tbuckley/cabot-search huggingface dataset:
Computationally guided personalized targeted ablation of persistent atrial fibrillation
Authors: Patrick M. Boyle, Tarek Zghaib, Sohail Zahid, Rheeda L. Ali, Dongdong Deng, William H. Franceschi, Joe B. Hakim, Michael J. Murphy, Adityo Prakosa, Stefan L. Zimmerman, Hiroshi Ashikaga, Joseph E. Marine, Aravindan Kolandaivelu, Saman Nazarian, David D. Spragg, Hugh Calkins, Natalia A. Trayanova
Journal: Nature Biomedical Engineering (2019)
Curative Allogeneic Stem Cell Transplantation Is Safe and Feasible in Adult Patients with Sickle Cell Disease Despite Lack of Matched Sibling Donor and Presence of Sickle Cell-Related Co-Morbidities
Authors: Amer Assal, Diane George, Monica Bhatia, Christian Gordillo, Nicole Howard, Ran Reshef, Markus Y Mapara
Journal: Blood (2018)
In uncontrolled type 2 diabetes, adjunctive semaglutide reduced HbA<sub>1c</sub>and body weight vs sitagliptin
Authors: Lorraine L. Lipscombe
Journal: Annals of Internal Medicine (2019)

Source Citation Rosenstock J, Allison D, Birkenfeld AL, et al; PIONEER 3 Investigators. Effect of additional oral semaglutide vs sitagliptin on glycated hemoglobin in adults with type 2 diabetes uncontrolled with metformin alone or with sulfonylurea: The PIONEER 3 randomized clinical trial. JAMA. 2019;321:1466-80. 30903796
Microbial findings, sensitivity and outcome in patients with postoperative peritonitis a retrospective cohort study
Authors: Rainer Grotelueschen, Marc Luetgehetmann, Johannes Erbes, Lena M. Heidelmann, Katharina Grupp, Karl Karstens, Tarik Ghadban, Matthias Reeh, Jakob R. Izbicki, Kai Bachmann
Journal: International Journal of Surgery (2019)
Prediction of response to chemotherapy by ERCC1 immunohistochemistry and ERCC1 polymorphism in ovarian cancer
Authors: K. D. Steffensen, M. Waldstrøm, U. Jeppesen, I. Brandslund, A. Jakobsen, G. University of Southern Denmark
Journal: Journal of Clinical Oncology (2007)

5568 Background: The response of tumor cells to platinum-based drugs involves DNA repair mechanisms. Platinum-DNA adducts are repaired by nucleotide excision repair (NER) enzymes that recognize the DNA damage and excise the platinum-DNA adducts from the injured DNA strand. Excision repair cross-complementation group 1 (ERCC1) is one of the genes that encode the proteins of the NER complex and several studies have linked ERCC1 to platinum resistance in cell lines and in human cancers. Cells with a high repair capacity, e.g. high level of ERCC1 expression may therefore be resistant to platinum-based chemotherapy, and conversely, polymorphisms within encoding DNA repair enzymes or low repair capacity may confer sensitivity. A common single nucleotide polymorphism (SNP) of ERCC1 at codon 118 have been proposed to impair ERCC1 translation and reduce ERCC1 protein expression and consequently influence the response to platinum based chemotherapy. The aim of this study was to evaluate ERCC1 expression and ERCC1 118 polymorphism in epithelial ovarian cancer and the potential association with response to platinum-based chemotherapy. Methods: Formalin-fixed, paraffin-embedded tissue sections from 159 patients with epithelial ovarian cancer, FIGO stage IIb-IV, were used for immunohistochemistry (monoclonal mouse antibody, clone 8F1, Neomarkers). ERCC1 codon 118 SNP genotyping was performed by real time PCR, Taqman SNP genotyping assay. Results: ERCC1 protein overexpression was found in 37.7 % of the tumors. The response rate (normalization of CA125 during platinum-based chemotherapy) was 63.6 % (35/55) in patients with ERCC1-negative tumors compared to only 35.6 % (16/45) in patients with ERCC1-positive tumors. (p = 0.0052, χ 2 ). Furthermore increasing immunohistochemical score (H-score) was associated with poorer response to chemotherapy. (p = 0.0006, Spearman`s). The T/T genotype (44 %) showed better response to chemotherapy than C/C + C/T (15 % + 41 %) variants (p=0.042). Conclusions: Patients with ERCC1-negative tumors appear to have significantly better response to platinumbased chemotherapy compared to patients with ERCC1-positive tumors. In addition the TT genotype seems to be favorable towards better response to platinum-based chemotherapy. No significant financial relationships to disclose.
FRI0245 Clinical course and outcome in mixed connective tissue disease
Authors: A Georgiadis, D Bougias, PV Voulgari, AA Drosos
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To investigate the clinical course and outcome of patients diagnosed with mixed connective tissue disease (MCTD). <h3>Methods</h3> Since 1981, forty-four patients with MCTD have been diagnosed and followed up until December 2000. We reevaluated all these patients by entering the demographic, clinical, laboratory, radiological and therapeutic disease characteristics in a database. <h3>Results</h3> Thirty-nine patients had the typical feature of MCTD, 3 developed diffuse systemic sclerosis and 2 systemic lupus erythematosus. Thirty-six were female and 3 male. The mean age was 51.6 (11), the disease duration was 12.9 (5.2) (range 1-25 years) and the mean follow up was 6.6 (4.9) (range 1-19 years). Almost all patients (95%) presented symptoms and signs of Raynaud's phenomenon, arthritis and arthralgias evolving the small joints of the hands. Pulmonary dysfunction was observed in 44%, while pulmonary hypertension and renal involvement in 5% of patients. All patients had positive U1Sn-RNP antibodies and high titers of antinuclear antibodies. Only 10% of our patients also had Ro (SSA) antibodies. <h3>Conclusion</h3> It seems that our patients presented the typical clinical and serological features of MCTD. The majority of our patients had favorable outcomes, with pulmonary dysfunction being the most frequent, while pulmonary hypertension and renal involvement was observed in only a few cases.
Systematic characterization of BAF mutations provides insights into intracomplex synthetic lethalities in human cancers
Authors: Sandra Schick, André F. Rendeiro, Kathrin Runggatscher, Anna Ringler, Bernd Boidol, Melanie Hinkel, Peter Májek, Loan Vulliard, Thomas Penz, Katja Parapatics, Christian Schmidl, Jörg Menche, Guido Boehmelt, Mark Petronczki, André C. Müller, Christoph Bock, Stefan Kubicek
Journal: Nature Genetics (2019)
Guidelines for evaluating papers on educational interventions
Journal: BMJ (1999)

Education is an important part of the work of most doctors, and the BMJ is interested to publish original studies that will be useful to doctors in their educational role.Unfortunately many of the accounts we receive of educational interventions comprise a thin description of the innovation and an evaluation that says little more than that the students liked the innovation.This is not good enough.The standard of papers evaluating educational interventions should be as high as that of any other original papers that we publish.We recognise, however, that many of the methodologies that are best for evaluating educational innovations are different from the methods with which BMJ readers are familiar-for instance, methods for evaluating new drugs.We thus set up a group of advisers, consisting of people expert in medical education, to produce guidelines that we could use when reviewing original papers that describe educational innovations.This is a first version of those guidelines.The guidelines are intended for authors, editors, reviewers, and readers.We have no doubt that they can be improved, and it might be that we should evolve different guidelines for those different groups.We are doing three things with these guidelines: x Publishing them today and inviting comment.The group that produced the guidelines will revise them in the light of the responses we receive;x Sending them to various groups and individuals interested in evaluating educational innovations and asking them to comment;x To see if the guidelines work in practice, we plan to use them in reviewing papers describing educational innovations. Guidelines for authors, editors, reviewers, and readers to evaluate papers on educational interventions1 Overview (a) Is the paper right for the BMJ? Papers on educational interventions are of several types.Retrospective and descriptive studies that describe a change in a programme or module, or the development of a new teaching method or curriculum, may be of interest to those involved in curriculum management, but are less likely to be of general enough interest for the BMJ.
Data Sharing For Research—Encouraging Signs Amid Ethical Tensions
Authors: Spencer Phillips Hey
Journal: JAMA Network Open (2019)

Jihoon Kim, MS; Hyeoneui Kim, RN, PhD; Elizabeth Bell, MPH; Tyler Bath, BS; Paulina Paul, MS; Anh Pham, BS; Xiaoqian Jiang, PhD; Kai Zheng, PhD; Lucila Ohno-Machado, MD, PhD
Daratumumab for eradication of minimal residual disease in high-risk advanced relapse of T-cell/CD19/CD22-negative acute lymphoblastic leukemia
Authors: Yishai Ofran, Shimrit Ringelstein-Harlev, Ilana Slouzkey, Tsila Zuckerman, Dana Yehudai-Ofir, Israel Henig, Ofrat Beyar-Katz, Michal Hayun, Avraham Frisch
Journal: Leukemia (2019)
NUQA: Estimating Cancer Spatial and Temporal Heterogeneity and Evolution through Alignment-Free Methods
Authors: Aideen C Roddy, Anna Jurek-Loughrey, Jose Souza, Alan Gilmore, Paul G O’Reilly, Alexey Stupnikov, David Gonzalez de Castro, Kevin M Prise, Manuel Salto-Tellez, Darragh G McArt
Journal: Molecular Biology and Evolution (2019)

Abstract Longitudinal next-generation sequencing of cancer patient samples has enhanced our understanding of the evolution and progression of various cancers. As a result, and due to our increasing knowledge of heterogeneity, such sampling is becoming increasingly common in research and clinical trial sample collections. Traditionally, the evolutionary analysis of these cohorts involves the use of an aligner followed by subsequent stringent downstream analyses. However, this can lead to large levels of information loss due to the vast mutational landscape that characterizes tumor samples. Here, we propose an alignment-free approach for sequence comparison—a well-established approach in a range of biological applications including typical phylogenetic classification. Such methods could be used to compare information collated in raw sequence files to allow an unsupervised assessment of the evolutionary trajectory of patient genomic profiles. In order to highlight this utility in cancer research we have applied our alignment-free approach using a previously established metric, Jensen–Shannon divergence, and a metric novel to this area, Hellinger distance, to two longitudinal cancer patient cohorts in glioma and clear cell renal cell carcinoma using our software, NUQA. We hypothesize that this approach has the potential to reveal novel information about the heterogeneity and evolutionary trajectory of spatiotemporal tumor samples, potentially revealing early events in tumorigenesis and the origins of metastases and recurrences. Key words: alignment-free, Hellinger distance, exome-seq, evolution, phylogenetics, longitudinal.
ADAMDEC1 Maintains a Growth Factor Signaling Loop in Cancer Stem Cells
Authors: Ana Jimenez-Pascual, James S. Hale, Anja Kordowski, Jamie Pugh, Daniel J. Silver, Defne Bayik, Gustavo Roversi, Tyler J. Alban, Shilpa Rao, Rui Chen, Thomas M. McIntyre, Giorgio Colombo, Giulia Taraboletti, Karl O. Holmberg, Karin Forsberg-Nilsson, Justin D. Lathia, Florian A. Siebzehnrubl
Journal: Cancer Discovery (2019)

Abstract Glioblastomas (GBM) are lethal brain tumors where poor outcome is attributed to cellular heterogeneity, therapeutic resistance, and a highly infiltrative nature. These characteristics are preferentially linked to GBM cancer stem cells (GSC), but how GSCs maintain their stemness is incompletely understood and the subject of intense investigation. Here, we identify a novel signaling loop that induces and maintains GSCs consisting of an atypical metalloproteinase, ADAMDEC1, secreted by GSCs. ADAMDEC1 rapidly solubilizes FGF2 to stimulate FGFR1 expressed on GSCs. FGFR1 signaling induces upregulation of ZEB1 via ERK1/2 that regulates ADAMDEC1 expression through miR-203, creating a positive feedback loop. Genetic or pharmacologic targeting of components of this axis attenuates self-renewal and tumor growth. These findings reveal a new signaling axis for GSC maintenance and highlight ADAMDEC1 and FGFR1 as potential therapeutic targets in GBM. Significance: Cancer stem cells (CSC) drive tumor growth in many cancers including GBM. We identified a novel sheddase, ADAMDEC1, which initiates an FGF autocrine loop to promote stemness in CSCs. This loop can be targeted to reduce GBM growth. This article is highlighted in the In This Issue feature, p. 1469
Incidence, Treatment Patterns, and Outcomes of Histiocytic Disorders in the United States: A Forty-Year Population Study
Authors: Sagar S. Patel, Girish Kunapareddy, Hetty E. Carraway, Aaron T. Gerds, Anjali S. Advani, Matt Kalaycio, Mikkael A. Sekeres, Sudipto Mukherjee
Journal: Blood (2017)
ModelTest-NG: A New and Scalable Tool for the Selection of DNA and Protein Evolutionary Models
Authors: Diego Darriba, David Posada, Alexey M Kozlov, Alexandros Stamatakis, Benoit Morel, Tomas Flouri
Journal: Molecular Biology and Evolution (2019)

ModelTest-NG is a reimplementation from scratch of jModelTest and ProtTest, two popular tools for selecting the best-fit nucleotide and amino acid substitution models, respectively. ModelTest-NG is one to two orders of magnitude faster than jModelTest and ProtTest but equally accurate and introduces several new features, such as ascertainment bias correction, mixture, and free-rate models, or the automatic processing of single partitions. ModelTest-NG is available under a GNU GPL3 license at https://github.com/ddarriba/modeltest , last accessed September 2, 2019.
Antitumor activity of pazopanib (P) and trametinib (T) in preclinical models of osteosarcoma (OS).
Authors: Giulia Chiabotto, Maria Laura Centomo, Alessandra Merlini, Lorenzo D'Ambrosio, Dario Sangiolo, Umberto Miglio, Maja Todorovic, Lucia Napione, Enrico Berrino, Federica Capozzi, Tiziana Venesio, Elena Maldi, Anna Sapino, Massimo Aglietta, Giovanni Grignani, Ymera Pignochino
Journal: Journal of Clinical Oncology (2019)

e22509 Background: Receptor tyrosine kinases (RTKs) and their signal transducers are suitable targets for the treatment of advanced OS. We evaluated the antitumor activity of the RTK inhibitor P and the MEK inhibitor T and deeply investigated molecular mechanisms behind their activity and potential escape. Methods: Flow cytometry and western blot analyses were carried out in 7 OS cell lines to study the expression of RTK P targets and the activation of their pathways, respectively. Cell viability and colony growth were evaluated after 72h and 7-day treatment respectively, with scalar doses of both single agents and their constant combination. Cell cycle distribution and apoptosis were evaluated by flow cytometry after 72h. In vivo antitumor activity was studied in NOD/SCID mice bearing MNNG-HOS xenografts after 3 weeks of treatment. Cell migration was studied by scratch assays. The involvement of MAPK-PI3K pathway key transducers was explored by Vantage 3D RNA Panel and Nanostring technology, validated by western blot and confirmed by silencing experiments. Results: P targets are expressed on OS cell lines and their pathways are activated. P+T have synergistic antitumor activity (combination index &lt; 1) in OS cell lines by inducing apoptosis (6/7) and inhibiting both ERK1/2(7/7) and AKT (7/7). Furthermore, in vivo antitumor activity was shown in OS bearing mice (tumor volume: P+T/untreated = 0.036, p = 0.002). P+T significantly down-modulated RTK EphaA2 (mean log2 fold change RNA P+T/untreated = -2.02±0.50) and induced Janus kinase MEK6 (mean log2 fold change RNA P+T/untreated = 2.9±0.51). EphA2 silencing reduced cellular proliferation and migration of OS cells. Impeding MEK6-up-regulation in P+T treated cells significantly increased the antitumor effect (51.5±14.3%) of the studied drugs. Conclusions: P+T exert antitumor activity in OS preclinical models through ERK and AKT inhibition and EphA2 downmodulation. MEK6-upregulation after P+T is likely implied in escape mechanism.
CD200 Is a Potent New Growth Factor in Multiple Myeloma through IGF-1R Interaction
Authors: Angélique Bruyer, Nicolas Robert, Stéphanie Boireau, Christophe Hirtz, Laurent Tiers, Laure Vincent, Guillaume Cartron, Dirk Hose, Anja Seckinger, Bernard Klein, Jerome Moreaux
Journal: Blood (2017)
Dabrafenib treatment in a patient with BRAF V600E ganglioglioma: circulating exosome-derived cancer RNA supports treatment choice and clinical monitoring
Authors: Francesco Pasqualetti, Giuliana Restante, Alessandra Gonnelli, Eleonora Rofi, Alessandro Molinari, Stefania Crucitta, Fabiola Paiar, Roberta Rudà, Romano Danesi, Riccardo Soffietti, Marzia Del Re
Journal: Neuro-Oncology (2019)
Comparative Genomic Characterization of the Multimammate Mouse Mastomys coucha
Authors: Aaron Hardin, Kimberly A Nevonen, Walter L Eckalbar, Lucia Carbone, Nadav Ahituv
Journal: Molecular Biology and Evolution (2019)

Mastomys are the most widespread African rodent and carriers of various diseases such as the plague or Lassa virus. In addition, mastomys have rapidly gained a large number of mammary glands. Here, we generated a genome, variome, and transcriptomes for Mastomys coucha. As mastomys diverged at similar times from mouse and rat, we demonstrate their utility as a comparative genomic tool for these commonly used animal models. Furthermore, we identified over 500 mastomys accelerated regions, often residing near important mammary developmental genes or within their exons leading to protein sequence changes. Functional characterization of a noncoding mastomys accelerated region, located in the HoxD locus, showed enhancer activity in mouse developing mammary glands. Combined, our results provide genomic resources for mastomys and highlight their potential both as a comparative genomic tool and for the identification of mammary gland number determining factors.
Loss of type VII collagen in squamous cell carcinoma results in increased invasion with disorganized epithelial differentiation and epithelial-mesenchymal transition
Authors: V. L. Martins, J. J. Vyas, K. J. Purdie, M. Chen, J. A. McGrath, A. Storey, A.P. South, E. A. O'Toole
Journal: British Journal of Dermatology (2008)
A Phase II Trial of Vandetanib in Children and Adults with Succinate Dehydrogenase–Deficient Gastrointestinal Stromal Tumor
Authors: John Glod, Fernanda I. Arnaldez, Lori Wiener, Melissa Spencer, J. Keith Killian, Paul Meltzer, Eva Dombi, Claudia Derse-Anthony, Joanne Derdak, Ramaprasad Srinivasan, W. Marston Linehan, Markku Miettinen, Seth M. Steinberg, Lee Helman, Brigitte C. Widemann
Journal: Clinical Cancer Research (2019)

Gastrointestinal stromal tumors (GIST) are resistant to cytotoxic chemotherapy and radiotherapy. Most GIST in children are wild-type for
Immunological Monitoring of CML Patients during First-Line Bosutinib and Imatinib Treatment
Authors: Anna Kreutzman, Perttu Koskenvesa, Kasanen Tiina, Ulla Olsson-Strömberg, Jesper Stentoft, Leif Stenke, Lene Udby, Bjorn T. Gjertsen, Kourosh Lotfi, Berit Markevän, Jeroen Janssen, Tim Brümmendorf, Johan Richter, Henrik Hjorth-Hansen, Satu Mustjoki
Journal: Blood (2016)
Surgery and Salvage Limited-Field Irradiation for Control of Cutaneous Squamous Cell Carcinoma With Microscopic Residual Disease
Authors: Emily Stamell Ruiz, Shlomo A. Koyfman, Jason Kass, Chrysalyne D. Schmults
Journal: JAMA Dermatology (2019)

This case series analyzes the outcomes of patients with primary cutaneous squamous cell carcinoma treated with limited-field irradiation for microscopic residual disease after surgery.
AB0200 Do ultrasound-guided corticosteroid injections provide short-term relief of symptoms in patients waiting total hip replacement?
Authors: Z Karim, AK Brown, PJO Connor, M Quinn, G Jackson, RJ Wakefield, PG Conaghan, P Emery
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Osteoarthritis is the commonest cause of total hip joint replacement. The indication for this procedure is pain and loss of function that has not responded adequately to conservative therapy. Maintaining good muscle strength and optimising weight are important to good outcome post-surgery. This is difficult when symptoms reduce patients? mobility. Corticosteroid injections are commonly used for short-term relief of joint symptoms. <h3>Objectives</h3> The primary aim of this pilot study is to determine whether corticosteroid injections improve pain and function in this group, and to identify any baseline features that predict response. <h3>Methods</h3> Patients with osteoarthritis or stable rheumatoid arthritis awaiting total hip replacement are invited to take part. Patients with a contraindication to intraarticular corticosteroid or impending replacement (within 3 months) are excluded. Baseline data collected includes the WOMAC index, VAS for pain and stiffness during rest and walking, and SF-36. These outcome measures are repeated at 2, 6 and 12 weeks. Patients have 40 mg triamcinolone with 2 mls of 1% lignocaine via ultrasound-guided injection into the hip. Degree of capsular distension, a possible marker of synovitis, is documented by US. Conventional radiographs of the affected hip are also obtained to assess degree of damage. <h3>Results</h3> 6 patients have been recruited to date in this ongoing study. Pain scores and functional changes have improved. Our experience suggests those with capsular distension are more likely to respond. <h3>Conclusion</h3> Any reduction in patient symptoms that improves pre-operative pain and mobility should improve patient well-being and could also improve outcome post-surgery. Any predictor of response would allow the application of more accurate risk-benefit assessment for this procedure.
The long-term clinical consequences of juvenile vulvar lichen sclerosus: A systematic review
Authors: Beth Morrel, Rachel van Eersel, Curt W. Burger, Wichor M. Bramer, Marianne J. ten Kate-Booij, Irene A.M. van der Avoort, Suzanne G.M.A. Pasmans
Journal: Journal of the American Academy of Dermatology (2019)
Addressing Limitations in Case-Control Study of Patients Undergoing Resuscitative Endovascular Balloon Occlusion of the Aorta
Authors: Yosuke Matsumura, Atsushi Shiraishi
Journal: JAMA Surgery (2019)

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