tbuckley/cabot-search huggingface dataset:
Prognostic utility of tumour infiltrating lymphocytes (TILs) and neutrophil-to-lymphocyte ratio (NLR) in early-stage triple negative breast cancer (TNBC).
Authors: Antonia Pearson, Pickett Justine, Connie Irene Diakos, Robert Dewar, David Chan, Alexander David Guminski, Anthony J. Gill, Alexander M. Menzies, Sally E. Baron-Hay
Journal: Journal of Clinical Oncology (2016)

1075 Background: Breast cancer has been associated with an immune response both systemically and within the tumour microenvironment. Recent data suggest TILs have a prognostic role in TNBC. We examined the prognostic utility of stromal TILs (sTILs) in early TNBC patients (pts) treated at a major tertiary referral centre and to determine if the addition of the peripheral blood NLR, a marker of systemic inflammation with demonstrated prognostic utility in a number of cancer types, increases the prognostic power. Methods: Tumour specimens from women with early stage TNBC who underwent curative resection between 2005 and 2012 were examined for sTILs. Consecutive pts were identified from the institution’s pathology database. sTILs were analysed from one representative hematoxylin and eosin-stained slide per pt following the 2014 international working group guidelines (Salgado et al, Annals of Oncology 2015), and reported as a percentage of the stromal tissue area occupied by lymphocytes. Primary endpoints were overall survival (OS) and disease-free survival (DFS). The pre-operative NLR was calculated, with a cut-off value of ≥ 3. High ( > 10%) and low ( ≤ 10%) sTILs groups were compared using a log-rank test. Results: 103 pts from 2005 - 2012 were included, with median follow up 5.2 years. Median age was 60 years. OS was significantly improved in TNBC pts with high compared to low sTILs (median OS not reached vs. 7.7 years, p = 0.036), but no difference was seen in DFS (p = 0.142). In pts with a high NLR, a low sTILs score was associated with poorer OS (3.4 years vs. median OS not reached, p = 0.003). There was no difference in outcome for pts with a low NLR regardless of sTILs (p = 0.809). Conclusions: Increased level of sTILs are associated with improved OS in TNBC, in accordance with previous reports. In pts with evidence of systemic inflammation as represented by a high NLR, low sTILs resulted in an even poorer prognosis. For pts without evidence of inflammation, no difference was seen in OS regardless of sTILs. We have identified a subgroup of TNBC pts with a poor prognosis in whom alternative treatments such as immunotherapy may be beneficial.
Serum cortisol mediates the relationship between fecal <i>Ruminococcus</i> and brain N-acetylaspartate in the young pig
Authors: Austin T. Mudd, Kirsten Berding, Mei Wang, Sharon M. Donovan, Ryan N. Dilger
Journal: Gut Microbes (2017)

A dynamic relationship between the gut microbiota and brain is pivotal in neonatal development. Dysbiosis of the microbiome may result in altered neurodevelopment; however, it is unclear which specific members of microbiota are most influential and what factors might mediate the relationship between the gut and the brain. Twenty-four vaginally-derived male piglets were subjected to magnetic resonance spectroscopy at 30 d of age. Ascending colon contents, feces, and blood were collected and analyzed for volatile fatty acids, microbiota relative abundance by 16s rRNA, and serum metabolites, respectively. A mediation analysis was performed to assess the mediatory effect of serum biomarkers on the relationship between microbiota and neurometabolites. Results indicated fecal Ruminococcus and Butyricimonas predicted brain N-acetylaspartate (NAA). Analysis of serum biomarkers indicated Ruminococcus independently predicted serum serotonin and cortisol. A 3-step mediation indicated: i) Ruminococcus negatively predicted NAA, ii) Ruminococcus negatively predicted cortisol, and iii) a significant indirect effect (i.e., the effect of fecal Ruminococcus through cortisol on NAA) was observed and the direct effect became insignificant. Thus, serum cortisol fully mediated the relationship between fecal Ruminococcus and brain NAA. Using magnetic resonance spectroscopy, this study used a statistical mediation analysis and provides a novel perspective into the potential underlying mechanisms through which the microbiota may shape brain development. This is the first study to link Ruminococcus, cortisol, and NAA in vivo, and these findings are substantiated by previous literature indicating these factors may be influential in the etiology of neurodevelopmental disorders.
Health promotion through sport: international sport federations’ priorities, actions and opportunities
Authors: Margo Mountjoy, A Costa, R Budgett, J Dvorak, L Engebretsen, S Miller, J Moran, J Foster, J Carr
Journal: British Journal of Sports Medicine (2017)

Objective To identify areas of priority and activity for international sportsfederations (IFs) with respect to athlete health and safety, and global health. Results serve to direct the work of the Association of Summer Olympic IF Medical and Scientific Consultative Group, the International Olympic Committee and to influence IFs’ planning and priorities. Methods The 28 IFs participating in the Summer Olympic Games (2016) were asked to rank the relative importance of 11 health-related topics and to report their activities or research initiatives on 27 identified topics using an electronic survey. A comparison with a similar survey (2012) was made. Results The response rate was 100%. In general, the ‘ fight against doping ’ had the highest priority followed by ‘image as a safe sport ’. The topics with the lowest importance ratings were ‘ increasing the number of elite athletes ’, and ‘ health of the general population ’. Despite ranking ‘ health of your athletes ,’ as a top priority, IFs are not addressing all aspects of athlete health. In comparison with 2012, there was a significant decrease in priority for IFs is ‘ health of the general population ’. Conclusion Despite the widespread knowledge of the importance of the promotion of physical activity (sport) on global health, the decreasing priority and programming of the IFs on physical activity promotion is concerning. Although IFs have prioritised the protection of the health of elite athletes, there are gaps in programming demonstrating that IFs are missing important areas of athlete health. Improving recreational athlete health programming could also benefit population health as well as improve IF fan base and sport participation.
Medical Assistance in Dying
Authors: Kieran L. Quinn, Allan S. Detsky
Journal: JAMA Internal Medicine (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
08.19 Variable domain n-linked glycosylation is a key feature of monoclonal acpa-igg
Authors: Katy A Lloyd, Johanna Steen, Phillip J Titcombe, Daniel L Mueller, Lars Klareskog, Vivianne Malmström, Caroline Grönwall
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Fab-glycosylation is found in ~15%–25% serum IgG and while its exact consequence remains unknown, it may alter IgG functionality. Recent data revealed extensive Fab-glycosylation in polyclonal anti-citrullinated protein autoantibodies (ACPA) from rheumatoid arthritis (RA) patients. Herein, we characterise the Fab-glycan profile of monoclonal ACPA. <h3>Materials and methods</h3> Among 200 single-cell isolated and recombinantly expressed monoclonal antibodies (mAbs) from RA patients, we selected 12 identified ACPA mAbs, four derived from synovial antibody secreting cells (ASC), and eight from peripheral antigen-tetramer sorted memory B cells. The ACPA had high somatic hypermutation (SHM) levels with an average of 49 VH and 35 VL mutations. For comparison, we selected 14 ASC synovial antibodies with mutation rate &gt;20 in VH or VL, and we also searched the literature for 19 highly-mutated broadly-neutralising HIV-derived antibodies (bnAbs). N-linked glycan motifs were identified using the NetNGlyc server. Glycosylation was verified in five ACPA IgG by enzymatic digestion with PNGase-F or Endo-S followed by SDS-PAGE. Antigen binding was investigated by CCP3 ELISA. VH-VL structure models were generated using the online tool PIGS and visualised by Jmol, and the GlyProt server was utilised for <i>in silico</i> glycosylation. <h3>Results</h3> The majority of ACPA exhibited variable region N-linked motifs (83.8%), compared to 14.3% of non-ACPA RA mAbs and 63.2% of bnAbs, featured in both framework and CDRs. When adjusted for SHM, N-linked motifs were significantly increased in ACPA compared to non-ACPA RA mAbs (p=0.001) or bnAbs (p=0.002). VH region motif rates were increased in ACPA compared to non-ACPA mAbs (p=0.002) and bnAbs (p=0.0004), while VL region motifs were only higher compared to non-ACPA (p=0.002). Deglycosylation revealed that N-linked motifs were indeed glycosylated, although preliminary data suggests glycan removal had no striking effect on antigen-binding. Homology-based structures predicted glycans to be primarily positioned outside of the potential antigen-binding site. <h3>Conclusions</h3> The results support that variable region glycosylation is a key feature of ACPA. Significant increases in N-linked motifs in ACPA compared to other highly-mutated antibodies signifies that this is not solely linked to hypermutation. Future studies are merited to further investigate the selection mechanisms and functional role of Fab-glycosylated autoantibodies.
Quality of reporting of phase II trials in oncology in highly ranked oncology journals.
Authors: Thomas Grellety, Aurelie Petit-Monéger, Abou Diallo, Simone Mathoulin-Pelissier, Antoine Italiano
Journal: Journal of Clinical Oncology (2013)

6582 Background: Phase II trials represent an essential step in the development of anti-cancer drugs. The aim of this study was to assess the quality of their reporting in highly-ranked oncology journals, to investigate predictive factors of quality and to develop better reporting guidelines for authors. Methods: We reviewed the tables of contents of 8 peer-reviewed oncology journals published between January 2011 and December 2011 and with a 2011 impact factor (IF) &gt;4: Br J Cancer, Eur J Cancer, Oncologist, J Clin Oncol, Lancet Oncol, JNCI, Clin Cancer Res and Ann Oncol. Two reviewers assessed the quality of each report by using a 44-point overall quality score (OQS; range, 0 to 44 points) inspired from the revised Consolidated Standards of Reporting Trials statement. Primary endpoint definition, justification of sample size and definition of the evaluable population for each endpoint, were assessed separately because of their crucial methodological importance using a 3-point key methodological score (KMS; range, 0 to 3). Exploratory analyses were used to identify predictive factors associated with the different scores. Results: 156 articles were included. Agreement between the reviewers for each item was good (kappa coefficient range: 0.62-1). The median OQS was 28 (range: 9-35). OQS sub-score analysis showed that reporting of statistical methods was particularly low with a mean of 2.5 (6 items). The median KMS was 2 (range 0-3). Primary endpoint definition, justification of sample size and definition of the evaluable population were reported only in 107 (68.6%), 121 (77.6%), and 52 (33.3%) cases, respectively. On multivariate analysis, reporting of clinicaltrial.gov registration was associated with improved OQS, OR = 3.2 (95CI, 1.5 to 7.1). No predictive factor for KMS were identified. Conclusions: Phases II trials reporting is still poor even in journals with strict editorial policies. This may lead to biased interpretation of phase II trial results. We have developed a checklist for use by authors, reviewers, and editors to improve reporting of these studies. As well as using a checklist during the preparation of their manuscript, we recommend that authors provide reviewers and readers with the last version of the study’s protocol.
Measures of chronic kidney disease and risk of incident peripheral artery disease: a collaborative meta-analysis of individual participant data
Authors: Kunihiro Matsushita, Shoshana H Ballew, Josef Coresh, Hisatomi Arima, Johan Ärnlöv, Massimo Cirillo, Natalie Ebert, Jade S Hiramoto, Heejin Kimm, Michael G Shlipak, Frank L J Visseren, Ron T Gansevoort, Csaba P Kovesdy, Varda Shalev, Mark Woodward, Florian Kronenberg, John Chalmers, Hisatomi Arima, Vlado Perkovic, Morgan E. Grams, Yingying Sang, Elke Schaeffner, Peter Martus, Adeera Levin, Ognjenka Djurdjev, Mila Tang, Gunnar Heine, Sarah Seiler, Adam Zawada, Insa Emrich, Mark Sarnak, Ronit Katz, Hermann Brenner, Ben Schöttker, Dietrich Rothenbacher, Kai-Uwe Saum, Anna Köttgen, Markus Schneider, Kai-Uwe Eckardt, Jamie Green, H Lester Kirchner, Alex R Chang, Corri Black, Angharad Marks, Gordon Prescott, Laura Clark, Nick Fluck, Sun Ha Jee, Yejin Mok, Gabriel Chodick, Varda Shalev, Jack F.M. Wetzels, Peter J Blankestijn, Arjan D van Zuilen, M Bots, Carmen Peralta, Jade Hiromoto, Ronit Katz, Mark Sarnak, Erwin Bottinger, Girish N Nadkarni, Stephen B Ellis, Rajiv Nadukuru, Timothy Kenealy, C Raina Elley, John F Collins, Paul L Drury, Stephan JL Bakker, Hiddo J Lambers Heerspink, Simerjot K Jassal, Jaclyn Bergstrom, Joachim H Ix, Elizabeth Barrett-Connor, Kamyar Kalantar-Zadeh, Juan J Carrero, Alessandro Gasparini, Abdul Rashid Qureshi, Peter Barany, Ale Algra, Yolanda van der Graaf, Marie Evans, Mårten Segelmark, Maria Stendahl, Staffan Schön, Navdeep Tangri, Maneesh Sud, David Naimark, Lars Lannfelt, Anders Larsson, Stein Hallan, Andrew S Levey, Jingsha Chen, Lucia Kwak, Morgan E. Grams, Yingying Sang
Journal: The Lancet Diabetes & Endocrinology (2017)
Infographic: Sports Biostatisticians as a critical member of all sports science and medical teams for injury prevention
Authors: Marti Casals, Sheree Bekker, Caroline F Finch
Journal: British Journal of Sports Medicine (2017)

The statistics profession has been heralded as one of the 21st century’s sexiest.1 Indeed, movies like Moneyball have brought the advent of data science in the sports arena into the mainstream.2 New technologies and the potential for Big Data provide compelling potential for the inclusion of statisticians in sports science and medicine teams.

Current methodological problems that exist in research and in sport science …
Plk1 regulates contraction of postmitotic smooth muscle cells and is required for vascular homeostasis
Authors: Guillermo de Cárcer, Paulina Wachowicz, Sara Martínez-Martínez, Jorge Oller, Nerea Méndez-Barbero, Beatriz Escobar, Alejandra González-Loyola, Tohru Takaki, Aicha El Bakkali, Juan A Cámara, Luis J Jiménez-Borreguero, Xosé R Bustelo, Marta Cañamero, Francisca Mulero, María de los Ángeles Sevilla, María Jose Montero, Juan Miguel Redondo, Marcos Malumbres
Journal: Nature Medicine (2017)
Defining the Immune Checkpoint Landscape in Patients (pts) with Acute Myeloid Leukemia (AML)
Authors: Naval Daver, Sreyashi Basu, Guillermo Garcia-Manero, Jorge E. Cortes, Farhad Ravandi, Jing Ning, Lianchun Xiao, Lopez Juliana, Steven M. Kornblau, Marina Konopleva, Michael Andreeff, Wilmer Flores, Carlos E Bueso-Ramos, Narmeen Somani, Jorge Blando, James Allison, Hagop M. Kantarjian, Padmanee Sharma
Journal: Blood (2016)
Abstract 327: Cardiac Regulation of Metabolic Homeostasis by Med13
Authors: Chad E Grueter, Kedryn K Baskin, Christine M Kusminski, William Holland, Philipp E Scherer, Eric N Olson
Journal: Circulation Research (2013)

Alterations in metabolism are a major component of cardiovascular disease associated with obesity and type 2 diabetes. The complex interplay between these three diseases poses a challenge for successful treatment and warrants further studies directed at understanding the intertissue communication between major metabolic organs. We previously identified a signaling pathway within the heart that modulates systemic energy homeostasis by regulation of Med13, a component of the kinase submodule of the Mediator Complex, in the heart. The Mediator Complex is a large, multiprotein complex that functions to integrate signal specific events with transcriptional activation and elongation in a context dependent manner. Our current work further delineates a mechanism by which Med13 in the heart functions to regulate whole body energy homeostasis. The increase in energy expenditure in Med13 transgenic (TG) mice is due in part to increased triglyceride uptake and beta-oxidation in white adipose tissue and liver. Additionally, the expression of Krebs Cycle and fatty acid oxidation genes are increased in adipose tissue and liver as measured by RNA seq and in metabolite production in Med13 Tg mice. Together, these results demonstrate the Mediator Complex regulates cardiac gene expression and metabolite production which communicates with energy depots within the body to modulate whole body energy homeostasis.
Abstract 60: Hypoxia Preserves the Quiescent Lineage Negative Phenotype of Cardiac Stem Cells Within the Niche
Authors: Fumihiro Sanada, Emily Mangano, Junghyung Kim, Christian Arranto, Joao Ferreira-Martins, Sergio Signore, Claudia Fiorini, Noriko Ide-Iwata, Ada Pesapane, Mario Ricciardi, Hanqiao Zheng, Narasimman Gurusamy, Ewa Wybieralska, Virginia Caballero, Maria Cimini, Polina Goichberg, Marcello Rota, Toru Hosoda, Jan Kajstura, Piero Anversa, Annarosa Leri
Journal: Circulation Research (2012)

In stem cell-regulated organs, a subset of niches is characterized by low oxygen tension. This metabolic adaptation offers a selective advantage to stem cells favoring the preservation of their quiescent undifferentiated phenotype. The objective of this work was to determine whether in the mouse heart cardiac niches constitute a heterogeneous compartment composed of hypoxic and normoxic niches, and whether differences in O 2 concentration affect the function of c-kit-positive cardiac stem cells (CSCs).To test this possibility, we studied first the in vivo uptake of the hypoxic marker pimonidazole (PIMO), which identifies intracellular O 2 concentration &lt;10 mmHg. Mice were sacrificed 2 hours after intraperitoneal administration of PIMO, and PIMO-labeling was analyzed. By immunolabeling, 15% of cardiac niches were characterized by a hypoxic microenvironment and more than 20% of isolated CSCs were PIMO-positive, as measured by flow-cytometry. The cell cycle protein Ki67 was restricted to the PIMO-negative CSC class, which contained early committed cells expressing c-kit together with the myocyte specific transcription factors GATA4 and Nkx2.5. Mice were then administered tirapazamine, a compound that kills selectively hypoxic cells. One day later, the fraction of PIMO-positive CSCs was markedly decreased but, at 5 days, this compartment was partly reconstituted. This compensatory response was coupled with increased proliferation of PIMO-negative CSCs, suggesting that normoxic CSCs have the ability to replenish hypoxic niches following injury. Subsequently, the effects of hypoxia were studied in human CSCs (hCSCs) exposed in vitro to 1% O 2 . With respect to cells cultured in normoxia, 1% O 2 led to upregulation of HIF1α in hCSCs which also showed lower levels of BrdU incorporation. These cellular responses were accompanied by an increase in transcripts for the stemness genes c-kit, Oct4, Nanog and Sox2, and a decrease in mRNA for myocyte and vascular genes. Apoptosis, measured by TdT labeling, did not differ in normoxic and hypoxic hCSCs. In conclusion, our data indicate that hypoxic and normoxic niches coexist in the myocardium, and that intracellular hypoxia regulates the quiescent primitive CSC phenotype.
Guidelines for Counseling Persons Infected with Human T-Lymphotropic Virus Type I (HTLV-I) and Type II (HTLV-II)
Journal: Annals of Internal Medicine (1993)

The human T-lymphotropic viruses type I (HTLV-I) and type II (HTLV-II) are closely related but distinct retroviruses that can infect humans. They differ from the human immunodeficiency viruses that cause the acquired immunodeficiency syndrome. Screening of the U.S. blood supply for HTLV-I/II, which began in 1988, identifies HTLV-I- and HTLV-II-infected persons who need to be counseled regarding their infections. This paper summarizes current information about the HTLV viruses and presents guidelines developed by the Centers for Disease Control and a United States Public Health Service working group for counseling persons infected with HTLV-I and HTLV-II.