tbuckley/cabot-search huggingface dataset:
15984 Psoriasis patients treated with ixekizumab were maintained longer on monotherapy compared with other biologics in real-world clinical practice settings: Results from IBM MarketScan databases
Authors: Craig L. Leonardi, Andrew Blauvelt, Baojin Zhu, WIlliam Malatestinic PharmD, William Joe Eastman, Jiaying Guo, David Shrom, Russel Burge, Mark Lebwohl
Journal: Journal of the American Academy of Dermatology (2020)
195TiP GLOW: Phase III study of first-line zolbetuximab + CAPOX versus placebo + CAPOX in Claudin18.2⁺/HER2⁻ advanced/metastatic gastric or gastroesophageal junction adenocarcinoma (G/GEJ)
Authors: R-H. Xu, J.A. Ajani, S-E. Al-Batran, Y-J. Bang, D. Catenacci, P.C. Enzinger, D.H. Ilson, S. Kim, F. Lordick, K. Shitara, E. van Cutsem, A. Arozullah, J.W. Park, M.A. Shah
Journal: Annals of Oncology (2020)
Impaired Skeletal Muscle Endurance in Adults With Complex Congenital Heart Disease is Associated With Local Muscle Oxygenation Kinetics
Authors: Camilla Sandberg, Albert G. Crenshaw, Guilherme H. Elcadi, Christina Christersson, Joanna Hlebowicz, Ulf Thilén, Bengt Johansson
Journal: Circulation (2018)

Introduction: Adults with complex congenital heart disease show reduced aerobic exercise capacity and impaired skeletal muscle function compared to healthy peers. Peripheral muscle factors are pres ...
The 2020 report of The Lancet Countdown on health and climate change: responding to converging crises
Authors: Nick Watts, Markus Amann, Nigel Arnell, Sonja Ayeb-Karlsson, Jessica Beagley, Kristine Belesova, Maxwell Boykoff, Peter Byass, Wenjia Cai, Diarmid Campbell-Lendrum, Stuart Capstick, Jonathan Chambers, Samantha Coleman, Carole Dalin, Meaghan Daly, Niheer Dasandi, Shouro Dasgupta, Michael Davies, Claudia Di Napoli, Paula Dominguez-Salas, Paul Drummond, Robert Dubrow, Kristie L Ebi, Matthew Eckelman, Paul Ekins, Luis E Escobar, Lucien Georgeson, Su Golder, Delia Grace, Hilary Graham, Paul Haggar, Ian Hamilton, Stella Hartinger, Jeremy Hess, Shih-Che Hsu, Nick Hughes, Slava Jankin Mikhaylov, Marcia P Jimenez, Ilan Kelman, Harry Kennard, Gregor Kiesewetter, Patrick L Kinney, Tord Kjellstrom, Dominic Kniveton, Pete Lampard, Bruno Lemke, Yang Liu, Zhao Liu, Melissa Lott, Rachel Lowe, Jaime Martinez-Urtaza, Mark Maslin, Lucy McAllister, Alice McGushin, Celia McMichael, James Milner, Maziar Moradi-Lakeh, Karyn Morrissey, Simon Munzert, Kris A Murray, Tara Neville, Maria Nilsson, Maquins Odhiambo Sewe, Tadj Oreszczyn, Matthias Otto, Fereidoon Owfi, Olivia Pearman, David Pencheon, Ruth Quinn, Mahnaz Rabbaniha, Elizabeth Robinson, Joacim Rocklöv, Marina Romanello, Jan C Semenza, Jodi Sherman, Liuhua Shi, Marco Springmann, Meisam Tabatabaei, Jonathon Taylor, Joaquin Triñanes, Joy Shumake-Guillemot, Bryan Vu, Paul Wilkinson, Matthew Winning, Peng Gong, Hugh Montgomery, Anthony Costello
Journal: The Lancet (2020)
Clopidogrel and Endothelial Injury After Percutaneous Coronary Interventions: Beyond the Antiplatelet Effects⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Goran Rudež, Hendricus J. Duckers, Maarten L. Simoons
Journal: Journal of the American College of Cardiology (2010)
Covid-19: Asymptomatic cases may not be infectious, Wuhan study indicates
Authors: Shaun Griffin
Journal: BMJ (2020)

Asymptomatic cases may not be infectious, Wuhan study indicates Shaun GriffinA mass screening programme of more than 10 million residents of Wuhan, China, performed after SARS-CoV-2 was brought under control, has identified 300 asymptomatic cases of covid-19, none of which was infectious.1
3D bioprinting of a biomimetic meniscal scaffold for application in tissue engineering
Authors: Zhou Jian, Tian Zhuang, Tian Qinyu, Peng Liqing, Li Kun, Luo Xujiang, Wang Diaodiao, Yang Zhen, Jiang Shuangpeng, Sui Xiang, Huang Jingxiang, Liu Shuyun, Hao Libo, Tang Peifu, Yao Qi, Guo Quanyi
Journal: Bioactive Materials (2020)

Appropriate biomimetic scaffolds created via 3D bioprinting are promising methods for treating damaged menisci. However, given the unique anatomical structure and complex stress environment of the meniscus, many studies have adopted various techniques to take full advantage of different materials, such as the printing combined with infusion, or electrospining, to chase the biomimetic meniscus, which makes the process complicated to some extent. Some researchers have tried to tackle the challenges only by 3D biopringting, while its alternative materials and models have been constrained. In this study, based on a multilayer biomimetic strategy, we optimized the preparation of meniscus-derived bioink, gelatin methacrylate (GelMA)/meniscal extracellular matrix (MECM), to take printability and cytocompatibility into account together. Subsequently, a customized 3D bioprinting system featuring a dual nozzle + multitemperature printing was used to integrate the advantages of polycaprolactone (PCL) and meniscal fibrocartilage chondrocytes (MFCs)-laden GelMA/MECM bioink to complete the biomimetic meniscal scaffold, which had the best biomimetic features in terms of morphology and components. Furthermore, cell viability, mechanics, biodegradation and tissue formation in vivo were performed to ensure that the scaffold had sufficient feasibility and functionality, thereby providing a reliable basis for its application in tissue engineering.
Should This Patient Be Screened for Pancreatic Cancer?
Authors: Eileen E. Reynolds, Chyke A. Doubeni, Mandeep S. Sawhney, Zahir Kanjee
Journal: Annals of Internal Medicine (2020)

Because pancreatic cancer is typically advanced at the time of diagnosis, it has a very low 5-year survival rate and may become the second leading cause of cancer death in the United States. A screening program to find early-stage pancreatic cancer is needed but has been challenging to develop because of the lack of an effective screening test. In 2019, the U.S. Preventive Services Task Force performed an evidence review and updated its guidance, confirming its 2004 "D" recommendation against routine screening for average-risk patients. Here, 2 experts review the updated guideline and recent evidence and discuss whether a patient with a family history of pancreatic cancer should undergo screening.
Response to: ‘Correspondence on ‘<i>Prevotella copri</i>in individuals at risk for rheumatoid arthritis’’ by Sun and Ni
Authors: Benoît Thomas P Gilbert, Axel Finckh, Deshire Alpizar Rodriguez
Journal: Annals of the Rheumatic Diseases (2020)

We read with great interest the letter by Sun and Ni.1 Our study described an increased relative abundance in Prevotella spp in individuals at risk of rheumatoid arthritis (RA), particularly in ‘pre-clinical RA stages’, among participants enrolled in a cohort of first-degree relatives of patients with RA (SCREEN-RA).2 Our findings are consistent with the mucosal origins hypothesis of RA development.3

Sun et al explored whether single nucleotide polymorphisms (SNPs) associated with gut microbiome and derived from a genome-wide association study (GWAS) were also associated with RA. The authors performed a Mendelian randomisation (MR) analysis to assess potential associations of ‘gut microbiome-associated-SNPs’ with RA and concluded that there was no causal relation between gut microbiome and RA. We respectfully would like to highlight some substantial differences between our study and Sun et al ’s study and …
Copy number evolution and its relationship with patient outcome—an analysis of 178 matched presentation-relapse tumor pairs from the Myeloma XI trial
Authors: James Croft, Sidra Ellis, Amy L. Sherborne, Kim Sharp, Amy Price, Matthew W. Jenner, Mark T. Drayson, Roger G. Owen, Sally Chown, Jindriska Lindsay, Kamaraj Karunanithi, Hannah Hunter, Walter M. Gregory, Faith E. Davies, Gareth J. Morgan, Gordon Cook, Lilit Atanesyan, Suvi Savola, David A. Cairns, Graham Jackson, Richard S. Houlston, Martin F. Kaiser
Journal: Leukemia (2020)

Abstract Structural chromosomal changes including copy number aberrations (CNAs) are a major feature of multiple myeloma (MM), however their evolution in context of modern biological therapy is not well characterized. To investigate acquisition of CNAs and their prognostic relevance in context of first-line therapy, we profiled tumor diagnosis–relapse pairs from 178 NCRI Myeloma XI (ISRCTN49407852) trial patients using digital multiplex ligation-dependent probe amplification. CNA profiles acquired at relapse differed substantially between MM subtypes: hyperdiploid (HRD) tumors evolved predominantly in branching pattern vs. linear pattern in t(4;14) vs. stable pattern in t(11;14). CNA acquisition also differed between subtypes based on CCND expression, with a marked enrichment of acquired del(17p) in CCND2 over CCND1 tumors. Acquired CNAs were not influenced by high-dose melphalan or lenalidomide maintenance randomization. A branching evolution pattern was significantly associated with inferior overall survival (OS; hazard ratio (HR) 2.61, P = 0.0048). As an individual lesion, acquisition of gain(1q) at relapse was associated with shorter OS, independent of other risk markers or time of relapse (HR = 2.00; P = 0.021). There is an increasing need for rational therapy sequencing in MM. Our data supports the value of repeat molecular profiling to characterize disease evolution and inform management of MM relapse.
Response to: ‘Correspondence on ‘Incidence trend of five common musculoskeletal disorders from 1990 to 2017 at the global, regional and national level: results from the Global Burden of Disease study 2017’ by Chiang<i>et al</i>
Authors: Ziyi Jin, Jinkou Zhao, Lingyun Sun
Journal: Annals of the Rheumatic Diseases (2020)

We appreciate Chiang et al 1 for their interest and comments on our research article entitled ‘Incidence trend of five common musculoskeletal disorders from 1990 to 2017 at the global, regional and national level: results from the global burden of disease study 2017’.2

For exact occupations, it is unfortunately impossible to divide patients with musculoskeletal (MSK) disorders into groups according to their occupations since there are no corresponding estimates from the Global Burden of Disease study 2017.3 4 We agree with your comments on effects of social risk factors and occupational risks between high and low human development index (HDI) countries1; in our study, a stable or increasing trend of age-standardised incidence rate (ASR) for low back pain (LBP) was observed.2 However, occupational risks attributable to ASR might be more likely to be modified among countries …
Meta-analysis of 208370 East Asians identifies 113 susceptibility loci for systemic lupus erythematosus
Authors: Xianyong Yin, Kwangwoo Kim, Hiroyuki Suetsugu, So-Young Bang, Leilei Wen, Masaru Koido, Eunji Ha, Lu Liu, Yuma Sakamoto, Sungsin Jo, Rui-Xue Leng, Nao Otomo, Viktoryia Laurynenka, Young-Chang Kwon, Yujun Sheng, Nobuhiko Sugano, Mi Yeong Hwang, Weiran Li, Masaya Mukai, Kyungheon Yoon, Minglong Cai, Kazuyoshi Ishigaki, Won Tae Chung, He Huang, Daisuke Takahashi, Shin-Seok Lee, Mengwei Wang, Kohei Karino, Seung-Cheol Shim, Xiaodong Zheng, Tomoya Miyamura, Young Mo Kang, Dongqing Ye, Junichi Nakamura, Chang-Hee Suh, Yuanjia Tang, Goro Motomura, Yong-Beom Park, Huihua Ding, Takeshi Kuroda, Jung-Yoon Choe, Chengxu Li, Hiroaki Niiro, Youngho Park, Changbing Shen, Takeshi Miyamoto, Ga-Young Ahn, Wenmin Fei, Tsutomu Takeuchi, Jung-Min Shin, Keke Li, Yasushi Kawaguchi, Yeon-Kyung Lee, Yongfei Wang, Koichi Amano, Dae Jin Park, Wanling Yang, Yoshifumi Tada, Ken Yamaji, Masato Shimizu, Takashi Atsumi, Akari Suzuki, Takayuki Sumida, Yukinori Okada, Koichi Matsuda, Keitaro Matsuo, Yuta Kochi, Leah C Kottyan, Matthew T Weirauch, Sreeja Parameswaran, Shruti Eswar, Hanan Salim, Xiaoting Chen, Kazuhiko Yamamoto, John B Harley, Koichiro Ohmura, Tae-Hwan Kim, Sen Yang, Takuaki Yamamoto, Bong-Jo Kim, Nan Shen, Shiro Ikegawa, Hye-Soon Lee, Xuejun Zhang, Chikashi Terao, Yong Cui, Sang-Cheol Bae
Journal: Annals of the Rheumatic Diseases (2020)

Objective Systemic lupus erythematosus (SLE), an autoimmune disorder, has been associated with nearly 100 susceptibility loci. Nevertheless, these loci only partially explain SLE heritability and their putative causal variants are rarely prioritised, which make challenging to elucidate disease biology. To detect new SLE loci and causal variants, we performed the largest genome-wide meta-analysis for SLE in East Asian populations. Methods We newly genotyped 10 029 SLE cases and 180 167 controls and subsequently meta-analysed them jointly with 3348 SLE cases and 14 826 controls from published studies in East Asians. We further applied a Bayesian statistical approach to localise the putative causal variants for SLE associations. Results We identified 113 genetic regions including 46 novel loci at genome-wide significance (p&lt;5×10 −8 ). Conditional analysis detected 233 association signals within these loci, which suggest widespread allelic heterogeneity. We detected genome-wide associations at six new missense variants. Bayesian statistical fine-mapping analysis prioritised the putative causal variants to a small set of variants (95% credible set size ≤10) for 28 association signals. We identified 110 putative causal variants with posterior probabilities ≥0.1 for 57 SLE loci, among which we prioritised 10 most likely putative causal variants (posterior probability ≥0.8). Linkage disequilibrium score regression detected genetic correlations for SLE with albumin/globulin ratio (r g =−0.242) and non-albumin protein (r g =0.238). Conclusion This study reiterates the power of large-scale genome-wide meta-analysis for novel genetic discovery. These findings shed light on genetic and biological understandings of SLE.
18859 Cutaneous manifestations of drug abuse
Authors: Francisca Regina Oliveira Carneiro, Lais Carneiro Dos Santos, Yasmin Maria Rocha Calderaro, Andrey de Almeida Carneiro, Lucas Solano Araújo da Silva, Samuel Soares Ribeiro, Beatriz Amaral Costa Savino, Nicole Garcia dos Santos Góes, Matheus dos Santos Cardoso, Amanda Wosny Guimarães, and Letícia Viana Martins Beltrão
Journal: Journal of the American Academy of Dermatology (2020)
Transoral outlet reduction: could additional sutures cause more harm?
Authors: Jad Farha, Selim Gebran, Mohamad I. Itani, Cem Simsek, Shahem Abbarh, Ariana Lopez, Zadid Haq, Kristen Koller, Margo Dunlap, Atif Adam, Mouen A. Khashab, Andreas Oberbach, Michael Schweitzer, Dilhana Badurdeen, Vivek Kumbhari
Journal: Endoscopy (2020)

The double purse-string pattern (DPSP) of transoral outlet reduction (TORe) should conceivably result in a more robust scaffolding for the gastrojejunal anastomosis (GJA). However, there is a paucity of literature pertaining to post-TORe stenosis as an adverse event. Our aim was to determine the rate of stenosis, its potential predictors, and other complications of DPSP TORe.We performed a retrospective analysis of a prospectively maintained database of 129 consecutive patients who underwent DPSP TORe between December 2015 and August 2019.The adverse event rate of TORe was 17.1 % (n = 22), with a 13.3 % (n = 17) rate of stenosis. Stenosis was not significantly associated with any baseline characteristics. GJA diameter pre- and post-TORe, the difference between these values, and procedure duration were not predictive of stenosis. Of patients who developed stenosis, 10 (58.8 %) responded to endoscopic balloon dilation and 7 (41.2 %) required stent placement.As the DPSP technique is a challenging procedure, with high complication rate and limited benefit, it should not be used for TORe.
Pan-cancer identification of clinically relevant genomic subtypes using outcome-weighted integrative clustering
Authors: Arshi Arora, Adam B. Olshen, Venkatraman E. Seshan, Ronglai Shen
Journal: Genome Medicine (2020)

Abstract Background Comprehensive molecular profiling has revealed somatic variations in cancer at genomic, epigenomic, transcriptomic, and proteomic levels. The accumulating data has shown clearly that molecular phenotypes of cancer are complex and influenced by a multitude of factors. Conventional unsupervised clustering applied to a large patient population is inevitably driven by the dominant variation from major factors such as cell-of-origin or histology. Translation of these data into clinical relevance requires more effective extraction of information directly associated with patient outcome. Methods Drawing from ideas in supervised text classification, we developed survClust , an outcome-weighted clustering algorithm for integrative molecular stratification focusing on patient survival. survClust was performed on 18 cancer types across multiple data modalities including somatic mutation, DNA copy number, DNA methylation, and mRNA, miRNA, and protein expression from the Cancer Genome Atlas study to identify novel prognostic subtypes. Results Our analysis identified the prognostic role of high tumor mutation burden with concurrently high CD8 T cell immune marker expression and the aggressive clinical behavior associated with CDKN2A deletion across cancer types. Visualization of somatic alterations, at a genome-wide scale (total mutation burden, mutational signature, fraction genome altered) and at the individual gene level, using circomap further revealed indolent versus aggressive subgroups in a pan-cancer setting. Conclusions Our analysis has revealed prognostic molecular subtypes not previously identified by unsupervised clustering. The algorithm and tools we developed have direct utility toward patient stratification based on tumor genomics to inform clinical decision-making. The survClust software tool is available at https://github.com/arorarshi/survClust .
Methyltransferase inhibitors restore SATB1 protective activity against cutaneous T cell lymphoma in mice
Authors: Carly M. Harro, Jairo Perez-Sanz, Tara Lee Costich, Kyle K. Payne, Carmen M. Anadon, Ricardo A. Chaurio, Subir Biswas, Gunjan Mandal, Kristen E. Rigolizzo, Kimberly B. Sprenger, Jessica A. Mine, Louise C. Showe, Xiaoqing Yu, Kebin Liu, Paulo C. Rodriguez, Javier Pinilla-Ibarz, Lubomir Sokol, Jose R. Conejo-Garcia
Journal: Journal of Clinical Investigation (2020)

Cutaneous T cell lymphoma (CTCL) has a poorly understood etiology and no known cure. Using conditional knockout mice, we found that ablation of the genomic organizer special AT-rich sequence-binding protein 1 (Satb1) caused malignant transformation of mature, skin-homing, Notch-activated CD4+ and CD8+ T cells into progressively fatal lymphoma. Mechanistically, Satb1 restrained Stat5 phosphorylation and the expression of skin-homing chemokine receptors in mature T cells. Notably, methyltransferase-dependent epigenetic repression of SATB1 was universally found in human Sézary syndrome, but not in other peripheral T cell malignancies. H3K27 and H3K9 trimethylation occluded the SATB1 promoter in Sézary cells, while inhibition of SUV39H1/2 methyltransferases (unlike EZH2 inhibition) restored protective SATB1 expression and selectively abrogated the growth of primary Sézary cells more effectively than romidepsin. Therefore, inhibition of methyltransferases that silence SATB1 could address an unmet need for patients with mycosis fungoides/Sézary syndrome, a set of incurable diseases.
Re: Adjuvant Radiotherapy Versus Early Salvage Radiotherapy plus Short-term Androgen Deprivation Therapy in Men with Localised Prostate Cancer After Radical Prostatectomy (GETUG-AFU 17): A Randomised, Phase 3 Trial
Authors: Lara Rodríguez-Sánchez, Gilles Crehange, Mostefa Bennamoun, Petr Macek, Xavier Cathelineau, Rafael Sanchez-Salas
Journal: European Urology (2020)
AB0072 Lymphocytotoxic antibody (lca) among iraqi sle patients and their relatives
Authors: AA Al-Shaikly, MM Hasan, KM Mousawy, S Salman
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To study the lymphocytotoxic antibodies (LCA) in SLE patients and their first degree relatives compared to matching controls. <h3>Methods</h3> Complement dependent microcytotoxicity test was used to asses the presence of LCA, their temperature dependence in addition to HLA specificity among 40 SLE patients, 184 of their first degree relatives in comparison to 100 subjects of a blood bank donor as a healthy control. <h3>Results</h3> Lyphocytotoxic activity was manifested in 70% of patients, 33.36% of relatives compared to 80% of control group. While cold dependent antibodies were higher among patients group (92.8%) compared to 35% of their relatives. The presence of these antibodies in a control group was less temperature dependent, since 62.5% of them reacted both at 22C° and 15C° and only 12.5% of them exhibited a sole reactivity of 15C°. No association between LCA and any of HLA antigen of both classes was detected, however, patients had a tendency to react with a large number of lymphocyte samples than did positive sera from other group. Generally, females, had a higher percentage of Lca (42.15%), yet, the highest percentage was reported among sisters, followed by mothers, while brothers exhibited the least frequency (15.15%). In contrast to females, male subjects reported the highest frequency of these antibodies among age group of &gt; 50 years. <h3>Conclusion</h3> Patients expressed a high positivity rate of cold LCA. Moreover, female first degree relatives showed higher positivity rates than male relatives or controls.
Sentinel node biopsy in patients with melanoma improves the accuracy of staging when added to clinicopathological features of the primary tumor
Authors: M.-A. El Sharouni, M.D. Stodell, T. Ahmed, K.P.M. Suijkerbuijk, A.E. Cust, A.J. Witkamp, V. Sigurdsson, P.J. van Diest, R.A. Scolyer, J.F. Thompson, C.H. van Gils, S.N. Lo
Journal: Annals of Oncology (2020)
J-Wave Syndromes Caused by Repolarization or Depolarization Mechanisms: A Debated Issue Among Experimental and Clinical Electrophysiologists**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Martin Borggrefe, Rainer Schimpf
Journal: Journal of the American College of Cardiology (2010)
Amplification-free long-read sequencing reveals unforeseen CRISPR-Cas9 off-target activity
Authors: Ida Höijer, Josefin Johansson, Sanna Gudmundsson, Chen-Shan Chin, Ignas Bunikis, Susana Häggqvist, Anastasia Emmanouilidou, Maria Wilbe, Marcel den Hoed, Marie-Louise Bondeson, Lars Feuk, Ulf Gyllensten, Adam Ameur
Journal: Genome biology (2020)

One ongoing concern about CRISPR-Cas9 genome editing is that unspecific guide RNA (gRNA) binding may induce off-target mutations. However, accurate prediction of CRISPR-Cas9 off-target activity is challenging. Here, we present SMRT-OTS and Nano-OTS, two novel, amplification-free, long-read sequencing protocols for detection of gRNA-driven digestion of genomic DNA by Cas9 in vitro.
Generating evidence for therapeutic effects: the need for well-conducted randomized trials
Authors: Robert M. Califf, Lesley H. Curtis, Robert A. Harrington, Adrian F. Hernandez, Eric D. Peterson
Journal: Journal of Clinical Investigation (2020)

In this viewpoint, Robert Califf, former commissioner of the U.S. Food and Drug Administration, and colleagues reflect on how to approach questions about which patient treatments and strategies work, particularly in light of the tremendous pressure on the government and biomedical research enterprise to quickly develop safe, effective therapies during the SARS-CoV-2 pandemic.
217O Pembrolizumab (pembro) combination therapies in patients with metastatic castration-resistant prostate cancer (mCRPC): Cohorts A-C of the phase Ib/II KEYNOTE-365 study
Authors: A.M. Joshua, H. Gurney, M. Retz, A. Tafreshi, P.C.C. Fong, N.D. Shore, E. Romano, M. Augustin, J.M. Piulats, W.R. Berry, M.P. Kolinsky, S.S. Sridhar, H.J. Conter, T. Todenhöfer, L.J. Appleman, H. Wu, C. Schloss, C.H. Poehlein, J.S. de Bono, E.Y. Yu
Journal: Annals of Oncology (2020)