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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

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

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

The potential of clustering methods for pre-test triage in sleep medicine: A systematic review.

Sleep disorders exhibit substantial heterogeneity, and traditional classifications may not fully capture clinically relevant subtypes. Clustering techniques can identify patient subgroups that improve phenotypic characterization and may support personalized management. This systematic review evaluated the application of clustering in sleep medicine, with particular focus on its potential use as a pre-test triage tool prior to formal sleep testing. PubMed/MEDLINE, Embase, Web of Science, and Scopus were searched to February 2025. Eligible studies applied clustering to classify sleep disorders in adults. Two reviewers independently conducted screening, data extraction, and risk-of-bias assessment using QUADAS-2. The protocol was registered on PROSPERO. Fifty-one studies (1983-2025) were included, predominantly focused on obstructive sleep apnea (OSA) (n = 38, 74%). Hierarchical clustering (n = 20) and K-means clustering (n = 14) were the most frequently used techniques. Internal validation was reported in only 18% of studies, and external validation was reported in only 1 study. Seven studies relied exclusively on baseline clinical, demographic, or questionnaire data, representing pre-test scenarios, whereas most incorporated polysomnography-derived variables, limiting their applicability to early clinical stratification. Hierarchical clustering was the most commonly applied method; however, the overall lack of validation limits confidence in the robustness and clinical applicability of identified phenotypes. The potential role of clustering as a pre-test triage strategy remains largely unexplored, as most studies focused on post-diagnostic phenotyping and were affected by incorporation bias. Future research should prioritize pre-test clinical variables, rigorously validate internally and externally, and adopt standardized methodological and reporting practices to facilitate clinical translation.

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↗

PubMed2026

Meningioma methylation profiling as a complement to WHO grading: a single-center experience.

OBJECTIVE: The methylation profile of meningiomas is a promising predictive tool that may improve risk stratification beyond WHO grading. This study aimed to evaluate the clinical relevance and real-world applicability of routine epigenetic testing in meningioma management. METHODS: The authors retrospectively analyzed patients who underwent meningioma resection between January 2021 and December 2023. Histopathological grading (WHO 2021) and methylation profiling (methylation class [MC]) with the MethylationEPIC v1.0 (850k) chip were performed by an independent neuropathologist. RESULTS: A total of 106 patients were included; 81 tumors (76%) were classified as WHO grade 1, 20 (19%) as grade 2, and 5 (5%) as grade 3. Epigenetically, 55 tumors (52%) were classified as benign, 18 (17%) as intermediate, and 2 (2%) as malignant; 31 (29%) could not be classified. Discordances between WHO grading and methylation profiling were observed in 18 of 74 cases. Tumor board decisions were made after a median of 8 days postoperatively, guided by WHO grading; however, the epigenetic report was only available after a median of 23 days. During follow-up, 20 patients experienced tumor progression. Progression was significantly associated with the MC (r = -0.4, p < 0.001) and tumor volume (r = 0.4, p = 0.0005), but not with WHO grading (r = 0.17, p = 0.084). However, the relatively high rate of unclassified tumors and delayed result availability limited the direct impact of MC profiling on immediate clinical decision-making. Interestingly, progression-free survival in MC-unclassified tumors mirrored that of the intermediate group. CONCLUSIONS: Methylation profiling demonstrates superior predictive accuracy for meningioma progression and complements WHO grading, especially in identifying malignant meningiomas. However, its current clinical utility is constrained by technical and logistical limitations. In real-world practice, epigenetic classification should therefore be considered a complementary tool rather than a replacement for established histopathological assessment.

Humans↗

PubMed2026

Diagnostic value of blood p-tau subtypes in Alzheimer's disease progression and pathology: systematic review and meta-analysis.

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease and the most likely to lead to dementia. With the availability of the latest therapies, the need for Alzheimer's disease diagnosis is now gradually increasing. Whereas blood phosphorylated-tau (p-tau) has demonstrated excellent performance in the prediction and diagnosis of disease progression and Aβ positivity in AD, there are differences between different p-tau subtypes. Therefore, a pooled analysis of different blood p-tau subtypes is of more important clinical value. METHOD: Relevant literature was screened by complete search in four databases, Pubmed, Embase, Cochrane Library and Scopus. Relevant data and AUC and their confidence intervals of the included literature were extracted and analyzed by classification according to p-tau subtypes. Quality assessment was performed using the QUADAS-2 tool. RESULT: Our results reveal that p-tau217 performs better in the diagnostic performance in most stages of AD, which is consistent with the guidelines. However, our results concluded that p-tau217 has poorer diagnostic performance in the stages of cognitive unimpaired or less cognitively impaired, especially in the Aβ positivity diagnosis of SCD and CU. Head-to-head meta-analyses formally confirmed that p-tau217 significantly outperforms p-tau181 across AD dementia, Aβ positivity, tau positivity, and biological staging (all P < 0.05), whereas no significant difference was observed between p-tau231 and p-tau181. CONCLUSION: By integrating single-arm pooled AUC estimates with formal head-to-head statistical comparisons, our study provides evidence-based support for plasma p-tau217 as the subtype with the most robust diagnostic performance across AD pathology and biological staging. Head-to-head analyses formally confirmed that p-tau217 significantly outperforms p-tau181 in Aβ positivity, Tau positivity, and biological staging.

Humans↗

PubMed2026

Responding to a protracted tuberculosis outbreak: lessons from multiple rounds of investigation in a Chinese boarding school.

PURPOSE: This study analysed a multi-semester pulmonary tuberculosis (PTB) cluster outbreak in a Chinese boarding school to provide evidence for future epidemic control. METHODS: Contacts were screened via symptoms, infection tests and chest radiography. Screening expanded progressively from close contacts to same-floor contacts, then all students and staff. Whole-genome sequencing (WGS) with single nucleotide polymorphism (SNP) and bioinformatics analysis was used for lineage classification, transmission clustering (≤12 SNPs defining a cluster) and drug resistance prediction. RESULTS: From 2020 to 2022, 20 students were diagnosed with PTB, half laboratory-confirmed. Most cases clustered in class 16 and were epidemiologically linked to the primary case (case 0), who had household PTB exposure. Case 0 and case 1 had diagnostic delays exceeding 3 and 6 months, respectively. WGS of five isolates (case 1, 3, 4, 9 and 10) collected over three semesters showed all belonged to lineage 2 and differed by ≤12 SNPs, confirming the same transmission chain. The infection rate in class 16 (46.34%) was significantly higher than other case classes (19.05%) and classes without cases (8.27%) (χ2 = 61.169, p < 0.001). No new cases were detected during a one-year follow-up of students involved in the outbreak after the final round of screening, nor among household contacts of all cases followed up to the present. CONCLUSIONS: Lack of entry health examinations facilitated the outbreak. Delayed diagnosis, incomplete contact screening and absence of preventive treatment led to cross-semester persistence. The infection rate disparity confirms class 16 as the outbreak epicentre. Improving community case management, extending contact follow-up and enhancing cluster outbreak measures are recommended to prevent future outbreaks.

Humans↗

PubMed2026

Clinicopathological response and survival outcomes of HER2-low versus HER2-zero early breast Cancer: A systematic review and Meta-analysis.

BACKGROUND: Breast cancer is the most common malignant tumor in women. Human epidermal growth factor receptor 2 (HER2) is a key biomarker for classification and treatment. A subgroup with HER2-low expression has been identified, but existing evidence is heterogeneous. This systematic review and meta-analysis compared pathological response and survival outcomes between HER2-low and HER2-zero early-stage breast cancer to clarify prognostic features. METHODS: This study followed PRISMA guidelines and was registered in PROSPERO (CRD420251120506). PubMed, Embase, Web of Science, ClinicalTrials.gov, and major oncology conferences were searched through September 2025. Cohort studies of early-stage breast cancer comparing HER2-low (IHC 1+/2+ and ISH-negative) vs. HER2-zero with extractable pCR, DFS, or OS data were included. Studies involving HER2-positive patients or inconsistent definitions were excluded. Meta-analyses were performed using RevMan 5.3. RESULTS: Twenty-eight studies involving 115,182 patients were included. HER2-low patients showed significantly lower pCR rates (OR = 0.58, 95% CI: 0.52-0.65). DFS favored HER2-low (multivariate HR = 0.75, 95% CI: 0.69-0.83), especially in HR+ tumors, with a weaker effect in HR- cases. OS also favored HER2-low (HR = 0.80, 95% CI: 0.72-0.89), mainly driven by the HR- subgroup; no OS difference was seen in HR+ tumors. Sensitivity analyses and funnel plots indicated robust results with no apparent publication bias. Overall study quality was high (17 high-quality, 11 moderate-quality). CONCLUSION: HER2-low early breast cancer shows lower pCR after neoadjuvant therapy but better long-term survival. These findings support the clinical relevance of HER2-low as a biologically meaningful subgroup within HER2-negative disease, while its status as a stable and independent subtype still requires further validation through prospective studies, standardized testing, and multi-omics investigation.

Humans↗

PubMed2026

CL16019, A Combination of Cissus quadrangularis and Boswellia serrata Extracts Promotes the Healing of Distal Radius Fractures: A Multicentric, Randomized, Open-Label Study.

OBJECTIVE: Distal radius fracture (DRF) is the most frequent injury to the upper limb. Complications include nonunion, wrist stiffness and instability, local discomfort, and tendon irritation. The purpose of the current open-label clinical study was to evaluate the safety, efficacy, and tolerability of CL16019, an herbal formulation of Cissus quadrangularis and Boswellia serrata extract, in accelerating fracture healing in volunteers with DRFs. METHODS: Fifty participants (both male and female; age: 30-50 years) with type I, IIA, or IIB DRFs (as per Lidstrom classification) were equally randomized and treated with standard treatment (ST) or ST + CL16019 for 60 days. The primary efficacy outcome was the radiographical bone fracture healing rate as scored by the Radius Union Scoring System (RUSS). Pain, swelling, and tenderness were among the clinical characteristics evaluated using the visual analog scale (VAS). Wrist function improvements were assessed using the Patient-Rated Wrist Evaluation Questionnaire (PRWEQ). The intergroup and intragroup results were analyzed using a paired t-test and an analysis of covariance model, respectively. RESULTS: The RUSS scores for the ST and ST + CL16019 groups at the end of the trial were 5.54 ± 1.77 and 7.96 ± 0.20, respectively, with a p-value <0.0001. In addition, the CL16019 volunteers showed substantial (p < 0.05) declines in their VAS and PRWEQ scores. The ST + CL16019 group demonstrated higher Physician Global Assessment and Subject Global Assessment scores. CONCLUSIONS: Supplementation of CL16019 along with standard therapy was found to enhance the bone fracture healing rate, possibly by accelerating the callus formation rate and enhancing cortical bridging. These findings imply that CL16019 might be a good adjunctive in addition to ST for the faster healing of DRFs. The trial was registered with the Clinical Trial Registry of India (CTRI) with the registration number CTRI/2021/12/039006, on December 29, 2021.

Humans↗

PubMed2026

Genome-wide identification and expression profiling of HSD3B and SDR42E1 genes in the Pacific oyster (Crassostrea gigas): potential associations with gonadal development.

Sex steroids are lipid-soluble signaling molecules that regulate sex differentiation, reproductive development and physiological homeostasis in animals. 3β-Hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase (3β-HSD) is a key steroidogenic enzyme, whereas SDR42E1, an extended short-chain dehydrogenase/reductase, has been implicated in sterol- and steroid-related metabolism. However, the composition, evolutionary relationships and expression patterns of the HSD3B- and SDR42E1-related genes in bivalve gonadal development remain poorly characterized. In this study, five PF01073-containing genes, comprising three CgHsd3b and two CgSdr42e1 genes, were identified in the Pacific oyster Crassostrea gigas. Phylogenetic analysis separated the proteins into HSD3B-related and SDR42E1-related groups, and gene-structure and motif analyses indicated subfamily-level divergence. All five proteins retained the SDR domain but differed in exon-intron structure and motif composition. Each contained the extended-SDR TGxxGxxG motif, whereas exact classical [ST]GxxxGxG and NNAG motifs were absent. Tyr- and Lys-equivalent residues were conserved, while the HSD3B1 Ser-equivalent position contained Thr in two C. gigas proteins and Ser in one. These features support their classification as extended-SDR proteins but do not establish enzymatic activity or substrate specificity. The three CgHsd3b genes were dispersed on one chromosome, whereas CgSdr42e1-1 and CgSdr42e1-2 were adjacent on another chromosome, suggesting a possible local duplication event for the CgSdr42e1 pair. Public RNA-seq data showed distinct tissue- and gonadal-stage expression patterns, with several genes displaying gonad-biased or female-stage-associated expression. Independent RT-qPCR profiling of the representative genes CgHsd3b-3 and CgSdr42e1-1 detected stage-dependent expression, although tissue rankings differed from those in the public RNA-seq datasets. These differences may reflect the use of independent biological samples, tissue composition, normalization procedures, and platform-specific measurements. Because enzymatic assays, metabolite measurements, cellular localization, and functional perturbation were not performed, the results identify candidate genes whose expression is associated with gonadal development rather than demonstrating regulatory roles. This study provides a comparative framework for future functional investigation of sterol- and steroid-related metabolism in bivalves.

Animals↗