tbuckley/cabot-search huggingface dataset:
Abstract 20533: Clinical Differences and Outcome of Late Left Ventricular Recovery in Takotsubo Syndrome
Authors: Stjepan Jurisic, Victoria Lucia Cammann, Sebastiano Gili, Ken Kato, Katharina Ding, Beatrice Bacchi, Jelena-Rima Ghadri, Christian Templin
Journal: Circulation (2017)

Introduction:  Takotsubo Syndrome (TTS) is an acute heart failure syndrome, characterized by a transient left ventricular dysfunction. Clinical implications of differences in left ventricular (LV) recovery time remain unclear.   Hypothesis:  We aimed to analyze clinical features of TTS patients with prolonged time period of LV recovery in order to determine clinical parameters and outcome of late LV recovery.   Methods:  From a multicenter international registry, we investigated LV recovery time, defined as resolution of all wall motion abnormalities present in the initial echocardiogram or ventriculography. A time period of ten days after confirmed diagnosis was determined as cut-off for late LV recovery.   Results:  A total of 406 TTS patients from 1998 to 2016 were enrolled, of which 191 (47.0%) presented with early LV recovery and 215 (53.0%) presented with late LV recovery. Patients with late LV recovery were more often male (12.6% vs 5.2%; P=0.01) and more frequently they presented with typical TTS form (76.3% vs 67.0%, P=0.04). Troponin levels on admission (median factor increase of the upper limit of normal (ULN), 7.29 vs 5.96; P=0.04), maximal brain natriuretic peptide levels (15.78 vs 7.23 (ULN); P=0.03) and maximal C-reactive protein levels (17.80 vs 5.90 mg/l; P   Conclusions:  The different time period in LV recovery is significantly correlated to the extent of the impaired myocardium, cardiac and inflammatory biomarkers as well as acute neurologic comorbidities. Patients with slower LV recovery showed worse long-term outcomes.
Antigraft Antibody-Mediated Expression of Metalloproteinases on Endothelial Cells
Authors: GwénolaBoulday, StéphanieCoupel, FloraCoulon, Jean-PaulSoulillou, BéatriceCharreau
Journal: Circulation Research (2001)

Abstract—Endothelial cell (EC) interaction with antigraft antibodies (Abs) mediates EC injury and activation involved in vascular graft rejection. The aim of this study was to identify EC genes regulated in response to antigraft Ab binding that contribute to the endothelium alterations implicated in graft rejection or survival. By means of RNA differential display, 13 cDNA fragments corresponding to genes differentially expressed in ECs incubated with antigraft Abs were identified. Among these cDNAs were found the tissue inhibitor of metalloproteinase-1 (TIMP-1) and a desintegrin and metalloproteinase (ADAM-10). We demonstrated that TIMP-1 and ADAM-10 mRNA and protein expression was rapidly upregulated in ECs in response to antigraft Ab binding. Our data showed that TIMP-1 was upregulated in response to human IgG but not IgM and anti-galactosyl (Gal) α1-3Gal human xenogeneic Abs. In contrast, upregulation of ADAM-10 in ECs was shown to be mostly mediated by anti–Galα1-3Gal IgM Abs. Specific effects of hum...
CXCL10 Inhibits Viral Replication Through Recruitment of Natural Killer Cells in Coxsackievirus B3-Induced Myocarditis
Authors: JiYuan, ZhenLiu, TravisLim, HuifangZhang, JianqingHe, ElizabethWalker, CourtneyShier, YinjingWang, YueSu, AlhousseynouSall, BruceMcManus, DechengYang
Journal: Circulation Research (2009)

Coxsackievirus (CV)B3 is the primary cause of viral myocarditis. We previously observed CXC chemokine ligand 10 (CXCL10) upregulation in the myocardium early in infection. However, the impact of CXCL10 in CVB3-induced myocarditis is unknown. Using isolated primary mouse cardiomyocytes we demonstrated for the first time that cardiomyocytes can express CXCL10 on interferon-γ stimulation. To explore the role of CXCL10 in CVB3-induced myocarditis, both CXCL10 transgenic and knockout mice were used. Following CVB3 challenges, the viral titer in the hearts inversely correlated with the levels of CXCL10 at early phase of infection before visible immune infiltration. Furthermore, as compared with the control mice, the decreased virus titers in the CXCL10 transgenic mouse hearts led to less cardiac damage and better cardiac function and vice verse in the knockout mice. This antiviral ability of CXCL10 might be through recruitment of natural killer (NK) cells to the heart and increased interferon-γ expression early...
Pollution and Global Health – An Agenda for Prevention
Authors: Philip J. Landrigan, Richard Fuller, Howard Hu, Jack Caravanos, Maureen L. Cropper, David Hanrahan, Karti Sandilya, Thomas C. Chiles, Pushpam Kumar, William A. Suk
Journal: Environmental Health Perspectives (2018)

Pollution is a major, overlooked, global health threat that was responsible in 2015 for an estimated 9 million deaths and great economic losses. To end neglect of pollution and advance prevention of pollution-related disease, we formed the Lancet Commission on Pollution and Health. Despite recent gains in understanding of pollution and its health effects, this Commission noted that large gaps in knowledge remain. To close these gaps and guide prevention, the Commission made research recommendations and proposed creation of a Global Observatory on Pollution and Health. We posit that successful pollution research will be translational and based on transdisciplinary collaborations among exposure science, epidemiology, data science, engineering, health policy, and economics. We envision that the Global Observatory on Pollution and Health will be a multinational consortium based at Boston College and the Harvard T.H. Chan School of Public Health that will aggregate, geocode, and archive data on pollution and pollution-related disease; analyze these data to discern trends, geographic patterns, and opportunities for intervention; and make its findings available to policymakers, the media, and the global public to catalyze research, inform policy, and assist cities and countries to target pollution, track progress, and save lives. https://doi.org/10.1289/EHP3141.
Cardiac Nonmyocytes in the Hub of Cardiac Hypertrophy
Authors: TakehiroKamo, HiroshiAkazawa, IsseiKomuro
Journal: Circulation Research (2015)

Cardiac hypertrophy is characterized by complex multicellular alterations, such as cardiomyocyte growth, angiogenesis, fibrosis, and inflammation. The heart consists of myocytes and nonmyocytes, such as fibroblasts, vascular cells, and blood cells, and these cells communicate with each other directly or indirectly via a variety of autocrine or paracrine mediators. Accumulating evidence has suggested that nonmyocytes actively participate in the development of cardiac hypertrophy. In this review, recent progress in our understanding of the importance of nonmyocytes as a hub for induction of cardiac hypertrophy is summarized with an emphasis of the contribution of noncontact communication mediated by diffusible factors between cardiomyocytes and nonmyocytes in the heart.
Importance of Cardiac Troponins I and T in Risk Stratification of Patients With Acute Pulmonary Embolism
Authors: StavrosKonstantinides, AnnetteGeibel, ManfredOlschewski, WolfgangKasper, NadineHruska, SebastianJäckle, LutzBinder
Journal: Circulation (2002)

Background— Assessment of risk and appropriate management of patients with acute pulmonary embolism (PE) remains a challenge. Cardiac troponins I (cTnI) and T (cTnT) are reliable indicators of myocardial injury and may be associated with right ventricular dysfunction in PE. Methods and Results— The present prospective study included 106 consecutive patients with confirmed acute PE. cTnI was elevated (≥0.07 ng/mL) in 43 patients (41%), and cTnT (≥0.04 ng/mL) was elevated in 39 (37%). Elevation of cTnI or cTnT was significantly associated with echocardiographically detected right ventricular dysfunction (P=0.001 and P<0.05, respectively). Moreover, a significant correlation was found between elevation of cTnI or cTnT and the two major end points overall mortality and complicated in-hospital course. The negative predictive value of cardiac troponins for major clinical events was 92% to 93%. Importantly, there was obvious escalation of in-hospital mortality, the rate of complications, and the incidence of rec...
Abstract 12219: Acyl CoA Lysocardiolipin Acyltransferase 1 Knockout Protects Against Hypoxia Induced Pulmonary Artery Hypertension and Cardiac Bioenergetic Dysfunction
Authors: Kennedy S Mdaki, Youhua Wang, Yuguang Shi
Journal: Circulation (2017)

Introduction: Cardiovascular disease remains one of the leading causes of death worldwide. Pulmonary artery hypertension (PAH) affects the lungs, pulmonary artery, and heart by histological modifications, increased arterial pressure, and reduced ventricular function respectively. We recently showed that Acyl CoA Lysocardiolipin Acyltransferase 1 (ALCAT1) mediates pathological remodeling of mitochondrial cardiolipin with aberrant fatty acyl chains that are highly sensitive to reactive oxygen and nitrogen species. Hypothesis: We hypothesize that ALCAT1 knockout (KO) may attenuate hypoxia induced pulmonary artery hypertension (PAH) and cardiac dysfunction. Methods: Adult C57BL/6 mice were divided into four groups (n = 5 per group), wild-type (WT), wild type exposed to hypoxia (WT-HP), ALCAT1 KO (AL), ALCAT1 KO exposed to Hypoxia (AL-HP). PAH was induced by a standard 3 to 4 weeks exposure, at an interval of 6 hours per day for six days per week, to 10% oxygen level in a hypoxia chamber. Cardiac function was ...
Abstract 4445: Post-transcriptional inhibition of PTPN23 by SND1: Potential mechanism for hepatocellular carcinoma
Authors: Nidhi H. Jariwala, Rachel G. Mendoza, Garcia Dawn, Lai Zhao, Mark A. Subler, Jolene J. Windle, Paul B. Fisher, Chen Yidong, Devanand Sarkar
Journal: Cancer Research (2018)

Abstract Oncoprotein SND1 regulates gene expression at a post-transcriptional level in multiple cancers including hepatocellular carcinoma (HCC). Staphylococcal nuclease domains of SND1 function as an RNAse and tudor domain facilitates protein-oligonucleotide interaction. In the present study, we aimed to identify RNA interactome of SND1 to obtain better insights into gene regulation by SND1. RNA interactome was identified by immunoprecipitation of RNA using anti-SND1 antibody from human HCC cells followed by RNA-sequencing (RIP-Seq). With an adjusted p value of &amp;lt;0.01 and &amp;gt;2-fold enrichment over control, 282 mRNAs were identified to significantly associate with SND1 protein. We focused on the tumor suppressor PTPN23 because its regulation by SND1 and its role in HCC are not known. PTPN23 levels were downregulated in human HCC cells versus normal hepatocytes and in human HCC tissues versus normal adjacent liver as revealed by immunohistochemistry. In human HCC cells, knocking down SND1 increased and overexpression of SND1 decreased PTPN23 protein. RNA binding and degradation assays revealed that SND1 specifically binds to and degrades 3'-UTR of PTPN23 mRNA. Tetracycline-inducible PTPN23 overexpression in human HCC cells resulted in significant inhibition in proliferation, migration and invasion and in vivo tumorigenesis. PTPN23 induction caused inhibition in activation of c-Met, EGFR, Src and FAK, suggesting that as a phosphatase PTPN23 inhibits activation of these oncogenic kinases. The present study unravels a novel function of SND1 in targeting PTPN23 and identifies PTPN23 as a unique tumor suppressor for HCC. PTPN23 might function as a homeostatic regulator of multiple kinases restraining their activation. Citation Format: Nidhi H. Jariwala, Rachel G. Mendoza, Garcia Dawn, Lai Zhao, Mark A. Subler, Jolene J. Windle, Paul B. Fisher, Chen Yidong, Devanand Sarkar. Post-transcriptional inhibition of PTPN23 by SND1: Potential mechanism for hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4445.
Abstract PR10: Development and characterization of novel/genetically defined mouse models of malignant peripheral nerve sheath tumor for preclinical therapeutics testing
Authors: Amish J. Patel, Jessica J. Sher, Yu Chen, Ping Chi
Journal: Clinical Cancer Research (2018)

Abstract Malignant peripheral nerve sheath tumor (MPNST) represents 5-10% of soft-tissue sarcomas, and can develop either sporadically, in patients with neurofibromatosis Type I (NF1), or in association with radiotherapy. Limited genetic information regarding their pathogenesis in humans has posed a challenge to developing authentic mouse models more reflective of the human disease. Recently, we discovered that these clinically distinct MPNST subtypes commonly share inactivating mutations in tumor suppressors NF1, CDKN2A, and PRC2 (Polycomb Repressive Complex 2). Using a combination of Cre-loxP-based genetically engineered mouse models (GEMMs) and stem/progenitor transplantation models, we show that inactivation of these tumor suppressors is sufficient to promote development of bona fide MPNSTs. We envision that further characterization of these models will provide a solid foundation for investigating MPNST biology and developing therapies in a genetically defined context more closely resembling the human disease. This abstract is also being presented as Poster B18. Citation Format: Amish J. Patel, Jessica J. Sher, Yu Chen, Ping Chi. Development and characterization of novel/genetically defined mouse models of malignant peripheral nerve sheath tumor for preclinical therapeutics testing [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr PR10.
Abstract 4164: Fasting protects mice from lethal radiation by promoting small intestinal stem cell survival
Authors: Marimar de la Cruz Bonilla, Kristina M. Stemler, Tara N. Fujimoto, Sabrina Jeter-Jones, Jessica M. Molkentine, Gabriela M. Asencio Torres, Cullen M. Taniguchi, Helen Piwnica-Worms
Journal: Cancer Research (2018)

Abstract Pancreatic cancer is the fourth leading cause of cancer-related deaths in the US. Surgical resection is the only potentially curative treatment; however, only 15%-20% of patients present with tumors that can be resected. There is no consensus regarding standard of care in unresectable cases, however many academic centers use stereotactic body radiotherapy (SBRT) to give tumor-directed radiotherapy (RT). Unfortunately, even this conformal technique can still cause severe gastrointestinal (GI) toxic effects caused by the proximity of the pancreatic head to the duodenum. Protecting the intestine from the toxic effects of radiation may enable dose escalation that could achieve more effective local control of disease. We and others have previously shown that a prolonged fast of 24 hours protects mice from lethal doses of etoposide. In this study, we extend and build on our previous finding to demonstrate that a similar 24 hour fast also protects from lethal doses of total abdominal radiation. Histologic analyses, using the Withers-Elkind microcolony assay, show that fasting protected small intestinal (SI) stem cells from radiation damage and promoted early regeneration. To show a proof-of-principle for the use of this radioporotective maneuver in cancer therapy, we developed an orthotopic model of pancreatic cancer using KPC tumor cells syngeneic to C57BL/6. Here, we show that fasting-mediated intestinal protection enabled dose escalated SBRT for treatment of these orthotopic tumors. RT with fasting radioprotection delayed tumor growth and improved survival compared to controls. Given this robust phenotype, we developed a 3D culture ex vivo assay using intestinal stem cell enriched epithelial spheroid cultures. We modified these intestinal spheroids with a bioluminescent reporter and used these cells to develop a modified clonogenic assay for 3D culture that can be used to identify novel radioprotectors, such as a fasting mimetic. Taken together, these results suggest that fasting protects small intestinal stem cells sufficiently to allow animals to receive potentially curative doses of abdominal radiation that would other wise be lethal. Future work will aim to identifying the mechanism by which fasting confers intestinal protection and drug candidates that can be used to mimic this fasting-mediated protection. Citation Format: Marimar de la Cruz Bonilla, Kristina M. Stemler, Tara N. Fujimoto, Sabrina Jeter-Jones, Jessica M. Molkentine, Gabriela M. Asencio Torres, Cullen M. Taniguchi, Helen Piwnica-Worms. Fasting protects mice from lethal radiation by promoting small intestinal stem cell survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4164.
Flare of Autoimmune Hepatitis Causing Acute on Chronic Liver Failure: Diagnosis and Response to Corticosteroid Therapy
Authors: Lovkesh Anand, Ashok Choudhury, Chhagan Bihari, Barjesh C. Sharma, Manoj Kumar, Rakhi Maiwall, Soek Siam Tan, Samir R. Shah, Saeed Hamid, Amna S. Butt, Wasim Jafri, Yogesh K. Chawla, Sunil Taneja, Ajay Duseja, Radha K. Dhiman, Mamun Al Mahtab, Hasmik Ghazinyan, Zhongping Duan, Yu Chen, Akash Shukla, Jinhua Hu, Zaigham Abbas, Sombat Treeprasertsuk, Laurentius A. Lesmana, Cosmas R Lesmana, Jose D. Sollano, Gian Carpio, Manoj K. Sahu, Guresh Kumar, Shiv K. Sarin
Journal: Hepatology (2018)

Autoimmune hepatitis (AIH) is considered less common in the Asia Pacific region. Due to this, AIH flare as a cause of acute on chronic liver failure (ACLF) is often overlooked and treatment delayed. We aimed at the defining clinical and histopathological spectrum and role of steroid therapy in AIH-ACLF. Patients with AIH-ACLF, prospectively recruited and followed between 2012 and 2017, were analyzed from the Asian Pacific Association for the Study of the Liver ACLF Research Consortium (AARC) data base. Diagnosis of AIH was confirmed using International Autoimmune Hepatitis Group score or simplified AIH score with histopathological evidence. Of 2,825 ACLF patients, 82 (2.9%) fulfilled criteria of AIH (age 42.1 ± 18.1 years, 70% female). At baseline, mean bilirubin was 18.6 ± 8.2 mg/dL, Child-Turcotte-Pugh score was 11.7 ± 1.4, and Model for End-Stage Liver Disease (MELD) score was 27.6 ± 6.5. Mean immunoglobulin G was 21.61 ± 7.32 g/dL, and this was elevated ≥1.1 times in 97% of cases; 49% were seronegative. Liver histology was available in 90%, with median histological activity index of 10 (interquartile range, 7-12); 90% with moderate to severe interface activity; 56% showing significant parenchymal necrosis (bridging and confluent necrosis); and cirrhosis in 42%. Twenty-eight (34%) patients received steroid therapy and showed shorter intensive care unit (ICU) stay (median 1.5 versus 4 days, P < 0.001) and improved 90-day survival (75% versus 48.1%, P = 0.02) with comparable incidence of sepsis (P = 0.32) compared to those who did not. Patients of advanced age, more severe liver disease (MELD >27; 83.3% sensitivity, 78.9% specificity, area under the receiver operating characteristic curve 0.86), presence of hepatic encephalopathy, and fibrosis grade ≥F3 had an unfavorable response to corticosteroid therapy. Conclusion: AIH presenting as ACLF is not uncommon in Asian patients; a low threshold for liver biopsy is needed to confirm the diagnosis as nearly half the patients are seronegative; early stratification to steroid therapy or liver transplantation (MELD >27, hepatic encephalopathy in ≥F3) would reduce ICU stay and improve outcomes.
Talazoparib in Patients with Advanced Breast Cancer and a Germline <i>BRCA</i> Mutation
Authors: Jennifer K. Litton, Hope S. Rugo, Johannes Ettl, Sara A. Hurvitz, Anthony Gonçalves, Kyung-Hun Lee, Louis Fehrenbacher, Rinat Yerushalmi, Lida A. Mina, Miguel Martin, Henri Roché, Young-Hyuck Im, Ruben G.W. Quek, Denka Markova, Iulia C. Tudor, Alison L. Hannah, Wolfgang Eiermann, Joanne L. Blum
Journal: New England Journal of Medicine (2018)

The poly(adenosine diphosphate-ribose) inhibitor talazoparib has shown antitumor activity in patients with advanced breast cancer and germline mutations in BRCA1 and BRCA2 ( BRCA1/2).We conducted a randomized, open-label, phase 3 trial in which patients with advanced breast cancer and a germline BRCA1/2 mutation were assigned, in a 2:1 ratio, to receive talazoparib (1 mg once daily) or standard single-agent therapy of the physician's choice (capecitabine, eribulin, gemcitabine, or vinorelbine in continuous 21-day cycles). The primary end point was progression-free survival, which was assessed by blinded independent central review.Of the 431 patients who underwent randomization, 287 were assigned to receive talazoparib and 144 were assigned to receive standard therapy. Median progression-free survival was significantly longer in the talazoparib group than in the standard-therapy group (8.6 months vs. 5.6 months; hazard ratio for disease progression or death, 0.54; 95% confidence interval [CI], 0.41 to 0.71; P<0.001). The interim median hazard ratio for death was 0.76 (95% CI, 0.55 to 1.06; P=0.11 [57% of projected events]). The objective response rate was higher in the talazoparib group than in the standard-therapy group (62.6% vs. 27.2%; odds ratio, 5.0; 95% CI, 2.9 to 8.8; P<0.001). Hematologic grade 3-4 adverse events (primarily anemia) occurred in 55% of the patients who received talazoparib and in 38% of the patients who received standard therapy; nonhematologic grade 3 adverse events occurred in 32% and 38% of the patients, respectively. Patient-reported outcomes favored talazoparib; significant overall improvements and significant delays in the time to clinically meaningful deterioration according to both the global health status-quality-of-life and breast symptoms scales were observed.Among patients with advanced breast cancer and a germline BRCA1/2 mutation, single-agent talazoparib provided a significant benefit over standard chemotherapy with respect to progression-free survival. Patient-reported outcomes were superior with talazoparib. (Funded by Medivation [Pfizer]; EMBRACA ClinicalTrials.gov number, NCT01945775 .).
Possible Association of Heart Failure Status With Synthetic Balance Between Aldosterone and Dehydroepiandrosterone in Human Heart
Authors: ShotaNakamura, MichihiroYoshimura, MasafumiNakayama, TeruhikoIto, YujiMizuno, EisakuHarada, TomohiroSakamoto, YoshihikoSaito, KazuwaNakao, HirofumiYasue, HisaoOgawa
Journal: Circulation (2004)

Background— Aldosterone is produced not only in the adrenal gland but also in the extra-adrenal tissues, including failing human heart. This study examined the production of dehydroepiandrosterone (DHEA) in human heart and elucidated the possible physiological significance. Method and Results— Using left ventricular tissues obtained at autopsy, reverse transcription–polymerase chain reaction followed by Southern blot analysis revealed the gene expressions of CYP17. By measuring plasma aldosterone and DHEA levels at the coronary sinuses and aortic roots during cardiac catheterization, we found that DHEA but not aldosterone was secreted from control subjects (P<0.0001 and P=0.74, respectively), whereas aldosterone but not DHEA was secreted from patients with heart failure (P=0.0017 and P=0.67, respectively). To examine the significance of DHEA, we measured myocyte cell sizes and the gene expression of B-type natriuretic peptide (BNP), using a neonatal rat cardiocyte culture system. We found that DHEA (10−8 ...