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Safety and Immunogenicity of Varicella Vaccination in Children and Adolescents Living With HIV: A Systematic Review.

INTRODUCTION: Preventing varicella-zoster virus infection is important in the management of human immunodeficiency virus (HIV)-positive persons. Varicella remains endemic worldwide, and HIV-positive persons can experience greater morbidity than the general population. We summarized the global literature on the safety and immunogenicity of the varicella vaccine in HIV-positive children. METHODS: Systematic review of original reports on varicella vaccination of HIV-positive children, published through December 31, 2024, including assessment of safety, immunologic responses and effectiveness after vaccination. RESULTS: Eighteen articles were analyzed. Local reactions were the most common adverse events, albeit infrequent (<21% and <10% of vaccinees after dose 1 and 2, respectively). Systemic reactions were also infrequent, consisting mostly of low-grade fever. A vaccine-related rash, reported in <5% of vaccinees, had fewer lesions and a shorter duration than typical varicella. Serious adverse events were reported only when the vaccine was inadvertently administered to children with severe HIV immunosuppression. Varicella vaccination had no clinically significant impact on plasma HIV RNA or CD4+ T-cell count after either dose. An antibody response was reported in 60%-79% of HIV-positive vaccinees after dose 2 and often declined more rapidly than in uninfected children. Cell-mediated immunity was detected in 67%-83% after dose 2. No significant differences in adverse events or short-term immune response after vaccination correlated with past or current CD4+ T-cell status. CONCLUSIONS: The varicella vaccine had a favorable safety profile and induced specific immune responses in most nonseverely immunocompromised HIV-positive children. The vaccine remains contraindicated for persons with severe HIV infection. Robust data on the durability of immune response and long-term effectiveness are needed.

Humans

Construction of precision clinical-proteomics risk model based on machine learning for predicting heart failure in type II diabetes mellitus.

BACKGROUND AND AIMS: Heart failure (HF) is a severe complication in type 2 diabetes mellitus (T2DM), but current risk stratification scores have limited predictive accuracy. We aimed to develop novel prediction tools integrating clinical variables with proteomics to improve risk stratification of hospitalization for HF in T2DM. METHODS AND RESULTS: In this study, we included 2111 UK Biobank participants with T2DM but no prior HF, and profiled 2920 proteins to predict 10-year incident HF hospitalization. Participants were randomly divided into training (70%), tuning (10%), and validation (20%) sets.Three prediction models were developed: a Clinical model based on demographic characteristics, comorbidities, medication use, and laboratory indices; a Protein model based on 40 proteins selected by the Light Gradient Boosting Machine (LGBM); and the Clinical OMics and Protein ASSessment for Heart Failure (COMPASS-HF) model, which integrated both clinical variables and the LGBM-selected proteins. Models were evaluated for area under the curve (AUC), sensitivity, and specificity. During follow-up, 168 participants (7.96%) developed incident HF. The COMPASS-HF model showed better discrimination than the Clinical model, with an AUC of 0.897 (95% CI: 0.850-0.945) versus 0.790 (95% CI: 0.723-0.856). It also demonstrated higher sensitivity (0.882; 95% CI: 0.725-0.967) and consistent performance in subgroups. COMPASS-HF effectively stratified risk of hospitalization for HF, with cumulative incidence rates of 31.9% in the high-risk group and 1.2% in the low-risk group. CONCLUSIONS: By combining clinical and proteomic variables, we developed a high-performance HF prediction model for T2DM, enabling precise risk stratification and informing early intervention strategies.

Humans

The Meaning and Significance of Breastfeeding for Biological Mothers of Children with Cleft Lip and/or Palate.

INTRODUCTION: Given the functional, emotional, and symbolic challenges imposed by cleft lip and/or palate (CL/P) on exclusive breastfeeding (EBF), mothers often experience early breastfeeding cessation with impacts on maternal identity and the mother-infant bond. This study aimed to explore the meanings, feelings, and experiences of mothers of children with CL/P regarding breastfeeding in the face of these adversities. METHODS: This qualitative study applied the Clinical-Qualitative Method as proposed by Turato. Six in-depth semistructured interviews were conducted with biological mothers of children with CL/P, recruited from a specialized craniofacial reference center in Brazil. Data were analyzed using a qualitative content analysis approach, grounded in psychodynamic concepts from the Medical Psychology theoretical framework. RESULTS: Based on the analysis of the collected material, three analytical categories were identified and constructed: (1) "Existential conflict regarding the inability to fulfill the ideal maternal role"; (2) "Duality between the need and the fear of caregiving"; and (3) "The anguish experienced between tangible and intangible support during breastfeeding."Conclusions:Although the inability to EBF in children with CL/P generates emotional distress, motherhood is reimagined through adaptive forms of care and bonding, highlighting gaps in institutional support and the need for more humanized, emotionally sensitive health practices.

Humans

Artificial Intelligence for Diagnosis, Risk Stratification, and Prognosis of Neuroblastoma - A Systematic Review and Meta-Analysis.

PURPOSE: To synthesizes evidence on artificial intelligence (AI) performance in neuroblastoma (NB) diagnosis, risk stratification, prognosis, and genomic characterization. MATERIALS AND METHODS: A systematic review and meta-analysis was conducted following PRISMA 2020 guidelines (PROSPERO: CRD42024539475) across five databases. Meta-analyses used random-effects models with logit-transformed Area Under the Curve (AUCs) and cluster-robust standard errors. AI models were classified as Machine Learning Models (MLM) or Hybrid Nomograms (HN) based on their construction methodology. RESULTS: Of 3,742 articles identified, 53 were included. MLMs demonstrated higher point estimates than radiologists in differential diagnosis (AUC: 0.87 vs. 0.83), though this difference was not statistically significant and carried substantial uncertainty. HNs achieved stronger performance in risk stratification (AUC: 0.87). AI-derived nomograms (AUC: 0.9) and gene signatures (AUC: 0.8) outperformed conventional prognostic markers descriptively. Chemotherapy response prediction remained below clinical utility thresholds across all model types. Only 33.9% of models reported calibration and 24.5% underwent external validation. CONCLUSIONS: AI demonstrates proof-of-concept across multiple NB clinical domains. However, clinical adoption remains premature given persistent gaps in external validation, calibration, dataset size, and pediatric-specific model development. Future studies should test these models prospectively in multicenter pediatric cohorts, ideally through COG or SIOPEN, using shared definitions for diagnosis, risk group, treatment response, and survival outcomes.

Humans

Medically Unexplained Symptoms: A Systematic Umbrella Review of Current Terminology and Reported Rationales.

OBJECTIVES: Toaddress current naming conventions for Medically Unexplained Symptoms (MUS) through a systematic umbrella review. The terminology used and the provided rationales were considered. METHODS: Registered with PROSPERO (CRD42024526020), this review searched 8 key databases, last on January 28, 2025. Reviews including medically unexplained symptoms (or synonym or subtype) in their systematic search terms were included (N=422). RESULTS: A total of 577 references to 111 terms were made across the reviews, with numerous reviews using the same overarching terms, including "functional" (n=233), "somatic" (or variants thereof, n=51), and "medically unexplained" (n=28). Thirty percent of terms (n=179) were to specific syndromes or terms that did not group together under an overarching term, suggesting substantial variability in terms, even though over 60% of authors were primarily associated with just 3 disciplines: medicine, allied health, and psychology. A subset of 23 reviews provided rationales, which were subjected to content analysis and a ROBIS (Risk of Bias in Systematic Reviews) risk-of-bias assessment. This analysis showed that rationales tended to (1) highlight differences between psychological, psychiatric, and other medical fields (n=7); (2) focus on the patient perspective and patient-practitioner therapeutic relationship (n=10); or (3) follow broad and/or commonly used terms (n=7). DISCUSSION: The current landscape of terminology used for MUS remains varied, nuanced, and inconsistent between disciplines. Moving forward to a more universal language accepted and used by both patients and practitioners would aid in the diagnosis, management, and treatment of MUS.

Humans

Assessment of Methodological Bias in Studies Reporting Racial Differences in Retinopathy of Prematurity in the United States.

PURPOSE: To assess methodological biases in studies reporting racial and ethnic differences in retinopathy of prematurity (ROP). METHODS: Systematic review of peer-reviewed studies published between 2014 and 2024 that reported on ROP outcome measures by race, ethnicity, or social determinants of health (SDOH). Three reviewers independently assessed each observation for selection and collider bias using definitions derived from perinatal epidemiology literature. Findings were also compared using a structured comparative synthesis between studies with and without identified methodological bias. RESULTS: A structured PubMed search identified 78 articles; 13&#x2009;met inclusion criteria, with one study contributing two distinct analytical approaches, yielding 14 total observations. Survivorship bias was identified in 6 of 14 observations (42.9%), primarily due to the exclusion of infants who died prior to ROP screening. Potential collider bias was most common, found in 9 of 14 observations (64.3%), and was introduced through adjustment or stratification by gestational age and/or birthweight. Three studies did not exhibit either assessed biases. Among studies with identified bias, 8 of 10 observations reported lower ROP risk among Black versus White infants, whereas 3 of 4 observations without identified bias reported higher ROP risk or incidence among Black infants. CONCLUSION: Methodological biases in ROP studies investigating race or ethnicity are prevalent. Adjustment for gestational age or birthweight may introduce spurious race-ROP associations and contribute to paradoxical findings. Further exploration of the impact of SDOH on disease outcomes may reduce the misattribution of race as a biological risk factor and improve the interpretation of ROP disparities.

Collider bias

Temporal evolution of minimally invasive pediatric urolithiasis treatment over 30 years.

Urolithiasis in children has increased substantially over the past 30 years, and surgical management maintains an important role in treatment. Technological advances such as lasers and miniaturization have broadened treatment options, and researchers investigate the best indications for each procedure. The aim was to identify publication trends in the field and explore reasons why Extracorporeal Shockwave Lithotripsy is being gradually less applied in the treatment of pediatric urolithiasis. A Reverse Systematic Review of the literature was conducted regarding the surgical treatment of urolithiasis in children. Five databases were screened, gathering all articles from inception that were evaluated in systematic reviews. We examined 123 publications, 197 reports, and 15,878 procedures, consisting of the largest studied population in the field. There was an increasing number of publications, although in progressively less prestigious journals. The number of studies on miniaturized percutaneous techniques and flexible ureteroscopy has increased closely with the rise in popularity of these procedures worldwide, mainly driven by studies from Asia, Europe, and North America. A trend of self-renewed interest is fueled by technological innovation and has led to fewer publications on Extracorporeal Shockwave Lithotripsy over the years. This review highlights the fact that, despite positive results in recent studies, the low popularity of ESWL within the scientific community is driving a decline in the technique's indications. Moreover, based on the findings of this study, key research priorities include continued reporting of high-quality outcomes, and technological progress in ESWL would contribute meaningfully to the field.

Humans

Integration of ear and hearing care services in low- and middle-income health systems: a systematic review and qualitative synthesis.

Hearing loss is a global public health burden and mostly affects those living in low- and middle-income countries (LMICs). One approach to address ongoing challenges is the World Health Organization's recommendation for the integration of ear and hearing care (EHC) services into healthcare packages. However, little is known about EHC integration approaches, particularly in LMICs additionally, these approaches have not been investigated through a health systems lens. This qualitative review aimed to describe the various approaches to the EHC service integration in LMICs and to identify enabling and constraining factors. We reviewed 17 studies, with a focus on LMICs, using adaptations of the Valentijn integration and World Health Organization EHC frameworks, following the PRISMA guidelines. Our investigation showed that most integration approaches were at micro or individual level. Enabling factors for integration of EHC services were training, mentorship, collaboration, technology, inclusion of EHC in healthcare packages and investment in EHC services. Barriers were challenges with training, facilities and equipment, policy implementation and resourcing of EHC services. We further described factors influencing healthcare seeking behaviour and the use of integrated EHC services, such as access and ability to pay, referral systems and communication and awareness. This study describes the complex nature of EHC integration and ways to support integration. Key considerations are the level of integration, training to address workforce issues and factors influencing service utilisation as we work towards health system strengthening.

Humans

Whole-transcriptome RNA sequencing and ceRNA network analyses provide novel insights into the antibacterial immune response of Hippocampus abdominalis against Vibrio harveyi.

Long non-coding RNAs (lncRNAs) stand as newly-arisen molecular types that exert regulatory effects, able to operate as competitive endogenous RNAs (ceRNAs) to engage microRNAs (miRNAs) in interaction, resulting in the recovery of target mRNA expression and activity. Increasing evidences indicate that the ceRNA network affects various biological processes in mammals, including development, cellular differentiation, metabolism, immune response, and disease pathogenesis. In teleost fish, the lncRNA-miRNA-mRNA regulatory networks have been reported occasionally. However, up to now, the roles of lncRNAs in the big-belly seahorse (Hippocampus abdominalis) remains unclear. In this study, we reported for the first time, via whole-transcriptome RNA sequencing, the lncRNA mediated ceRNA regulatory network in Vibrio harveyi-infected H. abdominalis. A total of 4197 differentially expressed mRNAs (DE-mRNAs), 1317 DE-lncRNAs, and 183 DE-miRNAs were identified. Furthermore, the crosstalk between miRNAs and lncRNAs as well as between miRNAs and mRNAs was inferred based on the negative correlations between miRNAs and their target lncRNAs/mRNAs. A core immune associated lncRNA-miRNA-mRNA putative regulatory network was thus constructed, comprising 211 lncRNA-miRNA and 224 mRNA-miRNA pairs. In conclusion, our findings provide an integrative overview of the ceRNA regulatory networks on the underlying immune responses to V. harveyi infection in the big-belly seahorse, and offer a solid theoretical foundation for the comparative immunological research of teleost fish.

Animals

Phylogenomics and female reproductive morphology reframe the classification of the Halymeniales (Rhodophyta).

The red algal order Halymeniales (Rhodophyta) exhibits remarkable morphological and taxonomic diversity but its higher-level relationships remain poorly resolved. Here, we present a comprehensive phylogenomic analysis based on newly generated plastid (170 protein-coding genes), mitochondrial (23 genes), and complete nuclear ribosomal cistron sequences from 56 taxa, complemented with an expanded rbcL dataset encompassing 334 sequences. Our results provide a robust phylogenomic framework for the Halymeniales, offering a taxonomic backbone for future systematic studies. The analyses consistently recover six early-diverging lineages (Acrodiscus, Isabbottia, Norrissia, Pachymenia, Zymurgia, and Tsengia) and two strongly supported larger clades (Halymenia s.l. and Grateloupia s.l.). While most small and recently described genera are monophyletic, several traditional genera (e.g., Halymenia, Cryptonemia, Grateloupia) are poly- or paraphyletic, requiring considerable taxonomic revision. At the family level, the data indicate that reinstatement of the Grateloupiaceae sensu Kim et al. (2021) would entail a revised circumscription of the Halymeniaceae and the recognition of at least five small families to accommodate the early-diverging lineages. Although such a revised classification would result in monophyletic families, it is not supported by morpho-anatomical characters. Instead, we propose a more stable two-family system, recognizing a broadly circumscribed Halymeniaceae that is sister to the Tsengiaceae. Female reproductive characters, particularly the structure of carpogonial and auxiliary cell ampullae, support this two-family system and further characterize many genus-level clades, although substantial convergence across lineages exists.

Phylogeny

Effectiveness of a Web-Based Educational eHealth Platform on Women's Health Literacy About Phthalate Exposure: Randomized Controlled Trial.

BACKGROUND: Phthalates are environmental endocrine-disrupting chemicals widely used in plastics, cosmetics, food packaging, and personal care products. Women may experience frequent exposure through everyday consumer and household products. Improving phthalate-related health literacy may support informed exposure-reduction decisions; however, conventional health education provides limited opportunities for repeated, interactive, and individually tailored learning. OBJECTIVE: This randomized controlled trial evaluated the effectiveness of an eHealth educational intervention (Phthalates Free) in improving women's overall and domain-specific phthalate-related health literacy and examined the association between platform engagement and health literacy outcomes. METHODS: A double-blind randomized controlled trial was conducted in the outpatient department of a regional teaching hospital in Taipei, Taiwan. A total of 114 women were randomly assigned to an intervention group (n=58) receiving a 6-month eHealth platform-based education program and a control group (n=56) receiving conventional paper-based education. Assessments were conducted at baseline (T0), 3 months (T1), and 6 months (T2). The Phthalate Health Literacy Scale (10 items; &#x3b1;=.90, content validity index=0.93) measured overall and domain-specific literacy (health care, disease prevention, and health promotion). Longitudinal outcomes were analyzed using generalized estimating equations based on all available observations according to participants' original randomized assignments, with adjustment for waist circumference and pregnancy history. Analysis of covariance (ANCOVA) was used to compare 6-month outcomes after adjustment for baseline scores. Platform engagement and perceived usability were assessed using back-end analytics and the System Usability Scale (SUS). RESULTS: At 6 months, the intervention group showed a significantly greater increase in total health literacy than the control group (+9.93 points, Wald &#x3c7;&#xb2;1=17.74; P<.001). Domain analyses revealed significant improvements in health care (+1.52; P=.001), disease prevention (+1.32; P=.001), and health promotion (+1.12; P=.001) domains. ANCOVA confirmed the between-group difference at T2 after adjusting for baseline scores (F1,109=11.43; P=.001; adjusted mean difference=7.15, 95% CI 2.96-11.34). Engagement analysis showed that high-engagement users (n=10) scored significantly higher in overall health literacy (t55=-3.00; P=.004) and all domains than general users. The SUS results (mean 84.7, SD 5.2; n=46, 79.3%) indicated high perceived usability. CONCLUSIONS: The Phthalates Free eHealth educational intervention significantly improved women's overall and domain-specific health literacy over 6 months. Higher platform engagement was associated with better health literacy outcomes. The intervention may serve as a practical adjunct to nurse-led education in outpatient and community settings by providing accessible, continuous, and evidence-based guidance on reducing phthalate exposure.

Humans

Parent-Child Communication after Parental Exposure to Potentially Traumatic Events: A Systematic Review.

Intergenerational traumatization poses a risk for the well-being of children whose parents have been exposed to potentially traumatic events (PTEs). Previous research has implied that parent-child communication may significantly contribute to the transmission of trauma across generations, but findings remain limited and inconclusive, particularly regarding the mechanisms and factors that could underlie this process. Therefore, the present paper performed a mixed methods systematic literature review to methodically map how PTE-exposed parents communicate with their children-both in general and about parental PTEs-and how such communication may contribute to trauma transmission. Five electronic databases were accessed to conduct keyword-led searches, yielding a final inclusion of 31 peer-reviewed, empirical studies that investigated parent-child communication among PTE-exposed parents and/or their nonexposed children. Parental PTE exposure was found to have a negative impact on general parent-child communication, often due to the presence of parental anger, irritability, and withdrawal. Conversations about parental PTEs showed substantial diversity in their frequency, content and style, with strategies of partial/modulated disclosure appearing most common. How parents approached PTE communication frequently stemmed from a desire to keep their children safe and unburdened by their previous experiences. Finally, both general communication and PTE communication were implied to contribute to trauma transmission, revealing a significant impact of parent-child communication on child functioning, identity, and well-being. Based on these key findings, the authors discuss meaningful implications for future research (i.e., prospective directions, addressing methodological concerns) and formulate suggestions for clinicians and policymakers surrounding the treatment of PTE-exposed parents and their offspring.

Humans

GSTT1 promotes stemness and FGFR inhibitor sensitivity in pancreatic cancer through regulation of CD133 (PROM1).

Pancreatic ductal adenocarcinoma (PDA) is among the deadliest malignancies, driven by metastatic progression and profound cellular heterogeneity. We previously identified glutathione S-transferase theta 1 (GSTT1) as a regulator of a slow-cycling, highly metastatic tumor cell population, suggesting that GSTT1High cells may possess stem-like properties. Here, we define the functional and molecular features of this subpopulation in metastatic PDA. Using a mCherry-tagged Gstt1 reporter system in metastatic murine PDAC cells, we enriched for Gstt1High cells and observed increased tumor sphere formation, accompanied by upregulation of stemness-associated genes including PROM1 (CD133) and activation of Wnt and FGF signaling pathways. In human PDA models, CD133HighGSTT1High cells exhibited enhanced tumor sphere initiation and expansion compared to other populations, defining a maximal stem-like state. Notably, sensitivity to FGFR inhibitors was observed only under tumor sphere conditions, highlighting a context-dependent therapeutic vulnerability. Mechanistically, FGFR3 expression correlated with GSTT1 and CD133 levels, and FGF signaling was required to sustain this state. GSTT1 knockdown reduced CD133 protein levels, impaired tumor sphere formation, and altered sensitivity to FGFR inhibition. These findings were largely recapitulated in patient-derived PDA organoids, where GSTT1 and PROM1 co-expression predicted increased tumor sphere formation and enhanced response to the multi-kinase inhibitor Nintedanib. Together, these results identify a GSTT1HighCD133High stem-like subpopulation in metastatic PDA and identify an FGFR-dependent signaling axis that sustains this state, representing a potential therapeutic vulnerability.

AC133 Antigen

The Impact of Nurse-to-Patient Ratios on Nurses' Burnout, Job Dissatisfaction, and Intention-to-Leave: A Systematic Review and Meta-Analysis.

BACKGROUND: Adequate nurse staffing is essential for ensuring workforce well-being and patient safety. Imbalanced nurse-to-patient ratios contribute to burnout, job dissatisfaction, and turnover, which compromise care quality. OBJECTIVE: This systematic review and meta-analysis evaluated the impact of nurse-to-patient ratios on nurse burnout, job dissatisfaction, intention-to-leave, and patient outcomes. METHODS: A systematic search of PubMed, Scopus, and Web of Science identified cross-sectional studies examining nurse-to-patient ratios and related outcomes. RESULTS: Eighteen studies involving 183&#x2005;876 nurses from 4085 hospitals were included. Higher nurse-to-patient ratios increased the odds of burnout (OR: 1.08), job dissatisfaction (OR: 1.10), and intention-to-leave (OR: 1.09). Each additional patient per nurse increased mortality and readmission risks by 7% to 8%, with decreased perceived care quality. CONCLUSION: Higher nurse-to-patient ratios adversely affect nurses and patients. Ensuring adequate staffing is critical to prevent burnout and maintain safe, high-quality care.

Humans

Late hiatal hernia after Roux-en-Y gastric bypass: a systematic review.

Obesity is a global public health issue. This condition is linked to gastroesophageal reflux disease (GERD) and hiatal hernia (HH), both of which are exacerbated by increased intra-abdominal pressure. Roux-en-Y gastric bypass (RYGB) is one of the most widely performed techniques for treating obesity and is considered a versatile option suitable for most patients. The development of a symptomatic HH and pouch migration can lead to various symptoms and complications. PubMed, EMBASE, and Cochrane Central were searched for studies with late HH after RYGB. We pooled outcomes for symptom resolution. Secondary outcomes were recurrence rate and operation characteristics (mesh use, cruroplasty, gastropexy, reoperation, length of stay, and operative time). A meta-analysis could not be conducted due to significant heterogeneity in HH. HH following RYGB presents with GERD (39-93.6%), obstructive symptoms (29%-88%), and abdominal pain (28.6%-71%). Diagnostic methods include endoscopy, computed tomography scans, and upper gastrointestinal series. Surgical management varies, with primary cruroplasty being the most common approach, sometimes incorporating mesh or fundoplication. Postoperative symptom resolution rates range from 42.9% to 100%, with HH recurrence occurring in 5%-6.54% of cases. Follow-up durations varied, showing improvement in most patients, though some continued to experience reflux and dysphagia HH contributes to obstructive and reflux symptoms, with contrast-enhanced imaging offering the highest diagnostic accuracy. Bioabsorbable mesh may reduce recurrence, highlighting the need for long-term monitoring.

Humans

Implementing a novel digital health platform for self-management of postmenopausal osteoporosis: A qualitative study of user experiences, perspectives and implementation outcomes.

BACKGROUND: Osteoporosis self-management requires scalable support, and digital health platforms may meet this need. This study aimed to characterise the experiences and perspectives of postmenopausal women who participated in a 12-month randomised controlled trial (RCT) of a digital voice assistant (DVA) delivered osteoporosis self-management intervention, and to assess key implementation outcomes. METHODS: This was a qualitative analysis of interviews with postmenopausal women from the intervention arm (DVA group) of the RCT. The DVA program broadcast education videos, medication reminders, home-based exercise, nutrition advice and monthly quizzes through a DVA device. Semi-structured interviews were recorded, transcribed and managed in NVivo through reflexive thematic analysis, guided by the Practical Planning for Implementation and Scale-Up and Proctor's implementation outcome taxonomy frameworks. Evidence weighting summarised participant coverage and code density. RESULTS: Twenty-two of 25 (88%) DVA group participants completed semi-structured interviews. Thematic analysis identified seven themes mapped to Proctor's implementation outcomes. Evidence weighting indicated strong support for the intervention's appropriateness and acceptability, moderate support for its adoption, fidelity, feasibility and sustainability, and limited support for costs. Participants valued clear audiovisual guidance, conversation-based interactions with natural language, and flexible home-based access to self-management. CONCLUSION: Digital health platforms for osteoporosis self-management appear feasible, acceptable and sustainable among postmenopausal women. Findings indicate that these platforms are approaching readiness for evaluation in implementation-focused settings, contingent on streamlined content, reliable delivery modalities, accessible user support, clear privacy regulations and pragmatic pricing models.

Humans

HYPNOSA: Study protocol for a prospective observational cohort of patients with obstructive sleep apnea.

BACKGROUND: Obstructive Sleep Apnea (OSA) is a common chronic disease that affects more than 20% of the adult population. One of the most frequent and characteristic symptoms of OSA is excessive daytime sleepiness (EDS). This symptom is typically treated in patients with OSA with the application of continuous positive airway pressure (CPAP), the gold-standard treatment for this disease. In some patients who are adequately treated with CPAP, residual excessive daytime sleepiness (REDS) persists. The prevalence, associations, and outcomes associated with REDS remain poorly understood. METHODS: Multicenter, prospective, observational cohort study including 1000 patients. Participants will undergo a sleep study for the diagnosis of obstructive sleep apnea (OSA), 24-h ambulatory blood pressure monitoring, clinical assessment, quality-of-life questionnaires, Epworth Sleepiness Scale, and collection of biochemical variables and biological samples. Patients with OSA will receive standard care, and those prescribed continuous positive airway pressure (CPAP) will be monitored for treatment adherence. OSA patients will be assessed at baseline and at 6, 12, and 24 months. DISSCUSION: We aim to establish a prospective observational cohort of patients with obstructive sleep apnea (OSA) treated with CPAP, with and without REDS. The HYPNOSA project will create the largest available registry of patients with OSA and REDS using real-world data, providing accurate prevalence estimates and long-term outcomes. Biological samples will be analyzed to assess the role of specific biomarkers. TRIAL REGISTRATION: Registered at ClinicalTrials.gov. Identifer: NCT06514482.

Adult

Identification of CXCL13 as an agonist and CXCL11 as an inverse agonist for the viral G protein-coupled receptor ORF74.

Kaposi's sarcoma-associated herpesvirus (KSHV) establishes latent infection in humans, but under conditions of immune suppression, it may reactivate and contribute to severe diseases, including Kaposi's sarcoma (KS) and B-cell malignancies. The KSHV genome encodes a single G protein-coupled receptor (GPCR), open reading frame 74 (ORF74), which shows homology to human chemokine receptors. Since its identification in 1996, ORF74 has subsequently been shown to interact with a broad range of human CXC chemokines, as well as CCL1 and the viral chemokine vCCL2. Compared with many human chemokine receptors, ORF74 displays high basal activity. These properties allow ORF74 to deregulate host cellular pathways through constitutive and chemokine-modulated signaling. In this study, we evaluated several human chemokines that, to our knowledge, had not previously been tested in ORF74-dependent cellular assays. Whereas CXCL9, CXCL14, CXCL16 and CXCL17 did not interact with ORF74, CXCL13 was identified as an additional ORF74 agonist and CXCL11 as an inverse agonist. CXCL13 dose-dependently induced ORF74-mediated Ca2+ release, &#x3b2;-arrestin1/2 recruitment and chemotaxis, and enhanced basal nuclear factor &#x3ba;B (NF-&#x3ba;B) activity in ORF74-expressing cells. In contrast, CXCL11 showed no detectable ORF74 agonist activity in the calcium mobilization or chemotaxis assay, but antagonized CXCL1-induced responses in both readouts. CXCL11 also elicited inverse agonist-like responses in &#x3b2;-arrestin1/2 recruitment assays and reduced basal NF-&#x3ba;B signaling. Our study thus reveals CXCL13 and CXCL11 as two additional chemokine ligands for ORF74, further expanding the pharmacological profile of this viral GPCR.

Humans