tbuckley/cabot-search huggingface dataset:
Abstract 111: Cdk5 is Associated in Cardiac Calcium Channelopathy
Authors: Masayuki Yazawa, LouJin Song
Journal: Circulation Research (2016)

Cardiac calcium channels play important roles in hearts. Mutations in Ca V 1.2 channels are associated with cardiac arrhythmias including long QT syndrome type 8 (LQTS8). Using human induced pluripotent stem cells (iPSCs) to generate human cardiomyocytes from LQTS8 patients, we reported that the G406R mutation (LQTS8, Timothy syndrome) affected channel inactivation, action potentials and calcium handling in human cardiomyocytes. We found that roscovitine, a cyclin-dependent kinase (CDK) inhibitor, rescued the phenotypes in LQTS8 cardiomyocytes. However, how roscovitine restores the physiological functions in the patient cardiomyocytes remains unclear. Our recent results using roscovitine analogs and CDK inhibitors suggested that CDK5 is involved in the molecular bases of LQTS8. We found that dominant negative forms and shRNA of CDK5 alleviated the phenotypes of the LQTS8 cardiomyocytes and that the expressions of phosphorylated ERK, EGR1 and CDK5R1, a CDK5 activator, significantly increased in the patient cardiomyocytes. The results reveal that calcium overload due to affected Ca V 1.2 inactivation activates ERK/EGR1 pathway, resulting in increased expression of CDK5R1. Biochemical assays supported a direct binding and phosphorylation of Ca V 1.2 channels by CDK5. Overall, the results demonstrated that CDK5 regulates Ca V 1.2 channels and that CDK5 inhibition could be a new therapeutic for LQTS8. This study demonstrates the role of ERK/EGR1/CDK5 in pathogenesis of cardiac arrhythmia. The outcomes of this study provide new insights into Ca V 1.2 channel regulation.
Abstract I13: Modulating the immune response with epigenetic agents
Authors: Nilofer S. Azad
Journal: Cancer Research (2019)

Abstract Epigenetic modulation offers the potential of altering key tumor-immune interactions to allow for more effective therapeutic targeting. Epigenetic abnormalities in cancer in the tumor-immune response will be discussed, as well as data that support the reversibility of these lesions with epigenetic modulators. Preclinical and emerging clinical data in solid tumors will be surveyed, with an eye towards how these data support the rationale of epigenetic-immunotherapy combinations in pancreatic cancer. Citation Format: Nilofer S. Azad. Modulating the immune response with epigenetic agents [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr I13.
Microglial microRNAs mediate sex-specific responses to tau pathology
Authors: Lay Kodama, Elmer Guzman, Jon I. Etchegaray, Yaqiao Li, Faten A. Sayed, Lu Zhou, Yungui Zhou, Lihong Zhan, David Le, Joe C. Udeochu, Claire D. Clelland, Zuolin Cheng, Guoqiang Yu, Qingyun Li, Kenneth S. Kosik, Li Gan
Journal: Nature Neuroscience (2019)
Spontaneous Clearance of Chronic Delta Hepatitis
Authors: Devika Kapuria, Gil Ben Yakov, Christopher Koh, Theo Heller
Journal: Hepatology (2019)

1Liver Disease BranchNational Institutes of HealthBethesdaMD 2Department of GastroenterologyUniversity of New MexicoAlbuquerqueNM * Address Correspondence and Reprint Requests to: Devika Kapuria, M.D. Department of Gastroenterology, MSC 10‐5550 1 University of New Mexico Albuquerque, NM 87131 E‐mail: [email protected] Tel.: +1‐505‐272‐4205
Cost of adverse events (AEs) with second-line (2L) immuno-oncology agents (IO) and chemotherapy (CHEMO) in advanced non-small cell lung cancer (aNSCLC) in the real-world
Authors: C.K. Wang, K. Gupte-Singh, A.J. Belli, D.C. Lane, A. Lakshmanan, A.D. Norden
Journal: Annals of Oncology (2019)
Genome-Wide Association Studies in Idiopathic Pulmonary Fibrosis: Bridging the Gap between Sequence and Consequence
Authors: Paolo Spagnolo, Jonathan A. Kropski
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Supported by grants from the Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy (BIRD163522 to P.S.), the NIH (R01HL145372 and K08130595 to J.A.K.), the Department of Defense (W81XWH1910415 to J.A.K.), and the Doris Duke Charitable Foundation (J.A.K.).
Is there an optimal conditioning for older patients with AML receiving allogeneic hematopoietic cell transplantation?
Authors: Stefan O. Ciurea, Piyanuch Kongtim, Ankur Varma, Gabriela Rondon, Julianne Chen, Samer Srour, Qaiser Bashir, Amin Alousi, Rohtesh Mehta, Betul Oran, Uday Popat, Chitra Hosing, Amanda Olson, Naval Daver, Marina Konopleva, Richard E. Champlin
Journal: Blood (2019)
Post-colonoscopy colorectal cancer: patients can be reassured that UK endoscopy is already engaged in quality assessment and continual improvement
Authors: Christopher J Healey, Siwan Thomas-Gibson
Journal: BMJ (2019)

Burr and colleagues suggest that quality improvement is needed to reduce variation in colonoscopy performance, as measured by post-colonoscopy colorectal cancer (PCCRC).1 This inter-hospital variation in colonoscopy quality has been known to UK gastroenterology since being shared by Roland Valori during the 2014 British Society of Gastroenterology (BSG) annual meeting. The importance of ensuring that colonoscopy does find bowel cancer consistently …
Beyond Angiogenesis: Exploiting Angiocrine Factors to Restrict Tumor Progression and Metastasis
Authors: Mahak Singhal, Hellmut G. Augustin
Journal: Cancer Research (2019)

Looking beyond tumor angiogenesis, the past decade has witnessed a fundamental change of paradigm with the discovery that the vascular endothelium does not just respond to exogenous cytokines, but exerts active "angiocrine" gatekeeper roles, controlling their microenvironment in an instructive manner. While vascular niches host disseminated cancer cells and promote their stemness, endothelial cell-derived angiocrine signals orchestrate a favorable immune milieu to facilitate metastatic growth. Here, we discuss recent advances in the field of tumor microenvironment research and propose angiocrine signals as promising targets of future mechanism-driven antimetastatic therapies, which may prove useful to synergistically combine with chemotherapy and immunotherapy.
Racial/Ethnic Differences in Dialysis Discontinuation and Survival after Hospitalization for Serious Conditions among Patients on Maintenance Dialysis
Authors: Abdulkareem Agunbiade, Abhijit Dasgupta, Michael M. Ward
Journal: Journal of the American Society of Nephrology (2019)

Racial and ethnic minorities on dialysis survive longer than whites, and are less likely to discontinue dialysis. Both differences have been attributed by some clinicians to better health among minorities on dialysis.To test if racial and ethnic differences in dialysis discontinuation reflected better health, we conducted a retrospective cohort study of survival and dialysis discontinuation among patients on maintenance dialysis in the US Renal Data System after hospitalization for either stroke (n=60,734), lung cancer (n=4100), dementia (n=40,084), or failure to thrive (n=42,950) between 2003 and 2014. We examined the frequency of discontinuation of dialysis and used simulations to estimate survival in minorities relative to whites if minorities had the same pattern of dialysis discontinuation as whites.Blacks, Hispanics, and Asians had substantially lower frequencies of dialysis discontinuation than whites in each hospitalization cohort. Observed risks of mortality were also lower for blacks, Hispanics, and Asians. In simulations that assigned discontinuation patterns similar to those found among whites across racial and ethnic groups, differences in survival were markedly attenuated and hazard ratios approached 1.0. Survival and dialysis discontinuation frequencies among American Indians and Alaska Natives were close to those of whites.Racial and ethnic differences in dialysis discontinuation were present among patients hospitalized with similar health events. Among these patients, survival differences between racial and ethnic minorities and whites were largely attributable to differences in the frequency of discontinuation of dialysis.
Mutant ASXL1 Promotes Expansion of the Phenotypic Hematopoietic Stem Cell Compartment
Authors: Takeshi Fujino, Susumu Goyama, Yuki Sugiura, Daichi Inoue, Satoshi Yamasaki, Akiko Matsumoto, Naru Sato, Hironobu Morinaga, Shiori Shikata, Tomofusa Fukuyama, Yosuke Tanaka, Shuhei Asada, Tsuyoshi Fukushima, Hiroaki Honda, Emi K Nishimura, Tatsuhiro Shibata, Makoto Suematsu, Toshio Kitamura
Journal: Blood (2019)
Accuracy, robustness and scalability of dimensionality reduction methods for single-cell RNA-seq analysis
Authors: Shiquan Sun, Jiaqiang Zhu, Ying Ma, Xiang Zhou
Journal: Genome biology (2019)

Dimensionality reduction is an indispensable analytic component for many areas of single-cell RNA sequencing (scRNA-seq) data analysis. Proper dimensionality reduction can allow for effective noise removal and facilitate many downstream analyses that include cell clustering and lineage reconstruction. Unfortunately, despite the critical importance of dimensionality reduction in scRNA-seq analysis and the vast number of dimensionality reduction methods developed for scRNA-seq studies, few comprehensive comparison studies have been performed to evaluate the effectiveness of different dimensionality reduction methods in scRNA-seq.We aim to fill this critical knowledge gap by providing a comparative evaluation of a variety of commonly used dimensionality reduction methods for scRNA-seq studies. Specifically, we compare 18 different dimensionality reduction methods on 30 publicly available scRNA-seq datasets that cover a range of sequencing techniques and sample sizes. We evaluate the performance of different dimensionality reduction methods for neighborhood preserving in terms of their ability to recover features of the original expression matrix, and for cell clustering and lineage reconstruction in terms of their accuracy and robustness. We also evaluate the computational scalability of different dimensionality reduction methods by recording their computational cost.Based on the comprehensive evaluation results, we provide important guidelines for choosing dimensionality reduction methods for scRNA-seq data analysis. We also provide all analysis scripts used in the present study at www.xzlab.org/reproduce.html.
Tumour mutational burden ring trial: Evaluation of targeted next-generation sequencing platforms for implementation in clinical practice
Authors: S. Lambin, D. Lambrechts, C. De Rop, N. D'Haene, G. Froyen, L. Heukamp, C. Huijsmans, B. Maes, B. Melendez, C. Van Campenhout, I. Vanden Bempt, A. van den Brule, S. Vander Borght, P. Vannuffel, P. Pauwels
Journal: Annals of Oncology (2019)
Baseline Global Longitudinal Strain Is Associated With All-Cause Mortality After Transcatheter Aortic Valve Replacement
Authors: Miho Fukui, Floyd Thoma, Ibrahim Sultan, Suresh Mulukutla, Hesham Elzomor, Joon S. Lee, John T. Schindler, Thomas G. Gleason, João L. Cavalcante
Journal: JACC. Cardiovascular imaging (2019)
The nonpolymorphic MHC Qa-1b mediates CD8+ T cell surveillance of antigen-processing defects
Authors: Cláudia C. Oliveira, Peter A. van Veelen, Bianca Querido, Arnoud de Ru, Marjolein Sluijter, Sandra Laban, Jan W. Drijfhout, Sjoerd H. van der Burg, Rienk Offringa, Thorbald van Hall
Journal: The Journal of Experimental Medicine (2009)

The nonclassical major histocompatibility complex (MHC) Qa-1b accommodates monomorphic leader peptides and functions as a ligand for germ line receptors CD94/NKG2, which are expressed by natural killer cells and CD8+ T cells. We here describe that the conserved peptides are replaced by a novel peptide repertoire of surprising diversity as a result of impairments in the antigen-processing pathway. This novel peptide repertoire represents immunogenic neoantigens for CD8+ T cells, as we found that these Qa-1b–restricted T cells dominantly participated in the response to tumors with processing deficiencies. A surprisingly wide spectrum of target cells, irrespective of transformation status, MHC background, or type of processing deficiency, was recognized by this T cell subset, complying with the conserved nature of Qa-1b. Target cell recognition depended on T cell receptor and Qa-1b interaction, and immunization with identified peptide epitopes demonstrated in vivo priming of CD8+ T cells. Our data reveal that Qa-1b, and most likely its human homologue human leukocyte antigen-E, is important for the defense against processing-deficient cells by displacing the monomorphic leader peptides, which relieves the inhibition through CD94/NKG2A on lymphocytes, and by presenting a novel repertoire of immunogenic peptides, which recruits a subset of cytotoxic CD8+ T cells.
Methyl Tertiary-Butyl Ether Exposure from Gasoline in the U.S. Population, NHANES 2001–2012
Authors: Lalith K. Silva, Michael F. Espenship, Brittany N. Pine, David L. Ashley, Víctor R. De Jesús, Benjamin C. Blount
Journal: Environmental Health Perspectives (2019)

Methyl tertiary-butyl ether (MTBE) was used as a gasoline additive in the United States during 1995-2006. Because of concerns about potential exposure and health effects, some U.S. states began banning MTBE use in 2002, leading to a nationwide phaseout in 2006.We investigated the change in blood MTBE that occurred during the years in which MTBE was being phased out of gasoline.We used data from the National Health and Nutrition Examination Survey (NHANES) from 2001-2012 to assess the change in blood MTBE over this period. We fit sample-weighted multivariate linear regression models to 12,597 human blood MTBE concentrations from the NHANES 2001-2002 to 2011-2012 survey cycles.The unweighted proportion of the individuals with MTBE blood levels above the limit of detection (LOD) of 1.4 ng/L was 93.9% for 2001-2002. This portion dropped to 25.4% for the period 2011-2012. Weighted blood MTBE median levels (ng/L) (25th and 75th percentiles) decreased from 25.8 (6.08, 68.1) ng/L for the period from 2001-2002 to 4.57 (1.44, 19.1) ng/L for the period from 2005-2006. For the entire postban period (2007-2012), MTBE median levels were below the detection limit of 1.4 ng/L.These decreases in blood MTBE coincided with multiple statewide bans that began in 2002 and a nationwide ban in 2006. The multivariate log-linear regression model for the NHANES 2003-2004 data showed significantly higher blood MTBE concentrations in the group who pumped gasoline less than 7 h before questionnaire administration compared to those who pumped gasoline more than 12 h before questionnaire administration (p=0.032). This study is the first large-scale, national-level confirmation of substantial decrease in blood MTBE levels in the general population following the phaseout of the use of MTBE as a fuel additive. https://doi.org/10.1289/EHP5572.
IFN-α kinoid in systemic lupus erythematosus: results from a phase IIb, randomised, placebo-controlled study
Authors: Frederic A Houssiau, Aikaterini Thanou, Minodora Mazur, Edgar Ramiterre, Danny Alexis Gomez Mora, Maria Misterska-Skora, Risto Alfredo Perich-Campos, Svetlana A Smakotina, Sergio Cerpa Cruz, Bassem Louzir, Thérèse Croughs, Michael Lucas Tee
Journal: Annals of the Rheumatic Diseases (2019)

Objective To evaluate the efficacy and safety of the immunotherapeutic vaccine interferon-α kinoid (IFN-K) in a 36-week (W) phase IIb, randomised, double-blind, placebo (PBO)-controlled trial in adults with active systemic lupus erythematosus (SLE) despite standard of care. Methods Patients with SLE (185) with moderate to severe disease activity and positive interferon (IFN) gene signature were randomised to receive IFN-K or PBO intramuscular injections (days 0, 7 and 28 and W12 and W24). Coprimary endpoints at W36 were neutralisation of IFN gene signature and the BILAG-Based Composite Lupus Assessment (BICLA) modified by mandatory corticosteroid (CS) tapering. Results IFN-K induced neutralising anti-IFN-α2b serum antibodies in 91% of treated patients and reduced the IFN gene signature (p&lt;0.0001). Modified BICLA responses at W36 did not statistically differ between IFN-K (41%) and PBO (34%). Trends on Systemic Lupus Erythematosus Responder Index-4, including steroid tapering at W36, favoured the IFN-K and became significant (p&lt;0.05) in analyses restricted to patients who developed neutralising anti-IFN-α2b antibodies. Attainment of lupus low disease activity state (LLDAS) at W36 discriminated the two groups in favour of IFN-K (53% vs 30%, p=0.0022). A significant CS sparing effect of IFN-K was observed from W28 onwards, with a 24% prednisone daily dose reduction at W36 in IFN-K compared with PBO (p=0.0097). The safety profile of IFN-K was acceptable. Conclusions IFN-K induced neutralising anti-IFN-α2b antibodies and significantly reduced the IFN gene signature with an acceptable safety profile. Although the clinical coprimary endpoint was not met, relevant secondary endpoints were achieved in the IFN-K group, including attainment of LLDAS and steroid tapering. Trial registration number NCT02665364 .
Reduced Risk of Relapse for Total Body Irradiation + Fludarabine Compared to Busulphan + Fludarabine As "Reduced-Toxicity" Conditioning for Patients with Acute Myeloid Leukemia Treated with Allohsct in First Complete Remission. a Study By the Acute Leukemia Working Party of the EBMT
Authors: Sebastian Giebel, Myriam Labopin, Malgorzata Maria Sobczyk Kruszelnicka, Matthias Stelljes, Jenny Byrne, Nathalie Fegueux, Dietrich W. Beelen, Montserrat Rovira, Alexandros Spyridonidis, Didier Blaise, Martin Bornhäuser, Ihsan Karadoğan, Bipin N. Savani, Arnon Nagler, Mohamad Mohty
Journal: Blood (2019)
Abstract 6282: Lowered Ratio of Low-density Lipoprotein Cholesterol to High-density Lipoprotein Cholesterol with Lipid lowering therapy Associated with Reduction of Cardiovascular Events in Primary Prevention: MEGA Study Post-hoc Analysis
Authors: Haruo Nakamura, Kyoichi Mizuno
Journal: Circulation (2008)

Background. Recently, it was reported that lowering the ratio of low-density lipoprotein cholesterol (LDL) to high-density lipoprotein cholesterol (HDL) [LDL/HDL ratio] with lipid lowering therapy ...
Nilotinib Vs Nilotinib Plus Pegylated Interferon α (Peg-IFN) Induction and Nilotinib or Peg-IFN Maintenance Therapy for Newly Diagnosed BCR-ABL1 Positive Chronic Myeloid Leukemia Patients in Chronic Phase (TIGER Study): The Addition of Peg-IFN Is Associated with Higher Rates of Deep Molecular Response
Authors: Andreas Hochhaus, Andreas Burchert, Susanne Saussele, Gabriela M Baerlocher, Tim H Brümmendorf, Paul La Rosée, Dominik Heim, Stefan W Krause, Philipp D le Coutre, Dietger Niederwieser, Thoralf Lange, Alice Fabarius, Mathias Hänel, Frank Stegelmann, Jiri Mayer, Arthur Gil, Danny Himsel, Joerg Hasford, Rüdiger Hehlmann, Thomas Ernst, Christian Fabisch, Markus Pfirrmann
Journal: Blood (2019)
“Asset exchange”—interactions between patient groups and pharmaceutical industry: Australian qualitative study
Authors: Lisa Parker, Alice Fabbri, Quinn Grundy, Barbara Mintzes, Lisa Bero
Journal: BMJ (2019)

Abstract Objective To understand and report on the nature of patient group interactions with the pharmaceutical industry from the perspective of patient group representatives by exploring the range of attitudes towards pharmaceutical industry sponsorship and how, why, and when interactions occur. Design Empirical qualitative interview study informed by ethics theory. Setting Australian patient groups. Participants 27 participants from 23 Australian patient groups that represented diverse levels of financial engagement with the pharmaceutical industry. Groups were focused on general health consumer issues or disease specific topics, and had regional or national jurisdictions. Analysis Analytic techniques were informed by grounded theory. Interview transcripts were coded into data driven categories. Findings were organised into new conceptual categories to describe and explain the data, and were supported by quotes. Results A range of attitudes towards pharmaceutical industry sponsorship were identified that are presented as four different types of relationship between patient groups and the pharmaceutical industry. The dominant relationship type was of a successful business partnership, and participants described close working relationships with industry personnel. These participants acknowledged a potential for adverse industry influence, but expressed confidence in existing strategies for avoiding industry influence. Other participants described unsatisfactory or undeveloped relationships, and some participants (all from general health consumer groups) presented their groups’ missions as incompatible with the pharmaceutical industry because of fundamentally opposing interests. Participants reported that interactions between their patient group and pharmaceutical companies were more common when companies had new drugs of potential interest to group members. Patient groups that accepted industry funding engaged in exchanges of “assets” with companies. Groups received money, information, and advice in exchange for providing companies with marketing, relationship building opportunities with key opinion leaders, coordinated lobbying with companies about drug access and subsidy, assisting companies with clinical trial recruitment, and enhancing company credibility. Conclusions An understanding of the range of views patient groups have about pharmaceutical company sponsorship will be useful for groups that seek to identify and manage any ethical concerns about these relationships. Patient groups that receive pharmaceutical industry money should anticipate they might be asked for specific assets in return. Selective industry funding of groups where active product marketing opportunities exist might skew the patient group sector’s activity towards pharmaceutical industry interests and allow industry to exert proxy influence over advocacy and subsequent health policy.
Control of Astrocyte Quiescence and Activation in a Synthetic Brain Hydrogel
Authors: Sualyneth Galarza, Alfred J. Crosby, ChangHui Pak, Shelly R. Peyton
Journal: Advanced Healthcare Materials (2020)

Bioengineers have designed numerous instructive brain extracellular matrix (ECM) environments with tailored and tunable protein compositions and biomechanical properties in vitro to study astrocyte reactivity during trauma and inflammation. However, a major limitation of both protein-based and synthetic model microenvironments is that astrocytes within fail to retain their characteristic stellate morphology and quiescent state without becoming activated under "normal" culture conditions. Here, a synthetic hydrogel is introduced, which for the first time demonstrates maintenance of astrocyte quiescence and activation on demand. With this synthetic brain hydrogel, the brain-specific integrin-binding and matrix metalloprotease-degradable domains of proteins are shown to control astrocyte star-shaped morphologies, and an ECM condition that maintains astrocyte quiescence with minimal activation can be achieved. In addition, activation can be induced in a dose-dependent manner via both defined cytokine cocktails and low molecular weight hyaluronic acid. This synthetic brain hydrogel is envisioned as a new tool to study the physiological role of astrocytes in health and disease.
Hepatic Lipoprotein Export and Remission of Human Type 2 Diabetes after Weight Loss
Authors: Ahmad Al-Mrabeh, Sviatlana V. Zhyzhneuskaya, Carl Peters, Alison C. Barnes, Shaden Melhem, Aaron Jesuthasan, Benjamin Aribisala, Kieren G. Hollingsworth, Georg Lietz, John C. Mathers, Naveed Sattar, Michael E.J. Lean, Roy Taylor
Journal: Cell Metabolism (2019)