tbuckley/cabot-search huggingface dataset:
Paediatric haemolytic uraemic syndrome related to Shiga toxin-producing Escherichia coli, an overview of 10 years of surveillance in France, 2007 to 2016
Authors: Mathias Bruyand, Patricia Mariani-Kurkdjian, Simon Le Hello, Lisa-A King, Dieter Van Cauteren, Sophie Lefevre, Malika Gouali, Nathalie Jourdan-da Silva, Alexandra Mailles, Marie-Pierre Donguy, Estelle Loukiadis, Delphine Sergentet-Thevenot, Chantal Loirat, Stéphane Bonacorsi, François-Xavier Weill, Henriette De Valk
Journal: Eurosurveillance (2019)

IntroductionHaemolytic uraemic syndrome (HUS) related to Shiga toxin-producing Escherichia coli (STEC) is the leading cause of acute renal failure in young children. In France, HUS surveillance in children aged < 15 years was implemented starting from 1996.AimWe present the results of this surveillance between 2007 and 2016.MethodsA voluntary nationwide network of 32 paediatric departments notifies cases. Two national reference centres perform microbiological STEC confirmation.ResultsOver the study period, the paediatric HUS incidence rate (IR) was 1.0 per 100,000 children-years, with a median of 116 cases/year. In 2011, IR peaked at 1.3 per 100,000 children-years, and decreased to 1.0 per 100,000 children-years in 2016. STEC O157 associated HUS peaked at 37 cases in 2011 and decreased to seven cases in 2016. Cases of STEC O26-associated HUS have increased since 2010 and STEC O80 associated HUS has emerged since 2012, with 28 and 18 cases respectively reported in 2016. Four STEC-HUS food-borne outbreaks were detected (three STEC O157 linked to ground beef and raw-milk cheese and one STEC O104 linked to fenugreek sprouts). In addition, two outbreaks related to person-to-person transmission occurred in distinct kindergartens (STEC O111 and O26).ConclusionsNo major changes in HUS IRs were observed over the study period of 10 years. However, changes in the STEC serogroups over time and the outbreaks detected argue for continuing epidemiological and microbiological surveillance.
The Influence of the Bone Marrow Niche on Drug Response Phenotypes of Blood Cancers
Authors: Sophie Rabe, Eva Schitter, Tobias Roider, Peter-Martin Bruch, Carolin Kolb, Marta Stolarczyk, Jennifer Hüllein, Junyan Lu, Christof von Kalle, Christoph Lutz, Peter Dreger, Carsten Mueller-Tidow, Thorsten Zenz, Wolfgang Huber, Sascha Dietrich
Journal: Blood (2018)
Intravascular Cells and Circulating Microparticles Induce Procoagulant Activity Via Phosphatidylserine Exposure in Venous Thromboembolism and Contribute to Altered Plasma Fibrin Clot Properties
Authors: Yan Kou, Lili Zou, Hui Liang, Li Hou, Tao Li, Yan Zhang, Baorong LI, Yingmiao LIU, Cong Zhang, Ruipeng Liu, Xinyi Zhao, Ying Wang, Jiaqi Jin, Yayan Bi, Jialan Shi, Junjie Kou
Journal: Blood (2018)
Progress Toward Regional Measles Elimination — Worldwide, 2000–2016
Authors: Alya Dabbagh, Minal K. Patel, Laure Dumolard, Marta Gacic-Dobo, Mick N. Mulders, Jean-Marie Okwo-Bele, Katrina Kretsinger, Mark J. Papania, Paul A. Rota, James L. Goodson
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

The fourth United Nations Millennium Development Goal, adopted in 2000, set a target to reduce child mortality by two thirds by 2015. One indicator of progress toward this target was measles vaccination coverage (1). In 2010, the World Health Assembly (WHA) set three milestones for measles control by 2015: 1) increase routine coverage with the first dose of a measles-containing vaccine (MCV1) among children aged 1 year to ≥90% at the national level and to ≥80% in every district; 2) reduce global annual measles incidence to <5 cases per million population; and 3) reduce global measles mortality by 95% from the 2000 estimate (2).* In 2012, WHA endorsed the Global Vaccine Action Plan,† with the objective of eliminating measles in four World Health Organization (WHO) regions by 2015 and in five regions by 2020. Countries in all six WHO regions have adopted goals for measles elimination by or before 2020. Measles elimination is defined as the absence of endemic measles virus transmission in a region or other defined geographic area for ≥12 months, in the presence of a high quality surveillance system that meets targets of key performance indicators. This report updates a previous report (3) and describes progress toward global measles control milestones and regional measles elimination goals during 2000-2016. During this period, annual reported measles incidence decreased 87%, from 145 to 19 cases per million persons, and annual estimated measles deaths decreased 84%, from 550,100 to 89,780; measles vaccination prevented an estimated 20.4 million deaths. However, the 2015 milestones have not yet been met; only one WHO region has been verified as having eliminated measles. Improved implementation of elimination strategies by countries and their partners is needed, with focus on increasing vaccination coverage through substantial and sustained additional investments in health systems, strengthening surveillance systems, using surveillance data to drive programmatic actions, securing political commitment, and raising the visibility of measles elimination goals.
Targeting DNA Damage Response Promotes Antitumor Immunity through STING-Mediated T-cell Activation in Small Cell Lung Cancer
Authors: Triparna Sen, B. Leticia Rodriguez, Limo Chen, Carminia M. Della Corte, Naoto Morikawa, Junya Fujimoto, Sandra Cristea, Thuyen Nguyen, Lixia Diao, Lerong Li, Youhong Fan, Yongbin Yang, Jing Wang, Bonnie S. Glisson, Ignacio I. Wistuba, Julien Sage, John V. Heymach, Don L. Gibbons, Lauren A. Byers
Journal: Cancer Discovery (2019)

Abstract Despite recent advances in the use of immunotherapy, only a minority of patients with small cell lung cancer (SCLC) respond to immune checkpoint blockade (ICB). Here, we show that targeting the DNA damage response (DDR) proteins PARP and checkpoint kinase 1 (CHK1) significantly increased protein and surface expression of PD-L1. PARP or CHK1 inhibition remarkably potentiated the antitumor effect of PD-L1 blockade and augmented cytotoxic T-cell infiltration in multiple immunocompetent SCLC in vivo models. CD8+ T-cell depletion reversed the antitumor effect, demonstrating the role of CD8+ T cells in combined DDR–PD-L1 blockade in SCLC. We further demonstrate that DDR inhibition activated the STING/TBK1/IRF3 innate immune pathway, leading to increased levels of chemokines such as CXCL10 and CCL5 that induced activation and function of cytotoxic T lymphocytes. Knockdown of cGAS and STING successfully reversed the antitumor effect of combined inhibition of DDR and PD-L1. Our results define previously unrecognized innate immune pathway–mediated immunomodulatory functions of DDR proteins and provide a rationale for combining PARP/CHK1 inhibitors and immunotherapies in SCLC. Significance: Our results define previously unrecognized immunomodulatory functions of DDR inhibitors and suggest that adding PARP or CHK1 inhibitors to ICB may enhance treatment efficacy in patients with SCLC. Furthermore, our study supports a role of innate immune STING pathway in DDR-mediated antitumor immunity in SCLC. See related commentary by Hiatt and MacPherson, p. 584. This article is highlighted in the In This Issue feature, p. 565
Pre-hospital advanced airway management for adults with out-of-hospital cardiac arrest: nationwide cohort study
Authors: Junichi Izawa, Sho Komukai, Koichiro Gibo, Masashi Okubo, Kosuke Kiyohara, Chika Nishiyama, Takeyuki Kiguchi, Tasuku Matsuyama, Takashi Kawamura, Taku Iwami, Clifton W Callaway, Tetsuhisa Kitamura
Journal: BMJ (2019)

To determine survival associated with advanced airway management (AAM) compared with no AAM for adults with out-of-hospital cardiac arrest.Cohort study between January 2014 and December 2016.Nationwide, population based registry in Japan (All-Japan Utstein Registry).Consecutive adult patients with out-of-hospital cardiac arrest, separated into two sub-cohorts by their first documented electrocardiographic rhythm: shockable (ventricular fibrillation or pulseless ventricular tachycardia) and non-shockable (pulseless electrical activity or asystole). Patients who received AAM during cardiopulmonary resuscitation were sequentially matched with patients at risk of AAM within the same minute on the basis of time dependent propensity scores.Survival at one month or at hospital discharge within one month.Of the 310 620 patients eligible, 8459 (41.2%) of 20 516 in the shockable cohort and 121 890 (42.0%) of 290 104 in the non-shockable cohort received AAM during cardiopulmonary resuscitation. After time dependent propensity score sequential matching, 16 114 patients in the shockable cohort and 236 042 in the non-shockable cohort were matched at the same minute. In the shockable cohort, survival did not differ between patients with AAM and those with no AAM: 1546/8057 (19.2%) versus 1500/8057 (18.6%) (adjusted risk ratio 1.00, 95% confidence interval 0.93 to 1.07). In the non-shockable cohort, patients with AAM had better survival than those with no AAM: 2696/118 021 (2.3%) versus 2127/118 021 (1.8%) (adjusted risk ratio 1.27, 1.20 to 1.35).In the time dependent propensity score sequential matching for out-of-hospital cardiac arrest in adults, AAM was not associated with survival among patients with shockable rhythm, whereas AAM was associated with better survival among patients with non-shockable rhythm.
A C-X-C Chemokine Receptor Type 2–Dominated Cross-talk between Tumor Cells and Macrophages Drives Gastric Cancer Metastasis
Authors: Zhijun Zhou, Guanggai Xia, Zhen Xiang, Mingyang Liu, Zhewei Wei, Jie Yan, Wei Chen, Jintao Zhu, Niranjan Awasthi, Xiaotian Sun, Kar-Ming Fung, Yulong He, Min Li, Changhua Zhang
Journal: Clinical Cancer Research (2019)

Abstract Purpose: C-X-C chemokine receptor type 2 (CXCR2) is a key regulator that drives immune suppression and inflammation in tumor microenvironment. CXCR2-targeted therapy has shown promising results in several solid tumors. However, the underlying mechanism of CXCR2-mediated cross-talk between gastric cancer cells and macrophages still remains unclear. Experimental Design: The expression of CXCR2 and its ligands in 155 human gastric cancer tissues was analyzed via immunohistochemistry, and the correlations with clinical characteristics were evaluated. A coculture system was established, and functional assays, including ELISA, transwell, cell viability assay, and qPCR, were performed to determine the role of the CXCR2 signaling axis in promoting gastric cancer growth and metastasis. A xenograft gastric cancer model and a lymph node metastasis model were established to study the function of CXCR2 in vivo. Results: CXCR2 expression is associated with the prognosis of patients with gastric cancer (P = 0.002). Of all the CXCR2 ligands, CXCL1 and CXCL5 can significantly promote migration of gastric cancer cells. Macrophages are the major sources of CXCL1 and CXCL5 in the gastric cancer microenvironment, and promote migration of gastric cancer cells through activating a CXCR2/STAT3 feed-forward loop. Gastric cancer cells secrete TNF-α to induce release of CXCL1 and CXCL5 from macrophages. Inhibiting CXCR2 pathway of gastric cancer cells can suppress migration and metastasis of gastric cancer in vitro and in vivo. Conclusions: Our study suggested a previously uncharacterized mechanism through which gastric cancer cells interact with macrophages to promote tumor growth and metastasis, suggesting that CXCR2 may serve as a promising therapeutic target to treat gastric cancer.
P054 IRF-1 is critical for the TNF-driven interferon response in rheumatoid fibroblast-like synoviocytes
Authors: M Bonelli, K Dalwigk, A Platzer, I Calvo, S Hayer, B Niederreiter, J Holinka, F Sevelda, T Pap, G Steiner, G Superti-Furga, J Smolen, H Kiener, T Karonitsch
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Young investigator. <h3>Introduction</h3> Rheumatoid arthritis (RA) is an autoimmune disease, which is characterized by persistent, synovial inflammation. Major drivers of synovial inflammation are cytokines and chemokines. Among them TNF activates fibroblast-like synoviocytes (FLS), which leads to the production of inflammatory mediators. The pathways and transcription factors that determine the inflammatory response in FLS are largely unexplored. Here, we investigated the potential contribution of the transcription-factor IRF1 to the inflammatory gene expression in FLS. <h3>Methods</h3> Expression of IRF1 in synovial tissues was assessed by immunohistochemistry (IHC). RA-FLS were isolated according to established protocols and cultured using 2-D or 3-D culture techniques. IRF1 expression in response to TNF was determined by western blots, qPCR or IHC. FLS were also stimulated with TNF in the presence or absence of IRF1 siRNA pools. Global changes of mRNA expression were assessed by RNA-sequencing. Janus kinase activity was blocked by baricitinib or tofacitinib. <h3>Results</h3> Our data reveal that TNF regulates the expression of IRF1 in human FLS as well as in the huTNFtg mouse model of arthritis. Transcriptomic analyses of IRF-1-deficient TNF-stimulated FLS define the interferon (IFN) pathway as a major target of IRF-1. Further experiments show that TNF-induced IRF-1 expression promotes the expression of IFN-β, which leads to an activation of the JAK-STAT pathway. Blockade of the JAK-STAT pathway, by the Janus kinase inhibitors baricitinib or tofacitinib, reduces the expression of IFN-regulated genes (IRGs), such as CXCL9, CXCL10, CXCL11 and TNFSF13B, in TNF-activated FLS. <h3>Conclusions</h3> Our data reveal that IRF1 is crucial for the IFN-response of FLS and support the idea that IRF1 plays a critical role for the development of synovial inflammation. <h3>Disclosure of Interest</h3> None declared.
Association of Out-of-Pocket Health Care Costs and Financial Burden for Patients With Alopecia Areata
Authors: Sara Jiayang Li, Arash Mostaghimi, Elizabeth Tkachenko, Kathie P. Huang
Journal: JAMA Dermatology (2019)

This survey study examines responses from 675 individuals with alopecia areata and analyzes the out-of-pocket financial burden for this patient population.
Glucocorticoids Regulate Bone Marrow B Lymphopoiesis After Stroke
Authors: Gabriel Courties, Vanessa Frodermann, Lisa Honold, Yi Zheng, Fanny Herisson, Maximilian J. Schloss, Yuan Sun, Jessy Presumey, Nicolas Severe, Camilla Engblom, Maarten Hulsmans, Sebastian Cremer, David Rohde, Mikael J. Pittet, David T. Scadden, Filip K. Swirski, Dong-Eog Kim, Michael A. Moskowitz, Matthias Nahrendorf
Journal: Circulation Research (2019)

After a stroke, patients frequently experience altered systemic immunity resulting in peripheral immunosuppression and higher susceptibility to infections, which is at least partly attributed to lymphopenia. The mechanisms that profoundly change the systemic leukocyte repertoire after stroke are incompletely understood. Emerging evidence indicates that stroke alters hematopoietic output of the bone marrow.To explore the mechanisms that lead to defects of B lymphopoiesis after ischemic stroke.We here report that ischemic stroke triggers brain-bone marrow communication via hormonal long-range signals that regulate hematopoietic B lineage decisions. Bone marrow fluorescence-activated cell sorter analyses and serial intravital microscopy indicate that transient middle cerebral artery occlusion in mice arrests B-cell development beginning at the pro-B-cell stage. This phenotype was not rescued in Myd88-/- and TLR4-/- mice with disrupted TLR (Toll-like receptor) signaling or after blockage of peripheral sympathetic nerves. Mechanistically, we identified stroke-induced glucocorticoid release as the main instigator of B lymphopoiesis defects. B-cell lineage-specific deletion of the GR (glucocorticoid receptor) in CD19-Cre loxP Nr3c1 mice attenuated lymphocytopenia after transient middle cerebral artery. In 20 patients with acute stroke, increased cortisol levels inversely correlated with blood lymphocyte numbers.Our data demonstrate that the hypothalamic-pituitary-adrenal axis mediates B lymphopoiesis defects after ischemic stroke.
Long-term Follow-up of Antibiotics vs Surgery for Appendicitis
Authors: Nicholas L. Syn
Journal: JAMA (2019)

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Systematic Review and Meta-Analysis of the Magnitude of Structural, Clinical, and Physician and Patient Barriers to Cancer Clinical Trial Participation
Authors: Joseph M Unger, Riha Vaidya, Dawn L Hershman, Lori M Minasian, Mark E Fleury
Journal: JNCI Journal of the National Cancer Institute (2018)

Barriers to cancer clinical trial participation have been the subject of frequent study, but the rate of trial participation has not changed substantially over time. Studies often emphasize patient-related barriers, but other types of barriers may have greater impact on trial participation. Our goal was to examine the magnitude of different domains of trial barriers by synthesizing prior research.We conducted a systematic review and meta-analysis of studies that examined the trial decision-making pathway using a uniform framework to characterize and quantify structural (trial availability), clinical (eligibility), and patient/physician barrier domains. The systematic review utilized the PubMed, Google Scholar, Web of Science, and Ovid Medline search engines. We used random effects to estimate rates of different domains across studies, adjusting for academic vs community care settings.We identified 13 studies (nine in academic and four in community settings) with 8883 patients. A trial was unavailable for patients at their institution 55.6% of the time (95% confidence interval [CI] = 43.7% to 67.3%). Further, 21.5% (95% CI = 10.9% to 34.6%) of patients were ineligible for an available trial, 14.8% (95% CI = 9.0% to 21.7%) did not enroll, and 8.1% (95% CI = 6.3% to 10.0%) enrolled. Rates of trial enrollment in academic (15.9% [95% CI = 13.8% to 18.2%]) vs community (7.0% [95% CI = 5.1% to 9.1%]) settings differed, but not rates of trial unavailability, ineligibility, or non-enrollment.These findings emphasize the enormous need to address structural and clinical barriers to trial participation, which combined make trial participation unachievable for more than three of four cancer patients.
AB0089 Histopathological change caused by biological treatment in rheumatoid arthritis synovial tissue
Authors: A. Kubota, T. Suguro, A. Nakajima, S. Masayuki, S. Masato, T. Kentaro, T. Kazuaki
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Multiple studies addressing the effects of biologics on the synovial tissue in rheumatoid arthritis (RA) patients have been reported. There are, however, few studies comparing histopathological changes in the synovial tissue in the same RA patients between before and after biologics treatment. <h3>Objectives</h3> We examined biologics impacts on RA synovial tissues based on pathological findings in them collected during surgeries for the same patient before and after biological drug usage. <h3>Methods</h3> Synovial tissues were collected from 34 RA joints before and after biologics. The average age and disease duration of the study subjects were 64.0 and 22.5, respectively. Synovial tissues were evaluated by hematoxylin. Histopathological changes in the synovial tissues were compared based on Rooney's score, and presence or absence of fibrinoid degeneration and proliferation of villi in the subsynovial tissue. We examined correlation between pathological findings in RA synovium and disease activity under biologics. Disease activity was assessed by CDAI. We examined the Histopathological changes in the Remission, Low disease activity group (RL group) and Moderate disease activity (M group). Etanercept, Infliximab, Tocilizumab, Adalimumab and Abatacept was used as biological drug for 18, 6, 5, 3 and 2 joints respectively. <h3>Results</h3> Rooney score between before and after biological usage improved from 28.4 to 12.0 showing significant difference. Significant improvement in Rooney score was observed in all items. Fibrinoid degeneration was observed in 29 cases (85.3%) and 6 cases (17.6%) before and after biologics treatment, respectively, demonstrating a significant reduction with biologics treatment. Proliferation of villi was observed in 32 cases (94.1%) and 11 (32.4%) before and after biologics treatment, respectively, demonstrating a significant reduction with biologics treatment. After biologics treatment, Rooney's score in RL group and M group were 10.4 and 15.3, respectively, showing a statistically significant difference. In addition, the M group had significantly higher scores in lymphoid follicle and lymphocyte infiltration compared to the RL group. <h3>Conclusions</h3> The study results demonstrated that biologics treatment significantly ameliorated inflammatory changes in the synovial lining layers and sublining layers. In addition, the results suggested that histopathological findings in the sublining layers reflected disease activity. <h3>Disclosure of Interest</h3> None declared
Author Correction: The copy number variation landscape of congenital anomalies of the kidney and urinary tract
Authors: Miguel Verbitsky, Rik Westland, Alejandra Perez, Krzysztof Kiryluk, Qingxue Liu, Priya Krithivasan, Adele Mitrotti, David A. Fasel, Ekaterina Batourina, Matthew G. Sampson, Monica Bodria, Max Werth, Charlly Kao, Jeremiah Martino, Valentina P. Capone, Asaf Vivante, Shirlee Shril, Byum Hee Kil, Maddalena Marasa, Jun Y. Zhang, Young-Ji Na, Tze Y. Lim, Dina Ahram, Patricia L. Weng, Erin L. Heinzen, Alba Carrea, Giorgio Piaggio, Loreto Gesualdo, Valeria Manca, Giuseppe Masnata, Maddalena Gigante, Daniele Cusi, Claudia Izzi, Francesco Scolari, Joanna A. E. van Wijk, Marijan Saraga, Domenico Santoro, Giovanni Conti, Pasquale Zamboli, Hope White, Dorota Drozdz, Katarzyna Zachwieja, Monika Miklaszewska, Marcin Tkaczyk, Daria Tomczyk, Anna Krakowska, Przemyslaw Sikora, Tomasz Jarmoliński, Maria K. Borszewska-Kornacka, Robert Pawluch, Maria Szczepanska, Piotr Adamczyk, Malgorzata Mizerska-Wasiak, Grazyna Krzemien, Agnieszka Szmigielska, Marcin Zaniew, Mark G. Dobson, John M. Darlow, Prem Puri, David E. Barton, Susan L. Furth, Bradley A. Warady, Zoran Gucev, Vladimir J. Lozanovski, Velibor Tasic, Isabella Pisani, Landino Allegri, Lida M. Rodas, Josep M. Campistol, Cécile Jeanpierre, Shumyle Alam, Pasquale Casale, Craig S. Wong, Fangming Lin, Débora M. Miranda, Eduardo A. Oliveira, Ana Cristina Simoes-e-Silva, Jonathan M. Barasch, Brynn Levy, Nan Wu, Friedhelm Hildebrandt, Gian Marco Ghiggeri, Anna Latos-Bielenska, Anna Materna-Kiryluk, Feng Zhang, Hakon Hakonarson, Virginia E. Papaioannou, Cathy L. Mendelsohn, Ali G. Gharavi, Simone Sanna-Cherchi
Journal: Nature Genetics (2019)