tbuckley/cabot-search huggingface dataset:
Abstract P288: The Association Between Moderate to Vigorous Physical Activity and Health-Related Quality of Life Among Hispanic/Latino Adults in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Authors: Priscilla Vasquez, Ramon Durazo-Arvizu, David Marquez, Maria Argos, Melissa Lamar, Angela Odoms-Young, Hector Gonzalez, Wassim Tarraf, Daniela Sotres-Alvarez, Rosie Murillo, Sheila Castaneda, Denise Vidot, Krista Perreira, Yasmin Mossavar-Rahmani, Jianwen Cai, Marc Gellman, Donghong Wu, Martha Davigus
Journal: Circulation (2018)

Background: Self-reported moderate to vigorous physical activity (MVPA) has been associated with better health-related quality of life (HRQoL), however research on quantitative MVPA in relation to HRQoL has been limited. In addition, the association of PA with physical and mental health components of HRQoL has not been examined. Hypothesis: Higher accelerometer-measured MVPA will be associated with better mental and physical HRQoL. Methods: Cross-sectional data from 12,179 adults ages 18-74 in 2008-11, who participated in HCHS/SOL and had complete data on key study variables. MVPA (minutes/week), measured by accelerometer, was grouped into 4 levels: inactive, low, moderate, and high. HRQoL was assessed using the Short-Form 12 (SF-12) questionnaire; the SF-12 mental and physical component summary (MCS; PCS) scores were computed (standardized to general US population norms with mean of 50 and standard deviation of 10; higher scores indicate better HRQoL). Multivariable linear regression models were used to derive adjusted means with 95% confidence intervals (CI) and to assess linear trends. All models were adjusted for covariates. The analyses were weighted for the study design and non-response. Results: PCS adjusted mean scores ranged from 46.8 (CI: 44.9, 48.6) among inactive persons to 51.3 (CI: 50.8, 51.8) among those with high levels of MVPA (p trend &lt;0.001). No significant differences in MCS scores were observed across MVPA levels (p = 0.64). Conclusion: MVPA was positively associated with better self-perceived physical health-related quality of life. Our findings align with studies examining self-reported MVPA and HRQoL. Future prospective studies should evaluate whether increasing MVPA can lead to improvements in HRQoL among the US Hispanic/Latino population.
Estrogens Enhance Human Hematopoietic Stem Cell Engraftment in a Xenogenic Transplantation Model
Authors: Sara Fañanas-Baquero, Israel Orman, Federico Becerra Aparicio, Silvia Bermudez de Miguel, Jordi Garcia Merino, Rosa M Yañez, Yolanda Fernandez, David Alfaro, Agustin Zapata, Juan A. Bueren, Jose C Segovia, Oscar Quintana Bustamante
Journal: Blood (2018)
Letter by Su and Li Regarding Article, “Erectile Dysfunction as an Independent Predictor of Future Cardiovascular Events: The Multi-Ethnic Study of Atherosclerosis”
Authors: Qiang Su, Qinghua Li
Journal: Circulation (2019)

We read with interest the study by Uddin et al 1 evaluating the association between erectile dysfunction and cardiovascular events that demonstrated that erectile dysfunction is an independent predictor of future cardiovascular events.In addition, this phenomenon is still significant in a subgroup analysis based on traditional cardiovascular disease risk factors, depression, and β-blocker use.After reading this article carefully, we have some suggestions to point out.First, as the authors described in this study, the participants in this study were patients with erectile dysfunction.Theoretically, those patients often take antierectile dysfunction drugs such as sildenafil, vardenafil, and tadalafil.These drugs might also increase the risk of cardiovascular diseases. 2However, the authors did not describe the anti-erectile dysfunction drugs in this study, which might increase the occurrence of a confounding bias.After these confounding factors are controlled for, the findings of this study may change.Second, after reading this article, we know that some patients with depression have also been included in this study.Patients with depression will often take some antidepressants.Several previous studies have pointed out that antidepressants (eg, amitriptyline, clomipramine, and maprotiline) significantly increase the risk of cardiovascular diseases (including cardiovascular disease death, nonfatal myocardial infarction, coronary surgical procedures, stroke, and heart failure). 3,4Similarly, the authors also have no detailed description of antidepressant drugs in this study, which may also lead to mix bias.We hypothesized that antidepressant drugs may also increase the risk of cardiovascular diseases, and the conclusion of this study may be different after adjustment for antidepressant drugs.Third, as the authors described in this study, "participants with erectile dysfunction were more likely to have diabetes mellitus (DM)."It is common knowledge that DM is a systemic metabolic disease that causes systemic vascular changes, including large vessels and small vessels, and certainly increases the incidence of cardiovascular diseases.Although logistic regression analysis was used to adjust for confounding factors, the results will be affected to a certain extent.In addition, the duration of DM has an important effect on this conclusion.The longer the duration of DM is, the higher the risk of cardiovascular diseases is.Furthermore, hypoglycemic drugs also affect the results of this study.For example, clinical studies have found that rosiglitazone significantly increased cardiovascular events in patients with DM, 5 and the use of rosiglitazone in China is strictly limited; advantages and disadvantages should be weighed before it is
Poor specific antibody response in patients with mucopolysaccaridosis
Authors: Marilia M. Moraes, Isabella B. Manhaes, Luiza M. Marino, Julio Cesar Gontijo, Barbara Luiza B. Cancado, Renan Augusto Pereira, Ellen Dantas, Carolina S. Aranda, Ana Maria Martins, Dirceu Sole, Beatriz Tavares Costa-Carvalho
Journal: Journal of Allergy and Clinical Immunology (2019)
GA CPI 613: A single arm, open-label phase I study of CPI-613 in combination with gemcitabine and nab-paclitaxel for patients with locally advanced or metastatic pancreatic cancer.
Authors: Angela Tatiana Alistar, Bonny Morris, Lawrence Harrison, Kai Bickenbach, Nancy Ginder, Jonathan Proulx, Laura McIlwain, Sanjeev Luther
Journal: Journal of Clinical Oncology (2019)

TPS459 Background: Pancreatic cancer is the third leading cause of cancer death in the USA. The most effective treatments for first-line metastatic pancreatic cancer are FOLFIRINOX and gemcitabine plus nab-paclitaxel, which provide a median overall survival of 11·1 months and 8·5 months with moderate toxicity. Safer and more effective treatments are needed. The glycolic and mitochondrial metabolism are aberrant in pancreatic cancer and translate into chemoresistance. Inhibition of glutamine metabolism can potentially synergize with therapies that increase intracellular reactive oxygen species such as Nab-Paclitaxel. CPI- 613 is a novel antimitocondrial developed by Rafael Pharmaceuticals that showed preclinical activity in pancreatic cancer cell lines as well as promising clinical activity in combination with modified FOLFIRINOX in patients with stage IV pancreatic cancer. Preclinical data suggests possible synergy of CPI- 613 with nab-paclitaxel. Methods: This is a single arm, open-label, nonblinded phase I study of CPI-613 in combination with gemcitabine and nab-paclitaxel in patients with locally advanced or metastatic pancreatic cancer. Key eligibility criteria include: histologically or cytologically documented and measurable locally advanced or metastatic pancreatic adenocarcinoma, ECOG performance status 0-2, first line treatment for both locally advanced or metastatic. CPI-613 will be infused intravenously with a starting dose of 500 mg/m 2 followed by 125 mg/m 2 nab-paclitaxel and 1,000 mg/m 2 gemcitabine on day 1, 8, 15 of a 28-day cycle. The study is comprised of a two-stage dose-escalation schema to evaluate the MTD of CPI-613. At least six months of treatment is planned for patients who have a response. Primary endpoint of the study is MTD of CPI 613 when combined with gemcitabine and nab-paclitaxel and secondary endpoints of the study are treatment related adverse events, CR and PR. This study was initiated in February 2018 at Atlantic Health System and within first seven months of the study, 11 out of 24 planned patients have been enrolled. Clinical trial information: NCT03435289.
EZH2 Inhibitor GSK126 Suppresses Antitumor Immunity by Driving Production of Myeloid-Derived Suppressor Cells
Authors: Shuo Huang, Zhongyu Wang, Jie Zhou, Jiani Huang, Li Zhou, Jing Luo, Yisong Y. Wan, Haixia Long, Bo Zhu
Journal: Cancer Research (2019)

Abstract Enhancer of zeste homolog (EZH2) is a key epigenetic regulator of gene expression and is frequently overexpressed in various cancer types, suggesting a role in oncogenesis. The therapeutic potential of EZH2 inhibitors is currently being explored, but their effect on antitumor immunity is largely unknown. Here we report that suppressing EZH2 activity using EZH2 inhibitor GSK126 resulted in increased numbers of myeloid-derived suppressor cells (MDSC) and fewer CD4+ and IFNγ+CD8+ T cells, which are involved in antitumor immunity. Addition of a neutralizing antibody against the myeloid differentiation antigen GR-1 or gemcitabine/5-fluorouracil–depleted MDSCs alleviated MDSC-mediated immunosuppression and increased CD4+ and CD8+ T-cell tumor infiltration and GSK126 therapeutic efficacy. Mechanistically, we identified a novel pathway of MDSC production in cancer in which EZH2 inhibition directs myeloid differentiation from primitive hematopoietic progenitor cells. These findings suggest that modulating the tumor immune microenvironment may improve the efficacy of EZH2 inhibitors. Significance: This study uncovers a potential mechanism behind disappointing results of a phase I clinical trial of EZH2 inhibitor GSK126 and identifies a translatable combinational strategy to overcome it.
Epithelial barrier repair and prevention of allergy
Authors: Elena Goleva, Evgeny Berdyshev, Donald Y.M. Leung
Journal: Journal of Clinical Investigation (2019)

Allergic diseases have in common a dysfunctional epithelial barrier, which allows the penetration of allergens and microbes, leading to the release of type 2 cytokines that drive allergic inflammation. The accessibility of skin, compared with lung or gastrointestinal tissue, has facilitated detailed investigations into mechanisms underlying epithelial barrier dysfunction in atopic dermatitis (AD). This Review describes the formation of the skin barrier and analyzes the link between altered skin barrier formation and the pathogenesis of AD. The keratinocyte differentiation process is under tight regulation. During epidermal differentiation, keratinocytes sequentially switch gene expression programs, resulting in terminal differentiation and the formation of a mature stratum corneum, which is essential for the skin to prevent allergen or microbial invasion. Abnormalities in keratinocyte differentiation in AD skin result in hyperproliferation of the basal layer of epidermis, inhibition of markers of terminal differentiation, and barrier lipid abnormalities, compromising skin barrier and antimicrobial function. There is also compelling evidence for epithelial dysregulation in asthma, food allergy, eosinophilic esophagitis, and allergic rhinosinusitis. This Review examines current epithelial barrier repair strategies as an approach for allergy prevention or intervention.
Evaluation of Peanut Sublingual Immunotherapy for Peanut Allergy: A Pilot Study
Authors: Mayumi Matsunaga, Akira Sakai, Yukiko Kato, Masaki Koda, Fumitaka Takayanagi, Yusuke Inuzuka, Yuko Mizoguchi, Akio Hakamata, Tomohide Taguchi, Osamu Natsume
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract 18240: Fluid Shear Stress Regulates Expression of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Through Mechanosensors in Endothelial Cells
Authors: Ji Yoon Lee, Jihwa Chung, Kyoung Hwa Kim, Shung Hyun An, Kihwan Kwon
Journal: Circulation (2016)

Vascular endothelial cells (ECs), which form the innermost layer of blood vessels, are exposed to fluid shear stress that modulates endothelial function and vascular pathophysiology. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) plays an important role in endothelial dysfunction and progression of atherosclerosis. However, expression patterns and regulatory mechanisms in ECs under different fluid shear stress (FSS) have remained unclear. We demonstrated the expression pattern of LOX-1 by comparing the normal laminar shear stress (LSS), extremely high LSS and oscillatory shear stress (OSS). Confluent human umbilical vein endothelial cells (HUVECs) were exposed to a unidirectional steady flow for normal LSS (shear stress of 20 dyne/cm2) or extremely high LSS (shear stress of 120 dyne/cm2), and a bidirectional disturbed flow (shear stress of ± 5 dyne/cm2) for OSS, under various time periods. Western blot and RT-PCR analyses in ECs showed that OSS has upregulated LOX-1 expression in both pro...
Glutathione <i>S</i>-Transferase Genotype Protects against <i>In Utero</i> Tobacco–linked Lung Function Deficits
Authors: Louisa Owens, Ingrid A. Laing, Jasminka Murdzoska, Guicheng Zhang, Steve W. Turner, Peter N. Le Souëf
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale:In utero tobacco exposure is associated with reduced lung function from infancy. Antioxidant enzymes from the glutathione S-transferase (GST) family may protect against these lung function deficits.Objectives: To assess the long-term effect of in utero smoke exposure on lung function into adulthood, and to assess whether GSTT1 and GSTM1 active genotypes have long-term protective effects on lung function.Methods: In this longitudinal study based on a general population (n = 253), lung function was measured during infancy and at 6, 11, 18, and 24 years. GSTM1 and GSTT1 genotype was analyzed in a subgroup (n = 179). Lung function was assessed longitudinally from 6 to 24 years (n = 199).Measurements and Main Results: Exposure to maternal in utero tobacco was associated with lower FEV1 and FVC longitudinally from 6 to 24 years (mean difference, -3.87% predicted, P = 0.021; -3.35% predicted, P = 0.035, respectively). Among those homozygous for the GSTM1-null genotype, in utero tobacco exposure was associated with lower FEV1 and FVC compared with those with no in utero tobacco exposure (mean difference, -6.2% predicted, P = 0.01; -4.7% predicted, P = 0.043, respectively). For those with GSTM1 active genotype, there was no difference in lung function whether exposed to maternal in utero tobacco or not. In utero tobacco exposure was associated with deficits in lung function among those with both GSTT1-null and GSTT1-active genotypes.Conclusions: Certain GST genotypes may have protective effects against the long-term deficits in lung function associated with in utero tobacco exposure. This offers potential preventative targets in antioxidant pathways for at-risk infants of smoking mothers.
ATG2B/Gskip in De Novo Acute Myeloid Leukemia (AML): High Prevalence of Germline Predisposition in French West Indies and Potential Role of Overexpression in Acquired AML
Authors: Jean Pegliasco, Barbara Panneau-Schmaltz, Jean-Edouard Martin, Samy Chraibi, Clemence Legoupil, Florence Pasquier, Christophe Willekens, Odile Bera, Olivier Caron, Jean-Henri Bourhis, Roseline Tang, Adel Ben-Ali, Maureen Lopez, Sophie Cotteret, Veronique Saada, Nathalie Auger, Jacques Delaunay, Pascale Cornillet-Lefebvre, Christian Recher, Stephane de Botton, William Vainchenker, Pascal Fuseau, Raouf Benabelali, Philippe Helias, Christophe Marzac, Isabelle Plo, Jean-Come Meniane, Christine Bellanné-Chantelot, Jean-Baptiste Micol
Journal: Blood (2018)
Erythrocyte Cytochrome b Reductase 1 Protein Levels and Structure in Sickle Cell Patients
Authors: Richard Kulmacz, Hamidreza Farzaneh, Kathryn L McElhinney, Jose M. Rodriguez, Nicole C. Thomason, Ehsan Irajizad, Vladimir Berka, Wen Liu, Modupe Idowu, Harinder S. Juneja
Journal: Blood (2018)
Efficacy of Early Convert to Dasatinib in Chronic Myeloid Leukemia Patients Who Inresponse or Intolerance to Imatinib
Authors: Liu Liang, Na Xu, Xuan Zhou, Huang JiXian, Chen Chen, Lin Tong, Wu wan-Er, Changxin Yin, Qifa Liu, Liu Xiaoli
Journal: Blood (2018)
A Novel Monoclonal Antibody Combination Plus DC/AML Fusion Vaccine Eradicates AML in an Immunocompetent Murine Model
Authors: Dina Stroopinsky, Jessica Liegel, Kathleen M. Mahoney, Jacalyn Rosenblatt, Benjamin L. Ebert, Richard M. Stone, Maryam Rahimian, Myrna Nahas, Shira Orr, Marzia Capelletti, Matthew Weinstock, Salvia Jain, Lina Bisharat, Haider Ghiasuddin, Adam Morin, Donald Kufe, Gordon J Freeman, David E. Avigan
Journal: Blood (2018)
Burden of medical co‐morbidities and benefit from surgical revascularization in patients with ischaemic cardiomyopathy
Authors: Andrew P. Ambrosy, Susanna R. Stevens, Hussein R. Al‐Khalidi, Jean L. Rouleau, Nadia Bouabdallaoui, Peter E. Carson, Christopher Adlbrecht, John G.F. Cleland, Rafal Dabrowski, Krzysztof S. Golba, Ileana L. Pina, Carla A. Sueta, Ambuj Roy, George Sopko, Robert O. Bonow, Eric J. Velazquez
Journal: European Journal of Heart Failure (2019)
Low Risk of Variceal Bleeding in Patients With Cirrhosis After Variceal Screening Stratified by Liver/Spleen Stiffness
Authors: Grace Lai‐Hung Wong, Lilian Yan Liang, Raymond Kwok, Aric Josun Hui, Yee‐Kit Tse, Henry Lik‐Yuen Chan, Vincent Wai‐Sun Wong
Journal: Hepatology (2019)

We previously demonstrated the possible noninferiority of a screening strategy for varices guided by liver and spleen stiffness measurement (LSSM) compared to universal endoscopic screening in detecting clinically significant varices in patients with cirrhosis. We now report the long-term outcome of the patients recruited in this trial for incident variceal bleeding and other hepatic events. This was a prospective follow-up study of a noninferiority, open-label, randomized controlled trial (NCT02024347) of 548 adult patients with known chronic liver diseases, radiological evidence of liver cirrhosis, and compensated liver function. The primary outcome of this prospective study was incident variceal bleeding confirmed with upper endoscopy. Between October 2013 and June 2016, 548 patients were randomized to an LSSM arm (n = 274) and a conventional arm (n = 274). Patients in both study arms were predominantly middle-aged men (mean age 59 years, male 68.9%) with viral hepatitis-related cirrhosis (85%). Upper endoscopy examination was performed in 127 (46.4%) patients in the LSSM arm and 263 (96.0%) in the conventional arm. During the follow-up period of 41.3 ± 12.6 months, 12/274 patients in the LSSM arm (4.4%) and 11/274 in the conventional arm (4.0%) developed incident variceal bleeding (log-rank test P = 0.724). The incident rates of hepatic events were also similar in both arms (P = 0.327). Conclusions: Patients with liver cirrhosis who had undergone LSSM-guided variceal screening were at similarly low risk of incident variceal bleeding in the future; patients with cirrhosis may first have LSSM measured to save up to half of the upper endoscopy examinations.
Direct Inhibition of Hepatitis B e Antigen by Core Protein Allosteric Modulator
Authors: Zhipeng Yan, Daitze Wu, Hui Hu, Jing Zeng, Xin Yu, Zhiheng Xu, Zheng Zhou, Xue Zhou, Guang Yang, John A.T. Young, Lu Gao
Journal: Hepatology (2019)

Hepatitis B e antigen (HBeAg) is an important immunomodulator for promoting host immune tolerance during chronic hepatitis B (CHB) infection. In patients with CHB, HBeAg loss and seroconversion represent partial immune control of CHB infection and are regarded as valuable endpoints. However, the current approved treatments have only a limited efficacy in achieving HBeAg seroconversion in HBeAg‐positive patients. Hepatitis B virus (HBV) core protein has been recognized as an attractive antiviral target, and two classes of core protein allosteric modulator (CpAM) have been discovered: the phenylpropenamides (PPAs) and the heteroaryldihydropyrimidines (HAPs). However, their differentiation and potential therapeutic benefit beyond HBV DNA inhibition remain to be seen. Here, we show that in contrast to PPA series compound AT‐130, a HAP CpAM, HAP_R01, reduced HBeAg levels in multiple in vitro and in vivo HBV experimental models. Mechanistically, we found that HAP_R01 treatment caused the misassembly of capsids formed by purified HBeAg in vitro . In addition, HAP_R01 directly reduces HBeAg levels by inducing intracellular precore protein misassembly and aggregation. Using a HAP_R01‐resistant mutant, we found that HAP_R01‐mediated HBeAg and core protein reductions were mediated through the same mechanism. Furthermore, HAP_R01 treatment substantially reduced serum HBeAg levels in an HBV mouse model. Conclusion: Unlike PPA series compound AT‐130, HAP_R01 not only inhibits HBV DNA levels but also directly reduces HBeAg through induction of its misassembly. HAP_R01, as well as other similar CpAMs, has the potential to achieve higher anti‐HBeAg seroconversion rates than currently approved therapies for patients with CHB. Our findings also provide guidance for dose selection when designing clinical trials with molecules from HAP series.
Abstract 20200: Feasibility and Safety of Intracoronary Acetylcholine Provocation Test in an Outpatient Department
Authors: Yuichi Saito, Hideki Kitahara, Toshihiro Shoji, Takashi Nakayama, Yoshihide Fujimoto, Yoshio Kobayashi
Journal: Circulation (2017)

Introduction: Intracoronary acetylcholine (ACh) provocation test is useful to diagnose vasospastic angina, which causes myocardial infarction, ventricular arrhythmia, or sudden cardiac arrest. Hypothesis: Although outpatient coronary angiography has been widely performed in the current clinical settings, feasibility and safety of ACh provocation test in an outpatient department are unclear. Methods: A total of 326 patients who electively underwent ACh provocation test in the hospitalization and an outpatient department were included. Coronary angiography was performed after insertion of a temporary pacing electrode in the right ventricle. The positive diagnosis of intracoronary ACh provocation test was defined as total or subtotal coronary artery narrowing accompanied by chest pain and/or ischemic electrocardiographic changes. Cardiac complications defined as composite of death, ventricular fibrillation or sustained ventricular tachycardia, myocardial infarction, cardiogenic shock and cardiac tamponade. I...
Calcium Influx through Plasma-Membrane Nanoruptures Drives Axon Degeneration in a Model of Multiple Sclerosis
Authors: Maarten E. Witte, Adrian-Minh Schumacher, Christoph F. Mahler, Jan P. Bewersdorf, Jonas Lehmitz, Alexander Scheiter, Paula Sánchez, Philip R. Williams, Oliver Griesbeck, Ronald Naumann, Thomas Misgeld, Martin Kerschensteiner
Journal: Neuron (2019)

Highlights•Cytoplasmic calcium accumulations predict axon degeneration in neuroinflammation•Release from the axoplasmic reticulum does not explain calcium accumulations•Calcium influx from the extracellular space drives axon degeneration•Nanoscale ruptures allow entry of calcium across the axonal plasma membraneSummaryAxon loss determines persistent disability in multiple sclerosis patients. Here, we use in vivo calcium imaging in a multiple sclerosis model to show that cytoplasmic calcium levels determine the choice between axon loss and survival. We rule out the endoplasmic reticulum, glutamate excitotoxicity, and the reversal of the sodium-calcium exchanger as sources of intra-axonal calcium accumulation and instead identify nanoscale ruptures of the axonal plasma membrane as the critical path of calcium entry.Graphical abstract
How Patients and Doctors' Characteristics Affect the Length of Doctor-Patient Visit in the Oncology and the Hemato-Oncology Outpatient Clinics
Authors: Adi Shacham Abulafia, Irina Amitai, Oren Pasvolsky, Orit Uziel, Dalia Zoref, Ariela Yosefi, Baruch Brenner, Pia Raanani, Uri Rozovski
Journal: Blood (2018)