tbuckley/cabot-search huggingface dataset:
Abstract 202: Emergence and Characterization of Premature Acute Coronary Syndrome in Young Adults with a Confirmed History of Kawasaki Disease in Japan: Clinical and Mechanistic Insight.
Authors: Yoshihide Mitani, Etsuko Tsuda, Hitoshi Kato, Shunichi Ogawa, Takashi Higaki, Toshiki Sawai, Yoshiaki Murase, Masako Fujiwara, Yosikazu Nakamura, Kei Takahashi, Mamoru Ayusawa, Tohru Kobayashi, Fukiko Ichida, Masaki Matsushima, Masahiro Kamada, Kenji Suda, Hiroyuki Ohashi, Hirofumi Sawada, Hiroyoshi Yokoi, Kenji Hamaoka
Journal: Circulation (2015)

Background: Sporadic cases of acute coronary syndrome (ACS) have been reported in adults with coronary sequelae presumably due to Kawasaki disease (KD). However, ACS in adults with a confirmed (whether followed-up or lost to follow-up) as well as unconfirmed history of KD is poorly characterized. Methods: To investigate ACS in such adults after KD during 2000-10, a nationwide survey was conducted in Japan. Results: A total of 67 patients (median age 35 yo, male 76%) were recruited. A diagnosis of KD was made in 32 during acute illness (Group A), in which 17 were lost to follow up. A KD diagnosis was made retrospectively in the other 35 patients from coronary imaging at ACS (Group B). Overall, 67 patients were characterized by demonstrable thrombosis (74%) as well as the presence of giant aneurysms (GAN) (≥8mm) (38%), severe stenosis (&gt;75%) (38%) and IVUS-derived calcification (92%) in culprit lesions. Group A represented younger age at ACS (26.5 yo vs. 40 yo in group B, p&lt;.001), lower conventional coronary risks (87% vs 65%, p=.043), low percentage of severe stenosis (25% vs. 50%, p=.302) and high proportion of IVUS-derived calcification (86% vs. 100%, p=.335). In group A, patients who were followed up before ACS represented a higher proportion of GAN in culprit lesions (69% vs. 29% in KD patients lost to follow up, p=.030) as well as a shorter interval from acute KD (20 y vs. 27 y, p=.008) and higher percentage of medication before ACS (87% vs. 0%, p&lt;.001). In the convalescence of acute KD in group A, the vessel size of prospective culprit lesion was 6.0-7.9mm in 36% and ≥8mm in 64%. Coronary angio, IVUS and MDCT of cases in 3 categories are presented. Conclusions: Premature ACS in young adults with a confirmed history of KD, significant coronary sequelae just after acute KD and low coronary risks is emerging in Japan. ACS in this population comprises two subtypes: ACS with GAN in culprit lesions in adults followed up for KD, as in childhood myocardial infarction in KD, and ACS in adults lost to follow up, characterized by the absence of GAN or severe stenosis and the presence of IVUS-derived calcification in culprit lesions, which was unmasked in this population. The present findings may give an insight into mechanisms in ACS, screening and medication, as well as recognition of KD in adulthood.
Abstract 12442: Hypercholesterolemia and Angiotensin II Induces Spontaneous Atherothrombotic Occlusion of balloon-injured Rabbit Iliac Arteries; Effects of Lipid-Lowering Therapies
Authors: Katsuya Honda
Journal: Circulation (2015)

Background: Atherothrombotic occlusion of a coronary artery with an intact fibrous cap is a major cause of acute coronary syndrome that is attributed to plaque erosion. We developed an animal model of spontaneous atherothrombotic occlusion of fibrous cap-intact arteries in rabbits. Methods and Results: We performed balloon injury in bilateral iliofemoral arteries in male Japanese white rabbits fed with high (2 %) cholesterol diet and infused with angiotensin II (50 ng/kg/min). Animals were divided into 3 groups; 1. no treatment, 2. Ezetimibe 0.6 mg/kg/day, and 3. Rosuvastatin 1.0 mg/kg/day. We examined the occurrence of atherothrombosis by high-resolution ultrasonograpy (Vevo2100) 3 times/week. (Fig. A) After the occurrence of acute thrombotic occlusion, the presence of thrombosis was confirmed by angiographic and histopathologic examination. Histochemical analysis in the atherothrombotic sites revealed; 1) no severe stenosis (% stenosis: 49±7), 2) no plaque rupture or lipid core, and 3) no PECAM1-positive endothelial layer. Interestingly, there were smooth muscle-like cells (αSMA+/SM1, SM2, SMemb and calponin-) with tissue factor expression at the neointima-thrombus interface. Oral treatment with Ezetimibe but not Rosuvastatin significantly reduced the incidence of atherothrombotic occlusion (Fig. B). Serum from the model rabbits induced TF in cultured rat smooth muscle cells. TF induction by serum from Ezetimibe-treated rabbits was significantly less compared with those from animals without treatment or with Rosuvastatin treatment (Fig. C). Conclusions: We established for the first time an appropriate animal model of spontaneous atherothromobotic occlusion in rabbits, which mimicked the pathological features of plaque erosion observed in human coronary arteries. This model may provide a clue to a mechanistic understanding and potential therapeutic approaches for plaque erosion.
Defining Target Vancomycin Trough Concentrations for Treating <i>Staphylococcus aureus</i> Infection in Infants Aged 0 to 90 Days
Authors: Amanda Gwee, Noel Cranswick, Brendan McMullan, Srinivas Bolisetty, Rodney W. Hunt, Nigel Curtis, Stephen B. Duffull
Journal: JAMA Pediatrics (2019)

This study analyzes data from a randomized clinical trial in infants 90 days and younger to develop a pharmacokinetic model to aid physicians in maintaining minimum inhibitory concentrations of vancomycin in young infants with Staphylococcus aureus infection.
Cancer Genome Interpreter annotates the biological and clinical relevance of tumor alterations
Authors: David Tamborero, Carlota Rubio-Perez, Jordi Deu-Pons, Michael P. Schroeder, Ana Vivancos, Ana Rovira, Ignasi Tusquets, Joan Albanell, Jordi Rodon, Josep Tabernero, Carmen de Torres, Rodrigo Dienstmann, Abel Gonzalez-Perez, Nuria Lopez-Bigas
Journal: Genome Medicine (2018)

While tumor genome sequencing has become widely available in clinical and research settings, the interpretation of tumor somatic variants remains an important bottleneck. Here we present the Cancer Genome Interpreter, a versatile platform that automates the interpretation of newly sequenced cancer genomes, annotating the potential of alterations detected in tumors to act as drivers and their possible effect on treatment response. The results are organized in different levels of evidence according to current knowledge, which we envision can support a broad range of oncology use cases. The resource is publicly available at http://www.cancergenomeinterpreter.org .
Global Quantitative Mapping of Enhancers in Rice by STARR-Seq
Authors: Jialei Sun, Na He, Longjian Niu, Yingzhang Huang, Wei Shen, Yuedong Zhang, Li Li, Chunhui Hou
Journal: Genomics Proteomics & Bioinformatics (2019)

Abstract Enhancers activate transcription in a distance-, orientation-, and position-independent manner, which makes them difficult to be identified. Self-transcribing active regulatory region sequencing (STARR-seq) measures the enhancer activity of millions of DNA fragments in parallel. Here we used STARR-seq to generate a quantitative global map of rice enhancers. Most enhancers were mapped within genes, especially at the 5′ untranslated regions (5′UTR) and in coding sequences. Enhancers were also frequently mapped proximal to silent and lowly-expressed genes in transposable element (TE)-rich regions. Analysis of the epigenetic features of enhancers at their endogenous loci revealed that most enhancers do not co-localize with DNase I hypersensitive sites (DHSs) and lack the enhancer mark of histone modification H3K4me1. Clustering analysis of enhancers according to their epigenetic marks revealed that about 40% of identified enhancers carried one or more epigenetic marks. Repressive H3K27me3 was frequently enriched with positive marks, H3K4me3 and/or H3K27ac, which together label enhancers. Intergenic enhancers were also predicted based on the location of DHS regions relative to genes, which overlap poorly with STARR-seq enhancers. In summary, we quantitatively identified enhancers by functional analysis in the genome of rice, an important model plant. This work provides a valuable resource for further mechanistic studies in different biological contexts.
SP0168 US FOR SYNOVIAL BIOPSIES – CLINICAL RELEVANCE AND SAFETY + DEMO
Authors: Andrew Filer
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> The introduction of ultrasound guidance to access synovial tissue samples has facilitated a rapid growth in tissue-related research. Ultrasound guidance enables operators to use less invasive approaches compared to a gold standard direct vision arthroscopy procedure while maintaining the quality of samples obtained. Patients find the procedures easy to tolerate and are willing to undergo repeat biopsy, facilitating the analysis of tissue samples in clinical trials and experimental medicine studies. Advanced analytic techniques including single cell analytics are now being used to exploit the tissue samples obtained in order to provide dramatic leaps in understanding of synovial pathology. <h3>Objectives:</h3> In this session the key aspects of the dominant techniques in use will be presented, including safety, patient tolerability and quality of output. The research and clinical utility of synovial biopsy will be discussed. Sonographic approaches to the major techniques will then be illustrated through video demonstrations, and competencies required to undertake training will be discussed alongside current EULAR initiatives for training. Finally, examples of research outputs generated through synovial biopsy will be explored alongside the logistics required to deliver such clinical studies. <h3>Disclosure of Interests:</h3> None declared
Microbiota therapy acts via a regulatory T cell MyD88/RORγt pathway to suppress food allergy
Authors: Azza Abdel-Gadir, Emmanuel Stephen-Victor, Georg K. Gerber, Magali Noval Rivas, Sen Wang, Hani Harb, Leighanne Wang, Ning Li, Elena Crestani, Sara Spielman, William Secor, Heather Biehl, Nicholas DiBenedetto, Xiaoxi Dong, Dale T. Umetsu, Lynn Bry, Rima Rachid, Talal A. Chatila
Journal: Nature Medicine (2019)
Prevalence of Chronic Pain and High-Impact Chronic Pain in Cancer Survivors in the United States
Authors: Changchuan Jiang, Haowei Wang, Qian Wang, Yiming Luo, Robert Sidlow, Xuesong Han
Journal: JAMA Oncology (2019)

This survey study uses data from the National Health Interview Survey to investigate the prevalence of, and socioeconomic risk factors for, chronic pain and high-impact chronic pain among cancer survivors in the United States.
c-Myc steers translation in lymphoma
Authors: Marie Cargnello, Ivan Topisirovic
Journal: The Journal of Experimental Medicine (2019)

Members of the MYC family of oncogenes are master regulators of mRNA translation. In this issue of JEM, Singh et al. (https://doi.org/10.1084/jem.20181726) demonstrate that c-Myc governs protein synthesis in lymphoma cells by interfering with SRSF1- and RBM42-mediated suppression of mRNA translation and by altering selection of translation initiation sites.
SAT0231 AGE AND THE CLINICAL FEATURES OF ADULT IGA VASCULITIS
Authors: Alojzija Hocevar, Jaka Ostrovrsnik, Ziga Rotar, Matija Tomsic
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> IgA vasculitis (IgAV) is a common vasculitis of adult population, yet the disease in adults is still poorly defined. <h3>Objectives</h3> The aim of our study was to evaluate the potential influence of age on the presentation of adult IgAV. <h3>Methods</h3> We analyzed medical records of adult, histologically proven IgAV cases, diagnosed and followed at our secondary/tertiary rheumatology center between January 2010 and December 2018. We stratified IgAV cases into four groups, based on the patient age at presentation (18-39, 40-59, 60-79 and ≥80 years). The clinical features were compared between the groups. <h3>Results</h3> During the 108-month observation period we identified 265 new IgAV cases (60.0% males, median (IQR) age 64 (45–77) years). Skin, joint, gastrointestinal tract (GIT) and renal involvement developed in 265, 103 (38.9%), 80 (30.2%), and 118 (44.5%) cases, respectively. Younger adults (≤40 years) more frequently reported an infection prior to IgAV, and developed arthritis or GIT involvement. Severe renal involvement was less common under the age of 40 years. The incidence of skin limited IgAV and of necrotic purpura increased with patient age. Follow-up data were available for 189 patients. During a median (IQR) follow-up of 12 (6–24) months, 29 (15.3%) patients relapsed. Relapsing disease was more frequent in younger adults (≤40 years), compared to older ones. Data on age related variations in the clinical presentation of IgAV are presented in Table 1. <h3>Conclusion</h3> We found subtle age related differences in the presentation and during follow up of adult IgAV. <h3>Disclosure of Interests</h3> None declared
ESAT-6 modulates Calcimycin-induced autophagy through microRNA-30a in mycobacteria infected macrophages
Authors: Assirbad Behura, Abtar Mishra, Saurabh Chugh, Shradha Mawatwal, Ashish Kumar, Debraj Manna, Amit Mishra, Ramandeep Singh, Rohan Dhiman
Journal: Journal of Infection (2019)
Reconciling the Discrepancies in Medicine's Relationship to Medical Marijuana
Authors: Russell Kamer
Journal: Annals of Internal Medicine (2019)

Letters18 June 2019Reconciling the Discrepancies in Medicine's Relationship to Medical MarijuanaRussell Kamer, MDRussell Kamer, MDNew York Medical College, White Plains, New York (R.K.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L19-0150 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Braun and Tulsky's commentary (1) continues the trend of normalizing marijuana use even though its safety and efficacy have not been proved. Like many cannabis activists, the authors reference the medicinal use of marijuana in the early 1900s. Heroin and cocaine also were readily available as patent medicines, but this does not generate a rationale to revisit their therapeutic use. The authors' history lesson does not support use of marijuana as medicine but instead serves as a reminder of the progress of medical practice. We now take for granted that the U.S. Food and Drug Administration certifies ...References1. Braun I, Tulsky J. Reconciling the discrepancies in medicine's relationship to medical marijuana. Ann Intern Med. 2018;169:646-7. [PMID: 30285072]. doi:10.7326/M18-1883 LinkGoogle Scholar2. Duke Integrative Medicine. What is Integrative Medicine? 2019. Accessed at www.dukeintegrativemedicine.org/about/what-is-integrative-medicine on 18 November 2018. Google Scholar3. Downs R. Feds approve marijuana imports from Canada for medical research. United Press International. 19 September 2018. Accessed at www.upi.com/Feds-approve-marijuana-imports-from-Canada-for-medical-research/6801537413569 on 18 November 2018. Google Scholar4. The Editorial Board. An opioid crisis foretold. The New York Times. 21 April 2018. Accessed at www.nytimes.com/2018/04/21/opinion/an-opioid-crisis-foretold.html on 18 November 2018. Google Scholar Author, Article, and Disclosure InformationAffiliations: New York Medical College, White Plains, New York (R.K.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/Forms.do?msNum=L19-0150. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoReconciling the Discrepancies in Medicine's Relationship to Medical Marijuana Ilana Braun and James Tulsky Metrics 18 June 2019Volume 170, Issue 12Page: 906-907KeywordsCannabisDrug administrationDrugsHeroinHistory of medicineMarijuanaMelatoninOpioidsResearch laboratoriesSafety ePublished: 18 June 2019 Issue Published: 18 June 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
PB2254 QUALITY OF LIFE AND DEMOGRAPHICS OF PATIENTS WITH IMMUNE THROMBOCYTOPENIA (ITP); DATA FROM THE PLATELET DISORDER SUPPORT ASSOCIATION (PDSA) PATIENT REGISTRY
Authors: A. Kruse, C. Kruse, N. Potthast, V. Boulanger, A. Seebald, S. Rossov, K. Milligan
Journal: HemaSphere (2019)

Background: Patients with the autoimmune disease ITP suffer from bleeding events as a result of low platelet counts. These events may manifest as bruises, petechiae, blood blisters, bloody stools, blood in urine, or even bleeding in the brain. Treatments vary by severity of disease but include medications (steroids, immunosuppressants, IVIG, TPO‐receptor agonists) and splenectomy. Both the disease and the treatments themselves impact quality of life for these patients, who commonly state concerns of anxiety and fatigue. Aims: In 2017, PDSA in collaboration with NORD launched the ITP Natural History Registry to understand patient characteristics, their disease, disease management, and quality of life. Here, we describe the demographics and quality of life for registrants to date. Methods: The PDSA Registry contains 6 surveys covering patient demographics, medical and diagnostic information, treatment utilization, disease progression, and quality of life. As of February 2019, 538 patients have completed 1,975 surveys. Results: Patients in the registry are mostly white (89%, 470/528), female (76%, 399/528), and reside in the US. 34% (170/499) of patients have Medicare, Medicaid, or both, while 62% (311/499) have commercial insurance. Average (median) age at diagnosis was 32 (31) years with 25% (125/502) younger than 18 years. Time from onset of symptoms to diagnosis was more than one year for 32% (169/528) of patients. In response to specific questions regarding anxiety and fatigue, 11% (32/285) of patients stated they were often or always feeling like they needed help for their anxiety and 36% (99/277) said that their fatigue bothered them quite a bit or very much. Of the 538 registrants, 288 provided data on treatment and 27% (78/288) indicated receiving a splenectomy. For patients who received a splenectomy, quality of life was rated as poor to fair for 23% (18/78) of patients. For patients who had not had a splenectomy, 19% (40/210) rated their quality of life as poor to fair, which is improved but not statistically different from the splenectomy group (z = 0.758, p = 0.447). Summary/Conclusion: Respondents in the PDSA ITP Natural History Registry are predominantly female, white, and diagnosed while young, with a fourth of patients under 18 at time of diagnosis. Disease awareness is suboptimal as indicated by the prolonged time to diagnosis, &gt;1 year, for a third of registrants. QoL is impacted in patients with ITP with it directionally worse, though not significantly different, for those who have had a splenectomy compared to those without. Data collection continues through the registry with the intent of raising disease awareness and understanding the impact of the disease.
Cooperation between Constitutive and Inducible Chemokines Enables T Cell Engraftment and Immune Attack in Solid Tumors
Authors: Denarda Dangaj, Marine Bruand, Alizée J. Grimm, Catherine Ronet, David Barras, Priyanka A. Duttagupta, Evripidis Lanitis, Jaikumar Duraiswamy, Janos L. Tanyi, Fabian Benencia, Jose Conejo-Garcia, Hena R. Ramay, Kathleen T. Montone, Daniel J. Powell, Phyllis A. Gimotty, Andrea Facciabene, Donald G. Jackson, Jeffrey S. Weber, Scott J. Rodig, Stephen F. Hodi, Lana E. Kandalaft, Melita Irving, Lin Zhang, Periklis Foukas, Sylvie Rusakiewicz, Mauro Delorenzi, George Coukos
Journal: Cancer Cell (2019)
Progression of Early Atherosclerosis and Intake of Vitamin C and Vitamin E from Supplements and Food. The <i>Los Angeles Atherosclerosis Study</i>
Authors: James H Dwyer, C. Noel Bairey Merz, Anne M Shirocre, Cheryl K Nordstrom, Kathleen M Dwyer
Journal: Circulation (2001)

P77 Background. In a previous report on antioxidant intake and 1.5 year progression of carotid intima-media thickness (IMT), we reported the unexpected finding that intake of vitamin C supplements was associated with increased IMT progression. The current paper extends those analyses to 3 years of follow-up. Methods. The cohort of 573 employed women and men was aged 40-60 years and free of CVD at entry. Common carotid IMT (by B-mode ultrasound), supplement intake (by questionnaire) and food intake (by 24-hr recalls) were measured over 3 examinations at 1.5 year intervals. IMT progression at the follow-ups (microns per year) was regressed on intake of antioxidants from different sources (average of baseline and 1.5 year follow-up) in a repeated measures model. Results. IMT progressed an average of 10.0 μm/yr (SD=16.5) among the 500 (87%) members of the cohort with follow-up. After adjustment for CVD risk factors, energy intake, and antioxidant intake from other sources, IMT progression (mean±SE) increased from 7.6±1.8 μm/yr among persons reporting no intake of vitamin C supplements to 20.3±2.6 μm/yr in the highest quartile of vitamin C supplement intake (≥857 mg/day)(p-trend=0.0005). In contrast, IMT progression declined from 10.2±1.4 μm/yr among persons reporting no intake of vitamin E supplements to 1.5±2.8 μm/yr among those in the highest quartile of vitamin E supplement intake (≥443 IU/day)(p-trend=0.02). Reduced progression was observed only in this top quartile of vitamin E supplement intake. Smaller reductions in IMT progression were also observed for high intake of vitamin C from food (indicative of a diet rich in fruits and vegetables) and intake of multiple vitamins (≥ 1 tablet/wk). Vitamin E from food was not associated with IMT progression. Conclusion. Vitamin C supplements may promote early atherosclerosis at higher doses, while vitamin E supplement intake above 450 IU/day may block early atherosclerotic progression. Our findings suggest that completed trials of vitamin E and CHD may have failed to detect benefits because of insufficient dose and intervention at later, rather than earlier, stages of disease.
HIV-specific humoral immune responses by CRISPR/Cas9-edited B cells
Authors: Harald Hartweger, Andrew T. McGuire, Marcel Horning, Justin J. Taylor, Pia Dosenovic, Daniel Yost, Anna Gazumyan, Michael S. Seaman, Leonidas Stamatatos, Mila Jankovic, Michel C. Nussenzweig
Journal: The Journal of Experimental Medicine (2019)

A small number of HIV-1–infected individuals develop broadly neutralizing antibodies to the virus (bNAbs). These antibodies are protective against infection in animal models. However, they only emerge 1–3 yr after infection, and show a number of highly unusual features including exceedingly high levels of somatic mutations. It is therefore not surprising that elicitation of protective immunity to HIV-1 has not yet been possible. Here we show that mature, primary mouse and human B cells can be edited in vitro using CRISPR/Cas9 to express mature bNAbs from the endogenous Igh locus. Moreover, edited B cells retain the ability to participate in humoral immune responses. Immunization with cognate antigen in wild-type mouse recipients of edited B cells elicits bNAb titers that neutralize HIV-1 at levels associated with protection against infection. This approach enables humoral immune responses that may be difficult to elicit by traditional immunization.