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Effectiveness of peer recovery support services for substance use disorders: A systematic review of healthcare utilization, behavioral health, and engagement outcomes.

BACKGROUND: Peer recovery support services (PRS) delivered by individuals with lived experience of substance use, are increasingly incorporated into substance use disorder (SUD) care systems to improve care engagement, reduce acute care use, and support recovery. However, existing systematic reviews have focused on substance use outcomes, with limited attention to healthcare utilization, psychosocial functioning, and outcomes across settings, and populations. METHODS: This systematic review, registered in PROSPERO (CRD42023469279), synthesized peer-reviewed studies from 2003 to 2026 evaluating PRS for individuals with alcohol or drug-related SUD. Using MEDLINE, Embase, PsycINFO, and CINAHL, the review included 53 studies primarily conducted in high-income countries that reported quantitative outcomes across substance use, healthcare utilization, behavioral health, and treatment engagement. Risk of bias was assessed using Cochrane RoB 2, ROBINS-I, and ROBINS-E tools. RESULTS: Overall, evidence was most favorable for selected treatment-linkage and engagement outcomes, whereas findings for substance use, emergency department use, hospitalization, overdose, and mortality were inconsistent. Uncontrolled longitudinal studies frequently reported improvements in depression and anxiety, but no randomized trials evaluated these outcomes, limiting causal inference. Exploratory cross-study patterns suggested that sustained navigation, practical assistance, and repeated peer contact were more often present in programs reporting favorable outcomes; however, these components were not independently evaluated. Substantial heterogeneity, frequent multicomponent interventions, high risk of bias in many nonrandomized studies, and limited long-term and economic data constrain conclusions. CONCLUSIONS: Findings support the promise of PRS while underscoring the need for more rigorous comparative studies, cost-effectiveness data, and further research in low- and middle-income countries.

Humans

Generation of spCAS9 expressing human mesenchymal stem cell line to study gene function during osteoblast differentiation.

Human bone marrow-derived stromal cells (hMSCs) are a great resource for studying how genes influence cell fate and differentiation into various cell types like osteoblasts, adipocytes, and chondrocytes, among other cell types. However, genetic manipulation of primary hMSCs has been challenging due to their short lifespan and cellular senescence after limited passaging. Their low and unstable transfection efficiency also complicates gene delivery or inactivation, hindering long-term functional studies. The limited lifespan has been effectively solved by immortalizing hMSCs with telomerase reverse transcriptase (hMSCs-TERT). The use of these cells is ideal for functional studies of osteoblast and adipocyte differentiation through genetic manipulation, providing a stable and reliable model. Here, we have engineered a stable CAS9 expressing hMSC-TERT cell line (hMSC-TERTCAS9) via lentiviral transduction. The constitutive expression of spCas9 enables efficient and reproducible gene editing. We demonstrate the potential of these hMSC-TERTCAS9 cells for generating gene disruptions using plasmid delivery of guide RNAs as a fast and efficient strategy for targeted genome editing. The edited cells can be sorted and expanded as single cells to obtain homogenous clonal cell lines with mono- as well as bi-allelic gene deletions, a crucial step for producing reliable experimental results. We further validate this cell line as a powerful tool for studying gene function during hMSC proliferation and differentiation, providing 3 distinct examples of its utility. Through the generation of indels, single-cell sorting, and clonal selection, we have efficiently inactivated the vitamin D receptor and created both larger (256 nucleotides) gene disruptions in Forkhead box protein O1 and precise removals of a small genomic sequence (73 nucleotides) coding for microRNA MIR675. This novel hMSC-TERTCAS9 cell line represents a significant advancement, offering a stable, efficient, and versatile platform for advanced genetic studies, high-throughput screening, and the creation of reliable cellular disease models.

CRISPR-Cas9

Safety and immunogenicity of an mRNA COVID-19 vaccine administered to adults: A phase 2, randomized, active-controlled trial.

We conducted a phase 2, randomized, active-controlled, observer-blind study (NCT05960097) among healthy adults ≥18 y of age who completed a primary COVID-19 mRNA vaccination series, with or without a booster, ≥3 months earlier. Participants were randomized (1:1:1:1:1) to either receive an investigational bivalent mRNA COVID-19 vaccine encoding ancestral D614G and Omicron BA.4-5 spike proteins (CV0701 mRNA vaccine) at one of three dose levels, an investigational monovalent mRNA COVID-19 vaccine encoding the Omicron BA.4-5 spike protein (CV0601 mRNA vaccine), or a licensed Original Wuhan/Omicron BA.4-5 bivalent mRNA COVID-19 vaccine. The primary objectives were to evaluate reactogenicity, safety and immunogenicity post-vaccination. Secondary and tertiary objectives were to further evaluate humoral and cell-mediated immunity post-vaccination. In total, 425 participants were vaccinated and 381 were included in the Day 29 per-protocol immunogenicity analysis. Most solicited events were mild to moderate. No vaccine-related serious adverse events or myocarditis/pericarditis cases were reported. For the CV0701 mRNA vaccine, a dose-dependent increase in Day 29 neutralizing titers against ancestral D614G and Omicron BA.4-5 was observed. Neutralizing titers against ancestral D614G and Omicron BA.4-5 declined by Days 91 and 181, but remained above baseline. Similar immune responses were observed for the CV0601 mRNA vaccine. At Day 8, CD4+ T cells (Th1 profile) increased in all study groups and CD8+ T cells increased in all study groups, except the lowest CV0701 dose group. The CV0701 and CV0601 mRNA vaccines elicited robust humoral and cellular immunity with an acceptable safety profile, comparable to a licensed, bivalent mRNA vaccine. Clinical Trial Registration EU CT number: 2023-504596-25-00 ClinicalTrials.gov: NCT05960097.

Humans

Feasibility, Satisfaction, and Preliminary Efficacy Trial of text4FATHER for Engaging Expectant Fathers in Infant Care from Pregnancy to Early Infancy.

Engaging fathers perinatally improves infant outcomes and parent well-being, yet few strategies share evidence with fathers. We explored the feasibility, acceptability, and preliminary efficacy of text4FATHER-a texting intervention designed to improve fathers' infant care beliefs, self-efficacy, behaviors, and partner support from mid-pregnancy to 2 months post-birth. In this exploratory pilot randomized controlled trial, 97 adult expectant fathers with less than a college degree were randomized to receive text4FATHER or not. Self-reported outcomes by fathers and mothers were assessed at baseline (mid-pregnancy) and 2 months post-birth. We analyzed intent-to-treat effects using random coefficient regression models. We found recruiting expectant fathers feasible; of eligible father-mother dyads, 123/163 consented (recruitment feasibility = 68%). All intervention fathers (100%) reported being satisfied with text4FATHER; 100% of mothers of intervention fathers also reported satisfaction with the father getting texts. First-time fathers' antenatal attachment beliefs and coparenting support were higher in text4FATHER condition vs. control from baseline to 7-month follow-up; increases in first-time fathers' confidence in fathering and infant care were also observed-the latter finding was corroborated by partners of first-time fathers. text4FATHER is a promising intervention, particularly for first-time expectant fathers with lower educational levels who have no natural clinical or public health touchpoints. Its efficacy and effectiveness should be confirmed using larger and more diverse samples.

Confidence

Self-selected goals outperform assigned goals in reducing mobile phone usage: Evidence from a randomized controlled trial.

Excessive smartphone use is increasingly recognized as a public-health concern, yet scalable approaches to help individuals regulate daily use remain limited. We examine whether allowing individuals to self-select reduction goals improves behavioral and psychological outcomes when incentives and average goal levels are held constant across conditions. In a twelve-week randomized controlled trial, (N = 149; over 9000 person-day observations), participants were assigned to (i) a self-selected condition (choosing a 10%, 20%, or 30% reduction in daily phone use), (ii) an assigned condition (assigned a 14% reduction goal), or (iii) a no-goal control condition. Participants who selected their own goals reduced phone use by 26 min more per day (73% larger reduction) and achieved their goals 11 percentage points more often than those assigned goals, despite identical incentives and average goal levels. Reductions in phone use and higher goal achievement were associated with improvements in perceived addiction, depressive, and anxiety symptoms. These psychological outcomes were secondary endpoints. Although the between-group estimates generally followed the same directional pattern as the behavioral outcomes, the sample size for these analyses was limited and the between-group differences were not statistically significant. These findings should therefore be interpreted with caution. Overall, the results provide causal field evidence that self-selection under this goal-setting design can improve behavioral outcomes. Allowing individuals to choose their own goals may strengthen engagement and support healthier digital behavior. Incorporating opportunities for goal-selection may represent a simple addition to digital-health and public-health interventions aimed at helping individuals moderate smartphone use and improve well-being.

Humans

Can't see the forest for the trees: The influence of marker type on inferred phylogenetic relationships in a cosmopolitan bat genus.

Fine-resolution information on species relationships and biological diversity is critically needed to guide conservation efforts amidst rapid environmental changes. Systematics, which forms the foundation of this knowledge, has been revolutionized by phylogenomics, utilizing genome-scale datasets. However, the use of diverse marker types, non-comparable taxon sampling, and outgroup selection can lead to conflicting phylogenetic hypotheses. These inconsistencies complicate study comparisons and hinder our ability to assess marker-specific impacts on phylogenetic resolution. The phylogenetic reconstruction of the bat genus Myotis, encompassing over 140 species and characterized by a rapid radiation in the last 20 million years, has been particularly influenced by these challenges. Achieving phylogenetic resolution in Myotis is particularly complex due to subtle interspecific differences in both morphological and molecular traits. Mitochondrial and nuclear markers often produce discordant trees, influenced by hybridization, introgression, and methodological variations. In this study, we employed a consistent taxonomic sample set of 44 Myotis taxa to evaluate the impact of five different genetic marker types on phylogenetic reconstruction. We observed significant discordance between topologies derived from conserved nuclear and mitochondrial markers and found that transposable elements were inadequate for resolving relationships across the entire genus. Our results also clarify the placement of previously problematic taxa within the genus. These findings emphasize the importance of aligning genetic marker choice with specific phylogenetic questions and highlight the influence of taxonomic and methodological variation on phylogenomic outcomes. This work provides a framework for improving phylogenetic inference in rapidly radiating groups and enhances our understanding of evolutionary history in Myotis.

Animals

Lifestyle interventions to prevent gestational and type 2 diabetes among migrant women from low- and middle-income countries: a systematic review.

Migrant women from low- and middle-income countries (LMICs) living in high-income settings experience disproportionately high risk of gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM). This review aimed to identify and synthesise culturally adapted lifestyle interventions for preventing or managing GDM and T2DM among migrant women from LMICs, focusing on intervention components, cultural adaptation strategies, and behavioural and metabolic outcomes. Five databases (PubMed, Embase, Scopus, CINAHL, Cochrane Central) were searched using Preferred Reporting Items for Systematic reviews and Meta-Analysis 2020 guidelines. Eligible studies included experimental designs involving lifestyle interventions delivered to migrant women from LMICs in high-income countries, reporting outcomes related to GDM or T2DM targeting behaviour change. Data were synthesised narratively; study quality was appraised using RoB2 for RCTs and a structured narrative approach for non-randomised designs. Certainty of evidence was evaluated using GRADE. Eight studies met the inclusion criteria. Sample sizes ranged from 28 to 641 participants. Intervention duration varied from 6 weeks to 12 months. Most interventions incorporated atleast one culturally tailored component, such as bilingual delivery, culturally adapted dietary education, or community-based engagement. Improvements were reported across dietary behaviours, physical activity, glycaemic measures, or diabetes-related knowledge; however, effect sizes were modest and inconsistent. Interventions combining dietary modification, physical activity, and culturally adapted delivery demonstrated greater improvements than exercise-only or digital-only programmes. Overall certainty of evidence ranged from low to moderate. Culturally adapted, multi-component lifestyle interventions show promise for improving behavioural and metabolic outcomes among migrant women from LMICs; however, the evidence base remains limited.

Humans

Skin cell suspension autograft as an evidence-based innovation in burn and wound treatment: A systematic review of global evidence across two decades.

BACKGROUND: Skin cell suspension autograft (SCSA) is a point-of-care approach to wound management facilitating epithelialization while reducing burden associated with conventional autografting. Despite growing clinical use of SCSA across diverse wound etiologies, the global clinical evidence describing its use has not yet been comprehensively synthesized. METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines to identify studies between January 2000 and December 2024 reporting clinical use of SCSA for wound closure. Data on patient demographics, wound characteristics, and treatment methods were extracted. Clinical, safety, and health economic outcomes were extracted for comparative studies evaluating SCSA against control treatments. RESULTS: Ninety-nine studies across 13 countries were included. Across the overall dataset, SCSA was used alone or in combination with autografting for burns, surgical wounds, traumatic injuries, inflammatory conditions, and chronic wounds. Among comparative studies (n=27), SCSA consistently reduced donor skin, and healing outcomes favored SCSA in 61%, while 39% reported equivalent outcomes. Pain and esthetic outcomes more frequently favored SCSA, while safety outcomes were generally similar, with some studies favoring comparators. Health-economic outcomes suggested potential reductions in length of stay and resource utilization, although findings were variable across studies. CONCLUSION: The available global evidence supports SCSA as a versatile modality for supporting epidermal coverage across wound types and clinical contexts. However, the findings should be interpreted in the context of the limitations of this review, which include heterogenous study designs, variable outcome reporting, predominance of non-randomized data, and the absence of a formal quantitative analysis. Nevertheless, the demonstrated clinical and economic benefits in comparative studies reinforce the role of SCSA as an evidence-based innovation for burn and wound treatment.

Humans

Decoding tumor immune microenvironment heterogeneity by single-cell and spatial multi-omics: From immunotherapy resistance to translational biomarkers.

Immune checkpoint blockade has transformed cancer therapy, yet primary and acquired resistance remain major clinical challenges. Increasing evidence indicates that immunotherapy resistance cannot be fully explained by tumor-intrinsic alterations or conventional biomarkers such as PD-L1 expression, tumor mutational burden, or microsatellite instability. Instead, therapeutic response is shaped by the tumor immune microenvironment (TIME) as a heterogeneous, spatially organized, and dynamically evolving ecosystem. Single-cell omics has revealed diverse immune and stromal cell states, including progenitor and terminally exhausted T cells, suppressive myeloid programs, B-cell/TLS-associated immune-reactive states, and CAF-mediated exclusion phenotypes. Spatial transcriptomics, spatial proteomics, and imaging-based approaches further demonstrate that these cell states assemble into distinct immune niches, including immune-inflamed, T-cell-excluded, myeloid-suppressive, metabolic/hypoxic, and TLS-associated niches. These spatial ecosystems determine whether antitumor immune cells can access malignant cells, receive antigen-presenting support, or become restrained by stromal, vascular, metabolic, and myeloid barriers. In this review, we summarize how single-cell and spatial multi-omics redefine TIME heterogeneity in immunotherapy resistance, highlight ligand-receptor communication networks linking cell states to spatial immune dysfunction, and discuss emerging translational biomarkers for patient stratification. We further propose that future immunotherapy biomarkers should evolve from static single-marker assays toward longitudinal, spatially resolved, and interpretable multi-omics models that guide precision combination immunotherapy.

Humans

Pathogenic Variants in HEPACAM Alter Protein Localization and Interactome in Astrocytes of the Developing Mouse Cortex.

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare leukodystrophy characterized by early-onset macrocephaly, white matter edema, seizures, and motor and cognitive decline. Approximately 25% of MLC patients carry HEPACAM pathogenic variants, many of which are dominant missense variants causing remitting MLC Type 2b. HEPACAM encodes hepatic and glial cell adhesion molecule (hepaCAM), also known as GlialCAM, an astrocyte-enriched transmembrane protein with important roles in astrocyte territory establishment, gap junction coupling, branching organization, synaptic function, and development of the gliovascular unit. The molecular mechanisms through which pathogenic variants in HEPACAM alter hepaCAM protein function in vivo and facilitate MLC pathogenesis during brain development remain largely unknown. Here, we used new viral tools and proximity-based proteomics to examine how three different dominant pathogenic variants alter hepaCAM subcellular localization and protein interactome in astrocytes of the developing mouse cortex. We found dramatic changes in hepaCAM distribution throughout the astrocyte, which were common to all mutants tested. We also observed significant changes in protein interactome between wild type and mutant hepaCAM, including decreased association with previously described hepaCAM-interacting proteins Connexin 43 and CLC-2. Moreover, we identified the epilepsy-associate potassium channel KCNQ2 as a novel hepaCAM interaction partner and found reduced association between KCNQ2 and pathogenic variants. Collectively, our data provide new insights into hepaCAM protein function in astrocytes during brain development, reveal altered protein dynamics of pathogenic variants, and provide a new resource to explore the molecular underpinnings of MLC pathogenesis.

Animals

[Study of a patient with azoospermia due to variant of MOV10L1 gene].

OBJECTIVE: To explore the clinical and genotypic characteristics of a patient with Sertoli cell-only syndrome (SCOS) due to variants of MOV10L1 gene. METHODS: A 27-year-old patient with Non-obstructive azoospermia (NOA) underwent routine semen analysis. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), estradiol (E2), prolactin (PRL), and testosterone (T) were determined by chemiluminescence assays. Peripheral blood samples were collected for G-banded karyotyping analysis. Multiplex PCR fluorescence detection was used to screen for AZF gene microdeletions. Whole exome sequencing (WES) and Sanger sequencing were performed simultaneously. Testicular biopsy tissues were subjected to Hematoxylin-Eosin (HE) staining to assess seminiferous tubule cell composition, and MOV10L1 protein expression was detected by immunohistochemical staining. Bioinformatics tools were employed to predict the pathogenicity of variants and their impact on protein structure and function. This study was approved by the Medical Ethics Committee of the Guangdong Institute of Reproductive Sciences [Ethics No.: 2023(01)]. RESULTS: The patient's two semen analyses had failed to detect any sperm. Hormone tests indicated elevated FSH (22.32 mIU/mL) and PRL (397.6 mIU/mL), while T (3.68 nmol/L) and E2 (38.32 pmol/L) were reduced. Chromosomal karyotyping revealed 46,XY, and no AZF gene deletion was detected. WES and Sanger sequencing detected compound heterozygous variants of the MOV10L1 gene, including a c.345C>A (p.C115X) nonsense variant and a c.3323C>T (p.T1108I) missense variant, with the former being unreported previously. HE staining showed only Sertoli cells in the seminiferous tubules, confirming the diagnosis of SCOS. Immunohistochemical staining revealed absent MOV10L1 protein expression in the testicular tissue. Based on the guidelines from American College of Medical Genetics and Genomics (ACMG), the c.345C>A (p.C115X) was classified as a pathogenic variant (PVS1+PM2_Supporting+PP4), while the c.3323C>T (p.T1108I) was deemed variant of uncertain significance (PM2_Supporting+PP3_Supporting+PP4). Bioinformatics analysis demonstrated that c.345C>A (p.C115X) may cause premature termination of protein translation, while c.3323C>T (p.T1108I) may disrupt the hydrophobicity of the RNA helicase domain, reducing the active pocket volume and decreasing its affinity for MILI protein. CONCLUSION: This study has diagnosed a case of SCOS due to compound heterozygous variants of the MOV10L1 gene, which also enriched its mutational spectrum.

Humans

Ablative radiotherapy in castration-resistant prostate cancer.

OBJECTIVE: To prove the oncological benefit of ablative radiotherapy in patients with up to five metastases from castration-resistant prostate cancer (CRPC) a single-centre randomised trial was initiated. PATIENTS AND METHODS: This monocentric, randomised, phase II clinical trial enrolled patients with up to five prostate-specific membrane antigen-positive bone or lymph node metastases developing prostate-specific antigen (PSA) progression during androgen deprivation (ADT) or ADT and androgen-receptor targeted therapy. Participants were randomised (2:1) to receive metastasis-directed therapy (MDT) or observation (OBS) without changing systemic therapy. The primary endpoint was the proportion of patients having PSA progression within 1 year, with statistical analyses conducted using intention-to-treat principles. Here, results of a planned interim analysis of the primary endpoint are reported. RESULTS: A total of 30 patients (12 in the observation arm and 18 in the MDT arm) were enrolled, PSA progression within 1 year occurred in 44% of the MDT group vs 75% in the OBS group (P = 0.14, not significant). The median time to PSA progression was significantly longer in the MDT arm (12.4 months) compared to the OBS arm (2.9 months, P = 0.03). The pre-defined criteria to discontinue the study were not met. Limitations include the single-centre design and small sample size at interim analysis. CONCLUSION: This pre-planned interim analysis of the primary endpoint did not meet the discontinuation criteria of the study protocol, suggesting that MDT in oligometastatic CRPC may extend the time to PSA progression without immediate change of systemic therapy. The continuation of the study in a multicentre setting is planned (Institutional funding by the TU Dresden, ClinicalTrials.gov identifier: NCT04141709).

Humans

Immersive virtual reality-assisted anatomy training improves endotracheal intubation performance in simulation: a randomized controlled trial among Chinese non-anesthesiology residents.

INTRODUCTION: This study aimed to compare immersive virtual reality (IVR)-assisted versus conventional anatomy training for teaching endotracheal intubation (ETI) to novice non-anesthesiology residents enrolled in China's Standardized Residency Training program. METHODS: A total of 90 non-anesthesiology residents without prior ETI experience were randomly assigned to either an IVR group receiving IVR-assisted anatomy training (n&#x2009;=&#x2009;45) or a control group receiving conventional anatomy training (n&#x2009;=&#x2009;45). All participants underwent a standardized teaching protocol. The primary endpoint was residents' ETI performance on a simulator, assessed using both the Global Rating Scale (GRS) and a task-specific checklist. The secondary endpoints included changes in written multiple-choice question (MCQ) scores and residents' evaluations of the course. RESULTS: In practical ETI assessments on a manikin, the IVR group achieved significantly higher scores on the task-specific checklist than the control group (90.34&#x2009;&#xb1;&#x2009;2.89 vs. 87.20&#x2009;&#xb1;&#x2009;3.29; p&#x2009;<&#x2009;0.001), whereas GRS scores were comparable between groups. Both groups showed significant post-training improvement in knowledge scores (p&#x2009;<&#x2009;0.001), with the IVR group showing a greater gain in theoretical knowledge (54.0% vs. 36.3%; p&#x2009;<&#x2009;0.001). Participants in the IVR group also expressed a stronger preference for their training method (80.8%) and reported higher levels of motivation, confidence, and enjoyment (all p&#x2009;<&#x2009;0.05). CONCLUSION: IVR-assisted anatomy training enhances the effectiveness of ETI training for novice non-anesthesiology residents, offering an interactive, engaging, and reproducible approach within China's Standardized Residency Training framework.

Humans

Acceptability of alcohol-based hand rub during neonatal care in rural Ugandan households: a qualitative study nested within the BabyGel trial.

BACKGROUND: Poor access to water, sanitation and hygiene exacerbates the spread of infections among newborns. The BabyGel cluster randomised trial assessed the effectiveness of a community-level alcohol-based hand rub with a training component in reducing infection or death rates among newborns in Uganda. OBJECTIVE: Nested in the BabyGel trial, this study investigated the acceptability of the BabyGel intervention among mothers and household members in Eastern Uganda, using the Theoretical Framework of Acceptability. METHODS: In 2022, we conducted individual semistructured interviews with mothers, and group interviews with mothers and other household members, all recruited from intervention-arm clusters. Thematic analysis combined inductive and deductive coding, structured by the framework's seven constructs: affective attitude, burden, ethicality, intervention coherence, opportunity costs, perceived effectiveness and self-efficacy. RESULTS: Twenty mothers and 14&#xa0;household members participated in 10 individual and 10 small group interviews. Participants found the intervention generally acceptable, appreciating its convenience and perceived protection against infection. Many described hand hygiene changes that persisted beyond the intervention period. However, concerns related to its harmful effects, spiritual beliefs and social tensions with visitors occasionally influenced its use. CONCLUSION: Alcohol-based hand rub combined with a training component was generally well accepted, driven by perceived health and practical benefits, although concerns related to safety, belief systems and social dynamics remained. Because data collection coincided with the COVID-19 pandemic, a period of heightened hygiene awareness, the acceptability observed could differ in nonpandemic periods. Culturally adapted education, community engagement and reinforcement of correct use may enhance acceptability and sustainability in similar settings.

Humans

Design, rationale, and baseline patient characteristics for the Sickle Cell Disease and CardiovAscular Risk-Red cell Exchange (SCD-CARRE) trial.

BACKGROUND: Despite wide utilization of automated red blood cell exchange (RBCX) transfusion in adult patients with sickle cell disease (SCD), no consensus or quality efficacy data exist on its use. The Sickle Cell Disease and CardiovAscular Risk- Red cell Exchange (SCD-CARRE) trial tests the hypothesis that an automated chronic RBCX transfusion strategy reduces acute health care encounters and death while improving quality of life and end-organ function (cardiac, pulmonary and renal) in participants with SCD that are at high risk of death. METHODS: Adult patients with SCD with elevated tricuspid regurgitant jet velocity (TRV) and/or chronic kidney disease were considered to be at high risk of death and were randomly assigned to RBCX plus standard of care vs standard of care alone. Participants assigned to RBCX received 12 months of exchange transfusions to maintain target pretransfusion hemoglobin S% < 30%, post-transfusion hemoglobin S% < 20%, and post-transfusion hemoglobin concentration &#x2265;10 g/dL. All study participants were managed according to NHLBI/ASH/ATS Expert Panel guidelines. The primary endpoint was the number of SCD acute health care encounters or death over 13 months. Secondary endpoints included measures of cardiovascular and renal function, exercise capacity, patient reported outcomes (all collected at baseline, and months 4, 8, and 12), and transfusion-related adverse events (collected monthly). RESULTS: Between 2020 and 2025, the SCD-CARRE trial randomized 173 participants at 23 sites across 3 countries. Enrolled participants had mean (SD) age of 45.8 (11.8) years and 54% were female. At baseline, participants had average TRV of 2.8 (0.5) m/s such that 45.9% had a TRV between 2.5 to 2.9 m/sec and 28.1% had a TRV &#x2265; 3.0 m/sec. The median (Q1, Q3) eGFR in this cohort was 60 (36, 110) mL/min/1.73 m2. The median (Q1, Q3) 6-minute walk test distance was 375 meters (309, 439), the median daily steps were 3,728 (2,187, 5,821), and participants experienced a median (Q1, Q3) of 2 (1, 5) pain episodes in the year prior to randomization. The trial results are pending. CONCLUSIONS: The SCD-CARRE trial successfully enrolled a cohort of n = 173 adults with SCD. This study highlights a rationale to evaluate the effect of automated chronic RBCX transfusion strategy plus standard of care as compared to standard of care alone in SCD patients at high risk of death with a focus on patient centered outcomes, preservation of cardiovascular function, end-organ complications and death. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT04084080, https://clinicaltrials.gov/study/NCT04084080.

Adult

Integrated bioinformatics analysis reveals cross-talking hub genes and therapeutic agents between sepsis and acute myocardial infarction.

BACKGROUND: Sepsis and acute myocardial infarction (AMI) are two significant diseases that may share overlapping etiological mechanisms. This study aims to systematically identify core genes common to both conditions and to explore their potential as therapeutic targets and drug candidates through an integrative analysis of clinical data and bioinformatics. METHODS: The AMI dataset was obtained from the GEO database, and RNA sequencing data were collected from blood samples of patients with sepsis at our hospital. Common genes were identified using differential expression gene analysis (DEG) and weighted gene co-expression network analysis (WGCNA). Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were performed. A protein-protein interaction (PPI) network was constructed, and hub genes were identified using the MCC/Degree algorithm. Diagnostic value was assessed via receiver operating characteristic curve analysis. Immune infiltration patterns, single-cell sequencing data, and molecular docking simulations were employed to evaluate immune relevance and identify potential therapeutic compounds. RESULTS: A total of 417 genes were identified between sepsis and AMI, with enrichment analysis revealing significant involvement in inflammatory responses. Three hub genes-JAK2, MYD88, and TIMP1-were selected for further investigation. ROC curves confirmed their strong diagnostic performance for both diseases. Immune infiltration analysis showed that these core genes were significantly correlated with the infiltration levels of various immune cell types. Molecular docking indicated that quercetin exhibited stable binding affinity with the proteins encoded by these genes. qPCR validation further confirmed the upregulation of these three genes, supporting the anti-inflammatory effects of quercetin as a potential targeted therapy. CONCLUSION: JAK2, MYD88, and TIMP1 were identified as shared core genes in sepsis and AMI. These genes not only serve as potential diagnostic biomarkers but also offer novel targets for developing common therapeutic strategies for both conditions. Furthermore, quercetin emerges as a promising candidate for targeted treatment.

Humans

Smartphone apps for obesity management: A systematic review using self-determination theory.

BACKGROUND: While bariatric surgery and pharmacotherapy are effective treatments for obesity, ongoing supportive care remains a challenge. Smartphone applications (apps) may assist with symptom management, but their effectiveness and practical use in obesity treatment is unclear. This review evaluated the effectiveness, acceptability, and feasibility of these apps in supporting individuals following obesity treatment. To better understand how these apps may promote sustained engagement and behaviour change, their design was analysed using Self-Determination Theory (SDT). METHODS: A systematic search was conducted across MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, SCOPUS, and CENTRAL databases. Eligible studies included randomised and non-randomised interventions involving adults (&#x2265;18&#xa0;years) with obesity (BMI&#xa0;&#x2265;&#xa0;30&#xa0;kg/m2) who had undergone bariatric surgery or pharmacotherapy. Interventions had to include an app designed to support post-treatment symptom management. Findings were synthesised narratively, and app features were mapped to SDT constructs of autonomy, competence, and relatedness. RESULTS: Five studies (three RCTs, two cohort studies) involving 1,133 participants were included (female: 78&#xa0;%; median age: 47.63&#xa0;years). Most apps targeted post-bariatric surgery care; only one focused on pharmacotherapy. Common features included tracking, reminders, and education, supporting autonomy and competence. Relatedness features such as communication and peer support were least represented. Two studies reported improvements in weight-related outcomes and one in medication adherence. Effects on quality of life, self-efficacy, and healthcare utilisation were not significant. Patient satisfaction was reported in one study, with 95&#xa0;% expressing positive feedback, though formal assessments of feasibility and acceptability were limited. CONCLUSION: Smartphone apps show potential to support obesity management, particularly after bariatric surgery. While some evidence suggests benefits for weight loss and adherence outcomes, the limited studies and variability of reporting prevent conclusive observations in other outcomes. Future app development should integrate behavioural theory to address psychological needs, nutritional risks and promote holistic self-management beyond weight control.

Female

Mul-PheG2P: decoupled learning and prediction-space fusion enables robust and interpretable multi-phenotype genomic prediction.

Genomic prediction of multiple phenotypes is crucial in modern plant breeding; however, existing methods struggle with negative transfer and lack interpretability, particularly across high-dimensional small-sample data and diverse species. To address this, we propose Mul-PheG2P, a novel paradigm based on decoupled learning and predictive space fusion. It employs a two-stage design: first training phenotype-specific encoders using genetic data, then decoupling phenotype-specific learning from cross-phenotype aggregation via an interpretable prediction layer. Mul-PheG2P outperforms existing methods across diverse crop datasets, including maize (Zea mays), wheat (Triticum aestivum), and tomato (Solanum lycopersicum). It provides a multi-scale interpretability chain: at the macro level, it quantifies phenotypic contributions via attention-based weighting; at the micro level, Integrated Gradients reveal the genetic basis of predictions. Notably, the model successfully identified the CCT (CONSTANS, CO-like, and TOC) motif regulating photoperiodism and the SQUAMOSA (SQUAMOSA promoter binding protein) promoter for inflorescence development, confirming its ability to capture functional biological mechanisms. These results highlight the high performance and interpretability of Mul-PheG2P, showcasing its value for low-cost, large-scale screening to advance precision breeding.

Phenotype