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RET inhibition overcomes resistance to combined CDK4/6 inhibitor and endocrine therapy in ER+ breast cancer

Background: Combined CDK4/6 inhibitor (CDK4/6i) and endocrine therapy significantly improve the outcome of patients with advanced estrogen receptor-positive (ER+) breast cancer. However, resistance to this treatment and disease progression remains a major clinical challenge. High expression of the receptor tyrosine kinase REarranged during Transfection (RET) has been associated with resistance to

Copy number signatures in cervical samples enable early detection of high-grade serous ovarian carcinoma

BackgroundThe lack of effective screening methods for the detection of ovarian cancer leads to late diagnosis and poor outcomes. High-grade serous ovarian carcinoma (HGSC) is strongly dominated by copy number alterations (CNAs), resulting from underlying mutational processes. Several studies have reported the detection of ovarian carcinoma-derived somatic mutations in cervical samples, uterine lav

Association between early airway intervention in the pre-hospital setting and outcomes in out of hospital cardiac arrest patients : A post-hoc analysis of the Target Temperature Management-2 (TTM2) trial

Introduction: Airway management is a critical component of out-of-hospital cardiac arrest (OHCA) resuscitation. The primary aim of this study was to describe pre-hospital airway management in adult patients post-OHCA. Secondary aims were to investigate whether tracheal intubation (TI) versus use of supraglottic airway device (SGA) was associated with patients’ outcomes, including ventilator-free d

Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death : meta-analysis of individual patient data for 10,801 women in 17 randomised trials

BACKGROUND: After breast-conserving surgery, radiotherapy reduces recurrence and breast cancer death, but it may do so more for some groups of women than for others. We describe the absolute magnitude of these reductions according to various prognostic and other patient characteristics, and relate the absolute reduction in 15-year risk of breast cancer death to the absolute reduction in 10-year re

The EBLM project - IX. Five fully convective M-dwarfs, precisely measured with CHEOPS and TESS light curves

Eclipsing binaries are important benchmark objects to test and calibrate stellar structure and evolution models. This is especially true for binaries with a fully convective M-dwarf component for which direct measurements of these stars' masses and radii are difficult using other techniques. Within the potential of M-dwarfs to be exoplanet host stars, the accuracy of theoretical predictions of the

Identification of FasL as a crucial host factor driving COVID-19 pathology and lethality

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

Fracture behavior of a composite of bone and calcium sulfate/hydroxyapatite

Calcium sulfate/hydroxyapatite (CaS/HA) biomaterials have been investigated for use in several orthopedic applications. However, the mechanical interactions between the composite of CaS/HA and bone at the microscale are still unknown. The aim of this study was to determine if and how augmentation with CaS/HA alters the fracture behavior of bone. Eleven cylinders of trabecular bone were drilled fro

Effect of High-Risk Obstructive Sleep Apnea on Clinical Outcomes in Adults with Coronavirus Disease 2019

Rationale: Coronavirus disease (COVID-19) is an ongoing pandemic, in which obesity, hypertension, and diabetes have been linked to poor outcomes. Obstructive sleep apnea (OSA) is associated with these conditions and may influence the prognosis of adults with COVID-19. Objectives: To determine the effect of OSA on clinical outcomes in patients with COVID-19. Methods: The current prospective observa

The VMC survey - XLVIII. Classical cepheids unveil the 3D geometry of the LMC

We employed the VISTA near-infrared YJKssurvey of the Magellanic System (VMC) to analyse the Y, J, and Ks light curves of δCepheid stars (DCEPs) in the Large Magellanic Cloud (LMC). Our sample consists of 4408 objects accounting for 97 per cent of the combined list of OGLE IV and Gaia DR2 DCEPs. We determined a variety of period-luminosity (PL) and period-Wesenheit PW relationships for Fundamental

Protein domain-dependent vesiculation of Lipoprotein A, a protein that is important in cell wall synthesis and fitness of the human respiratory pathogen Haemophilus influenzae

The human pathogen Haemophilus influenzae causes respiratory tract infections and is commonly associated with prolonged carriage in patients with chronic obstructive pulmonary disease. Production of outer membrane vesicles (OMVs) is a ubiquitous phenomenon observed in Gram-negative bacteria including H. influenzae. OMVs play an important role in various interactions with the human host; from neutr

Cryo-EM reveals the conformational epitope of human monoclonal antibody PAM1.4 broadly reacting with polymorphic malarial protein VAR2CSA

Malaria during pregnancy is a major global health problem caused by infection with Plasmodium falciparum parasites. Severe effects arise from the accumulation of infected erythrocytes in the placenta. Here, erythrocytes infected by late blood-stage parasites adhere to placental chondroitin sulphate A (CS) via VAR2CSA-type P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion proteins. Imm

One-year recovery from breast cancer : Importance of tumor and treatment-related factors, resilience, and sociodemographic factors for health-related quality of life

Aim: This study investigated the changes in health-related quality of life from diagnosis to 1 year after diagnosis in breast cancer (BC) patients and the influence of clinical, psychological, and sociodemographic variables. An additional aim was to explore the mediating and moderating effects of resilience on changes in health-related quality of life. Methods: A longitudinal population-based stud

European task force on atopic dermatitis position paper : treatment of parental atopic dermatitis during preconception, pregnancy and lactation period

Atopic dermatitis (AD) is a common inflammatory skin disease that affects both children and adults, including a large number of adults of reproductive age. Several guidelines for the treatment of AD exist, yet specific recommendations for the treatment of pregnant or lactating women and for adults planning to have a child are often lacking. This position paper from the European Task force on Atopi

Human pancreatic islet three-dimensional chromatin architecture provides insights into the genetics of type 2 diabetes

Genetic studies promise to provide insight into the molecular mechanisms underlying type 2 diabetes (T2D). Variants associated with T2D are often located in tissue-specific enhancer clusters or super-enhancers. So far, such domains have been defined through clustering of enhancers in linear genome maps rather than in three-dimensional (3D) space. Furthermore, their target genes are often unknown.

Alpha1-microglobulin and bikunin in rats with collagen II-induced arthritis : plasma levels and liver mRNA content

The plasma proteins alpha1-microglobulin (alpha1-m) and bikunin are synthesized in the liver as a common precursor which is cleaved just before secretion. Half of plasma alpha1-m is covalently linked to fibronectin and alpha1-inhibitor-3, and more than 95% of bikunin is part of pre-alpha-inhibitor, inter-alpha-inhibitor and related large molecules. Both alpha1-m and bikunin have been shown to be i

Migration strategies of raptors – spatio-temporal adaptations and constraints in travelling and foraging

Popular Abstract in Swedish Min avhandling handlar om flyttning, det vill säga hur levande organismer rör sig mellan olika områden för att utnyttja resurser, undvika födobrist och som en anpassning till klimat- och miljöfaktorer. Vi begränsar det hela till fåglar's flyttning och bland dem ska vi koncentrera os's på rovfåglar. Rovfåglar är beroende av sina bytesdjur, som till exempel kan vara andraMy dissertation is about bird migration and addresses questions about how raptors adapt to the fluctuating environments during the transition seasons between breeding and wintering. The migration is highly affected by local prey abundance, foraging strategies, weather conditions and landscape patterns along the migration routes as well as navigation and orientation mechanisms and cues. Interesting

The crystal structure of human adenylate kinase 6 : An adenylate kinase localized to the cell nucleus

Adenylate kinases (AKs) play important roles in nucleotide metabolism in all organisms and in cellular energetics by means of phosphotransfer networks in eukaryotes. The crystal structure of a human AK named AK6 was determined by in-house sulfur single-wavelength anomalous dispersion phasing methods and refined to 2.0-A resolution with a free R factor of 21.8%. Sequence analyses revealed that huma

The Dynamic Collections : a 3D Web Platform of Archaeological Artefacts designed for Data Reuse and Deep Interaction

The Dynamic Collections project is an ongoing initiative pursued by the Visual Computing Lab ISTI-CNR in Italy and the Lund University Digital Archaeology Laboratory-DARKLab, Sweden. The aim of this project is to explore the possibilities offered by a deep, structured interaction with a large set of digital replicas of archeological artefacts. The project developed and deployed a web-based platfor

Spatial Transcriptional Mapping Reveals Site-Specific Pathways Underlying Human Atherosclerotic Plaque Rupture

Background: Atherosclerotic plaque ruptures, triggered by blood flow–associated biomechanical forces, cause most myocardial infarctions and strokes. Objectives: This study aims to investigate the exact location and underlying mechanisms of atherosclerotic plaque ruptures, identifying therapeutic targets against cardiovascular events. Methods: Histology, electron microscopy, bulk and spatial RNA se