tbuckley/cabot-search huggingface dataset:
A tribute to Arno Motulsky
Authors: George Stamatoyannopoulos
Journal: Journal of Clinical Investigation (2018)

Motulsky was born and raised in the then-German town of Fischhausen on the Baltic Sea, but with the rise of Nazism, his family realized that they had to leave Germany.His father left for Cuba, waiting for a visa to enter the United States, and, in 1939, Arno, his mother, and two siblings left Hamburg for Cuba on a ship named the St. Louis.Famously, the almost one thousand Jewish refugees on board were denied entry into any port of the Caribbean or the US, and the ship had to return to Europe.Motulsky and his family were allowed entry into Belgium, but when the Germans invaded that country in 1940, Arno, then 17 years old, ended up in an internment camp in France.In 1941, he successfully escaped, crossed Spain into Portugal, sailed to America, and joined his father in Chicago.In 1943, Arno joined the US army and, having been accepted to the University of Illinois Medical School, was assigned by the army to a specialized program for rapid training of young physicians.He was released from the army in 1946, finished medical school in 1947, and began a residency in internal medicine.He followed this with a fellowship in hematology at the Michael Reese Hospital in Chicago in the laboratory of Carl Singer, where his research focused on the molecular characterization of the hemoglobin of sickle cell patients using an immunological approach.These experiments were conducted before the electrophoretic demonstration of hemoglobin S by Linus Pauling that established the concept of molecular disease.Sickle cell anemia and the hemoglobinopathies remained one of Arno's interests for the rest of his life.When the Korean War erupted in 1951, Arno went back into the army and was assigned to work at Walter Reed Hospital in Washington, D.C., where he joined the hematology unit of William Crosby to study hemolytic anemias.
Scaling up HCV-DAA treatment in patients on opioid substitution therapy (OST) – does alcohol and cannabis diminish cure rates? Data from the German Hepatitis C-Registry (DHC-R)
Authors: S. Christensen, P. Buggisch, S. Mauss, K. Boeker, T. Müller, H. Klinker, T. Zimmermann, Y. Serfert, B. Weber, J. Reimer, H. Wedemeyer, D.H. C-Register
Journal: Journal of Hepatology (2018)
Abstract 15706: Increased Cardiac Expression of the Receptor for Advanced Glycation End Products is Associated With Myocardial Apoptosis in Patients Post Coronary Artery Bypass Grafting and in Mice Following Myocardial Infarction
Authors: James Tsoporis, Jean-Francois Desjardins, Shehla Izhar, Vasileios Salpeas, Ioannis K Rizos, Thomas G Parker
Journal: Circulation (2016)

Introduction: On-pump coronary artery bypass graft (CABG) surgery often induces a systemic inflammatory response leading to myocardial injury and additional cardiomyocyte apoptosis. The receptor fo...
Impact of Healthy Lifestyle Factors on Life Expectancies in the US Population
Authors: Yanping Li, An Pan, Dong D. Wang, Xiaoran Liu, Klodian Dhana, Oscar H. Franco, Stephen Kaptoge, Emanuele Di Angelantonio, Meir Stampfer, Walter C. Willett, Frank B. Hu
Journal: Circulation (2018)

Americans have a shorter life expectancy compared with residents of almost all other high-income countries. We aim to estimate the impact of lifestyle factors on premature mortality and life expectancy in the US population.
Correlation of autotaxin levels, serum bile acids, and pruritus in a multiple-dose, open-label, multinational study of the ileal bile acid transport inhibitor A4250
Authors: E. Gonzales, E. Sturm, U. Baumann, F. Lacaille, H. Arnell, B. Fischler, M.H. Jørgensen, R. Thompson, J. Mattsson, M. Ekelund, E. Lindstrom, P.-G. Gillberg, K. Torfgard, P. Soni
Journal: Journal of Hepatology (2018)
Silencing of Long Noncoding RNA <i>MIR22HG</i> Triggers Cell Survival/Death Signaling via Oncogenes YBX1, MET, and p21 in Lung Cancer
Authors: Wenmei Su, Shumei Feng, Xiuyuan Chen, Xia Yang, Rui Mao, Chunfang Guo, Zhuwen Wang, Dafydd G. Thomas, Jules Lin, Rishindra M. Reddy, Mark B. Orringer, Andrew C. Chang, Zhixiong Yang, David G. Beer, Guoan Chen
Journal: Cancer Research (2018)

Abstract The long noncoding RNA (lncRNA) MIR22HG has previously been identified as a prognostic marker in hepatocellular carcinoma. Here, we performed a comprehensive analysis of lncRNA expression profiles from RNA-Seq data and report that MIR22HG plays a similar role in lung cancer. Analysis of 918 lung cancer and normal lung tissues and lung cancer cell lines revealed that MIR22HG was significantly downregulated in lung cancer; this decreased expression was associated with poor patient survival. MIR22HG bound and stabilized the YBX1 protein. Silencing of MIR22HG triggered both cell survival and cell death signaling through dysregulation of the oncogenes YBX1, MET, and p21. In this MIR22HG network, p21 played an oncogenic role by promoting cell proliferation and antiapoptosis in lung cancers. MIR22HG played a tumor-suppressive role as indicated by inhibition of multiple cell cycle–related genes in human primary lung tumors. These data show that MIR22HG has potential as a new diagnostic and prognostic marker and as a therapeutic target for lung cancer. Significance: The lncRNA MIR22HG functions as a tumor suppressor, with potential use a diagnostic/prognostic marker and therapeutic target in lung cancer. Cancer Res; 78(12); 3207–19. ©2018 AACR.
Expression and clinical significance of KiSS-1 and E-cadherin in gastric cardia adenocarcinoma
Authors: Li Dong Wang, Xiao Shan Feng, Zhan Hui Wang, Gong Ping Wang, She Gan Gao, Jiang Tao Sun, Jian Qiang Mi, Tan You Shan, Zhi Feng Qu, Jing Han, Luo Zhang
Journal: Cancer Research (2007)

5450   To investigate the expression and clinical significance of KiSS -1 and E-cadherin in gastric cardia adenocarcinoma (GCA), the present study was undertaken to characterize the changes of KiSS-1 and E-cadherin in protein level on the subjects with normal gastric cardia epithelia (n = 20) and GCA (n = 80). The Streptavidin Peroxidase (SP) method was performed to determine the expression of KiSS-1 and E-cadherin. Of the 80 surgical resected GCA specimen, there were 48 subjects with lymph node metastasis. Immunohistochemistry results showed that the positive immunostaining rates for KiSS-1 and E-cadherin were 65% (13/20) and 80% (16/20) in normal gastric cardia epithelia, and 36% (29/80) and 40% (32/80) in GCA, respectively. The difference was significant (P
The outcome of acute-on-chronic liver failure in the intensive care is similar to a propensity matched ICU population without liver disease
Authors: S. van der Merwe, P. Meersseman, L. Langouche, H. Korf, J.D. Plessis, M. Mekeirele, D. Cassiman, W. Laleman, F. Nevens, A. Wilmer, G. Van den Berghe
Journal: Journal of Hepatology (2018)
Human beta-defensin-1 is a highly predictive marker of mortality in patients with acute-on-chronic liver failure
Authors: I. Mani, L. Vasilieva, A. Alexopoulou, E. Hadziyannis, D. Agiasotelli, T. Alexopoulos, D. Zampetas, S. Ntourakis
Journal: Journal of Hepatology (2018)
P463Engineering myocardial tissue in vitro using stretchable microfiber scaffolds and human iPSC-derived cardiomyocytes
Authors: A Van Mil, M Castilho, M Maher, C H Metz, RGC Maas, G Hochleitner, J Groll, K Ito, J Malda, JPG Sluijter
Journal: Cardiovascular Research (2018)
TCTAP C-093 Complex PCI for RCA Ostial Chronic Total Occlusion with Ostial Left Main Disease
Authors: Chun-Yuan Chu, Wen-Hsien Lee, Po-Chao Hsu, Hung-Hao Lee, Cheng-An Chiu, Ho-Ming Su, Tsung-Hsien Lin, Chee-Siong Lee, Heueh-Wei Yen, Wen-Chol Voon, Wen-Ter Lai, Sheng-Hsiung Sheu
Journal: Journal of the American College of Cardiology (2018)
Mutations and prognosis in myelodysplastic syndromes: karyotype-adjusted analysis of targeted sequencing in 300 consecutive cases and development of a genetic risk model
Authors: Naseema Gangat, Mythri Mudireddy, Terra L. Lasho, Christy M. Finke, Maura Nicolosi, Natasha Szuber, Mrinal M. Patnaik, Animesh Pardanani, Curtis A. Hanson, Rhett P. Ketterling, Ayalew Tefferi
Journal: American Journal of Hematology (2018)

Abstract To develop a genetic risk model for primary myelodysplastic syndromes (MDS), we queried the prognostic significance of next‐generation sequencing (NGS)‐derived mutations, in the context of the Mayo cytogenetic risk stratification, which includes high‐risk (monosomal karyotype; MK), intermediate‐risk (non‐MK, classified as intermediate/poor/very poor, per the revised international prognostic scoring system; IPSS‐R), and low‐risk (classified as good/very good, per IPSS‐R). Univariate analysis in 300 consecutive patients with primary MDS identified TP53 , RUNX1 , U2AF1 , ASXL1 , EZH2 , and SRSF2 mutations as “unfavorable” and SF3B1 as “favorable” risk factors for survival; for the purposes of the current study, the absence of SF3B1 mutation was accordingly dubbed as an “adverse” mutation. Analysis adjusted for age and MK, based on our previous observation of significant clustering between MK and TP53 mutations, confirmed independent prognostic contribution from RUNX1 , ASXL1 , and SF3B1 mutations. Multivariable analysis that included age, the Mayo cytogenetics risk model and the number of adverse mutations resulted in HRs (95% CI) of 5.3 (2.5‐10.3) for presence of three adverse mutations, 2.4 (1.6‐3.7) for presence of two adverse mutations, 1.5 (1.02‐2.2) for presence of one adverse mutation, 5.6 (3.4‐9.1) for high‐risk karyotype, 1.5 (1.1‐2.2) for intermediate‐risk karyotype and 2.4 (1.8‐3.3) for age &gt;70 years; HR‐weighted risk point assignment generated a three‐tiered genetic risk model: high ( N = 65; 5‐year survival 2%), intermediate ( N = 100; 5‐year survival 18%), and low ( N = 135; 5‐year survival 56%). The current study provides a practically simple risk model in MDS that is based on age, karyotype, and mutations only.
Hepatic safety and biomarker assessments in sorafenib-experienced patients with advanced hepatocellular carcinoma treated with nivolumab in the CheckMate-040 study
Authors: T. Meyer, I. Melero, T. Yau, C. Hsu, M. Kudo, S.-P. Choo, J. Trojan, T. Welling, Y-K. Kang, W. Yeo, A. Chopra, A. Baakili, C.D. Cruz, H. Zhao, J. Neely, T. Crocenzi, A. El-Khoureiry, B. Sangro
Journal: Journal of Hepatology (2018)
Lympho- and Myeloproliferative Malignancies Occurring in the Same Host: Descripton of a Nationwide Discovery Cohort
Authors: JM Holst, TL Plesner, MB Pedersen, Henrik Frederiksen, MB Møller, M.R. Clausen, M. Ludvigsen, HB Ommen, J Stentoft, R. Wang, W Tam, G. Inghirami, Francesco Annibale D'Amore
Journal: Blood (2017)
A Real Life Evaluation of Efficacy and Safety of Ponatinib Therapy in CML Patients
Authors: Luigia Luciano, Giorgina Specchia, Bruno Martino, Vincenzo Accurso, Marco Santoro, Alessandra Malato, Nicola Sgherza, Michele Pizzuti, Fabio Stagno, Pellegrino Musto, Attilio Guarini, Fiorenza De Gregorio, Santina Basile, Fabrizio Pane
Journal: Blood (2017)
Gonadotropin-Releasing Hormone Agonists During Chemotherapy for Preservation of Ovarian Function and Fertility in Premenopausal Patients With Early Breast Cancer: A Systematic Review and Meta-Analysis of Individual Patient–Level Data
Authors: Matteo Lambertini, Halle C.F. Moore, Robert C.F. Leonard, Sibylle Loibl, Pamela Munster, Marco Bruzzone, Luca Boni, Joseph M. Unger, Richard A. Anderson, Keyur Mehta, Susan Minton, Francesca Poggio, Kathy S. Albain, Douglas J.A. Adamson, Bernd Gerber, Amy Cripps, Gianfilippo Bertelli, Sabine Seiler, Marcello Ceppi, Ann H. Partridge, Lucia Del Mastro
Journal: Journal of Clinical Oncology (2018)

Purpose The role of temporary ovarian suppression with gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy as a strategy to preserve ovarian function and fertility in premenopausal women remains controversial. This systematic review and meta-analysis using individual patient-level data was conducted to better assess the efficacy and safety of this strategy in patients with early breast cancer. Methods The trials in which premenopausal women with early breast cancer were randomly assigned to receive (neo)adjuvant chemotherapy alone or with concurrent GnRHa were eligible for inclusion. Primary end points were premature ovarian insufficiency (POI) rate and post-treatment pregnancy rate. Disease-free survival and overall survival were secondary end points. Because each study represents a cluster, statistical analyses were performed using a random effects model. Results A total of 873 patients from five trials were included. POI rate was 14.1% in the GnRHa group and 30.9% in the control group (adjusted odds ratio, 0.38; 95% CI, 0.26 to 0.57; P < .001). A total of 37 (10.3%) patients had at least one post-treatment pregnancy in the GnRHa group and 20 (5.5%) in the control group (incidence rate ratio, 1.83; 95% CI, 1.06 to 3.15; P = .030). No significant differences in disease-free survival (adjusted hazard ratio, 1.01; 95% CI, 0.72 to 1.42; P = .999) and overall survival (adjusted hazard ratio, 0.67; 95% CI, 0.42 to 1.06; P = .083) were observed between groups. Conclusion Our findings provide evidence for the efficacy and safety of temporary ovarian suppression with GnRHa during chemotherapy as an available option to reduce the likelihood of chemotherapy-induced POI and potentially improve future fertility in premenopausal patients with early breast cancer.
Prognostic value of neutrophil-to-lymphocyte ratio (NLR) in intestinal neuroendocrine tumors: An analysis of the U.S. Neuroendocrine Tumor Study Group.
Authors: Bradley A. Krasnick, Jesse T Davidson, Roheena Z. Panni, Martha McGilvray, Jorge Zarate Rodriguez, Alexandra G Lopez-Aguiar, Mary Dillhoff, Eliza W Beal, George A. Poultsides, Eleftherios Makris, Flavio G. Rocha, Angelena Crown, Kamran Idrees, William G. Hawkins, Steven M. Strasberg, Chet Hammill, William C. Chapman, Maria Majella Doyle, Shishir Maithel, Ryan Fields
Journal: Journal of Clinical Oncology (2018)

694 Background: Intestinal neuroendocrine tumors (NETs) can often be indolent, with survival commonly exceeding 10 years. However, a subset can be more aggressive. The search for a prognostic test based on preoperative lab results would be of benefit. An elevated NLR has been found to be predictive of diminished overall survival (OS) in several cancers, and we hypothesized that this same trend would hold true for intestinal NETs. Methods: Utilizing the 8 member institutions of the retrospective U.S. NET Study Group, patients undergoing resection of intestinal NETs were included. After excluding patients undergoing emergent surgery, those with preoperative sepsis or distant mets, and those with missing neutrophil/lymphocyte lab values, 281 patients were included for analysis. The cutoff values for NLR were determined using receiver operator curve (ROC) analysis. Univariate analysis was performed based on these groups. A Kaplan-Meier survival curve was created based off optimal NLR from ROC analysis. OS was calculated as date of surgery to date of death/ last follow-up. SPSS 23.0 was used for analysis. Results: Of the 281 patients identified, 9% were appendiceal, 9% colonic, 21% duodenal, 5% rectal, and 56% jejunal/ileal. Using a NLR of &gt;2.47, the ROC area under the curve was 0.609 ( p=0.002). Median survival for the 130 patients in the &lt;2.47 group was 159.8 months, versus 115.63 months in the ≥2.47 group (p =0.009). When comparing the NLR &lt;2.47 and ≥2.47 groups, mean age (57.5 vs. 59.0 years, respectively, p=0.642), ASA status (89% ASA 2 /3 in both groups, p=0.314), tumor Ki-67 status (Ki-67&gt;3% in 30% vs. 26%, respectively, p=0.57), and post-op complications (36 vs. 42%, respectively, p=0.310) were similar between groups. A significantly greater number of patients in the NLR high group had positive lymph nodes (60 vs. 47%, p =0.002). Conclusions: For patients undergoing curative resection of intestinal NETs with no distant mets, a preoperative NLR of ≥2.47 was significantly predictive of decreased OS, with those in the elevated NLR group having an OS 3.7 years less than those in the &lt;2.47 group. Future prospective data is warranted to further validate these findings.
Identification of the WAP 4-disulfide core domain 1 as a putative tumor suppressor gene in melanoma
Authors: Suhu Liu, Paul Howell, Suping Ren, Rajeev Samant, Adam Riker
Journal: Cancer Research (2008)

4278  Identification of the WAP four-disulfide core domain 1 as a putative tumor suppressor gene in melanoma  Introduction:  The WAP four-disulfide core domain 1 (WFDC1, PS20) gene functions as a secreted serine protease inhibitor previously shown to be a growth suppressor and putative tumor suppressor gene in prostate cancer. Here, we have identified the significant down-regulation of WFDC1 gene expression in human melanoma cells, further showing that WFDC1 re-expression is associated with a marked inhibition of tumor growth in a xenograft model.  Methods:  Comparative gene expression profiling was performed on 15 primary (PM) and 40 metastatic melanoma (MM) samples. Real-time quantitative RT-PCR (qRT-PCR) and Western blots were performed on newly established, short-term passaged, daughter melanoma cell lines. Promoter methylation status of WFDC1 was analyzed by Methylation-Specific Sequencing (MSS), followed by quantitative methylation-specific PCR (Q-MSP) in order to detect WFDC1 promoter methylation frequency. We also utilized the established melanoma cell line A375 (WFDC1 negative gene expression) to stably transfect the WFDC1 gene for further functional analysis.  Results:  cDNA microarray analysis revealed the reduced expression of WFDC1 in MM compared to PM samples, confirmed with qRT-PCR. Semi-quantitative RT-PCR demonstrated complete loss or reduced expression of WFDC1 mRNA in 7/16 (44%) melanoma cell lines. Western blot analysis showed WFDC1 as a secreted protein expressed by normal human epithelial melanocytes (NHEM), with reduced or lost protein expression in ~50% of melanoma cell lines. MSS analysis revealed DNA hypermethylation of promoter regions correlated with reduced or loss of WFDC1 expression in melanoma cell lines. Treatment with the demethylation agent, azacytidine, restored the mRNA and protein expression of WFDC1. The addition of Trichostatin A, a histone deacetylase inhibitor, did not show a synergistic effect upon WFDC1 gene expression. Q-MSP revealed 6/20 (30%) melanoma cell lines and 10/40 (25%) freshly procured melanoma tissues showing WFDC1 promoter hypermethylation. Cell cycle analysis, proliferation and invasion [scratch] assays did not show significant differences between control and stable WFDC1 transfectants. However, significant tumor growth inhibition was observed in a xenograft murine model with the WFDC1 stably transfected cell line.  Conclusion:  WFDC1 gene expression is markedly reduced or completely lost in ~50% of all melanoma samples examined. We show evidence that CpG island promoter DNA hypermethylation appears to be a dominant mechanism of gene silencing in several melanoma samples. Re-introduction of WFDC1 into melanoma cell lines lead to a significant level of tumor growth inhibition in a xenograft murine model. Further analysis is ongoing as to the cellular and molecular mechanisms involved in this process.
rBPI<sub>21</sub> (opebacan) promotes rapid trilineage hematopoietic recovery in a murine model of high‐dose total body irradiation
Authors: Kenneth J. Janec, Huaiping Yuan, James E. Norton Jr, Rowan H. Kelner, Christian K. Hirt, Rebecca A. Betensky, Eva C. Guinan
Journal: American Journal of Hematology (2018)

Abstract The complexity of providing adequate care after radiation exposure has drawn increasing attention. While most therapeutic development has focused on improving survival at lethal radiation doses, acute hematopoietic syndrome (AHS) occurs at substantially lower exposures. Thus, it is likely that a large proportion of such a radiation‐exposed population will manifest AHS of variable degree and that the medical and socioeconomic costs of AHS will accrue. Here, we examined the potential of rBPI 21 (opebacan), used without supportive care, to accelerate hematopoietic recovery after radiation where expected survival was substantial (42%‐75%) at 30 days. rBPI 21 administration was associated with accelerated recovery of hematopoietic precursors and normal marrow cellularity, with increases in megakaryocyte numbers particularly marked. This translated into attaining normal trilineage peripheral blood counts 2‐3 weeks earlier than controls. Elevations of hematopoietic growth factors observed in plasma and the marrow microenvironment suggest the mechanism is likely multifactorial and not confined to known endotoxin‐neutralizing and cytokine downmodulating activities of rBPI 21 . These observations deserve further exploration in radiation models and other settings where inadequate hematopoiesis is a prominent feature. These experiments also model the potential of therapeutics to limit the allocation of scarce resources after catastrophic exposures as an endpoint independent of lethality mitigation.
FIRST CLINICAL RESULTS WITH A NOVEL EUS-GUIDED THROUGH-THE-NEEDLE MICROBIOPSY FORCEPS FOR IMPROVED DIAGNOSTICS OF PANCREATIC CYSTS
Authors: B Kovacevic, J Gásdal Karstensen, P Klausen, A Toxværd, E Kalaitzakis, C Vestrup Rift, JH Storkholm, C Palnæs Hansen, J Preuss Hasselby, P Vilmann
Journal: Endoscopy (2018)

Pancreatic cysts represent a diagnostic dilemma as some of them may harbor malignancy or have potential for malignant transformation. Recently, a novel biopsy forceps (Moray™) has become available allowing endoscopic ultrasound (EUS) guided procurement of microbiopsy material from the cyst wall. There is at present very little experience with this device. The aim of this study was to evaluate the use of the micro-forceps in a clinical setting.
Real life experience with selective internal radiation therapy (SIRT) as part of multimodality treatment of advanced hepatocellular carcinoma (HCC)
Authors: F. van Boemmel, M. Asmus, T.-O. Petersen, T. Kahn, T. Lincke, S. Purz, S. Osama, D. Forstmeyer, F. Lordick, C. Domaratius, F. Gerhardt, D. Seehofer, R. Sucher, T. Berg
Journal: Journal of Hepatology (2018)
Voluntary Stopping Eating and Drinking Among Patients With Serious Advanced Illness—A Label in Search of a Problem?—Reply
Authors: Timothy E. Quill, Linda Ganzini, Robert D. Truog, Thaddeus Mason Pope
Journal: JAMA Internal Medicine (2018)

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