tbuckley/cabot-search huggingface dataset:
Orphan G Protein–Coupled Receptor GPRC5B Controls Smooth Muscle Contractility and Differentiation by Inhibiting Prostacyclin Receptor Signaling
Authors: Jorge Carvalho, Ramesh Chennupati, Rui Li, Stefan Günther, Harmandeep Kaur, Wencai Zhao, Sarah Tonack, Michael Kurz, Nadja Mößlein, Moritz Bünemann, Stefan Offermanns, Nina Wettschureck
Journal: Circulation (2020)

G protein-coupled receptors are important regulators of contractility and differentiation in vascular smooth muscle cells (SMCs), but the specific function of SMC-expressed orphan G protein-coupled receptor class C group 5 member B (GPRC5B) is unclear.We studied the role of GPRC5B in the regulation of contractility and dedifferentiation in human and murine SMCs in vitro and in iSM-Gprc5b-KO (tamoxifen-inducible, SMC-specific knockout) mice under conditions of arterial hypertension and atherosclerosis in vivo.Mesenteric arteries from SMC-specific Gprc5b-KOs showed ex vivo significantly enhanced prostacyclin receptor (IP)-dependent relaxation, whereas responses to other relaxant or contractile factors were normal. In vitro, knockdown of GPRC5B in human aortic SMCs resulted in increased IP-dependent cAMP production and consecutive facilitation of SMC relaxation. In line with this facilitation of IP-mediated relaxation, iSM-Gprc5b-KO mice were protected from arterial hypertension, and this protective effect was abrogated by IP antagonists. Mechanistically, we show that knockdown of GPRC5B increased the membrane localization of IP both in vitro and in vivo and that GPRC5B, but not other G protein-coupled receptors, physically interacts with IP. Last, we show that enhanced IP signaling in GPRC5B-deficient SMCs not only facilitates relaxation but also prevents dedifferentiation during atherosclerosis development, resulting in reduced plaque load and increased differentiation of SMCs in the fibrous cap.Taken together, our data show that GPRC5B regulates vascular SMC tone and differentiation by negatively regulating IP signaling.
Onco-i2b2 Project: A Bioinformatics Tool Integrating –Omics and Clinical Data to Support Translational Research
Authors: A. Zambelli, D. Segagni, V. Tibollo, A. Dagliati, A. Malovini, V. Fotia, S. Manera, R. Bellazzi
Journal: Annals of Oncology (2012)
Mutation position is an important determinant for predicting cancer neoantigens
Authors: Aude-Hélène Capietto, Suchit Jhunjhunwala, Samuel B. Pollock, Patrick Lupardus, Jim Wong, Lena Hänsch, James Cevallos, Yajun Chestnut, Ajay Fernandez, Nicolas Lounsbury, Tamaki Nozawa, Manmeet Singh, Zhiyuan Fan, Cecile C. de la Cruz, Qui T. Phung, Lucia Taraborrelli, Benjamin Haley, Jennie R. Lill, Ira Mellman, Richard Bourgon, Lélia Delamarre
Journal: The Journal of Experimental Medicine (2020)

Tumor-specific mutations can generate neoantigens that drive CD8 T cell responses against cancer. Next-generation sequencing and computational methods have been successfully applied to identify mutations and predict neoantigens. However, only a small fraction of predicted neoantigens are immunogenic. Currently, predicted peptide binding affinity for MHC-I is often the major criterion for prioritizing neoantigens, although little progress has been made toward understanding the precise functional relationship between affinity and immunogenicity. We therefore systematically assessed the immunogenicity of peptides containing single amino acid mutations in mouse tumor models and divided them into two classes of immunogenic mutations. The first comprises mutations at a nonanchor residue, for which we find that the predicted absolute binding affinity is predictive of immunogenicity. The second involves mutations at an anchor residue; here, predicted relative affinity (compared with the WT counterpart) is a better predictor. Incorporating these features into an immunogenicity model significantly improves neoantigen ranking. Importantly, these properties of neoantigens are also predictive in human datasets, suggesting that they can be used to prioritize neoantigens for individualized neoantigen-specific immunotherapies.
Impact of banning smoking in cars with children on exposure to second-hand smoke: a natural experiment in England and Scotland
Authors: Anthony A Laverty, Thomas Hone, Eszter P Vamos, Philip E Anyanwu, David Taylor-Robinson, Frank de Vocht, Christopher Millett, Nicholas S Hopkinson
Journal: Thorax (2020)

England banned smoking in cars carrying children in 2015 and Scotland in 2016. We used survey data from 3 years for both countries (N England =3483–6920, N Scotland =232–319) to assess effects of the English ban using logistic regression within a difference-in-differences framework. Among children aged 13–15 years, self-reported levels of regular exposure to smoke in cars for Scotland were 3.4% in 2012, 2.2% in 2014 and 1.3% in 2016 and for England 6.3%, 5.9% and 1.6%. The ban in England was associated with a −4.1% (95% CI −4.9% to −3.3%) absolute reduction (72% relative reduction) in exposure to tobacco smoke among children.
Photoplethysmography based atrial fibrillation detection: a review
Authors: Tania Pereira, Nate Tran, Kais Gadhoumi, Michele M. Pelter, Duc H. Do, Randall J. Lee, Rene Colorado, Karl Meisel, Xiao Hu
Journal: npj Digital Medicine (2020)

Abstract Atrial fibrillation (AF) is a cardiac rhythm disorder associated with increased morbidity and mortality. It is the leading risk factor for cardioembolic stroke and its early detection is crucial in both primary and secondary stroke prevention. Continuous monitoring of cardiac rhythm is today possible thanks to consumer-grade wearable devices, enabling transformative diagnostic and patient management tools. Such monitoring is possible using low-cost easy-to-implement optical sensors that today equip the majority of wearables. These sensors record blood volume variations—a technology known as photoplethysmography (PPG)—from which the heart rate and other physiological parameters can be extracted to inform about user activity, fitness, sleep, and health. Recently, new wearable devices were introduced as being capable of AF detection, evidenced by large prospective trials in some cases. Such devices would allow for early screening of AF and initiation of therapy to prevent stroke. This review is a summary of a body of work on AF detection using PPG. A thorough account of the signal processing, machine learning, and deep learning approaches used in these studies is presented, followed by a discussion of their limitations and challenges towards clinical applications.
Retrospective Analysis of the Difference of Prognosis between Unresectable and Recurrent Biliary Tract Cancer: Kansai Hepatobiliary Oncology Group (KHBO) 1001
Authors: K. Ikezawa, M. Kanai, T. Ajiki, T. Tsukamoto, H. Toyokawa, H. Terajima, H. Furuyama, H. Nagano, I. Ikai, N. Kuroda, M. Awane, T. Ochiai, S. Takemura, A. Miyamoto, T. Ioka
Journal: Annals of Oncology (2012)
Combining semiconductor-based sequencing with amplicon-based cancer gene panels: A rapid next-gen approach to clinical cancer genotyping.
Authors: Christopher L. Corless, Tanaya Neff, Michael C. Heinrich, Carol Beadling
Journal: Journal of Clinical Oncology (2012)

10591 Background: Bringing next-gen sequencing into clinical (CLIA-licensed) laboratories is an important step in the advancement of personalized cancer care. We have validated a new sequencing approach on the Ion Torrent (IT) PGM using the AmpliSeq Cancer Panel, which covers hotspot regions across 46 commonly mutated cancer genes. Methods: The AmpliSeq panel is comprised of 190 primer pairs that are co-amplified in a single tube to generate amplicons for sequencing. In our testing only 10ng of input DNA was used. Initial PCR was for 20 cycles, after which the amplicons were ligated with sequencing/barcode adapters, amplified for an additional 7 cycles, and then subjected to emulsion PCR. The resulting nanospheres were sequenced on an IT 316 chip. Results: We sequenced 44 samples of FFPE-derived tumor DNA that were previously genotyped on a mass spectroscopy (MS)-based panel. Samples were barcoded and sequenced in batches of 4, yielding an average of 2034 reads per amplicon (range: 95-5162) and an average read length of 76bp. Overall, 95.4% of reads were on target, and 79% of reads were AQ20 or better; 95% of the 190 amplicons had over 500 reads. All 42 known point mutations were accurately identified by the variant caller software. Seventeen in/dels from 4 to 63 bp in length were at least partially visible upon manual inspection of the read alignments, but some were not accurately called by the software. In addition, 22 new mutations were identified in gene regions not covered on our MS-based panel. We demonstrated sensitivity to the level of 5% mutant allele, and the correlation between allelic ratios measured by MS and IT sequencing was excellent (r 2 =0.81). Two DNA samples from laser-captured tumor worked well with the AmpliSeq Panel. Conclusions: Combining solid-state sequencing with a highly multiplexed PCR method for library construction is a rapid (48 hr) approach for next-gen sequencing of clinical cancer samples. The process is highly scalable and larger, cancer-specific amplicon panels are in development. Automated identification of in/dels remains a challenge in next-gen sequencing output.
Randomized, Open, Prospective, Phase II Clinical Trial of Doxorubicin (DOXO) vs. Trabectedin Plus Doxo in the First-Line Treatment of Patients (PTS) with Advanced Non-Operable and/or Metastatic Soft Tissue Sarcomas (STS): Geis-20 Study
Authors: J. Martin Broto, X. Garcia Del Muro, A. Lopez-Pousa, R. Las De Penas, J. Maurel, R. Cubedo, A. Redondo, J. Martinez-Trufero, J. Cruz Jurado, A.M. Poveda
Journal: Annals of Oncology (2012)
Increasing physical activity by four legs rather than two: systematic review of dog-facilitated physical activity interventions
Authors: Ryan E Rhodes, Maria Baranova, Hayley Christian, Carri Westgarth
Journal: British Journal of Sports Medicine (2020)

Regular walking is a critical target of physical activity (PA) promotion, and dog walking is a feasible PA intervention for a large segment of the population. The purpose of this paper was to review PA interventions that have involved canine interactions and to evaluate their effectiveness. A secondary aim of this review was to highlight the populations, settings, designs and intervention components that have been applied so as to inform future research.Systematic review.We carried out literature searches to August 2019 using six common databases.Studies included published papers in peer-reviewed journals and grey literature (theses and dissertations) in the English language that included any PA behaviour change design (ie, randomised controlled trial, quasi-experimental) that focused on canine-related intervention. We grouped findings by population, setting, medium, research design and quality, theory and behaviour change techniques applied.The initial search yielded 25 010 publications which were reduced to 13 independent studies of medium and high risks of bias after screening for eligibility criteria. The approaches to intervene on PA were varied and included loaner dogs, new dog owners and the promotion of walking among established dog owners. Findings were consistent in showing that canine-assisted interventions do increase PA (82% of the studies had changes favouring the canine-facilitated intervention). Exploratory subanalyses showed that specific study characteristics and methods may have moderated the effects. Compared with studies with longer follow-up periods, studies with shorter follow-up favoured behaviour changes of the canine intervention over the control condition.Canine-based PA interventions appear effective, but future research should move beyond feasibility and proof of concept studies to increase rigour, quality and generalisability of findings.
Case Definitions Used During the First 6 Months of the 10th Ebola Virus Disease Outbreak in the Democratic Republic of the Congo — Four Neighboring Countries, August 2018–February 2019
Authors: Alexandra M. Medley, Oscar Mavila, Issa Makumbi, Felicien Nizeyemana, Angela Umutoni, Hélène Balisanga, Yona Kenyi Manoah, Aimee Geissler, Sudhir Bunga, Gene MacDonald, Jaco Homsy, Joseph Ojwang, Raimi Ewetola, Pratima L. Raghunathan, Amanda MacGurn, Kimberly Singler, Sarah Ward, Shahrokh Roohi, Vance Brown, Trevor Shoemaker, Richard Lako, Adeline Kabeja, Allan Muruta, Leopold Lubula, Rebecca Merrill
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

On August 1, 2018, the Democratic Republic of the Congo (DRC) declared its 10th Ebola virus disease (Ebola) outbreak in an area with a high volume of cross-border population movement to and from neighboring countries. The World Health Organization (WHO) designated Rwanda, South Sudan, and Uganda as the highest priority countries for Ebola preparedness because of the high risk for cross-border spread from DRC (1). Countries might base their disease case definitions on global standards; however, historical context and perceived risk often affect why countries modify and adapt definitions over time, moving toward or away from regional harmonization. Discordance in case definitions among countries might reduce the effectiveness of cross-border initiatives during outbreaks with high risk for regional spread. CDC worked with the ministries of health (MOHs) in DRC, Rwanda, South Sudan, and Uganda to collect MOH-approved Ebola case definitions used during the first 6 months of the outbreak to assess concordance (i.e., commonality in category case definitions) among countries. Changes in MOH-approved Ebola case definitions were analyzed, referencing the WHO standard case definition, and concordance among the four countries for Ebola case categories (i.e., community alert, suspected, probable, confirmed, and case contact) was assessed at three dates (2). The number of country-level revisions ranged from two to four, with all countries revising Ebola definitions by February 2019 after a December 2018 peak in incidence in DRC. Case definition complexity increased over time; all countries included more criteria per category than the WHO standard definition did, except for the "case contact" and "confirmed" categories. Low case definition concordance and lack of awareness of regional differences by national-level health officials could reduce effectiveness of cross-border communication and collaboration. Working toward regional harmonization or considering systematic approaches to addressing country-level differences might increase efficiency in cross-border information sharing.
RNA-Seq profiling of deregulated miRs in CLL and their impact on clinical outcome
Authors: Gurvinder Kaur, Vivek Ruhela, Lata Rani, Anubha Gupta, Krishnamachari Sriram, Ajay Gogia, Atul Sharma, Lalit Kumar, Ritu Gupta
Journal: Blood Cancer Journal (2020)

Abstract Abnormal expression patterns of regulatory small non-coding RNA (sncRNA) molecules such as microRNAs (miRs), piwi-interacting RNAs (piRNAs), and small nucleolar RNAs (snoRNAs) play an important role in the development and progression of cancer. Identification of clinically relevant sncRNA signatures could, therefore, be of tremendous translational value. In the present study, genome-wide small RNA sequencing identified a unique pattern of differential regulation of eight miRs in Chronic Lymphocytic Leukemia (CLL). Among these, three were up-regulated (miR-1295a, miR-155, miR-4524a) and five were down-regulated (miR-30a, miR-423, miR-486*, let-7e, and miR-744) in CLL. Altered expression of all these eight differentially expressed miRs (DEMs) was validated by RQ-PCR. Besides, seven novel sequences identified to have elevated expression levels in CLL turned out to be transfer RNA (tRNA)/piRNAs (piRNA-30799, piRNA-36225)/snoRNA (SNORD43) related. Multivariate analysis showed that miR-4524a (HR: 1.916, 95% CI: 1.080–3.4, p value: 0.026) and miR-744 (HR: 0.415, 95% CI: 0.224–0.769, p value: 0.005) were significantly associated with risk and time to first treatment. Further investigations could help establish the scope of integration of these DEM markers into risk stratification designs and prognostication approaches for CLL.
Higher prevalence of homologous recombination deficiency in tumors from African Americans versus European Americans
Authors: Sanju Sinha, Khadijah A. Mitchell, Adriana Zingone, Elise Bowman, Neelam Sinha, Alejandro A. Schäffer, Joo Sang Lee, Eytan Ruppin, Bríd M. Ryan
Journal: Nature Cancer (2020)
Prospective Evaluation of Planar Bone Scintigraphy, SPECT/CT, 18F NAF PET/CT and Whole Body 1.5T MRI for Detection of Bone Metastases in High Risk Breast and Prostate Cancer Patients
Authors: A.K. Kuisma, I. Jambor, R. Huovinen, M. Sandell
Journal: Annals of Oncology (2012)
Temsirolimus vs Sorafenib As Second Line Therapy in Metastatic Renal Cell Carcinoma: Results from the Intorsect Trial
Authors: T. Hutson, B. Escudier, E. Esteban, G.A. Bjarnason, H.Y. Lim, K. Pittman, P. Senico, A. Niethammer, D. Lu, S. Hariharan, R.J. Motzer
Journal: Annals of Oncology (2012)
Tolerability of Cabazitaxel in Senior Adults with Metastatic Castration-Resistant Prostate Cancer (MCRPC) in Europe
Authors: A. Heidenreich, S. Bracarda, M. Mason, H. Ozen, L. Sengelov, W. Gerritsen, C. Papandreou, S. Fossa, S. Hitier, M. Climent
Journal: Annals of Oncology (2012)
Extranodal Non-Hodgkin Lymphomas in a Northern Portugal Institution - 2006/2010
Authors: L. Queiroz, A.D. Marques, M. Almeida, E. Couto, I. Trindade, C. Portela, J. Amorim, T. Macedo, R. Nabiço, H. Marques
Journal: Annals of Oncology (2012)
Development and Validation of the Asia-Pacific Proximal Colon Neoplasia Risk Score
Authors: Martin C.S. Wong, Rungsun Rerknimitr, Khean Lee Goh, Takahisa Matsuda, Hyun-Soo Kim, Deng-Chyang Wu, Kai Chun Wu, Khay Guan Yeoh, Vui Heng Chong, Furqaan Ahmed, Jose D. Sollano, Jayaram Menon, Han-Mo Chiu, Jingnan Li, Jessica Y.L. Ching, Joseph J.Y. Sung
Journal: Clinical Gastroenterology and Hepatology (2020)
54 The geographical distribution of colorectal polyps in the west of ireland population
Authors: D Storan, E Slattery
Journal: Gut (2017)

Background  BowelScreen, the faecal immunochemical test based national colorectal cancer screening programme, commenced in May 2013. There is a large variation in the global distribution of colorectal cancer, but there is limited data on local geographic variations.  Aim  The primary aim was to investigate for local variations in geographic distribution of colorectal polyps in the UHG BowelScreen catchment area.  Method  All screening colonoscopies completed were analysed for the presence of advanced pathology (i.e. polyp ≥10 mm and/or ≥5 polyps detected and/or tumour detected). Only towns with a population ≥1000 as per 2011 census figures were included.  Results  Between 2013 and 2016; 1191 colonoscopies were included, with 790 patients having a polyp detected (67% of the total cohort) of whom 295 (25%) found to have advanced pathology. 153/1191 (13%) had polyps>10 mm in size, 153/1191 (13%) had ≥5 polyps and 32/1191 (3%) had tumours diagnosed based on endoscopic appearance.  The prevalence of large polyps ranged from 3.2-32/10,000 per settlement. Similar trends were seen with respect to multiple polyps (from 0-23/10,000) and cancer (0-5/10,000). Hotspots of advanced findings were particularly notable in east Galway (Ballinasloe, Tuam, Loughrea) and mid Mayo (Swinford, Ballyhaunis, Belmullet).  Conclusions  There appears to be a wide local variation in the local geographic distribution of advanced colorectal polyps. This variation may be due to a combination of demographic, lifestyle, environmental or genetic differences in each area. Further study is needed, and could identify areas where bowel screen advertising could be intensified to improve participation rates and yields of endoscopy.
Effect of Corticosteroid Dose and Duration on 18-Fluorodeoxyglucose Positron Emission Tomography in Cardiac Sarcoidosis
Authors: David R. Okada, Elie Saad, Alison L. Wand, Jan M. Griffin, Edward K. Kasper, Edward H. Chen, Jonathan Chrispin, Harikrishna Tandri, Lilja B. Solnes, Nisha A. Gilotra
Journal: JACC. Cardiovascular imaging (2020)
A Phase II Trial of the Multi-Targeted Kinase Inhibitor Lenvatinib (E7080) in Advanced Medullary Thyroid Cancer (MTC)
Authors: M. Schlumberger, B. Jarzab, M.E. Cabanillas, B. Robinson, P. Furio, D.W. Ball, J.C. McCaffrey, K. Newbold, R. Allison, R.G. Martins, L. Licitra, M.H. Shah, D.L. Bodenner, R. Elisei, L.A. Burmeister, Y. Funahashi, R. Sellecchia, C. Andresen, J.P. O'Brien, S. Sherman
Journal: Annals of Oncology (2012)
Persistance of CD30 Expression in Embryonal Carcinoma (EC) Cells: A Retrospective Study in Multi-Relapsed or Chemotherapy (CT) Refractory Germ-Cell Tumor (GCT)
Authors: P. Giannatempo, A. Necchi, M. Colecchia, B. Paolini, N. Nicolai, D. Raggi, M. Catanzaro, D. Biasoni, R. Salvioni, A.M. Gianni
Journal: Annals of Oncology (2012)
Impact of BAL lymphocytosis and presence of honeycombing on corticosteroid treatment effect in fibrotic hypersensitivity pneumonitis: a retrospective cohort study
Authors: Laurens J. De Sadeleer, Frederik Hermans, Els De Dycker, Jonas Yserbyt, Johny A. Verschakelen, Eric K. Verbeken, Geert M. Verleden, Stijn E. Verleden, Wim A. Wuyts
Journal: European Respiratory Journal (2020)

According to a survey study conducted by Wijsenbeek et al. [1], 76% of respiratory physicians believe fibrotic hypersensitivity pneumonitis (fibrotic HP, fHP) should be treated with corticosteroids (CS) as first line treatment. However, data to support such a strategy are limited and confined to acute farmer's lung [2]. Classically, HP patients are classified according to symptom chronicity in acute and chronic HP [3]. Based on new data, however, a stratification according to the (radiological) presence of fibrosis seems more in line with prognosis [4]. In an earlier study, we demonstrated that CS treatment was only beneficial in non-fibrotic HP while CS was not effective in fHP, both in terms of survival, and decline in forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide ( D LCO) [5]. In the present study, we determined whether the presence of bronchoalveolar lavage lymphocytosis (BAL lymphocytosis, BALL) or honeycombing influences the treatment effect of CS in fHP patients. Low BAL lymphocytosis and presence of honeycombing predict poor outcome and absence of corticosteroid treatment effect in fibrotic hypersensitivity pneumonitis <http://bit.ly/2QUl0K6> We thank the patients who participated in this study.
Prognostic Factors in Early Stage Non-Small Cell Lung Cancer (NSCLC): The Importance of Number of Resected Lymph Nodes and Vascular Invasion
Authors: M. Caramanti, R. Berardi, A. Santinelli, A. Brunelli, A. Savini, P. Mazzanti, C. Pompili, M. Salati, C. Pierantoni, S. Cascinu
Journal: Annals of Oncology (2012)
At Last, One Indication for Left Ventricular Assist Devices—A Bridge to a Better and Longer Life
Authors: Allen S. Anderson
Journal: JAMA Cardiology (2020)

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