Complement factor H targeting antibody GT103 in refractory non-small cell lung cancer: a phase 1b dose escalation trial.

GT103 is a first-in-class, fully human, IgG3 monoclonal antibody targeting complement factor H that kills tumor cells and promotes anti-cancer immunity in preclinical models. We conducted a first-in-human phase 1b study dose escalation trial of GT103 in refractory non-small cell lung cancer to assess the safety of GT103 (NCT04314089). Dose escalation was performed using a "3 + 3" schema with primary objectives of determining safety, tolerability, PK profile and maximum tolerated dose (MTD) of GT103.

Addressing Methodological Challenges in Follow-Up RCTs During the COVID-19 Pandemic: The Impact of the Good Behavior Game and MyTeachingPartner™ on Teacher Burnout and Self-Efficacy.

Retention of early career teachers is a critical issue in education, with burnout and self-efficacy serving as important precursors to teachers leaving the field. An integration of the PAX Good Behavior Game (GBG; Barrish et al., 1969) and MyTeachingPartner (MTP; Allen et al.

Safety of Low-Dose Quetiapine for Insomnia in Older Adults.

Background And Objective: Quetiapine is a Food and Drug Administration (FDA) approved second-generation antipsychotic. It is also commonly used at low dose for its sedative properties to treat insomnia in the older population. Quetiapine at standard doses has been associated with increased risk of cerebrovascular events, cognitive decline, and mortality in patients with dementia, especially within older adults.

Targeted knockdown of ATM, ATR, and PDEδ increases Gag HIV-1 VLP production in HEK293 cells.

Several strategies have been developed in recent years to improve virus-like particle (VLP)-based vaccine production processes. Among these, the metabolic engineering of cell lines has been one of the most promising approaches. Based on previous work and a proteomic analysis of HEK293 cells producing Human Immunodeficiency Virus-1 (HIV-1) Gag VLPs under transient transfection, four proteins susceptible of enhancing VLP production were identified: ataxia telangiectasia mutated (ATM), ataxia telangiectasia and rad3-related (ATR), DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit delta (PDEδ).

International multicenter validation of AI-driven ultrasound detection of ovarian cancer.

Ovarian lesions are common and often incidentally detected. A critical shortage of expert ultrasound examiners has raised concerns of unnecessary interventions and delayed cancer diagnoses. Deep learning has shown promising results in the detection of ovarian cancer in ultrasound images; however, external validation is lacking.

Long COVID in transgender and gender nonbinary people in the United States.

Despite recommendations in the US National Research Action Plan on Long COVID, gender identity is rarely reported in research and surveillance used to guide public health programming and clinical care. We analyzed data from a cross-sectional study of COVID-19 in a nationwide sample of transgender and nonbinary (TNB) people (N = 2,134). Participants were surveyed between June 14, 2021 and May 1, 2022.

Dissecting tumor transcriptional heterogeneity from single-cell RNA-seq data by generalized binary covariance decomposition.

Profiling tumors with single-cell RNA sequencing has the potential to identify recurrent patterns of transcription variation related to cancer progression, and to produce therapeutically relevant insights. However, strong intertumor heterogeneity can obscure more subtle patterns that are shared across tumors. Here we introduce a statistical method, generalized binary covariance decomposition (GBCD), to address this problem.

Adipose tissue eQTL meta-analysis highlights the contribution of allelic heterogeneity to gene expression regulation and cardiometabolic traits.

Complete characterization of the genetic effects on gene expression is needed to elucidate tissue biology and the etiology of complex traits. In the present study, we analyzed 2,344 subcutaneous adipose tissue samples and identified 34,774 conditionally distinct expression quantitative trait locus (eQTL) signals at 18,476 genes. Over half of eQTL genes exhibited at least two eQTL signals.

The impact of common and rare genetic variants on bradyarrhythmia development.

To broaden our understanding of bradyarrhythmias and conduction disease, we performed common variant genome-wide association analyses in up to 1.3 million individuals and rare variant burden testing in 460,000 individuals for sinus node dysfunction (SND), distal conduction disease (DCD) and pacemaker (PM) implantation. We identified 13, 31 and 21 common variant loci for SND, DCD and PM, respectively.

Bayesian analysis of the rate of spontaneous malignant mesothelioma among BAP1 mutant mice in the absence of asbestos exposure.

Cancers of the mesothelium, such as malignant mesothelioma (MM), historically have been attributed solely to exposure to asbestos. Recent large scale genetic and genomic functional studies now show that approximately 20% of all human mesotheliomas are causally linked to highly penetrant inherited (germline) pathogenic mutations in numerous cancer related genes. The rarity of these mutations in humans makes it difficult to perform statistically conclusive genetic studies to understand their biological effects.

Mechanical regulation of macrophage metabolism by allograft inflammatory factor 1 leads to adverse remodeling after cardiac injury.

Myocardial infarction (MI) mobilizes macrophages, the central protagonists of tissue repair in the infarcted heart. Although necessary for repair, macrophages also contribute to adverse remodeling and progression to heart failure. In this context, specific targeting of inflammatory macrophage activation may attenuate maladaptive responses and enhance cardiac repair.

The anticancer activity of fucoidan coated selenium nanoparticles and curcumin nanoparticles against colorectal cancer lines.

Cancers still globally endanger millions of people yearly; the incidences/mortalities of colorectal cancers are particularly increasing. The natural nanoparticles (NPs) and marine biopolymers were anticipated to provide effectual safe significances for managing cancers. The transformation of curcumin to nano-curcumin (NCur) was conducted with gum Arabic.

Resting-state functional magnetic resonance imaging study on cerebrovascular reactivity changes in the precuneus of Alzheimer's disease and mild cognitive impairment patients.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory impairment and cognitive decline, ultimately culminating in dementia. This study aims to evaluate cerebrovascular reactivity (CVR) and functional connectivity (FC) in patients with AD and mild cognitive impairment (MCI) using resting-state functional magnetic resonance imaging (rs-fMRI), bypassing the requirement for hypercapnia. The study cohort comprised 53 AD patients, 38 MCI patients, and 39 normal control (NC) subjects.

Molecular and biological characterization of infectious full-length cDNA clones of two viruses in Paris yunnanensis, including a novel potyvirus.

Paris yunnanensis, also named as Rhizoma Paridis in the Chinese Pharmacopeia, is a perennial Chinese medicinal herb commonly grown in Southwest China. However, several viruses have been found infecting this plant in recent years. Using high-throughput sequencing (HTS) and Sanger sequencing, this study obtained the complete genome sequences of three capillovirus isolates and one potyvirus isolate.

Regional patterns and climatic predictors of viruses in honey bee (Apis mellifera) colonies over time.

Honey bee viruses are serious pathogens that can cause poor colony health and productivity. We analyzed a multi-year longitudinal dataset of abundances of nine honey bee viruses (deformed wing virus A, deformed wing virus B, black queen cell virus, sacbrood virus, Lake Sinai virus, Kashmir bee virus, acute bee paralysis virus, chronic bee paralysis virus, and Israeli acute paralysis virus) in colonies located across Canada to describe broad trends in virus intensity and occurrence among regions and years. We also tested climatic variables (temperature, wind speed, and precipitation) as predictors in an effort to understand possible drivers underlying seasonal patterns in viral prevalence.

Enhanced motivated behavior mediated by pharmacological targeting of the FGF14/Na1.6 complex in nucleus accumbens neurons.

Protein/protein interactions (PPI) play crucial roles in neuronal functions. Yet, their potential as drug targets for brain disorders remains underexplored. The fibroblast growth factor 14 (FGF14)/voltage-gated Na channel 1.

Non-invasive 4D transcranial functional ultrasound and ultrasound localization microscopy for multimodal imaging of neurovascular response.

A long-standing goal of neuroimaging is the non-invasive volumetric assessment of whole brain function and structure at high spatial and temporal resolutions. Functional ultrasound (fUS) and ultrasound localization microscopy (ULM) are rapidly emerging techniques that promise to bring advanced brain imaging and therapy to the clinic with the safety and low-cost advantages associated with ultrasound. fUS has been used to study cerebral hemodynamics at high temporal resolutions while ULM has been used to study cerebral microvascular structure at high spatial resolutions.

A higher order PUF complex is central to regulation of C. elegans germline stem cells.

PUF RNA-binding proteins are broadly conserved stem cell regulators. Nematode PUF proteins maintain germline stem cells (GSCs) and, with key partner proteins, repress differentiation mRNAs, including gld-1. Here we report that PUF protein FBF-2 and its partner LST-1 form a ternary complex that represses gld-1 via a pair of adjacent FBF binding elements (FBEs) in its 3'UTR.

Case Study Analysis of a Decision Coaching Intervention for Young Adults with Early Psychosis.

Young adults with early psychosis often disengage from essential early intervention services (i.e., Coordinated Specialty Care or CSC in the United States).

A multi-platform assessment of extracellular vesicles from the plasma and urine of women with preeclampsia.

Introduction: MicroRNAs (miRNAs), packaged within extracellular vesicles (EVs), have been used to interrogate the pathogenesis of preeclampsia and to identify its biomarkers. We have previously shown that miRNA species were differentially expressed in small plasma EVs from women with preeclampsia vs healthy controls. We sought to assess the use of rapid technologies for isolation of plasma and urine EVs from parturients with preeclampsia and determine differences in the expression of selected EV miRNA species.

Exploring the Sources and Experiences of Joy in Caregiving: Insights From Formal Caregivers in Long-Term Care.

Objectives: To explore and understand the sources and experiences of joy in caregiving among formal caregivers in Canadian long-term care (LTC).

Design: A qualitative study with interpretative descriptive design.

Setting And Participants: The participants consisted of 20 formal caregivers from a large public LTC home in British Columbia, Canada, focusing on those with at least 6 months of direct caregiving experience.

Hospital-Level Disparities in the Management and Outcomes of Pulmonary Embolism.

None.

Cigarette smoking and symptom burden: baseline results from 9 ECOG-ACRIN cancer clinical trials.

Context: Approximately 11% of cancer survivors smoke post-diagnosis.

Objective: Understanding the relationship between smoking and perceived cancer-related symptoms may inform tobacco treatment interventions for this population.

Methods: From 2017-2021, 740 adults in 9 ECOG-ACRIN trials provided baseline data.

A scoping review and consensus recommendations for emergency medical services buprenorphine (EMS-Bupe) programs.

Objectives: Emergency Medical Services (EMS) agencies are beginning to provide low-barrier access to treatment for opioid use disorder (OUD) through the development of EMS buprenorphine (EMS-Bupe) programs. However, evidence-based practices for these programs are lacking. Our aim was to review the current literature on EMS and emergency department (ED) based buprenorphine treatment programs to provide consensus recommendations on the EMS-Bupe program development.