tbuckley/cabot-search huggingface dataset:
Context matters—consensus molecular subtypes of colorectal cancer as biomarkers for clinical trials
Authors: E. Fontana, K. Eason, A. Cervantes, R. Salazar, A. Sadanandam
Journal: Annals of Oncology (2019)

The Colorectal Cancer Subtyping Consortium identified four gene expression consensus molecular subtypes, CMS1 (immune), CMS2 (canonical), CMS3 (metabolic), and CMS4 (mesenchymal), using multiple microarray or RNA-sequencing datasets of primary tumor samples mainly from early stage colon cancer patients. Consequently, rectal tumors and stage IV tumors (possibly reflective of more aggressive disease) were underrepresented, and no chemo- and/or radiotherapy pretreated samples or metastatic lesions were included. In view of their possible effect on gene expression and consequently subtype classification, sample source and treatments received by the patients before collection must be carefully considered when applying the classifier to new datasets. Recently, several correlative analyses of clinical trials demonstrated the applicability of this classification to the metastatic setting, confirmed the prognostic value of CMS subtypes after relapse and hinted at differential sensitivity to treatments. Here, we discuss why contexts and equivocal factors need to be taken into account when analyzing clinical trial data, including potential selection biases, type of platform, and type of algorithm used for subtype prediction. This perspective article facilitates both our clinical and research understanding of the application of this classifier to expedite subtype-based clinical trials.
Targeting CAR T Resistance Due to CD19 Loss with CD79b-Specific CAR T Cells in B-Cell Malignancies
Authors: Fuliang Chu, Jinsheng Weng, Shao-Qing Kuang, Xiaoyun Cheng, JingJing Cao, Jingwei Liu, Swathi Karri, Adithi Reddy, Sattva S. Neelapu
Journal: Blood (2018)
Impact of Induction Chemotherapy and Primary CNS Prophylaxis on Outcomes in High-Grade B-Cell Lymphoma with MYC and BCL2 and/or BCL6 Rearrangements (HGBL-DH/TH) or HGBL-NOS: An International Multi-Center Retrospective Analysis
Authors: John R Balendra, Alexander Glover, Liu Xin, Sanjay De Mel, Anand Jeyasekharan, Stephen G Jones, Mark Bishton, Chan Y. Cheah
Journal: Blood (2018)
p66Shc Contributes to Liver Fibrosis through the Regulation of Mitochondrial Reactive Oxygen Species
Authors: Yan Zhao, Zhecheng Wang, Dongcheng Feng, Huanyu Zhao, Musen Lin, Yan Hu, Ning Zhang, Li Lv, Zhenming Gao, Xiaohan Zhai, Xiaofeng Tian, Jihong Yao
Journal: Theranostics (2019)

Background: p66Shc is a redox enzyme that mediates mitochondrial reactive oxygen species (ROS) generation.p66Shc inhibition confers protection against liver injury, however, its functional contribution to liver fibrosis remains unclear.The aim of this study is to explore the involvement of p66Shc in liver fibrosis and underlying mechanism of p66Shc by focusing on mitochondrial ROS.Methods: p66Shc-silenced mice were injected with carbon tetrachloride (CCl 4 ).Primary hepatic stellate cells (HSCs) were performed with p66Shc silencing or overexpression prior to TGF-β1 stimulation.Results: p66Shc expression was progressively elevated in mice with CCl 4 -induced liver fibrosis, and p66Shc silencing in vivo significantly attenuated fibrosis development, reducing liver damage, oxidative stress and HSC activation, indicated by the decreased α-SMA, CTGF and TIMP1 levels.Furthermore, in primary HSCs, p66Shc-mediated mitochondrial ROS production played a vital role in mitochondrial morphology and cellular metabolism.Knockdown of p66Shc significantly inhibited mitochondrial ROS production and NOD-like receptor protein 3 (NLRP3) inflammasome activation, which were closely associated with HSC activation, indicated by the decreased α-SMA, CTGF and TIMP1 levels.However, p66Shc overexpression exerted the opposite effects, which were suppressed by a specific mitochondrial ROS scavenger (mito-TEMPO).More importantly, p66Shc expression was significantly increased in human with liver fibrosis, accompanied by NLRP3 inflammasome activation.Conclusions: p66Shc is a key regulator of liver fibrosis by mediating mitochondrial ROS production, which triggers NLRP3 inflammasome activation.
Deriving the optimal limit of detection for an HCV point-of-care test for viraemic infection: Analysis of a global dataset
Authors: J. Morgan Freiman, Jianing Wang, Philippa J. Easterbrook, C. Robert Horsburgh, Francesco Marinucci, Laura F. White, George Kamkamidze, Mel Krajden, Anne Loarec, Richard Njouom, Kihn V. Nguyen, Gamal Shiha, Reham Soliman, Sunil S. Solomon, Tengiz Tsertsvadze, Claudia M. Denkinger, Benjamin Linas
Journal: Journal of Hepatology (2019)
Bag-Mask Ventilation during Tracheal Intubation of Critically Ill Adults
Authors: Jonathan D. Casey, David R. Janz, Derek W. Russell, Derek J. Vonderhaar, Aaron M. Joffe, Kevin M. Dischert, Ryan M. Brown, Aline N. Zouk, Swati Gulati, Brent E. Heideman, Michael G. Lester, Alexandra H. Toporek, Itay Bentov, Wesley H. Self, Todd W. Rice, Matthew W. Semler
Journal: New England Journal of Medicine (2019)

Hypoxemia is the most common complication during tracheal intubation of critically ill adults and may increase the risk of cardiac arrest and death. Whether positive-pressure ventilation with a bag-mask device (bag-mask ventilation) during tracheal intubation of critically ill adults prevents hypoxemia without increasing the risk of aspiration remains controversial.
Restrictive FDA Requirements and the Development of Generic Topical Medications—Reply
Authors: David G. Li, Arash Mostaghimi
Journal: JAMA Dermatology (2019)

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 Dermatology 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 Dermatology journal
Abstract 2294: ROCK1 inhibition promotes the self-renewal of a novel mouse mammary cancer stem cell.
Authors: Jochen Maurer, David J. Castro, Robert G. Oshima
Journal: Cancer Research (2013)

Abstract The differentiation of stem-like tumor cells may contribute to the cellular heterogeneity of breast cancers. We report the propagation of highly enriched mouse mammary cancer stem cells that retain the potential to differentiate both in vivo and in culture and their use to identify chemical compounds that influence both self-renewal and differentiation. We identify epithelial tumor initiating cells (ETICs) that express lineage markers of both basal and luminal mammary cell lineages and retain the potential, from even single cells, to generate heterogeneous tumors similar to the tumor of origin. ETICs can progress through a Rho associated coiled-coil containing protein kinase 1 (ROCK1) dependent, epithelial to mesenchymal transition to generate mesenchymal tumor initiating cells (MTICs) capable of initiating tumors of limited heterogeneity. The propagation of ETICs may allow for the identification of new therapeutic compounds that may inhibit or prevent progression of some types of breast cancer. Citation Format: Jochen Maurer, David J. Castro, Robert G. Oshima. ROCK1 inhibition promotes the self-renewal of a novel mouse mammary cancer stem cell. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2294. doi:10.1158/1538-7445.AM2013-2294
Strokelike Episodes in a Patient With Chronic Gait Abnormalities
Authors: Jonathan D. Santoro, Tanuja Chitnis
Journal: JAMA Neurology (2019)

A 13-year-old boy with a longstanding history of gait imbalance presented with 2 episodes of acute-onset left hemibody weakness and dysarthria without changes in sensorium in a 24-hour period. What is your diagnosis?
Dysregulated Lung Commensal Bacteria Drive Interleukin-17B Production to Promote Pulmonary Fibrosis through Their Outer Membrane Vesicles
Authors: Daping Yang, Xi Chen, Jingjing Wang, Qi Lou, Yunwei Lou, Li Li, Honglin Wang, Jiangye Chen, Meng Wu, Xinyang Song, Youcun Qian
Journal: Immunity (2019)
Guy Charmot: epidemiologist and French war hero
Authors: Rebecca Wallersteiner
Journal: BMJ (2019)

Photo shows: From left to right: Bernard Sureau (1914-1989), Guy Charmot (1914-2019), Andre Dodin (1926-1995) at l’Hopital Pasteur in 1971.

Photo credit: L’Institut Pasteur Archives, Jacques Bourichon

Guy Charmot, epidemiologist and expert in tropical medicine, has died at the age of 104.

Born in Toulon in 1914, the son of Ulysse Charmot, a tax collector, and his wife, Claire, Guy wanted to become both a doctor and a soldier from a young age. He attended the Ecole de sante des armees in Bron and qualified as a doctor at Lyon military medical school in 1938. Drawn to service in France’s overseas colonies, he then went to Marseille to study tropical medicine and entered the French Defence Health Service.

After Charmot’s death, President Emmanuel Macron made a public announcement, an unprecedented tribute for a doctor, honouring “with emotion, the memory of a man who committed himself with exceptional courage and self sacrifice to the liberty and honour of France.” Although Charmot was proud of his war record, he was self effacing and rarely talked about it.

According to the Ordre de la Liberation, at the outbreak of the second world war Charmot served, briefly, in the Sarre sector with the 49th regiment d’artillerie coloniale. In 1940 he was posted to a bush …
Exome Sequencing Identifies Mecom Missense Variant As Prognostic Marker for Overall Survival of Elderly Acute Myeloid Patients Treated with Azacitidine
Authors: Pierre Bories, Naïs Prade, Bastien Cabarrou, Stéphanie Lagarde, Julien Plenecassagnes, Isabelle Luquet, Veronique De Mas, Thomas Filleron, Manon Cassou, Audrey Sarry, Luc Matthieu Fornecker, Célestine Simand, Sarah Bertoli, Hinrich Gronemeyer, Christian Recher, Eric Delabesse
Journal: Blood (2018)
Gluten Intake and Risk of Islet Autoimmunity and Progression to Type 1 Diabetes in Children at Increased Risk of the Disease: The Diabetes Autoimmunity Study in the Young (DAISY)
Authors: Nicolai A. Lund-Blix, Fran Dong, Karl Mårild, Jennifer Seifert, Anna E. Barón, Kathleen C. Waugh, Geir Joner, Ketil Størdal, German Tapia, Lars C. Stene, Randi K. Johnson, Marian J. Rewers, Jill M. Norris
Journal: Diabetes Care (2019)

To study the association of gluten intake with development of islet autoimmunity and progression to type 1 diabetes.The Diabetes Autoimmunity Study in the Young (DAISY) follows children with an increased risk of type 1 diabetes. Blood samples were collected at 9, 15, and 24 months of age, and annually thereafter. Islet autoimmunity was defined by the appearance of at least one autoantibody against insulin, IA2, GAD, or ZnT8 (zinc transporter 8) in at least two consecutive blood samples. Using food frequency questionnaires, we estimated the gluten intake (in grams per day) annually from 1 year of age. Cox regression modeling early gluten intake, and joint modeling of the cumulative gluten intake during follow-up, were used to estimate hazard ratios adjusted for confounders (aHR).By August 2017, 1,916 subjects were included (median age at end of follow-up 13.5 years), islet autoimmunity had developed in 178 participants, and 56 of these progressed to type 1 diabetes. We found no association between islet autoimmunity and gluten intake at 1-2 years of age or during follow-up (aHR per 4 g/day increase in gluten intake 1.00, 95% CI 0.85-1.17 and 1.01, 0.99-1.02, respectively). We found similar null results for progression from islet autoimmunity to type 1 diabetes. Introduction of gluten at <4 months of age was associated with an increased risk of progressing from islet autoimmunity to type 1 diabetes compared with introduction at 4-5.9 months (aHR 8.69, 95% CI 1.69-44.8).Our findings indicate no strong rationale to reduce the amount of gluten in high-risk children to prevent development of type 1 diabetes.
Abstract P1-13-02: Withdrawn
Authors: V Guarneri, MV Dieci, G Bisagni, AA Brandes, A Frassoldati, L Cavanna, A Musolino, F Giotta, G Cavazzini, O Garrone, E Bertone, K Cagossi, O Nanni, A Ferro, M Donadio, M Aieta, C Zamagni, F Piacentini, A Maiorana, M Ragazzi, MC Cucchi, P Querzoli, N Orsi, M Curtarello, L Urso, A Amadori, E Orvieto, R Vicini, S Balduzzi, R D'Amico, P Conte
Journal: Cancer Research (2018)

Abstract This abstract was withdrawn by the authors.
Tegavivint and the β-Catenin/ALDH Axis in Chemotherapy-Resistant and Metastatic Osteosarcoma
Authors: Motonari Nomura, Nino Rainusso, Yi-Chien Lee, Brian Dawson, Cristian Coarfa, Ruolan Han, Jeffrey L Larson, Ryan Shuck, Lyazat Kurenbekova, Jason T Yustein
Journal: JNCI Journal of the National Cancer Institute (2019)

Abstract Background The Wnt/β-catenin pathway is closely associated with osteosarcoma (OS) development and metastatic progression. We investigated the antitumor activity of Tegavivint, a novel β-catenin/transducin β-like protein 1 (TBL1) inhibitor, against OS employing in vitro, ex vivo, and in vivo cell line and patient-derived xenograft (PDX) models that recapitulate high risk disease. Methods The antitumor efficacy of Tegavivint was evaluated in vitro using established OS and PDX-derived cell lines. Use of an ex vivo three-dimensional pulmonary metastasis assay assessed targeting of β-catenin activity during micro- and macrometastatic development. The in vivo activity of Tegavivint was evaluated using chemoresistant and metastatic OS PDX models. Gene and protein expression were quantified by quantitative Reverse transcription polymerase chain reaction or immunoblot analysis. Bone integrity was determined via microCT. All statistical tests were two-sided. Results Tegavivint exhibited antiproliferative activity against OS cells in vitro and actively reduced micro- and macrometastatic development ex vivo. Multiple OS PDX tumors (n = 3), including paired patient primary and lung metastatic tumors with inherent chemoresistance, were suppressed by Tegavivint in vivo. We identified that metastatic lung OS cell lines (n = 2) exhibited increased stem cell signatures, including enhanced concomitant aldehyde dehydrogenase (ALDH1) and β-catenin expression and downstream activity, which were suppressed by Tegavivint (ALDH1: control group, mean relative mRNA expression = 1.00, 95% confidence interval [CI] = 0.68 to 1.22 vs Tegavivint group, mean = 0.011, 95% CI = 0.0012 to 0.056, P &lt; .001; β-catenin: control group, mean relative mRNA expression = 1.00, 95% CI = 0.71 to 1.36 vs Tegavivint group, mean = 0.45, 95% CI = 0.36 to 0.52, P &lt; .001). ALDH1high PDX-derived lung OS cells, which demonstrated enhanced metastatic potential compared with ALDHlow cells in vivo, were sensitive to Tegavivint. Toxicity studies revealed decreased bone density in male Tegavivint-treated mice (n = 4 mice per group). Conclusions Tegavivint is a promising therapeutic agent for advanced stages of OS via its targeting of the β-catenin/ALDH1 axis.
Breast Cancer, Version 1.2016
Authors: William J Gradishar, Benjamin O Anderson, Ron Balassanian, Sarah L Blair, Harold J Burstein, Amy Cyr, Anthony D Elias, William B Farrar, Andres Forero, Sharon Hermes Giordano, Matthew Goetz, Lori J Goldstein, Clifford A Hudis, Steven J Isakoff, P Kelly Marcom, Ingrid A Mayer, Beryl McCormick, Meena Moran, Sameer A Patel, Lori J Pierce, Elizabeth C Reed, Kilian E Salerno, Lee S Schwartzberg, Karen Lisa Smith, Mary Lou Smith, Hatem Soliman, George Somlo, Melinda Telli, John H Ward, Dottie A Shead, Rashmi Kumar
Journal: Journal of the National Comprehensive Cancer Network (2015)

These NCCN Guideline Insights highlight the important updates to the systemic therapy recommendations in the 2016 NCCN Guidelines for Breast Cancer. In the most recent version of these guidelines, the NCCN Breast Cancer Panel included a new section on the principles of preoperative systemic therapy. In addition, based on new evidence, the panel updated systemic therapy recommendations for women with hormone receptor–positive breast cancer in the adjuvant and metastatic disease settings and for patients with HER2-positive metastatic breast cancer. This report summarizes these recent updates and discusses the rationale behind them.
Long-Term Risk of Skin Cancer Among Childhood Cancer Survivors: A DCOG-LATER Cohort Study
Authors: Jop C Teepen, Judith L Kok, Leontien C Kremer, Wim J E Tissing, Marry M van den Heuvel-Eibrink, Jacqueline J Loonen, Dorine Bresters, Helena J van der Pal, Birgitta Versluys, Eline van Dulmen-den Broeder, Tamar Nijsten, Michael Hauptmann, Nynke Hollema, Wil V Dolsma, Flora E van Leeuwen, Cécile M Ronckers
Journal: JNCI Journal of the National Cancer Institute (2018)

Skin cancer is common after radiotherapy among childhood cancer survivors (CCSs). We studied risks and risk factors for subsequent skin cancers, with emphasis on radiation dose, exposed skin surface area, and chemotherapeutic agents.The DCOG-LATER cohort study includes 5-year Dutch CCSs diagnosed 1963-2001. Subsequent skin cancers were identified from record linkages with the Netherlands Cancer Registry and Dutch Pathology Registry. Incidence rates were compared with general population rates. Multivariable Cox regression models were used, applying a novel method of case-control sampling enabling use of tumor location in cohort analyses. All statistical tests were two-sided.Among 5843 CCSs, 259 developed 1061 basal cell carcinomas (BCCs) (standardized incidence ratio [SIR] = 29.8, 95% confidence interval [CI] = 26.3 to 33.6; excess absolute risk per 10 000 person-years (EAR) = 24.6), 20 had melanoma (SIR = 2.3, 95% CI = 1.4 to 3.5; EAR = 1.1), and 10 had squamous cell carcinoma (SIR = 7.5, 95% CI = 3.6 to 13.8; EAR = 0.8). Cumulative incidence of BCC 40 years after childhood cancer was 19.1% (95% CI = 16.6 to 21.8%) after radiotherapy vs 0.6% expected based on general population rates. After a first BCC, 46.7% had more BCCs later. BCC risk was associated with any radiotherapy to the skin compartment of interest (hazard ratio [HR] = 14.32, 95% CI = 10.10 to 20.29) and with estimated percentage in-field skin surface area (26-75%: HR = 1.99, 95% CI = 1.24 to 3.20; 76-100%: HR = 2.16, 95% CI = 1.33 to 3.53, vs 1-25% exposed; Ptrend among exposed = .002), but not with prescribed radiation dose and likelihood of sun-exposed skin-area. Of all chemotherapy groups examined, only vinca alkaloids increased BCC risk (HR = 1.54, 95% CI = 1.04 to 2.27).CCSs have a strongly, 30-fold increased BCC risk. BCC risk appears to increase with increasing skin surface area exposed. This knowledge underscores the need for awareness by survivors and their health care providers.
The nonlesional skin surface distinguishes atopic dermatitis with food allergy as a unique endotype
Authors: Donald Y. M. Leung, Agustin Calatroni, Livia S. Zaramela, Petra K. LeBeau, Nathan Dyjack, Kanwaljit Brar, Gloria David, Keli Johnson, Susan Leung, Marco Ramirez-Gama, Bo Liang, Cydney Rios, Michael T. Montgomery, Brittany N. Richers, Clifton F. Hall, Kathryn A. Norquest, John Jung, Irina Bronova, Simion Kreimer, C. Conover Talbot, Debra Crumrine, Robert N. Cole, Peter Elias, Karsten Zengler, Max A. Seibold, Evgeny Berdyshev, Elena Goleva
Journal: Science Translational Medicine (2019)

Patients with atopic dermatitis and food allergy have an immature epithelial barrier and type 2 immune activation in their skin.
Abstract 3233: Long-Term Durability of Endoluminal Stenting for Obstructive Lesions of the Subclavian Artery: Multicenter Registry in Japan
Authors: Sunao Nakamura, Kimihiko Kanno, Naoyuki Kurita, Mizuki Hirose, Osamu Hirashima, Satoko Tahara, Osamu Kakuda, Kensuke Fujiwara, Eiji Tada, Hiroyuki Sato, Koji Hozawa, Hitoshi Nakamura, Kazutoshi Yamamoto, Seiji Otani, Nobuyuki Makishima, Shotaro Nakamura, Jun Koyama
Journal: Circulation (2006)
P146 Golimumab in rheumatoid and psoriatic arthritis. The relationship between minimum serum concentration, anti-golimumab antibodies and activity of disease
Authors: J Uceda, MJ Fobelo, R Hernandez
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Young investigator. <h3>Introduction</h3> Currently there is very little information on optimal levels of golimumab in patients with polyarthritis. <h3>Objectives</h3> The main objective was to analyze the minimal serum concentration of golimumab (GOL), anti-golimumab antibodies (AcGOL) and its relation to the activity of the disease measured by DAS 28 index, in rheumatoid arthritis (RA) and psoriatic arthritis (PA). <h3>Methods</h3> We conducted a retrospective observational study with RA or PA patients on golimumab treatment between 2011 and 2016. We analized the age, sex, diagnosis, dose, dose interval, duration of treatment, concomitant disease modifying drugs (DMARs), minimum concentration of GOL (GOL Cmin), AcGOL and DAS28 levels. Sampling was performed on the day corresponding to the dose of golimumab, prior to administration, in order to obtain the minimum levels of the drug. The analytical technique used for the determination was the Promonitor® sandwich ELISA. <h3>Results</h3> 10 RA, 5 AP patients were selected. Median age 53 years. 67% women. All with golimumab 50 mg with an administration interval of 28 to 41 days. Duration of treatment 16.73 months (median). 80% underwent combination therapy with DMARDs. Only one patient (RA) presented levels of AcGOL, with undetectable Cmin, DAS28 of 4.05. Golimumab levels in patients without AcGOL and DAS28 &lt;3.2: 1 Cmin &lt;0.25 mcg/mL, 5 Cmin 0.26–0.5 mcg/mL, 1 Cmin 0.5–1.4 mcg/mL and 1 2mcg/mL Cmin. In patients with DAS28 &gt;3.2 were: 2 Cmin &lt;0.25 mcg/mL, 2 Cmin 0.26–0.5 mcg/mL, 2 Cmin 0.5–1.4 mcg/mL and 1 Cmin of 2.2 mcg/mL. <h3>Conclusions</h3> Very variable GOL Cmin values (&lt;0.25–2.2 mcg/mL) were obtained. 80% with DAS28 &lt;3.2 had a GOL Cm: 0.26–0.5 mcg/mL. Because of the limited information currently available on the optimal range of golimumab levels, further studies are needed to evaluate the relationship between serum drug levels and patient disease activity data. <h3>Disclosure of Interest</h3> None declared.
Targeting miRNA-551b, a "Stemness"-like microRNA, to Eradicate AML (Stem) Cells
Authors: Tània Martiáñez, Noortje Van Gils, David Christian De Leeuw, Eline Vermue, Arjo Rutten, Fedor Denkers, Han J.M.P. Verhagen, Jeroen J. W. M. Janssen, Gert J. Ossenkoppele, Connie Jimenez, Linda Smit
Journal: Blood (2018)