tbuckley/cabot-search huggingface dataset:
£30 million award to transform cardiovascular research
Authors: Nilesh J Samani
Journal: Cardiovascular Research (2018)

The British Heart Foundation's Big Beat Challenge is a unique and unmissable opportunity Every researcher-no matter their chosen specialism or area of interest-is aware of the big barriers that need to be overcome for progress to be made in their field.Across the range of heart and circulatory disease, the mountains that need to be climbed are many, major, and often multi-faceted.But most of the funding mechanisms we use to drive progress force people to think in small steps rather than giant leaps.That is about to change.The Big Beat Challenge is a global competition that will culminate in a single award of up to £30 million.This unique award will go to a multidisciplinary research team from anywhere in the world which can propose and deliver a transformational solution to a significant problem in any cardiovascular disease.
Abstract 21363: Etiologies and Trends of Readmission in Patients With Takotsubo Cardiomyopathy
Authors: Vishwa Kundoor, Byomesh Tripathi, Shilpkumar Arora, Nikhil Nalluri, Varun Kumar, Sopan Lahewala, Nirali Patel, Neil Patel, Prashant Patel, Madan Badal, Radha Gopalan, Nileshkumar Patel, Abhishek Deshmukh
Journal: Circulation (2017)

Introduction: Takotsubo cardiomyopathy (TTC) is diagnosed in 1-2% of the patients presenting with troponin positive suspected acute coronary syndromes(ACS). Rising trends of adverse events in patients with TTC, makes it imperative to explore causes and predictors of readmission in this patient population. Methods: National Readmission Data (NRD) 2013-14 was utilized to select study cohort. International Classification of Diseases, 9th Revision (ICD-9-CM) diagnostic code 429.83 was used to identify takotsubo cardiomyopathy. Admissions within 90 day of index admission were considered as early readmissions. Readmission etiologies were identified by ICD-9-CM code in primary diagnosis field of readmissions. Hierarchical multivariate models were used to evaluate predictors of early readmission. Results: A total of 12255 patients were identified during study period out of which 23.92% (n=2932 with 4224 readmissions) patients were readmitted within 90 days of discharge following index admission. Most common etiologies for readmission were cardiac (18.56%), respiratory (17.20%), GI renal (9.10%), infections (13.12%) and neurological complications (5.88%). Among cardiac complications acute heart failure was the most common etiology (7.48%). Highest number of readmissions happened on first day after discharge (n=125) and within 33 days after discharge, &gt;50% of readmissions took place (n=2136). Conclusions: Patients with TTC are highly likely to be readmitted with first month after discharge, most likely secondary to cardiac or respiratory complications. These findings warrant close post discharge transition to reduce morbidity and improve health care outcomes.
IL-17R–EGFR axis links wound healing to tumorigenesis in Lrig1+ stem cells
Authors: Xing Chen, Gang Cai, Caini Liu, Junjie Zhao, Chunfang Gu, Ling Wu, Thomas A. Hamilton, Cun-jin Zhang, Jennifer Ko, Liang Zhu, Jun Qin, Allison Vidimos, Shlomo Koyfman, Brian R. Gastman, Kim B. Jensen, Xiaoxia Li
Journal: The Journal of Experimental Medicine (2018)

Lrig1 marks a distinct population of stem cells restricted to the upper pilosebaceous unit in normal epidermis. Here we report that IL-17A–mediated activation of EGFR plays a critical role in the expansion and migration of Lrig1+ stem cells and their progenies in response to wounding, thereby promoting wound healing and skin tumorigenesis. Lrig1-specific deletion of the IL-17R adaptor Act1 or EGFR in mice impairs wound healing and reduces tumor formation. Mechanistically, IL-17R recruits EGFR for IL-17A–mediated signaling in Lrig1+ stem cells. While TRAF4, enriched in Lrig1+ stem cells, tethers IL-17RA and EGFR, Act1 recruits c-Src for IL-17A–induced EGFR transactivation and downstream activation of ERK5, which promotes the expansion and migration of Lrig1+ stem cells. This study demonstrates that IL-17A activates the IL-17R–EGFR axis in Lrig1+ stem cells linking wound healing to tumorigenesis.
Abstract 15055: Walnut-Enriched Diet Beneficially Alters Gut Microbiome in Healthy Caucasian Subjects
Authors: Charlotte Bamberger, Andreas Rossmeier, Katharina Lechner, Liya Wu, Elisa Waldmann, Julia Altenhofer, Kerstin Henze, Klaus G Parhofer
Journal: Circulation (2017)

Introduction: Regular walnut consumption is associated with better global and cardiovascular health. We have previously shown that 8 weeks of walnut consumption (43 g/day) significantly reduces LDL...
Critical role of C5a in sickle cell disease
Authors: Gregory M. Vercellotti, Agustin P. Dalmasso, Terry R. Schaid, Julia Nguyen, Chunsheng Chen, Marna E. Ericson, Fuad Abdulla, Trevor Killeen, Margaret A. Lindorfer, Ronald P. Taylor, John D. Belcher
Journal: American Journal of Hematology (2018)

Innate immune complement activation may contribute to sickle cell disease (SCD) pathogenesis. Ischemia‐reperfusion physiology is a key component of the inflammatory and vaso‐occlusive milieu in SCD and is associated with complement activation. C5a is an anaphylatoxin, a potent pro‐inflammatory mediator that can activate leukocytes, platelets, and endothelial cells, all of which play a role in vaso‐occlusion. We hypothesize that hypoxia‐reoxygenation (H/R) in SCD mice activates complement, promoting inflammation and vaso‐occlusion. At baseline and after H/R, sickle Townes‐SS mice had increased C3 activation fragments and C5b‐9 deposition in kidneys, livers and lungs and alternative pathway Bb fragments in plasma compared to control AA‐mice. Activated complement promoted vaso‐occlusion (microvascular stasis) in SS‐mice; infusion of zymosan‐activated, but not heat‐inactivated serum, induced substantial vaso‐occlusion in the skin venules of SS‐mice. Infusion of recombinant C5a induced stasis in SS, but not AA‐mice that was blocked by anti‐C5a receptor (C5aR) IgG. C5a‐mediated stasis was accompanied by inflammatory responses in SS‐mice including NF‐κB activation and increased expression of TLR4 and adhesion molecules VCAM‐1, ICAM‐1, and E‐selectin in the liver. Anti‐C5aR IgG blocked these inflammatory responses. Also, C5a rapidly up‐regulated Weibel‐Palade body P‐selectin and von Willebrand factor on the surface of human umbilical vein endothelial cells in vitro and on vascular endothelium in vivo. In SS‐mice, a blocking antibody to P‐selectin inhibited C5a‐induced stasis. Similarly, an antibody to C5 that blocks murine C5 cleavage or an antibody that blocks C5aR inhibited H/R‐induced stasis in SS‐mice. These results suggest that inhibition of C5a may be beneficial in SCD.
Abstract 16958: Anabolic-Androgenic Steroid Use is Associated With Premature Coronary Artery Disease
Authors: Amit Pursnani, Bryan Wai, Udo Hoffmann, Rory B Weiner, Stephanie K Isaacs, Gen Kanayama, James I Hudson, Harrison G Pope, Aaron L Baggish
Journal: Circulation (2013)

Background: Illicit anabolic-androgenic steroid (AAS) abuse is a world-wide public health problem. While mounting animal data and several recent human studies suggest that AAS abuse leads to premat...
Genetics of Human Primary Hypertension: Focus on Hormonal Mechanisms
Authors: Worapaka Manosroi, Gordon H Williams
Journal: Endocrine Reviews (2018)

Abstract Increasingly, primary hypertension is being considered a syndrome and not a disease, with the individual causes (diseases) having a common sign—an elevated blood pressure. To determine these causes, genetic tools are increasingly employed. This review identified 62 proposed genes. However, only 21 of them met our inclusion criteria: (i) primary hypertension, (ii) two or more supporting cohorts from different publications or within a single publication or one supporting cohort with a confirmatory genetically modified animal study, and (iii) 600 or more subjects in the primary cohort; when including our exclusion criteria: (i) meta-analyses or reviews, (ii) secondary and monogenic hypertension, (iii) only hypertensive complications, (iv) genes related to blood pressure but not hypertension per se, (v) nonsupporting studies more common than supporting ones, and (vi) studies that did not perform a Bonferroni or similar multiassessment correction. These 21 genes were organized in a four-tiered structure: distant phenotype (hypertension); intermediate phenotype [salt-sensitive (18) or salt-resistant (0)]; subintermediate phenotypes under salt-sensitive hypertension [normal renin (4), low renin (8), and unclassified renin (6)]; and proximate phenotypes (specific genetically driven hypertensive subgroup). Many proximate hypertensive phenotypes had a substantial endocrine component. In conclusion, primary hypertension is a syndrome; many proposed genes are likely to be false positives; and deep phenotyping will be required to determine the utility of genetics in the treatment of hypertension. However, to date, the positive genes are associated with nearly 50% of primary hypertensives, suggesting that in the near term precise, mechanistically driven treatment and prevention strategies for the specific primary hypertension subgroups are feasible.
Abstract 16957: Predictive Value of Cardiopulmonary Exercise Testing in Patients With Aortic Stenosis: Comparison With Traditional Echocardiographic Parameters
Authors: Debora Brala, Hector I Michelena, Maurice E Sarano, Grace Zhuang-Ke, Olaf Göing, Olaf Schulz, Wilhelm Haverkamp, Thomas G Allison
Journal: Circulation (2013)

Background: Prognosis of patients with aortic stenosis (AS) is currently based on echocardiographic severity parameters and patient-reported symptoms. The value of cardiopulmonary exercise testing ...
EGFR and c-MET Cooperate to Enhance Resistance to PARP Inhibitors in Hepatocellular Carcinoma
Authors: Qiongzhu Dong, Yi Du, Hui Li, Chunxiao Liu, Yongkun Wei, Mei-Kuang Chen, Xixi Zhao, Yu-Yi Chu, Yufan Qiu, Lunxiu Qin, Hirohito Yamaguchi, Mien-Chie Hung
Journal: Cancer Research (2018)

Abstract PARP1 inhibitors (PARPi) are currently used in the clinic for the treatment of ovarian and breast cancers, yet their therapeutic efficacy against hepatocellular carcinoma (HCC) has been disappointing. To ensure therapeutic efficacy of PARPi against HCC, a disease often diagnosed at intermediate to advanced stages with no effective treatment options, it is critical to identify not only biomarkers to predict PARPi resistance but also rational treatments to overcome this. Here, we report that a heterodimer of EGFR and MET interacts with and phosphorylates Y907 of PARP1 in the nucleus, which contributes to PARPi resistance. Inhibition of both EGFR and MET sensitized HCC cells to PARPi, and both EGFR and MET are known to be overexpressed in HCC. This report provides an explanation for the poor efficacy of PARPi against HCC and suggests combinatorial treatment consisting of EGFR, MET, and PARP inhibitors may be an effective therapeutic strategy in HCC. Significance: Regulation of PARP by the c-MET and EGFR heterodimer suggests a potentially effective combination therapy to sensitize HCC to PARPi.
Outcomes after Unrelated Cord Blood Transplantation (UCBT) in Patients with Chronic Myeloid Leukemia (CML): A Retrospective Study from the Cmwp-EBMT
Authors: Hugues De Lavallade, Giulia Sbianchi, Linda Koster, Jaime Sanz, Emanuele Angelucci, Gerard Socie, Isabelle Pietri, Hélène Labussière-Wallet, Jan J Cornelissen, Tobias Gedde-Dahl, Eefke J. Petersen, Francesca Bonifazi, Jorge Sierra, Martin Carre, Tony Marchand, Cecile Pochon, Nigel H Russel, Victoria Potter, Henrik Sengeloev, Per Ljungman, Simona Lapusan, Didier Blaise, Anna Paola Iori, Annalisa Ruggeri, Yves Chalandon, Ibrahim Yakoub-Agha
Journal: Blood (2018)
Rabies in a Dog Imported from Egypt — Connecticut, 2017
Authors: Yonette Hercules, Nelva J. Bryant, Ryan M. Wallace, Randall Nelson, Gabriel Palumbo, Jemeila N. Williams, J. Miguel Ocana, Sheryl Shapiro, Hilaire Leavitt, Sally Slavinsk, Alexandra Newman, David A. Crum, Brian E. Joseph, Lillian A. Orciari, Yu Li, Pamela Yager, Rene E. Condori, Kendra E. Stauffer, Clive Brown
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Importation of a rabid dog into the United States from Egypt, with documentation of rabies vaccination but no medical history, resulted in a six-state investigation and administration of rabies postexposure prophylaxis to multiple persons.
Abstract 294: The Relationship Between Oxygen Administration and Oxidative Stress During Hemorrhagic Shock and Resuscitation
Authors: Yukio Satoh, Masaru Suzuki, Akiko Shiroshita-Takeshita, Kei Hayashida, Shingo Hori
Journal: Circulation (2010)

Objective: Hemorrhagic shock (HS) causes tissue hypoxia and following inflammation. Although supplemental oxygen is commonly administered in patients during HS, it has been considered that hyperoxi...
Pomalidomide + Low-Dose Dexamethasone + Daratumumab in Relapsed and/or Refractory Multiple Myeloma after Lenalidomide-Based Treatment Failure
Authors: David S Siegel, Gary J. Schiller, Christy J. Samaras, Michael Sebag, Jesus G. Berdeja, Siddhartha Ganguly, Jeffrey V Matous, Kevin Song, Christopher S. Seet, Giampaolo Talamo, Mirelis Acosta-Rivera, Michael Bar, Donald P. Quick, Bertrand Anz, Gustavo Fonseca, Donna Reece, Amit Agarwal, Weiyuan Chung, Faiza Zafar, Nizar Bahlis
Journal: Blood (2018)
Real-Word Clinical Management of Patients Treated with Idelalisib in France: A Study of 529 Cases of Chronic Lymphocytic Leukemia (CLL) and Follicular Lymphoma (FL)
Authors: Anne-Sophie Michallet, Emmanuel Gyan, Pierre Feugier, Ana Nunes, Tarek Abdelhadi, Loic Ysebaert, Stéphane Leprêtre
Journal: Blood (2018)
Potential Impact of Consolidation Radiation Therapy for Advanced Hodgkin Lymphoma: A Secondary Modeling of SWOG S0816 with Receiver Operating Characteristic Analysis
Authors: Chul S. Ha, Hongli Li, Heiko Schoder, Chelsea C Pinnix, Elizabeth Brem, Nancy L. Bartlett, Andrew M. Evens, Eric D. Hsi, Lisa M. Rimsza, John P. Leonard, Brad S Kahl, Michael L. Leblanc, Sonali M. Smith, Louis S. Constine, Jonathan W. Friedberg
Journal: Blood (2018)
Correction to: Alterations of brain local functional connectivity in amnestic mild cognitive impairment
Authors: Dan Zheng, Wei Xia, Zhong Quan Yi, Pan Wen Zhao, Jian Guo Zhong, Hai Cun Shi, Hua Liang Li, Zhen Yu Dai, Ping Lei Pan
Journal: Translational Neurodegeneration (2018)

In the original publication of this article [1] surname of the first author is wrong.
A novel probiotic, Lactobacillus johnsonii 456, resists acid and can persist in the human gut beyond the initial ingestion period
Authors: Michael J. Davoren, Jared Liu, Jocelyn Castellanos, Norma I. Rodríguez-Malavé, Robert H. Schiestl
Journal: Gut Microbes (2018)

Probiotics are considered to have multiple beneficial effects on the human gastrointestinal tract, including immunomodulation, pathogen inhibition, and improved host nutrient metabolism. However, extensive characterization of these properties is needed to define suitable clinical applications for probiotic candidates. Lactobacillus johnsonii 456 (LBJ 456) was previously demonstrated to have anti-inflammatory and anti-genotoxic effects in a mouse model. Here, we characterize its resistance to gastric and bile acids as well as its ability to inhibit gut pathogens and adhere to host mucosa. While bile resistance and in vitro host attachment properties of LBJ 456 were comparable to other tested probiotics, LBJ 456 maintained higher viability at lower pH conditions compared to other tested strains. LBJ 456 also altered pathogen adhesion to LS 174T monolayers and demonstrated contact-dependent and independent inhibition of pathogen growth. Genome analyses further revealed possible genetic elements involved in host attachment and pathogen inhibition. Importantly, we show that ingestion of Lactobacillus johnsonii 456 over a one week yogurt course leads to persistent viable bacteria detectable even beyond the period of initial ingestion, unlike many other previously described probiotic species of lactic acid bacteria.
Abstract 15120: Nanoparticle-Mediated Delivery of Pitavastatin into Small Pulmonary Arteies by Intravenous Administration Attenuated the Progression of Already Established Monocrotaline-induced Pulmonary Arterial Hypertension in Rats
Authors: Kenzo Ichimura, Tetsuya Matoba, Ryoji Nagahama, Kaku Nakano, Kenji Sunagawa, Kensuke Egashira
Journal: Circulation (2014)

Background: Pulmonary arterial hypertension (PAH) is an intractable disease of small pulmonary artery in which multiple pathogenetic factors are involved. We have previously reported that poly(lactic acid/glycolic acid) (PLGA) nanoparticle (NP)-mediated targeting of pitavastatin into lungs by intratracheal instillation attenuated the development of PAH. In the present study we examined the effects of intravenous treatment with pitavastatin-NPs on the progression of already established PAH induced by monocrotaline (MCT). Methods and Results: Male Sprague-Dawley rats (200 to 230 g) were injected subcutaneously with 60 mg/kg MCT to induce PAH. At day 17 after MCT injection when PAH had been already established, animals were randomly divided into 4 groups, which treated with intravenous daily bolus administration of the following drugs for consecutive 4 days from 17 to 20 days after MCT injection; 1) vehicle, 2) FITC-NPs, 3) pitavastatin alone (1, 3, 10 or 30 mg/kg), or 4) pitavastatin-NPs (containing 1 or 3 mg/kg pitavastatin). Treatment with pitavastatin-NPs, but not with pitavastatin alone attenuated the progression of established PAH (Fig. A) associated with the reduction of inflammation and small pulmonary artery remodeling (stenosis and obstruction of pulmonary arterial branches) (Fig. B). In trace experiments, intravenous administration of FITC-NPs revealed the targeting of FITC-NPs into small pulmonary artery in rats with MCT-induced PAH, but not in normal animals. Importantly, in a separate protocol, treatment with pitavastatin-NPs improved the survival rate at day 35 (30% in pitavastatin-NP group vs. 61% in FITC-NP group, P&lt;0.05 by Kaplan-Meier). Conclusion: A novel NP-mediated targeting of pitavastatin into small pulmonary arteries by intravenous administration attenuated the progression of established PAH and improved survival associated with anti-inflammatory and anti-remodeling effects in a rat model of MCT-induced PAH.
Health-related Quality of Life for Abiraterone Plus Prednisone Versus Enzalutamide in Patients with Metastatic Castration-resistant Prostate Cancer: Results from a Phase II Randomized Trial
Authors: Daniel J. Khalaf, Katherine Sunderland, Bernhard J. Eigl, Christian K. Kollmannsberger, Nikita Ivanov, Daygen L. Finch, Conrad Oja, Joanna Vergidis, Muhammad Zulfiqar, Martin E. Gleave, Kim N. Chi
Journal: European Urology (2018)
Abstract 17700: Protective Role of Myelocytic Nitric Oxide Synthases in Hypoxic Pulmonary Hypertension in Mice
Authors: Masato Tsutsui, Takaaki Ogoshi, Takashi Kido, Sohsuke Yamada, Ke-Yong Wang, Yumiko Toyohira, Nobuyuki Yanagihara, Kazuhiro Yatera, Hiroshi Mukae
Journal: Circulation (2017)

Background: All three nitric oxide synthases (nNOS, iNOS, and eNOS) are expressed under pulmonary hypertensive conditions. Although the role of all the NOSs in pulmonary hypertension (PH) has been examined in pharmacological studies with non-selective NOSs inhibitors, obtained results are inconsistent possibly due to non-specificity of the agents. We addressed this point in our mice lacking all the NOSs. Methods and Results: Wild-type (WT), single nNOS-/-, iNOS-/-, eNOS-/-, and triple n/i/eNOSs-/- mice were exposed to hypoxia for 3 weeks. Hypoxic exposure significantly reduced survival rate only in the triple NOSs-/- genotype (P<0.05, n=14-34). Hypoxic exposure increased right ventricular (RV) pressure (RVP), RV hypertrophy (RVH), and medial thickening of small pulmonary arteries (MT) in all the genotypes. Notably, RVP were significantly worsened in the triple NOSs-/- genotype, and, to a lesser extent, in the eNOS-/- genotype, but not in the nNOS-/- or iNOS-/- genotype, as compared with the WT genotype, a...
Adoption of Medicare’s Transitional Care Management and Chronic Care Management Codes in Primary Care
Authors: Sumit D. Agarwal, Michael L. Barnett, Jeffrey Souza, Bruce E. Landon
Journal: JAMA (2018)

Adoption of Medicare's Transitional Care Management and Chronic Care Management Codes in Primary Care2][3] Transitional care management is designed to facilitate the transition from hospital to home and involves a dedicated office visit after hospital discharge as well as additional care coordination.Chronic care management is a comprehensive set of care coordination services provided monthly to patients with chronic illnesses.We examined the uptake of TCM and CCM nationally.
Phase 1 Study of CD19/CD22 Bispecific Chimeric Antigen Receptor (CAR) Therapy in Children and Young Adults with B Cell Acute Lymphoblastic Leukemia (ALL)
Authors: Liora M Schultz, Kara L. Davis, Christina Baggott, Christie Chaudry, Anne Cunniffe Marcy, Sharon Mavroukakis, Bita Sahaf, Katherine A Kong, Lori S Muffly, Stephen Kim, Everett H Meyer, Terry J. Fry, Haiying Qin, David B. Miklos, Crystal L. Mackall
Journal: Blood (2018)
Response to Comment on Cheung and Moses. Gestational Diabetes Mellitus: Is It Time to Reconsider the Diagnostic Criteria? Diabetes Care 2018;41:1337–1338
Authors: N. Wah Cheung, Robert G. Moses
Journal: Diabetes Care (2018)

We thank Dr. Sacks (1) for his supportive comments on a possible shift in the diagnostic criteria for gestational diabetes mellitus (GDM). The data that he has cited (2) lend further support for mean odds ratios (ORs) for pregnancy complications of 2.0 based on the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) data, rather than 1.75, as the thresholds on the glucose tolerance test for the diagnosis of GDM. To paraphrase his …