ScR and Tricco et al. [37]. The results and findings regarding the impacts of climate change on the health and safety of children and adolescents will be compiled, categorized, and presented using a qualitative narrative synthesis.
Short-term effects of alcohol detoxification on cardiovascular, hematological, and oxidative stress biomarkers: A prospective cohort study.
Emara AM, Alshammari AMA, Alhowail AH … +1 more , Elgharabawy RM
PLoS One · 2026 · PMID 42391248 · Full text
INTRODUCTION: Chronic alcohol consumption induces multisystem dysfunction, including cardiovascular instability, hematological alterations, and oxidative stress imbalance. However, the extent of short-term recovery follo...
INTRODUCTION: Chronic alcohol consumption induces multisystem dysfunction, including cardiovascular instability, hematological alterations, and oxidative stress imbalance. However, the extent of short-term recovery following structured detoxification remains incompletely characterized. OBJECTIVE: To evaluate the short-term effects of a standardized inpatient alcohol detoxification protocol on cardiovascular, hematological, and oxidative stress biomarkers. METHODS: A prospective observational before-and-after cohort study was conducted on 75 male participants, including 50 patients with alcohol use disorder and 25 healthy controls. Patients underwent a 21-day inpatient detoxification program comprising pharmacological stabilization and nutritional rehabilitation. Clinical and biochemical parameters-including body mass index, vital signs, lipid profile, complete blood counts, troponin-I, and oxidative stress markers (TBARS, glutathione peroxidase, and catalase)-were assessed at baseline and post-treatment. RESULTS: Compared to healthy controls, treatment-naïve patients with alcohol use disorder (AUD) exhibited significantly elevated baseline levels of lymphocytes, total cholesterol, low-density lipoprotein (LDL), thiobarbituric acid reactive substances (TBARS), and catalase (CAT), alongside significantly lower heart rate (HR), systolic blood pressure (SBP), neutrophil-to-lymphocyte ratio (NLR), high-density lipoprotein (HDL), and glutathione peroxidase (GPx). Baseline anthropometric, vital, hematological, and metabolic markers-including BMI, diastolic blood pressure (DBP), hemoglobin (Hb), platelets, total white blood cell count (WBCs), cardiac troponin-I (cTnI), and triglycerides-showed no statistically significant differences. Following a 21-day inpatient detoxification protocol, post-treatment assessments revealed significant increases in red blood cell parameters (RBCs, Hb, Hct), neutrophils, lymphocytes, NLR, and HDL. Conversely, standard detoxification induced significant reductions in cardiovascular, lipid, and oxidative stress indices, specifically HR, SBP, mean corpuscular volume (MCV), total WBCs, cTnI, total cholesterol, triglycerides, TBARS, and CAT. No significant post-treatment alterations were observed in BMI, DBP, platelet counts, LDL, or GPx. CONCLUSION: Short-term alcohol detoxification leads to partial recovery of cardiovascular and hematological parameters, while oxidative stress markers show limited normalization within the 21-day period. These findings highlight differential recovery patterns across biological systems following early abstinence.
Effects of ginger-loaded chitosan nanoparticles on growth, morphological and biochemical attributes of Sesamum indicum L.
Nasreen H, Ghaffar A, Yousaf S
PLoS One · 2026 · PMID 42391247 · Full text
Chitosan nanoparticles (ChNPs) have gained attention due to their biodegradability, biocompatibility, and non-toxicity, and are found in a wide range of agricultural products. The green synthesis and characterization of...
Chitosan nanoparticles (ChNPs) have gained attention due to their biodegradability, biocompatibility, and non-toxicity, and are found in a wide range of agricultural products. The green synthesis and characterization of ChNPs using ginger extract were evaluated for their effects on biochemical and morphological parameters in sesame (Sesamum indicum L.). Ginger-loaded ChNPs synthesis, size, structure, morphology, and crystallinity were confirmed via UV-Vis spectrophotometry, DLS (151.7 nm, ± 30 mV), FTIR, SEM, and XRD, respectively. Foliar applications of ChNPs (50 mg L-1 and 100 mg L-1) and pesticides confidor (2.5 mL L-1) confidor + talstar (2.5 mL L-1) were applied at flowering and capsule stages under controlled conditions. ChNPs at 100 mg L ⁻ ¹ significantly enhanced plant height 5.3%, leaf area 26.5%, number of capsules 43.6%, capsule weight (12.4%), stem diameter 34.4%, total chlorophyll 11.9%, and catalase activity 53.1% compared with the control (P < 0.05), while reducing peroxidase 85.7% and PAL 59%. In contrast, confidor and confidor + talstar treatments showed compromised effects. Present research demonstrated that green synthesized ChNPs have good potential for use in agriculture and can significantly increase sesame growth and yield.
Heart failure hospitalization in patients with and without type 2 diabetes: A population-based retrospective cohort study.
Shay AK, Tao W, Patnaik S … +5 more , Sullivan DK, Nascimbene A, Wang X, McCormick JB, Wu H
PLoS One · 2026 · PMID 42391246 · Full text
PURPOSE: Type 2 diabetes mellitus (T2DM) is a common comorbidity among patients with heart failure (HF). This study aims to describe how T2DM relates to HF hospitalization patterns across demographic groups and HF subtyp...
PURPOSE: Type 2 diabetes mellitus (T2DM) is a common comorbidity among patients with heart failure (HF). This study aims to describe how T2DM relates to HF hospitalization patterns across demographic groups and HF subtypes. METHODS: We conducted a population-based retrospective cohort study using 19 years of clinical data from Cerner Health Facts®, a nationwide electronic health record (EHR) database. Adult patients hospitalized with HF were identified using ICD-9/ICD-10 diagnosis codes and HF-related medications and were stratified by T2DM status. Measures included HF-related hospitalization count, length of first HF hospitalization, and age at first HF hospitalization. Comparisons were examined across HF subtypes (historically termed systolic, diastolic, other). Additionally, sensitivity analyses were conducted using alternative inclusion criteria to assess the robustness of the findings. RESULTS: We identified 137,785 HF patients from the EHR database, among whom 29.5% had T2DM. Overall HF hospitalization was more common in men than in women; however, diastolic HF was more prevalent among women and presented at older ages whereas systolic HF was more prevalent among men. Compared with patients without T2DM, patients with T2DM experienced higher HF hospitalization count (mean: 2.81 vs. 2.42, p < 0.001), and both longer stay (mean: 7.03 vs. 6.85 days, p < 0.001) and earlier age (mean: 68.9 vs. 70.4 years, p < 0.001) of initial HF hospitalization. Across HF subtypes, T2DM was more prevalent among patients with diastolic HF (31.4% diastolic vs. 29.5% systolic vs. 28.7% other), and patients with T2DM were younger at first HF hospitalization than those without T2DM, with the largest difference observed for diastolic HF (mean: 70.4 vs. 73.1 years, p < 0.001). CONCLUSIONS: In this large nationwide EHR cohort, T2DM was associated with more intensive HF hospitalization patterns and was more prevalent in the diastolic HF subtype. These findings highlight the relevance of diabetes status and HF subtype, in addition to demographic factors, in shaping HF-related healthcare utilization.
Key molecular mechanisms of mitochondrial metabolic pathways in specific cell subpopulations of pancreatic cancer based on scRNA-seq and bulk RNA-seq.
Liu J, Liu T, Yang L … +4 more , Hu Y, Luo C, Wu D, Yang X
PLoS One · 2026 · PMID 42391245 · Full text
BACKGROUND: Pancreatic cancer (PC) is a highly malignant tumor with increasing incidence, mortality, and a low five-year survival rate. Mitochondrial metabolic reprogramming plays a crucial role in tumor development, but...
BACKGROUND: Pancreatic cancer (PC) is a highly malignant tumor with increasing incidence, mortality, and a low five-year survival rate. Mitochondrial metabolic reprogramming plays a crucial role in tumor development, but the molecular mechanisms in different cell subpopulations of PC remain unclear. This study aims to integrate single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq to explore mitochondrial metabolism in PC. METHODS: Transcriptome datasets (GSE183795, GSE16515, GSE197177, and TCGA-PAAD) were downloaded from the GEO and TCGA databases. Differentially expressed genes (DEGs) were identified using the limma package for bulk RNA-seq and the Seurat package for scRNA-seq. Weighted gene co-expression network analysis (WGCNA) was performed to identify key modules and hub genes. Machine learning algorithms screened key genes, and functional enrichment analysis was conducted using clusterProfiler. PPI, ceRNA, and transcription factor networks explored gene regulation. Immune infiltration analysis, drug prediction, and molecular docking were conducted on key genes. The prognostic value of the key genes was evaluated using clinical data from TCGA. RESULTS: A total of 1238 bulk RNA-DEGs and 8231 scRNA-DEGs in fibroblasts were identified. Integration of both datasets revealed 536 DEGs. WGCNA identified 6 modules associated with PC. By intersecting DEGs, hub genes, and mitochondrial metabolism-related genes, 18 candidate genes were obtained. These genes were enriched in glucose metabolism and mitochondrial outer membrane pathways. Three key genes (IFI27, PKM, and RSAD2) were selected using machine learning. PPI, ceRNA, and transcription factor networks provided regulatory insights. Immune infiltration analysis showed significant differences in immune cells, particularly in T cells CD4 memory resting and macrophages M2. Drug prediction and molecular docking identified potential drugs for these genes. Survival analysis indicated that high expression of these genes correlated with poor prognosis. CONCLUSION: This study integrates scRNA-seq and bulk RNA-seq data to identify three key genes (IFI27, PKM, and RSAD2) and their immune-related mechanisms in PC. These findings offer new insights into the pathogenesis and potential therapeutic targets for PC.
Music-induced cortical plasticity: Protocol for a systematic review.
Osei Duah Junior I, Rodriguez DS, Germain CM
PLoS One · 2026 · PMID 42391241 · Full text
Music engages sensory, motor, cognitive, and emotional systems, making it a powerful model for studying experience-dependent neuroplasticity. Although research on music-related brain changes is expanding, integration of...
Music engages sensory, motor, cognitive, and emotional systems, making it a powerful model for studying experience-dependent neuroplasticity. Although research on music-related brain changes is expanding, integration of structural, functional, and cerebrovascular findings remains limited, and effects on higher-order cognitive processes remain unclear. This systematic review will primarily synthesize evidence on music-induced cortical adaptations, including structural changes (e.g., gray and white matter alterations), functional modifications in neural networks, and cerebrovascular dynamics. Further, associations with behavioral measures such as attentional control, executive functioning, and language processing will also be examined when these outcomes are directly linked to the neural adaptations across the adult lifespan (≥ 50 years). The protocol was prepared in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) guidelines and has been indexed in International Prospective Register of Systematic Reviews (PROSPERO ID: CRD420251159362). The systematic review will be conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Using controlled vocabularies and medical subject headings (MeSH), a systematic search will be conducted across PubMed, Scopus, Web of Science, PsycINFO, EMBASE, CENTRAL (Cochrane Central Register of Controlled Trials), and Google Scholar databases, and supplemented by citation tracking from relevant review articles. Eligible studies will include randomized controlled trials (RCTs), non-randomized controlled trials, quasi-experimental, and observational designs (longitudinal, case-control, cross-sectional studies). The primary outcome will be changes in brain structure, function, and cerebrovascular hemodynamic activity following music intervention. Cognitive measures will be reviewed and consolidated as secondary endpoints. Data extraction, risk of bias and quality assessment will be performed independently by two reviewers using validated instruments, including Cochrane Risk of Bias 2 (RoB 2.0), Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I), Risk Of Bias In Non-randomized Studies of Exposures (ROBINS-E), Strengthening the Reporting of Observational Studies in Epidemiology (STROBE), and National Heart, Lung, and Blood Institute (NHLBI) tools. A narrative synthesis will be conducted in accordance with Synthesis Without Meta-analysis (SWiM) guidelines, with meta-analyses undertaken where appropriate. Certainty of evidence will be assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) scale. Collectively, this protocol establishes a rigorous framework to systematically evaluate how music shapes the brain's structure, function, and vascular systems, and how these changes translate into cognitive and behavioral outcomes.
Siphonophore genome structure and the evolution of functional specialization.
Ahuja N, Schultz DT, Destanović D … +9 more , Church SH, Picciani N, Munro C, Kon-Nanjo K, Kon T, Mańko MK, Shi W, Simakov O, Dunn CW
PLoS One · 2026 · PMID 42391240 · Full text
Siphonophores (Cnidaria: Hydrozoa) are pelagic colonial marine invertebrates with many highly specialized bodies (zooids) within a single colony. Their unique biology and ecological importance have made them of particula...
Siphonophores (Cnidaria: Hydrozoa) are pelagic colonial marine invertebrates with many highly specialized bodies (zooids) within a single colony. Their unique biology and ecological importance have made them of particular interest, and motivate questions on their genomic structure, organization and content. To investigate siphonophores' genome biology and develop resources for future studies, we sequenced the genome of a single Nanomia septata to chromosome scale. The haploid genome is 1.7 GB across 8 chromosomes. Relative to closely related hydrozoan genomes, this is an expansion in length but a reduction, from 15, in chromosome number, indicating multiple chromosomal fusion events. We found no genomic features clearly associated with siphonophores' exceptional colony-level complexity. Gene families that play critical roles in cnidarian development have not expanded, and gene proximity was not generally correlated to their expression across zooids, except in male gonophores. To contextualize these observations, we sequenced 20 additional Nanomia specimens across the globe and mapped them to our chromosome-scale reference. Population genomic analyses support three previously recognized species of Nanomia, and at least one additional undescribed species. Present day overlapping geographic distribution of some Nanomia species raises the possibility of reproductive isolation in sympatry. Phylogenetic analyses of genome size indicate Nanomia septata and Nanomia cara have similarly large genomes around 1.7 GB, while Nanomia bijuga and an undescribed species show a secondary reduction to 0.7 GB. These results highlight how genomic factors have shaped colony organization and genome diversity within Nanomia.
Emotional understanding in Japanese children 3-6 years: Language ability mediates the relations between theory of mind and executive function.
Jung A, Uehara I
PLoS One · 2026 · PMID 42391239 · Full text
Previous research has documented associations between children's emotional understanding (EU) and social-cognitive abilities such as theory of mind (ToM) and executive function (EF); however, findings in preschool-aged c...
Previous research has documented associations between children's emotional understanding (EU) and social-cognitive abilities such as theory of mind (ToM) and executive function (EF); however, findings in preschool-aged children remain inconsistent. One potential explanation is that language ability, which develops rapidly during early childhood, has often not been examined concurrently with these abilities. The present study focused on individual differences in EU and examined how ToM, EF, and language ability relate to EU in Japanese preschool children, with particular attention to the mediating role of language. Participants were 90 children aged 3-6 years (M = 60.34 months, SD = 10.82). Children completed a false belief task, emotional understanding tasks, executive function tasks assessing cognitive flexibility and working memory, and a receptive vocabulary test. Correlational analyses, hierarchical multiple regression analyses, and bootstrapped mediation analyses were conducted. EU was positively associated with ToM, EF, and language ability. Language ability accounted for significant variance in EU beyond age and gender. When language ability was included in the model, the association between ToM and EU was no longer significant, whereas the association between EF and EU remained significant but was attenuated. Mediation analyses revealed significant indirect effects of both ToM and EF on EU through language ability, indicating that the association between ToM and EU was accounted for by language ability, whereas EF showed both direct and indirect associations with EU. These findings suggest that language ability plays a central role in linking social-cognitive abilities to emotional understanding in early childhood. Theory of mind was associated with emotional understanding primarily through language, whereas executive function showed both direct and indirect associations via language ability. By modeling multiple predictors simultaneously, this study provides an integrated account of individual differences in emotional understanding and elucidates the distinct pathways through which cognitive and social-cognitive skills are associated with emotional development.
DMS-informed secondary structure modeling of Epstein-Barr Virus LMP-1 pre-mRNA defines novel elements spanning introns.
Eich TO, Coppenbarger EC, Dapour AO … +1 more , Moss WN
PLoS One · 2026 · PMID 42391237 · Full text
The Epstein-Barr virus (EBV) infects over 95% of adults, establishing lifelong latency and contributing to the development of various malignancies, including Burkitt lymphoma and nasopharyngeal carcinoma. However, the RN...
The Epstein-Barr virus (EBV) infects over 95% of adults, establishing lifelong latency and contributing to the development of various malignancies, including Burkitt lymphoma and nasopharyngeal carcinoma. However, the RNA structures regulating the splicing of the critical EBV gene, latent membrane protein 1 (LMP1), remain uncharacterized. To identify these regulatory elements, we applied spliceosome inhibition with RNA probing and sequencing (SIRP-seq) to the BJAB-B1 cell line. By utilizing the spliceosome inhibitor pladienolide B, we enriched pre-mRNA species, enabling the detection of structural features within both the full-length pre-mRNA (LMP1-FL) and an alternatively spliced isoform retaining intron 2 (LMP1-AS). The resulting chemical probing datasets informed the RNA folding algorithms RNAfold and ScanFold to generate the first high-resolution secondary structure models for the LMP1 pre-mRNA, encompassing both exonic and intronic regions. Our results identify 11 novel, thermodynamically stable RNA structures, with several key elements positioned near splice junctions. Notably, three structures (Structures 8, 9, and 10) were identified near the 3' splice site of intron 2, appearing in alternative conformations that may influence splicing accessibility. Furthermore, these structures map to regions containing disease-relevant mutations associated with patient survival in Burkitt lymphoma. This structural framework provides new insights into how LMP1 splicing may be regulated by RNA structure and identifies potential novel therapeutic targets for mitigating EBV-associated diseases.
Spontaneous passage of common bile duct stones: predictive factors and impact on post-ERCP complications.
Wanchaitanawong W, Phinyo P, Kunlayawutipong T … +3 more , Chatkul N, Kijdamrongthum P, Thinrungroj N
PLoS One · 2026 · PMID 42391236 · Full text
BACKGROUND: Spontaneous passage of common bile duct stones (CBDSs) may render endoscopic retrograde cholangiopancreatography (ERCP) unnecessary. Although predictors of passage have been described, most prior studies were...
BACKGROUND: Spontaneous passage of common bile duct stones (CBDSs) may render endoscopic retrograde cholangiopancreatography (ERCP) unnecessary. Although predictors of passage have been described, most prior studies were limited by a small number of events, and the impact of spontaneous passage on post-ERCP complications remains under-investigated. This study aimed to identify clinical predictors of spontaneous passage and evaluate its association with post-ERCP complications. METHODS: We conducted a retrospective cohort study of patients diagnosed with CBDSs who underwent endoscopic ultrasonography (EUS) or ERCP at a tertiary referral center. Spontaneous passage was defined as the absence of stones confirmed during the procedure. Multivariable risk regression was used to identify predictors of passage and to assess the association between spontaneous passage and post-ERCP complications. RESULTS: Spontaneous passage was observed in 113 of 404 patients (28%). Independent predictors of spontaneous passage included younger age (RR 0.88 per 10 years; 95% CI 0.81-0.96), smaller CBDS size (RR 0.78 per 1 mm; 95% CI 0.71-0.85), and single CBDS (RR 1.64; 95% CI 1.04-2.61). Regarding complications, post-ERCP pancreatitis (PEP) occurred more frequently in patients with spontaneous passage compared to those without (16.5% vs 7.6%, P = 0.01). After adjusting for relevant confounders, including procedural factors, spontaneous passage remained an independent risk factor for PEP (RR 2.48, 95% CI 1.25-4.92). CONCLUSIONS: Spontaneous passage of CBDSs is an independent risk factor for PEP. Younger age, smaller stone size, and a single stone are significant predictors of passage. These findings suggest that pre-procedural risk stratification and non-invasive confirmation of ductal clearance may be beneficial in selecting appropriate candidates, potentially reducing unnecessary ERCP and associated complications.
A-eye: Automated 3D MRI segmentation and morphometric feature extraction for eye and orbit atlas construction.
Barranco J, Luyken AK, Jia Y … +11 more , Kebiri H, Stachs P, Gordaliza PM, Esteban O, Aleman Y, Sznitman R, Streckenbach F, Stachs O, Langner S, Franceschiello B, Cuadra MB
PLoS One · 2026 · PMID 42391233 · Full text
In this study we introduce automated 3D segmentation of the healthy human adult eye and orbit from Magnetic Resonance Images, to improve ophthalmic diagnostics and treatments. Past efforts have primarily focused on small...
In this study we introduce automated 3D segmentation of the healthy human adult eye and orbit from Magnetic Resonance Images, to improve ophthalmic diagnostics and treatments. Past efforts have primarily focused on small sample sizes and varied imaging modalities. Here, we leverage a large-scale dataset of T1-weighted MRI of 1245 subjects and the deep learning-based nnU-Net for MR-Eye segmentation tasks. The results showcase robust and accurate 3D segmentation of lens, globe, optic nerve, rectus muscles, and orbital fat. We also present the automated estimation of key ophthalmic morphometry biomarkers such as axial length and volumetry, while benchmarking correlations between body mass index and eye structure volumes. Quality control protocols are introduced through the pipeline to ensure the reliability of the segmented large-scale data, further enhancing the applicability of our algorithm in clinical research. As a major outcome we provide the first large-scale unbiased eye atlases (female, male, and combined) towards standardization of spatial normalization tools for MR-Eye.
Evaluation of anemia in non-enhanced and contrast-enhanced dual-energy CT using electron density imaging.
Kim C, Yeom SK, Choi H … +7 more , Shim E, Hwang SH, Yong HS, van Assen M, De Cecco CN, Sung HJ, Lee SR
PLoS One · 2026 · PMID 42391232 · Full text
Electron density (ED) imaging derived from dual-energy CT (DECT) quantifies tissue composition and may reflect changes in red blood cell (RBC) mass associated with anemia. This study aimed to evaluate the utility of ED f...
Electron density (ED) imaging derived from dual-energy CT (DECT) quantifies tissue composition and may reflect changes in red blood cell (RBC) mass associated with anemia. This study aimed to evaluate the utility of ED from DECT in assessing anemia severity using both non-enhanced CT (NECT) and contrast-enhanced CT (CECT), and to investigate its correlation with hemoglobin (Hb), hematocrit (Hct), and RBC count. In this retrospective study, 2,558 patients who underwent NECT and 2,545 who underwent CECT using a dual-layer spectral detector CT (Philips IQon) were included. Mean ED and mean CT attenuation (HU) were measured at five cardiac blood pool sites. Spearman's rank correlation analysis was performed between CT measurements and hematologic parameters. Partial correlation analysis adjusting for age and sex and non-parametric bootstrap internal validation were also conducted. Receiver operating characteristic (ROC) curve analysis was performed to determine diagnostic cutoff values for anemia detection. Mean ED significantly decreased with increasing anemia severity in both NECT and CECT cohorts (all p < 0.001). With NECT, mean ED showed positive correlations with Hb, Hct, and RBC count (rs = 0.726-0.770), with AUCs of 0.825-0.956 for anemia detection. With CECT, mean ED retained positive correlations with hematologic parameters (rs = 0.447-0.583), with AUCs of 0.727-0.895, while mean HU showed no meaningful correlation. After adjustment for age and sex, partial correlation coefficients remained substantial (NECT: rs = 0.694; CECT: rs = 0.509 for Hb), and bootstrap internal validation confirmed negligible overfitting bias. ED derived from DECT demonstrated diagnostic utility for anemia detection on NECT, unlike conventional HU, retained clinically relevant associations with hematologic parameters on CECT. ED-based anemia detection on CECT is best conceptualized as opportunistic detection, particularly for severe anemia, supplementary to laboratory testing. These findings require external validation across diverse DECT platforms before broader clinical implementation.
Assessment of maternal diet inflammatory status and inflammatory markers in human breast milk.
Slegers CB, Holmes MA, Biddulph C … +3 more , Maher J, Smoll NR, Dean MM
PLoS One · 2026 · PMID 42391231 · Full text
Human breast milk is a complex bioactive fluid containing multi-functional components that support many infant physiological functions. Maternal diet has been demonstrated to influence human milk components; however, how...
Human breast milk is a complex bioactive fluid containing multi-functional components that support many infant physiological functions. Maternal diet has been demonstrated to influence human milk components; however, how maternal diet impacts inflammatory markers in human milk remains unclear. This study investigated the association between maternal dietary inflammatory status, assessed using the Dietary Inflammatory Index (DII), and the profile of inflammatory markers in breast milk from healthy lactating women, quantified using cytometric bead array. Dietary intake of lactating mothers (n = 101) was assessed using a 24-hr food recall and categorised using the DII as either pro-inflammatory (score > 0) or anti-inflammatory (score < 0). Thirteen inflammatory markers were quantified in breast milk by flow cytometric bead array (13-plex panel: IL-4, IL-2, IP-10, IL-1β, TNF-α, MCP-1, IL-17A, IL-6, IL-10, IFN-γ, IL-12p70, IL-8, free active TGF-β1). All participant diets were categorised as anti-inflammatory diets (DII score range -4.83 to -1.22). Participants' food intake aligned with dietary guidelines (AUSNUT 2023) for lactating women, with most analysed food parameters classified as anti-inflammatory (19/27). Inflammatory marker analysis revealed a chemokine-dominant profile in breast milk with IP-10, MCP-1 and IL-8 present at the highest concentrations and detected in > 96% of participant human milk samples MCP-1 concentration was weakly associated with DII score (p = 0.025, r2 -0.23, Spearman correlation). This study is the first to investigate the inflammatory index of maternal diets in lactating mothers and characterise inflammatory markers in human milk. Further research is required to fully elucidate the relationship between dietary inflammatory status and inflammatory markers in breast milk and their potential impact on infant health, especially of a more diverse cohort.
Association of oral health knowledge, attitudes, and practice with dental caries status among 6-12-year-old Iranian orphaned children using the CAST index: A Cross-sectional study.
Jahanbakhti Z, Momeni Z
PLoS One · 2026 · PMID 42391229 · Full text
INTRODUCTION: Orphaned children face heightened vulnerability due to the absence of parental care and limited access to preventive services. Evidence linking oral health knowledge, attitudes, and practice (KAP) with clin...
INTRODUCTION: Orphaned children face heightened vulnerability due to the absence of parental care and limited access to preventive services. Evidence linking oral health knowledge, attitudes, and practice (KAP) with clinical outcomes in this population remains limited. This study aimed to assess oral health KAP among orphaned children in Karaj, Iran, and examine their associations with clinical indicators of dental caries, gingival status, and oral hygiene. METHODS: In this cross-sectional study, 72 children aged 6-12 years residing in four government-run quasi-family centers in Karaj were examined between October 2024 and January 2025 through a census sampling approach. Inclusion required age eligibility and informed consent, whereas children with systemic or developmental disorders or those receiving orthodontic treatment were excluded. Data were collected using a structured, validated questionnaire (α = 0.83) to assess KAP and demographic factors. Clinical examinations were performed by a calibrated examiner (ZJ) (Kappa = 87.68%) using the CAST, GI, and OHI-s indices. Logistic and linear regression models were used to examine predictor variables of KAP and oral health outcomes. RESULTS: The mean scores of knowledge, attitude, and practice were 3.16 ± 1.60 (out of 7), 33.52 ± 4.36 (out of 50), and 10.26 ± 2.72 (out of 20), respectively. Overall, 62.5% of children demonstrated fair oral hygiene (OHI-s = 1.75 ± 1.58) with mild gingival inflammation. CAST assessment indicated that fewer than one-third of primary molars were sound, while more than half of permanent first molars showed enamel caries. Regression analyses showed that frequent toothbrushing (p = 0.015, OR=0.52, 95% CI: 0.30-0.88) and more positive attitudes toward oral health (p = 0.013, OR=0.70, 95% CI: 0.53-0.93) were significant predictors of improved oral status, whereas knowledge and self-reported practice were not consistent predictors. CONCLUSIONS: Orphaned children in Karaj demonstrated moderate oral hygiene, a high prevalence of untreated dental caries, and limited awareness of oral health. Addressing these behavioral and systemic gaps through targeted, evidence-based interventions-particularly oral health education, caregiver involvement, and routine dental monitoring-may help improve oral health outcomes in this vulnerable population.
ICG fluorescence imaging-guided bile leak detection to reduce clinically relevant bile leakage after hepatectomy: A protocol for a systematic review and meta-analysis.
Hanaki T, Shibata Y, Sunada H … +3 more , Noma H, Ueki M, Fujiwara Y
PLoS One · 2026 · PMID 42391228 · Full text
BACKGROUND: Bile leakage remains a clinically relevant complication after hepatectomy and contributes to morbidity, prolonged drainage, extended hospital stay, and the need for reintervention. Intraoperative indocyanine...
BACKGROUND: Bile leakage remains a clinically relevant complication after hepatectomy and contributes to morbidity, prolonged drainage, extended hospital stay, and the need for reintervention. Intraoperative indocyanine green (ICG) fluorescence imaging can be used to visualize bile leaks from the transection plane or biliary stump, enabling targeted repair. However, evidence for the effect of this technique on clinically relevant bile leakage is heterogeneous and has not been systematically synthesized. METHODS AND ANALYSIS: This protocol describes a systematic review and meta-analysis of randomised controlled trials and comparative nonrandomised studies evaluating indocyanine green fluorescence imaging-guided intraoperative bile leak detection during hepatectomy. MEDLINE, Embase, Cochrane CENTRAL, and the Web of Science Core Collection will be searched from inception, along with trial registries and citation tracking. The primary outcome is clinically relevant postoperative bile leakage, defined as International Study Group of Liver Surgery (ISGLS) grade B or C. Secondary outcomes include any bile leakage, bile leak-related interventions, major postoperative complications, length of postoperative hospital stay, and mortality. Randomised and nonrandomised studies will be synthesized separately. A meta-analysis will be performed when the studies are sufficiently comparable; otherwise, the findings will be summarized narratively. Planned analyses include random-effects models, subgroup analyses stratified according to the route of indocyanine green administration, sensitivity analyses, and an assessment of the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. This protocol is registered in PROSPERO (CRD420261291065). This manuscript describes the planned methods only; study selection, data extraction, and evidence synthesis results will be reported in the completed systematic review. ETHICS AND DISSEMINATION: This study will use data from published studies and does not require ethics approval. The findings will be disseminated through peer-reviewed publications and conference presentations.
Association of baseline HBcAg and HBV DNA with persistent detectability of HBV RNA during NA therapy.
Wu L, Pan Z, Yu J … +8 more , Yue X, He F, Yu L, Pan L, Wu Y, Zhou C, Yan P, Pan H
PLoS One · 2026 · PMID 42391227 · Full text
OBJECTIVE: Even after long-term nucleos(t)ide analogue (NA) therapy achieves hepatitis B virus (HBV) DNA suppression in patients with chronic hepatitis B (CHB), serum HBV RNA may remain detectable. HBV RNA reflects intra...
OBJECTIVE: Even after long-term nucleos(t)ide analogue (NA) therapy achieves hepatitis B virus (HBV) DNA suppression in patients with chronic hepatitis B (CHB), serum HBV RNA may remain detectable. HBV RNA reflects intrahepatic viral transcriptional activity. This study identified baseline traits and predictors of persistent HBV RNA positivity during NA therapy after sustained HBV DNA suppression. METHODS: This retrospective study included 155 CHB patients who underwent liver biopsy before initiating NA therapy, subsequently achieved sustained HBV DNA suppression on continuous NA therapy. Patients were classified into two groups according to HBV RNA status during therapy. Baseline clinical, virological and histological variables were assessed by multivariate logistic regression. Correlations between HBV RNA and serological markers were also assessed. The diagnostic performance of the model was analyzed using area under the receiver operating characteristic (AUC) and boostrap internal validation. RESULTS: Overall, 47.7% achieved undetectable serum HBV RNA. Higher baseline HBV DNA and absence of intrahepatic hepatitis B core antigen (HBcAg) independently predicted persistent HBV RNA positivity (both P < 0.001). The combined assessment of HBcAg with HBV DNA improved predictive accuracy (AUC = 0.780), outperforming either marker alone. The AUC value of bootstrap internal validation was 0.756. Across the cohort, HBV RNA showed moderate correlation with hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B e antibody (HBeAb). Correlations were minimal in HBeAg-negative patients and most evident in HBeAg-positive patients. CONCLUSION: Incorporating HBcAg histology with baseline HBV DNA may enable more individualized treatment strategies during antiviral therapy. Correlations between HBV RNA and traditional markers are primarily observed in HBeAg-positive patients.
Toward evidence-based prescription of prosthetic ankle-foot devices: A multisite randomized crossover trial identifying performance-based, patient-reported, and biomechanical parameters sensitive to device type.
Maikos JT, Sidiropoulos AN, Chomack JM … +11 more , Herlihy DV, Hendershot BD, Pruziner AL, Phillips SL, Heckman JT, Moore TE, Gibbs McBride Z, Choi J, Dearth CL, Prosthetic Foot Prescription Consortia, Nelson LM
PLoS One · 2026 · PMID 42391225 · Full text
Prescription of prosthetic ankle-foot devices is constrained by imprecise clinical guidelines and inconsistent scientific evidence, hindering optimal device selection for individuals with lower limb loss. This multisite,...
Prescription of prosthetic ankle-foot devices is constrained by imprecise clinical guidelines and inconsistent scientific evidence, hindering optimal device selection for individuals with lower limb loss. This multisite, prospective, randomized crossover study aimed to identify patient-reported, performance-based, and biomechanical parameters sensitive to ankle-foot device type, providing a foundation for more objective and individualized prescription practices. Ninety-one individuals with unilateral transtibial limb loss completed the crossover trial, and 13 control participants without musculoskeletal impairment were enrolled to provide normative reference data. Participants were fitted with duplicate sockets and randomized to trial three ankle-foot device types: energy storing and returning, articulating, and powered. Participants were heterogeneous in demographic characteristics, including veterans, service members, and civilians. After one week of acclimation per device, participants completed performance-based (6-minute walk, Timed Up and Go, Four Square Step Test, Stair and Hill Assessment Indices, Amputee Mobility Predictor) and patient-reported (Prosthesis Evaluation Questionnaire, 12-Item Short Form Health Survey, Orthotics and Prosthetics Users' Survey) assessments; a subset (n = 29 completed) underwent full-body gait analysis to capture detailed biomechanical parameters. Biomechanical outcomes demonstrated the greatest sensitivity to device type, with 19 distinct parameters, primarily at the ankle, highlighting ankle mechanics as a key determinant of differences among prosthetic devices. Five Prosthesis Evaluation Questionnaire subscales were sensitive to device type, while performance-based measures showed no significant effects. Results revealed a dichotomy between biomechanical and patient-reported outcomes: Biomechanical parameters were more similar to control values for powered devices, whereas patient-reported outcomes favored non-powered devices. Linear discriminant analysis identified key gait features, including peak plantarflexion during preswing and peak ankle moment, which most strongly contributed to group separation and clinical discrimination. These findings identified distinct biomechanical and patient-reported parameters sensitive to ankle-foot device type and highlight the need for evidence-based, individualized prosthetic prescription to optimize device selection and improve patient outcomes.
Ketogenic diet therapies for the treatment of drug-resistant epilepsy in children and adults: A systematic review.
Vaccarezza MM, Sanguine VL, Balaciano G
PLoS One · 2026 · PMID 42391224 · Full text
Epilepsy is a common treatable neurological condition characterized by recurrent involuntary brain activity manifested in seizures. It is estimated that around 30% of patients with this disease do not respond to initial...
Epilepsy is a common treatable neurological condition characterized by recurrent involuntary brain activity manifested in seizures. It is estimated that around 30% of patients with this disease do not respond to initial pharmacological treatments, developing drug-resistant epilepsy. Among the non-pharmacological treatment options are ketogenic diet therapies (KDT) in its various forms. The objective of this study is to systematically review the randomized controlled trials investigating the use of KDTs in pediatric and adult drug-resistant epilepsy, according to Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. The following databases: Embase, PubMed/Medline, LILACS, and the Cochrane Library, were searched and studies fitting the inclusion and exclusion criteria were included for analysis. Randomized controlled trials (RCT) with a minimum follow-up of 28 days were included. There were 1193 articles retrieved after duplicates were removed and 17 met the inclusion criteria. Eleven studies included children (up to 12 yrs) and six included adolescents from 13 years old and adults. Follow-up ranged from 6 to 24 months. In children, 37% may achieve a reduction in seizure frequency of 50% or more with in any form of KDT (moderate-certainty evidence). In addition, about 6 more children per 100 may achieve a ≥ 90% reduction, although this is supported by low-certainty evidence. In adolescents and adults, KDT may lead to a ≥ 50% reduction in seizure frequency in 16 more individuals per 100 compared with usual care (moderate-certainty evidence), but its impact on a 90% or greater reduction is uncertain due to the limited number of reported events and imprecision in available studies. Side effects in children showed no significant differences compared to usual care (low certainty), while in adults, the impact remains uncertain (very low certainty). Adherence to treatment may be slightly lower with KDT in both children and adults/adolescents compared to usual treatment, though results are inconsistent. Regarding quality of life and cognitive and behavioral outcomes, studies are scarce, heterogeneous, and of very low certainty, limiting the ability to draw strong conclusions.
From knowledge to judgment: A three-year longitudinal analysis of artificial intelligence large language model performance on the Chinese national nurse licensing examination.
Zhan X, Yu W, Cai J … +1 more , Chen J
PLoS One · 2026 · PMID 42391223 · Full text
BACKGROUND: The rapid advancement of Large Language Models (LLMs) presents unprecedented opportunities for healthcare education and professional credentialing. However, comprehensive longitudinal analyses of their evolvi...
BACKGROUND: The rapid advancement of Large Language Models (LLMs) presents unprecedented opportunities for healthcare education and professional credentialing. However, comprehensive longitudinal analyses of their evolving capabilities in nursing contexts remain limited. OBJECTIVE: To conduct a three-year longitudinal performance analysis of major international and Chinese-native LLMs on the Chinese National Nurse Licensing Examination (NNLE) from July 2022 to June 2025, examining performance trajectories, comparative effectiveness, and domain-specific competencies. METHODS: We curated a comprehensive corpus of 9,800 multiple-choice questions from NNLE examinations (2022-2025) through validated educational resources. Fifteen leading LLMs were evaluated using standardized zero-shot prompting protocols, with temporal fidelity ensuring models were tested only on examinations administered after their release dates. Performance was measured as raw accuracy and benchmarked against the approximate 300-point passing threshold. Statistical analyses included trend analysis, comparative performance testing, and qualitative error categorization. RESULTS: LLM performance demonstrated a steep upward trajectory, with top-tier models achieving accuracy rates from 47.0% in 2022 to 78.8% in 2025. Chinese-native models consistently outperformed international counterparts. The mean Chinese-native advantage decreased from 6.1 percentage points in 2023 to 3.0 percentage points in 2025, while the top-model advantage remained present but non-monotonic, measuring 4.5, 3.0, and 3.8 percentage points in 2023, 2024, and 2025, respectively. Models exhibited superior performance in the knowledge-oriented Professional Practice section (81.6% average accuracy) versus the application-oriented Practical Skills section (70.9% average accuracy). Clinical reasoning failures, particularly in nursing intervention prioritization, constituted 43% of errors among top-performing models. CONCLUSION: While state-of-the-art LLMs demonstrate substantial codified nursing knowledge sufficient to achieve approximate passing thresholds on professional licensing examinations, significant deficiencies in complex clinical judgment persist, defining the current boundary between artificial intelligence capabilities and human professional competence. Critically, examination performance should not be interpreted as evidence of clinical readiness or autonomous practice capability.
OncoSeg2D: A deep framework for semantic segmentation of lung cancer in 2D CT scans.
Yu L, Dong X, Fa K … +1 more , Li Y
PLoS One · 2026 · PMID 42391222 · Full text
Lung cancer lesion segmentation in two-dimensional computed tomography (2D CT) images remains challenging due to blurred boundaries, heterogeneous morphologies, and annotation uncertainty, leading to unreliable delineati...
Lung cancer lesion segmentation in two-dimensional computed tomography (2D CT) images remains challenging due to blurred boundaries, heterogeneous morphologies, and annotation uncertainty, leading to unreliable delineations and reduced clinical usability. To address this research gap, we propose a novel 2D CT lung cancer semantic segmentation framework, OncoSeg2D, which explicitly tackles boundary ambiguity and morphological distortion through two complementary modules. Specifically, an Uncertainty-aware Boundary Modeling (UBM) module probabilistically represents tumor edges via learnable mean-variance estimation and gradient-weighted sampling, while a Morphology-Preserving Regularization (MPR) module constrains the segmentation with curvature, compactness, and convexity priors to maintain global shape consistency. The framework integrates these designs with multi-scale feature extraction from a SegFormer backbone and requires no additional annotations or three-dimensional (3D) reconstruction. Experiments conducted on the Medical Segmentation Decathlon Challenge dataset and the lung cancer segmentation dataset demonstrate that OncoSeg2D achieves IoU scores of 0.865 and 0.788, mIoU scores of 0.881 and 0.799, and Dice Similarity Coefficients (DSC) of 0.923 and 0.816, consistently outperforming conventional CNN-based models and mainstream Transformer-based methods. Compared with the SegFormer baseline, the proposed method improves mIoU by 3.8% and 4.0% on the two datasets, respectively, while reducing the Hausdorff distance from 5.61 to 3.41 and from 7.26 to 5.28, indicating superior boundary refinement and stronger global shape consistency. These results verify that explicitly integrating uncertainty modeling and morphological priors yields both higher accuracy and better interpretability. Overall, the proposed framework not only enhances segmentation accuracy but also improves clinical interpretability and reliability, offering a promising solution for lung cancer diagnosis assistance and therapeutic outcome monitoring.
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