tbuckley/cabot-search huggingface dataset:
Abstract 13007: LDL-Triglyceride Content, LDL-Cholesterol to LDL-Triglyceride Ratio,and Associations With Incident Cardiovascular Disease: Prospective Data From the Women’s Health Study
Authors: Edward K Duran, Aaron W Aday, Nancy R Cook, Julie E Buring, Paul M Ridker, Aruna D Pradhan
Journal: Circulation (2019)

Background: LDL-triglyceride (LDL-TG) and cholesterol (LDL-C) content are known to vary across LDL particle subclasses, with higher LDL-C:LDL-TG ratios thought to reflect normal lipid composition. ...
Abstract GMM-041: OVARIAN CANCER CELLS INDUCE A FEEDBACK RESPONSE TO PLATINUM-BASED CHEMOTHERAPY BY ACTIVATING AN ONCOGENIC RSK-EPHA2-GPRC5A SIGNALING SWITCH
Authors: Lidia Moyano-Galceran, Siri Pauliina Turunen, Elina Pietilä, Twana Alkasalias, Sara Corvigno, Elisabet Hjerpe, Ulrika Joneborg, Daria Bulanova, Mina Eriksson, Hanna Dahlstrand, Joseph Carlson, Kaisa Lehti
Journal: Clinical Cancer Research (2019)

Abstract Despite increased understanding of chemotherapy resistance, the effects of the chemotherapy itself on the oncogenic cancer cell properties and adaptive resistance mechanisms of the therapy-escaping metastatic cancer cells remain largely undefined. In this study, we show that the platinum-based chemotherapeutic drugs cisplatin and carboplatin induce a switch from the canonical EphA2 receptor tyrosine kinase activity to the stemness and invasion-associated, ligand independent signaling via EphA2 S897 phosphorylation. In patient-derived high grade serous ovarian cancer (HGSOC) cells and established ovarian cancer cell lines, the chemotherapy treatment led to a significant increase in the ratio between S897 and Y588 phosphorylation of EphA2 in conjunction with GPRC5A protein upregulation and beta1-integrin activation. Notably, high protein levels of GPRC5A were significantly associated to poor survival in patients with metastatic HGSOC, revealing a previously unknown association of this EphA2 interacting receptor with the clinical HGSOC outcome. Moreover, pharmacological inhibition of RSK serine-threonine kinases blocked both the EphA2 S897 phosphorylation and the GPRC5A induction coincident with markedly increased cisplatin and carboplatin sensitivity of the HGSOC cells ex vivo. These results identify a novel mechanism of chemotherapy-induced adaptive resistance via the RSK-EphA2-GPRC5A oncogenic signaling axis in HGSOC. Citation Format: Lidia Moyano-Galceran, Siri Pauliina Turunen, Elina Pietilä, Twana Alkasalias, Sara Corvigno, Elisabet Hjerpe, Ulrika Joneborg, Daria Bulanova, Mina Eriksson, Hanna Dahlstrand, Joseph Carlson, Kaisa Lehti. OVARIAN CANCER CELLS INDUCE A FEEDBACK RESPONSE TO PLATINUM-BASED CHEMOTHERAPY BY ACTIVATING AN ONCOGENIC RSK-EPHA2-GPRC5A SIGNALING SWITCH [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr GMM-041.
Risk of systemic lupus erythematosus in patients with idiopathic thrombocytopenic purpura: population-based cohort study
Authors: George N Goulielmos, Maria I Zervou
Journal: Annals of the Rheumatic Diseases (2020)

We read with great interest the article by Zhu et al .1 It was based on a national study regarding the association between idiopathic thrombocytopenic purpura (ITP) and the subsequent development of systemic lupus erythematosus (SLE), both representing clinically and genetically heterogeneous autoimmune diseases. According to the data presented in this study, the authors demonstrated that the patients with ITP had a 26 times higher risk of new-onset SLE in comparison with the control population.1 Prevalence of ITP has been reported to be ranging between 7% and 30% in patients with SLE, while clinical characteristics of ITP …
AB0138 Comparison of three oa treatment regiments in a typical population
Authors: ES Tsvetkova
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> A series of double-blind placebo and active comparator controlled studies meloxicam, a COX-2 inhibitor, has been found to be safe and effective in the treatment of osteoarthritis (OA) at dose of 7.5 mg daily. To assess the efficacy and the safety of meloxicam ?standard? and 15 mg daily doses a comparison of three OA treatment regiments in a typical population was performed. <h3>Objectives</h3> <h3>Methods</h3> In the open multicenter parallel-group study 630 pts with confirmed knee OA and a flare were treated with oral administration of meloxicam tablets [at regimens of 7.5 mg (1st group) or 15 mg (2nd group) daily or increasing ineffective 7.5 mg/d to 15 mg/d after 1 week (3d group)]. Treatment was for 4 weeks, with regular assessment for drug safety and efficacy by evaluation of adverse events (AE), vital signs, Likert scales for pain at rest, at on movement, synovitis and joint function, and the patient's and investigator's overall assessment of disease activity. <h3>Results</h3> The demographic, disease characteristics and gastrointestinal AE risk factors were similar across the treatment groups. Prior NSAID inefficacy was found in 25.5% pts. NSAID adverse events dropout have been estimated in 12.4% pts in past history. Anti-inflammatory and analgesics meloxicam properties were confirmed in three treatment regiments (p &lt; 0.001). The incidence of all AE was lower and without dropout at 15 mg/d of meloxicam (3.8%) than for 7.5 mg/d of drug (7.8% with 3.6% dropout). The incidence of non-serious gastrointestinal AE was 1.6% and 3.4% (with 1.2% dropout) correspondingly. The total AE frequency among 630 OA pts was 6.5% (with 2.5% dropout). <h3>Conclusion</h3> Meloxicam is a safe and effective medication for knee OA treatment, without dose-depended incidence of AE and dropout rates.
Doctors warned over “street benzos” linked to hospital admissions and deaths
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Doctors have been warned over illicit tablets being sold as the benzodiazepines diazepam, temazepam, and alprazolam that have been linked to recent admissions to hospital and deaths.1

The alert from Public Health England cited “significant evidence from toxicology results” and advised doctors, paramedics, and emergency departments to be aware of the issue and provide advice where necessary.

Tablets that have been flagged include ones marked with DAN 5620 on one side and 10 on the other, T-20, TEM 20, Bensedin, and MSJ. They may contain “dangerously potent benzodiazepines or their analogues such as flubromazolam, flualprazolam and …
Serologic diagnosis of honey bee venom allergy using five different Apis mellifera components (Api m 1-5)
Authors: L Cifuentes, M McIntyre, H Seismann, S Blank, I Braren, R Bredehorst, T Grunwald, E Spillner, U Darsow, J Ring, D Hovanec-Burns, M Ollert
Journal: Allergy (2011)
A dynamic CD2-rich compartment at the outer edge of the immunological synapse boosts and integrates signals
Authors: Philippos Demetriou, Enas Abu-Shah, Salvatore Valvo, Sarah McCuaig, Viveka Mayya, Audun Kvalvaag, Thomas Starkey, Kseniya Korobchevskaya, Lennard Y. W. Lee, Matthias Friedrich, Elizabeth Mann, Mikhail A. Kutuzov, Matteo Morotti, Nina Wietek, Heather Rada, Shamsideen Yusuf, Jehan Afrose, Anastasios Siokis, Philip Allan, Timothy Ambrose, Carolina Arancibia, Adam Bailey, Ellie Barnes, Elizabeth Bird-Lieberman, Jan Bornschein, Oliver Brain, Barbara Braden, Jane Collier, Jeremy Cobbold, Emma Culver, James East, Lucy Howarth, Paul Klenerman, Simon Leedham, Rebecca Palmer, Michael Pavlides, Fiona Powrie, Astor Rodrigues, Jack Satsangi, Alison Simmons, Peter Sullivan, Holm Uhlig, Alissa Walsh, Michael Meyer-Hermann, Ahmed Ashour Ahmed, David Depoil, Michael L. Dustin
Journal: Nature Immunology (2020)
Second-line and third-line therapy for autoimmune hepatitis: A position statement from the European Reference Network on Hepatological Diseases and the International Autoimmune Hepatitis Group
Authors: Ansgar W. Lohse, Marcial Sebode, Marianne H. Jørgensen, Henriette Ytting, Tom H. Karlsen, Deirdre Kelly, Michael P. Manns, Mette Vesterhus
Journal: Journal of Hepatology (2020)
Myelodysplastic Syndromes/Myeloproliferative Neoplasms Treated with 5-Azacytidine. Results from the Hellenic 5-Azacytidine Registry
Authors: Panagiotis Theodorou Diamantopoulos, Ioannis Kotsianidis, Argiris Symeonidis, Vassiliki Pappa, Athanasios Galanopoulos, Dimitrios Gogos, Paraskevi Roussou, Helen A. Papadaki, Aikaterini Palla, Eleftheria Hatzimichael, Maria Dimou, Sossana Delibasi, Menelaos Konstantinos Papoutselis, Alexandra Kourakli, Dimitrios Tsokanas, Niki Rougala, Panayiotis Panayiotidis, Nora-Athina Viniou
Journal: Blood (2017)
Super-enhancer-driven AJUBA is activated by TCF4 and involved in epithelial-mesenchymal transition in the progression of Hepatocellular Carcinoma
Authors: Chi Zhang, Shi Wei, Wei-Peng Sun, Kai Teng, Miao-Miao Dai, Feng-Wei Wang, Jie-Wei Chen, Han Ling, Xiao-Dan Ma, Zi-Hao Feng, Jin-Ling Duan, Mu-Yan Cai, Dan Xie
Journal: Theranostics (2020)

Background and Aims: Aberrant transcriptional programs are highly regulated processes that play important roles in the development and progression of hepatocellular carcinoma (HCC). Emerging evidence suggests that super-enhancers (SEs) often drive critical oncogene expression. However, SE-associated genes in HCC pathogenesis are still poorly understood. Methods: We performed integrative ChIP-seq and Hi-C analyses of HCC cells and identified ajuba LIM protein (AJUBA) as a SE-associated gene. We evaluated AJUBA expression in HCC using immunohistochemistry, immunoblotting, and qRT-PCR. ChIP and luciferase reporter assays were performed to demonstrate that transcription factor 4 (TCF4) bound to AJUBA-associated SEs. We then assessed the role of AJUBA in HCC using both in vitro and in vivo assays. Epithelial-mesenchymal transition (EMT) was examined using immunofluorescence and immunoblotting assays. Furthermore, we used immunoprecipitation and BiFC assays to explore the underlying mechanisms. Results: We identified AJUBA as a SE-associated oncogene in HCC regulated by TCF4. High AJUBA expression was related to an aggressive phenotype and unfavorable outcome in HCC patients. AJUBA knockdown significantly reduced cell migration and invasion capacities both in vitro and in vivo. Furthermore, AJUBA overexpression in HCC recruited tumor necrosis factor associated factor 6 (TRAF6), enhancing the phosphorylation of Akt and increasing Akt activity toward GSK-3β, thus promoting EMT. Conclusions: Our results provide functional and mechanistic links between the SE-associated gene AJUBA and tumor EMT in aggressive HCC.
Impact of Local Alloimmunity and Recipient Cells in Transplant Arteriosclerosis
Authors: Jingjing Cai, Jiacheng Deng, Wenduo Gu, Zhichao Ni, Yuanyuan Liu, Yogesh Kamra, Alka Saxena, Yanhua Hu, Hong Yuan, Qingzhong Xiao, Yao Lu, Qingbo Xu
Journal: Circulation Research (2020)

Rationale: Transplant arteriosclerosis is the major limitation to long-term survival of solid organ transplantation. Although both immune and nonimmune cells have been suggested to contribute to this process, the complex cellular heterogeneity within the grafts, and the underlying mechanisms regulating the disease progression remain largely uncharacterized. Objective: We aimed to delineate the cellular heterogeneity within the allografts, and to explore possible mechanisms underlying this process. Methods and Results: Here, we reported the transcriptional profiling of 11 868 cells in a mouse model of transplant arteriosclerosis by single-cell RNA sequencing. Unbiased clustering analyses identified 21 cell clusters at different stages of diseases, and focused analysis revealed several previously unknown subpopulations enriched in the allografts. Interestingly, we found evidence of the local formation of tertiary lymphoid tissues and suggested a possible local modulation of alloimmune responses within the grafts. Intercellular communication analyses uncovered a potential role of several ligands and receptors, including Ccl21a and Cxcr3 , in regulating lymphatic endothelial cell-induced early chemotaxis and infiltration of immune cells. In vivo mouse experiments confirmed the therapeutic potential of CCL21 and CXCR3 neutralizing antibodies in transplant arteriosclerosis. Combinational use of genetic lineage tracing and single-cell techniques further indicate the infiltration of host-derived c-Kit + stem cells as heterogeneous populations in the allografts. Finally, we compared the immune response between mouse allograft and atherosclerosis models in single-cell RNA-seq analysis. By analyzing susceptibility genes of disease traits, we also identified several cell clusters expressing genes associated with disease risk. Conclusions: Our study provides a transcriptional and cellular landscape of transplant arteriosclerosis, which could be fundamental to understanding the initiation and progression of this disease. CCL21/CXCR3 was also identified as important regulators of immune response and may serve as potential therapeutic targets in disease treatment.
Trends in US Suicide Deaths
Authors: Jack C. Lennon, Ikram Hassan
Journal: JAMA Pediatrics (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Abstract 15256: Frataxin Deficiency Induces Endothelial Replication Stress and DNA Damage to Promote Pulmonary Hypertension
Authors: Miranda K Culley, Jingsi Zhao, Ying Tang, Vinny Negi, Qiujun Yu, Yi Yin Tai, Adam Handen, Gil Speyer, Seungchan Kim, Mingxia Gu, Marlene Rabinovitch, Dror Perk, Stephen Y Chan
Journal: Circulation (2018)

Background: Endothelial iron-sulfur (Fe-S) cluster deficiency promotes pulmonary hypertension (PH), but the pathogenic mechanisms are incompletely defined. Frataxin (FXN) controls Fe-S cluster asse...
Differential immune activation profile of SARS-CoV-2 and SARS-CoV infection in human lung and intestinal cells: Implications for treatment with IFN-β and IFN inducer
Authors: Huiping Shuai, Hin Chu, Yuxin Hou, Dong Yang, Yixin Wang, Bingjie Hu, Xiner Huang, Xi Zhang, Yue Chai, Jian-Piao Cai, Jasper Fuk-Woo Chan, Kwok-Yung Yuen
Journal: Journal of Infection (2020)

ObjectivesRespiratory and intestinal tract are two primary target organs of SARS-CoV-2 infection. However, detailed characterization of the host-virus interplay in infected human lung and intestinal epithelial cells is lacking.MethodsWe utilized immunofluorescence assays, flow cytometry, and RT-qPCR to delineate the virological features and the innate immune response of the host cells against SARS-CoV-2 infection in two prototype human cell lines representing the human lung (Calu3) and intestinal (Caco2) epithelium when compared with SARS-CoV.ResultsLung epithelial cells were significantly more susceptible to SARS-CoV-2 compared to SARS-CoV. However, SARS-CoV-2 infection induced an attenuated pro-inflammatory cytokines/chemokines induction and type I and type II IFN responses. A single dose of 10 U/mL interferon-β (IFNβ) pretreatment potently protected both Calu3 and Caco2 against SARS-CoV-2 infection. Interestingly, SARS-CoV-2 was more sensitive to the pretreatment with IFNβ and IFN inducer than SARS-CoV in Calu3.ConclusionsDespite robust infection in both human lung and intestinal epithelial cells, SARS-CoV-2 could attenuate the virus-induced pro-inflammatory response and IFN response. Pre-activation of the type I IFN signaling pathway primed a highly efficient antiviral response in the host against SARS-CoV-2 infection, which could serve as a potential therapeutic and prophylactic maneuver to COVID-19 patients.
Disagreements Within the US Food and Drug Administration Regarding Approval of Novel Therapeutic Agents, 2011-2015
Authors: Andrea MacGregor, Audrey D. Zhang, Joshua D. Wallach, Joseph S. Ross, Matthew Herder
Journal: JAMA Network Open (2020)

This cross-sectional study examines the frequency of disagreements within the US Food and Drug Administration (FDA) regarding approval of novel therapeutic agents.
Genetics of extreme human longevity to guide drug discovery for healthy ageing
Authors: Zhengdong D. Zhang, Sofiya Milman, Jhih-Rong Lin, Shayne Wierbowski, Haiyuan Yu, Nir Barzilai, Vera Gorbunova, Warren C. Ladiges, Laura J. Niedernhofer, Yousin Suh, Paul D. Robbins, Jan Vijg
Journal: Nature Metabolism (2020)
THU0566 THE EFFECT OF KINESIO-TAPING ON CHRONIC NONSPECIFIC LOW BACK PAIN: PRELIMINARY RESULTS OF A DOUBLE BLINDED RANDOMIZED CLINICAL TRIAL.
Authors: I. Aachari, K. Samia, T. Latifa, T. Fatima Zahrae, S. Afilal, F. Safaa, T. El Joumani, S. Bahloul, H. Rkain, I. Hmamouchi, R. Abouqal, F. Allali
Journal: Annals of the Rheumatic Diseases (2020)

Background: The technique of Kinesio-Taping is a method of adhesive bandage exerting traction on the skin which would favorably influence the muscular and articular systems by reducing the pressure exerted on the subcutaneous mechanoreceptors thus reducing pain and muscle tension. Objectives: The aim of this study is to assess the effectiveness of Kinesio-Taping in the short and medium term on pain and function in patients with chronic nonspecific low back pain compared to a placebo. Methods: We conducted a double-blind, two-arm randomized clinical trial. The study should include a total of 70 patients randomized into 2 groups: Kinesio-Taping (n = 35) and control group (n = 35). To this date we have included 46 patients. All patients receives four I-shaped adhesive strips arranged in a star-like shape and applied to the most painful region of the lower back with a tension between 25% to 30% in the taping group. The placebo group received a taping procedure with no tension. Taping is applied three times (at baseline, fourth and eighth day). Patients are assessed at baseline, on day 14 and at 4 weeks by the Arabic version of the Oswestry Physical and Functional Disability Index (ODI) which is the primary outcome. The secondary outcomes are the assessment of pain and functional disability according to the visual analog scale (VAS) evaluated on a scale of 0 to 10, as well as Rolland-Morris score. Results: Both groups were comparable at baseline concerning the demographical and clinical characteristics (P &gt; 0.05) (table 1). The result of repeated measures ANOVA showed a significant change in ODI score and in VAS for pain and functional disability as well as Rolland-Morris score in both groups. Using the ANCOVA, controlling for pre-test scores, a significant difference was found between the two groups (table 2). Table 1. Clinical characteristics of study population. Conclusion: Our clinical trial offers preliminary evidence on the superiority of Kinesio-Taping in the treatment chronic back pain compared to placebo concerning the reduction of pain and disability. Thus, it can be used as a complementary method in chronic non-specific low back pain. Table 2. Primary and secondary outcomes in the Kinesio-Taping and placebo group. Disclosure of Interests: None declared
Scope and Characteristics of Choosing Wisely in Cancer Care Recommendations by Professional Societies
Authors: Alison S. Baskin, Ton Wang, Nicholas L. Berlin, Ted A. Skolarus, Lesly A. Dossett
Journal: JAMA Oncology (2020)

This quality improvement study describes the cancer types, treatments, and services often targeted in the recommendations generated by oncology societies for the Choosing Wisely campaign.
Current Status and Challenges of DNA Base Editing Tools
Authors: You Kyeong Jeong, Beomjong Song, Sangsu Bae
Journal: Molecular Therapy (2020)

CRISPR-mediated DNA base editors, which include cytosine base editors (CBEs) and adenine base editors (ABEs), are promising tools that can induce point mutations at desired sites in a targeted manner to correct or disrupt gene expression. Their high editing efficiency, coupled with their ability to generate a targeted mutation without generating a DNA double-strand break (DSB) or requiring a donor DNA template, suggests that DNA base editors will be useful for treating genetic diseases, among other applications. However, this hope has recently been challenged by the discovery of DNA base editor shortcomings, including off-target DNA editing, the generation of bystander mutations, and promiscuous deamination effects in both DNA and RNA, which arise from the main DNA base editor constituents, a Cas nuclease variant and a deaminase. In this review, we summarize information about the DNA base editors that have been developed to date, introduce their associated potential challenges, and describe current efforts to minimize or mitigate those issues of DNA base editors.
Multidisciplinary Management of Advanced Kidney Cancer
Authors: Chad A. LaGrange, M. Dror Michaelson, Colleen H. Tetzlaff
Journal: Journal of the National Comprehensive Cancer Network (2020)

A number of therapeutic options are available for the treatment of advanced kidney cancer, including targeted therapy, immunotherapy, and nephrectomy. Choice of therapy for advanced kidney cancer is guided by risk stratification. Immunotherapy combinations are generally superior to vascular endothelial growth factor -based monotherapy, and overall survival rates continue to increase substantially. With new systemic therapy options, additional improvements have been noted in durable responses to treatment and in quality of life. Nephrectomy remains an important consideration in selected patients, particularly those with minimal burden of metastatic disease. Managing the adverse events of treatment of advanced kidney cancer requires close attention and multidisciplinary collaboration.