tbuckley/cabot-search huggingface dataset:
Glutamate triggers the expression of functional ionotropic and metabotropic glutamate receptors in mast cells
Authors: Md Abdul Alim, Mirjana Grujic, Paul W. Ackerman, Per Kristiansson, Pernilla Eliasson, Magnus Peterson, Gunnar Pejler
Journal: Cellular and Molecular Immunology (2020)

Mast cells are emerging as players in the communication between peripheral nerve endings and cells of the immune system. However, it is not clear the mechanism by which mast cells communicate with peripheral nerves. We previously found that mast cells located within healing tendons can express glutamate receptors, raising the possibility that mast cells may be sensitive to glutamate signaling. To evaluate this hypothesis, we stimulated primary mast cells with glutamate and showed that glutamate induced the profound upregulation of a panel of glutamate receptors of both the ionotropic type (NMDAR1, NMDAR2A, and NMDAR2B) and the metabotropic type (mGluR2 and mGluR7) at both the mRNA and protein levels. The binding of glutamate to glutamate receptors on the mast cell surface was confirmed. Further, glutamate had extensive effects on gene expression in the mast cells, including the upregulation of pro-inflammatory components such as IL-6 and CCL2. Glutamate also induced the upregulation of transcription factors, including Egr2, Egr3 and, in particular, FosB. The extensive induction of FosB was confirmed by immunofluorescence assessment. Glutamate receptor antagonists abrogated the responses of the mast cells to glutamate, supporting the supposition of a functional glutamate-glutamate receptor axis in mast cells. Finally, we provide in vivo evidence supporting a functional glutamate-glutamate receptor axis in the mast cells of injured tendons. Together, these findings establish glutamate as an effector of mast cell function, thereby introducing a novel principle for how cells in the immune system can communicate with nerve cells.
Tandem CTCF sites function as insulators to balance spatial chromatin contacts and topological enhancer-promoter selection
Authors: Zhilian Jia, Jingwei Li, Xiao Ge, Yonghu Wu, Ya Guo, Qiang Wu
Journal: Genome biology (2020)

Abstract Background CTCF is a key insulator-binding protein, and mammalian genomes contain numerous CTCF sites, many of which are organized in tandem. Results Using CRISPR DNA-fragment editing, in conjunction with chromosome conformation capture, we find that CTCF sites, if located between enhancers and promoters in the protocadherin ( Pcdh ) and β-globin clusters, function as an enhancer-blocking insulator by forming distinct directional chromatin loops, regardless whether enhancers contain CTCF sites or not. Moreover, computational simulation in silico and genetic deletions in vivo as well as dCas9 blocking in vitro revealed balanced promoter usage in cell populations and stochastic monoallelic expression in single cells by large arrays of tandem CTCF sites in the Pcdh and immunoglobulin heavy chain ( Igh ) clusters. Furthermore, CTCF insulators promote, counter-intuitively, long-range chromatin interactions with distal directional CTCF sites, consistent with the cohesin “loop extrusion” model. Finally, gene expression levels are negatively correlated with CTCF insulators located between enhancers and promoters on a genome-wide scale. Thus, single CTCF insulators ensure proper enhancer insulation and promoter activation while tandem CTCF topological insulators determine balanced spatial contacts and promoter choice. Conclusions These findings have interesting implications on the role of topological chromatin insulators in 3D genome folding and developmental gene regulation.
Surgery versus combined treatment with curettage and imiquimod for nodular basal cell carcinoma: One-year results of a noninferiority, randomized, controlled trial
Authors: Kelly A.E. Sinx, Patty J. Nelemans, Nicole W.J. Kelleners-Smeets, Veronique J.L. Winnepenninckx, Aimee H.M.M. Arits, Klara Mosterd
Journal: Journal of the American Academy of Dermatology (2020)
Rho-a and Rac-1 GTPases Play Major and Differential Roles in SDF1α- Induced Cell Adhesion and Chemotaxis in Multiple Myeloma.
Authors: Abdel kareem Azab, Feda Azab, Costas M Pitsillides, Hai T. Ngo, Xiaoying Jia, Molly R. Melhem, Judith Runnels, Aldo M. Roccaro, Antonio Sacco, Nicholas Burwick, Charles P Lin, Kenneth C Anderson, Irene M. Ghobrial
Journal: Blood (2008)
Assessment of Acute Hospital Use and Transfers for Management of Pediatric Seizures
Authors: Urbano L. França, Michael L. McManus
Journal: JAMA Network Open (2020)

<h3>Importance</h3> The availability of pediatric hospital care for common conditions is decreasing across the US. The consequences of this decrease on access to care for specific conditions need to be evaluated. <h3>Objective</h3> To evaluate the degree of regionalization of pediatric seizure care in the US by characterizing the activity of hospital systems in 6 diverse states. <h3>Design, Setting, and Participants</h3> This retrospective cross-sectional study used inpatient and emergency department administrative data sets from all acute care hospitals in Arkansas, Florida, Kentucky, Maryland, Massachusetts, and New York from 2014. All patients younger than 18 years who visited a hospital and had a primary diagnosis of seizures were included. Data were analyzed between January and June 2019. <h3>Main Outcomes and Measures</h3> Characteristics of hospital encounters and pediatric Hospital Capability Index scores of transferring and admitting hospitals. <h3>Results</h3> Among 57 930 encounters with pediatric patients with seizures (median [range] age, 4 [1-11] years; 31 968 [55.2%] boys) identified in 621 acute care hospitals, 15 467 patients (26.7%) were admitted as inpatients and 3748 patients (6.5%) were transferred between acute care hospitals. Among encounters that resulted in transfers between hospitals, seizure was the only diagnosis in 1554 patients (41.5%). A total of 42 463 encounters began as emergency department visits, of which 38 173 encounters (90.0%) resulted in routine discharge. While 536 hospitals (86.3%) transferred children with seizures, only 232 hospitals (37.4%) ever admitted them and only 63 hospitals (10.1%) ever received a pediatric seizure transfer. The median (interquartile range) pediatric Hospital Capability Index score of all hospitals was 0.10 (0.02-0.28), while that of hospitals occasionally admitting pediatric seizure patients was 0.34 (0.22-0.55). However, although most patients who were admitted had brief stays (ie, ≤2 days) and no comorbidities, three-quarters of all admissions (12 002 admissions [77.6%]) were to very highly capable centers (ie, hospitals with pediatric Hospital Capability Index scores &gt;0.75). Across all states, the number of referral hospitals for pediatric seizures was less than the number of Dartmouth Atlas Hospital Referral Regions (47 referral hospitals vs 63 hospital referral regions). <h3>Conclusions and Relevance</h3> These findings suggest that although children with seizures are seen in almost all acute care hospital emergency departments, most hospitals transfer children who require admission. Condition-specific interhospital dependency challenges standard definitions of network adequacy and should be accounted for in emergency medical service planning, access to care policies, and health services research.
Mental health effects of school closures during COVID-19
Authors: Joyce Lee
Journal: The Lancet Child & Adolescent Health (2020)

The coronavirus disease 2019 (COVID-19) pandemic—and the social distancing measures that many countries have implemented—have caused disruptions to daily routines. As of April 8, 2020, schools have been suspended nationwide in 188 countries, according to UNESCO. Over 90% of enrolled learners (1·5 billion young people) worldwide are now out of education. The UNESCO Director-General Audrey Azoulay warned that "the global scale and speed of the current educational disruption is unparalleled".
In screen-detected type 2 diabetes, intensive therapy did not differ from usual care for CV events at 10 years
Authors: Michael Tanner
Journal: Annals of Internal Medicine (2020)

Source Citation Griffin SJ, Rutten GEHM, Khunti K, et al. Long-term effects of intensive multifactorial therapy in individuals with screen-detected type 2 diabetes in primary care: 10-year follow-up of the ADDITION-Europe cluster-randomised trial. Lancet Diabetes Endocrinol. 2019;7:925-37. 31748169
<i>QuickStats:</i> Percentage* of Adults Aged ≥18 Years Who Did Not Take Their Medication as Prescribed or Asked for Lower-Cost Medication to Save Money Among Those Prescribed Medication in the Past 12 Months,† by Number of Chronic Conditions§ — National Health Interview Survey, 2018¶
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

¶ 0 10 20 30 100 Did not take medication as prescribed Asked doctor for a lower cost medication Percentage Overall No chronic conditions 1-2 chronic conditions ≥3 chronic conditions * With 95% confidence intervals indicated by error bars.† Based on the following questions asked of adults prescribed medication in the past 12 months: During the past 12 months, were any of the following true for you? 1) You skipped medication doses to save money, 2) You took less medication to save money, 3) You delayed filling a prescription to save money, or 4) You asked your doctor for a lower-cost medication to save money.The category "Did not take medication as prescribed" includes adults who skipped medication doses, took less medication, or delayed filling a prescription.§ The number of chronic conditions is based on reporting ever being diagnosed with: hypertension, coronary heart disease, stroke, diabetes, cancer, arthritis, hepatitis, chronic obstructive pulmonary disease (COPD) or asthma, or reporting weak or failing kidneys in the past 12 months.COPD was defined as ever having COPD or emphysema or having chronic bronchitis during the past 12 months.¶ Estimates are based on household interviews of a sample of the civilian, noninstitutionalized, U.S. population and are derived from the National Health Interview Survey Sample Adult component.In 2018, among adults aged ≥18 years who were prescribed medication in the past 12 months, the percentage who did not take their medication as prescribed to save money increased with the number of reported chronic conditions, from 6.2% with no chronic conditions to 9.1% with 1-2 chronic conditions and 14.0% with ≥3 chronic conditions.The percentage who asked their doctor for a lower-cost medication also increased with the number of reported chronic conditions from 15.1% among those with no chronic conditions to 18.4% among those with 1-2 chronic conditions and 27.4% among those with ≥3 chronic conditions.
Cxcl10+ monocytes define a pathogenic subset in the central nervous system during autoimmune neuroinflammation
Authors: Amir Giladi, Lisa Katharina Wagner, Hanjie Li, Dorothea Dörr, Chiara Medaglia, Franziska Paul, Anat Shemer, Steffen Jung, Simon Yona, Matthias Mack, Achim Leutz, Ido Amit, Alexander Mildner
Journal: Nature Immunology (2020)
Presence of VEGF-R3 in the serum of metastatic malignant melanoma patients: Relationship with clinicobiological parameters
Authors: R. Mouawad, J. Meric, J. Spano, D. Khayat, G. Auclerc, O. Rixe, C. Soubrane
Journal: Journal of Clinical Oncology (2006)

18004 Background: The presence of metastases is a strong indicator of poor survival in many types of cancer. It has recently been shown that vascular endothelial growth factor-C (VEGF-C), and its receptor Flt-4 (VEGF-R3) are increased in a variety of tumours and may play a pivotal role in the promotion of metastasis. We previously demonstrated that high soluble VEGF-C level was correlated to high tumor burden. Objectives: This study was designed to i) detect and evaluate whether soluble VEGF-R3 play a role in metastatic malignant melanoma patients ii) to determine if they have any relationship with clinicobiological parameters, clinical response and survivals. Methods: Using a sensitive enzyme-linked immunosorbent assays, VEGF-R3 was retrospectively measured in sera of 60 patients with a fully documented history of melanoma disease in comparison with 30 healthy controls. Disease free survival (DFS) and overall survival (OS) were calculated from the beginning of treatment until either the progression (DFS) or death (OS) and analyzed using the Kaplan-Meier method. Results: Pretreatment circulating VEGF-R3 was detectable in all samples from either melanoma patients or healthy donors. Furthermore, median level of sVEGF-R3 was significantly higher (p = 0.000015) in melanoma patients as compared to healthy donors. (38890 vs 30773 pg/ml respectively). No significant association was noted between sVEGF-R3 levels and gender, age or LDH level. Median serum VEGF-R3 level was significantly higher in patients with high tumor burden as compared to patients with low tumor burden (p = 0.045). The pretreatment sVEGF-R3 level was significantly different (p = 0.025) between responder (n = 27) and non-responding patients (n = 33). Lastly, the relapse-free survival was higher in the group with low sVEGF-R3 concentration compared to the high one’s (14.1 vs 11,9 months) as well as for OS (14.3 Vs 12.6 months) but theses differences were not significant (χ 2 = 2,30, p = 0.12 &amp; χ 2 = 0.74, p = 0.37 respectively). Conclusion: these results suggest that high pretreatment sVEGF-R3 level is related to bad prognosis in melanoma patients. No significant financial relationships to disclose.
Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area
Authors: Safiya Richardson, Jamie S. Hirsch, Mangala Narasimhan, James M. Crawford, Thomas McGinn, Karina W. Davidson, Douglas P. Barnaby, Lance B. Becker, John D. Chelico, Stuart L. Cohen, Jennifer Cookingham, Kevin Coppa, Michael A. Diefenbach, Andrew J. Dominello, Joan Duer-Hefele, Louise Falzon, Jordan Gitlin, Negin Hajizadeh, Tiffany G. Harvin, David A. Hirschwerk, Eun Ji Kim, Zachary M. Kozel, Lyndonna M. Marrast, Jazmin N. Mogavero, Gabrielle A. Osorio, Michael Qiu, Theodoros P. Zanos
Journal: JAMA (2020)

There is limited information describing the presenting characteristics and outcomes of US patients requiring hospitalization for coronavirus disease 2019 (COVID-19).To describe the clinical characteristics and outcomes of patients with COVID-19 hospitalized in a US health care system.Case series of patients with COVID-19 admitted to 12 hospitals in New York City, Long Island, and Westchester County, New York, within the Northwell Health system. The study included all sequentially hospitalized patients between March 1, 2020, and April 4, 2020, inclusive of these dates.Confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by positive result on polymerase chain reaction testing of a nasopharyngeal sample among patients requiring admission.Clinical outcomes during hospitalization, such as invasive mechanical ventilation, kidney replacement therapy, and death. Demographics, baseline comorbidities, presenting vital signs, and test results were also collected.A total of 5700 patients were included (median age, 63 years [interquartile range {IQR}, 52-75; range, 0-107 years]; 39.7% female). The most common comorbidities were hypertension (3026; 56.6%), obesity (1737; 41.7%), and diabetes (1808; 33.8%). At triage, 30.7% of patients were febrile, 17.3% had a respiratory rate greater than 24 breaths/min, and 27.8% received supplemental oxygen. The rate of respiratory virus co-infection was 2.1%. Outcomes were assessed for 2634 patients who were discharged or had died at the study end point. During hospitalization, 373 patients (14.2%) (median age, 68 years [IQR, 56-78]; 33.5% female) were treated in the intensive care unit care, 320 (12.2%) received invasive mechanical ventilation, 81 (3.2%) were treated with kidney replacement therapy, and 553 (21%) died. As of April 4, 2020, for patients requiring mechanical ventilation (n = 1151, 20.2%), 38 (3.3%) were discharged alive, 282 (24.5%) died, and 831 (72.2%) remained in hospital. The median postdischarge follow-up time was 4.4 days (IQR, 2.2-9.3). A total of 45 patients (2.2%) were readmitted during the study period. The median time to readmission was 3 days (IQR, 1.0-4.5) for readmitted patients. Among the 3066 patients who remained hospitalized at the final study follow-up date (median age, 65 years [IQR, 54-75]), the median follow-up at time of censoring was 4.5 days (IQR, 2.4-8.1).This case series provides characteristics and early outcomes of sequentially hospitalized patients with confirmed COVID-19 in the New York City area.
Abstract A07: The involvement of a type VII secretion system in the interactions between <i>Streptococcus gallolyticus subspecies gallolyticus</i> and colorectal cancer
Authors: John Culver Taylor, Jacob Rutherford, Maria Nunez, Yi Xu
Journal: Cancer Research (2020)

Abstract Colorectal cancer (CRC) is the 2nd-3rd most common cancer worldwide and is a leading cause of cancer-related death. Increasing evidence suggests that the gut microbiome plays an important role in the development of CRC. One such organism of the gut microbiome that plays an important role in CRC is Streptococcus gallolyticus subspecies gallolyticus (Sgg). Previously, we reported that Sgg stimulates CRC cell proliferation in a β-catenin dependent manner. Using an azoxymethane-induced mouse model of CRC, we have also shown that Sgg-treated mice had significantly higher tumor burden in the colon compared to mice treated with saline or negative control bacteria, suggesting that Sgg actively promotes the development of CRC. The mechanism underlying Sgg’s role in CRC development, however, has yet to be elucidated. The type VII secretion system (T7SS), also called the Esx secretion system, is a specialized secretion system found primarily in Firmicutes and Actinobacteria and has been shown to play an important role in virulence in Staphylococcus aureus and Mycobacterium tuberculosis. Here, we examined the genome of Sgg and found that it encodes a putative T7SS (SggT7SS) highly similar to the T7SS in S. aureus with respect to sequence identity and gene organization. We further showed that the SggT7SS is functional. To investigate if the SggT7SS is involved in the connection between Sgg and CRC, we generated an Sgg mutant lacking the core components of the T7SS secretion machinery. Functional characterization of the mutant indicates that SggT7SS is intimately involved in the interactions between Sgg and CRC cells. Taken together, our results suggest that a T7SS system may be important in inducing specific host responses to Sgg in the context of CRC. Studies to further elucidate the activities of T7SS and its role in Sgg’s contribution to CRC are currently under way. Citation Format: John Culver Taylor, Jacob Rutherford, Maria Nunez, Yi Xu. The involvement of a type VII secretion system in the interactions between Streptococcus gallolyticus subspecies gallolyticus and colorectal cancer [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr A07.
Telomerase Reverse Transcriptase Promoter Mutations Identify a Genomically Defined and Highly Aggressive Human Pleural Mesothelioma Subgroup
Authors: Christine Pirker, Agnes Bilecz, Michael Grusch, Thomas Mohr, Barbara Heidenreich, Viktoria Laszlo, Paul Stockhammer, Daniela Lötsch-Gojo, Johannes Gojo, Lisa Gabler, Sabine Spiegl-Kreinecker, Balazs Dome, Ariane Steindl, Thomas Klikovits, Mir Alireza Hoda, Marko Jakopovic, Miroslav Samarzija, Katja Mohorcic, Izidor Kern, Barbara Kiesel, Luka Brcic, Felicitas Oberndorfer, Leonhard Müllauer, Walter Klepetko, Wolfgang M. Schmidt, Rajiv Kumar, Balazs Hegedus, Walter Berger
Journal: Clinical Cancer Research (2020)

Human malignant pleural mesothelioma (MPM) is characterized by dismal prognosis. Consequently, dissection of molecular mechanisms driving malignancy is of key importance. Here we investigate whether activating mutations in the telomerase reverse transcriptase (
Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzumab for treatment-naive chronic lymphocytic leukaemia (ELEVATE-TN): a randomised, controlled, phase 3 trial
Authors: Jeff P Sharman, Miklos Egyed, Wojciech Jurczak, Alan Skarbnik, John M Pagel, Ian W Flinn, Manali Kamdar, Talha Munir, Renata Walewska, Gillian Corbett, Laura Maria Fogliatto, Yair Herishanu, Versha Banerji, Steven Coutre, George Follows, Patricia Walker, Karin Karlsson, Paolo Ghia, Ann Janssens, Florence Cymbalista, Jennifer A Woyach, Gilles Salles, William G Wierda, Raquel Izumi, Veerendra Munugalavadla, Priti Patel, Min Hui Wang, Sofia Wong, John C Byrd
Journal: The Lancet (2020)
Ebola virus glycoprotein stimulates IL-18–dependent natural killer cell responses
Authors: Helen R. Wagstaffe, Elizabeth A. Clutterbuck, Viki Bockstal, Jeroen N. Stoop, Kerstin Luhn, Macaya Douoguih, Georgi Shukarev, Matthew D. Snape, Andrew J. Pollard, Eleanor M. Riley, Martin R. Goodier
Journal: Journal of Clinical Investigation (2020)

BACKGROUND. NK cells are activated by innate cytokines and viral ligands to kill virus-infected cells. These functions are enhanced during secondary immune responses and after vaccination by synergy with effector T cells and virus-specific antibodies. In human Ebola virus infection, clinical outcome is strongly associated with the initial innate cytokine response, but the role of NK cells has not been thoroughly examined.
Laparoscopy-assisted versus balloon enteroscopy-assisted ERCP after Roux-en-Y gastric bypass
Authors: Christer Julseth Tønnesen, Juliet Young, Tom Glomsaker, Tom Mala, Magnus Løberg, Michael Bretthauer, Erle Refsum, Lars Aabakken
Journal: Endoscopy (2020)

Background Patients who have undergone Roux-en-Y gastric bypass (RYGB) are at increased risk of biliary disease necessitating endoscopic retrograde cholangiopancreatography (ERCP). The most widely used approaches to perform ERCP after RYGB are laparoscopy-assisted ERCP (LA-ERCP) and balloon enteroscopy-assisted ERCP (BEA-ERCP). There are few studies comparing these procedures. We aimed to compare the performance, benefits, and harms of LA-ERCP and BEA-ERCP in RYGB patients. Methods We identified all RYGB patients who underwent ERCP at two tertiary care endoscopy centers in Oslo, Norway between May 2013 and December 2017. One center performed BEA-ERCP, the other LA-ERCP. Procedure success was defined as fulfillment of the therapeutic or diagnostic aim, according to the procedure description. Adverse events were classified according to the Clavien–Dindo grading system. Results During the study period, 40 BEA-ERCP and 39 LA-ERCP procedures were performed in 68 patients. Procedure success rate was 72.5 % for BEA-ERCP and 87.2 % for LA-ERCP (P = 0.14). Adverse events occurred in 18 % of BEA-ERCP and 28 % of LA-ERCP (P = 0.23). Serious adverse events (Clavien–Dindo grade ≥ 3b) occurred in 2.5 % of BEA-ERCP and 7.7 % of LA-ERCP procedures (P = 0.36). Concomitant cholecystectomy was performed in 25 of the 39 LA-ERCP procedures. The median procedure times for LA-ERCP performed with and without concomitant cholecystectomy were 201 minutes and 140 minutes, respectively, and for BEA-ERCP was 125 minutes. Conclusions In experienced hands, both LA-ERCP and BEA-ERCP have high success rates after RYGB. The choice of approach should be individualized according to patient characteristics and available physician competence.
Impaired Condensin Complex and Aurora B kinase underlie mitotic and chromosomal defects in hyperdiploid B-cell ALL
Authors: Oscar Molina, Meritxell Vinyoles, Isabel Granada, Heleia Roca-Ho, Francisco Gutierrez-Agüera, Luis Valledor, Carlos Manuel López-López, Pablo Rodríguez-González, Juan Luis Trincado, Sofía Tirados-Menéndez, Deepali Pal, Paola Ballerini, Monique L. Den Boer, Isabel Plensa, Maria del Mar Perez-Iribarne, Sandra Rodriguez-Perales, Maria JOSE Calasanz, Manuel Ramírez, Rene Rodríguez, Mireia Camos, Maria Calvo, Clara Bueno, Pablo Menendez
Journal: Blood (2020)