tbuckley/cabot-search huggingface dataset:
Prediction of Subclinical Coronary Artery Disease With Breast Arterial Calcification and Low Bone Mass in Asymptomatic Women
Authors: Yeonyee E. Yoon, Kyoung Min Kim, Jong Soo Han, Si-Hyuck Kang, Eun Ju Chun, Soyeon Ahn, Sun Mi Kim, Sang Il Choi, Bo La Yun, Jung-Won Suh
Journal: JACC. Cardiovascular imaging (2018)
Efficacy of transdermal granisetron patch in controlling chemotherapy-induced nausea and vomiting in gastrointestinal cancer patients.
Authors: Loretta A. Williams, Christine Brown, Deborah Braccia
Journal: Journal of Clinical Oncology (2015)

e20660 Background: Patients with gastrointestinal (GI) cancer are at risk of chemotherapy-induced nausea and vomiting (CINV) due to the common use of highly emetogenic chemotherapy regimens. Depending on tumor location, patients with GI cancer can also experience limited gut motility and absorptive capacity, potentially decreasing the effectiveness of oral prophylactic medication. A granisetron transdermal system (GTS) has been shown to be as effective as oral granisetron in controlling CINV across multiple tumor types. This post-hoc analysis specifically examined efficacy and safety of GTS in patients with gastrointestinal cancer. Methods: A randomized, phase 3 study has been published comparing GTS (7 day application) to oral (2 mg/day) in patients receiving either moderately or highly emetogenic chemotherapy for 3-5 days. Data for this analysis were limited to patients with gastrointestinal cancer (n = 53). The rates of complete control (CC; no vomiting and/or retching, mild nausea, no rescue medication) and complete response (CR; no vomiting and/or retching, no rescue medication) using either GTS or oral were compared. Need for rescue medication and patient’s global satisfaction (assessed using a 10 cm visual analog scale) were also compared. Results: 53 gastrointestinal cancer patients (27 GTS, 26 oral) were included. The majority of patients received a cisplatin-based regimen (43 patients; 81%) for 3 days (36 patients; 68%) or 4 - 5 days (17 patients; 32%); 94% received highly emetogenic chemotherapy (Hesketh level 5). The CC and CR rates (both 70%) in the GTS group were similar to rates in the oral population (CC = 69%, CR = 73%). The lack of need for rescue medication was similar for GTS and oral (81% both groups; p= 0.95) and patient’s global satisfaction were not different between groups (8.50 cm vs. 8.22 cm; p= 0.48). The only treatment related adverse event with GTS was one case of constipation. Conclusions: This retrospective analysis suggests GTS may be an effective option for prevention of CINV in patients with GI cancer who are at high risk of CINV and could experience challenges with oral medication due to tumor sequelae. A larger, confirmatory prospective study is warranted
Reporting of The CONSORT extension for Stepped-Wedge Cluster Randomised Trials: Extension of the CONSORT 2010 statement with explanation and elaboration
Authors: Karla Hemming, Monica Taljaard, Joanne E McKenzie, Richard Hooper, A Copas, JA Thompson, M Dixon-Woods, A Aldcroft, A Doussau, M Grayling, C Kristunas, CE Goldstein, MK Campbell, Alan Girling, S Eldridge, MJ Campbell, Richard Lilford, C Weijer, A Forbes, JM Grimshaw
Journal: BMJ (2018)
FRI-091-HGF protector effect in intrahepatic cholestasis
Authors: Elsy Soraya Salas Silva, Arturo Simoni Nieves, Maria Valeria Razori, Jonatan Barrera Chimal, Jocelyn López Ramírez, Leticia Bucio-Ortiz, Luis Enrique Gómez Quiroz, Marcelo Gabriel Roma, María Concepción Gutiérrez Ruiz
Journal: Journal of Hepatology (2019)
Brain metastatic disease in adenocarcinoma of the lung and type of EGFR mutation (EGFRMUT).
Authors: Nafisa Abdelhafiez, Ashwaq Aman Mohammed Alolayan, Ahmed Gasmelseed, Tabrez Pasha, Nagham Ramzi Sheblaq, Mohammad Alkyait, Abdul Rahman Jazieh
Journal: Journal of Clinical Oncology (2015)

e19067 Background: Brain metastasis (BM) is a common finding in patients with lung cancer. Our study aims at evaluating the incidence and outcome of patients with (BM) with EGFRMUT. Methods: This is a retrospective study conducted in a tertiary medical center in Riyadh, Saudi Arabia. All patients with adenocarcinoma of lung primary diagnosed and tested for EGFR mutation between 2006-2014 were included. Demographic, clinical data, smoking history, histopathological diagnosis, EGFRMUT and survival data were collected. Results: Data of 78 patients were included; (60.26%) were males, almost all of them were Saudi (76 patients), median age was 61 years (41-81) and the majority were nonsmoker (60%). Brain metastasis was seen in 21 patients (26.92%) and 47% of them presented with synchronous disease. 36 patients were harboring EGFR mutation (46.15%), 19 patients had exon 19 mutation (52.78%), 13 patients exon18 (36.11%),3 patient exon 21 (8.3%) and one patients expressed exon 20 mutation (2.78%). In a univariate analysis, the incidence of BM was higher among females (p = 0.0152) and EGFRMUT patients (p = 0.0274) but the significance disappeared in the multivariate analysis. However, patients with exon 19 mutation showed higher incidence of BM when compared with the wild type in both univariate (P = 0.0037) and multivariate analysis(CI 1.653 – 18.672)(P = 0.0056). Patients with brain metastasis and EGFRMUT survived longer compared with patients without brain metastasis in both wild and EGFRMUT group but it was not statistically significant. Conclusions: Patients with exon 19 mutation (not other mutations) were found to have higher rate of BM compared to wild type and this did not impact the overall survival negatively. Larger confirmatory studies and exploration of pathogenesis are warranted.
242. Pro-Proliferative Functions of Drosophila Small Mitochondrial Heat Shock Protein 22 in Human Cells
Journal: Molecular Therapy (2010)

Aging is a complex process accompanied by a decreased capacity of cells to cope with random damages induced by reactive oxygen species, the natural by-products of energy metabolism, leading to protein aggregation in various components of the cell. Chaperones are important players in the aging process as they prevent protein misfolding and aggregation. Small chaperones, such as small heat shock proteins, are involved in the refolding and/or disposal of protein aggregates, a feature of many age-associated diseases. In Drosophila melanogaster, mitochondrial Hsp22 (DmHsp22), is localized in the mitochondrial matrix and is preferentially up-regulated during aging. Its overexpression results in an extension of life span (>30%) (Morrow, G., Samson, M., Michaud, S., and Tanguay, R. M. (2004) FASEB J. 18, 598–599 and Morrow, G., Battistini, S., Zhang, P., and Tanguay, R. M. (2004) J. Biol. Chem. 279, 43382–43385). Long lived flies expressing Hsp22 also have an increased resistance to oxidative stress and maintain locomotor activity longer. In the present study, the cross-species effects of Hsp22 expression were tested. DmHsp22 was found to be functionally active in human cells. It extended the life span of normal fibroblasts, slowing the aging process as evidenced by a lower level of the senescence associated β-galactosidase. DmHsp22 expression in human cancer cells increased their malignant properties including anchorage-independent growth, tumor formation in nude mice, and resistance to a variety of anticancer drugs. We report that the DmHsp22 interacts and inactivates wild type tumor suppressor protein p53, which may be one possible way of its functioning in human cells.
SAT-225-The risk of hepatic decompensation is reduced, but not abolished after direct-acting antivirals: The role of portal hypertension
Authors: Elton Dajti, Federico Ravaioli, Antonio Colecchia, Giovanni Marasco, Maria Letizia Bacchi Reggiani, Luigina Vanessa Alemanni, Mariarosa Tamé, Stefano Brillanti, Francesco Azzaroli, Giuseppe Mazzella, Davide Festi
Journal: Journal of Hepatology (2019)
THU-437-The Global Epidemiology on non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in patients with type 2 diabetes mellitus: A systematic review and meta-analysis
Authors: Zobair Younossi, Pegah Golabi, Leyla Deavila, James Paik, Manirath Srishord, Natsu Fukui, Ying Qiu, Leah Burns, Arian Afendy, Fatema Nader
Journal: Journal of Hepatology (2019)
Progerin accumulation in nucleus pulposus cells impairs mitochondrial function and induces intervertebral disc degeneration and therapeutic effects of sulforaphane
Authors: Xiaolong Xu, Di Wang, Chao Zheng, Bo Gao, Jing Fan, Pengzhen Cheng, Baohua Liu, Liu Yang, Zhuojing Luo
Journal: Theranostics (2019)

Progerin, a truncated unprocessed lamin A protein, causes tissue aging and degeneration. In this study we explored the role of progerin in the pathogenesis of intervertebral disc degeneration (IDD). We also examined the effect of sulforaphane (SFN) on progerin accumulation and mitochondrial dysfunction in IDD. Methods: The role of progerin in IDD was explored using human nucleus pulposus (NP) tissues, rat NP cells, and Lmna G609G knock-in mice. Immunostaining, X-ray imaging, and Western blotting were performed to assess the phenotypes of intervertebral discs. Alterations in senescence and apoptosis were evaluated by SA-β-galactosidase, immunofluorescence, flow cytometry, and TUNEL assays. Mitochondrial function was investigated by JC-1 staining, transmission electron microscopy, and determination of the level of ATP and the activities of mitochondrial enzymes. Results: The progerin level was elevated in degenerated human NP tissues. Lmna G609G/G609G mice displayed IDD, as evidenced by increased matrix metalloproteinase-13 expression and decreased collagen II and aggrecan expression and disc height. Furthermore, progerin overexpression in rat NP cells induced mitochondrial dysfunction (decreased ATP synthesis, mitochondrial membrane potential, and activities of mitochondrial complex enzymes), morphologic abnormalities, and disrupted mitochondrial dynamic (abnormal expression of proteins involved in fission and fusion), resulting in apoptosis and senescence. SFN ameliorated the progerin-induced aging defects and mitochondrial dysfunction in NP cells and IDD in Lmna G609G/G609G mice. Conclusions: Progerin is involved in the pathogenesis of IDD. Also, SFN alleviates progerin‑induced IDD, which is associated with amelioration of aging defects and mitochondrial dysfunction. Thus, SFN shows promise for the treatment of IDD.
Prevalence of children exposed to secondhand smoke at home and in the car in Azores (Portugal)
Authors: J. Precioso, S. Frias, C.N. Silva, V. Rocha, J. Cunha-Machado, F. Gonçalves, I. Sousa
Journal: Pulmonology (2019)

To identify the prevalence of exposure to secondhand smoke (SHS) at home and in the car among children attending the 4th grade in Azores.This is a cross-sectional study that assessed children's exposure to SHS in a convenience sample of school children attending the 4th grade in all primary schools of Azores. The entire population of 4th graders from all elementary schools in Azores were asked to participate in the study (n=2463) in 2017. A validated self-reported questionnaire was administered to 2092 students who delivered the signed informed consent form. We analyzed frequencies, contingency tables, and performed Chi-square tests.Results showed that 56.1% (95% CI 54.0-58.2) children reported having, at least, one smoking parent. Overall exposure to SHS at home was 38.4% (95% CI 36.3-40.6), and overall exposure to SHS in the car was 27.6% (95% CI 25.8-29.3). Children whose parents were smokers reported being more exposed to SHS at home (63.6%; 95% CI 58.6-68.3) than children whose parents were non-smokers (32.3%; 95% CI 30.2-34.6).The results showed that the children's exposure to SHS in Azores is high and it tends to be higher than the prevalence found in mainland Portugal. Having parents who smoke is a major risk factor for children's exposure to SHS at home. These data justify a population-wide intervention plan for preventing tobacco consumption and children's exposure to SHS in Azores.
SAT-094-Effects of branched-chain amino acids on the progression of advanced liver disease: A Korean nationwide, multicenter, prospective, observational, cohort study
Authors: Jung Gil Park, Won Young Tak, Soo Young Park, Young Oh Kweon, Se Young Jang, Yu Rim Lee, Si Hyun Bae, Do Young Kim, June Sung Lee, Ki Tae Suk, In Hee Kim, Heonju Lee, Woo Jin Chung, Byoung KukJang, Jeong Ill Suh, Jeong Heo, Hyun Young Woo, MyungJin Oh, Won Kee Lee
Journal: Journal of Hepatology (2019)
Clinical response of psoriasis to subcutaneous methotrexate correlates with inhibition of cutaneous T helper 1 and 17 inflammatory pathways
Authors: K. Reich, J.L.K. Reich, T.M. Falk, N. Blödorn‐Schlicht, U. Mrowietz, R. Kiedrowski, C. Pfeiffer, J. Niesmann, Y. Frambach, R.B. Warren
Journal: British Journal of Dermatology (2019)
Efficacy of Fish Oil and/or Probiotic Intervention on the Incidence of Gestational Diabetes Mellitus in an At-Risk Group of Overweight and Obese Women: A Randomized, Placebo-Controlled, Double-Blind Clinical Trial
Authors: Outi Pellonperä, Kati Mokkala, Noora Houttu, Tero Vahlberg, Ella Koivuniemi, Kristiina Tertti, Tapani Rönnemaa, Kirsi Laitinen
Journal: Diabetes Care (2019)

To assess whether the risk of gestational diabetes mellitus (GDM) may be lowered and glucose metabolism improved by daily administration of fish oil and/or probiotic supplements in overweight and obese pregnant women.We randomized in a double-blind manner 439 women (mean 13.9 ± 2.1 gestational weeks [gw]) into four intervention groups: fish oil + placebo, probiotics + placebo, fish oil + probiotics, and placebo + placebo. Fish oil (1.9 g docosahexaenoic acid and 0.22 g eicosapentaenoic acid) and probiotic supplements (Lactobacillus rhamnosus HN001 and Bifidobacterium animalis ssp. lactis 420, 1010 colony-forming units each) were provided for daily consumption from randomization beyond delivery. Primary outcomes were the incidence of GDM diagnosed with oral glucose tolerance test targeted at 24-28 gw and the change in fasting glucose between randomization and late pregnancy (mean 35.2 ± 0.9 gw). Insulin concentration, insulin resistance HOMA2-IR index, and pregnancy outcomes were determined, as were adverse effects related to the intervention. Analyses were by intent to treat.No differences were found among the intervention groups in the maternal and neonatal pregnancy outcomes or side effects related to the intervention (P > 0.05). The proportion of women with GDM (94 of 377; fish oil + placebo, 23 of 96, 24.0%; probiotics + placebo, 25 of 99, 25.3%; fish oil + probiotics, 26 of 91, 28.6%; and placebo + placebo, 20 of 91, 22.0%) and the change in glucose, insulin, or HOMA2-IR (n = 364) did not differ among the intervention groups (P > 0.11 for all comparisons).An intervention with fish oil and/or probiotics during pregnancy seemed to be both safe and well tolerated but conferred no benefits in lowering the risk of GDM or improving glucose metabolism in overweight and obese women.
THU-003-European multicenter validation of autoantibodies against huntingtin-interacting protein 1-related protein for the diagnosis of autoimmune hepatitis in adults
Authors: Bastian Engel, Jana Diestelhorst, Maciej K. Janik, Zachou Kalliopi, Christoph Schramm, Maria Carlota Londoño, HABES Sarah, Claudine Lalanne, Simon Pape, Joost Ph Drenth, Luigi Muratori, Amédée Renand, Isabel Graupera, Ansgar W. Lohse, George Dalekos, Piotr Milkiewicz, Michael P. Manns, Elmar Jaeckel, Richard Taubert
Journal: Journal of Hepatology (2019)
Duration of Immunity and Effectiveness of Diphtheria-Tetanus–Acellular Pertussis Vaccines in Children
Authors: Matthieu Domenech de Cellès, Pejman Rohani, Aaron A. King
Journal: JAMA Pediatrics (2019)

The United States has experienced a nationwide resurgence of pertussis since the mid-1970s, despite high estimated vaccine coverage. Short-lived immunity induced by diphtheria-tetanus-acellular pertussis (DTaP) vaccines in young children is widely believed to be responsible for this growing burden, but the duration of protection conferred by DTaP vaccines remains incompletely quantified.To assess the duration of immunity and the effectiveness of DTaP vaccines in US children.A mathematical, age-structured model of pertussis transmission, previously validated empirically on incidence data in Massachusetts, was used in this simulation study to assess the duration of DTaP immunity most consistent with the empirical values of the relative increase in the odds of acquiring pertussis from recent epidemiologic studies in the United States. The study included 5 simulated cohorts of children born between January 1, 2001, and December 31, 2005, followed up between the ages of 5 and 9 years (study period, January 1, 2006, to December 31, 2014). Statistical analysis was performed from May 1 to December 1, 2017.Vaccination with DTaP according to the US immunization schedule, with a range of assumptions regarding the degree of waning immunity.Vaccine effectiveness and relative change in the odds of acquiring pertussis (odds ratio) in children aged 5 to 9 years, duration of DTaP immunity, and vaccine population-level impact.This study found a marked association between the degree of waning immunity, vaccine effectiveness, and the odds ratio. Counterintuitively, the odds ratio was positively associated with vaccine effectiveness, as a consequence of nonlinear, age-assortative transmission dynamics. Based on the empirical odds ratios (1.33; 95% CI, 1.23-1.43), it was estimated that vaccine effectiveness exceeded 75% in children aged 5 to 9 years and that more than 65% of children remained immune to pertussis 5 years after the last DTaP dose.The results of this study suggest that temporal trends in the odds of acquiring pertussis are an unreliable measure of the durability of vaccine-induced protection. They further demonstrate that DTaP vaccines confer imperfect, but long-lived protection. Control strategies should be based on the best available estimates of vaccine properties and the age structure of the transmission network.
FRI-309-Hepatitis B virus B and T cell specific responses are reduced in adults with a body mass index &gt; 35 and non-alcoholic fatty liver disease and in a mice model of NAFLD compared to adults with a BMI of &gt; 35 patients and normal animals
Authors: Shivali Joshi, Rachelle Davis, Mang Ma, Edward Tam, Curtis Cooper, Alnoor Ramji, Erin Kelly, Saumya Jayakumar, Mark G Swain, Craig Jenne, Carla Coffin
Journal: Journal of Hepatology (2019)
FRI-411-Nurse-led out-patient-clinic for patients with cirrhosis
Authors: Hanne Bennick, Anne Kjaergaard Danielsen, Lene Dupont, Marthe Forbord Huss Joensson, Marie Louise Sjoedin Hamberg, Ane Soegaard Teisner, Mette Lehmann Andersen
Journal: Journal of Hepatology (2019)
QuatCy: A Heptamethine Cyanine Modification With Improved Characteristics
Authors: Sopida Thavornpradit, Syed Muhammad Usama, G. Kate Park, Jaya P. Shrestha, Shinsuke Nomura, Yoonji Baek, Hak Soo Choi, Kevin Burgess
Journal: Theranostics (2019)

A major restriction on optical imaging techniques is the range of available fluorophores that are compatible with aqueous media without aggregation, absorb light above 750 nm with high extinction coefficients, fluoresce with relatively high quantum yields, and resist photodecomposition. Indocyanine green (ICG or A in this paper) is an important example of a fluorophore that fits this description. Other dyes that are becoming increasingly prevalent are select heptamethine cyanine dyes (Cy7) which feature a cyclohexyl framework to rigidify the conjugated alkenes, and meso-chlorine substitution; MHI-148 (B) is one example. Methods: Research described here was initiated to uncover the consequences of a simple isoelectronic substitution to MHI-148 that replaces a cyclohexyl methylene with a dialkyl ammonium fragment. Solubility experiments were carried out in aqueous and cell culture media, photophysical properties including fluorescence quantum yields, brightness and stability were measured. Moreover, in vivo pharmacokinetics, distribution and tumor seeking properties were also explored. Results: Modification to incorporate dialkyl ammonium fragment leads to a brighter, more photostable fluorophore, with a decreased tendency to aggregation, complementary solubility characteristics, and a lower cytotoxicity. Conclusion: All the above-mentioned parameters are favorable for many anticipated applications of the new dye we now call quaternary cyanine-7 or QuatCy.
Identification of potentially actionable mutations in RTKs in melanoma detected by next generation sequencing (NGS).
Authors: Jan Kemnade, Jason Roszik, Aron Joon, Franceso Stingo, Veera Baladandayuthapani, Alexander J. F. Lazar, Scott Eric Woodman, Michael A. Davies
Journal: Journal of Clinical Oncology (2015)

9064 Background: The success of personalized cancer therapies targeting patients with specific actionable mutations underscores the need to expand the search for relevant mutations with functional and/or clinical consequences. Cutaneous melanomas have a high mutation burden due to ultraviolet radiation exposure, thus necessitating approaches to distinguish driver versus passenger mutations. Here we report the analysis of the nature and location of somatic mutations in 16 receptor tyrosine kinases (RTKs) in a cutaneous melanoma cohort analyzed by next generation sequencing (NGS). Methods: NGS for all exons of 201 cancer-related genes was performed on tumor and germline DNA from pts with non-acral cutaneous melanoma (n = 108). Somatic mutations in RTKs (MET, PDGFRA, PDGFRB, KIT, EGFR, ERBB2, ERBB3, RET, IGF1R, EPHA3, DDR1, DDR2, ALK, JAK1, JAK2, JAK3) were mapped to the tyrosine kinase domain (TKD), other functional regions (i.e. transmembrane domains, binding domains) or conserved protein domains (ORD), or regions of unknown significance (RUS) in each gene. The COSMIC database was analyzed for presence of the same mutations in other tumors. Results: Missense mutations were detected in all 16 RTKs. The number of mutations identified in each RTK ranged from 2 (IGF1R) to 24 (EPHA3), with a median of 7.5 mutations per RTK. The average incidence of mutations found in the TKD region for each RTK was 29% and ranged from 0% (ERBB2, ERBB3) to 80% (JAK2). For the ORD regions the average was 34%, ranging from 0% (ERBB2, ERBB3, RET, DDR2) to 61.5% (MET). For the RUS regions the average was 37%, ranging from 0% (PDGFRB, DDR1) to 100% (ERRB2, ERRB3). Mutations detected in 11 of the RTKs were also identified in cancer sequencing datasets available on COSMIC. Conclusions: The prevalence of mutations in the TKD, ORD, and RUS regions varied significantly among the 16 RTKs in the cutaneous melanoma cohort. Overall ~62% of the mutations mapped to regions with potential functional significance, and ~16% have been reported previously in other cancers. Integration of these analyses with predicted structural and functional consequences may be used to prioritize candidate actionable mutations for in-depth characterization.