tbuckley/cabot-search huggingface dataset:
Senescence: The Last Half of Life.
Authors: G Stanley Hall
Journal: JAMA (1922)

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A new PET-CT score for locally-advanced inoperable NSCLC stage III patients treated with chemoradiotherapy
Authors: O. Roengvoraphoj, C. Eze, J. Taugner, A. Gjika, A. Tufman, L. Käsmann, I. Hadi, E. Mille, C. Belka, F. Manapov
Journal: Annals of Oncology (2019)

Background: FDG-PET/CT is an integral part of staging and radiation treatment planning for patients with stage III non-small cell lung cancer (NSCLC). In this study, we analysed the correlation between different PET parameters and survival in NSCLC patients treated with chemoradiotherapy (CRT). Methods: Ninety-nine consecutive patients with NSCLC stage IIIA-B and good performance status, who underwent FDG-PET-CT before the start of CRT were analysed. Maximum standardized uptake value of primary tumor (SUVmax_PT) and range between the two most distant PET-positive (SUV≥3) lymph nodes in two directions (cranio-caudal and transversal) were analysed for their correlation with patient survival. The cranio-caudal distance was defined as A- and the transversal as B-line. The area under the ROC curve (AUC) as well as the cut-off SUVmax, A- and B-lines were calculated. Results: Median survival for the entire cohort was 20.8 months (95% CI: 15.3-26.3). Patients with SUVmax_PT ≥ 8 had poor overall survival (OS) (19 vs. 40 months in patients with SUVmax ≥ 8 and <8, p < 0.0001). A-line was not associated with OS, whereas B-line < 3.7 cm improved OS significantly (30 vs. 16 months in patients with B-line < 3.7 and ≥3.7cm, p = 0.001). The sum of A- and B-lines with the cut-off at 6.7cm correlated with overall survival significantly (29 vs. 18 months in patients with sum < 6.7 and ≥6.7cm, p = 0.04). The PET-CT score was generated on the basis of PET parameters correlated with OS in univariate analysis. The patients were divided into 4 subgroups. The low-risk subgroup (0 points) included patients with SUVmax_PT< 8, B-line < 3.7 cm and the sum of A- and B-lines < 6.7 cm (n = 20, 21.3%). Twenty-eight patients (29.5%) had 1 point (intermediate risk), 20 (21.3%) had 2 points (high) and 26 patients (27.7%) had 3 points (very high risk). Median OS in terms of low/intermediate/high and very high risk subgroups was 40 (95% CI: 0-83)/27 (95% CI: 15-39)/26 (95% CI: 15-37) and 14 months (95% CI: 13-14), (p = 0.0001). Conclusions: A new PET-CT score was developed for patients with inoperable stage III NSCLC treated with definitive CRT. Initial SUVmax_PT < 8, B-line < 3.7 cm and PET-CT score were predictors of patient long-term outcome. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Enhanced Microbial Bile Acid Deconjugation and Impaired Ileal Uptake in Pregnancy Repress Intestinal Regulation of Bile Acid Synthesis
Authors: Caroline Ovadia, Alvaro Perdones‐Montero, Konstantina Spagou, Ann Smith, Magali H. Sarafian, Maria Gomez‐Romero, Elena Bellafante, Louise C.D. Clarke, Fouzia Sadiq, Vanya Nikolova, Alice Mitchell, Peter H. Dixon, Natalie Santa‐Pinter, Annika Wahlström, Shadi Abu‐Hayyeh, Julian R.F. Walters, Hanns‐Ulrich Marschall, Elaine Holmes, Julian R. Marchesi, Catherine Williamson
Journal: Hepatology (2019)

Pregnancy is associated with progressive hypercholanemia, hypercholesterolemia, and hypertriglyceridemia, which can result in metabolic disease in susceptible women. Gut signals modify hepatic homeostatic pathways, linking intestinal content to metabolic activity. We sought to identify whether enteric endocrine signals contribute to raised serum bile acids observed in human and murine pregnancies, by measuring fibroblast growth factor (FGF) 19/15 protein and mRNA levels, and 7α‐hydroxy‐4‐cholesten‐3‐one. Terminal ileal farnesoid X receptor (FXR)‐mediated gene expression and apical sodium bile acid transporter (ASBT) protein concentration were measured by qPCR and western blotting. Shotgun whole‐genome sequencing and ultra‐performance liquid chromatography tandem mass spectrometry were used to determine the cecal microbiome and metabonome. Targeted and untargeted pathway analyses were performed to predict the systemic effects of the altered metagenome and metabolite profiles. Dietary CA supplementation was used to determine whether the observed alterations could be overcome by intestinal bile acids functioning as FXR agonists. Human and murine pregnancy were associated with reduced intestinal FXR signaling, with lower FGF19/15 and resultant increased hepatic bile acid synthesis. Terminal ileal ASBT protein was reduced in murine pregnancy. Cecal bile acid conjugation was reduced in pregnancy because of elevated bile salt hydrolase‐producing Bacteroidetes . CA supplementation induced intestinal FXR signaling, which was not abrogated by pregnancy, with strikingly similar changes to the microbiota and metabonome as identified in pregnancy. Conclusion : The altered intestinal microbiota of pregnancy enhance bile acid deconjugation, reducing ileal bile acid uptake and lowering FXR induction in enterocytes. This exacerbates the effects mediated by reduced bile acid uptake transporters in pregnancy. Thus, in pregnant women and mice, there is reduced FGF19/15‐mediated hepatic repression of hepatic bile acid synthesis, resulting in hypercholanemia.
FRI-058-Randomized controlled trial to compare efficacy of albumin dialysis using MARS versus new adsorbent recirculation for pruritus treatment
Authors: Jan Stange, Hartmut Schmidt, Steffen Mitzner, Sebastian Koball, Christian Wilms, Hans Ulrich Gerth, Michael Hinz, Tarek Hassanein, Andreas Kortgen, Christoph Sponholz, Matthias Dollinger, Raoul Benedikt Sauer, Alexandra Rivera Luna, Victoria Rivera Luna
Journal: Journal of Hepatology (2019)
Effect of renin-angiotensin system blockers on survival of metastatic non-small cell lung cancer patients receiving erlotinib.
Authors: Adnan Aydiner, Rumeysa Ciftci, Fatma Sen
Journal: Journal of Clinical Oncology (2015)

e19151 Background: We aimed to determine whether renine-angiotensin system blockers (RASBs), which include angiotensin converting enzyme inhibitors and angiotensin II receptor blockers, improve the overall survival (OS) of patients with metastatic non-small cell lung cancer (NSCLC). Methods: The medical charts of 117 patients with metastatic NSCLC were retrospectively assessed. Thirty-seven patients (RASB group) using RASBs during systemic treatment were compared with 80 controls (control = C group) who did not use RASBs following the diagnosis of NSCLC. The histological subtype, performance status, age, gender, smoking status, comorbidities, other medications, chemotherapeutics (CT), and erlotinib that were received in any line of treatment were recorded. We compared the OS of the patients in the RASB and C groups. Results: The median (±SD) age of the patients was 61(±1) years and all patients were administered systemic treatment (CT or erlotinib). The RASB group was more likely to be smokers, have hypertension and ischemic heart disease, and use erlotinib, thiazides, beta-blockers and calcium-channel blockers (p < 0.05 for all) compared with the C group. The median follow-up period was longer for RASB group than C group (17 vs 11 months, p = 0.033). The most commonly prescribed RASB agent was valsartan (n = 12/37). At the time of the analysis, 83.7% of patients had died. In the univariate analysis the median OS was longer in the RASB group compared with the C group (17(±4.1) vs 12 (±1.4) months, p = 0.016). Interestingly, further analyses revealed that RASBs significantly improved OS only if used with erlotinib concurrently (34±1.8 vs 25±5 months, p = 0.002). However, the benefit of RASBs on OS disappeared in the multivariate analysis. Conclusions: The use of RASBs during erlotinib treatment may prolong OS of patients with metastatic NSCLC.
Risk Factors for Severe Liver Disease in Patients With Type 2 Diabetes
Authors: Karl Björkström, Stefan Franzén, Björn Eliasson, Mervete Miftaraj, Soffia Gudbjörnsdottir, Ylva Trolle-Lagerros, Ann-Marie Svensson, Hannes Hagström
Journal: Clinical Gastroenterology and Hepatology (2019)
PS-136-Can lenvatinib meet clinical needs of patients with unresectable hepatocellular carcinoma? Multicenter analysis
Authors: Atsushi Hiraoka, Takashi Kumada, Koichi Takaguchi, Kazuya Kariyama, tsuji kunihiko, Ei Itobayashi, Hironori Ochi, Kazuto Tajiri, Hirooka Masashi, Noritomo Shimada, Toru Ishikawa, Akemi Tsutsui, Hiroshi Shibata, Toshifumi Tada, Hidenori Toyoda, Kazuhiro Nouso, Norio Itokawa, Kouji Joko, Masanori Atsukawa, Michitaka Imai, Kojiro Michitaka, Yoichi Hiasa, Masatoshi Kudo
Journal: Journal of Hepatology (2019)
Abstract P096: Trends in Lifestyle Habits in US Youth Ages 6 to 19 Years: National Health and Nutrition Examination Survey 2003 to 2014
Authors: Amanda M Perak, Hongyan Ning, Linda V Van Horn, Sarah D de Ferranti, Donald M Lloyd-Jones
Journal: Circulation (2018)

Introduction: The AHA emphasizes healthy lifestyle habits in 4 domains for pediatric cardiovascular health: nutrition, body size, physical activity, and smoking. We tested the hypothesis that in recent years among US youth, nutrition and smoking improved, while body size and physical activity did not. Methods: We analyzed cross-sectional data in 15,712 youths aged 6-19 years from 6 NHANES surveys: 2003-04, 2005-06, 2007-08, 2009-10, 2011-12, and 2013-14. We applied survey weights to generate US population-level estimates and used multivariate linear regression to test for time-dependent linear trends in lifestyle habits, separately by sex and age group (6-11 vs. 12-19 years). Results: See Table. Favorable linear trends were seen across age and sex groups in many nutrient intakes, particularly total energy, solid fats, and added sugars; fiber intake also improved among 6-11 year-old youths. However, prevalence of ideal intakes as defined by clinical guidelines remained low. Favorable trends were also seen in smoking and secondhand smoke exposure. On the other hand, body mass index and waist to height ratio showed no time-dependent trends, except for a small increasing linear trend in the prevalence of obesity for 12-19 year-old youths. Similarly, for physical activity and screen time, the only significant linear trend was decreasing mean physical activity among 12-19 year-old females. Conclusions: US youth have generally improved nutrition and avoidance of smoking in recent years, although these habits remain suboptimal in the population. Body size and physical activity are not improving, and may be worsening in adolescents.
Obesity causes pulmonary dysbiosis affecting innate immune response in murine asthma model
Authors: Marina Caçador Ayupe, Flávia Márcia de Castro e Silva, Erick Esteves de Oliveira, Marcilene Gomes Evangelista Ambrósio, Pollyana Amaral Salvador Freitas, Julliane Dutra Medeiros, Gilson Costa Macedo, Juciane Maria de Castro Andrade, Dionéia Evangelista Cesar, Ana Paula Ferreira
Journal: Allergy (2019)

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Renal cell carcinoma: A focus on elderly population in clinical trials.
Authors: Jane Sze Yin Sui, MinYuen Teo, John Patrick Buckley, David James Gallagher, John McCaffrey
Journal: Journal of Clinical Oncology (2015)

e20514 Background: Treatment for renal cell carcinoma (RCC) has evolved over the last decades from immunotherapies (IT) to targeted therapies (TT). As the incidence of renal cell carcinoma grows, management of RCC becomes a challenging task especially in the aging population. TT is the most frequently used treatment option in older population with metastatic RCC. However, this is under-represented of older population in majority of the clinical trials. Methods: We performed a systemic review on all relevant research literatures from PubMed database published from 1995 to 2014 including Phase II and Phase III studies. We searched the citation on “renal cell carcinoma” to identify all clinical trials. We identified studies which specifically included older patients aged ≥ 65 years old. Results: Ninety-four studies were identified from 1995 to 2014, of which n = 70(74.5%) were Phase II and n = 24(25.5%) were Phase III. Median age was 60 years (range: 52-72). Median upper range of reported age was 78 years (range: 65-89). Only n = 11(11.7%) studies looked at patients ≥ 65 years old, of which n = 5(7.1%) were Phase II and n = 6(25.0%) were Phase III. Majority of studies with documented ≥ 65 years were recent with 7.4% (2011-2014), 3.2% (2005-2010), 1.1% (2004-2000) and none ( < 2000). The median age of patients receiving TT was 60 years and 59 years for IT group. In the TT cohort, 7/30 (23%) studies were represented by ≥ 65 years as compared to IT cohort, 4/46 (8.7%) studies were identified. The degree of underrepresentation is more pronounced in IT group. Overall, the median age, upper limit of age range and proportions of patients appears unchanged over two decades. Conclusions: Older patients with cancer are underrepresented in clinical trials settings especially in the treatment of RCC. Older patients are likely to be excluded from clinical trials due to multiple co-morbidities and ECOG performance status. Hence, we recommend more future clinical studies to be conducted focusing on the older populations. This might be challenging but is warranted in this aging society.
LBP-14-Magnetic Resonance Biomarkers for Early Phase Steatohepatitis Clinical Trials: Short Term Evaluation in Adolescents, Transitoriness or Stability in Steatosis (STEATOSIS)
Authors: Nidhi Goyal, Catherine Sawh, Jorge Angeles, Particia Ugalde-Nicalo, James Proudfoot, Kimberly Newton, Michael Middleton, Claude Sirlin, Jeffrey Schwimmer
Journal: Journal of Hepatology (2019)
THU-333-The HSD17B13:TA (rs72613567) splice variant protects against severity of non-alcoholic fatty liver disease but not fibrosis
Authors: Rafael Paternostro, Katharina Staufer, Stefan Traussnigg, Albert Stattermayer, Emina Halilbasic, Omar Keritam, Judith Stift, Gerhard Prager, Petra Munda, Peter ferencl, Michael Trauner
Journal: Journal of Hepatology (2019)
SAT-129-Type 2 diabetes in patients with liver cirrhosis: prevalence, associated factors and influence on survival
Authors: Maria Torner, Ana Gomez, Carmen Álvarez-Navascués, Valle Cadahía-Rodrigo, Maria Varela, Maria Luisa Gonzalez Dieguez, Carlos Rodríguez, Manuel Rodríguez
Journal: Journal of Hepatology (2019)
Diffuse large B-cell non-Hodgkin’s lymphoma in the vulnerable/frail elderly. A multicentric randomized phase II trial from the GOELAMS/LYSA group.
Authors: Pierre-Louis Soubeyran, Kamel Laribi, Carine A. Bellera, Pascal Godmer, Emmanuel Gyan, Joel Ceccaldi, Charles Foussard, Olivier Tournilhac, Laurence Juhel, Barbara Lortal, Isabelle Soubeyran, Thierry Lamy, Remy Gressin
Journal: Journal of Clinical Oncology (2015)

e20523 Background: Many elderly patients with DLBCL cannot tolerate R-CHOP. The objective of this randomized phase II trial was to assess in frail older patients efficacy of two regimens, R-COP (standard R-CHOP without doxorubicin) and R-COPY (R-COP + liposomal doxorubicin- Myocet at 40 mg/m² IV at d1), associated with comprehensive geriatric assessment (CGA). Methods: DLBCL patients aged ≥ 70 years with stage II-IV disease, poor physiological functioning [performance status (PS) 3 or left ventricular ejection fraction (LVEF) < 50% or creatinine clearance (CrCl) < 50 ml/mn or serum bilirubine (SB) < 30µmol/l or severe comorbidities (SCom)] were included and received R-COP or R-COPY for 6 cycles then 2 cycles of rituximab. CGA was performed in all patients. Geriatric intervention was allowed. Results: Patients were considered frail for the following reasons: PS 3 (47.8%), low CrCl (64.2%), low LVEF and SCom (11.9% each) or high SB (3%). Overall, 83.6% of patients had 2 or 3 adverse prognostic factors according to the aaIPI. CGA was frequently impaired: Basic (39%) or Instrumental Activities of Daily Living (66%), Mini Nutritional Assessment (64%) or Geriatric Depression Scale (42%). After accrual of 20 patients in each arm, R-COPY, with a 60% CR-CRu rate, was stopped because of excess severe toxicity (ST) [febrile neutropenia (FN) and toxic death]. R-COP was pursued up to 47 patients: at the end of treatment, CR+CRu rate was 40.4% but 10 patients experienced ST. 48.9% of R-COP patients did not complete treatment because of progression, death or toxicity. With a median follow-up of 29 months, 2-year survival rates were 39.4% and 50% in the R-COP and R-COPY arms respectively. Overall, among the 14 FN events, only one died from toxicity which may lead to reconsider our ST definition. Conclusions: None of the two regimens appear appropriate in this population of frail elderly but R-COPY is more efficient and toxicity with mainly FN may be manageable. Yet the most frail patients should be identified by CGA at baseline and treated palliatively. However, efforts should be pursued to identify appropriate combinations of targeted treatments with improved efficacy-toxicity ratio. Clinical trial information: NCT00911183.
Acute Noncardiac Organ Failure in Acute Myocardial Infarction With Cardiogenic Shock
Authors: Saraschandra Vallabhajosyula, Shannon M. Dunlay, Abhiram Prasad, Kianoush Kashani, Ankit Sakhuja, Bernard J. Gersh, Allan S. Jaffe, David R. Holmes, Gregory W. Barsness
Journal: Journal of the American College of Cardiology (2019)
Agonist c-Met Monoclonal Antibody Augments the Proliferation of hiPSC-derived Hepatocyte-Like Cells and Improves Cell Transplantation Therapy for Liver Failure in Mice
Authors: Lunzhi Yuan, Yali Zhang, Xuan Liu, Yao Chen, Liang Zhang, Jiali Cao, Xiaoling Li, Mingfeng Wang, Kun Wu, Jun Zhang, Gang Liu, Qiyi Tang, Quan Yuan, Tong Cheng, Ningshao Xia
Journal: Theranostics (2019)

Rationale: Hepatocyte-like cells (HLCs) derived from human induced pluripotent stem cells (hiPSCs) have been developed to address the shortage of primary human hepatocytes (PHHs) for therapeutic applications.However, the in vivo repopulation capacity of HLCs remains limited.This study investigated the roles of agonist antibody activating the c-Met receptor in promoting the in vivo proliferation and repopulation of engrafted PHHs and/or HLCs in mice with liver injuries due to different causes.Methods: An agonist c-Met receptor antibody (5D5) was used to treat PHHs and hiPSC-HLCs in both cell culture and hepatocyte-engrafted immunodeficient mice mimicking various inherited and acquired liver diseases.The promoting roles and potential influence on the hepatic phenotype of the 5D5 regimen in cell transplantation-based therapeutic applications were systematically evaluated.Results: In hiPSC-HLC cell cultures, 5D5 treatment significantly stimulated c-Met receptor downstream signalling pathways and accelerated cell proliferation in dose-dependent and reversible manners.In contrast, only slight but nonsignificant promotion was observed in 5D5-treated PHHs.In vivo administration of 5D5 greatly promoted the expansion of implanted hiPSC-HLCs in fumarylacetoacetate hydrolase (Fah) deficient mice, resulting in significantly increased human albumin levels and high human liver chimerism (over 40%) in the transplanted mice at week 8 after transplantation.More importantly, transplantation of hiPSC-HLCs in combination with 5D5 significantly prolonged animal survival and ameliorated liver pathological changes in mice with acute and/or chronic liver injuries caused by Fas agonistic antibody treatment, carbon tetrachloride treatment and/or tyrosinemic stress.Conclusion: Our results demonstrated that the proliferation of hiPSC-HLCs can be enhanced by antibody-mediated modulation of c-Met signalling and facilitate hiPSC-HLC-based therapeutic applications for life-threatening liver diseases.
Tau Protein Disrupts Nucleocytoplasmic Transport in Alzheimer’s Disease
Authors: Bahareh Eftekharzadeh, J. Gavin Daigle, Larisa E. Kapinos, Alyssa Coyne, Julia Schiantarelli, Yari Carlomagno, Casey Cook, Sean J. Miller, Simon Dujardin, Ana S. Amaral, Jonathan C. Grima, Rachel E. Bennett, Katharina Tepper, Michael DeTure, Charles R. Vanderburg, Bianca T. Corjuc, Sarah L. DeVos, Jose Antonio Gonzalez, Jeannie Chew, Svetlana Vidensky, Fred H. Gage, Jerome Mertens, Juan Troncoso, Eckhard Mandelkow, Xavier Salvatella, Roderick Y.H. Lim, Leonard Petrucelli, Susanne Wegmann, Jeffrey D. Rothstein, Bradley T. Hyman
Journal: Neuron (2019)