tbuckley/cabot-search huggingface dataset:
Abstract 18331: Systemic Administration of Allogenic Fetal Membrane-derived MSC Ameliorates Experimental Autoimmune Myocarditis via Suppression of Th1/Th17 Immunity
Authors: Kenichi Yamahara, Makiko Ohshima, Ken Ishikane, Kazuhiko Harada, Hidetoshi Tsuda, Kentaro Otani, Makoto Kodama, Kenji Kangawa, Tomoaki Ikeda
Journal: Circulation (2012)

Background: We have reported that systemic administration of autologous bone marrow or allogenic fetal membrane (FM)-derived mesenchymal stem cells (MSCs) similarly attenuated experimental autoimmune myocarditis (EAM) (JMCC 42:88-97 2007, 49:753-61 2010). Since rat EAM is a T-helper (Th) cell-mediated autoimmune disease, and recent evidence has indicated that MSCs exert an immunosuppressive effect on Th cell activity, we focused on Th cell differentiation in allogenic FM-MSC administered EAM rats. Methods and Results: EAM was induced in Lewis rats by injecting porcine cardiac myosin (day 0). Allogenic FM-MSCs, obtained from major histocompatibility complex mismatched ACI rats, were intravenously injected (5×10[[Unable to Display Character: &amp;#8309;]] cells/rat) on day 7, 10, or 14 (MSCd7, MSCd10, or MSCd14 groups, respectively). At day 21, echocardiography confirmed that reduced ejection fraction in the untreated EAM group (63±2%) was significantly improved in the MSCd10 and MSCd14 groups (74±1 and 75±2%, respectively, P&lt;0.01). CD68 immunostaining revealed that prominent macrophage infiltration in the myocardium of the EAM group (1466±93 cells/mm²) was significantly decreased in the MSCd10 group (958±139 cells/mm², P&lt;0.05). To evaluate Th cell differentiation, flow cytometry was performed to determine the percentage of interferon (IFN)-γ positive Th1 and interleukin (IL)-17 positive Th17 cells in peripheral CD4-positive Th cells. The percentage of Th1 cells at day 16 was significantly lower in the MSCd10 (1.3±0.2%) and MSCd14 (1.6±0.3%) groups compared to the EAM group (2.4±0.3%, P&lt;0.05), as was the percentage of Th17 cells in the MSCd10 group (1.9±0.5%) compared to the EAM group (2.2±0.9%, P&lt;0.05). In addition, human CD4+ Th cells co-cultured with human FM-MSCs exhibited reduced Th1 and Th17 cell differentiation and proliferation, with increased expression of immunosuppressive molecules including indoleamine 2,3-dioxygenase 2 and IL-6 in co-cultured FM-MSCs. Conclusion: Our findings demonstrate the protective effects of intravenously administered FM-MSCs in EAM due to profound suppression of Th1/Th17 cells and provide a new perspective for the treatment of acute myocarditis.
A multicentre controlled pre–post trial of an implementation science intervention to improve venous thromboembolism prophylaxis in critically ill patients
Authors: Henry T. Stelfox, Rebecca Brundin-Mather, Andrea Soo, Jeanna Parsons Leigh, Daniel J. Niven, Kirsten M. Fiest, Christopher James Doig, Danny J. Zuege, Barry Kushner, Fiona Clement, Sharon E. Straus, Deborah J. Cook, Sean M. Bagshaw, Khara M. Sauro
Journal: Intensive Care Medicine (2019)
Kinetic Profiling of Clinical Symptoms and Basophil Parameters During Treatment of Chronic Spontaneous Urticaria with Omalizumab
Authors: Kirti J. Johal, Donald W. MacGlashan, John T. Schroeder, Eric T. Oliver, Kristin L. Chichester, Sarbjit S. Saini
Journal: Journal of Allergy and Clinical Immunology (2019)
Cardiac sodium-dependent glucose cotransporter 1 is a novel mediator of ischaemia/reperfusion injury
Authors: Zhao Li, Vineet Agrawal, Mohun Ramratnam, Ravi K Sharma, Stephen D’Auria, Abigail Sincoular, Margurite Jakubiak, Meredith L Music, William J Kutschke, Xueyin N Huang, Lindsey Gifford, Ferhaan Ahmad
Journal: Cardiovascular Research (2019)

We previously reported that sodium-dependent glucose cotransporter 1 (SGLT1) is highly expressed in cardiomyocytes and is further up-regulated in ischaemia. This study aimed to determine the mechanisms by which SGLT1 contributes to ischaemia/reperfusion (I/R) injury.Mice with cardiomyocyte-specific knockdown of SGLT1 (TGSGLT1-DOWN) and wild-type controls were studied. In vivo, the left anterior descending coronary artery was ligated for 30 min and reperfused for 48 h. Ex vivo, isolated perfused hearts were exposed to 20 min no-flow and up to 2 h reperfusion. In vitro, HL-1 cells and isolated adult murine ventricular cardiomyocytes were exposed to 1 h hypoxia and 24 h reoxygenation (H/R). We found that TGSGLT1-DOWN hearts were protected from I/R injury in vivo and ex vivo, with decreased infarct size, necrosis, dysfunction, and oxidative stress. 5'-AMP-activated protein kinase (AMPK) activation increased SGLT1 expression, which was abolished by extracellular signal-related kinase (ERK) inhibition. Co-immunoprecipitation studies showed that ERK, but not AMPK, interacts directly with SGLT1. AMPK activation increased binding of the hepatocyte nuclear factor 1 and specificity protein 1 transcription factors to the SGLT1 gene, and HuR to SGLT1 mRNA. In cells, up-regulation of SGLT1 during H/R was abrogated by AMPK inhibition. Co-immunoprecipitation studies showed that SGLT1 interacts with epidermal growth factor receptor (EGFR), and EGFR interacts with protein kinase C (PKC). SGLT1 overexpression activated PKC and NADPH oxidase 2 (Nox2), which was attenuated by PKC inhibition, EGFR inhibition, and/or disruption of the interaction between EGFR and SGLT1.During ischaemia, AMPK up-regulates SGLT1 through ERK, and SGLT1 interacts with EGFR, which in turn increases PKC and Nox2 activity and oxidative stress. SGLT1 may represent a novel therapeutic target for mitigating I/R injury.
Abstract 15019: Cardiomyocyte Loss of Mouse Zo-1 Causes Abnormal Conduction but is Dispensable for Contractile Function
Authors: Jianlin Zhang, Kevin Vincent, Matthew Klos, Angela K Peter, Hongqiang Cheng, Selina M Huang, Jordan K Towne, Yusu Gu, Nancy D Dalton, Ruixia Li, Kirk L Peterson, Ju Chen, Andrew D McCulloch, Robert S Ross, Kirk U Knowlton
Journal: Circulation (2017)

Introduction: Zonula occludens-1 (ZO-1) is a scaffolding protein that regulates signal transduction, transcription, and cellular communication in many cell types. Global ZO-1 knockout mice die at e...
Effects of chronic exercise interventions on executive function among children and adolescents: a systematic review with meta-analysis
Authors: Yue Xue, Yanxiang Yang, Tao Huang
Journal: British Journal of Sports Medicine (2019)

To synthesise randomised controlled trials (RCTs) regarding the effects of chronic exercise interventions on different domain-specific executive functions (EFs) among children and adolescents.Systematic review with meta-analysis.PsycINFO, PubMed, SPORTDiscus, Academic Search Premier, Embase and Web of Science were searched.RCTs or cluster RCT design, which employ chronic exercise interventions and target healthy children (age 6-12 years) and adolescents (age 13-17 years). We defined chronic exercise as physical activity (PA) which consists of multiple exercise sessions per week and lasts for an extended period of time (typically over 6 weeks).We included 19 studies, with a total of 5038 participants. The results showed that chronic exercise interventions improved overall EFs (standardised mean difference (SMD)=0.20, 95% CI 0.09 to 0.30, p<0.05) and inhibitory control (SMD=0.26, 95% CI 0.08 to 0.45, P<0.05). In meta regression, higher body mass index was associated with greater improvements in overall EFs performance (β=0.03, 95% CI 0.0002 to 0.06, p<0.05), whereas age and exercise duration were not. In subgroup analysis by intervention modality, sports and PA programme (SMD=0.21, 95% CI 0.12 to 0.31, p<0.05) and curricular PA (SMD=0.39, 95% CI 0.08 to 0.69, p<0.05) improved overall EFs performance, but integrated PA did not (SMD=0.02, 95% CI -0.05 to 0.09, p>0.05). Interventions with a session length < 90 minutes improved overall EFs performance (SMD=0.24, 95%CI 0.10 to 0.39, p=0.02), but session length ≥ 90 minutes did not (SMD=0.05, 95%CI -0.03 to 0.14). No other moderator was found to have an effect.Despite small effect sizes, chronic exercise interventions, implemented in curricular or sports and PA programme settings, might be a promising way to promote multiple aspects of executive functions, especially inhibitory control.
Dupilumab Suppresses Inflammatory Biomarkers in Asthma Patients With or Without Allergic Rhinitis: Post Hoc Analysis of the LIBERTY ASTHMA QUEST Study
Authors: Jonathan Corren, Jean Bousquet, William W. Busse, Jorge F. Maspero, Nicola A. Hanania, Linda B. Ford, Megan Rice, Yufang Lu, Paul Rowe, Sivan Harel, Heribert Staudinger, Marcella Ruddy, Neil M.H. Graham, Nikhil Amin, Ariel Teper
Journal: Journal of Allergy and Clinical Immunology (2019)
Racial/Ethnic Disparities in Neonatal Outcomes
Authors: Luigi Gagliardi
Journal: JAMA Pediatrics (2019)

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
Graft-versus-host disease propagation depends on increased intestinal epithelial tight junction permeability
Authors: Sam C. Nalle, Li Zuo, Ma. Lora Drizella M. Ong, Gurminder Singh, Alicia M. Worthylake, Wangsun Choi, Mario Cabrero Manresa, Anna P. Southworth, Karen L. Edelblum, Gregory J. Baker, Nora E. Joseph, Peter A. Savage, Jerrold R. Turner
Journal: Journal of Clinical Investigation (2019)

Graft-versus-host disease (GVHD) is a complication of hematopoietic stem cell transplantation (HSCT) that affects multiple organs. GVHD-associated intestinal damage can be separated into two distinct phases, initiation and propagation, which correspond to conditioning-induced damage and effector T cell activation and infiltration, respectively. Substantial evidence indicates that intestinal damage induced by pretransplant conditioning is a key driver of GVHD initiation. Here, we aimed to determine the impact of dysregulated intestinal permeability on the subsequent GVHD propagation phase. The initiation phase of GVHD was unchanged in mice lacking long MLCK (MLCK210), an established regulator of epithelial tight junction permeability. However, MLCK210-deficient mice were protected from sustained barrier loss and exhibited limited GVHD propagation, as indicated by reduced histopathology, fewer CD8+ effector T cells in the gut, and improved overall survival. Consistent with these findings, intestinal epithelial MLCK210 expression and enzymatic activity were similarly increased in human and mouse GVHD biopsies. Intestinal epithelial barrier loss mediated by MLCK210 is therefore a key driver of the GVHD propagation. These data suggest that inhibition of MLCK210-dependent barrier regulation may be an effective approach to limiting GVHD progression.
Nintedanib in metastatic appendiceal carcinoma.
Authors: Birendra Kc, Mufti Naeem Ahmad, Kunal C. Kadakia, Reza Nazemzadeh, Mohamed E. Salem, Seungjean Chai, John Stuart Salmon, James Thomas Symanowski, Danielle Boselli, Jimmy J. Hwang
Journal: Journal of Clinical Oncology (2019)

TPS723 Background: Appendiceal carcinomas are rare with an incidence of about 0.12 cases per 1,000,000 people per year. There is limited, mostly retrospective data in the treatment of metastatic appendiceal carcinomas. Generally, fluoropyrimidine-based therapy is used in the first line, adapting regimens for metastatic colorectal cancer. However, beyond progression, no treatments have shown clear activity. In appendiceal cancer, high vascular endothelial growth factor receptor (VEGFR)2 expression has been correlated with poor survival. Moreover, malignant ascites has been demonstrated to have elevated levels of VEGF. Nintedanib is an oral tyrosine kinase inhibitor of VEGFR which demonstrated activity in lung and ovarian cancer in clinical trials, and has undergone investigation in heavily pretreated metastatic colorectal cancer. Given the analogies between appendiceal and colorectal cancer and potentially ovarian cancer, and the limited information about the optimal treatment of metastatic appendiceal carcinomas, further investigation with nintedanib is warranted. Methods: This is a single arm, open label, investigator initiated, two-stage phase II trial (NCT 03287947) in metastatic appendiceal cancer patients after failure (defined as progression on or within 6 months or intolerance) of initial fluoropyrimidine-based therapy and at least one measurable site of disease. The trial started enrolling patients in June 2018, and up to 39 subjects will be enrolled. They will be treated with 200 mg of oral nintedanib twice daily and undergo disease evaluation every two months. The primary objective of this study is to evaluate the disease control rate (DCR), the composite of objective response and stable disease per RECIST 1.1. Secondary objectives include evaluation of safety and toxicity, objective response rate (ORR), 6-month progression free survival (PFS) and overall survival (OS). DCR, ORR &amp; 6-month PFS will be estimated with the corresponding 95% Clopper-Pearson confidence interval. PFS &amp; OS will be estimated using Kaplan-Meier techniques. Exploratory objectives include evaluation of serum VEGF, ascites VEGF, hypertension and paracentesis frequency in subjects with ascites at study entry. Clinical trial information: NCT 03287947.
Heart Failure With Preserved Ejection Fraction and Diabetes
Authors: Kelly McHugh, Adam D. DeVore, Jingjing Wu, Roland A. Matsouaka, Gregg C. Fonarow, Paul A. Heidenreich, Clyde W. Yancy, Jennifer B. Green, Natasha Altman, Adrian F. Hernandez
Journal: Journal of the American College of Cardiology (2019)
Different time-dependent changes of risk for evolution in chronic lymphocytic leukemia with mutated or unmutated antigen B cell receptors
Authors: Theodoros Moysiadis, Panagiotis Baliakas, Davide Rossi, Mark Catherwood, Jonathan C. Strefford, Julio Delgado, Achilles Anagnostopoulos, Chrysoula Belessi, Niki Stavroyianni, Sarka Pospisilova, David Oscier, Gianluca Gaidano, Elias Campo, Richard Rosenquist, Paolo Ghia, Kostas Stamatopoulos
Journal: Leukemia (2019)
A Tumor Suppressor Role for Bank1 in B-Cell Precursor Acute Lymphoblastic Leukemia
Authors: Franziska Auer, Rodríguez-Hernández Guillermo, Inés González-Herrero, Oscar Blanco, Diego Alonso-López, Javier De Las Rivas, Rafael Jimenez, Francisco J. García-Criado, Maria B. García-Cenador, Carolina Vicente-Dueñas, Arndt Borkhardt, Isidro Sanchez-Garcia, Julia Hauer
Journal: Blood (2018)
Phase 1 Trial of an RNA Interference Therapy for Acute Intermittent Porphyria
Authors: Eliane Sardh, Pauline Harper, Manisha Balwani, Penelope Stein, David Rees, D. Montgomery Bissell, Robert Desnick, Charles Parker, John Phillips, Herbert L. Bonkovsky, Daphne Vassiliou, Craig Penz, Amy Chan-Daniels, Qiuling He, William Querbes, Kevin Fitzgerald, Jae B. Kim, Pushkal Garg, Akshay Vaishnaw, Amy R. Simon, Karl E. Anderson
Journal: New England Journal of Medicine (2019)

Induction of delta aminolevulinic acid synthase 1 (ALAS1) gene expression and accumulation of neurotoxic intermediates result in neurovisceral attacks and disease manifestations in patients with acute intermittent porphyria, a rare inherited disease of heme biosynthesis. Givosiran is an investigational RNA interference therapeutic agent that inhibits hepatic ALAS1 synthesis.
Predictors of lymphopenia in esophageal cancer patients receiving photon or proton radiation therapy: A dosimetric analysis.
Authors: David M. Routman, Thomas J Whitaker, Courtney N. Day, William S. Harmsen, Michelle A. Neben-Wittich, Michael G. Haddock, Christopher Leigh Hallemeier, Kenneth Merrell
Journal: Journal of Clinical Oncology (2019)

147 Background: Lymphopenia during radiation therapy (RT) has been associated with worse oncologic outcomes in a number of malignancies, including esophageal cancer (EC). No studies to date have investigated specific dosimetric parameters associated with this lymphopenia in EC. We performed an analysis of RT dose to multiple organs at risk (OARs) to investigate associations with grade 4 lymphopenia (G4L). Methods: Consecutive EC patients receiving curative intent chemoradiotherapy +/- surgery between July of 2015 and December of 2017 were included. Lymphocyte nadir was defined as the lowest lymphocyte count during RT. G4L was defined as absolute lymphocyte count &lt;200/mm 3 . Dose to OARs including aorta, body, bone marrow, heart, liver, lung, and spleen were calculated. Univariate logistic regression analyses were performed for each OAR at the 1, 5, 10, 15, 20, 30, 35, 40, and 50 Gy levels with volume receiving dose ‘x’(VxGy) analyzed as a continuous variable per 10% increase. Clinical tumor volume (CTV) and RT modality (photon vs. proton) as well clinical factors including sex, stage (I/II vs. III/IV), age (per 10 year increase), and BMI (per 5 unit increase) were also analyzed. Results: One hundred forty-four pts were identified for inclusion. Seventy-nine pts received photon RT and 65 proton RT. Chemotherapy was weekly carbotaxol (99%). G4L at nadir was 40% overall (56% photon, 22% proton). By organ, body V1-V30Gy (OR 1.45-8.18, p&lt;0.01), heart V1-V30Gy (OR 1.24-1.49, p&lt;0.01), liver V1-V35Gy (OR 1.23-2.75, p&lt;0.01), lung V1-V30Gy (OR 1.26-5.73 p&lt;0.01), and spleen V1-V40Gy (OR 1.26-1.49 p&lt;0.01) were highly associated with G4L whereas dose to aorta and bone marrow were not. Advanced stage (OR, 3.92 p&lt;0.01), photon vs. proton (OR 4.58 p&lt;0.01), and CTV (per 100 cc’s (OR=1.21, p&lt;0.01)) were also associated with G4L. Sex, age, and BMI were not associated with G4L. Conclusions: Low to intermediate dose volumes to OARs including body, spleen, liver, lungs, and heart were associated with G4L. These findings provide rational for the differences seen in rates of G4L for photon versus proton RT.
Single-Cell Profiling Reveals Distinct Tumor Subtypes and Their Associated T-Cell Environments in Follicular Lymphoma
Authors: Xuehai Wang, Deanne Gracias, Michael Nissen, Elizabeth Chavez, Gabriela Cristina Segat, Manabu Kusakabe, Guillermo Simkin, Stepen Grinek, Tomohiro Aoki, Andrew Tran Thien-An Nguyen, Randy D. Gascoyne, David W. Scott, Ryan Brinkman, Christian Steidl, Andrew P. Weng
Journal: Blood (2018)
Novel genetically-modified chimpanzee adenovirus and MVA-vectored respiratory syncytial virus vaccine safely boosts humoral and cellular immunity in healthy older adults
Authors: Christopher A. Green, Charles J. Sande, Elisa Scarselli, Stefania Capone, Alessandra Vitelli, Alfredo Nicosia, Laura Silva-Reyes, Amber J. Thompson, Catherine M. de Lara, Kathryn S. Taylor, Kathryn Haworth, Claire L. Hutchings, Tamsin Cargill, Brian Angus, Paul Klenerman, Andrew J. Pollard
Journal: Journal of Infection (2019)
Imaging and Impact of Myocardial Fibrosis in Aortic Stenosis
Authors: Rong Bing, João L. Cavalcante, Russell J. Everett, Marie-Annick Clavel, David E. Newby, Marc R. Dweck
Journal: JACC. Cardiovascular imaging (2019)

Aortic stenosis is characterized both by progressive valve narrowing and the left ventricular remodeling response that ensues. The only effective treatment is aortic valve replacement, which is usually recommended in patients with severe stenosis and evidence of left ventricular decompensation. At present, left ventricular decompensation is most frequently identified by the development of typical symptoms or a marked reduction in left ventricular ejection fraction <50%. However, there is growing interest in using the assessment of myocardial fibrosis as an earlier and more objective marker of left ventricular decompensation, particularly in asymptomatic patients, where guidelines currently rely on nonrandomized data and expert consensus. Myocardial fibrosis has major functional consequences, is the key pathological process driving left ventricular decompensation, and can be divided into 2 categories. Replacement fibrosis is irreversible and identified using late gadolinium enhancement on cardiac magnetic resonance, while diffuse fibrosis occurs earlier, is potentially reversible, and can be quantified with cardiac magnetic resonance T
A Phase 2 Study of Actinium-225 (225Ac)-Lintuzumab in Older Patients with Previously Untreated Acute Myeloid Leukemia (AML) Unfit for Intensive Chemotherapy
Authors: Laura E. Finn, Moshe Levy, Johnnie J. Orozco, Jae H. Park, Ehab Atallah, Michael Craig, Alexander E. Perl, David A. Scheinberg, Dragan Cicic, Gregory Richard Bergonio, Mark S. Berger, Joseph G. Jurcic
Journal: Blood (2017)
Ten New Cases of Hermansky-Pudlak Syndrome in the Iberian Peninsula: Identification of Novel Genetic Variants in HPS3, HPS4, HPS6 and DTNBP1 Associated with Significant Clinical Complications
Authors: Jose Maria Bastida, Sara Morais, Veronica Palma-Barqueros, Rocio Benito, Nuria Bermejo, Mutlu Karkucak, Maria Trapero-Marugan, Natalia Bohdan, Monica Pereira, Ana Marín-Quílez, Jorge Oliveira, Yusuf Yucel, Rosario Santos, Jose Padilla, Kamila Janusz, Ana Hortal, Vicente Vicente Garcia, Jesús-María Hernández-Rivas, Maria L Lozano, Jose Ramon González-Porras, Margarida Lima, Jose Rivera
Journal: Blood (2018)
Bone Marrow Biopsy Impacts Response Assessment in a Minority of Patients with Follicular Lymphoma and Diffuse Large B-Cell Lymphoma Treated with Immunochemotherapy: Results from the Randomized Phase III GALLIUM and GOYA Trials
Authors: Sarah C. Rutherford, Michael Herold, Wolfgang Hiddemann, Lale Kostakoglu, Robert Marcus, Maurizio Martelli, Laurie H Sehn, Marek Trněný, Judith Trotman, Umberto Vitolo, Tina Nielsen, Federico Mattiello, Deniz Sahin, Gila Sellam, Peter Martin
Journal: Blood (2018)