Pembrolizumab and chemotherapy in high-risk, early-stage, ER/HER2 breast cancer: a randomized phase 3 trial.

Addition of pembrolizumab to neoadjuvant chemotherapy followed by adjuvant pembrolizumab improved outcomes in patients with high-risk, early-stage, triple-negative breast cancer. However, whether the addition of neoadjuvant pembrolizumab to chemotherapy would improve outcomes in high-risk, early-stage, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER/HER2) breast cancer remains unclear. We conducted a double-blind, placebo-controlled phase 3 study (KEYNOTE-756) in which patients with previously untreated ER/HER2 grade 3 high-risk invasive breast cancer (T1c-2 (≥2 cm), cN1-2 or T3-4, cN0-2) were randomly assigned (1:1) to neoadjuvant pembrolizumab 200 mg or placebo Q3W given with paclitaxel QW for 12 weeks, followed by four cycles of doxorubicin or epirubicin plus cyclophosphamide Q2W or Q3W.

Parallel-transmission spatial spectral pulse design with local specific absorption rate control: Demonstration for robust uniform water-selective excitation in the human brain at 7 T.

Purpose: To propose a novel method for parallel-transmission (pTx) spatial-spectral pulse design and demonstrate its utility for robust uniform water-selective excitation (water excitation) across the entire brain.

Theory And Methods: Our design problem is formulated as a magnitude-least-squares minimization with joint RF and k-space optimization under explicit specific-absorption-rate constraints. For improved robustness against off-resonance effects, the spectral component of the excitation target is prescribed to have a water passband and a fat stopband.

Orphan GPCR GPRC5C Facilitates Angiotensin II-Induced Smooth Muscle Contraction.

Background: GPCRs (G-protein-coupled receptors) play a central role in the regulation of smooth muscle cell (SMC) contractility, but the function of SMC-expressed orphan GPCR class C group 5 member C (GPRC5C) is unclear. The aim of this project is to define the role of GPRC5C in SMC in vitro and in vivo.

Methods: We studied the role of GPRC5C in the regulation of SMC contractility and differentiation in human and murine SMC in vitro, as well as in tamoxifen-inducible, SMC-specific GPRC5C knockout mice under basal conditions and in vascular disease in vivo.

Maternal diabetes and risk of attention-deficit/hyperactivity disorder in offspring in a multinational cohort of 3.6 million mother-child pairs.

Previous studies report an association between maternal diabetes mellitus (MDM) and attention-deficit/hyperactivity disorder (ADHD), often overlooking unmeasured confounders such as shared genetics and environmental factors. We therefore conducted a multinational cohort study with linked mother-child pairs data in Hong Kong, New Zealand, Taiwan, Finland, Iceland, Norway and Sweden to evaluate associations between different MDM (any MDM, gestational diabetes mellitus (GDM) and pregestational diabetes mellitus (PGDM)) and ADHD using Cox proportional hazards regression. We included over 3.

AlScN Lamb Wave Contour Mode Resonators.

This article presents the lamb wave contour mode resonators (CMRs) based on 22% aluminum scandium nitride (AlScN) thin film with λ of 12-24 [Formula: see text], and operating in [Formula: see text] mode. We report the design, fabrication, and characterization of 500 nm-thick AlScN CMRs, which take advantage of optimized stress control of co-sputtered AlScN thin films and vertical inductively coupled plasma (ICP) etching profile. The experimental results are compared to theoretical predictions by finite element analysis (FEA).

Randomised phase II trial of gemcitabine and nab-paclitaxel with necuparanib or placebo in untreated metastatic pancreas ductal adenocarcinoma.

Background: Necuparanib, a rationally engineered low-molecular-weight heparin, combined with gemcitabine/nab-paclitaxel showed an encouraging safety and oncologic signal in a phase Ib trial. This randomised multicentre phase II trial evaluates the addition of necuparanib or placebo to gemcitabine/nab-paclitaxel in untreated metastatic pancreatic ductal adenocarcinoma (PDAC).

Patients And Methods: Eligibility included 18 years, histologically or cytologically confirmed metastatic PDAC, measurable disease and Eastern Co-Operative Oncology Group performance status of 0-1.

Shock Tube Measurement of the CH + CH → CH + CH Rate Constant.

The rate constant for the CH + CH → CH + CH reaction was studied behind reflected shock waves at temperatures between 1369 and 1626 K and pressures from 8.6 to 47.4 atm in mixtures of methane, ethane, and argon.

Discovery of a ZIP7 inhibitor from a Notch pathway screen.

The identification of activating mutations in NOTCH1 in 50% of T cell acute lymphoblastic leukemia has generated interest in elucidating how these mutations contribute to oncogenic transformation and in targeting the pathway. A phenotypic screen identified compounds that interfere with trafficking of Notch and induce apoptosis via an endoplasmic reticulum (ER) stress mechanism. Target identification approaches revealed a role for SLC39A7 (ZIP7), a zinc transport family member, in governing Notch trafficking and signaling.

Anisotropy in the magnetic interaction and lattice-orbital coupling of single crystal NiTeO.

This investigation reports on anisotropy in the magnetic interaction, lattice-orbital coupling and degree of phonon softening in single crystal NiTeO (NTO) using temperature- and polarization-dependent X-ray absorption spectroscopic techniques. The magnetic field-cooled and zero-field-cooled measurements and temperature-dependent Ni L-edge X-ray magnetic circular dichroism spectra of NTO reveal a weak Ni-Ni ferromagnetic interaction close to ~60 K (T: temperature of the onset of spin ordering) with a net alignment of Ni spins (the uncompensated components of the Ni moments) along the crystallographic c-axis, which is absent from the ab-plane. Below the Néel temperature, T~ 52 K, NTO is stable in the antiferromagnetic state with its spin axis parallel to the c-axis.

Mutation Clearance after Transplantation for Myelodysplastic Syndrome.

Background: Allogeneic hematopoietic stem-cell transplantation is the only curative treatment for patients with myelodysplastic syndrome (MDS). The molecular predictors of disease progression after transplantation are unclear.

Methods: We sequenced bone marrow and skin samples from 90 adults with MDS who underwent allogeneic hematopoietic stem-cell transplantation after a myeloablative or reduced-intensity conditioning regimen.

A pluripotent stem cell-based model for post-implantation human amniotic sac development.

Development of the asymmetric amniotic sac-with the embryonic disc and amniotic ectoderm occupying opposite poles-is a vital milestone during human embryo implantation. Although essential to embryogenesis and pregnancy, amniotic sac development in humans remains poorly understood. Here, we report a human pluripotent stem cell (hPSC)-based model, termed the post-implantation amniotic sac embryoid (PASE), that recapitulates multiple post-implantation embryogenic events centered around amniotic sac development.

The Nuclear Receptor, Nor-1, Induces the Physiological Responses Associated With Exercise.

Skeletal muscle remodels metabolic capacity, contractile and exercise phenotype in response to physiological demands. This adaptive remodeling response to physical activity can ameliorate/prevent diseases associated with poor diet and lifestyle. Our previous work demonstrated that skeletal muscle-specific transgenic expression of the neuron-derived orphan nuclear receptor, Nor-1 drives muscle reprogramming, improves exercise endurance, and oxidative metabolism.

Theoretical study of the mechanisms and kinetics of the reactions of hydroperoxy (HO2) radicals with hydroxymethylperoxy (HOCH2O2) and methoxymethylperoxy (CH3OCH2O2) radicals.

The reactions of hydroperoxy radicals with hydroxymethylperoxy and methoxymethylperoxy radicals were studied using the hybrid density functional theory and the coupled-cluster theory with complete basis set extrapolation. In contrast with the unsubstituted alkylperoxy reactions, it was found that OH-substitution has a significant effect on the reaction mechanism. Several hydrogen bonding reaction precursors exist at the start of the reaction.

Cytochrome P450 2C8 ω3-long-chain polyunsaturated fatty acid metabolites increase mouse retinal pathologic neovascularization--brief report.

Objective: Regulation of angiogenesis is critical for many diseases. Specifically, pathological retinal neovascularization, a major cause of blindness, is suppressed with dietary ω3-long-chain polyunsaturated fatty acids (ω3LCPUFAs) through antiangiogenic metabolites of cyclooxygenase and lipoxygenase. Cytochrome P450 epoxygenases (CYP2C8) also metabolize LCPUFAs, producing bioactive epoxides, which are inactivated by soluble epoxide hydrolase (sEH) to transdihydrodiols.

Measurement of splitting scales in → events at [Formula: see text] with the ATLAS detector.

A measurement of splitting scales, as defined by the clustering algorithm, is presented for final states containing a boson produced in proton-proton collisions at a centre-of-mass energy of 7 TeV. The measurement is based on the full 2010 data sample corresponding to an integrated luminosity of 36 pb which was collected using the ATLAS detector at the CERN Large Hadron Collider. Cluster splitting scales are measured in events containing bosons decaying to electrons or muons.

[The morphology and thickness of cornea in patients with Marfan syndrome].

Objective: To search for the characteristics of MFS in corneal morphology and thickness.

Methods: Twenty-four patients (48 eyes) with MFS and 24 healthy age- and gender-matched volunteers (48 eyes) were recruited in this clinical prospective, and comparative series study. Firstly, biomicroscopic examination and Type-A ultrasonometry was conducted to search for ectopia lentis and axis length.

Cellular distribution of the neutral amino acid transporter subtype ASCT2 in mouse brain.

ASCT2 is an ASC (alanine-, serine-, cysteine-preferring) neutral amino acid exchanger that may regulate CNS function by transporting amino acid substrates including L-serine, L-cysteine, L-glutamine, L-glutamate and D-serine. Despite the potentially important role of ASCT2 in influencing metabolic and signaling functions of these amino acids in brain, there has been little description of its distribution in brain tissue. We employed a commercially available human ASCT2 antibody in immunohistochemistry studies in adult mouse brain and found a wide regional distribution for ASCT2 that was limited to dendrites labeled by anti-microtubule-associated protein-2 in cortex, hippocampus and striatum.