A Global Collaborative Comparison of SARS-CoV-2 Antigenicity Across 15 Laboratories.

Setting up a global SARS-CoV-2 surveillance system requires an understanding of how virus isolation and propagation practices, use of animal or human sera, and different neutralisation assay platforms influence assessment of SARS-CoV-2 antigenicity. In this study, with the contribution of 15 independent laboratories across all WHO regions, we carried out a controlled analysis of neutralisation assay platforms using the first WHO International Standard for antibodies to SARS-CoV-2 variants of concern (source: NIBSC). Live virus isolates (source: WHO BioHub or individual labs) or spike plasmids (individual labs) for pseudovirus production were used to perform neutralisation assays using the same serum panels.

Venous Endothelial Cell Transcriptomic Profiling Implicates METAP1 in Preeclampsia.

Background: Preeclampsia is a hypertensive disorder of pregnancy characterized by systemic endothelial dysfunction. The pathophysiology of preeclampsia remains incompletely understood. This study used human venous endothelial cell (EC) transcriptional profiling to investigate potential novel mechanisms underlying EC dysfunction in preeclampsia.

Mechanistic basis for the emergence of EPS1 as a catalyst in salicylic acid biosynthesis of Brassicaceae.

Salicylic acid (SA) production in Brassicaceae plants is uniquely accelerated from isochorismate by EPS1, a newly identified enzyme in the BAHD acyltransferase family. We present crystal structures of EPS1 from Arabidopsis thaliana in both its apo and substrate-analog-bound forms. Integrating microsecond-scale molecular dynamics simulations with quantum mechanical cluster modeling, we propose a pericyclic rearrangement lyase mechanism for EPS1.

Gut microbiota strain richness is species specific and affects engraftment.

Despite the fundamental role of bacterial strain variation in gut microbiota function, the number of unique strains of a species that can stably colonize the human intestine is still unknown for almost all species. Here we determine the strain richness (SR) of common gut species using thousands of sequenced bacterial isolates with paired metagenomes. We show that SR varies across species, is transferable by faecal microbiota transplantation, and is uniquely low in the gut compared with soil and lake environments.

Caregiving and Hypertension in Younger Black Women: The Jackson Heart Study.

Background: Caregiving has been associated with high blood pressure in middle-aged and older women, but this relationship is understudied among younger Black women, a population at high risk for hypertension. We examined the associations of caregiving stress and caregiving for high-needs dependents with incident hypertension among reproductive-age women in the JHS (Jackson Heart Study), a cohort of community-dwelling Black adults.

Methods: We included 453 participants, aged 21 to 44 years, with blood pressure <140/90 mm Hg, and not taking antihypertensive medication at baseline (2000-2004).

FZD5 controls intestinal crypt homeostasis and colonic Wnt surrogate agonist response.

The rapidly regenerating intestinal epithelium requires crypt intestinal stem cells (ISCs). Wnt/β-catenin signaling maintains crypt homeostasis and Lgr5+ ISCs, and WNT ligands bind Frizzled receptors (FZD1-10). Identifying specific FZD(s) essential for intestinal homeostasis has been elusive; however, bioengineered antagonists blocking Wnt binding to FZD5 and FZD8 deplete the gut epithelium in vivo, highlighting potential roles.

Integrated molecular and functional characterization of the intrinsic apoptotic machinery identifies therapeutic vulnerabilities in glioma.

Genomic profiling often fails to predict therapeutic outcomes in cancer. This failure is, in part, due to a myriad of genetic alterations and the plasticity of cancer signaling networks. Functional profiling, which ascertains signaling dynamics, is an alternative method to anticipate drug responses.

Comparative Outcome Analysis of Lenvatinib Versus Sorafenib for Recurrence of Hepatocellular Carcinoma After Liver Transplantation.

Background: Hepatocellular carcinoma (HCC) recurs after liver transplantation (LT) in ~17% of patients. We aimed to retrospectively compare the outcomes of patients treated with different tyrosine kinase inhibitors (TKIs) for recurrent HCC post-LT.

Methods: Patients with recurrent HCC post-LT between 2006 and 2019 were included.

Interleukin-6, C-Reactive Protein, and Recurrence After Stroke: A Time-Course Analysis of Individual-Participant Data.

Background: Inflammation promotes atherogenesis. Randomized controlled trials of anti-inflammatory therapies for prevention after stroke have not yet demonstrated clear benefit. IL-6 (interleukin-6) and hsCRP (high-sensitivity C-reactive protein) are independently associated with major adverse cardiovascular events poststroke and may guide patient selection in future randomized controlled trials.

Asia-inclusive drug development leveraging principles of ICH E5 and E17 guidelines: Case studies illustrating quantitative clinical pharmacology as a foundational enabler.

With the International Conference on Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) E17 guidelines in effect from 2018, the design of Asia-inclusive multiregional clinical trials (MRCTs) has been streamlined, thereby enabling efficient simultaneous global development. Furthermore, with the recent regulatory reforms in China and its drug administration joining the ICH as a full regulatory member, early participation of China in the global clinical development of novel investigational drugs is now feasible. This would also allow for inclusion of the region in the geographic footprint of pivotal MRCTs leveraging principles of the ICH E5 and E17.

Procoagulant platelet activation promotes venous thrombosis.

Platelets are key players in cardiovascular disease, and platelet aggregation represents a central pharmacologic target, particularly in secondary prevention. However, inhibition of adenosine diphosphate and thromboxane signaling has low efficacy in preventing venous thromboembolism, necessitating the inhibition of the plasmatic coagulation cascade in this disease entity. Anticoagulation carries a significantly higher risk of bleeding complications, highlighting the need of alternative therapeutic approaches.

Salt-Responsive Gut Microbiota Induces Sex-Specific Blood Pressure Changes.

Background: Tryptophan metabolism is important in blood pressure regulation. The tryptophan-indole pathway is exclusively mediated by the gut microbiota. ACE2 (angiotensin-converting enzyme 2) participates in tryptophan absorption, and a lack of ACE2 leads to changes in the gut microbiota.

A Bibliometric Analysis of Inflammation in Hydrocephalus.

Background: Hydrocephalus ranks among the most prevalent neurosurgical conditions worldwide, with a growing body of literature suggesting a potential association with inflammation. Employing bibliometric methods, this research visually analyzes the scholarly output on inflammation in hydrocephalus over the past 2 decades and provides a scientific framework for delineating research pathways and addressing key issues in this field.

Methods: Publications sourced from the Web of Science Core Collection as of July 18, 2024 encompassed articles and reviews in English spanning from January 1, 2000, to December 31, 2024.

Genotype inference from aggregated chromatin accessibility data reveals genetic regulatory mechanisms.

Background: Understanding the genetic causes for variability in chromatin accessibility can shed light on the molecular mechanisms through which genetic variants may affect complex traits. Thousands of ATAC-seq samples have been collected that hold information about chromatin accessibility across diverse cell types and contexts, but most of these are not paired with genetic information and come from diverse distinct projects and laboratories.

Results: We report here joint genotyping, chromatin accessibility peak calling, and discovery of quantitative trait loci which influence chromatin accessibility (caQTLs), demonstrating the capability of performing caQTL analysis on a large scale in a diverse sample set without pre-existing genotype information.

Characteristics of Medical Quality in Tertiary Traditional Chinese Medicine Hospitals by TOPSIS and RSR Methods.

Performance evaluation is important for improving medical quality and services. But, there is a lack of research for medical quality in traditional Chinese medicine (TCM) hospitals. This study examines the medical quality and various indicators of tertiary public traditional Chinese medicine hospitals in Gansu Province, to establish a foundation for improving the medical and management standards of these hospitals.