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Alternative splicing and ACMG-AMP-2015-based classification of PALB2 genetic variants : An ENIGMA report

Background: PALB2 monoallelic loss-of-function germ-line variants confer a breast cancer risk comparable to the average BRCA2 pathogenic variant. Recommendations for risk reduction strategies in carriers are similar. Elaborating robust criteria to identify loss-of-function variants in PALB2 - without incurring overprediction - is thus of paramount clinical relevance. Towards this aim, we have perf

Response of submerged macrophyte communities to external and internal restoration measures in north temperate shallow lakes

Submerged macrophytes play a key role in north temperate shallow lakes by stabilizing clear-water conditions. Eutrophication has resulted in macrophyte loss and shifts to turbid conditions in many lakes. Considerable efforts have been devoted to shallow lake restoration in many countries, but long-term success depends on a stable recovery of submerged macrophytes. However, recovery patterns vary w

Enhanced Quadrupole and Octupole Strength in Doubly Magic Sn 132

The first 2+ and 3- states of the doubly magic nucleus Sn132 are populated via safe Coulomb excitation employing the recently commissioned HIE-ISOLDE accelerator at CERN in conjunction with the highly efficient MINIBALL array. The Sn132 ions are accelerated to an energy of 5.49 MeV/nucleon and impinged on a Pb206 target. Deexciting γ rays from the low-lying excited states of the target and the pro

Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer

BACKGROUND: Abiraterone acetate, a drug that blocks endogenous androgen synthesis, plus prednisone is indicated for metastatic castration-resistant prostate cancer. We evaluated the clinical benefit of abiraterone acetate plus prednisone with androgen-deprivation therapy in patients with newly diagnosed, metastatic, castration-sensitive prostate cancer.METHODS: In this double-blind, placebo-contro

Gaia Data Release 3 : Summary of the content and survey properties

Context. We present the third data release of the European Space Agency's Gaia mission, Gaia DR3. This release includes a large variety of new data products, notably a much expanded radial velocity survey and a very extensive astrophysical characterisation of Gaia sources. Aims. We outline the content and the properties of Gaia DR3, providing an overview of the main improvements in the data proces

Nuclear physics midterm plan at Legnaro National Laboratories (LNL)

The next years will see the completion of the radioactive ion beam facility SPES (Selective Production of Exotic Species) and the upgrade of the accelerators complex at Istituto Nazionale di Fisica Nucleare – Legnaro National Laboratories (LNL) opening up new possibilities in the fields of nuclear structure, nuclear dynamics, nuclear astrophysics, and applications. The nuclear physics community ha

Pharmacological inhibition of ABCC3 slows tumour progression in animal models of pancreatic cancer

BACKGROUND: Pancreatic Ductal Adenocarcinoma (PDAC) is an aggressive and lethal disease, lacking effective therapeutic approaches. Available therapies only marginally prolong patient survival and are frequently coupled with severe adverse events. It is therefore pivotal to investigate novel and safe pharmacological approaches. We have recently identified the ABC transporter, ABCC3, whose expressio

IgM anti-malondialdehyde low density lipoprotein antibody levels indicate coronary heart disease and necrotic core characteristics in the Nordic Diltiazem (NORDIL) study and the Integrated Imaging and Biomarker Study 3 (IBIS-3)

Background: Certain immunoglobulins (Ig) are proposed to have protective functions in atherosclerosis.Objectives: We tested whether serum levels of IgG and IgM autoantibodies against malondialdehyde low density lipoprotein (MDA-LDL) are associated with clinical coronary heart disease (CHD) and unfavorable plaque characteristics.Methods: NORDIL was a prospective study investigating adverse cardiova

P2Y12 receptor inhibitors in patients with non-STelevation acute coronary syndrome in the real world : Use, patient selection, and outcomes from contemporary European registries

Aims Non-ST-elevation acute coronary syndrome (NSTE-ACS) is present in about 60-70% of patients admitted with acute coronary syndromes in clinical practice. This study provides a 'real-life' overview of NSTE-ACS patient characteristics, dual antiplatelet therapy clinical practice, and outcomes at both the time of discharge from hospital and up to 1-year post-discharge. Methods and results A total

Function, evolution, and structure of J-domain proteins

Hsp70 chaperone systems are very versatile machines present in nearly all living organisms and in nearly all intracellular compartments. They function in many fundamental processes through their facilitation of protein (re)folding, trafficking, remodeling, disaggregation, and degradation. Hsp70 machines are regulated by co-chaperones. J-domain containing proteins (JDPs) are the largest family of H

The GALAH survey : Chemical tagging of star clusters and new members in the Pleiades

The technique of chemical tagging uses the elemental abundances of stellar atmospheres to 'reconstruct' chemically homogeneous star clusters that have long since dispersed. The GALAH spectroscopic survey - which aims to observe one million stars using the Anglo- Australian Telescope - allows us to measure up to 30 elements or dimensions in the stellar chemical abundance space, many of which are no

Tumor PIK3CA genotype and prognosis in early-stage breast cancer : A pooled analysis of individual patient data

Purpose Phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations are frequently observed in primary breast cancer. We evaluated their prognostic relevance by performing a pooled analysis of individual patient data. Patients and Methods Associations between PIK3CA status and clinicopathologic characteristics were tested by applying Cox regression models adjusted fo

Barriers and facilitators associated with long-term follow-up care for childhood, adolescent, and young adult cancer survivors : a systematic review

Background: Optimal long-term follow-up (LTFU) care for survivors of childhood, adolescent and young adult (CAYA) cancer can improve or maintain their quality of life by prevention and early treatment of late effects. However, optimal LTFU care is not provided to all CAYA cancer survivors. This systematic review sought to identify associated barriers, facilitators and other factors of LTFU care fo

Impact of immunochemotherapy regimens on outcomes of patients with primary mediastinal B-cell lymphoma in the IELSG37 trial

The IELSG37 trial enrolled 545 patients with primary mediastinal B-cell lymphoma (PMBCL) and demonstrated that consolidation radiotherapy (RT) can be omitted in patients with complete metabolic response, defined by the Lugano classification as Deauville score (DS) 1 to 3. This report evaluates outcomes after different frontline rituximab- and doxorubicin-based immunochemotherapy regimens chosen ac

Treatment Trajectories in Metastatic Hormone-sensitive Prostate Cancer : A PIONEER+ Big Data Analysis

BACKGROUND AND OBJECTIVE: The treatment landscape for metastatic hormone-sensitive prostate cancer (mHSPC) is evolving rapidly. Real-world data (RWD) are essential to understand actual treatment use and outcomes. This study aimed to describe treatment trajectories and clinical outcomes in a large, multicenter RWD cohort under the PIONEER project. METHODS: Eight European and US databases (2016-2020

Sex dependence of postoperative pulmonary complications - A post hoc unmatched and matched analysis of LAS VEGAS

STUDY OBJECTIVE: Male sex has inconsistently been associated with the development of postoperative pulmonary complications (PPCs). These studies were different in size, design, population and preoperative risk. We reanalysed the database of 'Local ASsessment of Ventilatory management during General Anaesthesia for Surgery study' (LAS VEGAS) to evaluate differences between females and males with re

The long and short of it : Distinct natural crystal packing strategies of Cry toxins from Bacillus thuringiensis

Bacillus thuringiensis (Bt) strains naturally produce pesticidal proteins as nanocrystalline inclusions that are extraordinarily stable in aqueous environments, but which dissolve selectively at specific pH conditions. These proteins have been used in agriculture for >50 years and are critical to global food security. The majority of previously determined Bt Cry protein structures lack the extende

Plasma p-tau217 and tau-PET predict future cognitive decline among cognitively unimpaired individuals : implications for clinical trials

Plasma p-tau217 and tau positron emission tomography (PET) are strong prognostic biomarkers in Alzheimer’s disease (AD), but their relative performance in predicting future cognitive decline among cognitively unimpaired (CU) individuals is unclear. In a head-to-head comparison study including nine cohorts and 1,474 individuals, we show that plasma p-tau217 and medial temporal lobe tau-PET signal d

Progenitor exhausted PD-1+ T cells are cellular targets of immune checkpoint inhibition in atherosclerosis

Immune checkpoint inhibitors (ICIs), targeting checkpoint receptors such as programmed cell death protein 1 (PD-1), are associated with increased risk of cardiovascular events, but the underlying mechanisms remain poorly understood. Here we show that PD-1 + T cells from murine atherosclerotic aortas mainly display a progenitor exhausted phenotype (PD-1 intSlamf6 +Tim3 -), produce IFNγ in vivo, exh