tbuckley/cabot-search huggingface dataset:
Association of Racial Differences With End-of-Life Care Quality in the United States
Authors: Rashmi K. Sharma, Vicki A. Freedman, Vincent Mor, Judith D. Kasper, Pedro Gozalo, Joan M. Teno
Journal: JAMA Internal Medicine (2017)

This cross-sectional analysis of survey data collected from 2011 to 2015 for the National Health and Aging Trends Study assesses whether racial differences in the quality of end-of-life care persist in the United States.
Abstract 15165: Sterol Regulatory Element-Binding Protein-1 Participates in the Development of Cardiac Injury Partly via Chronic Inflammation
Authors: Satoshi Sakai, Yoshimi Nakagawa, Nobutake Shimojo, Keisuke Kuga, Satoshi Homma, Takashi Miyauchi, Hitoshi Shimano, Kazutaka Aonuma
Journal: Circulation (2011)

Background:  Sterol regulatory element-binding protein (SREBP)-1, which is a transcription factor positively regulating triglyceride synthesis, contributes to organ damages in the liver and kidney; one of phenotypes is represented by fibrotic infiltration. However, it is unclear whether SREBP-1 contributes to the cardiac pathogenesis.   Purpose:  To elucidate whether SREBP-1 contributes to the development of cardiac injury.   Methods and Results:  We made hypertension and cardiac hypertrophy model by 2-week infusion of angiotensin II (A-II) (1.44 mg/kg body weight/day). Mice were divided into followings (n=5∼6 in each group): wild with vehicle (WC), wild with A-II (WA), SREBP-1 knockout mice (SREBP-KO) with vehicle (SC), and SREBP-KO with A-II (SA). WA and SA showed significant elevation in blood pressure and cardiac hypertrophy compared to WC and SC, respectively. Ejection fraction (EF) was significantly lower in WA than in WC (71±2 % vs 80±2 %, P   Conclusion:  These data suggest that SREBP-1 positively contributes to A-II-induced cardiac injury partly via the involvement of slowly progressed inflammation, which may be induced by the attenuated responses of antioxidant gene program.
Pancreatic Ductal Adenocarcinoma Subtyping Using the Biomarkers Hepatocyte Nuclear Factor-1A and Cytokeratin-81 Correlates with Outcome and Treatment Response
Authors: Alexander Muckenhuber, Anne Katrin Berger, Anna Melissa Schlitter, Katja Steiger, Björn Konukiewitz, Andreas Trumpp, Roland Eils, Jens Werner, Helmut Friess, Irene Esposito, Günter Klöppel, Güralp O. Ceyhan, Moritz Jesinghaus, Carsten Denkert, Marcus Bahra, Albrecht Stenzinger, Martin R. Sprick, Dirk Jäger, Christoph Springfeld, Wilko Weichert
Journal: Clinical Cancer Research (2017)

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is associated with a dismal prognosis and poor therapeutic response to current chemotherapy regimens in unselected patient populations. Recently, it has been shown that PDAC may be stratified into functionally and therapeutically relevant molecular subgroups and that some of these subtypes can be recapitulated by IHC for KRT81 [quasi-mesenchymal (QM)/squamous/basal-like] and HNF1A (non-QM, overlap with exocrine/ADEX subtype).Experimental Design: We validated the different outcome of the HNF1A/KRT81 PDAC subtypes in two independent cohorts of surgically treated patients and examined the treatment response to chemotherapy in a third cohort of unresectable patients. The first two cohorts included 262 and 130 patients, respectively, and the third independent cohort comprised advanced-stage PDAC patients who were treated with either FOLFIRINOX (64 patients) or gemcitabine (61 patients).Results: In both cohorts with resected PDAC, the HNF1A-positive subtype showed the best, the KRT81-positive subtype the worst, and the double-negative subtype an intermediate survival (P < 0.013 and P < 0.009, respectively). In the chemotherapy cohort, the survival difference between the double-negative and the HNF1A-positive subtype was lost, whereas the dismal prognosis of KRT81-positive PDAC patients was retained (P < 0.021). Patients with a KRT81-positive subtype did not benefit from FOLFIRINOX therapy, whereas those with HNF1A-positive tumors responded better compared with gemcitabine-based treatment (P < 0.038).Conclusions: IHC stratification recapitulating molecular subtypes of PDAC using HNF1A and KRT81 is associated with significantly different outcomes and responses to chemotherapy. These results may pave the way toward future pretherapeutic biomarker-based stratification of PDAC patients. Clin Cancer Res; 24(2); 351-9. ©2017 AACR.
The Importance of Population-Based Estimates of Melanocytic Pathology
Authors: Katy J. L. Bell, Anne E. Cust, Richard A. Scolyer
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
The influence of hypoxia on tumor cell proliferation, cell cycle, apoptosis and on the cytotoxic effects of gemcitabine and cisplatin, in vitro.
Authors: An Wouters, Bea Pauwels, Hilde Lambrechts, Greet Pattyn, Elke Fordel, Jan Vermorken, Filip Lardon
Journal: Cancer Research (2007)

2418  The efficacy of many cytotoxic drugs and radiation is directly linked up with adequate oxygen tension. As it is well established that hypoxic regions are frequently found in solid tumors, this implies that tumors often contain viable cells that are more resistant to chemotherapy and radiotherapy.  In this study, we investigated the influence of moderate hypoxia on different tumor cell lines. In addition, the cytotoxicity of gemcitabine (dFdC) and cisplatin (CDDP) was studied under hypoxic conditions.  The human tumor cell lines investigated are A549 (lung carcinoma cell line, wt p53), A549-E6 (transfected cell line with abrogated p53) and A549-LXSN (vector transfected control). For hypoxia experiments, cells were kept in a humidified chamber continuously flushed with a premixed gas of 1% O2, 5% CO2 and 94% N2. At different time points (1h, 24h and 48h hypoxia; 24h and 96h reoxygenation), control cells and cells growed under hypoxic conditions were sampled. Growth curve studies determined the influence on cell proliferation. The effect of hypoxia on cell cycle and apoptosis was flow cytometrically examined by the Vindelov method and Annexin V - PI labeling, respectively. To validate the hypoxic conditions, expression of VEGF was measured by real time qPCR.  For the cytotoxicity experiments, cells were treated with gemcitabine (0 - 100 nM) or cisplatin (0 - 10 μM), exposed to hypoxia for 24h, reoxygenated and washed, whereafter the chemosensitivity was assessed by the SRB assay.  Hypoxia (1% O2) for 24 or 48h inhibited cell proliferation in all cell lines examined, but only significantly at some time points. No apoptosis induction was noticed, neither after 1, 24 or 48h hypoxia, neither after 48h hypoxia followed by 24 or 96h reoxygenation. We observed a small but non-significant increase in G1 phase and a small decrease in the number of cells in S phase after 48h hypoxia in A549 and A549-LXSN. In A549-E6, only minimal differences in the cell cycle distribution between normoxic and hypoxic cells were seen. In all cell lines, the expression of VEGF was increased after 24h hypoxia, and even more pronounced after 48h hypoxia.  Preliminary results suggest a slight decrease in sensitivity for gemcitabine in all cell lines under hypoxic conditions, whereby the difference between normoxic and hypoxic cells is less pronounced in A549-E6. For cisplatin, hypoxic exposure induced chemoresistance in A549 and A549-LXSN cells, while in A549-E6, hypoxia resulted in a slightly higher sensitivity. These results suggest that p53 could be involved in mediating chemosensitivity under hypoxic conditions.  In conclusion, an in vitro model was established to examine the cytotoxic and radiosensitizing effects of cytotoxic agents under hypoxic conditions.
A distinct hematopoietic stem cell population for rapid multilineage engraftment in nonhuman primates
Authors: Stefan Radtke, Jennifer E. Adair, Morgan A. Giese, Yan-Yi Chan, Zachary K. Norgaard, Mark Enstrom, Kevin G. Haworth, Lauren E. Schefter, Hans-Peter Kiem
Journal: Science Translational Medicine (2017)

A population of hematopoietic stem cells with superior engraftment and repopulating abilities has been identified in nonhuman primates.
Does Tranexamic Acid Cause Venous Thromboembolism After Trauma?
Authors: Eric W. Etchill, Raymond Fang, Elliott R. Haut
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
McEnhancer: predicting gene expression via semi-supervised assignment of enhancers to target genes
Authors: Dina Hafez, Aslihan Karabacak, Sabrina Krueger, Yih-Chii Hwang, Li-San Wang, Robert P. Zinzen, Uwe Ohler
Journal: Genome biology (2017)

Transcriptional enhancers regulate spatio-temporal gene expression. While genomic assays can identify putative enhancers en masse, assigning target genes is a complex challenge. We devised a machine learning approach, McEnhancer, which links target genes to putative enhancers via a semi-supervised learning algorithm that predicts gene expression patterns based on enriched sequence features. Predicted expression patterns were 73–98% accurate, predicted assignments showed strong Hi-C interaction enrichment, enhancer-associated histone modifications were evident, and known functional motifs were recovered. Our model provides a general framework to link globally identified enhancers to targets and contributes to deciphering the regulatory genome.
Metformin Alters Upper Small Intestinal Microbiota that Impact a Glucose-SGLT1-Sensing Glucoregulatory Pathway
Authors: Paige V. Bauer, Frank A. Duca, T.M. Zaved Waise, Brittany A. Rasmussen, Mona A. Abraham, Helen J. Dranse, Akshita Puri, Catherine A. O’Brien, Tony K.T. Lam
Journal: Cell Metabolism (2017)
Oral fexinidazole for late-stage African Trypanosoma brucei gambiense trypanosomiasis: a pivotal multicentre, randomised, non-inferiority trial
Authors: Victor Kande Betu Ku Mesu, Wilfried Mutombo Kalonji, Clélia Bardonneau, Olaf Valverde Mordt, Séverine Blesson, François Simon, Sophie Delhomme, Sonja Bernhard, Willy Kuziena, Jean-Pierre Fina Lubaki, Steven Lumeya Vuvu, Pathou Nganzobo Ngima, Hélène Mahenzi Mbembo, Médard Ilunga, Augustin Kasongo Bonama, Josué Amici Heradi, Jean Louis Lumaliza Solomo, Guylain Mandula, Lewis Kaninda Badibabi, Francis Regongbenga Dama, Papy Kavunga Lukula, Digas Ngolo Tete, Crispin Lumbala, Bruno Scherrer, Nathalie Strub-Wourgaft, Antoine Tarral
Journal: The Lancet (2017)
Programmed Death-Ligand 1 Immunohistochemistry Testing: A Review of Analytical Assays and Clinical Implementation in Non–Small-Cell Lung Cancer
Authors: Reinhard Büttner, John R. Gosney, Birgit Guldhammer Skov, Julien Adam, Noriko Motoi, Kenneth J. Bloom, Manfred Dietel, John W. Longshore, Fernando López-Ríos, Frédérique Penault-Llorca, Giuseppe Viale, Andrew C. Wotherspoon, Keith M. Kerr, Ming-Sound Tsao
Journal: Journal of Clinical Oncology (2017)

Purpose Three programmed death-1/programmed death-ligand 1 (PD-L1) inhibitors are currently approved for treatment of non-small-cell lung cancer (NSCLC). Treatment with pembrolizumab in NSCLC requires PD-L1 immunohistochemistry (IHC) testing. Nivolumab and atezolizumab are approved without PD-L1 testing, though US Food and Drug Administration-cleared complementary PD-L1 tests are available for both. PD-L1 IHC assays used to assess PD-L1 expression in patients treated with programmed death-1/PD-L1 inhibitors in clinical trials include PD-L1 IHC 28-8 pharmDx (28-8), PD-L1 IHC 22C3 pharmDx (22C3), Ventana PD-L1 SP142 (SP142), and Ventana PD-L1 SP263 (SP263). Differences in antibodies and IHC platforms have raised questions about comparability among these assays and their diagnostic use. This review provides practical information to help physicians and pathologists understand analytical features and comparability of various PD-L1 IHC assays and their diagnostic use. Methods We reviewed and summarized published or otherwise reported studies (January 2016 to January 2017) on clinical trial and laboratory-developed PD-L1 IHC assays (LDAs). Studies assessing the effect of diagnostic methods on PD-L1 expression levels were analyzed to address practical issues related to tissue samples used for testing. Results High concordance and interobserver reproducibility were observed with the 28-8, 22C3, and SP263 clinical trial assays for PD-L1 expression on tumor cell membranes, whereas lower PD-L1 expression was detected with SP142. Immune-cell PD-L1 expression was variable and interobserver concordance was poor. Inter- and intratumoral heterogeneity had variable effects on PD-L1 expression. Concordance among LDAs was variable. Conclusion High concordance among 28-8, 22C3, and SP263 when assessing PD-L1 expression on tumor cell membranes suggests possible interchangeability of their clinical use for NSCLC but not for assessment of PD-L1 expression on immune cells. Development of LDAs requires stringent standardization before their recommendation for routine clinical use.
Imaging tumor burden by [18F]FDG-PET scanning and osteoblast activity by [99mTc]MDP-SPECT/CT in the 5TGM1 mouse model of myeloma bone disease
Authors: Babatunde O. Oyajobi, Beth Goins, Anjana Gupta, Cristina L. Zavaleta, Barry Grubbs, Joseph K. Agyin, Christi Wideman, Zheng Wang, Williams T. Phillips, I. Ross Garrett, Gregory R. Mundy
Journal: Cancer Research (2005)

3819   The associated high morbidity and mortality rates associated with multiple myeloma (MM) are due to complications resulting from its effects on the skeleton. These complications including pathological fractures reflect, in part, tumor-induced osteolysis as well as failure of new bone formation. Lack of suitable pre-clinical models of MM bone disease that closely reflect changes seen in humans has hampered development of novel anti-myeloma agents. Standard histological techniques, which are the current gold standards for monitoring skeletal tumor progression and osteoblast function, are labor-intensive and invasive and therefore limit the use of mouse models for rapidly assessing efficacy new treatment modalities. To remedy these shortcomings, we have applied state-of-the-art small animal nuclear imaging modalities [positron emission tomography (microPET) and single photon emission computed tomography (microSPECT/CT)], similar to those utilized clinically, to the murine 5TGM1 model of MM bone disease. PET scans were performed using [18F]-fluorodeoxyglucose (FDG) to provide functional measurements of tumor burden and preliminary studies demonstrate accumulation of FDG in tumors in the skeleton. Since 5TGM1 myeloma cells are engineered to express green fluorescent protein (GFP), we also compared sensitivity of PET with whole body optical GFP imaging and found that PET was more sensitive. To demonstrate the feasibility of using SPECT to assess osteoblast function in the 5TGM1 model, we performed bone scintigraphic scans after administration of [99Tc]-hydroxymethylene diphosphonate (MDP) and found that overall skeletal uptake was reduced in tumor-bearing mice. Biodistribution studies further indicated that uptake was suppressed in all bones of 5TGM1-bearing mice in comparison to soft tissues of the same mice or to bones of non-tumor bearing mice. Consistent with these findings, cancellous bone volumes and bone formation rates, determined by dynamic bone histomorphometry, are significantly reduced in the 5TGM1 model. In conclusion, microPET should facilitate real-time, longitudinal monitoring of tumor growth and spread or regression in response to therapy within skeletons of individual live animals and SPECT/CT should enable concurrent spatial localization of increased osteoblastic activity in response to investigative bone anabolic therapy. Together, these novel imaging capabilities increase the utility of the 5TGM1 model beyond what would otherwise be possible using two-dimensional radiography and bone histomorphometry, and should have a substantial impact not only on identifying novel anti-myeloma therapies, but also in studies to gain mechanistic insights to these novel therapies.
CFTR Modulator Therapy for Cystic Fibrosis
Authors: Hartmut Grasemann
Journal: New England Journal of Medicine (2017)

Cystic fibrosis is a disease of abnormal ion transport through epithelium that results in progressive lung disease as well as the involvement of other organs including the pancreas, gut, and liver. Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR), and inheritance is autosomal recessive, meaning that people with cystic fibrosis carry two CFTR mutations, one on each allele. In general, CFTR mutations cause reduced quantity or function of CFTR protein at the cell surface, but the specific mechanisms leading to CFTR deficiency are quite distinct among different classes of mutations (
Mechanisms, Consequences, and Prevention of Coronary Graft Failure
Authors: Mario Gaudino, Charalambos Antoniades, Umberto Benedetto, Saswata Deb, Antonino Di Franco, Gabriele Di Giammarco, Stephen Fremes, David Glineur, Juan Grau, Guo-Wei He, Daniele Marinelli, Lucas B. Ohmes, Carlo Patrono, John Puskas, Robert Tranbaugh, Leonard N. Girardi, David P. Taggart, Marc Ruel, Faisal G. Bakaeen
Journal: Circulation (2017)

Graft failure occurs in a sizeable proportion of coronary artery bypass conduits. We herein review relevant current evidence to give an overview of the incidence, pathophysiology, and clinical consequences of this multifactorial phenomenon. Thrombosis, endothelial dysfunction, vasospasm, and oxidative stress are different mechanisms associated with graft failure. Intrinsic morphological and functional features of the bypass conduits play a role in determining failure. Similarly, characteristics of the target coronary vessel, such as the severity of stenosis, the diameter, the extent of atherosclerotic burden, and previous endovascular interventions, are important determinants of graft outcome and must be taken into consideration at the time of surgery. Technical factors, such as the method used to harvest the conduits, the vasodilatory protocol, the storage solution, and the anastomotic technique, also play a major role in determining graft success. Furthermore, systemic atherosclerotic risk factors, such as age, sex, diabetes mellitus, hypertension, and dyslipidemia, have been variably associated with graft failure. The failure of a coronary graft is not always correlated with adverse clinical events, which vary according to the type, location, and reason for failed graft. Intraoperative flow verification and secondary prevention using antiplatelet and lipid-lowering agents can help reducing the incidence of graft failure.
Lear as an Aging Musician
Authors: Thomas Dorsett
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Abstract #5368: Pharicin A induces mitotic catastrophe by perturbing chromosome congression and spindle checkpoint
Authors: Ying Huang, Han-Zhang Xu, Ying-Li Wu, Han-Dong Sun, Wei Dai, Guo-Qiang Chen
Journal: Cancer Research (2009)

Microtubule poisons such as paclitaxel represent a potent and effective class of anticancer compounds. In the past decades, great efforts have been directed to identify novel natural products with a mode of action similar to paclitaxel but with a minimal side effect. In this study, we report the functional characterization of a new ent-kaurene diterpenoid termed pharicin A, which was originally isolated from Isodon xerophilus, a perennial shrub frequently used in Chinese folk medicine for tumor treatment. Pharicin A induces mitotic arrest in several cancer cell lines tested based on their morphology, DNA content, histone H3 serine-10 phosphorylation, and mitotic marker protein analyses. Pharicin A stabilizes the formation of mitotic spindles, which is coupled with an increased phosphorylation of Cdc27 and BubR1. Pharicin A treatment also results in an enhanced interaction between Cdc20 and spindle checkpoint components including Mad2 and BubR1. Moreover, pharicin A-induced mitotic arrest in HeLa cells is tightly associated with the presence of unaligned chromosomes at spindle pole regions, which are highly enriched in BubR1, CENP-E and Sgo1. Although pharicin A stabilizes microtubules both in vitro and in vivo, it induces mitotic arrest in paclitaxel-resistant cells. Combined, our study strongly suggests that pharicin A represents a novel class of small molecule compounds capable of perturbing the spindle checkpoint activation in tumor cells.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5368.
CEA decrease to predict DpR and clinical outcome in cetuximab therapy regardless of tumor sidedness: JACCRO CC-05/06
Authors: Yu Sunakawa, Akihito Tsuji, Tadamichi Denda, Yoshihiko Segawa, Yuji Negoro, Masato Nakamura, Ken Shimada, Masahito Kotaka, Masashi Fujii, Wataru Ichikawa
Journal: Annals of Oncology (2017)