Effect of semaglutide 2.4 mg on use of antihypertensive and lipid-lowering treatment in five randomized controlled STEP trials.

Objective: The objective of this study was to assess antihypertensive and lipid-lowering treatment changes in participants receiving semaglutide 2.4 mg versus placebo across pooled populations from five Semaglutide Treatment Effect in People with Obesity (STEP) trials.

Methods: Efficacy and safety of semaglutide 2.

It is time to reconsider the use of naturally-occurring endotoxins in endotoxin recovery studies: Part 2 of a BioPhorum harmonized endotoxin recovery study.

The evaluation of Naturally Occurring Endotoxins (NOEs) for Low Endotoxin Recovery (LER) studies has been a topic in the industry and regulatory agencies have been hesitant to endorse NOE use in LER studies over purified Lipopolysaccharide (LPS) standards such as Control Standard Endotoxin (CSE) or Reference Standard Endotoxin (RSE). In a recent study involving 11 BioPhorum member companies across 13 sites, NOEs prepared in high and low nutrient conditions were evaluated in two common monoclonal antibody buffer formulations: 10 mM Sodium Citrate, 0.05 % Polysorbate 80, pH 6.

Curating retrospective multimodal and longitudinal data for community cohorts at risk for lung cancer.

Background: Large community cohorts are useful for lung cancer research, allowing for the analysis of risk factors and development of predictive models.

Objective: A robust methodology for (1) identifying lung cancer and pulmonary nodules diagnoses as well as (2) associating multimodal longitudinal data with these events from electronic health record (EHRs) is needed to optimally curate cohorts at scale.

Methods: In this study, we leveraged (1) SNOMED concepts to develop ICD-based decision rules for building a cohort that captured lung cancer and pulmonary nodules and (2) clinical knowledge to define time windows for collecting longitudinal imaging and clinical concepts.

The role of dairy food intake for improving health among black Americans across the life continuum: A summary of the evidence.

Decades of health data show major health disparities occurring at every life stage between Black and White Americans. These disparities include greater mortality rates among Black mothers and their offspring, higher levels of malnutrition and obesity among Black children and adolescents, and a higher burden of chronic disease and lower life expectancy for Black adults. Although nutrition is only one of many factors that influence human health and well-being across the life continuum, a growing body of research continues to demonstrate that consuming a healthy dietary pattern is one of the most dominant factors associated with increased longevity, improved mental health, improved immunity, and decreased risk for obesity and chronic disease.

A review of dairy food intake for improving health among black adults in the US.

The adult life stage encompasses a range of new experiences, opportunities, and responsibilities that impact health and well-being. During this life stage, health disparities continue to increase for Black Americans, with Black adults having a disproportionate burden of obesity, chronic diseases, comorbidities, and worse treatment outcomes compared to their White peers. While many of the underlying factors for these disparities can be linked to longstanding sociopolitical factors such as systemic racism, food insecurity, and poor access to healthcare, there are also several modifiable risk factors that are known to significantly impact health outcomes, such as improving diet quality, increasing physical activity, and not smoking.

Executive summary: The role of dairy food intake for improving health among Black Americans across the life continuum.

Given the complex relationships that many Black individuals have with dairy foods, due to issues with lactose intolerance or other cultural factors, the National Medical Association has made considerable efforts to examine the role that dairy foods play in the health and well-being of Black Americans. Over the last two decades, the National Medical Association and its partners have produced multiple reports on the value of including adequate milk and dairy foods in the diets of Black Americans. These publications have highlighted the impact that inadequate consumption of dairy foods and nutrients have on chronic disease risks.

A review of dairy food intake for improving health among black geriatrics in the US.

The transition to older adulthood is generally marked by progressive declines in body composition, metabolism, cognitive function, and immunity. For socially disadvantaged geriatric populations such as Black Americans, this life stage may also include additional stressors, including dealing with discrimination, poor access to healthcare, and food insecurity. These types of chronic stressors are linked to a higher allostatic load, which is associated with accelerated biological aging, higher rates of adverse health outcomes, and an overall lower quality of life.

Psychosocial Peer Support to Address Mental Health and Burnout of Health Care Workers Affected by COVID-19: A Qualitative Evaluation.

Health care workers in the U.S. are experiencing alarming rates of burnout.

Obesity among African American people in the United States: A review.

Obesity is a growing public health crisis in the United States and is associated with a substantial disease burden due to an increased risk for multiple complications, including cardiovascular and metabolic diseases. As highlighted in this review, obesity disproportionately affects the African American population, women in particular, regardless of socioeconomic status. Structural racism remains a major contributor to health disparities between African American people and the general population, and it limits access to healthy foods, safe spaces to exercise, adequate health insurance, and medication, all of which impact obesity prevalence and outcomes.

Characterization of the molecular mechanisms of silicon uptake in coccolithophores.

Coccolithophores are an important group of calcifying marine phytoplankton. Although coccolithophores are not silicified, some species exhibit a requirement for Si in the calcification process. These species also possess a novel protein (SITL) that resembles the SIT family of Si transporters found in diatoms.

The impact of forced degradation conditions on mAb dimer formation and subsequent influence on aggregation propensity.

Monoclonal antibody (mAb) aggregation can present major challenges for the development of biotherapeutics. An understanding of the molecular mechanisms of mAb aggregation is highly desirable both because it allows the performance of informed risk assessments regarding the criticality of mAb aggregates and because it may facilitate rational stabilization of aggregation prone regions. Here, we report the generation and isolation of dimer species of an IgG4 mAb (mAb1) that were present in stressed material under differing levels of temperature stress.

Computational modelling of diatom silicic acid transporters predicts a conserved fold with implications for their function and evolution.

Diatoms are an important group of algae that can produce intricate silicified cell walls (frustules). The complex process of silicification involves a set of enigmatic integral membrane proteins that are thought to actively transport the soluble precursor of biosilica, dissolved silicic acid. Full-length silicic acid transporters are found widely across the diatoms while homologous shorter proteins have now been identified in a range of other organisms.

Rotavirus RNA chaperone mediates global transcriptome-wide increase in RNA backbone flexibility.

Due to genome segmentation, rotaviruses must co-package eleven distinct genomic RNAs. The packaging is mediated by virus-encoded RNA chaperones, such as the rotavirus NSP2 protein. While the activities of distinct RNA chaperones are well studied on smaller RNAs, little is known about their global effect on the entire viral transcriptome.

The proximity of the N- and C- termini of bovine knob domains enable engineering of target specificity into polypeptide chains.

Cysteine-rich knob domains can be isolated from the ultralong heavy-chain complementarity-determining region (CDR) 3, which are unique to a subset of bovine antibodies, to create antibody fragments of ~4 kDa. Advantageously, the N- and C- termini of these small binding domains are in close proximity, and we propose that this may offer a practical route to engineer extrinsic binding specificity into proteins. To test this, we transplanted knob domains into various loops of rat serum albumin, targeting sites that were distal to the interface with the neonatal Fc receptor.

Correction: Breadth and function of antibody response to acute SARS-CoV-2 infection in humans.

[This corrects the article DOI: 10.1371/journal.ppat.

The SARS-CoV-2 RNA polymerase is a viral RNA capping enzyme.

SARS-CoV-2 is a positive-sense RNA virus responsible for the Coronavirus Disease 2019 (COVID-19) pandemic, which continues to cause significant morbidity, mortality and economic strain. SARS-CoV-2 can cause severe respiratory disease and death in humans, highlighting the need for effective antiviral therapies. The RNA synthesis machinery of SARS-CoV-2 is an ideal drug target and consists of non-structural protein 12 (nsp12), which is directly responsible for RNA synthesis, and numerous co-factors involved in RNA proofreading and 5' capping of viral RNAs.

Detection of Isopeptide Bonds in Monoclonal Antibody Aggregates.

Purpose: A major difficulty in monoclonal antibody (mAb) therapeutic development is product aggregation. In this study, intermolecular isopeptide bonds in mAb aggregates were characterized for the first time. We aim to propose a mechanism of covalent aggregation in a model antibody using stressed studies at raised temperatures to aid in the understanding of mAb aggregation pathways.

Pharmacotherapeutic options for weight regain after bariatric surgery.

Purpose Of Review: We sought to critically evaluate the recent literature published over the past 3 years on the topic of weight regain after bariatric surgery in children, adolescents, and adults, with an emphasis on clinically- relevant information for pharmacologic treatment of weight regain after metabolic and bariatric surgery.

Findings: There are multiple pharmacotherapeutic agents available to treat obesity in children, adolescents, and adults; these agents have varying efficacy and indications for use and have been studied in a variety of clinical and research scenarios. We present an overview of these findings.

Two doses of SARS-CoV-2 vaccination induce robust immune responses to emerging SARS-CoV-2 variants of concern.

The extent to which immune responses to natural infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and immunization with vaccines protect against variants of concern (VOC) is of increasing importance. Accordingly, here we analyse antibodies and T cells of a recently vaccinated, UK cohort, alongside those recovering from natural infection in early 2020. We show that neutralization of the VOC compared to a reference isolate of the original circulating lineage, B, is reduced: more profoundly against B.

Correlative multi-scale cryo-imaging unveils SARS-CoV-2 assembly and egress.

Since the outbreak of the SARS-CoV-2 pandemic, there have been intense structural studies on purified viral components and inactivated viruses. However, structural and ultrastructural evidence on how the SARS-CoV-2 infection progresses in the native cellular context is scarce, and there is a lack of comprehensive knowledge on the SARS-CoV-2 replicative cycle. To correlate cytopathic events induced by SARS-CoV-2 with virus replication processes in frozen-hydrated cells, we established a unique multi-modal, multi-scale cryo-correlative platform to image SARS-CoV-2 infection in Vero cells.

Structure of an H3N2 influenza virus nucleoprotein.

Influenza A viruses of the H1N1 and H3N2 subtypes are responsible for seasonal epidemic events. The influenza nucleoprotein (NP) binds to the viral genomic RNA and is essential for its replication. Efforts are under way to produce therapeutics and vaccines targeting the NP.

Inclusion of cGAMP within virus-like particle vaccines enhances their immunogenicity.

Cyclic GMP-AMP (cGAMP) is an immunostimulatory molecule produced by cGAS that activates STING. cGAMP is an adjuvant when administered alongside antigens. cGAMP is also incorporated into enveloped virus particles during budding.