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PubMed2026

Identification of molecular subtypes in clear cell renal cell carcinoma based on chromatin regulators and tumor immune microenvironment profiling.

In the histological classification of renal cell carcinoma, clear cell renal cell carcinoma (ccRCC) accounts for the highest proportion and is the most common subtype. Despite advances in management, it continues to be associated with considerable incidence and mortality. Although surgery and systemic therapies are available, their efficacy is constrained by pronounced intratumoral heterogeneity and treatment resistance. Identifying robust biomarkers and clarifying the underlying biological mechanisms are therefore essential to improving diagnosis, risk stratification and therapeutic decision-making. In this work, we identified two ccRCC molecular subtypes displaying divergent chromatin regulator (CR) profiles and different clinical prognoses. Using the genes differentially expressed between these subgroups, we constructed a CR-related score (CRS) that effectively stratified patients according to survival. More analysis concluded that the low expression of CR was more linked with the immune-activated tumors, which encompassed the immune pathway enrichment, as well as the elevation of numerous immune cell subtypes. Moreover, elevated CRS was associated with improved immunotherapy responsiveness. Drug-sensitivity analyses nominated several candidate agents, and SMARCD3 knockdown in 786-O cells inhibited proliferation and migration and reduced sensitivity to masitinib. Collectively, these findings support the prognostic and therapeutic relevance of CR-related states in ccRCC and provide a framework for future experimental validation of chromatin-regulated tumor-immune interactions.

Humans↗

PubMed2026

Multimodal intervention benefits: Responder analysis of J-MINT PRIME Kanagawa trial.

INTRODUCTION: The J-MINT PRIME Kanagawa trial was an 18-month multimodal intervention (incorporating exercise, nutrition, and metabolic management) for dementia prevention. Because the primary analysis showed no significant benefits, we performed an exploratory responder analysis to identify responsive subpopulations. METHODS: We analyzed the Full Analysis Set comprising 188 participants. Classification and regression tree (CART) analysis, applied to the intervention arm, identified baseline predictors of cognitive improvement. These rules were then applied to the entire cohort to evaluate treatment effects on the Mini-Mental State Examination (MMSE) using fully adjusted mixed-effects models for repeated measures (MMRM). RESULTS: CART identified a "Target Group" (N = 108) characterized by baseline profiles such as an MMSE score < 28 or specific metabolic ranges (e.g., LDL-C < 135 mg/dL). Within this target group, the intervention significantly preserved MMSE trajectories compared with the control group (group × time interaction, P = 0.022). In contrast, the Non-Target Group (N = 80), consisting of high-functioning individuals (MMSE ≥ 28), exhibited no significant group × time interaction. DISCUSSION: Multimodal interventions may effectively preserve global cognition in older adults with sub-threshold cognitive decline. Careful targeting of appropriate populations, while considering potential longitudinal measurement artifacts (e.g., practice effects), is essential. These findings provide a hypothesis-generating framework that warrants external validation in future prevention trials.

Humans↗

PubMed2026

Failure modes and effects analysis for clinical implementation of online adaptive radiotherapy: A systematic review.

BACKGROUND: The accuracy of radiotherapy is limited by anatomical variations occurring over time scales ranging from sub-seconds to days. Online Adaptive Radiotherapy (OART) addresses this by enabling daily plan adaptation based on real-time imaging. While OART offers improved dose conformity, its dynamic, time-constrained workflow introduces novel failure modes that challenge traditional quality assurance protocols. PURPOSE: This study aims to synthesize the existing literature on Failure Modes and Effects Analysis (FMEA) for OART to systematically catalog risks and identify mitigation strategies. METHODS: A systematic literature search was conducted to identify studies applying FMEA to OART workflows. Eleven studies were included, covering MR-guided (ViewRay MRIdian, Elekta Unity), CBCT-guided (Varian Ethos), and MR-enhanced C-arm linac systems. To address heterogeneity in risk scoring methodologies (e.g., TG-100 10-point scales vs. 5-point rankings), extracted failure modes were harmonized into a standardized three-tier risk classification system (Class I: Low, Class II: Intermediate, Class III: High). RESULTS: A total of 300 unique failure modes were identified, with 49.6 percent classified as high-risk (Class III). Analysis revealed that the majority of high-risk failures were concentrated in the online treatment delivery phase, specifically within human-computer interactions and anatomical contouring steps. CONCLUSIONS: This study supports the development of tailored, robust QA frameworks that prioritize human factors and process consistency to guide safe implementation in diverse clinical settings.

Humans↗

PubMed2026

Factors influencing the enhancement of the new iron triangle in healthcare organisations.

PURPOSE: A new paradigm, "healthcare's new iron triangle," has been developed to emphasise the technological perspective of healthcare delivery, focusing on automation, value and empathy. The study aims to build a conceptual model and to identify factors for the enhancement of the new iron triangle in healthcare organisations. DESIGN/METHODOLOGY/APPROACH: The healthcare organisation is the primary focus point of the current study. To determine the factors, a survey of the literature and healthcare experts' opinions was conducted. The healthcare professionals validated the identified factors. Data for this study were gathered using a closed-ended questionnaire and scheduled interviews. The study employed "Total Interpretive Structural Modeling methodology and Matriced' Impacts Croise´s Multiplication Appliqué´ a UN Classement/Cross-Impact Matrix Multiplication Applied to a Classification (MICMAC) analysis" to address the "why" and "how" the factors interact and prioritise the identified factors. FINDINGS: The study found that organisational structure (F8), artificial intelligence (F1), innovation (F2) and human resources (F5) are the driving or key factors of the study. RESEARCH LIMITATIONS/IMPLICATIONS: The study primarily focused on identifying factors for the enhancement of a new iron triangle in healthcare organisations. The scope could eventually be expanded to explore more areas. PRACTICAL IMPLICATIONS: Academics and other stakeholders will have a better understanding of the key drivers for the enhancement of the new iron triangle in healthcare organisations. ORIGINALITY/VALUE: In this study, total interpretive structural modeling and cross-impact MICMAC analysis are proposed as an innovative approach to address the new iron triangle in healthcare organisations.

Humans↗

PubMed2026

Non-tobacco nicotine dependence and postoperative complications after total ankle arthroplasty: A propensity-matched cohort study.

BACKGROUND: The clinical impact of non-tobacco nicotine dependence (NTND) is poorly defined. This study evaluated the association between NTND and complications following total ankle arthroplasty (TAA). METHODS: A retrospective cohort study using the TriNetX Research Network was performed. Adults undergoing primary TAA (Current Procedural Terminology [CPT] 27702) between 2010 and 2025 were included. Patients were categorized into NTND (International Classification of Diseases, Tenth Revision [ICD-10]: F17, excluding tobacco-specific codes) and nonsmoker cohorts. Propensity score matching (1:1) yielded 939 NTND patients and 939 controls. Ninety-day medical and wound complications and ≥ 2-year mechanical outcomes were assessed. RESULTS: NTND patients had higher rates of 90-day readmission (11.7% vs 6.5%; OR 1.9), wound disruption (4.3% vs 2.6%; OR 1.7), surgical site infection (3.1% vs 1.6%; OR 2.0), and sepsis (2.4% vs 1.1%; OR 2.3). At a minimum 2-year follow-up, NTND was not associated with increased risk of mechanical complications. CONCLUSION: These findings challenge the assumption that smokeless nicotine products are benign in the perioperative setting and support incorporating NTND screening and cessation counseling into preoperative optimization protocols. Future prospective studies are warranted to further characterize the dose-dependent effects of non-tobacco nicotine exposure and to evaluate the impact of perioperative cessation strategies on outcomes following TAA. LEVEL OF EVIDENCE: IV.

Humans↗

PubMed2026

Measuring economic efficiency in adult intensive care units: A systematic review of methods, metrics, and evidence.

OBJECTIVES: Intensive care units (ICUs) consume substantial hospital resources, yet "efficiency" is inconsistently defined and measured. This study systematically reviewed how economic efficiency has been conceptualised and quantified in adult ICUs and appraised the quality of evidence. METHODS: Following PRISMA 2020 and a PROSPERO-registered protocol (CRD420251107866), we searched MEDLINE, Embase, CINAHL, Cochrane Library and Web of Science (2000-August 2025), plus global grey sources. Eligible studies explicitly defined efficiency and reported an efficiency metric/model linking ICU inputs (e.g., staff, beds/capacity, time, consumables, or costs) to outputs/outcomes (e.g., throughput/discharges, length of stay/resource use, risk-adjusted mortality). Dual independent screening and extraction were performed. Study quality was appraised using MMAT, and findings were synthesised narratively (SWiM), given heterogeneity. RESULTS: 39 studies (2001-2025) from 17 countries were included, all from high-income or upper-middle-income settings. Four methodological families were identified: (1) frontier modelling (predominantly DEA; occasional SFA/RFDH), (2) benchmarking indicators (risk-adjusted mortality and LOS/resource-use ratios; "efficiency matrix" quadrant classification), (3) cost-outcome evaluations, and (4) operational/process metrics. Across families, variation in decision-making units, input/output selection, and risk adjustment limited comparability; long-term and patient-reported outcomes were absent, and equity considerations were uncommon. CONCLUSIONS: ICU efficiency research is feasible but fragmented and often methodologically limited. Standardised definitions, validated risk adjustment, uncertainty quantification, and inclusion of patient-centred and equity-relevant outcomes are needed before efficiency metrics can reliably inform value-based decision making.

Intensive Care Units↗

PubMed2026

Xerophthalmia and ocular manifestations of vitamin A deficiency in children in high-income countries: A systematic review.

Xerophthalmia is a vision-threatening eye condition caused by vitamin A deficiency (VAD). Cases of xerophthalmia in high-income countries (HICs) are vulnerable to misdiagnosis, causing delays in treatment and adverse visual outcomes. We define the features, causes and complications of VAD and xerophthalmia in children of HICs. Our study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines (CRD42024492023). We performed a search for eligible articles on Scopus, Web of Science, Cochrane, PubMed and Medline. Cases reporting on children under 18 years of age residing in HICs with ocular features of VAD were eligible for inclusion. The search yielded 2474 results; 43 case reports and case series met the inclusion criteria consisting of a total of 61 cases (mean age 9.9 ± 4.2 years, range 3-17 years). Xerophthalmia was graded according to the most advanced finding for each case: 21.3% had night blindness only; 29.5% had conjunctival xerosis or Bitot spots; 29.5% had corneal xerosis, ulceration or scarring; 1.6% had xerophthalmia fundus only; and 18.0% had ocular manifestations associated with VAD that are not encompassed under the WHO classification. These features included swollen optic discs, optic neuropathy, or ocular dryness. Restrictive dietary practises were the most common mechanism of deficiency (75%), and autism was the most common underlying condition (49%). This shows that VAD remains a cause of severe visual impairment in HICs, especially when associated with delays in diagnosis and treatment. Further research is required to establish the prevalence of xerophthalmia in HICs.

Humans↗

PubMed2026

Improving insurance deduction identification: a hybrid artificial intelligence model using machine learning and expert systems.

PURPOSE: Financial challenges in healthcare systems worldwide, especially in low- and middle-income countries like Iran, have increased hospitals' reliance on insurance reimbursements. Unrecognized insurance deductions often cause severe financial shortages, making efficient deduction management crucial. This study aimed to design a hybrid intelligent system for identifying and predicting insurance deductions by combining machine learning and expert system frameworks. DESIGN/METHODOLOGY/APPROACH: A mixed-methods design was applied in four stages. First, a scoping review identified the causes and patterns of insurance deductions. Second, interviews with 15 insurance experts produced a validated checklist and a dataset from inpatient billing records. Third, using the CRISP-DM methodology, machine learning algorithms were developed and tested in SPSS Modeler alongside a fuzzy expert system developed in MATLAB. Finally, the model was validated using the holdout method. FINDINGS: Four categories of deduction drivers were identified: service provision, registration errors, document submission issues, and revenue conversion processes. The CHAID decision tree outperformed other algorithms with a 99% precision rate and the lowest Mean Absolute Error (9.43). A brief assessment of potential overfitting was conducted to ensure that the CHAID model's high accuracy was interpreted cautiously and supported by the validation results. The fuzzy expert system with validated rules was adaptable for deduction classification, especially for cases unsuitable for quantitative modeling. ORIGINALITY/VALUE: The hybrid model improves detection and prevention of deductions, offering actionable insights for hospital administrators, insurers, and policymakers. Its implementation can enhance hospital information systems, streamline claims processing, and optimize revenue management amid financial constraints.

Machine Learning↗

PubMed2026

Longitudinal whole-genome analysis of bluetongue virus identifies conserved serotype-specific genomes and distinct genomic constellations within a Colorado sheep flock (2021-2023).

Bluetongue virus (BTV) is a segmented double-stranded RNA virus of ruminants transmitted by Culicoides spp. biting midges. Although the genome consists of ten segments, classification into serotypes is primarily based on genome segment 2. However, reassortment among genomic segments is a major driver of BTV evolution and diversity. This study used longitudinal whole-genome sequencing to characterize BTV genomes collected from 2021 to 2023 within a single sheep flock in Colorado, where multiple serotypes co-circulate. Whole-genome sequences were generated from fourteen blood samples representing four serotypes: BTV-6, -11, -13, and -17. Longitudinal sampling identified multiple BTV serotypes within individual sheep across consecutive years. Tanglegram analysis comparing segment phylogenies to the segment 2 tree demonstrated incongruent topologies across all genomic segments, suggestive of reassortment or the circulation of distinct genomic constellations. Nucleotide-level comparisons revealed high sequence homology among same-serotype samples from the same year, while the greatest genetic divergence was observed among BTV-17 genomes collected in different years. Additionally, all BTV-13 genomes contained a previously undescribed nonsynonymous substitution in segment 10 predicted to extend the encoded protein by three amino acids. Together, these findings demonstrate that highly conserved BTV genomes and distinct genomic constellations can be detected at the flock level across multiple years. This longitudinal whole-genome approach reveals the genetic complexity of endemic BTV populations, including novel variants and genomic patterns consistent with reassortment that are lost with conventional serotyped-based approaches, highlighting the need to integrate whole-genome characterization into endemic BTV monitoring programs.

Animals↗

PubMed2026

Routine methods misidentify Serratia spp.: Limitations of MALDI-TOF MS revealed by whole-genome sequencing.

Accurate species-level identification within the genus Serratia remains challenging due to extensive phenotypic overlap and high genomic relatedness among closely related and recently described taxa. This study presents an evaluation of routine and genome-based identification approaches applied to clinical Serratia isolates, integrating phenotypic assays, MALDI-TOF MS (Bruker Daltonics), 16S rRNA gene sequencing, and Whole-Genome Sequencing (WGS). A total of 103 isolates collected from a teaching hospital were analyzed. WGS was performed on a subset of isolates. Conventional biochemical methods classified all isolates as Serratia marcescens, whereas MALDI-TOF MS identified 60.1% as S. marcescens, 11.6% as S. ureilytica, and 28.1% just at the genus level. Peak analysis from MALDI-TOF MS revealed specific peaks associated with S. marcescens and S. ureilytica, but limited discriminatory power. WGS of six isolates initially identified as S. ureilytica by MALDI-TOF MS revealed reclassification as Serratia sarumanii (n = 5) and Serratia montpellierensis (n = 1), supported by Average Nucleotide Identity (ANI), Average Amino Acid Identity (AAI), and Digital DNA-DNA Hybridization (dDDH) thresholds. In contrast, 16S rRNA analysis showed limited species-level resolution. Phylogenomic and SNP-based analyses confirmed these classifications with strong support. Overall, this study underscores the critical role of high-resolution genomic approaches for precise species identification and highlights the need for continuous expansion and curation of MALDI-TOF MS reference databases to support reliable clinical diagnostics and epidemiological surveillance of emerging Serratia species.

Spectrometry, Mass, Matrix-Assisted Laser Desorpti↗

PubMed2026

Psychiatric Diagnoses and Psychotropic Medications Among Military-Affiliated Adolescents and Young Adults With Polycystic Ovary Syndrome.

PURPOSE: To study rates of psychiatric diagnoses and psychotropic medication prescription among U.S. military-affiliated adolescents and young adults (AYA) with polycystic ovary syndrome (PCOS). METHODS: This retrospective matched cohort study included U.S. military-affiliated AYA (aged 15-21 years) enrolled in TRICARE Prime for at least 6 months during the surveillance period (January 2016 to October 2023). Military-affiliated AYA were grouped into three categories: individuals diagnosed with PCOS (N = 6,911), age-matched individuals with no diagnosed PCOS symptoms (N = 35,814), and individuals with diagnosed symptoms suggestive of PCOS (N = 2,136). The presence of a psychiatric diagnoses and prescriptions for psychotropic medications were obtained via the International Classification of Diseases, 10th Revision, Clinical Modification codes and National Drug codes, respectively. RESULTS: AYA with diagnosed PCOS had higher odds of having a psychiatric diagnosis and being prescribed a psychotropic medication compared to an age-matched comparison group (psychiatric diagnosis odds ratio [OR] = 2.48 [2.35-2.62], medication OR = 2.14 [2.03-2.25]) and individuals with symptoms suggestive of PCOS (psychiatric diagnosis OR = 1.11 [1.003-1.23], medication OR = 1.16 [1.05-1.28]). DISCUSSION: The odds of psychiatric comorbidities and psychotropic medication prescription were more than twice as high as among U.S. military-affiliated AYA with PCOS. More research is needed to determine whether health-care utilization and military-related factors impact mental health outcomes among AYA with PCOS. Additionally, tailored, multidisciplinary mental health services for AYA with PCOS are needed.

Humans↗

PubMed2026

Screening for neurofibromatosis type 1-related optic pathway gliomas: a systematic review.

BACKGROUND: Neurofibromatosis-type 1 (NF1) is a genetic disorder characterized by developing optic pathway gliomas (OPGs) in 15%-20% of patients with higher estimates where consanguinity is prevalent. Clinically, NF1-OPG might be unpredictable with the risk of OPG progression and visual impairment. The optimal time for screening is controversial. We aim to identify the mean/median age at diagnosis of NF1-OPG and its clinical spectrum. METHODS: A systematic review of PubMed, Web of Science, and Embase databases was conducted for English-language publications from January 1993 to October 2025, exploring the visual screening of OPGs in NF1 patients, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered in the Prospective Register of Systematic Reviews (PROSPERO ID: CRD420251036244). Inclusion criteria focused on studies reporting the age at OPG diagnosis and visual manifestations in NF1 patients. Data were extracted on demographics, age at NF1 and OPG diagnosis, tumour location (using the Dodge classification), and presenting symptoms. Sixteen studies met the inclusion criteria. RESULTS: Among 4 739 NF1 patients, 818 had OPGs, with prevalence ranging from 4.2% to 46.7%. The age at NF1 diagnosis ranged from 0 to 132 months (mean: 18-38 months), and at OPG diagnosis from 0-240 months (median: 29-58 months). Approximately 58.4% of OPGs were asymptomatic, and 25% were above the age of 5 years. Among symptomatic patients, the most frequent presentations included decreased visual acuity (62%), abnormal optic disc (45%), proptosis (20%), strabismus (12%), and visual field defects (7%). CONCLUSIONS: NF1-related OPGs typically present early within 6 years of age. Early ophthalmologic and/or radiologic screening at the time of NF1 diagnosis enhances the detection of silent OPGs.

Humans↗

PubMed2026

From commensal to pathobiont: The emergence of virulence-enhanced Escherichia coli in China's food-animal systems - insights with future implications.

A fundamental shift in Escherichia coli epidemiology is being driven by convergence of virulence determinants and antimicrobial resistance within linked human-animal-environment systems. In China, the rapid growth of food-animal production, extensive antimicrobial use, and complex food networks are accelerating the emergence and dissemination of virulence-enhanced E. coli pathobionts. This review synthesizes recent epidemiological, genomics, and outbreak data to characterize China's evolving landscape of food-animal-associated E. coli. We highlight a significant shift from classical pathotypes to hybrid lineages that simultaneously carry virulence factors and last-resort antibiotic resistance determinants, including mcr-1, tet(X4), and blaNDM. These traits disseminate rapidly via plasmid-mediated horizontal gene transfer, facilitating rapid adaptation and enabling cross-sectoral One Health transmission. National surveillance, foodborne outbreak investigations, and whole-genome sequencing data show that food-animal reservoirs are active evolutionary niches that drive pathogen diversity and fitness, rather than serving merely as contamination sources. Whole-genome sequencing also pinpoints high-risk clones (e.g., ST394) and plasmid-mediated co-selection of virulence and AMR. The emergence of hybrid pathotypes (e.g., STEC/ETEC) and AMR-virulence co-selection challenges traditional classification and limits the effectiveness of conventional surveillance approaches. The 2017 colistin ban reduced mcr-1, yet ongoing resistance and emerging tet(X4) demand integrated surveillance. Collectively, these findings call for reconceptualizing E. coli as a dynamic genomic entity embedded within a unified ecological network. Addressing this threat requires an integrated One Health strategy including genomic surveillance, agricultural antimicrobial stewardship, and coordinated food-environment-clinical monitoring to prevent high-risk clone emergence and global spread.

Animals↗

PubMed2026

Ruling out pediatric bacterial epididymo-orchitis with urinalysis - The case for minimizing unnecessary antibiotic prescription.

INTRODUCTION: Epididymo-orchitis in pediatric patients is predominantly non-bacterial, often stemming from viral or reactive etiologies. Despite guidelines recommending conservative management for non-bacterial cases, antibiotic overtreatment remains prevalent in the outpatient setting. We evaluated the diagnostic accuracy of urinalysis in ruling out bacterial infection to support antibiotic stewardship in this population. METHODS: We conducted a cross-sectional diagnostic accuracy study using electronic health records from a large health maintenance organization in Israel. The cohort included patients younger than 18 years with a diagnosis of epididymo-orchitis or clinically overlapping entities (acute scrotum, appendage torsion) who had paired urinalysis and urine culture results within one week of diagnosis. Logistic regression and ROC curve analysis were performed to assess the ability of urinalysis parameters to predict positive urine cultures. RESULTS: Of 682 eligible cases, confirmed bacterial infection was rare, occurring in only 17 patients (2.5%). Nitrite positivity was the strongest independent predictor of infection (OR 43.98; p < 0.001). A prediction model incorporating all urinalysis parameters yielded an area under the curve (AUC) of 0.825 and achieved a 97.7% classification accuracy for correctly predicting negative cultures. Despite the low prevalence of infection, antibiotics were prescribed in 237 cases (34.7%). Urinary anatomic abnormalities were significantly associated with culture positivity. CONCLUSIONS: Bacterial coinfection in pediatric epididymo-orchitis is uncommon. Urinalysis serves as a highly accurate screening tool to rule out bacterial etiology. A negative urinalysis supports withholding antibiotics in this setting, reserving treatment for children with positive markers or known anatomic abnormalities. This evidence-based approach This evidence-based approach has the potential to reduce unnecessary antibiotic exposure, however prospective studies are needed to validate these findings before broad implementation.

Humans↗

PubMed2026

Exploratory proteomic and metabolomic profiling of pleural effusions identifies histone H4 and alanine as promising complementary markers for pleural tuberculosis.

The diagnosis of pleural tuberculosis (Pl-TB) remains challenging. Histopathological analysis and pathogen detection in pleural biopsies are informative but limited. We investigated differentially expressed proteins and metabolites in pleural effusions from patients with Pl-TB, malignancies, and other pathologies. A proteomic analysis of pooled pleural effusions identified 45 proteins exclusively detected or upregulated in Pl-TB samples, many linked to infectious processes. Conversely, 18 proteins were uniquely found or upregulated in malignant pleural effusions, mainly associated with detoxification and hemostasis. To validate these findings, we employed targeted proteomics in individual samples. Eight proteins were validated: S100-A9, histone H4, insulin-like growth factor-binding protein 2, fibrinogen beta chain, ficolin-3, immunoglobulin heavy constant alpha 1, sulfhydryl oxidase 1, and histidine-rich glycoprotein. Additionally, NMR-based metabolomics identified 13 metabolites with differential abundance between Pl-TB and non-TB samples. Notably, N-acetyl-glycoprotein and the branched-chain amino acids, alanine and lysine differed between groups. Proteomic and metabolomic analyses revealed distinct molecular profiles between Pl-TB and non-TB patients, despite intra-group variability. To address this, we applied classification models. Histone H4 and alanine consistently emerged as discriminative features. Overall, this study provides novel insights into the molecular landscape of Pl-TB. The combined quantification of proteins and metabolites may improve differential diagnosis, although should be further validated in larger, independent cohorts before clinical application.

Humans↗

PubMed2026

New Evidence in Heart Failure: 2026 Update.

Heart failure (HF) remains a major cause of morbidity, mortality, impaired quality of life and healthcare expenditure worldwide. The global burden of HF continues to increase due to population aging, improved survival, and the growing prevalence of cardiovascular, renal, and metabolic comorbidities. Simultaneously, the pace of scientific progress in HF has accelerated considerably. Recent advances have refined our understanding of HF epidemiology, prognosis, and disease trajectories, including emerging concepts of HF improvement, remission, and recovery. The Second Universal Definition of HF has also updated the classification framework, moving beyond the traditional ejection fraction-based categories. HF is now broadly classified into two major phenotypes: heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Novel mechanistic insights highlight the role of inflammation, immune activation, metabolic dysfunction, mitochondrial biology, and multisystem interactions in HF progression. There has also been significant progress in the characterization and management of major comorbidities, including chronic kidney disease (CKD), diabetes, obesity, atrial fibrillation (AF), pulmonary hypertension, frailty, malnutrition, and cancer. Diagnostic innovations include novel biomarkers, multi-omics technologies, artificial intelligence-based approaches, advanced imaging techniques, congestion assessment tools, and emerging digital health solutions. Important advances have occurred in specific HF aetiologies, including cardiomyopathies, cardiac amyloidosis (CA), myocarditis, arrhythmia-induced cardiomyopathy (AiCM), and Chagas cardiomyopathy. Therapeutic developments continue to reshape HF management across the spectrum of left ventricular ejection fraction. Recent evidence has focused on optimization of guideline-directed medical therapy in HFrEF, expansion of evidence-based therapies in HFpEF, and growing roles for sodium-glucose cotransporter-2 inhibitors, finerenone, incretin-based therapies, and transcatheter valve interventions. Collectively, these advances support the transition from a predominantly phenotype-based approach towards a more personalized and biologically informed model of HF care, with the potential to further improve outcomes across the entire HF spectrum.

Journal Article↗

PubMed2026

Quality assessment, prognostic factors, and biomarkers for brain tumor analysis: a comprehensive systematic review.

The brain tumors possess different causative factors and properties, making their diagnosis and treatment difficult. Growth of these cancers usually leads to compression of the adjacent nerves and obstruction of the flow of cerebrospinal fluid, thus leading to increase in intracranial pressure. This affects the working of brain in many ways; thus, the difficulty involved in its treatment. With the improvements in technology in neuroimaging, including Diffusion Tensor Imaging (DTI), Positron Emission Tomography (PET), and multiparametric Magnetic Resonance Imaging (mpMRI), the diagnosis process has become easy. The effectiveness of any form of therapy in such patients depends primarily on their prognosis. While it is a common practice that physicians determine the prognosis of the disease by considering the age of the patient, histological grade of the tumor, and resection status, now this method has become more comprehensive by adding molecular signature and genetic analyses to the list of criteria. Next-generation sequencing (NGS) allows a reliable molecular classification. It increases the level of risk stratification, facilitating the application of therapies tailored to individual patients. Thus, molecular oncology has greatly changed our views on brain tumors' pathology and prognosis while neoadjuvant treatments aim at increasing the survival rate. On the other hand, radiogenomics is a field of study that combines non-invasive imaging phenotypes and genomic information in order to find unique molecular signatures of tumors without collecting samples from tumors. Molecular biomarkers are absolutely essential in the diagnosis of cancer, treatment monitoring, and recurrence of cancer. Advances in liquid biopsy technology, particularly the methods for circulating tumor DNA (ctDNA) and Extracellular Vesicle (EV) based analysis, have enabled the possibility of non-invasive monitoring of the progression of the tumors over time. This review highlights key studies and important scientific works about imaging technologies, biomarkers, and prognostic factors of malignant brain tumors.

Humans↗

PubMed2026

Non-motor symptoms and healthcare utilization before diagnosis of myasthenia gravis: a nationwide cohort study.

BACKGROUND: Non-motor symptoms have been reported prior to myasthenia gravis (MG) diagnosis. However, the temporal patterns of non-motor symptoms and healthcare utilization before MG diagnosis remain unclear. METHODS: We conducted a retrospective, population-based cohort study using the Korean National Health Insurance Service (KNHIS) database from 2011 to 2021. Incident MG cases were identified using the International Classification of Diseases, Tenth and Rare Intractable Disease codes. Individuals younger than 20  years or with missing health screening data were excluded. Each MG case was matched 1:10 by age, sex, and index date to controls. Non-motor symptoms and healthcare utilization were defined using operational criteria derived from KNHIS claims data. Rate ratios (RRs) and 95 % confidence intervals (CIs) were estimated across four prespecified intervals (0-1, 1-2, 2-5, and 5-10  years) before MG diagnosis. RESULTS: We included 8,355 MG patients and 83,550 controls (mean age, 53.7  years; male, 44 %). MG patients had higher rates of any non-motor symptoms over 10  years(RR 1.34; 95 % CI 1.30-1.39), with the sharpest increase in the year before diagnosis. Depression, anxiety, migraine, constipation, and insomnia consistently showed higher RRs across all intervals. Hospitalizations (RR 1.66; 95 % CI 1.61-1.71) and outpatient clinic visits (RR 1.10; 95 % CI 1.04-1.17) were consistently higher across 10  years, peaking during the 0-1 year before MG diagnosis. CONCLUSION: Non-motor symptoms and healthcare utilization increased years before MG diagnosis. Earlier recognition of these symptom patterns may facilitate timelier evaluation for MG and improve diagnostic pathways.

Humans↗