tbuckley/cabot-search huggingface dataset:
The immunosuppressive activity of artemisinin‐type drugs towards inflammatory and autoimmune diseases
Authors: Thomas Efferth, Franz Oesch
Journal: Medicinal Research Reviews (2021)

The sesquiterpene lactone artemisinin from Artemisia annua L. is well established for malaria therapy, but its bioactivity spectrum is much broader. In this review, we give a comprehensive and timely overview of the literature regarding the immunosuppressive activity of artemisinin-type compounds toward inflammatory and autoimmune diseases. Numerous receptor-coupled signaling pathways are inhibited by artemisinins, including the receptors for interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α), β3-integrin, or RANKL, toll-like receptors and growth factor receptors. Among the receptor-coupled signal transducers are extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), AKT serine/threonine kinase (AKT), mitogen-activated protein kinase (MAPK)/extracellular signal regulated kinase (ERK) kinase (MEK), phospholipase C γ1 (PLCγ), and others. All these receptors and signal transduction molecules are known to contribute to the inhibition of the transcription factor nuclear factor κ B (NF-κB). Artemisinins may inhibit NF-κB by silencing these upstream pathways and/or by direct binding to NF-κB. Numerous NF-κB-regulated downstream genes are downregulated by artemisinin and its derivatives, for example, cytokines, chemokines, and immune receptors, which regulate immune cell differentiation, apoptosis genes, proliferation-regulating genes, signal transducers, and genes involved in antioxidant stress response. In addition to the prominent role of NF-κB, other transcription factors are also inhibited by artemisinins (mammalian target of rapamycin [mTOR], activating protein 1 [AP1]/FBJ murine osteosarcoma viral oncogene homologue [FOS]/JUN oncogenic transcription factor [JUN]), hypoxia-induced factor 1α (HIF-1α), nuclear factor of activated T cells c1 (NF-ATC1), Signal transducers and activators of transcription (STAT), NF E2-related factor-2 (NRF-2), retinoic-acid-receptor-related orphan nuclear receptor γ (ROR-γt), and forkhead box P-3 (FOXP-3). Many in vivo experiments in disease-relevant animal models demonstrate therapeutic efficacy of artemisinin-type drugs against rheumatic diseases (rheumatoid arthritis, osteoarthritis, lupus erythematosus, arthrosis, and gout), lung diseases (asthma, acute lung injury, and pulmonary fibrosis), neurological diseases (autoimmune encephalitis, Alzheimer's disease, and myasthenia gravis), skin diseases (dermatitis, rosacea, and psoriasis), inflammatory bowel disease, and other inflammatory and autoimmune diseases. Randomized clinical trials should be conducted in the future to translate the plethora of preclinical results into clinical practice.
O14-2 Evaluation of comprehensive geriatric assessment in elderly patients with pancreaticobiliary cancer
Authors: Yukari Suzuki, Kei Saito, Yousuke Nakai, Akiyuki Inokuma, Kensaku Noguchi, Sachiko Kanai, Tatsuya Sato, Ryunosuke Hakuta, Kazunaga Ishigaki, Tomotaka Saito, Naminatsu Takahara, Tsuyoshi Hamada, Suguru Mizuno, Hirofumi Kogure, Kazuhiko Koike
Journal: Annals of Oncology (2021)
P48-8 A case of primary lung cancer that led to the diagnosis of SMARCA4-deficient thoracic sarcoid tumor by oncogene panel testing
Authors: Nana Iriguchi, Atsushi Horiike, Tomoyuki Ishiguro, Ryotaro Ohkuma, Shigetoshi Nishihara, Satoshi Matsukuma, Hirotsugu Ariizumi, Reiko Yoshida, Yutaro Kubota, Ryosuke Hanaoka, Satoshi Wada, Junji Tsurutani, Kiyoshi Yoshimura, Toshiko Yamochi, Kengo Takeuchi, Shunji Takahashi, Seigo Nakamura, Takuya Tsunoda
Journal: Annals of Oncology (2021)
Abstract 12614: Endocardial Fibroelastosis is Associated With Morbidity and Mortality in Patients With Small Left Heart Structures Undergoing Biventricular Conversion
Authors: Meaghan J Beattie, Lynn A Sleeper, Minmin Lu, Sarah Teele, Sitaram Emani, Roger E Breitbart, Jesse Esch, Joshua Salvin, Urvi Kapoor, Olubunmi Oladunjoye, Puja Banka
Journal: Circulation (2019)

Introduction: A subset of patients with borderline hypoplastic left-sided structures (BHLSS) may be candidates for single to biventricular conversion (BiVC), but significant long-term morbidity and...
O3-1 A phase II study on the efficacy of nivolumab in patients with cancer of unknown primary (CUP) (NivoCUP)
Authors: Emi Noguchi, Junko Tanizaki, Kohei Akiyoshi, Masanori Toyoda, Hiroki Ueda, Yuichi Takiguchi, Yukinori Ozaki, Yoshihiko Segawa, Shin Takahashi, Yoshiko Okikawa, Yasuhiro Kidera, Kazuya Fukuoka, Yasushi Nakamura, Yasutaka Chiba, Kazuko Sakai, Kan Yonemori, Hironobu Minami, Kazuto Nishio, Kazuhiko Nakagawa, Hidetoshi Hayashi
Journal: Annals of Oncology (2021)
Standard therapy of Mycobacterium avium complex pulmonary disease shows limited efficacy in an open source hollow fibre system that simulates human plasma and epithelial lining fluid pharmacokinetics
Authors: Mike Marvin Ruth, Jelmer Raaijmakers, Erik van den Hombergh, Rob Aarnoutse, Elin M. Svensson, Budi O. Susanto, Ulrika S.H. Simonsson, Heiman Wertheim, Wouter Hoefsloot, Jakko van Ingen
Journal: Clinical Microbiology and Infection (2021)

Mycobacterium avium complex (MAC) bacteria can cause chronic pulmonary disease (PD). Current treatment regimens of azithromycin, ethambutol and rifampicin have culture conversion rates of around 65%. Dynamic, preclinical models to assess the efficacy of treatment regimens are important to guide clinical trial development. The hollow fibre system (HFS) has been applied but reports lack experimental details.We simulated the human pharmacokinetics of azithromycin, ethambutol and rifampicin both in plasma and epithelial lining fluid (ELF) in a HFS, exposing THP-1 cells infected with M. avium to the triple-drug regimen for 3 weeks. We accounted for drug-drug interactions and protein-binding and provide all laboratory protocols. We differentiated the effects on the intracellular and extracellular mycobacterial population.The antibiotic concentrations in the HFS accurately reflected the time to peak concentration (Tmax), the peak concentration (Cmax) and half-life of azithromycin, rifampicin and ethambutol in plasma and ELF reported in literature. We find that plasma drug concentrations fail to hold the MAC bacterial load static (ΔLog10 CFU/mLControl:Regimen = 0.66 ± 0.76 and 0.45 ± 0.28 at 3 and 21 days); ELF concentrations do hold the bacterial load static for 3 days and inhibit bacterial growth for the duration of the experiment (ΔLog10 CFU/mLControl:Regimen = 1.1 ± 0.1 and 1.64 ± 0.59 at 3 and 21 days).In our model, the current therapy against MAC is ineffective, even when accounting for antibiotic accumulation at the site of infection and intracellularly. New treatment regimens need to be developed and be compared with currently recommended regimens in dynamic models prior to clinical evaluation. With the publication of all protocols we aim to open this technology to new users.
National Poliomyelitis Immunization Days-People's Republic of China, 1993
Authors: Yang B, Dai Z, Wang Z, Wang K, Zhang R, Zhang J, Jiang T
Journal: JAMA (1993)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Radiographic Graft Surveillance in Lung Transplantation: Prognostic Role of Parametric Response Mapping
Authors: Elizabeth A. Belloli, Tian Gu, Yizhuo Wang, Dharshan Vummidi, Dennis M. Lyu, Michael P. Combs, Aamer Chughtai, Susan Murray, Craig J. Galbán, Vibha N. Lama
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Chronic lung allograft dysfunction (CLAD) results in significant morbidity after lung transplantation. Potential CLAD occurs when lung function declines to 80-90% of baseline. Better noninvasive tools to prognosticate at potential CLAD are needed. Objectives: To determine whether parametric response mapping (PRM), a computed tomography (CT) voxel-wise methodology applied to high-resolution CT scans, can identify patients at risk of progression to CLAD or death. Methods: Radiographic features and PRM-based CT metrics quantifying functional small airway disease (PRMfSAD) and parenchymal disease (PRMPD) were studied at potential CLAD (n = 61). High PRMfSAD and high PRMPD were defined as ⩾30%. Restricted mean modeling was performed to compare CLAD-free survival among groups. Measurements and Main Results: PRM metrics identified the following three unique signatures: high PRMfSAD (11.5%), high PRMPD (41%), and neither (PRMNormal; 47.5%). Patients with high PRMfSAD or PRMPD had shorter CLAD-free median survival times (0.46 yr and 0.50 yr) compared with patients with predominantly PRMNormal (2.03 yr; P = 0.004 and P = 0.007 compared with PRMfSAD and PRMPD groups, respectively). In multivariate modeling adjusting for single- versus double-lung transplant, age at transplant, body mass index at potential CLAD, and time from transplant to CT scan, PRMfSAD ⩾30% or PRMPD ⩾30% continue to be statistically significant predictors of shorter CLAD-free survival. Air trapping by radiologist interpretation was common (66%), was similar across PRM groups, and was not predictive of CLAD-free survival. Ground-glass opacities by radiologist read occurred in 16% of cases and were associated with decreased CLAD-free survival (P < 0.001). Conclusions: PRM analysis offers valuable prognostic information at potential CLAD, identifying patients most at risk of developing CLAD or death.
Association of a Combination of Healthy Lifestyle Behaviors With Reduced Risk of Incident Systemic Lupus Erythematosus
Authors: May Y. Choi, Jill Hahn, Susan Malspeis, Emma F. Stevens, Elizabeth W. Karlson, Jeffrey A. Sparks, Kazuki Yoshida, Laura Kubzansky, Karen H. Costenbader
Journal: Arthritis & Rheumatology (2021)

While previous studies have demonstrated an association between individual factors related to lifestyle and the risk of systemic lupus erythematosus (SLE), it is unclear how the combination of these factors might affect the risk of incident SLE. This study was undertaken to prospectively evaluate whether a combination of healthy lifestyle factors is associated with a lower risk of incident SLE and its subtypes (anti-double-stranded DNA [anti-dsDNA]-positive and anti-dsDNA-negative SLE).
Epigenetic scarring of exhausted T cells hinders memory differentiation upon eliminating chronic antigenic stimulation
Authors: Mohamed S. Abdel-Hakeem, Sasikanth Manne, Jean-Christophe Beltra, Erietta Stelekati, Zeyu Chen, Kito Nzingha, Mohammed-Alkhatim Ali, John L. Johnson, Josephine R. Giles, Divij Mathew, Allison R. Greenplate, Golnaz Vahedi, E. John Wherry
Journal: Nature Immunology (2021)
International versus national growth charts for identifying small and large-for-gestational age newborns: A population-based study in 15 European countries
Authors: Alice Hocquette, Mélanie Durox, Rachael Wood, Kari Klungsøyr, Katarzyna Szamotulska, Sylvan Berrut, Tonia Rihs, Theopisti Kyprianou, Luule Sakkeus, Aline Lecomte, Irisa Zile, Sophie Alexander, Jeannette Klimont, Henrique Barros, Miriam Gatt, Jelena Isakova, Béatrice Blondel, Mika Gissler, Jennifer Zeitlin
Journal: The Lancet Regional Health - Europe (2021)

To inform the on-going debate about the use of universal prescriptive versus national intrauterine growth charts, we compared perinatal mortality for small and large-for-gestational-age (SGA/LGA) infants according to international and national charts in Europe.We classified singleton births from 33 to 42 weeks of gestation in 2010 and 2014 from 15 countries (N = 1,475,457) as SGA (birthweight <10th percentile) and LGA (>90th percentile) using the international Intergrowth-21st newborn standards and national charts based on the customised charts methodology. We computed sex-adjusted odds ratios (aOR) for stillbirth, neonatal and extended perinatal mortality by this classification using multilevel models.SGA and LGA prevalence using national charts were near 10% in all countries, but varied according to international charts with a north to south gradient (3.0% to 10.1% and 24.9% to 8.0%, respectively). Compared with appropriate for gestational age (AGA) infants by both charts, risk of perinatal mortality was increased for SGA by both charts (aOR[95% confidence interval (CI)]=6.1 [5.6-6.7]) and infants reclassified by international charts from SGA to AGA (2.7 [2.3-3.1]), but decreased for those reclassified from AGA to LGA (0.6 [0.4-0.7]). Results were similar for stillbirth and neonatal death.Using international instead of national charts in Europe could lead to growth restricted infants being reclassified as having normal growth, while infants with low risks of mortality could be reclassified as having excessive growth.InfAct Joint Action, CHAFEA Grant n°801,553 and EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking ConcePTION grant n°821,520. AH received a PhD grant from EHESP.
Nuclear accumulation of CHMP7 initiates nuclear pore complex injury and subsequent TDP-43 dysfunction in sporadic and familial ALS
Authors: Alyssa N. Coyne, Victoria Baskerville, Benjamin L. Zaepfel, Dennis W. Dickson, Frank Rigo, Frank Bennett, C. Patrick Lusk, Jeffrey D. Rothstein
Journal: Science Translational Medicine (2021)

Nuclear accumulation of CHMP7 leads to multiple cellular pathologies that can be mitigated via CHMP7 ASOs in familial and sporadic ALS iPSNs.
PS1-2 Pembrolizumab vs chemotherapy for MSI-high/dMMR metastatic colorectal cancer: Asia subgroup of phase 3 KEYNOTE-177
Authors: Takayuki Yoshino, Tae Won Kim, Wei Peng Yong, Kai-Keen Shiu, Benny Vittrup Jensen, Lars Henrik Jensen, Denis Smith, Rocio Garcia-Carbonero, Julia Alcaide-Garcia, Peter Gibbs, Christelle de la Fouchardiere, Fernando Rivera, Elena Elez, Johanna Bendell, Dung T. Le, Ping Yang, Mohammed Farooqui, Patricia Marinello, Luis A. Diaz, Thierry Andre
Journal: Annals of Oncology (2021)
Abstract 16555: Effect Of Alcohol Consumption On The Risk Of Adverse Events In Atrial Fibrillation
Authors: Chewan Lim, Tae-Hoon Kim, Myung-Jin Cha, Jung Myung Lee, Junbeom Park, Jin-Kyu Park, Ki-woon Kang, Jaemin Shim, Jun Kim, Hyung Wook Park, Eue-keun Choi, Jin-Bae Kim, Young Soo Lee, Boyoung Joung
Journal: Circulation (2019)

Introduction: Although heavy consumption of alcohol is well known to be associated with incident atrial fibrillation (AF), there are a paucity of data on the relationship between alcohol consumptio...
2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: Executive Summary
Authors: Bernard J. Gersh, Barry J. Maron, Robert O. Bonow, Joseph A. Dearani, Michael A. Fifer, Mark S. Link, Srihari S. Naidu, Rick A. Nishimura, Steve R. Ommen, Harry Rakowski, Christine E. Seidman, Jeffrey A. Towbin, James E. Udelson, Clyde W. Yancy
Journal: Circulation (2011)
Undetected carriage explains apparent Staphylococcus aureus acquisition in a non-outbreak healthcare setting
Authors: James R Price, Maho Yokoyama, Kevin Cole, Jonathan Sweetman, Laura Behar, Simon Stoneham, Daire Cantillon, Simon J Waddell, Jonathan Hyde, Ruhina Alam, Derrick Crook, John Paul, Martin J Llewelyn
Journal: Journal of Infection (2021)

ObjectivesPrevious studies have been unable to identify patient or staff reservoirs for the majority of the nosocomial S. aureus acquisitions which occur in the presence of good infection control practice. We set out to establish the extent to which undetected pre-existing carriage explains apparent nosocomial S. aureus acquisition.MethodsOver two years elective cardiothoracic admissions were screened for S. aureus carriage before and during hospital admission. Routine screening (nose/groin/wound sampling), was supplemented by sampling additional body sites (axilla/throat/rectum) and culture-based methods optimised to detect fastidious phenotypes (small colony variants, cell wall deficient variants) and molecular identification by PCR.Results35% of participants (53/151) were S. aureus carriers according to routine pre-healthcare screening; increasing to 42% (63/151) when additional body sites and enhanced cultures were employed. 71% (5/7) of apparent acquisitions were explained by pre-existing carriage using augmented measures. Enhanced culture identified a minority of colonised individuals (3/151 including 1 MRSA carrier) who were undetected by routine and additional screening cultures. 4/14 (29%) participants who became culture-negative during admission had S. aureus genomic material detected at discharge.ConclusionsConventional sampling under-estimates carriage of S. aureus and this explains the majority of apparent S. aureus acquisitions among elective cardiothoracic patients.
Natural killer cell immunosuppressive function requires CXCR3-dependent redistribution within lymphoid tissues
Authors: Ayad Ali, Laura M. Canaday, H. Alex Feldman, Hilal Cevik, Michael T. Moran, Sanjeeth Rajaram, Nora Lakes, Jasmine A. Tuazon, Harsha Seelamneni, Durga Krishnamurthy, Eryn Blass, Dan H. Barouch, Stephen N. Waggoner
Journal: Journal of Clinical Investigation (2021)

NK cell suppression of T cells is a key determinant of viral pathogenesis and vaccine efficacy. This process involves perforin-dependent elimination of activated CD4+ T cells during the first 3 days of infection. Although this mechanism requires cell-cell contact, NK cells and T cells typically reside in different compartments of lymphoid tissues at steady state. Here, we showed that NK cell suppression of T cells is associated with transient accumulation of NK cells within T cell–rich sites of the spleen during lymphocytic choriomeningitis virus infection. The chemokine receptor CXCR3 was required for this relocation and suppression of antiviral T cells. Accordingly, NK cell migration was mediated by type I IFN–dependent promotion of CXCR3 ligand expression. In contrast, adenoviral vectors that weakly induced type I IFN and did not stimulate NK cell inhibition of T cells also did not promote measurable redistribution of NK cells to T cell zones. Exogenous IFN rescued NK cell migration during adenoviral vector immunization. Thus, type I IFN and CXCR3 were critical for properly positioning NK cells to constrain antiviral T cell responses. Development of strategies to curtail migration of NK cells between lymphoid compartments may enhance vaccine-elicited immune responses.
Humoral and cellular immunity to SARS-CoV-2 vaccination in renal transplant versus dialysis patients: A prospective, multicenter observational study using mRNA-1273 or BNT162b2 mRNA vaccine
Authors: Julian Stumpf, Torsten Siepmann, Tom Lindner, Claudia Karger, Jörg Schwöbel, Leona Anders, Robert Faulhaber-Walter, Jens Schewe, Heike Martin, Holger Schirutschke, Kerstin Barnett, Jan Hüther, Petra Müller, Torsten Langer, Thilo Pluntke, Kirsten Anding-Rost, Frank Meistring, Thomas Stehr, Annegret Pietzonka, Katja Escher, Simon Cerny, Hansjörg Rothe, Frank Pistrosch, Harald Seidel, Alexander Paliege, Joachim Beige, Ingolf Bast, Anne Steglich, Florian Gembardt, Friederike Kessel, Hannah Kröger, Patrick Arndt, Jan Sradnick, Kerstin Frank, Anna Klimova, René Mauer, Xina Grählert, Moritz Anft, Arturo Blazquez-Navarro, Timm H Westhoff, Ulrik Stervbo, Torsten Tonn, Nina Babel, Christian Hugo
Journal: The Lancet Regional Health - Europe (2021)

Dialysis and kidney transplant patients are vulnerable populations for COVID-19 related disease and mortality.
Epstein–Barr Virus–Encoded Circular RNA CircBART2.2 Promotes Immune Escape of Nasopharyngeal Carcinoma by Regulating PD-L1
Authors: Junshang Ge, Jie Wang, Fang Xiong, Xianjie Jiang, Kunjie Zhu, Yian Wang, Yongzhen Mo, Zhaojian Gong, Shanshan Zhang, Yi He, Xiayu Li, Lei Shi, Can Guo, Fuyan Wang, Ming Zhou, Bo Xiang, Yong Li, Guiyuan Li, Wei Xiong, Zhaoyang Zeng
Journal: Cancer Research (2021)

Epstein-Barr virus (EBV) infection is an established cause of nasopharyngeal carcinoma (NPC) and is involved in a variety of malignant phenotypes, including tumor immune escape. EBV can encode a variety of circular RNAs (circRNA), however, little is known regarding the biological functions of these circRNAs in NPC. In this study, EBV-encoded circBART2.2 was found to be highly expressed in NPC where it upregulated PD-L1 expression and inhibited T-cell function in vitro and in vivo. circBART2.2 promoted transcription of PD-L1 by binding the helicase domain of RIG-I and activating transcription factors IRF3 and NF-κB, resulting in tumor immune escape. These results elucidate the biological function of circBART2.2, explain a novel mechanism of immune escape caused by EBV infection, and provide a new immunotherapy target for treating NPC. SIGNIFICANCE: This work demonstrates that circBART2.2 binding to RIG-I is essential for the regulation of PD-L1 and subsequent immune escape in nasopharyngeal carcinoma.
FDA: Stop Using Medtronic’s Heartware Ventricular Assist Device
Authors: Bridget M. Kuehn
Journal: JAMA (2021)

After more than 100 complaints of malfunctions involving Medtronic’s Heartware Ventricular Assist Device (HVAD) that resulted in 14 deaths and 13 device removals, the FDA has urged physicians not to use the device. The company simultaneously announced that it had ceased sales and distribution.
Use of endoscopic sleeve to achieve full-thickness endoscopic resection of malignant polyp under direct vision
Authors: Shinya Urakawa, Teijiro Hirashita, Yuka Hirashita, Kentaro Matsuo, Lea Lowenfeld, Jeffrey W. Milsom
Journal: Endoscopy (2021)

Therapeutic decisions for early-stage colon cancer discovered after polypectomy are complex [1]. Surgical colectomy is associated with a low rate of residual cancer, but significant morbidity. In select patients, endoscopic full-thickness resection (EFTR) may be an option [2] [3]. We report EFTR using an endoscopic sleeve (Dilumen; Lumendi) with multiple endoscopic tools.