• Making Symptoms Visible: The Impact of Real-Time PROM Integration in Pediatric Oncology.
    1 day ago
    Background/Objectives: Children undergoing cancer treatment experience multiple distressing symptoms that often go undetected in routine care. This study evaluated the potential impact of integrating the Symptom Screening in Pediatrics Tool (SSPedi) into clinical workflows, focusing on symptom detection and implications for service delivery. Methods: Seventy children (aged 4-18 years) receiving active treatment, and/or their caregivers completed SSPedi weekly for eight weeks (n = 479 completions). Medical records were audited for documentation of symptom assessments and symptom prevalence. SSPedi completions were categorized using a clinical algorithm (low, moderate, immediate concerns) and compared with score-only threshold. Results: The most bothersome symptoms were appetite changes (12%), fatigue (11%), nausea/vomiting (9%) and pain (9%). Severe bother detected by SSPedi was more frequent while hospitalized than at home (e.g., appetite changes 17% versus 9%). Documentation rates of severe symptoms in medical records were substantially lower than SSPedi reports-12% when SSPedi was completed at home and 49% when completed in hospital. Applying the clinical algorithm flagged 58% of SSPedi completions as an immediate concern in home and 63% in hospital, compared with score-only thresholds (31% at home and 17% in hospital). Algorithm-based alerts for immediate concerns would have triggered almost twice as many phone calls as score-based thresholds (168 vs. 91). Conclusions: Routine PROM integration could improve symptom detection and timely intervention. Clinical algorithms enhance sensitivity but increase alert burden, highlighting the need to review thresholds and redesign workflows.
    Cancer
    Care/Management
  • Thrombo-inflammatory endothelial signatures in JAK2 -mutated myeloproliferative neoplasms.
    1 day ago
    Classical myeloproliferative neoplasms (MPN)-essential thrombocythemia, polycythemia vera, and primary myelofibrosis-are characterized by clonal hematopoiesis, overproduction of mature blood cells, and a high burden of thromboembolic events. Although thrombosis is the leading cause of morbidity and mortality in MPN, the contribution of the vascular endothelium remains incompletely defined. We investigated patient-derived endothelial colony-forming cells (ECFCs) as a surrogate for vascular endothelium in individuals with JAK2 V617F-mutated MPN.

    ECFCs were cultured from peripheral blood of patients with MPN and healthy controls, phenotyped for thrombo-inflammatory and adhesive markers, tested for JAK2 V617F, and profiled by bulk RNA sequencing. Functional assays assessed endothelial-dependent factor Xa generation. Transcriptomes were benchmarked against public HUVEC reference datasets processed through an identical quantification pipeline.

    ECFCs were obtained more frequently and in greater numbers from patients with MPN than from controls, indicating enhanced endothelial regenerative or activation potential. MPN ECFCs exhibited increased von Willebrand factor and P-selectin expression and release, along with elevated endothelial cell-dependent factor Xa generation, consistent with a thrombo-inflammatory, procoagulant phenotype. JAK2 V617F was not detected in any ECFC colonies, supporting a non-clonal origin of these endothelial abnormalities. Transcriptomic analysis identified 289 differentially expressed genes in MPN versus control ECFCs, with pathway enrichment revealing coordinated dysregulation of blood coagulation, platelet activation, plasminogen regulation, vascular permeability, extracellular matrix organization, and angiogenesis. Benchmarking against HUVEC datasets confirmed strong endothelial identity of ECFC-derived cells, with MPN-associated changes reflecting endothelial activation rather than loss of endothelialness.

    ECFCs from patients with JAK2-mutated MPN display functional and transcriptomic signatures of endothelial dysfunction in the absence of detectable driver mutations. These findings support a model in which a primed, thrombo-inflammatory endothelium cooperates with clonal hematopoiesis to promote the heightened thrombotic risk characteristic of MPN.
    Cancer
    Policy
  • Affect-focused psychodynamic psychotherapy for mothers diagnosed with cancer - A feasibility study.
    1 day ago
    Parents with cancer face elevated psychological distress, often exacerbated by parenting responsibilities. Affect-Focused Psychodynamic Therapy (AFPT) has shown efficacy in improving emotion regulation, psychological well-being and self-compassion, but its feasibility and preliminary effect in this population remains unexplored.

    The aim of this study was to evaluate the feasibility, acceptability, safety, and preliminary effects on symptoms of depression and anxiety, of AFPT delivered via videoconferencing for parents with cancer.

    The intervention consisted of 10 sessions of AFPT, specifically affect phobia therapy. Qualitative data were collected through post-intervention interviews and analysed using inductive content analysis. Quantitative data were collected through self-report questionnaires at pre-intervention, post-intervention, and at 6-month follow-up measuring symptoms of depression and anxiety (primary outcome), parenting concerns, emotion regulation, self-efficacy, adaptive affective functioning, closeness in the family and self-rated health. Quantitative data were analysed using dependent-samples t-tests, with Cohen's d for effect sizes, and McNemar tests.

    Fifteen mothers with cancer participated in the study. Results demonstrated efficient recruitment, acceptable study procedures, complete retention, and a relevant and beneficial intervention rated 8.4/10 in helpfulness. Moreover, findings showed significant reductions in symptoms of depression (Cohen's d = 1.29) and of anxiety (Cohen's d = 1.06) from pre- to post-intervention, maintained at 6-month follow-up, together with improvements in a majority of the secondary outcomes.

    Videoconferencing AFPT appears feasible, acceptable, and safe to use for mothers with cancer, with promising preliminary effects in reducing psychological distress. These findings support further evaluation of the intervention to determine its efficacy in this population using a randomized controlled trial.
    Cancer
    Mental Health
    Policy
  • Respiratory Infection-Related Pathogens in the Pediatric Intensive Care Unit During 2019-2024 in Hubei, China.
    1 day ago
    Respiratory infections are a leading cause of hospitalization and mortality in children, and the pediatric intensive care unit (PICU) is a critical setting for managing severe cases. However, the epidemiological patterns of respiratory pathogens in the PICU remain insufficiently characterized. In this retrospective study, we analyzed respiratory pathogen testing results from 2126 pediatric patients admitted to the PICU of Wuhan Children's Hospital between 2019 and 2024. The pathogen spectrum and epidemiological characteristics were evaluated across age groups and seasons. Respiratory syncytial virus (RSV, 18.06%) was the most frequently detected viral pathogen, while Streptococcus pneumoniae (6.96%) was the predominant non-viral pathogen. The overall infection burden was highest in children aged ≤ 1 year (53.75%) and 3 < age ≤ 6 years (54.70%), indicating that early childhood represents a high-risk period for severe respiratory infections requiring intensive care. Pathogen distribution varied significantly across age groups. Distinct seasonal patterns were observed for several respiratory pathogens, particularly among viral pathogens, whereas non-viral pathogens showed more variable seasonal distributions. Furthermore, screening for 10 common pathogens accounted for 75% of PICU respiratory infections, highlighting the clinical utility of multiplex molecular detection. This study delineates the pathogen spectrum of respiratory tract infections in the PICU and characterizes their age- and season-specific epidemiological patterns. This study defines the pathogen spectrum and age- and season-specific patterns of respiratory infections in the PICU, providing evidence to support targeted pathogen surveillance, optimized multiplex diagnostics, and risk-informed infection control strategies in pediatric critical care.
    Chronic respiratory disease
    Care/Management
  • Molecular Lineage Replacement and Shifted Seasonality of Pediatric Respiratory Syncytial Virus on Tropical Hainan Island, China, 2021-2024.
    1 day ago
    Respiratory syncytial virus (RSV) resurged in many regions after the relaxation of stringent non-pharmaceutical interventions (NPIs) implemented during the COVID-19 pandemic. Here, we characterized the epidemiological patterns and molecular evolution of RSV among pediatric inpatients with acute respiratory tract infections (ARTIs) on tropical Hainan Island, China. We retrospectively analyzed 32,329 children (≤18 years) hospitalized at Hainan Women and Children's Medical Center from January 2021 to December 2024. RSV positivity was determined using targeted next-generation sequencing. In total, 4483/32,329 (13.86%) patients were RSV-positive, with a high positivity in 2021 (20.27%, 957/4721), marked suppression in 2022 (2.03%, 106/5227) during intensive NPIs, and a rebound in 2023-2024 (15.31%, 1490/9732; 15.26%, 1930/12,649). RSV positivity was higher in boys than girls (14.42% vs. 13.00%). Seasonality shifted from a summer-autumn peak in 2021 to a spring-summer predominance in 2023-2024. Among 56 sequenced RSV-positive specimens (29 RSV-A; 27 RSV-B), all RSV-A strains belonged to genotype ON1 (lineages A.D.3 and A.D.5.2), and all RSV-B strains belonged to genotype BA9 (lineages B.D.4.1.1, B.D.E.1, and B.D.E.2). Subtype dominance transitioned from RSV-A (2021-2023; mainly A.D.3) to RSV-B in 2024 (all B.D.E.1). Lineage-specific amino-acid and predicted N-glycosylation changes were observed, including loss of the N179 site in A.D.5.2 and acquisition of N258 in B.D.E.1. These findings indicate that RSV circulation on tropical Hainan was strongly suppressed during intensive NPIs and re-established after policy relaxation, accompanied by earlier seasonal activity and clear lineage replacement, underscoring the need for sustained genomic surveillance to inform locally tailored clinical preparedness and immunization strategies.
    Chronic respiratory disease
    Care/Management
  • Clinical Outcomes and Molecular Epidemiology of Human Metapneumovirus in Romanian Hospitalized Patients.
    1 day ago
    Human metapneumovirus (hMPV) is an important cause of acute respiratory tract infections. This study aimed to describe the clinical characteristics, outcomes, and molecular features of hMPV infection among hospitalized patients in Romania. We performed an analysis of prospectively collected surveillance data from patients hospitalized with influenza-like illness or severe acute respiratory infection and tested by RT-PCR for the presence of respiratory viruses between November 2023 and May 2025. Only cases of hMPV monoinfection were analyzed. Clinical, laboratory, and outcome data were analyzed, and a subset of samples with high viral load underwent genetic sequencing of the hMPV fusion (F) gene. A total of 71 patients met the criteria. Children accounted for 62.0% of cases. The clinical features were nonspecific, dominated by cough (87.3%), fever (80.3%), and nasal congestion (47.9%). Adults were significantly more likely to develop dyspnea and respiratory failure requiring oxygen supplementation (51.9% vs. 6.8%, p < 0.001). The median length of hospital stay was 5 days (interquartile range: 2, 7 days), and dyspnea at admission was the strongest factor associated with prolongation of hospitalization. The rate of intensive care unit admission was 4.2%, and overall outcomes were favorable, with no deaths recorded. Molecular analysis revealed the circulation of different hMPV subclades across consecutive seasons, with A2b1 predominating in 2023-2024 and A2b2 in 2024-2025. hMPV infection in hospitalized patients presents with nonspecific clinical features and shows distinct age-related patterns of severity and complications. Early identification of respiratory involvement, particularly dyspnea at presentation, may support risk stratification and optimized clinical management. Preliminary molecular data indicate dynamic circulation of hMPV subclades, underscoring the value of integrated clinical and molecular surveillance. These findings support the inclusion of hMPV in the differential diagnosis of severe acute respiratory infections and highlight the importance of continued monitoring in the post-pandemic period.
    Chronic respiratory disease
    Care/Management
  • The Complexity of Immunoglobulin A Immune Responses in Respiratory Syncytial Virus Infection.
    1 day ago
    Respiratory syncytial virus (RSV) remains a leading cause of severe lower respiratory tract disease in infants worldwide. Despite extensive study in animal models and humans, fundamental age-dependent differences in mucosal immunity continue to limit the development of durable protective strategies in early life. Compared to adults, infants mount weaker humoral responses to RSV, underscoring the urgent need for effective vaccines in this age group. Immunoglobulin A (IgA), the dominant antibody isotype at respiratory mucosal surfaces, plays a central role in limiting viral replication and disease severity during RSV infection. While IgA limits RSV severity in adults, infants fail to generate robust IgA responses. Impaired IgA responses in infancy reflect unique immune regulatory pathways that shape early-life antiviral immunity. Emerging evidence highlights a critical role for regulatory B cells (Bregs), particularly neonatal Bregs (nBregs), in suppressing antiviral responses, limiting class switch recombination, and contributing to severe RSV disease. This review summarizes current evidence on IgA regulation during RSV infection, with particular emphasis on age-specific B-cell responses and the emerging role of Bregs. Improved understanding of these mechanisms has direct implications for the rational design of vaccines and immunomodulatory strategies tailored to infants.
    Chronic respiratory disease
    Policy
  • Long-term Risk of Bleeding Events in Patients Taking Antithrombotic Agents for Cerebrovascular or Cardiovascular Disease.
    1 day ago
    Antithrombotic agents are essential for preventing cerebrovascular and cardiovascular diseases; however, bleeding complications remain a major concern, particularly among elderly patients and those receiving combination therapy.

    We designed the Bleeding with Antithrombotic Therapy 2 (BAT2) Study, a prospective multicenter registry involving hospitals from a clinical research network in Japan, to clarify the risk of bleeding events in patients taking antithrombotic agents for cerebrovascular and cardiovascular diseases in recent clinical settings.

    This prospective, multicenter, observational study followed bleeding and ischemic events for up to 2 years in patients with cerebrovascular and cardiovascular diseases. The primary outcome was major bleeding, and secondary outcomes included intracranial hemorrhage (ICH).

    The 5,250 patients enrolled comprised 3,134 (70±11 years old; male, 66.6%; HASBLED ≥3, 32.8%) treated with single antiplatelet therapy (SAPT), 551 (71±11 years; 25.8%; 40.8%, respectively) with dual antiplatelet therapy (DAPT), 870 (75±10 years; 37.1%; 39.8%, respectively) with direct oral anticoagulant (DOAC) alone, 433 (72±12 years; 34.2%; 41.4%, respectively) with warfarin alone, 143 (76±8 years; 16.8%; 42.7%, respectively) with DOAC plus antiplatelet agents (AP); and 119 (73±12 years; 18.5%; 47.5%, respectively) with warfarin plus AP. During follow-up (median, 1.98 years), 93 patients experienced major bleeding and 55 developed ICH. Compared to the SAPT group (37 events, 0.63%/year), the DOAC (18 events, 1.12%/year; adjusted hazard ratio [aHR] 1.94, 95% confidence interval [CI] 1.09-3.46), warfarin (16 events, 2.02%/year; 3.44, 1.90-6.23), and DOAC plus AP groups (6 events, 2.24%/year; 3.07, 1.28-7.35) exhibited significantly higher risks of major bleeding after multivariable adjustment. DAPT (aHR 2.47, 95%CI 1.11-5.48), warfarin (5.38, 2.65-10.92), and DOAC plus AP (3.86, 1.30-11.47) had significantly higher risks of ICH than SAPT. The DAPT (2.28, 95%CI 1.65-3.14), DOAC plus AP (1.96, 1.08-3.56) and warfarin plus AP (2.83, 1.62-4.92) groups showed significantly higher risks of ischemic events compared to the SAPT group.

    Oral anticoagulant alone and DOAC with antiplatelet therapy were associated with higher risks of major bleeding events than SAPT in long-term follow-up for patients with stroke and cardiovascular disease.Data access statement:The dataset of the BAT2 study is available to the investigators who participated in this study group upon submission of a reasonable study plan.

    ClinicalTrials.gov (NCT02889653) and the University Hospital Medical Information Network clinical trial registry in Japan (UMIN 000023669).
    Cardiovascular diseases
    Access
    Care/Management
  • Machine Learning-Informed Nano Co-Assembly Inhibits Fibroblast Activation Protein and Improves Drug Delivery in Fibrotic Tissue.
    1 day ago
    Nanoparticle-based drug delivery faces persistent challenges, including complex fabrication processes and limited lesional accumulation. Here we introduce SP-13786 (SP), a precise small-molecule inhibitor of fibroblast activation protein (FAP), as a universal and effective excipient enabling facile co-precipitation into stable nanoparticles (SCAN) with diverse hydrophobic drugs. Screening of 861 compounds revealed a broadly enhanced colloidal stability and drug loading by SP. Corresponding simulations and explainable machine learning (XML) showed SCAN assembly hinges on balanced aromaticity, rigidity, and nitrogen-mediated interaction, offering interpretable framework for co-assembly nanomedicine. Biological assessment demonstrate that SCAN enhances drug delivery and therapeutic efficacy in FAP-positive cells, therefore attentuate the fibrosis-induced drug penetration barriers, increasing drug accumulation within the fibrotic tissue. The improved bioavailability correlate with superior therapeutic outcomes in multiple disease models with progressive fibrosis. Overall, we establish SP as a versatile nanotherapeutic platform combining simplicity in preparation, mechanistic insights provided by XML, and broad applicability for diseases characterized by pathological fibrosis and impaired drug delivery.
    Cardiovascular diseases
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  • Energy potential, health benefits, antinutrient reduction methods, and nutritional properties of Indian millets: a review.
    1 day ago
    Millet production has significantly increased to fulfill the nutritional needs of the increased population across the globe. Around the world, millions of people suffer from shortages of food and hunger. In the last few years, food supply has been influenced by many factors, such as changes in climate, increased population, and a slowing economy. Furthermore, many countries face undernutrition and overnutrition problems. Achieving nutritional and food security requires a transformative shift in the agricultural sector. Providing everyone with access to cheap, healthy, and affordable food as well as a nutritious diet is one way to reach our goal. The present study uses preferred reporting items for systematic review and meta-analyses (PRISM) to study the search strategy for recent advancements. Bioactive substances, minerals, and properties of cereal grains are impacted by various processing methods like parboiling, decoration, heating, soaking, germination, and fermentation. This paper aims to study the nutrient qualities and processing of antinutrient reduction methods, the nutritional composition of millets, their effects on consumption, and the nutritional characteristics of medicinal use. The highest dietary fiber content is in pearl millets (11.49%), followed by maize (10.20%). Millets contain carbohydrates, antioxidants, and biologically active compounds such as phenolic acids, carotenoids, flavonoids, minerals, and vitamins. The appropriate consumption of millets helps to reduce diseases like diabetes, cardiovascular diseases, inflammation, and malnutrition because of their low glycemic index, being gluten-free, and increased major nutrients. But overdose of millet consumption causes goitrogenic effects, kidney stones, thyroid dysfunction, allergic reactions, high sugar levels, and weight gain. Considering the modifications within millets' nutritional value brought on by the process may benefit the food business, scientists, and consumers in choosing the best processing method to maximize nutrient content, boost nutrient bioavailability, and assist in promoting food and nutrition security.
    Cardiovascular diseases
    Access