tbuckley/cabot-search huggingface dataset:
Two waves of coeliac disease incidence in Sweden: a nationwide population-based cohort study from 1990 to 2015
Authors: David Bergman, James King, Benjamin Lebwohl, Mark S Clements, Bjorn Roelstraete, Gilaad G Kaplan, Peter HR Green, Joseph A Murray, Jonas F Ludvigsson
Journal: Gut (2021)

Objectives To assess the incidence of biopsy-verified coeliac disease (CD) in Sweden and examine the incidence of duodenal/jejunal biopsies with normal mucosa over time as a proxy for CD awareness and investigation. Design Nationwide population-based cohort study 1990–2015 based on biopsy reports indicating villous atrophy (VA) or normal mucosa in the duodenum/jejunum. Results We identified 44 771 individuals (63% females) with a biopsy report specifying VA and 412 279 (62% females) with a biopsy report indicating normal mucosa (without a prior biopsy indicating VA). The median age at diagnosis of CD was 28 years. The mean age-standardised incidence rate during the study period was 19.0 per 100 000 person-years (95% CI 17.3 to 20.8). The incidence reached a peak in 1994 for both sexes and a second higher peak in 2002–2003 for females and in 2006 for males. The lifetime risk of developing CD was 1.8% (2.3% in females and 1.4% in males). Prior to 2015, there was a parallel rise in rates for biopsies showing normal duodenal/jejunal mucosa. Conclusions In Sweden, the incidence of CD increased until 2002–2003 in females and until 2006 in males. Since then, the incidence of CD has declined despite increasing duodenal/jejunal biopsies, suggesting that increased awareness and investigation are unlikely to elevate the incidence of the disease in Sweden. Across a lifetime, 1 in 44 females and 1 in 72 males are expected to be diagnosed with CD in Sweden, indicating a relatively high societal burden of disease.
BCMA-Specific ADC MEDI2228 and Daratumumab Induce Synergistic Myeloma Cytotoxicity via IFN-Driven Immune Responses and Enhanced CD38 Expression
Authors: Lijie Xing, Su Wang, Jiye Liu, Tengteng Yu, Hailin Chen, Kenneth Wen, Yuyin Li, Liang Lin, Phillip A. Hsieh, Shih-Feng Cho, Gang An, Lugui Qiu, Krista Kinneer, Nikhil Munshi, Kenneth C. Anderson, Yu-Tzu Tai
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Efforts are required to improve the potency and durability of CD38- and BCMA-based immunotherapies in human multiple myeloma. We here delineated the molecular and cellular mechanisms underlying novel immunomodulatory effects triggered by BCMA pyrrolobenzodiazepine (PBD) antibody drug conjugate (ADC) MEDI2228 which can augment efficacy of these immunotherapies. Experimental Design: MEDI2228-induced transcriptional and protein changes were investigated to define significantly impacted genes and signaling cascades in multiple myeloma cells. Mechanisms whereby MEDI2228 combination therapies can enhance cytotoxicity or overcome drug resistance in multiple myeloma cell lines and patient multiple myeloma cells were defined using in vitro models of tumor in the bone marrow (BM) microenvironment, as well as in human natural killer (NK)-reconstituted NOD/SCID gamma (NSG) mice bearing MM1S tumors. Results: MEDI2228 enriched IFN I signaling and enhanced expression of IFN-stimulated genes in multiple myeloma cell lines following the induction of DNA damage–ATM/ATR-CHK1/2 pathways. It activated cGAS-STING-TBK1-IRF3 and STAT1-IRF1–signaling cascades and increased CD38 expression in multiple myeloma cells but did not increase CD38 expression in BCMA-negative NK effector cells. It overcame CD38 downregulation on multiple myeloma cells triggered by IL6 and patient BM stromal cell-culture supernatant via activation of STAT1-IRF1, even in immunomodulatory drug (IMiD)- and bortezomib-resistant multiple myeloma cells. In vitro and in vivo upregulation of NKG2D ligands and CD38 in MEDI2228-treated multiple myeloma cells was further associated with synergistic daratumumab (Dara) CD38 MoAb-triggered NK-mediated cytotoxicity of both cell lines and autologous drug-resistant patient multiple myeloma cells. Conclusions: These results provide the basis for clinical evaluation of combination MEDI2228 with Dara to further improve patient outcome in multiple myeloma.
Abstract 5765: 3T MRI Molecular Imaging of Benfluorex Treatment of Metabolic Syndrome with {alpha}v{beta}3-Integrin Targeted Nanoparticles
Authors: Kejia Cai, Wenjing Huang, Todd A Williams, Huiying Zhang, Shelton D Caruthers, Gregory M Lanza, Samuel A Wickline, Patrick M Winter
Journal: Circulation (2008)

1.5T MRI with αvβ3-integrin targeted gadolinium nanoparticle contrast agents (NP) can detect stage I atherosclerosis in experimental animals by localizing specifically to inflammatory plaque components within minutes after injection. We hypothesized that NP could serve as an early surrogate biomarker of therapeutic efficacy for benfluorex treatment of metabolic syndrome in diabetic JCR-LA:cp rats on a 3T clinical scanner. Six week old JCR-LA:cp rats (n=6) received benfluorex in their feed (0.069% wt/wt) for 16 weeks, while control animals (n=5) received regular diet. The abdominal aorta was imaged (T1w spin echo) in 4 cross-sections at baseline and 2-hour post-injection (IV, 1.0 ml/kg NP) every 4 wks with a 3.0 T whole-body clinical MRI scanner, and total aortic wall signal was computed across all sections. Treatment of diabetic JCR-LA:cp rats with benfluorex reduced food consumption and body weight (16.0%; p<0.05); and fasting plasma insulin, leptin and triglyceride were decreased by 52.6%, 18.2% and 36....
浅大腿動脈‐深部大腿動脈分岐部のステント留置術 クロスオーバーとステント留置術のみの戦略との比較
Authors: Yamawaki Masahiro, Muramatsu Toshiya, Tsukahara Reiko, Itoh Yoshiaki, Sakai Tsuyoshi, Ishimori Hiroshi, Hirano Keisuke, Nakano Masatsugu, Sasaki Shinya, Araki Motoharu, Moriyama Akiyoshi, Takimura Hideyuki, Sakamoto Yasunari, Komatsu Ikki
Journal: Circulation (2010)
Covid-19: Evidence used to support mass lateral flow testing was flawed, experts say
Authors: Gareth Iacobucci
Journal: BMJ (2021)

<h3>Abstract</h3> Two distinct mechanisms for primordial germ cell (PGC) specification are observed within Bilatera: early determination by maternal factors or late induction by zygotic cues. Here we investigate the molecular basis for PGC specification in <i>Nematostella</i>, a representative pre-bilaterian animal where PGCs arise as paired endomesodermal cell clusters during early development. We first present evidence that the putative PGCs delaminate from the endomesoderm upon feeding, migrate into the gonad primordia, and mature into germ cells. We then show that the PGC clusters arise at the interface between <i>hedgehog1</i> and <i>patched</i> domains in the developing mesenteries and use gene knockdown, knockout and inhibitor experiments to demonstrate that Hh signaling is required for both PGC specification and general endomesodermal patterning. These results provide evidence that the <i>Nematostella</i> germline is specified by inductive signals rather than maternal factors, and support the existence of zygotically-induced PGCs in the eumetazoan common ancestor.
NF‐κB Regulation of LRH‐1 and ABCG5/8 Potentiates Phytosterol Role in the Pathogenesis of Parenteral Nutrition–Associated Cholestasis
Authors: Swati Ghosh, Michael W. Devereaux, Aimee L. Anderson, Sarah Gehrke, Julie A. Reisz, Angelo D’Alessandro, David J. Orlicky, Mark Lovell, Karim C. El Kasmi, Colin T. Shearn, Ronald J. Sokol
Journal: Hepatology (2021)

Background and Aims Chronically administered parenteral nutrition (PN) in patients with intestinal failure carries the risk for developing PN-associated cholestasis (PNAC). We have demonstrated that farnesoid X receptor (FXR) and liver X receptor (LXR), proinflammatory interleukin-1 beta (IL-1β), and infused phytosterols are important in murine PNAC pathogenesis. In this study we examined the role of nuclear receptor liver receptor homolog 1 (LRH-1) and phytosterols in PNAC. Approach and Results In a C57BL/6 PNAC mouse model (dextran sulfate sodium [DSS] pretreatment followed by 14 days of PN; DSS-PN), hepatic nuclear receptor subfamily 5, group A, member 2/LRH-1 mRNA, LRH-1 protein expression, and binding of LRH-1 at the Abcg5/8 and Cyp7a1 promoter was reduced. Interleukin-1 receptor–deficient mice (Il-1r−/−/DSS-PN) were protected from PNAC and had significantly increased hepatic mRNA and protein expression of LRH-1. NF-κB activation and binding to the LRH-1 promoter were increased in DSS-PN PNAC mice and normalized in Il-1r−/−/DSS-PN mice. Knockdown of NF-κB in IL-1β–exposed HepG2 cells increased expression of LRH-1 and ABCG5. Treatment of HepG2 cells and primary mouse hepatocytes with an LRH-1 inverse agonist, ML179, significantly reduced mRNA expression of FXR targets ATP binding cassette subfamily C member 2/multidrug resistance associated protein 2 (ABCC2/MRP2), nuclear receptor subfamily 0, groupB, member 2/small heterodimer partner (NR0B2/SHP), and ATP binding cassette subfamily B member 11/bile salt export pump (ABCB11/BSEP). Co-incubation with phytosterols further reduced expression of these genes. Similar results were obtained by suppressing the LRH-1 targets ABCG5/8 by treatment with small interfering RNA, IL-1β, or LXR antagonist GSK2033. Liquid chromatography–mass spectrometry and chromatin immunoprecipitation experiments in HepG2 cells showed that ATP binding cassette subfamily G member 5/8 (ABCG5/8) suppression by GSK2033 increased the accumulation of phytosterols and reduced binding of FXR to the SHP promoter. Finally, treatment with LRH-1 agonist, dilauroyl phosphatidylcholine (DLPC) protected DSS-PN mice from PNAC. Conclusions This study suggests that NF-κB regulation of LRH-1 and downstream genes may affect phytosterol-mediated antagonism of FXR signaling in the pathogenesis of PNAC. LRH-1 could be a potential therapeutic target for PNAC.
P17-8 Clinical impact of next-generation sequencing in patients with breast cancer: A single institute study
Authors: Kazuki Nozawa, Masaya Hattori, Daiki Takatsuka, Syoko Sakamoto, Yuka Endo, Nanae Horisawa, Yuri Ozaki, Kayoko Sugino, Ayumi Kataoka, Yayoi Adachi, Haruru Kotani, Akiyo Yoshimura, Masataka Sawaki, Hiroji Iwata
Journal: Annals of Oncology (2021)
Efficacy of a novel enhanced-affinity glucocorticoid on ocular symptoms, Fluticasone furoate nasal spray (FFNS) 110 lg once-daily, in grass pollen-sensitive patients
Authors: I Sidorenko, Brigita Šitkauskienė, Rain Jõgi, Wytske Fokkens, Jacqueline van Tongeren, M Faris, A Ellsworth, M Caldwell
Journal: Allergy (2007)
Pulse therapy with vincristine and dexamethasone for childhood acute lymphoblastic leukaemia (CCCG-ALL-2015): an open-label, multicentre, randomised, phase 3, non-inferiority trial
Authors: Wenyu Yang, Jiaoyang Cai, Shuhong Shen, Ju Gao, Jie Yu, Shaoyan Hu, Hua Jiang, Yongjun Fang, Changda Liang, Xiuli Ju, Xuedong Wu, Xiaowen Zhai, Xin Tian, Ningling Wang, Aiguo Liu, Hui Jiang, Runming Jin, Lirong Sun, Minghua Yang, Alex W K Leung, Kaili Pan, Yingchi Zhang, Jing Chen, Yiping Zhu, Hui Zhang, Chunfu Li, Jun J Yang, Cheng Cheng, Chi-Kong Li, Jingyan Tang, Xiaofan Zhu, Ching-Hon Pui
Journal: The Lancet Oncology (2021)
Spinal muscular atrophy: From approved therapies to future therapeutic targets for personalized medicine
Authors: Helena Chaytow, Kiterie M.E. Faller, Yu-Ting Huang, Thomas H. Gillingwater
Journal: Cell Reports Medicine (2021)

Spinal muscular atrophy (SMA) is a devastating childhood motor neuron disease that, in the most severe cases and when left untreated, leads to death within the first two years of life. Recent therapeutic advances have given hope to families and patients by compensating for the deficiency in survival motor neuron (SMN) protein via gene therapy or other genetic manipulation. However, it is now apparent that none of these therapies will cure SMA alone. In this review, we discuss the three currently licensed therapies for SMA, briefly highlighting their respective advantages and disadvantages, before considering alternative approaches to increasing SMN protein levels. We then explore recent preclinical research that is identifying and targeting dysregulated pathways secondary to, or independent of, SMN deficiency that may provide adjunctive opportunities for SMA. These additional therapies are likely to be key for the development of treatments that are effective across the lifespan of SMA patients.
Comprehensive Methylation Analysis in Pediatric Patients with Acute Myeloid Leukemia —the JCCG Study, JPLSG AML-05-
Authors: Genki Yamato, Tomoko Kawai, Norio Shiba, Kentaro Ohki, Yusuke Hara, Nobutaka Kiyokawa, Daisuke Tomizawa, Akira Shimada, Jun Okubo, Myoung-JA Park, Manabu Sotomatsu, Hirokazu Arakawa, Souichi Adachi, Takashi Taga, Keizo Horibe, Kenichiro Hata, Yasuhide Hayashi
Journal: Blood (2017)
Shorter Courses of Antibiotics for Urinary Tract Infection in Men
Authors: Daniel J. Morgan, K. C. Coffey
Journal: JAMA (2021)

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
Unexpected suppression of tumorigenesis by c-MYC via TFAP4-dependent restriction of stemness in B lymphocytes
Authors: Elena Tonc, Yoshiko Takeuchi, Chun Chou, Yu Xia, Melanie Holmgren, Chika Fujii, Saravanan Raju, Gue Su Chang, Masahiro Iwamoto, Takeshi Egawa
Journal: Blood (2021)
Extracellular Vesicles as an Emerging Treatment Option for Intervertebral Disc Degeneration: Therapeutic Potential, Translational Pathways, and Regulatory Considerations
Authors: Tyler J. DiStefano, Keti Vaso, George Danias, Henry N. Chionuma, Jennifer R. Weiser, James C. Iatridis
Journal: Advanced Healthcare Materials (2021)

Emergent approaches in regenerative medicine look toward the use of extracellular vesicles (EVs) as a next-generation treatment strategy for intervertebral disc (IVD) degeneration (IVDD) because of their ability to attenuate chronic inflammation, reduce apoptosis, and stimulate proliferation in a number of tissue systems. Yet, there are no Food and Drug Administration (FDA)-approved EV therapeutics in the market with an indication for IVDD, which motivates this article to review the current state of the field and provide an IVD-specific framework to assess its efficacy. In this systematic review, 29 preclinical studies that investigate EVs in relation to the IVD are identified, and additionally, the regulatory approval process is reviewed in an effort to accelerate emerging EV-based therapeutics toward FDA submission and timeline-to-market. The majority of studies focus on nucleus pulposus responses to EV treatment, where the main findings show that stem cell-derived EVs can decelerate the progression of IVDD on the molecular, cellular, and organ level. The findings also highlight the importance of the EV parent cell's pathophysiological and differentiation state, which affects downstream treatment responses and therapeutic outcomes. This systematic review substantiates the use of EVs as a promising cell-free strategy to treat IVDD and enhance endogenous repair.
Functional immune cell–astrocyte interactions
Authors: Liliana M. Sanmarco, Carolina M. Polonio, Michael A. Wheeler, Francisco J. Quintana
Journal: The Journal of Experimental Medicine (2021)

Astrocytes are abundant glial cells in the central nervous system (CNS) that control multiple aspects of health and disease. Through their interactions with components of the blood–brain barrier (BBB), astrocytes not only regulate BBB function, they also sense molecules produced by peripheral immune cells, including cytokines. Here, we review the interactions between immune cells and astrocytes and their roles in health and neurological diseases, with a special focus on multiple sclerosis (MS). We highlight known pathways that participate in astrocyte crosstalk with microglia, NK cells, T cells, and other cell types; their contribution to the pathogenesis of neurological diseases; and their potential value as therapeutic targets.
MO19-5 The association between prices and clinical benefit of approved drugs for solid tumors in Japan
Authors: Yuki Matsubara, Kazunori Honda, Takatsugu Ogata, Taiko Nakazawa, Kyoko Kato, Kazuki Nozawa, Yukiya Narita, Toshiki Masuishi, Hideaki Bando, Shigenori Kadowaki, Masashi Ando, Kei Muro
Journal: Annals of Oncology (2021)
Recent ultra-rare inherited variants implicate new autism candidate risk genes
Authors: Amy B. Wilfert, Tychele N. Turner, Shwetha C. Murali, PingHsun Hsieh, Arvis Sulovari, Tianyun Wang, Bradley P. Coe, Hui Guo, Kendra Hoekzema, Trygve E. Bakken, Lara H. Winterkorn, Uday S. Evani, Marta Byrska-Bishop, Rachel K. Earl, Raphael A. Bernier, Xueya Zhou, Pamela Feliciano, Jacob Hall, Irina Astrovskaya, Simon Xu, Chang Shu, Joseph Obiajulu, Leo Brueggeman, Jessica Wright, Olena Marchenko, Chris Fleisch, Timothy S. Chang, LeeAnne Green Snyder, Sarah D. Barns, Bing Han, William Harvey, Andrew Nishida, Ryan Doan, Aubrey Soucy, Brian J. O’Roak, Timothy W. Yu, Daniel Geschwind, Jacob Michaelson, Natalia Volfovsky, Yufeng Shen, Wendy K. Chung, Michael C. Zody, Evan E. Eichler
Journal: Nature Genetics (2021)
Phase II study of ET-743 in advanced soft-tissue sarcoma (ASTS) in adult: A STBSG-EORTC trial
Authors: A Le Cesne, I Judson, J Radford, JY Blay, A Van Oosterom, S Rodenhuis, P Lorigan, ED Di Paola, J Jimeno, J Verweij
Journal: Annals of Oncology (2000)
P-181 Exploratory randomized phase II trial for optimizing treatment dosage and duration of adjuvant S-1 plus oxaliplatin in patients with stage III colon cancer (SOAP trial)
Authors: Y. Suwa, J. Watanabe, H. Suwa, M. Ozawa, M. Momiyama, A. Ishibe, N. Sugano, S. Yamagishi, M. Ota, H. Sekido, Y. Saigusa, I. Endo
Journal: Annals of Oncology (2021)
MO29-5 RELAY+: Exploratory study of RAM+GEF in untreated patients with EGFR M+ NSCLC: Updates on efficacy, safety and biomarker
Authors: Makoto Nishio, Kazuto Nishio, Martin Reck, Edward B. Garon, Fumio Imamura, Tomoya Kawaguchi, Hiroyuki Yamaguchi, Satoshi Ikeda, Katsuya Hirano, Carla Visseren-Grul, Matteo Ceccarelli, Sameera R. Wijayawardana, Annamaria Zimmermann, Gosuke Homma, Tomoko Matsui, Sotaro Enatsu, Kazuhiko Nakagawa
Journal: Annals of Oncology (2021)
Abstract 14114: Evaluation for Predicting the Risk of In-Hospital Mortality in Patients With Acute Myocardial Infarction Using Multicenter Registry Database in Japan
Authors: Hiroyuki Yokoyama, Junichi Kotani, Masahiro Suzuki, Teruo Shiraki, Hiromi Matubara, Hideo Kusuoka
Journal: Circulation (2011)

Objectives: There was no established measurement of in-hospital mortality for acute myocardial infarction (AMI) in Japan. We investigate to develop and validate the risk adjustment in-hospital mort...
MO2-5 Impact of pre-treatment AXL expression on EGFR-TKI efficacy in EGFR-mutated non-small cell lung cancer patients
Authors: Akihiro Yoshimura, Tadaaki Yamada, Shinji Atagi, Hirokazu Taniguchi, Kyoichi Kaira, Isao Matsumoto, Satoshi Watanabe, Satoru Miura, Takeshi Kitazaki, Hiroyuki Yamaguchi, Junji Uchino, Koichi Takayama, Seiji Yano
Journal: Annals of Oncology (2021)
Endoscopic submucosal dissection followed by laparoscopic collection of a giant duodenal lipoma causing repeated pancreatitis
Authors: Takaya Shimura, Tomotaka Okubo, Yusuke Okuda, Hiroyasu Iwasaki, Takahito Katano, Akihisa Kato, Hiromi Kataoka
Journal: Endoscopy (2021)

A 53-year-old woman underwent laparoscopic cholecystectomy for suspected gallstone pancreatitis. However, pancreatitis occurred every few months even after cholecystectomy. Fluoroscopic and endoscopic images showed a giant submucosal tumor approximately 6 cm in size. The stalk originated from the para-ampulla in the second portion of the duodenum and the tumor head was located in the proximal jejunum over the ligament of Treitz ([Fig. 1], [Fig. 2]). Computed tomography revealed a giant lipoma extending from the third portion of the duodenum to the proximal jejunum, and the ampulla and pancreas head were pulled and deviated to the third portion by the giant lipoma ([Fig. 3]). We suspected that the repeated pancreatitis might be caused by the mechanical traction of the giant duodenal lipoma.
i2dash: Creation of Flexible, Interactive, and Web-Based Dashboards for Visualization of Omics Data
Authors: Arsenij Ustjanzew, Jens Preussner, Mette Bentsen, Carsten Kuenne, Carsten Looso
Journal: Genomics Proteomics & Bioinformatics (2021)

Data visualization and interactive data exploration are important aspects of illustrating complex concepts and results from analyses of omics data. A suitable visualization has to be intuitive and accessible. Web-based dashboards have become popular tools for the arrangement, consolidation, and display of such visualizations. However, the combination of automated data processing pipelines handling omics data and dynamically generated, interactive dashboards is poorly solved. Here, we present i2dash, an R package intended to encapsulate functionality for the programmatic creation of customized dashboards. It supports interactive and responsive (linked) visualizations across a set of predefined graphical layouts. i2dash addresses the needs of data analysts/software developers for a tool that is compatible and attachable to any R-based analysis pipeline, thereby fostering the separation of data visualization on one hand and data analysis tasks on the other hand. In addition, the generic design of i2dash enables the development of modular extensions for specific needs. As a proof of principle, we provide an extension of i2dash optimized for single-cell RNA sequencing analysis, supporting the creation of dashboards for the visualization needs of such experiments. Equipped with these features, i2dash is suitable for extensive use in large-scale sequencing/bioinformatics facilities. Along this line, we provide i2dash as a containerized solution, enabling a straightforward large-scale deployment and sharing of dashboards using cloud services. i2dash is freely available via the R package archive CRAN (https://CRAN.R-project.org/package=i2dash).