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.
View Article and Find Full Text PDFObjectives: Hypothermic lung preservation at 10 °C has been recently shown to enhance quality of healthy donor lungs during ischemia. This study aims to show generalizability of the 10 °C lung preservation using an endotoxin-induced lung injury with specific focus on the benefits of post-transplant lung function and mitochondrial preservation.
Methods: Lipopolysaccharide (3 mg/kg) was injected intratracheally in rats to induce lung injury.
HIV-1 antiretroviral therapy is highly effective but fails to eliminate a reservoir of latent proviruses, leading to a requirement for life-long treatment. How the site of integration of authentic intact latent proviruses might impact their own or neighboring gene expression or reservoir dynamics is poorly understood. Here, we report on proviral and neighboring gene transcription at sites of intact latent HIV-1 integration in cultured T cells obtained directly from people living with HIV, as well as engineered primary T cells and cell lines.
View Article and Find Full Text PDFIn recent years, significant progress has been made in 5q Spinal Muscular Atrophy therapeutics, emphasizing the importance of early diagnosis and intervention for better clinical outcomes. Characterized by spinal cord motor neuron degeneration, 5q-SMA leads to muscle weakness, swallowing difficulties, respiratory insufficiency, and skeletal deformities. Recognizing the pre-symptomatic phases supported by screening and confirmatory genetic tests is crucial for early diagnosis.
View Article and Find Full Text PDFNat Commun
July 2024
Patritumab deruxtecan (HER3-DXd) exhibits promising efficacy in breast cancer, with its activity not directly correlated to baseline ERBB3/HER3 levels. This research investigates the genetic factors affecting HER3-DXd's response in women with early-stage hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancer. In the SOLTI-1805 TOT-HER3 trial, a single HER3-DXd dose was administered to 98 patients across two parts: 78 patients received 6.
View Article and Find Full Text PDFSepsis results from systemic, dysregulated inflammatory responses to infection, culminating in multiple organ failure. Here, we demonstrate the utility of CD5L for treating experimental sepsis caused by cecal ligation and puncture (CLP). We show that CD5L's important features include its ability to enhance neutrophil recruitment and activation by increasing circulating levels of CXCL1, and to promote neutrophil phagocytosis.
View Article and Find Full Text PDFTwo of every three persons living with dementia reside in low- and middle-income countries (LMICs). The projected increase in global dementia rates is expected to affect LMICs disproportionately. However, the majority of global dementia care costs occur in high-income countries (HICs), with dementia research predominantly focusing on HICs.
View Article and Find Full Text PDFIntroduction: This study aimed to assess the clinical, economic, and humanistic impact of short-bowel syndrome/chronic intestinal failure (SBS/CIF) in Portugal.
Methods: This is a retrospective multicenter cohort chart review study, with a cross-sectional component for quality-of-life (QoL) evaluation. Inclusion criteria comprised patients with SBS/CIF, aged ≥1 year, with stable parenteral nutrition (PN).
BMS-986263 is a retinoid-conjugated lipid nanoparticle delivering small interfering RNA designed to inhibit synthesis of HSP47 protein, a collagen-specific chaperone protein involved in fibrosis development. This is a phase I, open-label, two-part study evaluating pharmacokinetics and safety of BMS-986263 in participants with hepatic impairment (HI). Part 1 (n = 24) of this study enrolled two cohorts with mild and moderate HI and a separate cohort of age- and body mass index (BMI)-matched participants with normal hepatic function.
View Article and Find Full Text PDFNutrients
July 2023
Obesity is a troubling public health problem as it increases risks of sleep disorders, respiratory complications, systemic arterial hypertension, cardiovascular diseases, type 2 diabetes mellitus, and metabolic syndrome (MetS). As a measure to counteract comorbidities associated with severe obesity, bariatric surgery stands out. This study aimed to investigate the adiponectin/leptin ratio in women with severe obesity with and without MetS who had undergone Roux-en-Y gastric bypass (RYGB) and to characterize the biochemical, glucose, and inflammatory parameters of blood in women with severe obesity before and after RYGB.
View Article and Find Full Text PDFDespite mRNA vaccination, elderly individuals remain especially vulnerable to severe consequences of SARS-CoV-2 infection. Here, we compare the memory B cell responses in a cohort of elderly and younger individuals who received mRNA booster vaccinations. Plasma neutralizing potency and breadth were similar between the two groups.
View Article and Find Full Text PDFObjective: To determine risk factors for the development of long coronavirus disease 2019 (COVID-19) in healthcare personnel (HCP).
Methods: We conducted a case-control study among HCP who had confirmed symptomatic COVID-19 working in a Brazilian healthcare system between March 1, 2020, and July 15, 2022. Cases were defined as those having long COVID according to the Centers for Disease Control and Prevention definition.
Migratory insertions of alkenes into metal-carbon (M-C) bonds are elementary steps in diverse catalytic processes. In the present work, a radical-type migratory insertion that involves concerted but asynchronous M-C homolysis and radical attack was revealed by computations. Inspired by the radical nature of the proposed migratory insertion, a distinct cobalt-catalyzed radical-mediated carbon-carbon (C-C) cleavage mechanism was proposed for alkylidenecyclopropanes (ACPs).
View Article and Find Full Text PDFIntroduction: The aim of this study was to evaluate Dysphagia Days as a measure of symptom improvement in patients with eosinophilic esophagitis from the HEROES study.
Methods: Dysphagia Days, defined as a yes answer to the following question: During any meal today, did food go down slowly or get stuck in your throat or chest? was assessed for cendakimab vs placebo.
Results: A statistically significant reduction in the mean number of Dysphagia Days experienced was observed with cendakimab 360 mg vs placebo at week 16 (-4.
Antibody responses are characterized by increasing affinity and diversity over time. Affinity maturation occurs in germinal centers by a mechanism that involves repeated cycles of somatic mutation and selection. How antibody responses diversify while also undergoing affinity maturation is not as well understood.
View Article and Find Full Text PDFAspergillosis is an invasive fungal disease associated with high mortality. Antifungal susceptibility testing (AFST) is receiving increasing consideration for managing patients, as well as for surveilling emerging drug resistance, despite having time-consuming and technically complex reference methodologies. The Sensititre YeastOne (SYO) and Etest methods are widely utilized for yeasts but have not been extensively evaluated for Aspergillus isolates.
View Article and Find Full Text PDFIndividuals who receive a third mRNA vaccine dose show enhanced protection against severe COVID-19, but little is known about the impact of breakthrough infections on memory responses. Here, we examine the memory antibodies that develop after a third or fourth antigenic exposure by Delta or Omicron BA.1 infection, respectively.
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