tbuckley/cabot-search huggingface dataset:
SAT0031 Fine epitope mapping of immunodominant peptide epitopes by affinity matrix technology using yersinia-hsp60-specific synovial cd4<sup>+</sup>t-cells in reactive arthritis (rea) patients
Authors: A Thiel, P Wu, D Stauch, M Rudwaleit, A Radbruch, J Sieper
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> A T cell response to persitent bacterial antigen is present in patients with reactive arthritis (ReA). A better characterisation of this response might lead to new treatments. <h3>Objectives</h3> To identify immundominant Yer-hsp60-derived CD4 T cell epitopes in Yersinia-induced reactive arthritis (ReA). <h3>Methods</h3> In two patients with Yersinia-induced ReA synovial fluid (SF) T cell response were first investigated after <i>in vitro</i> stimulation with the Yersinia-derived protein hsp60. Fixed cells were stained with antibodies against CD4, CD8, CD69 and against the cytokine IFNgamma;. Patients with reacting CD4<sup>+</sup> Th cells were retested and live IFNgamma-secreting cells were isolated with the affinity matrix technology after short term stimulation with Yer-hsp60. Cells were expanded within 2 to 5 weeks and retested with overlapping 18 mer peptides from the Yer-hsp60 protein performing cytometric analysis of fixed cells after short term stimulation with peptided pulsed autologous PBMCs. <h3>Results</h3> Live antigen-specific IFNgamma;-secreting CD4<sup>+</sup> T cells were enriched to a purity of 80 to 90%. After two weeks <i>in vitro</i> expansion still 80% of the short-term cultivated T cells reacted with IFNgamma-production upon Yer-hsp60 stimulation, while reaction upon stimulation with a irrelevant protein was below 1%. T cells were further expanded antigen-specifically for 3 weeks and their fine specificity was further mapped to one peptide in each patient (AA 139–156 and AA 7–30 of Yer-hsp60/GroEL). Tese peptides was also recognised by the patient's CD4<sup>+</sup> T cells when whole blood or synovial fluid was stimulated for 6 h. <h3>Conclusion</h3> This approach allows a sensitive and fast epitope mapping of immunodominant epitopes possibly involved in the pathogenesis of ReA.
Association of Prodromal Type 1 Diabetes With School Absenteeism of Danish Schoolchildren: A Population-Based Case-Control Study of 1,338 Newly Diagnosed Children
Authors: Peter R. Thingholm, Amanda Gaulke, Tine M. Eriksen, Jannet Svensson, Niels Skipper
Journal: Diabetes Care (2020)

OBJECTIVE To investigate school absenteeism before the clinical diagnosis of type 1 diabetes in children who develop the disease. RESEARCH DESIGN AND METHODS This population-based, retrospective case-control study involved all Danish children who developed type 1 diabetes and attended public schools (n = 1,338) from 2010 to 2017. Those children were matched at a 1-to-5 ratio, on the basis of sex and date of birth, to children without diabetes (n = 6,690). Case and control absenteeism were compared monthly, starting with 12 months prior to the type 1 diabetes diagnosis through 12 months after diagnosis. RESULTS Before the diabetes diagnosis (7–12 months), the mean number of days absent from school per month was 0.93 (SD 1.78) among children with diabetes and 0.93 (1.82) among control children (difference −0.004 days, P = 0.94). From 4 months before the diagnosis, children who developed diabetes had a statistically significant increase in absenteeism compared with control children (difference 0.24 days, P &amp;lt; 0.05). CONCLUSIONS Children who were diagnosed with type 1 diabetes had increased school absenteeism 4 months before diagnosis.
Letter to the Editor: Liver Biochemistries in Hospitalized Chinese Patients With Severe Coronavirus Disease 2019
Authors: Ya Gao, Ming Liu, Shuzhen Shi, Jinhui Tian
Journal: Hepatology (2021)

Potential conflict of interest: Nothing to report. TO THE EDITOR: We read with interest the article by Kovalic et al.(1) on elevated liver biochemistries in hospitalized Chinese patients with severe coronavirus disease 2019 (COVID‐19). This important work showed that comorbidities, such as coronary artery disease (CAD) and cerebrovascular disease, are more prevalent in hospitalized Chinese patients with severe/critical COVID‐19 and that these patients are more likely to manifest with abnormal liver chemistries. However, several issues that may affect the results should be noted. First, this study only searched three English‐language databases. However, in the early days of the COVID‐19 epidemic, most of the evidence came from China. Therefore, restricting the search may lead to important biases in the retrieved studies because many articles were published in Chinese. Furthermore, the authors clarified that they only included studies written in English, but two Chinese studies (studies of Peng and Liu) were included for analyses. Second, the search terms used by the authors are not comprehensive because articles may report the liver biochemical data in the basic characteristics section; therefore, many studies investigating the epidemiology of patients with COVID‐19 may have been missed. Moreover, data of this study were as of March 22, 2020. The literature searches should be updated because many important studies have since been published. Third, another issue is the huge heterogeneity of meta‐analyses. In some analyses, the I2 value is >80%, which seriously affects the credibility of the results. However, the authors synthesized the data without exploring the sources of heterogeneity through additional analyses (e.g., sensitivity analyses), although they treated this as a limitation. In addition, they clarified that if no significant heterogeneity was found (I2 < 50%), the fixed‐effects model was used. However, in some meta‐analyses (e.g., CAD) with I2 < 50%, the authors used the random‐effects model. Fourth, this meta‐analysis incorporated six studies with a small sample size of 586 patients, and some meta‐analyses only included one or two primary studies. Therefore, the results should be interpreted with caution. Fifth, the Cochrane Collaboration recommended that authors use the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool for all important outcomes in their systematic reviews.(2) Thus, it is valuable for authors to assess the quality of evidence of their results using GRADE. Sixth, research protocols help to increase the transparency of the review methods and avoid bias in outcome reporting.(3) However, the authors did not report information about registration, which may result in the post hoc modification of methods. Finally, fewer than 10 studies were included for meta‐analyses, which is unsuitable for conducting Egger's test. We believe that addressing these issues can further enhance the value of this study.
Comorbid acne inversa and Dowling–Degos disease due to a single <i>NCSTN</i> mutation: is there enough evidence? Reply from the authors
Authors: S. Garcovich, P.M. Tricarico, C.N. Meddour, G. Giovanardi, K. Peris, S. Crovella, M. Boniotto
Journal: British Journal of Dermatology (2020)

Linked Articles: Hermasch et al. Br J Dermatol 2021; 184:374. Garcovich et al. Br J Dermatol 2020; 183:758–759.
Covid-19: Doctors call for action after patients are left unable to get tests
Authors: Abi Rimmer
Journal: BMJ (2020)

Covid-19: Doctors call for action after patients are left unable to get tests Abi RimmerThe BMA has called on the government to "get a grip" on the covid-19 testing system, after the service's leader revealed that laboratories were at a "critical pinch-point."Writing on Twitter, Sarah-Jane Marsh, director of testing at NHS Test and Trace, apologised to patients who were unable to get a covid-19 test.
Annals Graphic Medicine - Progress?
Authors: Abey K. Thomas
Journal: Annals of Internal Medicine (2020)

Web Exclusives15 September 2020Annals Graphic Medicine - Progress?FREEAbey K. Thomas, MDAbey K. Thomas, MDUT Southwestern Medical Center, Dallas, Texas (A.K.T.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G20-0003 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: UT Southwestern Medical Center, Dallas, Texas (A.K.T.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G20-0003.Author/Illustrator Information: Abey K. Thomas, MD, is an internal medicine hospitalist and a mentor to medical students at the University of Texas Southwestern Medical Center in Dallas, Texas (e-mail, abeyk.[email protected]edu; Twitter, @abeythomas).This article was published at Annals.org on 8 September 2020. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 September 2020Volume 173, Issue 6Page: W120-W121KeywordsConflicts of interestDisclosureHealth careHospitalists ePublished: 8 September 2020 Issue Published: 15 September 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Personalized cancer therapy prioritization based on driver alteration co-occurrence patterns
Authors: Lidia Mateo, Miquel Duran-Frigola, Albert Gris-Oliver, Marta Palafox, Maurizio Scaltriti, Pedram Razavi, Sarat Chandarlapaty, Joaquin Arribas, Meritxell Bellet, Violeta Serra, Patrick Aloy
Journal: Genome Medicine (2020)

Abstract Identification of actionable genomic vulnerabilities is key to precision oncology. Utilizing a large-scale drug screening in patient-derived xenografts, we uncover driver gene alteration connections, derive driver co-occurrence (DCO) networks, and relate these to drug sensitivity. Our collection of 53 drug-response predictors attains an average balanced accuracy of 58% in a cross-validation setting, rising to 66% for a subset of high-confidence predictions. We experimentally validated 12 out of 14 predictions in mice and adapted our strategy to obtain drug-response models from patients’ progression-free survival data. Our strategy reveals links between oncogenic alterations, increasing the clinical impact of genomic profiling.
Care during covid-19 must be humane and person centred
Authors: Angela Coulter, Tessa Richards
Journal: BMJ (2020)

In recent years, there has been an increasing awareness among physicians of the value of therapeutic interventions in patients suffering from lung cancer and mesothelioma. A search for an optimal approach using surgery, irradiation and chemotherapy in different settings of the tumour disease, including curatively aimed adjuvant chemotherapy after locoregional surgery or radiotherapy, has resulted in gradually improved survival rates. Still, early detection is crucial if there is to be a possibility of curing patients or prolonging life in cases of relapsed disease. Several studies have been initiated in which surrogate markers are evaluated in comparison to chest X-rays and computer tomography. The present review focuses on the predictive and prognostic value of using serological cytokeratins as tumour markers for patients suffering from thoracic malignancies.
TREM-2 defends the liver against hepatocellular carcinoma through multifactorial protective mechanisms
Authors: Aitor Esparza-Baquer, Ibone Labiano, Omar Sharif, Aloña Agirre-Lizaso, Fiona Oakley, Pedro M Rodrigues, Ekaterina Zhuravleva, Colm J O'Rourke, Elizabeth Hijona, Raul Jimenez-Agüero, Ioana Riaño, Ana Landa, Adelaida La Casta, Marco Y W Zaki, Patricia Munoz-Garrido, Mikel Azkargorta, Felix Elortza, Andrea Vogel, Gernot Schabbauer, Patricia Aspichueta, Jesper B Andersen, Sylvia Knapp, Derek A Mann, Luis Bujanda, Jesus Maria Banales, Maria Jesus Perugorria
Journal: Gut (2020)

Objective Hepatocellular carcinoma (HCC) is a prevalent and aggressive cancer usually arising on a background of chronic liver injury involving inflammatory and hepatic regenerative processes. The triggering receptor expressed on myeloid cells 2 (TREM-2) is predominantly expressed in hepatic non-parenchymal cells and inhibits Toll-like receptor signalling, protecting the liver from various hepatotoxic injuries, yet its role in liver cancer is poorly defined. Here, we investigated the impact of TREM-2 on liver regeneration and hepatocarcinogenesis. Design TREM-2 expression was analysed in liver tissues of two independent cohorts of patients with HCC and compared with control liver samples. Experimental HCC and liver regeneration models in wild type and Trem-2 -/- mice, and in vitro studies with hepatic stellate cells (HSCs) and HCC spheroids were conducted. Results TREM-2 expression was upregulated in human HCC tissue, in mouse models of liver regeneration and HCC. Trem-2 -/- mice developed more liver tumours irrespective of size after diethylnitrosamine (DEN) administration, displayed exacerbated liver damage, inflammation, oxidative stress and hepatocyte proliferation. Administering an antioxidant diet blocked DEN-induced hepatocarcinogenesis in both genotypes. Similarly, Trem-2 -/- animals developed more and larger tumours in fibrosis-associated HCC models. Trem-2 -/- livers showed increased hepatocyte proliferation and inflammation after partial hepatectomy. Conditioned media from human HSCs overexpressing TREM-2 inhibited human HCC spheroid growth in vitro through attenuated Wnt ligand secretion. Conclusion TREM-2 plays a protective role in hepatocarcinogenesis via different pleiotropic effects, suggesting that TREM-2 agonism should be investigated as it might beneficially impact HCC pathogenesis in a multifactorial manner.
Association between proton pump inhibitor use and mortality in patients with hepatocellular carcinoma receiving tyrosine kinase inhibitor
Authors: Chun-Ying Wu, Hsiu J Ho, Chen-Yi Wu, Yi-Ju Chen, Teng-Yu Lee, Yao-Chun Hsu, Jaw-Town Lin
Journal: Gut (2020)

We read with great interest the recent work by Xu et al ,1 and Wang et al ,2 on the role of sorafenib in the treatment of hepatocellular carcinoma (HCC). Tyrosine kinase inhibitors (TKIs) are standard therapy for advanced stage HCC.3 However, the effectiveness of TKIs is less than ideal and studies are trying to discover methods to improve their effectiveness.1 2 Most orally administrated TKIs are weak bases and their absorption may be impaired by proton pump inhibitors (PPIs) due to suppression of intragastric acidity.4 5 Concomitant PPI use is found associated with increased overall mortality in patients with lung cancer,6 7 but not known in patients with HCC.

We conducted a nationwide cohort study based on Taiwan’s National Health Insurance Research Database (NHIRD).8 9 In the NHIRD, we identified all hospitalised patients with HCC admitted with a primary diagnosis of HCC (International Classification of Diseases (ICD)-9 code: 155.0 and ICD-10 code: C22) and validated by inclusion in the Registry for Catastrophic …
Human-Gut-DNA Virome Variations across Geography, Ethnicity, and Urbanization
Authors: Tao Zuo, Yang Sun, Yating Wan, Yun Kit Yeoh, Fen Zhang, Chun Pan Cheung, Nan Chen, Juan Luo, Wen Wang, Joseph J.Y. Sung, Paul K.S. Chan, Kunhua Wang, Francis K.L. Chan, Yinglei Miao, Siew C. Ng
Journal: Cell Host & Microbe (2020)
CONVERT - THE CHALLENGES OF OPENING CENTRES AND RECRUITING PATIENTS TO AN INTERNATIONAL MULTI-CENTRE CHEMO-RADIOTHERAPY TRIAL IN LIMITED-STAGE SMALL CELL LUNG CANCER
Authors: Corinne Faivre-Finn, Linda Ashcroft, Andrea Bezjak, Adityanarayan Bhatnagar, Felipe Cardenal, Sally Falk, Pierre Fournel, Nicki Groom, Susan Harden, Cecile Le Pechoux, Paul Lorigan, Rhona Mcmenemin, Nazia Mohammed, Mary O'Brien, Laetitia Padovani, Michael Snee, Veerle F. Surmont, Elena Wilson, Fiona Blackhall
Journal: Journal of Thoracic Oncology (2013)
SP0091 E-selectin deletion constructs allow the study of differential binding of mononuclear and polymorphonuclear leukocytes to e-selectin in inflammation
Authors: R Hallmann, A Krause, M Laschinger, B Engelhardt, RO Hynes, M Hammel
Journal: Annals of the Rheumatic Diseases (2001)

<h3></h3> Endothelial cell activation is an important step in the inflammatory cascade which leads to the extravasation of leukocytes into the site of inflammation. The rolling of leukocytes is the beginning of this cascade and is mediated by the selectins. We have analysed the binding of both polymorphonuclear granulocytes and mononuclear cells to E-selectin presented exclusively by activated vascular endothelial cells. Four different monoclonal antibodies inhibited this adhesion differentially, and deletion constructs of E-selectin expressed on endothelial cells were also functionally distinguishable by their interaction with granulocytes and lymphocytes, respectively. Different binding mechanisms for these leukocyte subsets to endothelial E-selectin are proposed and signalling mechanisms via E-selectin, in particular Ca<sup>2+</sup> signals into the leukocyte will be discussed.
Hepatic insulin-degrading enzyme regulates glucose and insulin homeostasis in diet-induced obese mice
Authors: Beatriz Merino, Cristina M. Fernández-Díaz, Cristina Parrado-Fernández, Carlos M. González-Casimiro, Tamara Postigo-Casado, Carmen D. Lobatón, Malcolm A. Leissring, Irene Cózar-Castellano, Germán Perdomo
Journal: Metabolism (2020)

The insulin-degrading enzyme (IDE) is a metalloendopeptidase with a high affinity for insulin. Human genetic polymorphisms in Ide have been linked to increased risk for T2DM. In mice, hepatic Ide ablation causes glucose intolerance and insulin resistance when mice are fed a regular diet.ObjectiveThese studies were undertaken to further investigate its regulatory role in glucose homeostasis and insulin sensitivity in diet-induced obesity.MethodsTo this end, we have compared the metabolic effects of loss versus gain of IDE function in mice fed a high-fat diet (HFD).ResultsWe demonstrate that loss of IDE function in liver (L-IDE-KO mouse) exacerbates hyperinsulinemia and insulin resistance without changes in insulin clearance but in parallel to an increase in pancreatic β-cell function. Insulin resistance was associated with increased FoxO1 activation and a ~2-fold increase of GLUT2 protein levels in the liver of HFD-fed mice in response to an intraperitoneal injection of insulin. Conversely, gain of IDE function (adenoviral delivery) improves glucose tolerance and insulin sensitivity, in parallel to a reciprocal ~2-fold reduction in hepatic GLUT2 protein levels. Furthermore, in response to insulin, IDE co-immunoprecipitates with the insulin receptor in liver lysates of mice with adenoviral-mediated liver overexpression of IDE.ConclusionsWe conclude that IDE regulates hepatic insulin action and whole-body glucose metabolism in diet-induced obesity via insulin receptor levels.
COVID-19 and pneumothorax: a multicentre retrospective case series
Authors: Anthony W. Martinelli, Tejas Ingle, Joseph Newman, Iftikhar Nadeem, Karl Jackson, Nicholas D. Lane, James Melhorn, Helen E. Davies, Anthony J. Rostron, Aldrin Adeni, Kevin Conroy, Nick Woznitza, Matthew Matson, Simon E. Brill, James Murray, Amar Shah, Revati Naran, Samanjit S. Hare, Oliver Collas, Sarah Bigham, Michael Spiro, Margaret M. Huang, Beenish Iqbal, Sarah Trenfield, Stephane Ledot, Sujal Desai, Lewis Standing, Judith Babar, Razeen Mahroof, Ian Smith, Kai Lee, Nairi Tchrakian, Stephanie Uys, William Ricketts, Anant R.C. Patel, Avinash Aujayeb, Maria Kokosi, Alexander J.K. Wilkinson, Stefan J. Marciniak
Journal: European Respiratory Journal (2020)

Introduction Pneumothorax and pneumomediastinum have both been noted to complicate cases of coronavirus disease 2019 (COVID-19) requiring hospital admission. We report the largest case series yet described of patients with both these pathologies (including nonventilated patients). Methods Cases were collected retrospectively from UK hospitals with inclusion criteria limited to a diagnosis of COVID-19 and the presence of either pneumothorax or pneumomediastinum. Patients included in the study presented between March and June 2020. Details obtained from the medical record included demographics, radiology, laboratory investigations, clinical management and survival. Results 71 patients from 16 centres were included in the study, of whom 60 had pneumothoraces (six with pneumomediastinum in addition) and 11 had pneumomediastinum alone. Two of these patients had two distinct episodes of pneumothorax, occurring bilaterally in sequential fashion, bringing the total number of pneumothoraces included to 62. Clinical scenarios included patients who had presented to hospital with pneumothorax, patients who had developed pneumothorax or pneumomediastinum during their inpatient admission with COVID-19 and patients who developed their complication while intubated and ventilated, either with or without concurrent extracorporeal membrane oxygenation. Survival at 28 days was not significantly different following pneumothorax (63.1±6.5%) or isolated pneumomediastinum (53.0±18.7%; p=0.854). The incidence of pneumothorax was higher in males. 28-day survival was not different between the sexes (males 62.5±7.7% versus females 68.4±10.7%; p=0.619). Patients aged ≥70 years had a significantly lower 28-day survival than younger individuals (≥70 years 41.7±13.5% survival versus &lt;70 years 70.9±6.8% survival; p=0.018 log-rank). Conclusion These cases suggest that pneumothorax is a complication of COVID-19. Pneumothorax does not seem to be an independent marker of poor prognosis and we encourage continuation of active treatment where clinically possible.
Outcomes of Intensive Systolic Blood Pressure Reduction in Patients With Intracerebral Hemorrhage and Excessively High Initial Systolic Blood Pressure
Authors: Adnan I. Qureshi, Wei Huang, Iryna Lobanova, William G. Barsan, Daniel F. Hanley, Chung Y. Hsu, Cheng-Li Lin, Robert Silbergleit, Thorsten Steiner, Jose I. Suarez, Kazunori Toyoda, Haruko Yamamoto
Journal: JAMA Neurology (2020)

The safety and efficacy of intensive systolic blood pressure reduction in patients with intracerebral hemorrhage who present with systolic blood pressure greater than 220 mm Hg appears to be unknown.
INCREASED INNATE AND ADAPTIVE IMMUNE PRESSURE IS RESPONSIBLE FOR THE REDUCED TRANSCRIPTIONAL ACTIVITY OF INTRAHEPATIC COVALENTLY CLOSED CIRCULAR (CCC) DNA THAT OCCURS IN HBEAG-NEGATIVE CHRONIC HEPATITIS B (CHB)
Authors: Alex J Thompson, J Judy Chang, Narelle A Skinner, Sharon Lewin, Kumar Visvanathan, Paul V Desmond, Stephen Locarnini
Journal: Hepatology (2008)