Impact of pandemic service changes on ethnic inequalities in maternal and perinatal outcomes in England: a population-based study.

Objective: In the UK and worldwide, there are substantial ethnic inequalities in maternal and perinatal care and outcomes. We aim to assess the impact of the unprecedented change in care provision during the COVID-19 pandemic on inequalities in adverse maternity outcomes.

Design: Retrospective cohort study using structured electronic health record data.

Core temperature and mental status of two runners experiencing exertional heat stroke after a road race.

Prehospital management of exertional heat stroke (EHS) consists of monitoring rectal temperature (T) while aggressively cooling via cold water immersion. Recent recommendations suggest using central nervous system (CNS) dysfunction to determine cessation of cooling when T is not available. We examined cognitive responses of two runners with EHS after a road race.

Targeting peptide antigens using a multiallelic MHC I-binding system.

Identifying highly specific T cell receptors (TCRs) or antibodies against epitopic peptides presented by class I major histocompatibility complex (MHC I) proteins remains a bottleneck in the development of targeted therapeutics. Here, we introduce targeted recognition of antigen-MHC complex reporter for MHC I (TRACeR-I), a generalizable platform for targeting peptides on polymorphic HLA-A*, HLA-B* and HLA-C* allotypes while overcoming the cross-reactivity challenges of TCRs. Our TRACeR-MHC I co-crystal structure reveals a unique antigen recognition mechanism, with TRACeR forming extensive contacts across the entire peptide length to confer single-residue specificity at the accessible positions.

Change in interleukin (IL)-6, 8, and 10 and its association with an increase in core temperature following a 7-mile running race in the warm weather.

The purposes of this study were 1) to investigate if cytokines were increased following a running road-race, and 2) to examine associations between cytokines and hyperthermia. Seventy-seven recreational runners participated in this study which occurred at the 7-mile race in the heat (ambient temperature, 25.0-26.

CRCINA inaugural symposium: A meeting on tumor and immune ecosystems.

The CRCINA inaugural symposium, a meeting on tumor and immune ecosystems, took place in the vibrant and picturesque city of Nantes. The meeting gathered world-renowned experts in cancer biology and immunology. It showcased the most advanced science on mechanisms driving cellular heterogeneity, plasticity, and signaling in normal and cancer cellular ecosystems, which contribute to cancer development, progression, and therapeutic resistance.

ISG15 Drives Immune Pathology and Respiratory Failure during Systemic Lymphocytic Choriomeningitis Virus Infection.

ISG15, an IFN-stimulated gene, plays a crucial role in modulating immune responses during viral infections. Its upregulation is part of the host's defense mechanism against viruses, contributing to the antiviral state of cells. However, altered ISG15 expression can also lead to immune dysregulation and pathological outcomes, particularly during persistent viral infections.

A comprehensive engineering strategy improves potency and manufacturability of a near pan-neutralizing antibody against HIV.

Anti-HIV envelope broadly neutralizing antibodies (bnAbs) are alternatives to conventional antiretrovirals with the potential to prevent and treat infection, reduce latent reservoirs, and/or mediate a functional cure. Clinical trials with "first generation" bnAbs used alone or in combination show promising antiviral effects but also highlight that additional engineering of "enhanced" antibodies will be required for optimal clinical utility, while preserving or enhancing cGMP manufacturing capability. Here we report the engineering of an anti-CD4 binding-site (CD4bs) bnAb, N49P9.

Modelling pollutants transport scenarios based on the X-Press Pearl disaster.

The MV X-Press Pearl accident near Sri Lanka in May 2021 released several pollutants into the ocean, including 1843.3 t of urea, raising concerns about the impact on the region. This study uses a coupled ocean (NEMO)-biogeochemistry (ERSEM) model to simulate urea dispersion under various scenarios.

COVID-19 Vaccine Safety in Pregnancy, A Nested Case-Control Study in Births From April 2021 to March 2022, England.

Objective: Assessment of COVID-19 vaccine safety in pregnancy using population-based data.

Design: Matched case-control study nested in a retrospective cohort.

Setting: April 2021-March 2022, England.

Importance of the Cysteine-Rich Domain of Snake Venom Prothrombin Activators: Insights Gained from Synthetic Neutralizing Antibodies.

Snake venoms are cocktails of biologically active molecules that have evolved to immobilize prey, but can also induce a severe pathology in humans that are bitten. While animal-derived polyclonal antivenoms are the primary treatment for snakebites, they often have limitations in efficacy and can cause severe adverse side effects. Building on recent efforts to develop improved antivenoms, notably through monoclonal antibodies, requires a comprehensive understanding of venom toxins.

Exertional Heat Stroke Best Practices in U.S. Emergency Medical Services Guidelines.

Background: Exertional heat illnesses (EHIs), specifically exertional heat stroke (EHS), are a top cause of nonaccidental death among U.S. laborers.

Synthetic integrin antibodies discovered by yeast display reveal αV subunit pairing preferences with β subunits.

Integrins are cell surface receptors that mediate the interactions of cells with their surroundings and play essential roles in cell adhesion, migration, and homeostasis. Eight of the 24 integrins bind to the tripeptide Arg-Gly-Asp (RGD) motif in their extracellular ligands, comprising the RGD-binding integrin subfamily. Despite similarity in recognizing the RGD motif and some redundancy, these integrins can selectively recognize RGD-containing ligands to fulfill specific functions in cellular processes.

A positive deviant approach to examining the impact of Covid-19 on ethnic inequalities in maternal and neonatal outcomes.

Objectives: During the COVID-19 pandemic, rapid and heterogeneous changes were made to maternity care. Identification of changes that may reduce maternal health inequalities is a national priority. The aim of this project was to use data collected about care and outcomes to identify NHS Trusts in the UK where inequalities in outcomes reduced during the pandemic and explore through interviews how the changes that occurred may have led to a reduction in inequalities.

Exertional Heatstroke Survivors' Knowledge and Beliefs About Exertional Heatstroke Diagnosis, Treatment, and Return to Play.

Context: Little information exists regarding what exertional heatstroke (EHS) survivors know and believe about EHS best practices. Understanding this would help clinicians focus educational efforts to ensure survival and safe return-to-play following EHS.

Objective: We sought to better understand what EHS survivors knew about EHS seriousness (eg, lethality and short- and long-term effects), diagnosis and treatment procedures, and recovery.

Necrosulfonamide causes oxidation of PCM1 and impairs ciliogenesis and autophagy.

Centriolar satellites are high-order assemblies, scaffolded by the protein PCM1, that gravitate as particles around the centrosome and play pivotal roles in fundamental cellular processes notably ciliogenesis and autophagy. Despite stringent control mechanisms involving phosphorylation and ubiquitination, the landscape of post-translational modifications shaping these structures remains elusive. Here, we report that necrosulfonamide (NSA), a small molecule known for binding and inactivating the pivotal effector of cell death by necroptosis MLKL, intersects with centriolar satellites, ciliogenesis, and autophagy independently of MLKL.

Synthetic development of a broadly neutralizing antibody against snake venom long-chain α-neurotoxins.

Snakebite envenoming is a major global public health concern for which improved therapies are urgently needed. The antigenic diversity present in snake venom toxins from various species presents a considerable challenge to the development of a universal antivenom. Here, we used a synthetic human antibody library to find and develop an antibody that neutralizes long-chain three-finger α-neurotoxins produced by numerous medically relevant snakes.

Accelerating AI Innovation in Healthcare Through Mentorship.

The adoption of Artificial Intelligence (AI) in the Canadian healthcare system falls behind that of other countries. Socio-technological considerations such as organizational readiness and a limited understanding of the technology are a few barriers impeding its adoption. To address this need, this study implemented a five-month AI mentorship program with the primary objective of developing participants' AI toolset.

Synthetic integrin antibodies discovered by yeast display reveal αV subunit pairing preferences with β subunits.

Eight of the 24 integrin heterodimers bind to the tripeptide Arg-Gly-Asp (RGD) motif in their extracellular ligands, and play essential roles in cell adhesion, migration, and homeostasis. Despite similarity in recognizing the RGD motif and some redundancy, these integrins can selectively recognize RGD-containing ligands including fibronectin, vitronectin, fibrinogen, nephronectin and the prodomain of the transforming growth factors to fulfill specific functions in cellular processes. Subtype-specific antibodies against RGD-binding integrins are desirable for investigating their specific functions.

The centrosomal protein 131 participates in the regulation of mitochondrial apoptosis.

Centriolar satellites are multiprotein aggregates that orbit the centrosome and govern centrosome homeostasis and primary cilia formation. In contrast to the scaffold PCM1, which nucleates centriolar satellites and has been linked to microtubule dynamics, autophagy, and intracellular trafficking, the functions of its interactant CEP131 beyond ciliogenesis remain unclear. Using a knockout strategy in a non-ciliary T-cell line, we report that, although dispensable for centriolar satellite assembly, CEP131 participates in optimal tubulin glycylation and polyglutamylation, and microtubule regrowth.

Exertional Heat Stroke Survival at the Falmouth Road Race: 180 New Cases With Expanded Analysis.

Context: A high number of exertional heat stroke (EHS) cases occur during the Falmouth Road Race.

Objectives: To extend previous analyses of EHS cases during the Falmouth Road Race by assessing or describing (1) EHS and heat exhaustion (HE) incidence rates, (2) EHS outcomes as they relate to survival, (3) the effect of the environment on these outcomes, and (4) how this influences medical provider planning and preparedness.

Design: Descriptive epidemiologic study.

Broadening a SARS-CoV-1-neutralizing antibody for potent SARS-CoV-2 neutralization through directed evolution.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need for strategies to rapidly develop neutralizing monoclonal antibodies that can function as prophylactic and therapeutic agents and to help guide vaccine design. Here, we demonstrate that engineering approaches can be used to refocus an existing antibody that neutralizes one virus but not a related virus. Through a rapid affinity maturation strategy, we engineered CR3022, a SARS-CoV-1-neutralizing antibody, to bind to the receptor binding domain of SARS-CoV-2 with >1000-fold increased affinity.