tbuckley/cabot-search huggingface dataset:
SAT0307 PROGRESSION OF SUBCLINICAL MYOCARDIAL INVOLVEMENT IN PATIENTS WITH SYSTEMIC SCLEROSIS
Authors: D. Benfaremo, G. Stronati, L. Manfredi, L. Zuliani, A. Ferrarini, C. Fischetti, C. Dichiara, F. Guerra, A. Dello Russo, A. Gabrielli
Journal: Annals of the Rheumatic Diseases (2020)

Background: Systemic sclerosis (SSc) is a progressive autoimmune disease affecting the skin as well as internal organs, including the heart. A few studies have identified a subclinical heart involvement in patients with no pulmonary hypertension. Changes in myocardial deformation are consistent with the idea of SSc-related cardiomyopathy as a primary condition affecting the heart globally through microvascular dysfunction and subsequent myocardial fibrosis. Objectives: The aim of the present study is to describe the progression of myocardial deformation in patients with SSc and no overt cardiac disease. Methods: Prospective longitudinal study enrolling consecutive SSc patients referred to the Clinica Medica, University Hospital ‘Ospedali Riuniti’, Ancona, Italy, from February 2016 to December 2018. All patients fulfilled the 2013 ACR/EULAR classification criteria for SSc. Patients with structural heart disease, heart failure, atrial fibrillation or pulmonary hypertension were excluded. Disease subset, antibodies pattern, cardiovascular risk factors and involvement of other organ systems were recorded for each patient. An echocardiographic exam was performed for all patients at baseline and during their follow-up evaluation. Standard and speckle-tracking derived variables for the systolic and diastolic function of the left ventricle (LV) and right ventricle (RV) were acquired. Speckle tracking analysis software (EchoPAC 13.0; GE Medical Systems, Milwaukee, USA) was used to assess the GLS of the left and right ventricle, excluding the ventricular septum from right ventricular GLS calculations. Results: Seventy-two patients (68 females, age 56.6±15.4 years) were enrolled. Common echocardiographic parameters of left and right systolic function were within normal range at baseline and did not change during follow-up. Mean GLS, however, worsened for both left (from -19.8±3.5% to -18.7±3.5%, p=.034) and right ventricle (from -20.9±6.1% to -18.7±5.4%, p=.013) during a median follow-up of 20 months (1st-3rd quartile 12-24 months). The increased impairment registered in SSc patients was homogenous across endocardial layers (LV from -22.5±-3.9 to -21.4±3.9, p=.041; RV from -24.2±6.2 to -20.6±5.9, p=.001), mesocardial layers (LV -19.7±3.6 to -18.7±3.5, p=.043; RV from -21.3±5.9 to -18.8±5.7, p=.012) and epicardial layers (LV from -17.1±3.0 to -16.4±3.1, p=.112, RV -18.8±6.3 to -16.0±8.4, p=.035), as well as myocardial segments. No difference in progression rate was observed stratifying patients according to disease subset or other clinical parameters. Conclusion: GLS impairment progressed over a 20-month follow-up period in a cohort of SSc patients without clinically overt cardiac involvement. Further studies are needed to assess the significance of subclinical heart involvement and its progression in patients with SSc. Disclosure of Interests: None declared
A novel strategy for the diagnosis, prognosis, treatment, and chemoresistance of hepatocellular carcinoma: DNA methylation
Authors: Aimei Liu, Qinghua Wu, Dapeng Peng, Irma Ares, Arturo Anadón, Bernardo Lopez‐Torres, María‐Rosa Martínez‐Larrañaga, Xu Wang, María‐Aránzazu Martínez
Journal: Medicinal Research Reviews (2020)

The cancer mortality rate of hepatocellular carcinoma (HCC) is the second highest in the world and the therapeutic options are limited. The incidence of this deadly cancer is rising at an alarming rate because of the high degree of resistance to chemo- and radiotherapy, lack of proper, and adequate vaccination to hepatitis B, and lack of consciousness and knowledge about the disease itself and the lifestyle of the people. DNA methylation and DNA methylation-induced epigenetic alterations, due to their potential reversibility, open the access to develop novel biomarkers and therapeutics for HCC. The contribution to these epigenetic changes in HCC development still has not been thoroughly summarized. Thus, it is necessary to better understand the new molecular targets of HCC epigenetics in HCC diagnosis, prevention, and treatment. This review elaborates on recent key findings regarding molecular biomarkers for HCC early diagnosis, prognosis, and treatment. Currently emerging epigenetic drugs for the treatment of HCC are summarized. In addition, combining epigenetic drugs with nonepigenetic drugs for HCC treatment is also mentioned. The molecular mechanisms of DNA methylation-mediated HCC resistance are reviewed, providing some insights into the difficulty of treating liver cancer and anticancer drug development.
MR imaging features of diffuse intrinsic pontine glioma and relationship to overall survival: report from the International DIPG Registry
Authors: James L Leach, James Roebker, Austin Schafer, Joshua Baugh, Brooklyn Chaney, Christine Fuller, Maryam Fouladi, Adam Lane, Renee Doughman, Rachid Drissi, Mariko DeWire-Schottmiller, David S Ziegler, Jane E Minturn, Jordan R Hansford, Stacie S Wang, Michelle Monje-Deisseroth, Paul G Fisher, Nicholas G Gottardo, Hetal Dholaria, Roger Packer, Katherine Warren, Sarah E S Leary, Stewart Goldman, Ute Bartels, Cynthia Hawkins, Blaise V Jones
Journal: Neuro-Oncology (2020)

Abtract Background This study describes imaging features of diffuse intrinsic pontine glioma (DIPG) and correlates with overall survival (OS) and histone mutation status in the International DIPG Registry (IDIPGR). Methods Four hundred cases submitted to the IDIPGR with a local diagnosis of DIPG and baseline MRI were evaluated by consensus review of 2 neuroradiologists; 43 cases were excluded (inadequate imaging or alternative diagnoses). Agreement between reviewers, association with histone status, and univariable and multivariable analyses relative to OS were assessed. Results On univariable analysis imaging features significantly associated with worse OS included: extrapontine extension, larger size, enhancement, necrosis, diffusion restriction, and distant disease. On central review, 9.5% of patients were considered not to have DIPG. There was moderate mean agreement of MRI features between reviewers. On multivariable analysis, chemotherapy, age, and distant disease were predictors of OS. There was no difference in OS between wild-type and H3 mutated cases. The only imaging feature associated with histone status was the presence of ill-defined signal infiltrating pontine fibers. Conclusions Baseline imaging features are assessed in the IDIPGR. There was a 9.5% discordance in DIPG diagnosis between local and central review, demonstrating need for central imaging confirmation for prospective trials. Although several imaging features were significantly associated with OS (univariable), only age and distant disease were significant on multivariable analyses. There was limited association of imaging features with histone mutation status, although numbers are small and evaluation exploratory.
Incidence, casualties and risk characteristics of civilian explosion blast injury in China: 2000—2017 data from the state Administration of Work Safety
Authors: Xu Wang, Juan Du, Zhuo Zhuang, Zheng-Guo Wang, Jian-Xin Jiang, Ce Yang
Journal: Military Medical Research (2020)

Abstract Background Civilian explosion blast injury is more frequent in developing countries, including China. However, the incidence, casualties, and characteristics of such incidents in China are unknown. Methods This is a retrospective analysis of the State Administration of Work Safety database. Incidents during a period from January 1, 2000 to April 30, 2017 were included in the analysis. The explosions were classified based on the number of deaths into extraordinarily major, major, serious and ordinary type. Descriptive statistics was used to analyze the incidence and characteristics of the explosions. Correlation analysis was performed to examine the potential correlations among various variables. Results Data base search identified a total of 2098 explosions from 2000 to 2017, with 29,579 casualties: 15,788 deaths (53.4%), 12,637 injured (42.7%) and 1154 missing (3.9%). Majority of the explosions were serious type (65.4%). The number of deaths (39.5%) was also highest with the serious type ( P = 0.006). The highest incidence was observed in the fourth quarter of the year (October to December), and at 9:00–11:00 am and 4:00–6:00 pm of the day. The explosions were most frequent in coal-producing provinces (Guizhou and Shanxi Province). Coal mine gas explosions resulted majority of the deaths (9620, 60.9%). The number of explosion accidents closely correlated with economic output (regional economy and national GDP growth rate) ( r = − 0.372, P = 0.040; r = 0.629, P = 0.028). Conclusions The incidence and civilian casualties due to explosions remain unacceptabe in developing China. Measures that mitigate the risk factors are of urgently required.
Acyl‐Coenzyme A Thioesterase 9 Traffics Mitochondrial Short‐Chain Fatty Acids Toward De Novo Lipogenesis and Glucose Production in the Liver
Authors: Sandra Steensels, Jixuan Qiao, Yanzhen Zhang, Kristal M. Maner‐Smith, Nourhan Kika, Corey D. Holman, Kathleen E. Corey, W. Clay Bracken, Eric A. Ortlund, Baran A. Ersoy
Journal: Hepatology (2020)

Background and Aims Obesity‐induced pathogenesis of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is associated with increased de novo lipogenesis (DNL) and hepatic glucose production (HGP) that is due to excess fatty acids. Acyl‐coenzyme A (CoA) thioesterase (Acot) family members control the cellular utilization of fatty acids by hydrolyzing (deactivating) acyl‐CoA into nonesterified fatty acids and CoASH. Approach and Results Using Caenorhabditis elegans , we identified Acot9 as the strongest regulator of lipid accumulation within the Acot family. Indicative of a maladaptive function, hepatic Acot9 expression was higher in patients with obesity who had NAFLD and NASH compared with healthy controls with obesity. In the setting of excessive nutrition, global ablation of Acot9 protected mice against increases in weight gain, HGP, steatosis, and steatohepatitis. Supportive of a hepatic function, the liver‐specific deletion of Acot9 inhibited HGP and steatosis in mice without affecting diet‐induced weight gain. By contrast, the rescue of Acot9 expression only in the livers of Acot9 knockout mice was sufficient to promote HGP and steatosis. Mechanistically, hepatic Acot9 localized to the inner mitochondrial membrane, where it deactivated short‐chain but not long‐chain fatty acyl‐CoA. This unique localization and activity of Acot9 directed acetyl‐CoA away from protein lysine acetylation and toward the citric acid (TCA) cycle. Acot9‐mediated exacerbation of triglyceride and glucose biosynthesis was attributable at least in part to increased TCA cycle activity, which provided substrates for HGP and DNL. β‐oxidation and ketone body production, which depend on long‐chain fatty acyl‐CoA, were not regulated by Acot9. Conclusions Taken together, our findings indicate that Acot9 channels hepatic acyl‐CoAs toward increased HGP and DNL under the pathophysiology of obesity. Therefore, Acot9 represents a target for the management of NAFLD.
Abstract IA09: Tumor organoid cultures as a platform for functional genomics
Authors: Mathew Garnett
Journal: Cancer Research (2020)

Abstract In an era of genomics-guided precision medicine, there is an increasing need for models that reflect the hallmarks of cancer and the molecular diversity of patient tumors. New cell culturing methods are transforming our ability to derive cell models from healthy and diseased tissues, with increased success rates, and linked to patient genomic and clinical data. I will update on our efforts as part of the Human Cancer Models Initiative (HCMI) to create a new biobank of molecularly annotated tumor organoids as a community resource. Furthermore, I will present how we are beginning to use these organoid cultures for chemical and genetic screens to identify new molecular targets and biomarkers of therapy response. These early studies are laying the foundation for a next-generation tumor organoid functional genomics platform to help guide the development of future precision cancer medicines. Citation Format: Mathew Garnett. Tumor organoid cultures as a platform for functional genomics [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 IA09.
AB1054 CLINICAL CHARACTERISTICS OF PATIENTS WITH UVEITIS FROM AN AUTOIMMUNE OCULAR DISEASE UNIT
Authors: A. Paats, V. Valinotti, J. Coronel, S. Riquelme, N. Colman
Journal: Annals of the Rheumatic Diseases (2020)

Background: The eye, particularly the uvea due to its substantial vascularization, can be a target for various inmune reactions. Etiology is unknown in most cases of inflamatory ocular disease. Ocassionally, ocular symptoms may be the first manifestation of some systemic diseases and its appearence, therefore, can lead us to the diagnosis and institution of treatment that, if performed early, can avoid irreversible sequelae. Aim: Describe the experience at 12 months of an autoinmune ocular disease unit. Objectives: to describe the clinical characteristics of patients diagnosed with uveitis and its association with systemic disease. Methods: Retrospective, descriptive study. We included patients diagnosed with uveitis attending the Autoimmune Eye Disease Unit from January 2019 to December 2019. Qualitative variables were expressed as frequencies and percentages and quantitative variables as means and standard deviation. Results: A total of 40 patients were included, 72.5% were women (26/40). Mean age of disease onset was 38 ± 17.2 years and the average diagnostic delay was 19.4 ± 46.8 months. The most frequent chief complaint was decrease in visual acuity, cited in 43.8% of the consults (25/57). Involvement was bilateral in 55% of cases (22/40). In order of decreasing frequency, diagnosis found were: Anterior uveitis in 47.5% (19/40), panuveitis in 35% (14/40), posterior uveitis in 10% (4/40) and intermediate uveitis in 7.5% (3/40). There was a recurrence (2 or more episodes of uveitis) in 65.7% (25/38) of patients and 58.8% (20/34) of them presented some sequelae. Prior to their first episode of uveitis, 12.5% (5/40) of patients had already been diagnosed with an autoimmune disease, the most common of which was spondyloarthropathy (3/5). Meanwhile, 33.3% (13/39) were diagnosed with a systemic disease from their first episode of uveitis. Regarding laboratory tests, 46.4% (13/28) of patients presented acute phase reactants, 13% (3/23) had positive serum antibodies and 41.6% (5/12) were HLA-B27 positive. Concerning treatment, 76.3% of patients required systemic corticosteroids (29/38) and 75% received at least one immunosuppressive drug (30/40). Out of this group, 30% needed a second immunosuppressive drug. Response to treatment was good in 63.6% of patients (21/33), partial in 18.1% (6/33), poor despite treatment in 6% (2/33) and poor due to lack of adherence in 12.1% (4/33). Conclusion: In our cohort, there was a predominance of female, middle-aged patients with bilateral involvement. Anterior uveitis was the most frequent diagnosis. In one-third of patients, the first episode of uveitis led to diagnosis of a systemic disease. Most of our patients presented some type of sequel or local complication and required systemic treatment with corticosteroids and immunosuppressants. Disclosure of Interests: None declared
Use of <i>Sports Hernia</i> to Describe Groin Pain in Athletes
Authors: Kristian Thorborg, Per Hölmich
Journal: JAMA Surgery (2020)

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Spatial distribution of dysplasia in Barrett’s esophagus segments before and after endoscopic ablation therapy: a meta-analysis
Authors: Shashank Garg, Jesse Xie, Sumant Inamdar, Sheila L. Thomas, Arvind J. Trindade
Journal: Endoscopy (2020)

Background Dysplasia in Barrett’s esophagus (BE) is focal and difficult to locate. The aim of this meta-analysis was to understand the spatial distribution of dysplasia in BE before and after endoscopic ablation therapy. Methods A systematic search was performed of multiple databases to July 2019. The location of dysplasia prior to ablation was determined using a clock-face orientation (right or left half of the esophagus). The location of the dysplasia post-ablation was classified as within the tubular esophagus or at the top of the gastric folds (TGF). Results 13 studies with 2234 patients were analyzed. Pooled analysis from six studies (819 lesions in 802 patients) showed that before ablation, dysplasia was more commonly located in the right half versus the left half (odds ratio [OR] 4.3; 95 % confidence interval [CI] 2.33 – 7.93; P &lt; 0.001). Pooled analysis from seven studies showed that dysplasia after ablation recurred in 101 /1432 patients (7.05 %; 95 %CI 5.7 % – 8.4 %). Recurrence of dysplasia was located more commonly at the TGF (n = 68) than in the tubular esophagus (n = 34; OR 5.33; 95 %CI 1.75 – 16.21; P = 0.003). Of the esophageal lesions, 90 % (27 /30) were visible, whereas only 46 % (23 /50) of the recurrent dysplastic lesions at the TGF were visible (P &lt; 0.001). Conclusion Before ablation, dysplasia in BE is found more frequently in the right half of the esophagus versus the left. Post-ablation recurrence is more commonly found in the TGF and is non-visible, compared with the tubular esophagus, which is mainly visible.
Antibody signature induced by SARS-CoV-2 spike protein immunogens in rabbits
Authors: Supriya Ravichandran, Elizabeth M. Coyle, Laura Klenow, Juanjie Tang, Gabrielle Grubbs, Shufeng Liu, Tony Wang, Hana Golding, Surender Khurana
Journal: Science Translational Medicine (2020)

Understanding antibody epitope diversity and affinity generated by SARS-CoV-2 spike antigens in rabbits can aid COVID-19 vaccine development.
Covid-19: transforming healthcare will require collaboration and innovative policies
Authors: Eliza Lai-Yi Wong, Eng-kiong Yeoh, Dong Dong
Journal: BMJ (2020)

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AB0287 HEMATOLOGICAL SIDE EFFECTS OF BIOLOGICAL THERAPY IN RHEUMATOLOGY: DATA FROM THE TUNISIAN REGISTER
Authors: H. Bettaieb, S. Boussaid, S. Jemmali, S. Rekik, E. Cheour, H. Sahli, M. Elleuch, L. Abdelmoula, A. Laatar, W. Hamdi, S. Kochbati, E. Bouajina, M. Younes, N. Bargaoui, S. Baklouti
Journal: Annals of the Rheumatic Diseases (2020)

Background: During the last decade, the treatment of chronic inflammatory rheumatism (CIR) has been greatly improved with the advent of biotherapy.However, the use of biological treatment can lead to a number of side effects including abnormalities in the blood count. Objectives: The aim of this study was to assess the different hematological side effects of biological treatment in patients with rheumatoid arthritis (RA) and spondyloarthitis (SA). Methods: This study included patients with RA (ACR/EULAR 2010) and SA (ASAS 2009) registred with the Tunisian Biologic National Registry (BINAR).Patients were followed and treated with biologics for 2 years of less. Clinical data relative to biological treatment, including haematological side effects, have been collected. Results: Two hundred and ninety-eight patients (178 women and 111 men) were included in the study. The mean age was 49.2 ± 14.1 years. The male/female ratio was 0.6. The mean diseases durations for RA and SA were respectively 6.7 ± 3.5 years and 6.5 ±3.6 years. Anti-TNFα agents were prescribed in 87.9% of patients (n = 263) with respectively: Infliximab (20.4%) Etanercept (23.1%), Adalimumab (24.6%) and Certolizumab (26.5%). Tocilizumab and Rituximab were prescribed in 10.4% and 5% of the patients, respectively. Blood count abnormalities were noted in 15.4 % of patients (n=46). Neutropenia was the most frequently anomaly met on the hemogram (9.1%) followed by anemia (3.4%) and thrombocytopenia (3%). Pancytopenia was found in 11.4% of patients (n=34). The median time between biological therapy initiation and the onset of hematologic manifestations was 4.8 months [1-12]. Biological treatment was interrupted in two patients. In the other cases, the biological treatment was maintained with close monitoring of blood cell count. No case of death related to these hematological disturbances has been reported. Conclusion: In our registry, hematological side effects of biological treatment were found in 15.4% of cases and were noted with a median delay of 4.8 [1-12] months after the treatment initiation. Further studies are needed to confirm our preliminary results. Disclosure of Interests: None declared
Hospital staff take the knee in Boston
Authors: Tom Moberly
Journal: BMJ (2020)

David L Ryan/Boston Globe/Getty Images

Members of staff kneel during a vigil on the lawn of Brigham and Women’s Hospital in Boston, Massachusetts, on 5 June as part of global Black Lives Matter protests against racial injustice and in memory of George Floyd, killed by the police in Minneapolis on 25 May.

Protests also took part in the UK, …