tbuckley/cabot-search huggingface dataset:
The occupations at increased risk of COPD: analysis of lifetime job-histories in the population-based UK Biobank Cohort
Authors: Sara De Matteis, Deborah Jarvis, Andrew Darnton, Sally Hutchings, Steven Sadhra, David Fishwick, Lesley Rushton, Paul Cullinan
Journal: European Respiratory Journal (2019)

Occupational exposures are important, preventable causes of chronic obstructive pulmonary disease (COPD). Identification of COPD high-risk jobs is key to focus preventive strategies, but a definitive job-list is unavailable. We addressed this issue by evaluating the association of lifetime job-histories and lung function data in the population-based UK Biobank cohort, whose unprecedented sample size allowed analyses restricted to never-smokers to rule out the most important confounder, tobacco smoking. COPD was spirometrically defined as forced expiratory volume in 1 s/forced vital capacity ratio below the lower limit of normal. Lifetime job-histories were collected via OSCAR (Occupations Self-Coding Automatic Recording), a new validated online tool that automatically codes jobs into the UK Standard Occupational Classification v.2000. Prevalence ratios for COPD by employment duration in each job compared to lifetime office workers were estimated using robust Poisson regression adjusted for age, sex, centre and smoking. Only associations confirmed among never-smokers and never-asthmatics were considered reliable. From the 116 375 participants with complete job-histories, 94 551 had acceptable/repeatable spirometry data and smoking information and were included in the analysis. Six occupations showed an increased COPD risk among never-smokers and never-asthmatics; most of these also with positive exposure-response trends. Interesting new findings included sculptors, gardeners and warehouse workers. COPD patients, especially never-smokers, should be asked about their job-history for better disease management. Focussed preventive strategies in COPD high-risk jobs are warranted.
Less antibiotics but no inferior effect for bacterial arthritis
Authors: Jian Tian, Chao Cheng, Fangjie Zhang
Journal: Annals of the Rheumatic Diseases (2019)

We read with deep interest the article by Gjika et al ,1 which was aimed at assessing either 2 or 4 weeks of antibiotic therapy after surgical drainage of native joint bacterial arthritis in adults. The results indicated that the effects of the 2-week targeted antibiotic treatment were not inferior when compared with those of the 4-week treatment, and at least the hospitalisation time for hand and wrist arthritis was significantly shortened. This conclusion might be of great significance for surgeons to decide on how to prescribe antibiotics and for patients, who might have received fewer antibiotics without inferior effect, and might help reduce medical costs and bacterial resistance.

It is a daunting task to rectify the abuse of antibiotics in China2 in the past decade. The Chinese government was actively rectifying antibiotic …
Abstract 5102: Deep learning method for the classification of CNV based on the next generation target sequencing
Authors: Jidong Lang, Geng Tian
Journal: Cancer Research (2019)

Abstract Background: Copy number variations (CNVs) are of great importance to many cancers. Recently, the next-generation sequencing has made detecting CNV by sequencing possible. Traditional CNV determination methods involve expensive experiments, which is costly. Recently, several algorithms were proposed the detection of CNV, but none of them could utilize only the coverage information at a specific gene to make the determination of CNV at the gene. Methods: We collected 1132 samples with 51 mesenchymal-epithelial transition factor (MET) CNV samples and 1081 samples with no CNVs. We split the exons of MET to multiple 50-bp windows with the stride of 40-bp. At each window the supporting reads were counted, and reads numbers at each exons were piled up, generating a matrix. The training set containing 38 CNV-positive matrices and 38 CNV-negative matrices were extracted from all the matrices, leaving the others as the test set. The deep learning network, convolutional neural network (CNN) were applied to distinguish between the CNV-positive matrices and the CNV-negative matrices. For comparison, logistic regression model was also applied for the classification task. Results: The training set were split into 5 pieces containing 15 samples each and 5-fold cross validation were run for the CNN or the logistic regression model. After running 10 5-fold cross validation, we got an accuracy of 85.73 ± 9.24% for CNN and the average accuracy of 87.07 ± 8.99% for the logistic regression model. We chose 3 best models in both CNN and logistic regression models for the determination of the test set. The CNN models gained the accuracy of 71.84 ± 2.19% while the logistic regression models gained the accuracy of 69.70 ± 2.56%. Furthermore, the Area Under Curve (AUC) of the CNN models were 0.6335 ± 0.0124, higher than that of the logistic regression models which was 0.5666 ± 0.0115. Conclusions: We proposed a method to determine the samples with CNV by using the convolutional neural network with only the coverage information within the specific region. It provides the possibility of CNV detection for cancer patients using only the next generation sequencing data. Citation Format: Jidong Lang, Geng Tian. Deep learning method for the classification of CNV based on the next generation target sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5102.
Clinical Efficacy and Biological Regulations of ω–3 PUFA-Derived Endocannabinoids in Major Depressive Disorder
Authors: Bo Yang, Lin Lin, Richard P. Bazinet, Yu-Chuan Chien, Jane Pei-Chen Chang, Senthil Kumaran Satyanarayanan, Huanxing Su, Kuan-Pin Su
Journal: Psychotherapy and Psychosomatics (2019)

Endocannabinoids (ECs) are one type of bioactive endogenous neuroinflammatory mediator derived from polyunsaturated fatty acids (PUFAs), which may regulate the emotional processes. Here, we assessed the effect of ω-3 PUFAs on EC levels, which may be the novel targets for the ω-3 PUFAs' antidepressive effects.We conducted a 12-week double-blind, nonplacebo, randomized controlled trial. Eighty-eight major depressive disorder (MDD) participants were randomly assigned to receive eicosapentaenoic acid (EPA, 3.0 g/day), docosahexaenoic acid (DHA, 1.4 g/day), or a combination of EPA (1.5 g/d) and DHA (0.7 g/day). Eighty-five participants completed the trial, and their clinical remission and plasma PUFA-derived EC levels (pmol/mL) were measured.The cumulative rates of clinical remission were significantly higher in the EPA and EPA + DHA groups than the DHA group (51.85 and 53.84 vs. 34.37%; p =0.027 and p =0.024, respectively). EPA and EPA + DHA treatments increased the eicosapentaenoylethanolamide (EPEA) levels compared to DHA treatment (0.33 ± 0.18 and 0.35 ± 0.24 vs. 0.08 ± 0.12; p =0.002 and p =0.001, respectively), while EPA + DHA treatment increased the docosahexaenoylethanolamide levels more than EPA treatment (1.34 ± 2.09 vs. 0.01 ± 1.79; p =0.006). Plasma EPEA levels were positively correlated with rates of clinical remission (hazard ratio: 1.60, 95% confidence interval: 1.08-2.39).Treatments enriched with EPA increased plasma EPEA levels, which was positively associated with clinical remission. This finding may suggest that levels of plasma EPEA play a potential novel endogenous therapeutic target in MDD.
Neoadjuvant systemic therapy in melanoma: recommendations of the International Neoadjuvant Melanoma Consortium
Authors: Rodabe N Amaria, Alexander M Menzies, Elizabeth M Burton, Richard A Scolyer, Michael T Tetzlaff, Robert Antdbacka, Charlotte Ariyan, Roland Bassett, Brett Carter, Adil Daud, Mark Faries, Leslie A Fecher, Keith T Flaherty, Jeffrey E Gershenwald, Omid Hamid, Angela Hong, John M Kirkwood, Serigne Lo, Kim Margolin, Jane Messina, Michael A Postow, Helen Rizos, Merrick I Ross, Elisa A Rozeman, Robyn P M Saw, Vernon Sondak, Ryan J Sullivan, Janis M Taube, John F Thompson, Bart A van de Wiel, Alexander M Eggermont, Michael A Davies, Paolo A Ascierto, Andrew J Spillane, Alexander C J van Akkooi, Jennifer A Wargo, Christian U Blank, Hussein A Tawbi, Georgina V Long, Miles C Andrews, Donald A Berry, Matthew S Block, Genevieve M Boland, Kathryn B Bollin, Matteo S Carlino, Richard D Carvajal, Jonathan Cohen, Diwakar Davar, Keith A Delman, Reinhard Dummer, Michael D Farwell, David E Fisher, Alberto Fusi, Isabella C Glitza, Tanja D de Gruijl, David E Gyorki, Axel Hauschild, Tina J Hieken, James Larkin, David H Lawson, Celeste Lebbe, Jeffrey E Lee, Michael C Lowe, Jason J Luke, Grant A McArthur, David F McDermott, Jennifer L McQuade, Tara C Mitchell, Teresa M Petrella, Peter A Prieto, Igor Puzanov, Caroline Robert, April K Salama, Shaneen Sandhu, Dirk Schadendorf, Alexander N Shoushtari, Jeffrey A Sosman, Susan M Swetter, Ken K Tanabe, Samra Turajlic, Douglas S Tyler, Scott E Woodman, Frances C Wright, Jonathan S Zager
Journal: The Lancet Oncology (2019)
Abstract CT001: Biomarkers of systemic inflammation associated to reduced clinical activity of atezolizumab monotherapy in patients with metastatic triple negative breast cancer
Authors: Yijin Li, Marcella Fassò, Leisha A. Emens, Luciana Molinero
Journal: Cancer Research (2019)

Abstract Background: Immune checkpoint blockade by anti-PD-L1 antibody atezolizumab has demonstrated clinical benefits in metastatic triple negative breast cancer (mTNBC). IL-6 and IL-8 myeloid inflammation is linked to poor prognosis in cancer patients treated with chemotherapy, but its association with single agent atezolizumab-treated patients with mTNBC remains unknown. In this study, we investigated the association of biomarkers (BM) of systemic inflammation with clinical outcomes in patients with mTNBC treated with atezolizumab monotherapy. Methods: Baseline pre-treatment plasma samples were collected from mTNBC patients enrolled in the Phase I atezolizumab monotherapy clinical trial PCD4989g (NCT01375842, n = 116). IL-6, IL-8 and CRP were tested by ELISA or Luminex assays and their levels were assessed for association with baseline clinical demographic characteristics and atezolizumab clinical activity for response rate (ORR), progression free (PFS) and overall survival (OS). Results: Baseline IL-6, IL-8, and CRP levels were positively associated with the clinical prognostic traits ECOG performance status (&amp;gt;0), presence of liver metastases, large size of target lesions (&amp;gt;=6.5cm), and increased LDH (&amp;gt;=1.5xULN). Elevated baseline IL-6 and CRP, but not IL-8, were also linked with later lines of therapy (&amp;gt;=2). Univariate analyses showed that IL-6 (&amp;gt;=15pg/ml), IL-8 (&amp;gt;=11.4pg/ml) and CRP (&amp;gt;=3mg/L) were associated with reduced OS and PFS (Table), but only CRP was associated to reduced ORR. Multivariate analyses considering the aforementioned clinical demographic variables showed that IL-6 (HR 2.00 [1.16-3.38]); and CRP (HR 2.74 [1.49-5.28]), but not IL-8 (HR 1.07 [0.78-1.74]), were associated with OS. Conclusion: The systemic IL-6/CRP inflammatory axis is an independent factor linked with poor outcomes of mTNBC patients treated with atezolizumab monotherapy and may play unique roles in affecting the anti-tumor activity in this hard to treat patient population. Table (univariate)BMLow mPFSBMHigh mPFSPFS HR (CI 95%)BMLow mOSBMHigh mOSOS HR (CI 95%)IL-6 (&amp;gt;=15pg/ml)1.45 mo1.35 mo1.87 (1.23-2.83)12.6 mo2.6 mo2.55 (1.63-4.01)IL-8 (&amp;gt;=11.4pg/ml)1.94mo1.34 mo2.00 (1.36-2.95)12.6 mo6.42 mo2.05 (1.34-3.14)CRP (&amp;gt;=3mg/L)2.50 mo1.35 mo2.07 (1.31-3.25)20.5 mo6.9 mo3.33 (1.91-5.79) Citation Format: Yijin Li, Marcella Fassò, Leisha A. Emens, Luciana Molinero. Biomarkers of systemic inflammation associated to reduced clinical activity of atezolizumab monotherapy in patients with metastatic triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT001.
Reply to Piet R. Dirix, Carole Mercier, and Luc Y. Dirix's Letter to the Editor re: Fabian Lohaus, Klaus Zöphel, Steffen Löck, et al. Can Local Ablative Radiotherapy Revert Castration-resistant Prostate Cancer to an Earlier Stage of Disease? Eur Urol 2019;75:548–51
Authors: Tobias Hölscher, Fabian Lohaus, Manfred Wirth, Esther G.C. Troost
Journal: European Urology (2019)
Abstract 4838: Leflunomide inhibits the growth of LKB1-inactivated tumors in both xenograft and immunocompetent genetically engineered mouse models
Authors: Rui Jin, Xiuju Liu, Wei Peng, Yijian Fan, Boxuan Liu, Shuanying Yang, Chun-gen Xing, Melissa Gilbert-Ross, Adam Marcus, Wei Zhou
Journal: Cancer Research (2019)

Abstract Introduction: LKB1 is the third mostly frequently mutated gene in lung adenocarcinoma, and is mutually exclusive with EGFR mutations. Furthermore, a recent clinical trial indicated that lung cancers with LKB1 mutations are unlikely to respond to immune checkpoint therapy. Therefore, there is an urgent need for novel therapies for LKB1-inactivated lung cancer. We previously demonstrated that leflunomide preferentially induces apoptosis in LKB1-null lung cancer cell lines in vitro. Here, we evaluated the effect of leflunomide in both a xenograft model and immune-competent genetically engineered mouse model (GEMM). Methods: LKB1-null H460 xenograft mice were treated with leflunomide (35mg/kg/day) for 23 days through oral gavage and tumor volume was measured every the other day. KrasG12D/Lkb1-/-Luciferase GEMM mice were treated with leflunomide (30mg/kg/day) for 44 days and tumor burden was measured by bioluminescence imaging (BLI) score every week. At the end of experiments, tumors were dissected, weighed, and analyzed by immunohistochemistry. Results: Although leflunomide is an FDA-approved agent to treat rheumatoid arthritis, its immune suppression function did not facilitate but inhibited the growth of KrasG12DLkb1-/- lung adenocarcinoma. This suppression was also observed in H460 xenografts, and leflunomide treatment did not alter animal weight in either model. Furthermore, distant cancer metastasis was not observed in leflunomide-treated GEMM. In residual tumors from the treated group, cleaved caspase-3 was not detectable but there was a significant decrease in Ki67 staining. This is consistent with our in vitro findings that leflunomide primarily inhibits cell proliferation through the promotion of G1 cell cycle arrest. Conclusion: Our findings indicate that leflunomide may be a viable reagent for the treatment of LKB1-mutated lung adenocarcinoma. Citation Format: Rui Jin, Xiuju Liu, Wei Peng, Yijian Fan, Boxuan Liu, Shuanying Yang, Chun-gen Xing, Melissa Gilbert-Ross, Adam Marcus, Wei Zhou. Leflunomide inhibits the growth of LKB1-inactivated tumors in both xenograft and immunocompetent genetically engineered mouse models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4838.
Abstract 711: p53 causes butein-mediated apoptosis of chronic myeloid leukemia cells
Authors: SeoYeon Lee, Yu-Jeong Choi, Myeong-sun Kim, Sooyeon Kang, Ji Hye Kim, Sang Mi Woo, Seong-Gyu Ko, Sukjoong Oh
Journal: Cancer Research (2019)

Abstract Progression of chronic myeloid leukemia, marked by the oncogenic Bcr-Abl mutation, is tightly associated with an alteration of the p53 pathway. It is known that butein extracted from various plants represses cancer growth. Although the anticancer effects of butein are widely accepted, the mechanisms by which butein induces apoptosis of chronic myeloid leukemia cells remains to be elucidated. The present study demonstrated that butein-induced apoptosis was mediated by p53. KBM5 chronic myeloid leukemia (CML) cells expressing wild-type p53 were more sensitive to butein compared with p53-null K562 CML cells in terms of apoptotic cell death. In addition, butein arrested KBM5 cells at S-phase and altered the expression levels of certain cyclins and the p53-downstream targets, MDM2 and p21. In addition, while butein reduced the protein expression of MDM2 in the KBM5 and K562 cells, it resulted in proteasome-independent MDM2 degradation in p53-expressing KBM5 cells, however, not in p53-null K562 cells. Therefore, the present study suggested that p53 causes the butein-mediated apoptosis of leukemic cells. Citation Format: SeoYeon Lee, Yu-Jeong Choi, Myeong-sun Kim, Sooyeon Kang, Ji Hye Kim, Sang Mi Woo, Seong-Gyu Ko, Sukjoong Oh. p53 causes butein-mediated apoptosis of chronic myeloid leukemia cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 711.
Tetraploidy in Acute Myeloid Leukemia Is Associated with Poor Outcomes Regardless of the Presence of Favorable Risk Features, and Requires an Allogeneic Stem Cell Transplant in First Remission
Authors: Bachir Berbari, Matthew E. Behrens, Lindsey J. Hathaway, Bachir Farah, Ali Baghian, Georges E. Tanios, Theresa C. Brown, John J. Schmieg, Hana Safah, Nakhle S. Saba
Journal: Blood (2017)
Corrigendum to “NIR-controlled morphology transformation and pulsatile drug delivery based on multifunctional phototheranostic nanoparticles for photoacoustic imaging-guided photothermal-chemotherapy” [Biomaterials 176 (2018) 1–12]
Authors: Jun Yang, Shaodong Zhai, Huan Qin, He Yan, Da Xing, Xianglong Hu
Journal: Biomaterials (2019)
Abstract 3851: An Aurora kinase inhibitor BPR6K471 inhibits tumor growth and reduces the cancer stem cell-like properties of small cell lung cancer
Authors: Chun-Ping Chang, Yi-Yu Ke, Wen-Hsing Lin, Dai-Hui Jhuo, Wan-Ping Wang, Chia-Hua Tsai, Yen-Ting Chen, Yu-Jie Su, Ming-Chun Hung, Zhong-Wei Wu, Po-Chu Kuo, Teng-Kuang Yeh, Ching-Ping Chen, Jen-Shin Song, Chiun-Tong Chen, Chuan Shih, Ya-Hui Chi
Journal: Cancer Research (2019)

Abstract Small cell lung cancer (SCLC) is one the most aggressive tumors with poor survival rate. SCLC patients often present with metastasis at time of diagnosis, excluding surgery as a treatment option. While patients show high response rate to standard chemotherapy such as cisplatin/etoposide, they soon develop drug resistance and disease progression. Therefore, new therapeutic strategies are urgently needed for SCLC. Several characteristics of SCLC such as aggressiveness and drug resistance could attribute to the existence of a cancer stem cell (CSC) subpopulation in SCLC. The SCLC cell line NCI-H446 has been shown to present high degree of stemness and express stem cell markers including CD133, OCT4, MYC and Nestin. Here we develop a pyrimidine-based small molecule BPR6K471 which potently inhibits Aurora kinase activities in enzymatic- and cell- based assays. BPR6K471 efficiently (IC50 = 66 nM) inhibits proliferation of NCI-H446, and reduces the expression of stem-cell markers. In addition, intravenous injection of BPR6K471 inhibits &amp;gt;90 % progression of NCI-H446 in a mouse xenograft model. These results suggest that targeting Aurora kinases may be a potential therapeutic strategy to combat the CSC subpopulation in SCLC. Citation Format: Chun-Ping Chang, Yi-Yu Ke, Wen-Hsing Lin, Dai-Hui Jhuo, Wan-Ping Wang, Chia-Hua Tsai, Yen-Ting Chen, Yu-Jie Su, Ming-Chun Hung, Zhong-Wei Wu, Po-Chu Kuo, Teng-Kuang Yeh, Ching-Ping Chen, Jen-Shin Song, Chiun-Tong Chen, Chuan Shih, Ya-Hui Chi. An Aurora kinase inhibitor BPR6K471 inhibits tumor growth and reduces the cancer stem cell-like properties of small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3851.
Abstract 16259: Beneficial Effect of Factor Xa Antagonists on Recurrence After Pulmonary Vein Isolation in Paroxysmal Atrial Fibrillation Patients With Less Overloaded Left Atrium
Authors: Masamichi Yano, Masami Nishino, Kohei Ukita, Akito Kawamura, Motoki Yasunaga, Kyosuke Yanagawa, Hitoshi Nakamura, Yutaka Matsuhiro, Keisuke Yasumura, Koji Yasumoto, Akihiro Tanaka, Naoki Mori, Daisuke Nakamura, Yasuyuki Egami, Ryu Shutta, Jun Tanouchi
Journal: Circulation (2017)

Background: Several reports demonstrated that inflammation was associated with inducibility of atrial fibrillation (AF). On the other hand, recent studies have reported that factor Xa induced an in...
Abstract 1671: Characterization of a gene signature predictive of cancer patient survival prognosis and chemo-response
Authors: Paul Tran, Shuchun Li, Hai-Tao Liu, Lynn Tran, Sharad Purohit, Boying Dun, Jin-Xiong She
Journal: Cancer Research (2019)

Abstract Precision oncology aims to match cancer patients with drugs based on their unique molecular profiles. The MATCH trial results indicate ~80% of cancer patients do not benefit from screening cancer patients for actionable genomic aberrations. We aim to identify potentially druggable gene signatures that are molecular drivers of poor survival outcome for these cancer patients. We analyze data from The Cancer Genome Atlas (TCGA) to identify patient groups with differential survival characteristics using gene expression data. We applied a univariate Cox regression model to identify genes associated with patient survival and identified a 67 gene signature of highly correlated genes significant for cell cycle related gene ontologies on over-representation analysis. Patients from the TCGA dataset whose tumors have a higher gene expression score are more likely to have worse survival prognosis compared to tumors with a lower gene expression score, demonstrated through Kaplan-Meier survival analysis and univariate and multivariate Cox proportional hazard models. This suggests we have identified a co-regulated gene expression network associated with cellular proliferation which predicts overall and recurrence-free survival in many of the cancers in the TCGA dataset. We further analyzed data from the NCI-60 Human Tumor Cell Lines Screen and found the cellular proliferation gene signature expression is correlated with response to cell cycle inhibitors. We then validated this finding using resistant cell lines and gene knockdown models in vitro. This gene signature may provide an important tool for selecting patients for chemotherapy administration. Citation Format: Paul Tran, Shuchun Li, Hai-Tao Liu, Lynn Tran, Sharad Purohit, Boying Dun, Jin-Xiong She. Characterization of a gene signature predictive of cancer patient survival prognosis and chemo-response [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1671.