tbuckley/cabot-search huggingface dataset:
A Comprehensive Assessment of Serial Transient elastography in various Liver disease Etiologies at the Toronto Liver Centre (CASTLE-TLC)
Authors: M. Elkashab, H. Dallali, S. Kausar, M. Farshadi, M. Khurram, O. Muraru, M. Khan, J. Palmart, S. Loo, M. Magnes, K. Boctor
Journal: Journal of Hepatology (2018)
Long-term immunological and clinical impact of HCV eradication with direct acting antivirals in patients with HCV-associated cryoglobulinemia vasculitis
Authors: M. Bonacci, S. Lens, Z. Mariño, S. Rodriguez-Tajes, Concepció Bartres, M. Ramos-Casals, José Hernández-Rodríguez, X. Forns
Journal: Journal of Hepatology (2018)
Clinical features and outcome of advanced or metastatic gastric cancer in young adult,analysis of 97 cacses.
Authors: Izuma Nakayama, Keisho Chin, Yosuke Kumekawa, Takeru Wakatsuki, Mariko Ogura, Takashi Ichimura, Daisuke Takahari, Mitsukuni Suenaga, Masato Ozaka, Eiji Shinozaki, Nobuyuki Mizunuma
Journal: Journal of Clinical Oncology (2015)

e15022 Background: Younger gastric cancer (GC) patients have known to have different clinicopathological characteristics. They have higher proportion of women, diffuse type histology, or poorer outcome than older GC patients. Few studies were reported previously about younger advanced or metastatic GC cases. Methods: The subject was metastatic, unresectable or recurrent GC patient who were younger than 40 years and received systemic chemotherapy in our institute. We reviewed medical records of 3,802 GC patients who visited our institute from January, 2005 to December, 2014 retrospectively. GC in young adult was defined as cancer diagnosed at less than 40 years old. StageII/ III GC patients with no recurrence and patients visited as second opinion were excluded. Results: During this period, 225 patients were diagnosed as GC in young adults. Among them, 190 patients were advanced or metastatic cases and 97 patients were managed at our hospital. Baseline characteristics of patients (N = 97) were as follow : median age, 35 (range, 16-39), male/female: 39/58, PS 0-1/2: 79/8, metastatic/locally advanced: 95/2, differentiated/undifferentiated-type: 8/81, EGJ/stomach: 10/79, peritoneum metastases/liver metastases: 65/8, HER2 positive/negative: 7/28, surgery of primary site yes/no: 47/50. Median OS and PFS were 14.0 and 5.2 months respectively. PFS of patients (N = 51) received S-1 or Capecitabine plus cisplatin as first line were 7.0 months. In univariate analysis, poor performance status (PS) and liver metastases were significantly associated with poor prognosis. Multivariate analysis revealed only PS had significant association with prognosis. Conclusions: There were some differences in patient characteristics between young adults and population including older ages. There were higher proportion of female and undifferentiated tumor in young adult. PFS and OS of GC in young adults were comparable to that of previous Japanese pivotal trials, SPIRITS or JCOG9912.
First-in-human study of PET and optical dual-modality image-guided surgery in glioblastoma using <sup>68</sup>Ga-IRDye800CW-BBN
Authors: Deling Li, Jingjing Zhang, Chongwei Chi, Xiong Xiao, Junmei Wang, Lixin Lang, Iqbal Ali, Gang Niu, Liwei Zhang, Jie Tian, Nan Ji, Zhaohui Zhu, Xiaoyuan Chen
Journal: Theranostics (2018)

Purpose: Despite the use of fluorescence-guided surgery (FGS), maximum safe resection of glioblastoma multiforme (GBM) remains a major challenge.It has restricted surgeons between preoperative diagnosis and intraoperative treatment.Currently, an integrated approach combining preoperative assessment with intraoperative guidance would be a significant step in this direction.Experimental design: We developed a novel 68 Ga-IRDye800CW-BBN PET/near-infrared fluorescence (NIRF) dual-modality imaging probe targeting gastrin-releasing peptide receptor (GRPR) in GBM.The preclinical in vivo tumor imaging and FGS were first evaluated using an orthotopic U87MG glioma xenograft model.Subsequently, the first-in-human prospective cohort study (NCT 02910804) of GBM patients were conducted with preoperative PET assessment and intraoperative FGS.Results: The orthotopic tumors in mice could be precisely resected using the near-infrared intraoperative system.Translational cohort research in 14 GBM patients demonstrated an excellent correlation between preoperative positive PET uptake and intraoperative NIRF signal.The tumor fluorescence signals were significantly higher than those from adjacent brain tissue in vivo and ex vivo (p < 0.0001).Compared with pathology, the sensitivity and specificity of fluorescence using 42 loci of fluorescence-guided sampling were 93.9% (95% CI 79.8%-99.3%)and 100% (95% CI 66.4%-100%), respectively.The tracer was safe and the extent of resection was satisfactory without newly developed neurologic deficits.Progression-free survival (PFS) at 6 months was 80% and two newly diagnosed patients achieved long PFS.Conclusions: This initial study has demonstrated that the novel dual-modality imaging technique is feasible for integrated pre-and intraoperative targeted imaging via the same molecular receptor and improved intraoperative GBM visualization and maximum safe resection.
Molecular Profiling and Clonal Tracking of Secreted Rheumatoid Factors in Primary Sjögren's Syndrome
Authors: Jing J. Wang, Joanne H. Reed, Alex D. Colella, Amanda J. Russell, William Murray‐Brown, Tim K. Chataway, Katherine J. L. Jackson, Christopher C. Goodnow, Tom P. Gordon
Journal: Arthritis & Rheumatology (2018)

Objective Rheumatoid factors ( RF s) are associated with systemic disease in primary Sjögren's syndrome ( SS ) and may be pathogenic as mixed cryoglobulins. Current detection methods cannot resolve RF s at a molecular level. This study was undertaken to perform the first proteomic and transcriptomic analysis of secreted and membrane‐bound IgM‐ RF in primary SS and identify unique heavy‐chain peptide signatures for RF clonotype tracking. Methods Purified heavy chains of serum RF s from 15 patients with primary SS were subjected to de novo mass spectrometric sequencing. The circulating B cell Ig repertoire was determined by massively parallel sequencing of IGH RNA from matched peripheral blood mononuclear cells (n = 7). RF ‐specific heavy‐chain third complementarity‐determining region ( CDR 3) peptides were identified by searching RF heavy‐chain peptide sequences against the corresponding IGH RNA sequence libraries. Heavy‐chain CDR 3 peptides were used as biomarkers to track serum RF clonotypes using quantitative multiple reaction monitoring. Results Serum RF s were clonally restricted and composed of shared sets of IgM heavy‐chain variable region (Ig V H ) 1–69, 3–15, 3–7, and 3–74 subfamilies. Cryoprecipitable RF s from patients with mixed cryoglobulinemia ( MC ) were distinguishable from nonprecipitating RF s by a higher frequency of amino acid substitutions and identification of stereotypic heavy‐chain CDR 3 transcripts. Potentially pathogenic RF clonotypes were detected in serum by multiple reaction monitoring years before patients presented with MC . Levels of Ig V H 4–34 IgM‐ RF decreased following immunosuppression and remission of MC . Conclusion Cryoprecipitable RF clonotypes linked to vasculitis in primary SS have different molecular profiles than nonprecipitating RF s, suggesting different underlying mechanisms of production. The combined omics workflow presented herein provides molecular biomarkers for tracking and removal of pathogenic RF clones.
The association between serum folate level and toxicity of capecitabine.
Authors: Stephen Lam Chan, Brigette Ma, Frankie Mo, Anthony WH Chan, Kenneth C.W. Wong, Daisy Lam, Florence Mok, Lin Chen, Anthony T. C. Chan, Allen K.C. Chan
Journal: Journal of Clinical Oncology (2016)

3566 Background: During capecitabine treatment, it has been suggested that the rate of toxicity differs between Western and Eastern patients (pt), and serum folate is associated with more toxicity in the Caucasian population. We conducted a prospective study to determine the association between serum folate level and toxicity during capecitabine treatment in Chinese pt. Methods: Key inclusion criteria: colon cancer pt with a plan of capecitabine or capecitabine-based treatment. Exclusion criteria included ECOG PS > 2; concomitant administration of radiotherapy or irinotecan; creatinine clearance < 30ml/min. After consent, relevant data of each pt were documented at baseline and serum was taken for assay of folate level. Pt were started 3-weekly capecitabine 2500mg/m2/day D1-14 alone or capecitabine 2000mg/m2/day D1-14 when combined with oxaliplatin. The toxicity of the first 4 cycles was determined by investigators according to CTCAE 4.0. The primary objective was to determine the association between serum folate level and the rate of ≥ Grade 2 toxicity. Results: Total 193 patients were recruited from Oct 2013 to Sept 2015, of which 136 of them were eligible. The median age was 60 years (Range 26-82). Tumor stage: Stage II (13; 9.6%); Stage III (78; 57.3%) and Stage IV (45; 33.1%). 36 pt had capecitabine alone and 100 pt underwent capecitabine combinational treatment. The rate of G2 andG3 toxicity was 30.9% and 12.5%, respectively. The G2 toxicity rate (type) was 49.3% (Nausea); 11.8% (Vomiting); 25.0% (diarrhea); 13.2% (mucositis); 5.9% (pigmentation); 25.7% (Hand-foot reaction); 19.1% (neutropenia). The mean serum folate was 27.4nmol/L (range: 12.8-45.4; SD: 27.4). Serum folate level was associated with more ≥ G2 toxicity (p = 0.0043; OR = 1.086) and remained an independent predictor of ≥ G2 toxicity (p = 0.0186; OR = 1.072) after adjustment with demographics, renal and liver function parameters. Using cutoff at 75thpercentile, more pts had ≥ G2 toxicity in the high folate group (91.4% vs. 69.3%; p = 0.0183) than the low folate group. Conclusions: Serum folate level is associated with higher rate of ≥ G2 toxicity during capecitabine treatment in Chinese population. Further dietary studies are under planning. (Supported by HMRF 01120226).
PGD2/DP2 receptor activation promotes severe viral bronchiolitis by suppressing IFN- <b>λ</b> production
Authors: Rhiannon B. Werder, Jason P. Lynch, Jennifer C. Simpson, Vivian Zhang, Nick H. Hodge, Matthew Poh, Elizabeth Forbes-Blom, Christina Kulis, Mark L. Smythe, John W. Upham, Kirsten Spann, Mark L. Everard, Simon Phipps
Journal: Science Translational Medicine (2018)

RSV-induced prostaglandin D2 release contributes to disease severity by impairing IFN-λ production.
Nonalcoholic fatty liver disease is the most common cause of hepatocellular carcinoma (HCC) in individuals without cirrhosis: A United States multicenter study
Authors: A. Delemos, L. Dakhoul, P. Roche, E. Miller, H.A. Sbeih, E. Mao, A. Scanga, E.V. Gomez, S. Gawrieh, N. Chalasani, J. Wattacheril
Journal: Journal of Hepatology (2018)
Metformin Targets Mitochondrial Glycerophosphate Dehydrogenase to Control Rate of Oxidative Phosphorylation and Growth of Thyroid Cancer <i>In Vitro</i> and <i>In Vivo</i>
Authors: Shilpa Thakur, Brianna Daley, Kelli Gaskins, Vasyl V. Vasko, Myriem Boufraqech, Dhaval Patel, Carole Sourbier, Jeff Reece, Sheue-Yann Cheng, Electron Kebebew, Sunita Agarwal, Joanna Klubo-Gwiezdzinska
Journal: Clinical Cancer Research (2018)

Purpose: Mitochondrial glycerophosphate dehydrogenase (MGPDH) is the key enzyme connecting oxidative phosphorylation (OXPHOS) and glycolysis as well as a target of the antidiabetic drug metformin in the liver. There are no data on the expression and role of MGPDH as a metformin target in cancer. In this study, we evaluated MGPDH as a potential target of metformin in thyroid cancer and investigated its contribution in thyroid cancer metabolism.Experimental Design: We analyzed MGPDH expression in 253 thyroid cancer and normal tissues by immunostaining and examined its expression and localization in thyroid cancer-derived cell lines (FTC133, BCPAP) by confocal microscopy. The effects of metformin on MGPDH expression were determined by qRT-PCR and Western blot analysis. Seahorse analyzer was utilized to assess the effects of metformin on OXPHOS and glycolysis in thyroid cancer cells. We analyzed the effects of metformin on tumor growth and MGPDH expression in metastatic thyroid cancer mouse models.Results: We show for the first time that MGPDH is overexpressed in thyroid cancer compared with normal thyroid. We demonstrate that MGPDH regulates human thyroid cancer cell growth and OXPHOS rate in vitro Metformin treatment is associated with downregulation of MGPDH expression and inhibition of OXPHOS in thyroid cancer in vitro Cells characterized by high MGPDH expression are more sensitive to OXPHOS-inhibitory effects of metformin in vitro and growth-inhibitory effects of metformin in vitro and in vivoConclusions: Our study established MGPDH as a novel regulator of thyroid cancer growth and metabolism that can be effectively targeted by metformin. Clin Cancer Res; 24(16); 4030-43. ©2018 AACR.
Abstract 11553: Percutaneous Coronary Intervention Outcomes in the Elderly: A Single Regional Centre Experience
Authors: Mohamed O Mohamed, Hamid S Khan, Alex Zaphiriou, John N Townend, Sagar N Doshi, Peter F Ludman, Sohail Q Khan
Journal: Circulation (2016)

Background: Ischaemic heart disease is responsible for a significant health care burden in the elderly. The benefit from coronary revascularization with PCI in very elderly patients remains unclear. Purpose: We sought to assess the morbidity and mortality of very elderly patients (VEP; age ≥80 years) undergoing PCI, and compare outcomes to elderly patients (EP; 70-79 years). Methods: 820 consecutive patients (age ≥70 years) undergoing PCI over a three-year period were included (Jan 2012 to Jan 2015). Baseline characteristics, procedural details and clinical outcomes at three points of follow up (in-hospital, 30-day and 1-year) were recorded and patients were classified in to two groups, EP (n=508, 65% males) and VEP (n=312, 67% males). Results: 875 PCI procedures were evaluated, 553 (62%) in the EP group and 322 (38%) performed in VEP group. Baseline characteristics were similar in both groups. All comparative data are expressed as VEP vs. EP with p&lt;0.05 unless otherwise stated. VEP were more likely than EP to undergo PCI for ACS [STEMI (35.3% vs. 22.0%), NSTEMI (47.9% vs. 44.7%)]. EP were more likely to have PCI for stable angina. VEP were more likely to receive three or more stents than EP (19.6% vs. 13.1%). Uni-variable relative risk analyses of mortality and post-procedural complications are shown in Figure 1. Global unadjusted in-hospital mortality was higher in the VEP group (9.1% vs. 4.9%). Global mortality was also higher in the VEP group at 30-day follow up (10.3% vs. 7.5%) and 1-year end point (18.6% vs. 8.7%). Among the post procedure complications, major bleeding requiring transfusion and renal failure were higher in the VEP, whilst stroke rates were not statistically different. Conclusions: Very elderly patients undergoing PCI have higher mortality and complication rate compared to elderly patients. The higher risk of complications may in part be explained by their higher likelihood to present with an ACS and more complex anatomy.
TCTAP A-146 Optimal Frequency for Accurate Measurement of Age-related Changes in Electrical Impedance of Vascular Endothelial Cell by Using Micro-electrochemical Impedance Spectroscopy for Diagnosis of Senescence
Authors: Jung-Joon Cha, Juhun Lim, Jong-Hyun Lee
Journal: Journal of the American College of Cardiology (2018)
P145Distinct alterations between transcriptomic profiles of fibrotic porcine hearts induced by cardiac remodeling, hypertrophy, or cardiotoxicity
Authors: J Winkler, D Lukovic, K Zlabinger, A Gugerell, A Spannbauer, D Traxler, N Pavo, J Bergler-Klein, M Gyongyosi
Journal: Cardiovascular Research (2018)
Lysyl oxidase-like protein 2 (LOXL2) modulates barrier function in cholangiocytes in cholestasis
Authors: Marion J. Pollheimer, Silvia Racedo, Amanda Mikels-Vigdal, Derek Marshall, Christopher Bowlus, Carolin Lackner, Tobias Madl, Tom H. Karlsen, Johannes R. Hov, Susan K. Lyman, Joanne Adamkewicz, Victoria Smith, Emmanuel Moreau, Gernot Zollner, Tor Jacob Eide, Tatjana Stojakovic, Hubert Scharnagl, Hans-Jürgen Gruber, Rudolf E. Stauber, Michael Trauner, Peter Fickert
Journal: Journal of Hepatology (2018)
Inhalation treatment of primary lung cancer using liposomal curcumin dry powder inhalers
Authors: Tongtong Zhang, Yanming Chen, Yuanyuan Ge, Yuzhen Hu, Miao Li, Yiguang Jin
Journal: Acta Pharmaceutica Sinica B (2018)

Lung cancer is the leading cause of cancer-related deaths. Traditional chemotherapy causes serious toxicity due to the wide bodily distribution of these drugs. Curcumin is a potential anticancer agent but its low water solubility, poor bioavailability and rapid metabolism significantly limits clinical applications. Here we developed a liposomal curcumin dry powder inhaler (LCD) for inhalation treatment of primary lung cancer. LCDs were obtained from curcumin liposomes after freeze-drying. The LCDs had a mass mean aerodynamic diameter of 5.81 μm and a fine particle fraction of 46.71%, suitable for pulmonary delivery. The uptake of curcumin liposomes by human lung cancer A549 cells was markedly greater and faster than that of free curcumin. The high cytotoxicity on A549 cells and the low cytotoxicity of curcumin liposomes on normal human bronchial BEAS-2B epithelial cells yielded a high selection index partly due to increased cell apoptosis. Curcumin powders, LCDs and gemcitabine were directly sprayed into the lungs of rats with lung cancer through the trachea. LCDs showed higher anticancer effects than the other two medications with regard to pathology and the expression of many cancer-related markers including VEGF, malondialdehyde, TNF-α, caspase-3 and BCL-2. LCDs are a promising medication for inhalation treatment of lung cancer with high therapeutic efficiency.
<b>Solar-Powered Oxygen Delivery in Low-Resource Settings</b>
Authors: Michael T. Hawkes, Andrea L. Conroy, Sophie Namasopo, Ravi Bhargava, Kevin C. Kain, Qaasim Mian, Robert O. Opoka
Journal: JAMA Pediatrics (2018)

This randomized clinical noninferiority trial compares solar-powered oxygen delivery vs standard oxygen delivery using compressed oxygen cylinders among children younger than 13 years with hypoxemic illness at 2 resource-constrained hospitals in Uganda.
The levels of middle surface HBVantigen increase in patients with HBV-driven liver cancer despite prolonged virological suppression: implications for a novel marker of HBV-driven hepatocarcinogenesis
Authors: G. Brancaccio, R. Salpini, L. Colagrossi, V. Fini, M. Cantone, A. Battisti, L. Piermatteo, Y. Oda, C.F. Perno, G.B. Gaeta, V. Svicher
Journal: Journal of Hepatology (2018)
Modified DCF (mDCF) regimen seems to be as effective as original DCF in advanced gastric cancer (AGC).
Authors: Serkan Keskin, Fatma Sen, Fatma Aydogan, Meltem Ekenel, Leyla Kilic, Sezer Saglam, Burak Sakar, Rian Disci, Faruk Aykan
Journal: Journal of Clinical Oncology (2012)

e14628 Background: The aim of this retrospective study (from January 2007 to December 2011) was to investigate the efficacy and tolerability of mDCF schedule for chemotherapy naïve AGC patients. Methods: Patients (n=54) with locally inoperable or distant metastasis, and performance status of 0–2 were eligible. The triplet combination chemotherapy consists of docetaxel 60 mg/m 2 day 1, cisplatin 60 mg/m 2 day 1, 5-flourouracil 600 mg/m 2 for 5 days continuous infusion were administered every 21 days, up to 9 cycles. Prophylactic G-CSF was not allowed. Two of the patients treated with second line cisplatin/capecitabine. None of the patients treated with radiotherapy. Results: In all, 36 (67%) patients were male and 18 (33%) were female; median age was 59 years (range: 23-80 years). Majority of patients (n=46, 85%) were metastatic disease and 8 (15%) of them were locally advanced disease. Liver metastasis and peritonitis carcinomatosa were found in 20 (%43) and 18 (39%) of the 46 cases, respectively. The median cycle of chemotherapy was 6 (ranging from 1 to 9 cycles). In assessing fifty patients for response evaluation, one had complete response. The partial responses achieved in 27 (54%) patients. Seventeen patients (34%) had stable disease and 5 (10%) progressed. Of 2% (n=4) and 11% (n=6) of the patients developed severe (grade 3-4) neutropenia and anemia, respectively. One patient developed febrile neutropenia. Severe thrombocytopenia, hepatic and renal toxicity were not seen. During median follow-up time (8.1 months, range: 1.3-24), 28 (52%) patients were died. The overall and progression-free survival were 11.6 [95% CI: 10.2-13] and 7.7 [95% CI: 6.8-8.7] months, respectively. Conclusions: Although this was not a prospective comparative study, the mDCF regimen seems to be as effective as original DCF in AGC with acceptable and manageable side effects.
Sex Differences in High-Intensity Statin Use Following Myocardial Infarction in the United States
Authors: Sanne A.E. Peters, Lisandro D. Colantonio, Hong Zhao, Vera Bittner, Yuling Dai, Michael E. Farkouh, Keri L. Monda, Monika M. Safford, Paul Muntner, Mark Woodward
Journal: Journal of the American College of Cardiology (2018)
P541Evaluation of plasma exosomal miRNA-1, miRNA-133 and miRNA-208 levels in a porcine model during acute myocardial infarction
Authors: C Mueller, A Spannbauer, D Traxler, D Lukovic, A Borger, K Zlabinger, J Winkler, A Gugerell, M Gyongyosi
Journal: Cardiovascular Research (2018)
Encoding activities of non-coding RNAs
Authors: Yanan Pang, Chuanbin Mao, Shanrong Liu
Journal: Theranostics (2018)

The universal expression of various non-coding RNAs (ncRNAs) is now considered the main feature of organisms' genomes.Many regions in the genome are transcribed but not annotated to encode proteins, yet contain small open reading frames (smORFs).A widely accepted opinion is that a vast majority of ncRNAs are not further translated.However, increasing evidence underlines a series of intriguing translational events from the ncRNAs, which were previously considered to lack coding potential.Recent studies also suggest that products derived from such novel translational events display important regulatory functions in many fundamental biological and pathological processes.Here we give a critical review on the potential coding capacity of ncRNAs, in particular, about what is known and unknown in this emerging area.We also discuss the possible underlying coding mechanisms of these extraordinary ncRNAs and possible roles of peptides or proteins derived from the ncRNAs in disease development and theranostics.Our review offers an extensive resource for studying the biology of ncRNAs and sheds light into the use of ncRNAs and their corresponding peptides or proteins for disease diagnosis and therapy.
CD44 targeting biocompatible and biodegradable hyaluronic acid cross-linked zein nanogels for curcumin delivery to cancer cells: In vitro and in vivo evaluation
Authors: Hae-Yong Seok, N. Sanoj Rejinold, Kamali Manickavasagam Lekshmi, Kondareddy Cherukula, In-Kyu Park, Yeu-Chun Kim
Journal: Journal of Controlled Release (2018)