tbuckley/cabot-search huggingface dataset:
Tumor Gene Testing May Help Guide Breast Cancer Treatment Decisions
Authors: Anita Slomski
Journal: JAMA (2016)

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IL-6 and PD-L1 antibody blockade combination therapy reduces tumour progression in murine models of pancreatic cancer
Authors: Thomas A Mace, Reena Shakya, Jason R Pitarresi, Benjamin Swanson, Christopher W McQuinn, Shannon Loftus, Emily Nordquist, Zobeida Cruz-Monserrate, Lianbo Yu, Gregory Young, Xiaoling Zhong, Teresa A Zimmers, Michael C Ostrowski, Thomas Ludwig, Mark Bloomston, Tanios Bekaii-Saab, Gregory B Lesinski
Journal: Gut (2016)

Objective Limited efficacy of immune checkpoint inhibitors in pancreatic ductal adenocarcinoma (PDAC) has prompted investigation into combination therapy. We hypothesised that interleukin 6 (IL-6) blockade would modulate immunological features of PDAC and enhance the efficacy of anti-programmed death-1-ligand 1 (PD-L1) checkpoint inhibitor therapy. Design Transcription profiles and IL-6 secretion from primary patient-derived pancreatic stellate cells (PSCs) were analyzed via Nanostring and immunohistochemistry, respectively. In vivo efficacy and mechanistic studies were conducted with antibodies (Abs) targeting IL-6, PD-L1, CD4 or CD8 in subcutaneous or orthotopic models using Panc02, MT5 or KPC-luc cell lines; and the aggressive, genetically engineered PDAC model (Kras LSL−G12D , Trp53 LSL−R270H , Pdx1-cre, Brca2 F/F (KPC-Brca2 mice)). Systemic and local changes in immunophenotype were measured by flow cytometry or immunohistochemical analysis. Results PSCs (n=12) demonstrated prominent IL-6 expression, which was localised to stroma of tumours. Combined IL-6 and PD-L1 blockade elicited efficacy in mice bearing subcutaneous MT5 (p&lt;0.02) and Panc02 tumours (p=0.046), which was accompanied by increased intratumoural effector T lymphocytes (CD62L − CD44 − ). CD8-depleting but not CD4-depleting Abs abrogated the efficacy of combined IL-6 and PD-L1 blockade in mice bearing Panc02 tumours (p=0.0016). This treatment combination also elicited significant antitumour activity in mice bearing orthotopic KPC-luc tumours and limited tumour progression in KPC-Brca2 mice (p&lt;0.001). Histological analysis revealed increased T-cell infiltration and reduced α-smooth muscle actin cells in tumours from multiple models. Finally, IL-6 and PD-L1 blockade increased overall survival in KPC-Brca2 mice compared with isotype controls (p=0.0012). Conclusions These preclinical results indicate that targeted inhibition of IL-6 may enhance the efficacy of anti-PD-L1 in PDAC.
Vaccination with Dendritic Cell Myeloma Fusions Alone or in Conjunction with Stem Cell Transplantation for Patients with Multiple Myeloma.
Authors: David Avigan, Jacalyn Rosenblatt, Baldev Vasir, Zekui Wu, Adam Bissonnette, Claire MacNamara, Lynne Uhl, Corrine Lenahan, Kenneth Miller, Robin Joyce, James D. Levine, Joanne Proper, Patricia Forino, Dilani Dombagoda, Paul Richardson, Nikhil C. Munshi, Donald Kufe
Journal: Blood (2006)
Abstract C42: DNA methyltransferase 1 (Dnmt1) is a key regulator of TGFβ-mediated endothelial-to-mesenchymal transition
Authors: Lin Xiao, Andrew C. Dudley
Journal: Cancer Research (2016)

Abstract Cancer-associated fibroblasts (CAFs) are prominent in the tumor microenvironment and they fuel tumor angiogenesis, tumor growth, and metastasis. CAFs are identified by smooth muscle actin and type collagen 1 expression, they promote intratumoral desmoplasia and fibrosis, and they are derived from multiple cellular precursors including tumor endothelial cells (TECs) through a TGFβ-regulated process termed endothelial-to-mesenchymal transition (EndMT). Recently, we uncovered two distinct TEC populations: TGFβ-responders that undergo rapid EndMT accompanied by CAF marker up-regulation in response to TGFβ and TGFβ non-responders that are comparatively resistant to TGFβ-induced EndMT. From a biochemical screen, we found that 5-Azacytidine, a small-molecule inhibitor of DNA methyltransferases (DNMTs), converts TGFβ non-responders into responders suggesting that TGFβ responsiveness is dictated by epigenetic mechanisms. siRNA silencing of Dnmt1 is sufficient to promote TGFb-induced EndMT in non-responders, whereas Dnmt3a or Dnmt3b are not involved. Chronic (&amp;gt; 7 days) TGFβ stimulation also suppresses Dnmt1 expression and drives the conversion of non-responders into responders indicating that TGFβ may un-silence CAF-specific genes in TECs in part by antagonizing DNMT1 expression/activity. Our findings shed light on the epigenetic mechanisms that regulate TGFβ- and EndMT-mediated conversion of TECs into CAFs. Targeting these mechanisms could inhibit tumor growth and spread. Citation Format: Lin Xiao, Andrew C. Dudley. DNA methyltransferase 1 (Dnmt1) is a key regulator of TGFβ-mediated endothelial-to-mesenchymal transition. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr C42.
High Throughput Minor Histocompatibility Antigen Discovery by Whole Genome Association Scanning.
Authors: Cornelis A.M. van Bergen, Edith D. van der Meijden, Caroline E. Rutten, Simone A.P. van Luxemburg, Elisabeth G.A. Lurvink, M. Willy Honders, Jeanine J. Houwing, M. Lourdes Sampietro, Roelof Willemze, J.H. Frederik Falkenburg, Marieke Griffioen
Journal: Blood (2009)
Forty-One Recent Cases of Invasive Zygomycosis From a Global Clinical Registry.
Authors: Maria J.G.T. Rueping, Werner J. Heinz, Anupma J. Kindo, Volker Rickerts, Cornelia Lass-Floerl, Claudia Beisel, Raoul Herbrecht, Yehudah Roth, Gerda Silling, Andrew Ullmann, Kersten Borchert, Gerlinda Egerer, Johann Maertens, Georg Maschmeyer, Arne Simon, Morad Wattad, Guido Fischer, Joerg J. Vehreschild, Meinolf Karthaus, Oliver A. Cornely
Journal: Blood (2009)
Babies should sleep in parents’ bedroom for as long as a year, says US guidance
Authors: Gareth Iacobucci
Journal: BMJ (2016)

Babies should sleep in their parents’ bedroom for six months and ideally as long as a year to decrease the risk of sleep related death, new guidance from the American Academy of Pediatrics (AAP) says.

In its first updated recommendations since 2011 on preventing sudden infant death syndrome (SIDS) and other sleep related infant deaths,1 the AAP said that sharing a room with parents for at least six months, but ideally a year, cuts the risk of SIDS by as much as 50%.

Drawing …
Circadian Clock Interaction with HIF1α Mediates Oxygenic Metabolism and Anaerobic Glycolysis in Skeletal Muscle
Authors: Clara Bien Peek, Daniel C. Levine, Jonathan Cedernaes, Akihiko Taguchi, Yumiko Kobayashi, Stacy J. Tsai, Nicolle A. Bonar, Maureen R. McNulty, Kathryn Moynihan Ramsey, Joseph Bass
Journal: Cell Metabolism (2016)
Movement for movement: exercise as everybody's business?
Authors: Ann B Gates, Roger Kerry, Fiona Moffatt, Ian K Ritchie, Adam Meakins, Jane S Thornton, Simon Rosenbaum, Alan Taylor
Journal: British Journal of Sports Medicine (2016)

Exercise as medicine, is well established.1 However, the art of knowledge transfer and implementation of exercise/physical activity (PA) remains poorly embedded in society, strategy and clinical practice in all aspects of health.2 The reality of this situation is grim. Insufficient PA is 1 of the 10 leading risk factors for death worldwide, so exercise professionals and PA advocates have much work to do.

The purpose of this editorial is to point towards a strategic plan which responds to the clear limitations of the current multiagency infrastructure for PA. We propose that this strategy should now consider how stakeholders can meet the calls of existing collaborative plans by working specifically as a community of practice3 (figure 1).



Figure 1 
A community of practice for exercise and physical activity (PA). Based on Wenger-Trayner and Wenger-Trayner.3



If the projected healthcare burden4 is realised, there will be no shortage of patients, in terms of healthcare ‘business’. Musculoskeletal problems and non-communicable diseases will dominate the landscape of tomorrow's patient care models.5 We will need all expert hands on deck to support …
Effectiveness of one dose of oral cholera vaccine in response to an outbreak: a case-cohort study
Authors: Andrew S Azman, Lucy A Parker, John Rumunu, Fisseha Tadesse, Francesco Grandesso, Lul L Deng, Richard Laku Lino, Bior K Bior, Michael Lasuba, Anne-Laure Page, Lameck Ontweka, Augusto E Llosa, Sandra Cohuet, Lorenzo Pezzoli, Dossou Vincent Sodjinou, Abdinasir Abubakar, Amanda K Debes, Allan M Mpairwe, Joseph F Wamala, Christine Jamet, Justin Lessler, David A Sack, Marie-Laure Quilici, Iza Ciglenecki, Francisco J Luquero
Journal: The Lancet Global Health (2016)

Oral cholera vaccines represent a new effective tool to fight cholera and are licensed as two-dose regimens with 2-4 weeks between doses. Evidence from previous studies suggests that a single dose of oral cholera vaccine might provide substantial direct protection against cholera. During a cholera outbreak in May, 2015, in Juba, South Sudan, the Ministry of Health, Médecins Sans Frontières, and partners engaged in the first field deployment of a single dose of oral cholera vaccine to enhance the outbreak response. We did a vaccine effectiveness study in conjunction with this large public health intervention.We did a case-cohort study, combining information on the vaccination status and disease outcomes from a random cohort recruited from throughout the city of Juba with that from all the cases detected. Eligible cases were those aged 1 year or older on the first day of the vaccination campaign who sought care for diarrhoea at all three cholera treatment centres and seven rehydration posts throughout Juba. Confirmed cases were suspected cases who tested positive to PCR for Vibrio cholerae O1. We estimated the short-term protection (direct and indirect) conferred by one dose of cholera vaccine (Shanchol, Shantha Biotechnics, Hyderabad, India).Between Aug 9, 2015, and Sept 29, 2015, we enrolled 87 individuals with suspected cholera, and an 898-person cohort from throughout Juba. Of the 87 individuals with suspected cholera, 34 were classified as cholera positive, 52 as cholera negative, and one had indeterminate results. Of the 858 cohort members who completed a follow-up visit, none developed clinical cholera during follow-up. The unadjusted single-dose vaccine effectiveness was 80·2% (95% CI 61·5-100·0) and after adjusting for potential confounders was 87·3% (70·2-100·0).One dose of Shanchol was effective in preventing medically attended cholera in this study. These results support the use of a single-dose strategy in outbreaks in similar epidemiological settings.Médecins Sans Frontières.
Mutant TIRAP Gene Polymorphism Is Associated with Outcomes in HLA Genoidentical Bone Marrow Transplants Recipients with Leukemia.
Authors: Vanderson Rocha, Raphael Porcher, Nabil Kabbara, Regis Peffault de Latour, Marie Robin, Wagnara Chaves, Celso A. Rodrigues, Henrique Bittencourt, Marli Tavela, Agnes Devergie, Patricia Ribaud, Eliane Gluckman, Gerard Socie, Marco Antonio Zago
Journal: Blood (2007)
Retrospective review of toxicities and response of two commonly used regimens (FOLFOX6 and XELOX) in stage IV colorectal cancer
Authors: M. Mullane, T. Lad, B. Cleveland, B. Yim, D. Tamkus, D. Osafo
Journal: Journal of Clinical Oncology (2006)

13568 Background: Oxaliplatin and 5FU based regimens have become standard first line treatment for stage IV colorectal cancer. At our institution predominately the regimens FOLFOX6 (oxaliplatin/infusional 5FU via a central venous catheter) and XELOX (oxaliplatin/ capecitabine given orally) are used. We performed a retrospective review of 40 patients to see if any differences, primarily in toxicities, but also in response, emerged. Methods: . Twenty consecutive patients with Stage IV colorectal cancer who received FOLFOX6 as initial therapy and twenty consecutive patients who received initial XELOX, with the oxaliplatin given via a peripheral IV, were analyzed. The decision to administer FOLFOX6 or XELOX was not made for clinical reasons, but came about from logistical difficulties placing central venous catheters in our institution, due to cost and operating time. Comparisons were performed with a Mann Whitney test. The two groups were well matched in terms of sex, age, and performance status. Response evaluations were made based on RECIST criteria. Results: Toxicities compared in the two groups (FOLFOX6 v. XELOX) were gastrointestinal, &gt;Gr. II (5 v. 20%); dermatologic, &gt;Gr. III (0 v. 35%); bone marrow, &gt; Gr. II (15 v. 20%); neurologic, &gt;Gr. III peripheral neuropathy (10 v. 10%); and development of arm pain/discomfort (0 v. 30%). The two toxicities reaching a significant difference, with the higher incidence from XELOX, were &gt; Grade II dermatitis (p= 0.03) and development of arm pain (p=0.05). The response rate of FOLFOX6 was 75% and that for XELOX was 55% (p value of 0.144). Conclusions: Our conclusions from this analysis are that the two regimens are comparable in terms of response, but that FOLFOX6 may be preferable in order to avoid severe dermatitis and if XELOX is the treatment choice, serious consideration should given to administer the oxaliplatin via a central catheter. No significant financial relationships to disclose.
Identifying caregivers and their meaning for patients with metastatic solid tumors: A prospective study at a community-based oncology group practice in Germany.
Authors: U. Mergenthaler, J. Heymanns, H. Koeppler, C. van Roye, J. Thomalla, R. Weide
Journal: Journal of Clinical Oncology (2010)

e19637 Background: Relief of psycho-social distress is an important aspect in the treatment of patients with metastatic cancer. Therefore it is important to find out which persons are called on most frequently to find help in dealing with this situation. We also evaluated to what extend the patients considered these persons as actually helpful. Methods: 202 patients with metastatic solid tumors visiting the practice between April and July 2009 were screened for psycho-social distress using the Distress Thermometer (DT) and Problem List (PL). Thereafter a standardized personal interview was held where patients were asked to name their important contact persons. For each contact person the patient was asked to indicate if this contact was helpful or not and if yes, in which way it was helpful. Results: The 202 observed patients showed a mean distress level of 4.4 with 29% of patients indicating a distress score > 5.0. 92% named physical problems as a source of distress while emotional, practical, familial, or spiritual problems were causing distress in 63%, 14%, 12% and 4% respectively. 84% of patients named their oncologist as an important person to help them with their distress. Partner, children, friends and general practitioner were important persons for 71%, 64%, 53% and 52% respectively. 97% of patients seeking help from their oncologist described this as helpful. 24 patients (12%) had contacted a psychologist. This was helpful for 17 (71%) of these patients. There is a correlation between distress level and number of different persons contacted. (r=.305; p<0.001). The most helpful aspect for all contact persons was “Listening” except for oncologists (“Therapy”) and Cancer Counselling Service (“Information/Advice”). Conclusions: Psycho-social distress in patients with metastatic solid tumors is mostly caused by physical and by emotional problems. Most patients treated in an oncology practice reported a network of care-giving persons as helpful in the coping process. Thus it is of utmost importance to identify patients without care care giving persons and to improve support for main care givers. No significant financial relationships to disclose.
Quantitation of faecal<i>Fusobacterium</i>improves faecal immunochemical test in detecting advanced colorectal neoplasia
Authors: Sunny H Wong, Thomas N Y Kwong, Tai-Cheong Chow, Arthur K C Luk, Rudin Z W Dai, Geicho Nakatsu, Thomas Y T Lam, Lin Zhang, Justin C Y Wu, Francis K L Chan, Simon S M Ng, Martin C S Wong, Siew C Ng, William K K Wu, Jun Yu, Joseph J Y Sung
Journal: Gut (2016)

<h3>Objective</h3> There is a need for an improved biomarker for colorectal cancer (CRC) and advanced adenoma. We evaluated faecal microbial markers for clinical use in detecting CRC and advanced adenoma. <h3>Design</h3> We measured relative abundance of <i>Fusobacterium nucleatum</i> (<i>Fn</i>), <i>Peptostreptococcus anaerobius</i> (<i>Pa</i>) and <i>Parvimonas micra</i> (<i>Pm</i>) by quantitative PCR in 309 subjects, including 104 patients with CRC, 103 patients with advanced adenoma and 102 controls. We evaluated the diagnostic performance of these biomarkers with respect to faecal immunochemical test (FIT), and validated the results in an independent cohort of 181 subjects. <h3>Results</h3> The abundance was higher for all three individual markers in patients with CRC than controls (p&lt;0.001), and for marker <i>Fn</i> in patients with advanced adenoma than controls (p=0.022). The marker <i>Fn</i>, when combined with FIT, showed superior sensitivity (92.3% vs 73.1%, p&lt;0.001) and area under the receiver-operating characteristic curve (AUC) (0.95 vs 0.86, p&lt;0.001) than stand-alone FIT in detecting CRC in the same patient cohort. This combined test also increased the sensitivity (38.6% vs 15.5%, p&lt;0.001) and AUC (0.65 vs 0.57, p=0.007) for detecting advanced adenoma. The performance gain for both CRC and advanced adenoma was confirmed in the validation cohort (p=0.0014 and p=0.031, respectively). <h3>Conclusions</h3> This study identified marker <i>Fn</i> as a valuable marker to improve diagnostic performance of FIT, providing a complementary role to detect lesions missed by FIT alone. This simple approach may improve the clinical utility of the current FIT, and takes one step further towards a non-invasive, potentially more accurate and affordable diagnosis of advanced colorectal neoplasia.
85th Annual Report on Medical Education in the United States Executive Summary
Authors: Anne E. Crowley
Journal: JAMA (1985)

This is the 85th EDUCATION ISSUE ofThe Journal. The first report on medical education in the United States was published in the Sept 21, 1901, issue of<i>JAMA</i>. The spectrum on the cover of the current issue illustrates the continuum of medical education. The individual will move in and out of this continuum several times during his practicing career. The spectrum also suggests the variety of persons involved in the health care professions. <h3>HIGHLIGHTS OF THE 85th REPORT ON MEDICAL EDUCATION</h3><h3>Revision of Standards</h3> The recently approved document "Functions and Structure of a Medical School," reprinted in Section I, is an indication of the change occurring in medical education. The document contains the standards for an accredited program leading to the MD degree. Keeping pace with the advances in science and medicine, the medical education community has enhanced the standards by which medical education programs are appraised. <h3>Medical School</h3>
Bevacizumab (BEV) and the risk of arterial thromboembolic events (ATE) in patients with renal cell carcinoma and other cancers: A large comprehensive meta-analysis of more than 13,000 patients.
Authors: G. R. Azzi, F. A. Schutz, Y. Je, T. K. Choueiri
Journal: Journal of Clinical Oncology (2010)

4609 Background: Bevacizumab (BEV), a humanized monoclonal antibody targeting the vascular endothelial growth factor (VEGF), is a therapeutic agent used in a variety of neoplasms. Arterial thromoboembolic events (ATE) have been described with BEV in a limited number of studies. We did a systematic and up-to-date review of the literature and a meta-analysis of randomized controlled trials (RCT) to fully characterize the ATE risk associated with BEV use. Methods: We performed a literature search on MEDLINE for studies reported from January 1966 to December 31, 2009. Abstracts presented at the American Society of Clinical Oncology (ASCO) held between 2004 and 2009 were also searched for relevant clinical trials. Randomized phase II and III trials were identified and included in the meta-analysis. Summary incidence, relative risks (RR), and 95% confidence intervals (CI) were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies. Results: A total of 13026 patients from 20 randomized trials were included in the meta-analysis. Overall relative risk for ATE with BEV based therapy vs. controls was 1.46 (95% CI, 1.11-1.93, p=.007). A stratified analysis by underlying malignancy demonstrated the highest RR with renal cell carcinoma (RCC) patients, RR=3.95 (95% CI, 1.10-14.15, p=0.035) and colorectal cancer patients, RR=1.88 (95% CI, 1.29-2.75, p=0.001). Stratification by BEV dosage showed no difference between low-dose (2.5mg/kg/wk) and high-dose (5mg/kg/wk) (p=0.948). No evidence of publication bias (Begg test, p=0.77; Egger test, p=0.23) or heterogeneity among studies was detected. Conclusions: Data from more than 13,000 patients enrolled in 20 RCT show that BEV treatment is associated with a significant increase in the risk of arterial thromboembolic events. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott Laboratories, Agennix, Bayer/Onyx Pharmaceuticals, Genentech, GlaxoSmithKline, Novartis, Pfizer