tbuckley/cabot-search huggingface dataset:
SAT0236 A longitudinal evaluation of the effect of a decision-support system on outcome in rheumatoid arthritis
Authors: J Fransen, G Stucki, T Langenegger, M Seitz, BA Michel
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Management of patients with RA is challenging and poses specific problems. With the help of a decision-support system (Swiss Clinical Quality Management in RA) that gives the rheumatologist feedback on treatment outcomes, the treatment strategy can be adjusted. It is assumed that control of disease activity avoids or reduces signs and symptoms in the short term, and reduces the development of joint damage and disability in the long term. <h3>Objectives</h3> To study if the decision-support system is effective in a) reducing disease activity, and b) maintaining the level of joint damage and disability in RA patients. <h3>Methods</h3> 264 RA patients from 63 rheumatologists were included in a longitudinal evaluation, starting with a 3 month control period P0 (no feedback) followed by a 12 month intervention period P1 (with provision of feedback). Patients are nested in physicians, crossed with time nested in period. The main outcome variable is the Rheumatoid Arthritis Disease Activity Index (RADAI), a questionnaire on signs and symptoms in RA. The RADAI ranges from 0–10, higher scores indicate more disease activity. Disease activity (DAS28), disability (HAQ), and joint damage (X-ray score) were additionally measured in P1. To compare the development of the RADAI in P0 with P1, multilevel analysis (linear regression with random coefficients) was used; the unit of time is 30 days. For analysing differences in P1 for DAS28, HAQ and X-ray score, the paired t-test was used. <h3>Results</h3> All patients had at least 1 feedback report at start of P1, 40% had 2, 23% had 3–6 reports. The regression model shows no time effect for RADAI in P0: -0.02 (p = 0.75) and a small time effect in P1: -0.04 (p &lt; 0.0001). The latter means ca. -0.5 RADAI point in 12 months. The difference between P0 and P1 is significant (p = 0.0011). The time effects were not influenced by: age, gender, disease duration, baseline level of disease activity, number of consultations, or changes in DMARD therapy. Of the 202 patients on DMARD therapy during P1, n = 114 had the same therapy at begin and end. Over P1, the DAS28 was reduced with -0.4 (1.2) points (p &lt; 0.0001), the HAQ remained stable with -0.1 (0.4) points (p = 0.03), and the X-ray score increased with +6.4 (10.4) points (p &lt; 0.0001). <h3>Conclusion</h3> These results point to a significant but small effect of a decision-support system in reducing disease activity in RA. Over 12 months, the medication strategy was changed in only a minority of patients. The SCQM may increase its efforts to stimulate physicans to adjust treatment, e.g. by the implementation of explicit treatment guidelines. Other possible reasons for suboptimal effectiveness need to be explored, including limited treatment options and medication compliance.
Abstract 197: Metabolic Syndrome Severely Alters Major Metabolic Pathways in the Pig Myocardium
Authors: Maryam Karimi, Olivia Ziegler, Jun Feng, Anny Usheva
Journal: Circulation (2019)

Introduction: Obesity and metabolic syndrome (MetS) are rapidly expanding worldwide. One of the most concerning implications of this trend is the association between MetS and the increased risk of cardiovascular disease (CVD) . There is a little data on cross-talk between metabolomics alterations and myocardial functionality. Hypothesis: Because of the pleiotropic nature of CVD and of MetS, it is unlikely that single metabolite or metabolic pathway underlies the development of CVD in MetS. Understanding the global metabolic state of the MS myocardium using high throughput metabolomics and transcriptomics may provide novel insights. Methods: Yorkshire swine received obesogenic diet (MetS). Control (LD) animals received regular chow. Tissue samples from identical myocardial left ventricular territories are analyzed by: targeted LC/MS-MS for LV polar metabolites, MetaboAnalyst 4.0; RNA-seq. Results: MetS vs LD demonstrates: elevated blood fasting glucose, triglycerides, LDL, cholesterol, blood pressure. LC-MS-MS shows diet impact on 287 metabolites availability in MetS together with altered gene expression of traditional enzymes that are involved in C - glycolysis, fatty acids metabolism, ketone body formation, transport, and utilization. Conclusions: Transcriptionally controlled fuel gauge in the MetS heart enzymatically turns down glucose and fatty acids oxidation and activates nutritional ketolysis. This study represents a significant step towards characterizing the metabolic state of the heart in MetS and provides potential avenues for therapeutic advance.
OP0011 Construction of a physical map and identification of candidate genes for familial chondrocalcinosis at chromosome 5p15
Authors: A Pendleton, GD Wright, MD Doherty, R Shiang, A Hughes
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> A gene for familial chondrocalcinosis was previously mapped to a locus (CCAL2) on chromosome 5p.<sup>1</sup> The purpose of the study was to identify this gene and investigate its role in the pathogenesis of calcium pyrophosphate arthropathy and osteoarthritis. <h3>Objectives</h3> <h3>Methods</h3> A combination of physical cloning and candidate gene approach were employed to define CCAL2. Novel expressed sequence tags (ESTs) with expression in cartilage and which mapped to the critical region were identified from EST databases of GenBank. PCR generated DNA fragments from ESTs were radiolabelled using radioactive phosphorus and used as probes in Southern blot hybridization of high density plasmid artificial chromosome (PAC) filters. PACs were identified following autoradiography of the hybridisation membranes and the selected PACs were supplied by the UK HGMP resource centre in Cambridge. The Online Mendelian Inheritance in Man OMIM cytogenetic map was used to identify possible candidate genes within or near the critical region. <h3>Results</h3> Six novel ESTs with high cartilage expression, identified 55 PACs following Southern blot hybridization. End sequencing of the PACs allowed the construction of a contig containing 25 PACs across the critical region. Two candidate genes were identified form OMIM. The first gene TRIO codes for a transmembrane multidomain protein which promotes the exchange of GDP for GTP in the extracellular matrix. An abnormality in this pathway is likely to produce an increase in extracellular triphosphate, which has a key role in inorganic pyrophosphate metabolism. The second gene ANK has only recently been mapped to the same location and it is responsible for articular calcification with associated arthritis in mice. <h3>Conclusion</h3> The CCAL2 region has been physically mapped and two strong candidate genes are being screened for possible disease causing mutations. This gene should provide a greater understanding of pyrophosphate metabolism and of osteoarthritis with which there is a common association. <h3>Reference</h3> Hughes AE, McGibbon D, Woodward E, Dixey J, Doherty M. Hum Mol Genet. 1995;<b>4</b>:1225–8
COVID-19 infection in gastrointestinal (GI) cancer patients receiving systemic anticancer treatment (SACT) during the outbreak of the pandemic: The Guy's Cancer Centre experience.
Authors: Eirini Tsotra, Charalampos Gousis, Beth Russell, Charlotte Moss, Kieran Palmer, Ana Montes, Nicholas R. Maisey, Anne Rigg, Kasia Owczarczyk, Asad Qureshi, Victoria Harris, Paul J. Ross, Debashis Sarker, Kiruthikah Thillai, Julien DeNaurois, Jose Roca, Sarah Ngan, Mieke Van Hemelrijck, Ailsa Sita-Lumsden, Saoirse Dolly
Journal: Journal of Clinical Oncology (2021)

455 Background: The COVID-19 pandemic has prompted difficult decisions around the use of SACT. These were based on limited early data suggesting cancer patients receiving SACT were at an increased risk of COVID-19 severe infection and death. Our study aim was to identify the COVID-19 infection and mortality rates of GI cancer patients receiving SACT. Methods: All GI patients receiving SACT at Guy’s Cancer Centre between March, and May 31, 2020 were included. Demographic data (age, ethnicity, socio-economic status (SES)) and cancer characteristics (stage, SACT type, intent and treatment-line) were collected. COVID-19 infection was confirmed by PCR and severity defined by the World Health Organisation (WHO) classification. Patients with clinical or radiological diagnosis alone were excluded. Results: Of 417 GI patients receiving SACT during the study period, 345 (82.7%) received chemotherapy (alone or combined with targeted/biological treatment), 68 (16.3%) targeted/biological treatment alone and 4 (1%) immunotherapy. 14 (3.4%) patients were diagnosed with COVID-19, 13 were on chemotherapy and 1 on targeted/biological treatment. Commonest cancers in the COVID-19 positive group were colorectal (57.1%) and hepatobiliary (21.4%), followed by oesophago-gastric (14.3%) and neuroendocrine tumours (7.1%); 57.1% had stage IV disease. 64.3% of the positive patients were male (compared to 57.3% in the COVID-19 negative population), mean age was 57.7 years (63.1 years) and 85.7% had low SES (79.7%). 8 (57.1%) patients had severe infection and there were 3 (21.4%) COVID-19 related deaths. All the patients who died from COVID-19 were male and were receiving palliative chemotherapy. Only one patient was neutropenic (grade 1) when diagnosed with COVID-19. Conclusions: The rate of COVID-19 infection in our population was relatively low (3.4 %). Of the 14 COVID-19 positive patients, 57.1% had severe infection, 21.4% died (compared to 3.7% mortality in the non-infected group) and all but one were on chemotherapy. This prospective data, from a large UK comprehensive Cancer Centre, provides some evidence that continuing SACT through the pandemic is relatively safe. The risk of COVID-19 related infection and death must be off-set against the cancer-related morbidity and mortality associated with treatment delays.
Multi‐functional Nanodrug Based on a Three‐dimensional Framework for Targeted Photo‐chemo Synergetic Cancer Therapy
Authors: Enyun Xing, Yingying Du, Juanjuan Yin, Minghui Chen, Mengyao Zhu, Xiaona Wen, Jialiang Xu, Yaqing Feng, Shuxian Meng
Journal: Advanced Healthcare Materials (2021)

Abstract Targeted synergistic therapy has broad prospects in tumor treatments. Here, a multi‐functional nanodrug GDYO‐CDDP/DOX@DSPE‐PEG‐MTX (GCDM) based on three traditional anticancer drugs (doxorubicin (DOX), cisplatin (CDDP) and methotrexate (MTX)) modified graphdiyne oxide (GDYO) is described, for diagnosis and targeted cancer photo‐chemo synergetic therapy. In this system, for the first time, these three traditional anti‐cancer drugs have played new roles and can reduce multidrug resistance through synergistic anti‐tumor effects. Cisplatin can be hybridized with GDYO to form a multifunctional and well‐dispersed three‐dimensional framework, which can not only be used as nano‐drug carriers to achieve high drug loading rates (40.3%), but also exhibit excellent photothermal conversion efficiency (47%) and good photodynamic effects under NIR irradiation. Doxorubicin (DOX) is loaded onto GDYO‐CDDP through π ‐ π stacking, which is used as an anticancer drug and as a fluorescent probe for nanodrug detection. Methotrexate (MTX) can be applied in tumor targeting and play a role in synergistic chemotherapy with DOX and CDDP. The synthesized multi‐functional nanodrug GCDM has good biocompatibility, active targeting, long‐term retention, sustained drug release, excellent fluorescence imaging capabilities, and remarkable photo‐chemo synergistic therapeutic effects.
Global prevalence of hepatitis C virus in women of childbearing age in 2019: a modelling study
Authors: Ellen Dugan, Sarah Blach, Mia Biondi, Zongzhen Cai, Mindi DePaola, Chris Estes, Jordan Feld, Ivane Gamkrelidze, Shyamasundaran Kottilil, Siya Ma, Poonam Mathur, Shauna Montoya, Devin Razavi-Shearer, Kathryn Razavi-Shearer, Sarah Robbins-Scott, Jonathan Schmelzer, Homie Razavi
Journal: The Lancet. Gastroenterology & hepatology (2021)
In situ triggering antitumor efficacy of alcohol-abuse drug disulfiram through Cu-based metal-organic framework nanoparticles
Authors: Lin Hou, Yanlong Liu, Wei Liu, Mervat Balash, Hongling Zhang, Yi Zhang, Huijuan Zhang, Zhenzhong Zhang
Journal: Acta Pharmaceutica Sinica B (2021)

Although approved as an alcohol-abuse drug, disulfiram (DSF) exhibited potential anticancer activity when chelated with copper (Cu). However, the low level of intrinsic Cu, toxicity originated from exogenous Cu supplementation, and poor stability of DSF
THU0014 Increased soluble intercellular adhesion molecule 1 levels and decreased erythrocyte superoxide dismutase activity in patients with rheumatoid arthritis: a possible association with the disease activity
Authors: M Ugur, K Senel, A Kiziltunç
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> We investigated the serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) and the activity of erythrocyte superoxide dismutase (SOD) in rheumatoid arthritis (RA). We also sought whether there was a correlation between sICAM-1 and erythrocyte SOD and whether the levels of sICAM-1 reflected disease activity. <h3>Methods</h3> Levels of sICAM-1 were measured in serum of 42 patients with active RA and 30 control subjects by an enzyme-linked immunosorbant assay. SOD activity was determined in erythrocytes isolated from patients with active RA and from controls. <h3>Results</h3> The serum levels of sICAM-1 were significantly higher in the patients with RA than in the control subjects (p &lt; 0.001). In contrast, the activities of erythrocyte SOD were significantly lower in RA patients than those in healthy controls (p &lt; 0.001). A significant negative correlation was found between the levels of sICAM-1 and erythrocyte SOD activity (r = ?0.39, p &lt; 0.01). There was a statistically significant positive correlation between sICAM-1 levels with Ritchie articular index (RAI) score and C-reactive protein (CRP) (r = 0.32, p &lt; 0.05; r = 0.44, p &lt; 0.01, respectively), whereas no significant correlation was observed between sICAM-1 and erythrocyte sedimentation rate (ESR) (r = 0.21, p &gt; 0.05). <h3>Conclusion</h3> These results show that the increased levels of sICAM-1 present in active RA patients might be due to the decreased activity of erythrocyte SOD, and increased levels of sICAM-1 may also reflect disease status or activity.
Covid-19: Medical community split over vaccine interval policy as WHO recommends six weeks
Authors: Elisabeth Mahase
Journal: BMJ (2021)

Covid-19: Medical community split over vaccine interval policy as WHO recommends six weeks Elisabeth MahaseThe medical community appears to be split over whether the UK has made the right decision in delaying the second Pfizer BioNTech vaccine dose from three weeks to 12, in order to administer more first doses of the vaccine to people who are at risk. 1
Abstract 14207: Impact of Cardiac Rehabilitation on Reducing Rehospitalization and Subsequent Medical Expenses in Patients With Acute Coronary Syndrome
Authors: Yuya Yokota, Yoshitaka Iso, Fumiyoshi Tsunoda, Makoto Shoji, Hiroshi Suzuki, Toshiro Shinke, Shinji Koba
Journal: Circulation (2019)

Introduction: Exercise-based Cardiac rehabilitation (CR) reduces cardiovascular events (CEs) in patients with acute coronary syndrome (ACS). However, it remains unclear whether CR can reduce total ...
Systematic comparison of 20 European COVID-19 vaccination strategies: recommendations for mental illness
Authors: Livia J. De Picker, Benedetta Vai, Marisa Casanova Dias, Igor Branchi, Francesco Benedetti, Michael E. Benros, Alessandra Borsini, Juan Carlos Leza, Hillka Kärkkäinen, Miia Männikkö, Carmine M. Pariante, Ekin Sönmez Güngör, Anna Szczegelniak, Ryad Tamouza, Afra van der Markt, Paolo Fusar-Poli, Julian Beezhold, Marion Leboyer
Journal: The Lancet Psychiatry (2021)
Abstract 2473: <i>NR4A1</i> suppresses cancer replication stress through R-loop-dependent inhibition of immediate early gene transcriptional elongation
Authors: Hongshan Guo, Gabriel Golczer, Shyamala Maheswaran, Michael S. Lawrence, Daniel A. Haber
Journal: Cancer Research (2021)

Abstract Deregulation of oncogenic proliferative signals triggers replication stress in cancer cells to which they must adapt. Immediate early genes (IEGs), identified by their rapid stress-induced transient bursts of expression, are critical to integrating downstream signaling pathways. In studying tumor initiation by patient-derived breast cancer cells, we observed acquisition of open chromatin domains at the genebody and 3'-UTR of IEGs, uniquely across the genome. Through in vivo and in vitro modeling, we show that the IEG and orphan nuclear receptor NR4A1 localizes across multiple IEG genebodies, where it binds to RNA Pol II, arresting transcriptional elongation and generating extensive R-loops and accessible chromatin. Acute stress promptly removes NR4A1 from IEG genebodies, triggering immediate release of their poised transcripts. In breast cancer cells, NR4A1 overexpression increases tumorigenesis; conversely, its deletion leads to uncompensated replication stress, chromosomal instability and mitotic catastrophe, driven by deregulation of its IEG target FOS. A large fraction of primary breast and other cancers exhibit open genebody chromatin at IEGs, consistent with preserved NR4A1 function. Thus, NR4A1 mediates a novel transcriptional elongation checkpoint, unique to stress-induced genes and required for their rapid bursts of expression. Cancers that have retained this mechanism in adapting to chronic replication stress may be dependent on NR4A1 for proliferation. Citation Format: Hongshan Guo, Gabriel Golczer, Shyamala Maheswaran, Michael S. Lawrence, Daniel A. Haber. NR4A1 suppresses cancer replication stress through R-loop-dependent inhibition of immediate early gene transcriptional elongation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2473.
AB0625 IS PULMONARY ARTERIAL HYPERTENSION, ASSOCIATED WITH SYSTEMIC SCLEROSIS REVERSIBLE?
Authors: A. Volkov, N. Yudkina, E. Nikolaeva, M. Starovoytova, O. Alekseeva, I. Nikishina, E. Nasonov
Journal: Annals of the Rheumatic Diseases (2020)

Background: Systemic sclerosis (SSc) is one of the frequent causes of the pulmonary arterial hypertension (PAH) which found in 6-15% patient with SSc. Patients with PAH, associated with SSc have a poorer prognosis than other forms of PAH. 6 World Symposium of PH lowered diagnostic cut-off to 21 mm Hg in hope of improved survival. PAH reversibility is described in congenital heart defects, HIV and some tumors Objectives: The aim of the study to detect reversibility of PAH associated with SSc. Methods: Hemodynamics (mean pulmonary artery pressure (MPAP), pulmonary artery wedge pressure (PAWP), cardiac output (CO) and pulmonary vascular resistance (PVR)), functional class (NYHA), 6-minute walk distance (6MWD), biomarkers and DLCO were assessed. Patients with pulmonary fibrosis and left heart diseases were excluded. Results: The study includes 56 patients receiving start-up monotherapy with 1st generation PAH-specific drugs: bosentan (25 patients) and sildenafil (31 patients). The median age of the patients was 51.5 (37; 58) years. At the time of diagnosis, the MPAP in the sildenafil group was 49 (30; 50) mm Hg, bosentan - 50 (42; 56) mm Hg, differences not significant (p = 0.11). During observation against the background of sildenafil intake, the MPAP decreased by -3 (-7; 0) mm Hg, bosentan -6 (-13; -2) mm Hg. Decreasing of MPAP ≤ 21 mm Hg was at seven patients receiving sildenafil. Initial hemodynamic values in this group of patients was MPAP 25 (21; 27) mm Hg., RAP 2 (1; 5) mm Hg, PAWP 7 (6; 10) mm Hg., CV 5.9 (4.7; 6.7) l/min, PVR 3.0 (1.5; 4.2) Wood Unit. Among patients taking sildenafil, there were seven who had MPAP less than 35 mmHg, and among patients taking bosentan, there were 4 patients with less than 35 mmHg. However, the decreasing was observed only group who received sildenafil. ROC – analysis shown that cut-off for reversible is 29 mm Hg (AUC 0,977, sensitivity 97%, and specificity 100%) Conclusion: In patients with PAH, associated with SSc, on sildenafil treatment, at MPAP &lt; 29 mm Hg reversibility is possible. Further study is required. Disclosure of Interests: None declared
Geographical and socioeconomic disparities in opioid access in Mexico, 2015–19: a retrospective analysis of surveillance data
Authors: David Goodman-Meza, Joseph Friedman, Mariah M Kalmin, Emmanuel Aguilar-Posada, Marissa J Seamans, Sara Velazquez-Moreno, Clara Fleiz, Michael Shin, Jaime Arredondo-Sanchez, Steffanie A Strathdee, Steve Shoptaw
Journal: The Lancet Public Health (2021)

In 2015, Mexico implemented regulatory changes and an electronic system to improve access to prescription opioids. We aimed to investigate trends in opioid dispensing after the implementation of these changes and assess how opioid dispensing varied geographically and by socioeconomic status.In this retrospective analysis of prescription medication surveillance data, we analysed dispensing data for group 1 medications (all opioids, including morphine, methadone, hydromorphone, oxycodone, tapentadol, fentanyl, sufentanil, and remifentanil) obtained from the Federal Commission for the Protection against Sanitary Risk database for 32 states and six large metropolitan areas in Mexico. We calculated crude annual opioid prescriptions per 10 000 people at the national, state, and municipal levels. Adapting methods from the report of the Lancet Commission on Palliative Care and Pain Relief, we calculated the need for palliative opioids by state, and then assessed the observed opioid dispensing rates as a percentage of expected need by geographical socioeconomic status. Within the six major metropolitan areas, we mapped the geocoded location of opioid prescriptions and assessed the association between opioid dispensing and socioeconomic status as well as the association between opioid dispensing and time to US border crossing for areas on the US-Mexico border.Between June 25, 2015, and Oct 7, 2019, opioid dispensing rates increased by an average of 13% (95% CI 6·8-19·6) per quarter (3 months). The overall national opioid dispensing rate during the study period was 26·3 prescriptions per 10 000 inhabitants. States with a higher socioeconomic status had higher opioid dispensing rates than states with lower socioeconomic status (rate ratio [RR] 1·88, 95% CI 1·33-2·58, p=0·00016) after controlling for the estimated opioid requirement per state, the presence of methadone clinics, and the presence of tertiary hospitals and cancer centres. The same association between opioid dispensing and socioeconomic status was observed in the metropolitan areas, and in those metropolitan areas on the US-Mexico border a 20% decrease (RR 0·80, 95% CI 0·75-0·86) in opioid dispensation was observed per each SD increase (SD 17·1 min) in travel time to the border.Measures introduced by the Mexican federal Government to increase opioid access for patients with palliative care needs were only marginally successful in raising opioid prescription rates. Opioid access should be improved for patients with palliative care needs who live in geographical areas of lower socioeconomic status.US National Institutes of Health.