tbuckley/cabot-search huggingface dataset:
Abstract IA09: Challenges in the identification of inherited risk of ovarian cancer
Authors: Barbara M. Norquist
Journal: Clinical Cancer Research (2020)

Abstract We have come a long way since the 1990s in our understanding of inherited risk and in the genetic testing options that are available to our patients. Despite the clear benefits of identifying inherited risk, there are many barriers in place to genetic testing, and most women with ovarian cancer are still not undergoing these tests. The need for genetic testing currently exceeds the availability of genetic counselors, and creative solutions will need to be explored. The Stand Up To Cancer Ovarian Cancer Dream Team is conducting the MAGENTA (MAking GENetic Testing Accessible) trial. MAGENTA utilizes genetic testing at home with a mailed kit, electronic results delivery, and telephonic genetic counseling. This and other ideas will have to be explored in order to increase genetic testing rates. With the recent publication of SOLO-1 demonstrating a large benefit for PARP inhibitor maintenance therapy in the primary setting for women with advanced BRCA-mutated OC, identifying germline and somatic BRCA1 and BRCA2 mutations at the time of diagnosis is paramount and likely to soon be considered standard of care for treatment planning. The most optimal method for detecting both germline and somatic mutations is currently up for debate. Our University of Washington Department of Laboratory Medicine is currently offering tumor and germline sequencing in parallel using both tumor and blood samples, allowing for simultaneous detection of germline and somatic mutations, with methods optimized for each approach. Data from this ongoing project will be presented. Finally, in order to optimize the identification of inherited risk, we need to better understand which genes are implicated in ovarian cancer risk and treatment response. The advent of multiplex gene testing has allowed us to detect mutations in many genes using a single test, increasing efficiency and decreasing costs. The primary downside of multiplex testing is that as more genes are sequenced, the likelihood of identifying uncertain results also increases, either in the form of variants of uncertain significance (VUS) or damaging mutations in genes with uncertain contributions to cancer risk. Available data on risks of ovarian cancer with mutations in genes other than BRCA1 and BRCA2 will be reviewed. Citation Format: Barbara M. Norquist. Challenges in the identification of inherited risk of ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr IA09.
ANTI-CARBAMYLATED PROTEIN ANTIBODIES (ANTI-CARP) PRECEDE THE ONSET OF RHEUMATOID ARTHRITIS
Authors: J. Shi, L. van de Stadt, N. Levarht, T. Huizinga, D. Hamann, D. van Schaardenburg, R. Toes, L. Trouw
Journal: Annals of the Rheumatic Diseases (2013)
Functional Role of the Secretin/Secretin Receptor Signaling During Cholestatic Liver Injury
Authors: Nan Wu, Leonardo Baiocchi, Tianhao Zhou, Lindsey Kennedy, Ludovica Ceci, Fanyin Meng, Keisaku Sato, Chaodong Wu, Burcin Ekser, Konstantina Kyritsi, Debjyoti Kundu, Lixian Chen, Vik Meadows, Antonio Franchitto, Domenico Alvaro, Paolo Onori, Eugenio Gaudio, Ilaria Lenci, Heather Francis, Shannon Glaser, Gianfranco Alpini
Journal: Hepatology (2020)

iver diseases are a major health concern and affect a large proportion of people worldwide.There are over 100 types of liver disorders, including cirrhosis, cholangiocarcinoma (CCA), hepatocellular carcinoma, and hepatitis.Despite the relevant number of people who are affected by liver diseases, and the increased awareness with regard to these disorders, the number of deaths corresponding to liver injury is expected to increase in the foreseeable future.One of the possible reasons for this is that a complete comprehension of the mechanisms of hepatic damage involving specific liver anatomical districts is lacking, and, as a consequence, current treatments available are suboptimal.A major burden in the clinical setting are chronic cholestatic liver diseases (e.g., primary biliary cholangitis [PBC], primary sclerosing cholangitis [PSC], biliary atresia), which target the biliary epithelium and are characterized by cholestasis. (1,2)Because the secretin (Sct)/secretin receptor (SR) axis (expressed only by cholangiocytes in the liver) (3,4) is the major regulator of ductal bile secretion, (5,6) it is intuitive that this axis plays a key role in the maintenance of biliary homeostasis during the progression of cholangiopathies.For instance, PBC is characterized by reduced bicarbonate secretion, a phenomenon possibly impeding the formation of an HCO - 3 canalicular film ("bicarbonate umbrella") on bile ducts, which has protective properties against highly concentrated bile acids (BAs). (1,7,8)In this review, we examined the molecular mechanisms by which the Sct/SR axis regulates biliary function and the homeostasis of the biliary epithelium in normal and pathophysiological conditions. Sct/SR aXIS: tHe BaSICSSct, a neuroendocrine, gastrointestinal peptide of 27 amino acids is secreted primarily by the intestinal S cells located in the Lieberkühn crypts.There is evidence that Sct is also secreted by other epithelia in different organs including the pancreas, intestine and liver, thus exerting various biological effects in
Roy William Lamb
Authors: Marion Lamb
Journal: BMJ (2020)

From 1962 to 1993, Roy William Lamb (“Larry”) was a GP and anaesthetist in Stroud, Gloucestershire. He grew up in the East End of London during the war years and trained at Charing Cross Hospital in the Strand—the first member of his family to access a university education.

Roy served his rural community with great skill and dedication. He provided obstetric care at the maternity hospital, sessions in casualty at the local hospital, and he was a highly skilled GP anaesthetist including for paediatric ear, nose, and throat surgery. He provided high quality out of hours care for his practice for his entire career—attending patients in their homes for everything from palliative care to mental health …
Augmented Lipocalin-2 Is Associated with Chronic Obstructive Pulmonary Disease and Counteracts Lung Adenocarcinoma Development
Authors: Warapen Treekitkarnmongkol, Maya Hassane, Ansam Sinjab, Kyle Chang, Kieko Hara, Zahraa Rahal, Jiexin Zhang, Wei Lu, Smruthy Sivakumar, Tina L. McDowell, Jacob Kantrowitz, Jianling Zhou, Wenhua Lang, Li Xu, Joshua K. Ochieng, Sayuri Nunomura-Nakamura, Shanshan Deng, Carmen Behrens, Maria Gabriela Raso, Junya Fukuoka, Alexandre Reuben, Edwin J. Ostrin, Edwin Parra, Luisa M. Solis, Avrum E. Spira, Florencia McAllister, Tina Cascone, Ignacio I. Wistuba, Seyed Javad Moghaddam, Paul A. Scheet, Junya Fujimoto, Humam Kadara
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Early pathogenesis of lung adenocarcinoma (LUAD) remains largely unknown. We found that, relative to wild-type littermates, the innate immunomodulator Lcn2 (lipocalin-2) was increased in normal airways from mice with knockout of the airway lineage gene Gprc5a (Gprc5a−/−) and that are prone to developing inflammation and LUAD. Yet, the role of LCN2 in lung inflammation and LUAD is poorly understood.Objectives: Delineate the role of Lcn2 induction in LUAD pathogenesis.Methods: Normal airway brushings, uninvolved lung tissues, and tumors from Gprc5a−/− mice before and after tobacco carcinogen exposure were analyzed by RNA sequencing. LCN2 mRNA was analyzed in public and in-house data sets of LUAD, lung squamous cancer (LUSC), chronic obstructive pulmonary disease (COPD), and LUAD/LUSC with COPD. LCN2 protein was immunohistochemically analyzed in a tissue microarray of 510 tumors. Temporal lung tumor development, gene expression programs, and host immune responses were compared between Gprc5a−/− and Gprc5a−/−/Lcn2−/− littermates.Measurements and Main Results: Lcn2 was progressively elevated during LUAD development and positively correlated with proinflammatory cytokines and inflammation gene sets. LCN2 was distinctively elevated in human LUADs, but not in LUSCs, relative to normal lungs and was associated with COPD among smokers and patients with LUAD. Relative to Gprc5a−/− mice, Gprc5a−/−/Lcn2−/− littermates exhibited significantly increased lung tumor development concomitant with reduced T-cell abundance (CD4+) and richness, attenuated antitumor immune gene programs, and increased immune cell expression of protumor inflammatory cytokines.Conclusions: Augmented LCN2 expression is a molecular feature of COPD-associated LUAD and counteracts LUAD development in vivo by maintaining antitumor immunity.
Drug survival of systemic and biological treatments for moderate‐to‐severe atopic dermatitis in adults: a multicentre retrospective observational study
Authors: J.J. Pereyra‐Rodriguez, J. Domínguez‐Cruz, R. Ruiz‐Villaverde, J.F. Silvestre, M. Galán, L. Curto, I. Figueras, E. Serra‐Baldrich, J.C. Armario‐Hita
Journal: British Journal of Dermatology (2020)
Abstract PR09: <i>STAG2</i> mutations alter topologic organization of the genome and cis-mediated interactions
Authors: Didier Surdez, Sakina Zaidi, Sandrine Grossetête, Virginie Raynal, Sylvain Baulande, Véronique Hill, Olivier Delattre
Journal: Cancer Research (2020)

Abstract STAG2 is one of the most recurrently mutated genes in human cancer, including in Ewing sarcoma, an aggressive bone tumor driven by the chimeric EWSR1-FLI1 transcription factor. We and others have shown that STAG2 mutations occurs in approximately 20% of Ewing sarcoma, leading most frequently to complete loss of function (LOF) of its protein. We also showed that STAG2 mutations were associated with poor outcome for these patients. However, functional mechanisms associated with these mutations are still poorly understood. STAG2 encodes an integral member of the cohesin complex, a ring-shaped multiprotein structure, which is important for proper sister chromatid cohesion and release during mitosis. Cohesin, together with CTCF, is also essential to shape the architecture of the genome through its ring structure that allows for chromatin loops formation. Here, we investigated STAG2 and STAG1 functions using isogenic proficient and deficient Ewing sarcoma models. Using extensive characterization of these models by transcriptomics and epigenetics approaches, we demonstrate that STAG2 LOF has a major impact on the expression of genes associated with enhancer features, highlighting STAG2 and EWSR1-FLI1 convergent effects. Using chromatin conformation capture methods, we further show that this transcriptomic modulation results from a STAG2 LOF specific topologic alteration of the genome. This work therefore unravels a new fundamental role of STAG2 in topologic organization of the genome and in gene regulation. This abstract is also being presented as Poster B53. Citation Format: Didier Surdez, Sakina Zaidi, Sandrine Grossetête, Virginie Raynal, Sylvain Baulande, Véronique Hill, Olivier Delattre. STAG2 mutations alter topologic organization of the genome and cis-mediated interactions [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr PR09.
Identification of asthma phenotypes based on extrapulmonary treatable traits
Authors: Patricia Duarte Freitas, Rafaella França Xavier, Vanessa Marie McDonald, Peter Gerard Gibson, Laura Cordova-Rivera, Karina Couto Furlanetto, Joice Mara de Oliveira, Regina Maria Carvalho-Pinto, Alberto Cukier, Rafael Stelmach, Celso Ricardo Fernandes Carvalho
Journal: European Respiratory Journal (2020)

Asthma is a heterogeneous and complex disease, and a description of asthma phenotypes based on extrapulmonary treatable traits has not been previously reported. The objective of this study was to identify and characterise clusters based on clinical, functional, anthropometrical and psychological characteristics in participants with moderate-to-severe asthma. This was a cross-sectional multicentre study involving centres from Brazil and Australia. Participants (n=296) with moderate-to-severe asthma were consecutively recruited. Physical activity and sedentary time, clinical asthma control, anthropometric data, pulmonary function and psychological and health status were evaluated. Participants were classified by hierarchical cluster analysis and the clusters compared using ANOVA, Kruskal­–Wallis and Chi-squared tests. Multiple logistic and linear regression models were performed to evaluate the association between variables. We identified four clusters: 1) participants with controlled asthma who were physically active; 2) participants with uncontrolled asthma who were physically inactive and more sedentary; 3) participants with uncontrolled asthma and low physical activity, who were also obese and experienced anxiety and/or depression symptoms; and 4) participants with very uncontrolled asthma who were physically inactive, more sedentary, obese and experienced anxiety and/or depression symptoms. Higher levels of sedentary time, female sex and anxiety symptoms were associated with increased odds of exacerbation risk, while being more active showed a protective factor for hospitalisation. Asthma control was associated with sex, the occurrence of exacerbation, physical activity and health status. Physical inactivity, obesity and symptoms of anxiety and/or depression were associated with worse asthma outcomes, and closely and inextricably associated with asthma control. This cluster analysis highlights the importance of assessing extrapulmonary traits to improve personalised management and outcomes for people with moderate and severe asthma.
Comparison of clinical laboratory tests between bacterial sepsis and SARS-CoV-2-associated viral sepsis
Authors: Chao Ren, Ren-Qi Yao, Di Ren, Ying Li, Yong-Wen Feng, Yong-Ming Yao
Journal: Military Medical Research (2020)

Abstract Sepsis is a life-threatening condition that is characterized by multiple organ dysfunction due to abnormal host response to various pathogens, like bacteria, fungi and virus. The differences between viral and bacterial sepsis are indeed of great significance to deepen the understanding of the pathogenesis of sepsis, especially under pandemics of SARS-CoV-2 infection.
LncRNA-SLC16A1-AS1 induces metabolic reprogramming during Bladder Cancer progression as target and co-activator of E2F1
Authors: Stella Logotheti, Stephan Marquardt, Shailendra K. Gupta, Christin Richter, Berdien A.H. Edelhäuser, David Engelmann, Julia Brenmoehl, Christoph Söhnchen, Nico Murr, Michael Alpers, Krishna P. Singh, Olaf Wolkenhauer, Dirk Heckl, Alf Spitschak, Brigitte M. Pützer
Journal: Theranostics (2020)

Long non-coding RNAs (lncRNAs) have emerged as integral components of E2F1-regulated gene regulatory networks (GRNs), but their implication in advanced or treatment-refractory malignancy is unknown. Methods: We combined high-throughput transcriptomic approaches with bioinformatics and structure modeling to search for lncRNAs that participate in E2F1-activated prometastatic GRNs and their phenotypic targets in the highly-relevant case of E2F1-driven aggressive bladder cancer (BC). RNA immunoprecipitation was performed to verify RNA-protein interactions. Functional analyses including qRT-PCR, immunoblotting, luciferase assays and measurement of extracellular fluxes were conducted to validate expression and target gene regulation. Results: We identified E2F1-responsive lncRNA-SLC16A1-AS1 and its associated neighboring protein-coding gene, SLC16A1/MCT1, which both promote cancer invasiveness. Mechanistically, upon E2F1-mediated co-transactivation of the gene pair, SLC16A1-AS1 associates with E2F1 in a structure-dependent manner and forms an RNA-protein complex that enhances SLC16A1/MCT1 expression through binding to a composite SLC16A1-AS1:E2F1-responsive promoter element. Moreover, SLC16A1-AS1 increases aerobic glycolysis and mitochondrial respiration and fuels ATP production by fatty acid β-oxidation. These metabolic changes are accompanied by alterations in the expression of the SLC16A1-AS1:E2F1-responsive gene PPARA, a key mediator of fatty acid β-oxidation. Conclusions: Our results unveil a new gene regulatory program by which E2F1-induced lncRNA-SLC16A1-AS1 forms a complex with its transcription factor that promotes cancer metabolic reprogramming towards the acquisition of a hybrid oxidative phosphorylation/glycolysis cell phenotype favoring BC invasiveness.
Reply
Authors: Dana E. Orange, Nathalie E. Blachere, Mayu O. Frank, Salina Parveen, Edward F. DiCarlo, Serene Mirza, Tania Pannellini, Caroline S. Jiang, Mark P. Figgie, Vivian P. Bykerk, Ellen M. Gravallese, Ana-Maria Orbai, Sarah L. Mackie, Susan M. Goodman
Journal: Arthritis & Rheumatology (2020)

We are grateful for the interest in our manuscript describing synovial histology features that associate with patient reports of morning stiffness in rheumatoid arthritis1 . Jain et al raise an important point; not all joints in a patient with rheumatoid arthritis are affected equally at any given time, making it challenging to associate studies of synovium from only one joint with assessments of global patient symptoms. We had discovered that morning stiffness duration was associated with the presence of fibrin and neutrophils in synovium, however, neither of the questions used in this analysis focus on any particular joint and it is likely that joints other than the arthroplasty joint influenced patient responses.
Comparison of Peripheral Blood Stem Cell Mobilization with Etoposide or Cyclophosphamide in Patients with Multiple Myeloma
Authors: Sung-Hoon Jung, Seo-Yeon Ahn, Seung-Shin Lee, Jae-Sook Ahn, Deok-Hwan Yang, Yeo-Kyeoung Kim, Hyeoung-Joon Kim, Je-Jung Lee
Journal: Blood (2017)
Targeting IL-6 in COVID-19. Response to: ‘Rational use of tocilizumab in COVID-19’ by Jain and Sharma
Authors: Pier Leopoldo Capecchi, Pietro Enea Lazzerini
Journal: Annals of the Rheumatic Diseases (2020)

<h3>Objective:</h3> To analyze clinical features and myopathology changes in muscle fibers, connective tissue, and vessels in 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibody–associated myopathies. <h3>Methods:</h3> Retrospective review of records and myopathologic features of 49 consecutive patients with myopathies and serum HMGCR antibodies. <h3>Results:</h3> Clinical features included onset age from 12 to 83 years, female predominance (67%), proximal, symmetric weakness (84%), muscle discomfort (78%), dysphagia (35%), systemic features, including skin rash and interstitial lung disease (37%), statin use (38%), and a high serum creatine kinase (83%). Myopathology included muscle fiber necrosis or regeneration (66%), myonuclear pathology (43%), perimysial connective tissue damage (61%), and lymphocytic foci (27%). <h3>Conclusions:</h3> Patients with HMGCR antibody–associated myopathies present with weakness and muscle discomfort and often have damage to both perimysial connective tissue and muscle fibers, with necrosis and myonuclear pathology. Only a minority of patients with HMGCR antibody–associated myopathies have a history of statin exposure.
AB1302-HPR ASSOCIATIONS OF SLEEP ON GOUT PREVALENCE AND SERUM URIC ACID CONCENTRATIONS
Authors: P. Kachur, S. Tadepalli, C. Pramil
Journal: Annals of the Rheumatic Diseases (2020)

Background: Sleep deprivation and sleep inconsistency have been associated with modulation of the immune and inflammatory response systems with effects that include higher risk for psychosis, cardiovascular disease, and increased susceptibility to infection. One hypothesized mechanism to explain these findings is an association with pro-inflammatory states. Objectives: In a first-of-its kind study, we examined associations between sleep quantity and gout using the largest public US dataset available; the National Health and Nutrition Examination Survey (NHANES). Methods: NHANES data from 2009 to 2014 was selected based on questionnaire responses and laboratory studies. The resulting data set was analyzed for serum uric acid (SUA) levels (cut-off &gt;6.0 mg/dL in females and &gt;7.0 mg/dL in males), and gout risk factors. Analysis of variance, means, proportions, as well as univariate and multiple logistic regression models were used to evaluate the associations between sleep quantity, SUA and gout. Results: 10,410 survey participants from 2003 to 2014 were included in the study. A total of 280 (2.7%) had gout. Gout prevalence ranged between 4.0% and 4.7% between high, normal, and low sleep groups. Multivariate analyses showed a significant association between extremely low sleep levels (OR = 0.53 and CI = 0.34 to 0.83), and gout, which was also seen with SUA level association (OR = 0.41 and CI = 0.32 to 0.52). However, in the broader sense, lower than normal (&lt;7 hours) and higher than normal (&gt;9 hours) levels of sleep had no significant associations with either gout prevalence or SUA, likely due to a non-linear relationship of SUA to sleep levels. Conclusion: Despite numerous adverse effects found with low sleep levels, our study does not show a strong association between sleep quantity and gout prevalence or SUA levels. References: [1]Hasday et al. “ Nocturnal increase of urinary uric acid: creatinine ration. A biological correlate of sleep-associated hypoxemia .” AM Rev Respir Dis 1981, 135:534 [2]Lavie, Lena. “ Obstructive sleep apnoea syndrome-an oxidative stress disorder ” Sleep Medicine Reviews 2003, 7:35 1 [3]Roddy et al. “ The Association of Gout with Sleep Disorders: a cross-sectional study in primary care. ”BMC Musculoskeletal Disorders 2013, 14:119 [4]Sahebjani H. “ Changes in urinary uric acid excretion in obstructive sleep apean before and after therapy with nasal continuous positive airway pressure .” Chest 1998’ 113: 1604 [5]Taheri et al. “ Short Sleep Duration is Associated with Reduced Leptin, Elevated Ghrelin, and Increased Body Mass Index ” PLOS Medicine 2004, 1:210 Disclosure of Interests: None declared
A Phase II Study of THP-COP (pirarubicin, cyclophosphamide, vincristine and prednisolone) in Patients with Newly Diagnosed Advanced Peripheral T-Cell Lymphoma: THP-3 Study of Japan Hematopoietic Malignancy Clinical Study Group (HMCSG)
Authors: Michinori Ogura, Ken Ohmachi, Ritsuro Suzuki, Yoshiko Atsuta, Tatsuya Ito, Kazuma Ohyashiki, Shingo Yano, Michihiro Hidaka, Kiyoshi Ando, Noriko Fukuhara, Yoshihisa Morishita, Takayo Suzuki, Kunihiro Tsukasaki, Naoki Kobayashi, Kenji Tsukamoto, Yukiyasu Ozawa, Tomomitsu Hotta, Tomohiro Kinoshita
Journal: Blood (2017)
Hydrogel-mediated co-transplantation of retinal pigmented epithelium and photoreceptors restores vision in an animal model of advanced retinal degeneration
Authors: Nikolaos Mitrousis, Sabiha Hacibekiroglu, Margaret T. Ho, Yves Sauvé, Andras Nagy, Derek van der Kooy, Molly S. Shoichet
Journal: Biomaterials (2020)