tbuckley/cabot-search huggingface dataset:
Abiraterone + prednisone (Abi) +/- veliparib (Vel) for patients (pts) with metastatic castration-resistant prostate cancer (CRPC): NCI 9012 updated clinical and genomics data.
Authors: Maha Hussain, Stephanie Daignault, Przemyslaw Twardowski, Costantine Albany, Mark N. Stein, Lakshmi Priya Kunju, Dan R. Robinson, Kathleen A. Cooney, Robert B. Montgomery, Emmanuel S. Antonarakis, Daniel H. Shevrin, Paul Gettys Corn, Young E. Whang, David C. Smith, Megan Veresh Caram, Scott A. Tomlins, Karen E. Knudsen, Walter Michael Stadler, Felix Yi-Chung Feng, Arul M. Chinnaiyan
Journal: Journal of Clinical Oncology (2017)

5001 Background: In preclinical CRPC models, PARP1 inhibition synergizes with AR targeted therapy, especially in ETS fusion-positive tumors. We hypothesized: 1. Co-targeting PARP-1 + AR is superior to AR inhibition and 2. ETS +ve predicts response. Methods: Pts had metastatic (mets) disease biopsy (bx), stratified by IHC-ETS status and randomized to Abi (Arm A) or Abi + Vel (Arm B). Primary endpoint: PSA response rate (RR &gt; = 50% decline). Secondary endpoints: safety, objective RR (ORR), progression free survival (PFS), and molecular analysis including if DNA repair gene deficiency (DRD: BRCA 1, BRCA 2, ATM, FANCA, PALB2, RAD51B, RAD51C) predicts response. 148 pts stratified by IHC-ETS status were randomized to detect a 20% PSA RR improvement assuming a 5% 1-sided type I error and 80% power. An elastic net multivariable Cox model was used to analyze PFS. Mets bx underwent targeted exon sequencing and capture transcriptome analysis. Results: 72 pts were randomly assigned to Arm A and 76 to Arm B. PSA RR: Arm A 63.9%, Arm B 72.4% (p = 0.27). ORR: Arm A 45%, Arm B 52.2%, p = 0.51. Median PFS: Arm A 10.1 months (m), Arm B 11.3 m, p = 0.95. More Arm-B pts were on therapy for 12+ (45% vs 38%) and 18+ cycles (22% vs 17%). ETS status had no impact. Mets tissue sequencing (N = 80): 42 pts (53%) were ETS +ve, 19 (25%) had DRD, 47 (59%) had AR amplification/copy gain, 32 (40%) had PTEN mutation (mut), 33 (41%) had TP53 mut, 37 (46%) had PIK3CA activation (a) and 12 (15%) had WNT-a. Irrespective of arm pts with DRD had a higher PSA and ORR ( &gt; = 87%) vs wild type (58%, 39%; p = 0.013, p = 0.002, respectively), higher PSA decline rate of &gt; = 90% (74% vs 26%, p = 0.0004) and longer median PFS (95% CI): DRD 16.6 m (11 - NR) vs wild type: 8 m (5.4 – 13.3); p = 0.02. PFS was longer in pts with normal PTEN (13.5 vs 6.2 m, p = 0.02), TP53 (13.3 vs 7.8 m, p = 0.04) and PIK3CA (10.3 vs 8.3 m, p = 0.03). Controlling for clinical factors, DRD, PTEN, TP53 and PIK3CA are associated with PFS in this order of importance. Conclusions: There was a modest trend in favor of Abi + Vel but no difference by ETS. Pts with DRD, normal PTEN,TP53 and PIK3CA had better PFS raising new hypotheses regarding the importance of integrating molecular analysis in therapeutic trials. Clinical trial information: NCT01576172.
Randomized phase III trial of low-molecular-weight heparin enoxaparin in addition to standard treatment in small-cell lung cancer: the RASTEN trial
Authors: L. Ek, E. Gezelius, B. Bergman, P.O. Bendahl, H. Anderson, J. Sundberg, M. Wallberg, U. Falkmer, S. Verma, M. Belting
Journal: Annals of Oncology (2017)

Coagulation activation and venous thromboembolism (VTE) are hallmarks of malignant disease and represent a major cause of morbidity and mortality in cancer. Coagulation inhibition with low-molecular-weight heparin (LMWH) may improve survival specifically in small-cell lung cancer (SCLC) patients by preventing VTE and tumor progression; however, randomized trials with well-defined patient populations are needed to obtain conclusive data. The aim of RASTEN was to investigate the survival effect of LMWH enoxaparin in a homogenous population of SCLC patients.
Inhibition of therenin-angiotensin systemand the left ventricularadaptation to mitral regurgitation**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: William H. Gaasch, Gerard P. Aurigemma
Journal: Journal of the American College of Cardiology (2002)
Restoration of skin pigmentation after deep partial or full-thickness burn injury
Authors: Niann-Tzyy Dai, Hsin-I Chang, Yi-Wen Wang, Keng-Yen Fu, Tai-Chun Huang, Nien-Chi Huang, Jhen-Kai Li, Pai-Shan Hsieh, Lien-Guo Dai, Chao-Kuei Hsu, Peter K. Maitz
Journal: Advanced Drug Delivery Reviews (2017)
Noninvasive Imaging of CD206-Positive M2 Macrophages as an Early Biomarker for Post-Chemotherapy Tumor Relapse and Lymph Node Metastasis
Authors: Chenran Zhang, Xinhe Yu, Liquan Gao, Yang Zhao, Jianhao Lai, Dehua Lu, Rui Bao, Bing Jia, Lijun Zhong, Fan Wang, Zhaofei Liu
Journal: Theranostics (2017)

Tumor relapse after initial regression post-chemotherapy is a major challenge in cancer treatment, as it usually leads to local-regional recurrence or inoperable distant metastasis.M2 macrophages diminish the tumor-inhibitory effect of chemotherapy and correlate with distant metastasis and poor prognosis.In this study, we investigated whether molecular imaging of M2 macrophages could serve as an early biomarker for tumor relapse after chemotherapy and tumor lymph node metastasis in preclinical mouse models.Methods: We developed M2 macrophage-targeted probes for near-infrared fluorescence (NIRF) imaging and single-photon emission computed tomography (SPECT) using an anti-CD206 monoclonal antibody.The specific targeting capacity and potential applications of the NIRF and SPECT probes were investigated in subcutaneous tumor and lymph node metastasis models of 4T1 murine breast cancer.Results: M2 macrophage infiltration was significantly increased in the 4T1 tumors that later underwent relapse but not in non-relapsing 4T1 tumors after cyclophosphamide treatment.Through NIRF imaging and SPECT using our synthesized probes, the infiltration of M2 macrophages in relapsing tumors and tumor lymph node metastasis could be sensitively detected.Importantly, early prediction of tumor relapse by molecular imaging of M2 macrophages resulted in an effective eradication of tumors upon combination with additional radiotherapy.Conclusion: Our findings demonstrate that M2 macrophage-targeted imaging allows for noninvasively predicting post-chemotherapy tumor relapse and sensitively detecting the metastatic lymph nodes in vivo.This imaging strategy could provide a better understanding of cancer progression, enable early prediction of tumor resistance, and have implications on the rational design of cancer therapeutics.
Epigenomic characterization of a p53-regulated 3p22.2 tumor suppressor that inhibits STAT3 phosphorylation via protein docking and is frequently methylated in esophageal and other carcinomas
Authors: Lili Li, Juan Xu, Guohua Qiu, Jianming Ying, Zhenfang Du, Tingxiu Xiang, Kai Yau Wong, Gopesh Srivastava, Xiao-Feng Zhu, Tony S Mok, Anthony Tc Chan, Francis Kl Chan, Richard F Ambinder, Qian Tao
Journal: Theranostics (2017)

Rationale: Oncogenic STAT3 signaling activation and 3p22-21.3 locus alteration are common in multiple tumors, especially carcinomas of the nasopharynx, esophagus and lung. Whether these two events are linked remains unclear. Our CpG methylome analysis identified a 3p22.2 gene, DLEC1, as a methylated target in esophageal squamous cell (ESCC), nasopharyngeal (NPC) and lung carcinomas. Thus, we further characterized its epigenetic abnormalities and functions. Methods: CpG methylomes were established by methylated DNA immunoprecipitation. Promoter methylation was analyzed by methylation-specific PCR and bisulfite genomic sequencing. DLEC1 expression and clinical significance were analyzed using TCGA database. DLEC1 functions were analyzed by transfections followed by various cell biology assays. Protein-protein interaction was assessed by docking, Western blot and immunoprecipitation analyses. Results: We defined the DLEC1 promoter within a CpG island and p53-regulated. DLEC1 was frequently downregulated in ESCC, lung and NPC cell lines and primary tumors, but was readily expressed in normal tissues and immortalized normal epithelial cells, with mutations rarely detected. DLEC1 methylation was frequently detected in ESCC tumors and correlated with lymph node metastasis, tumor recurrence and progression, with DLEC1 as the most frequently methylated among the established 3p22.2 tumor suppressors (RASSF1A, PLCD1 and ZMYND10/BLU). DLEC1 inhibits carcinoma cell growth through inducing cell cycle arrest and apoptosis, and also suppresses cell metastasis by reversing epithelial-mesenchymal transition (EMT) and cell stemness. Moreover, DLEC1 represses oncogenic signaling including JAK/STAT3, MAPK/ERK, Wnt/β-catenin and AKT pathways in multiple carcinoma types. Particularly, DLEC1 inhibits IL-6-induced STAT3 phosphorylation in a dose-dependent manner. DLEC1 contains three YXXQ motifs and forms a protein complex with STAT3 via protein docking, which blocks STAT3-JAK2 interaction and STAT3 phosphorylation. IL-6 stimulation enhances the binding of DLEC1 with STAT3, which diminishes their interaction with JAK2 and further leads to decreased STAT3 phosphorylation. The YXXQ motifs of DLEC1 are crucial for its inhibition of STAT3 phosphorylation, and disruption of these motifs restores STAT3 phosphorylation through abolishing DLEC1 binding to STAT3. Conclusions: Our study demonstrates, for the first time, predominant epigenetic silencing of DLEC1 in ESCC, and a novel mechanistic link of epigenetic DLEC1 disruption with oncogenic STAT3 signaling in multiple carcinomas.
From Paris to Vienna—The Varied Names and Descriptions of Cutaneous Lupus Erythematosus in the 19th Century
Authors: Connie R. Shi, Peter H. Schur, Vinod E. Nambudiri
Journal: JAMA Dermatology (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 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
Precision medicine in airway diseases: moving to clinical practice
Authors: Alvar Agustí, Mona Bafadhel, Richard Beasley, Elisabeth H. Bel, Rosa Faner, Peter G. Gibson, Renaud Louis, Vanessa M. McDonald, Peter J. Sterk, Mike Thomas, Claus Vogelmeier, Ian D. Pavord
Journal: European Respiratory Journal (2017)

On February 21, 2017, a European Respiratory Society research seminar held in Barcelona discussed how to best apply precision medicine to chronic airway diseases such as asthma and chronic obstructive pulmonary disease. It is now clear that both are complex and heterogeneous diseases, that often overlap and that both require individualised assessment and treatment. This paper summarises the presentations and discussions that took place during the seminar. Specifically, we discussed the need for a new taxonomy of human diseases, the role of different players in this scenario (exposome, genes, endotypes, phenotypes, biomarkers and treatable traits) and a number of unanswered key questions in the field. We also addressed how to deploy airway precision medicine in clinical practice today, both in primary and specialised care. Finally, we debated the type of research needed to move the field forward.
Sport, sex and age increase risk of illness at the Rio 2016 Summer Paralympic Games: a prospective cohort study of 51 198 athlete days
Authors: Wayne Derman, Martin P Schwellnus, Esme Jordaan, Phoebe Runciman, Cheri Blauwet, Nick Webborn, Jan Lexell, Peter Van de Vliet, Yetsa Tuakli-Wosornu, James Kissick, Jaap Stomphorst
Journal: British Journal of Sports Medicine (2017)

To describe the epidemiology of illness at the Rio 2016 Summer Paralympic Games.A total of 3657 athletes from 78 countries, representing 83.5% of all athletes at the Games, were monitored on the web-based injury and illness surveillance system (WEB-IISS) over 51 198 athlete days during the Rio 2016 Summer Paralympic Games. Illness data were obtained daily from teams with their own medical support through the WEB-IISS electronic data capturing systems.The total number of illnesses was 511, with an illness incidence rate (IR) of 10.0 per 1000 athlete days (12.4%). The highest IRs were reported for wheelchair fencing (14.9), para swimming (12.6) and wheelchair basketball (12.5) (p<0.05). Female athletes and older athletes (35-75 years) were also at higher risk of illness (both p<0.01). Illnesses in the respiratory, skin and subcutaneous and digestive systems were the most common (IRs of 3.3, 1.8 and 1.3, respectively).(1) The rate of illness was lower than that reported for the London 2012 Summer Paralympic Games; (2) the sports with the highest risk were wheelchair fencing, para swimming and wheelchair basketball; (3) female and older athletes (35-75 years) were at increased risk of illness; and (4) the respiratory system, skin and subcutaneous system and digestive system were most affected by illness. These results allow for comparison at future Games.
Risk of uveitis and inflammatory bowel disease in people with psoriatic arthritis: a population-based cohort study
Authors: Rachel Charlton, Amelia Green, Gavin Shaddick, Julia Snowball, Alison Nightingale, William Tillett, Catherine H Smith, Neil McHugh
Journal: Annals of the Rheumatic Diseases (2017)

Objectives To determine the risk of uveitis and inflammatory bowel disease (IBD) in patients with psoriatic arthritis (PsA) compared with the general population and patients with psoriasis. Methods A cohort study using data from the UK Clinical Practice Research Datalink between 1998 and 2014. Patients with incident PsA aged 18–89 years were identified and matched to a cohort of patients with psoriasis and a general population cohort. The incidence of uveitis, all IBD, Crohn’s disease and ulcerative colitis was calculated for each study cohort and adjusted relative risks (RR adj ) were calculated using conditional Poisson regression. Results 6783 incident cases of PsA were identified with a median age of 49 years. The risk of uveitis was significantly higher in the PsA cohort than in the general population and psoriasis cohorts (RR adj 3.55, 95% CI 2.21 to 5.70 and RR adj 2.13, 95% CI 1.40 to 3.24, respectively). A significant increase was observed for Crohn’s disease (RR adj 2.96, 95% CI 1.46 to 6.00 and RR adj 3.60, 95% CI 1.83 to 7.10) but not for ulcerative colitis (RR adj 1.30, 95% CI 0.66 to 2.56 and RR adj 0.98, 95% CI 0.50 to 1.92). Conclusions In a primary care-based incidence cohort of patients with PsA, there were substantial risks of developing uveitis and/or Crohn’s disease, but not ulcerative colitis, when compared with the general population and psoriasis controls.
Fractional exhaled nitric oxide as a predictor of response to inhaled corticosteroids in patients with non-specific respiratory symptoms and insignificant bronchodilator reversibility: a randomised controlled trial
Authors: David B Price, Roland Buhl, Adrian Chan, Daryl Freeman, Elizabeth Gardener, Clifford Godley, Kevin Gruffydd-Jones, Lorcan McGarvey, Ken Ohta, Dermot Ryan, Jörgen Syk, Ngiap Chuan Tan, TzeLee Tan, Mike Thomas, Sen Yang, Priyanka Raju Konduru, Marcus Ngantcha, Martina Stagno d'Alcontres, Therese S Lapperre
Journal: The Lancet Respiratory Medicine (2017)
El impacto de la ola de calor sobre la mortalidad diaria en Inglaterra y Gales y la utilización de cálculos de mortalidad semanales rápidos
Authors: H Johnson, S Kovats, G McGregor, J Stedman, M Gibbs, H Walton
Journal: Eurosurveillance (2005)

En este articulo se describe un analisis retrospectivo del impacto de la ola de calor de 2003 sobre la mortalidad en Inglaterra y Gales, comparandolo con las estimaciones rapidas de la Oficina de estadisticas nacionales (Office for National Statistics, ONS), del sistema de notificacion de rutina de las defunciones semanales. Los datos de mortalidad entre el 4 y el 13 agosto de 2003, cuando las temperaturas fueron muy superiores a las normales para Inglaterra, se compararon con las medias para los mismos periodos entre 1998 y 2002. La ola de calor de agosto de 2003 se asocio a un aumento importante de la mortalidad a corto plazo, especialmente en Londres. Las concentraciones de ozono y de particulas en el aire tambien alcanzaron un nivel alto durante la ola de calor. Globalmente, se observaron en Inglaterra y Gales 2.139 defunciones en exceso (16%), siendo los mayores de 75 anos los mas afectados. El area de Londres, con un aumento del 59% de defunciones en los mayores de 75 anos, fue la region mas afectada por la ola de calor. El exceso estimado de mortalidad supera el de otras olas recientes en el Reino Unido. 
Cada semana la ONS transmite el numero estimado de defunciones. La primera indicacion clara de un ascenso substancial se publico el 21 de agosto de 2003. Se proporciono asi una primera evaluacion rapida del numero de defunciones atribuibles a la ola de calor, que refleja el patron de defunciones diarias asociadas a los dias mas calidos, pero subestima el exceso de mortalidad detectado por el ultimo analisis.
TCT-656 Intravascular Ultrasound Morphologic Comparison of In-stent Chronic Total Occlusion Versus Non-Occlusive In-stent Restenosis
Authors: Dong Yin, Gary Mintz, Kosaku Goto, Kisaki Amemiya, Lei Song, Zhijing Zhao, Myong Hwa Yamamoto, Khady Fall, Ajay Jayant Kirtane, Ziad Ali, Tamim Nazif, Jeffrey W. Moses, Manish Parikh, Michael B. Collins, Martin Leon, Gregg Stone, Masahiko Ochiai, Dimitri Karmpaliotis, Akiko Maehara
Journal: Journal of the American College of Cardiology (2017)
The Polycomb-Dependent Epigenome Controls β Cell Dysfunction, Dedifferentiation, and Diabetes
Authors: Tess Tsai-Hsiu Lu, Steffen Heyne, Erez Dror, Eduard Casas, Laura Leonhardt, Thorina Boenke, Chih-Hsiang Yang, None Sagar, Laura Arrigoni, Kevin Dalgaard, Raffaele Teperino, Lennart Enders, Madhan Selvaraj, Marius Ruf, Sunil J. Raja, Huafeng Xie, Ulrike Boenisch, Stuart H. Orkin, Francis C. Lynn, Brad G. Hoffman, Dominic Grün, Tanya Vavouri, Adelheid M. Lempradl, J. Andrew Pospisilik
Journal: Cell Metabolism (2018)

To date, it remains largely unclear to what extent chromatin machinery contributes to the susceptibility and progression of complex diseases. Here, we combine deep epigenome mapping with single-cell transcriptomics to mine for evidence of chromatin dysregulation in type 2 diabetes. We find two chromatin-state signatures that track β cell dysfunction in mice and humans: ectopic activation of bivalent Polycomb-silenced domains and loss of expression at an epigenomically unique class of lineage-defining genes. β cell-specific Polycomb (Eed/PRC2) loss of function in mice triggers diabetes-mimicking transcriptional signatures and highly penetrant, hyperglycemia-independent dedifferentiation, indicating that PRC2 dysregulation contributes to disease. The work provides novel resources for exploring β cell transcriptional regulation and identifies PRC2 as necessary for long-term maintenance of β cell identity. Importantly, the data suggest a two-hit (chromatin and hyperglycemia) model for loss of β cell identity in diabetes.
Abstract 12530: Tristetraprolin-mediated mRNA Degradation of Mitochondrial Electron Transport Chain Proteins Protects the Heart Against Iron Deficiency
Authors: Tatsuya Sato, Hsiang-Chun Chang, María T Martínez-Pastor, Sergi Puig, Marina Bayeva, Perry Blackshear, Lisa D Wilsbacher, Hossein Ardehali
Journal: Circulation (2016)

Introduction: Iron deficiency is the most common nutrient deficiency in the world, and cells respond to iron deficiency by activating iron regulatory proteins (IRP) to increase cellular iron uptake and availability. Although iron overload can cause cardiomyopathy, iron deficiency does not normally lead to cardiac damage. Tristetraprolin (TTP) is a tandem zinc finger protein that binds to the AU-rich elements (AREs) in the 3’ untranslated regions (UTR) of mRNA molecules and causes their degradation. We recently showed that TTP plays a role in iron conservation in the cell by targeting and degrading the mRNA for the iron importer, transferrin receptor 1. However, it is not clear how cells respond to conditions when cellular iron uptake and availability are not sufficient to match the demand. We hypothesized that TTP protects against cardiac dysfunction under iron deficiency by targeting the mRNAs of Fe/S cluster-containing proteins in the mitochondria. Results: To assess the effects of TTP on mitochondria, we first performed an unbiased in silico screen and identified a number of mRNAs that contain the consensus TTP-binding sequence in their 3’ UTR. Of those, steady-state levels of several mRNAs were increased with TTP deletion. However, only the mRNAs of three genes were shown to be bound by and be degraded by TTP protein: NDUFS1 in complex I, UQCRFS1 in complex III and mitochondrial aconitase. Interestingly, these proteins need Fe/S clusters to be active, suggesting that their protein levels are decreased in the absence of Fe/S cluster availability. We also demonstrate that in the absence of TTP and with iron deficiency, complex III gets formed with UQCRFS1, but without the required Fe/S cluster, which leads to the production of reactive oxygen species (ROS) and cellular injury. Finally, mice with systemic deletion of TTP display cardiac dysfunction under iron deficiency, demonstrating a major role for TTP in maintaining normal cellular function under iron deficiency. Conclusions: Our results provide a pathway that is activated in parallel to the IRPs and leads to degradation of mitochondrial mRNAs that require Fe/S clusters. This response to iron deficiency is critical to prevent excessive ROS production and cardiac damage.
Current applications of multiparameter flow cytometry in plasma cell disorders
Authors: T Jelinek, R Bezdekova, M Zatopkova, L Burgos, M Simicek, T Sevcikova, B Paiva, R Hajek
Journal: Blood Cancer Journal (2017)

Multiparameter flow cytometry (MFC) has become standard in the management of patients with plasma cell (PC) dyscrasias, and could be considered mandatory in specific areas of routine clinical practice. It plays a significant role during the differential diagnostic work-up because of its fast and conclusive readout of PC clonality, and simultaneously provides prognostic information in most monoclonal gammopathies. Recent advances in the treatment and outcomes of multiple myeloma led to the implementation of new response criteria, including minimal residual disease (MRD) status as one of the most relevant clinical endpoints with the potential to act as surrogate for survival. Recent technical progress led to the development of next-generation flow (NGF) cytometry that represents a validated, highly sensitive, cost-effective and widely available technique for standardized MRD evaluation, which also could be used for the detection of circulating tumor cells. Here we review current applications of MFC and NGF in most PC disorders including the less frequent solitary plasmocytoma, light-chain amyloidosis or Waldenström macroglobulinemia.