Supporting implementation of universal prevention initiatives in K-12 schools: impacts on fidelity through organizational readiness and team functioning in a cluster-randomized trial.

Background: Rural School Support Strategies (RS3) is a bundle of implementation supports (including training, technical assistance, and a virtual learning collaborative) designed for the scale-up of universal prevention initiatives. This study addresses mechanisms of action, exploring whether positive effects of RS3 on implementation fidelity are attributable to improvements in functioning of school implementation teams, and increases in organizational readiness.

Methods: Data are from a cluster-randomized hybrid Type 3 implementation-effectiveness trial of RS3 among rural Idaho schools implementing Positive Behavioral Interventions and Supports (PBIS).

Association between the changes in the estimated glucose disposal rate and new-onset cardiovascular disease in middle-aged and elderly individuals: A nationwide prospective cohort study in China.

Aims: Previous studies have shown that eGDR and TyG, as indicators of insulin resistance (IR), were key risk factors for cardiovascular disease (CVD). Our study further explored the relationship between eGDR change and new-onset CVD, and compared the predictive value of eGDR change, eGDR and TyG.

Materials And Methods: A total of 2895 participants without CVD at baseline from the China Health and Retirement Longitudinal Study (CHARLS) were included, using K-means clustering and cumulative eGDR to measure eGDR change between 2012 and 2015.

Uncovering potential causal genes for undiagnosed congenital anomalies using an in-house pipeline for trio-based whole-genome sequencing.

Background: Congenital anomalies (CAs) encompass a wide spectrum of structural and functional abnormalities during fetal development, commonly presenting at birth. Identifying the cause of CA is essential for accurate diagnosis and treatment. Using a target-gene approach, genetic variants could be found in certain CA patients.

Sexual Health Advocacy for Guys (SHAG): a randomized trial of the impact of a text-messaging program on HIV incidence and STI testing among a national sample of sexual minority cisgender adolescent and young adult men.

Background: Disparities in sexually transmitted infections (STI) including human immunodeficiency virus (HIV) among sexual minority boys and young men are substantial. Effective HIV and STI prevention programs that include access to pre-exposure prophylaxis (PrEP) medication do not consistently include younger sexual minority men. Text-messaging programs for HIV prevention have been associated with increases in HIV testing among sexual minority adolescent boys, but these programs have not incorporated a focus on PrEP or STIs beyond HIV.

Comparative genomics analyses of Actinobacteriota identify Golgi phosphoprotein 3 (GPP34) as a widespread ancient protein family associated with sponge symbiosis.

Background: Sponges harbor microbial communities that play crucial roles in host health and ecology. However, the genetic adaptations that enable these symbiotic microorganisms to thrive within the sponge environment are still being elucidated. To understand these genetic adaptations, we conducted a comparative genomics analysis on 350 genomes of Actinobacteriota, a phylum commonly associated with sponges.

Implementation processes and capacity-building needs in Ontario maternal-newborn care hospital settings: a cross-sectional survey.

Background: Maternal-newborn care does not always align with the best available evidence. Applying implementation science to change initiatives can help move evidence-informed practices into clinical settings. However, it remains unknown to what extent current implementation practices in maternal-newborn care align with recommendations from implementation science, and how confident nurses, other health professionals, and leaders are completing steps in the implementation process.

Advances in Novel Targeted Therapies for Pancreatic Adenocarcinoma.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with limited therapeutic options and poor prognosis. Recent advances in targeted therapies have opened new avenues for intervention in PDAC, focusing on key genetic and molecular pathways that drive tumor progression.

Methods: In this review, we provide an overview on advances in novel targeted therapies in pancreatic adenocarcinoma.

Comparing Single-Hospital and National Models to Predict 30-Day Inpatient Mortality.

Background: Advances in artificial intelligence and machine learning have facilitated the creation of mortality prediction models which are increasingly used to assess quality of care and inform clinical practice. One open question is whether a hospital should utilize a mortality model trained from a diverse nationwide dataset or use a model developed primarily from their local hospital data.

Objective: To compare performance of a single-hospital, 30-day all-cause mortality model against an established national benchmark on the task of mortality prediction.

Aberrant splicing in Huntington's disease accompanies disrupted TDP-43 activity and altered m6A RNA modification.

Huntington's disease (HD) is caused by a CAG repeat expansion in the HTT gene, leading to altered gene expression. However, the mechanisms leading to disrupted RNA processing in HD remain unclear. Here we identify TDP-43 and the N6-methyladenosine (m6A) writer protein METTL3 to be upstream regulators of exon skipping in multiple HD systems.

A multiplex method for rapidly identifying viral protease inhibitors.

With current treatments addressing only a fraction of pathogens and new viral threats constantly evolving, there is a critical need to expand our existing therapeutic arsenal. To speed the rate of discovery and better prepare against future threats, we establish a high-throughput platform capable of screening compounds against 40 diverse viral proteases simultaneously. This multiplex approach is enabled by using cellular biosensors of viral protease activity combined with DNA-barcoding technology, as well as several design innovations that increase assay sensitivity and correct for plate-to-plate variation.

Co-occurring Psychopathology in Children With and Without Autism Spectrum Disorder (ASD): Differences by Sex in the ECHO Cohorts.

Purpose: Our goals were to: 1) examine the occurrence of behavioral and emotional symptoms in children on the autism spectrum in a large national sample, stratifying by sex, and 2) evaluate whether children with increased autism-related social communication deficits also experience more behavioral and emotional problems.

Methods:  Participants (n = 7,998) were from 37 cohorts from the Environmental influences on Child Health Outcomes (ECHO) Program. Cross-sectional information on demographic factors, parent-report of an ASD diagnosis by clinician, Social Responsiveness Scale (SRS) scores, and Child Behavior Checklist (CBCL) scores were obtained for children aged 2.

Impact of extended-course oral nirmatrelvir/ritonavir in established Long COVID: a case series.

Background: Prior case series suggest that a 5-day course of oral Paxlovid (nirmatrelvir/ritonavir) benefits some people with Long COVID, within and/or outside of the context of an acute reinfection. To the best of our knowledge, there have been no prior case series of people with Long COVID who have attempted longer courses of nirmatrelvir/ritonavir.

Methods: We documented a case series of 13 individuals with Long COVID who initiated extended courses (>5 days; range: 7.

Respiratory Outcomes and Aspergillus Serology Following Elexacaftor/Tezacaftor/Ivacaftor Therapy in People with Cystic Fibrosis and a History of Aspergillus fumigatus Infection.

Purpose: The study evaluated the effects of elexacaftor/tezacaftor/ivacaftor (ETI) therapy in people with cystic fibrosis (pwCF) and a clinical history of Aspergillus fumigatus (AF) infection.

Methods: This prospective cohort study included pwCF who initiated ETI therapy and had received antifungal treatment in the preceding five years due to allergic bronchopulmonary aspergillosis (ABPA group) or other AF-related clinical manifestations (AF group). A control group of pwCF with no prior respiratory cultures positive for AF was also included.

Joint EANM/EANO/RANO/SNMMI practice guideline/procedure standard for PET imaging of brain metastases: version 1.0.

This joint practice guideline/procedure standard was collaboratively developed by the European Association of Nuclear Medicine (EANM), the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the European Association of Neuro-Oncology (EANO), and the PET task force of the Response Assessment in Neurooncology Working Group (PET/RANO). Brain metastases are the most common malignant central nervous system (CNS) tumors. PET imaging with radiolabeled amino acids and to lesser extent [F]FDG has gained considerable importance in the assessment of brain metastases, especially for the differential diagnosis between recurrent metastases and treatment-related changes which remains a limitation using conventional MRI.

Acceptability of the Fit2ThriveMB mHealth physical activity promotion intervention in women with metastatic breast cancer.

Purpose: Increasing physical activity (PA) is safe and associated with improved health outcomes in patients with metastatic breast cancer (MBC). Mobile health (mHealth) PA interventions that allow for remote monitoring and tailoring to abilities may be particularly useful for MBC patients. However, limited data exist on the acceptability of these interventions for MBC patients.

Metabolic rewiring in skin epidermis drives tolerance to oncogenic mutations.

Skin epithelial stem cells correct aberrancies induced by oncogenic mutations. Oncogenes invoke different strategies of epithelial tolerance; while wild-type cells outcompete β-catenin-gain-of-function (βcatGOF) cells, Hras cells outcompete wild-type cells. Here we ask how metabolic states change as wild-type stem cells interface with mutant cells and drive different cell-competition outcomes.

Intellectual frameworks to understand complex biochemical systems at the origin of life.

Understanding the emergence of complex biochemical systems, such as protein translation, is a great challenge. Although synthetic approaches can provide insight into the potential early stages of life, they do not address the equally important question of why the complex systems of life would have evolved. In particular, the intricacies of the mechanisms governing the transfer of information from nucleic acid sequences to proteins make it difficult to imagine how coded protein synthesis could have emerged from a prebiotic soup.

The identification of a SARs-CoV2 S2 protein derived peptide with super-antigen-like stimulatory properties on T-cells.

Severe COVID-19 can trigger a cytokine storm, leading to acute respiratory distress syndrome (ARDS) with similarities to superantigen-induced toxic shock syndrome. An outstanding question is whether SARS-CoV-2 protein sequences can directly induce inflammatory responses. In this study, we identify a region in the SARS-CoV-2 S2 spike protein with sequence homology to bacterial super-antigens (termed P3).

Effect of DLPFC rTMS on anhedonia and alpha asymmetry in depressed patients.

Anhedonia, a core symptom of depression, has been defined as the loss of pleasure or lack of reactivity to pleasurable stimuli. Considering the relevance of alpha asymmetry to MDD and anhedonia, we explored the effect of dorsolateral prefrontal cortex (DLPFC) stimulation on frontal and posterior EEG alpha asymmetry (FAA and PAA, respectively), in this exploratory investigation. 61 participants randomly received sham (n = 11), bilateral (BS; n = 25), or unilateral stimulation (US; n = 25) of the DLPFC.

Using telemedicine and virtual healthcare to improve clinical follow-up for survivors of sexual assault and intimate partner violence: a 7-year investigation of emergency department cases.

Introduction: The primary objective was to evaluate the effectiveness of telemedicine for improving clinical follow-up for survivors of sexual assault and intimate partner violence after an emergency department (ED) visit. The Sexual Assault and Partner Abuse Care Program (SAPACP) is an ED-based clinic for survivors of sexual assault/intimate partner violence. Virtual Visit, a telemedicine platform, was introduced at SAPACP in January 2020, allowing patients to attend follow-up virtually.

Impact of an Antenatal Family-based Behavioral Treatment with a Nutrition and Exercise Lifestyle Intervention Program on Infant Weight-for-length at Birth.

Background: World Health Organization (WHO) growth standards, including weight-for-length, are used to monitor infant size. Excessive infant weight-for-length at or above the 85th percentile is a risk for childhood overweight. Although antenatal interventions like the nutrition and exercise lifestyle intervention program (NELIP) have successfully prevented excessive gestational weight gain, strategies to improve the intervention remain of interest.

Knockout or inhibition of DHPS suppresses ovarian tumor growth and metastasis by attenuating the TGFβ pathway.

Deoxyhypusine synthase (DHPS) is an enzyme encoded by the DHPS gene, with high expression in various cancers, including ovarian cancer (OC). DHPS regulates the translation initiation factor EIF5A, and EIF5A2 knockout inhibits OC tumor growth and metastasis by blocking the epithelial-to-mesenchymal transition (EMT) and the TGFβ pathway. In this study, we show that DHPS is amplified in OC patients, and its elevated expression correlates with poor survival.

Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

Selumetinib in adults with NF1 and inoperable plexiform neurofibroma: a phase 2 trial.

The MEK inhibitor selumetinib induces objective responses and provides clinical benefit in children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PNs). To evaluate whether similar outcomes were possible in adult patients, in whom PN growth is generally slower than in pediatric patients, we conducted an open-label phase 2 study of selumetinib in adults with NF1 PNs. The study was designed to evaluate objective response rate (primary objective), tumor volumetric responses, patient-reported outcomes and pharmacodynamic effects in PN biopsies.