tbuckley/cabot-search huggingface dataset:
The<i>ORMDL3</i>Asthma Gene Regulates<i>ICAM1</i>and Has Multiple Effects on Cellular Inflammation
Authors: Youming Zhang, Saffron A. G. Willis-Owen, Sarah Spiegel, Clare M. Lloyd, Miriam F. Moffatt, William O. C. M. Cookson
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: Polymorphisms on chromosome 17q21 confer the major genetic susceptibility to childhood-onset asthma. Risk alleles positively correlate with ORMDL3 (orosomucoid-like 3) expression. The locus influences disease severity and the frequency of human rhinovirus (HRV)–initiated exacerbations. ORMDL3 is known to regulate sphingolipid synthesis by binding serine palmitoyltransferase, but its role in inflammation is incompletely understood.Objectives: To investigate the role of ORMDL3 in cellular inflammation.Methods: We modeled a time series of IL1B-induced inflammation in A549 cells, using cytokine production as outputs and testing effects of ORMDL3 siRNA knockdown, ORMDL3 overexpression, and the serine palmitoyltransferase inhibitor myriocin. We replicated selected findings in normal human bronchial epithelial cells. Cytokine and metabolite levels were analyzed by analysis of variance. Transcript abundances were analyzed by group means parameterization, controlling the false discovery rate below 0.05.Measurements and Main Results: Silencing ORMDL3 led to steroid-independent reduction of IL6 and IL8 release and reduced endoplasmic reticulum stress after IL1B stimulation. Overexpression and myriocin conversely augmented cytokine release. Knockdown reduced expression of genes regulating host–pathogen interactions, stress responses, and ubiquitination: in particular, ORMDL3 knockdown strongly reduced expression of the HRV receptor ICAM1. Silencing led to changes in levels of transcripts and metabolites integral to glycolysis. Increased levels of ceramides and the immune mediator sphingosine-1-phosphate were also observed.Conclusions: The results show ORMDL3 has pleiotropic effects during cellular inflammation, consistent with its substantial genetic influence on childhood asthma. Actions on ICAM1 provide a mechanism for the locus to confer susceptibility to HRV-induced asthma.
TAS-102 in metastatic colorectal cancer (mCRC) - predictive and prognostic factors in a European patient population
Authors: Radka Obermannova, Peter Grell, Josef Dvorak, Michal Vocka, Stanislav John, Helena Tuskova, Tomas Buchler, Lubos Petruzelka, Rostislav Vyzula
Journal: Annals of Oncology (2018)
P3.16-13 Long-Term Outcomes of Stereotactic Body Radiation Therapy for Stage I Non-Small Cell Lung Cancer in Patients Less Than 70 Years of Age
Authors: Z. Chen, T. Akita, Y. Maehara, R. Saito, S. Aoki, K. Marino, T. Komiyama, H. Onishi
Journal: Journal of Thoracic Oncology (2018)
A pan-cancer landscape analysis reveals a subset of endometrial stromal and pediatric tumors defined by internal tandem duplications of BCOR
Authors: L. Juckett, D.I. Lin, R. Madison, C. Patriquin, G.M. Frampton, V.A. Miller, J.S. Ross, J. Chung, A.B. Schrock, S.M. Ali, J.A. Elvin
Journal: Annals of Oncology (2018)
Long-Term Potentiation Requires a Rapid Burst of Dendritic Mitochondrial Fission during Induction
Authors: Sai Sachin Divakaruni, Adam M. Van Dyke, Ramesh Chandra, Tara A. LeGates, Minerva Contreras, Poorna A. Dharmasri, Henry N. Higgs, Mary Kay Lobo, Scott M. Thompson, Thomas A. Blanpied
Journal: Neuron (2018)
Carcinoma of unknown origin: Deep genomic profile helps to achieve an accurate diagnosis
Authors: A.B. Fernandez Díaz, V. Iranzo Gonzalez-Cruz, A.J. Cunquero Tomas, C. Avila Andrade, E. Jantus-Lewintre, S. Calabuig Fariñas, J.E. Ales, M. Valero, G. D'Errico, R.A. Pazo Cid, A. Gallego Martínez, A. Viana, S. Ponce Aix, J.A. Pérez-Fidalgo, A. Terradez, A. Rodrigo, L. Alvarez, G. Beniuga, M. Martorell, C. Camps
Journal: Annals of Oncology (2018)
Effectiveness of exercise interventions in the prevention of excessive gestational weight gain and postpartum weight retention: a systematic review and meta-analysis
Authors: Stephanie-May Ruchat, Michelle F Mottola, Rachel J Skow, Taniya S Nagpal, Victoria L Meah, Marina James, Laurel Riske, Frances Sobierajski, Amariah J Kathol, Andree-Anne Marchand, Megan Nuspl, Ashley Weeks, Casey E Gray, Veronica J Poitras, Alejandra Jaramillo Garcia, Nick Barrowman, Linda G Slater, Kristi B Adamo, Gregory A Davies, Ruben Barakat, Margie H Davenport
Journal: British Journal of Sports Medicine (2018)

Gestational weight gain (GWG) has been identified as a critical modifier of maternal and fetal health. This systematic review and meta-analysis aimed to examine the relationship between prenatal exercise, GWG and postpartum weight retention (PPWR).Systematic review with random effects meta-analysis and meta-regression. Online databases were searched up to 6 January 2017.Studies of all designs in English, Spanish or French were eligible (except case studies and reviews) if they contained information on the population (pregnant women without contraindication to exercise), intervention (frequency, intensity, duration, volume or type of exercise, alone ["exercise-only"] or in combination with other intervention components [eg, dietary; "exercise + co-intervention"]), comparator (no exercise or different frequency, intensity, duration, volume or type of exercise) and outcomes (GWG, excessive GWG (EGWG), inadequate GWG (IGWG) or PPWR).Eighty-four unique studies (n=21 530) were included. 'Low' to 'moderate' quality evidence from randomised controlled trials (RCTs) showed that exercise-only interventions decreased total GWG (n=5819; -0.9 kg, 95% CI -1.23 to -0.57 kg, I2=52%) and PPWR (n=420; -0.92 kg, 95% CI -1.84 to 0.00 kg, I2=0%) and reduced the odds of EGWG (n=3519; OR 0.68, 95% CI 0.57 to 0.80, I2=12%) compared with no exercise. 'High' quality evidence indicated higher odds of IGWG with prenatal exercise-only (n=1628; OR 1.32, 95% CI 1.04 to 1.67, I2=0%) compared with no exercise.Prenatal exercise reduced the odds of EGWG and PPWR but increased the risk of IGWG. However, the latter result should be interpreted with caution because it was based on a limited number of studies (five RCTs).
Afatinib (AFA) plus bevacizumab (BEV) combination after osimertinib (OSIME) failure for aDvanced EGFR-mutant non-small cell lung cancer (NSCLC): A multicenter prospective single arm phase II study (ABCD-study)
Authors: A. Hata, N. Katakami, K. Nishino, M. Mori, T. Yokoyama, T. Kurata, M. Tachihara, N. Takase, H. Daga, T. Kijima, S. Morita, K. Sakai, K. Nishio, M. Satouchi, S. Negoro
Journal: Annals of Oncology (2018)
Logical fallacies in the running shoe debate: let the evidence guide prescription
Authors: Christopher Napier, Richard W Willy
Journal: British Journal of Sports Medicine (2018)

For the past 40 years, running shoes have been prescribed on the basis of matching shoe features to foot morphology to prevent running-related injuries (RRI). Yet, traditional shoe prescription has not prevented RRIs—consider five quality randomised controlled trials (RCT) and observational cohort studies.1–5 In contrast, a recent investigation6 found that motion control shoes protected against injury in experienced runners who had pronated feet. There are likely important methodological reasons for the discrepancies between these studies, such as differing definitions of RRI and various experience levels among runners. Nonetheless, there remains a lack of conclusive evidence to support traditional shoe prescription to prevent RRIs.7 

Alternative shoe prescription paradigms have emerged. While minimalist shoes have historically received the most attention from researchers, clinicians and runners, the more recent paradigms of maximalism, zero-drop shoes and choosing a shoe based on comfort appear to be gaining in popularity (see figure 1 for examples).



Figure 1 
Examples of various shoe paradigms. Clockwise from top left: traditional (Brooks Epinephrine 18), minimalist (New Balance Minimus Trail 10), zero-drop (Altra Torin …
Abstract 14992: Identification and Characterization of Orally Bio-Available Anti-Atherosclerosis Agents
Authors: Nabil A Elshourbagy, Harold V Meyers, Shaker A Mousa
Journal: Circulation (2016)

Our goal is to develop a new drug to lower the risk of coronary heart disease (CHD) by focusing on the regression and prevention of atherosclerosis. Although much progress has been made in the cont...
Neuroethics Questions to Guide Ethical Research in the International Brain Initiatives
Authors: Jordan Amadio, Guo-Qiang Bi, Paul Frederick Boshears, Adrian Carter, Anna Devor, Kenji Doya, Hermann Garden, Judy Illes, L. Syd M. Johnson, Lyric Jorgenson, Bang-Ook Jun, Inyoung Lee, Patricia Michie, Tsuyoshi Miyakawa, Eisuke Nakazawa, Osamu Sakura, Hagop Sarkissian, Laura Specker Sullivan, Stepheni Uh, David Winickoff, Paul Root Wolpe, Kevin Chien-Chang Wu, Akira Yasamura, Jialin C. Zheng, Karen S. Rommelfanger, Sung-Jin Jeong, Arisa Ema, Tamami Fukushi, Kiyoto Kasai, Khara M. Ramos, Arleen Salles, Ilina Singh
Journal: Neuron (2018)
DeepTag: inferring diagnoses from veterinary clinical notes
Authors: Allen Nie, Ashley Zehnder, Rodney L. Page, Yuhui Zhang, Arturo Lopez Pineda, Manuel A. Rivas, Carlos D. Bustamante, James Zou
Journal: npj Digital Medicine (2018)

Large scale veterinary clinical records can become a powerful resource for patient care and research. However, clinicians lack the time and resource to annotate patient records with standard medical diagnostic codes and most veterinary visits are captured in free-text notes. The lack of standard coding makes it challenging to use the clinical data to improve patient care. It is also a major impediment to cross-species translational research, which relies on the ability to accurately identify patient cohorts with specific diagnostic criteria in humans and animals. In order to reduce the coding burden for veterinary clinical practice and aid translational research, we have developed a deep learning algorithm, DeepTag, which automatically infers diagnostic codes from veterinary free-text notes. DeepTag is trained on a newly curated dataset of 112,558 veterinary notes manually annotated by experts. DeepTag extends multitask LSTM with an improved hierarchical objective that captures the semantic structures between diseases. To foster human-machine collaboration, DeepTag also learns to abstain in examples when it is uncertain and defers them to human experts, resulting in improved performance. DeepTag accurately infers disease codes from free-text even in challenging cross-hospital settings where the text comes from different clinical settings than the ones used for training. It enables automated disease annotation across a broad range of clinical diagnoses with minimal preprocessing. The technical framework in this work can be applied in other medical domains that currently lack medical coding resources.
Effect of the polymorphisms rs1476413, rs1801131, rs4846052 and rs6541003 of the MTHFR gene on prostate cancer in a high cardiovascular risk population
Authors: J.B. Ramirez Sabio, J.V. Sorlí, C. Ortega-Azorín, J.A. Pérez-Fidalgo, E.M. Asensio, D. Corella
Journal: Annals of Oncology (2018)
First-in-human study of the monopolar spindle 1 (Mps1) kinase inhibitor BAY 1161909 in combination with paclitaxel in subjects with advanced malignancies
Authors: P. Lorusso, S.P. Chawla, J. Bendell, A.F. Shields, G. Shapiro, P. Rajagopalan, C. Cyris, I. Bruns, J. Mei, F. Souza, D. Rasco, J.P. Eder, A.W. Tolcher
Journal: Annals of Oncology (2018)
Protein Kinase C Epsilon Deletion in Adipose Tissue, but Not in Liver, Improves Glucose Tolerance
Authors: Amanda E. Brandon, Bing M. Liao, Barbara Diakanastasis, Benjamin L. Parker, Katy Raddatz, Sophie A. McManus, Liam O'Reilly, Erica Kimber, A. Gabrielle van der Kraan, Dale Hancock, Darren C. Henstridge, Peter J. Meikle, Gregory J. Cooney, David E. James, Saskia Reibe, Mark A. Febbraio, Trevor J. Biden, Carsten Schmitz-Peiffer
Journal: Cell Metabolism (2018)
Abstract 19446: Role of miR-181 Family in the Heart: A Tale of Two Intracellular Compartments
Authors: Samarjit Das, Mark J Kohr, Brittany Dunkerly, Djahida Bedja, Oliver A Kent, Anthony K Leung, Jorge Henao-Mejia, Richard A Flavell, Charles Steenbergen
Journal: Circulation (2015)

Recent reports suggest that mi(cro)RNAs, non-coding RNAs, can regulate numerous human genes. miRNAs play an important role in physiologic and pathologic processes of cardiovascular health. We identified a nuclear encoded miRNA (miR-181c) that translocates into mitochondria to regulate a mitochondrial gene, and ultimately affects mitochondrial function. To investigate how miR-181c leads to cardiac injury, we designed miR-181-sponges, RNA molecules with ten repeated complimentary miR-181 “seed” sequences, and generated a set of stable-H9c2 cells by transfecting either a scrambled- or the miR-181-sponge-sequences. Sponge-H9c2 showed a significant decrease in ROS production and reduced basal mitochondrial respiration, and significant protection against Doxorubicin-induced oxidative stress. However, chronic down-regulation of the entire miR-181 family also stimulates PTEN expression, and thus the sponge decreased PI3K signaling. Thus, protection against Doxorubicin is enhanced when we treated sponge-H9c2 with siRNA against PTEN. We hypothesize that miR-181a/b targets PTEN in the cytosol and miR-181c targets mt-COX1 in the mitochondria. To extend this finding, miR-181a/b-/- and miR-181c/d-/- mice were used. miR-181a/b-/- shows a significant decrease in cardiac function at baseline compared to both miR-181c/d-/- and WT groups. Basal mitochondrial ROS production was significantly decreased in miR-181c/d-/- compare to WT or miR-181a/b-/-. Using both Electron Microscopy and light-scattering at 540 nm by isolated heart mitochondria, we found that the mitochondria are smaller in the miR-181c/d-/- , and genomic DNA-qPCR showed the number of mitochondria was markedly higher in the miR-181c/d-/- heart compared to the WT or 181a/b-/- groups. miR-181c/d-/- showed a significant decrease, while miR-181a/b-/- showed a significant increase in infarct size compared to WT, when the hearts were challenged with ischemia-reperfusion injury. Taken together, the miR-181 family regulates important signaling pathways in oxidative stress, notably with detrimental results by targeting mt-COX1 (miR-181c), or with protection by targeting PTEN (miR-181a/b).
Role of platelets and platelet receptors in cancer metastasis
Authors: Martin Schlesinger
Journal: Journal of Hematology & Oncology (2018)

The interaction of tumor cells with platelets is a prerequisite for successful hematogenous metastatic dissemination. Upon tumor cell arrival in the blood, tumor cells immediately activate platelets to form a permissive microenvironment. Platelets protect tumor cells from shear forces and assault of NK cells, recruit myeloid cells by secretion of chemokines, and mediate an arrest of the tumor cell platelet embolus at the vascular wall. Subsequently, platelet-derived growth factors confer a mesenchymal-like phenotype to tumor cells and open the capillary endothelium to expedite extravasation in distant organs. Finally, platelet-secreted growth factors stimulate tumor cell proliferation to micrometastatic foci. This review provides a synopsis on the current literature on platelet-mediated effects in cancer metastasis and particularly focuses on platelet adhesion receptors and their role in metastasis. Immunoreceptor tyrosine-based activation motif (ITAM) and hemi ITAM (hemITAM) comprising receptors, especially, glycoprotein VI (GPVI), FcγRIIa, and C-type lectin-like-2 receptor (CLEC-2) are turned in the spotlight since several new mechanisms and contributions to metastasis have been attributed to this family of platelet receptors in the last years.
Colon cancer molecular subtype intratumoral heterogeneity and its prognostic impact: An extensive molecular analysis of the PETACC-8
Authors: P. Laurent-Puig, L. Marisa, M. Ayadi, Y. Blum, R. Balogoun, C. Pilati, K. Le Malicot, C. Lepage, J.F. Emile, R. Salazar, D. Aust, A. Duval, J. Selves, D. Guenot, G. Milano, J.-F. Seitz, J. Taieb, V. Boige, A. de Reyniès
Journal: Annals of Oncology (2018)
Heart failure in the outpatient versus inpatient setting: findings from the BIOSTAT‐CHF study
Authors: João Pedro Ferreira, Marco Metra, Ify Mordi, John Gregson, Jozine M. ter Maaten, Jasper Tromp, Stefan D. Anker, Kenneth Dickstein, Hans L. Hillege, Leong L. Ng, Dirk J. van Veldhuisen, Chim C. Lang, Adriaan A. Voors, Faiez Zannad
Journal: European Journal of Heart Failure (2018)
Experimental social rejection increases dyspnoea perception and neural processing of respiratory sensations in healthy subjects
Authors: Michaela Herzog, Josef Sucec, Milica Vukovic, Ilse Van Diest, Omer Van den Bergh, Andreas von Leupoldt
Journal: European Respiratory Journal (2018)

Patients suffering from dyspnoea frequently report social rejection as a severe limitation of their lives [1]. While the effects of different social challenges on the respiratory system are already established in animal models [2, 3], little is known about potential consequences of social rejection on the perception and neural processing of dyspnoea in humans. Detrimental effects of social rejection are well documented for other aversive somatic symptoms [4, 5]. The current study examined whether social rejection would increase perceived dyspnoea and whether this would be paralleled by increased neural processing of respiratory sensations as measured with respiratory-related evoked potentials (RREPs) in the electroencephalogram (EEG). Social rejection is associated with increased dyspnoea perception and neural processing of respiratory sensations <http://ow.ly/p5hA30mcZMS>
<i>32 Shades of Neuroethics—A Review of the Routledge Handbook of Neuroethics</i>, edited by L. Syd M Johnson and Karen S. Rommelfanger<sup>1</sup>
Authors: John Noel M. Viaña, Frederic Gilbert
Journal: The American Journal of Bioethics (2018)

A slice of the human brain overlaid with gradients of
different colors on its cover welcomes readers to L. Syd
M Johnson’s and Karen S. Rommelfanger’s The Routledge
Handbook of Neuroethics (Johnson and Rommelfanger
2018). Inside, readers find 509 pages dedicated to neuroethics,
divided into four main parts and 32 chapters. The
32 chapters of this handbook present a wide range of
captivating material, encompassing the work of 61 top
scholars on subjects ranging from dissecting the identity
of neuroethics to elucidating the role of neuroscience in
animal ethics.
Cabozantinib in metastatic renal cell carcinoma (mRCC): Data from UK expanded access program (EAP)
Authors: A. Gomez de Liano Lista, B. Venugopal, K. Fife, S. Symeonides, N.S. Vasudev, S.M. Rudman, S. Vohra, L. Khasati, C. Pettinger, B. Szabados, L. Morrison, T. Powles, E. Boleti
Journal: Annals of Oncology (2018)
Ushering in the cardiac role of Ubiquilin1
Authors: Xi Fang, Christa Trexler, Ju Chen
Journal: Journal of Clinical Investigation (2018)

Protein quality control (PQC) mechanisms are essential for maintaining cardiac function, and alterations in this pathway influence multiple forms of heart disease. Since heart disease is the leading cause of death worldwide, understanding how the delicate balance between protein synthesis and degradation is regulated in the heart demands attention. The study by Hu et al. reveals that the extraproteasomal ubiquitin receptor Ubiquilin1 (Ubqln1) plays an important role in cardiac ubiquitination-proteasome coupling, particularly in response to myocardial ischemia/reperfusion injury, thereby suggesting that this may be a new avenue for therapeutics.
GW29-e0359 A disintegrin and metalloproteinase with thrombospondin type 1 motifs5 (ADAMTS5): a novel soluble biomarker of coronary artery disease
Authors: Zhen Wang, Jing Ye, Menglong Wang, Jianfang Liu, Yao Xu, Huimin Jiang, Di Ye, Jiangbin Chen, Zeng Tao, Yingzhong Lin, Jun Wan
Journal: Journal of the American College of Cardiology (2018)
Abstract 11455: Mechanism Underlying Increased eNOS Expression and Neuroprotection in Mice With Targeted Deletion of ROCK2
Authors: Yukio Hiroi, Kensuke Noma, Hyung-Hwan Kim, Yuxin Li, Ryuji Okamoto, Jianxin Sun, Michael A Michael A. Moskowitz, James K Liao
Journal: Circulation (2014)

Background: The Rho kinases (ROCK1 and ROCK2) are important regulators of the actin cytoskeleton. We have recently shown that ROCK activity is increased during the onset of ischemic stroke and that the ROCK inhibitor, fasudil, decreased the severity of focal cerebral ischemia, in part, through the upregulation of endothelial nitric oxide synthase (eNOS). However, the precise mechanism by which ROCK regulates eNOS expression is unknown. Methods and Results: Using RNA affinity chromatography with 3’UTR of eNOS mRNA followed by MALDI-TOF-MS analysis, we have identified eukaryotic elongation factor 1 alpha 1 (eEF1A1) as an actin-binding protein, which directly binds to eNOS mRNA and regulates eNOS mRNA stability. Overexpression of eEF1A1 decreased, and knock-down of eEF1A1 by siRNA increased, eNOS expression. Protein kinase assays using eEF1A1 with purified ROCK1 and ROCK2 showed that eEF1A1 is strongly phosphorylated by ROCK2, but not ROCK1, and that eEF1A1 phosphorylation by ROCK2 is required for binding to and destabilization of eNOS mRNA. Indeed, treatment of human endothelial cells (EC) with fasudil decreased eEF1A1 phosphorylation, but not expression. This was associated with increased eNOS mRNA stability and expression, and NO production. Furthermore, compared to that of WT and ROCK1+/- mice, eNOS mRNA stability and expression were increased in ECs from ROCK2+/- mice and endothelium-dependent relaxation was enhanced in both ROCK2+/- and EC-specific ROCK2 KO mice (EC-ROCK2-/-). These results correlated with decreased cerebral infarct size and neurological deficits in both ROCK2+/- and EC-ROCK2-/- mice subjected to transient focal cerebral ischemia. When ROCK2+/- mice were place on eNOS-/- background (double mutant ROCK2+/-/eNOS-/- mice), the neuroprotective effects observed in ROCK2+/- mice were abolished, indicating that eNOS mediates neuroprotective effects in ROCK2-deficient mice. Conclusion: ROCK2 negatively regulates eNOS expression by phosphorylating eEF1A1, which is required for eEF1A1 to bind to eNOS mRNA. The binding of eEF1A1 decreases eNOS mRNA stability and expression. These findings suggest a novel mechanism by which ROCK2 could impair endothelial function and worsen cerebral ischemia.