Designing and Delivering a Poetry Workshop for Clinician Well-Being During the COVID-19 Pandemic: A Case Study.

Context: Facilitated poetry writing workshops are used in healthcare settings as a therapeutic approach to address stressful factors that negatively influence clinician well-being. However, owing to the novelty of this intervention and a tendency to combine poetry with other types of narrative-based techniques, proponents of poetic medicine are calling for harmonization across programs in the US. This would facilitate the study of poetry in medicine and the multiple facets of well-being it is said to promote.

Discovery of VU6016235: A Highly Selective, Orally Bioavailable, and Structurally Distinct Tricyclic M Muscarinic Acetylcholine Receptor Positive Allosteric Modulator (PAM).

Herein, we report structure-activity relationship (SAR) studies to develop novel tricyclic M PAM scaffolds with improved pharmacological properties. This endeavor involved a "tie-back" strategy to replace a 5-amino-2,4-dimethylthieno[2,3-]pyrimidine-6-carboxamide core, which led to the discovery of two novel tricyclic cores. While both tricyclic cores displayed low nanomolar potency against both human and rat M and were highly brain-penetrant, the 2,4-dimethylpyrido[4',3':4,5]thieno[2,3-]pyrimidine tricycle core provided lead compound, , with an overall superior pharmacological and drug metabolism and pharmacokinetics (DMPK) profile, as well as efficacy in a preclinical antipsychotic animal model.

People who share encounters with racism are silenced online by humans and machines, but a guideline-reframing intervention holds promise.

Are members of marginalized communities silenced on social media when they share personal experiences of racism? Here, we investigate the role of algorithms, humans, and platform guidelines in suppressing disclosures of racial discrimination. In a field study of actual posts from a neighborhood-based social media platform, we find that when users talk about their experiences as targets of racism, their posts are disproportionately flagged for removal as toxic by five widely used moderation algorithms from major online platforms, including the most recent large language models. We show that human users disproportionately flag these disclosures for removal as well.

Development of Airway Hemorrhage Simulation Scenarios With Pilot of an Airway Team Leader Assessment Tool.

Introduction: Airway hemorrhage requires rapid treatment to prevent adverse patient outcomes. Simulation education programs are challenged to recreate learning environments with adequate fidelity for team management of airway hemorrhage.

Methods: We developed Airway Hemorrhage Simulation Scenarios consisting of low-cost partial-task simulators to mimic airway hemorrhage (nasopharyngeal, oropharyngeal, expanding neck hematoma) and multiple methods to assess team leader performance in emergent airway management [Airway Team Leader Assessment Tool (ATLAT), Airway Checklist Performance, and Global Performance Rating].

Discovery of VU6008677: A Structurally Distinct Tricyclic M Positive Allosteric Modulator with Improved CYP450 Profile.

This Letter details our efforts to develop novel tricyclic muscarinic acetylcholine receptor subtype 4 (M) positive allosteric modulator (PAM) scaffolds with improved pharmacological properties. This endeavor involved a "tie-back" strategy to replace the 3-amino-5-chloro-4,6-dimethylthieno[2,3-]pyridine-2-carboxamide core, which led to the discovery of two novel tricyclic cores: an 8-chloro-9-methylpyrido[3',2':4,5]thieno[3,2-]pyrimidin-4-amine core and 8-chloro-7,9-dimethylpyrido[3',2':4,5]furo[3,2-]pyrimidin-4-amine core. Both tricyclic cores displayed low nanomolar potency against human M and greatly reduced cytochrome P450 inhibition when compared with parent compound .

Observers of social media discussions about racial discrimination condemn denial but also adopt it.

Sharing experiences with racism (racial discrimination disclosure) has the power to raise awareness of discrimination and spur meaningful conversations about race. Sharing these experiences with racism on social media may prompt a range of responses among users. While previous work investigates how disclosure impacts disclosers and listeners, we extend this research to explore the impact of observing discussions about racial discrimination online-what we call vicarious race talk.

The association of body composition phenotypes before chemotherapy with epithelial ovarian cancer mortality.

Background: The association of body composition with epithelial ovarian carcinoma (EOC) mortality is poorly understood. To date, evidence suggests that high adiposity is associated with decreased mortality (an obesity paradox), but the impact of muscle on this association has not been investigated. Herein, we define associations of muscle and adiposity joint-exposure body composition phenotypes with EOC mortality.

Tissue distribution and retention drives efficacy of rapidly clearing VHL-based PROTACs.

Background: Proteolysis-targeting chimeras (PROTACs) are being developed for therapeutic use. However, they have poor pharmacokinetic profiles and their tissue distribution kinetics are not known.

Methods: A typical von Hippel-Lindau tumor suppressor (VHL)-PROTAC C-A947 (BRM degrader)-was synthesized and its tissue distribution kinetics was studied by quantitative whole-body autoradiography (QWBA) and tissue excision in rats following IV dosing.

An investigation of racial and ethnic disparities in donor sperm availability in the United States.

Objective: To determine whether the racial and ethnic distribution of sperm donors contributing to US sperm banks differs from the demographics of the US population and those of US donor sperm recipients undergoing treatment with in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).

Design: Cross-sectional study.

Setting: United States donor sperm banks, US Census, and fertility clinics reporting to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System.

Heterologous Ad26.COV2.S booster after primary BBIBP-CorV vaccination against SARS-CoV-2 infection: 1-year follow-up of a phase 1/2 open-label trial.

Background: Inactivated whole-virus vaccination elicits immune responses to both SARS-CoV-2 nucleocapsid (N) and spike (S) proteins, like natural infections. A heterologous Ad26.COV2.

A common polymorphism in the Intelectin-1 gene influences mucus plugging in severe asthma.

By incompletely understood mechanisms, type 2 (T2) inflammation present in the airways of severe asthmatics drives the formation of pathologic mucus which leads to airway mucus plugging. Here we investigate the molecular role and clinical significance of intelectin-1 (ITLN-1) in the development of pathologic airway mucus in asthma. Through analyses of human airway epithelial cells we find that ITLN1 gene expression is highly induced by interleukin-13 (IL-13) in a subset of metaplastic MUC5AC mucus secretory cells, and that ITLN-1 protein is a secreted component of IL-13-induced mucus.

Fatty acid metabolism promotes TRPV4 activity in lung microvascular endothelial cells in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a morbid disease characterized by significant lung endothelial cell (EC) dysfunction. Prior work has shown that microvascular endothelial cells (MVECs) isolated from animals with experimental PAH and patients with PAH exhibit significant abnormalities in metabolism and calcium signaling. With regards to metabolism, we and others have shown evidence of increased aerobic glycolysis and evidence of increased utilization of alternate fuel sources (such as fatty acids) in PAH EC.

Phenylalanine requirements using the direct amino acid oxidation technique, and the effects of dietary phenylalanine on food intake, gastric emptying, and macronutrient metabolism in adult cats.

Despite Phe being an indispensable amino acid for cats, the minimum Phe requirement for adult cats has not been empirically defined. The objective of study 1 was to determine the minimum Phe requirement, where Tyr is in excess, in adult cats using the direct amino acid oxidation (DAAO) technique. Four adult male cats were used in an 8 × 4 Latin rectangle design.

Generative design of large-scale fluid flow structures via steady-state diffusion-based dehomogenization.

A computationally efficient dehomogenization technique was developed based on a bioinspired diffusion-based pattern generation algorithm to convert an orientation field into explicit large-scale fluid flow channel structures. Due to the transient nature of diffusion and reaction, most diffusion-based pattern generation models were solved in both time and space. In this work, we remove the temporal dependency and directly solve a steady-state equation.

Use of N-(4-aminophenyl)piperidine derivatization to improve organic acid detection with supercritical fluid chromatography-mass spectrometry.

The analysis of organic acids in complex mixtures by LC-MS can often prove challenging, especially due to the poor sensitivity of negative ionization mode required for detection of these compounds in their native (i.e., underivatized or untagged) form.

Development of a Selective and High Affinity Radioligand, [H]VU6013720, for the M Muscarinic Receptor.

M muscarinic receptors are highly expressed in the striatum and cortex, brain regions that are involved in diseases such as Parkinson's disease, schizophrenia, and dystonia. Despite potential therapeutic advantages of specifically targeting the M receptor, it has been historically challenging to develop highly selective ligands, resulting in undesired off-target activity at other members of the muscarinic receptor family. Recently, we have reported first-in-class, potent, and selective M receptor antagonists.

Discrepancies in Ratings of Behavioral Healthcare Interventions Among Evidence-Based Program Resources Websites.

Decision makers in the behavioral health disciplines could benefit from tools to assist them in identifying and implementing evidence-based interventions. One tool is an evidence-based program resources website (EBPR). Prior studies documented that when multiple EBPRs rate an intervention, they may disagree.

Single Ad26.COV2.S booster dose following two doses of BBIBP-CorV vaccine against SARS-CoV-2 infection in adults: Day 28 results of a phase 1/2 open-label trial.

Background: The inactivated COVID-19 whole-virus vaccine BBIBP-CorV has been extensively used worldwide. Heterologous boosting after primary vaccination can induce higher immune responses against SARS-CoV-2 than homologous boosting. The safety and immunogenicity after 28 days of a single Ad26.

Inhibiting membrane rupture with NINJ1 antibodies limits tissue injury.

Plasma membrane rupture (PMR) in dying cells undergoing pyroptosis or apoptosis requires the cell-surface protein NINJ1. PMR releases pro-inflammatory cytoplasmic molecules, collectively called damage-associated molecular patterns (DAMPs), that activate immune cells. Therefore, inhibiting NINJ1 and PMR may limit the inflammation that is associated with excessive cell death.

Combined COVID-19 vaccination and hepatitis C virus screening intervention in marginalised populations in Spain.

Background: COVID-19 has hindered hepatitis C virus (HCV) and HIV screening, particularly in marginalised groups, who have some of the highest rates of these conditions and lowest rates of COVID-19 vaccination. We assessed the acceptability of combining HCV testing with COVID-19 vaccination in a centre for addiction services (CAS) in Barcelona and a mobile testing unit (MTU) in Madrid, Spain.

Methods: From 28/09/2021 to 30/06/2022, 187 adults from marginalised populations were offered HCV antibody (Ab) testing along with COVID-19 vaccination.

Alirocumab and Coronary Atherosclerosis in Asymptomatic Patients with Familial Hypercholesterolemia: The ARCHITECT Study.

Background: The effect of alirocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, on coronary plaque burden in patients with familial hypercholesterolemia has not been addressed. Our aim was to assess changes in coronary plaque burden and its characteristics after treatment with alirocumab by quantification and characterization of atherosclerotic plaque throughout the coronary tree on the basis of a noninvasive analysis of coronary computed tomographic angiography in asymptomatic subjects with familial hypercholesterolemia receiving optimized and stable treatment with maximum tolerated statin dose with or without ezetimibe.

Methods: This study is a phase IV, open-label, multicenter, single-arm clinical trial to assess changes in coronary plaque burden and its characteristics after 78 weeks of treatment with alirocumab in patients with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease.

CA-125 Early Dynamics to Predict Overall Survival in Women with Newly Diagnosed Advanced Ovarian Cancer Based on Meta-Analysis Data.

(1) Background: Cancer antigen 125 (CA-125) is a protein produced by ovarian cancer cells that is used for patients' monitoring. However, the best ways to analyze its decline and prognostic role are poorly quantified. (2) Methods: We leveraged individual patient data from the Gynecologic Cancer Intergroup (GCIG) meta-analysis (N = 5573) to compare different approaches summarizing the early trajectory of CA-125 before the prediction time (called the landmark time) at 3 or 6 months after treatment initiation in order to predict overall survival.