IL-2 family cytokines IL-9 and IL-21 differentially regulate innate and adaptive type 2 immunity in asthma.

Background: Asthma is often accompanied by type 2 immunity rich in IL-4, IL-5, and IL-13 cytokines produced by T2 lymphocytes or type 2 innate lymphoid cells (ILC2s). IL-2 family cytokines play a key role in the differentiation, homeostasis, and effector function of innate and adaptive lymphocytes.

Objective: IL-9 and IL-21 boost activation and proliferation of T2 and ILC2s, but the relative importance and potential synergism between these γ common chain cytokines are currently unknown.

Physicochemical properties of abnormal blood acid-base buffering.

This paper describes two new features ) development of physicochemically based, two-compartment models describing acid-base-state changes in normal and abnormal blood and ) use of model results to view and describe physicochemical properties of blood, in terms of Pco as the causative independent variable and effected [H] changes as the dependent variable. Models were derived from an in vitro experimental study, where normal blood was made both hypoproteinemic and hyperalbuminemic and then equilibrated with CO. Strong-ion gap (SIG) values were selected to match model and experimental pH.

Structural and Biofunctional Insights into the Cyclo(Pro-Pro-Phe-Phe-) Scaffold from Experimental and In Silico Studies: Melanoma and Beyond.

Short peptides have great potential as safe and effective anticancer drug leads. Herein, the influence of short cyclic peptides containing the Pro-Pro-Phe-Phe sequence on patient-derived melanoma cells was investigated. Cyclic peptides such as cyclo(Leu-Ile-Ile-Leu-Val-Pro-Pro-Phe-Phe-), called CLA, and cyclo(Pro-homoPro-βhomoPhe-Phe-), called P11, exert the cytotoxic and the cytostatic effects in melanoma cells, respectively.

Observation of the non-linear Meissner effect.

A long-standing theoretical prediction is that in clean, nodal unconventional superconductors the magnetic penetration depth λ, at zero temperature, varies linearly with magnetic field. This non-linear Meissner effect is an equally important manifestation of the nodal state as the well studied linear-in-T dependence of λ, but has never been convincingly experimentally observed. Here we present measurements of the nodal superconductors CeCoIn and LaFePO which clearly show this non-linear Meissner effect.

Sotorasib for Lung Cancers with p.G12C Mutation.

Background: Sotorasib showed anticancer activity in patients with p.G12C-mutated advanced solid tumors in a phase 1 study, and particularly promising anticancer activity was observed in a subgroup of patients with non-small-cell lung cancer (NSCLC).

Methods: In a single-group, phase 2 trial, we investigated the activity of sotorasib, administered orally at a dose of 960 mg once daily, in patients with p.

Deciphering the Transcriptomic Heterogeneity of Duodenal Coeliac Disease Biopsies.

Coeliac disease (CD) is a clinically heterogeneous autoimmune disease with variable presentation and progression triggered by gluten intake. Molecular or genetic factors contribute to disease heterogeneity, but the reasons for different outcomes are poorly understood. Transcriptome studies of tissue biopsies from CD patients are scarce.

Efficacy of Selpercatinib in Fusion-Positive Non-Small-Cell Lung Cancer.

Background: fusions are oncogenic drivers in 1 to 2% of non-small-cell lung cancers (NSCLCs). In patients with fusion-positive NSCLC, the efficacy and safety of selective RET inhibition are unknown.

Methods: We enrolled patients with advanced fusion-positive NSCLC who had previously received platinum-based chemotherapy and those who were previously untreated separately in a phase 1-2 trial of selpercatinib.

Pathogenic Autoimmunity in Atherosclerosis Evolves From Initially Protective Apolipoprotein B-Reactive CD4 T-Regulatory Cells.

Background: Throughout the inflammatory response that accompanies atherosclerosis, autoreactive CD4 T-helper cells accumulate in the atherosclerotic plaque. Apolipoprotein B (apoB), the core protein of low-density lipoprotein, is an autoantigen that drives the generation of pathogenic T-helper type 1 (T1) cells with proinflammatory cytokine secretion. Clinical data suggest the existence of apoB-specific CD4 T cells with an atheroprotective, regulatory T cell (T) phenotype in healthy individuals.

Injuries associated with electronic nicotine delivery systems: A systematic review.

Background: Since its introduction on the market in 2007, the number of reports on injuries caused by the overheating, ignition, or explosion of electronic nicotine delivery systems (ENDSs) has increased significantly. These injuries appear to have different causes, the most important one being lithium-ion battery overheating to the point of ignition or explosion.

Methods: A literature search for all relevant studies concerning ENDS-related traumatic injuries of all kinds was conducted, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses protocol.

TGFβ (Transforming Growth Factor-Beta)-Activated Kinase 1 Regulates Arteriovenous Fistula Maturation.

Objective: Arteriovenous fistulae (AVF) are the optimal conduit for hemodialysis access but have high rates of primary maturation failure. Successful AVF maturation requires wall thickening with deposition of ECM (extracellular matrix) including collagen and fibronectin, as well as lumen dilation. TAK1 (TGFβ [transforming growth factor-beta]-activated kinase 1) is a mediator of noncanonical TGFβ signaling and plays crucial roles in regulation of ECM production and deposition; therefore, we hypothesized that TAK1 regulates wall thickening and lumen dilation during AVF maturation.

Synthesis, experimental and in silico studies of N-fluorenylmethoxycarbonyl-O-tert-butyl-N-methyltyrosine, coupled with CSD data: a survey of interactions in the crystal structures of Fmoc-amino acids.

Recently, fluorenylmethoxycarbonyl (Fmoc) amino acids (e.g. Fmoc-tyrosine or Fmoc-phenylalanine) have attracted growing interest in biomedical research and industry, with special emphasis directed towards the design and development of novel effective hydrogelators, biomaterials or therapeutics.

Initial pupil status is a strong predictor for in-hospital mortality after aneurysmal subarachnoid hemorrhage.

Prognosis of patients with high-grade aneurysmal subarachnoid hemorrhage (aSAH) is only insufficiently displayed by current standard prognostic scores. This study aims to evaluate the role of pupil status for mortality prediction and provide improved prognostic models. Anonymized data of 477 aSAH patients admitted to our medical center from November 2010 to August 2018 were retrospectively analyzed.

Diagnostic value of plasma phosphorylated tau181 in Alzheimer's disease and frontotemporal lobar degeneration.

With the potential development of new disease-modifying Alzheimer's disease (AD) therapies, simple, widely available screening tests are needed to identify which individuals, who are experiencing symptoms of cognitive or behavioral decline, should be further evaluated for initiation of treatment. A blood-based test for AD would be a less invasive and less expensive screening tool than the currently approved cerebrospinal fluid or amyloid β positron emission tomography (PET) diagnostic tests. We examined whether plasma tau phosphorylated at residue 181 (pTau181) could differentiate between clinically diagnosed or autopsy-confirmed AD and frontotemporal lobar degeneration.

Randomised clinical trial of ferric citrate hydrate on anaemia management in haemodialysis patients with hyperphosphataemia: ASTRIO study.

Ferric citrate hydrate (FC) is an iron-based phosphate binder approved for hyperphosphataemia in patients with chronic kidney disease. We conducted a randomised controlled trial to evaluate the effects of FC on anaemia management in haemodialysis patients with hyperphosphataemia. We 1:1 randomised 93 patients who were undergoing haemodialysis and being treated with non-iron-based phosphate binders and erythropoiesis-stimulating agents (ESA) to receive 24 weeks of FC or to continue their non-iron-based phosphate binders (control) in a multicentre, open-label, parallel-design.

Machine learning-powered antibiotics phenotypic drug discovery.

Identification of novel antibiotics remains a major challenge for drug discovery. The present study explores use of phenotypic readouts beyond classical antibacterial growth inhibition adopting a combined multiparametric high content screening and genomic approach. Deployment of the semi-automated bacterial phenotypic fingerprint (BPF) profiling platform in conjunction with a machine learning-powered dataset analysis, effectively allowed us to narrow down, compare and predict compound mode of action (MoA).

Distribution of cerebral microbleeds in the East and West: Individual participant meta-analysis.

Objective: We investigated differences in the anatomical distribution of cerebral microbleeds (CMBs) on MRI, hypothesized to indicate the type of underlying cerebral small vessel disease (SVD), between Eastern and Western general populations.

Methods: We analyzed data from 11 studies identified by a PubMed search between 1996 and April 2014 according to the Preferred Reporting Items for a Systematic Review and Meta-analysis of Individual Participant Data. Study quality measures indicated low or medium risk of bias.

Observation of Weakened V-V Dimers in the Monoclinic Metallic Phase of Strained VO_{2}.

Emergent order at mesoscopic length scales in condensed matter can provide fundamental insight into the underlying competing interactions and their relationship with the order parameter. Using spectromicroscopy, we show that mesoscopic stripe order near the metal-insulator transition (MIT) of strained VO_{2} represents periodic modulations in both crystal symmetry and V-V dimerization. Above the MIT, we unexpectedly find the long-range order of V-V dimer strength and crystal symmetry become dissociated beyond ≈200  nm, whereas the conductivity transition proceeds homogeneously in a narrow temperature range.

Transforming Growth Factor-β1 Inhibits Pseudoaneurysm Formation After Aortic Patch Angioplasty.

Objective: Pseudoaneurysms remain a significant complication after vascular procedures. We hypothesized that TGF-β (transforming growth factor-β) signaling plays a mechanistic role in the development of pseudoaneurysms.

Approach And Results: Rat aortic pericardial patch angioplasty was associated with a high incidence (88%) of pseudoaneurysms at 30 days, with increased smad2 phosphorylation in small pseudoaneurysms but not in large pseudoaneurysms; TGF-β1 receptors were increased in small pseudoaneurysms and preserved in large pseudoaneurysms.

The "mortality ascent": Hourly risk of death for hemodynamically unstable trauma patients at Level II versus Level I trauma centers.

Background: Severely injured trauma patients have higher in-hospital mortality at Level II versus Level I trauma centers (TCs). To better understand these differences, we sought to determine if there were any periods during which hemodynamically unstable trauma patients are at higher risk of death at Level II versus Level I TCs within the first 24 hours postadmission.

Study Design: Trauma patients aged 18 years to 64 years, with Injury Severity Score of 15 or greater, systolic blood pressure less than 90 mm Hg at admission, and treated at Level II or Level I TCs, were identified using the 2007 to 2012 National Trauma Data Bank.

Neural Stem Cell Therapy and Rehabilitation in the Central Nervous System: Emerging Partnerships.

The goal of regenerative medicine is to restore function through therapy at levels such as the gene, cell, tissue, or organ. For many disorders, however, regenerative medicine approaches in isolation may not be optimally effective. Rehabilitation is a promising adjunct therapy given the beneficial impact that physical activity and other training modalities can offer.

White Matter Lesion Progression: Genome-Wide Search for Genetic Influences.

Background And Purpose: White matter lesion (WML) progression on magnetic resonance imaging is related to cognitive decline and stroke, but its determinants besides baseline WML burden are largely unknown. Here, we estimated heritability of WML progression, and sought common genetic variants associated with WML progression in elderly participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium.

Methods: Heritability of WML progression was calculated in the Framingham Heart Study.

Assessment of a candidate marker constituent predictive of a dietary substance-drug interaction: case study with grapefruit juice and CYP3A4 drug substrates.

Dietary substances, including herbal products and citrus juices, can perpetrate interactions with conventional medications. Regulatory guidances for dietary substance-drug interaction assessment are lacking. This deficiency is due in part to challenges unique to dietary substances, a lack of requisite human-derived data, and limited jurisdiction.