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BACKGROUND: Larotrectinib is a first-in-class, highly selective tropomyosin receptor kinase (TRK) inhibitor approved to treat adult and pediatric patients with TRK fusion-positive cancer. The aim of this study was to evaluate the efficacy and safety of larotrectinib in patients with TRK fusion-positive primary central nervous system (CNS) tumors.METHODS: Patients with TRK fusion-positive primary C
CONTEXT: - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can undergo maternal-fetal transmission, heightening interest in the placental pathology findings from this infection. Transplacental SARS-CoV-2 transmission is typically accompanied by chronic histiocytic intervillosaaitis together with necrosis and positivity of syncytiotrophoblast for SARSCoV-2. Hofbauer cells are placental
Background: Since the publication of the European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis (LVV) in 2009, several relevant randomised clinical trials and cohort analyses have been published, which have the potential to change clinical care and therefore supporting the need to update the original recommendations. Methods: Using EULAR standardis
Sparse open clusters can be found at high galactic latitudes where loosely populated clusters are more easily detected against the lower stellar background. Because most star formation takes place in the thin disc, the observed population of clusters far from the Galactic plane is hard to explain. We combined spectral parameters from the GALAH survey with the Gaia DR2 catalogue to study the dynami
A momentum resolved resonant inelastic X-ray scattering (qRIXS) experimental station with continuously rotatable spectrometers and parallel detection is designed to operate at different beamlines at synchrotron and free electron laser (FEL) facilities. This endstation, currently located at the Advanced Light Source (ALS), has five emission ports on the experimental chamber for mounting the high-th
The amyloid cascade hypothesis has strongly impacted the Alzheimer's disease research agenda and clinical trial designs over the past decades, but precisely how amyloid-β pathology initiates the aggregation of neocortical tau remains unclear. We cannot exclude the possibility of a shared upstream process driving both amyloid-β and tau in an independent manner instead of there being a causal relati
Objectives: To develop EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in patients with autoimmune inflammatory rheumatic diseases (AIIRD). Methods: An international Task Force (TF) (22 members/15 countries) formulated recommendations, supported by systematic literature review findings. Level of evidence and grade of recommendation were assigned for each
Understanding how hematopoietic stem and progenitor cells (HSPCs) are regulated is of central importance for the development of new therapies for blood disorders and stem cell transplantation. To date, HSPC regulation has been extensively studied in vitro and in animal models, but less is known about the mechanisms in vivo in humans. Here, in a genome-wide association study on 13,167 individuals,
Background: Multiple risk scores claim to predict the probability of postoperative pancreatic fistula (POPF) after pancreatoduodenectomy. It is unclear which scores have undergone external validation and are the most accurate. The aim of this study was to identify risk scores for POPF, and assess the clinical validity of these scores. Methods: Areas under receiving operator characteristic curve (A
Objective: The optimal duration of venoarterial extracorporeal membrane oxygenation (VA-ECMO) in patients affected by postcardiotomy cardiogenic shock (PCS) remains controversial. The present study was conducted to investigate the effect of VA-ECMO duration on hospital outcomes. Design: Retrospective analysis of an international registry. Setting: Multicenter study including 19 tertiary university
Context. With its origin coming from several sources (Big Bang, stars, cosmic rays) and given its strong depletion during its stellar lifetime, the lithium element is of great interest as its chemical evolution in the Milky Way is not well understood at present. To help constrain stellar and galactic chemical evolution models, numerous and precise lithium abundances are necessary for a large range
In cancer, the primary tumour's organ of origin and histopathology are the strongest determinants of its clinical behaviour, but in 3% of cases a patient presents with a metastatic tumour and no obvious primary. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we train a deep learning classifier to predict cancer type based on patterns of somatic passenger mu
Background: Neuropsychiatric symptoms (NPS) are prevalent in the early clinical stages of Alzheimer’s disease (AD) according to proxy-based instruments. Little is known about which NPS clinicians report and whether their judgment aligns with proxy-based instruments. We used natural language processing (NLP) to classify NPS in electronic health records (EHRs) to estimate the reporting of NPS in sym
Background: Cleft lip with cleft palate (CLP) is a congenital condition that affects both the oral cavity and the lips. This study estimated the prevalence and mortality of CLP using surveillance data collected from birth defect registries around the world. Methods: Data from 22 population- and hospital-based surveillance programs affiliated with the International Clearinghouse for Birth Defects S
BACKGROUND: Minimally invasive pancreatoduodenectomy (MIPD) has emerged as an alternative to open pancreatoduodenectomy (OPD). However, the extent of variation in the use and outcomes of MIPD in relation to OPD among countries is unclear as international studies using registry data are lacking. This study aimed to investigate the use, patient selection, and outcomes of MIPD and OPD in four transat
The relationship between the evolutionary dynamics observed in contemporary populations (microevolution) and evolution on timescales of millions of years (macroevolution) has been a topic of considerable debate. Historically, this debate centers on inconsistencies between microevolutionary processes and macroevolutionary patterns. Here, we characterize a striking exception: emerging evidence indic
The concept of pre-diabetes has led to provision of measures to reduce disease progression through identification of subjects at risk of diabetes. We previously considered the idea of pre-asthma in relation to allergic asthma and considered that, in addition to the need to improve population health via multiple measures, including reduction of exposure to allergens and pollutants and avoidance of
The dysregulated immune response and inflammation resulting in severe COVID-19 are still incompletely understood. Having recently determined that aberrant death-ligand-induced cell death can cause lethal inflammation, we hypothesized that this process might also cause or contribute to inflammatory disease and lung failure following SARS-CoV-2 infection. To test this hypothesis, we developed a nove
