tbuckley/cabot-search huggingface dataset:
Abstract 503: Nicotinamide Riboside Modulates Late Sodium Current and Cardiac Repolarization
Authors: Daniel S Matasic, Pravda Quinones, Charles Brenner, Barry London
Journal: Circulation Research (2019)

Background: Boosting NAD + content within the heart has emerged as a cardioprotective strategy against heart failure-related remodeling, ischemic injury, and arrhythmias. Our group recently demonstrated that the bioavailable NAD + precursor Nicotinamide Riboside (NR) drives Sirtuin 1-mediated deacetylation of the main cardiac sodium channel Na v 1.5 to increase peak sodium current (I Na ), a major determinant of cardiac excitability and action potential conduction. However, the effects of NAD + precursors and NR on cardiac repolarization are relatively unexplored. Objective: To evaluate the effects of NR on late Na + current and cardiac repolarization. Methods: To study the in vitro effects of NR, whole-cell patch clamp was utilized to measure I Na and late sodium current (I NaL ) in myocytes isolated from 1-3 day old neonatal rats (NRCMs). To study the in vivo effects of NR, 4-5 month-old C57BL/6 mice were placed on either a control diet or a diet supplemented with NR (1%). EKGs were performed at baseline, 6 weeks, and 12 weeks post-diet. Results: NR increased peak I Na (500 uM: +60.1 ± 26%, 5 mM: +74.7 ± 39%) with a non-significant change in absolute I NaL (500 uM: -12.8 ± 9%, 5 mM: -32.4 ± 20%) , leading to decreased I NaL when normalized to peak current (500 uM: -45.2 ± 7.8%, 5 mM: -51.6 ± 9.8%, Figure A,B). Additionally, 12-week dietary NR supplementation shortened QT c in NR-treated mice (-9.1 ± 4.6%) but not in control mice (+1.7 ± 1.3%, Figure C). Conclusion: NAD + supplementation with NR is potentially anti-arrhythmic by decreasing I NaL and shortening QT c . Potential mechanisms include mitigating the effects of oxidative stress and/or modulation of PKA and PKC phosphorylation of Na v 1.5.
Improving Adjuvant Endocrine Treatment Tailoring in Premenopausal Women With Hormone Receptor–Positive Breast Cancer
Authors: Matteo Lambertini, Eva Blondeaux, Francesco Perrone, Lucia Del Mastro
Journal: Journal of Clinical Oncology (2019)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.
Ruxolitinib in Refractory Acute and Chronic Graft-Versus-Host Disease: A Multi-Center Survey Study
Authors: Virginia Escamilla Gomez, Valentín García Gutiérrez, Teresa Caballero-Velázquez, Nancy Rodríguez-Torres, Ildefonso Espigado, Lucia Lopez Corral, Dolores Caballero, Irene García-Cadenas, Rodrigo Martino, Silvanna Daniela Saavedra Gerosa, Ariadna Pérez Martínez, Pedro Antonio González Sierra, Maria De La Cruz Viguria Alegria, Teresa Zudaire, Ingrid Magnolia Parra Salinas, Marc Poch, Marta González Vincent, Miguel Ángel Díaz Pérez, Blanca Molina Angulo, Isabel Sanchez-Ortega, Rocio Parody Porras, Christelle M Ferra Coll, Guillermo Orti, David Valcarcel, Rafael De La Camara, Paula Molés, Jaime Sanz, Juan Montoro Gómez, Kyra Velázquez-Kennedy, José A. Pérez-Simón
Journal: Blood (2017)
Shiga-like Toxin Producing E. coli Identified in Patients with Multiple Myeloma (MM) Hospitalized Due to Acute Onset Diarrhea; First Report on the Clinical Use of the Biofire Film Array Gastrointestinal Panel
Authors: Natalia Kreiniz, Tamar Tadmor, Aaron Polliack, Asala Abu-Ahmad, Orit Golan-Shani, Paz Alona
Journal: Blood (2018)
Dual Targeting of Cell-Cycle Checkpoint Kinase and Unfolded Protein Response As a Novel Therapeutic Approach for High-Risk Multiple Myeloma with TP53 Deletion or Mutations
Authors: Yuka Tanaka, Takayuki Tabayashi, Yasuyuki Takahashi, Yuta Kimura, Tatsuki Tomikawa, Junichi Watanabe, Tomoe Anan-Nemoto, Morihiko Sagawa, Reiko Watanabe, Michihide Tokuhira, Masahiro Kizaki
Journal: Blood (2018)
Abstract 323: A Novel Human Specific Long Noncoding RNA PG1 Controls Human Cardiogenesis via Regulating Beta-catenin Activity
Authors: Lei Han, Yang Li, Lei Yang
Journal: Circulation Research (2019)

Long noncoding RNAs (lncRNAs) can regulate gene expression, signaling pathway, cellular and tissue functions at various stages. Recently, accumulating evidences suggest that lncRNAs play important roles in cell fate specification and organ development. We found hundreds of lncRNAs, which show lineage-specific expressions in human embryonic stem (ES) cell-derived multipotential cardiovascular progenitor cells (MCPs), cardiomyocytes (CMs), smooth muscle cells (SMs) or endothelial cells (ECs), by using whole transcriptome sequencing. Among MCP-specific lncRNAs, we identified a novel human lncRNA, PG1, which controls cardiovascular differentiation from human pluripotent stem cells. We found PG1 could regulate the early segregation of nascent mesoderm cells towards cardiac verse hematopoietic fate. Knockout of PG1 in human induced pluripotent stem (iPS) cells and H1 ES cells by CRISPR/Cas9 significantly increased hematopoietic differentiation from pluripotent stem cells when compared with wild type controls. Furthermore, our data suggest PG1 could bind beta-catenin protein to modulate Wnt signaling activity to regulate nascent mesoderm specification. In summary, we identified a novel human specific lncRNA, PG1, which plays an essential role in early stage human heart development.
Abstract 15957: Trends in Practice and Outcomes From 2011-2015 for Surgical Aortic Valve Replacement - Update From the German Aortic Valve Registry on 42,776 Patients
Authors: Stephan Ensminger, Buntaro Fujita, Timm Bauer, Helge Möllmann, Andreas Beckmann, Raffi Bekeredjian, Sabine Bleiziffer, Elke Schäfer, Christian W Hamm, Friedrich W Mohr, Hugo A Katus, Wolfgang Harringer, Thomas Walther, Christian Frerker
Journal: Circulation (2017)

Introduction: Surgical aortic valve replacement (sAVR) is in focus in the presence of alternative, less invasive approaches. The purpose of this analysis was to characterize current trends of patie...
Association of Treatment With 5α-Reductase Inhibitors and Prostate Cancer Mortality Among Older Adults
Authors: Abhishek Kumar, Vinit Nalawade, Paul Riviere, Reith R. Sarkar, J. Kellog Parsons, James D. Murphy, Brent S. Rose
Journal: JAMA Network Open (2019)

This cohort study examines the association between use of 5α-reductase inhibitors and prostate cancer mortality among US Medicare beneficiaries.
Pulmonary IL‐33 orchestrates innate immune cells to mediate respiratory syncytial virus‐evoked airway hyperreactivity and eosinophilia
Authors: Yi‐Hsiu Wu, Alan Chuan‐Ying Lai, Po‐Yu Chi, Christina Li‐Ping Thio, Wei‐Yu Chen, Ching‐Hui Tsai, Yungling Leo Lee, Nicholas W. Lukacs, Ya‐Jen Chang
Journal: Allergy (2019)

Abstract Background Respiratory syncytial virus (RSV) infection is epidemiologically linked to asthma. During RSV infection, IL‐33 is elevated and promotes immune cell activation, leading to the development of asthma. However, which immune cells are responsible for triggering airway hyperreactivity (AHR), inflammation and eosinophilia remained to be clarified. We aimed to elucidate the individual roles of IL‐33‐activated innate immune cells, including ILC2s and ST2 + myeloid cells, in RSV infection‐triggered pathophysiology. Methods The role of IL‐33/ILC2 axis in RSV‐induced AHR inflammation and eosinophilia were evaluated in the IL‐33‐deficient and YetCre‐13 Rosa‐DTA mice. Myeloid‐specific, IL‐33‐deficient or ST2‐deficient mice were employed to examine the role of IL‐33 and ST2 signaling in myeloid cells. Results We found that IL‐33‐activated ILC2s were crucial for the development of AHR and airway inflammation, during RSV infection. ILC2‐derived IL‐13 was sufficient for RSV‐driven AHR, since reconstitution of wild‐type ILC2 rescued RSV‐driven AHR in IL‐13‐deficient mice. Meanwhile, myeloid cell‐derived IL‐33 was required for airway inflammation, ST2 + myeloid cells contributed to exacerbation of airway inflammation, suggesting the importance of IL‐33 signaling in these cells. Local and peripheral eosinophilia is linked to both ILC2 and myeloid IL‐33 signaling. Conclusions This study highlights the importance of IL‐33‐activated ILC2s in mediating RSV‐triggered AHR and eosinophilia. In addition, IL‐33 signaling in myeloid cells is crucial for airway inflammation.
Unexplained liver dysfunction in a young Chinese man with eosinophilia
Authors: Zhuwan Lyu, Qi Miao, Pan Jiang, Xiao Xiao, Xiaoyu Chen, Qixia Wang, Xiong Ma
Journal: Gut (2019)

A 37-year-old man complained of a 7 months’ history of yellowish skin and sclera accompanied by fatigue, pruritus and dry mouth, with a history of subcutaneous masses on his elbow. Hard and fixed subcutaneous masses were noted on his palm and periauricular region, the largest of which was approximately 2 cm in diameter (figure 1A). Mildly tortuous veins on his abdominal wall above the umbilicus were detected (figure 1B). The patient had no history of liver disease. Family history was not contributory. Laboratory tests demonstrated a leucocyte count of 2.9×109/L (3.97–9.15×109/L), 7.9% eosinophil (0.5%–5%), a total bilirubin of 94.5μmol/L, gamma-glutamyl transpeptidase of 67.8 U/L (11–50 U/L) and serum IgG of 23.3 g/L (7–16 g/L), IgG4 of 3.48 g/L (0.08–1.4 g/L) and IgE of 256 IU/mL (0–100 IU/mL). Coagulation function tests revealed prothrombin time of 14.8 s (9.4–12.5 s), international normalised ratio (INR) of 1.33 and …
The global effect of extreme weather events on nutrient supply: a superposed epoch analysis
Authors: Caro S Park, Elisabeth Vogel, Leila M Larson, Samuel S Myers, Mark Daniel, Beverley-Ann Biggs
Journal: The Lancet Planetary Health (2019)

BackgroundTo date, the effects of extreme weather events on nutrient supply within the population have not been quantified. In this study, we investigated micronutrient, macronutrient, and fibre supply changes during 175 extreme weather events within 87 countries in the year that a major extreme weather event occurred, with a targeted focus on low-income settings.MethodsWe collected data from the International Disasters Database and the Global Expanded Nutrient Supply model for the period 1961–2010, and applied superposed epoch analysis to calculate the percentage change in nutrient supply during the year of an extreme weather event relative to its historical context. We composited globally and by subgroup (EU, landlocked developing countries, least developed countries, low-income food deficit countries, and net food-importing developing countries). Lastly, we reported nutrient supply changes in terms of recommended dietary allowance for children aged 1–3 years.FindingsGlobally, all micronutrient supplies had a modest negative percentage change during the year of an extreme weather event; of these effects, those that reached an α=0·05 significance level included calcium, folate, thiamin, vitamin B6, and vitamin C, with nutrient supply changes ranging from −0·40 to −1·73% of the average supply. The effect of an extreme weather event was especially magnified among landlocked developing countries and low-income food deficit countries, with significant nutrient supply changes ranging from −1·61 to −7·57% of the average supply. Furthermore, the observed nutrient supply deficits in landlocked developing countries constituted a large percentage (ranging from 1·95 to 39·19%) of what a healthy child's sufficient average dietary intake should be.InterpretationThe global effects of extreme weather events on nutrient supply found in this study are modest in isolation; however, in the context of nutrient needs for healthy child development in low-income settings, the effects observed are substantial.FundingAustralian-American Fulbright Commission.
Vorinostat (SAHA) Inhibits STAT6 Phosphorylation and Transcription, Downregulates Bcl-xL, and Induces Apoptosis in Hodgkin Lymphoma (HL) Cell Lines.
Authors: Daniela Buglio, Georgios Georgakis, Kazuhiko Arima, Yong-Jun Liu, Anas Younes
Journal: Blood (2007)
No Influence of Peripheral Blood CD34+ and CD3+ Graft Cell Counts on Outcomes after Reduced-Intensity Conditioning Transplantation Using Post-Transplant Cyclophosphamide
Authors: Alice Garnier, Thierry Guillaume, Pierre Peterlin, Amandine Le Bourgeois, Alix Duquesne, Marion Eveillard, Beatrice Mahe, Viviane Dubruille, Nicolas Blin, Cyrille Touzeau, Thomas Gastinne, Anne Lok, Antoine Bonnet, Steven LE Gouill, Philippe Moreau, Marie C Bene, Patrice Chevallier
Journal: Blood (2018)
Abstract 545: A Multifunctional Genetic Probe for Investigating Mitochondrial Calcium Dynamics in Cardiac Cells
Authors: Patrick J Ernst, Ningning Xu, Meng Zhao, Jianyi (Jay) Zhang, Xiaoguang (Margaret) Liu, Lufang Zhou
Journal: Circulation Research (2019)

Introduction: Calcium cycling plays a critical role in regulating function of cardiomyocytes (CMs) under both physiological and pathological conditions. Among their many important functions, mitochondria are known to involve in calcium handling. However, little is known about the calcium dynamics of human stem cell-derived cardiomyocytes (hiPSC-CM) and what little is known shows much greater variability than what is seen in adult cardiomyocytes. Methods: We produced adenovirus encoding the red Ca 2+ indicator RCaMP prepended with a mitochondrial targeting sequence fused to the green Ca 2+ indicator GCaMP with a cleavable linker. We then used this virus to induce expression of this calcium probe in CMs &amp; recorded calcium activity with a confocal microscope. Results &amp; Discussion: Mitochondrial targeting was confirmed by confocal imaging showing GCaMP (green), mRCaMP (red), and costaining with Mitotracker Deep Red (Magenta) (Figure 1A, 1B). Probe functionality was validated by observing beat-by-beat calcium dynamics in paced neonatal rat CMs with and without blocking mitochondrial calcium uptake with the mitochondrial calcium uniport inhibitor Ru360. Recording GCaMP and mRCaMP dynamics in adult CMs (Figure 1C) showed synchronous beat-by-beat calcium activity in the cytosol and mitochondria. However, iPSC-CMs (Figure 1D) showed variable mitochondrial activity, with some synchronous mitochondria and some showing inverse activity. Conclusions: hiPSC-CMs and adult CMs show differences in beat-by-beat mitochondrial calcium dynamics, offering a potential investigatory target for improving the therapeutic effect of stem cell-derived heart therapies.
Abstract 600: Anti-Angiogenic Effects of Circulating Exosomes From Patients With Acute Coronary Syndrome: Potential Role of miR-199a and miR-125a
Authors: Ana Paula V Dantas, Joaquim Bobi, Luis Ortega-Paz, Ahmed Amin, Margarida Pujol-Lopez, Iolanda Lazaro, Manel Sabate, Salvatore Brugaletta
Journal: Circulation Research (2019)

Circulating exosomes have a great impact in human health as a biomarker or as messengers in intercellular signaling. In this study we aimed to determine how miRNA profile in circulating exosomes interfere with angiogenic phenotype of endothelial cell (EC) during acute event of coronary syndrome. Exosomes were purified from serum of patients with non-ST segment elevation myocardial infarction in the acute phase (NSTEMI, n=34) during percutaneous coronary intervention. Healthy donors (n=23) were included as control. Purified exosomes were quantified and characterized by nanoparticle tracking analysis (Nanosight). Healthy EC (HUVEC) were treated for 48h with labeled exosomes (5x10 5 particles/1x10 6 cells) and tested for their angiogenic potential (migration and tube formation) and mRNA expression. Exosome miRNA profile was determined by miRNA array. Exosomes levels were markedly increased in NSTEMI (1.3x10 9 particle/ml) vs control (7.5x10 8 particle/ml; p=0.02). HUVEC treatment with healthy exosomes improve migration and tube formation compared to untreated HUVEC. Nevertheless, exosomes from NSTEMI patients, in the acute phase lack their pro-angiogenic potential (Fig A). Network analysis of exosome miRNA and HUVEC mRNA expression revealed a correlation of increased miR-199a and miR-125a expression with decrease of components involved in EC sprout and stabilization (Fig B). Circulating exosomes have an important role in the control of angiogenesis. However, in the acute phase of NSTEMI intercellular communication via exosome is modified and exert an inhibitory effect on angiogenesis. These results could contribute to the progression and outcomes of the disease.
Seronegative autoimmune autonomic ganglionopathy from dual immune checkpoint inhibition in a patient with metastatic melanoma
Authors: Catherine A. Gao, Urs M. Weber, Aldo J. Peixoto, Sarah A. Weiss
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Immune checkpoint inhibitors have improved clinical outcomes including survival in several malignancies but have also been associated with a range of immune-related adverse events (irAEs). Neurological irAEs are rare compared to the more typical skin, gastrointestinal, and endocrine toxicities, and are often underrecognized and challenging to diagnose. Here, we report a case of seronegative autoimmune autonomic ganglionopathy (AAG) induced by dual immune checkpoint inhibitor therapy (ICI) in a patient with metastatic melanoma. <h3>Case presentation</h3> A patient with metastatic melanoma was treated with ipilimumab and nivolumab. He developed a constellation of new symptoms including nausea, fatigue, and severe orthostatic hypotension refractory to fluid resuscitation. An infectious, cardiac, neurologic, and endocrine workup were unrevealing. Cardiovascular autonomic testing revealed poor sympathetic nervous system responses. He was diagnosed with seronegative AAG and significantly improved with immunomodulatory therapies including IVIG and steroids as well as varying doses of midodrine and fludrocortisone. He was able to restart nivolumab without recurrence of his symptoms. However, the AAG reoccurred when he was re-challenged with ipilimumab and nivolumab due to disease progression. While the AAG was manageable with steroids at that time, unfortunately his melanoma became resistant to ICI. <h3>Conclusions</h3> Immune checkpoint inhibitors can have a wide range of unusual, rare irAEs, including neurotoxicity such as AAG. Clinicians should maintain suspicion for this toxicity so that treatment can be rapidly provided to avoid disability.
Incidence and impact of K-ras mutation in colorectal cancer (CRC) in a minority population.
Authors: Donny Dietz, Albert S. Braverman, Constantine A Axiotis, Ratesh Khillan, Gurinder Singh Sidhu
Journal: Journal of Clinical Oncology (2013)

e14690 Background: K-ras mutation in CRC is known to occur in around 40% of the general population. It implies a poor prognosis, and resistance to anti- EGFR monoclonal therapy. The incidence of Kras mutation in African American (AA) patients with CRC is not known. Methods: Records of patients treated for CRC at Kings County Hospital and Downstate Hospital; in Brooklyn from 2005-12 were reviewed. Results: Of 116 patients’ records, 90 were informative for presenting stage, K-ras expression or both; all but one were AA, and 60 of 90 (67%) were male. Their ages ranged from 36 to 86 (median 64) years. The stages at presentation were known in 76; 3% were stage I, 17% stage II, 35% stage III and 45% stage IV. Follow-up periods ranged from 14 to 2381 days (median 409). K-ras mutation analysis was performed by a single commercial laboratory in 68 patients who had, or were suspected of having advanced disease. Codons 12 and 13 in K-ras exon 2 were analyzed. Of these 68 patients 31 (45%) bore K-ras mutations. K-ras mutation status was known in 9 stage I and II pts, and 6 of 9 pts (67%) bore mutations. After 233-967 days follow-up (median 474) 8 of 9 patients were alive. The 3 pts with wild type K-ras were a median of 70 years of age, 67% were female, and all were alive at median of 266 days (range 239-122-) follow up. Of the 16 stage III patients whose K-ras was analyzed, 7 (44%) were mutated. These 7 pts were a median of 66 years of age, and 86% were male. After 398 days median follow up 57% had relapsed and 45% had died. The 9 stage III pts with wild type K-ras were a median of 70 years of age and 78% were male. After a median follow up of 600 days, 2 were relapse-free, 7 had relapsed and 6 had died. Of the 34 stage IV pts, K-ras was analyzed in 29 and mutated in 12 (41%). Of the mutated patients, 83% were female and the median age 57. Their median survival was 557 days (56-1627). The 17 pts with wild type K-ras were 67% female with a median age of 59. Their median survival was 711 days (25-2040). The presenting CEA levels were similar in wild type and mutated patients. Conclusions: The prevalence of K-ras mutations, and the better prognosis of wild type K-ras in advanced CRC in AA patients, is similar to that of the general American population. The relapse rate of stage 3 AA patients seems higher in both wild type and mutated pts.
Abstract 445: Monitoring the Hemodynamic Status During Three Trimesters of Pregnancy and Non-pregnancy Periods
Authors: Chih-Yu Chen, Chi-Wei Chang, Sheng-Hung Wang, Gin-Chung Wang
Journal: Circulation Research (2019)

Pregnancy is an important stage in women and is associated with delicate cardiovascular adaptation from non-pregnancy to pregnancy. Maternal hemodynamic changes are made to provide sufficient nutrients and oxygen to support the normal growth of the developing fetus. This study was designed to assess maternal hemodynamic status during three trimesters of pregnancy and non-pregnancy periods. Total 326 women (84 pregnant women and 242 age-matched non-pregnant women of childbearing age) between the ages of 20 and 44 participated in this non-invasive observational study. In this cross-sectional study, enrolled participants underwent blood pressure and radial pressure pulse measurements. In order to compare the hemodynamic status of different subjects, we recorded the systolic and diastolic blood pressure and calculated the first five harmonic amplitudes(C1~C5) and phases(P1~P5) of radial pulse wave using Fourier transform method. Compared with non-pregnant women, the maternal systolic and diastolic blood pressures were lower, and heart rate, C2, C4, and P1 were higher in pregnant women (Table 1). Those hemodynamic changes may be due to decreased arterial stiffness and peripheral arterial vasodilatation in pregnancy. In summary, a series of changes in maternal hemodynamic status can be observed during the trimesters of pregnancy, including lowering blood pressure and increasing harmonics of radial pulse. This study demonstrates the feasibility of non-invasive monitoring of the hemodynamic status of pregnant women, which could be used for early detection of pregnancy disorder.