tbuckley/cabot-search huggingface dataset:
Mechanisms of GLP-1 receptor–independent renoprotective effects of the dipeptidyl peptidase type 4 inhibitor linagliptin in GLP-1 receptor knockout mice with 5/6 nephrectomy
Authors: Ahmed A. Hasan, Karoline von Websky, Christoph Reichetzeder, Oleg Tsuprykov, Mohamed M.S. Gaballa, Jingli Guo, Shufei Zeng, Denis Delić, Harald Tammen, Thomas Klein, Burkhard Kleuser, Berthold Hocher
Journal: Kidney International (2019)

Dipeptidyl peptidase type 4 (DPP-4) inhibitors were reported to have beneficial effects in experimental models of chronic kidney disease. The underlying mechanisms are not completely understood. However, these effects could be mediated via the glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP1R) pathway. Here we investigated the renal effects of the DPP-4 inhibitor linagliptin in Glp1r-/- knock out and wild-type mice with 5/6 nephrectomy (5/6Nx). Mice were allocated to groups: sham+wild type+placebo; 5/6Nx+ wild type+placebo; 5/6Nx+wild type+linagliptin; sham+knock out+placebo; 5/6Nx+knock out+ placebo; 5/6Nx+knock out+linagliptin. 5/6Nx caused the development of renal interstitial fibrosis, significantly increased plasma cystatin C and creatinine levels and suppressed renal gelatinase/collagenase, matrix metalloproteinase-1 and -13 activities; effects counteracted by linagliptin treatment in wildtype and Glp1r-/- mice. Two hundred ninety-eight proteomics signals were differentially regulated in kidneys among the groups, with 150 signals specific to linagliptin treatment as shown by mass spectrometry. Treatment significantly upregulated three peptides derived from collagen alpha-1(I), thymosin β4 and heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) and significantly downregulated one peptide derived from Y box binding protein-1 (YB-1). The proteomics results were further confirmed using western blot and immunofluorescence microscopy. Also, 5/6Nx led to significant up-regulation of renal transforming growth factor-β1 and pSMAD3 expression in wild type mice and linagliptin significantly counteracted this up-regulation in wild type and Glp1r-/- mice. Thus, the renoprotective effects of linagliptin cannot solely be attributed to the GLP-1/GLP1R pathway, highlighting the importance of other signaling pathways (collagen I homeostasis, HNRNPA1, YB-1, thymosin β4 and TGF-β1) influenced by DPP-4 inhibition.
P116 Basic characteristics of adipose-derived mesenchymal stem cells of ankylosing spondylitis patients
Authors: E Kuca-Warnawin, U Skalska, M Plebanczyk, I Janicka, U Musialowicz, K Bonek, P Głuszko, E Kontny
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Post-doctoral fellow. <h3>Introduction</h3> Application of mesenchymal stem/stromal cells (MSCs), endowed with immunosuppressive and regenerative properties, may be promising option for successful therapy of ankylosing spondylitis (AS) patients, characterised by inflammation and pathological bone remodelling. Adipose tissue is an easily accessible, rich source of MSCs. Biology of MSCs in AS is poorly understood and data describing MSCs from adipose tissue (ASCs) are missing. <h3>Objectives</h3> The aim of this study was to perform comparative basic characterisation of ASCs of AS patients (AS/ASCs) and ASCs line originating from healthy volunteers (hASCs). <h3>Methods</h3> AS/ASCs of 15 AS patients and commercially available hASC lines were used. Phenotype and expression of adhesion molecules (ICAM-1, VCAM-1) on ASCs were evaluated by flow cytometry. Basal and cytokine (tumor necrosis factor +interferon g or interleukin-23)-induced secretion of nine factors (TGFß, IL-6, galectin, LIF, IL-1Ra, PGE<sub>2</sub>, sHLA-G, TSG6 and kynurenines) known to mediate immunomodulatory activity of MSCs was measured by ELISAs. ASCs were co-cultured with either anti-CD3/CD28-stimulated CD4<sup>+</sup> T lymphocytes or mitogen-stimulated peripheral blood mononuclear cells (PBMCs) of allogeneic healthy volunteers. Expression of activation markers (HLA-DR, CD25, CD69) on T cells and these cells proliferation were evaluated by flow cytometry. <h3>Results</h3> There were no significant differences in the phenotype, expression of adhesion molecules and secretory potential between hASCs and AS/ASCs. Inhibition of T cell proliferation was found in both co-culture systems, while modulation of activation markers expression (CD25 down-regulation, CD69 up-regulation) on CD4<sup>+</sup> T and CD8<sup>+</sup> T cell subsets was stated in ASCs-PBMCs co-cultures only and hASCs and AS/ASCs exerted similar effects. <h3>Conclusions</h3> AS/ASCs have phenotype and basic biological features (i.e. secretory potential, some attributes related to immunomodulatory activities) comparable to hASCs. <h3>Acknowledgements</h3> This work was supported by the National Science Centre in Poland (Grant No. 2016/21/B/NZ5/00500) and by the NIGRiR Statutory Grant (Grant No. S/6). <h3>Disclosure of Interest</h3> None declared.
Public Perceptions on Why Women Receive Less Bystander Cardiopulmonary Resuscitation Than Men in Out-of-Hospital Cardiac Arrest
Authors: Sarah M. Perman, Shelby K. Shelton, Christopher Knoepke, Kathryn Rappaport, Daniel D. Matlock, Kathleen Adelgais, Edward P. Havranek, Stacie L. Daugherty
Journal: Circulation (2019)

Background: Women who suffer an out-of-hospital cardiac arrest receive bystander cardiopulmonary resuscitation (CPR) less often than men. Understanding public perceptions of why this occurs is a necessary first step toward equitable application of this potentially life-saving intervention. Methods: We conducted a national survey of members of the public using Mechanical Turk, Amazon’s crowdsourcing platform, to determine reasons why women might receive bystander CPR less often than men. Eligible participants were adults (≥18 years) located in the United States. Responses were excluded if the participant was not able to define CPR correctly. Participants were asked to answer the following free-text question: “Do you have any ideas on why women may be less likely to receive CPR than men when they collapse in public?” Descriptive statistics were used to define the cohort. The free-text response was coded using open coding, and major themes were identified via classical content analysis. Results: In total, 548 subjects were surveyed. Mean age was 38.8 years, and 49.8% were female. Participants were geographically distributed as follows: 18.5% West, 9.2% Southwest, 22.0% Midwest, 27.5% Southeast, and 22.9% Northeast. After analysis, 3 major themes were detected for why the public perceives that women receive less bystander CPR. They include the following: (1) sexualization of women’s bodies; (2) women are weak and frail and therefore prone to injury; and (3) misperceptions about women in acute medical distress. Overall, 41.9% (227) were trained in CPR while 4.4% reported having provided CPR in a medical emergency. Conclusions: Members of the general public perceive fears about inappropriate touching, accusations of sexual assault, and fear of causing injury as inhibiting bystander CPR for women. Educational and policy efforts to address these perceptions may reduce the sex differences in the application of bystander CPR.
Abstract IA18: The application of integrative sequencing for precision oncology
Authors: Arul Chinnaiyan
Journal: Cancer Research (2015)

Abstract Studies of the genomic landscape of human cancers have demonstrated that most solid cancers have a multitude of mutations, a subset of which may be actionable with current drugs. Thus, the personalization of therapy for cancer will require molecular characterization of unique and shared genetic aberrations. Patients who have advanced/refractory cancer and are candidates for clinical trials could potentially benefit by identifying eligibility for targeted drugs based on the actionable genes in their specific tumor. Growing technological advances in genomic sequencing has now made it possible to consider the use of sequence data in a clinical setting. MI-ONCOSEQ initiative brings together expertise at the University of Michigan including clinical oncology, cancer genetics, bioinformatics, clinical pathology, social and behavioral sciences, and bioethics in order to implement clinical cancer sequencing. Our study identifies patients with advanced or refractory cancers that are eligible for clinical trials, consent them to the study, obtain biospecimens (tumor tissue, germline tissue) and store clinical data. The clinical sequencing team processes biospecimens, performs comprehensive sequencing and analysis of tumors to identify point mutations, copy number changes, rearrangements/gene fusions, and aberrant gene expression. Finally, a multi-disciplinary Sequencing Tumor Board deliberates on return of actionable or incidental genomic results. Citation Format: Arul Chinnaiyan. The application of integrative sequencing for precision oncology. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr IA18.
A Multicenter Retrospective Analysis of Clinicopathologic Features of Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma
Authors: Jun Ho Yi, Lee Gyeong-Won, Young Rok Do, Hong Jung Yong, Cheolwon Suh, Yoon Seok Choi, Seong Yoon Lee, Byeong Seok Sohn, Byung-Su Kim, Seok Jin Kim, Won-Seog Kim
Journal: Blood (2018)
Abstract 2359: Characterization of a lung cancer growth factor, LASEP3, as a serological and prognostic biomarker and a therapeutic target.
Authors: Atsushi Takano, Yusuke Nakamura, Yataro Daigo
Journal: Cancer Research (2013)

Abstract To identify novel biomarkers or therapeutic targets for lung cancers, we have been screening genes encoding transmembrane/secretory proteins that are up-regulated in lung cancers, using cDNA microarrays. During this process, we identified a secreted protein, LASEP3 (lung cancer-associated serum protein 3) as a candidate. Immunohistochemical analysis showed that strong positive staining of LASEP3 was observed in 198 (54.8%) of 361 NSCLCs (non-small cell lung cancer). High level of LASEP3 expression was associated with poor prognosis of NSCLC patients. (P=0.0183 by log-rank test). Serum LASEP3 levels were higher in NSCLC patients than in healthy volunteers. The proportion of serum LASEP3-positive cases was 160 (61.8%) of 259 NSCLCs, while 6 (5.5%) of 109 healthy volunteers were falsely diagnosed. Moreover serum LASEP3 levels were significantly higher in breast and colon cancer patients than in healthy volunteers. A combined assay using both LASEP3 and CEA increased sensitivity because 79.5% of the NSCLC patients were then diagnosed as positive, whereas only 7.3% of 109 healthy volunteers were falsely diagnosed as positive. In addition, the use of both LASEP3 and proGRP increased sensitivity because 78.3% of the lung SCLC patients were diagnosed as positive, whereas only 6.6% of 121 healthy volunteers were falsely diagnosed. LASEP3 protein was overexpressed in breast, cervical and colon cancer tissues. Furthermore, treatment of lung cancer cells with LASEP3-siRNAs suppressed its expression and suppressed cell growth and invasion. To clarify the mechanism of tumor suppression by siRNAs against LASEP3, we performed flow cytometric analysis of the tumor cells transfected with these siRNAs. We found a significant increase of the cells at the G0/G1 phase. These data suggest that LASEP3 is a diagnostic and prognostic biomarker and therapeutic target for lung and various type of human cancer. Citation Format: Atsushi Takano, Yusuke Nakamura, Yataro Daigo. Characterization of a lung cancer growth factor, LASEP3, as a serological and prognostic biomarker and a therapeutic target. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2359. doi:10.1158/1538-7445.AM2013-2359 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Derivation and Validation of a Major Toxicity Risk Score Among Nonsteroidal Antiinflammatory Drug Users Based on Data From a Randomized Controlled Trial
Authors: Daniel H. Solomon, Ming Shao, Kathy Wolski, Steven Nissen, M. Elaine Husni, Nina Paynter
Journal: Arthritis & Rheumatology (2019)

Objective While nonsteroidal antiinflammatory drugs ( NSAID s) are commonly used in rheumatology, they can cause major toxicity. Improving the risk/benefit ratio requires a more precise understanding of risk. This study was undertaken to derive and validate a risk score for major toxicity among NSAID users enrolled in a randomized controlled trial. Methods Patients enrolled in a randomized controlled trial who had known cardiovascular disease or risk factors as well as osteoarthritis or rheumatoid arthritis were divided into derivation and validation cohorts. Patients were randomized to receive celecoxib, naproxen, or ibuprofen at typical dosages. The risk score was designed to predict the 1‐year occurrence of major toxicity among NSAID users, including major adverse cardiovascular events, acute kidney injury, significant gastrointestinal events, and mortality. Variables significantly associated with major toxicity were candidates for inclusion in the final regression model. After derived models were found to have a similar model fit in the validation set, the cohorts were combined, allowing calculation of a risk score. Results In the derivation cohort, significant variables included age, male sex, history of cardiovascular disease, hypertension, diabetes mellitus, tobacco use, statin use, elevated serum creatinine level, hematocrit level, and type of arthritis. The C‐index was 0.73 in the validation cohort and 0.71 in the total cohort; the model was well calibrated. Of the total population with complete data (n = 23,735), 1,080 participants (4.6%) had a predicted 1‐year risk of major toxicity of &lt;1%, 16,273 (68.6%) had a predicted risk of 1–4%, and 6,382 (26.9%) had a predicted risk of &gt;4%. Conclusion The risk score accurately categorizes the 1‐year risk of major toxicity among NSAID users and may be useful in identifying patients who can safely use these agents.
Die another way: Ferroptosis drives tuberculosis pathology
Authors: Etienne Meunier, Olivier Neyrolles
Journal: The Journal of Experimental Medicine (2019)

In this issue of JEM, Amaral et al. (https://doi.org/10.1084/jem.20181776) provide the first evidence that ferroptosis, a newly described form of regulated cell death, is detrimental for the host during a Mycobacterium tuberculosis infection. This finding has important implications for the development of host-directed therapies for tuberculosis.
Emergency room medicine: 2
Authors: G. Dunea
Journal: BMJ (1995)

The nurse was pleasant and anxious to help.

“I am from Thailand,” she said; “but I have a Canadian husband,” she added.

“Yes, I know Bangkok,” I replied, “I was there several years ago.”

When I suggested I was tired of waiting, she explained that they had closed nine hospitals in Montreal.

“Yet 70% of Canadians are satisfied,” she said. “Everybody is equal and all receive the same care.”

“In your public hospitals in America patients sometimes wait for 12 hours,” interjected another nurse.

Nevertheless, we were ready to give up. The trouble had started that morning when my wife's knee suddenly gave out. She developed excruciating pain and could no longer bear weight, so I …
<i><scp>IL</scp>‐10 </i><scp>mRNA</scp> levels in whole blood cells correlate with house dust mite allergen immunotherapy efficacy
Authors: Claire Guéguen, Sonia Luce, Vincent Lombardi, Véronique Baron‐Bodo, Philippe Moingeon, Laurent Mascarell
Journal: Allergy (2019)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Thrombalexin (a cytotopic thrombin inhibitor), successfully suppresses the innate immune response in a model of hepatocyte transplantation and may be a promising approach to improving cell engraftment
Authors: Charlotte A. Lee, Anil Dhawan, Ragai R. Mitry, Paradzai Chitongo, Simon Walker, Raquel Fernandez-Dacosta, Celine Filippi, Sharon Lehec, Valeria Iansante, Richard Smith, Emer Fitzpatrick
Journal: Hepatology (2016)
Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome–Associated Renal Cell Carcinoma Showing High FDG Uptake
Authors: Zhengguang Xiao, Aisheng Dong, Yang Wang
Journal: Clinical Nuclear Medicine (2019)

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome is a rare autosomal-dominant disease, characterized by the development of cutaneous and uterine leiomyomas and renal cell carcinoma (RCC). Approximately 20% to 30% of patients with HLRCC syndrome develop RCC resembling sporadic type 2 papillary RCC, which is aggressive and associated with a poor prognosis. Information on the clinical usefulness of FDG PET/CT in HLRCC syndrome-associated RCC is limited. We present a case of HLRCC syndrome-associated RCC showing high FDG uptake in both the primary RCC and retroperitoneal lymph node metastases. In addition, the patient had 2 hypermetabolic uterine leiomyomas.
Abstract 5035: MicroRNA expression profiles classify renal cell carcinoma subtypes
Authors: Sven Wach, Anne Theil, Christine Stoehr, Arndt Hartmann, Arif B. Ekici, Helge Taubert, Bernd Wullich
Journal: Cancer Research (2012)

Abstract Background: Renal cell carcinoma (RCC) accounts for about 2-4% of all human malignancies. Hereby, the entity of papillary RCC (pRCC) is the second most common entity with about 10-15% of all RCC. According to histomorphological characteristics pRCCs can be further subdivided in two distinct subtypes. Type 2 pRCCs are correlated with a worse clinical outcome than type 1 pRCCs. In order to characterize these RCC subtypes we studied microRNA (miRNA) expression profiles of primary pRCCs type 1 and 2 as well as clear cell RCC (ccRCC). Material and Methods: We performed comparative miRNA expression profiling using Affymetrix miRNA microarrays. Ten to fifteen samples were analyzed for each subtype containing matched pairs of microdissected malignant and nonmalignant tissue. Hierarchical clustering was used to identify characteristic miRNA expression signatures. The expression of selected miRNAs was validated using quantitative PCR. Results: Hierarchical clustering was not able to identify miRNA expression signatures characteristic for all RCC subtypes, highlighting the heterogeneity among RCC tumors. But when stratified according to histological subtypes, tumor and nonmalignant tissue samples could be separated from each other. Interestingly, pRCC tumors of type 1 and 2 displayed a characteristic miRNA expression profile making it possible to separate these two tumor subtypes. A differential expression of miRNAs miR-200c, mir-143, miR-145, miR-210 and miR-10b could be confirmed by qRT-PCR in a cohort of pRCC samples (p&amp;lt;0.05; paired t-test). Applying a binary logistic regression model, a combination of only three of these miRNA miRNAs was sufficient to correctly determine the subtype of all pRCC tumor samples. Conclusion: Our findings demonstrate that miRNA expression in RCC is heterogeneous but there are characteristic miRNA expression profiles within RCC subtypes. In pRCC, specific miRNAs may reflect a molecular correlate to the histological differences between the two subtypes, which in turn are correlated to the clinical outcome. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5035. doi:1538-7445.AM2012-5035
Review of US Medical School Finances, 1995-1996
Authors: J L Ganem, J Krakower
Journal: JAMA (1997)

For the 1995-1996 fiscal year, all 125 accredited US medical schools responded to the annual medical school questionnaire of the Liaison Committee on Medical Education, part l-A. Using data from the financial portion of the questionnaire, we identify patterns of financing medical education during the past 3 years and the practice plan arrangements adopted by medical schools, including their organizational and legal structures. This financial review details differences in how public and private medical schools are being funded and funding changes during the past 3 years. The reported data show that revenues supporting medical school programs and activities totaled more than $31 billion in 1995-1996, an increase of 5.4% in inflation-adjusted dollars during the previous year. Compared with the previous year, revenues, in current and constant dollars, increased in almost every category in 1995-1996.
Abdominal Pain and Vomiting in a Pregnant Woman Who Has Had a Gastric Bypass Procedure
Authors: Peter N. Fedorka, Sameer B. Murali, David R. Rajaratnam
Journal: JAMA (2019)

A 31-year-old G2P1 woman who had undergone gastric bypass 4 years prior and is 36 weeks pregnant presents with acute abdominal signs and symptoms that persist after an uncomplicated delivery; a CT scan reveals mesenteric vascular compromise. What is the diagnosis and what would you do next?
Phenotypic variability and disparities in treatment and outcomes of childhood arthritis throughout the world: an observational cohort study
Authors: Alessandro Consolaro, Gabriella Giancane, Alessandra Alongi, Evert Hendrik Pieter van Dijkhuizen, Amita Aggarwal, Sulaiman M Al-Mayouf, Francesca Bovis, Jaime De Inocencio, Erkan Demirkaya, Berit Flato, Dirk Foell, Stella Maris Garay, Călin Lazăr, Daniel J Lovell, Carolina Montobbio, Paivi Miettunen, Dimitrina Mihaylova, Susan Nielsen, Ilonka Orban, Ingrida Rumba-Rozenfelde, Claudia Saad Magalhães, Nahid Shafaie, Gordana Susic, Maria Trachana, Nico Wulffraat, Angela Pistorio, Alberto Martini, Nicolino Ruperto, Angelo Ravelli, Reem Abdwani, Yahya Aghighi, Maya-Feriel Aiche, Constantin Ailioaie, Nuray Aktay Ayaz, Safiya Al-Abrawi, Ekaterina Alexeeva, Jordi Anton, Adriana Apostol, Olga Arguedas, Tadej Avcin, Patrizia Barone, Lillemor Berntson, Alina Lucica Boteanu, Yaryna Boyko, Ruben Burgos-Vargas, Inmaculada Calvo Penades, Gaëlle Chédeville, Rolando Cimaz, Adele Civino, Rita Consolini, Tamas Constantin, Ruben Cuttica, Tomas Dallos, Neil Martin, Silvia Magni Manzoni, Carmen De Cunto, Pavla Dolezalova, Maria Ekelund, Yasser El Miedany, Graciela Espada, Anne Estmann Christensen, Ivan Foeldvari, Romina Gallizzi, Gerd Ganser, Valeria Gerloni, Johannes-Peter Haas, Liora Harel, Miroslav Harjacek, Soad Hashad, Troels Herlin, Cristina Herrera, Michael Hofer, Dirk Holzinger, Gerd Horneff, Hans-Iko Huppertz, Nicolae Iagăru, Amparo Ibanez Estrella, Maka Ioseliani, Rik Joos, Sheila Knupp Oliveira, Sylvia Kamphuis, Ozgur Kasapcopur, Maria Martha Katsicas, Raju Khubchandani, Anuela Kondi, Liisa Kröger, Francesco La Torre, Matilda Laday, Pekka Lahdenne, Maria Cristina Maggio, Maria Greca Magnolia, Clara Malagon, Merja Malin, Silvana Martino, Jose Antonio Melo-Gomes, Pablo Mesa-del-Castillo, Andrea Militaru, Kirsten Minden, Angela Miniaci, Mohammad Hasan Moradinejad, Zoilo Morel Ayala, Irina Nikishina, Ximena Norambuena, Ellen Berit Nordal, Karaman Pagava, Violeta Panaviene, Serena Pastore, Sara Pieropan, Rosa Anna Podda, Chris Pruunsild, Anne Putto-Laurila, Pierre Quartier, Agustin Remesal, Donato Rigante, Sarah Ringold, Lidia Rutkowska-Sak, Marite Rygg, Rotraud Katharina Saurenmann, Sujata Sawhney, Christiaan Scott, Reza Shiari, Elzbieta Smolewska, Betul Sozeri, Joost Frans Swart, Flavio Sztajnbok, Marta Torcoletti, Elena Tsitsami, Nikolay Tzaribachev, Erbil Unsal, Yosef Uziel, Paula Vähäsalo, Boriana Varbanova, Veronika Vargova, Richard Vesely, Gordana Vijatov-Djuric, Soamarat Vilaiyuk, Jelena Vojinovic, Olga Vougiouka, Pamela Weiss, Carine Wouters
Journal: The Lancet Child & Adolescent Health (2019)