tbuckley/cabot-search huggingface dataset:
A multi-institutional collaborative pediatric bone tumor program for improving access to specialized care.
Authors: Raya Hamad Saab, Miguel Abboud, Samar Muwakkit, Peter Noun, Gladys Gemayel, Elie Bechara, Hassan Khalifeh, Roula Farah, Nabil Kabbara, Tarek El Khoury, Rachid Haidar, Said Saghieh, Toufic Eid, Samir Akel, Nabil Khoury, Matthew J. Krasin, Sima Jeha, Hassan Mohamed El Solh
Journal: Journal of Clinical Oncology (2015)

e21020 Background: Osteosarcoma and Ewing sarcoma are the most common malignant bone tumors in pediatrics. Average 5-year survival rates of 60-70% are achieved with current multimodality therapy. Local control modalities aiming at preserving function greatly influence quality of life of long term survivors. In developing countries, the limited availability of multidisciplinary care, expertise in specialized surgeries, and in pediatric radiation therapy, forms barriers to achieving optimal outcomes. Methods: We established a multi-institutional Collaborative Pediatric Bone Tumor Program, where children newly diagnosed with bone tumors have access to specialized local control at a tertiary Children’s Cancer Center. Central review of pathology, staging and treatment planning was performed in a multidisciplinary tumor board setting. Patients received chemotherapy locally on a unified treatment plan; local control was done at the Children’s Cancer Center at no cost to families through a program development initiative led by St Jude Children’s Research Hospital (SJCRH). Challenging cases were discussed with SJCRH team via teleconference. Results: Over 2.5 years, 30 patients were enrolled. Nationalities were Lebanese (15), Iraqi (8), and Syrian (7). Seventeen patients (57%) had Ewing sarcoma, 13 (43%) had osteosarcoma. Nineteen (63%) had localized disease. Protocol adherence was > 90%. Local control included 3 expandable and 6 standard prostheses, 3 fibular allografts, 7 simple resections and 3 amputations. Eleven patients received radiation therapy, and in 5 it was the sole mode of local control. At a median follow up of 16 months (range 5-29), 20 patients (67%) are in CR, 7 (23%) had disease progression or relapse, 2 (7%) were lost to follow-up in CR, and 1 (3%) died of toxicity. Conclusions: A collaborative bone tumor program in Lebanon resulted in timely local control and protocol adherence at 8 collaborating centers. Overall survival and functional outcome were comparable to those of international published series. Facilitating access to specialized multidisciplinary care, resolution of financial barriers, and close coordination, all contributed to the success of the program.
Heterocellular Contact Can Dictate Arterial Function
Authors: Xiaohong Shu, Claire A. Ruddiman, T.C. Stevenson Keller, Alexander S. Keller, Yang Yang, Miranda E. Good, Angela K. Best, Linda Columbus, Brant E. Isakson
Journal: Circulation Research (2019)

Resistance arteries and conduit arteries rely on different relative contributions of endothelial-derived hyperpolarization versus nitric oxide to achieve dilatory heterocellular signaling. Anatomically, resistance arteries use myoendothelial junctions (MEJs), endothelial cell projections that make contact with smooth muscle cells. Conduit arteries have very few to no MEJs.Determine if the presence of MEJs in conduit arteries can alter heterocellular signaling.We previously demonstrated that PAI-1 (plasminogen activator inhibitor-1) can regulate formation of MEJs. Thus, we applied pluronic gel containing PAI-1 directly to conduit arteries (carotid arteries) to determine if this could induce formation of MEJs. We found a significant increase in endothelial cell projections resembling MEJs that correlated with increased biocytin dye transfer from endothelial cells to smooth muscle cells. Next, we used pressure myography to investigate whether these structural changes were accompanied by a functional change in vasodilatory signaling. Interestingly, PAI-1-treated carotids underwent a switch from a conduit to resistance artery vasodilatory profile via diminished nitric oxide signaling and increased endothelial-derived hyperpolarization signaling in response to the endothelium-dependent agonists acetylcholine and NS309. After PAI-1 application, we also found a significant increase in carotid expression of endothelial alpha globin, a protein predominantly expressed in resistance arteries. Carotids from mice with PAI-1, but lacking alpha globin (Hba1-/-), demonstrated that l-nitro-arginine methyl ester, an inhibitor of nitric oxide signaling, was able to prevent arterial relaxation.The presence or absence of MEJs is an important determinant for influencing heterocellular communication in the arterial wall. In particular, alpha globin expression, induced within newly formed endothelial cell projections, may influence the balance between endothelial-derived hyperpolarization and nitric oxide-mediated vasodilation.
Abstract P050: Correlates of Serum Cortisol and its Prognostic Value in the Community
Authors: Justin B Echouffo Tcheugui, Meghan I Short, Solomon K Musani, Vanessa Xanthakis, Ramachandran S Vasan
Journal: Circulation (2018)

Introduction: Community-based data on correlates of serum cortisol are scarce. We investigated the sources of variability in morning serum cortisol, and its relation to cardiometabolic outcomes in a large biracial sample. Hypothesis: Serum cortisol is monotonically associated with cardiometabolic outcomes, an effect that is potentiated by aldosterone. Methods: We included 2896 whites (Framingham Heart Study [Generation 3], 53% women, mean age 44 years) and 2479 blacks (Jackson Heart Study, 52% women, mean age 53 years). Cohort-and sex-specific linear regression was used to identify cortisol correlates. Heritability was derived using the variance-components method. Cohort- and sex-specific logistic regression was used to relate cortisol to progression in blood pressure (BP) or fasting blood glucose (FBG) categories, and incidence of hypertension (HTN), diabetes (DM) or metabolic syndrome (MetS). Results: Serum cortisol was higher in blacks compared to whites (age-adjusted mean: 13.1 vs 10.2 μg/dL in men [ P &lt;0.001] and 12.7 vs. 8.1 μg/dL in women [ P &lt;0.001]). Serum cortisol was positively related to age and smoking in blacks, DM, menopausal status and use of hormonal therapy (replacement or contraception) in both racial groups (P &lt;0.005). Body mass index and glomerular filtration rate were inversely associated with cortisol in whites and blacks (P &lt;0.01). The age- and sex-adjusted heritability of serum cortisol was 0.20 in whites and 0.11 in blacks ( P ≤0.005). Serum cortisol was not associated with outcomes ( Table ). In blacks, concomitantly high cortisol (&gt;median) and high aldosterone (&gt;median) was associated with incident HTN (odd ratio [OR]: 1.90 [95%CI: 1.14, 3.16]) and DM (1.75 [1.17, 2.62]) compared to normal aldosterone and cortisol; ORs in whites were 1.15 (0.81, 1.63) for HTN and 0.95 (0.52, 1.74) for DM. Conclusions: Serum cortisol is a heritable trait influenced by clinical factors. Conjointly high aldosterone and cortisol levels in blacks is associated with increased risk of HTN and DM in blacks, not in whites.
THU-222-The application of novel HBV pgRNA assay to predict HBeAg clearance on long-term nucleos (t)ide analogues
Authors: Pir Ahmad Shah, Idriss Rajab, Saad Choudhry, Jeffrey Gersch, Vijayram Malladi, Rizwan Ishtiaq, Mary Kuhns, Gavin Cloherty, Daryl Lau
Journal: Journal of Hepatology (2019)
Choline Uptake and Metabolism Modulate Macrophage IL-1β and IL-18 Production
Authors: Elsa Sanchez-Lopez, Zhenyu Zhong, Alexandra Stubelius, Shannon R. Sweeney, Laela M. Booshehri, Laura Antonucci, Ru Liu-Bryan, Alessia Lodi, Robert Terkeltaub, Juan Carlos Lacal, Anne N. Murphy, Hal M. Hoffman, Stefano Tiziani, Monica Guma, Michael Karin
Journal: Cell Metabolism (2019)
SAT-191-Host genome integration of hepatitis B is prolific and is the primary contributor to viral HBs antigen gene expression
Authors: Ondrej Podlaha, George Wu, Bryan Downie, Raghuraman Raghuraman Ramamurthy, Anuj Gaggar, Mani Subramanian, Zhishen Ye, Zhaoshi Jiang
Journal: Journal of Hepatology (2019)
SAT-477-Impact of skeletal muscle quality and quantity on outcomes following curative therapy of hepatocellular carcinoma
Authors: Tomoaki Nakajima, Hirokazu Suii, Ryoji Tatsumi, Masakatsu Yamaguchi, Mutsuumi Kimura, Tomohiro Arakawa, Yasuaki Kuwata, Itaru Ozeki, Takumi Ohmura, Shuhei Hige, Yoshiyasu Karino, Joji Toyota
Journal: Journal of Hepatology (2019)
FRI-101-FGL2 deficiency resists viral fulminant hepatitis through abrogating inflammatory macrophage activation
Authors: Fang Xiao, Hongwu Wang, Ran Tao, Xinxin Weng, Peng Wang, Di Wu, Xiaojing Wang, Weiming Yan, Dong Xi, Xiaoyang Wan, Qin Ning
Journal: Journal of Hepatology (2019)
Sirtuin‐1/Mitochondrial Ribosomal Protein S5 Axis Enhances the Metabolic Flexibility of Liver Cancer Stem Cells
Authors: Zhihao Wei, Jiankun Jia, Gang Heng, Huailong Xu, Juanjuan Shan, Guiqin Wang, Chungang Liu, Jianyu Xia, Haijun Zhou, Min Wu, Zhi Yang, Meiling Wang, Zhouxing Xiong, Hong Huang, Limei Liu, Cheng Qian
Journal: Hepatology (2019)

Metabolic reprogramming endows cancer cells with the ability to adjust metabolic pathways to support heterogeneously biological processes. However, it is not known how the reprogrammed activities are implemented during differentiation of cancer stem cells (CSCs). In this study, we demonstrated that liver CSCs relied on the enhanced mitochondrial function to maintain stemness properties, which is different from aerobic glycolysis playing main roles in the differentiated non‐CSCs. We found that liver CSCs exhibit increased mitochondrial respiratory capacity and that complex‐I of mitochondria was necessary for stemness properties of liver CSCs through regulation of mitochondrial respiration. Bioinformatics analysis reveals that mitochondrial ribosomal protein S5 (MRPS5) is closely related with the function of complex‐I. Further experiments confirmed that MRPS5 promoted the production of nicotinamide adenine dinucleotide (NAD + ), which is necessary for enhanced mitochondrial function in liver CSCs. MRPS5 played a critical role for liver CSCs to maintain stemness properties and to participate in tumor progression. Mechanistically, the acetylation status of MRPS5 is directly regulated by NAD + dependent deacetylase sirtuin‐1 (SIRT1), which is abundant in liver CSCs and decreased during differentiation. Deacetylated MRPS5 locates in mitochondria to promote the function complex‐I and the generation of NAD + to enhance mitochondrial respiration. Conversely, the acetylated MRPS5 gathered in nuclei leads to increased expression of glycolytic proteins and promotion of the Warburg Effect. Therefore, liver CSCs transform mitochondrial‐dependent energy supply to a Warburg phenotype by the dual function of MRPS5. Clinical analysis of SIRT1 and MRPS5 expression in tumor tissues showed the SIRT1 High /Cytoplasmic‐MRPS5 High profile was associated with patients with hepatocellular carcinoma with poor prognosis. Conclusion: SIRT1/MRPS5 axis participates in metabolic reprogramming to facilitate tumor progression and may serve as a promising therapeutic target of liver cancer.
Radiomic-based quantitative CT analysis to predict the invasiveness of pure ground-glass lung adenocarcinoma
Authors: F. Xv, W. Zhu, H. Hu
Journal: Annals of Oncology (2019)

Background: Lung cancer is till one of the leading causes of cancer-related deaths and lung adenocarcinoma is the most common type. Compared with invasive adenocarcinoma, adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) are considered as indolent lung adenocarcinoma with good prognosis. However, AIS, MIA and even some early-stage invasive adenocarcinoma can be shown as pure ground-glass nodules on computed tomorgraphy images, which is quite difficult for clinicians to make a precise diagnosis and a suitable treatment plan. Thus, we aim to investigate the performance of radiomic-based quantitative analysis on CT images in identifying invasiveness of lung adenocarcinoma manifesting as pure ground-glass nodules. Methods: 275 lung adenocarcinoma cases with 322 pure ground-glass nodules from January 2015 to October 2017 were enrolled in this retrospective study. All lesions were resected surgically and confirmed pathologically. Clinical data like age, gender, smoking status of all cases were collected from digital medical records. Radiomic feature extraction was performed using Python with semi-automatically segmented tumor regions on CT scans which was contoured with an in-house developed plugin for 3D-Slicer. The predictive performance of the prediction models was evaluated through the receiver operating characteristic curve (ROC). Results: Among 322 nodules, 48(15%) were Adenocarcinoma in situ (AIS), 102(32%) were minimally invasive adenocarcinoma (MIA) and 172(53%) were invasive adenocarcinoma. All nodules were divided into training and validation cohort randomly with a ratio of 2:1 to establish prediction models. The values of the area under the curve were 0.716 (95%CI:0.600 0.832) and 0.827 (95%CI:0.729 0.925) with the diagnostic accuracy of 59.3% and 69.1% for radiomic and combined models, respectively. Conclusions: Radiomic model built via quantitative CT analysis can help to identify the invasiveness of lung adenocarcinoma represented as pure ground-glass nodules. Combining this model with clinical features can significantly improve its prediction performance. Legal entity responsible for the study: Fangyi Xv. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
TCTAP A-011 Early Invasive Versus Conservative Treatment Strategies in Octogenarians with Acute Coronary Syndrome: One-year Clinical Outcome, a Single Centre Experience
Authors: Vipin Mughilassery Thomachan, Abdullah M.A. Shehab, Ahmed Siddiqui, Ali Shamsi, Gohar Jamil
Journal: Journal of the American College of Cardiology (2019)
LBP-09-Liver humanization of Fah –/–/Rag2 –/–/Il2rg –/–andnbsp;NOD mice with human hepatocytes homozygous for M148I PNPLA3 allows the assessment of specific genotype contribution to NASH development in vivo.
Authors: Lander Foquet, Rob Copenhaver, Leslie Wakefield, Bin Li, John Bial, Markus Grompe
Journal: Journal of Hepatology (2019)
Multimodal treatment of pulmonary artery sarcoma: A single center experience.
Authors: Simona Secondino, Valentina Grazioli, Roberto Dore, Francesco Valentino, Maurizio Pin, Giovanna Carla Callegari, Marco Paulli, Paolo Pedrazzoli, Andrea D'Armini
Journal: Journal of Clinical Oncology (2015)

10552 Background: Pulmonary artery sarcoma (PAS) is a rare disease arising from the endothelial cells of the pulmonary artery wall, generally presenting with pulmonary hypertension (PI). The therapeutic approach, mainly based on surgery, either pneumonectomy or pulmonary endarterectomy (PEA), depends on the extension of the disease and the patient’s clinical condition. The prognosis is extremely poor as survival rarely exceeds 1 year from diagnosis. Methods: From October 2010 to December 2014, 8 patients (pts) referred to our Institution for symptoms of acute or chronic pulmonary thromboembolic disease were diagnosed to have PAS. Five pts had PI, one with severe hemodynamic instability requiring emergency surgical treatment. Median age was 64 years (range 32-77), 5 pts were female. In 6 pts the disease was bilateral, and 3 had lung metastases. Results: All pts underwent PEA, none having life threatening complications from surgery. Pathology showed 4 high grade and 4 intermediate grade sarcomas. Following PEA and a short course of cardiopulmonary rehabilitation, 7 pts were able to received conventional chemotherapy (CT) with doxorubicin and ifosfamide, starting a median of 42 days (range 22-69) from surgery. Two pts also received radiotherapy after completion of the CT program. Four pts have died for disease progression at 6, 6, 8, and 26 months from surgery while 4 are alive, three being disease free at 8, 15, and 40 months. Conclusions: In pts with PAS a multimodal approach including PEA, CT and radiotherapy is feasible. Other than improving quality of life, it appears to considerably extend life expectancy.
THU-132-Decentralised care with generic direct antivirals is effective in the management of patients with hepatitis C in a public health care setting: The Punjab model
Authors: Radha Krishan Dhiman, Gagandeep Singh Grover, Madhumita Premkumar, Sunil Taneja, Ajay Duseja, Sanjeev Arora, Sahaj Rathi, Sandeep Satsangi, Akash Roy
Journal: Journal of Hepatology (2019)
Application of Artificial Intelligence for Preoperative Diagnostic and Prognostic Prediction in Epithelial Ovarian Cancer Based on Blood Biomarkers
Authors: Eiryo Kawakami, Junya Tabata, Nozomu Yanaihara, Tetsuo Ishikawa, Keita Koseki, Yasushi Iida, Misato Saito, Hiromi Komazaki, Jason S. Shapiro, Chihiro Goto, Yuka Akiyama, Ryosuke Saito, Motoaki Saito, Hirokuni Takano, Kyosuke Yamada, Aikou Okamoto
Journal: Clinical Cancer Research (2019)

We aimed to develop an ovarian cancer-specific predictive framework for clinical stage, histotype, residual tumor burden, and prognosis using machine learning methods based on multiple biomarkers.Overall, 334 patients with epithelial ovarian cancer (EOC) and 101 patients with benign ovarian tumors were randomly assigned to "training" and "test" cohorts. Seven supervised machine learning classifiers, including Gradient Boosting Machine (GBM), Support Vector Machine, Random Forest (RF), Conditional RF (CRF), Naïve Bayes, Neural Network, and Elastic Net, were used to derive diagnostic and prognostic information from 32 parameters commonly available from pretreatment peripheral blood tests and age.Machine learning techniques were superior to conventional regression-based analyses in predicting multiple clinical parameters pertaining to EOC. Ensemble methods combining weak decision trees, such as GBM, RF, and CRF, showed the best performance in EOC prediction. The values for the highest accuracy and area under the ROC curve (AUC) for segregating EOC from benign ovarian tumors with RF were 92.4% and 0.968, respectively. The highest accuracy and AUC for predicting clinical stages with RF were 69.0% and 0.760, respectively. High-grade serous and mucinous histotypes of EOC could be preoperatively predicted with RF. An ordinal RF classifier could distinguish complete resection from others. Unsupervised clustering analysis identified subgroups among early-stage EOC patients with significantly worse survival.Machine learning systems can provide critical diagnostic and prognostic prediction for patients with EOC before initial intervention, and the use of predictive algorithms may facilitate personalized treatment options through pretreatment stratification of patients.
Brain metastases in lung adenocarcinoma: A retrospective study.
Authors: Michael Moutsos, Andriani Charpidou, Konstantinos N. Syrigos
Journal: Journal of Clinical Oncology (2015)

e19068 Background: Lung cancer is the second most frequent cause of malignant disease and a significant cause of morbidity and mortality. Lung adenocarcinoma is a common origin of brain metastatic disease. Therapeutic options include symptomatic treatment, surgery, stereotactic radiosurgery, whole-brain radiotherapy and chemotherapy. The goal of this study is to review retrospectively several epidemiologic data of brain metastatic disease in lung adenocarcinoma and to discuss the potential correlation between these variables and the presence of brain metastases as well as their impact on patients’ survival. Methods: Medical files of 586 patients with lung adenocarcinoma from Oncology Unit of Sotiria General Hospital of Athens were reviewed. Among them, 161 patients had brain metastases and we explored a potential correlation between brain metastatic disease and variables sex, age and smoke. A survival analysis also took place to investigate which factors have a statistically significant impact on survival of these patients. Results: In our study, median survival of 161 patients with lung adenocarcinoma and brain metastatic disease is 7 months. Only age younger than 60 years old was found to have a statistically significant correlation with presence of brain metastases. Performance status was also an independent prognostic factor of survival: the bigger the PS the worse the outcome. Conclusions: As brain metastases in lung adenocarcinoma are frequent with high morbidity and poor prognosis, prospective studies with high statistical power need to be carried out to further define the correlation between epidemiologic factors and the presence of brain metastases as well as the role of available therapeutic options aiming at prolonging survival and maximizing quality of life of patients.
THU-209-Dynamics of a transient elastography-based risk prediction model for hepatocellular carcinoma treated with antiviral therapy in chronic hepatitis B: A multi-center retrospective cohort study from the Korean Transient Elastography Study Group
Authors: Hye Yeon Chon, Yeon Seok Seo, Jung il Lee, Byung Seok Kim, Byoung KukJang, Sang Gyune Kim, In Hee Kim, Jin-Woo Lee, Hana Park, Moon Young Kim, Soung Won Jeong, Han Ah Lee, Ki Tae Suk, Sun Young Yim, Soon Ho Um, Hyun Woong Lee, Kwan Sik Lee, Jeong Eun Song, Chang Hyeong Lee, Woo Jin Chung, Jae Seok Hwang, Jeong-Ju Yoo, Young Seok Kim, Dong Joon Kim, Chang Hun Lee, Jung Hwan Yu, Young Eun Chon, Yeon Jung Ha, Mi Na Kim, Joo Ho Lee, Seong Gyu Hwang, Seong Hee Kang, Soon Koo Baik, Jae Young Jang, SangJun Suh, Young KulJung, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Kwang-Hyub Han, HyungJoon Yim, Seung Up Kim
Journal: Journal of Hepatology (2019)
A new approach to endoscopic submucosal tunneling dissection: the “Speedboat-RS2” device
Authors: Zacharias P. Tsiamoulos, Joseph Sebastian, Nipin Bagla, Christopher Hancock, Brian P. Saunders
Journal: Endoscopy (2019)

The “Speedboat-RS2” (Creo Medical Ltd., Wales, UK) is the first multimodality device incorporating bipolar radiofrequency (BRF) energy cutting, microwave coagulation (MWC), an integrated needle for submucosal injection, and a rotatable blade with a heat-insulated hull.
FRI-027-Serum bile acids significantly associate with the fibrogenesis biomarker Pro-C3: analysis of a randomized, placebo-controlled trial of NGM282 in patients with primary sclerosing cholangitis
Authors: Gideon Hirschfield, Lei Ling, Mark Jaros, Kathline H. Kim, Bryan Baxter, Alex Depaoli, Marlyn J. Mayo, Ulrich Beuers
Journal: Journal of Hepatology (2019)
Abstract 10978: Visceral Abdominal Fat as a Marker of Accelerated Progression of Noncalcified Coronary Plaque
Authors: Atsuko Imai, Sei Komatsu, Tomoki Ohara, Teruaki Kamata, Jyunichi Yoshida, Kazuaki Miyaji, Mitsuhiko Takewa, Kazuhisa Kodama
Journal: Circulation (2012)

[Introduction] Excess visceral abdominal fat (VAT) is more strongly associated with risk factors of coronary artery disease (CAD) than body mass index (BMI) or waist circumference. [Hypothesis] We tested the hypothesis that adding VAT measurements to CAD risk factors provides better risk assessment for CAD progression. [Methods] This prospective cohort study comprised 553 CAD patients with coronary plaque with ≤ 50% coronary stenosis as assessed by computed tomography (CT) angiography. Quantification of VAT area was performed together with CT angiography using abdominal CT scanning. [Results] After a mean 42±8 month follow-up, 324 patients underwent repeated CT scans for worsening angina symptoms without findings of positive ischemia. Increased segments of noncalcified plaque were seen in 156 (48%) and increases above the median calcium score were seen in 166 (51%) patients. The risk for progression of noncalcified plaque increased steadily with higher VAT quartiles, independent of CAD risk factors. Patie...
PS-156-Antigen suppression effect of the core protein allosteric modulator R07049389 in AAV-HBV mice is accompanied by transient upregulation of immune-cell gene signatures in the liver
Authors: Xue Zhou, Jitao David Zhang, Yuan Zhou, Xiaojun Tian, Youjun Yu, Lue Dai, Jie Zhao, John Young, Lu Gao
Journal: Journal of Hepatology (2019)