tbuckley/cabot-search huggingface dataset:
HDAC3 inhibition ameliorates ischemia/reperfusion-induced brain injury by regulating the microglial cGAS-STING pathway
Authors: Yajin Liao, Jinbo Cheng, Xiangxi Kong, Shuoshuo Li, Xiaoheng Li, Meijuan Zhang, He Zhang, Tianli Yang, Yuan Dong, Jun Li, Yun Xu, Zengqiang Yuan
Journal: Theranostics (2020)

Rationale: It is known that neuroinflammation plays a critical and detrimental role in the development of cerebral ischemia/reperfusion (I/R), but the regulation of the cyclic GMP-AMP synthase (cGAS)-mediated innate immune response in I/R-induced neuroinflammation is largely unexplored. This study aimed to investigate the function and regulatory mechanism of cGAS in I/R-induced neuroinflammation and brain injury, and to identify possible strategies for the treatment of ischemic stroke. Methods: To demonstrate that microglial histone deacetylase 3 (HDAC3) regulates the microglial cGAS-stimulator of interferon genes (cGAS-STING) pathway and is involved in I/R-induced neuroinflammation and brain injury, a series of cell biological, molecular, and biochemical approaches were utilized. These approaches include transient middle cerebral artery occlusion (tMCAO), real-time polymerase chain reaction (PCR), RNA sequencing, western blot, co-immunoprecipitation, chromosome-immunoprecipitation, enzyme-linked immunosorbent assay (ELISA), dual-luciferase reporter assay, immunohistochemistry, and confocal imaging. Results: The microglial cGAS- STING pathway was activated by mitochondrial DNA, which promoted the formation of a pro-inflammatory microenvironment. In addition, we revealed that HDAC3 transcriptionally promoted the expression of cGAS and potentiated the activation of the cGAS-STING pathway by regulating the acetylation and nuclear localization of p65 in microglia. Our in vivo results indicated that deletion of cGAS or HDAC3 in microglia attenuated I/R-induced neuroinflammation and brain injury. Conclusion: Collectively, we elucidated that the HDAC3-p65-cGAS-STING pathway is involved in the development of I/R-induced neuroinflammation, identifying a new therapeutic avenue for the treatment of ischemic stroke.
Abstract 14115: E-vaping Induces Pulmonary Arterial Hypertension via Pathological Remodeling in the Lungs and Right Heart
Authors: Matthew Peterson, Yohannes Getiye Estifanos, Shaonil Binti, Olivia Glassock, Alyssa Sanders, Aspen Smith, Luiza Bosch, Guanglong He
Journal: Circulation (2019)

Widespread use of electronic-cigarette (EC) “vaping” as a cessation aid or cigarette smoking alternative prompted this investigation into the cardiopulmonary effects of chronic EC vapor inhalation....
Route and duration of antibiotic therapy in acute cellulitis: A systematic review and meta-analysis of the effectiveness and harms of antibiotic treatment
Authors: Elizabeth L.A. Cross, Harriet Jordan, Rebecca Godfrey, Igho J. Onakpoya, Annalie Shears, Katy Fidler, Timothy E.A. Peto, A. Sarah Walker, Martin J Llewelyn
Journal: Journal of Infection (2020)
Biologically active isoquinoline alkaloids covering 2014–2018
Authors: Xiao‐Fei Shang, Cheng‐Jie Yang, Susan L. Morris‐Natschke, Jun‐Cai Li, Xiao‐Dan Yin, Ying‐Qian Liu, Xiao Guo, Jing‐Wen Peng, Masuo Goto, Ji‐Yu Zhang, Kuo‐Hsiung Lee
Journal: Medicinal Research Reviews (2020)

Abstract Isoquinoline alkaloids, an important class of N ‐based heterocyclic compounds, have attracted considerable attention from researchers worldwide since the early 19th century. Over the past 200 years, many compounds from this class were isolated, and most of them and their analogs possess various bioactivities. In this review, we survey the updated literature on bioactive alkaloids and highlight research achievements of this alkaloid class during the period of 2014–2018. We reviewed over 400 molecules with a broad range of bioactivities, including antitumor, antidiabetic and its complications, antibacterial, antifungal, antiviral, antiparasitic, insecticidal, anti‐inflammatory, antioxidant, neuroprotective, and other activities. This review should provide new indications or directions for the discovery of new and better drugs from the original naturally occurring isoquinoline alkaloids.
Poster Session 4: HBV: Diagnostics, Epidemiology, Prevention, Natural History
Journal: Hepatology (2014)

dence of Toxoplasmosis was 0.6%.A subgroup analysis was conducted on liver and small bowel transplant patients within this cohort.In this subgroup analysis, 39 liver and small bowel recipients met criteria and the overall incidence of PCP in this sub-group was found to be 0%.In the 39 pediatric liver and small bowel transplant patients on pentamidine the incidence of adverse events leading to discontinuation was 2.5% (1 of 39 patients).The incidence of Toxoplasmosis in the liver and small bowel transplant recipients was found to be 0%.Conclusion: In a three year time span a 0% PCP breakthrough rate was found in small bowel and liver transplant patients receiving IV pentamidine prophylaxis.Although sulfamethoxazole/trimethoprim is considered first line for PCP prophylaxis, based on the results of this study, IV pentamidine could be considered a safe and effective second line alternative for pediatric transplant recipients in general and liver and small bowel patients in particular.
Seeing (Hearing Loss) With Fresh Eyes
Authors: Wendy Landier
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Mitochondrial DNA drives abscopal responses to radiation that are inhibited by autophagy
Authors: Takahiro Yamazaki, Alexander Kirchmair, Ai Sato, Aitziber Buqué, Marissa Rybstein, Giulia Petroni, Norma Bloy, Francesca Finotello, Lena Stafford, Esther Navarro Manzano, Francisco Ayala de la Peña, Elena García-Martínez, Silvia C. Formenti, Zlatko Trajanoski, Lorenzo Galluzzi
Journal: Nature Immunology (2020)
Standardizing Brain Death Globally
Authors: Wade S. Smith
Journal: JAMA Neurology (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 Neurology 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 Neurology journal
Assessing Parent Decisions About Child Participation in a Behavioral Health Intervention Study and Utility of Informed Consent Forms
Authors: Stephanie A. Kraft, Kathryn M. Porter, Devan M. Duenas, Erin Sullivan, Maya Rowland, Brian E. Saelens, Benjamin S. Wilfond, Seema K. Shah
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Obtaining informed consent is an important ethical obligation for clinical research participation that is imperfectly implemented. Research on improving consent processes often focuses on consent forms, but little is known about consent forms' influence on decision-making compared with other types of engagement. <h3>Objective</h3> To evaluate whether parents decide whether to enroll their children in research before or after they receive the consent form. <h3>Design, Setting, and Participants</h3> An online survey of 88 parents who enrolled or declined to enroll their child in a weight management intervention study between January 2, 2018, and June 24, 2019, was conducted; surveys were completed between February 2, 2018, and July 9, 2019. A 31-item survey asked about impressions of the study throughout the enrollment process, timing of enrollment decisions, and decision-making factors. Responses were summarized descriptively and subgroups were compared using the Fisher exact test or χ<sup>2</sup>test. <h3>Main Outcomes and Measures</h3> Self-reported timing of enrollment decision. <h3>Results</h3> A total of 106 parents were approached and gave permission for their contact information to be shared with the study team; 22 additional parents declined to allow their information to be shared, and 24 lost contact with the partner study before they could be asked for permission. A total of 88 parents (67 enrollees, 21 decliners) completed the survey (83% participation rate); 79 of 88 reporting gender (instead of sex, as biological sex was not relevant to survey) information were women (91%), 66 participants (75%) were non-Hispanic White, and 63 participants (72%) had annual household incomes greater than or equal to $70 000. No significant differences in respondent characteristics between enrollees and decliners were identified. Fifty-nine parents (67%) responded that they decided whether to enroll in the weight management study before receiving the consent form. Only 17 of 69 parents (25%) who remembered receiving the consent form responded that it taught them new information. <h3>Conclusions and Relevance</h3> The findings of this study suggest that interventions to improve informed consent forms may have limited influence on decision-making because many research decisions occur before review of the consent form. It appears that regulatory review and interventions to improve decision-making should focus more on early engagement (eg, recruitment materials). Future studies should test timing of decisions in other types of research with different populations and clinical settings.
<i>TP53</i> mutations in myelodysplastic syndromes and secondary AML confer an immunosuppressive phenotype
Authors: David A. Sallman, Amy F. McLemore, Amy L. Aldrich, Rami S. Komrokji, Kathy L. McGraw, Abhishek Dhawan, Susan Geyer, Hsin-An Hou, Erika A. Eksioglu, Amy Sullivan, Sarah Warren, Kyle J. MacBeth, Manja Meggendorfer, Torsten Haferlach, Steffen Boettcher, Benjamin L. Ebert, Najla H. Al Ali, Jeffrey E. Lancet, John L. Cleveland, Eric Padron, Alan F. List
Journal: Blood (2020)
Antirheumatic Disease Therapies for the Treatment of COVID‐19: A Systematic Review and Meta‐Analysis
Authors: Michael Putman, Yu Pei Eugenia Chock, Herman Tam, Alfred H. J. Kim, Sebastian E. Sattui, Francis Berenbaum, Maria I. Danila, Peter Korsten, Catalina Sanchez-Alvarez, Jeffrey A. Sparks, Laura C. Coates, Candace Palmerlee, Andrea Peirce, Arundathi Jayatilleke, Sindhu R. Johnson, Adam Kilian, Jean Liew, Larry J. Prokop, M. Hassan Murad, Rebecca Grainger, Zachary S. Wallace, Alí Duarte-García
Journal: Arthritis & Rheumatology (2020)

Antirheumatic disease therapies have been used to treat coronavirus disease 2019 (COVID-19) and its complications. We conducted a systematic review and meta-analysis to describe the current evidence.A search of published and preprint databases in all languages was performed. Included studies described ≥1 relevant clinical outcome for ≥5 patients who were infected with severe acute respiratory syndrome coronavirus 2 and were treated with antirheumatic disease therapy between January 1, 2019 and May 29, 2020. Pairs of reviewers screened articles, extracted data, and assessed risk of bias. A meta-analysis of effect sizes using random-effects models was performed when possible.The search identified 3,935 articles, of which 45 were included (4 randomized controlled trials, 29 cohort studies, and 12 case series). All studies evaluated hospitalized patients, and 29 of the 45 studies had been published in a peer-reviewed journal. In a meta-analysis of 3 cohort studies with a low risk of bias, hydroxychloroquine use was not significantly associated with mortality (pooled hazard ratio [HR] 1.41 [95% confidence interval (95% CI) 0.83, 2.42]). In a meta-analysis of 2 cohort studies with some concerns/higher risk of bias, anakinra use was associated with lower mortality (pooled HR 0.25 [95% CI 0.12, 0.52]). Evidence was inconclusive with regard to other antirheumatic disease therapies, and the majority of other studies had a high risk of bias.In this systematic review and meta-analysis, hydroxychloroquine use was not associated with benefit or harm regarding COVID-19 mortality. The evidence supporting the effect of other antirheumatic disease therapies in COVID-19 is currently inconclusive.
Abstract 12784: Circulating Mature Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Level Predicts Diminished Response to Statin Therapy in Patients With Coronary Artery Disease
Authors: Kuyama Naoto, Kataoka Yu, Mariko Harada-Shiba, Mika Hori, Masatsune Ogura, Yasuhide Asaumi, Teruo Noguchi, Satoshi Yasuda, Yu Kataoka
Journal: Circulation (2019)

Background: The degree of lowering LDL-C by a statin considerably varies in each individual, which associates with worse outcomes. These observations underscore additional approach to predict the r...
OP0194 IMMUNOSUPPRESSIVE EFFECT OF TOLEROGENIC DENDRITIC CELLS ON AUTOLOGOUS T-CELLS IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: Y. Kurochkina, T. Tyrinova, O. Leplina, M. Tikhonova, A. Sizikov, O. Chumasova, A. Ostanin, E. Chernykh
Journal: Annals of the Rheumatic Diseases (2020)

Background: Dendritic cells (DCs) are known to contribute to the pathogenesis of rheumatoid arthritis (RA) through presentation of cartilage glycoprotein, production of proinflammatory cytokines and activation of Th1/Th17 responses. Along with stimulating activity, DCs may exhibit suppressive functions via capacity to induce T cell apoptosis/anergy and to generate regulatory T cells. Since these DCs have potential to control autoreactive T-lymphocytes, the enhancing of tolerogenic properties of DCs seems to be a new important strategy in treatment of RA. However, it remains unclear whether autoreactive T lymphocytes are sensitive to the immunosuppressive effects of DC. Objectives: The aim of our study is to investigate the mechanisms of the inhibitory effect of dexamethasone-modified DCs (dexDCs) in patients with RA on autologous T cells. Methods: Twenty patients with RA with high and moderate activity of disease were recruited in this study. All patients fullfield ACR/EULAR criteria (2010). All studies were performed after receiving informed consent. DCs were generated from blood monocytes culturing for 5 days with GM-CSF and IFN-α in the presence dexamethasone, applied on third day. LPS as maturation stimuli was added on fourth day. The study evaluated the ability of dexDCs to induce T cell apoptosis, inhibit the production of Th1 and Th17 cytokines in auto-mixed leukocytes culture (MLC), induce the activation of T-regulatory cells, and inhibit the purified protein derivative (PPD)-specific immune response. Results: We revealed that dexDCs markedly suppressed the production of IFN-γ and IL-17, while the decreasing of IL-4 and IL-13 was less pronounced. Thus, in comparison with Th2 cells, Th1 and Th17 T lymphocytes were more sensitive to suppressor effects of dexDCs. We also revealed a significant increasing of cells in the stage of late apoptosis (An+Pi+) during the cultivation of autologous T cells with dexDCs. We have also proved the suppressive effect of dexDCs on culture T cells that are co-cultivated with mature DCs (reduction of proliferation from 2700 cpm to 1500 cpm, p=0.0015). In addition, we have shown the ability of dexDCs to induce T-regulatory cells with a phenotype CD4+IL10+Tr1. In conclusion, we have shown the ability of PPD-loaded dexDCs to inhibit the proliferative response of both mature DCS and mature dexDCs-loaded PPD, that indicates the ability of dexDCs to possess antigen-specific suppression. Conclusion: The data obtained indicate that, dexDCs from RA patients have an immunosuppressive effect on autologous T cells through the induction of apoptosis, anergia and activation of T regulatory cells that authorise their application as a DCs-vaccine. Disclosure of Interests: None declared
Abstract 21176: Can Intramural Iron Serve as a New Marker of Vulnerable Plaque?
Authors: Yu Liu, Nitin Garg, Joseph J Maleszewski, Steven M Jorgensen, Jia Wang, Xinhui Duan, Shuai Leng, Lifeng Yu, Kay Parker, Cynthia H McCollough, Erik L Ritman, Birgit Kantor
Journal: Circulation (2010)

Intraplaque hemorrhage is considered a sign and potentially a contributor of plaque instability. We hypothesize that subsequent iron deposits from plaque hemorrhage could be used, measured, and ima...
Antibody response against SARS-CoV-2 spike protein and nucleoprotein evaluated by four automated immunoassays and three ELISAs
Authors: Jan Van Elslande, Bram Decru, Stijn Jonckheere, Eric Van Wijngaerden, Els Houben, Patricia Vandecandelaere, Christophe Indevuyst, Melissa Depypere, Stefanie Desmet, Emmanuel André, Marc Van Ranst, Katrien Lagrou, Pieter Vermeersch
Journal: Clinical Microbiology and Infection (2020)
Treating Migraine in Children and Adolescents
Authors: Amy A. Gelfand, Peter J. Goadsby
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
Combined lenvatinib and pembrolizumab as salvage therapy in advanced adrenal cortical carcinoma
Authors: Sara Bedrose, Kevin Charles Miller, Lina Altameemi, Mohamed S Ali, Sameh Nassar, Naveen Garg, Marilyne Daher, Keith D Eaton, Jeffrey Thomas Yorio, Davey B Daniel, Matthew Campbell, Keith C Bible, Mabel Ryder, Ashish V Chintakuntlawar, Mouhammed Amir Habra
Journal: Journal for ImmunoTherapy of Cancer (2020)

There is no effective systemic therapy for metastatic adrenal cortical carcinoma (ACC) after failure of platinum-based chemotherapy. The efficacies of single-agent oral multikinase inhibitors (MKIs) or salvage immune checkpoint inhibitors (CPIs) have been very limited. It is unknown whether combining CPIs, such as pembrolizumab (PEM), with other therapies, such as MKIs, could yield higher response rates in ACC, yet this combination has shown promise in other cancers. Herein, we describe the first case series using PEM in combination with the MKI lenvatinib (LEN) in patients with progressive, metastatic ACC.A retrospective case series describing the use of LEN/PEM as salvage therapy in patients with progressive/metastatic ACC.Eight patients were treated with the LEN/PEM combination therapy. Half were female, and the median age at time of diagnosis was 38 years (range 21-49). Three (37.5%) patients had hormonally active ACC. The median number of prior lines of systemic therapy was 4 (range 2-9). Six (75%) patients had had disease progression on prior CPIs and five (62.5%) patients had progressed on prior MKI therapy. The median progression-free survival was 5.5 months (95% CI 1.8-not reached) and median duration of therapy was 8.5 months (range 2-22). Two (25%) patients had a partial response, one (12.5%) patient had stable disease, and five (62.5%) patients had progressive disease. None of the eight patients stopped therapy because of adverse events.In our small cohort of heavily pretreated patients with ACC, the combination of LEN/PEM was associated with objective responses in a subset of patients without significant toxicity. This combination should be formally investigated in phase II clinical trial with robust correlative studies to identify predictors for response.
Trib1 promotes acute myeloid leukemia progression by modulating the transcriptional programs of Hoxa9
Authors: Seiko Yoshino, Takashi Yokoyama, Yoshitaka Sunami, Tomoko Takahara, Aya Nakamura, Yukari Yamazaki, Shuichi Tsutsumi, Hiroyuki Aburatani, Takuro Nakamura
Journal: Blood (2020)
Response to: ‘Comment on ‘Implication of baseline levels and early changes of C-reactive protein for subsequent clinical outcomes of patients with rheumatoid arthritis treated with tocilizumab’’ by Pethoe-Schramm<i>et al</i>
Authors: Inbal Haya Shafran, Farideh Alasti, Josef S Smolen, Daniel Aletaha
Journal: Annals of the Rheumatic Diseases (2020)

We would like to thank Dr Pethoe-Schramm and colleagues for their comment on our paper1 and the diligent assessment of the data we presented.2 The authors addressed each of our Figures sequentially and, therefore, it will be a pleasure to respond here accordingly.

Before doing so, we would like to mention that in contrast to other studies, like the one by Wang et al 3 which we also referred to in our paper, we approached the analyses by using Clinical Disease Activity Index (CDAI)  criteria (endorsed by ACR-EULAR for this purpose) rather than remission criteria by the Disease Activity Score using 28 joint counts (DAS28) .4 5 As often described, DAS28 <2.6 is an inappropriate  endpoint because many patients still have residual swollen joints which are drivers of joint damage.6 7 Moreover, acute phase reactants are highly weighted in the formula.8 9 Consequently, DAS28  rates are exaggerated and misleading in the context of interleukin-6 (IL-6) inhibition by cytokine receptor inhibitors like tocilizumab or pathway inhibitors like Janus kinase inhibitors;10 11 moreover, these issues cannot be overcome by lowering the threshold for the  cutpoint.5 12 Finally, since DAS28 includes an acute phase reactant, using it as an outcome to evaluate the role of C-reactive protein (CRP) cannot be seen as independent of CRP and, therefore, may be circular.

Equally importantly, we did not start by asking the question of the ‘distribution of baseline… concentrations of…CRP’ in relation to achieving DAS28 <2.6 or not, but rather asked the question, which CRP-levels those patients who achieved stringent  at endpoint had at baseline and compared this with baseline CRP levels in patients who had other disease activity states at endpoint and not just non-remission. Thus, …