tbuckley/cabot-search huggingface dataset:
MIPSS70+ V2.0 and Revised Cytogenetics Changes Predict Outcomes of Allogeneic Transplantation with Fludarabine and Melphalan Conditioning in Patients with Myelofibrosis
Authors: Haris Ali, Ibrahim Aldoss, Dongyun Yang, Saloomeh Mokhtari, Samer K. Khaled, Ahmed Aribi, Michelle Afkhami, Monzr Al Malki, Thai Cao, Matthew Mei, Margaret O'Donnell, Amandeep Salhotra, Vinod A. Pullarkat, Lixin Yang, Anthony S. Stein, Guido Marcucci, Stephen J Forman, Ryotaro Nakamura, Raju Pillai, David S Snyder
Journal: Blood (2018)
Randomised controlled trials in severe asthma: selection by phenotype or stereotype
Authors: Laurie Pahus, Dany Jaffuel, Isabelle Vachier, Arnaud Bourdin, Carey Meredith Suehs, Nicolas Molinari, Pascal Chanez
Journal: European Respiratory Journal (2019)

<b>The poor representability of real-life patients in severe asthma RCTs is closely related to the selection of end-points. A composite criterion to evaluate the benefit/risk balance rather than separate end-points would broaden the eligible population.</b>http://ow.ly/JLel30naY1Y
C-X-C Motif Chemokine Receptor 4 Blockade Promotes Tissue Repair After Myocardial Infarction by Enhancing Regulatory T Cell Mobilization and Immune-Regulatory Function
Authors: Yong Wang, Klaus Dembowsky, Eric Chevalier, Philipp Stüve, Mortimer Korf-Klingebiel, Matthias Lochner, L. Christian Napp, Heike Frank, Eva Brinkmann, Anna Kanwischer, Johann Bauersachs, Mariann Gyöngyösi, Tim Sparwasser, Kai C. Wollert
Journal: Circulation (2019)

Background: Acute myocardial infarction (MI) elicits an inflammatory response that drives tissue repair and adverse cardiac remodeling. Inflammatory cell trafficking after MI is controlled by C-X-C motif chemokine ligand 12 (CXCL12) and its receptor, C-X-C motif chemokine receptor 4 (CXCR4). CXCR4 antagonists mobilize inflammatory cells and promote infarct repair, but the cellular mechanisms are unclear. Methods: We investigated the therapeutic potential and mode of action of the peptidic macrocycle CXCR4 antagonist POL5551 in mice with reperfused MI. We applied cell depletion and adoptive transfer strategies using lymphocyte-deficient Rag1 knockout mice; DEREG mice, which express a diphtheria toxin receptor–enhanced green fluorescent protein fusion protein under the control of the promoter/enhancer region of the regulatory T (T reg ) cell–restricted Foxp3 transcription factor; and dendritic cell-depleted CD11c-Cre iDTR mice. Translational potential was explored in a porcine model of reperfused MI using serial contrast-enhanced magnetic resonance imaging. Results: Intraperitoneal POL5551 injections in wild-type mice (8 mg/kg at 2, 4, 6, and 8 days) enhanced angiogenesis in the infarct border zone, reduced scar size, and attenuated left ventricular remodeling and contractile dysfunction at 28 days. Treatment effects were absent in splenectomized wild-type mice, Rag1 knockout mice, and T reg cell–depleted DEREG mice. Conversely, treatment effects could be transferred into infarcted splenectomized wild-type mice by transplanting splenic T reg cells from POL5551-treated infarcted DEREG mice. Instructive cues provided by infarct-primed dendritic cells were required for POL5551 treatment effects. POL5551 injections mobilized T reg cells into the peripheral blood, followed by enhanced T reg cell accumulation in the infarcted region. Neutrophils, monocytes, and lymphocytes displayed similar mobilization kinetics, but their cardiac recruitment was not affected. POL5551, however, attenuated inflammatory gene expression in monocytes and macrophages in the infarcted region via T reg cells. Intravenous infusion of the clinical-stage POL5551 analogue POL6326 (3 mg/kg at 4, 6, 8, and 10 days) decreased infarct volume and improved left ventricular ejection fraction in pigs. Conclusions: These data confirm CXCR4 blockade as a promising treatment strategy after MI. We identify dendritic cell–primed splenic T reg cells as the central arbiters of these therapeutic effects and thereby delineate a pharmacological strategy to promote infarct repair by augmenting T reg cell function in vivo.
Abstract 10300: The Effects of the Bone Morphogenetic Protein Receptor Type 2 Mutation on the Right Ventricle in Pulmonary Arterial Hypertension
Authors: Cathelijne E van der Bruggen, Chris Happé, Pia Trip, Onno A Spruijt, Nina Rol, Arjan C Houweling, Barbara Girerd, Peter Dorfmüller, Olaf Mercier, Marc Humbert, Louis M Handoko, Jolanda van der Velden, Anton Vonk Noordegraaf, Harm Jan Bogaard, Marie José Goumans, Frances S de Man
Journal: Circulation (2015)

Introduction: The effects of a mutation in the bone morphogenetic protein receptor 2 gene (BMPR2) gene on right ventricular (RV)adaptation are currently unknown. Therefore, we investigated RV function in PAH patients with and without BMPR2 mutation by combining in vivo measurements with molecular and histological analysis of human RV and left ventricular (LV) tissue. Methods: 97 idiopathic or familial PH patients were genetically screened for the presence of a BMPR2 mutation. 28 patients carried a BMPR2 muation, 69 did not. In vivo measurements were assessed using right heart catheterization (RHC)and cardiac magnetic resonance imaging.To investigate the role of TGF-β and BMPRII signaling, human RV and LV tissue were studied in controls (n=6), mutation carriers (n=5) and non-carriers (n=11). Results: Despite a similar mean pulmonary artery pressure (noncarriers 54±15 vs. mutation carriers 55±9 mmHg)and pulmonary vascular resistance (755 (483-1043) vs. 931 (624-1311) dynes*s/cm 5 ), mutation carriers presented with a more severely compromised RV function (RV ejection fraction: 37.6±12.8 vs. 29.0±9 %: p&lt;0.05, cardiac index 2.7±0.9 vs. 2.2±0.4 l/min/m 2 ). Differences continued to exist after treatment. TGF-β and BMPRII signaling, as well as hypertrophy, fibrosis, capillary density and inflammation were similar between mutation carriers and non-carriers. Conclusions: Despite a similar afterload, RV function is severely more affected in BMPR2 mutation carriers compared to non-carriers. However, these differences cannot be explained by a different TGF-B, BMPR2 signaling or cardiac adaptation.
A game of cat and mouse: cat ownership and the relationship between mouse exposure and respiratory outcomes among dual-sensitized inner-city children with asthma
Authors: Meghan F. Davis, Jean Curtin-Brosnan, Susan L. Balcer-Whaley, Roger Peng, Meredith C. McCormack, Elizabeth C. Matsui
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract 20325: Severe Chronotropic Incompetence at the Completion of Phase Ii Cardiac Rehabilitation Leads to a Risk of Poor Long-Term Cardiovascular Prognosis
Authors: Mariko Ehara, Kenichi Shibata, Masataka Kameshima, Mayumi Konaka, Hiroaki Fujiyama, Masaki Katoh, Yukie Higashida, Akiko Shimada, Sumio Yamada, Yasuhide Okawa
Journal: Circulation (2017)

Introduction: Impaired chronotropic response (ICR) has been reported as a risk factor of reduced exercise tolerance, and often relates to the future prognosis. The purpose of the present study is to assess the clinical impact of ICR persistent at the completion of phase II cardiac rehabilitation (RH) on a long-term cardiovascular prognosis. Methods: We enrolled 247 consecutive patients (68 y.o. on average, 165 male) who participated in phase II cardiac rehabilitation program at least for 3 months (8.5 month on average). All underwent cardiopulmonary exercise test (CPX) at the initial and completion period of rehabilitation. Using CPX data, following 2 parameters were assessed: 1) Heart rate (HR) reserve (HRR) from CPX data, calculated as the following formula: HRR = (peak HR - resting HR) / (220 - age - resting HR). Using the established criteria, HRR <0.80, or <0.62 on beta-blocker (BB) regimen, was regarded as impaired. 2) HR recovery: defined as HR difference between at the peak exercise and 1-minute...
Abstract 19586: Patient-Physician Discordance in Reporting Symptoms of Peripheral Artery Disease: Findings From the PORTRAIT Registry
Authors: Tarek A Hammad, Kim G. Smolderen, John A. Spertus, Philip G. Jones, Mehdi H. Shishehbor
Journal: Circulation (2017)

Objective: A critical step in rendering care for patients with peripheral artery disease (PAD) is for physicians to accurately recognize patients’ symptoms, which may often be atypical. We sought t...
Detection of Myocardial Iron Overload with Magnetic Resonance By Native T1 and T2* Mapping Using a Segmental Approach
Authors: Alessia Pepe, Laura Pistoia, Nicola Martini, Daniele De Marchi, Andrea Barison, Aurelio Maggio, Piera Giovangrossi, Simona Bulgarelli, F. Mehtap Pasin, Roberto Sarli, Antonella Massa, Gaetano Roccamo, Mauro Caini, Vincenzo Positano, Antonella Meloni
Journal: Blood (2018)
Response by Sawaki et al to Letter Regarding Article, “Visceral Adipose Tissue Drives Cardiac Aging Through Modulation of Fibroblast Senescence by Osteopontin Production”
Authors: Daigo Sawaki, Gabor Czibik, Maria Pini, Zaineb Mezdari, Yanyan Zhang, Corneliu Henegar, Geneviève Derumeaux
Journal: Circulation (2019)
A strategy for high‐dimensional multivariable analysis classifies childhood asthma phenotypes from genetic, immunological, and environmental factors
Authors: Norbert Krautenbacher, Nicolai Flach, Andreas Böck, Kristina Laubhahn, Michael Laimighofer, Fabian J. Theis, Donna P. Ankerst, Christiane Fuchs, Bianca Schaub
Journal: Allergy (2019)

Associations between childhood asthma phenotypes and genetic, immunological, and environmental factors have been previously established. Yet, strategies to integrate high-dimensional risk factors from multiple distinct data sets, and thereby increase the statistical power of analyses, have been hampered by a preponderance of missing data and lack of methods to accommodate them.We assembled questionnaire, diagnostic, genotype, microarray, RT-qPCR, flow cytometry, and cytokine data (referred to as data modalities) to use as input factors for a classifier that could distinguish healthy children, mild-to-moderate allergic asthmatics, and nonallergic asthmatics. Based on data from 260 German children aged 4-14 from our university outpatient clinic, we built a novel multilevel prediction approach for asthma outcome which could deal with a present complex missing data structure.The optimal learning method was boosting based on all data sets, achieving an area underneath the receiver operating characteristic curve (AUC) for three classes of phenotypes of 0.81 (95%-confidence interval (CI): 0.65-0.94) using leave-one-out cross-validation. Besides improving the AUC, our integrative multilevel learning approach led to tighter CIs than using smaller complete predictor data sets (AUC = 0.82 [0.66-0.94] for boosting). The most important variables for classifying childhood asthma phenotypes comprised novel identified genes, namely PKN2 (protein kinase N2), PTK2 (protein tyrosine kinase 2), and ALPP (alkaline phosphatase, placental).Our combination of several data modalities using a novel strategy improved classification of childhood asthma phenotypes but requires validation in external populations. The generic approach is applicable to other multilevel data-based risk prediction settings, which typically suffer from incomplete data.
A multicenter, phase Ib/2 study of varlitinib plus gemcitabine and cisplatin (gem/cis) for treatment of naïve, advanced, or metastatic biliary tract cancer (BTC).
Authors: Do-Youn Oh, Wei-Peng Yong, Li-Tzong Chen, Ji-Won Kim, Alex Yuang-Chi Chang, Jin Hyun Park, Chih-Yi Hsieh, Hsuan-Jen Shih, Nicola McIntyre, Ying-Chen Chen, Wei-Ling Chang, Mark McHale, Bertil Lindmark
Journal: Journal of Clinical Oncology (2019)

319 Background: BTC is a rapidly progressing cancer with limited response to chemotherapy. First line therapy (gem/cis) was defined in the ABC-02 study (Valle et al), where a 26% response was seen. HER family receptors are overexpressed and may be involved in tumour proliferation and survival in BTC. Varlitinib, a reversible tyrosine kinase inhibitor of EGFR, HER2, and HER4, shows potent activity as monotherapy in preclinical BTC models and clinical activity in BTC patients (pts) in phase (ph) 1 trials. We conducted a ph Ib/2 study of varlitinib plus gem/cis in BTC to understand the safety profile and determine the maximum tolerated dose (MTD) of the combination. Methods: A modified 3+3+3 escalation design was used in Ph1b, with 2 varlitinib dose levels (200 and 300 mg BID) plus gem/cis on Day 1 and 8 in a 3 week cycle. The primary objectives are to determine the MTD and to characterize the safety profile. Secondary objectives are to assess the preliminary efficacy and to evaluate the pharmacokinetics of varlitinib and any circulating metabolites. Results: As of 10 Sep 2018, 21 pts were enrolled (11 in 200 mg cohort and 10 in 300 mg cohort, with 9 and 4 evaluable for MTD, respectively). Dose limiting toxicities (DLTs) were observed in 3 pts (1 G3 unconjugated hyperbilirubinemia and 1 G3 ALT transaminitis/G4 AST transaminitis in 200 mg cohort; 1 G4 thrombocytopenia/G3 febrile neutropenia/G3 AST elevation in 300 mg cohort). In 19 pts who were on varlitinib ≥ 1 month, 7 had partial response and 10 achieved stable disease (all &gt; 12 weeks), giving the overall response rate of 37% and the disease control rate of 89%. The median PFS for the 200 mg cohort was 248 days and was not reached for the 300 mg cohort. The most common (≥ 30%) all-grade adverse events (AEs) regardless of causality were thrombocytopenia (62%), neutropenia (52%), anorexia (38%), nausea (38%), diarrhoea (38%), and anaemia (33%); the most common (≥ 15%) grade ≥ 3 AEs were neutropenia (48%), thrombocytopenia (33%), and anaemia (19%). Conclusions: Varlitinib plus gem/cis was well tolerated in the 200 mg cohort; the 300 mg cohort is ongoing. Preliminary anti-tumour activity was observed. Data will be updated at the time of presentation. Clinical trial information: NCT02992340.
Loss of cannabinoid receptor 1 promotes intestinal tumor growth
Authors: Dingzhi Wang, Haibin Wang, Wei Ning, Michael Backlund, Sudhansu Dey, Raymond DuBois
Journal: Cancer Research (2008)

4190  Dysregulation of certain bioactive lipid signaling pathways is known to contribute to progression of cancer. Endocannabinoids, a class of bioactive lipids, activate G-protein-coupled cannabinoid receptors, CB1 and CB2. Although endocannabinoid signaling is important for certain aspects of gastrointestinal homoeostasis, the role of the cannabinoid receptors in colorectal cancer has not been defined. Here we show that CB1 expression was silenced in human colorectal cancer due to methylation of the CB1 promoter. Our genetic and pharmacologic studies reveal that loss or inhibition of CB1 accelerated the intestinal adenoma growth in ApcMin/+ mice whereas activation of CB1 attenuated the intestinal tumor growth by inducing cell death via downregulation of the anti-apoptotic factor survivin. This downregulation of survivin by CB1 is mediated by a cAMP-dependent PKA signaling pathway. These results indicate that the endogenous cannabinoid system represent a potential therapeutic target for the prevention or treatment of colorectal cancer.
Observer models of perceptual development
Authors: Marko Nardini, Tessa M. Dekker
Journal: Behavioral and Brain Sciences (2018)

Abstract We agree with Rahnev &amp; Denison (R&amp;D) that to understand perception at a process level, we must investigate why performance sometimes deviates from idealised decision models. Recent research reveals that such deviations from optimality are pervasive during perceptual development. We argue that a full understanding of perception requires a model of how perceptual systems become increasingly optimised during development.
Efficacy and Safety of Once-Weekly Cyclophosphamide-Bortezomib-Dexamethasone (CBD) Regimen As Induction Therapy Prior to Autologous Stem Cell Transplantation in Japanese Patients with Newly Diagnosed Multiple Myeloma. -a Phase 2 Multicenter Trial-
Authors: Daisuke Kudo, Takuya Komeno, Chikashi Yoshida, Ikuyo Ota Tsutsumi, Kazuteru Ohashi, Kazuhiko Kakihana, Takeshi Kobayashi, Noriko Doki, Yuho Najima, Aiko Igarashi, Mitsuo Hori, Yasushi Okoshi, Takayuki Fujio, Atsushi Shinagawa, Masahide Yamamoto, Hina Takano, Takashi Kumagai, Koh Yamamoto, Shigeo Toyota, Yuichi Nakamura, Hiroshi Kojima
Journal: Blood (2018)
Contamination of Hospital Plumbing
Authors: Evan S. Snitkin
Journal: JAMA Network Open (2019)

Joost Hopman, MD; Corianne Meijer, MSc; Nikki Kenters, BSc; Jordy P. M. Coolen, MSc; Mohammad R. Ghamati, MD; Shaheen Mehtar, MD, PhD; Reinout van Crevel, MD, PhD; Wim J. Morshuis, MD, PhD; Ad F. T. M. Verhagen, MD, PhD; Michel M. van den Heuvel, MD, PhD; Andreas Voss, MD, PhD; Heiman F. L. Wertheim, MD, PhD
Assessing Spinal Cerebrospinal Fluid Leaks in Spontaneous Intracranial Hypotension With a Scoring System Based on Brain Magnetic Resonance Imaging Findings
Authors: Tomas Dobrocky, Lorenz Grunder, Philipe S. Breiding, Mattia Branca, Andreas Limacher, Pascal J. Mosimann, Pasquale Mordasini, Felix Zibold, Levin Haeni, Christopher M. Jesse, Christian Fung, Andreas Raabe, Christian T. Ulrich, Jan Gralla, Jürgen Beck, Eike I. Piechowiak
Journal: JAMA Neurology (2019)

Various signs may be observed on brain magnetic resonance imaging (MRI) in patients with spontaneous intracranial hypotension (SIH). However, the lack of a classification system integrating these findings limits decision making in clinical practice.To develop a probability score based on the most relevant brain MRI findings to assess the likelihood of an underlying spinal cerebrospinal fluid (CSF) leak in patients with SIH.This case-control study in consecutive patients investigated for SIH was conducted at a single hospital department from February 2013 to October 2017. Patients with missing brain MRI data were excluded. Three blinded readers retrospectively reviewed the brain MRI scans of patients with SIH and a spinal CSF leak, patients with orthostatic headache without a CSF leak, and healthy control participants, evaluating 9 quantitative and 7 qualitative signs. A predictive diagnostic score based on multivariable backward logistic regression analysis was then derived. Its performance was validated internally in a prospective cohort of patients who had clinical suspicion for SIH.Likelihood of a spinal CSF leak based on the proposed diagnostic score.A total of 152 participants (101 female [66.4%]; mean [SD] age, 46.1 [14.3] years) were studied. These included 56 with SIH and a spinal CSF leak, 16 with orthostatic headache without a CSF leak, 60 control participants, and 20 patients in the validation cohort. Six imaging findings were included in the final scoring system. Three were weighted as major (2 points each): pachymeningeal enhancement, engorgement of venous sinus, and effacement of the suprasellar cistern of 4.0 mm or less. Three were considered minor (1 point each): subdural fluid collection, effacement of the prepontine cistern of 5.0 mm or less, and mamillopontine distance of 6.5 mm or less. Patients were classified into groups at low, intermediate, or high probability of having a spinal CSF leak, with total scores of 2 points or fewer, 3 to 4 points, and 5 points or more, respectively, on a scale of 9 points. The discriminatory ability of the proposed score could be demonstrated in the validation cohort.This 3-tier predictive scoring system is based on the 6 most relevant brain MRI findings and allows assessment of the likelihood (low, intermediate, or high) of a positive spinal imaging result in patients with SIH. It may be useful in identifying patients with SIH who are leak positive and in whom further invasive myelographic examinations are warranted before considering targeted therapy.
How Best to Resuscitate Patients With Septic Shock?
Authors: Derek C. Angus
Journal: JAMA (2019)

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Abstract 18040: Activated Factor X Signaling Pathway via Protease-Activated Receptor-2 is a Novel Therapeutic Target to Prevent Atrial Fibrillation
Authors: Takeshi Soeki, Tomomi Matsuura, Daiju Fukuda, Etsuko Uematsu, Takeshi Tobiume, Tomoya Hara, Kenya Kusunose, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Hirotsugu Yamada, Tetsuzo Wakatsuki, Masataka Sata
Journal: Circulation (2017)

Background: Atrial fibrillation (AF) is the most common type of arrhythmia seen in clinical practice. Recent studies have suggested that inflammation contributes to the pathogenesis of AF. On the o...
Abstract 19234: Variation in Early Mortality Following Isolated Coronary Artery Bypass Grafting Surgery in Australia and New Zealand
Authors: Isuru Ranasinghe, Dennis Horton, Clementine Labrosciano, Tracy Air, John F Beltrame, Christopher Zeitz, Rosanna Tavella
Journal: Circulation (2017)

Background: Variation in early outcomes of coronary artery bypass grafting (CABG) surgery are uncertain. We assessed variation in early mortality after isolated CABG surgery at all public and selec...
Consolidation with a Short Course of Daratumumab Improves Complete Response Rates in Patients with AL Amyloidosis or Lcdd
Authors: Efstathios Kastritis, Maria Gavriatopoulou, Fotiou Despina, Ioanna Dialoupi, Dimitrios C. Ziogas, Magdalini Migkou, Maria Roussou, Nikolaos Kanellias, Maria Irini Tselegkidi, Argyrios Ntalianis, Evangelos Eleutherakis-Papaiakovou, Aristea-Maria Papanota, Asimina Papanikolaou, Erasmia Psimenou, Anastasia Gatou, Charikleia Gakiopoulou, Marilyn Spyropoulou-Vlachou, Despina Katopi, Christine Ivy Liacos, Despina Mparmparousi, Evangelos Terpos, Meletios A Dimopoulos
Journal: Blood (2018)
Hoxblinc Is Aberrantly Expressed in Acute Myeloid Leukemia and Functions As a Potent Oncogenic Long Non-Coding RNA in Leukemogenesis
Authors: Ganqian Zhu, Huacheng Luo, Shi Chen, Qian Lai, Ying Guo, Olga A Guryanova, Yi Qiu, Feng-Chun Yang, Wei Li, Stephen D. Nimer, Suming Huang, Mingjiang Xu
Journal: Blood (2018)
Ex Vivo Gene-Edited Cell Therapy for Sickle Cell Disease: Disruption of the BCL11A Erythroid Enhancer with Zinc Finger Nucleases Increases Fetal Hemoglobin in Plerixafor Mobilized Human CD34+ Cells
Authors: Kevin Moran, Hui Ling, Samuel Lessard, Benjamin Vieira, Vu Hong, Michael C. Holmes, Andreas Reik, Denny Dang, David Gray, Dana Levasseur, Pauline Rimmele
Journal: Blood (2018)
Oxygen after surgery: review questions WHO advice that high levels reduce infection
Authors: Nigel Hawkes
Journal: BMJ (2019)

World Health Organization guidelines on using high levels of oxygen during and after surgery have been questioned after claims that research by an Italian surgeon lacks credibility.

Mario Schietroma of the University of L’Aquila in central Italy is the author of many surgical studies, including several that found that liberal oxygen use reduced the risk of infection after surgery. Two papers by his group formed part of the evidence WHO considered in preparing its 2016 guideline.

The guideline states: “Adult patients undergoing general anaesthesia with endotracheal intubation for surgical procedures should receive 80% fraction of inspired oxygen intraoperatively and, if feasible, in the immediate post-operative period.” …