tbuckley/cabot-search huggingface dataset:
β-Blocker Use in Pregnancy and the Risk for Congenital Malformations
Authors: Brian T. Bateman, Uffe Heide-Jørgensen, Kristjana Einarsdóttir, Anders Engeland, Kari Furu, Mika Gissler, Sonia Hernandez-Diaz, Helle Kieler, Anna-Maria Lahesmaa-Korpinen, Helen Mogun, Mette Nørgaard, Johan Reutfors, Randi Selmer, Krista F. Huybrechts, Helga Zoega
Journal: Annals of Internal Medicine (2018)

Background: β-Blockers are a class of antihypertensive medications that are commonly used in pregnancy. Objective: To estimate the risks for major congenital malformations associated with first-trimester exposure to β-blockers. Design: Cohort study. Setting: Health registries in the 5 Nordic countries and the U.S. Medicaid database. Patients: Pregnant women with a diagnosis of hypertension and their offspring. Measurements: First-trimester exposure to β-blockers was assessed. Outcomes were any major congenital malformation, cardiac malformations, cleft lip or palate, and central nervous system (CNS) malformations. Propensity score stratification was used to control for potential confounders. Results: Of 3577 women with hypertensive pregnancies in the Nordic cohort and 14 900 in the U.S. cohort, 682 (19.1%) and 1668 (11.2%), respectively, were exposed to β-blockers in the first trimester. The pooled adjusted relative risk (RR) and risk difference per 1000 persons exposed (RD1000) associated with β-blockers were 1.07 (95% CI, 0.89 to 1.30) and 3.0 (CI, −6.6 to 12.6), respectively, for any major malformation; 1.12 (CI, 0.83 to 1.51) and 2.1 (CI, −4.3 to 8.4) for any cardiac malformation; and 1.97 (CI, 0.74 to 5.25) and 1.0 (CI, −0.9 to 3.0) for cleft lip or palate. For CNS malformations, the adjusted RR was 1.37 (CI, 0.58 to 3.25) and the RD1000 was 1.0 (CI, −2.0 to 4.0) (based on U.S. cohort data only). Limitation: Analysis was restricted to live births, exposure was based on dispensed medication, and cleft lip or palate and CNS malformations had few outcomes. Conclusion: The results suggest that maternal use of β-blockers in the first trimester is not associated with a large increase in the risk for overall malformations or cardiac malformations, independent of measured confounders. Primary Funding Source: The Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Söderström König Foundation.
Essential roles of mitochondrial biogenesis regulator Nrf1 in retinal development and homeostasis
Authors: Takae Kiyama, Ching-Kang Chen, Steven W Wang, Ping Pan, Zhenlin Ju, Jing Wang, Shinako Takada, William H Klein, Chai-An Mao
Journal: Molecular Neurodegeneration (2018)

Mitochondrial dysfunction has been implicated in the pathologies of a number of retinal degenerative diseases in both the outer and inner retina. In the outer retina, photoreceptors are particularly vulnerable to mutations affecting mitochondrial function due to their high energy demand and sensitivity to oxidative stress. However, it is unclear how defective mitochondrial biogenesis affects neural development and contributes to neural degeneration. In this report, we investigated the in vivo function of nuclear respiratory factor 1 (Nrf1), a major transcriptional regulator of mitochondrial biogenesis in both proliferating retinal progenitor cells (RPCs) and postmitotic rod photoreceptor cells (PRs). We used mouse genetic techniques to generate RPC-specific and rod PR-specific Nrf1 conditional knockout mouse models. We then applied a comprehensive set of tools, including histopathological and molecular analyses, RNA-seq, and electroretinography on these mouse lines to study Nrf1-regulated genes and Nrf1's roles in both developing retinas and differentiated rod PRs. For all comparisons between genotypes, a two-tailed two-sample student's t-test was used. Results were considered significant when P < 0.05. We uncovered essential roles of Nrf1 in cell proliferation in RPCs, cell migration and survival of newly specified retinal ganglion cells (RGCs), neurite outgrowth in retinal explants, reconfiguration of metabolic pathways in RPCs, and mitochondrial morphology, position, and function in rod PRs. Our findings provide in vivo evidence that Nrf1 and Nrf1-mediated pathways have context-dependent and cell-state-specific functions during neural development, and disruption of Nrf1-mediated mitochondrial biogenesis in rod PRs results in impaired mitochondria and a slow, progressive degeneration of rod PRs. These results offer new insights into the roles of Nrf1 in retinal development and neuronal homeostasis and the differential sensitivities of diverse neuronal tissues and cell types of dysfunctional mitochondria. Moreover, the conditional Nrf1 allele we have generated provides the opportunity to develop novel mouse models to understand how defective mitochondrial biogenesis contributes to the pathologies and disease progression of several neurodegenerative diseases, including glaucoma, age-related macular degeneration, Parkinson's diseases, and Huntington's disease.
GW29-e1518 Altered long non-coding RNA expression profile in rabbit atria with atrial fibrillation: TCONS_00016478 modulates atrial energy metabolic remodeling through PGC-1α/ PPARγ pathway
Authors: Jianhua Li, Zhan Li, Juanjuan Du, Xiaomeng Jia, Donglu Liu, Shenzhou Ma, Yinglong Hou
Journal: Journal of the American College of Cardiology (2018)
Abstract 13732: Implantable Cardioverter Defibrillators Reduce Mortality in Patients with Chronic Kidney Disease: A Meta-Analysis
Authors: Nader Makki, Paari Dominic Swaminathan, Brian Olshansky
Journal: Circulation (2012)

Background---Current guidelines recommend a primary prevention implantable cardioverter defibrillator (ICD) in NYHA class II or III heart failure patients with an ejection fraction of ≤35%. However, those clinical trials that form the basis of the current guidelines, largely exclude patients with chronic kidney disease (CKD) (defined as kidney damage or estimated glomerular filtration rate eGFR <60ml/min/1.73 m2 for at least 3 months). Studies addressing the mortality benefits of ICD in CKD patients have so far been inconclusive. Objective---To evaluate the effects of ICD on all-cause mortality in CKD patients based on current data Methods---We performed two separate meta-analyses to assess all-cause mortality between: 1) ICD patients with and without CKD and 2) CKD patients (meeting primary or secondary prevention criteria for ICD) with and without ICDs. Medline and Embase were searched from 1966 - 2011. A manual search by cross-referencing was also performed. Meta-analysis of sixteen observational studi...
Abstract 9920: Outcomes Associated With Lead Abandonment versus Lead Extraction Strategies for Revision of Sterile Leads: An NCDR® Analysis
Authors: Emily P Zeitler, Yongfei Wang, Kumar Dharmarajan, Kevin J Anstrom, Eric D Peterson, James P Daubert, Jeptha P Curtis, Sana M Al-Khatib
Journal: Circulation (2015)

Introduction: While implantable cardioverter defibrillator (ICD) systems are lifesaving, leads often require replacement over time. When ICD leads require replacement, the existing lead can either be left in (abandoned) or be extracted, yet there are insufficient comparative data between these 2 strategies. Methods: We examined in-hospital events among propensity matched subjects undergoing lead replacement where the existing lead was either abandoned or extracted from National Cardiovascular Data Registry (NCDR) ICD Registry (2010 - 2011). Six month complication and 90-day and 1-year mortality rates were examined in a subset of Medicare subjects. We excluded those procedures involving infection and those performed by a cardiothoracic surgeon (extraction predetermined). Results: After 1:1 matching, we had 41744 subjects with in hospital outcomes, of which 2362 were Medicare aged and had 6-month complications and survival information. About 1/4 were women; average age was 66 yrs overall and 75 yrs in the Medicare cohort. In hospital events included 2.22% (n=463) and 3.63% (n=758) procedure related complications, and death in 0.21% (n=44) and 0.45% (n=94) in abandonment and extraction patients, respectively (p&lt;0.001 for both). In the Medicare cohort, at 6 months, there was no difference with respect to bleeding (4.92% vs 5.40%), tamponade (0.38% vs 0.66%), infection (2.27 % vs 3.03%), upper extremity thrombosis (0.76% vs 0.95%), pulmonary embolism (0.28% vs 0.57%), or urgent surgery (1.70% vs 0.85%) (p&gt;0.05 for all). At 90 days and 1 year, there was no difference in survival (p=0.55) (See Figure). Conclusion: Among propensity-matched patients undergoing ICD lead replacement, there were more in-hospital complications and deaths among extraction versus abandonment subjects. Among a Medicare subset, there were no differences in longer term outcomes. Thus, abandonment may be a reasonable alternative to extraction for sterile lead revision in some cases.
Liraglutide, Sitagliptin, and Insulin Glargine Added to Metformin: The Effect on Body Weight and Intrahepatic Lipid in Patients With Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease
Authors: Jinhua Yan, Bin Yao, Hongyu Kuang, Xubin Yang, Qin Huang, Tianpei Hong, Yushu Li, Jingtao Dou, Wenying Yang, Guijun Qin, Huijuan Yuan, Xinhua Xiao, Sihui Luo, Zhongyan Shan, Hongrong Deng, Ying Tan, Fen Xu, Wen Xu, Longyi Zeng, Zhuang Kang, Jianping Weng
Journal: Hepatology (2018)

To investigate the effect of antidiabetic agents on nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM), 75 patients with T2DM and NAFLD under inadequate glycemic control by metformin were randomized (1:1:1) to receive add‐on liraglutide, sitagliptin, or insulin glargine in this 26‐week trial. The primary endpoint was the change in intrahepatic lipid (IHL) from baseline to week 26 as quantified by magnetic resonance imaging–estimated proton density fat fraction (MRI‐PDFF). Secondary endpoints included changes in abdominal adiposity (subcutaneous adipose tissue [SAT] and visceral adipose tissue [VAT]), glycated hemoglobin, and body weight from baseline to week 26. We analysed data from intent‐to‐treat population. MRI‐PDFF, VAT, and weight decreased significantly with liraglutide (15.4% ± 5.6% to 12.5% ± 6.4%, P &lt; 0.001; 171.4 ± 27.8 to 150.5 ± 30.8, P = 0.003; 86.6 ± 12.9 kg to 82.9 ± 11.1 kg, P = 0.005, respectively) and sitagliptin (15.5% ± 5.6% to 11.7% ± 5.0%, P = 0.001; 153.4 ± 31.5 to 139.8 ± 27.3, P = 0.027; 88.2 ± 13.6 kg to 86.5 ± 13.2 kg, P = 0.005, respectively). No significant change in MRI‐PDFF, VAT, or body weight was observed with insulin glargine. SAT decreased significantly in the liraglutide group (239.9 ± 69.0 to 211.3 ± 76.1; P = 0.020) but not in the sitagliptin and insulin glargine groups. Changes from baseline in MRI‐PDFF, VAT, and body weight were significantly greater with liraglutide than insulin glargine but did not differ significantly between liraglutide and sitagliptin. Conclusion: Combined with metformin, both liraglutide and sitagliptin, but not insulin glargine, reduced body weight, IHL, and VAT in addition to improving glycemic control in patients with T2DM and NAFLD.
Abstract 13186: Rare and Low Frequency Variants Associated With Hypertension and Systolic Blood Pressure in Taiwan Chinese Families
Authors: Lisa de las Fuentes, Karen L Schwander, Yun Ju Sung, Chao Agnes Hsiung, Wayne Sheu, James E Hixson, Kent D Taylor, Jerome I Rotter, D. C Rao, Ida Chen
Journal: Circulation (2016)

Introduction: Hypertension (HTN) and related disorders constitute a major public-health burden. While genome-wide association studies have identified common variants for HTN, &lt;2.5% of blood pressure (BP) variance has been explained. Hypothesis: Exome sequencing in families highly enriched for HTN will identify novel rare and low frequency variants associated with HTN and systolic blood pressure (SBP) with larger effect sizes. Methods: Exome sequencing in 150 hypertensive sib-pairs (300 subjects) and 300 unrelated controls identified 6,000 top variants which were then genotyped in SAPPHIRe families (N=1,100) and 1,100 unrelated matched controls. Single-variant analysis and four gene-based association tests (burden and SKAT tests using minor allele frequency thresholds of 1% [T1] and 5% [T5]) were performed for HTN and SBP. Bonferroni-adjusted significance level (5.4•10 -5 ) was used. Results: Novel rare and low frequency variants with significant/suggestive association and biologic plausibility for roles in BP regulation were identified: PLA2G4B-SPTBN5 (7 variants, burden T1 p-value 1.3•10 -6 for SBP and burden T1 p-value 4.2•10 -5 for HTN); RGS2 (1 variant, burden T1 p-value 1.4•10 -5 for SBP and burden T1 p-value 8.9•10 -4 for HTN); BCHE (4 variants, burden T1 p-value 3.4•10 -5 for SBP and burden T1 p-value 5.6•10 -4 for HTN); STRADA (5 variants, burden T1 p-value 5.8•10 -5 for HTN); DYNC2LI1 (8 variants, SKAT T1 p-value 9.9•10 -5 for SBP); TNK1-PLSCR3 (8 variants, SKAT T5 p-value 3.5•10 -4 for SBP). PLAG4B , BCHE and RGS2, identified by both SBP and HTN analyses, are notable for roles played in the synthesis and signal transduction of vasomodulatory peptides in the vascular endothelium and vascular smooth muscle. DYNC2LI1 and STRADA play roles in the regulation of renal water and salt handling via aquaporin and sodium-chloride cotransporters, respectively. Murine PLSCR3 knock-out models lead to a metabolic syndrome phenotype in mice. Conclusions: Several significant and promising rare and low frequency variants associated with HTN and SBP were identified. Studies are underway to replicate the most promising loci. Identification of the causal variants for HTN may lead to novel drug targets and interventions.
Abstract 13071: Impact of Arterial Stiffening on Cardiovascular Markers and Incidence of Cardiovascular Event in Normotensive Patients Without History of Cardiovascular Disease
Authors: Keishi Ichikawa, Satoru Sakuragi
Journal: Circulation (2016)

Introduction: Arterial stiffness has been proposed as an important predictor of cardiovascular (CV) event in various groups, such as end-stage kidney disease and hypertensive patients. Although, blood pressure (BP) is one of the most important determinants of arterial stiffening, there are some cases who have a discrepancy between BP and arterial stiffness. In this study, we evaluated the impact of arterial stiffening on impairment of cardiac parameters and incidence of CV event in patients with normal blood pressure. Methods: A total of 320 outpatients with normal BP defined as systolic BP less than 140mmHg were enrolled. At baseline, all subjects underwent echocardiography and MDCT. Coronary artery calcification (CAC) was evaluated with Agatston method and CAC score (CACs) was calculated. Arterial stiffness was also assessed with pulse wave velocity (PWV) between brachial and ankle. The subjects were divided into two groups according to the PWV: high PWV group (PWV≥18m/sec, n=89) and low PWV group (PWV&lt;18m/sec, n=231). Cardiac parameters as well as incidence of CV events during the follow-up period were compared between the two groups. Results: In linear regression analysis, PWV was significantly associated with CACs and NT-proBNP after adjustment for confounding factors. In multivariate logistic regression analysis, PWV over 18m/sec was significantly associated with CACs over 400 with a hazard ratio of 2.466 (95%CI: 1.012-6.009, p=0.047). Kaplan-Meier analysis showed that high PWV group had higher rate of CV event during the follow-up period of 575 days (20% vs 6%, p=0.0003). In multivariate Cox regression analysis, PWV over 18m/sec was an independent predictor for future CV events with an odds ratio of 2.534 (95%CI: 1.045-6.146, p=0.040). Conclusions: Arterial stiffening assessed by PWV is a strong determinants of impairment of cardiac parameters as well as future CV event even in normotensive patients.
Molecular and Functional Characterization of Disease-Propagating Stem Cells in Juvenile Myelomonocytic Leukemia
Authors: E Louka, B Povinelli, A Rodriguez-Meira, G Buck, A Hamblin, C Booth, A Roy, N Elliott, D Iskander, J de la Fuente, N J Fordham, S I Obyrne, S Inglott, A G Rao, I Roberts, A J Mead
Journal: Blood (2017)
Individually shortened duration versus standard duration of elastic compression therapy for prevention of post-thrombotic syndrome: a cost-effectiveness analysis
Authors: Elham E Amin, Arina J ten Cate-Hoek, Annemieke C Bouman, Karina Meijer, Lidwine Tick, Saskia Middeldorp, Guy Mostard, Marije ten Wolde, Simone van den Heiligenberg, Sanne van Wissen, Marlene van de Poel, Sabina Villalta, Erik Serné, Hans Martin Otten, Edith Klappe, Paolo Prandoni, Martin H Prins, Hugo ten Cate, Manuela A Joore
Journal: The Lancet Haematology (2018)
Gα12 ablation exacerbates liver steatosis and obesity by suppressing USP22/SIRT1-regulated mitochondrial respiration
Authors: Tae Hyun Kim, Yoon Mee Yang, Chang Yeob Han, Ja Hyun Koo, Hyunhee Oh, Su Sung Kim, Byoung Hoon You, Young Hee Choi, Tae-Sik Park, Chang Ho Lee, Hitoshi Kurose, Mazen Noureddin, Ekihiro Seki, Yu-Jui Yvonne Wan, Cheol Soo Choi, Sang Geon Kim
Journal: Journal of Clinical Investigation (2018)

Nonalcoholic fatty liver disease (NAFLD) arises from mitochondrial dysfunction under sustained imbalance between energy intake and expenditure, but the underlying mechanisms controlling mitochondrial respiration have not been entirely understood. Heterotrimeric G proteins converge with activated GPCRs to modulate cell-signaling pathways to maintain metabolic homeostasis. Here, we investigated the regulatory role of G protein α12 (Gα12) on hepatic lipid metabolism and whole-body energy expenditure in mice. Fasting increased Gα12 levels in mouse liver. Gα12 ablation markedly augmented fasting-induced hepatic fat accumulation. cDNA microarray analysis from Gna12-KO liver revealed that the Gα12-signaling pathway regulated sirtuin 1 (SIRT1) and PPARα, which are responsible for mitochondrial respiration. Defective induction of SIRT1 upon fasting was observed in the liver of Gna12-KO mice, which was reversed by lentivirus-mediated Gα12 overexpression in hepatocytes. Mechanistically, Gα12 stabilized SIRT1 protein through transcriptional induction of ubiquitin-specific peptidase 22 (USP22) via HIF-1α increase. Gα12 levels were markedly diminished in liver biopsies from NAFLD patients. Consistently, Gna12-KO mice fed a high-fat diet displayed greater susceptibility to diet-induced liver steatosis and obesity due to decrease in energy expenditure. Our results demonstrate that Gα12 regulates SIRT1-dependent mitochondrial respiration through HIF-1α–dependent USP22 induction, identifying Gα12 as an upstream molecule that contributes to the regulation of mitochondrial energy expenditure.
Secreted bacterial adenosine deaminase is an evolutionary precursor of adenosine deaminase growth factor
Authors: Maksym Skaldin, Minna Tuittila, Andrey V Zavialov, Anton V Zavialov
Journal: Molecular Biology and Evolution (2018)

Adenosine deaminases (ADAs) play a pivotal role in regulating the level of adenosine, an important signaling molecule that controls a variety of cellular responses. Two distinct ADAs, ADA1 and adenosine deaminase growth factor (ADGF aka ADA2), are known. Cytoplasmic ADA1 plays a key role in purine metabolism and is widely distributed from prokaryotes to mammals. On the other hand, secreted ADGF/ADA2 is a cell-signaling protein that was thought to be present only in multicellular organisms. Here, we discovered a bacterial homologue of ADGF/ADA2. Bacterial and eukaryotic ADGF/ADA2 possess the dimerization and PRB domains characteristic for the family, have nearly identical catalytic sites, and show similar catalytic characteristics. Most surprisingly, the bacterial enzyme has a signal sequence similar to that of eukaryotic ADGF/ADA2 and is specifically secreted into the extracellular space, where it may potentially control the level of extracellular adenosine. This finding provides the first example of evolution of an extracellular eukaryotic signaling protein from a secreted bacterial analogue with identical activity and suggests a potential role of ADGF/ADA2 in bacterial communication.
Impact of Surveillance Imaging Modality on Survival After Recurrence in Patients With Favorable-Histology Wilms Tumor: A Report From the Children’s Oncology Group
Authors: Elizabeth A. Mullen, Yueh-Yun Chi, Emily Hibbitts, James R. Anderson, Katarina J. Steacy, James I. Geller, Daniel M. Green, Geetika Khanna, Marcio H. Malogolowkin, Paul E. Grundy, Conrad V. Fernandez, Jeffrey S. Dome
Journal: Journal of Clinical Oncology (2018)

The use of computed tomography (CT) for routine surveillance to detect recurrence in patients with Wilms tumor (WT) has increased in recent years. The utility of CT, despite increased risk and cost, to improve outcome for these patients is unknown. We conducted a retrospective analysis with patients enrolled in the fifth National Wilms Tumor Study (NWTS-5) to determine if surveillance with CT correlates with improved overall survival (OS) after recurrence compared with chest x-ray (CXR) and abdominal ultrasound (US).
The Ratio of Peripheral Regulatory T Cells to Lox-1<sup>+</sup> Polymorphonuclear Myeloid-derived Suppressor Cells Predicts the Early Response to Anti–PD-1 Therapy in Patients with Non–Small Cell Lung Cancer
Authors: Hye Ryun Kim, Su-Myeong Park, Sang-Uk Seo, Inkyung Jung, Hong In Yoon, Dmitry I. Gabrilovich, Byoung Chul Cho, Seung-Yong Seong, Sang-Jun Ha, Je-In Youn
Journal: American Journal of Respiratory and Critical Care Medicine (2018)
Prenatal 25-hydroxyvitamin D deficiency affects development of atopic dermatitis via DNA methylation
Authors: Hyun-Ju Cho, Youn Ho Sheen, Mi-Jin Kang, Seung-Hwa Lee, So-Yeon Lee, Jisun Yoon, Sungsu Jung, Si Hyeon Lee, Young-Ho Kim, Song-I Yang, Eun Lee, Ju-Hee Seo, Kangmo Ahn, Kyung Won Kim, Dong In Suh, Hye-Sung Won, Mi-Young Lee, Soo Hyun Kim, Suk-Joo Choi, Ja-Young Kwon, Jong Kwan Jun, Sung-Ok Kwon, Se-Young Oh, Soo-Jong Hong
Journal: Journal of Allergy and Clinical Immunology (2018)
Abstract 19214: Does Melody Pulmonary Valve Replacement Improve Exercise Tolerance Over a Five-Year Period?
Authors: Bryant Priromprintr, Michael J Silka, Jonathan Rhodes, Anjan S Batra
Journal: Circulation (2016)

Introduction: Percutaneous Melody valve implant is an alternative to surgical valve replacement for right ventricular outflow tract (RVOT) conduit obstruction or insufficiency. However, the long-te...
Immune-related adverse events (irAEs) predict therapeutic efficacy of an anti-PD-1 antibody in cancer patients
Authors: J. Rogado, N. Romero Laorden, J.M. Sanchez Torres, A.I. Ballesteros Garcia, V.E. Pacheco-Barcia, R. Arranz, R. Mondéjar Solís, P. Gullón, A. Lorenzo, R. Colomer Bosch
Journal: Annals of Oncology (2018)
Phase I study of BI 754111 (anti-LAG-3) plus BI 754091(anti-PD-1) in patients (pts) with advanced solid cancers, followed by expansion in pts with microsatellite stable metastatic colorectal cancer (mCRC), anti-PD-(L)1-pretreated non-small cell lung cancer (NSCLC) and other solid tumors
Authors: M.L. Johnson, M.R. Patel, S.V. Ulahannan, A. Hansen, B. George, Q.S.-C. Chu, M. Elgadi, M. Ge, C. Duffy, R. Graeser, S. Khedkar, S.F. Jones, H. Burris
Journal: Annals of Oncology (2018)
Autoimmune Thyroiditis and Depression—Reply
Authors: Teja Wolfgang Grömer, Eva-Maria Siegmann, Helge H.O. Müller
Journal: JAMA Psychiatry (2018)

In Reply We have read the Letters1-3 concerning our article on autoimmune thyroiditis (AIT) with interest and thank the different authors for their time and effort. There were many positive reactions to the contents of the article.
The β2-microgloulin is associated with the prognosis in patients with peripheral t-cell lymphoma, not otherwise specified
Authors: B.S. Sohn, S.-N. Lim, J. Kim, D.H. Yoon, S. Kim, J. Huh, S.-E. Park, Y.J. Yuh, C. Suh
Journal: Annals of Oncology (2018)