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Activation of the nuclear factor (erythroid‐derived 2)‐like 2 (NFE2L2 or NRF2) transcription factor is a critical and evolutionarily conserved cellular response to oxidative stress, metabolic stress, and xenobiotic insult. Deficiency of NRF2 results in hypersensitivity to a variety of stressors, whereas its aberrant activation contributes to several cancer types, most commonly squamous cell carcinomas of the esophagus, oral cavity, bladder, and lung. Between 10% and 35% of patients with squamous cell carcinomas display hyperactive NRF2 signaling, harboring activating mutations and copy number amplifications of the NFE2L2 oncogene or inactivating mutations or deletions of KEAP1 or CUL3, the proteins of which co‐complex to ubiquitylate and degrade NRF2 protein. To better understand the role of NRF2 in tumorigenesis and more broadly in development, we engineered the endogenous Nfe2l2 genomic locus to create a conditional mutant LSL‐Nrf2E79Q mouse model. The E79Q mutation, one of the most commonly observed NRF2‐activating mutations in human squamous cancers, codes for a mutant protein that does not undergo KEAP1/CUL3‐dependent degradation, resulting in its constitutive activity. Expression of NRF2 E79Q protein in keratin 14 (KRT14)‐positive murine tissues resulted in hyperplasia of squamous cell tissues of the tongue, forestomach, and esophagus, a stunted body axis, decreased weight, and decreased visceral adipose depots. RNA‐seq profiling and follow‐up validation studies of cultured NRF2E79Q murine esophageal epithelial cells revealed known and novel NRF2‐regulated transcriptional programs, including genes associated with squamous cell carcinoma (e.g. Myc), lipid and cellular metabolism (Hk2, Ppard), and growth factors (Areg, Bmp6, Vegfa). These data suggest that in addition to decreasing adipogenesis, KRT14‐restricted NRF2 activation drives hyperplasia of the esophagus, forestomach, and tongue, but not formation of squamous cell carcinoma. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article discusses the U.S. Court of Appeals for Third Circuit decision in In re American Capital Equipment, LLC rejecting the proposed plan at disclosure statement stage as patently unconfirmable. It mentions that a disclosure statement, a statement offering the context of a proposed plan, should be disseminated to voting parties to ensure that stakeholders are able to render an informed judgment with respect to a proposed plan.

In patients with left ventricular systolic dysfunction (LVSD), the rate at which oxygen uptake (VO2) increases on initiation of exercise is inadequate to match metabolic demands. To gain mechanistic insights into delayed VO2 kinetics in LVSD, we simultaneously assessed hemodynamic measurements, ventilatory parameters, and peripheral oxygen usage during exercise.Forty-two patients with symptomatic LVSD (age, 59±2 years [mean±SEM]; LV ejection fraction, 30±1%) and 17 controls (LV ejection fraction, 68±1%) underwent maximum upright cycle ergometry cardiopulmonary exercise testing. Hemodynamic monitoring and first-pass radionuclide ventriculography were performed at rest and during exercise. VO2 kinetics were quantified by mean response time (MRT), which was significantly longer in patients with LVSD compared with controls (64±3 versus 45±5 s; P=0.004). In LVSD patients, MRT was associated with higher biventricular filling pressures and reduced cardiac output during early exercise. LVSD patients with MRT ≥60 s, compared with LVSD subjects with MRT <60 s, demonstrated greater impairment in right ventricular-pulmonary vascular function during exercise as evidenced by lower right ventricular ejection fraction (35±2 versus 45±2%; P=0.03), steeper increment in transpulmonary gradient relative to cardiac output (3.7 versus 2.2 mm Hg/L; P<0.001), and increased ventilatory dead-space fraction (17±1 versus 12±2%; P=0.03). In contrast, MRT was not associated with LV ejection fraction (rest, exercise), PaO2, hemoglobin, or resting pulmonary function test results.Delayed oxygen uptake on initiation of exercise (ie, MRT ≥60 s) in LVSD is closely related to impaired right ventricular-pulmonary vascular function and may represent an important surrogate for inability to augment RV performance during physical activity in patients with heart failure. [ABSTRACT FROM AUTHOR]

The article focuses on single employer liability for related entities under the U.S. Worker Adjustment and Retraining Notification Act of 1988, also known as the WARN Act. Topics include investor control over failing companies, parent company control over corporate direction, and mass employee termination events.

The article presents information on the impact of intellectual property on the global economy and the related uncertainty for the bankruptcy practitioners. The security interests in intellectual property, asset-based financing and the infringement of debtor's title or lender's priority are discussed. The rules for perfect security interest allocation in intellectual property based on the Uniform Commercial Code of the U.S. federal systems are also discussed.

The article discusses the decision of the Bankruptcy Court for the Southern District of New York in the case In re Chemtura Corp. The case provides information on the appropriate treatment of make-whole and no-call provisions pertaining to Chapter 11 of the U.S. Bankruptcy Code. It focuses on the provisions for approving a plan settlement and the legitimacy of a lender's right of recovery for damages. It further explains the framework for analyzing the provisions which can support valid claims.