Design of SARS-CoV-2 RBD Immunogens to Focus Immune Responses Towards Conserved Coronavirus Epitopes.

SARS-CoV-2 continues to evolve, with new variants emerging that evade pre-existing immunity and limit the efficacy of existing vaccines. One approach towards developing superior, variant-proof vaccines is to engineer immunogens that preferentially elicit antibodies with broad cross-reactivity against SARS-CoV-2 and its variants by targeting conserved epitopes on spike. The inner and outer faces of the Receptor Binding Domain (RBD) are two such conserved regions targeted by antibodies that recognize diverse human and animal coronaviruses.

Segmentectomy vs Lobectomy for Non-Small Cell Lung Cancer: The Impact of Tumor Location.

Background: The technical complexity of segmentectomy and preservation of lung parenchyma compared with lobectomy vary by lobe. This study evaluated the impact of non-small cell lung cancer tumor location on segmentectomy use and outcomes.

Methods: Outcomes after lobectomy or segmentectomy for cT1N0M0 (≤2 cm) non-small cell lung cancer patients stratified by tumor location in smaller (right upper/middle) vs larger (bilateral lower/left upper) lobes were evaluated with logistic regression, Kaplan-Meier curves, and Cox proportional hazards methods.

Assessment of Extracellular Particles Directly in Diluted Plasma and Blood by Interferometric Light Microscopy. A Study of 613 Human and 163 Canine Samples.

Extracellular nanoparticles (EPs) are a subject of increasing interest for their biological role as mediators in cell-cell communication; however, their harvesting and assessment from bodily fluids are challenging, as processing can significantly affect samples. With the aim of minimizing processing artifacts, we assessed the number density () and hydrodynamic diameter () of EPs directly in diluted plasma and blood using the following recently developed technique: interferometric light microscopy (ILM). We analyzed 613 blood and plasma samples from human patients with inflammatory bowel disease (IBD), collected in trisodium citrate and ethylenediaminetetraacetic acid (EDTA) anticoagulants, and 163 blood and plasma samples from canine patients with brachycephalic obstructive airway syndrome (BOAS).

Treatment pattern and clinical outcomes of remdesivir in hospitalized COVID-19 patients with severe chronic kidney disease: a database analysis of acute care hospitals in Japan.

Background: There is limited evidence on clinical outcomes and treatment pattern in Japanese patients with severe chronic kidney disease (CKD), hospitalized for coronavirus disease-2019 (COVID-19). We aimed to describe patient characteristics, treatment pattern, and clinical outcomes in Japanese patients with severe CKD, hospitalized for COVID-19 who received remdesivir (RDV).

Methods: We used the anonymized claims database from Medical Data Vision Co.

Stimulus-invariant aspects of the retinal code drive discriminability of natural scenes.

Everything that the brain sees must first be encoded by the retina, which maintains a reliable representation of the visual world in many different, complex natural scenes while also adapting to stimulus changes. This study quantifies whether and how the brain selectively encodes stimulus features about scene identity in complex naturalistic environments. While a wealth of previous work has dug into the static and dynamic features of the population code in retinal ganglion cells (RGCs), less is known about how populations form both flexible and reliable encoding in natural moving scenes.

High in the Cloud: Alcohol-, Cannabis-, and Co-Use Before and During Remote Research Participation.

Objective: The use of crowdsourcing for addiction research has increased exponentially in recent years, but the extent to which the populations we expect results to generalize to might be engaging in substance use while participating in remote research has not been formally quantified. Understanding rates of day-of-study substance use on crowdsourcing platforms may be especially relevant given immediately recent use can alter cognitive and behavioral decision-making processes (e.g.

Treatment patterns and clinical outcomes of immunocompromised patients with COVID-19 receiving remdesivir in the inpatient setting in Japan.

Introduction: Remdesivir (RDV) was approved in Japan for the treatment of coronavirus disease 2019 (COVID-19) in May 2020. However, large-scale research describing the characterized use of RDV in the inpatient setting in Japan is limited. This study aimed to describe the treatment patterns and clinical outcomes of immunocompromised patients with COVID-19 treated with RDV.

Discovery of Highly Selective Inhibitors of Microtubule-Associated Serine/Threonine Kinase-like (MASTL).

By virtue of its role in cellular proliferation, microtubule-associated serine/threonine kinase-like (MASTL) represents a novel target and a first-in-class (FIC) opportunity to provide a new impactful therapeutic agent to oncology patients. Herein, we describe a hit-to-lead optimization effort that resulted in the delivery of two highly selective MASTL inhibitors. Key strategies leveraged to enable this work included structure-based drug design (SBDD), analysis of lipophilic efficiency (LipE) and novel synthesis.

Experience with reduced-nicotine cigarettes and whether this decreases smoking and substitution for full-nicotine cigarettes.

Studies suggest that reduced-nicotine cigarettes decrease nicotine intake and dependence. However, questions remain about reduced-nicotine cigarette abuse liability, whether reduced-nicotine cigarette exposure lowers reduced- and full-nicotine cigarette use, and whether reduced-nicotine cigarettes substitute for full-nicotine cigarettes. This randomized, double-blind laboratory study used operant behavioral economics to examine abuse liability of cigarettes with varying nicotine content.

Engineering immunogens that select for specific mutations in HIV broadly neutralizing antibodies.

Vaccine development targeting rapidly evolving pathogens such as HIV-1 requires induction of broadly neutralizing antibodies (bnAbs) with conserved paratopes and mutations, and in some cases, the same Ig-heavy chains. The current trial-and-error search for immunogen modifications that improve selection for specific bnAb mutations is imprecise. Here, to precisely engineer bnAb boosting immunogens, we use molecular dynamics simulations to examine encounter states that form when antibodies collide with the HIV-1 Envelope (Env).

The Role of Primary Care Providers in Lung Cancer Screening: A Cross-Sectional Survey.

Background: Multidisciplinary lung cancer screening (LCS) programs that perform shared decision-making visits (SDMV) and follow up annual low dose computed tomography (LDCT) have been emerging. We hypothesize that primary care providers (PCPs) prefer to refer patients to LCS programs instead of facilitating the screening process themselves.

Methods: This is a mixed-methods, cross-sectional study in which an online survey was administered to PCPs between April 2023 and June 2023.

Management of Vulnerable Patients Hospitalized for COVID-19 With Remdesivir: A Retrospective Comparative Effectiveness Study of Mortality in US Hospitals.

Background: Coronavirus disease 2019 (COVID-19) remains a major public health concern, with continued resurgences of cases and substantial risk of mortality for hospitalized patients. Remdesivir has become standard-of-care for hospitalized COVID-19 patients. Given the continued evolution of the disease, clinical management of COVID-19 relies on evidence from the current endemic period.

Remdesivir Effectiveness in Reducing the Risk of 30-Day Readmission in Vulnerable Patients Hospitalized for COVID-19: A Retrospective US Cohort Study Using Propensity Scores.

Background: Reducing hospital readmission offer potential benefits for patients, providers, payers, and policymakers to improve quality of healthcare, reduce cost, and improve patient experience. We investigated effectiveness of remdesivir in reducing 30-day coronavirus disease 2019 (COVID-19)-related readmission during the Omicron era, including older adults and those with underlying immunocompromising conditions.

Methods: This retrospective study utilized the US PINC AI Healthcare Database to identify adult patients discharged alive from an index COVID-19 hospitalization between December 2021 and February 2024.

Remdesivir-Associated Survival Outcomes Among Immunocompromised Patients Hospitalized for COVID-19: Real-world Evidence From the Omicron-Dominant Era.

Background: Patients with immunocompromising conditions are at increased risk for coronavirus disease 2019 (COVID-19)-related hospitalizations and deaths. Randomized clinical trials provide limited enrollment, if any, to provide information on the outcomes in such patients treated with remdesivir.

Methods: Using the US PINC AI Healthcare Database, we identified adult patients with immunocompromising conditions, hospitalized for COVID-19 between December 2021 and February 2024.

Naturalistic substance use before/during MTurk research participation is associated with increased substance demand and craving.

Although crowdsourcing platforms are widely used in substance-use research, it is unclear what percentage of participants use substances at the time of participation and how this might affect data quality, behavioral outcomes, or decision making. We conducted a secondary analysis of data collected on MTurk for a two-session, within-subject experiment recruiting individuals who regularly use alcohol, cannabis, cigarettes, or opioids. We analyzed 527 observations collected across two sessions (Session 1: = 303, Session 2: = 224) on measures of substance use before (within 3 hr)/during participation, data quality, demand in hypothetical purchase tasks, delay discounting, and craving.

Ganaxolone Therapy After Preterm Birth Restores Cerebellar Oligodendrocyte Maturation and Myelination in Guinea Pigs.

The postnatal environment is challenging for the preterm neonate with exposure to hypoxic and excitotoxic events, amplified by premature loss of placentally derived neurosteroids. Between preterm birth and term equivalent age (TEA), cerebellar development continues despite these challenges. We hypothesize that neurosteroid replacement therapy during this time will support optimal cerebellar development.

Lower mortality risk associated with remdesivir + dexamethasone versus dexamethasone alone for the treatment of patients hospitalized for COVID-19.

Background: Treatment guidelines were developed early in the pandemic when much about COVID-19 was unknown. Given the evolution of SARS-CoV-2, real-world data can provide clinicians with updated information. The objective of this analysis was to assess mortality risk in patients hospitalized for COVID-19 during the Omicron period receiving remdesivir+dexamethasone versus dexamethasone alone.

Greater ipsilateral rectus muscle atrophy after robotic thoracic surgery compared with open and video-assisted thoracoscopic surgery approaches.

Objective: Robotic thoracic surgery provides another minimally invasive approach in addition to video-assisted thoracoscopic surgery (VATS) that yields less pain and faster recovery compared with open surgery. However, robotic incisions are generally placed more inferiorly, which may increase the risk of intercostal nerve injury that affects the abdominal wall. We hypothesized that a robotic approach causes greater ipsilateral rectus muscle atrophy compared with open and VATS approaches.

Cryoablation Without Excision for Early-Stage Breast Cancer: ICE3 Trial 5-Year Follow-Up on Ipsilateral Breast Tumor Recurrence.

Background: The ICE3 trial evaluated the safety and efficacy of cryoablation in women aged ≥60 years with low-risk, early-stage breast cancers, aiming to provide a non-operative treatment option and avoid potential surgical risks. This study presents 5-year follow-up trial results.

Methods: The ICE3 trial is an Institutional Review Board-approved, prospective, multicentered, non-randomized trial including women ≥ 60 years of age with unifocal, ultrasound visible, invasive ductal carcinoma ≤ 1.