tbuckley/cabot-search huggingface dataset:
Ten principles for climate, environment and respiratory health
Authors: Maeve Barry, Isabella Annesi-Maesano
Journal: European Respiratory Journal (2017)

While not a meteorological fact, it is nonetheless commonly believed that every cloud has a silver lining. It seems they may also have a developed sense of irony as within days of announcing plans to pull the United States out of the United Nations Framework Convention on Climate Change (UNFCCC) Paris Agreement, President Trump moved to show his climate credentials by proposing to cover his Mexican border wall with solar panels. Despite such changes, The Lancet has noted that the response to the cloud of climate change could offer "…the greatest global health opportunity of the 21st century…" [1]. After all, while environmental and public health professionals are sensitised to the link between climate and health, key decisions on the necessary policy shifts in energy or transport are made elsewhere. These decisions must take health considerations into account [2] and health professionals have a key role to play in ensuring this connection between climate, environment and health. In such a complex space it can be difficult to see which position health professionals should take. In response to this question and, in particular, in support of the Marrakesh Ministerial Declaration on Health, Environment and Climate Change, a working group of the European Respiratory Society (ERS) Environment and Health Committee (EHC) has proposed ten principles for climate, environment and respiratory health. This editorial outlines these principles, which are as follows: Urgent policy action is needed to tackle climate change, improve our environment and promote lung health <http://ow.ly/WXPJ30gq7XQ>
A Systems Approach to Prostate Cancer Classification—Letter
Authors: Elin Thysell, Erik Bovinder Ylitalo, Emma Jernberg, Anders Bergh, Pernilla Wikström
Journal: Cancer Research (2017)

A molecular classification system with clinical impact has been lacking for prostate cancer until You and colleagues published “Integrated Classification of Prostate Cancer Reveals a Novel Luminal Subtype with Poor Prognosis” ([1][1]). Gene expression profiles were used to stratify localized
Xenograft models of relapsing and chemoresistant human small cell lung cancer
Authors: Yiyu Zou, Xuan Qiu, Roam Perez-Soler
Journal: Cancer Research (2007)

2208   Relapsing small cell lung cancer (SCLC) is an incurable condition. To develop more effective therapeutic approaches for this condition, clinically relevant SCLC animal models are needed. We have developed in vivo SCLC models that have the potential of fitting this important need. Methods: Human SCLC cell lines were inoculated into nude mice subcutaneously (sc) or intravenously (iv). When the tumors were established (5~7 mm), mice were treated with cisplatin using an optimized schedule until the tumors were invisible or reduced in size by >90%. Tumor regrew in >80 % of mice about 5-7 weeks later. Relapsing tumors were resected and reimplanted in tumor-naive mice to develop chemoresistant in vivo models of SCLC. Results: Adherent cells from cultures of cell lines H69 AR and H446 grow rapidly when inoculated sc, but induce a low number of lung metastases after iv inoculation. Cells in suspension from cultures of cell lines H69, H82, H345 and H660 grow rapidly when inoculated sc and also induce a large number of lung metastases in close to 100% of mice after iv inoculation. Expression of the anti-apoptotic genes of the Bcl-2 family is inversely related to initial in vivo cisplatin sensitivity. Most tumors regrow upon discontinuation of initial cisplatin therapy. All relapsed tumors are highly resistant to cisplatin therapy (average resistance index increased >2.4-fold). Relapsed tumors can be implanted to other tumor-naive nude mice with a 100% taking rate. Detailed molecular characterization of these resistant tumor models is ongoing and will be presented. Summary: The tumor models develop retain the basic characteristics of human SCLC: high hematogenous metastatic potential, high responsiveness to initial chemotherapy, high relapsing potential, and early development of resistance to chemotherapy. The models are currently been used to test new therapeutic modalities for this disease.  Acknowledgement: Supported by NIH grant 1 R21 CA104297 to Y Zou.
Abstract 18759: Safety and Cost Effectiveness of Same Day Discharge After Elective Percutaneous Coronary Interventions: A Large Rural Single Center Experience
Authors: Wah Wah Htun, Rajakrishnan Vijayakrishnan, Alan Awdisho, Ibrahim Syed, Sanjeet Kaur, Beni Verma, Ashley M Ferrari, Yvette M Henry, James C Blankenship, Peter B Berger
Journal: Circulation (2015)

Background: Stable patients (pts) undergoing an uncomplicated elective percutaneous coronary intervention (PCI) typically stay in the hospital overnight after their procedure. Many studies suggest that in carefully selected pts, discharge within hours after the PCI appears to be safe. There are no studies, however, comparing the economic impact of same day versus next day discharge. Objective: We sought to evaluate the safety and economic impact of same day discharge after an uncomplicated PCI compared with those after an overnight observation stay.. Methods: We performed a retrospective review of pts who underwent elective PCI and were discharged the same day vs. next day (from observation status) at Geisinger Medical Center between 1/1/2008 to 9/15/2013. The same-day discharge program for selected pts (“outpatient PCI”) was initiated in 2010. Guidelines for same day discharge included negative troponins at 4 hours; readiness for discharge before 8:00 pm; freedom from CHF; LVEF &gt;40%; live within &lt;60 miles; no impediment to obtaining immediate medical attention after discharge if needed; BMI &lt;40, and no severe aortic regurgitation. Thirty-day outcomes were analyzed. Results: A total of 1164 elective PCI pts were identified; 280 (24%) were discharged the same day (Group 1) and 884 (76%) stayed overnight (Group 2), by physician preference. The radial route was used in 47% of pts, and increased over time. No same day discharge pts were readmitted within 24 hours. At 30 days, there were no differences between Group 1 vs. 2 in frequency of access site complications (0% vs. 0.01%), peri-procedural MI (0 % vs. 0.006%), urgent care/ED visit or readmission (0.05% vs. 0.08%) (P=NS all comparisons). Stent thrombosis and death did not occur in either group in the first 24 hr post PCI. The average charges were $67,471 for pts discharged the same day, 17% less than the $81,175 for those who spent a night being observed in the hospital (P &lt; 0.0001). Conclusions: Same day discharge after an uncomplicated PCI and 4 hour observation period was safe and resulted in significantly reduced charges.
Molecular Design and Characterization of a Novel, Vwf Independent Coagulation Factor VIII (LAFATE)
Authors: Eui-Cheol Jo, Injae Oh, Seung-hoon Lee, Mee Sook Oh, Jae Hwan Ryu, Yong Jae Kim, Jin-hyeon Park, So Ra Kim, Myung Eun Jung
Journal: Blood (2017)
Evolutionary basis of HLA-DPB1 alleles affects acute GVHD in unrelated donor stem cell transplantation
Authors: Satoko Morishima, Takashi Shiina, Shingo Suzuki, Seishi Ogawa, Aiko Sato-Otsubo, Koichi Kashiwase, Fumihiro Azuma, Toshio Yabe, Masahiro Satake, Shunichi Kato, Yoshihisa Kodera, Takehiko Sasazuki, Yasuo Morishima
Journal: Blood (2017)
T(15;17)-PML/RAR-Induced Leukemogenesis: Long-Term Repopulating Hematopoietic Stem Cells as the Initial Target and More Mature Progenitors as the Potential Targets for Final Leukemic Transformation.
Authors: Claudia Oancea, Brigitte Rüster, Jessica Roos, Afsar Ali Mian, Tatjana Micheilis, Hannelore Held, Anjali Dubey, Hubert Serve, Reinhard Henschler, Martin Ruthardt
Journal: Blood (2009)
Whole-Exome Sequencing of Cell-Free DNA Reveals Temporo-spatial Heterogeneity and Identifies Treatment-Resistant Clones in Neuroblastoma
Authors: Mathieu Chicard, Leo Colmet-Daage, Nathalie Clement, Adrien Danzon, Mylène Bohec, Virginie Bernard, Sylvain Baulande, Angela Bellini, Paul Deveau, Gaëlle Pierron, Eve Lapouble, Isabelle Janoueix-Lerosey, Michel Peuchmaur, Nadège Corradini, Anne Sophie Defachelles, Dominique Valteau-Couanet, Jean Michon, Valérie Combaret, Olivier Delattre, Gudrun Schleiermacher
Journal: Clinical Cancer Research (2017)

Purpose: Neuroblastoma displays important clinical and genetic heterogeneity, with emergence of new mutations at tumor progression.Experimental Design: To study clonal evolution during treatment and follow-up, an innovative method based on circulating cell-free DNA (cfDNA) analysis by whole-exome sequencing (WES) paired with target sequencing was realized in sequential liquid biopsy samples of 19 neuroblastoma patients.Results: WES of the primary tumor and cfDNA at diagnosis showed overlap of single-nucleotide variants (SNV) and copy number alterations, with 41% and 93% of all detected alterations common to the primary neuroblastoma and cfDNA. CfDNA WES at a second time point indicated a mean of 22 new SNVs for patients with progressive disease. Relapse-specific alterations included genes of the MAPK pathway and targeted the protein kinase A signaling pathway. Deep coverage target sequencing of intermediate time points during treatment and follow-up identified distinct subclones. For 17 seemingly relapse-specific SNVs detected by cfDNA WES at relapse but not tumor or cfDNA WES at diagnosis, deep coverage target sequencing detected these alterations in minor subclones, with relapse-emerging SNVs targeting genes of neuritogenesis and cell cycle. Furthermore a persisting, resistant clone with concomitant disappearance of other clones was identified by a mutation in the ubiquitin protein ligase HERC2Conclusions: Modelization of mutated allele fractions in cfDNA indicated distinct patterns of clonal evolution, with either a minor, treatment-resistant clone expanding to a major clone at relapse, or minor clones collaborating toward tumor progression. Identification of treatment-resistant clones will enable development of more efficient treatment strategies. Clin Cancer Res; 24(4); 939-49. ©2017 AACR.
Abstract 19634: Myocardial Deformation Findings Suggest Early Diastolic Dysfunction in Preterm Infants and Adaptation to Ongoing Myocardial Diastolic Dysfunction During Maturation
Authors: Akiko Hirose, Nee Khoo, Khalid Aziz, Najlaa Al-Rajaa, Jutta Van den boom, Winnie Savard, Paul Brooks, Lisa K. Hornberger
Journal: Circulation (2012)

Background We have recently demonstrated that the ventricular filling in the preterm infant occurs less so in early diastole than observed in term infants of comparable postnatal age using traditional parameters which are preload sensitive. In the present study we sought to re-explore ventricular function using more preload independent parameters including myocardial deformation and twist to better characterize the evolution of myocardial function following preterm delivery. We hypothesized differences exist in early filling myocardial deformation rates and twist in the preterm heart. Methods We prospectively enrolled preterm infants (PI, n=30; GA 27.43±1.23 weeks) at 28 days of age who were clinically stable. After excluding structural pathology, spectral and tissue Doppler velocity and 2-dimensional deformation assessments were made with comparison to 30 healthy term infants of similar postnatal age (27±6.8 days). In 16 preterm infants, follow up echocardiography was performed near term (corrected GA 38.5±2.3 weeks). Results Compared to healthy controls, PI at 28 days had decreased peak mitral valve (MV) E wave velocity (p&lt;0.05), E/A ratio (p&lt;0.01), annular e’ velocity (p&lt;0.0001), e[[Unable to Display Character: ]]/a[[Unable to Display Character: ]] ratio (p&lt;0.0001), and increased MV E/e’ (p&lt;0.01), and at followup MV e[[Unable to Display Character: ]]/a[[Unable to Display Character: ]] (p&lt;0.05) and E/e’ (p&lt;0.01) remained abnormal compared to controls.There was no significant difference in left ventricular (LV) twist and twist rate, or longitudinal strain and strain rate (SR). Basal circumferential early diastolic SR (eSR), however, was lower in PI at 28days compared to term controls (p&lt;0.01), and there was greater late diastolic SR at followup of PI close to term (p&lt;0.05) Despite higher heart rates in PI at 28 days (162±15 vs. 141±15 bpm), there was no significant linear relationship between HR and any of the functional parameters assessed. Conclusion Myocardial deformation and twist suggest preterm infants have normal left ventricular systolic function. The subtle reduction in early diastolic SR in PI at 28 days supports early diastolic differences from controls. The presence of increased late diastolic SR at followup near term may indicate adaptation to persistent diastolic dysfunction consistent with ongoing myocardial maturational delay in postnatal life.
The association of the level of serum of interleukin-10 and its polymorphism gene with the risk and the prognosis for colorectal cancer in Tunisia
Authors: J.A. Braham, M. Balti, B.A. Mouna, B. Sinda, H. Meriem, A. Zribi, B.N. Sonia, F. Sana, A. Haddaoui
Journal: Annals of Oncology (2017)
Efficacy and safety of adrenocorticotropic hormone gel in refractory dermatomyositis and polymyositis
Authors: Rohit Aggarwal, Galina Marder, Diane Carol Koontz, Preeya Nandkumar, Zengbiao Qi, Chester V Oddis
Journal: Annals of the Rheumatic Diseases (2017)

Aim To evaluate the efficacy, safety, tolerability and steroid-sparing effect of repository corticotropin injection (RCI), in an open-label clinical trial, in refractory adult polymyositis (PM) and dermatomyositis (DM). Methods Adults with refractory PM and DM were enrolled by two centres. Inclusion criteria included refractory disease defined as failing glucocorticoid and/or ≥1 immunosuppressive agent, as well as active disease defined as significant muscle weakness and &gt;2 additional abnormal core set measures (CSMs) or a cutaneous 10 cm Visual Analogue Scale score of ≥3 cm and at least three other abnormal CSMs. All patients received RCI of 80 units subcutaneously twice weekly for 24 weeks. The primary end point for the trial was the International Myositis Assessment and Clinical Studies definition of improvement. Secondary end points included safety, tolerability, steroid-sparing as well as the 2016 American College of Rheumatology (ACR)/European League Against Rheumatism myositis response criteria (EULAR) Results Ten of the 11 enrolled subjects (6 DM, 4 PM) completed the study. Seven of 10 met the primary end point of efficacy at a median of 8 weeks. There was a significant decrease in prednisone dose from baseline to conclusion (18.5 (15.7) vs 2.3 (3.2); P&lt;0.01). Most individual CSMs improved at week 24 compared with the baseline, with the muscle strength improving by &gt;10% and the physician global by &gt;40%. RCI was considered safe and tolerable. No patient developed significant weight gain or an increase of haemoglobin A1c or cushingoid features. Conclusion Treatment with RCI was effective in 70% of patients, safe and tolerable, and led to a steroid dose reduction in patients with adult myositis refractory to glucocorticoid and traditional immunosuppressive drugs. Trial registration number NCT01906372 ; Results.
A proteolytic fragment of histone deacetylase 4 protects the heart from failure by regulating the hexosamine biosynthetic pathway
Authors: Lorenz H Lehmann, Zegeye H Jebessa, Michael M Kreusser, Axel Horsch, Tao He, Mariya Kronlage, Matthias Dewenter, Viviana Sramek, Ulrike Oehl, Jutta Krebs-Haupenthal, Albert H von der Lieth, Andrea Schmidt, Qiang Sun, Julia Ritterhoff, Daniel Finke, Mirko Völkers, Andreas Jungmann, Sven W Sauer, Christian Thiel, Alexander Nickel, Michael Kohlhaas, Michaela Schäfer, Carsten Sticht, Christoph Maack, Norbert Gretz, Michael Wagner, Ali El-Armouche, Lars S Maier, Juan E Camacho Londoño, Benjamin Meder, Marc Freichel, Hermann-Josef Gröne, Patrick Most, Oliver J Müller, Stephan Herzig, Eileen E M Furlong, Hugo A Katus, Johannes Backs
Journal: Nature Medicine (2017)
Hematopoietic stem cell gene therapy for IFNγR1 deficiency protects mice from mycobacterial infections
Authors: Miriam Hetzel, Adele Mucci, Patrick Blank, Ariane Hai Ha Nguyen, Jan Schiller, Olga Halle, Mark-Philipp Kühnel, Sandra Billig, Robert Meineke, Daniel Brand, Vanessa Herder, Wolfgang Baumgärtner, Franz-Christoph Bange, Ralph Goethe, Danny Jonigk, Reinhold Förster, Bernhard Gentner, Jean-Laurent Casanova, Jacinta Bustamante, Axel Schambach, Ulrich Kalinke, Nico Lachmann
Journal: Blood (2017)
Abstract 9533: Retention of Endothelial Progenitor Cells in Bone Marrow in a Murine Model of Endogenous Tissue Plasminogen Activator (tPA) Deficiency in Response to Critical Limb Ischemia
Authors: Hon-Kan Yip, Sarah Chua, Tzu -Hsien Tsai, Jiunn-Jye Sheu
Journal: Circulation (2013)

Background: This study tested the hypothesis that tissue plasminogen activator (tPA) is crucial for regulating endothelial progenitor cell (EPC) mobilization from bone marrow to circulation in murine critical limb ischemia (CLI) by ligating left femoral artery. Methods and Results: Wild-type (C57BL/6) (n=40) mice were equally divided into group 1A (sham control), group 2A (CLI), group 3A [control-tPA (4.0 mg/kg, intravenously at 3h after CLI)], group 4A (CLI-tPA). Similarly, tPA knock-out (tPA -/- ) mice (n=40) were equally divided into group 1B (sham control) group 2B (CLI), group 3B [control-tPA (4.0 mg/kg)], group 4B (CLI-tPA). The circulating levels of EPCs (C-kit/CD31+, Sca-1/KDR+, CXCR4/CD34+) were lower in groups 1B and 2B than in groups 1A and 2A, respectively (all p&lt;0.01), and were reversed after tPA treatment (3B vs. 3A or 4B vs. 4A, p&gt;0.05) at 6h and 18h post-CLI. Levels of these biomarkers decreased again 14 days after CLI in tPA -/- mice compared to those in wild-type between the respective groups (all p&lt;0.01). Laser Doppler flowmetry showed a higher ratio of ischemic-to-normal blood flow in 2A than in 2B and in 4A than in 4B by day 14 after CLI (all p&lt;0.05). Angiogenesis at protein (CXCR4, SDF-1α, VEGF) and cellular (CXCR4+, SDF-1α +, and CD31+ cells) levels were highest in animals with CLI-tPA, significantly higher in mice with CLI only than in sham controls for both wild-type and tPA -/- mice (p&lt;0.01). Conclusion: tPA played an essential role in augmenting circulating EPCs, angiogenesis, and blood flow in the ischemic limb in a murine model. Key words: tissue plasminogen activator, critical limb ischemia, angiogenesis, circulating endothelial progenitor cells
Transcription Factor IRF4 Promotes CD8+ T Cell Exhaustion and Limits the Development of Memory-like T Cells during Chronic Infection
Authors: Kevin Man, Sarah S. Gabriel, Yang Liao, Renee Gloury, Simon Preston, Darren C. Henstridge, Marc Pellegrini, Dietmar Zehn, Friederike Berberich-Siebelt, Mark A. Febbraio, Wei Shi, Axel Kallies
Journal: Immunity (2017)
A first-in-human phase I/II clinical trial assessing novel mRNA-lipoplex nanoparticles encoding shared tumor antigens for potent melanoma immunotherapy
Authors: L. Heesen, R. Jabulowsky, C. Loquai, J. Utikal, C. Gebhardt, J. Hassel, R. Kaufmann, A. Pinter, E. Derhovanessian, M. Diken, L. Kranz, H. Haas, S. Attig, A. Kuhn, P. Langguth, D. Schwarck-Kokarakis, D. Jäger, S. Grabbe, Ö Türeci, U. Sahin
Journal: Annals of Oncology (2017)
Abstract 16658: Pannexin-1 Channels on Endothelial Cells Modulates Aortic Aneurysm Formation
Authors: Ashish K Sharma, Michael Spinosa, Morgan D Salmon, Gang Su, Adishesh K Narahari, Brant E Isakson, Kodi S Ravichandran, Gilbert R Upchurch
Journal: Circulation (2016)

Objective: The pathogenesis of aortic aneurysm (AA) formation involves vascular remodeling and inflammation. Pannexin-1 (Panx1) channels are expressed on endothelial cells and modulate cellular ATP...
Combination of interferon-alpha and 5-fluorouracil against human hepatocellular carcinoma cells and its underlying mechanism for therapeutic efficacy
Authors: Shinji Oie, Fumihito Hosoi, Yuichiro Maruyama, Yuji Basaki, Ken-Ichi Matsuo, Tadafumi Terada, Hirohisa Yano, Masamichi Kojiro, Mayumi Ono, Michihiko Kuwano
Journal: Cancer Research (2005)

4948  The combined chemotherapy of interferon (IFN)-alpha and 5-fluorouracil (5-FU) has been reported to show some improved effects in patients with advanced hepatocellular carcinoma (HCC) but the rationale of this combination therapy is not completely elucidated. By using 6 human HCC cell lines (HAK-1A, HAK-1B, KYN-1, KYN-2, KYN-3 and KIM-1) in culture, we examined how combination of IFN-alpha and 5-FU could exert its antiproliferation effect on HCC cells at molecular basis, and we obtained following results. (1) We first determined antiproliferation effects by combination of IFN-alpha and 5-FU by isobologram analysis methods, and classified these HCC cell lines into two groups, one that showed synergistic effects including HAK-1A, KYN-1 and KYN-2 (S-group) and the other that showed additive effects including HAK-1B, KYN-3, and KIM-1 (A-group). (2) We next examined whether IFN-alpha specifically modulated expression of drug sensitivity-relevant enzymes of 5-FU, such as thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphorylasly transferase (OPRT), thymidine phosphorylase (TP), uridine phosphorylase (UP), thymidine kinase (TK). IFN-alpha modulated expression of above 5-FU-related genes at various levels in 6 HCC cell lines by RT-PCR and Western blot analysis but such changes appeared not to be directly associated with classification of either S- or A-group. (3) We then examined whether 5-FU specifically modulated expression of IFN-alpha receptor family, IFNAR1 and IFNAR2. Expression of IFNAR1 was specifically up-regulated in three HCC cell lines in S group when exposed to 5-FU, but not in those in A group. Taken together, we would like to discuss if 5-FU-induced modulation of IFN receptor gene expression could play a pivotal role in therapeutic efficacy of this combination of 5-FU and IFN-alpha.
Characterizing an Ultra–High-Risk Subset of Patients With Hypopharynx and Larynx Cancer
Authors: Ryan K. Orosco, Ezra E. Cohen
Journal: JAMA Oncology (2017)

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