tbuckley/cabot-search huggingface dataset:
MicroRNAs are Involved in Maize Immunity Against <i>Fusarium Verticillioides</i> Ear Rot
Authors: Zijian Zhou, Yan Cao, Tao Li, Xinghao Wang, Jiafa Chen, Hang He, Wen Yao, Jianyu Wu, Huiyong Zhang
Journal: Genomics Proteomics & Bioinformatics (2020)

Abstract Fusarium ear rot (FER) caused by Fusarium verticillioides is one of the most common diseases affecting maize production worldwide. FER results in severe yield losses and grain contamination with health-threatening mycotoxins. Although most studies to date have focused on comprehensive analysis of gene regulation in maize during defense responses against F. verticillioides infection, less is known about the role of microRNAs (miRNAs) in this process. We used deep sequencing to compare small RNA libraries from the maize kernels of susceptible (N6) or resistant (BT-1) inbred lines from uninfected plants and upon F. verticillioides infection. We found that pathogen exposure was accompanied by dynamic alterations in expression levels of multiple miRNAs, including new members of previously annotated miRNA families. A combination of transcriptomic, degradomic, and bioinformatics analyses revealed that F. verticillioides-responsive miRNAs and their potential target genes displayed opposite expression patterns in the susceptible and resistant genotypes. Functional category analysis uncovered preferential enrichment of the pathogen-responsive miRNAs and their targets in the phenylpropanoid metabolic processes, plant–pathogen interactions, and plant phytohormone signal transduction pathways. Furthermore, transgenic maize plants overexpressing miR408b exhibited reduced resistance to F. verticillioides infection in a susceptible maize line. These findings provide new insights into the regulatory roles of miRNAs in maize immunity against FER and new resources for breeding disease resistance into maize.
Effects of treatment on morbidity in hypertension. Results in patients with diastolic blood pressures averaging 115 through 129 mm Hg
Journal: JAMA (1967)

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Employment Outcomes Among Cancer Survivors in the United States: Implications for Cancer Care Delivery
Authors: Janet S de Moor, Erin E Kent, Timothy S McNeel, Katherine S Virgo, Jennifer Swanberg, J Kathleen Tracy, Matthew P Banegas, Xuesong Han, Jin Qin, K Robin Yabroff
Journal: JNCI Journal of the National Cancer Institute (2020)

The national prevalence of employment changes after a cancer diagnosis has not been fully documented. Cancer survivors who worked for pay at or since diagnosis (n = 1490) were identified from the 2011, 2016, and 2017 Medical Expenditure Panel Survey and Experiences with Cancer supplement. Analyses characterized employment changes due to cancer and identified correlates of those employment changes. Employment changes were made by 41.3% (95% confidence interval [CI] = 38.0% to 44.6%) of cancer survivors, representing more than 3.5 million adults in the United States. Of these, 75.4% (95% CI = 71.3% to 79.2%) took extended paid time off and 46.1% (95% CI = 41.6% to 50.7%) made other changes, including switching to part-time or to a less demanding job. Cancer survivors who were younger, female, non-White, or multiple races and ethnicities, and younger than age 20 years since last cancer treatment were more likely to make employment changes. Findings highlight the need for patient-provider communication about the effects of cancer and its treatment on employment.
Abstract IA19: The Drug Rediscovery Protocol: Getting the most out of approved drugs
Authors: Emile E. Voest
Journal: Clinical Cancer Research (2020)

Abstract Large-scale genetic tumor profiling can identify increasing numbers of potentially actionable molecular variants for which approved anticancer drugs are available. In daily practice, however, when patients with such variants are treated with drugs outside of their approved label, successes and failures are not systematically collected or shared. Therefore, we initiated the Drug Rediscovery Protocol (DRUP), an innovative and adaptive precision oncology trial aimed at identifying signals of activity in cohorts of patients with defined tumor types and molecular variants, treated with anticancer drugs outside their approved label. Eligible patients have exhausted (or declined) standard therapies and have malignancies with potentially actionable variants for which no approved anticancer drugs are available. We use a stepwise approach per cohort of first 8 patients, and when at least one patient experienced clinical benefit that cohort expands to 24 patients. Presently, we have reviewed &amp;gt;1,100 submitted patient cases and included and treated &amp;gt;500 patients. We found an overall clinical benefit rate (defined as complete or partial response, or stable disease ≥16 weeks) of 29% although the formal analysis is per cohort. The potential of DRUP was illustrated by the identification of a successful cohort of patients with microsatellite instable tumors receiving nivolumab or durvalumab, and tumors with HRD treated with olaparib. Our results have led to a personalized reimbursement model for nivolumab in patients with MSI tumors that is supported by all regulatory parties. The DRUP hereby facilitates defined use of approved drugs beyond their label in (rare) cancer subgroups, identifies early signals of activity in these subgroups, accelerates clinical translation of new insights, and creates a publicly available knowledge-base for future decision making. Citation Format: Emile E. Voest. The Drug Rediscovery Protocol: Getting the most out of approved drugs [abstract]. In: Proceedings of the AACR Special Conference on Advancing Precision Medicine Drug Development: Incorporation of Real-World Data and Other Novel Strategies; Jan 9-12, 2020; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_1):Abstract nr IA19.
Abstract 14709: High Density Lipoprotein From Patients With Coronary Artery Disease Impairs Endothelial Cell Proliferation by Regulating Long Non-coding RNAs
Authors: Jingsong Ou, Xiang liu, Hua-Ming Li, Zhi-Wei Mo, Yan Li, Tian-Tian Wang, Zhi-Jun Ou, Ying-Qi Xu
Journal: Circulation (2017)

Introduction: Previous clinical trials designed to stimulate coronary vascular growth (therapeutic angiogenesis) using growth factors, e.g, vascular endothelial growth factor (VEGF), in patients wi...
Abstract B30: Locoregional control in laryngeal and hypopharyngeal cancer patients treated with radiotherapy using direct gross tumor volume to planning target volume expansion
Authors: Adam R. Burr, Paul M. Harari, Matthew E. Witek
Journal: Clinical Cancer Research (2020)

Abstract Purposes/Objectives(s): To evaluate clinical outcomes and patterns of failure using a direct gross tumor volume to planning target volume expansion in patients treated for laryngeal or hypopharyngeal squamous cell carcinomas. Methods and Materials: We performed a retrospective review of patients with laryngeal or hypopharyngeal squamous cell carcinomas treated between 2002-2017 with primary radiotherapy with or without concurrent systemic therapy. Patient and disease characteristics associated with disease control and clinical outcomes were analyzed by Cox proportional hazards regression and Kaplan-Meier analyses. Deformable image registration between imaging at the time of failure and the treatment planning scan was used to determine patterns of failure. Results: Seventy-nine patients with laryngeal or hypopharyngeal squamous cell carcinoma were identified with a median follow-up of 54 months among surviving patients. Overall survival at 5 years was 62.9% (95% CI: 51.1%-74.7%). Five-year primary tumor control was 71.6% (95% CI: 61.4%-81.8%) and regional control was 78.8% (95% CI: 68.4%-89.2%). A total of 28 patients experienced a locoregional recurrence, of whom 18 had treatment plans available. Of these, 89% (n=16) experienced failures that were 95% contained within the high-dose treatment volume. One patient failed in an intermediate-dose volume and 1 exhibited a marginal failure in the high-dose volume. There were no factors associated with overall survival or locoregional control on multivariate analysis. Conclusion: Management of patients with laryngeal or hypopharyngeal squamous cell carcinoma using definitive radiotherapy and a high-dose planning target volume created without a gross tumor volume to clinical tumor volume expansion resulted in high locoregional control, with the vast majority of failures occurring within the high-dose field. These data support prospective evaluation of this technique. Citation Format: Adam R. Burr, Paul M. Harari, Matthew E. Witek. Locoregional control in laryngeal and hypopharyngeal cancer patients treated with radiotherapy using direct gross tumor volume to planning target volume expansion [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr B30.
AB0368 TREATMENT OF SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS WITH BELIMUMAB – PROSPECTIVE OBSERVATION OVER 2 YEARS
Authors: S. Dimitrov, S. Hristova, S. Bogdanova-Petrova, T. Shivacheva
Journal: Annals of the Rheumatic Diseases (2020)

Background: Systemic lupus erythematosus (SLE) is autoimmune connective tissue disorder of unclear etiology. It is characterized by autoantibody production and a variety of clinical manifestations. The introduction of biological treatment over the past few years provided an opportunity for a disease control. Objectives: The aim was to assess the effectiveness and safety profile of Belimumab in the treatment programs of SLE patients during a 2 year period. Methods: We initiated a prospective observational study of SLE patients in the Rheumatology Department in University Hospital St Marina – Bulgaria. The study comprises data from 26 patients at baseline before Belimumab treatment initiation and data after 6, 12, 18 and 24 months of treatment. All patients were with moderate disease activity according to SELENA – SLEDAI index and were on treatment with immunosuppressive drug (azathioprine) and glucocorticoids (GCs). We observed the change in the dosage of glucocorticoids over the observed period, the number of flares of SLE, as well the SELENA – SLEDAI index change. Safety profile of Belimumab was also registered. Results: We included 26 patients with SLE over a period of 4 years – between 2015 and 2019. The mean age was 45.8 + 11.4 years and 94% were Caucasian females. All patients were on a stable dosage of GCs at least 3 months before the first infusion of Belimumab and azathioprine 100 mg daily. Ninety percent of patients were diagnosed with SLE for more than 6 years according to ACR – SLE criteria. All of SLE patients were with moderate disease activity. Main reasons for biological treatment decision were persistent mucocutaneous manifestations (20%), polyarthritis (15%), haematological disturbances (35%) and persistent immunological markers (30%). One patient was excluded from the study due to infusion- related flush and severe hypotension reaction while the rest 25 completed the observation. We investigated and analyzed haematological results, ANA, anti – ds DNA, anti – Sm autoantibodies and complement fractions at baseline as well on the 12th and 24th month of treatment. The mean SELENA – SLEDAI index changed from 8.9 to 4.5 after 12 months of treatment and remained unchanged until the end of the study. We observed a mean reduction of GCs daily dosage from 12 mg to 6 mg after 18 months. Conclusion: Biological treatment with Belimumab added to the standard treatment with GCs and AZA in patients with non-lupus nephritis SLE patients adds additional benefits. Our results show that there is a reduction in SLEDAI index as well as reduction in daily GCs intake. Safety profile is not different from the one reported previously. Disclosure of Interests: None declared
Off-label use of tofacitinib: a potential treatment option for SAPHO syndrome
Authors: Wenhui Xie, Hong Huang, Zhuoli Zhang
Journal: Annals of the Rheumatic Diseases (2020)

Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome is a rare and often under-reported autoimmune disease, characterised by prominent cutaneous and articular inflammation.1 SAPHO syndrome is initially classified within spondyloarthritis, whereas recent evidence indicated that it is preferable as a primitive inflammatory osteitis. There are currently no formal evidence-based guidelines regarding the management of SAPHO syndrome, although variable degrees of efficacy of pharmacological therapies have been previously described, including non-steroidal anti-inflammatory drugs, glucocorticoids, disease-modifying antirheumatic drugs, bisphosphonates and even antibiotics.2 Moreover, antitumour necrosis factor (TNF), interleukin (IL)-1 receptor antagonist also showed beneficial effect to the refractory SAPHO patients.3 …
SAT0068 Intra-articular hylan gf20 (synvisc) in the management of patellofemoral osteoarthritis of the knee (poak)
Authors: S Clarke, V Lock, J Duddy, JH Newman, JR Kirwan
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Anterior knee pain and patellofemoral osteoarthritis of the knee (POAK) are disabling and often difficult to manage. Intra-articular (IA) hyaluronate reduces pain in patients with tibiofemoral disease but its effect in POAK has not been studied prospectively. <h3>Objectives</h3> To make a preliminary assessment of the potential effect of IA Hylan GF20 (Synvisc) on patients with isolated POAK. <h3>Methods</h3> Out Patients aged more than 35 years with anterior knee pain and predominant POAK on plain radiographs, MRI or arthroscopy were recruited to an uncontrolled, prospective pilot study. Patients with significant tibiofemoral disease were excluded. Patients received 2 ml of IA Hylan GF20 on 3 successive weeks. The primary outcome was change in the patients' global assessment of their disease on a 100 mm visual analogue scale (VAS). Secondary outcome included WOMAC, and Oxford Outcome Score. Data were collected at baseline, 5, 12 and 26 weeks. <h3>Results</h3> Of the 39 enrolled patients 31 have radiographic (joint space narrowing) POAK and the remainder MRI (6) or arthroscopic (2) evidence of POAK but normal radiographs. The mean (95% CI) age is 56 (3.5) years and BMI 30 (1.9), 22 are women and 28 have currently reached 26 weeks. Mean patients' global assessment was reduced from 64 (7.1) at entry to 47 (10.3), 37 (10.0) and 40 (11.7) at each time point and these changes were significantly different from baseline (paired T-test: P = 0.001, 0.00004, 0.006 respectively). 15/28 (54%) cases improved by &gt;20 mm VAS at 26 weeks. Significant changes also occurred in pain on stair climbing (WOMAC Question A2: 77.6, 52.3, 51.3, 50.1) and Oxford Outcome Score (Total Score: 36.1, 32.9, 31.0, 30.9). Adverse knee events followed 16 of 116 injections but only two patients were unable to complete the course of injections. <h3>Conclusion</h3> The apparent clinical benefit of Hylan GF20 persists to 26 weeks, beyond that expected of IA glucocorticoids. These positive data on the effect of Hylan GF20 in POAK suggest a randomised controlled trial be performed.
FRI0476 RHEUMATIC MANIFESTATIONS DURING INFLAMMATORY BOWEL DISEASE
Authors: M. Boudabbous, H. Gdoura, L. Chtourou, A. Amouri, L. Mnif, N. Tahri
Journal: Annals of the Rheumatic Diseases (2020)

Background: Rheumatologic manifestations are frequent extraintestinal manifestations (MEI) of chronic inflammatory bowel disease (IBD). Some of these manifestations develop in parallel with the underlying disease, others evolve on their own account. They sometimes lead to reconsider the initial therapy for intestinal purposes. Objectives: The aim of our study is to specify the epidemioclinical characteristics of osteoarticular manifestations of chronic inflammatory bowel disease and their possible impact on intestinal disease Methods: This is a retrospective study conducted between January 2000 and December 2015 including patients hospitalized in our department for chronic inflammatory bowel disease (IBD). Results: During the study period, 206 patients with IBD were hospitalized in our department, 78 of whom had rheumatic MEI (frequency equal to 37.8%). These 78 patients were divided into 48 men and 30 women with a sex ratio of 1.6 and an average age of 40.7 ± 13.6 years (18–79). They had Crohn’s disease in 60% of the cases. The average length of service for IBDs was 83 ± 73 months (4–360). Osteoarticular MEIs were peripheral in 56.4% of cases, axial in 29.5% of cases, mixed in 6.41% of cases with the presence of osteopenia in 6.41% of cases and osteoporosis in 1 28%. The activity of IBD associated with these MEI was moderate with an average number of outbreaks / year of 1.6 ± 0.8. These patients were treated with salicylates in 30.7% of the cases using corticosteroid therapy at least once in 23% of the cases. Maintenance treatment based on immunosuppressants was found in 38.46% of cases and anti-TNF alfa in 10.25% of cases. During follow-up, 3 patients died (3.84%). There was no significant difference between patients with IBD with rheumatic MEI and without rheumatic MEI regarding epidemiological data and disease activity. Conclusion: Rheumatic MEIs are found in almost 40% of IBDs. They affect men more frequently than women and Crohn’s disease than UC. They are rather peripheral and do not associate with a more important activity of the disease. References: [1]Journal of the Canadian Association of Gastroenterology, 2019, 2(S1), S73–S80 doi: 10.1093/jcag/gwy053 Supplement Article Disclosure of Interests: None declared
SURVEILLANCE AND MONITORING: Toxics Report Improves, but Data Still Limited
Authors: Bob Weinhold
Journal: Environmental Health Perspectives (2009)

In the United States, only coal-and oil-fired power plants must report.**Each country's PRTR differs in the types of activities required to report under this sector.Water supply, sewage treatment** (200) 6 % Transportation equipment mfg.(285) 3 % Oil and gas extraction (production)*** (137) 15 % Chemicals mfg.(451) 3 % Paper products mfg.(115) 2 % Primary metals mfg.(246) 6 % Petroleum products mfg.(40) 3 % Services/support activities: mining, quarrying, oil/gas extraction*** (50) 58 % Fabricated metals mfg.(282) 2 % Waste management and remediation services* (127) 2 % Electrical equipment mfg.(76) 10 % Plastics and rubber mfg.(57) 5 % Generation and distribution of electricity* (49) 10 % Mining and quarrying (except oil and gas)** (33) 69 % Transportation equipment mfg.(206) 3 % Chemicals mfg.(324) 3 % *Only hazardous waste/solvent recovery facilities must report.**Only coal-and oil-fired power plants must report.***Each country's PRTR differs
Long‐term safety of certolizumab pegol in plaque psoriasis: pooled analysis over 3 years from three phase III, randomized, placebo‐controlled studies
Authors: A. Blauvelt, C. Paul, P. Kerkhof, R.B. Warren, A.B. Gottlieb, R.G. Langley, F. Brock, C. Arendt, M. Boehnlein, M. Lebwohl, K. Reich
Journal: British Journal of Dermatology (2020)

Certolizumab pegol (CZP) is an Fc-free, PEGylated anti-tumour necrosis factor biologic.To report 3-year safety data from three phase III trials of CZP in adults with plaque psoriasis.Data were pooled from CIMPASI-1 (NCT02326298), CIMPASI-2 (NCT02326272) and CIMPACT (NCT02346240). Included patients had moderate-to-severe plaque psoriasis of ≥ 6 months' duration; had been randomized to CZP 200 mg every 2 weeks (Q2W) (400 mg at weeks 0, 2 and 4) or CZP 400 mg Q2W; and had received at least one dose of CZP with up to 144 weeks of exposure. Treatment-emergent adverse events (TEAEs) were classified using MedDRA v18·1. Reported incidence rates (IRs) are incidence of new cases per 100 patient-years (PY).Over 144 weeks, 995 patients received at least one dose of CZP (exposure: 2231·3 PY); 731 and 728 received at least one dose of CZP 200 mg Q2W (1211·4 PY) and/or 400 mg Q2W (1019·9 PY), respectively. The IR [95% confidence interval (CI)] of TEAEs was 144·9 (135·3-155·0) for all patients, 134·1 (123·2-145·7) for CZP 200 mg Q2W and 158·3 (145·5-171·9) for CZP 400 mg Q2W. The IR (95% CI) of serious TEAEs for all patients was 7·5 (6·4-8·8); the IRs were 6·7 (5·2-8·3) and 8·7 (6·9-10·8) for CZP 200 mg and 400 mg Q2W, respectively. Overall, 3·2% of patients reported serious infections (2·2% within each of the CZP 200 and 400 mg Q2W groups). Overall, there was one case of active tuberculosis, 16 malignancies in 14 patients and seven deaths (two considered treatment-related). The cumulative IR of TEAEs did not increase over time.No new safety signals were identified compared with previously reported data. Risk did not increase with longer or higher CZP exposure.