tbuckley/cabot-search huggingface dataset:
COL1A1 copy number alterations detected in array-based comparative genomic hybridization (aCGH) inmyeloproliferative neoplasms: Implications for molecular pathogenesis and targeted therapy.
Authors: Michael R. Savona, Pranil Chandra, Zeqiang Ma, Shile Liang, R. Seth Cooper, Eric Raefsky, Victor G. Gian, Richard Hockett, Jesus G. Berdeja, P. Alan Lennon
Journal: Journal of Clinical Oncology (2013)

e22139 Background: Myeloproliferative neoplasms (MPNs) are a heterogeneous group of tumors marked by clonal proliferation of myeloid cells with variable marrow changes and clinical findings. Though progress has been made since the discovery of the JAK2V617F mutation, few data exist on the genetic distinction amongst these disorders, or pathogenesis of fibrosis seen in MPNs. Methods: Array-based comparative genomic hybridization (aCGH) was performed on genomic DNA extracted from marrow aspirate using an Agilent 180K oligonucleotide array platform in order to discover recurrent genetic aberrations, cooperating mutations, and gain insight into the hierarchy of molecular pathogenesis of fibrosis. BM aspirate from 17 pts were analyzed. Copy number alterations (CNAs) were compared to a reference set and mapped to functional genes. Genes with CNA were subjected to gene ontology, pathway and clustering analysis. Results: aCGH yielded copy number gains or losses in 17 out of 17 cases, 11 of which had normal karyotype and/or FISH. Numerous CNAs were identified within genes found in a variety of cellular pathways. In particular, alterations in COL1A1, NFKb and PDGFRb were implicated in this MPN cohort in 12, 8, and 6, pts, respectively. Interestingly, only patients with COL1A1 CNA had aberrancy within NFKb and PDGFRb. The remaining 5 pts had abnormal aCGH, but normal signals at these 3 genes. Conclusions: aCGH is a valuable tool which may be used to distinguish MPNs, particularly when standard testing does not. The presence of the COL1A1 aberration in 12/17 cases edifies evolving study of the role of TGFB superfamily in development of fibrosis and provides potential targets to exploit in the treatment of MPNs. Though aberrations within COL1A1 have not been previously reported in MPNs, a gene fusion involving COL1A1 and PDGFRb is found in 90% of dermatofibrosarcoma protuberans. The cooperation between these genes is currently under study in a larger cohort of pts with MPNs. [Table: see text]
Pregnancy Is a Poor Prognostic Factor for AML Outcome
Authors: Vera V. Troitskaya, Elena N. Parovichnikova, Andrey N. Sokolov, Alina Kokhno, Zalina T. Fidarova, Anna A. Sidorova, Olga A. Gavrilina, Gennadii M. Galstian, Aleksei Bazhenov, Larisa A. Kuzmina, Mikhail Yu. Drokov, Sergei Makhinya, Oleg Latishkevich, Alexandra Zvereva, Valery G Savchenko
Journal: Blood (2016)
On the brink of conflict: the people of South Asia deserve better
Authors: Zulfiqar A Bhutta, Samiran Nundy
Journal: BMJ (2017)

Countries must work together for enduring peace and wellbeing in the region

Nearly two decades ago, coinciding with overt nuclear tests conducted by Pakistan and India, we highlighted in The BMJ the huge risks of beginning a nuclear race in the subcontinent1 and its massive costs.2 Today, South Asia is once again at the brink of conflict, with massive deployment of armies on the borders between Pakistan and India. Insurgency and unrest affect major regions in Kashmir, Baluchistan, Assam, and the tribal and Maoist controlled areas in both India and Pakistan.3 Afghanistan has seen incessant conflict and suffering since the Soviet invasion in 1979. Nepal has emerged from decades of a debilitating Maoist insurgency, and Sri Lanka has just begun rebuilding the north after years of war and devastation.

Terrorism, which had been relatively rare, is now a daily threat affecting the lives and livelihoods of millions in South Asian states. Conflict, civic unrest, and insurgency have cost the region dearly. Despite continued economic growth and development, South Asia remains one of the poorest and most unequal regions of the world. Alarmingly, poor social …
A phase III, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of idelalisib (GS-1101) in combination with rituximab for previously treated indolent non-Hodgkin lymphomas (iNHL).
Authors: John Leonard, Pier Luigi Zinzani, Wojciech Jurczak, Mathias J. Rummel, Gilles A. Salles, Eva Kimby, Hendrik-Tobias Arkenau, Andrew John Davies, David Michael Johnson, Shelley Evans, Roger D. Dansey, Wayne R. Godfrey, Brad S. Kahl
Journal: Journal of Clinical Oncology (2013)

TPS8617 Background: PI3K-delta is critical for activation, proliferation and survival of B cells and plays a role in homing and retention in lymphoid tissues. PI3Kδ signaling is hyperactive in many B-cell malignancies. Idelalisib is a first-in-class, targeted, highly selective, oral inhibitor of PI3Kδ that reduces proliferation, enhances apoptosis, and inhibits homing and retention of malignant B cells in lymphoid tissues (Lannutti et al, 2011). Phase 1 trials demonstrated that idelalisib is highly active in pts with heavily pretreated iNHL: pts experienced reductions in disease-associated chemokines, profound and rapid reductions in lymphadenopathy, and durable clinical benefit with acceptable safety profile (de Vos et al, 2011). Methods: 375 pts with previously treated iNHL, who have measurable lymphadenopathy, have received prior anti-CD20-antibody-containing therapy, and who have iNHL that is not refractory to rituximab (R) are randomized in a 2:1 ratio into Arm A or Arm B. In Arm A, pts receive idelalisib at 150 mg BID continuously + R at 375 mg/m 2 (weekly x 4 then every 8 weeks x 4). In Arm B, pts receive placebo BID instead of idelalisib. Stratification factors include tumor type (follicular lymphoma vs others), tumor burden (high vs low), and time since completion of last prior therapy for iNHL (&lt;18 months vs ≥18 months). The primary endpoint is PFS and key secondary endpoints include ORR, lymph node response rate, CR rate, and OS. This is an event-driven trial and primary endpoint evaluation will be based on independent central review. For the primary efficacy analysis, the difference in PFS between the treatment arms will be assessed in the ITT analysis set using Kaplan-Meier methods and the stratified log-rank test. The study opened for enrollment in Dec 2012 (NCT01732913). Clinical trial information: NCT01732913.
Improvement of Canine XSCID by In Vivo Gene Therapy Using RD114/TR-Pseudotyped SIV Lentiviral Vectors.
Authors: Morvarid Moayeri, Suk See De Ravin, Douglas R. Kennedy, Nora Naumann, Yasuhiro Ikeda, Peter J. Felsburg, Harry L. Malech
Journal: Blood (2006)
The US Preventive Services Task Force 2017 Draft Recommendation Statement on Screening for Prostate Cancer
Authors: Kirsten Bibbins-Domingo, David C. Grossman, Susan J. Curry
Journal: JAMA (2017)

This Viewpoint from the US Preventive Services Task Force (USPSTF) introduces their 2017 draft recommendation statement on screening for prostate cancer, explains how it differs from their 2012 recommendation, and invites public comment.
INJURIES IN ELITE U18 FIELD HOCKEY PLAYERS AT A MAJOR TOURNAMENT
Authors: Laura-Anne Furlong, Udo Rolle
Journal: British Journal of Sports Medicine (2017)

Background There is little data on injuries in elite U18 field hockey players, which limits development of appropriate evidence-based injury prevention strategies. Objective Quantify incidence and characteristics of injuries in elite U18 field hockey players at a major tournament. Design Prospective injury surveillance. Setting 2016 EuroHockey Youth Championships, Ireland. Participants Sixteen national representative teams; 8 in each of the boys and girls competitions. Main Outcome Measurements Number of, type, mechanism and site of injuries occurring on the pitch where play was stopped for the player to receive attention. Results Across the six-day tournament, 39 injuries were reported (20 in boys competition, 19 in girls; average: 0.98 injuries per match). In the boys competition, fifteen contusions were observed primarily due to being hit by the ball/stick, with fractures (2), being winded (2) and sprains (1) also reported. Most injuries (15) occurred in the lower limb or torso, with three in the upper limb and two to the head/face where players collided with each other. Three injuries occurred when struck by the ball defending penalty corners, resulting in two lower limb contusions and one fractured finger. In the girls competition, 10 of 19 injuries were contusions, also primarily due to being hit by the ball/stick. Sprains (3), lacerations (2), being winded (2), strains (1) and cramp (1) were also reported. Ten occurred in the lower limb, five to the head/face (four due to being hit by the stick), one to the upper limb and three to the torso. Two injuries occurred defending penalty corners, resulting in contusions to the thigh and hand. Conclusions Injury incidence in elite U18 field hockey is low but the high number of injuries due to being struck by the ball or stick highlights the importance of design and use of appropriate protective equipment for youth athletes.
Resident memory T cells in the skin mediate durable immunity to melanoma
Authors: Brian T. Malik, Katelyn T. Byrne, Jennifer L. Vella, Peisheng Zhang, Tamer B. Shabaneh, Shannon M. Steinberg, Aleksey K. Molodtsov, Jacob S. Bowers, Christina V. Angeles, Chrystal M. Paulos, Yina H. Huang, Mary Jo Turk
Journal: Science Immunology (2017)

Tissue-resident memory T (TRM) cells have been widely characterized in infectious disease settings; however, their role in mediating immunity to cancer remains unknown. We report that skin-resident memory T cell responses to melanoma are generated naturally as a result of autoimmune vitiligo. Melanoma antigen-specific TRM cells resided predominantly in melanocyte-depleted hair follicles and were maintained without recirculation or replenishment from the lymphoid compartment. These cells expressed CD103, CD69, and CLA (cutaneous lymphocyte antigen), but lacked PD-1 (programmed cell death protein-1) or LAG-3 (lymphocyte activation gene-3), and were capable of making IFN-γ (interferon-γ). CD103 expression on CD8 T cells was required for the establishment of TRM cells in the skin but was dispensable for vitiligo development. CD103+ CD8 TRM cells were critical for protection against melanoma rechallenge. This work establishes that CD103-dependent TRM cells play a key role in perpetuating antitumor immunity.
TCTAP A-061 Bioresorbable Vascular Scaffold for Treating Chronic Total Occlusion Lesions: Single Center and Real World Experiences
Authors: Yi-Chih Wang, Sheng-Fu Liu, Cho-Kai Wu, Jen-Kuang Lee, Chia-Ti Tsai, Lian-Yu Lin, Ching-Chang Huang, Chih-Fan Yeh, Ying-Hsien Chen, Mao-Shin Lin, Yen-Hung Lin, Po-Yuan Chang, Paul Hsien-Li Kao, Chii-Ming Lee, Fu-Tien Chiang, Juey-Jen Hwang
Journal: Journal of the American College of Cardiology (2017)
Rapid Prospective Identification of Non-Germinal Center B Cell-Like (GCB) Diffuse Large B-Cell Lymphoma (DLBCL) Patients for Targeted Trials: Early Results From PYRAMID, A Phase 2 Randomized Study of R-CHOP ± Bortezomib In Newly Diagnosed Non-GCB DLBCL.
Authors: Kevin Doner, Ian W. Flinn, Brian K. Ulrich, Stephen J. Noga, Naveed M. Chowhan, Steven W. Papish, Tallat Mahmood, James A Reeves, Nicholas J. Di Bella, Gerald J. Robbins, Radhakrishnan Ramchandren, Sein Aung, William Lawler, Sudha Parasuraman, Maria M. Corvez, George Mulligan, John P. Leonard
Journal: Blood (2010)
HER2-Specific Chimeric Antigen Receptor–Modified Virus-Specific T Cells for Progressive Glioblastoma
Authors: Nabil Ahmed, Vita Brawley, Meenakshi Hegde, Kevin Bielamowicz, Mamta Kalra, Daniel Landi, Catherine Robertson, Tara L. Gray, Oumar Diouf, Amanda Wakefield, Alexia Ghazi, Claudia Gerken, Zhongzhen Yi, Aidin Ashoori, Meng-Fen Wu, Hao Liu, Cliona Rooney, Gianpietro Dotti, Adrian Gee, Jack Su, Yvonne Kew, David Baskin, Yi Jonathan Zhang, Pamela New, Bambi Grilley, Milica Stojakovic, John Hicks, Suzanne Z. Powell, Malcolm K. Brenner, Helen E. Heslop, Robert Grossman, Winfried S. Wels, Stephen Gottschalk
Journal: JAMA Oncology (2017)

<h3>Importance</h3> Glioblastoma is an incurable tumor, and the therapeutic options for patients are limited. <h3>Objective</h3> To determine whether the systemic administration of HER2-specific chimeric antigen receptor (CAR)–modified virus-specific T cells (VSTs) is safe and whether these cells have antiglioblastoma activity. <h3>Design, Setting, and Participants</h3> In this open-label phase 1 dose-escalation study conducted at Baylor College of Medicine, Houston Methodist Hospital, and Texas Children’s Hospital, patients with progressive HER2-positive glioblastoma were enrolled between July 25, 2011, and April 21, 2014. The duration of follow-up was 10 weeks to 29 months (median, 8 months). <h3>Interventions</h3> Monotherapy with autologous VSTs specific for cytomegalovirus, Epstein-Barr virus, or adenovirus and genetically modified to express HER2-CARs with a CD28.ζ-signaling endodomain (HER2-CAR VSTs). <h3>Main Outcomes and Measures</h3> Primary end points were feasibility and safety. The key secondary end points were T-cell persistence and their antiglioblastoma activity. <h3>Results</h3> A total of 17 patients (8 females and 9 males; 10 patients ≥18 years [median age, 60 years; range, 30-69 years] and 7 patients &lt;18 years [median age, 14 years; range, 10-17 years]) with progressive HER2-positive glioblastoma received 1 or more infusions of autologous HER2-CAR VSTs (1 × 10<sup>6</sup>/m<sup>2</sup>to 1 × 10<sup>8</sup>/m<sup>2</sup>) without prior lymphodepletion. Infusions were well tolerated, with no dose-limiting toxic effects. HER2-CAR VSTs were detected in the peripheral blood for up to 12 months after the infusion by quantitative real-time polymerase chain reaction. Of 16 evaluable patients (9 adults and 7 children), 1 had a partial response for more than 9 months, 7 had stable disease for 8 weeks to 29 months, and 8 progressed after T-cell infusion. Three patients with stable disease are alive without any evidence of progression during 24 to 29 months of follow-up. For the entire study cohort, median overall survival was 11.1 months (95% CI, 4.1-27.2 months) from the first T-cell infusion and 24.5 months (95% CI, 17.2-34.6 months) from diagnosis. <h3>Conclusions and Relevance</h3> Infusion of autologous HER2-CAR VSTs is safe and can be associated with clinical benefit for patients with progressive glioblastoma. Further evaluation of HER2-CAR VSTs in a phase 2b study is warranted as a single agent or in combination with other immunomodulatory approaches for glioblastoma.
TLR sensing of bacterial spore-associated RNA triggers host immune responses with detrimental effects
Authors: Min-Kyung Choo, Yasuyo Sano, Changhoon Kim, Kei Yasuda, Xiao-Dong Li, Xin Lin, Mary Stenzel-Poore, Lena Alexopoulou, Sankar Ghosh, Eicke Latz, Ian R. Rifkin, Zhijian J. Chen, George C. Stewart, Hyonyong Chong, Jin Mo Park
Journal: The Journal of Experimental Medicine (2017)

The spores of pathogenic bacteria are involved in host entry and the initial encounter with the host immune system. How bacterial spores interact with host immunity, however, remains poorly understood. Here, we show that the spores of Bacillus anthracis (BA), the etiologic agent of anthrax, possess an intrinsic ability to induce host immune responses. This immunostimulatory activity is attributable to high amounts of RNA present in the spore surface layer. RNA-sensing TLRs, TLR7, and TLR13 in mice and their human counterparts, are responsible for detecting and triggering the host cell response to BA spores, whereas TLR2 mediates the sensing of vegetative BA. BA spores, but not vegetative BA, induce type I IFN (IFN-I) production. Although TLR signaling in itself affords protection against BA, spore RNA–induced IFN-I signaling is disruptive to BA clearance. Our study suggests a role for bacterial spore–associated RNA in microbial pathogenesis and illustrates a little known aspect of interactions between the host and spore-forming bacteria.
Incidence, course, and management of toxicities associated with cobimetinib in combination with vemurafenib in the coBRIM study
Authors: B. Dréno, A. Ribas, J. Larkin, P.A. Ascierto, A. Hauschild, L. Thomas, J.-J. Grob, D.O. Koralek, I. Rooney, J.J. Hsu, E.F. McKenna, G.A. McArthur
Journal: Annals of Oncology (2017)
Development of pancreatic cancers during long-term follow-up of side-branch intraductal papillary mucinous neoplasms
Authors: Y. Sawai, K. Yamao, V. Bhatia, T. Chiba, N. Mizuno, A. Sawaki, K. Takahashi, M. Tajika, Y. Shimizu, Y. Yatabe, A. Yanagisawa
Journal: Endoscopy (2011)

Correction to: Development of pancreatic cancers during long-term follow-up of side-branch intraductal papillary mucinous neoplasmsEndoscopy 2010; 42(12): 1077-1084DOI: 10.1055/s-0030-1255971
Impact of Aortic Valve Calcification and Sex on Hemodynamic Progression and Clinical Outcomes in AS
Authors: Lionel Tastet, Maurice Enriquez-Sarano, Romain Capoulade, Joseph Malouf, Phillip A. Araoz, Mylène Shen, Hector I. Michelena, Éric Larose, Marie Arsenault, Élisabeth Bédard, Philippe Pibarot, Marie-Annick Clavel
Journal: Journal of the American College of Cardiology (2017)
TCTAP A-166 Study of Clinical, Echocardiographic and Hemodynamic Characteristics of Male and Female Patients Undergoing Percutaneous Transvenous Mitral Commissurotomy
Authors: Toufiqur Rahman, Abdullah Al Shafi Majumder, Afzalur Rahman, Mir Jamal Uddin
Journal: Journal of the American College of Cardiology (2017)
Building the foundations for sustainable development: a case for global investment in the capabilities of adolescents
Authors: Peter Sheehan, Kim Sweeny, Bruce Rasmussen, Annababette Wils, Howard S Friedman, Jacqueline Mahon, George C Patton, Susan M Sawyer, Eric Howard, John Symons, Karin Stenberg, Satvika Chalasani, Neelam Maharaj, Nicola Reavley, Hui Shi, Masha Fridman, Alison Welsh, Emeka Nsofor, Laura Laski
Journal: The Lancet (2017)
Diagnosis of Bacterial Infection Using a 2-Transcript Host RNA Signature in Febrile Infants 60 Days or Younger
Authors: Myrsini Kaforou, Jethro A. Herberg, Victoria J. Wright, Lachlan J. M. Coin, Michael Levin
Journal: JAMA (2017)

This study compares the diagnostic accuracy of a 2-transcript vs 66-transcript host RNA disease risk score for distinguishing bacterial from viral infection in febrile infants ≤60 days old presenting to the emergency department.
Gender Differences in Symptom Impact in Primary Biliary Cirrhosis (PBC): Evidence From the UK-PBC Patient Cohort for a Direct Role for Autonomic Dysfunction in Fatigue
Authors: Greta Pells, George Mells, Julia Newton, Michael Heneghan, James Neuberger, Darren Day, Samantha Ducker, Richard Sandford, Graeme Alexander, David Jones
Journal: Hepatology (2012)

Gender Differences in Symptom Impact in Primary Biliary Cirrhosis (PBC): Evidence From the UK-PBC Patient Cohort for a Direct Role for Autonomic Dysfunction in Fatigue: 2020  Greta Pells;George Mells;Julia Newton;Michael Heneghan;James Neuberger;Darren Day;Samantha Ducker;Richard Sandford;Graeme Alexander;David Jones; Hepatology
Blood-brain barrier traversal by African trypanosomes requires calcium signaling induced by parasite cysteine protease
Authors: Olga V. Nikolskaia, Ana Paula C. de A. Lima, Yuri V. Kim, John D. Lonsdale-Eccles, Toshihide Fukuma, Julio Scharfstein, Dennis J. Grab
Journal: Journal of Clinical Investigation (2008)

The Trypanosoma species used in this study included a clinically relevant human CSF isolate and bloodstream form (BSF) from a patient with sleeping sickness.A cloned derivative from this parasite termed "IL1852" was originally identified as a T.b. gambiense and was denoted accordingly in the manuscript.However, the authors recently discovered that IL1852 contains the SRA gene, a characteristic only encountered in T.b. rhodesiense (1).Therefore, because ILRI T.b. gambiense IL2343, a clone derivative of STIB386AA that was derived from TH144/78E(020), was later reclassified as a T.b. rhodesiense (2), the authors have reclassified IL1852 as a T.b. rhodesiense to maintain accuracy.While the reclassification affects certain aspects of the conclusions of this work, it does not invalidate the key finding of a difference in the BBB traversal between human and animal trypanosomes that correlates with the greater incidence of CNS infection in human compared with animal parasites.
In Reply:
Authors: Mitch Dowsett, Jack Cuzick, Chris Wale, Tony Howell, Joan Houghton, Michael Baum, Aman Buzdar
Journal: Journal of Clinical Oncology (2006)

We read with interest the data and comments of Ponzone et al regarding our hypothesis-generating article 1 on the possible differential sensitivity of anastrozole and tamoxifen to breast cancer based on progesterone receptor (PgR) status.Their focus is on the possible explanation of our results by human epidermal growth factor receptor 2 (HER-2) status being higher in PgRϪ tumors and HER-2-positive tumors being possibly more sensitive to aromatase inhibitors than to tamoxifen.Although the HER-2 positivity rates in their ERϩ patients are higher than we generally find, we concur with their view that it is unlikely that this correlation with HER-2 fully explains our data.In a separate series of 617 ERϩ patients, we found 19.5% of the PgRϪ tumors were HER-2ϩ compared with just 7.3% in the PgRϩ group. 2 It seems implausible that an effect in only about one fifth of the PgRϪ patients could explain the profound effects on the outcome seen.We are currently collecting the archival tumors blocks from the Anastrozole or Tamoxifen Alone or in Combination (ATAC) trial to allow systematic centralized analysis of these key parameters.However, we would like to take this opportunity to emphasize that the data that we presented were an unplanned retrospective subgroup analysis and that the extent to which the observations are generalizable depends on their reproducibility in independent studies.
Leonine Facies, Flushing, and Systemic Symptoms
Authors: Marta Prieto-Barrios, Pablo Luis Ortiz-Romero, Jose Luis Rodriguez-Peralto
Journal: JAMA Dermatology (2017)

A man in his 50s with history of hypertension and pulmonary tumor resected 10 years earlier presented with generalized phymatous changes over his entire face as well as pustular lesions and a diffuse erythema that gave him an appearance of leonine facies. What is your diagnosis?
The Role Which Viruses may Play in the Causation of Paraneoplastic Neurological Syndromes
Authors: H. E. Webb
Journal: Neuro-Oncology (1980)

Viruses may be involved in damaging the central nervous system in several different ways in association with neoplasia. Viral meningitis may occur as a result of immunosuppression produced by the disease process itself or by the drugs and irradiation used in therapy. (1, 2) The actual virus involved in a particular case is seldom identified. Animal models such as Marek's disease (3), a herpes virus infection, in chickens causing lymphomas, polyneuritis and encephalitis have particular interest in relation to what may happen in human reticuloses and their associated neurological complications (4). Certain viruses of the Papova group which heavily infect the oligodendroglia and cause focal demyelination in progressive multi-focal leucoencephalopathy (5) are tumour forming themselves when inoculated into baby hamsters (6). Also, certain human tumours of the CNS have shown some evidence that the cells may have been infected with viruses and that this may have played some part in the tumour formation itself (7). The varied problems posed by the pathogenic potential of viruses in the CNS in relation to malignant diseases will be discussed with particular reference as to how our knowledge might be advanced further in this field.
Case 11-2017 — A 61-Year-Old Woman with Leg Swelling, Back Pain, and Hydronephrosis
Authors: Ephraim P. Hochberg, Michael F. Bierer, Karen M. Winkfield, Yi-Bin Chen, Victorine V. Muse, Abner Louissaint
Journal: New England Journal of Medicine (2017)

A 61-year-old woman presented with a 3-month history of leg swelling and back pain. Imaging revealed a large retroperitoneal mass with hydronephrosis. A diagnostic procedure was performed, and management decisions were made.