tbuckley/cabot-search huggingface dataset:
NO2 and PM2.5 Exposures and Lung Function in Swiss Adults: Estimated Effects of Short-Term Exposures and Long-Term Exposures with and without Adjustment for Short-Term Deviations
Authors: Alexandra Strassmann, Kees de Hoogh, Martin Röösli, Sarah R. Haile, Alexander Turk, Matthias Bopp, Milo A. Puhan
Journal: Environmental Health Perspectives (2021)

Background: The impact of nitrogen dioxide (NO2) and particulate matter with an aerodynamic diameter of less than or equal to 2.5.microns (PM2.5)exposures on lung function has been investigated mainly in children and less in adults.Furthermore, it is unclear whether short-term deviations of air pollutant concentration need to be considered in long-term exposure models.Objectives: The aims of this study were to investigate the association between short-term air pollution exposure and lung function and to assess whether short-term deviations of air pollutant concentration should be integrated into long-term exposure models.Methods: Shortterm (daily averages 0-7 d prior) and long-term (1-and 4-y means) NO2 and PM2.5 concentrations were modeled using satellite, land use, and meteorological data calibrated on ground measurements.Forced expiratory volume within the first second (FEV1) of forced exhalation and forced vital capacity (FVC) were measured during a LuftiBus assessment (2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)) and linked to exposure information from the Swiss National Cohort for 36,085 adults (ages 18-95 y).We used multiple linear regression to estimate adjusted associations, and additionally adjusted models of long-term exposures for short-term deviations in air pollutant concentrations.Results: A 10μg/m3 increase in NO2 and PM2.5 on the day of the pulmonary function test was associated with lower FEV1 and FVC (NO2: FEV1 -8.0 ml [95% confidence interval: -13.4,-2.7], FVC -16.7 ml [-23.4,-10.0];PM2.5: FEV1 -15.3 ml [-21.9, -8.7], FVC -18.5 ml [-26.5, -10.5]).A 10μg/m3 increase in 1-y mean NO2 was also associated with lower FEV1 (-7.7 ml; -15.9, 0.5) and FVC (-21.6 ml; -31.9, -11.4), as was a 10μg/m3 increase in 1-y mean PM2.5 (FEV1: -42.2 ml; -56.9, -27.5;FVC: -82.0 ml; -100.1, -63.9).These associations were robust to adjustment for short-term deviations in the concentration of each air pollutant.Conclusions: Short-and long-term air pollution exposures were negatively associated with lung function, in particular long-term PM2.5 exposure with FVC.Our findings contribute substantially to the evidence of adverse associations between air pollution and lung function in adults.
Antiplatelet Therapy and Coronary Artery Bypass Graft Surgery: A Fallow Land**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Gilles Montalescot, Jean-Sébastien Hulot, Jean-Philippe Collet
Journal: Journal of the American College of Cardiology (2010)
SAT0454 EARLY CLINICAL EFFICACY OF ROMOSOZUMAB IN PATIENTS WITH RHEUMATOID ARTHRITIS AND PRIMARY OSTEOPOROSIS
Authors: Y. Kanayama, R. Sugimoto
Journal: Annals of the Rheumatic Diseases (2020)

Background: Romosozumab (ROM), a monoclonal antibody that binds sclerostin, increases bone formation and decreases bone resorption. And although it is a novel therapeutic agent for osteoporosis, which has shown high effects of increasing bone density and inhibiting fragile fracture in overseas clinical trials. However the clinical efficacy in daily clinical practice is unknown. Objectives: To evaluate the early clinical efficacy of ROM in patients with osteoporosis between rheumatoid arthritis (RA-OP) and primary osteoporosis (P-OP) for 6 months. Methods: RA patients diagnosed according to the 2010 ACR/EULAR criteria. RA-OP and P-OP patients met at least one of the following criteria were eligible; a bone mineral density T score of -2,5 or less at the lumber spine or total hip and either one or more moderate or severe vertebral fractures or two or more mild vertebral fractures. All patients were initiated ROM from between March and June, 2019. The total number of patients was 15 cases, including 8 RA-OP and 7 P-OP. All patients received continuous ROM therapy more than 6 months. The DMB dose was 210mg at once every 1 months. In all cases native or activated vitamin D has been used. We reviewed the results for 6 months about the increase and decrease of bone mineral density (BMD) of lumbar spine(LS) and total hip(TH) by DEXA and bone turnover markers, intact n-terminal propeptide type I procollagen(PINP) and tartrate-resistant acid phopshatate form 5b(TRACP-5b). Results: The gender was all female. The mean age was 71.8 ± 8.7; disease duration of RA-OP patients was 23.0 ± 15.1 years; the body mass index was 19.9 ± 3.2 and the FRAX was 32.5 ± 14.9. Clinical findings related to RA-OP at baseline were as follows; CRP 0.97 ± 0.77; DAS-CRP 3.22 ± 0.41; HAQ 1.41 ± 0.94 in RA-OP patients and in the all patients, bone turnover markers and bone mineral density at baseline were as follows; P1NP 72.2 ± 39.8; TRACP-5b 539 ± 212; LS-BMD and T-score 0.80 ± 0.20 g/cm 2 and -2.75 ± 1.36 and TH-BMD 0.55 ± 0.07 g/cm 2 and -3.18 ± 0.55 g/cm 2 . The rate of increased P1NP from baseline to 1, 3 and 6 months were each -96.8 ± 80.8% at 1 month, 106.8 ± 115.6% at 3 month and 90.7 ± 115.7% at 6 month and decreased TRAC-5b were -20.4 ± 20.6% at 1 month, -80.8 ± 19.6% at 3 month and -1.8 ± 50.8% at 6 month. The rate of increased LS-BMD from baseline to 6 months were 11.0 ± 8.0% and TH-BMD were 5.3 ± 3.8% (Fig. 1, 2). Conclusion: Early clinical efficacy of ROM for RA-OP and P-OP was extremely effective and has the high potential to be an important option in the treatment of osteoporosis. Disclosure of Interests: None declared
Should Society Allow Research Ethics Boards to Be Run As For-Profit Enterprises?
Authors: Ezekiel J Emanuel, Trudo Lemmens, Carl Elliot
Journal: PLoS Medicine (2006)

An important mechanism for protecting human research participants is the prior approval of a clinical study by a research ethics board, known in the United States as an institutional review board (IRB). Traditionally, IRBs have been run by volunteer committees of scientists and clinicians working in the academic medical centers where the studies they review are being carried out. However, for-profit organizations are increasingly being hired to conduct ethics reviews. Proponents of for-profit IRBs argue that these IRBs are just as capable as academic IRBs at providing high-quality ethics reviews. Critics argue that for-profit IRBs have a conflict of interest because they generate their income from clients who have a direct financial interest in obtaining approval.
Associations of Skeletal Muscle With Symptom Burden and Clinical Outcomes in Hospitalized Patients With Advanced Cancer
Authors: Emily van Seventer, J. Peter Marquardt, Amelie S. Troschel, Till D. Best, Nora Horick, Chinenye Azoba, Richard Newcomb, Eric J. Roeland, Michael Rosenthal, Christopher P. Bridge, Joseph A. Greer, Areej El-Jawahri, Jennifer Temel, Florian J. Fintelmann, Ryan D. Nipp
Journal: Journal of the National Comprehensive Cancer Network (2021)

Low muscle mass (quantity) is common in patients with advanced cancer, but little is known about muscle radiodensity (quality). We sought to describe the associations of muscle mass and radiodensity with symptom burden, healthcare use, and survival in hospitalized patients with advanced cancer.We prospectively enrolled hospitalized patients with advanced cancer from September 2014 through May 2016. Upon admission, patients reported their physical (Edmonton Symptom Assessment System [ESAS]) and psychological (Patient Health Questionnaire-4 [PHQ-4]) symptoms. We used CT scans performed per routine care within 45 days before enrollment to evaluate muscle mass and radiodensity. We used regression models to examine associations of muscle mass and radiodensity with patients' symptom burden, healthcare use (hospital length of stay and readmissions), and survival.Of 1,121 patients enrolled, 677 had evaluable muscle data on CT (mean age, 62.86 ± 12.95 years; 51.1% female). Older age and female sex were associated with lower muscle mass (age: B, -0.16; P<.001; female: B, -6.89; P<.001) and radiodensity (age: B, -0.33; P<.001; female: B, -1.66; P=.014), and higher BMI was associated with higher muscle mass (B, 0.58; P<.001) and lower radiodensity (B, -0.61; P<.001). Higher muscle mass was significantly associated with improved survival (hazard ratio, 0.97; P<.001). Notably, higher muscle radiodensity was significantly associated with lower ESAS-Physical (B, -0.17; P=.016), ESAS-Total (B, -0.29; P=.002), PHQ-4-Depression (B, -0.03; P=.006), and PHQ-4-Anxiety (B, -0.03; P=.008) symptoms, as well as decreased hospital length of stay (B, -0.07; P=.005), risk of readmission or death in 90 days (odds ratio, 0.97; P<.001), and improved survival (hazard ratio, 0.97; P<.001).Although muscle mass (quantity) only correlated with survival, we found that muscle radiodensity (quality) was associated with patients' symptoms, healthcare use, and survival. These findings underscore the added importance of assessing muscle quality when seeking to address adverse muscle changes in oncology.
Genetic Insights into Alzheimer's Disease
Authors: Caitlin S. Latimer, Katherine L. Lucot, C. Dirk Keene, Brenna Cholerton, Thomas J. Montine
Journal: Annual Review of Pathology Mechanisms of Disease (2021)

Alzheimer's disease (AD) is a pervasive, relentlessly progressive neurodegenerative disorder that includes both hereditary and sporadic forms linked by common underlying neuropathologic changes and neuropsychological manifestations. While a clinical diagnosis is often made on the basis of initial memory dysfunction that progresses to involve multiple cognitive domains, definitive diagnosis requires autopsy examination of the brain to identify amyloid plaques and neurofibrillary degeneration. Over the past 100 years, there has been remarkable progress in our understanding of the underlying pathophysiologic processes, pathologic changes, and clinical phenotypes of AD, largely because genetic pathways that include but expand beyond amyloid processing have been uncovered. This review discusses the current state of understanding of the genetics of AD with a focus on how these advances are both shaping our understanding of the disease and informing novel avenues and approaches for development of potential therapeutic targets.
Abstract 13461: Severe, but Not Mild Decreases in Nicotinamide Adenine Dinucleotide (NAD) Cause Heart Failure
Authors: Timothy S Luongo, Lin Wang, Karthikeyani Chellappa, Melanie R McReynolds, Daniel P Kelly, Joshua D Rabinowitz, Joseph A Baur
Journal: Circulation (2019)

Nicotinamide adenine dinucleotide (NAD) plays essential roles in energy metabolism and cell signaling pathways. NAD functions as a coenzyme by accepting electrons during glycolysis and the TCA cycl...
THU0003 Altered gene expression in rheumatoid arthritis synovial fibroblasts after few culture passages
Authors: U Müller-Ladner, E Neumann, M Judex, F Kullmann, J Grifka, K Masuda, S Gay, J Schölmerich
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> Inflammation, synovial hyperplasia and articular destruction are typical features of rheumatoid arthritis (RA) pathophysiology modulated by activated synovial fibroblasts. To evaluate distinct metabolic pathways and gene expression, for the majority of experimental settings cultured RA synovial fibroblasts derived from synovial tissue samples are used. To analyse, whether RA synovial fibroblasts can be cultured for an extended period of time without changes in their gene expression pattern, a combination of RNA arbitrarily primed PCR (RAP-PCR) and cDNA array was used. <h3>Methods</h3> RA synovial fibroblasts of 2 patients with RA were isolated and cultured under standard conditions for up to 9 passages. RNA was extracted from these cells after each of the passages 2–9. RAP-PCR was performed and the PCR reactions were hybridised to cDNA expression array membranes (Atlas™, Clontech). For gene expression analysis, cDNA expression array membranes with 190 tumour suppressor genes and oncogenes and 9 control genes were used. The gene expression pattern of RA samples after each passage was compared to the pattern of the previous and following passages. <h3>Results</h3> RA synovial fibroblasts showed a stable cDNA expression pattern for passages 2 to 4. After passages 5 to 6, expression pattern started to change (approximately 5% of the expressed genes). After passages 7 to 8, expression pattern of more than 5% of the 190 analysed tumour suppressor genes and oncogenes were altered. Of these, oncogene (e.g. bcl-1) and tumour suppressor-associated gene (e.g. EB-1 and CDK tyrosine kinase) expression had changed. Of interest, cell proliferation and growth decreased after passages 6 to 7 but distinct oncogenes and tumour-suppressor genes (e.g. jun-B and bcl-1) were still found to be upregulated. <h3>Conclusion</h3> The results of this study reveal that gene expression of cultured RA synovial fibroblasts starts to alter after few passages indicating that future experimental settings need to address this potential problem for interpretation of gene expression. In addition, the data support the hypothesis that lack of downregulation of oncogenes and tumour suppressor genes might be responsible for the long-term aggressive growth of RA synovial fibroblasts observed in RA joints.
Association of Race/Ethnicity and Other Demographic Characteristics With Use of Physical Restraints in the Emergency Department
Authors: Ambrose H. Wong, Travis Whitfill, Emmanuel C. Ohuabunwa, Jessica M. Ray, James D. Dziura, Steven L. Bernstein, Richard Andrew Taylor
Journal: JAMA Network Open (2021)

This cross-sectional study assesses the association of race/ethnicity and other demographic factors with risk of receiving physical restraint during an emergency department (ED) visit.
siRNA Therapeutics against Respiratory Viral Infections—What Have We Learned for Potential COVID‐19 Therapies?
Authors: Aditi Mehta, Thomas Michler, Olivia M. Merkel
Journal: Advanced Healthcare Materials (2021)

Abstract Acute viral respiratory tract infections (AVRIs) are a major burden on human health and global economy and amongst the top five causes of death worldwide resulting in an estimated 3.9 million lives lost every year. In addition, new emerging respiratory viruses regularly cause outbreaks such as SARS‐CoV‐1 in 2003, the "Swine flu" in 2009, or most importantly the ongoing SARS‐CoV‐2 pandemic, which intensely impact global health, social life, and economy. Despite the prevalence of AVRIs and an urgent need, no vaccines—except for influenza—or effective treatments were available at the beginning of the COVID‐19 pandemic. However, the innate RNAi pathway offers the ability to develop nucleic acid‐based antiviral drugs. siRNA sequences against conserved, essential regions of the viral genome can prevent viral replication. In addition, viral infection can be averted prophylactically by silencing host genes essential for host–viral interactions. Unfortunately, delivering siRNAs to their target cells and intracellular site of action remains the principle hurdle toward their therapeutic use. Currently, siRNA formulations and chemical modifications are evaluated for their delivery. This progress report discusses the selection of antiviral siRNA sequences, delivery techniques to the infection sites, and provides an overview of antiviral siRNAs against respiratory viruses.
AB0260 SARCOPENIA AND RHEUMATOID ARTHRITIS
Authors: V. Povoroznyuk, N. Dzerovych, O. Ivanyk, T. Karasevska
Journal: Annals of the Rheumatic Diseases (2020)

Background: Nowadays in the field of syndromes and diseases associated with age, scientists focus especial attention on the problem of sarcopenia, which combines an increased risk of falls, deterioration of life quality, impaired functional activity, reduced life expectancy and increased mortality of patients. In 2016, sarcopenia has been included in the International Classification of Diseases. There are the primary and secondary forms of sarcopenia. Objectives: The aim of this study was to evaluate the bone mineral density, lean mass, frequency of pre-sarcopenia and analyze correlation among the activity parameters, duration of the disease, life quality and lean mass indices in women with rheumatoid arthritis. Methods: 461 women aged 40-87 years (age - 57.17 ± 0.71 years) were examined, among them 71 patients with rheumatoid arthritis and 390 controls. We conducted the clinical and laboratory examination. Pain intensity was evaluated by the visual analogue scale, the quality of life – by the HAQ questionnaire. Lean mass, bone mineral density were measured by the X-ray absorptiometry (Prodigy, GEHC Lunar, Madison, WI, USA). Pre-sarcopenia was determined when an appendicular lean mass index was less than 5.72 kg/m2 (V. Povoroznyuk, N. Dzerovych, 2016). Results: Patients with rheumatoid arthritis had a significantly lower femoral neck mineral density (p = 0.002), lean mass of the total body (p = 0.01) and appendicular lean mass (p &lt;0.01). We didn’t find any significant connection among the activity parameters (C-reactive protein, ESR, pain VAS, DAS-28), duration of the disease, life quality and lean mass indices in patients with rheumatoid arthritis. However, a significant correlation was found between the number of swollen joints and lean mass of upper limbs (r=0.67; р=0.02).The frequency of pre-sarcopenia in women with rheumatoid arthritis was 49 %, in the control group – 18 %. Conclusion: Patients with rheumatoid arthritis had not only bone tissue, but also skeletal muscle tissue disorders, resulting in a significant deterioration of functional capacity and quality of life. Given the significant medical and social significance of the problem, further studies into the mechanisms of pathogenesis, development of diagnostic methods, prevention and treatment of sarcopenia in patients with rheumatoid arthritis are required. Disclosure of Interests: None declared
A comprehensive enhancer screen identifies TRAM2 as a key and novel mediator of YAP oncogenesis
Authors: Li Li, Alejandro P. Ugalde, Colinda L. G. J. Scheele, Sebastian M. Dieter, Remco Nagel, Jin Ma, Abhijeet Pataskar, Gozde Korkmaz, Ran Elkon, Miao-Ping Chien, Li You, Pin-Rui Su, Onno B. Bleijerveld, Maarten Altelaar, Lyubomir Momchev, Zohar Manber, Ruiqi Han, Pieter C. van Breugel, Rui Lopes, Peter ten Dijke, Jacco van Rheenen, Reuven Agami
Journal: Genome biology (2021)

Frequent activation of the co-transcriptional factor YAP is observed in a large number of solid tumors. Activated YAP associates with enhancer loci via TEAD4-DNA-binding protein and stimulates cancer aggressiveness. Although thousands of YAP/TEAD4 binding-sites are annotated, their functional importance is unknown. Here, we aim at further identification of enhancer elements that are required for YAP functions.We first apply genome-wide ChIP profiling of YAP to systematically identify enhancers that are bound by YAP/TEAD4. Next, we implement a genetic approach to uncover functions of YAP/TEAD4-associated enhancers, demonstrate its robustness, and use it to reveal a network of enhancers required for YAP-mediated proliferation. We focus on EnhancerTRAM2, as its target gene TRAM2 shows the strongest expression-correlation with YAP activity in nearly all tumor types. Interestingly, TRAM2 phenocopies the YAP-induced cell proliferation, migration, and invasion phenotypes and correlates with poor patient survival. Mechanistically, we identify FSTL-1 as a major direct client of TRAM2 that is involved in these phenotypes. Thus, TRAM2 is a key novel mediator of YAP-induced oncogenic proliferation and cellular invasiveness.YAP is a transcription co-factor that binds to thousands of enhancer loci and stimulates tumor aggressiveness. Using unbiased functional approaches, we dissect YAP enhancer network and characterize TRAM2 as a novel mediator of cellular proliferation, migration, and invasion. Our findings elucidate how YAP induces cancer aggressiveness and may assist diagnosis of cancer metastasis.
Next-generation sequencing analysis suggests varied multistep mutational pathogenesis for endocrine mucin-producing sweat gland carcinoma with comments on INSM1 and MUC2 suggesting a conjunctival origin
Authors: Joseph G. Mathew, Anita S. Bowman, Jad Saab, Klaus J. Busam, Kishwer Nehal, Melissa Pulitzer
Journal: Journal of the American Academy of Dermatology (2021)
Implication of PIGA genotype on erythrocytes phenotype in Paroxysmal Nocturnal Hemoglobinuria
Authors: Carmelo Gurnari, Simona Pagliuca, Bhumika J. Patel, Hassan Awada, Sunisa Kongkiatkamon, Laila Terkawi, Misam Zawit, Seth Corey, Alan E. Lichtin, Hetty E. Carraway, Adam Wahida, Valeria Visconte, Jaroslaw P. Maciejewski
Journal: Leukemia (2021)
ggtreeExtra: Compact Visualization of Richly Annotated Phylogenetic Data
Authors: Shuangbin Xu, Zehan Dai, Pingfan Guo, Xiaocong Fu, Shanshan Liu, Lang Zhou, Wenli Tang, Tingze Feng, Meijun Chen, Li Zhan, Tianzhi Wu, Erqiang Hu, Yong Jiang, Xiaochen Bo, Guangchuang Yu
Journal: Molecular Biology and Evolution (2021)

Abstract We present the ggtreeExtra package for visualizing heterogeneous data with a phylogenetic tree in a circular or rectangular layout (https://www.bioconductor.org/packages/ggtreeExtra). The package supports more data types and visualization methods than other tools. It supports using the grammar of graphics syntax to present data on a tree with richly annotated layers and allows evolutionary statistics inferred by commonly used software to be integrated and visualized with external data. GgtreeExtra is a universal tool for tree data visualization. It extends the applications of the phylogenetic tree in different disciplines by making more domain-specific data to be available to visualize and interpret in the evolutionary context.
Supporting every school to become a foundation for healthy lives
Authors: Didier Jourdan, Nicola J Gray, Margaret M Barry, Sonja Caffe, Christophe Cornu, Fatou Diagne, Fadi El Hage, Mychelle Y Farmer, Sean Slade, Michael Marmot, Susan M Sawyer
Journal: The Lancet Child & Adolescent Health (2021)