Cell competition drives bronchiolization and pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive respiratory scarring disease arising from the maladaptive differentiation of lung stem cells into bronchial epithelial cells rather than into alveolar type 1 (AT1) cells, which are responsible for gas exchange. Here, we report that healthy lungs maintain their stem cells through tonic Hippo and β-catenin signaling, which promote Yap/Taz degradation and allow for low-level expression of the Wnt target gene Myc. Inactivation of upstream activators of the Hippo pathway in lung stem cells inhibits this tonic β-catenin signaling and Myc expression and promotes their Taz-mediated differentiation into AT1 cells.

Private sector business interactions with bereaved people: UK Commission on Bereavement secondary analysis.

Objectives: Evidence suggests that 61% of adults who were bereaved in the past 5 years had difficulties with at least one practical or administrative task following bereavement. We aimed to explore individual's experiences of interacting with private sector businesses following a bereavement.

Methods: Qualitative secondary analysis of data collected via an online survey within the UK Commission on Bereavement.

Haptoglobin phenotype and intensive glycemic control for coronary artery disease risk reduction in people with type two diabetes: The Veterans Affairs Diabetes Trial.

Background: Intensive glycemic control reduced the risk of coronary artery disease (CAD) events among White ACCORD study participants with the haptoglobin (Hp)2-2 phenotype, and not among participants without the Hp2-2 phenotype. It is unknown whether these results persist in a population with more severe diabetes.

Methods: Haptoglobin phenotype was measured in 1746 (97 %) samples from the Veterans Affairs Diabetes Trial (VADT) randomized controlled trial.

Cell competition drives bronchiolization and pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive scarring disease arising from the maladaptive differentiation of lung stem cells into bronchial epithelial cells rather than into alveolar type 1 (AT1) cells, which are responsible for gas exchange. Here, we report that healthy lungs maintain their stem cells through tonic Hippo and β-catenin signaling, which promote Yap/Taz degradation and allow for low level expression of the Wnt target gene . Inactivation of upstream activators of the Hippo pathway in lung stem cells inhibits this tonic β-catenin signaling and expression and promotes their Taz mediated differentiation into AT1 cells.

Relationship Between Time-Varying Achieved High-Density Lipoprotein Cholesterol and Risk of Coronary Events Depends on Haptoglobin Phenotype Within the ACCORD Lipid Study.

Background The Hp (haptoglobin)2-2 phenotype (~40% of people) is associated with dysfunctional high-density lipoprotein (HDL) that is heavily oxidized in hyperglycemia, which may explain why raising HDL-cholesterol (HDL-C) does not reliably prevent coronary artery disease (CAD) in diabetes. Methods and Results In this observational study using longitudinal data from the ACCORD (Action to Control Cardiovascular Risk in Diabetes) lipid trial, time-varying (achieved) HDL-C updated at 4, 8, and 12 months, and annually thereafter over a mean of 4.7 years, was analyzed in relation to risk of CAD and secondary outcomes using Cox proportional hazards regression with time-varying covariables among participants with (n=1781) and without (n=3191) the Hp2-2 phenotype.

The Relationship Between Time-Varying Achieved HbA1c and Risk of Coronary Events Depends on Haptoglobin Phenotype Among White and Black ACCORD Participants.

Objective: Intensive glycemic therapy reduced coronary artery disease (CAD) events among White participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study with the haptoglobin (Hp)2-2 phenotype, while participants without the Hp2-2 phenotype had no CAD benefit. The association between achieved glycated hemoglobin (HbA1c) and CAD for each Hp phenotype remains unknown.

Research Design And Methods: Achieved HbA1c was similar in each phenotype throughout the study.

Protocol for the use of signal amplification by exchange reaction-fluorescence in situ hybridization on adult formalin-fixed paraffin-embedded mouse lung tissue.

Fluorescence in situ hybridization (FISH) is a useful tool for analyzing RNA expression, but difficulties arise with low-abundance RNA and in tissues that are formalin-fixed paraffin-embedded (FFPE) because reagents can be expensive. In this protocol, we adapt a previously designed FISH amplification protocol (SABER [signal amplification by exchange reaction]) for adult mouse FFPE lung sections by using probes that are extended and branched to amplify the signal. We combine FISH and immunostaining to identify cell-specific RNA.

Hippo signaling impairs alveolar epithelial regeneration in pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) consists of fibrotic alveolar remodeling and progressive loss of pulmonary function. Genetic and experimental evidence indicates that chronic alveolar injury and failure to properly repair the respiratory epithelium are intrinsic to IPF pathogenesis. Loss of alveolar type 2 (AT2) stem cells or mutations that either impair their self-renewal and/or impair their differentiation into AT1 cells can serve as a trigger of pulmonary fibrosis.

Global evidence of gender equity in academic health research: a scoping review.

Objectives: To chart the global literature on gender equity in academic health research.

Design: Scoping review.

Participants: Quantitative studies were eligible if they examined gender equity within academic institutions including health researchers.

Niche-mediated repair of airways is directed in an occupant-dependent manner.

In injured airways of the adult lung, epithelial progenitors are called upon to repair by nearby mesenchymal cells via signals transmitted through the niche. Currently, it is unclear whether repair is coordinated by the mesenchymal cells that maintain the niche or by the airway epithelial cells that occupy it. Here, we show that the spatiotemporal expression of Fgf10 by the niche is primarily orchestrated by the niche's epithelial occupants-both those that reside prior to, and following, injury.

Incidence and Progression of Fibrotic Lung Disease in an At-Risk Cohort.

Relatives of patients with familial interstitial pneumonia (FIP) are at increased risk for pulmonary fibrosis and develop preclinical pulmonary fibrosis (PrePF). We defined the incidence and progression of new-onset PrePF and its relationship to survival among first-degree relatives of families with FIP. This is a cohort study of family members with FIP who were initially screened with a health questionnaire and chest high-resolution computed tomography (HRCT) scan, and approximately 4 years later, the evaluation was repeated.

Comparative-effectiveness research of COVID-19 treatment: a rapid scoping review.

Objectives: The COVID-19 pandemic has stimulated growing research on treatment options. We aim to provide an overview of the characteristics of studies evaluating COVID-19 treatment.

Design: Rapid scoping review DATA SOURCES: Medline, Embase and biorxiv/medrxiv from inception to 15 May 2021.

Ataxia telangiectasia mutated is required for efficient proximal airway epithelial cell regeneration following influenza A virus infection.

Children and young adults with mutant forms of ataxia telangiectasia mutated (ATM), a kinase involved in DNA damage signaling and mitochondrial homeostasis, suffer from recurrent respiratory infections, immune deficiencies, and obstructive airways disease associated with disorganized airway epithelium. We previously showed in mice how Atm was required to mount a protective immune memory response to influenza A virus [IAV; Hong Kong/X31 (HKx31), H3N2]. Here, Atm wildtype (WT) and knockout (Atm-null) mice were used to investigate how Atm is required to regenerate the injured airway epithelium following IAV infection.

Anti-vascular endothelial growth factor therapy for age-related macular degeneration: a systematic review and network meta-analysis.

Background: The comparative safety and efficacy between anti-vascular endothelial growth factor agents (anti-VEGFs) and between combined therapies for patients with neovascular age-related macular degeneration (nAMD) is unclear. We conducted a systematic review to examine the comparative safety and efficacy anti-VEGFs for adults with nAMD.

Methods: Studies were identified through MEDLINE, EMBASE, and Cochrane CENTRAL (inception to June 3, 2019), grey literature, and scanning reference lists.

Haptoglobin Phenotype Modifies the Effect of Fenofibrate on Risk of Coronary Event: ACCORD Lipid Trial.

Objective: The haptoglobin (Hp)2-2 phenotype (∼35-40% of people) is associated with increased oxidation and dysfunctional HDL in hyperglycemia and may explain why drugs designed to pharmacologically raise HDL cholesterol and lower triglycerides have not reliably prevented cardiovascular disease in diabetes. We aimed to determine whether the effect of adding fenofibrate versus placebo to simvastatin on the risk of coronary artery disease (CAD) events depends on Hp phenotype in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) lipid trial.

Research Design And Methods: Cox proportional hazards regression models quantified the relationship between fenofibrate therapy and CAD events in the ACCORD lipid trial in participants with the Hp2-2 phenotype (n = 1,795) separately from those without (n = 3,201).

Low-dose hyperoxia primes airways for fibrosis in mice after influenza A infection.

It is well known that supplemental oxygen used to treat preterm infants in respiratory distress is associated with permanently disrupting lung development and the host response to influenza A virus (IAV). However, many infants who go home with normally functioning lungs are also at risk for hyperreactivity after a respiratory viral infection. We recently reported a new, low-dose hyperoxia mouse model (40% for 8 days; 40×8) that causes a transient change in lung function that resolves, rendering 40×8 adult animals functionally indistinguishable from room air controls.

Addressing risks to biodiversity arising from a changing climate: The need for ecosystem restoration in the Tana River Basin, Kenya.

Climate change is projected to have significant effects on the distribution of species globally, but research into the implications in parts of Africa has been limited. Using species distribution modelling, this study models climate change-related risks to the terrestrial biodiversity (birds, mammals, reptiles, amphibians and plants) of Kenya's economically-important and ecologically diverse Tana River Basin. Large reductions in species richness are projected with just 2°C warming (relative to preindustrial levels) with birds and plants seeing the greatest impact.

Investigating the potential impact of 1.5, 2 and 3 °C global warming levels on crop suitability and planting season over West Africa.

West African rainfed agriculture is highly vulnerable to climate variability and change. Global warming is projected to result in higher regional warming and have a strong impact on agriculture. This study specifically examines the impact of global warming levels (GWLs) of 1.

Parallel Signaling through IRE1α and PERK Regulates Pancreatic Neuroendocrine Tumor Growth and Survival.

Master regulators of the unfolded protein response (UPR), IRE1α and PERK, promote adaptation or apoptosis depending on the level of endoplasmic reticulum (ER) stress. Although the UPR is activated in many cancers, its effects on tumor growth remain unclear. Derived from endocrine cells, pancreatic neuroendocrine tumors (PanNET) universally hypersecrete one or more peptide hormones, likely sensitizing these cells to high ER protein-folding stress.

Ataxia-telangiectasia mutated is required for the development of protective immune memory after influenza A virus infection.

Ataxia-telangiectasia (A-T), caused by mutations in the A-T mutated () gene, is a neurodegenerative disorder affecting ∼1 in 40,000-100,000 children. Recurrent respiratory infections are a common and challenging comorbidity, often leading to the development of bronchiectasis in individuals with A-T. The role of ATM in development of immune memory in response to recurrent respiratory viral infections is not well understood.