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PubMed2026

Electrocardiographic correlates of pacing induced cardiomyopathy and response to cardiac resynchronization therapy.

BACKGROUND: Chronic right ventricular (RV) pacing (RVP) causes pacing-induced cardiomyopathy (PICM) in only a small number of patients. We evaluated ECG correlates of (i) PICM and (ii) response to cardiac resynchronization therapy (CRT) upgrade. METHODS: We conducted a retrospective case-control study by including all CRT upgrades for PICM (LVEF <50%) at our center between 2014 and 2018. Controls were patients with ≥5 ECGs all demonstrating RVP over ≥2 years and all echocardiographic LVEF ≥50%. Root-summed-squared (3D) ECG was obtained from reconstructed vectorcardiographic X-Y-Z leads. Predictors of PICM and CRT response were assessed as area under ROC curve (AUC) for pre-CRT and Δ (post-CRT - pre-CRT) ECG intervals and QRS voltage-time-integrals (VTI). RESULTS: We included 104 patients with CRT upgrade for PICM (age 73.7 ± 10.5 years, female 29.1%, QRS duration 167.8 ± 25.2 ms, LVEF 28.8 ± 8.0%, ΔLVEF 13.8 ± 10.3%) and 178 controls without PICM (age 73.2 ± 14.9 years, female 52.8%, QRS duration 144.0 ± 20.9 ms, LVEF 56.7 ± 5.2%). PICM was best identified by VTIQRS-3D (AUC 0.851; VTIQRS-3D ≥ 80 μVs sensitivity 87.5%, specificity 63.5%), VTIQRS-Y (0.846), and QRS duration (0.775). CRT response (LVEF increase ≥10% at 3-12 months) occurred in 73/104 (70.2%) patients. Lack of CRT response was best predicted by longer pre-CRT QRS duration (AUC 0.640; QRS duration ≥180 ms sensitivity 45.2%, specificity 83.6%), and less ΔVTIQRS-3D (0.609) and ΔVTIQRS-X (0.608). CONCLUSION: In patients with chronic RVP, VTIQRS-3D ≥ 80 μVs can be used as a screening test for echocardiographic confirmation of PICM. RV-paced QRS duration >180 ms, on the other hand, identifies those who may not respond to CRT upgrade.

Humans↗

PubMed2026

Quantitative susceptibility mapping in neurodegenerative diseases: An umbrella review of iron-related biomarkers and mechanisms.

Pathological iron accumulation is a common pathophysiological hallmark across multiple neurodegenerative diseases (NDDs), motivating the need for accurate, non-invasive quantification methods. Quantitative susceptibility mapping (QSM) is an advanced magnetic resonance imaging (MRI) technique that enables in vivo measurement of tissue magnetic susceptibility (χ), providing a sensitive proxy for iron content. This umbrella review systematically evaluates the diagnostic accuracy, clinical correlations, and distinct iron distribution patterns of QSM in major NDDs, such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and atypical Parkinsonism. We included 15 (13/15 were rated Low or Critically Low on AMSTAR 2) systematic reviews and meta-analyses (through July 15, 2026); however, the findings should be interpreted cautiously because of heterogeneity and the low methodological quality. A Corrected Covered Area (CCA) analysis demonstrated only slight overlap of primary studies across the included reviews (CCA = 5.42%). Collectively, the evidence indicates that QSM provides comparable or higher diagnostic sensitivity and reliability than conventional R2* and SWI techniques, particularly for deep gray matter structures. The findings support significant iron overload in the substantia nigra, particularly in the pars compacta, as a robust biomarker for PD that correlates with motor severity and disease duration. Furthermore, regional iron profiling in the basal ganglia is critical for differential diagnosis; specifically, elevated χ in the putamen and globus pallidus effectively distinguishes multiple system atrophy and progressive supranuclear palsy from idiopathic PD. Distinctively, AD and ALS exhibit specific χ alterations in the thalamus, motor cortex, and hippocampus, reflecting divergent iron-related pathophysiological mechanisms, which correlate with cognitive impairment and upper motor neuron signs. Overall, QSM shows diagnostic promise and offers mechanistic insights into iron-related neurodegenerative processes.

Humans↗

PubMed2026

Divergent evolutionary strategies in spider venoms: A comparative proteomic profiling of four sympatric species from Yunnan.

Spider venoms comprise complex cocktails of bioactive molecules evolved for predation and defense, representing a valuable resource for biological research and pharmaceutical discovery. In this study, we performed a systematic analysis of venom gland extracts from four common spider species indigenous to Yunnan, China: Agelena limbata, Hippasa lycosina, Lycosa grahami, and Sinopoda pengi. Using an integrated transcriptomic and proteomic targeted profiling approach, we successfully annotated 141 distinct toxins. Comparative analysis revealed significant interspecific heterogeneity, suggesting distinct evolutionary trajectories and "weapon system economics." Both A. limbata and L. grahami exhibited a "peptide-dominant" profile anchored by neurotoxic peptides and isomerases, optimized for rapid chemical paralysis. In contrast, S. pengi displayed a distinct "protein-dominant" signature enriched with high-molecular-weight enzymes and CAP superfamily proteins, likely functioning to facilitate tissue degradation and toxin diffusion. Occupying an intermediate position, H. lycosina demonstrated a hybrid composition. These findings suggest that although these species share the same geographical range, their venom systems have undergone divergent evolutionary adaptations driven by specific ecological niches and hunting strategies. This study represents the first systematic proteomic characterization of these venom components, providing a valuable reservoir of molecular candidates while highlighting the bioinformatic nuances of analyzing whole-gland homogenates.

Animals↗

PubMed2026

Artificial Intelligence for Diagnosing Meibomian Gland Dysfunction: A Systematic Review and Meta-Analysis of Diagnostic Test Accuracy Studies.

PURPOSE: To identify, appraise, and synthesize the performance of artificial intelligence-based meibography reading as compared with human graders in diagnosing meibomian gland dysfunction. METHODS: We followed Cochrane methodology and reporting guidelines for diagnostic test accuracy reviews. To assess potential risk of bias and applicability, we used a modified Quality Assessment of Diagnostic Accuracy Studies-2 checklist. We applied bivariate logistic models to estimate summary sensitivity and specificity when appropriate and used the GRADE framework to rate the certainty of the evidence. RESULTS: We identified 14 eligible studies involving 5511 predominantly middle-aged participants (average age: 27-55 years) who were primarily female (≥54.5%). A total of 18,926 meibography images were obtained through noncontact infrared (11 studies) or in vivo confocal microscopy (three studies). Two studies reported external validation of deep learning models, 12 reported internally validated models, and one reported both. All but one study had high risk of bias in at least one domain; 12 studies raised high or intermediate concern about applicability. Based on three external evaluations, the summary sensitivity and specificity for diagnosing meibomian gland dysfunction from normal glands were 97.5% (95% confidence interval: 77.5%-99.8%) and 85.5% (95% confidence interval: 47.3%-97.5%). Sources of heterogeneity in internally validated models included study population, case mix, and others. The overall evidence was very low to low certainty because of imprecision, high risk of bias, and concerns about applicability. CONCLUSIONS: Artificial intelligence-based meibography grading appears less accurate than human graders. Future studies should adopt rigorous designs, including a more diverse participant pool (or image set), and external validation.

Humans↗

PubMed2026

Integration of single-cell transcriptomics and genomic mutation analysis identifies an immunotherapy-resistant tumor subcluster and validates ARNTL2 as a malignant driver in lung adenocarcinoma.

BACKGROUND: Immunotherapy resistance in lung adenocarcinoma (LUAD) remains a critical clinical challenge, and the mechanisms underlying resistance-associated intratumoral heterogeneity are poorly characterized. METHODS: We performed single-cell RNA sequencing of LUAD patients receiving neoadjuvant immunotherapy (responders vs. non-responders), integrating inferCNV, GSVA, and differential expression analyses. Cluster-specific genes were validated across seven independent cohorts (TCGA-LUAD, GSE13213, GSE26939, GSE29016, GSE30219, GSE31210, GSE42127). A multi-algorithm machine learning framework was used to construct a prognostic model, and the immune microenvironment was characterized using TCIA scoring, seven infiltration algorithms, and ESTIMATE. ARNTL2 function was assessed by CCK-8 and Transwell assays in A549 and H1299 cells. RESULTS: Non-responders showed significant enrichment of epithelial cells, depletion of cytotoxic T/NK cells, and elevated copy number variation burden versus responders (p < 0.0001). A resistance-enriched malignant subcluster (Cluster 2) exhibited hyperproliferative and metabolic reprogramming signatures with upregulated KRT17, S100A2, and CST6, which showed tumor-specific overexpression, adverse prognostic value, and genomic amplification across cohorts. CoxBoost combined with survivalSVM achieved optimal predictive performance (C-index = 0.686), yielding robust risk stratification (HR: 2.54-10.51, all p < 0.05). Low-risk patients showed greater immune infiltration and higher TCIA immunophenoscores. ARNTL2 was an independent prognostic factor (HR: 2.07-4.64) strongly correlated with risk score (r = 0.69), and its knockdown suppressed proliferation and invasion in both LUAD cell lines (all p < 0.05). CONCLUSION: This study identifies a resistance-associated malignant subcluster in LUAD, constructs a validated CoxBoost + survivalSVM prognostic model with robust immune stratification, and establishes ARNTL2 as a core oncogenic driver and therapeutic target.

ARNTL2↗

PubMed2026

Evaluating the persistence of semen under controlled environmental conditions.

When semen is deposited at a crime scene, it may be exposed to harmful environmental conditions. It is important to understand to what extent the different components of semen, specifically acid phosphatase (AP), prostate specific antigens (PSA), sperm and DNA, may become less detectable after exposure to high temperatures and varying levels of humidity. In this study, semen (50 μL) was deposited onto squares of black cotton and exposed to 45 °C and a relative humidity (RH) of 10 or 80% for 0, 7, 14, 21 or 28 days (n = 5 per day, per climate condition). Source testing included AP test reagent, ABAcard® p30 immunoassay kits, and hematoxylin and eosin staining. DNA was extracted using the DNA IQ™ System (Promega, Australia) and quantified using Quantfiler Trio™ (Thermo Fisher Scientific, Australia). Over the 28-day period under both RH conditions, the time taken for a positive AP test to develop increased significantly (p < 0.01) and the number of sperm observed decreased significantly (p < 0.01). All ABAcard® p30 tests were positive regardless of exposure time or conditions. No impact on the quantity of DNA recovered was observed when semen was exposed to 45 °C and 10% RH, with a higher median quantity of DNA recovered at day 28 compared to day 0. In contrast, when the RH was raised to 80%, the median quantity of DNA recovered was substantially less at day 28 (81.5 ng, IQR: 87.5 ng) compared to day 0 (181.5 ng, IQR: 1172.4 ng). This study highlights the impact that temperature and RH may have on the persistence of AP, PSA, sperm and DNA over time.

Humans↗

PubMed2026

Awake Craniotomy for Eloquent Region Glioblastoma Classified by Tumor Location-A Retrospective and Prospective Cohort Study.

INTRODUCTION: The efficacy of awake craniotomy (AC) with intraoperative mapping for glioblastoma (GBM) in eloquent regions remains debated. This study aims to evaluate functional and survival outcomes of GBM patients undergoing AC stratified by tumor locations. METHODS: A combined retrospective (2015-2023, n = 114: 43 AC vs. 71 standard craniotomy) and prospective cohort (2023-2025, n = 28: 13 AC vs. 15 standard craniotomy) of GBM patients with motor/language-eloquent tumors was analyzed. Tumors were classified into motor subtypes (I: precentral gyrus; II: premotor/supplementary motor; III: internal capsule posterior limb; IV: other) and language subtypes (I: Broca's/precentral; II: postcentral/supramarginal gyrus; III: Wernicke's; IV: insular; V: other). Outcomes included extent of resection (EOR), postoperative motor/language recovery, overall survival (OS), and progression-free survival (PFS). RESULTS: The retrospective cohort demonstrated that AC has advantages in functional preservation across various motor/language subtypes. However, AC was associated with significantly deteriorated survival outcomes specifically in precentral gyrus GBMs. A prospective cohort study, enrolling only precentral gyrus GBMs for validation, yielded results consistent with the retrospective findings: worsened OS and PFS (OS: HR = 3.223, p = 0.0450; PFS: HR = 2.374, p = 0.0476); reduced EOR (AC: 74.3% ± 5.3%; standard craniotomy: 86.9% ± 12.3%, p = 0.0470); and better motor recovery. CONCLUSIONS: Functional preservation and survival outcomes of AC in GBM exhibited subtype-specific correlations with tumor locations. AC with intraoperative mapping effectively preserves neurological function in GBM patients. However, for tumors involving the precentral gyrus, the AC approach carries greater risks than benefits and should be considered with caution. TRIAL REGISTRATION: Strategic Intervention on Preserving Motor Function During Awake Craniotomy: NCT05143788. Strategic Intervention on Preserving Language Function During Awake Craniotomy: NCT05143775.

Adult↗

PubMed2026

Endoscopic Ultrasound-Guided Versus Transjugular Portal Pressure Measurements: Systematic Review and Meta-Analysis.

PURPOSE: Published reviews of endoscopic ultrasound-guided portal pressure gradient (EUS-PPG) have emphasized feasibility and safety. We performed a systematic review and meta-analysis specifically to evaluate how closely EUS-based portal pressure measurements track invasive comparator measurements in prospective paired studies and to summarize agreement, technical success, and adverse events. METHODS: We searched major databases through January 2026 for prospective cohorts reporting same-patient EUS-based portal pressure measurement and invasive hemodynamic measurements. Correlations were pooled with random-effects models and analyzed separately for studies comparing EUS-PPG with hepatic venous pressure gradient (HVPG) and studies comparing EUS-based portal measurements with direct portal venous pressure. Agreement and threshold discordance were summarized descriptively. RESULTS: Six prospective cohorts (127 attempted procedures) were included. In studies using HVPG as the comparator, the pooled correlation was 0.82 (95% CI, 0.72-0.89; I2 = 0%). In studies comparing EUS-based portal measurements with direct portal venous pressure, the pooled correlation was 0.86 (95% CI, 0.72-0.93; I2 = 16.9%). Technical success was 95.3%. EUS-PPG-attributed adverse events occurred in 2.4% of procedures, with no procedure-related deaths. Agreement data were limited. Reported limits of agreement were wide (approximately - 6 to + 7 mmHg), and discrepancies of 5 mmHg or greater occurred in 4 of 30 paired measurements. CONCLUSIONS: EUS-based portal pressure measurement is feasible and shows a strong association with invasive hemodynamic comparators, but the evidence base remains small (six cohorts, 127 attempted procedures). Further study will be necessary to establish patient-level agreement, procedural reproducibility, EUS-specific clinically significant portal hypertension thresholds, and whether HVPG-based decision thresholds can be transferred to EUS-derived measurements.

Humans↗

PubMed2026

Enhancing Hemoglobin Bart's hydrops fetalis syndrome prevention: a single-tube multiplex real-time PCR assay for the comprehensive detection of four significant α0-thalassemia deletions (--SEA, --THAI, --CR, and --SA) found in Thailand.

BACKGROUND: Hemoglobin (Hb) Bart's hydrops fetalis is a major public health concern in Southeast Asia, particularly in Thailand. Current screening strategies target the two most common α0 -thalassemia deletions (--SEA and --THAI). METHOD: In this study, we developed a single-tube multiplex real-time PCR assay for the simultaneous detection of four clinically relevant α0-thalassemia deletions (--SEA, --THAI, --CR, and --SA). The assay was validated using 538 clinical samples with diverse thalassemia genotypes and compared against conventional gap-PCR as the reference method. Analytical performance, including sensitivity, specificity, and limit of detection (LOD), was evaluated. In addition, clinical utility was assessed in 22 prenatal diagnosis cases at risk of Hb Bart's hydrops fetalis. RESULTS: The study cohort demonstrated substantial genetic heterogeneity, comprising 43 distinct genotypes. The developed assay achieved 100% sensitivity and specificity for all targeted deletions, with complete concordance with gap-PCR results. No cross-reactivity was observed with α+-thalassemia. The assay demonstrated a high analytical sensitivity with a LOD of 9.76 × 10-3 ng per reaction. Whereas in prenatal diagnosis, all 22 fetal genotypes were accurately identified, including five cases of homozygous --SEA and one rare compound heterozygous --SEA/--CR fetus. CONCLUSIONS: This study presents a rapid, accurate, and cost-effective multiplex real-time PCR assay capable of detecting both common and rare α0-thalassemia deletions in a single reaction. The assay demonstrates strong potential for implementation in routine clinical laboratories and large-scale population screening, contributing to improved prevention and control of severe thalassemia syndromes in high-prevalence regions.

Humans↗

PubMed2026

Diagnostic Performance of Machine Learning for Systemic Lupus Erythematosus: Systematic Review and Meta-Analysis.

BACKGROUND: Early and accurate diagnosis of systemic lupus erythematosus (SLE) and its organ involvement is essential. Previous reviews of machine learning (ML) in SLE combined heterogeneous tasks and validation strategies and may have overinterpreted model performance. OBJECTIVE: This study evaluated the diagnostic performance of ML and deep learning (DL) models for 3 clinically distinct SLE-related tasks: SLE classification or diagnosis, lupus nephritis (LN) diagnosis, and neuropsychiatric systemic lupus erythematosus (NPSLE) discrimination. We also assessed methodological quality and certainty of evidence. METHODS: PubMed, Embase, Cochrane Library, Web of Science, and IEEE Xplore were searched from January 2014 to April 2026. Eligible peer-reviewed diagnostic accuracy studies developed or validated ML or DL models for 1 of the 3 prespecified tasks, used an accepted reference standard, and provided data for a 2×2 contingency table. Bivariate random-effects meta-analyses with the Hartung-Knapp-Sidik-Jonkman adjustment were used to pool sensitivity and specificity. We reported 95% prediction intervals (PIs), assessed risk of bias using the Quality Assessment of Diagnostic Accuracy Studies for Artificial Intelligence tool (QUADAS-AI; Viknesh Sounderajah [Imperial College London]), and evaluated certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation framework for diagnostic test accuracy. RESULTS: Twenty-nine studies were included: 17 for SLE classification, 5 for LN diagnosis, and 7 for NPSLE discrimination. In the primary task-stratified analysis, pooled sensitivity was 0.91 (95% CI 0.86-0.94; 95% PI 0.56-0.99), and pooled specificity was 0.94 (95% CI 0.91-0.96; 95% PI 0.69-0.99), with low heterogeneity (I²=23.9% and 22.9%, respectively). DL models showed a sensitivity of 0.93 and specificity of 0.95, compared with 0.88 and 0.94 for traditional ML models. Certainty of evidence was high for most analyses but low for LN diagnosis because of inconsistency and imprecision. All studies were retrospective, and only 9 of 29 (31%) performed independent external validation. Overall risk of bias was high or unclear in 22 of 29 (75.9%) studies. No study reported model calibration, decision-curve analysis, or net clinical benefit. CONCLUSIONS: ML models showed promising diagnostic accuracy across 3 distinct SLE-related tasks, but wide PIs, limited external validation, and pervasive risk of bias restrict conclusions about real-world generalizability. Prospective multicenter studies with standardized tasks and reference standards, independent external validation, and formal assessment of calibration and clinical utility are required before clinical implementation.

Humans↗

PubMed2026

Efficacy of current approaches to non-invasive diagnosis of skin cancer and the potential impact of artificial intelligence: A systematic review and meta-analysis.

BACKGROUND: Skin cancer is one of the most prevalent malignancies worldwide, particularly within Caucasian populations. This systematic review and meta-analysis aimed to quantitatively review the current literature on non-invasive diagnosis of skin cancer and evaluate the current evidence to support the use of tools in addition to, or in replacement of clinician face-to-face assessment. METHODS: A literature search was conducted for publications in PubMed, Medline and Embase databases. Articles describing accuracy, sensitivity, specificity and outcomes of their mode of assessment were included. A total of 208 articles met the inclusion criteria. RESULTS AND CONCLUSION: This systematic review and meta-analysis showed that the diagnostic performance of artificial intelligence (AI) in the interpretation of dermatoscopic images was high for melanoma diagnosis, basal cell carcinoma or malignancy, in comparison to dermatoscopic assessment alone by clinicians and experts. Although AI interpretation of images demonstrated higher sensitivity for melanoma diagnosis in comparison to clinical assessment combined with dermatoscopic assessment, it is unclear if this is also the case for basal cell carcinoma and squamous cell carcinoma diagnosis. Reflectance confocal microscopy, a non-invasive high resolution imaging technique, is known to have a high sensitivity for diagnosing cutaneous malignancy, and this may have applications within secondary care. Therefore, AI could help reduce resource burden and aid in clinical assessment, particularly within primary care settings.

Humans↗

PubMed2026

AI-enabled viral genomics: from virus discovery to host prediction and emerging variant forecasting.

The rapid expansion of metagenomic sequencing has generated vast repositories of viral sequence data that far outpace our capacity to interpret them using conventional approaches. Highly divergent sequences, sparse functional annotation, and taxonomically uneven sampling present fundamental challenges for reference-dependent methods, which lose sensitivity precisely for novel and understudied viruses with high public health relevance. Artificial intelligence (AI) provides a new avenue to address these challenges by enabling predictive inference from viral genomes and proteins while reducing dependence on sequence similarity. In this Review, we discuss representative advances in AI for virus discovery, taxonomic classification and functional annotation, prediction of host range and zoonotic potential, and efforts toward forecasting emerging variants. These advances are transforming viral genomics from a largely descriptive discipline into one with increasing predictive capability. We also critically assess the major challenges that constrain current approaches, including the availability of high-quality and representative datasets, rigorous model evaluation, biological interpretability and responsible governance for increasingly capable AI models.

Artificial Intelligence↗

PubMed2026

Application of Three-Dimensionally Printed Surgical Guides in Precise Sacral Tumor Excision and Defect Reconstruction.

OBJECTIVE: Precise resection of sacral tumors remains technically demanding due to their deep anatomical location and close proximity to critical neurovascular structures. Conventional freehand techniques often result in suboptimal resection margins, excessive blood loss, and compromised lumbopelvic stability. This study evaluated whether patient-specific three-dimensional (3D)-printed guiding templates improve surgical accuracy and perioperative outcomes in sacral tumor resection and reconstruction. METHODS: Nineteen patients undergoing en bloc sacral tumor resection (S1-S3 involvement) with spinopelvic reconstruction (2006-2020) were retrospectively analyzed. Patients were divided into a 3D-printing group (n = 10) and a conventional freehand group (n = 9). In the 3D-printing group, computer-aided design and 3D-printed templates were used for osteotomy, screw placement, and defect reconstruction. Perioperative metrics, surgical accuracy, and complications were compared between groups using Welch's t-test and the Hodges-Lehmann method; oncologic events during follow-up were recorded descriptively. RESULTS: The 3D-printing group demonstrated significantly shorter operative time (456.5 ± 62.36 vs. 574.44 ± 114.58 min, p = 0.012), reduced blood loss (4081.40 ± 838.99 vs. 5090.0 ± 1059.67 mL, p = 0.034), and fewer fluoroscopic exposures (4.2 ± 0.79 vs. 10.0 ± 1.58, p < 0.001) compared with the conventional group. Osteotomy accuracy was also superior in the 3D-printing group, with significantly lower angular deviation (3.33° ± 0.45° vs. 6.79° ± 2.16°, p = 0.0012). Postoperative complication rates were comparable (30% vs. 44.4%, p = 0.649), but hospital stay was significantly shorter in the 3D-printing group (10.7 ± 2.71 vs. 18.11 ± 4.01 days, p < 0.001). CONCLUSION: Patient-specific 3D-printed guiding templates enhance precision in sacral tumor excision and reconstruction, improving surgical efficiency and perioperative safety. This computer-assisted, template-guided approach represents a valuable advancement for complex sacral oncologic surgery.

Humans↗

PubMed2026

Thyroid-joint crosstalk: a systematic review and meta-analysis of thyroid autoimmunity and dysfunction in juvenile idiopathic arthritis.

BACKGROUND: Recent observational studies outlined the concomitant presence of autoimmune diseases in children with juvenile idiopathic arthritis (JIA), including endocrine autoimmunity. Despite the growing evidence of thyroid involvement in JIA, available data are heterogeneous and fragmented. We aimed to systematically review the available evidence on the prevalence of thyroid autoantibody positivity and thyroid dysfunction in patients with JIA. METHODS: PubMed/Medline, Cochrane, and Scopus databases were approached to identify studies reporting data on thyroid autoantibody positivity and dysfunction in children with JIA. RESULTS: A total of 15 studies were included in the final analysis, encompassing 19 015 children with JIA (13 225 females, 69.6%) with a weighted mean age of 8.0 years (range 1.8-21 years). The pooled prevalence estimates of antithyroid antibody positivity and thyroid dysfunction were 0.04 (95% CI: 0.03-0.05) and 0.04 (95% CI: 0.03-0.08), respectively. The risk difference for thyroid autoantibody positivity between children with JIA and controls was 0.08 (95% CI: 0.02-0.14). Possible risk factors were analyzed: the presence of family history for thyroid autoimmune disease (odds ratio - OR 3.91, 95% CI 1.86-8.25), concurrent Antinuclear Antibodies (ANA) positivity (OR 1.62, 95% CI 1.13-2.31), and older age (MD 2.10 years, 95% CI 1.32-2.89) were associated with thyroid autoantibody positivity and/or thyroid dysfunction in children with JIA. No significant difference emerged for the specific JIA form. CONCLUSION: Thyroid dysfunction may be detected in children with JIA, with a significant risk difference in comparison to healthy controls. Specific clinical characteristics, such as family history, ANA positivity, and older age at JIA onset, may suggest which patients should benefit from thyroid autoantibody screening.

Humans↗

PubMed2026

A conserved distal-tail helical extension defines a tailspike attachment architecture in Gram-negative siphophages.

Rapid growth of bacteriophage genome collections has outpaced functional annotation of tail-tip proteins, limiting comparative analysis of host-recognition structures. Starting from a shared distal-tail gene organization in the Salmonella phages 9NA and Jersey, I developed a morphogenetic bioinformatic framework integrating gene synteny, sequence comparison, profile hidden Markov model (HMM) screening, structural evidence, structure-aware searching, and AlphaFold modeling. Comparison with the experimentally characterized lambda and Sf11 tail assemblies identified a predominantly alpha-helical C-terminal extension of the distal-tail (DT) protein associated with tailspike attachment, termed the distal-tail helical extension (DT-helix). Screening 541,986 proteins from 5167 complete NCBI RefSeq tailed-phage genomes, followed by evidence-based evaluation of sequence, genomic context, and structural architecture, identified 165 curated DT-helical-extension-associated phages. Their DT proteins segregated into six sequence groups. In the four principal multi-member groups, cognate tailspikes showed group-specific conservation in proximal N-terminal regions but substantially greater downstream diversity, consistent with sequence constraint at the DT-tailspike attachment boundary. A complementary ProstT5/Foldseek search supported the established groups but revealed no convincing additional highly divergent family. Together with the experimentally characterized Sf11 attachment interface, these findings define a recurrent morphogenetic architecture linking conserved distal-tail scaffolds to more variable receptor-binding proteins across siphophages infecting Gram-negative bacteria. Although universal exchangeability is not established, the identified scaffold-receptor-binding boundaries provide a framework for molecular characterization and rational phage engineering. Accession-level information for the 165 curated phages is available through PhageTailDB.

Viral Tail Proteins↗

PubMed2026

Glucocorticoids and placental 11βHSD2 - A systematic review of human studies and animal models.

CONTEXT: Elevated prenatal glucocorticoid (GC) exposure is linked to adverse offspring outcomes. The placental enzyme 11β-hydroxysteroid-dehydrogenase-type-2 (11βHSD2) protects the fetus by converting maternal derived cortisol to inactive cortisone. Although in vitro studies suggest GC mediated upregulation of 11βHSD2, in vivo evidence remains inconclusive. METHODS: PubMed, Embase, and PsycInfo were searched in October 2024 for human and mammalian animal studies on endogenous or exogenous GCs during pregnancy and associations with placental 11βHSD2 (mRNA, protein, activity, gene methylation). Narrative synthesis was conducted due to heterogeneity precluding meta-analysis. RESULTS: Eighteen studies (eight human, ten animal populations) met inclusion criteria. Exogenous GC exposure was associated with modifications in placental 11βHSD2 expression in animal models, with effects varying by substance, timing, and species. Dexamethasone trended towards increased expression in rodents, whereas betamethasone increased expression in non-human primates but not rodents. Human studies on endogenous GCs showed inconsistent associations with 11βHSD2 changes. In asthmatic pregnancies, moderate inhaled GC-use maintained enzyme activity compared to untreated patients. No convincing sex-specific trend emerged. CONCLUSIONS: GC exposure alters placental 11βHSD2 in a substance- and species-specific way; translational relevance remains limited based on current literature. Future studies should employ technological advances and include GC-sensitive biomarkers to clarify mechanisms of maternal-fetal stress transmission.

Female↗

PubMed2025

Enhanced fracture detection on radiographs with AI assistance for clinicians: a systematic review and meta-analysis.

BACKGROUND: Emergency radiographic interpretation for fractures is prone to missed or misdiagnoses. Artificial intelligence (AI) is expected to become a powerful tool to assist clinicians in fracture detection. PURPOSE: A systematic review and meta-analysis was performed to assess whether AI improves clinicians' ability to detect fractures on radiographs. MATERIALS AND METHODS: A literature search was conducted in PubMed, Web of Science, and Cochrane Library for studies published between January 1, 2010, and October 10, 2025. A meta-analysis of diagnostic accuracy studies was performed using a Summary Receiver Operating Characteristic (SROC) curve. The quality of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Subgroup analysis and meta-regression were conducted to explore potential sources of heterogeneity. RESULTS: A total of 26 studies were included . The pooled sensitivity of clinicians increased from 77% (95% CI: 72-81) to 87% (95% CI: 83-90) with AI assistance, while the pooled specificity improved from 88% (95% CI: 85-90) to 92% (95% CI: 89-94). The corresponding AUC values were 0.90 (95% CI: 0.87-0.92) before and 0.95 (95% CI: 0.93-0.97) after AI assistance. Eight studies were rated as high risk of bias. Subgroup analysis and meta-regression identified potential sources of heterogeneity, including fracture location, AI model type, high risk of bias, and reference standards. CONCLUSION: AI assistance significantly improves clinicians' diagnostic performance in detecting fractures on radiographs for extremity and trunk fractures.

Humans↗

PubMed2026

Unveiling the power of TIIC: A prognostic tool for esophageal adenocarcinoma.

BACKGROUND: Esophageal adenocarcinoma (EAC) remains a lethal malignancy with limited prognostic tools for guiding immunotherapy. Tumor-infiltrating immune cells (TIICs) play a critical role in EAC prognosis and treatment response. METHODS: We integrated single-cell RNA sequencing and bulk transcriptome data from TCGA and GEO databases. TIIC-specific RNAs were identified via tissue specificity index calculation combined with machine learning feature selection. Twenty machine learning algorithms were benchmarked to construct an optimal TIIC signature score (TIIC-Score) based on the comprehensive C-index. Immunotherapy response, genomic mutation, and copy number variation were analyzed. Summary-data-based Mendelian randomization (SMR) and two-sample Mendelian randomization (MR) were performed to explore genetic associations. Core prognostic TIIC-related genes were functionally validated in esophageal cancer cell lines through loss-of-function assays. RESULTS: The TIIC-Score demonstrated robust prognostic value for 1-, 2-, and 3-year overall survival across multiple cohorts, outperforming 22 published models. High TIIC-Score was associated with poor survival and increased chromosomal instability. Mutation profiling revealed high frequencies of TP53 (78.2%), TTN (48.7%), and SYNE1 (30.8%). MR analysis identified a significant association between gastro-oesophageal reflux and EAC risk at SNP rs8130507. Functionally, CCNI was upregulated in esophageal cancer cells, and its knockdown suppressed malignant phenotypes while promoting apoptosis, supporting its pro-tumorigenic role. CONCLUSION: The TIIC-Score provides a novel prognostic framework for EAC that effectively stratifies patient risk and may help identify individuals most likely to benefit from immunotherapy.

Esophageal adenocarcinoma↗