tbuckley/cabot-search huggingface dataset:
Variation in Endoscopic Activity Assessment and Endoscopy Score Validation in Adults With Eosinophilic Esophagitis
Authors: Alain M. Schoepfer, Ikuo Hirano, Michael Coslovsky, Marie C. Roumet, Marcel Zwahlen, Claudia E. Kuehni, David Hafner, Jeffrey A. Alexander, Evan S. Dellon, Nirmala Gonsalves, John Leung, Christian Bussmann, Margaret H. Collins, Robert O. Newbury, Thomas C. Smyrk, John T. Woosley, Guang-Yu Yang, Yvonne Romero, David A. Katzka, Glenn T. Furuta, Sandeep K. Gupta, Seema S. Aceves, Mirna Chehade, Jonathan M. Spergel, Gary W. Falk, Brian A. Meltzer, Gail M. Comer, Alex Straumann, Ekaterina Safroneeva, Sami R. Achem, Amindra S. Arora, Oral Alpan, David Armstrong, Stephen E. Attwood, Joseph H. Butterfield, Michael D. Crowell, Kenneth R. DeVault, Eric Drouin, Benjamin Enav, Felicity T. Enders, David E. Fleischer, Amy Foxx-Orenstein, Dawn L. Francis, Gordon H. Guyatt, Lucinda A. Harris, Amir F. Kagalwalla, Hirohito Kita, Murli Krishna, James J. Lee, John C. Lewis, Kaiser Lim, G. Richard Locke, Joseph A. Murray, Cuong C. Nguyen, Diana M. Orbelo, Shabana F. Pasha, Francisco C. Ramirez, Javed Sheikh, Sarah B. Umar, Catherine R. Weiler, John M. Wo, Tsung-Teh Wu, Kathleen J. Yost
Journal: Clinical Gastroenterology and Hepatology (2018)
Abstract 16060: The Role of Gli1 in Polycystic Kidney Disease Endothelial Cells
Authors: Federico Franchi, Karen M Peterson, Ezequiel J Tolosa, Peter C Harris, Martin E Fernandez-Zapico, Martin G Rodriguez-Porcel
Journal: Circulation (2017)

Introduction: We have recently reported that Polycystic Kidney Disease (PKD), a common renal ciliopathy, has vascular defects even prior to the development of hypertension or renal dysfunction. The...
Intra-breath measures of respiratory mechanics in healthy African infants detect risk of respiratory illness in early life
Authors: Diane M. Gray, Dorottya Czovek, Lauren McMillan, Lidija Turkovic, Jacob A.M. Stadler, Anessa Vanker, Bence L. Radics, Zoltán Gingl, Graham L. Hall, Peter D. Sly, Heather J. Zar, Zoltán Hantos
Journal: European Respiratory Journal (2018)

Lower respiratory tract illness (LRTI) is a leading cause of mortality and morbidity in children. Sensitive and noninvasive infant lung function techniques are needed to measure risk for and impact of LRTI on lung health. The objective of this study was to investigate whether lung function derived from the intra-breath forced oscillation technique (FOT) was able to identify healthy infants at risk of LRTI in the first year of life.Lung function was measured with the novel intra-breath FOT, in 6-week-old infants in a South African birth cohort (Drakenstein Child Health Study). LRTI during the first year was confirmed by study staff. The association between baseline lung function and LRTI was assessed with logistic regression and odds ratios determined using optimal cut-off values.Of the 627 healthy infants with successful lung function testing, 161 (24%) had 238 LRTI episodes subsequently during the first year. Volume dependence of respiratory resistance (ΔR) and reactance (ΔX) was associated with LRTI. The predictive value was stronger if LRTI was recurrent (n=50 (31%): OR 2.5, ΔX), required hospitalisation (n=38 (16%): OR 5.4, ΔR) or was associated with wheeze (n=87 (37%): OR 3.9, ΔX).Intra-breath FOT can identify healthy infants at risk of developing LRTI, wheezing or severe illness in the first year of life.
Inhibition of monoacylglycerol lipase for the treatment of liver disease: tempting but still playing with fire
Authors: Claus Hellerbrand
Journal: Gut (2018)

Lipolytic enzymes have received huge attention due to their crucial role in lipid metabolism and as potential pharmacological targets against obesity and its related disorders. Non-alcoholic fatty liver disease (NAFLD) is highly associated with obesity and today, NAFLD is considered to be the most common chronic liver disorders worldwide.1 The NAFLD pathology covers a wide spectrum of changes, ranging from simple steatosis to non-alcoholic steatohepatitis, progressive fibrosis/cirrhosis and hepatocellular carcinoma (HCC). The underlying mechanisms, particularly those that drive disease progression, are only incompletely understood.1 Central drivers appear to be quantitative and qualitative alterations in lipid metabolic pathways in hepatocytes.1 2 In addition, the impact of altered lipid metabolism in non-parenchymal liver cells and immune cells is increasingly recognised.1 3 Importantly, lipids are stored within the cells and act as signalling molecules or precursors thereof, which further enhances the level of complexity how alterations in the lipid metabolism affect the course of obesity-related diseases.

In this regard, monoacylglycerol lipase (MAGL) plays a particularly critical role.4 In the 70th of the last century, MAGL was originally purified from adipose tissue, where it was found to be most abundant besides the brain and the liver.4 Traditionally, MAGL functions as a key lipolytic enzyme in the mobilisation of lipid stores for energy supply or lipid synthesis. MAGL is the rate-limiting enzyme in the hydrolysis of monoacylglyerides (MG) into glycerol and fatty acids. MGs are intermediary lipids deriving from the degradation of phospholipids and neutral lipids. In addition to its role in MG metabolisms, MAGL is a critical component of the endocannabinoid system, as it is catalysing the hydrolysis of 2-arachidonoyl glycerol (2-AG), the most abundant endogenous agonist of cannabinoid receptors in the body. Furthermore, 2-AG is an important source for arachidonic …
Primary results of ALESIA: Phase III, randomised open-label study of alectinib (ALC) vs crizotinib (CRZ) in Asian patients (pts) with treatment-naïve ALK+ advanced non-small-cell lung cancer (NSCLC)
Authors: C. Zhou, Y. Lu, S.-W. Kim, T. Reungwetwattana, J. Zhou, Y. Zhang, J. He, J.-J. Yang, Y. Cheng, S.H. Lee, L. Bu, T. Xu, L. Yang, C. Wang, P.N. Morcos, E. Mitry, Z. Li
Journal: Annals of Oncology (2018)
Second round results from the Manchester ‘Lung Health Check’ community-based targeted lung cancer screening pilot
Authors: Phil A Crosbie, Haval Balata, Matthew Evison, Melanie Atack, Val Bayliss-Brideaux, Denis Colligan, Rebecca Duerden, Josephine Eaglesfield, Timothy Edwards, Peter Elton, Julie Foster, Melanie Greaves, Graham Hayler, Coral Higgins, John Howells, Klaus Irion, Devinda Karunaratne, Jodie Kelly, Zoe King, Judith Lyons, Sarah Manson, Stuart Mellor, Donna Miller, Amanda Myerscough, Tom Newton, Michelle O’Leary, Rachel Pearson, Julie Pickford, Richard Sawyer, Nick J Screaton, Anna Sharman, Maggi Simmons, Elaine Smith, Ben Taylor, Sarah Taylor, Anna Walsham, Angela Watts, James Whittaker, Laura Yarnell, Anthony Threlfall, Phil V Barber, Janet Tonge, Richard Booton
Journal: Thorax (2018)

We report results from the second annual screening round (T1) of Manchester’s ‘Lung Health Check’ pilot of community-based lung cancer screening in deprived areas (undertaken June to August 2017). Screening adherence was 90% (n=1194/1323): 92% of CT scans were classified negative, 6% indeterminate and 2.5% positive; there were no interval cancers. Lung cancer incidence was 1.6% (n=19), 79% stage I, treatments included surgery (42%, n=9), stereotactic ablative radiotherapy (26%, n=5) and radical radiotherapy (5%, n=1). False-positive rate was 34.5% (n=10/29), representing 0.8% of T1 participants (n=10/1194). Targeted community-based lung cancer screening promotes high screening adherence and detects high rates of early stage lung cancer.
Abstract 13715: Colchicine Acutely Suppresses the NLRP3 Inflammasome in Acute Coronary Syndrome Patients Monocytes
Authors: Stacy Robertson, Cloe Payet, Gonzalo J Martinez, Jennifer Barraclough, David Celermajer, Christina Bursill, Sanjay Patel
Journal: Circulation (2015)

Objectives: Inflammasome activation, with subsequent release of pro-inflammatory cytokines IL-1β and IL-18, has recently been implicated in atherosclerosis-associated inflammation. Here, in acute coronary syndrome (ACS) patients, we assessed (1) inflammasome activation in circulating monocytes and (2) whether short-term oral colchicine, a recognized anti-inflammatory agent that has been shown to be cardio-protective in clinical studies, might acutely suppress inflammasome-dependent inflammation. Methods: ACS patients (n=21) were randomized to oral colchicine (1.5mg) or no treatment, and compared with untreated healthy controls. Venous samples were drawn pre- (day 1) and 24h post- (day 2) treatment. Cultured monocytes were stimulated with ATP which facilitates the release of cleaved cytokines. Analysis of key inflammasome markers was performed in cell media and lysates. Results: Monocytes from untreated ACS patients secreted significantly higher levels of cleaved IL-1β and IL-18 vs healthy controls (p&lt;0.05 for both; Fig A). Colchicine treatment in ACS patients markedly reduced intracellular pro- and cleaved IL-1β protein levels as well as secreted cleaved IL-1β protein levels (Fig A) vs pre-treatment levels. Colchicine treatment significantly reduced pro-caspase-1 mRNA levels and secreted caspase1 protein levels (p&lt;0.05) vs untreated patients (Fig B). IL-18 levels were unaffected by treatment. In untreated ACS patients, inflammasome-related protein levels did not significantly change between day 1 and day 2 Conclusion: We show here, for the first time, that (1) monocytes from ACS patients are “primed” to secrete inflammasome-related cytokines and (2) short-term colchicine acutely and markedly suppresses monocyte caspase-1 activity, thereby reducing cellular protein secretion of IL-1β. These data, therefore, provide mechanistic insights into a potential role for colchicine in suppressing coronary inflammation in ACS patients.
Acute myeloid leukemia with minimal differentiation (AML M0) mimicking acute lymphoblastic leukemia
Authors: Vignesh Shanmugam, David M. Dorfman
Journal: American Journal of Hematology (2018)

A 68-year-old man presented with a history of several months of weakness and weight loss, and was found to be pancytopenic (WBC = 2.02 K/μL, hemoglobin = 8.1 g/dL, hematocrit = 24.4%, platelet count = 23 K/μL). Bone marrow aspiration and biopsy revealed the presence of 45% minimally differentiated blasts with scant, agranular cytoplasm (Image 1A) with coarse, granular, block-like periodic acid-Schiff (PAS) positivity (Image 1B), raising the possibility of acute lymphoblastic leukemia. Flow cytometric analysis revealed that the blasts, gated based on dim CD45 and minimal side scatter (Image 1C; red cells), were positive for CD34, myeloid markers CD13 and CD117, HLA-DR, and terminal deoxynucleotidyl transferase (TdT), and negative for myeloperoxidase (MPO), and other myeloid and monocytic markers (Image 1C). A small subset of blasts appeared to be weakly positive for B-cell markers CD19 (Image 1C) and CD22 and for T-cell marker CD7, but were negative for other B- and T-cell markers. Immunostaining of the bone marrow biopsy revealed the presence of 40% CD34-positive blasts that were negative for B-cell markers CD19, CD22, CD79a. Cytogenetic analysis revealed the presence of trisomy eight in a subset of cells (47,XY, +8[9]/46,XY[11]). Based on the expression of two myeloid markers by flow cytometric analysis, and the absence of significant staining for lymphoid markers, the patient was diagnosed with acute myeloid leukemia with minimal differentiation (AML M0). AML M0 typically occurs in infants and older adults, and shows no morphologic or cytochemical evidence of myeloid differentiation. Blasts often resemble lymphoblasts, as in the current case, with agranular cytoplasm and absence of cytochemical staining for MPO and other myeloid markers. Coarse, granular, block-like PAS positivity is typically seen in acute lymphoblastic leukemia; however, PAS positivity has also been reported in cases of acute myeloid leukemia. In AML M0, evidence of myeloid differentiation is based on expression of at least two myeloid markers by immunostaining, usually CD13 and CD117, as seen in the current case. TdT positivity, typically observed in cases of acute lymphoblastic leukemia, is seen in 50% of cases of AML M0, but blasts are negative for B- and T-cell markers. In contrast, in acute undifferentiated leukemia, blasts express no more than one membrane marker for myeloid lineage, and are negative for MPO, T-cell marker CD3, and do not exhibit strong staining for B-cell marker CD19. AML M0 may exhibit complex karyotypes and unbalanced abnormalities, such as −5, del(5q), −7, del(7q), +8, as seen in the current case, and del(11q). This case illustrates how AML M0 may have a morphologic and cytochemical appearance of acute lymphoblastic leukemia, including cytochemical staining for PAS and immunostaining for TdT. It is important to recognize that these cases are of myeloid origin, so that patients may be treated with appropriate therapy for AML.
Abstract 9473: Quantifying the Impact of Early Term Gestation Delivery Upon Resource Demands Following Neonatal Congenital Heart Surgery
Authors: Andrew H Smith, David A Parra, Bret A Mettler, David P Bichell, Ann Kavanaugh-McHugh
Journal: Circulation (2014)

Background: Evidence suggests inferior outcomes among term neonates with serious congenital heart disease delivered at 37 through 38 weeks (early term) gestation compared to their term (39 through ...
Abstract 16970: Statin Reduce Mortality and Major Cardiovascular Events in End-stage Renal Disease Patient, a Taiwan Cohort Study
Authors: Kai-Hung Cheng, Chih-Sheng Chu, Yu-Han Chang, Tzongshi Lu, Wen-Ter Lai
Journal: Circulation (2015)

Introduction and Hypothesis: Coronary artery disease (CAD) is the leading cause of mortality in end-stage renal disease (ESRD) patients. Vitamin D deficiency is common in patients with ESRD, and therapeutic use of Calcitriol may improve cardiovascular outcomes. Studies indicate that Statin can reduce incidences of major adverse cardiac events (MACE), and mortality in CAD. However, both 4D and AURORA studies report Statin cannot reduce MACE and mortality in ESRD patients. The goal of our study is to assess the effects of Statin and Calcitriol administration in ESRD. Methods: A total of 837 subjects selected from 12342 ESRD patients from Taiwan’s National Health Insurance Research Database were stratified into four groups (Control (n=498), S: Statin (n=131), C: Calcitriol (n=130), SC: Statin and Calcitriol (n=78)). We analyze their mediation history for twelve years since their ESRD diagnosed. One way ANOVA with Bonferroni correction, chi-square test, fisher's exact and Cox proportional hazard regression were used for statistics. Statistical significances were set at a P&lt; 0.05. Results: Our data (Adjusted Hazard Ratio (HR), 95% Confidence Interval (CI)) showed that mortality was significant reduced when treated with Statin (0.6, 0.43-0.84), Calcitriol, (0.5, 0.35-0.72), Statin and Calcitriol (0.51, 0.31-0.82) in comparison with control group, respectively. Interestingly, these significant changes were first observed at 10th-year in S and SC groups, but at 12th-year in C group. In addition, Statin reduced MACE (0.55, 0.37-0.81) and heart failure (0.51, 0.27-0.95) incidences. Furthermore, Calcitriol also reduced MACE (0.37, 0.23-0.59), stroke (0.34, 0.16-0.72) and heart failure (0.46, 0.25-0.86) incidences as well as SC treatment decreased MACE (0.38, 0.22-0.68), stroke (0.45, 0.21-0.97), and heart failure (0.26, 0.09-0.73) incidences. Conclusions: Our data show for the first time that Statin alone can reduce incidences of mortality, MACE and heart failure but not stroke in ESRD. And, combination of Statin and Calcitriol provides best outcomes in ESRD patients with heart failure among these groups. This finding may provide important information in developing therapeutic strategies for the roles of Statin and Calcitriol in ESRD.
Retrospective analysis of efficacy and safety of cell-free and concentrated ascites reinfusion therapy in pancreatic cancer patients with malignant ascites
Authors: K. Harada, Y. Kobayashi, S. Nozawa, K. Sakurai, K. Suto, A. Yoshikawa, R. Sasaki, R. Abiko, H. Ebata, I. Sano, H. Oda, T. Miyagishima
Journal: Annals of Oncology (2018)
Whole-Genome Sequencing to Characterize Monogenic and Polygenic Contributions in Patients Hospitalized With Early-Onset Myocardial Infarction
Authors: Amit V. Khera, Mark Chaffin, Seyedeh M. Zekavat, Ryan L. Collins, Carolina Roselli, Pradeep Natarajan, Judith H. Lichtman, Gail D’Onofrio, Jennifer Mattera, Rachel Dreyer, John A. Spertus, Kent D. Taylor, Bruce M. Psaty, Stephen S. Rich, Wendy Post, Namrata Gupta, Stacey Gabriel, Eric Lander, Yii-Der Ida Chen, Michael E. Talkowski, Jerome I. Rotter, Harlan M. Krumholz, Sekar Kathiresan
Journal: Circulation (2019)

Background: The relative prevalence and clinical importance of monogenic mutations related to familial hypercholesterolemia and of high polygenic score (cumulative impact of many common variants) pathways for early-onset myocardial infarction remain uncertain. Whole-genome sequencing enables simultaneous ascertainment of both monogenic mutations and polygenic score for each individual. Methods: We performed deep-coverage whole-genome sequencing of 2081 patients from 4 racial subgroups hospitalized in the United States with early-onset myocardial infarction (age ≤55 years) recruited with a 2:1 female-to-male enrollment design. We compared these genomes with those of 3761 population-based control subjects. We first identified individuals with a rare, monogenic mutation related to familial hypercholesterolemia. Second, we calculated a recently developed polygenic score of 6.6 million common DNA variants to quantify the cumulative susceptibility conferred by common variants. We defined high polygenic score as the top 5% of the control distribution because this cutoff has previously been shown to confer similar risk to that of familial hypercholesterolemia mutations. Results: The mean age of the 2081 patients presenting with early-onset myocardial infarction was 48 years, and 66% were female. A familial hypercholesterolemia mutation was present in 36 of these patients (1.7%) and was associated with a 3.8-fold (95% CI, 2.1–6.8; P &lt;0.001) increased odds of myocardial infarction. Of the patients with early-onset myocardial infarction, 359 (17.3%) carried a high polygenic score, associated with a 3.7-fold (95% CI, 3.1–4.6; P &lt;0.001) increased odds. Mean estimated untreated low-density lipoprotein cholesterol was 206 mg/dL in those with a familial hypercholesterolemia mutation, 132 mg/dL in those with high polygenic score, and 122 mg/dL in those in the remainder of the population. Although associated with increased risk in all racial groups, high polygenic score demonstrated the strongest association in white participants ( P for heterogeneity=0.008). Conclusions: Both familial hypercholesterolemia mutations and high polygenic score are associated with a &gt;3-fold increased odds of early-onset myocardial infarction. However, high polygenic score has a 10-fold higher prevalence among patients presents with early-onset myocardial infarction. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00597922.
Dynamic molecular monitoring reveals that SWI–SNF mutations mediate resistance to ibrutinib plus venetoclax in mantle cell lymphoma
Authors: Rishu Agarwal, Yih-Chih Chan, Constantine S. Tam, Tane Hunter, Dane Vassiliadis, Charis E. Teh, Rachel Thijssen, Paul Yeh, Stephen Q. Wong, Sarah Ftouni, Enid Y. N. Lam, Mary Ann Anderson, Christiane Pott, Omer Gilan, Charles C. Bell, Kathy Knezevic, Piers Blombery, Kathleen Rayeroux, Adrian Zordan, Jason Li, David C. S. Huang, Meaghan Wall, John F. Seymour, Daniel H. D. Gray, Andrew W. Roberts, Mark A. Dawson, Sarah-Jane Dawson
Journal: Nature Medicine (2018)
Relapses After CAR-T Therapy
Authors: Jennifer Abbasi
Journal: JAMA (2018)

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Safety and efficacy of midostaurin in patients with newly diagnosed FLT3-mutated AML
Authors: P.-N. Wang, A.Y.H. Leung, J.H. Jang, S. Voloshin, L. O'Sullivan-Djentuh, K. Suzuki, S. Ifrah, G. Le Gouadec, T. Kakizume, H. Kitagawa, K. Malek, Y. Miyazaki
Journal: Annals of Oncology (2018)
Long-term mechanical function and integration of an implanted tissue-engineered intervertebral disc
Authors: Sarah E. Gullbrand, Beth G. Ashinsky, Edward D. Bonnevie, Dong Hwa Kim, Julie B. Engiles, Lachlan J. Smith, Dawn M. Elliott, Thomas P. Schaer, Harvey E. Smith, Robert L. Mauck
Journal: Science Translational Medicine (2018)

Tissue-engineered intervertebral discs demonstrate long-term functional integration in rat and goat disc replacement models.
Primary resistance mechanisms revealed in Asian TKI-sensitizing EGFR mutations NSCLC patient populations
Authors: Q.-X. Zhang, C. Xu, W.-X. Wang, W. Zhuang, Z.-B. Song, Y.-C. Zhu, Y.-P. Chen, G. Chen, M.-Y. Fang, T.-F. Lv, Y. Song
Journal: Annals of Oncology (2018)
Breast-tumor-targeted therapy with a Salmonella typhimurium LEU-ARG auxotroph
Authors: Ming Zhao, Meng Yang, Xiao-Ming Li, Xiuying Tan, Skukuan Li, Huaiyu Ma, Zhijian Yang, Robert M. Hoffman
Journal: Cancer Research (2006)

2171  We have previously developed an auxotrophic bacteria strain (A1) of Salmonella typhimurium that requires Leu and Arg that selectively targets the human PC-3 prostate in nude mouse models. The A1 strain selectively grew in the prostate tumors causing tumor regression. In sharp contrast, normal tissue is cleared of A1 bacteria even in nude mice with no apparent side effects. A1 is Leu/Arg-dependent but receives sufficient nutritional support from the neoplastic tissue. A1 grew throughout the tumor, including viable malignant tissue. This in contrast to anaerobic bacterial species and strains previously developed for cancer therapy where growth was confined to necrotic or hypoxic areas of the tumor. Growth in viable regions of the tumor may account, in part, for the A1’s unique antitumor efficacy. In the present report, in order to increase and broaden A1’s tumor-targeting capability, A1 sublines were re-isolated after infection of human colon tumors growing in nude mice. A tumor-isolated A1 subline (A1-1) had increased targeting for tumor cells in vivo as well as in vitro. Treatment with A1-1 resulted in effective tumor targeting and significant tumor shrinkage in mice with subcutaneous or orthotopic human MARY-X breast cancer xerographs. Survival of the treated animals was significantly prolonged. Forty percent of treated mice were cured completely and survived as long as control non-tumor-bearing mice. These results suggest that amino-acid auxotrophic S. typhimurium, which selectively infects and attacks viable tumor tissue, have potential for breast cancer therapy in the clinic.