Pooled safety analysis and management of sotorasib-related adverse events in KRAS G12C-mutated advanced non-small cell lung cancer.

Introduction: We describe the safety of sotorasib monotherapy in patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) and discuss practical recommendations for managing key risks.

Methods: Incidence rates of treatment-related adverse events (TRAEs) were pooled from 4 clinical trials: CodeBreaK 100 (NCT03600883), CodeBreaK 101 (NCT04185883), CodeBreaK 105 (NCT04380753), and CodeBreaK 200 (NCT04303780) and graded according to CTCAE v5.0.

Outcomes and predictive factors for fluid resolution following three loading injections of faricimab for treatment-naïve neovascular age-related macular degeneration.

To evaluate the outcomes and predictive factors for fluid resolution following three loading injections of faricimab for neovascular age-related macular degeneration(AMD). This retrospective study included patients diagnosed with treatment-naïve neovascular AMD who received three monthly injections of faricimab. Changes in best-corrected visual acuity(BCVA) and central retinal thickness(CRT) following treatment were evaluated.

Joining Natural and Synthetic DNA Using Biversal Nucleotides: Efficient Sequencing of Six-Nucleotide DNA.

By rearranging hydrogen bond donor and acceptor groups within a standard Watson-Crick geometry, DNA can add eight independently replicable nucleotides forming four additional not found in standard Terran DNA. For many applications, the orthogonal pairing of standard and nonstandard pairs offers a key advantage. However, other applications require standard and nonstandard nucleotides to communicate with each other.

Glia-like taste cells mediate an intercellular mode of peripheral sweet adaptation.

The sense of taste generally shows diminishing sensitivity to prolonged sweet stimuli, referred to as sweet adaptation. Yet, its mechanistic landscape remains incomplete. Here, we report that glia-like type I cells provide a distinct mode of sweet adaptation via intercellular crosstalk with chemosensory type II cells.

Oncolytic immunotherapy with nivolumab in muscle-invasive bladder cancer: a phase 1b trial.

There is a critical unmet need for safe and efficacious neoadjuvant treatment for cisplatin-ineligible patients with muscle-invasive bladder cancer. Here we launched a phase 1b study using the combination of intravesical cretostimogene grenadenorepvec (oncolytic serotype 5 adenovirus encoding granulocyte-macrophage colony-stimulating factor) with systemic nivolumab in cisplatin-ineligible patients with cT2-4aN0-1M0 muscle-invasive bladder cancer. The primary objective was to measure safety, and the secondary objective was to assess the anti-tumor efficacy as measured by pathologic complete response along with 1-year recurrence-free survival.

Machine learning for forecasting initial seizure onset in neonatal hypoxic-ischemic encephalopathy.

Objective: This study was undertaken to develop a machine learning (ML) model to forecast initial seizure onset in neonatal hypoxic-ischemic encephalopathy (HIE) utilizing clinical and quantitative electroencephalogram (QEEG) features.

Methods: We developed a gradient boosting ML model (Neo-GB) that utilizes clinical features and QEEG to forecast time-dependent seizure risk. Clinical variables included cord blood gas values, Apgar scores, gestational age at birth, postmenstrual age (PMA), postnatal age, and birth weight.

Ferroptosis-Mediated Inflammation Promotes Pulmonary Hypertension.

Background: Mitochondrial dysfunction, characterized by impaired lipid metabolism and heightened reactive oxygen species generation, results in lipid peroxidation and ferroptosis. Ferroptosis is an inflammatory mode of cell death that promotes complement activation and macrophage recruitment. In pulmonary arterial hypertension (PAH), pulmonary arterial endothelial cells exhibit cellular phenotypes that promote ferroptosis.

Prognostic Value of Pulmonary Artery Systolic Pressure in Severe Rheumatic Mitral Stenosis.

Background: Current guidelines recommend intervention for asymptomatic rheumatic mitral stenosis (MS) with mitral valve area ≤1.5 cm based on indicators including pulmonary arterial systolic pressure (PASP) >50 mm Hg and new-onset atrial fibrillation; however, evidence supporting this is lacking.

Methods: This single-center retrospective study included patients with rheumatic MS between 2006 and 2022.

Arg92Leu-cTnT Alters the cTnC-cTnI Interface Disrupting PKA-Mediated Relaxation.

Background: Impaired left ventricular relaxation, high filling pressures, and dysregulation of Ca homeostasis are common findings contributing to diastolic dysfunction in hypertrophic cardiomyopathy (HCM). Studies have shown that impaired relaxation is an early observation in the sarcomere-gene-positive preclinical HCM cohort, which suggests the potential involvement of myofilament regulators in relaxation. A molecular-level understanding of mechanism(s) at the level of the myofilament is lacking.

Exploring Deep Learning Applications using Ultrasound Single View Cines in Acute Gallbladder Pathologies: Preliminary results.

Rationale And Objectives: In this preliminary study, we aimed to develop a deep learning model using ultrasound single view cines that distinguishes between imaging of normal gallbladder, non-urgent cholelithiasis, and acute calculous cholecystitis requiring urgent intervention.

Methods: Adult patients presenting to the emergency department between 2017-2022 with right-upper-quadrant pain were screened, and ultrasound single view cines of normal imaging, non-urgent cholelithiasis, and acute cholecystitis were included based on final clinical diagnosis. Longitudinal-view cines were de-identified and gallbladder pathology was annotated for model training.

The influence of socioeconomic status on individual attitudes and experience with clinical trials.

Background: Characterizing perceptions of clinical trials among the socioeconomically disadvantaged is necessary for understanding how social determinants of health such as socioeconomic disparities in education and income can affect people's awareness of and exposure to clinical trials METHODS: A survey was distributed in spring 2023 among a survey taking sample stratified by demographic variables to reflect the U.S.

Population: The survey assessed the socioeconomic status of the respondent and related covariates, as well as outcome measures including interest in joining a clinical trial, concerns relating to participation, and whether the respondent had previously been asked to participate.

Ligand-Dependent and G Protein-Dependent Properties for the Sweet Taste Heterodimer, TAS1R2/1R3.

The heterodimeric sweet taste receptor, TAS1R2/1R3, is a class C G protein-coupled receptor (GPCR) that couples to gustducin (Gt), a G protein (GP) specifically involved in taste processing. This makes TAS1R2/1R3 a possible target for newly developing low caloric ligands that taste sweet to address obesity and diabetes. The activation of TAS1R2/1R3 involves the insertion of the GαP C-terminus of the GP into the GPCR in response to ligand binding.

Molecular recognition of an odorant by the murine trace amine-associated receptor TAAR7f.

There are two main families of G protein-coupled receptors that detect odours in humans, the odorant receptors (ORs) and the trace amine-associated receptors (TAARs). Their amino acid sequences are distinct, with the TAARs being most similar to the aminergic receptors such as those activated by adrenaline, serotonin, dopamine and histamine. To elucidate the structural determinants of ligand recognition by TAARs, we have determined the cryo-EM structure of a murine receptor, mTAAR7f, coupled to the heterotrimeric G protein G and bound to the odorant N,N-dimethylcyclohexylamine (DMCHA) to an overall resolution of 2.

Tissue-Based Predictors of Impaired Right Ventricular Strain in Coronary Artery Disease: A Multicenter Stress Perfusion Study.

Background: Right ventricular (RV) dysfunction is known to impact prognosis, but its determinants in coronary artery disease are poorly understood. Stress cardiac magnetic resonance (CMR) has been used to assess ischemia and infarction in relation to the left ventricle (LV); the impact of myocardial tissue properties on RV function is unknown.

Methods: Vasodilator stress CMR was performed in patients with known coronary artery disease at 7 sites between May 2005 and October 2018.

CT-Guided Epidural Contrast Injection for the Identification of Dural Defects.

Post-dural puncture headache is an increasingly recognized cause of chronic headache. Outside of clinical history and myelography that requires an additional dural puncture, there is no reliable diagnostic test to evaluate for persistent dural defects. We describe the injection of iodinated contrast into the dorsal epidural space under CT guidance in 5 patients as a potential tool to visualize persistent dural defects.

Randomized Controlled Trial on the Effects of Home-Based Breathing Exercises on Respiratory Function and Fatigue in COVID-19-Cured Young Patients.

This study investigates the effects of home-based Kakao Healthcare breathing exercises and stretching on respiratory function and fatigue in COVID-19-cured patients. A total of 35 participants performed four movements of home-based breathing exercises and five respiratory muscle stretching exercises four times a week for four weeks. Respiratory function was measured using forced vital capacity(FVC), forced expiratory volume in one second(FEV1), FEV1/FVC ratio, and peak expiratory flow(PEF).

Cognitive and Salience Network Connectivity Changes following a Single Season of Repetitive Head Impact Exposure in High School Football.

Background And Purpose: During a season of high school football, adolescents with actively developing brains experience a considerable number of head impacts. Our aim was to determine whether repetitive head impacts in the absence of a clinically diagnosed concussion during a season of high school football produce changes in cognitive performance or functional connectivity of the salience network and its central hub, the dorsal anterior cingulate cortex.

Materials And Methods: Football players were instrumented with the Head Impact Telemetry System during all practices and games, and the helmet sensor data were used to compute a risk-weighted exposure metric (RWEcp), accounting for the cumulative risk during the season.

Public Views on Whether the Use of Pharmaceutical Neuroenhancements Should Be Allowed.

Background And Objectives: Some individuals are using drugs to try to enhance cognitive and social-affective functioning and asking physicians for off-label prescriptions for neuroenhancement (e.g., stimulants).