Lerodalcibep and evolocumab for the treatment of homozygous familial hypercholesterolaemia with PCSK9 inhibition (LIBerate-HoFH): a phase 3, randomised, open-label, crossover, non-inferiority trial.

Background: Lerodalcibep, a small binding anti-PCSK9 protein (adnectin), showed effective LDL cholesterol reduction in heterozygous familial hypercholesterolaemia. We aimed to assess the safety and efficacy of lerodalcibep and evolocumab in a globally diverse homozygous familial hypercholesterolaemia population.

Methods: This phase 3, randomised, open-label, crossover, non-inferiority study consisted of two 24-week treatment periods separated by an 8-week washout.

Convergent validity of a person-dependent definition of a low back pain flare.

Unlabelled: Exacerbations of existing low back pain (LBP) or new LBP episodes are colloquially referred to as "flares". Although the experience of flares is common to many people with LBP, few validated measures enable people to self-report if they are experiencing a flare. This study examined the convergent validity of a person-dependent definition of flares ("a worsening of your low back pain that lasts from hours to weeks") as compared to (1) LBP intensity, (2) LBP-related pain interference, and (3) analgesic use, in a large, prospective research study of Veterans with LBP.

A forward genetic screen identifies potassium channel essentiality in SHH medulloblastoma maintenance.

Distinguishing tumor maintenance genes from initiation, progression, and passenger genes is critical for developing effective therapies. We employed a functional genomic approach using the Lazy Piggy transposon to identify tumor maintenance genes in vivo and applied this to sonic hedgehog (SHH) medulloblastoma (MB). Combining Lazy Piggy screening in mice and transcriptomic profiling of human MB, we identified the voltage-gated potassium channel KCNB2 as a candidate maintenance driver.

High cellular plasticity state of medulloblastoma local recurrence and distant dissemination.

Medulloblastoma (MB), a heterogeneous pediatric brain tumor, poses challenges in the treatment of tumor recurrence and dissemination. To characterize cellular diversity and genetic features, we comprehensively analyzed single-cell/nucleus RNA sequencing (sc/snRNA-seq), single-nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq), and spatial transcriptomics profiles and identified distinct cellular populations in SHH (sonic hedgehog) and Group_3 subgroups, with varying proportions in local recurrence or dissemination. Local recurrence showed higher cycling tumor cell enrichment, whereas disseminated lesions had a relatively notable presence of differentiated subsets.

Genomic re-sequencing reveals mutational divergence across genetically engineered strains of model archaea.

Unlabelled: Archaeal molecular biology has been a topic of intense research in recent decades as their role in global ecosystems, nutrient cycles, and eukaryotic evolution comes to light. The hypersaline-adapted archaeal species and serve as important model organisms for understanding archaeal genomics, genetics, and biochemistry, in part because efficient tools enable genetic manipulation. As a result, the number of strains in circulation among the haloarchaeal research community has increased in recent decades.

God Knows Best: Exploring the God Locus of Health Control, Race-Ethnicity, and Risk-Taking and Protective Behaviors Interrelationship in the USA.

The health implications of engaging in risk-taking or protective behaviors can have long-lasting effects on an individual's life. In recent years, there has been a growing interest in how religious attitudes and beliefs influence an individual's health behaviors. However, research on the role of the God Locus of Health Control (GLHC) in the religion-health literature is lacking.

ZIC1 is a context-dependent medulloblastoma driver in the rhombic lip.

Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma).

Gender and Intersecting Barriers and Facilitators to Access the HIV Cascade of Care in Manitoba, Canada, Before and During the COVID-19 Pandemic: A Qualitative Study.

Marginalized groups in Manitoba, Canada, especially females and people who inject drugs, are overrepresented in new HIV diagnoses and disproportionately affected by HIV and structural disadvantages. Informed by syndemic theory, our aim was to understand people living with HIV's (PLHIV) gendered and intersecting barriers and facilitators across the cascade of HIV care before and during the COVID-19 pandemic. This study was co-designed and co-led alongside people with lived experience and a research advisory committee.

A robust benchmark for detecting low-frequency variants in the HG002 Genome In A Bottle NIST reference material.

Somatic mosaicism is an important cause of disease, but mosaic and somatic variants are often challenging to detect because they exist in only a fraction of cells. To address the need for benchmarking subclonal variants in normal cell populations, we developed a benchmark containing mosaic variants in the Genome in a Bottle Consortium (GIAB) HG002 reference material DNA from a large batch of a normal lymphoblastoid cell line. First, we used a somatic variant caller with high coverage (300x) Illumina whole genome sequencing data from the Ashkenazi Jewish trio to detect variants in HG002 not detected in at least 5% of cells from the combined parental data.

Alcohol Alters Skeletal Muscle Bioenergetic Function: A Scoping Review.

Bioenergetic pathways uniquely support sarcomere function which, in turn, helps to maintain functional skeletal muscle (SKM) mass. Emerging evidence supports alcohol (EtOH)-induced bioenergetic impairments in SKM and muscle precursor cells. We performed a scoping review to synthesize existing evidence regarding the effects of EtOH on SKM bioenergetics.

Evaluating the representativeness of a cohort study of low back pain: Using electronic health record data to make direct comparisons of study participants with non-participants from the study population.

Representativeness is an important component of generalizability. Few studies have rigorously examined the representativeness of randomized trials or observational studies of pain or musculoskeletal conditions with regards to a wide range of factors beyond age, sex, race, and ethnicity. We conducted the first study of a pain condition that uses individual-level data to directly compare the enrolled study sample to the population from which it was drawn.

Burnout amongst chiropractic faculty, practitioners, and trainees: a scoping review.

Objective: The purpose of this scoping review was to summarize the literature pertaining to burnout and chiropractic.

Methods: A literature review was performed in accordance with Preferred Reporting of Systematic Reviews and Meta-Analysis Extension for Scoping Reviews (PRISMA-ScR). A literature review was performed by combining the term "chiropractic" with terms relevant to professional burnout (e.

Opioid Sparing Anesthesia for Adult Spinal Deformity Surgery Reduces Postoperative Pain, Length of Stay, Opioid Consumption, and Opioid-Related Complications: A Propensity-Matched Analysis.

Study Design: This study was a retrospective propensity-matched study of patients receiving opioid sparing anesthesia (OSA) and those who did not receive an opioid sparing anesthesia regimen.

Objectives: To determine whether patients undergoing spine fusion for deformity fared better with an OSA regimen than those not having an OSA regimen.

Summary Of Background Data: There has been a tremendous focus on opioid overuse.

TULIPs decorate the three-dimensional genome of PFA ependymoma.

Posterior fossa group A (PFA) ependymoma is a lethal brain cancer diagnosed in infants and young children. The lack of driver events in the PFA linear genome led us to search its 3D genome for characteristic features. Here, we reconstructed 3D genomes from diverse childhood tumor types and uncovered a global topology in PFA that is highly reminiscent of stem and progenitor cells in a variety of human tissues.

Results From the Big Ten COVID-19 Cardiac Registry: Impact of SARS-COV-2 on Myocardial Involvement.

Objective: COVID-19 has been associated with myocardial involvement in collegiate athletes. The first report from the Big Ten COVID-19 Cardiac Registry (Registry) was an ecological study that reported myocarditis in 37 of 1597 athletes (2.3%) based on local clinical diagnosis.

Early rhombic lip Protogenin stem cells in a human-specific neurovascular niche initiate and maintain group 3 medulloblastoma.

We identify a population of Protogenin-positive (PRTG) MYC NESTIN stem cells in the four-week-old human embryonic hindbrain that subsequently localizes to the ventricular zone of the rhombic lip (RL). Oncogenic transformation of early Prtg rhombic lip stem cells initiates group 3 medulloblastoma (Gr3-MB)-like tumors. PRTG stem cells grow adjacent to a human-specific interposed vascular plexus in the RL, a phenotype that is recapitulated in Gr3-MB but not in other types of medulloblastoma.

Timely PAH Identification in Adults With Repaired Congenital Heart Disease? The ACHD-QuERI Registry Insights.

Background: The Quality Enhancement Research Initiative (QuERI) in adults with congenital heart disease (ACHD) was developed to improve detection of pulmonary arterial hypertension (PAH) after repair of systemic-to-pulmonary arterial shunt lesions.

Objectives: This study sought to standardize use of accepted criteria for PAH diagnosis and evaluate utility in at-risk patients with ACHD.

Methods: Patients ≥18 years of age with ACHD repaired ≥1 year before enrollment and with additional risk factors for developing PAH were eligible.

Transcatheter Interventions in Adult Congenital Heart Disease.

Congenital heart disease (CHD) is the most common congenital birth defect with an incidence of 1 in 100. Current survival to adulthood is expected in 9 out of 10 children with severe CHD as the diagnostic, interventional, and surgical success improves. The adult CHD (ACHD) population is increasingly diverse, reflecting the broad spectrum of CHD and evolution of surgical techniques to improve survival.

Catalyzing communities of research rigour champions.

The biomedical sciences must maintain and enhance a research culture that prioritizes rigour and transparency. The US National Institute of Neurological Disorders and Stroke convened a workshop entitled 'Catalyzing Communities of Research Rigor Champions' that brought together a diverse group of leaders in promoting research rigour and transparency (identified as 'rigour champions') to discuss strategies, barriers and resources for catalyzing technical, cultural and educational changes in the biomedical sciences. This article summarizes 2 days of panels and discussions and provides an overview of critical barriers to research rigour, perspectives behind reform initiatives and considerations for stakeholders across science.