Impact of co-mutations and transcriptional signatures in non-small cell lung cancer patients treated with adagrasib in the KRYSTAL-1 trial.

Background: KRAS inhibitors are revolutionizing the treatment of NSCLC, but clinico-genomic determinants of treatment efficacy warrant continued exploration.

Methods: Patients with advanced KRASG12C-mutant NSCLC treated with adagrasib (KRYSTAL-1-NCT03785249) were included in the analysis. Pre-treatment NGS data were collected per protocol.

Discovery of MDI-114215: A Potent and Selective LIMK Inhibitor To Treat Fragile X Syndrome.

LIMKs are serine/threonine and tyrosine kinases responsible for controlling cytoskeletal dynamics as key regulators of actin stability, ensuring synaptic health through normal synaptic bouton structure and function. However, LIMK1 overactivation results in abnormal dendritic synaptic development that characterizes the pathogenesis of Fragile X Syndrome (FXS). As a result, the development of LIMK inhibitors represents an emerging disease-modifying therapeutic approach for FXS.

Statin Use and Hyperglycemia: Do Statins Cause Diabetes?

Purpose Of Review: Atherosclerotic cardiovascular disease (ASCVD) and diabetes are leading causes of morbidity and mortality in the United States and globally. Statin medications, a cornerstone of ASCVD prevention and treatment strategies, have been demonstrated to cause hyperglycemia and new onset diabetes mellitus (NODM). The purpose of this review is to summarize existing and emerging knowledge around the intersection of statins and these two important clinical problems.

A Prescription Produce Program integrating lifestyle behavior counseling and health education: A program description and evaluation.

Prescription Produce Programs (PPPs) are increasingly being used to address food insecurity and healthy diets. Yet, limited evidence exists on the effectiveness of integrating lifestyle counseling within a PPP to promote dietary and health behaviors. To describe the implementation of a 6- or 12-week PPP integrating lifestyle counseling to low-income adults.

A thermodynamic investigation into protein-excipient interactions involving different grades of polysorbate 20 and 80.

Developing stable biopharmaceutical formulations is of paramount importance and is typically achieved by incorporating surfactants as stabilising agents, such as polysorbate 20 and 80. However, little is known about the effect surfactant grade has on formulation stability. This study evaluates the effect of regular grade and Super-refined™ polysorbates 20 and 80 and their interaction with model proteins, namely β-lactoglobulin (β-Ig), human serum albumin (HSA) and immunoglobulin gamma (IgG), using isothermal titration calorimetry (ITC) and differential scanning calorimetry (DSC).

A scoping review of universal school-based resilience programs for adolescents.

Resilience, broadly defined as effective adaptation to stress, adversity, or change, is an important capacity to foster in adolescence. To date, there has been little review of the literature on universal school-based resilience programs for teens. The current scoping review had three aims.

Engaging Interprofessional Health Students in a Prescription Produce Plan.

Nursing students participated in an interprofessional student-led prescription produce program (PPP) serving low-income older adults attending a community-based wellness and care coordination program. Students engaged in an online training module covering nutrition education and health promotion, integral components of a PPP. Ninety-five percent of students self-rated themselves as somewhat confident/very confident to participate in the PPP after completing an online learning module.

CROI 2024 BHIVA working group summary.

The Conference on Retroviruses and Opportunistic Infections (CROI) is usually the most significant HIV conference of the year in terms of basic and clinical scientific output. CROI 2024 in Denver, USA, felt very much back to 'business as usual' following COVID-19 disruptions that had impacted preceding years, but also felt more global and outward- facing. The British HIV Association supports a working group to attend CROI annually and deliver feedback in the UK.

A Cross-Sectional Evaluation of the Virtual Outpatient Management of People With Mpox.

Background: To report on the implementation and outcomes of a virtual ward established for the management of mpox during the 2022 outbreak, we conducted a 2-center, observational, cross-sectional study over a 3-month period.

Methods: All patients aged ≥17 years with laboratory polymerase chain reaction-confirmed monkeypox virus managed between 14 May and 15 August 2022, at the Hospital for Tropical Diseases at University College London Hospitals National Health Service (NHS) Foundation Trust and sexual health services at Central North and West London NHS Foundation Trust, were included. Main outcomes included the proportion of patients managed exclusively on the virtual ward, proportion of patients requiring inpatient admission, proportion of patients with human immunodeficiency virus, and duration of lesion reepithelialization.

Laboratory infrared spectra and fragmentation chemistry of sulfur allotropes.

Sulfur is one of six life-essential elements, but its path from interstellar clouds to planets and their atmospheres is not well known. Astronomical observations in dense clouds have so far been able to trace only 1 percent of cosmic sulfur, in the form of gas phase molecules and volatile ices, with the missing sulfur expected to be locked in a currently unidentified form. The high sulfur abundances inferred in icy and rocky solar system bodies indicate that an efficient pathway must exist from volatile atomic sulfur in the diffuse interstellar medium to some form of refractory sulfur.

The SOS1 Inhibitor MRTX0902 Blocks KRAS Activation and Demonstrates Antitumor Activity in Cancers Dependent on KRAS Nucleotide Loading.

KRAS is the most frequently mutated oncogene in human cancer and facilitates uncontrolled growth through hyperactivation of the receptor tyrosine kinase (RTK)/mitogen-activated protein kinase (MAPK) pathway. The Son of Sevenless homolog 1 (SOS1) protein functions as a guanine nucleotide exchange factor (GEF) for the RAS subfamily of small GTPases and represents a druggable target in the pathway. Using a structure-based drug discovery approach, MRTX0902 was identified as a selective and potent SOS1 inhibitor that disrupts the KRAS:SOS1 protein-protein interaction to prevent SOS1-mediated nucleotide exchange on KRAS and translates into an anti-proliferative effect in cancer cell lines with genetic alterations of the KRAS-MAPK pathway.

Growth and impact of Project ECHO for workforce development in age-friendly care.

Background: Use of the Project ECHO® (Extension for Community Healthcare Outcomes) model in geriatrics has increased dramatically largely because of the Health Resources and Services Administration-funded Geriatrics Workforce Enhancement Programs (GWEP) utilizing it as a key tool for age-friendly, interprofessional workforce development. This manuscript describes the scope and impact of geriatrics ECHOs under the GWEP.

Methods: A survey of GWEPs was conducted to measure the reach, foci, evaluation methods, and other characteristics of ECHO networks.

Embedding Recovery Principles in Staff Orientation: A New Way of Delivering Multidisciplinary Mental Health Orientation.

Purpose: Recovery-focused mental health treatment continues to grow, yet staff are often uncertain how best to define and implement it. As a quality assurance activity, we examined the effect of a novel orientation program embedded with a recovery framework structure, philosophy, and content, together with true lived experience codesign, on knowledge of recovery principles and acceptability.

Method: Staff of a new sub-acute adolescent mental health inpatient center completed a 6-week orientation in early 2020.

Cardiometabolic health in people with HIV: expert consensus review.

Objectives: To develop consensus data statements and clinical recommendations to provide guidance for improving cardiometabolic health outcomes in people with HIV based on the knowledge and experience of an international panel of experts.

Methods: A targeted literature review including 281 conference presentations, peer-reviewed articles, and background references on cardiometabolic health in adults with HIV published between January 2016 and April 2022 was conducted and used to develop draft consensus data statements. Using a modified Delphi method, an international panel of 16 experts convened in workshops and completed surveys to refine consensus data statements and generate clinical recommendations.

Discovery of Pyridopyrimidinones that Selectively Inhibit the H1047R PI3Kα Mutant Protein.

The H1047R mutation of is highly prevalent in breast cancers and other solid tumors. Selectively targeting PI3Kα over PI3Kα is crucial due to the role that PI3Kα plays in normal cellular processes, including glucose homeostasis. Currently, only one PI3Kα-selective inhibitor has progressed into clinical trials, while three pan mutant (H1047R, H1047L, H1047Y, E542K, and E545K) selective PI3Kα inhibitors have also reached the clinical stage.

Downscaling platelet cryopreservation: Are platelets frozen in tubes comparable to standard cryopreserved platelets?

Background: Platelet cryopreservation extends the shelf-life to at least 2 years. However, platelets are altered during the freeze/thaw process. Downscaling platelet cryopreservation by freezing in tubes would enable rapid screening of novel strategies to improve the quality of cryopreserved platelets (CPPs).

Homophobia in the provision of sexual health care in the UK.

Decision making in the provision of health care is influenced by not only scientific evidence but also by the systems in which decisions are made. We consider national decisions made in the UK related to sexually transmitted infection prevention in gay, bisexual, and other men who have sex with men (GBMSM), with three specific examples-HIV pre-exposure prophylaxis, mpox (formerly known as monkeypox) vaccination, and doxycycline prophylaxis. We suggest that entrenched societal and political homophobia results in unacceptable delays and limitations to accessing highly effective interventions and that these delays result in harm from preventable transmissions of HIV, mpox, and syphilis.

Cross-sectional survey of sexual health professionals' experiences and perceptions of the 2022 mpox outbreak in the UK.

Objective: To understand the experiences and perceptions of sexual health professionals responding to the May 2022 mpox outbreak in the UK.

Design: Cross-sectional, anonymous, online survey collecting quantitative and qualitative data. Convenience sample recruited via an international network of sexual health and HIV clinicians responding to mpox and promoted through clinical associations and social media.

Heterotopic Ossification and Platelet-Rich Plasma in Core Muscle Injuries: A Single-Institution Experience Over 6 Years.

Background: A 2015 study of platelet-rich plasma (PRP) for groin injuries in National Football League (NFL) players alerted the authors to the possibility that PRP is associated with heterotopic ossification (HO). The current study of athletes seen between 2014 and 2019 provides a more comprehensive analysis of that observation.

Purpose/hypothesis: This report describes the early results of groin surgery for athletes who had experienced failed PRP therapy performed by different practitioners and with an assortment of PRP techniques.

The small protein MntS evolved from a signal peptide and acquired a novel function regulating manganese homeostasis in Escherichia coli.

Small proteins (<50 amino acids) are emerging as ubiquitous and important regulators in organisms ranging from bacteria to humans, where they commonly bind to and regulate larger proteins during stress responses. However, fundamental aspects of small proteins, such as their molecular mechanism of action, downregulation after they are no longer needed, and their evolutionary provenance, are poorly understood. Here, we show that the MntS small protein involved in manganese (Mn) homeostasis binds and inhibits the MntP Mn transporter.