Spatial transcriptomic validation of a biomimetic model of fibrosis enables re-evaluation of a therapeutic antibody targeting LOXL2.

Matrix stiffening by lysyl oxidase-like 2 (LOXL2)-mediated collagen cross-linking is proposed as a core feedforward mechanism that promotes fibrogenesis. Failure in clinical trials of simtuzumab (the humanized version of AB0023, a monoclonal antibody against human LOXL2) suggested that targeting LOXL2 may not have disease relevance; however, target engagement was not directly evaluated. We compare the spatial transcriptome of active human lung fibrogenesis sites with different human cell culture models to identify a disease-relevant model.

Challenges and Opportunities for Commercializing Technologies in the Pulmonary Arena: An Official American Thoracic Society Report.

"Translational medicine" has been a buzzword for over two decades. The concept was intended to be lofty, to reflect a new "bench-to-bedside" approach to basic and clinical research that would bridge fields, close gaps, accelerate innovation, and shorten the time and effort it takes to bring novel technologies from basic discovery to clinical application. Has this approach been successful and lived up to its promise? Despite incredible scientific advances and innovations developed within academia, successful clinical translation into real-world solutions has been difficult.

Timing Is Important-Management of Metabolic Syndrome According to the Circadian Rhythm.

Physiological processes occur in accordance with a rhythm regulated by the endogenous biological clock. This clock is programmed at the molecular level and synchronized with the daily light-dark cycle, as well as activities such as feeding, exercise, and social interactions. It consists of the core clock genes, Circadian Locomotor Output Cycles Protein Kaput (CLOCK) and Brain and Muscle Arnt-Like protein 1 (BMAL1), and their products, the period (PER) and cryptochrome (CRY) proteins, as well as an interlocked feedback loop which includes reverse-strand avian erythroblastic leukemia (ERBA) oncogene receptors (REV-ERBs) and retinoic acid-related orphan receptors (RORs).

A novel Bayesian framework for harmonizing information across tissues and studies to increase cell type deconvolution accuracy.

Computational cell type deconvolution on bulk transcriptomics data can reveal cell type proportion heterogeneity across samples. One critical factor for accurate deconvolution is the reference signature matrix for different cell types. Compared with inferring reference signature matrices from cell lines, rapidly accumulating single-cell RNA-sequencing (scRNA-seq) data provide a richer and less biased resource.

Metagenomic sequencing of the bronchoalveolar lavage extracellular virome and cellular transcriptome of sarcoidosis patients does not detect rubella virus.

Background:   Sarcoidosis is a multisystem granulomatous inflammatory disease of unclear etiology that involves the lung, skin and other organs, with an unknown antigenic trigger. Recently, evidence has been found in both immune deficient and immune competent patients for rubella virus in cutaneous granulomas. These granulomatous lesions share overlapping features with cutaneous sarcoidosis, raising the question of rubella virus in sarcoidosis.

Pseudohypoxic HIF pathway activation dysregulates collagen structure-function in human lung fibrosis.

Extracellular matrix (ECM) stiffening with downstream activation of mechanosensitive pathways is strongly implicated in fibrosis. We previously reported that altered collagen nanoarchitecture is a key determinant of pathogenetic ECM structure-function in human fibrosis (Jones et al., 2018).

From Burden to Depressive Symptoms in Informal Caregivers during the COVID-19 Pandemic: A Path Analysis.

Background: The objective of this study was to assess the complex relationship between the multiple determinants of the caregiving process, the caregiver burden, and depression during the COVID-19 pandemic in Serbia.

Methods: A cross-sectional study was conducted on a nationally representative sample (n = 798) during the COVID-19 pandemic in Serbia from March to September 2020. A nine-section questionnaire designed for this study included the characteristics of caregivers, characteristics of care and care recipients, COVID-19 related questions, and the following standardized instruments: 12-Item Short-Form Health Survey, Fatigue Severity Scale, Activities of Daily Living Scale and Instrumental Activities of Daily Living Scale, Zarit Caregiver Burden Scale, and Beck Depression Inventory.

Integrated transcriptomic analysis of human tuberculosis granulomas and a biomimetic model identifies therapeutic targets.

Tuberculosis (TB) is a persistent global pandemic, and standard treatment for it has not changed for 30 years. Mycobacterium tuberculosis (Mtb) has undergone prolonged coevolution with humans, and patients can control Mtb even after extensive infection, demonstrating the fine balance between protective and pathological host responses within infected granulomas. We hypothesized that whole transcriptome analysis of human TB granulomas isolated by laser capture microdissection could identify therapeutic targets, and that comparison with a noninfectious granulomatous disease, sarcoidosis, would identify disease-specific pathological mechanisms.

Transcriptomics of bronchoalveolar lavage cells identifies new molecular endotypes of sarcoidosis.

Background: Sarcoidosis is a multisystem granulomatous disease of unknown origin with a variable and often unpredictable course and pattern of organ involvement. In this study we sought to identify specific bronchoalveolar lavage (BAL) cell gene expression patterns indicative of distinct disease phenotypic traits.

Methods: RNA sequencing by Ion Torrent Proton was performed on BAL cells obtained from 215 well-characterised patients with pulmonary sarcoidosis enrolled in the multicentre Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study.

PHAIR: a biosensor for pH measurement in air-liquid interface cell culture.

In many biological systems, pH can be used as a parameter to understand and study cell dynamics. However, measuring pH in live cell culture is limited by the sensor ion specificity, proximity to the cell surface, and scalability. Commercially available pH sensors are difficult to integrate into a small-scale cell culture system due to their size and are not cost-effective for disposable use.

Gene coexpression networks reveal novel molecular endotypes in alpha-1 antitrypsin deficiency.

Background: Alpha-1 antitrypsin deficiency (AATD) is a genetic condition that causes early onset pulmonary emphysema and airways obstruction. The complete mechanisms via which AATD causes lung disease are not fully understood. To improve our understanding of the pathogenesis of AATD, we investigated gene expression profiles of bronchoalveolar lavage (BAL) and peripheral blood mononuclear cells (PBMCs) in AATD individuals.

The Burnout Syndrome in Medical Academia: Psychometric Properties of the Serbian Version of the Maslach Burnout Inventory-Educators Survey.

The aim of this study was to assess the psychometric properties of the Maslach Burnout Inventory-Educators Survey (MBI-ES). The presence of burnout syndrome, its relationship with personality traits, intention to change career and work abroad were assessed in a cross-sectional multi-center trial conducted among educators at three medical faculties in the Western Balkans during 2019. Translation and cultural adaptation were made based on internationally accepted principles.

Bioactive Plasma Mitochondrial DNA Is Associated With Disease Progression in Scleroderma-Associated Interstitial Lung Disease.

Objective: Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is characterized by variable clinical outcomes, activation of innate immune pattern-recognition receptors (PRRs), and accumulation of α-smooth muscle actin (α-SMA)-expressing myofibroblasts. The aim of this study was to identify an association between these entities and mitochondrial DNA (mtDNA), an endogenous ligand for the intracellular DNA-sensing PRRs Toll-like receptor 9 (TLR-9) and cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING), which has yet to be determined.

Methods: Human lung fibroblasts (HLFs) from normal donors and SSc-ILD explants were treated with synthetic CpG DNA and assayed for α-SMA expression and extracellular mtDNA using quantitative polymerase chain reaction for the human MT-ATP6 gene.

Copper Electrodeposition from Deep Eutectic Solvents-Voltammetric Studies Providing Insights into the Role of Substrate: Platinum vs Glassy Carbon.

We report on the effect of the substrate on electrochemical deposition of Cu from deep eutectic solvent ethaline. We investigated the polarization behavior during electrodeposition of Cu on Pt and glassy carbon (GC) from both Cu and Cu containing ethaline using cyclic voltammetry (CV). Formation of bulk Cu deposits on both substrates underwent nucleation and growth processes; however, the nucleation was considerably sluggish on GC compared to Pt.

Transcriptional regulatory model of fibrosis progression in the human lung.

To develop a systems biology model of fibrosis progression within the human lung we performed RNA sequencing and microRNA analysis on 95 samples obtained from 10 idiopathic pulmonary fibrosis (IPF) and 6 control lungs. Extent of fibrosis in each sample was assessed by microCT-measured alveolar surface density (ASD) and confirmed by histology. Regulatory gene expression networks were identified using linear mixed-effect models and dynamic regulatory events miner (DREM).

Assessment of health systems guidance using the Appraisal of Guidelines for Research and Evaluation - Health Systems (AGREE-HS) instrument.

Health systems guidance (HSG) documents contain systematically developed statements or recommendations intended to address a health system challenge. The concept of HSG is fairly new and considerable effort has been undertaken to build tools to support the contextualization of recommendations. One example is the Appraisal of Guidelines for REsearch and Evaluation - Health Systems (AGREE-HS), created by international stakeholders and researchers, to assist in the development, reporting and evaluation of HSG.

Data challenges of biomedical researchers in the age of omics.

Background: High-throughput technologies are rapidly generating large amounts of diverse omics data. Although this offers a great opportunity, it also poses great challenges as data analysis becomes more complex. The purpose of this study was to identify the main challenges researchers face in analyzing data, and how academic libraries can support them in this endeavor.

Engaging cancer patients in clinical practice guideline development: a pilot study.

Background: Patient engagement is a key quality component of cancer guideline development; however, the optimal strategy for engaging patients in guideline development remains unclear. The feasibility and efficacy of two patient engagement models was tested by Cancer Care Ontario's cancer guideline development program, the Program in Evidence-Based Care (pebc).

Methods: In model 1, patients participated in the guideline development process as active members of a working group.

Validity and usability testing of a health systems guidance appraisal tool, the AGREE-HS.

Background: Health systems guidance (HSG) provides recommendations to address health systems challenges. No tools exist to inform HSG developers and users about the components of high quality HSG and to differentiate between HSG of varying quality. In response, we developed a tool to assist with the development, reporting and appraisal of HSG - the Appraisal of Guidelines for Research and Evaluation-Health Systems (AGREE-HS).

Impact of Transcriptomics on Our Understanding of Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a lethal fibrotic lung disease characterized by aberrant remodeling of the lung parenchyma with extensive changes to the phenotypes of all lung resident cells. The introduction of transcriptomics, genome scale profiling of thousands of RNA transcripts, caused a significant inversion in IPF research. Instead of generating hypotheses based on animal models of disease, or biological plausibility, with limited validation in humans, investigators were able to generate hypotheses based on unbiased molecular analysis of human samples and then use animal models of disease to test their hypotheses.

Predictions and Outcomes of Atrial Fibrillation in the Patients with Acute Myocardial Infarction.

The large epidemiological studies demonstrated that atrial fibrillation is correlated with high mortality and adverse events in patients with acute myocardial infarction. The aim of this study was to determinate predictors of atrial fibrillation develop during the hospital period in patients with acute myocardial infarction as well as short- and long-term mortality depending on the atrial fibrillation presentation. The 600 patients with an acute myocardial infarction were included in the study and follow-up 84 months.

Transcriptome profiles in sarcoidosis and their potential role in disease prediction.

Purpose Of Review: Sarcoidosis is a systemic disease defined by the presence of nonnecrotizing granuloma in the absence of any known cause. Although the heterogeneity of sarcoidosis is well characterized clinically, the transcriptome of sarcoidosis and underlying molecular mechanisms are not. The signal of all transcripts, small and long noncoding RNAs, can be detected using microarrays or RNA-Sequencing.

Blood groups and acute aortic dissection type III.

Introduction: Acute aortic type III dissection is one of the most catastrophic events, with in-hospital mortality ranging between 10% and 12%. The majority of patients are treated medically, but complicated dissections, which represent 15% to 20% of cases, require surgical or thoracic endovascular aortic repair (TEVAR). For the best outcomes adequate blood transfusion support is required.

Challenges and insights in implementing coordinated care between oncology and primary care providers: a Canadian perspective.

We report here on the current state of cancer care coordination in Canada and discuss challenges and insights with respect to the implementation of collaborative models of care. We also make recommendations for future research. This work is based on the findings of the Canadian Team to Improve Community-Based Cancer Care Along the Continuum (canimpact) casebook project.