tbuckley/cabot-search huggingface dataset:
Abstract 442: Caregiver Burden, Stress, Depression, and Quality of Life in Family Caregivers of Patients with Heart Failure
Authors: Jeong-ah Ahn
Journal: Circulation Research (2019)

Background: Heart failure (HF) is a chronic disease, which is considered an important strategy to support HF patients for lifetime self-management and monitoring of worsening signs and symptoms of patients at home. However, the necessity of management throughout the whole life demands a great deal of challenge and coping of HF patients as well as their family caregivers. Purpose: We aimed to explore the levels of caregiver burden, stress, depression, and quality of life (QOL) in family caregivers of patients with HF, and to identify the relationships among the variables. Methods: A descriptive and exploratory study design was used. After approval of institutional review board, 64 family caregivers of patients with HF were recruited from a cardiovascular outpatient clinic at a university-affiliated hospital in Korea, between September 2018 and January 2019. We assessed the caregiver burden using Montgomery’s scale, stress by heart rate variability measurement, depression using geriatric depression scale, and QOL using WHO-QOL scale. Results: Participants’ mean age was 52.0 years, and the average length of care was 7.5 years. Most of them were the patient’s wife or child (female), and half of them had their own health problems such as hypertension and back pain. The total mean score of caregiver burden, stress, depression, and QOL of family caregivers were 68.5 (out of 95), 39.8 (out of 100), 8.0 (out of 15), and 93.8 (out of 140), respectively. Their QOL showed negative correlations with caregiver burden and stress, and the levels of caregiver burden and stress increased with HF disease period. Conclusion: Healthcare providers should be aware of the importance of support for family caregivers of patients with HF. It is necessary to develop practical strategies to improve the QOL and to alleviate caregiver burden, stress and depression of family caregivers. And ultimately, it will enable them for positive participation in the comprehensive disease management with patients with HF.
Abstract 486: Deficiency of Myocardial miR-17-92 Cluster Exacerbates Ischemic Injury in Diabetic Mice
Authors: Arun Samidurai, Sean K Roh, Rakesh C Kukreja, Fadi N Salloum, Anindita Das
Journal: Circulation Research (2019)

Background: Dysregulation of miRNAs is associated with the pathogenesis of cardiovascular diseases. miR-17-92 cluster has been identified as a negative regulator of inflammation in rheumatoid arthritis. In diabetes, the persistent activation of NLRP3 inflammasome contributes to cardiac dysfunction and the severity of I/R. NLRP3 inflammasome consists of cryopyrin, apoptosis-associated speck-like protein (ASC), and procaspase-1 protein. The inflammasome triggers caspase-1 induced programmed cell death known as pyroptosis. Considering the pivotal role of NLRP3 in diabetes, we investigated the anti-inflammatory role of miR-17-92 cluster against I/R injury. Methods and Results: Adult male wild type and cardiac-specific miR-17-92-deficient mice were fed high-fat-diet (HFD) for 16 weeks before subjecting the heart to ex vivo I (30 min)/R (1 h) in Langendorff mode. HFD-fed mice exhibited impaired glucose tolerance with increased body weight and blood glucose levels (Figs. A, B, C). Tamoxifen-treatment (20 mg/kg, i.p. for 5 days) significantly reduced cardiac miR-17 and miR-20a in HFD-fed miR-17-92-defient mice (Figs. D, E), which resulted in increased myocardial infarct size and cardiac dysfunction following myocardial I/R injury as compared to WT mice (Figs. F, G). ASC aggregation and caspase 1 activity following simulated ischemia/reoxygenation were increased in isolated adult cardiomyocytes from diabetic tamoxifen-inducible miR-17-92-deficient mice as compared to WT mice (Figs. H &amp; I). Conclusion: miR-17-92 plays a critical role in attenuating exacerbated myocardial I/R injury in diabetic mice by regulating NLRP3 inflammasome.
Air pollution exposure and interstitial lung diseases: have we identified all the harmful environmental exposures?
Authors: Maribel Casas
Journal: Thorax (2019)

Interstitial lung disease encompasses a heterogeneous group of disorders characterised by excessive deposition of collagen within the extracellular matrix and thickening of the pulmonary insterstitium. Many interstitial lung diseases are linked with known environmental exposures including tobacco smoke (idiopathic pulmonary fibrosis), inhaled dust, mould or other irritants (hypersensitivity pneumonitis) and occupational exposures (ie, silicosis, asbestosis).1 However, the role of potentially relevant environmental exposures is difficult to establish due to the long latency period of these disorders (eg, 40–50 years for asbestosis). In a recent advance in the detection of early stage interstitial lung disease, interstitial lung abnormalities (ILA)—radiological abnormalities on chest CT—have been postulated as an indicator of subclinical interstitial lung disease,2 opening the door to further discoveries. Exposure to traffic-related air pollution has been postulated as being another potential risk factor. The proposed mechanism of action for this effect is pulmonary and systemic inflammation, oxidative stress and dysregulated fibrogenesis.3 

In 2016, outdoor air pollution was responsible for >3 million premature deaths,4 and it is estimated that 91% of the world’s population lives in places where air pollution exceeds the limits stipulated by WHO guidelines.5 Exposure to air pollution has been linked to many conditions, including cardiovascular disease, obesity and neurological disorders, as well as an increase in the incidence of respiratory disorders and related mortality.4 The American Lung Association recently emphasised that high levels of air pollution could be priming an epidemic of chronic respiratory diseases, such as COPD.6 In the field of interstitial lung disease, however, air pollution has received very little attention to date.7–10 

In Thorax , Rice et al 11 have shown, for the first time, that long-term exposure to elemental carbon (EC), a marker of traffic pollution, may increase the risk of the development and progression of ILA. …
Association Between Aspirin Use and Biliary Tract Cancer Survival
Authors: Sarah S. Jackson, Ruth M. Pfeiffer, Zhiwei Liu, Lesley A. Anderson, Huei-Ting Tsai, Shahinaz M. Gadalla, Jill Koshiol
Journal: JAMA Oncology (2019)

This database study analyzes the association between aspirin use and survival in patients with biliary tract cancer.
Rapamycin Promote the Inhibition Rate of Proliferation on SHI-1 Cells and Enhance the Efficacy of Chemotherapy in Npg Leukemia Mice
Authors: Jing Xu, Zhenjiang Li, Jifu Zheng, Qiong Wu, Qingming Wang, Aiping Tang, Yuan Song, Yan Fei
Journal: Blood (2018)
Primary Prevention of Cow’s Milk Sensitization and Food Allergy by Avoiding Supplementation With Cow’s Milk Formula at Birth
Authors: Mitsuyoshi Urashima, Hidetoshi Mezawa, Mai Okuyama, Takashi Urashima, Daishi Hirano, Noriko Gocho, Hiroshi Tachimoto
Journal: JAMA Pediatrics (2019)

Cow's milk formula (CMF) is used to supplement breastfeeding (BF) at birth without clear clinical evidence to support the practice.To determine whether avoiding supplementation with CMF at birth can decrease risks of sensitization to cow's milk protein and/or clinical food allergy, including cow's milk allergy (CMA), overall and in subgroups stratified by 25-hydroxyvitamin D (25[OH]D) levels.The Atopy Induced by Breastfeeding or Cow's Milk Formula (ABC) trial, a randomized, nonblinded clinical trial, began enrollment October 1, 2013, and completed follow-up May 31, 2018, at a single university hospital in Japan. Participants included 330 newborns at risk for atopy; of these, 312 were included in the analysis. Data were analyzed from September 1 through October 31, 2018.Immediately after birth, newborns were randomized (1:1 ratio) to BF with or without amino acid-based elemental formula (EF) for at least the first 3 days of life (BF/EF group) or BF supplemented with CMF (≥5 mL/d) from the first day of life to 5 months of age (BF plus CMF group).The primary outcome was sensitization to cow's milk (IgE level, ≥0.35 allergen units [UA]/mL) at the infant's second birthday. Secondary outcomes were immediate and anaphylactic types of food allergy, including CMA, diagnosed by oral food challenge test or triggered by food ingestion, with food-specific IgE levels of at least 0.35 UA/mL. Subgroup analysis was prespecified by tertiles of serum 25(OH)D levels at 5 months of age.Of the 312 infants included in the analysis (160 female [51.3%] and 152 male [48.7%]), 151 of 156 (96.8%) in the BF/EF and BF plus CMF groups were followed up until their second birthday. The primary outcome occurred in 24 infants (16.8%) in the BF/EF group, which was significantly fewer than the 46 infants (32.2%) in the BF plus CMF group (relative risk [RR], 0.52; 95% CI, 0.34-0.81). The middle tertile of the 25(OH)D subgroup, but not the low and high tertiles, had a significant interaction with the intervention (RR, 0.19; 95% CI, 0.07-0.50; P = .02). The prevalence of food allergy at the second birthday was significantly lower in the BF/EF than in the BF plus CMF groups for immediate (4 [2.6%] vs 20 [13.2%]; RR, 0.20; 95% CI, 0.07-0.57) and anaphylactic (1 [0.7%] vs 13 [8.6%]; RR, 0.08; 95% CI, 0.01-0.58) types.The evidence suggests that sensitization to cow's milk and food allergy, including CMA and anaphylaxis, are primarily preventable by avoiding CMF supplementation for at least the first 3 days of life.http://umin.ac.jp Identifier: UMIN000011577.
AMP-activated protein kinase links acetyl-CoA homeostasis to BRD4 recruitment in acute myeloid leukemia
Authors: Yajian Jiang, Tianyuan Hu, Tao Wang, Xiangguo Shi, Ayumi Kitano, Kenneth Eagle, Kevin A. Hoegenauer, Marina Y. Konopleva, Charles Y. Lin, Nicolas L. Young, Daisuke Nakada
Journal: Blood (2019)
Comparative Results of Gene Therapy for Adenosine Deaminase Deficiency with or without PEG-ADA Withdrawal and Myelosuppressive Chemotherapy.
Authors: Robert Sokolic, Greg Podsakoff, Linda Muul, Barbara Engel, Jayashree Jagadeesh, Elizabeth Garabedian, Denise Carbonaro, Laura Tuschong, Joanna Ireland, Michael Hershfield, John Tisdale, Cynthia Dunbar, Alan Wayne, Donald Kohn, Fabio Candotti
Journal: Blood (2007)
Mutational Profile and Analysis of Lower-Risk Myelodysplastic Syndromes (MDS) Patients Treated with Luspatercept: Phase 2 PACE-MDS Study
Authors: Uwe Platzbecker, Philipp Kiewe, Ulrich Germing, Katharina S. Götze, Karin Mayer, Markus P. Radsak, Thomas Wolff, Joerg Chromik, Dawn Wilson, Xiaosha Zhang, Chris Rovaldi, Abderrahmane Laadem, Matthew Leigh Sherman, Kenneth Morris Attie, Joseph Reynolds, Peter Guest Linde, Aristoteles Giagounidis
Journal: Blood (2017)
Preliminary validation of the NTM Module: a patient-reported outcome measure for patients with pulmonary nontuberculous mycobacterial disease
Authors: Emily Henkle, Kevin L. Winthrop, Gregory P. Ranches, Wesley Plinke, Hana K. Litvin, Alexandra L. Quittner
Journal: European Respiratory Journal (2019)

Introduction Nontuberculous mycobacteria (NTM) cause chronic, debilitating pulmonary disease. Patient-reported outcomes provide measures of symptoms, functioning and treatment response. Here we describe the preliminary validation of the recently developed NTM Module. Methods The study population included Northwest NTM Biobank patients in whom Mycobacterium avium complex (MAC) was isolated and who had ever met the 2007 American Thoracic Society/Infectious Diseases Society of America pulmonary disease criteria. The NTM Module was administered at enrolment and 12 months; a subset also completed the Quality of Life Questionnaire–Bronchiectasis (QOL-B). The NTM Module generates four domain scores (0–100; higher scores indicate better functioning) reflecting NTM-specific symptoms (NTM Symptoms, Body Image, Digestive Symptoms and Eating Problems). We described patient characteristics and mean scores, and evaluated psychometric properties, including response to treatment at 12 months, for each domain. Results Overall, 203 patients with pulmonary MAC disease were included. Average enrolment scores ranged from 76 (NTM Symptoms) to 84 (Eating Problems). Ceiling effects were observed for Body Image (26% of participants) and Eating Problems (52%). Internal consistency (Cronbach's alpha) ranged from 0.67 (Digestive Symptoms) to 0.89 (Eating Problems). The intraclass correlation for test–retest reproducibility (n=27) ranged from 0.72 (Body Image) to 0.94 (Eating Problems). Patients starting treatment (n=35) had statistically significant increases in scores for NTM Symptoms (+5, p=0.04), Digestive Symptoms (+7, p=0.002), Body Image (+7, p=0.03) and QOL-B Respiratory Symptoms (n=25, +10, p=0.006). NTM Symptoms scores increased by 15 points (p=0.002) in the 16 patients with scores ≤80 at enrolment. Conclusion The NTM Module generally performs well as a valid patient-reported outcome for pulmonary MAC disease and was responsive to MAC treatment.
Efficacy of Newer Combinations and Fibril-Targeting for AL Amyloidosis: A Systematic Review of Transplant and Innovative Non-Transplant Therapies
Authors: Shaunak Pandya, Nadia Carenina Nunes Cavalcante Parr, Muhammad Sardar, Christine Chiu, Maria Serafini, Faiz Anwer
Journal: Blood (2018)
Abstract 374: Etv2 Transcriptionally Regulates <i>Yes1</i> and Promotes Cell Proliferation During Embryogenesis
Authors: Bhairab Singh, Wuming Gong, Satyabrata Das, Joshua Theisen, Javier Sierra-Pagan, Demetris Yannopoulos, Erik Skie, Pruthvi Shah, Mary Garry, Daniel Garry
Journal: Circulation Research (2019)

Etv2, an Ets-transcription factor, governs the specification of the earliest hemato-endothelial progenitors during embryogenesis. While the transcriptional networks during hemato-endothelial development have been well described, the mechanistic details are incompletely defined. In the present study, we described a new role for Etv2 as a regulator of cellular proliferation via Yes1 in mesodermal lineages. Analysis of an Etv2-ChIPseq dataset revealed significant enrichment of Etv2 peaks in the upstream regions of cell cycle regulatory genes relative to non-cell cycle genes. Our bulk-RNAseq analysis using the doxycycline-inducible Etv2 ES/EB system showed increased levels of cell cycle genes including E2f4, Gadd45g and Ccne1 as early as 6h following Etv2 induction. Further, EdU-incorporation studies demonstrated that the induction of Etv2 resulted in a ~2.5-fold increase in cellular proliferation, supporting a proliferative role for Etv2 during differentiation. Next, we identified Yes1 as the top-ranked candidate that was expressed in Etv2-EYFP + cells at E7.75 and E8.25 using single cell RNA-seq analysis. Doxycycline-mediated induction of Etv2 led to an increase in Yes1 transcripts in a dose-dependent fashion. In contrast, the level of Yes1 was reduced in Etv2 null embryoid bodies. Using bioinformatics algorithms, biochemical, and molecular biology techniques, we show that Etv2 binds to the promoter region of Yes1 and functions as a direct upstream regulator of Yes1 during embryogenesis. These studies enhance our understanding of the mechanisms whereby Etv2 governs mesodermal fate decisions early during embryogenesis.
Multiple Functional Donor Polymorphisms in IL1RL1 region Associate with Death Due to GvHD or Infection after Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplantation (HCT) for AML and MDS
Authors: Ezgi Karaesmen, Theresa E. Hahn, Alexander Dile, Abbas Rizvi, Junke Wang, Tao Wang, Michael D. Haagenson, Leah Preus, Qianqian Zhu, Qian Liu, Li Yan, Song Liu, Christopher Haiman, Daniel Stram, Loreall Pooler, Xin Cheng, David Van Den Berg, Guy Brock, Amy Webb, Philip L. McCarthy, Stephen R. Spellman, Stephanie J. Lee, Sophie Paczesny, Lara E. Sucheston-Campbell
Journal: Blood (2018)
Should Fibrinogen Concentrate Replace Cryoprecipitate in Cardiac Surgery?
Authors: Aaron S. Hess, John R. Hess, Douglas B. Coursin
Journal: JAMA (2019)

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Hevylite™ Assays Detect a Hidden Immunoparesis Associated with Adverse Biology in Myeloma Precursor Disease: A Prospective Clinical Study
Authors: Rene Costello, Karina Espana, Neha Korde, Mary Kwok, Adriana Zingone, Mary Ann Yancey, Marcia Mulquin, Irina Maric, Katherine Calvo, Prashant Ramesh Tembhare, Constance Yuan, Maryalice Stetler-Stevenson, Ola Landgren
Journal: Blood (2011)
Abstract 867: NAD <sup>+</sup> Repletion Reverses HFpEF by Attenuating Myocardial Metabolic Dysfunction
Authors: Dan Tong, Gabriele G Schiattarella, Nan Jiang, Francisco Altamirano, Pamela A Szweda, Abdallah Elnwasany, Dong I Lee, Luke I Szweda, David A Kass, Thomas G Gillette, Joseph A Hill
Journal: Circulation Research (2019)

Background: Heart failure with preserved ejection fraction (HFpEF) is a highly prevalent clinical condition associated with significant morbidity, mortality and health care expenses. Yet, no effective treatment has been identified. We recently demonstrated that concomitant metabolic and hypertensive stress in mice elicited by a combination of high fat diet (HFD) and constitutive nitric oxide synthase inhibition by N [w] -nitro-l-arginine methyl ester (L-NAME) faithfully recapitulates the numerous and myriad features of human HFpEF (paper in press at Nature ). Methods: Wild type C57Bl6 mice were fed with HFD and L-NAME via drinking water for 5-8 weeks. Myocardial mitochondrial morphology was assessed by electron microscopy. Mitochondrial function was assessed by measuring oxygen consumption rates using an oxygen electrode. Protein expression and modification were assessed by Western blotting and immunoprecipitation. Results: Using this novel mouse model, we discovered significant impairment of mitochondrial fatty acid oxidation (FAO) associated with hyperacetylation of key FAO enzymes in HFpEF myocardium. Mechanistically, downregulation of Sirtuin3, the major mitochondrial deacetylase, and deficiency of its co-substrate nicotinamide adenine dinucleotide (NAD + ), culminated in mitochondrial protein hyperacetylation. Strikingly, supplementation with nicotinamide riboside (NR), a NAD + precursor, led to dramatic improvement of mitochondrial function, and importantly, amelioration of the HFpEF phenotype. Conclusion: In summary, we have unveiled that protein hyperacetylation-mediated mitochondrial dysfunction is a crucial mechanism of HFpEF pathogenesis. This is, to our knowledge, the first study identifying a specific signature of metabolic remodeling in HFpEF heart. We also demonstrated the therapeutic effect of NAD + repletion in a preclinical HFpEF model. In next steps, confirming this benefit in a clinical trial is warranted.
Abstract 299: Engineering Rodent TRPV1 to Mimic Chicken TRPV1 Reduces Capsaicin-induced Calcium Influx in H9C2 Cells
Authors: Shufang He, Pritam Sinharoy, Eric Richard Gross
Journal: Circulation Research (2019)

Background and Aim: Birds, unlike mammals, are resistant to the spicy hot sensation when consuming chili peppers. The inability for birds to sense the hot sensation is accredited to genetic divergence in the transient receptor potential vanilloid 1 (TRPV1) when compared to mammals. Recently, we described how TRPV1 is important for regulating myocardial ischemia-reperfusion injury in rodents. Here, we tested our hypothesis that K710 is a crucial mediator of capsaicin-induced calcium influx in myocardial H9C2 cells. Methods and Results: Sequence alignment of the C-terminus TRP domain of TRPV1 among species was performed. Unlike mammals having K710 TRPV1, birds instead have N710 TRPV1 (Fig 1A). Site-directed mutagenesis of K710N was performed on wild type (WT) rTRPV1 with a pCMV6-entry vector. The empty vector, WT and K710N plasmids were transfected into H9C2 cells and the cellular localization of TRPV1 channel were detected by immunofluorescent staining and channel activity by capsaicin challenge with live cell calcium imaging with Fura-2AM. Interestingly, the K710N mutation caused the TRPV1 channel to be retained intracellularly and co-localized with PDI, an endoplasmic reticulum marker (Fig 1B, Bar=25μM). K701N cells treated with 1μM capsaicin showed a reduced response to capsaicin compared to wild type TRPV1 transfected cells (Fig 1C-E, 011±0.01 in WT vs . 0.03±0.01 in K710N, n=10, P&lt;0.01). Conclusions: Site-directed mutagenesis of K710N caused rTRPV1 to be insensitive to capsaicin and suggests a potential target for limiting calcium influx from myocardial ischemia-reperfusion injury which could be a novel protective strategy to prevent damage from a heart attack.
Potent Cell-Cycle Inhibition and Upregulation of Immune Response with Abemaciclib and Anastrozole in neoMONARCH, Phase II Neoadjuvant Study in HR+/HER2− Breast Cancer
Authors: Sara A. Hurvitz, Miguel Martin, Michael F. Press, David Chan, María Fernandez-Abad, Edgar Petru, Regan Rostorfer, Valentina Guarneri, Chiun-Sheng Huang, Susana Barriga, Sameera Wijayawardana, Manisha Brahmachary, Philip J. Ebert, Anwar Hossain, Jiangang Liu, Adam Abel, Amit Aggarwal, Valerie M. Jansen, Dennis J. Slamon
Journal: Clinical Cancer Research (2019)

neoMONARCH assessed the biological effects of abemaciclib in combination with anastrozole in the neoadjuvant setting.Postmenopausal women with stage I-IIIB HR+/HER2- breast cancer were randomized to a 2-week lead-in of abemaciclib, anastrozole, or abemaciclib plus anastrozole followed by 14 weeks of the combination. The primary objective evaluated change in Ki67 from baseline to 2 weeks of treatment. Additional objectives included clinical, radiologic, and pathologic responses, safety, as well as gene expression changes related to cell proliferation and immune response.Abemaciclib, alone or in combination with anastrozole, achieved a significant decrease in Ki67 expression and led to potent cell-cycle arrest after 2 weeks of treatment compared with anastrozole alone. More patients in the abemaciclib-containing arms versus anastrozole alone achieved complete cell-cycle arrest (58%/68% vs. 14%, P < 0.001). At the end of treatment, following 2 weeks lead-in and 14 weeks of combination therapy, 46% of intent-to-treat patients achieved a radiologic response, with pathologic complete response observed in 4%. The most common all-grade adverse events were diarrhea (62%), constipation (44%), and nausea (42%). Abemaciclib, anastrozole, and the combination inhibited cell-cycle processes and estrogen signaling; however, combination therapy resulted in increased cytokine signaling and adaptive immune response indicative of enhanced antigen presentation and activated T-cell phenotypes.Abemaciclib plus anastrozole demonstrated biological and clinical activity with generally manageable toxicities in patients with HR+/HER2- early breast cancer. Abemaciclib led to potent cell-cycle arrest, and in combination with anastrozole, enhanced immune activation.