tbuckley/cabot-search huggingface dataset:
Air Pollution as a Risk Factor for Incident Chronic Obstructive Pulmonary Disease and Asthma. A 15-Year Population-based Cohort Study
Authors: Saeha Shin, Li Bai, Richard T. Burnett, Jeffrey C. Kwong, Perry Hystad, Aaron van Donkelaar, Eric Lavigne, Scott Weichenthal, Ray Copes, Randall V. Martin, Alexander Kopp, Hong Chen
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Current evidence on the relationship between long-term exposure to air pollution and new onset of chronic lung disease is inconclusive.Objectives: To examine associations of incident chronic obstructive pulmonary disease (COPD) and adult-onset asthma with past exposure to fine particulate matter ≤ 2.5 μm in diameter (PM2.5), nitrogen dioxide (NO2), ozone (O3), and the redox-weighted average of NO2 and O3 (Ox) and characterize the concentration-response relationship.Methods: We conducted a population-based cohort study of all Ontarians, aged 35-85 years, from 2001 to 2015. A 3-year moving average of residential exposures to selected pollutants with a 1-year lag were estimated during follow-up. We used Cox proportional hazard models and Aalen additive-hazard models to quantify the pollution-disease associations and characterized the shape of these relationships using newly developed nonlinear risk models.Measurements and Main Results: Among 5.1 million adults, we identified 340,733 and 218,005 incident cases of COPD and asthma, respectively. We found positive associations of COPD with PM2.5 per interquartile-range (IQR) increase of 3.4 μg/m3 (hazard ratio, 1.07; 95% confidence interval, 1.06-1.08), NO2 per IQR increase of 13.9 ppb (1.04; 1.02-1.05), O3 per IQR increase of 6.3 ppb (1.04; 1.03-1.04), and Ox per IQR increase of 4.4 ppb (1.03; 1.03-1.03). By contrast, we did not find strong evidence linking these pollutants to adult-onset asthma. In addition, we quantified that each IQR increase in pollution exposure yielded 3.0 (2.4-3.6), 3.2 (2.0-4.3), 1.9 (1.3-2.5), and 2.3 (1.7-2.9) excess cases of COPD per 100,000 adults for PM2.5, NO2, O3, and Ox, respectively. Furthermore, most pollutant-COPD relationships exhibited supralinear shapes.Conclusions: Air pollution was associated with a higher incidence of COPD but was not associated with a higher incidence of adult-onset asthma.
HM43239, a Novel Small Molecule Inhibitor of FLT3, in Acute Myeloid Leukemia (AML) with and without FMS-like Tyrosine Kinase 3 (FLT3) Mutations: Phase 1/2 Study
Authors: Naval Daver, Kyoo Hyung Lee, Chul Won Jung, Yoon Sung Soo, Martha L. Arellano, Brian A Jonas, Jiyeon Yoon, Sooa Jung, Young Su Noh, Inhwan Bae, Song Kim
Journal: Blood (2020)
Abstract 219: NAD Redox Imbalance Accelerates Diabetic Cardiomyopathy via Protein Acetylation and Oxidative Stress
Authors: Ying Ann Chiao, Christine Light, Xiaojian Shi, Rong Tian, Junichi Sadoshima, Haiwei Gu, Chi Fung Lee
Journal: Circulation Research (2020)

Diabetes is long linked to lowered NAD/NADH ratio, aka NAD redox imbalance, but its causal role to diabetic cardiomyopathy is not established. We used mouse models with latent decrease in cardiac NAD/NADH ratio (cardiac-specific Ndufs4-KO, cKO) and elevated cardiac NAD levels to directly test whether cardiac NAD redox imbalance accelerates diabetic cardiomyopathy. Control and cKO mice were subjected to 8-week T1D stress, and longitudinal cardiac function was measured by echocardiography. Accelerated declines in systolic and diastolic function were observed in T1D cKO mice. Insulin depletion and hyperglycemia were similar in T1D control and T1D cKO mice, and serum metabolomic analyses showed unchanged aqueous and lipid metabolite levels. These metabolite results suggested that T1D control and cKO hearts were stressed under similar diabetic conditions. Importantly, elevation of cardiac NAD levels to attenuate NAD redox imbalance mitigated the accelerated functional declines in T1D cKO hearts. The data from mouse models with manipulated NAD redox states suggested that NAD redox imbalance accelerates diabetic cardiomyopathy. Cardiac fibrosis levels were not different in T1D control and cKO hearts, while transcript levels of fibrotic genes, including Adamts proteinases, integrins, laminins, matrix metalloproteinases and collagens, also showed no difference. Therefore, the accelerated functional declines in T1D cKO hearts are not due to altered extracellular matrix environment, but are rather due to cardiomyocyte dysfunction. We next determined whether the accelerated cardiac dysfunction is mediated via protein acetylation and oxidative stress. NAD-dependent global protein acetylation and inhibitory acetylation of superoxide dismutase 2 were elevated in T1D cKO hearts. Inhibition of SOD2 concomitantly promoted elevation of protein oxidation levels in T1D cKO hearts. The results suggested that NAD redox balance-dependent protein acetylation regulates oxidative stress to promote diabetic cardiomyopathy.
Defining remission of type 2 diabetes in research studies: A systematic scoping review
Authors: Mireille Captieux, Regina Prigge, Sarah Wild, Bruce Guthrie
Journal: PLoS Medicine (2020)

Background Remission has been identified as a top priority by people with type 2 diabetes. Remission is commonly used as an outcome in research studies; however, a widely accepted definition of remission of type 2 diabetes is lacking. A report on defining remission was published (but not formally endorsed) in Diabetes Care, an American Diabetes Association (ADA) journal. This Diabetes Care report remains widely used. It was the first to suggest 3 components necessary to define the presence of remission: (1) absence of glucose-lowering therapy (GLT); (2) normoglycaemia; and (3) for duration ≥1 year. Our aim is to systematically review how remission of type 2 diabetes has been defined by observational and interventional studies since publication of the 2009 report. Methods and findings Four databases (MEDLINE, EMBASE, Cochrane Library, and CINAHL) were searched for studies published from 1 September 2009 to 18 July 2020 involving at least 100 participants with type 2 diabetes in their remission analysis, which examined an outcome of type 2 diabetes remission in adults ≥18 years and which had been published in English since 2009. Remission definitions were extracted and categorised by glucose-lowering therapy, glycaemic thresholds, and duration. A total of 8,966 titles/abstracts were screened, and 178 studies (165 observational and 13 interventional) from 33 countries were included. These contributed 266 definitions, of which 96 were unique. The 2009 report was referenced in 121 (45%) definitions. In total, 247 (93%) definitions required the absence of GLT, and 232 (87%) definitions specified numeric glycaemic thresholds. The most frequently used threshold was HbA1c<42 mmol/mol (6.0%) in 47 (20%) definitions. Time was frequently omitted. In this study, a total of 104 (39%) definitions defined time as a duration. The main limitations of this systematic review lie in the restriction to published studies written in English with sample sizes of over 100. Grey literature was not included in the search. Conclusions We found that there is substantial heterogeneity in the definition of type 2 diabetes remission in research studies published since 2009, at least partly reflecting ambiguity in the 2009 report. This complicates interpretation of previous research on remission of type 2 diabetes and the implications for people with type 2 diabetes. Any new consensus definition of remission should include unambiguous glycaemic thresholds and emphasise duration. Until an international consensus is reached, studies describing remission should clearly define all 3 components of remission. Systematic review registration PROSPERO CRD42019144619
Integrated Cytof, Scrna-Seq and Cite-Seq Analysis of Bone Marrow Immune Microenvironment in the Mmrf Commpass Study
Authors: Lijun Yao, Reyka G Jayasinghe, Beena E Thomas, Swati S Bhasin, Nicolas Fernandez, Taxiarchis Kourelis, Deon Doxie, David E. Avigan, Madhav V. Dhodapkar, Shaji K. Kumar, Ravi Vij, Shaadi Mehr, Mark Hamilton, Hearn Jay Cho, Daniel Auclair, Sacha Gnjatic, Manoj Bhasin, Li Ding
Journal: Blood (2020)
Selinexor in Combination with R-CHOP for Frontline Treatment of Non-Hodgkin Lymphoma: Results of a Phase 1b Study
Authors: Erlene K. Seymour, Yiwei Li, Amro Aboukameel, Radhakrishnan Ramchandren, Golbon Sterbis, Jay Yang, Divaya Bhutani, Ramzi Mohammad, Asfar Sohail Azmi, Jeff Zonder
Journal: Blood (2020)
AB0946 PARTICULARITY OF MULTIFOCAL INFECTIOUS SPONDYLODISCITIS
Authors: S. Miladi, K. Saadaoui, A. Fazaa, S. Mariem, K. Ouenniche, L. Souabni, S. Kassab, S. Chkili, L. Zakraoui, A. Laatar
Journal: Annals of the Rheumatic Diseases (2020)

Background: Infectious spondylodiscitis is an infection of the intervertebral disc with damage to the vertebrae. Multiple stage involvement may lead to serious complications. Better understand of this infection is mandatory for optimal management. Objectives: The objective of our study was to describe the clinical, biological aspects and the course of this disease. Methods: This is a retrospective study including cases of infectious spondylodiscitis collected in a single rheumatology center between 2002 and 2018. Multi focal spondylodiscitis was defined as an attainment of 2 or more disc levels. Clinical, biological and evolution of this disease were reported. Results: Among the 52 cases of infectious spondylodiscitis collected, thirteen patients had multi-stage involvement of the spine. The sex ratio M/F in this group = 0.44 with an average age of 52 ± 14.32 years [31 – 76 years]. Diabetes mellitus was observed in 3 patients, chronic renal failure in one case and immunosuppressive therapy in one case. At the moment of the diagnosis, inflammatory back pain was present in all patients, fever was noted in 8 patients (61.5%), neurological deficit in 2 patients (15.4%) and weight loss in 4 cases (30.8%). The diagnosis time delay was 22 ± 15.9 weeks [2 – 60 weeks]. The mean CRP was 70.16 mg / L ± 55.5 [3.4 - 178] and the ESR was on average 79 mm ± 31.28 [6 - 125]. Diagnosis was confirmed by MRI in all cases. A prevertebral abscess was observed in 7 cases (%), an epiduritis in 5 patients (38.5%) and a psoas abscess in two cases (15.2%). The cervical spine was affected in 3 cases, the dorsal spine as well as the lumbar spine were affected in 12 cases. The involvment of 2 vertebral sites was the most frequent with 7 cases. A maximum of 5 site was noted in 3 cases. The thoracolumbar spine was the most affected with 11 cases (84.6%), the cervico-thoraco-lumbar involvement was found in only one case (7.7%). The bacteriological diagnosis was done by the disco-vertebral biopsy in 6 cases (46.2%), the brucellar serology in 3 cases (26.1%) and a strong presumption of tuberculosis (with positive IDR or Quantiferon) in 4 cases (30.8%). Mycobaterium tuberculosis was isolated in 8 patients (61.5%), brucella melitensis in 3 patients (23.1%) and staphylococcus aureus was found in 2 cases (15.4%). The outcome was favorable in all patients with appropriate antibiotic therapy after an average follow-up of 10.9 months ± 2.19. Conclusion: Multifocal infectious spondylodiscitis is a serious disorder which mainly affects immunocompromised patients and the specific germs are the most incriminated. Disclosure of Interests: None declared
Elevated P21 (CDKN1a) Mediates Apoptosis of Beta-Thalassemic Erythroid Cells in Mice but Its Ablation Doesn't Improve Erythroid Maturation
Authors: Miao Lin, Vijay Menon, Raymond Liang, Tasleem Arif, Laura Breda, Stefano Rivella, Saghi Ghaffari
Journal: Blood (2020)
Phase 2 Study of Zanubrutinib in Patients with Relapsed/Refractory B-Cell Malignancies Intolerant to Ibrutinib/Acalabrutinib
Authors: Mazyar Shadman, Jeff P Sharman, Moshe Y. Levy, Jamal Misleh, Syed F. Zafar, Benjamin B. Freeman, John M. Burke, Jennifer L. Cultrera, Habte A. Yimer, Dih-Yih Chen, Xiaoping Zhang, Aileen Cohen, Sunhee Ro, Jane Huang, Ian W. Flinn
Journal: Blood (2020)
Abstract 359: Cardiac-specific Deletion of Prohibitin-1 Leads to Fetal Demise, Gross Mitochondrial Abnormalities and Heart Failure in Adolescent Mice
Authors: Ran Huo, Kathy Zimmerman, Robert M Weiss, Noelle C Bowdler, Ethan J Anderson
Journal: Circulation Research (2020)

Prohibitins (PHB1, 2) are lipid raft-associated proteins which form a multimeric, alternating ring-like structure in cellular membranes, and are particularly abundant in mitochondria and plasma membranes, but have also been found in nuclei. These pleiotropic proteins are associated with numerous signaling pathways responsible for cell differentiation, growth, and metabolism. In mitochondria, PHBs are thought to act as scaffold-like chaperone proteins responsible for stabilizing enzymes responsible for electron transport and oxidative phosphorylation (OXPHOS), minimizing reactive oxygen species (ROS), and coordinating fission/fusion. However, the extent to which PHB1 regulates mitochondria and electromechanical function of the heart, is not known. We established a cardiac-specific PHB1-deficient mouse strain by crossing floxxed phb1 mice with mice expressing Cre recombinase under control of myosin heavy chain (MHC) promoter. The vast majority of cardiac-specific PHB1-deficient mice (cPHB1ko) died in utero during pregnancy (E12-E15). Uterine sonography of the expired cPHB1ko embryos showed significantly decreased crown-rump length and increased placenta thickness with large amount of fluids, restricted uterine artery flow and detachment between amnion and chorion compared with normal embryos (P &lt; 0.001). The few that were born develop severe dilated cardiomyopathy, resulting in mortality by 8-9 weeks of age. Heart weight/body weight ratio is ~2-fold greater in the KO mice vs. WT. Echocardiography reveals severely enlarged right atria and ventricles in cPHB1ko mice, corresponding to significantly decreased ejection faction (EF), increased end diastolic volume (EDV) and end systolic volume (ESV) compared to wild-type littermates (P &lt; 0.05). In mitochondria, cPHB1ko mice have derangements in OXPHOS as evidenced by decreased pyruvate and palmitoylcarnitine-supported respiration and ATP production. Moreover, both the rate of calcium uptake (P = 0.05) and the total calcium retention capacity (P &lt; 0.01) were diminished in the KO mice. These preliminary findings implicate PHB1 as a critical regulator of myocardial development and function, due in part to its role in maintaining OXPHOS and controlling metabolism.
Grading Chromophobe Renal Cell Carcinoma: Evidence for a Four-tiered Classification Incorporating Coagulative Tumor Necrosis
Authors: Svetlana Avulova, John C. Cheville, Christine M. Lohse, Sounak Gupta, Theodora A. Potretzke, Matvey Tsivian, R. Houston Thompson, Stephen A. Boorjian, Bradley C. Leibovich, Aaron M. Potretzke
Journal: European Urology (2020)
Abstract 468: Previously Unrecognized Intronic Variants in the Dystrophin Gene Identified as Possible Contributors to Dilated Cardiomyopathy
Authors: Alex Gyftopoulos, Tamara Ashvetiya, Yi-Ju Chen, Libin Wang, Charles H Williams, Young Wook Chun, James A Perry, Charles C Hong
Journal: Circulation Research (2020)

Nonischemic dilated cardiomyopathy (DCM) often has a genetic etiology, however, its prevalence and etiologies are not completely understood. The UK Biobank comprises clinical and genetic data for greater than 500,000 individuals with enrollees 40-69 years of age. Our group created a custom phenotype of heart failure using ICD-10 codes for several subtypes of heart failure diagnoses including DCM. We then compared the individuals included in the custom heart failure phenotype to control individuals in a 20-to-1 fashion to identify genetic differences. Data were compared using Mixed Model Analysis for Pedigrees/Populations (MMAP) mixed-model regression. We identified 8 unlinked intronic variants in the dystrophin gene ( DMD ) that, when separated by self-identified race, occurred with a combined minor allele frequency of 0.15 in individuals with heart failure who identified as being of African descent. The combined minor allele frequency of these variants was 0.05 in individuals who self-identified as being of European descent. One variant of DMD in particular (rs139029250), was identified with a minor allele frequency of 0.05 in African British with DCM. The unadjusted odds ratio of a diagnosis of heart failure in individuals with rs129029250 was 4.65. When separated by gender, the unadjusted odds ratios are 2.02 for females and 6.44 for males. DMD is most notably known for its role in Duchenne and Becker muscular dystrophy, both of which are known to cause dilated cardiomyopathy in affected individuals. However, none of the individuals (36 female and 43 male) identified in our analysis with rs129029250 have been diagnosed with Duchenne muscular dystrophy, Becker muscular dystrophy, or a primary disorder of muscle (ICD code G70). Additionally, these individuals have an intronic variant of DMD , while Duchene and Becker muscular dystrophy are both due to exonic mutations. These findings suggest a possible common variant in the DMD gene that may contribute to DCM in individuals of African descent.
Clinical Features of Myelodisplastic Syndromes in a Colombian Population: Retrospective Analysis of Two Large Referral Centers
Authors: Claudia Lucia Sossa, Virginia Abello, Angela María Peña, Luis Antonio Salazar, Manuel Rosales, Maria Luna-Gonzalez, Claudia Marcela Chalela, David Leonardo Reyes, Katherine Espinosa, María Alejandra Amaya, Nestor Gamboa-Cely, Luisa Sanchez-Sossa, Sergio Serrano, Daniel Espinosa, Claudia Patricia Casas, Sara Ines Jimenez, Jose Sandoval-Sus, Carlos Alberto Orozco Oviedo, Xueyi Chen, Maria Helena Solano
Journal: Blood (2020)
Exposure-Response (E-R) for Ocular Safety Endpoints for Belantamab Mafodotin (Belamaf), a B-Cell Maturation Antigen (BCMA)-Targeting Agent, in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) in the DREAMM-2 Study
Authors: Geraldine Ferron-Brady, Chetan Rathi, Jon Collins, Herbert Struemper, Joanna Opalinska, Roxanne C Jewell
Journal: Blood (2020)
Anti-CD20-Mediated B Cell Depletion Is Associated with Reduced Osteoclastogenic Signals and Bone Mass Preservation: Clinical Observation in Patients with Follicular Lymphoma Supplemented By Animal Studies in a Murine Model
Authors: Albert Kolomansky, Irit Kay, Nathalie Ben-Califa, Anton Gorodov, Zamzam Awida, Ofer Sadovnic, Maria Ibrahim, Tamar Liron, Sahar Hiram-Bab, Howard S. Oster, Nadav Sarid, Chava Perry, Yankel Gabet, Moshe Mittelman, Drorit Neumann
Journal: Blood (2020)
Laboratory Findings Associated With Severe Illness and Mortality Among Hospitalized Individuals With Coronavirus Disease 2019 in Eastern Massachusetts
Authors: Victor M. Castro, Thomas H. McCoy, Roy H. Perlis
Journal: JAMA Network Open (2020)

<h3>Importance</h3> The coronavirus disease 2019 (COVID-19) pandemic has placed unprecedented stress on health systems across the world, and reliable estimates of risk for adverse hospital outcomes are needed. <h3>Objective</h3> To quantify admission laboratory and comorbidity features associated with critical illness and mortality risk across 6 Eastern Massachusetts hospitals. <h3>Design, Setting, and Participants</h3> Retrospective cohort study of all individuals admitted to the hospital who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by polymerase chain reaction across these 6 hospitals through June 5, 2020, using hospital course, prior diagnoses, and laboratory values in emergency department and inpatient settings from 2 academic medical centers and 4 community hospitals. The data were extracted on June 11, 2020, and the analysis was conducted from June to July 2020. <h3>Exposures</h3> SARS-CoV-2. <h3>Main Outcomes and Measures</h3> Severe illness defined by admission to intensive care unit, mechanical ventilation, or death. <h3>Results</h3> Of 2511 hospitalized individuals who tested positive for SARS-CoV-2 (of whom 50.9% were male, 53.9% White, and 27.0% Hispanic, with a mean [SD ]age of 62.6 [19.0] years), 215 (8.6%) were admitted to the intensive care unit, 164 (6.5%) required mechanical ventilation, and 292 (11.6%) died. L1-regression models developed in 3 of these hospitals yielded an area under the receiver operating characteristic curve of 0.807 for severe illness and 0.847 for mortality in the 3 held-out hospitals. In total, 212 of 292 deaths (72.6%) occurred in the highest-risk mortality quintile. <h3>Conclusions and Relevance</h3> In this cohort, specific admission laboratory studies in concert with sociodemographic features and prior diagnosis facilitated risk stratification among individuals hospitalized for COVID-19.
Phospho-Proteomic Profiling of T-Cell Acute Lymphoblastic Leukemia Identifies Targetable Kinase Activities and Novel Treatment Combination Strategies
Authors: Valentina Cordo', Rico Hagelaar, Sander Piersma, Richard Goeij-de Haas, Thang V Pham, Jelle Dylus, Guido Zaman, Connie Jimenez, Jules P.P. Meijerink
Journal: Blood (2020)
Polatuzumab Vedotin-Based Salvage Chemotherapy in the Third-Line or Above Treatment for Diffuse Large B-Cell Lymphoma
Authors: Cheng-Hong Tsai, Feng Ming Tien, Hsin-An Hou, Jia-Hau Liu, Shang-Ju Wu, Yu-Wen Wang, Chien-Chin Lin, Bor-Sheng Ko, Wen-Chien Chou, Yun-Chu Lin, Chieh-Lung Cheng, Li-Chun Lu, Sung-Hsin Kuo, Ruey-Long Hong, Tai-Chung Huang, Ming Yao
Journal: Blood (2020)
The cost-effectiveness profile of sex-neutral HPV immunisation in European tender-based settings: a model-based assessment
Authors: Venetia Qendri, Johannes A Bogaards, Iacopo Baussano, Fulvio Lazzarato, Simopekka Vänskä, Johannes Berkhof
Journal: The Lancet Public Health (2020)

In many European countries, human papillomavirus (HPV) vaccine uptake among girls has remained below target levels, supporting the scope for vaccination of boys. We aimed to investigate if sex-neutral HPV vaccination can be considered cost-effective compared with girls-only vaccination at uptake levels equal to those among girls and under tender-based vaccination costs achieved throughout Europe.
BAHCC1 binds H3K27me3 via a conserved BAH module to mediate gene silencing and oncogenesis
Authors: Huitao Fan, Jiuwei Lu, Yiran Guo, Dongxu Li, Zhi-Min Zhang, Yi-Hsuan Tsai, Wen-Chieh Pi, Jeong Hyun Ahn, Weida Gong, Yu Xiang, David F. Allison, Huimin Geng, Shenghui He, Yarui Diao, Wei-Yi Chen, Brian D. Strahl, Ling Cai, Jikui Song, Gang Greg Wang
Journal: Nature Genetics (2020)