Emergency response

PURPOSE: Datopotamab deruxtecan (Dato-DXd) is an antibody-drug conjugate consisting of a humanized antitrophoblast cell-surface antigen 2 (TROP2) monoclonal antibody linked to a potent, exatecan-derived topoisomerase I inhibitor payload via a plasma-stable, selectively cleavable linker. PATIENTS AND METHODS: TROPION-PanTumor01 (ClinicalTrials.gov identifier: NCT03401385) is a phase I, dose-escalation, and dose-expansion study evaluating Dato-DXd in patients with previously treated solid tumors...

BACKGROUND AND OBJECTIVES: Climate change is a major threat to the health of people worldwide. The health care system deals with the immediate health-related effects of climate change and, at the same time, is a major emitter of greenhouse gas. This study aimed to investigate (a) the awareness and perception of climate change among family medicine residency program directors, and (b) the state of climate change education in family medicine residency programs. METHODS: The Council of Academic Family Medicine Educational Research Alliance (CERA) conducted a cross-sectional survey of family medicine program directors in the United States in April 2023...

Cancer immunotherapy has emerged as a promising therapeutic strategy to combat cancer effectively. However, it is hard to observe and quantify how this in vivo process happens. Three-dimensional (3D) microfluidic vessel-tumor models offer valuable capability to study how immune cells transport during cancer progression. We presented an advanced 3D vessel-supported tumor model consisting of the endothelial lumen and vessel network for the study of T cells' transportation. The process of T cell transport through the vessel network and interaction with tumor spheroids was represented and monitored in vitro...

AIM: This study aims to explore regional variation and identify regions within Australia with high incidence of out-of-hospital cardiac arrest (OHCA) and low rates of bystander cardiopulmonary resuscitation (CPR). METHOD: Adult OHCAs of presumed medical aetiology occurring across Australia between 2017 and 2019 were mapped onto local government areas (LGA) using the location of arrest coordinates. Bayesian spatial models were applied to provide "smoothed" estimates of OHCA incidence and bystander CPR rates (for bystander-witnessed OHCAs) for each LGA...

The signaling molecule auxin sits at the nexus of plant biology and coordinates essentially all growth and developmental processes in plants. Auxin molecules are transported throughout plant tissues and are capable of evoking highly specific physiological responses in plant cells by inducing various molecular pathways. In many of these pathways, proteolysis plays a crucial role for correct physiological responses. This review provides a chronology of the discovery and characterisation of the auxin receptor, which is a fascinating example of separate research trajectories ultimately converging on the discovery of a core auxin signaling hub which relies on degradation of a family of transcriptional inhibitor proteins - the Aux/IAAs...

The complex resonance of dielectric quality factor Q , combined with a capacitance tunability n higher than 3:1 without any dispersion, was achieved in the voltage-tunable interdigital capacitors (IDCs) based on epitaxial Ba0.8 Sr0.2 TiO3 ferroelectric thin films across the microwave L (1-2 GHz), S (2-4 GHz), and C (4-8 GHz) bands at room temperature. The resonant Q and n features were driven by the microwave responses of the ferroelectric nanodomains engineered in the films. To promote their application in space radiation environments, the evolutions of Q and n both as functions of frequency f (1-8 GHz) and applied electric field E (0-240 kV/cm) were systematically investigated under a series of gamma-ray irradiations up to 100 kGy...

Knowledge tracing (KT) refers to predicting learners' performance in the future according to their historical responses, which has become an essential task in intelligent tutoring systems. Most deep learning-based methods usually model the learners' knowledge states via recurrent neural networks (RNNs) or attention mechanisms. Recently emerging graph neural networks (GNNs) assist the KT model to capture the relationships such as question-skill and question-learner. However, non-pairwise and complex higher-order information among responses is ignored...

OBJECTIVE: Intestinal ultrasound (IUS) is an emerging modality for assessing disease activity, extent, and treatment response in ulcerative colitis. This study aimed to evaluate the potential of IUS in predicting severe flares, the need for rescue therapy (corticosteroid failure), and colectomy in patients with ulcerative colitis. METHODS: We conducted a retrospective review of medical records, collecting clinical and IUS data. The Milan Ultrasound Criteria (MUC) score was used to assess ulcerative colitis severity...

PURPOSE: A strong immunosuppressive tumor microenvironment (TME) represents the major barrier responsible for the failure of current immunotherapy approaches in treating Glioblastoma Multiforme (GBM). Within the TME, the regulatory T cells (Tregs) exert immunosuppressive effects on CD8+ T cell - mediated anti-cancer immune killing. Consequently, targeting and inhibiting their immunosuppressive function emerges as an effective therapeutic strategy for GBM. The present study aimed to investigate the mechanisms and effects of Suberanilohydroxamic Acid (SAHA), a histone deacetylase inhibitor, on immunosuppressive Tregs...

The acetylation of α-tubulin on lysine 40 is a well-studied post-translational modification which has been associated with the presence of long-lived stable microtubules that are more resistant to mechanical breakdown. The discovery of α-tubulin acetyltransferase 1 (ATAT1), the enzyme responsible for lysine 40 acetylation on α-tubulin in a wide range of species, including protists, nematodes, and mammals, dates to about a decade ago. However, the role of ATAT1 in different cellular activities and molecular pathways has been only recently disclosed...

The global burden of osteoporosis continues to rise with an ageing population. Untreated osteoporotic fractures not only heighten the risk of subsequent fractures but are associated with excess mortality. Although primary care guidelines consistently stress the importance of secondary fracture prevention, fewer than 20% of patients are appropriately treated for osteoporosis following an initial osteoporotic fracture. This worldwide phenomenon is known as the osteoporosis care gap. This literature review examines the barriers to secondary fracture prevention in primary care and evaluates the effectiveness of targeted primary care interventions...

PURPOSE: As online health information-seeking surges, concerns mount over the quality and safety of accessible content, potentially leading to patient harm through misinformation. On one hand, the emergence of Artificial Intelligence (AI) in healthcare could prevent it; on the other hand, questions raise regarding the quality and safety of the medical information provided. As laryngeal cancer is a prevalent head and neck malignancy, this study aims to evaluate the utility and safety of three large language models (LLMs) as sources of patient information about laryngeal cancer...

The principle of continuity demands the existence of prior molecular states and common ancestors responsible for extant macromolecular structure. Here, we focus on the emergence and evolution of loop prototypes - the elemental architects of protein domain structure. Phylogenomic reconstruction spanning superkingdoms and viruses generated an evolutionary chronology of prototypes with six distinct evolutionary phases defining a most parsimonious evolutionary progression of cellular life. Each phase was marked by strategic prototype accumulation shaping the structures and functions of common ancestors...

Once considered passive cells of the central nervous system (CNS), glia are now known to actively maintain the CNS parenchyma; in recent years, the evidence for glial functions in CNS physiology and pathophysiology has only grown. Astrocytes, a heterogeneous group of glial cells, play key roles in regulating the metabolic and inflammatory landscape of the CNS and have emerged as potential therapeutic targets for a variety of disorders. This review will outline astrocyte functions in the CNS in healthy ageing, obesity, and neurodegeneration, with a focus on the inflammatory responses and mitochondrial function, and will address therapeutic outlooks...

PURPOSE: ARO-HIF2 is an siRNA drug designed to selectively target hypoxia-inducible factor-2α (HIF2α) interrupting downstream pro-oncogenic signaling in clear cell renal cell carcinoma (ccRCC). The aims of this Phase 1 study (AROHIF21001) were to evaluate safety, tolerability, pharmacokinetics, and establish a recommended Phase 2 dose. PATIENTS AND METHODS: Subjects with ccRCC and progressive disease after at least 2 prior therapies that included VEGF and immune checkpoint inhibitors were progressively enrolled into dose-escalation cohorts of ARO-HIF2 administered intravenously at 225, 525, or 1,050 mg weekly...

N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-quinone) is a widespread contaminant of emerging concern resulting from oxidation of 6PPD, which is an antidegradant substance added to tires. The recent identification of 6PPD-quinone as the cause of acute mortality in coho salmon has quickly motivated studies on 6PPD-quinone toxicity to other species. Subsequent findings have shown that 6PPD-quinone toxicity is highly species specific. Closely related species can differ widely in response to 6PPD-quinone from extremely sensitive to tolerant...

Mycobacterium abscessus is an emerging opportunistic pathogen responsible for chronic lung diseases, especially in patients with cystic fibrosis. Treatment failure of M. abscessus infections is primarily associated with intrinsic or acquired antibiotic resistance. However, there is growing evidence that antibiotic tolerance, i.e., the ability of bacteria to transiently survive exposure to bactericidal antibiotics through physiological adaptations, contributes to the relapse of chronic infections and the emergence of acquired drug resistance...

Simultaneous utilization of photogenerated electrons and holes to achieve overall redox reactions is attractive but still far from practical application. The emerging step (S)-scheme mechanism has proven to be an ideal approach to inhibit charge recombination and supply photoinduced charges with highest redox potentials. Herein, a hierarchical phosphotungstic acid (H3PW12O40, HPW)@Znln2S4 (ZISW) heterojunction was prepared through one-pot hydrothermal method for simultaneous hydrogen (H2) evolution and benzyl alcohol upgrading...

In response to the escalating demand for sustainable agricultural methodologies, the utilization of microbial volatile organic compounds (VOCs) as antagonists against phytopathogens has emerged as a viable eco-friendly alternative. Microbial volatiles exhibit rapid diffusion rates, facilitating prompt chemical interactions. Moreover, microorganisms possess the capacity to emit volatiles constitutively, as well as in response to biological interactions and environmental stimuli. In addition to volatile compounds, these bacteria demonstrate the ability to produce soluble metabolites with antifungal properties, such as APE Vf, pyoverdin, and fragin...

BACKGROUND: In 2022, suicide was the second leading cause of external death in Spain (the first among young people aged 15-29 years). This study aims to analyze the presence of myths among emergency first responders and identify the most prevalent false beliefs among them. METHODS: The research is a observational and descriptive study carried out using a questionnaire composed of a total of 25 myths, with the response options being true or false. A total of 543 professionals took part in the study...