Development and Characterization of a High-Affinity Selective Galectin-3 Mouse Tool Compound in Mouse Models of Cancer.

The interest in galectin-3 as a drug target in the cancer and fibrosis space has grown during the past few years with several new classes of compounds being developed. The first orally available galectin-3 inhibitor, (h-galectin-3 K = 0.025 μM), is currently in phase 2 clinical trials.

Diagnostic development and needs for laser driven MeV x-ray radiography.

Laser-driven MeV x-ray radiography of dynamic, dense objects demands a small, high flux source of energetic x-rays to generate an image with sufficient quality. Understanding the multi-MeV x-ray spectrum underscores the ability to extrapolate from the current laser sources to new future lasers that might deploy this radiography modality. Here, we present a small study of the existing x-ray diagnostics and techniques.

Renal response status to predict long-term renal survival in patients with lupus nephritis: results from the Toronto Lupus Cohort.

Objective: To evaluate modified versions of the Belimumab International Study in Lupus Nephritis (BLISS-LN) belimumab study primary efficacy renal response (mPERR) and complete renal response (mCRR) criteria (excluding mandatory corticosteroid tapering) as predictors of real-world, long-term renal outcomes among patients with lupus nephritis (LN).

Methods: This retrospective, observational study (GSK Study 212866) used deidentified data between 1970 and 2015 from the University of Toronto Lupus Cohort from adults diagnosed with systemic lupus erythematosus and biopsy-proven Class III±V, IV±V or V LN. At 24 months postbiopsy, patients were retrospectively indexed as responders/non-responders based on mPERR (estimated glomerular filtration rate (eGFR) ≤20% below biopsy value/≥60 mL/min/1.

Galectin-1 Induces the Production of Immune-Suppressive Cytokines in Human and Mouse T Cells.

Galectin-1 is implicated in several pro-tumourigenic mechanisms and is considered immune-suppressive. The pharmacological inhibition of galectin-1 may be beneficial in cancers in which galectin-1 is overexpressed and driving cancer progression. This study aimed to further characterise the immunosuppressive cytokines influenced by galectin-1 in in vitro immune cell cultures and an in vivo inflammatory model using a recently discovered selective inhibitor of galectin-1, GB1908.

Effect of GB1107, a novel galectin-3 inhibitor on pro-fibrotic signalling in the liver.

Background And Purpose: Galectin-3 (Gal-3) is a pro-fibrotic β-galactoside binding lectin highly expressed in fibrotic liver and implicated in hepatic fibrosis. GB1107 is a novel orally active Gal-3 small molecule inhibitor that has high affinity for Gal-3 >1000-fold selectively over other galectins. The aim of this study was to characterise GB1107 and galectin-3 in vitro and in vivo in the context of fibrosis signalling and liver disease.

Large-cell Basaloid Adenocarcinoma of the Lung: A Clinicopathologic Study of 12 Cases of a Distinctive Form of Lung Cancer Often Mistaken for Large-cell Neuroendocrine Carcinoma.

A distinctive form of lung adenocarcinoma that closely mimics large-cell neuroendocrine carcinoma is described. The tumors arose in 6 women and 6 men aged 46-86 years (mean=58.4).

Sleeping for two: a randomized controlled trial of cognitive behavioral therapy for insomnia in pregnancy.

Study Objectives: Insomnia and sleep problems are common in pregnancy and have potentially negative impacts on both parental and infant health. This study examined the sleeping for two adaptation of cognitive behavioral therapy for insomnia (CBT-I) in pregnancy.

Methods: A parallel (1:1) randomized controlled trial evaluated CBT-I (n=32) compared to a treatment as usual (TAU) waitlist (n=32) among pregnant individuals from Alberta, Canada experiencing insomnia.

Identifying, quantifying, and mitigating background with the time-resolved x-ray diffraction platform at the National Ignition Facility.

The time-resolved x-ray diffraction platform at the National Ignition Facility (NIF) fields electronic sensors closer to the exploding laser-driven target than any other NIF diagnostic in order to directly detect diffracted x rays from highly compressed materials. We document strategies to characterize and mitigate the unacceptably high background signals observed in this geometry. We specifically assess the possible effects of electromagnetic pulse, x-ray fluorescence, hot electrons, and sensor-specific non-x-ray artifacts.

Neutron imaging of the deuterium-tritium tamping gas volume in an inertial confinement fusion hohlraum.

To benchmark the accuracy of the models and improve the predictive capability of future experiments, the National Ignition Facility requires measurements of the physical conditions inside inertial confinement fusion hohlraums. The ion temperature and bulk motion velocity of the gas-filled regions of the hohlraum can be obtained by replacing the helium tamping gas in the hohlraum with deuterium-tritium (DT) gas and measuring the Doppler broadening and Doppler shift of the neutron spectrum produced by nuclear reactions in the hohlraum. To understand the spatial distribution of the neutron production inside the hohlraum, we have developed a new penumbral neutron imager with a 12 mm diameter field of view using a simple tungsten alloy spindle.

Time resolved x-ray diffraction using the flexible imaging diffraction diagnostic for laser experiments (FIDDLE) at the National Ignition Facility (NIF): Preliminary assessment of diffraction precision.

The Flexible Imaging Diffraction Diagnostic for Laser Experiments (FIDDLE) is a new diagnostic at the National Ignition Facility (NIF) designed to observe in situ solid-solid phase changes at high pressures using time resolved x-ray diffraction. FIDDLE currently incorporates five Icarus ultrafast x-ray imager sensors that take 2 ns snapshots and can be tuned to collect X-rays for tens of ns. The platform utilizes the laser power at NIF for both the laser drive and the generation of 10 keV X-rays for ∼10 ns using a Ge backlighter foil.

Testing the Effectiveness of a Mobile Smartphone App Designed to Improve the Mental Health of Junior Physicians: Protocol for a Randomized Controlled Trial.

Background: Shift (Black Dog Institute) is the first mobile health smartphone app created to support the mental health of junior physicians. Junior physicians experience demanding work conditions, leading to high levels of psychological distress and burnout. However, they are often concerned about the potential career impacts of seeking mental health support.

Developing time-resolved x-ray diffraction diagnostics at the National Ignition Facility (invited).

As part of a program to measure phase transition timescales in materials under dynamic compression, we have designed new x-ray imaging diagnostics to record multiple x-ray diffraction measurements during a single laser-driven experiment. Our design places several ns-gated hybrid CMOS (hCMOS) sensors within a few cm of a laser-driven target. The sensors must be protected from an extremely harsh environment, including debris, electromagnetic pulses, and unconverted laser light.

Nodular Fasciitis of the Buccal Mucosa with a Novel USP6 Gene Rearrangement: A Case Report and Review of the Literature.

Nodular fasciitis is a rare but benign fibroblastic proliferation that typically presents as a solitary lesion with rapid growth and variable mitotic activity. The lesions usually occur on the extremities and occasionally in the head/neck region. Involvement of the buccal mucosa is extremely rare with only few reports in the literature; in this case report, we describe a 41 year old female who presented with a 6-month history of a stable intraoral lump at the junction of the upper and lower lip.

Mental health training for physicians supervising resident physicians: a cluster randomised controlled trial.

Objective: To evaluate an online training program for physician supervisors with the aim of promoting a mentally healthy workplace by improving their use of both responsive and preventive mental health support strategies.

Study Design: Cluster randomised, waitlist-controlled trial.

Setting, Participants: Royal Australasian College of Physicians fellows who were supervising at least one resident physician in any of the 31 primary health networks in Australia and 20 district health boards in New Zealand (health network clusters).

Electrical design of the flexible imaging diffraction diagnostic for laser experiments (FIDDLE) at the National Ignition Facility (NIF)-Requirements, design, and performance.

The Flexible Imaging Diffraction Diagnostic for Laser Experiments (FIDDLE) is a newly developed diagnostic for imaging time resolved diffraction in experiments at the National Ignition Facility (NIF). It builds on the successes of its predecessor, the Gated Diffraction Development Diagnostic (G3D). The FIDDLE was designed to support eight Daedalus version 2 sensors (six more hCMOS sensors than any other hCMOS-based diagnostic in NIF to date) and an integrated streak camera.

Sleeping for two: A randomized controlled trial of cognitive behavioural therapy for insomnia (CBTI) delivered in pregnancy and secondary impacts on symptoms of postpartum depression.

Background: Insomnia in pregnancy is common and highly comorbid with depression.

Objective: To investigate if: 1) depressive symptoms decrease after cognitive behavioural therapy for insomnia (CBTI) delivered in pregnancy, and 2) changes in insomnia symptoms represent a mechanism linking CBT-I treatment and reduced symptoms of postpartum depression.

Methods: A two-arm, single-blind, parallel groups randomized controlled trial (RCT) design was used to evaluate the impact of a 5-week CBT-I intervention adapted for pregnant people with insomnia (N = 62).

Inflammatory Giant Cell Carcinoma of the Lung: Clinicopathologic, Immunohistochemical, and Next-generation Sequencing Study of 14 Cases.

A distinctive histological variant of poorly differentiated, sarcomatoid, non-small cell lung carcinoma characterized by a discohesive population of giant tumor cells associated with prominent interstitial inflammatory cell infiltrates is described. The tumors occurred in 7 women and 7 men, 42 to 72 years of age (mean: 56 y). They predominantly affected the upper lobes and measured 1.

Insulinoma-Associated Protein-1 Expression in Lymphoepithelial Carcinoma of the Thymus: A Potential Pitfall for Diagnosis With Neuroendocrine Carcinomas of the Thymus.

Context.—: Insulinoma-associated protein-1 (INSM1) is a recently developed immunohistochemical marker claimed to be highly specific and sensitive for the diagnosis of neuroendocrine malignancies. Recent studies, however, have demonstrated that this marker can also be expressed in non-neuroendocrine neoplasms including squamous cell carcinoma of the thymus.

Non-small cell lung carcinoma with clear cell features: a clinicopathologic, immunohistochemical, and molecular study of 31 cases.

Non-small cell lung carcinoma with predominantly clear cell features is a rare histologic presentation of lung carcinoma. We have examined 31 cases of lung carcinomas showing extensive clear cell features. The patients were 10 women and 21 men aged 47-92 years (mean: 70 years).

Discovery of the Selective and Orally Available Galectin-1 Inhibitor GB1908 as a Potential Treatment for Lung Cancer.

We have previously described a new series of selective and orally available galectin-1 inhibitors resulting in the thiazole-containing glycomimetic GB1490. Here, we show that the introduction of polar substituents to the thiazole ring results in galectin-1-specific compounds with low nM affinities. X-ray structural analysis of a new ligand-galectin-1 complex shows changes in the binding mode and ligand-protein hydrogen bond interactions compared to the GB1490-galectin-1 complex.

Defining the mechanism of galectin-3-mediated TGF-β1 activation and its role in lung fibrosis.

Integrin-mediated activation of the profibrotic mediator transforming growth factor-β1 (TGF-β1), plays a critical role in idiopathic pulmonary fibrosis (IPF) pathogenesis. Galectin-3 is believed to contribute to the pathological wound healing seen in IPF, although its mechanism of action is not precisely defined. We hypothesized that galectin-3 potentiates TGF-β1 activation and/or signaling in the lung to promote fibrogenesis.