PDX models for functional precision oncology and discovery science.

Precision oncology relies on detailed molecular analysis of how diverse tumours respond to various therapies, with the aim to optimize treatment outcomes for individual patients. Patient-derived xenograft (PDX) models have been key to preclinical validation of precision oncology approaches, enabling the analysis of each tumour's unique genomic landscape and testing therapies that are predicted to be effective based on specific mutations, gene expression patterns or signalling abnormalities. To extend these standard precision oncology approaches, the field has strived to complement the otherwise static and often descriptive measurements with functional assays, termed functional precision oncology (FPO).

CT Imaging Assessment of Response to Treatment in Allergic Bronchopulmonary Aspergillosis in Adults With Bronchial Asthma.

Background: One of the major challenges in managing allergic bronchopulmonary aspergillosis remains consistent and reproducible assessment of response to treatment.

Research Question: What are the most relevant changes in CT scan parameters over time for assessing response to treatment?

Study Design And Methods: In this ancillary study of a randomized clinical trial (NebuLamB), patients with asthma with available CT scan and without exacerbation during a 4-month allergic bronchopulmonary aspergillosis exacerbation treatment period (corticosteroids and itraconazole) were included. Changed CT scan parameters were assessed by systematic analyses of CT scan findings at initiation and end of treatment.

Effects of Simulation Fidelity on Health Care Providers on Team Training-A Systematic Review.

This systematic review, following PRISMA standards, aimed to assess the effectiveness of higher versus lower fidelity simulation on health care providers engaged in team training. A comprehensive search from January 1, 2011 to January 24, 2023 identified 1390 studies of which 14 randomized (n = 1530) and 5 case controlled (n = 257) studies met the inclusion criteria. The certainty of evidence was very low due to a high risk of bias and inconsistency.

Unsupervised machine learning improves risk stratification in newly diagnosed multiple myeloma: an analysis of the Spanish Myeloma Group.

The International Staging System (ISS) and the Revised International Staging System (R-ISS) are commonly used prognostic scores in multiple myeloma (MM). These methods have significant gaps, particularly among intermediate-risk groups. The aim of this study was to improve risk stratification in newly diagnosed MM patients using data from three different trials developed by the Spanish Myeloma Group.

IL-26 inhibits hepatitis C virus replication in hepatocytes.

Background & Aims: Interleukin-26 (IL-26) is a proinflammatory cytokine that has properties atypical for a cytokine, such as direct antibacterial activity and DNA-binding capacity. We previously observed an accumulation of IL-26 in fibrotic and inflammatory lesions in the livers of patients with chronic HCV infection and showed that infiltrating CD3 lymphocytes were the principal source of IL-26. Surprisingly, IL-26 was also detected in the cytoplasm of hepatocytes from HCV-infected patients, even though these cells do not produce IL-26, even when infected with HCV.

Nebulised liposomal amphotericin-B as maintenance therapy in allergic bronchopulmonary aspergillosis: a randomised, multicentre trial.

Background: In allergic bronchopulmonary aspergillosis (ABPA), prolonged nebulised antifungal treatment may be a strategy for maintaining remission.

Methods: We performed a randomised, single-blind, clinical trial in 30 centres. Patients with controlled ABPA after 4-month attack treatment (corticosteroids and itraconazole) were randomly assigned to nebulised liposomal amphotericin-B or placebo for 6 months.

Genomic relatedness of a canine Lactococcus garvieae to human, animal and environmental isolates.

Lactococcus (L.) garvieae is a zoonotic fish pathogen that can also cause bacteraemia and endocarditis in humans and has been isolated from healthy or diseased domestic animals. Nevertheless L.

Multiple myeloma and SARS-CoV-2 infection: clinical characteristics and prognostic factors of inpatient mortality.

There is limited information on the characteristics, prognostic factors, and outcomes of patients with multiple myeloma (MM) hospitalized with COVID-19. This retrospective case series investigated 167 patients reported from 73 hospitals within the Spanish Myeloma Collaborative Group network in March and April, 2020. Outcomes were compared with 167 randomly selected, contemporary, age-/sex-matched noncancer patients with COVID-19 admitted at six participating hospitals.

Associating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET.

The HIV-1 envelope glycoprotein (Env) trimer mediates cell entry and is conformationally dynamic. Imaging by single-molecule fluorescence resonance energy transfer (smFRET) has revealed that, on the surface of intact virions, mature pre-fusion Env transitions from a pre-triggered conformation (state 1) through a default intermediate conformation (state 2) to a conformation in which it is bound to three CD4 receptor molecules (state 3). It is currently unclear how these states relate to known structures.

Compact radio emission indicates a structured jet was produced by a binary neutron star merger.

The binary neutron star merger event GW170817 was detected through both electromagnetic radiation and gravitational waves. Its afterglow emission may have been produced by either a narrow relativistic jet or an isotropic outflow. High-spatial-resolution measurements of the source size and displacement can discriminate between these scenarios.

Five-Year Clinical Outcome and Valve Durability After Transcatheter Aortic Valve Replacement in High-Risk Patients.

Background: The FRANCE-2 registry (French Aortic National Corevalve and Edwards) previously reported good early- and medium-term clinical and echocardiographic efficacy for transcatheter aortic valve replacement. We here report 5-year follow-up results from the registry.

Methods: The registry includes all consecutive patients undergoing transcatheter aortic valve replacement for severe aortic stenosis in France.

Transcarotid Compared With Other Alternative Access Routes for Transcatheter Aortic Valve Replacement.

Background The optimal access for patients undergoing transcatheter aortic valve replacement (TAVR) who are not candidates for a transfemoral approach has not been elucidated. The purpose of this study was to compare the safety, feasibility, and early clinical outcomes of transcarotid TAVR compared with thoracic approaches. Methods and Results From a multicenter consecutive cohort of 329 alternative-access TAVR patients (2012-2017), we identified 101 patients who underwent transcarotid TAVR and 228 patients who underwent a transapical or transaortic TAVR.

Randomized clinical trial of ultrasonic scissors versus conventional haemostasis to compare complications and economics after total thyroidectomy (FOThyr).

Background: The benefits of single-use ultrasonic scissors in thyroid surgery are still debated. Although this device has been shown to reduce operating time compared with conventional haemostasis, its cost-effectiveness has never been demonstrated. The aim of this study was to evaluate the efficacy, cost-effectiveness and safety of ultrasonic scissors for total thyroidectomy.

Radiosensitivity and transgenerational effects in non-human species.

The ALLIANCE working group on effects of ionising radiation on wildlife brings together European researchers to work on the topics of radiosensitivity and transgenerational effects in non-human biota. Differences in radiation sensitivity across species and phyla are poorly understood, but have important implications for understanding the overall effects of radiation and for radiation protection; for example, sensitive species may require special attention in monitoring and radiation protection, and differences in sensitivity between species also lead to overall effects at higher levels (community, ecosystem), since interactions between species can be altered. Hence, understanding the mechanisms of interspecies radiation sensitivity differences may help to clarify mechanisms underpinning intraspecies variation.

Measurement of the -boson mass in pp collisions at with the ATLAS detector.

A measurement of the mass of the boson is presented based on proton-proton collision data recorded in 2011 at a centre-of-mass energy of 7 TeV with the ATLAS detector at the LHC, and corresponding to of integrated luminosity. The selected data sample consists of candidates in the channel and candidates in the channel. The -boson mass is obtained from template fits to the reconstructed distributions of the charged lepton transverse momentum and of the boson transverse mass in the electron and muon decay channels, yielding where the first uncertainty is statistical, the second corresponds to the experimental systematic uncertainty, and the third to the physics-modelling systematic uncertainty.

Topological cell clustering in the ATLAS calorimeters and its performance in LHC Run 1.

The reconstruction of the signal from hadrons and jets emerging from the proton-proton collisions at the Large Hadron Collider (LHC) and entering the ATLAS calorimeters is based on a three-dimensional topological clustering of individual calorimeter cell signals. The cluster formation follows cell signal-significance patterns generated by electromagnetic and hadronic showers. In this, the clustering algorithm implicitly performs a topological noise suppression by removing cells with insignificant signals which are not in close proximity to cells with significant signals.

Reconstruction of primary vertices at the ATLAS experiment in Run 1 proton-proton collisions at the LHC.

This paper presents the method and performance of primary vertex reconstruction in proton-proton collision data recorded by the ATLAS experiment during Run 1 of the LHC. The studies presented focus on data taken during 2012 at a centre-of-mass energy of [Formula: see text] TeV. The performance has been measured as a function of the number of interactions per bunch crossing over a wide range, from one to seventy.

Search for lepton-flavour-violating decays of the Higgs and bosons with the ATLAS detector.

Direct searches for lepton flavour violation in decays of the Higgs and bosons with the ATLAS detector at the LHC are presented. The following three decays are considered: [Formula: see text], [Formula: see text], and [Formula: see text]. The searches are based on the data sample of proton-proton collisions collected by the ATLAS detector corresponding to an integrated luminosity of 20.

RNA-binding protein HuR enhances mineralocorticoid signaling in renal KC3AC1 cells under hypotonicity.

Mineralocorticoid receptor (MR) mediates the sodium-retaining action of aldosterone in the distal nephron. Herein, we decipher mechanisms by which hypotonicity increases MR expression in renal principal cells. We identify HuR (human antigen R), an mRNA-stabilizing protein, as an important posttranscriptional regulator of MR expression.

Contrast-enhanced MR microscopy of amyloid plaques in five mouse models of amyloidosis and in human Alzheimer's disease brains.

Gadolinium (Gd)-stained MRI is based on Gd contrast agent (CA) administration into the brain parenchyma. The strong signal increase induced by Gd CA can be converted into resolution enhancement to record microscopic MR images. Moreover, inhomogeneous distribution of the Gd CA in the brain improves the contrast between different tissues and provides new contrasts in MR images.

HuR-Dependent Editing of a New Mineralocorticoid Receptor Splice Variant Reveals an Osmoregulatory Loop for Sodium Homeostasis.

Aldosterone and the Mineralocorticoid Receptor (MR) control hydroelectrolytic homeostasis and alterations of mineralocorticoid signaling pathway are involved in the pathogenesis of numerous human diseases, justifying the need to decipher molecular events controlling MR expression level. Here, we show in renal cells that the RNA-Binding Protein, Human antigen R (HuR), plays a central role in the editing of MR transcript as revealed by a RNA interference strategy. We identify a novel Δ6 MR splice variant, which lacks the entire exon 6, following a HuR-dependent exon skipping event.

Measurements of top-quark pair differential cross-sections in the [Formula: see text] channel in collisions at [Formula: see text] TeV using the ATLAS detector.

This article presents measurements of [Formula: see text] differential cross-sections in a fiducial phase-space region, using an integrated luminosity of 3.2 fb[Formula: see text] of proton-proton data at a centre-of-mass energy of [Formula: see text] TeV recorded by the ATLAS experiment at the LHC in 2015. Differential cross-sections are measured as a function of the transverse momentum and absolute rapidity of the top quark, and of the transverse momentum, absolute rapidity and invariant mass of the [Formula: see text] system.

Performance of algorithms that reconstruct missing transverse momentum in [Formula: see text]= 8 TeV proton-proton collisions in the ATLAS detector.

The reconstruction and calibration algorithms used to calculate missing transverse momentum ([Formula: see text] ) with the ATLAS detector exploit energy deposits in the calorimeter and tracks reconstructed in the inner detector as well as the muon spectrometer. Various strategies are used to suppress effects arising from additional proton-proton interactions, called pileup, concurrent with the hard-scatter processes. Tracking information is used to distinguish contributions from the pileup interactions using their vertex separation along the beam axis.

IL-26 Confers Proinflammatory Properties to Extracellular DNA.

In physiological conditions, self-DNA released by dying cells is not detected by intracellular DNA sensors. In chronic inflammatory disorders, unabated inflammation has been associated with a break in innate immune tolerance to self-DNA. However, extracellular DNA has to complex with DNA-binding molecules to gain access to intracellular DNA sensors.

Search for triboson [Formula: see text] production in collisions at [Formula: see text] [Formula: see text] with the ATLAS detector.

This paper reports a search for triboson [Formula: see text] production in two decay channels ([Formula: see text] and [Formula: see text] with [Formula: see text]) in proton-proton collision data corresponding to an integrated luminosity of 20.3 [Formula: see text] at a centre-of-mass energy of 8 [Formula: see text] with the ATLAS detector at the Large Hadron Collider. Events with exactly three charged leptons, or two leptons with the same electric charge in association with two jets, are selected.