Structure and function of a near fully-activated intermediate GPCR-Gαβγ complex.

Unraveling the signaling roles of intermediate complexes is pivotal for G protein-coupled receptor (GPCR) drug development. Despite hundreds of GPCR-Gαβγ structures, these snapshots primarily capture the fully activated complex. Consequently, the functions of intermediate GPCR-G protein complexes remain elusive.

A retrospective analysis of medical student authorship in highest impact radiology journal publications.

Objectives: To assess medical student authorship in radiology research, focusing on the prevalence and impact of student articles, demographic trends, and potential barriers and opportunities for involvement.

Methods: We retrospectively assessed original research and review papers from 2018 to 2022 in the top five radiology journals based on their 2022 Impact Factor. Three reviewers manually validated and classified articles by medical student (MS) and non-MS authorship.

Characterization of LIPUS Parameters Suitable for Hip Bone Fracture.

Objective: To investigate the effects of ultrasound treatment on the healing of hip bone fractures using frequencies of 0.5 MHz and 1.5 MHz with constant intensity (30 mW/cm) at the fractured site.

Interleukin-17: A pleiotropic cytokine implicated in inflammatory, infectious, and malignant disorders.

IL-17A, referred to as IL-17, is the founding member of a family of pro-inflammatory cytokines, including IL-17B, IL-17C, IL-17D, IL-17E (or IL-25), and IL-17F, which act via receptors IL-17RA to IL-17RE, and elicit potent cellular responses that impact diverse diseases. IL-17's interactions with various cytokines include forming a heterodimer with IL-17F and being stimulated by IL-23's activation of Th17 cells, which can lead to inflammation and autoimmunity. IL-17 is implicated in infectious diseases and inflammatory disorders such as rheumatoid arthritis and psoriasis, promoting neutrophil recruitment and anti-bacterial immunity, but potentially exacerbating fungal and viral infections, revealing its dual role as protective and pathologic.

Problem Adaptation Therapy for Older Adults with Chronic Pain and Negative Emotions in Primary Care (PATH-Pain): A Randomized Clinical Trial.

Objective: To test the efficacy of Problem Adaptation Therapy for Pain (PATH-Pain) versus Usual Care (UC) in reducing pain-related disability, pain intensity, and depression among older adults with chronic pain and negative emotions.

Design: RCT assessing the between-group differences during the acute (0-10 weeks) and follow-up (weeks 11-24) phase of treatment.

Setting: A geriatrics primary care site.

Pharmacotherapy of type 1 diabetes - part 1: Yesterday.

Introduction: Type 1 diabetes is a unique autoimmune attack on the β cell of the pancreatic islet resulting in progressive destruction of these cells and as a result the ability of the body to maintain insulin production. The consequences of insulin deficiency are very severe, and the disease was fatal prior to the ability to extract insulin from animal pancreas in 1921. We review progress in the treatment of childhood type 1 diabetes over the past 100 years.

Interobserver agreement and practice patterns for grading of colorectal carcinoma: World Health Organization (WHO) classification of tumours 5th edition versus American Joint Committee on Cancer (AJCC) 8th edition staging manual.

Aims: The current American Joint Committee on Cancer (AJCC) staging manual and the College of American Pathologists (CAP) colorectal carcinoma (CRC) protocol specify use of a four-tiered grading system (i.e. grades 1-4; well-differentiated-undifferentiated) for CRC, based on percentage of gland formation.

Impact of changes in primary care attachment: a scoping review.

Objectives: Primary care attachment represents an inclusive, equitable and cost-effective way of enhancing health outcomes globally. However, the growing shortage of family physicians threatens to disrupt patient-provider relationships. Understanding the consequences of these disruptions is essential for guiding future research and policy.

Ultrasound-Guided Maxillary Nerve Block in Nasal Surgery.

Emphasis on enhanced recovery after surgery (ERAS) protocols and opioid use reduction have led to a growing interest in alternative pain management strategies. This study describes and evaluates the ultrasound-guided suprazygomatic maxillary (SZM) nerve blocks for patients undergoing functional and cosmetic nasal surgery as an adjunct to postoperative pain management. A retrospective, multicenter analysis was conducted on patients who underwent functional nasal surgery and rhinoplasty and evaluated the impact of SZM blocks on intraoperative anesthetic and opioid use, postoperative pain scores recorded in the PACU, and PACU length.

Healthy Lifestyle in the First 1000 Days and Overweight and Obesity Throughout Childhood.

Objectives: Investigate associations of different family healthy lifestyle scores (HLS) during the first 1000 days with childhood overweight and obesity (OWOB).

Methods: Cohort-specific analyses were conducted on participants (n = 25 006) from 4 European birth cohorts (The study on the pre- and early postnatal determinants of child health and development [EDEN], Elfe, France; Generation R, the Netherlands; and Lifeways, Ireland). Three composite HLSs were calculated: a maternal pregnancy HLS based on prepregnancy body mass index (BMI) and diet quality, physical activity, smoking status, and alcohol consumption during pregnancy; a parental pregnancy HLS additionally considering paternal BMI and smoking status; and an infancy HLS based on breastfeeding duration, age of solid food introduction, and exposure to passive smoking.

Cotadutide reversible self-assembly based long-acting injectable depot for sustained delivery of GLP-1 glucagon receptor agonists with controlled burst release.

Cota is a lipidated dual GLP-1 and Glucagon receptor agonist that was investigated for the treatment of various metabolic diseases, it is designed for once daily subcutaneous administration. Invasive daily injections often result in poor patient compliance with chronic disease, and here, we demonstrate an innovative strategy of encapsulating reversible cota self-assembled fibers within an in-situ forming depot of low molecular weight poly(lactic-co-glycolic) acid (LWPLGA) for sustained delivery GLP-1 and Glucagon receptor agonist with controlled burst release. This could be a suitable alternative to other sustained delivery strategies for fibrillating peptides.

Sexual identity, sexual behavior, and drug use behaviors among people who use drugs in the rural U.S.

Introduction: People who use drugs (PWUD) are at risk of HIV infection, but the frequency and distribution of transmission-associated behaviors within rural communities is not well understood. Further, while interventions designed to more explicitly affirm individuals' sexual orientation and behaviors may be more effective, descriptions of behavior variability by orientation are lacking. We sought to describe how disease transmission behaviors and overdose risk vary by sexual orientation and activity among rural PWUD.

Mutations in hnRNP A1 drive neurodegeneration and alternative RNA splicing of neuronal gene targets.

RNA binding protein dysfunction is a pathogenic feature of multiple neurological diseases, including multiple sclerosis (MS). Neurodegeneration (the loss of, or damage to neurons and axons) is the primary driver of disease progression in MS. Herein, we utilized a novel, neuron-specific model of neurodegeneration by transducing primary mouse neurons with mutant forms of the RNA binding protein heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) identified from MS patients, including one within the M9-nuclear localization sequence of hnRNP A1 (A1(P275S)) and a second in the prion-like domain of hnRNP A1 (A1(F263S)) to test the hypothesis that neuronal hnRNP A1 dysfunction drives neurodegeneration in MS.

Nivolumab plus ipilimumab versus nivolumab in microsatellite instability-high metastatic colorectal cancer (CheckMate 8HW): a randomised, open-label, phase 3 trial.

Background: CheckMate 8HW prespecified dual primary endpoints, assessed in patients with centrally confirmed microsatellite instability-high or mismatch repair-deficient status: progression-free survival with nivolumab plus ipilimumab compared with chemotherapy as first-line therapy and progression-free survival with nivolumab plus ipilimumab compared with nivolumab alone, regardless of previous systemic treatment for metastatic disease. In our previous report, nivolumab plus ipilimumab showed superior progression-free survival versus chemotherapy in first-line microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer in the CheckMate 8HW trial. Here, we report results from the prespecified interim analysis for the other primary endpoint of progression-free survival for nivolumab plus ipilimumab versus nivolumab across all treatment lines.

Chromosome-scale genome assembly reveals how repeat elements shape non-coding RNA landscapes active during newt limb regeneration.

Newts have large genomes harboring many repeat elements. How these elements shape the genome and relate to newts' unique regeneration ability remains unknown. We present here the chromosome-scale assembly of the 20.

Associations Between Leisure-Time Physical Activity and Mortality by Sociodemographic Factors.

Background: The 2018 Physical Activity Guidelines 2nd Edition Advisory Committee Scientific Report recommended research to understand whether the health benefits of physical activity (PA) differed by sociodemographic factors. This study examined associations between meeting PA guidelines in leisure time and all-cause, heart disease, and cancer mortality across sociodemographic characteristics.

Methods: Nationally representative data on 567,483 eligible US adults from the 1998-2018 US National Health Interview Survey and 2019 public-use linked mortality files were used.

Analysis of TEM micrographs with deep learning reveals APOE genotype-specific associations between HDL particle diameter and Alzheimer's dementia.

High-density lipoprotein (HDL) particle diameter distribution is informative in the diagnosis of many conditions, including Alzheimer's disease (AD). However, obtaining an accurate HDL size measurement is challenging. We demonstrated the utility of measuring the diameter of more than 1,800,000 HDL particles with the deep learning model YOLOv7 (you only look once) from micrographs of 183 HDL samples, including patients with dementia or normal cognition (controls).

Toward cognitive models of misophonia.

Misophonia is a disorder in which specific common sounds such as another person breathing or chewing, or the ticking of a clock, cause an atypical negative emotional response. Affected individuals may experience anger, irritability, annoyance, disgust, and anxiety, as well as physiological autonomic responses, and may find everyday environments and contexts to be unbearable in which their 'misophonic stimuli' (often called 'trigger sounds') are present. Misophonia is gradually being recognized as a genuine problem that causes significant distress and has negative consequences for individuals and their families.

Atezolizumab plus bevacizumab as first-line treatment of unresectable hepatocellular carcinoma: interim analysis results from the phase IIIb AMETHISTA trial.

Background: The treatment of advanced hepatocellular carcinoma (HCC) with atezolizumab and bevacizumab led to significant improvements in overall survival (OS), progression-free survival (PFS), and response rate compared with sorafenib in the phase III IMbrave150 trial. The etiology of background liver disease can differ between Eastern and Western populations, leading to a potentially different impact of systemic therapies; therefore the unequal representation must be considered in the IMbrave150 trial. To provide further data on the safety and effectiveness of atezolizumab and bevacizumab, the phase IIIb AMETHISTA (Atezolizumab plus bevacizumab in METastatic HCC Italian Safety TriAl) ran in a Western (Italian) population of patients with advanced HCC.

Spatiotemporal distribution of marine aerosols and gaseous species over the North Pacific Ocean.

Observational studies of marine aerosols are essential for understanding the global aerosol budget and its environmental impacts. This study presents simultaneous in-situ measurements of major ionic components (Cl, NO, SO, NH, K, Ca, Na, and Mg) in aerosols and gaseous species (HCl, HNO, HONO, SO, and NH) over the North Pacific Ocean from July 4 to 15 and September 19 to October 3, 2022. Using high temporal resolution instruments aboard the Republic of Korea's icebreaker research vessel Araon, this study aimed to (1) report the spatial and temporal distributions of aerosols and gaseous species, (2) estimate the source contributions of continental anthropogenic pollutants, and (3) assess the influence of aerosol chemical composition and gaseous species on aerosol acidity and water content.

Has the documentation of chest injuries and the development of systemic complications in patients with long bone fractures changed over time?-A systematic literature review and meta-analysis by the IMPACT expert group.

Introduction: Blunt chest trauma represents a major risk factor for complications in polytrauma patients. Various scoring systems have emerged, but their impact is not fully appreciated. This review evaluates changes in chest trauma scoring over time and potential shifts in complication rates linked to modified surgical approaches in long bone fractures.

Radiofrequency-thermocoagulation in pediatric epilepsy surgery: A systematic review and pooled analysis of cases.

Objective: To conduct a systematic review on radiofrequency thermocoagulation (RF-TC) in pediatric epilepsy surgery. In addition, due to the low number of dedicated pediatric series, to conduct a pooled analysis of cases published in the literature.

Methods: We conducted a literature search using PUBMED and EMBASE which produced 432 results.

Degradation of antibiotic pollutants and simultaneous CO capture over hollow MnO/light/peroxymonosulfate (PMS)-CaO system.

Antibiotic organic pollutants not only pose a significant threat to human health but also generate a large amount of carbon dioxide (CO) during the treatment process of advanced oxidation processes (AOPs). Herein, the antibiotics aqueous solution was firstly degraded and mineralized by light-assisted peroxymonosulfate (PMS) activation over hollow manganese dioxide (MnO) catalyst and then the corresponding released CO was effectively captured by calcium oxide (CaO) particles in the same sealed reactor, achieving wastewater treatment with zero carbon releasing. Under simulated light conditions, hollow MnO is excited to generate electron-hole pairs.