tbuckley/cabot-search huggingface dataset:
MicroRNA-195 Regulates Metabolism in Failing Myocardium Via Alterations in Sirtuin 3 Expression and Mitochondrial Protein Acetylation
Authors: Xiaokan Zhang, Ruiping Ji, Xianghai Liao, Estibaliz Castillero, Peter J. Kennel, Danielle L. Brunjes, Marcus Franz, Sven Möbius-Winkler, Konstantinos Drosatos, Isaac George, Emily I. Chen, Paolo. C. Colombo, P. Christian Schulze
Journal: Circulation (2018)

Heart failure leads to mitochondrial dysfunction and metabolic abnormalities of the failing myocardium coupled with an energy-depleted state and cardiac remodeling. The mitochondrial deacetylase sirtuin 3 (SIRT3) plays a pivotal role in the maintenance of mitochondrial function through regulating the mitochondrial acetylome. It is interesting to note that unique cardiac and systemic microRNAs have been shown to play an important role in cardiac remodeling by modulating key signaling elements in the myocardium.Cellular signaling was analyzed in human cardiomyocyte-like AC16 cells, and acetylation levels in rodent models of SIRT3-/-and transgenic microRNA-195 (miR-195) overexpression were compared with wild type. Luciferase assays, Western blotting, immunoprecipitation assays, and echocardiographic analysis were performed. Enzymatic activities of pyruvate dehydrogenase (PDH) and ATP synthase were measured.In failing human myocardium, we observed induction of miR-195 along with decreased expression of the mitochondrial deacetylase SIRT3 that was associated with increased global protein acetylation. We further investigated the role of miR-195 in SIRT3-mediated metabolic processes and its impact on regulating enzymes involved in deacetylation. Proteomic analysis of the total acetylome showed increased overall acetylation, and specific lysine acetylation of 2 central mitochondrial metabolic enzymes, PDH and ATP synthase, as well. miR-195 downregulates SIRT3 expression through direct 3'-untranslated region targeting. Treatments with either sirtuin inhibitor nicotinamide, small interfering RNA-mediated SIRT3 knockdown or miR-195 overexpression enhanced acetylation of PDH complex and ATP synthase. This effect diminished PDH and ATP synthase activity and impaired mitochondrial respiration.SIRT3-/- and miR-195 transgenic mice consistently showed enhanced global protein acetylation, including PDH complex and ATP synthase, associated with decreased enzymatic activity.Altogether, these data suggest that increased levels of miR-195 in failing myocardium regulate a novel pathway that involves direct SIRT3 suppression and enzymatic inhibition via increased acetylation of PDH and ATP synthase that are essential for cardiac energy metabolism.
A Single Mutation Unlocks Cascading Exaptations in the Origin of a Potent Pitviper Neurotoxin
Authors: A Carl Whittington, Andrew J Mason, Darin R Rokyta
Journal: Molecular Biology and Evolution (2017)

Evolutionary innovations and complex phenotypes seemingly require an improbable amount of genetic change to evolve. Rattlesnakes display two dramatically different venom phenotypes. Type I venoms are hemorrhagic with low systemic toxicity and high expression of tissue-destroying snake venom metalloproteinases. Type II venoms are highly neurotoxic and lack snake venom metalloproteinase expression and associated hemorrhagic activity. This dichotomy hinges on Mojave toxin (MTx), a phospholipase A2 (PLA2) based β-neurotoxin expressed in Type II venoms. MTx is comprised of a nontoxic acidic subunit that undergoes extensive proteolytic processing and allosterically regulates activity of a neurotoxic basic subunit. Evolution of the acidic subunit presents an evolutionary challenge because the need for high expression of a nontoxic venom component and the proteolytic machinery required for processing suggests genetic changes of seemingly little immediate benefit to fitness. We showed that MTx evolved through a cascading series of exaptations unlocked by a single nucleotide change. The evolution of one new cleavage site in the acidic subunit unmasked buried cleavage sites already present in ancestral PLA2s, enabling proteolytic processing. Snake venom serine proteases, already present in the venom to disrupt prey hemostasis, possess the requisite specificities for MTx acidic subunit proteolysis. The dimerization interface between MTx subunits evolved by exploiting a latent, but masked, hydrophobic interaction between ancestral PLA2s. The evolution of MTx through exaptation of existing functional and structural features suggests complex phenotypes that depend on evolutionary innovations can arise from minimal genetic change enabled by prior evolution.
Risk Factors Of Severe Asthma Exacerbations: A Real World Study
Authors: K Verhamme, M Engelkes, M De Ridder, E Svensson, K Berencsi, D Prieto-Alhambra, C Giaquinto, F Lapi, G Picelli, N Boudiaf, F C Albers, S Cockle, E Bradford, R Suruki, P Rijnbeek, M Sturkenboom
Journal: American Journal of Respiratory and Critical Care Medicine (2016)
Sleeve Gastrectomy for Weight Loss
Authors: Nancy Puzziferri, Jaime P. Almandoz
Journal: JAMA (2018)

Paulina Salminen, MD, PhD; Mika Helmiö, MD; Jari Ovaska, MD, PhD; Anne Juuti, MD, PhD; Marja Leivonen, MD, PhD; Pipsa Peromaa-Haavisto, MD, PhD; Saija Hurme, MSc; Minna Soinio, MD, PhD; Pirjo Nuutila, MD, PhD; Mikael Victorzon, MD, PhD
Racial Differences in 21-Gene Recurrence Scores Among Patients With Hormone Receptor–Positive, Node-Negative Breast Cancer
Authors: Andreana N. Holowatyj, Michele L. Cote, Julie J. Ruterbusch, Kristina Ghanem, Ann G. Schwartz, Fawn D. Vigneau, David H. Gorski, Kristen S. Purrington
Journal: Journal of Clinical Oncology (2018)

Purpose The 21-gene recurrence score (RS) breast cancer assay is clinically used to quantify risk of 10-year distant recurrence by category (low, < 18; intermediate, 18 to 30; high, ≥ 31) for treatment management among women diagnosed with hormone receptor-positive, human epidermal growth factor receptor 2-negative, lymph node-negative breast cancer. Although non-Hispanic black (NHB) women have worse prognosis compared with non-Hispanic white (NHW) women, the equivalency of 21-gene RS across racial groups remains unknown. Patients and Methods Using the Metropolitan Detroit Cancer Surveillance System, we identified women who were diagnosed with hormone receptor-positive, human epidermal growth factor receptor 2-negative, lymph node-negative invasive breast cancer between 2010 and 2014. Multinomial logistic regression was used to quantify racial differences in 21-gene RS category. Results We identified 2,216 women (1,824 NHW and 392 NHB) with invasive breast cancer who met clinical guidelines for and underwent 21-gene RS testing. The mean RS was significantly higher in NHBs compared with NHWs (19.3 v 17.0, respectively; P = .0003), where NHBs were more likely to present with high-risk tumors compared with NHWs (14.8% v 8.3%, respectively; P = .0004). These differences were limited to patients younger than 65 years at diagnosis, among whom NHBs had significantly higher RS compared with NHWs (20 to 49 years: 23.6 v 17.3, respectively; P < .001 and 50 to 64 years: 19.6 v 17.4, respectively; P = .023). NHBs remained more likely to have high-risk tumors compared with NHWs after adjusting for age, clinical stage, tumor grade, and histology (odds ratio [OR], 1.75; 95% CI, 1.18 to 2.59). Conclusion NHBs who met clinical criteria for 21-gene RS testing had tumors with higher estimated risks of distant recurrence compared with NHWs. Further study is needed to elucidate whether differences in recurrence are observed for these women, which would have clinical implications for 21-gene RS calibration and treatment recommendations in NHB patients.
Systematic review of atopic dermatitis disease definition in studies using routinely collected health data
Authors: M.P. Dizon, A.M. Yu, R.K. Singh, J. Wan, M.-M. Chren, C. Flohr, J.I. Silverberg, D.J. Margolis, S.M. Langan, K. Abuabara
Journal: British Journal of Dermatology (2018)

Routinely collected electronic health data obtained for administrative and clinical purposes are increasingly used to study atopic dermatitis (AD). Methods for identifying AD patients in routinely collected electronic health data differ, and it is unknown how this might affect study results.To evaluate how patients with AD have been identified in studies using routinely collected electronic health data, to determine whether these methods were validated and to estimate how the method for identifying patients with AD affected variability in prevalence estimates.We systematically searched PubMed, Embase and Web of Science for studies using routinely collected electronic health data that reported on AD as a primary outcome. Studies of localized AD and other types of dermatitis were excluded. The protocol for this review was registered in PROSPERO (CRD42016037968).In total, 59 studies met eligibility criteria. Medical diagnosis codes for inclusion and exclusion, number of occasions of a code, type of provider associated with a code and prescription data were used to identify patients with AD. Only two studies described validation of their methods and no study reported on disease severity. Prevalence estimates ranged from 0·18% to 38·33% (median 4·91%) and up to threefold variation in prevalence was introduced by differences in the method for identifying patients with AD.This systematic review highlights the need for clear reporting of methods for identifying patients with AD in routinely collected electronic health data to allow for meaningful interpretation and comparison of results.
Circulating tumor cells as a prognostic factor in patients with small cell lung cancer.
Authors: Satoshi Igawa, Jiichiro Sasaki, Noriyuki Masuda
Journal: Journal of Clinical Oncology (2013)

7592 Background: Research on the detection of circulating tumor cells (CTCs) in peripheral blood is currently an important field of research. The aim of this study was to evaluate a new method of detecting CTCs in the peripheral blood of small cell lung cancer (SCLC) patients by using the telomerase-specific replication-selective adenovirus OBP-401. Methods: We prospectively enrolled 30 consecutive newly diagnosed SCLC patients who were being started on chemotherapy or chemoradiotherapy as the subjects of this study. We collected peripheral blood specimens from the SCLC patients and detected viable CTCs in them after incubation with a telomerase-specific, replication-selective, oncolytic adenoviral agent carrying the green fluorescent protein (GFP) gene. We also investigated whether the CTC count per 7.5 ml of peripheral venous blood was associated with the outcome of SCLC. Results: CTCs were detected in 96% of the patients (29 of the 30 patients). The group of 22 patients with a CTC count of &lt; 2 before treatment (baseline) had a significantly longer median survival time than the group of 8 patients with a CTC count of ≥ 2 before treatment (14.8 months and 3.9 months, respectively, P = 0.001). The results of a multivariate analysis showed that the baseline CTC count was an independent prognostic factor for survival (hazard ratio = 5.11, P = 0.038). Conclusions: CTCs in the peripheral blood of SCLC patients can be detected by the OBP-401assay, and based on the results of this study the CTC count before treatment appears to be a strong prognostic factor.
Chromogranin A is a Potent Prognostic Biomarker in Acute Heart Failure, and its Fragment Catestatin Regulates Cardiomyocyte Calcium Homeostasis by Camkii delta Inhibition
Authors: Anett Hellebo Ottesen, Cathrine R. Carlson, William E. Louch, Rune Forström Johansen, Mats Stridsberg, Hilde Jarstadmarken, Magnar Björas, Arne Didrik Hoiseth, Jon Brynildsen, Torbjorn Omland, Geir Christensen, Helge Rosjö
Journal: Circulation Research (2015)

Chromogranin A is a Potent Prognostic Biomarker in Acute Heart Failure, and its Fragment Catestatin Regulates Cardiomyocyte Calcium Homeostasis by Camkii delta Inhibition
KIR3DL2 expression in patients with adult T-cell lymphoma/leukaemia
Authors: C. Hurabielle, C. Leboeuf, C. Ram-Wolff, V. Meignin, J. Rivet, M.-D. Vignon-Pennamen, C. Bonnafous, H. Sicard, C. Fite, E. Raffoux, B. Arnulf, E. Oksenhendler, F. Sicre de Fontbrune, R. Peffault de Latour, G. Socié, J.-D. Bouaziz, C. Lebbé, A. Bensussan, A. Janin, M. Bagot, M. Battistella
Journal: British Journal of Dermatology (2018)
Associations between Total and Speciated Pollen Counts and Several Morbidity Measures in the Contiguous United States from 2008 to 2015
Authors: Jeremy J. Hess, Fiona Lo, Claudia L. Brown, Kristie L. Ebi, Arie Manangan, George Luber, Paul J. Schramm, Lewis Ziska, Cecilia Bitz, Shubhayu Saha
Journal: Journal of Allergy and Clinical Immunology (2018)
Abstract 18986: Heart Failure Admissions Under Observation versus Short Inpatient Stay: A Cohort Study
Authors: Ahmad Masri, Andrew D Althouse, Jeffrey McKibben, Floyd Thoma, Michael A Mathier, Ravi Ramani, Jeffrey Teuteberg, Oscar C Marroquin, Joon S Lee, Suresh R Mulukutla
Journal: Circulation (2016)

Background:  Many patients with heart failure (HF) are admitted for decongestion and have an unpredictable response to therapy. Based on the current practice, patients get admitted either under observation or inpatient stays, a designation which may be more reflective of administrative practices than patient status. We sought to understand the outcomes of patients admitted under observation vs inpatient status who remained in-hospital for less than 2 days.   Methods:  From 2008 through 2015, our multi-site health system saw 21,339 patients totaling 52,493 admissions with a primary diagnosis of HF. Patients were excluded if they underwent cardiac surgery (n=611), heart transplant (n=187), LVAD (n=198), or if they died during hospitalization (n=1839). Of the remaining 50,654 discharges, two groups were identified; group I (admitted under inpatient status, discharged within 2 days) and group II (admitted under observation). Outcomes were HF readmission, all-cause readmission and all-cause mortality within 1 year of discharge.   Results:  8,709 admissions (17%) under inpatient status resulted in discharge within 2 days; 2,648 admissions (5%) were designated under observation. HF readmission rate at 1 year was 55.3% in group I vs 66.5% in group II; HR 0.75 (95% CI 0.71-0.80), p    Conclusion:  Patients admitted with inpatient status who are discharged within 2 days had lower readmission rates and equivalent mortality to patients admitted for observation, suggesting that the difference between these groups is more administrative designation than reflection of patient status at time of admission. A revised treatment-based algorithm and admission rules are needed to guide physicians and shape healthcare policy.
An aberrant SREBP-dependent lipogenic program promotes metastatic prostate cancer
Authors: Ming Chen, Jiangwen Zhang, Katia Sampieri, John G. Clohessy, Lourdes Mendez, Enrique Gonzalez-Billalabeitia, Xue-Song Liu, Yu-Ru Lee, Jacqueline Fung, Jesse M. Katon, Archita Venugopal Menon, Kaitlyn A. Webster, Christopher Ng, Maria Dilia Palumbieri, Moussa S. Diolombi, Susanne B. Breitkopf, Julie Teruya-Feldstein, Sabina Signoretti, Roderick T. Bronson, John M. Asara, Mireia Castillo-Martin, Carlos Cordon-Cardo, Pier Paolo Pandolfi
Journal: Nature Genetics (2018)
Impaired Recovery of Left Ventricular Function in Patients With Cardiomyopathy and Left Bundle Branch Block
Authors: Edward Sze, Zainab Samad, Allison Dunning, Kristen Bova Campbell, Zak Loring, Brett D. Atwater, Karen Chiswell, Joseph A. Kisslo, Eric J. Velazquez, James P. Daubert
Journal: Journal of the American College of Cardiology (2018)
A comparative analysis of human bone marrow–resident and peripheral memory B cells
Authors: Sonya C. Becker, Martin Szyska, Angela Mensen, Katharina Hellwig, Raik Otto, Lisa Olfe, Hans-Dieter Volk, Thomas Dörner, Bernd Dörken, Carmen Scheibenbogen, Jörg Schröder, Andreas C. Hocke, Il-Kang Na
Journal: Journal of Allergy and Clinical Immunology (2018)
Enhanced preclinical antitumor activity of M7824, a bifunctional fusion protein simultaneously targeting PD-L1 and TGF-β
Authors: Yan Lan, Dong Zhang, Chunxiao Xu, Kenneth W. Hance, Bo Marelli, Jin Qi, Huakui Yu, Guozhong Qin, Aroop Sircar, Vivian M. Hernández, Molly H. Jenkins, Rachel E. Fontana, Amit Deshpande, George Locke, Helen Sabzevari, Laszlo Radvanyi, Kin-Ming Lo
Journal: Science Translational Medicine (2018)

Blockade of PD-L1 and TGF-β pathways with M7824 activates effective innate and adaptive antitumor immune responses.
Mortality Among American Indians and Alaska Natives
Authors: Feyza Sancar, Jennifer Abbasi, Karen Bucher
Journal: JAMA (2018)

Mortality Among American Indians and Alaska NativesIn 1990-2009, all-cause mortality among American Indian and Alaska Native (AI/AN) persons residing in Contract Health Services Delivery Area (CHSDA) counties was approximately 46% greater than among white persons (AI/ANs, 1166 per 100 000 vs whites, 799 per 100 000).Disparities in all-cause mortality between AI/ANs compared with whites occurred primarily among those aged 25 to 44 years.Leading Causes of Death, 1999Death, -2009 Regardless of sex, AI/ANs were more likely to die of diabetes, chronic liver disease, accidents, and suicide than whites.
Relative Roles of Race Versus Socioeconomic Position in Studies of Health Inequalities: A Matter of Interpretation
Authors: Amani M. Nuru-Jeter, Elizabeth K. Michaels, Marilyn D. Thomas, Alexis N. Reeves, Roland J. Thorpe, Thomas A. LaVeist
Journal: Annual Review of Public Health (2018)

An abundance of research has documented health inequalities by race and socioeconomic position (SEP) in the United States. However, conceptual and methodological challenges complicate the interpretation of study findings, thereby limiting progress in understanding health inequalities and in achieving health equity. Fundamental to these challenges is a lack of clarity about what race is and the implications of that ambiguity for scientific inquiry. Additionally, there is wide variability in how SEP is conceptualized and measured, resulting in a lack of comparability across studies and significant misclassification of risk. The objectives of this review are to synthesize the literature regarding common approaches to examining race and SEP health inequalities and to discuss the conceptual and methodological challenges associated with how race and SEP have been employed in public health research. Addressing health inequalities has become increasingly important as the United States trends toward becoming a majority-minority nation. Recommendations for future research are presented.
Polypoidal Choroidal Vasculopathy
Authors: Chui Ming Gemmy Cheung, Timothy Y.Y. Lai, Paisan Ruamviboonsuk, Shih-Jen Chen, Youxin Chen, K. Bailey Freund, Fomi Gomi, Adrian H. Koh, Won-Ki Lee, Tien Yin Wong
Journal: Ophthalmology (2018)
Abstract 20782: Discharge Hospice Referral is Associated With Lower 30-Day All-Cause Readmission in Hospitalized Patients With Heart Failure: A Propensity-Matched Study of the Medicare-Linked OPTIMIZE-HF
Authors: Helen Sheriff, Phillip H Lam, Cherinne Arundel, Daniel J Dooley, Gurusher Panjrath, Ross D Fletcher, Marc Blackman, Javed Butler, Prakash Deedwania, Michel White, Ioannis Kanonidis, Charity Morgan, Wen-Chih Wu, Wilbert S Aronow, Richard M Allman, Gregg C Fonarow, Ali Ahmed
Journal: Circulation (2016)

Background:  Heart failure (HF) is the leading cause for 30-day all-cause readmission - a target for Medicare cost reduction in the Affordable Care Act. Findings from a single state suggest that a discharge hospice referral was associated with lower 30-day all-cause readmission among Medicare beneficiaries hospitalized for HF during 1998-2001 (PMID: 26019151). We examined this association in a more contemporary national cohort of hospitalized patients with HF.   Methods:  In the Medicare-linked OPTIMIZE-HF registry, of the 25345 hospitalized patients with HF 479 (2%) received a discharge hospice referral. Of the 24866 patients who did not receive a hospice referral, 5053 (20%) died and were considered hospice eligible (6-month life expectancy is a Medicare hospice eligibility criterion). Propensity scores for hospice referral were estimated for each of the 5532 (479+5053) patients and were used to match 360 hospice-referral patients with 360 hospice-eligible patients who were balanced on 78 baseline characteristics. The 720 matched patients had a mean (±SD) age of 80 (±10) years, a mean (±SD) EF of 40% (±18%), 52% were women, and 09% African American.   Results:  30-day all-cause readmission occurred in 42% and 6% of matched hospice-referral and hospice-eligible patients, resp. (HR, 0.17; 95% CI, 0.12-0.25;  Figure ). While 30-day mortality was higher in the hospice referral group (61% vs 27%), the higher mortality was unlikely to have explained this lower readmission rate. At 6 month, mortality was lower in the hospice referral group (81% vs 100% in the hospice-eligible group, by definition) and yet hospice referral was associated with lower 6-month all-cause readmission (HR, 0.16; 95% CI, 0.11-0.22). Patients in the hospice referral group had lower 30-day and 6-month HF readmissions.   Conclusion:  Among hospitalized patients with HF, a discharge hospice referral was associated with lower 30-day all-cause readmission, which persisted during longer term follow-up.
Guidance of super-enhancers in regulation of IL-9 induction and airway inflammation
Authors: Xiang Xiao, Yihui Fan, Junhui Li, Xiaolong Zhang, Xiaohua Lou, Yaling Dou, Xiaomin Shi, Peixiang Lan, Yue Xiao, Laurie Minze, Xian Chang Li
Journal: The Journal of Experimental Medicine (2018)

Th9 cells are prominently featured in allergic lung inflammation, but the mechanism that regulates IL-9 induction in T helper cells remains poorly defined. Here we demonstrate that formation of super-enhancers (SEs) is critical in robust induction of IL-9 and that assembly of the Il9 SEs in Th cells requires OX40-triggered chromatin acetylation. Mechanistically, we found that OX40 costimulation induces RelB expression, which recruits the histone acetyltransferase p300 to the Il9 locus to catalyze H3K27 acetylation. This allows binding of the SE factor Brd4 to organize assembly of the SE complex, which in turn drives robust IL-9 expression and Th9 cell induction. Thus, Th9 cells are strongly induced upon OX40 stimulation, and disruption of SEs abolished Th9 cell induction in vitro and inhibited Th9 cell–mediated allergic airway inflammation in vivo. Together, our data suggest that formation of SEs is essential in IL-9 expression and Th9 cell induction. These findings may have important clinical implications.