tbuckley/cabot-search huggingface dataset:
A Single-center Evaluation of Prophylactic Mastectomy Outcomes: Revisiting Safety Profile and Risk Factors
Authors: P.P. Bletsis, A. Bucknor, A. Chatta, P. Kamali, R. Flecha-Hirsch, A.D. Chen, B. van der Lei, A.M. Tobias, B.T. Lee, S.J. Lin
Journal: International Journal of Surgery (2017)
79. Real Time Fluorescent Tracking of Dynamic Variegation by Retrovirus Vectors in Stem Cells
Journal: Molecular Therapy (2005)

Top of pageAbstract
Epigenetic programming is mitotically heritable and affects gene expression without altering DNA sequence. The transition from active to inactive gene expression is referred to as gene silencing. Transgenes are often subject to partial gene silencing known as variegation. Variegation is highly dynamic in embryonic stem cells (ESC) with frequent switching between expressing and silent states.

To examine variegation of a retrovirus vector in real time, a novel cell culture apparatus was used for long term imaging and eGFP transgene expression tracking over 4 days. A high resolution time course DIC and fluorescence image time sequence was obtained that examines variegation in expression levels of an MSCV-PGK-eGFP retrovirus vector in a mouse ESC colony. With this approach we recorded eGFP transgene expression levels from seven founder ESCs and their progeny over seven generations.

We report that the variegated ESC line contained lineages that were stably off or stably on, indicating that their epigenetic program was stable over many generations. At the same time, other genetically identical lineages switched through an unstable but symmetrically inherited epigenetic program that initially produced similarly expressing or silenced progeny. Nevertheless, changes in expression patterns accumulate over subsequent generations indicating that the epigenetic program in these unstable lineages continues to change over time. In addition, dramatic asymmetric reprogramming can occasionally occur between siblings. To our knowledge, this is the first real time tracking of transgene variegation in mammalian cells and reveals a surprising diversity of epigenetic states. Our novel approach documents the dynamics and stability of retrovirus variegation in stem cells, and may facilitate efforts to overcome variegation through vector redesign or drug intervention.
Universal test and treat and the HIV epidemic in rural South Africa: a phase 4, open-label, community cluster randomised trial
Authors: Collins C Iwuji, Joanna Orne-Gliemann, Joseph Larmarange, Eric Balestre, Rodolphe Thiebaut, Frank Tanser, Nonhlanhla Okesola, Thembisa Makowa, Jaco Dreyer, Kobus Herbst, Nuala McGrath, Till Bärnighausen, Sylvie Boyer, Tulio De Oliveira, Claire Rekacewicz, Brigitte Bazin, Marie-Louise Newell, Deenan Pillay, François Dabis, Till Bärnighausen, Kobus Herbst, Collins Iwuji, Thembisa Makowa, Kevi Naidu, Marie-Louise Newell, Nonhlanhla Okesola, Tulio de Oliveira, Deenan Pillay, Tamsen Rochat, Frank Tanser, Johannes Viljoen, Thembelihle Zuma, Nuala McGrath, Eric Balestre, François Dabis, Sophie Karcher, Joanna Orne-Gliemann, Melanie Plazy, Mélanie Prague, Rodolphe Thiébaut, Thierry Tiendrebeogo, Sylvie Boyer, Hermann Donfouet, Andrea Gosset, Laura March, Camelia Protopopescu, Bruno Spire, Alexandra Calmy, Joseph Larmarange, Maxime Inghels, Hassimiou Diallo, Vincent Calvez, Anne Derache, Anne-Geneviève Marcelin, Rosemary Dray-Spira, France Lert, Kamal El Farouki, Richard Lessells, Kenneth Freedberg, John Imrie, Marie-Laure Chaix, Colin Newell, Jan Hontelez, Brigitte Bazin, Claire Rekacewicz
Journal: The Lancet HIV (2017)
In patients with advanced non-small cell lung cancer (NSCLC) LAG-3 is expressed on activated TILs and predicts resistance to PD-1 axis blockers
Authors: I. Datar, M.F. Sanmamed, J. Choi, J. Wang, B.S. Henick, T. Badri, L.D. Mejias, M. Lozano, J.L. Gracia, V. Velcheti, R. Herbst, I. Melero, L. Chen, K.A. Schalper
Journal: Annals of Oncology (2017)
GP who falsified prescriptions to treat his depression is suspended for 12 months
Authors: Clare Dyer
Journal: BMJ (2017)

A GP who created false prescriptions in the name of his real patients to treat himself for depression at NHS expense has been suspended from the UK medical register for 12 months.

Graeme Little, 41, created 439 prescriptions in the names of three of his patients who had diabetes, a condition which entitled them to free prescriptions. His fraudulent prescribing came to light after a pharmacist telephoned one of the patients to say his prescription was ready. The patient replied that he had never used that pharmacy.

Little, a partner in a Teesside practice, was arrested in August 2016 and this March pleaded guilty at Teesside Crown Court to …
Call for increased pharmacovigilance of gabapentin
Authors: Alyssa M Peckham, Kathleen A Fairman, David A Sclar
Journal: BMJ (2017)

Huybrechts and colleagues find increased risk of neonatal drug withdrawal when gabapentin and opioids are co-prescribed.1 We conducted the first large scale assessment of the prevalence and clinical consequences of gabapentin misuse.23 The top 1% of gabapentin users consumed or diverted 19% of total gabapentin supply at mean (median) 11 274 (9534) mg/day; nearly 25% of these users exceeded 12 822 mg/day.2 Additionally, 24% …
Buparlisib plus fulvestrant in postmenopausal women with hormone-receptor-positive, HER2-negative, advanced breast cancer progressing on or after mTOR inhibition (BELLE-3): a randomised, double-blind, placebo-controlled, phase 3 trial
Authors: Angelo Di Leo, Stephen Johnston, Keun Seok Lee, Eva Ciruelos, Per E Lønning, Wolfgang Janni, Ruth O'Regan, Marie-Ange Mouret-Reynier, Dimitar Kalev, Daniel Egle, Tibor Csőszi, Roberto Bordonaro, Thomas Decker, Vivianne C G Tjan-Heijnen, Sibel Blau, Alessio Schirone, Denis Weber, Mona El-Hashimy, Bharani Dharan, Dalila Sellami, Thomas Bachelot
Journal: The Lancet Oncology (2017)
Aldehyde Dehydrogenase Activity in the Leukemic Stem Cell Compartment Uncovers Opposing Methylation Patterns of Leukemia Stem Cells in AML
Authors: Lauren Suarez, Tingting Qin, Kristen Meldi, Manjusha Thakar, Sarah Sakoian, Gabriel Ghiaur, Jonathan M. Gerber, Hetty E. Carraway, Maria E Figueroa, Steven D. Gore
Journal: Blood (2016)
Abstract 752: Outcomes of More Than 100 Patients with Type A Aortic Intramural Hematoma: A Single Center Experience
Authors: Jae-kwan Song, Ji Hye Yim, Sung Sik Kim, Sung-Hwan Kim, Myung-Zoon Yi, Jong-Min Song, Duk-Hyun Kang
Journal: Circulation (2008)

Data regarding the outcome of type A aortic intramural hematoma (AIH) are based on relatively small numbers of the subjects and controversial opinions for treatment option are available. We evaluated 357 patients with type A acute aortic syndrome (AAS) managed in our center between April 1993 and March 2008 to delineate clinical features, management, and outcomes of acute AIH by comparing these patients with those with classic aortic dissection (AD). One hundred one (28.3%) patients had AIH with higher mean age (65±10 versus 56±14 years, p&lt;.001) and higher prevalence of hypertension (67.3% versus 52.3%, p&lt;.001) compared with 256 patients with AD. Emergent surgery was done in 208 patients (81.3%) with AD and 16 (15.8%) with AIH (p&lt;.001). Eight five (84.2%) patients with AIH received initial medical treatment and among them 25 patients (29.4%) underwent timed surgery during admission due to various reasons including development of AD (n=10) and increase of hematoma thickness (n=7). Overall in-hospital mortality was lower in AIH (7.9% versus 17.2%, p=0.025) and markedly lower mortality was observed in patients without emergent surgery (7.1% versus 63.3%, p&lt;.001). The 30-month cumulative survival rates according to the treatment options were not different in AIH group, whereas significant difference was observed in AD group. AIH comprised significant proportion of type A AAS and showed different clinical features and more favorable response to medical treatment compared to classic AD. Contrary to AD, survival benefit of emergent surgery could not be confirmed in AIH.
The global burden of tuberculosis: results from the Global Burden of Disease Study 2015
Authors: Hmwe H Kyu, Emilie R Maddison, Nathaniel J Henry, John Everett Mumford, Ryan Barber, Chloe Shields, Jonathan C Brown, Grant Nguyen, Austin Carter, Timothy M Wolock, Haidong Wang, Patrick Y Liu, Marissa Reitsma, Jennifer M Ross, Amanuel Alemu Abajobir, Kalkidan Hassen Abate, Kaja Abbas, Mubarek Abera, Semaw Ferede Abera, Habtamu Abera Hareri, Muktar Ahmed, Kefyalew Addis Alene, Nelson Alvis-Guzman, Joshua Amo-Adjei, Jason Andrews, Hossein Ansari, Carl Abelardo Antonio, Palwasha Anwari, Hamid Asayesh, Tesfay Mehari Atey, Sachin Atre, Aleksandra Barac, Justin Beardsley, Neeraj Bedi, Isabela Bensenor, Addisu Shunu Beyene, Zahid Ahmad Butt, Pere-Joan Cardona, Devasahayam Christopher, Lalit Dandona, Rakhi Dandona, Kebede Deribe, Amare Deribew, Rebecca Ehrenkranz, Maysaa El Sayed Zaki, Aman Endries, Tesfaye R Feyissa, Florian Fischer, Ruoyan Gai, Alberto L Garcia-Basteiro, Tsegaye Tewelde Gebrehiwot, Hailay Gesesew, Belete Getahun, Philimon Gona, Amador Goodridge, Harish Gugnani, Hassan Haghparast-Bidgoli, Gessessew Bugssa Hailu, Hamid Yimam Hassen, Esayas Hilawe, Nobuyuki Horita, Kathryn H Jacobsen, Jost B Jonas, Amir Kasaeian, Muktar Sano Kedir, Laura Kemmer, Yousef Khader, Ejaz Khan, Young-Ho Khang, Abdullah T Khoja, Yun Jin Kim, Parvaiz Koul, Ai Koyanagi, Kristopher J Krohn, G Anil Kumar, Michael Kutz, Rakesh Lodha, Hassan Magdy And El Razek, Reza Majdzadeh, Tsegahun Manyazewal, Ziad Memish, Walter Mendoza, Haftay Berhane Mezgebe, Shafiu Mohammed, Felix Akpojene Ogbo, In-Hwan Oh, Eyal Oren, Aaron Osgood-Zimmerman, David Pereira, Dietrich Plass, Farshad Pourmalek, Mostafa Qorbani, Anwar Rafay, Mahfuzar Rahman, Rajesh Kumar Rai, Puja C Rao, Sarah E Ray, Robert Reiner, Nickolas Reinig, Saeid Safiri, Joshua A Salomon, Logan Sandar, Benn Sartorius, Morteza Shamsizadeh, Muki Shey, Desalegn Markos Shifti, Hirbo Shore, Jasvinder Singh, Chandrashekhar T Sreeramareddy, Soumya Swaminathan, Scott J Swartz, Fentaw Tadese, Bemnet Amare Tedla, Balewgizie Sileshi Tegegne, Belay Tessema, Roman Topor-Madry, Kingsley Nnanna Ukwaja, Olalekan A. Uthman, Vasiliy Vlassov, Stein Emil Vollset, Tolassa Wakayo, Solomon Weldegebreal, Ronny Westerman, Abdulhalik Workicho, Naohiro Yonemoto, Seok-Jun Yoon, Marcel Yotebieng, Mohsen Naghavi, Simon I Hay, Theo Vos, Christopher JL Murray
Journal: The Lancet Infectious Diseases (2017)

An understanding of the trends in tuberculosis incidence, prevalence, and mortality is crucial to tracking of the success of tuberculosis control programmes and identification of remaining challenges. We assessed trends in the fatal and non-fatal burden of tuberculosis over the past 25 years for 195 countries and territories.
Peripheral Neuropathy Induced by Microtubule-Targeted Chemotherapies: Insights into Acute Injury and Long-term Recovery
Authors: Krystyna M. Wozniak, James J. Vornov, Ying Wu, Ying Liu, Valentina A. Carozzi, Virginia Rodriguez-Menendez, Elisa Ballarini, Paola Alberti, Eleonora Pozzi, Sara Semperboni, Brett M. Cook, Bruce A. Littlefield, Kenichi Nomoto, Krista Condon, Sean Eckley, Christopher DesJardins, Leslie Wilson, Mary A. Jordan, Stuart C. Feinstein, Guido Cavaletti, Michael Polydefkis, Barbara S. Slusher
Journal: Cancer Research (2017)

Abstract Chemotherapy-induced peripheral neuropathy (CIPN) is a major cause of disability in cancer survivors. CIPN investigations in preclinical model systems have focused on either behaviors or acute changes in nerve conduction velocity (NCV) and amplitude, but greater understanding of the underlying nature of axonal injury and its long-term processes is needed as cancer patients live longer. In this study, we used multiple independent endpoints to systematically characterize CIPN recovery in mice exposed to the antitubulin cancer drugs eribulin, ixabepilone, paclitaxel, or vinorelbine at MTDs. All of the drugs ablated intraepidermal nerve fibers and produced axonopathy, with a secondary disruption in myelin structure within 2 weeks of drug administration. In addition, all of the drugs reduced sensory NCV and amplitude, with greater deficits after paclitaxel and lesser deficits after ixabepilone. These effects correlated with degeneration in dorsal root ganglia (DRG) and sciatic nerve and abundance of Schwann cells. Although most injuries were fully reversible after 3–6 months after administration of eribulin, vinorelbine, and ixabepilone, we observed delayed recovery after paclitaxel that produced a more severe, pervasive, and prolonged neurotoxicity. Compared with other agents, paclitaxel also displayed a unique prolonged exposure in sciatic nerve and DRG. The most sensitive indicator of toxicity was axonopathy and secondary myelin changes accompanied by a reduction in intraepidermal nerve fiber density. Taken together, our findings suggest that intraepidermal nerve fiber density and changes in NCV and amplitude might provide measures of axonal injury to guide clinical practice. Significance: This detailed preclinical study of the long-term effects of widely used antitubulin cancer drugs on the peripheral nervous system may help guide clinical evaluations to improve personalized care in limiting neurotoxicity in cancer survivors. Cancer Res; 78(3); 817–29. ©2017 AACR.
A prospective international observational prevalence study on prone positioning of ARDS patients: the APRONET (ARDS Prone Position Network) study
Authors: C. Guérin, P. Beuret, J. M. Constantin, G. Bellani, P. Garcia-Olivares, O. Roca, J. H. Meertens, P. Azevedo Maia, T. Becher, J. Peterson, A. Larsson, M. Gurjar, Z. Hajjej, F. Kovari, A. H. Assiri, E. Mainas, M. S. Hasan, D. R. Morocho-Tutillo, L. Baboi, J. M. Chrétien, G. François, L. Ayzac, L. Chen, L. Brochard, A. Mercat
Journal: Intensive Care Medicine (2017)
Repaglinide versus insulin for newly diagnosed diabetes in patients with cystic fibrosis: a multicentre, open-label, randomised trial
Authors: Manfred Ballmann, Dominique Hubert, Baroukh M Assael, Doris Staab, Alexandra Hebestreit, Lutz Naehrlich, Tanja Nickolay, Nicole Prinz, Reinhard W Holl, Ute Staden, Martin Claßen, Antje Schuster, Uwe Mellies, Hans-Georg Posselt, Matthias Wiebel, Ernst Rietschel, Martin Stern, Helmut Teschler, Christina Smaczny, Thomas Köhnlein, Vera Wienhausen-Wilke, Andreas Claaß, Thomas Biedermann, Gerd Dockter, Holger Köster, Helge Hebestreit, Ernst-Hinrich Ballke, Hans-Eberhard Heuer, Wolfgang Kamin, Peter Küster, Rüdiger Szczepanski, Klaus-Michael Keller, Horst Generlich, Hans-Georg Bresser, Matthias Kopp, Egbert Herting, Hans-Joachim Feickert, Jürgen Hautz, Birgit Schilling, Egbert Meyer, Marcus A Mall, Wolfram Wiebicke, Friedrich-Karl Tegtmeyer, Marguerite Honer, Helen Mosnier-Pudar, Gérard Lenoir, Jean-Jacques Robert, Laurence Kessler, Laurence Weiss, Raphaële Nove-Josserand, Marie-Christine Vantyghem, Anne Munck, Nathalie Wizla, Sylvie Leroy, Guy-André Loeuille, Raphaël Serreau, Fawzia Aissat, Gabriela H Thalhammer, Isidor Huttegger, Irmgard Eichler, Manfred Götz
Journal: The Lancet Diabetes & Endocrinology (2017)
Mutations and karyotype in myelodysplastic syndromes: TP53 clusters with monosomal karyotype, RUNX1 with trisomy 21, and SF3B1 with inv(3)(q21q26.2) and del(11q)
Authors: Ayalew Tefferi, Dame Idossa, Terra L. Lasho, Mythri Mudireddy, Christy Finke, Sahrish Shah, Maura Nicolosi, Mrinal M. Patnaik, Animesh Pardanani, Naseema Gangat, Curt A. Hanson, Rhett P. Ketterling
Journal: Blood Cancer Journal (2017)

Next-generation sequencing (NGS) studies have now established the presence of sometimes multiple somatic mutations in the majority of patients with myelodysplastic syndromes (MDS) 1, 2 .Some of these mutations, including ASXL1, TP53, RUNX1, EZH2, and SRSF2, have been shown to adversely affect overall or leukemia-free survival, independent of each other and conventional risk models 2 .More recent studies have further suggested associations of certain mutations in MDS with specific cytogenetic abnormalities.In this regard, one study employed NGS in 22 MDS patients with der(1;7)(q10;p10) and 32 with -7/del(7q) 3 ; the most frequently mutated genes in the former were RUNX1 (41%), ASXL1 (23%), EZH2 (18%), and DNMT3A (18%) and in the latter TP53 (28%), ASXL1 28%, SETBP1 (22%), and TET2 (19%).Accordingly, the authors suggested an association between der(1;7)(q10;p10) and RUNX1 mutations 3 .In another NGS study of 43 patients with del(5q)-associated MDS, recurrent mutations among 22 patients with del(5q) syndrome included ASXL1 (14%), TET2 (14%), SF3B1 (9%), TP53 (5%), RUNX1 (5%), DNMT3A (5%), and WT1 (5%) 4 ; more advanced cases displayed higher frequency of TP53 mutations.Such observations carry both pathogenetic and practical relevance, especially in deciphering the prognostic interaction between mutations and karyotype.
Inactivation of multiple tumor-suppressor genes involved in negative regulation of the cell cycle, MTS1/p16INK4A/CDKN2, MTS2/p15INK4B, p53, and Rb genes in primary lymphoid malignancies
Authors: A Hangaishi, S Ogawa, N Imamura, S Miyawaki, Y Miura, N Uike, C Shimazaki, N Emi, K Takeyama, S Hirosawa, N Kamada, Y Kobayashi, Y Takemoto, T Kitani, K Toyama, S Ohtake, Y Yazaki, R Ueda, H Hirai
Journal: Blood (1996)
Comprehensive Mutation and Copy Number Profiling in Archived Circulating Breast Cancer Tumor Cells Documents Heterogeneous Resistance Mechanisms
Authors: Costanza Paoletti, Andi K. Cani, Jose M. Larios, Daniel H. Hovelson, Kimberly Aung, Elizabeth P. Darga, Emily M. Cannell, Paul J. Baratta, Chia-Jen Liu, David Chu, Maryam Yazdani, Allen R. Blevins, Valeria Sero, Nahomi Tokudome, Dafydd G. Thomas, Christina Gersch, Anne F. Schott, Yi-Mi Wu, Robert Lonigro, Dan R. Robinson, Arul M. Chinnaiyan, Farideh Z. Bischoff, Michael D. Johnson, Ben H. Park, Daniel F. Hayes, James M. Rae, Scott A. Tomlins
Journal: Cancer Research (2017)

Addressing drug resistance is a core challenge in cancer research, but the degree of heterogeneity in resistance mechanisms in cancer is unclear. In this study, we conducted next-generation sequencing (NGS) of circulating tumor cells (CTC) from patients with advanced cancer to assess mechanisms of resistance to targeted therapy and reveal opportunities for precision medicine. Comparison of the genomic landscapes of CTCs and tissue metastases is complicated by challenges in comprehensive CTC genomic profiling and paired tissue acquisition, particularly in patients who progress after targeted therapy. Thus, we assessed by NGS somatic mutations and copy number alterations (CNA) in archived CTCs isolated from patients with metastatic breast cancer who were enrolled in concurrent clinical trials that collected and analyzed CTCs and metastatic tissues. In 76 individual and pooled informative CTCs from 12 patients, we observed 85% concordance in at least one or more prioritized somatic mutations and CNA between paired CTCs and tissue metastases. Potentially actionable genomic alterations were identified in tissue but not CTCs, and vice versa. CTC profiling identified diverse intra- and interpatient molecular mechanisms of endocrine therapy resistance, including loss of heterozygosity in individual CTCs. For example, in one patient, we observed CTCs that were either wild type for
Predictive effect of cytokines in non-small cell lung cancer
Authors: R.M. Huber, J. Stump, S. Reu, Y. Jiang, C. Karches, J.S. Gosálvez, J. Neumann, S. Kobold, A. Tufman, R. Hatz, H. Winter
Journal: Annals of Oncology (2017)
Radiological abnormalities following bronchial thermoplasty: is the pathophysiology understood?
Authors: Julia Nella Sofia d'Hooghe, Peter Iwan Bonta, Inge Alma Henrica van den Berk, Jouke Tabe Annema
Journal: European Respiratory Journal (2017)

Radiological abnormalities after BT seems related to the severity of endobronchial mucosal injury after BT <http://ow.ly/ZGeA30gLZa3> We read with great interest the paper by Debray et al. [1] reporting on early radiological lung abnormalities on computed tomography (CT) of the chest after bronchial thermoplasty (BT). The described findings in 13 patients are in line with our observations in 12 patients with severe asthma treated with BT in the TASMA trial ([www.clinicaltrials.gov][1] identifier number [NCT02225392][2]). Transient radiological abnormalities were seen after all 36 BT procedures, predominantly consisting of peribronchial consolidations with ground-glass opacities (figure 1a and c), partial occlusions/filling of bronchial lumen and atelectasis. Furthermore, we also observed a residual bronchial dilatation in a single case [2]. [1]: http://www.clinicaltrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02225392&atom=%2Ferj%2F50%2F6%2F1701537.atom
Erratum: Corrigendum: ADAM10-mediated ephrin-B2 shedding promotes myofibroblast activation and organ fibrosis
Authors: David Lagares, Parisa Ghassemi-Kakroodi, Caroline Tremblay, Alba Santos, Clemens K Probst, Alicia Franklin, Daniela M Santos, Paula Grasberger, Neil Ahluwalia, Sydney B Montesi, Barry S Shea, Katharine E Black, Rachel Knipe, Meryem Blati, Murray Baron, Brian Wu, Hassan Fahmi, Rajiv Gandhi, Annie Pardo, Moisés Selman, Jiangping Wu, Jean-Pierre Pelletier, Johanne Martel-Pelletier, Andrew M Tager, Mohit Kapoor
Journal: Nature Medicine (2017)
The Success of State Newborn Screening Policies for Critical Congenital Heart Disease
Authors: Alex R. Kemper, Wendy K. K. Lam, Joseph A. Bocchini
Journal: JAMA (2017)

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ZAP-70 in Signaling, Biology, and Disease
Authors: Byron B. Au-Yeung, Neel H. Shah, Lin Shen, Arthur Weiss
Journal: Annual Review of Immunology (2017)

T cells possess an array of functional capabilities important for host defense against pathogens and tumors. T cell effector functions require the T cell antigen receptor (TCR). The TCR has no intrinsic enzymatic activity, and thus signal transduction from the receptor relies on additional signaling molecules. One such molecule is the cytoplasmic tyrosine kinase ZAP-70, which associates with the TCR complex and is required for initiating the canonical biochemical signal pathways downstream of the TCR. In this article, we describe recent structure-based insights into the regulation and substrate specificity of ZAP-70, and then we review novel methods for determining the role of ZAP-70 catalytic activity-dependent and -independent signals in developing and mature T cells. Lastly, we discuss the disease states in mouse models and humans, which range from immunodeficiency to autoimmunity, that are caused by mutations in ZAP-70.