tbuckley/cabot-search huggingface dataset:
Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases
Authors: Kazuyoshi Ishigaki, Masato Akiyama, Masahiro Kanai, Atsushi Takahashi, Eiryo Kawakami, Hiroki Sugishita, Saori Sakaue, Nana Matoba, Siew-Kee Low, Yukinori Okada, Chikashi Terao, Tiffany Amariuta, Steven Gazal, Yuta Kochi, Momoko Horikoshi, Ken Suzuki, Kaoru Ito, Satoshi Koyama, Kouichi Ozaki, Shumpei Niida, Yasushi Sakata, Yasuhiko Sakata, Takashi Kohno, Kouya Shiraishi, Yukihide Momozawa, Makoto Hirata, Koichi Matsuda, Masashi Ikeda, Nakao Iwata, Shiro Ikegawa, Ikuyo Kou, Toshihiro Tanaka, Hidewaki Nakagawa, Akari Suzuki, Tomomitsu Hirota, Mayumi Tamari, Kazuaki Chayama, Daiki Miki, Masaki Mori, Satoshi Nagayama, Yataro Daigo, Yoshio Miki, Toyomasa Katagiri, Osamu Ogawa, Wataru Obara, Hidemi Ito, Teruhiko Yoshida, Issei Imoto, Takashi Takahashi, Chizu Tanikawa, Takao Suzuki, Nobuaki Sinozaki, Shiro Minami, Hiroki Yamaguchi, Satoshi Asai, Yasuo Takahashi, Ken Yamaji, Kazuhisa Takahashi, Tomoaki Fujioka, Ryo Takata, Hideki Yanai, Akihide Masumoto, Yukihiro Koretsune, Hiromu Kutsumi, Masahiko Higashiyama, Shigeo Murayama, Naoko Minegishi, Kichiya Suzuki, Kozo Tanno, Atsushi Shimizu, Taiki Yamaji, Motoki Iwasaki, Norie Sawada, Hirokazu Uemura, Keitaro Tanaka, Mariko Naito, Makoto Sasaki, Kenji Wakai, Shoichiro Tsugane, Masayuki Yamamoto, Kazuhiko Yamamoto, Yoshinori Murakami, Yusuke Nakamura, Soumya Raychaudhuri, Johji Inazawa, Toshimasa Yamauchi, Takashi Kadowaki, Michiaki Kubo, Yoichiro Kamatani
Journal: Nature Genetics (2020)
ERCP plus endoscopic ultrasound-guided biliary drainage versus percutaneous transhepatic biliary drainage for malignant hilar biliary obstruction: a multicenter observational open-label study
Authors: Pradermchai Kongkam, Theerapat Orprayoon, Chaloemphon Boonmee, Passakorn Sodarat, Orathai Seabmuangsai, Chatchawan Wachiramatharuch, Yutthaya Auan-Klin, Khanh Cong Pham, Abbas Ali Tasneem, Stephen J. Kerr, Rommel Romano, Sureeporn Jangsirikul, Wiriyaporn Ridtitid, Phonthep Angsuwatcharakon, Thawee Ratanachu-ek, Rungsun Rerknimitr
Journal: Endoscopy (2020)

Abstract Background Endoscopic retrograde cholangiopancreatography (ERCP) may not provide complete biliary drainage in patients with Bismuth III/IV malignant hilar biliary obstruction (MHBO). Complete biliary drainage is accomplished by adding percutaneous transhepatic biliary drainage (PTBD). We prospectively compared recurrent biliary obstruction (RBO) rates between combined ERCP and endoscopic ultrasound-guided biliary drainage (EUS-BD) vs. bilateral PTBD. Methods Patients with MHBO undergoing endoscopic procedures (group A) were compared with those undergoing bilateral PTBD (group B). The primary outcome was the 3-month RBO rate. Results 36 patients were recruited into groups A (n = 19) and B (n = 17). Rates of technical and clinical success, and complications of group A vs. B were 84.2 % (16/19) vs. 100 % (17/17; P = 0.23), 78.9 % (15/19) vs. 76.5 % (13/17; P &gt; 0.99), and 26.3 % (5/19) vs. 35.3 % (6/17; P = 0.56), respectively. Within 3 and 6 months, RBO rates of group A vs. group B were 26.7 % (4/15) vs. 88.2 % (15/17; P = 0.001) and 22.2 % (2/9) vs. 100 % (9/9; P = 0.002), respectively. At 3 months, median number of biliary reinterventions in group A was significantly lower than in group B (0 [interquartile range] 0–1 vs. 1 [1–2.5]), respectively (P &lt; 0.001). Median time to development of RBO was longer in group A than in group B (92 [56–217] vs. 40 [13.5–57.8] days, respectively; P = 0.06). Conclusions Combined ERCP and EUS procedures provided significantly lower RBO rates at 3 and 6 months vs. bilateral PTBD, with similar complication rates and no significant mortality difference.
THU0140 COMORBIDITIES AMONG KOREAN WOMEN WITH RHEUMATOID ARTHRITIS IN CHILDBEARING YEARS: A NATIONWIDE POPULATION-BASED STUDY
Authors: M. K. Chung, H. S. Lim, J. S. Park, C. H. Lee, J. Lee
Journal: Annals of the Rheumatic Diseases (2020)

Background: Rheumatoid arthritis is a chronic systemic inflammatory disease known to be associated with many comorbidities. Many women with rheumatoid arthritis (RA) are diagnosed with the disease before completing childbearing, but the risk of comorbidities associated with RA among women in childbearing years is not known. Objectives: We aimed to investigate the risk of comorbidities among Korean women with RA in childbearing years. Methods: From National Health Insurance Service data of 2009-2016, containing inpatient and outpatient claim information for approximately 97% of the Korean population, we identified 20-44 year aged-women with RA and controls without rheumatic diseases such as RA, systemic lupus erythematosus, and ankylosing spondylitis. Prevalence of comorbidities including cancer (Ca), hypertension (HTN), hyperlipidemia (HLD), and diabetes mellitus (DM) were analyzed. The rheumatic diseases and comorbidities were defined by International Classification of Disease (ICD)-10 codes for disease classifications. The comorbidities associated with RA were defined by the ICD-10 codes presented after the RA diagnosis. Results: Total 23,756 women with RA and 208,941 controls were identified. Women with RA had significantly higher prevalence of all comorbidities analyzed compared with the controls (49.92% vs 25.58%, p&lt;0.001). In women with RA, Ca (OR 1.14), DM (OR 1.22), HTN (OR 1.56), and HLD (OR 2.44) occurred significantly more often compared with the controls (p&lt;0.001). Conclusion: During childbearing years, women with RA are more susceptible to comorbidities leading to a significant burden in this specific population of Korean women in childbearing years. References: [1]Dougados M: Comorbidities in rheumatoid arthritis. Current opinion in rheumatology 2016, 28(3):282-288. [2]Choi IA, Park SH, Cha HS, Park W, Kim HA, Yoo DH, Baek HJ, Lee SG, Lee YJ, Park YB et al: Prevalence of co-morbidities and evaluation of their monitoring in Korean patients with rheumatoid arthritis: comparison with the results of an international, cross-sectional study (COMORA). International journal of rheumatic diseases 2018, 21(7):1414-1422. Table 1. Risk of comorbidities associated with RA among Korean women in childbearing years during 2009-2016 RA (n=23,756) Controls (n=208,941) p-value OR 95% CI n (%) n (%) Any comorbidities 10,859 (45.71) 53,423 (25.57) &lt;.0001 2.30 2.234-2.367 Ca 1,235 (5.20) 8,845 (4.23) &lt;.0001 1.14 1.072-1.217 DM 1,885 (7.93) 12,606 (6.03) &lt;.0001 1.22 1.155-1.285 HTN 3,274 (13.78) 17,052 (8.16) &lt;.0001 1.56 1.495-1.628 HLD 8,046 (33.87) 34,672 (16.60) &lt;.0001 2.44 2.367-2.516 RA, rheumatoid arthritis; Ca, cancer; DM, diabetes mellitus; HTN, hypertension; HLD, hyperlipidemia; OR, odds ratio; CI, confidence interval Disclosure of Interests: None declared
Atlas of group A streptococcal vaccine candidates compiled using large-scale comparative genomics (vol 51, pg 1035, 2019)
Authors: Mark R Davies, Liam McIntyre, Ankur Mutreja, Jake A Lacey, John A Lees, Rebecca J Towers, Sebastian Duchene, Pierre R Smeesters, Hannah R Frost, David J Price, Matthew Tg Holden, Sophia David, Philip M Giffard, Kate A Worthing, Anna C Seale, James A Berkley, Simon R Harris, Tania Rivera-Hernandez, Olga Berking, Amanda J Cork, Rosangela Sla Torres, Trevor Lithgow, Richard A Strugnell, Rene Bergmann, Patric Nitsche-Schmitz, Gusharan S Chhatwal, Stephen D Bentley, John D Fraser, Nicole J Moreland, Jonathan R Carapetis, Andrew C Steer, Julian Parkhill, Allan Saul, Deborah A Williamson, Bart J Currie, Steven Yc Tong, Gordon Dougan, Mark J Walker
Journal: Nature Genetics (2019)
Functional Impairment, Symptom Burden, and Clinical Outcomes Among Hospitalized Patients With Advanced Cancer
Authors: Daniel E. Lage, Areej El-Jawahri, Charn-Xin Fuh, Richard A. Newcomb, Vicki A. Jackson, David P. Ryan, Joseph A. Greer, Jennifer S. Temel, Ryan D. Nipp
Journal: Journal of the National Comprehensive Cancer Network (2020)

Background: National guidelines recommend regular measurement of functional status among patients with cancer, particularly those who are elderly or high-risk, but little is known about how functional status relates to clinical outcomes among hospitalized patients with advanced cancer. The goal of this study was to investigate how functional impairment is associated with symptom burden and healthcare utilization and clinical outcomes. Patients and Methods: We conducted a prospective observational study of patients with advanced cancer with unplanned hospitalizations at Massachusetts General Hospital from September 2014 through March 2016. Upon admission, nurses assessed patients’ activities of daily living (ADLs; mobility, feeding, bathing, dressing, and grooming). Patients with any ADL impairment on admission were classified as having functional impairment. We used the revised Edmonton Symptom Assessment System (ESAS-r) and Patient Health Questionnaire-4 to assess physical and psychological symptoms, respectively. Multivariable regression models were used to assess the relationships between functional impairment, hospital length of stay, and survival. Results: Among 971 patients, 390 (40.2%) had functional impairment. Those with functional impairment were older (mean age, 67.18 vs 60.81 years; P &lt;.001) and had a higher physical symptom burden (mean ESAS physical score, 35.29 vs 30.85; P &lt;.001) compared with those with no functional impairment. They were also more likely to report moderate-to-severe pain (74.9% vs 63.1%; P &lt;.001) and symptoms of depression (38.3% vs 23.6%; P &lt;.001) and anxiety (35.9% vs 22.4%; P &lt;.001). Functional impairment was associated with longer hospital length of stay (β = 1.29; P &lt;.001) and worse survival (hazard ratio, 1.73; P &lt;.001). Conclusions: Hospitalized patients with advanced cancer who had functional impairment experienced a significantly higher symptom burden and worse clinical outcomes compared with those without functional impairment. These findings provide evidence supporting the routine assessment of functional status on hospital admission and using this to inform discharge planning, discussions about prognosis, and the development of interventions addressing patients’ symptoms and physical function.
Risks to children during the covid-19 pandemic: some essential epidemiology
Authors: Sunil S Bhopal, Jayshree Bagaria, Raj Bhopal
Journal: BMJ (2020)

Difficult and varying decisions are being made worldwide about ways to protect children from covid-19.Green warns of the dangers of scarring a generation through curtailment of child protection systems during the pandemic. 1 Given multiple unknowns, we think that caution from parents and carers is natural, not least because the rare inflammatory syndrome reported in recent weeks remains under investigation. 2 But caution in the form of shielding is not risk-free, and children cannot be kept at home if they are to thrive.To help decision making we have compiled information for parents, teachers, clinicians, and policy makers grappling with this quandary.We examined mortality data for 0-19 year olds, showing that across France, Germany, Italy, Korea, Spain, the United Kingdom, and the United States there were 44 deaths from covid-19 in 0-19 year olds (total population 135 691 226) up to 19 May 2020. 3 4 Over a normal three month period, in these countries, published Global Burden of Disease data estimate that more than 13 000 deaths would be expected from all causes in this age group, including over 1000 from unintentional injury and 308 from lower respiratory tract infection including influenza. 5 Covid-19, by this estimate, was responsible for about 0.333% of deaths of 0-19 year olds.Results were similar for each country.We are regularly updating a data table including deaths by age categories and country, and we welcome feedback (https://tinyurl.com/childcovid;this table and fuller details also in press 6 ).Given these data, we think the medical community should inform parents, carers, teachers, clinicians, and decision makers that the direct impact of covid-19 on children is currently small in comparison with other risks and that the main reason we are keeping children at home is to protect adults.This conclusion might change as the pandemic evolves, so the epidemiology of covid-19 in children should be closely monitored.
Association of Electronic Health Record Use With Physician Fatigue and Efficiency
Authors: Saif Khairat, Cameron Coleman, Paige Ottmar, Dipika Irene Jayachander, Thomas Bice, Shannon S. Carson
Journal: JAMA Network Open (2020)

<h3>Importance</h3> The use of electronic health records (EHRs) is directly associated with physician burnout. An underlying factor associated with burnout may be EHR-related fatigue owing to insufficient user-centered interface design and suboptimal usability. <h3>Objective</h3> To examine the association between EHR use and fatigue, as measured by pupillometry, and efficiency, as measured by mouse clicks, time, and number of EHR screens, among intensive care unit (ICU) physicians completing a simulation activity in a prominent EHR. <h3>Design, Setting, and Participants</h3> A cross-sectional, simulation-based EHR usability assessment of a leading EHR system was conducted from March 20 to April 5, 2018, among 25 ICU physicians and physician trainees at a southeastern US academic medical center. Participants completed 4 simulation patient cases in the EHR that involved information retrieval and task execution while wearing eye-tracking glasses. Fatigue was quantified through continuous eye pupil data; EHR efficiency was characterized through task completion time, mouse clicks, and EHR screen visits. Data were analyzed from June 1, 2018, to August 31, 2019. <h3>Main Outcomes and Measures</h3> Primary outcomes were physician fatigue, measured by pupillometry (with lower scores indicating greater fatigue), and EHR efficiency, measured by task completion times, number of mouse clicks, and number of screens visited during EHR simulation. <h3>Results</h3> The 25 ICU physicians (13 women; mean [SD] age, 33.2 [6.1] years) who completed a simulation exercise involving 4 patient cases (mean [SD] completion time, 34:43 [11:41] minutes) recorded a total of 14 hours and 27 minutes of EHR activity. All physician participants experienced physiological fatigue at least once during the exercise, and 20 of 25 participants (80%) experienced physiological fatigue within the first 22 minutes of EHR use. Physicians who experienced EHR-related fatigue in 1 patient case were less efficient in the subsequent patient case, as demonstrated by longer task completion times (<i>r</i> = −0.521;<i>P</i> = .007), higher numbers of mouse clicks (<i>r</i> = −0.562;<i>P</i> = .003), and more EHR screen visits (<i>r</i> = −0.486;<i>P</i> = .01). <h3>Conclusions and Relevance</h3> This study reports high rates of fatigue among ICU physicians during short periods of EHR simulation, which were negatively associated with EHR efficiency and included a carryover association across patient cases. More research is needed to investigate the underlying causes of EHR-associated fatigue, to support user-centered EHR design, and to inform safe EHR use policies and guidelines.
Prevalence and Impact of Myocardial Injury in Patients Hospitalized With COVID-19 Infection
Authors: Anuradha Lala, Kipp W. Johnson, James L. Januzzi, Adam J. Russak, Ishan Paranjpe, Felix Richter, Shan Zhao, Sulaiman Somani, Tielman Van Vleck, Akhil Vaid, Fayzan Chaudhry, Jessica K. De Freitas, Zahi A. Fayad, Sean P. Pinney, Matthew Levin, Alexander Charney, Emilia Bagiella, Jagat Narula, Benjamin S. Glicksberg, Girish Nadkarni, Donna M. Mancini, Valentin Fuster
Journal: Journal of the American College of Cardiology (2020)
Clinical, environmental and histological distribution of<i>BRAF</i>,<i>NRAS</i>and<i>TERT</i>promoter mutations among patients with cutaneous melanoma: a retrospective study of 563 patients*
Authors: E. Manrique‐Silva, S. Rachakonda, D. Millán‐Esteban, Z. García‐Casado, C. Requena, V. Través, R. Kumar, E. Nagore
Journal: British Journal of Dermatology (2020)

The distinct somatic mutations that define clinical and histopathological heterogeneity in cutaneous melanoma could be dependent on host susceptibility to exogenous factors like ultraviolet radiation. Firstly, to characterize patients with cutaneous melanoma clinically and pathologically based on the mutational status of BRAF, NRAS and TERT promoter. Secondly, to elucidate the modified features due to the presence of TERT promoter mutations over the background of either BRAF or NRAS mutations. We performed a retrospective study on 563 patients with melanoma by investigating somatic mutations in BRAF, NRAS and TERT promoter. We observed co‐occurrence of TERT promoter mutations with BRAF and NRAS mutations in 26.3% and 6.9% of melanomas, respectively. Multivariate analysis showed an independent association between BRAF mutations and a decreased presence of cutaneous lentigines at the melanoma site, and an increased association with the presence of any MC1R polymorphism. We also observed an independent association between TERT promoter mutations and increased tumour mitotic rate. Co‐occurrence of BRAF and TERT promoter mutations was independently associated with occurrence of primary tumours at usually sun‐exposed sites, lack of histological chronic sun damage in surrounding unaffected skin at the melanoma site, and increased tumour mitotic rate. Co‐occurrence of NRAS and TERT promoter mutations was independently associated with increased tumour mitotic rate. The presence of TERT promoter together with BRAF or NRAS mutations was associated with statistically significantly worse survival. The presence of TERT promoter mutations discriminates BRAF‐ and NRAS‐mutated tumours and indicates a higher involvement of ultraviolet‐induced damage and tumours with worse melanoma‐specific survival than those without any mutation. These observations refine classification of patients with melanoma based on mutational status.
AB0933 PHYSICAL ACTIVITY DECREASES PAIN AND INFLAMMATION IN GOUT PATIENTS
Authors: N. Schlesinger, K. Jablonski, E. Schwarz, N. Young
Journal: Annals of the Rheumatic Diseases (2020)

Background: Despite the high prevalence of gout, there has been little investigation into the relationship between physical activity and gout. Objectives: To investigate whether physically active gout patients, as assessed by the International Physical Activity Questionnaire (IPAQ) long form, have lower pain scores, decreased inflammation, assessed by C-reactive protein (CRP) levels and less flares. Methods: During scheduled appointments, gout patients not experiencing a flare at the time of visit were recruited from our clinics and consented to participate in the study. IPAQ were completed. Clinical data collected during the visit included age, years since diagnosis, flares per year, perceived pain at the time of visit and in the past 4 weeks, and C-reactive protein (CRP) levels. Results: Thirty gout patients were recruited. Ages 31-86 (mean 61); duration of gout: one- 43 years (mean 9). IPAQ, separated gout patients into physically active (n=16) and physically inactive cohorts (n=14) (p&lt;0.001. Physically active gout patients had over 12-fold fewer gout flares per year (p&lt;0.01); 10-fold less CRP (p&lt;0.01, a 4.6-fold decrease in perceived pain at the time of visit (p&lt;0.01), and a 2.8-fold decrease in perceived pain over the past 4-week period (p&lt;0.05). Conclusion: This is the first study using a validated physical activity tool, IPAQ, to assess physical activity in gout patients. In this study, physically active gout patients were found to have lower CRP levels, less flares per year, and decreased pain perception compared to those that are not physically active, highlighting, the importance of incorporating physical activity as a possible adjunct treatment option during intervals between flares. References: [1]Benatti FB, Pedersen BK. Exercise as an anti-inflammatory therapy for rheumatic diseases-myokine regulation. Nat Rev Rheumatol 2015;11:86-97. [2]Hagströmer M, Oja P, Sjöström M. The International Physical Activity Questionnaire (IPAQ): a study of concurrent and construct validity. Public Health Nutr 2006;9:755-62. [3]Young NA, Jablonski K, Sharma J, Thomas E, Snoad B, Hampton J, et al. Low and Moderate Intensity Exercise Suppresses Inflammatory Responses in an Acute Mouse Model of Gout and Suggests Therapeutic Efficacy [abstract]. Arthritis Rheumatol. 2017;69 (suppl 10). Disclosure of Interests: Naomi Schlesinger Grant/research support from: Pfizer, AMGEN, Consultant of: Novartis, Horizon Pharma, Selecta Biosciences, Olatec, IFM Therapeutics, Mallinckrodt Pharmaceuticals, Speakers bureau: Takeda, Horizon, Kyle jablonski: None declared, Emmy schwarz: None declared, Nicholas Young: None declared
Abstract PR14: A multiscale map of recurrently mutated systems in cancer
Authors: Fan Zheng, Keiichiro Ono, Erica Silva, Danielle Swaney, Minkyu Kim, Julia Shangguan, Dexter Pratt, Xiaolin Nan, Nevan Krogan, Trey Ideker
Journal: Cancer Research (2020)

Abstract Interpreting cancer genomes requires a broad understanding of the composition and organization of cellular processes under selective pressure for mutations. Here, we integrate systematic screens for protein interaction with tumor genetic analysis to elucidate a multiscale hierarchical map of 378 protein systems recurrently altered in one or more cancer types. Diverse gene mutations converge on commonly mutated systems, from small protein complexes in specific tumor types to large molecular assemblies and organelles disrupted in most cancers. Unexpected findings include collagen structural alterations with significant prognostic value; mutations impacting the desmosome in 65% melanomas; complexes related to splicing and DNA repair; and an expanded actomyosin cluster involving PIK3CA. The map implicates 556 cancer genes, many well supported by functional assays, including canonical genes implicated in new tissues (e.g., BRCA1/2 mutations in bladder cancer). This work explains mutational heterogeneity as a collection of convergence points across scales of cell biology. This abstract is also being presented as Poster B52. Citation Format: Fan Zheng, Keiichiro Ono, Erica Silva, Danielle Swaney, Minkyu Kim, Julia Shangguan, Dexter Pratt, Xiaolin Nan, Nevan Krogan, Trey Ideker. A multiscale map of recurrently mutated systems in cancer [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr PR14.