tbuckley/cabot-search huggingface dataset:
Cross-reactive antibodies against dust mite-derived enolase induce neutrophilic airway inflammation
Authors: Jianli Lin, Nana Huang, Jing Li, Xiaoyu Liu, Qing Xiong, Chengshen Hu, Desheng Chen, Lvxin Guan, Kexin Chang, Dan Li, Stephen Kwok-Wing Tsui, Nanshan Zhong, Zhigang Liu, Ping-Chang Yang
Journal: European Respiratory Journal (2020)

Background and aims Neutrophilic inflammation is a hallmark of some specific asthma phenotypes; its aetiology is not yet fully understood. House dust mite (HDM) is the most common factor in the pathogenesis of airway inflammation. This study aims to elucidate the role of cross-antibodies against HDM-derived factors in the development of neutrophilic inflammation in the airway. Methods Blood samples were collected from asthma patients with chronic neutrophilic asthma for analysis of HDM-specific cross-reactive antibodies. The role of an antibody against HDM-derived enolase (EnoAb) in the impairment of airway epithelial barrier function and induction of airway inflammation was assessed in a cell culture model and an animal model. Results High similarity (72%) of the enolase gene sequences was identified between HDM and human. Serum EnoAb was detected in patients with chronic neutrophilic asthma. The EnoAb bound to airway epithelial cells to form complexes with enolase, which activated complement, impaired airway epithelial barrier functions and induced neutrophilic inflammation in the airway tissues. Conclusions HDM-derived enolase can induce specific cross-antibodies in humans, which induce neutrophilic inflammation in the airway.
Built Environment Approaches to Increase Physical Activity: A Science Advisory From the American Heart Association
Authors: John D. Omura, Susan A. Carlson, David R. Brown, David P. Hopkins, William E. Kraus, Beth A. Staffileno, Randal J. Thomas, Felipe Lobelo, Janet E. Fulton
Journal: Circulation (2020)

Engaging in regular physical activity is one of the most important things people can do to improve their cardiovascular health; however, population levels of physical activity remain low in the United States. Effective population-based approaches implemented in communities can help increase physical activity among all Americans. Evidence suggests that built environment interventions offer one such approach. These interventions aim to create or modify community environmental characteristics to make physical activity easier or more accessible for all people in the places where they live. In 2016, the Community Preventive Services Task Force released a recommendation for built environment approaches to increase physical activity. This recommendation is based on a systematic review of 90 studies (search period, 1980-June 2014) conducted using methods outlined by the Guide to Community Preventive Services. The Community Preventive Services Task Force found sufficient evidence of effectiveness to recommend combined built environment strategies. Specifically, these strategies combine interventions to improve pedestrian or bicycle transportation systems with interventions to improve land use and environmental design. Components of transportation systems can include street pattern design and connectivity, pedestrian infrastructure, bicycle infrastructure, and public transit infrastructure and access. Components of land use and environmental design can include mixed land use, increased residential density, proximity to community or neighborhood destinations, and parks and recreational facility access. Implementing this Community Preventive Services Task Force recommendation in communities across the United States can help promote healthy and active living, increase physical activity, and ultimately improve cardiovascular health.
THU0150 Progression of radiological damage in patients with rheumatoid arthritis in remission; a prospective two year follow-up study
Authors: ET Molenaar, AE Voskuyl, HJ Dinant, PD Bezemer, BA Dijkmans
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To investigate the progression of radiological damage in patients with RA in remission during a follow-up of 2 years. <h3>Methods</h3> RA patients (n = 187), in remission according to the ACR/Pinals criteria were included. Radiographs of hands and feet were made at baseline and after 2 years. Radiological damage was assessed according to the Sharp-van der Heijde method (range score 0–448; (SHS)). SHS at baseline and after 2 years were compared in the complete group and in subgroups of patients with persistent remission and in those suffering an exacerbation (Wilcoxon test). As riskfactors for radiological progression were analysed: number of tender and swollen joint, Ritchie score, Disease Activity Score (DAS), serum rheumatoid factors, Visual Analogue Scale for physicians impression of disease activity (VAS, range 0–100), and Health Assessment Questionnaire (HAQ) score. <h3>Results</h3> At baseline and after 2 years, the mean SHS of the complete group were 49 and 51 (p &lt; 0.001). In the subgroup with persistent remission, the mean SHS were 52 and 53 (P = 0.004). No significant correlations were found between radiological damage and variables at baseline (rho0.1). In the subgroup of patients with an exacerbation, the mean SHS were 46 and 51 (p &lt; 0.001). Progression of radioolgical damage correlated significantly with the following baseline variables: SHS(rho = 0.40), HAQ-score (rho = 0.28), IgM-RF (rho = 0.29), IgA-RF (0.25); but not with the DAS or VAS. <h3>Conclusion</h3> Radiological damage proceeds in RA patients in remission and is not related to disease activity.
Comorbidities in patients with palmoplantar plaque psoriasis
Authors: Ran Greenberg, Tomer Goldsmith, David Zeltser, Itzhak Shapira, Shlomo Berliner, Ori Rogowski, Shani Shenhar-Tsarfaty, Eli Sprecher, Hagit Matz
Journal: Journal of the American Academy of Dermatology (2020)
AB0224 Incidence and prevalence of rheumatic conditions in southern europe.(halkidiki study)
Authors: EP Roussou
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Halkidiki is a region/prefecture of 106.000 inhabitants mostly suburban and rural which attracts approximately 1 million visitors during summer months of June, July, August and September. There is a district hospital, 5 health centres an Orthopaedic unit based at the hospital and 3 Orthopaedic doctors practising privately in addition to the single Rheumatologist practising in the area. <h3>Objectives</h3> In order to assess incidence and prevalence of rheumatic conditions in rural and suburban East Meditterannean basin of Southern Europe, medical notes were analysed from a total number of 226 patients who presented themselves to a single Rheumatologist practising in the prefecture of Halkidiki within 3 years from September 1997 to September 2000. <h3>Methods</h3> Medical cases were excluded as well as patients visiting the region temporarily. Rheumatology in the region is practised in the community and patients were either self referred or other specialist's referrals. From the 226 patients there were 56 males and 170 females (m:f = 1:3). Their median age was 56.3 (range 11–84). <h3>Results</h3> Seventy seven patients out of 226 (34%) had autoimmune conditions. From these 30 patients had RA of whom 18 patients were newly diagnosed. Forty four patients (19.4%) had OA, 17 patients (7.5%) had spine complains (sciatica, cervical spondylosis, scoliosis) 22 patients (9.7%) upper limp [frozen shoulder (n = 9), carpal tunnel (n = 8), flexor tendon nodule (n = 3), epicondylitis (n = 2)] and 5 patients (2.2%) had lower limp complaints (calcaneal spur, trochanderic bursitis). Twenty two patients (9.7%) had seronegative arthritis (Ankylosing Spondylitis n = 5, Psoriatic Arthritis n = 13, Reactive Arthritis n = 3, Ulcerative colitis n = 2). Twenty four patients (10.6%) had thyroid related disorders, 14 patients (6.1%) osteoporosis, 12 patients (5.3%) had gout and 5 patients (2.2%) had liver disease related arthralgia. Two cases were undiagnosed. <h3>Conclusion</h3> Most cases presented to a Rheumatologist in Southern Europe are of degenerative origin or soft tissue rheumatism complaints. Many specialities look after these patients particularly orthopaedics. Rheumatoid Arthritis revealed an incidence of 6/100.000 per year. Psoriatic Arthritis showed an incidence of 3.5/100.000 per year. Polymyalgia Rheumatica/Temporal arteritis showed incidence of 4/100.000 per year being second common autoimmune disease after RA. Finally thyroid related (autoimmune or functional) arthralgia is found quite common in the region being third among muskuloskeletal disorders after OA and RA.
Association of Weight Loss Between Early Adulthood and Midlife With All-Cause Mortality Risk in the US
Authors: Wubin Xie, Dielle J. Lundberg, Jason M. Collins, Stephen S. Johnston, Jason R. Waggoner, Chia-Wen Hsiao, Samuel H. Preston, JoAnn E. Manson, Andrew C. Stokes
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Describing potential mortality risk reduction associated with weight loss between early adulthood and midlife is important for informing primary and secondary prevention efforts for obesity. <h3>Objective</h3> To examine the risk of all-cause mortality among adults who lost weight between early adulthood and midlife compared with adults who were persistently obese over the same period. <h3>Design, Setting, and Participants</h3> Combined repeated cross-sectional analysis was conducted using data from the National Health and Nutrition Examination Survey III (1988-1994) and continuous waves collected in 2-year cycles between 1999 and 2014. The data analysis was conducted from February 10, 2019, to April 20, 2020. Individuals aged 40 to 74 years at the time of survey (baseline) were included in the analyses (n = 24 205). <h3>Exposures</h3> Weight history was assessed by self-reported weight at age 25 years, at 10 years before baseline (midlife: mean age, 44 years; interquartile range, 37-55), and measured weight at baseline. Body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) at each time was categorized as normal (18.5-24.9), overweight (25.0-29.9), and obese (≥30.0). Weight change patterns were assessed from age 25 years (early adulthood) to 10 years before baseline (midlife). <h3>Main Outcomes and Measures</h3> Incident all-cause mortality using linked data from the National Death Index. <h3>Results</h3> Of the 24 205 participants, 11 617 were women (49.0%) and 11 567 were non-Hispanic White (76.9%). The mean (SD) BMI was 29.0 (6.1) at baseline. During a mean (SD) follow-up of 10.7 (7.2) years, 5846 deaths occurred. Weight loss from obese to overweight was associated with a 54% (hazard ratio, 0.46; 95% CI, 0.27-0.77) reduction in mortality risk compared with individuals with stable obesity between early adulthood and midlife. An estimated 3.2% (95% CI, 1.6%-4.9%) of early deaths could have been avoided if those who maintained an obese BMI instead lost weight to an overweight BMI by midlife. Overall, an estimated 12.4% (95% CI, 8.1%-16.5%) of early deaths may be attributable to having weight in excess of the normal BMI range at any point between early and mid-adulthood. <h3>Conclusions and Relevance</h3> In this study, weight loss from obesity to overweight between early adulthood through midlife appeared to be associated with a mortality risk reduction compared with persistent obesity. These findings support the importance of population-based approaches to preventing weight gain across the life course and a need for greater emphasis on treating obesity early in life.
Detection of ctDNA in plasma of patients with clinically localised prostate cancer is associated with rapid disease progression
Authors: Edmund Lau, Patrick McCoy, Fairleigh Reeves, Ken Chow, Michael Clarkson, Edmond M. Kwan, Kate Packwood, Helen Northen, Miao He, Zoya Kingsbury, Stefano Mangiola, Michael Kerger, Marc A. Furrer, Helen Crowe, Anthony J. Costello, David J. McBride, Mark T. Ross, Bernard Pope, Christopher M. Hovens, Niall M. Corcoran
Journal: Genome Medicine (2020)

Abstract Background DNA originating from degenerate tumour cells can be detected in the circulation in many tumour types, where it can be used as a marker of disease burden as well as to monitor treatment response. Although circulating tumour DNA (ctDNA) measurement has prognostic/predictive value in metastatic prostate cancer, its utility in localised disease is unknown. Methods We performed whole-genome sequencing of tumour-normal pairs in eight patients with clinically localised disease undergoing prostatectomy, identifying high confidence genomic aberrations. A bespoke DNA capture and amplification panel against the highest prevalence, highest confidence aberrations for each individual was designed and used to interrogate ctDNA isolated from plasma prospectively obtained pre- and post- (24 h and 6 weeks) surgery. In a separate cohort ( n = 189), we identified the presence of ctDNA TP53 mutations in preoperative plasma in a retrospective cohort and determined its association with biochemical- and metastasis-free survival. Results Tumour variants in ctDNA were positively identified pre-treatment in two of eight patients, which in both cases remained detectable postoperatively. Patients with tumour variants in ctDNA had extremely rapid disease recurrence and progression compared to those where variants could not be detected. In terms of aberrations targeted, single nucleotide and structural variants outperformed indels and copy number aberrations. Detection of ctDNA TP53 mutations was associated with a significantly shorter metastasis-free survival (6.2 vs. 9.5 years (HR 2.4; 95% CIs 1.2–4.8, p = 0.014). Conclusions CtDNA is uncommonly detected in localised prostate cancer, but its presence portends more rapidly progressive disease.
Effects of a major deletion in the SARS-CoV-2 genome on the severity of infection and the inflammatory response: an observational cohort study
Authors: Barnaby E Young, Siew-Wai Fong, Yi-Hao Chan, Tze-Minn Mak, Li Wei Ang, Danielle E Anderson, Cheryl Yi-Pin Lee, Siti Naqiah Amrun, Bernett Lee, Yun Shan Goh, Yvonne C F Su, Wycliffe E Wei, Shirin Kalimuddin, Louis Yi Ann Chai, Surinder Pada, Seow Yen Tan, Louisa Sun, Purnima Parthasarathy, Yuan Yi Constance Chen, Timothy Barkham, Raymond Tzer Pin Lin, Sebastian Maurer-Stroh, Yee-Sin Leo, Lin-Fa Wang, Laurent Renia, Vernon J Lee, Gavin J D Smith, David Chien Lye, Lisa F P Ng
Journal: The Lancet (2020)
OP0108 Aggressive lymphomas (diffuse large b cell lymphomas) are overrepresented in ra patients
Authors: E Baecklund, C Sundström, A Ekbom, N Feltelius, L Klareskog
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Patients with rheumatoid arthritis (RA) have an increased risk to develop lymphomas. In a previous case-control study we found a strong association between high disease activity in RA and the risk of lymphoma. To get a better understanding of the biological background of this connexion we examined lymphoma subtypes in RA patients. <h3>Objectives</h3> To study the distribution of lymphoma subtypes in RA patients compared to the general population. <h3>Methods</h3> In a population-based cohort of 11,683 patients with RA in the Uppsala Health Care region in Sweden,42 cases of lymphoma were identified through record linkages with the Swedish cancer registry 1965 through 1984. The medical records and paraffin embedded lymphoma tissues were collected. The lymphomas were reclassified according to the recently described REAL classification. The distribution was compared to lymphoma subtypes in the general population according to the Non-Hodgkin´s Lymphoma (NHL) Classification Project.<sup>1</sup> <h3>Results</h3> One patient was excluded as the RA diagnosis was wrong. Tissues from 36 of the remaining patients were found and reviewed. NHL was found in 33 patients, Hodgkin´s disease in 2 and 1 patient did not have lymphoma. Compared with the expected there was a more than 2-fold increased number of diffuse large B-cell lymphoma (22 patients,69% of NHL´s compared with 31% expected). Few of the patients had been treated with immunosuppressive drugs. <h3>Conclusion</h3> The distribution of lymphoma subtypes in RA patients differs from the expected. This supports the idea of a specific underlying mechanism behind lymphoma development in RA patients. This mechanism may also be of importance for RA development and activity. Genetics and other characteristics of those RA patients who develop lymphomas deserve further studies. <h3>Reference</h3> The Non-Hodgkin's Lymphoma Classification Project: A Clinical Evaluation of the International Lymphoma Study Group. Blood 1997;89(11):3909–18
National Patterns in Prescription Opioid Use and Misuse Among Cancer Survivors in the United States
Authors: Vikram Jairam, Daniel X. Yang, Vivek Verma, James B. Yu, Henry S. Park
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Prescription opioids are frequently prescribed to treat cancer-related pain. However, limited information exists regarding rates of prescription opioid use and misuse in populations with cancer. <h3>Objectives</h3> To estimate the prevalence and likelihood of prescription opioid use and misuse in adult cancer survivors compared with respondents without cancer and to identify characteristics associated with prescription opioid use and misuse in adult cancer survivors. <h3>Design, Setting, and Participants</h3> This cross-sectional study is a retrospective, population-based study using data from 169 162 respondents to the National Survey on Drug Use and Health from January 2015 to December 2018. Survey data sets were queried for all respondents aged 18 years or older. Those with a reported history of cancer were termed<i>cancer survivors</i>and further divided into<i>more recent</i>(had cancer within 12 months of survey) and<i>less recent</i>(had cancer more than 12 months prior to survey) cohorts. Respondents with nonmelanoma skin cancer were excluded. <h3>Main Outcomes and Measures</h3> Prescription opioid use and misuse within the past 12 months. <h3>Results</h3> Among 169 162 respondents, 5139 (5.2%) were cancer survivors, with 1243 (1.2%) and 3896 (4.0%) reporting having more recent and less recent cancer histories, respectively. Higher rates of prescription opioid use were observed among more recent cancer survivors (54.3%; 95% CI, 50.2%-58.4%; odds ratio [OR], 1.86; 95% CI, 1.57-2.20;<i>P</i> &lt; .001) and less recent cancer survivors (39.2%; 95% CI, 37.3%-41.2%; OR, 1.18; 95% CI, 1.08-1.28;<i>P</i> &lt; .001) compared with respondents without cancer (30.5%, reference group). Rates of prescription opioid misuse were similar among more recent (3.5%; 95% CI, 2.4%-5.2%; OR, 1.27; 95% CI, 0.82-1.96;<i>P</i> = .36) and less recent (3.0%; 95% CI, 2.4%-3.6%; OR, 1.03; 95% CI, 0.83-1.28;<i>P</i> = .76) survivors compared with respondents without cancer (4.3%, reference group). Younger age (aged 18-34 years vs ≥65 years: OR, 7.06; 95% CI, 3.03-16.41;<i>P</i> &lt; .001), alcohol use disorder (OR, 3.22; 95% CI, 1.45-7.14;<i>P</i> = .005), and nonopioid drug use disorder (OR, 14.76; 95% CI, 7.40-29.44;<i>P</i> &lt; .001) were associated with prescription opioid misuse among cancer survivors. <h3>Conclusions and Relevance</h3> In this study, prescription opioid use was higher among more and less recent cancer survivors compared with the population without a history of cancer. Rates of prescription opioid misuse were low and similar among all 3 cohorts. These findings suggest that higher prescription opioid use among cancer survivors may not correspond to increased short-term or long-term misuse.
Resurgence of covid-19 in Japan
Authors: Kazuki Shimizu, George Wharton, Haruka Sakamoto, Elias Mossialos
Journal: BMJ (2020)

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A Preclinical Trial and Molecularly Annotated Patient Cohort Identify Predictive Biomarkers in Homologous Recombination–deficient Pancreatic Cancer
Authors: Yifan Wang, Jin Yong Patrick Park, Alain Pacis, Robert E. Denroche, Gun Ho Jang, Amy Zhang, Adeline Cuggia, Celine Domecq, Jean Monlong, Maria Raitses-Gurevich, Robert C. Grant, Ayelet Borgida, Spring Holter, Chani Stossel, Simeng Bu, Mehdi Masoomian, Ilinca M. Lungu, John M.S. Bartlett, Julie M. Wilson, Zu-Hua Gao, Yasser Riazalhosseini, Jamil Asselah, Nathaniel Bouganim, Tatiana Cabrera, Louis-Martin Boucher, David Valenti, James Biagi, Celia M.T. Greenwood, Paz Polak, William D. Foulkes, Talia Golan, Grainne M. O'Kane, Sandra E. Fischer, Jennifer J. Knox, Steven Gallinger, George Zogopoulos
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Pancreatic ductal adenocarcinoma (PDAC) arising in patients with a germline BRCA1 or BRCA2 (gBRCA) mutation may be sensitive to platinum and PARP inhibitors (PARPi). However, treatment stratification based on gBRCA mutational status alone is associated with heterogeneous responses. Experimental Design: We performed a seven-arm preclinical trial consisting of 471 mice, representing 12 unique PDAC patient-derived xenografts, of which nine were gBRCA mutated. From 179 patients whose PDAC was whole-genome and transcriptome sequenced, we identified 21 cases with homologous recombination deficiency (HRD), and investigated prognostic biomarkers. Results: We found that biallelic inactivation of BRCA1/BRCA2 is associated with genomic hallmarks of HRD and required for cisplatin and talazoparib (PARPi) sensitivity. However, HRD genomic hallmarks persisted in xenografts despite the emergence of therapy resistance, indicating the presence of a genomic scar. We identified tumor polyploidy and a low Ki67 index as predictors of poor cisplatin and talazoparib response. In patients with HRD PDAC, tumor polyploidy and a basal-like transcriptomic subtype were independent predictors of shorter survival. To facilitate clinical assignment of transcriptomic subtype, we developed a novel pragmatic two-marker assay (GATA6:KRT17). Conclusions: In summary, we propose a predictive and prognostic model of gBRCA-mutated PDAC on the basis of HRD genomic hallmarks, Ki67 index, tumor ploidy, and transcriptomic subtype.
SARS-CoV-2-Specific T Cells Exhibit Phenotypic Features of Helper Function, Lack of Terminal Differentiation, and High Proliferation Potential
Authors: Jason Neidleman, Xiaoyu Luo, Julie Frouard, Guorui Xie, Gurjot Gill, Ellen S. Stein, Matthew McGregor, Tongcui Ma, Ashley F. George, Astrid Kosters, Warner C. Greene, Joshua Vasquez, Eliver Ghosn, Sulggi Lee, Nadia R. Roan
Journal: Cell Reports Medicine (2020)

Convalescing coronavirus disease 2019 (COVID-19) patients mount robust T cell responses against SARS-CoV-2, suggesting an important role of T cells in viral clearance. To date, the phenotypes of SARS-CoV-2-specific T cells remain poorly defined. Using 38-parameter CyTOF, we phenotyped longitudinal specimens of SARS-CoV-2-specific CD4+ and CD8+ T cells from nine individuals who recovered from mild COVID-19. SARS-CoV-2-specific CD4+ T cells were exclusively Th1 cells and predominantly Tcm cells with phenotypic features of robust helper function. SARS-CoV-2-specific CD8+ T cells were predominantly Temra cells in a state of less terminal differentiation than most Temra cells. Subsets of SARS-CoV-2-specific T cells express CD127, can proliferate homeostatically, and can persist for over 2 months. Our results suggest that long-lived and robust T cell immunity is generated following natural SARS-CoV-2 infection and support an important role of SARS-CoV-2-specific T cells in host control of COVID-19.