tbuckley/cabot-search huggingface dataset:
THU-378-Messenger RNA transcriptome profiling reveals a distinct phenotype of human bone marrow mesenchymal stem cell-derived hepatocytes
Authors: Jun Li, Dongyan Shi, Jiaojiao Xin, Wenchao Ding, Jing Jiang, Qian Zhou, Suwan Sun, Yinyun Lu, Beibei Guo, Xingping Zhou
Journal: Journal of Hepatology (2019)
Retrospective study about lung carcinoid: Our experience in a Spanish hospital
Authors: D.S. Cabrero, P. Cruz, J. de Castro, O. Higuera, A. Pertejo, I. Esteban, L. Gutierrez, J. Villamayor, L. Ostios, D. Viñal, J. Miranda
Journal: Annals of Oncology (2019)

Background: Pulmonary carcinoids are a very rare group of neoplasia. Typical are the most frequent ones, with earlier onset than atypical carcinoids. There is no clear relationship with smoke. Most are indolent and carcinoid syndrome is rare. In the localized disease, surgery is the best choice. In locally advanced disease, radical radiotherapy can be considered. For the metastatic disease, systemic treatment with somatostatin analogs, multi-kinase inhibitors or chemotherapy can be proposed. Methods: We conducted a descriptive and retrospective study including all patients diagnosed with pulmonary carcinoid tumor between January 2013 and January 2018 were included (both localized and metastatic). Other neuroendocrine tumors of the lung were excluded. A Kaplan Meier survival analysis was carried out for each variable to study the overall survival. Results: Of the 42 patients included in the study, most were women (55% vs 45%) and were diagnosed in early stages (83%). Only 14% debuted with metastatic involvement. The main location was the right lung (60%). In 42%, the smoking status is known. Of them, 19% were smokers and 24%, ex-smokers (19% never smoked). 80.5% were diagnosed by cytology (88% as typical and 7.1% as atypical). 12% presented synchronous lung cancer (mostly adenocarcinoma). Localized disease was treated by surgery, mainly by lobectomy (54%). Stage IV patients (66.6%) received systemic treatment with analogs. At the time of the study, 92.7% were still alive (7.3% had died). There were significant differences between tumor stages (p < 0.05) to survival. Even so, there wereńt differences related to age, smoking status or type of surgery. Conclusions: Most of these tumors exhibit a non-aggressive behavior. According to the previous bibliography, the vast majority are diagnosed in early stages. Radical surgery remains as the gold standard. Experienced centers, can use cytology as a diagnostic method, with less morbidity than biopsy. We didńt found a clear association with smoking status, though there was a clear trend towards to the group related to smoke. According to the literature, overall survival of these patients is long and mainly related to the tumor stage (survival at 2 years is > 85%). More studies will be needed to be able to clarify the prognostic impact of factors. Legal entity responsible for the study: Hospital Universitario la Paz - Servicio de Oncología Médica. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Arrhythmogenic propensity of the fibrotic substrate after atrial fibrillation ablation: a longitudinal study using magnetic resonance imaging-based atrial models
Authors: Rheeda L Ali, Joe B Hakim, Patrick M Boyle, Sohail Zahid, Bhradeev Sivasambu, Joseph E Marine, Hugh Calkins, Natalia A Trayanova, David D Spragg
Journal: Cardiovascular Research (2019)

Abstract Aims Inadequate modification of the atrial fibrotic substrate necessary to sustain re-entrant drivers (RDs) may explain atrial fibrillation (AF) recurrence following failed pulmonary vein isolation (PVI). Personalized computational models of the fibrotic atrial substrate derived from late gadolinium enhanced (LGE)-magnetic resonance imaging (MRI) can be used to non-invasively determine the presence of RDs. The objective of this study is to assess the changes of the arrhythmogenic propensity of the fibrotic substrate after PVI. Methods and results Pre- and post-ablation individualized left atrial models were constructed from 12 AF patients who underwent pre- and post-PVI LGE-MRI, in six of whom PVI failed. Pre-ablation AF sustained by RDs was induced in 10 models. RDs in the post-ablation models were classified as either preserved or emergent. Pre-ablation models derived from patients for whom the procedure failed exhibited a higher number of RDs and larger areas defined as promoting RD formation when compared with atrial models from patients who had successful ablation, 2.6 ± 0.9 vs. 1.8 ± 0.2 and 18.9 ± 1.6% vs. 13.8 ± 1.5%, respectively. In cases of successful ablation, PVI eliminated completely the RDs sustaining AF. Preserved RDs unaffected by ablation were documented only in post-ablation models of patients who experienced recurrent AF (2/5 models); all of these models had also one or more emergent RDs at locations distinct from those of pre-ablation RDs. Emergent RDs occurred in regions that had the same characteristics of the fibrosis spatial distribution (entropy and density) as regions that harboured RDs in pre-ablation models. Conclusion Recurrent AF after PVI in the fibrotic atria may be attributable to both preserved RDs that sustain AF pre- and post-ablation, and the emergence of new RDs following ablation. The same levels of fibrosis entropy and density underlie the pro-RD propensity in both pre- and post-ablation substrates.
Primary paediatric cutaneous mucinoses
Authors: F. Rongioletti
Journal: British Journal of Dermatology (2019)

Primary cutaneous mucinoses are a heterogeneous group of diseases characterized by the abnormal deposition of glycosaminoglycans (mucin) in the skin. This is the main histopathological clue resulting in distinctive clinical presentations. They are usually diseases of adult age and are uncommon in children, in whom diagnosis and management are difficult tasks. In particular, the classification of primary cutaneous mucinoses occurring in childhood is a difficult and confusing challenge because of the very limited number of described cases and overlaps in their clinicopathological features in the absence of reports of homogeneous case series. The aim of this review is to help dermatologists and paediatricians to identify patients with cutaneous mucinoses at a paediatric age and to enable institution of appropriate management. A classification of primary paediatric cutaneous mucinoses is also proposed. New investigations have yielded significant insights into a classification of paediatric cutaneous mucinoses. The current update tries to offer a more meaningful guide to the diagnosis and treatment of these rare diseases in paediatric patients. What's already known about this topic? The nosography of primary cutaneous mucinoses occurring in childhood is confusing because of the very limited number of cases and overlaps in their clinicopathological features in the absence of homogeneous case series. The diagnosis and management of paediatric patients with cutaneous mucinoses are also difficult as these diseases are rarely seen in children. What does this study add? New investigations have yielded significant insights into a classification of paediatric cutaneous mucinoses. The current update tries to offer a more meaningful guide to diagnosis and treatment of these rare diseases in patients of paediatric age.
γ-Catenin-Dependent Signals Maintain BCR-ABL1+ B Cell Acute Lymphoblastic Leukemia
Authors: Noemie Luong-Gardiol, Imran Siddiqui, Irene Pizzitola, Beena Jeevan-Raj, Mélanie Charmoy, Yun Huang, Anja Irmisch, Sara Curtet, Georgi S. Angelov, Maxime Danilo, Mélanie Juilland, Beat Bornhauser, Margot Thome, Oliver Hantschel, Yves Chalandon, Gianni Cazzaniga, Jean-Pierre Bourquin, Joerg Huelsken, Werner Held
Journal: Cancer Cell (2019)
Safety and Efficacy of Romiplostim in over 200 Children with Immune Thrombocytopenia (ITP): Results of an Integrated Database of 5 Clinical Trials
Authors: Michael D. Tarantino, Jenny M. Despotovic, John Roy, John Grainger, Nichola Cooper, Donald Beam, Ashok Raj, Alexey A. Maschan, June Kim, Melissa Jeanne Eisen
Journal: Blood (2018)
PS-159-Intestinal dysbiosis fuels liver disease progression via NLRP3 in the Mdr2−/− mouse model of primary sclerosing cholangitis
Authors: Lijun Liao, Kai Markus Schneider, Galvez Eric, Mick Frissen, Hanns-Ulrich Marschall, Huan Sun, Maximilian Hatting, Annika Wahlström, Johannes Haybäck, Philip Puchas, Antje Mohs, Peng Jin, Ina Bergheim, Anika Nier, Julia Hennings, Johanna Reissing, Zimmermann Henning Wolfgang, Thomas Longerich, Till Strowig, Christian Liedtke, Francisco Javier Cubero, Christian Trautwein
Journal: Journal of Hepatology (2019)
Effect on Health Care Expenditures During Nationwide Implementation of the Diabetes Prevention Program as a Health Insurance Benefit
Authors: Ronald T. Ackermann, Raymond Kang, Andrew J. Cooper, David T. Liss, Ann M. Holmes, Margaret Moran, Chandan Saha
Journal: Diabetes Care (2019)

OBJECTIVE Lifestyle interventions slow development of type 2 diabetes by half, but the impact of health payer reimbursement for delivery of intervention programs is not well known. We evaluated net commercial health payer expenditures when offering reimbursement for access to YMCA’s Diabetes Prevention Program (YDPP) in 42 states. RESEARCH DESIGN AND METHODS We used a nonequivalent comparison group design to evaluate net health care expenditures for adults with prediabetes who attended one or more YDPP visit between 1 July 2009 and 31 May 2013 (“YDPP users”). Rolling, 1:1 nearest neighbor propensity score (PS) matching was used to identify a comparison group of nonusers. Administrative data provided measures of YDPP attendance, body weight at YDPP visits, and health care expenditures. Random effects, difference-in-difference regression was used to estimate quarterly health care expenditures before and after participants’ first visit to YDPP. RESULTS Worksite screening identified 9.7% of the target population; 39.1% of those identified (19,933 participants through June 2015) became YDPP users. Mean weight loss for YDPP users enrolled before June 2013 (n = 1,725) was 7.5 lb (3.4%); 29% achieved ≥5% weight loss. Inclusive of added costs to offer YDPP, there were no statistically significant differences in mean per-person net health care expenditures between YDPP users and PS-matched nonusers over 2 years ($0.2 lower [95% CI $56 lower to $56 higher]). Mean reimbursement to the YMCA was $212 per YDPP user, with 92.8% of all expenditures made for those who attended at a high rate (≥9 completed YDPP visits). CONCLUSIONS Worksite screening was inefficient for identifying the population with prediabetes, but those identified achieved modest YDPP attendance and clinically meaningful weight loss. Over 2 years, added costs to offer the intervention were modest, with neutral effects on net health care costs.
Demonstration of high mitochondrial metabolism by upregulation of MCT1 and TOMM20 as characteristic of anaplastic thryoid cancer.
Authors: Jennifer Maria Johnson, Mehri Mollaee, Paolo Cotzia, Adam Luginbuhl, David Cognetti, Tingting Zhan, Madalina Tuluc, Ubaldo E. Martinez Outschoorn, Joseph Curry
Journal: Journal of Clinical Oncology (2015)

e22258 Background: Anaplastic thyroid cancer (ATC) is characterized by an aggressive phenotype with high growth kinetics and morbid local invasion. Genetic analyses have repeatedly shown that pathways involved in cellular metabolism are altered in ATC, in particular receptor tyrosine kinases, PI3AKT, and MAPK, highlighting the importance of energy utilization in ATC. Monocarboxylate Transporter 1 (MCT1) is a transporter protein capable of both importing monocarboxylate fuel and exporting lactate to protect cells from catastrophic oxidative stress. Upregulation has already been demonstrated in multiple human malignancies including colon, lung, head and neck squamous, glial, breast, ovary, and prostate cancer. Translocase of the Outer Mitochondrial Membrane Member 20 (TOMM20) is the main import pore for proteins into the mitochondria. Expression of this protein has been shown to correlate both with mitochondrial mass and function (respiration). Taken together these two markers can identify tissues with high metabolic activity. Methods: 15 anaplastic thyroid cancer samples, 12 papillary thyroid cancers, and 8 non-cancerous thyroid controls were stained for expression of MCT1 and TOMM20 by immunohistochemistry. Staining was assessed visually for intensity for MCT1 and by Aperio digital image analysis for TOMM20 with an algorithm developed in our laboratory. Results: 13 out of 15 anaplastic thyroid specimens stained strongly for MCT1, at a rate significantly higher than both non-cancerous and papillary thyroid cancer specimens (p =3.3 x 10-5and 0.00069, respectively). TOMM20 is expressed in all 3 tissue types, but with a high intensity of staining only in the malignant tissues (p = 0.0044) with no appreciable difference between the papillary thyroid and anaplastic types. Conclusions: Our characterization of anaplastic thyroid cancer with these markers is consistent with high mitochondrial metabolism. Furthermore our work highlights the possibility of a therapeutic intervention with MCT1 blockade in this difficult to treat malignancy.
Seven electrocardiographs for seven clinical research studies
Authors: John R Zalcberg
Journal: BMJ (2019)

Picture a small hospital room of 2 m2 crammed with seven almost identical electrocardiographs.1 Each provides typical electrocardiograms to measure electrical abnormalities of the heart with appropriate sensitivity and specificity. Each was procured separately for a specific clinical study and can be used for only that purpose. There are …
The effect of sociodemographic factors and therapy on survival in pediatric liver cancers: A SEER population study.
Authors: Minzhi Xing, Hyun Sik Kim
Journal: Journal of Clinical Oncology (2015)

10076 Background: To investigate long-term survival in pediatric primary liver cancers, including hepatoblastoma & hepatocellular carcinoma (HCC) based on sociodemographic factors & therapy in a large-scale population study. Methods: The Surveillance, Epidemiology and End Results (SEER) database was queried for pediatric cancer patients with the liver as the primary site (C22.0), diagnosed 1973-2011. Overall survival (OS) was stratified by tumor & patient characteristics. Analysis of OS via therapy was further stratified based on socio-demographic factors. Kaplan-Meier & Cox proportional hazard models were used to assess independent predictors for OS. Results: Of 1145 newly diagnosed pediatric cancer patients with liver as primary site, 1012 had primary liver cancers, of whom 725 had hepatoblastoma and 287 had HCC, median age 2yrs, 60.47% male. Overall median OS was 210.7±6.4 mo. Median OS significantly correlated with younger age at diagnosis ( < 2 vs. ≥ 2yrs, 240.7 vs. 159.7 mo, p < .001), ethnicity (white, black, other; 193.1, 81.6, 166.5 mo; p = .0136), geographic location (Alaska, East, Northern Plains, Southwest, Pacific Coast; 106.2, 91.6, 173.1, 112.0, 144.3; p = .0144), median family income ( ≥ $75k vs. < $75k/year, 194.1 vs. 184.5 months, p = .013), and regional education levels (% bachelor degree or above, ≥ 25% vs. < 25%, 198.5 vs. 191.5 months, p < .0247). Surgery was performed in 684 patients (67.6%), 40 patients received radiation (3.95%), 15 patients received both surgery and radiation (1.48%), and 274 patients received best supportive care (27.0%). OS was significantly lower in patients who received best supportive care (22.6 mo) compared to surgery (275.4 mo, p < .001), radiation (77.3 mo, p < .001), or both surgery & radiation (171.3 mo, p < .001). Favorable sociodemographic factors significantly correlated with higher therapy rates. Conclusions: In pediatric primary liver cancers, socio-demographic factors including younger age at diagnosis, white ethnicity, higher family income & higher regional education levels correlated with prolonged survival. Significantly higher survival with treatment was observed; favorable socio-demographic factors predicted higher treatment rates.
PS-172-Acute adipocyte death preferentially induces liver injury and inflammation via the activation of CCR2+ macrophages and lipolysis
Authors: Seung-Jin Kim, Dechun Feng, Adrien Guillot, Shen Dai, Fengming Liu, Seonghwan Hwang, Richard Parker, Wonhyo Seo, Yong He, Grzegorz Godlewski, Won-Il Jeong, Yuhong Lin, Xuebin Qin, George Kunos, Bin Gao
Journal: Journal of Hepatology (2019)
FRI-305-Long acting GLP-1/Glucagon co-agonist ameliorates steatosis, inflammation and fibrogenesis in a rodent model of NASH
Authors: Jenny Egecioglu Norlin, Elisabeth Galsgaard, Anne Bugge, Thomas Hansen, Jesper Lau, Kirsten Raun, Markus Robert Latta, Dorte Holst
Journal: Journal of Hepatology (2019)
SAT-479-Analysis of the relationship between serum creatinine/cystatin C ratio and muscle mass in patients with hepatocellular carcinoma
Authors: Hirotaka Oura, Sadahisa Ogasawara, Yoshihiko Ooka, Kazufumi Kobayashi, Susumu Maruta, Hiroaki Kanzaki, Kengo Kanayama, Takahiro Maeda, Yuko Kusakabe, Soichiro Kiyono, Masato Nakamura, Tomoko Saito, Eiichiro Suzuki, Shingo Nakamoto, Shin Yasui, Akinobu Tawada, Tetsuhiro Chiba, Makoto Arai, Tatsuo Kanda, Hitoshi Maruyama, Naoya Kato
Journal: Journal of Hepatology (2019)
FRI-056-Obeticholic acid as adjunctive therapy in Primary Biliary Cholangitis: A review of early real-world experience
Authors: Surain Roberts, Marwa Ismail, Gowthami Kanagalingam, Andrew L. Mason, Mark G Swain, Catherine Vincent, Eric Yoshida, Cynthia Tsien, Jennifer Flemming, Harry Janssen, Gideon Hirschfield, Bettina Hansen, Aliya Gulamhusein
Journal: Journal of Hepatology (2019)
Lessons from conducting mouse clinical trial (MCT) on a cohort of NSCLC patient derived xenografts (PDXs).
Authors: Henry Li, Zhun Wang, Sheng Guo, Xuesong Huang, Jean-Pierre Wery
Journal: Journal of Clinical Oncology (2015)

e18505 Background: Patient-derived xenograft (PDX) is increasingly used to evaluate oncology drugs. PDX, reflective of original patient pathology and genomics, is predictive of response to treatment. Cohort of PDX mirror diversity of corresponding patient populations. Mouse clinical trial (MCT) on cohort of PDXs (randomized, controlled and statistically powered, as in human trial) can potentially guide clinical development or use of cancer therapy. Methods: We previously described a cohort of NSCLC PDXs (>200)1 and now are conducting mouse clinical trials by randomly enrolling PDX subjects from this cohort to assess antitumor activities of 3 drugs, cisplatin, paclitaxel and X per method described previously2. We assessed the antitumor activity using various clinically relevant endpoints (DT/DC, RECIST, OS, PFS), and evaluated information gain from the MCT to guide clinic use of these agents. Results: Two chemotherapy demonstrated statistic significant anti-tumor activities in the cohort with medium PFS of 41 days for paclitaxel, 37 days for cisplatin and 28 days for placebo. The differences between the two treated vs. placebo are significant (p-values 0.001 and 0.03 respectively), but not significant between the two treated (p-value of 0.47). OS analysis yielded the same conclusions (medium 95, 67 and 41 days, respectively, p-value <0.001, 0.002 and 0.23 in the same order). Analysis revealed that 2 agents’ activity do not overlap among the individuals, implying: 1) subjects resistant to one (e.g. 1st line treatment) might still respond another (2nd line treatment); 2) the combination of these 2 makes sense for the diseases. Due to all these models have been genomic-profiled, it is also possible to identify markers predictive of response. Similarly, an investigational agent X was found to have superior activity over both cisplatin and paclitaxel in the same cohort. Its activity overlaps with neither, suggesting it can potentially be developed as either 1st or 2ndline treatment in clinical development. Conclusions: Our study indicated that MCT could be a powerful tool to guide clinical use and development of new cancer agents.
Correlation of molecular status and anatomic sites of metastases at diagnosis of EGFR positive non-small cell lung cancer (NSCLC): A single institution experience
Authors: K. Krpina, B. Budimir, S. Kukulj, A. Marušić, M. Jakopović, M. Samaržija
Journal: Annals of Oncology (2019)

Background: A significant proportion of NSCLC patients carry mutations in the epidermal growth factor receptor (EGFR) kinase domain, in most cases with the presence of a deletion mutation in exon 19 or L858R point mutation. The aim of our analysis was to examine the patterns of metastatic spread in IV stage nsclc and whether it varies by EGFR mutation status. Methods: All patients (pts) with stage IV NSCLC from 2014-2017, without a recent history of cancer, were diagnosed at our department in which anatomic sites of metastasis, before initial treatment, were recorded. Tumor tissues were further processed, and data on molecular testing (EGFR; ex19, ex 20, ex21 L858R) were extracted. Correlation between molecular status and anatomic sites of mets was assessed. Results: We reviewed 206 pts with stage IV NSCLC, EGFR positive. Further molecular analysis: Ex 19 (n = 118 + 57.2%), Ex 20 (n = 20 + 9.7%), Ex 21 L 858R (n = 69; 33.4%). Most frequent mets sites were bone (28.2%), lung (27.9%), brain (22.8%) and supraclavicular lmph (18.2%). Pts with Ex20 had more brain mets (38.9%) than pts with ex21 (7%), for ex 20 no significant result. Statistic significance was Ex20 with lymp supraclavicular (p = 0.006), Ex20 with effusion pericardi (p = 0.021). Interesting Ex21 L858R with meta hepatis (p = 0.044) and Ex19with meta hepatis (p = 0.083). Conclusions: Molecular status of NSCLC is associated with biological behavior. Most frequent meta site were bone, at diagnosis 39.2% of EGFR + pts. Because of better prognosis for EGFR+ pts screening and prevention of skeletal-related events in NSCLC pts is reasonable. Legal entity responsible for the study: Kristina Krpina. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.