tbuckley/cabot-search huggingface dataset:
Age Dependency of the Prognostic Impact of Tumor Genomics in Localized Resectable <i>MYCN</i>-Nonamplified Neuroblastomas. Report From the SIOPEN Biology Group on the LNESG Trials and a COG Validation Group
Authors: Inge M. Ambros, Gian-Paolo Tonini, Ulrike Pötschger, Nicole Gross, Véronique Mosseri, Klaus Beiske, Ana P. Berbegall, Jean Bénard, Nick Bown, Huib Caron, Valérie Combaret, Jerome Couturier, Raffaella Defferrari, Olivier Delattre, Marta Jeison, Per Kogner, John Lunec, Barbara Marques, Tommy Martinsson, Katia Mazzocco, Rosa Noguera, Gudrun Schleiermacher, Alexander Valent, Nadine Van Roy, Eva Villamon, Dasa Janousek, Ingrid Pribill, Evgenia Glogova, Edward F. Attiyeh, Michael D. Hogarty, Tom F. Monclair, Keith Holmes, Dominique Valteau-Couanet, Victoria Castel, Deborah A. Tweddle, Julie R. Park, Sue Cohn, Ruth Ladenstein, Maja Beck-Popovic, Bruno De Bernardi, Jean Michon, Andrew D. J. Pearson, Peter F. Ambros
Journal: Journal of Clinical Oncology (2020)

For localized, resectable neuroblastoma without
Truncated HDAC9 identified by integrated genome-wide screen as the key modulator for paclitaxel resistance in triple-negative breast cancer
Authors: Bi Lian, Yu-Chen Pei, Yi-Zhou Jiang, Meng-Zhu Xue, Da-Qiang Li, Xiao-Guang Li, Yi-Zi Zheng, Xi-Yu Liu, Feng Qiao, Wei-Li Sun, Hong Ling, Min He, Ling Yao, Xin Hu, Zhi-Ming Shao
Journal: Theranostics (2020)

Rationale: Paclitaxel resistance is a major concern when treating triple-negative breast cancer (TNBC) patients. We aimed to identify candidates causing paclitaxel resistance and explore their significance in TNBC therapeutics. Methods: A genome-wide CRISPR screening, integrated with transcriptome analyses, was performed to identify candidates involved in paclitaxel-resistant TNBCs. Cell proliferation, cytotoxicity, immunofluorescent staining, and xenograft assays were conducted to verify the phenotypes of paclitaxel resistance induced by candidate genes, both in vitro and in vivo. RNA sequencing, Western blotting, and chromatin immunoprecipitation assays were used to explore the underlying mechanisms. Results: MEF2-interacting transcriptional repressor (MITR), the truncated isoform of histone deacetylase 9 (HDAC9) lacking the deacetylation domain, was enriched in paclitaxel-resistant cells. Elevated MITR expression resulted in increased interleukin-11 (IL11) expression and activation of downstream JAK/STAT3 signaling. Mechanistically, MITR counteracted MEF2A-induced transcriptional suppression of IL11, ultimately causing paclitaxel resistance. By contrast, pharmacological inhibition of JAK1/2 by ruxolitinib reversed paclitaxel resistance both in vitro and in vivo. Conclusion: Our in vitro and in vivo genetic and cellular analyses elucidated the pivotal role of MITR/MEF2A/IL11 axis in paclitaxel resistance and provided a novel therapeutic strategy for TNBC patients to overcome poor chemotherapy responses.
Newborn Screening Practices and Alpha-Thalassemia Detection — United States, 2016
Authors: M.A. Bender, Careema Yusuf, Tim Davis, M. Christine Dorley, Maria del Pilar Aguinaga, Amanda Ingram, Ming S. Chan, Joseph C. Ubaike, Kathryn Hassell, Jelili Ojodu, Mary Hulihan
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Alpha-thalassemia comprises a group of inherited disorders in which alpha-hemoglobin chain production is reduced.Depending on the genotype, alpha-thalassemia results in moderate to profound anemia, hemolysis, growth delays, splenomegaly, and increased risk for thromboembolic events; certain patients might require chronic transfusions.Although alpha-thalassemia is not a core condition of the United States Recommended Uniform Screening Panel* for state newborn screening programs, methodologies used by some newborn screening programs to detect sickle cell disease, which is a core panel condition, also detect a quantitative marker of alpha-thalassemia, hemoglobin (Hb) Bart's, an abnormal type of hemoglobin.The percentage of Hb Bart's detected correlates with alpha-thalassemia severity.The Association of Public Health Laboratories' Hemoglobinopathy Workgroup conducted a survey of state newborn screening programs' alpha-thalassemia screening methodologies and reporting and follow-up practices.Survey findings indicated that 41 of 44 responding programs (93%) report some form of alphathalassemia results and 57% used a two-method screening protocol.However, the percentage of Hb Bart's used for thalassemia classification, the types of alpha-thalassemia reported, and the recipients of this information varied widely.These survey findings highlight the opportunity for newborn screening programs to revisit their policies as they reevaluate their practices in light of the recently released guideline from the Clinical and Laboratory Standards Institute (CLSI) on Newborn Screening for Hemoglobinopathies (1).Although deferring to local programs for policies, the report used a cutoff of 25% Hb Bart's in its decision tree, a value many programs do not use.Standardization of screening and reporting might lead to more timely diagnoses and health care services and improved outcomes for persons with a clinically significant alpha-thalassemia.Thalassemias are the most common single gene disorders (2), with approximately 5% of the world's population having an alpha-thalassemia variant (3).Public health data for the United States are lacking, but in California, 1 in 10,000 newborns has an alpha-thalassemia syndrome (4).Prevalence is highest among Laotians and Cambodians and is also found * https://www.hrsa.gov/advisory-committees/heritable-disorders/rusp/index.html.
Responsive Polymer Brush Design and Emerging Applications for Nanotheranostics
Authors: Danyang Li, Lizhou Xu, Jing Wang, Julien E. Gautrot
Journal: Advanced Healthcare Materials (2020)

Responsive polymer brushes are a category of polymer brushes that are capable of conformational and chemical changes in response to external stimuli. They offer unique opportunities for the control of bio-nano interactions due to the precise control of chemical and structural parameters such as the brush thickness, density, chemistry, and architecture. The design of responsive brushes at the surface of nanomaterials for theranostic applications has developed rapidly. These coatings can be generated from a very broad range of nanomaterials, without compromising their physical, photophysical, and imaging properties. Although the use of responsive brushes for nanotheranostic remains in its early stages, in this review, the aim is to present how the systems developed to date can be combined to control sensing, imaging, and controlled delivery of therapeutics. The recent developments for such design and associated methods for the synthesis of responsive brushes are discussed. The responsive behaviors of homo polymer brushes and brushes with more complex architectures are briefly reviewed, before the applications of responsive brushes as smart delivery systems are discussed. Finally, the recent work is summarized on the use of responsive polymer brushes as novel biosensors and diagnostic tools for the detection of analytes and biomarkers.
Spatial Distribution of Vulnerable Plaques
Authors: Makoto Araki, Tsunenari Soeda, Hyung Oh Kim, Vikas Thondapu, Michele Russo, Osamu Kurihara, Hiroki Shinohara, Yoshiyasu Minami, Takumi Higuma, Hang Lee, Taishi Yonetsu, Tsunekazu Kakuta, Ik-Kyung Jang
Journal: JACC. Cardiovascular imaging (2020)
CSPG4-Specific CAR.CIK Lymphocytes as a Novel Therapy for the Treatment of Multiple Soft-Tissue Sarcoma Histotypes
Authors: Valeria Leuci, Chiara Donini, Giovanni Grignani, Ramona Rotolo, Giulia Mesiano, Erika Fiorino, Loretta Gammaitoni, Lorenzo D'Ambrosio, Alessandra Merlini, Elisa Landoni, Enzo Medico, Sonia Capellero, Lidia Giraudo, Giulia Cattaneo, Ilenia Iaia, Ymera Pignochino, Marco Basiricò, Elisa Vigna, Alberto Pisacane, Franca Fagioli, Soldano Ferrone, Massimo Aglietta, Gianpietro Dotti, Dario Sangiolo
Journal: Clinical Cancer Research (2020)

No effective therapy is available for unresectable soft-tissue sarcomas (STS). This unmet clinical need prompted us to test whether chondroitin sulfate proteoglycan 4 (CSPG4)-specific chimeric antigen receptor (CAR)-redirected cytokine-induced killer lymphocytes (CAR.CIK) are effective in eliminating tumor cells derived from multiple STS histotypes in vitro and in immunodeficient mice.The experimental platform included patient-derived CAR.CIK and cell lines established from multiple STS histotypes. CAR.CIK were transduced with a retroviral vector encoding second-generation CSPG4-specific CAR (CSPG4-CAR) with 4-1BB costimulation. The functional activity of CSPG4-CAR.CIK was explored in vitro, in two- and three-dimensional STS cultures, and in three in vivo STS xenograft models.CSPG4-CAR.CIK were efficiently generated from patients with STS. CSPG4 was highly expressed in multiple STS histotypes by in silico analysis and on all 16 STS cell lines tested by flow cytometry. CSPG4-CAR.CIK displayed superior in vitro cytolytic activity against multiple STS histotypes as compared with paired unmodified control CIK. CSPG4-CAR.CIK also showed strong antitumor activity against STS spheroids; this effect was associated with tumor recruitment, infiltration, and matrix penetration. CSPG4-CAR.CIK significantly delayed or reversed tumor growth in vivo in three STS xenograft models (leiomyosarcoma, undifferentiated pleomorphic sarcoma, and fibrosarcoma). Tumor growth inhibition persisted for up to 2 weeks following the last administration of CSPG4-CAR.CIK.This study has shown that CSPG4-CAR.CIK effectively targets multiple STS histotypes in vitro and in immunodeficient mice. These results provide a strong rationale to translate the novel strategy we have developed into a clinical setting.
Minimum information about clinical artificial intelligence modeling: the MI-CLAIM checklist
Authors: Beau Norgeot, Giorgio Quer, Brett K. Beaulieu-Jones, Ali Torkamani, Raquel Dias, Milena Gianfrancesco, Rima Arnaout, Isaac S. Kohane, Suchi Saria, Eric Topol, Ziad Obermeyer, Bin Yu, Atul J. Butte
Journal: Nature Medicine (2020)
sn-spMF: matrix factorization informs tissue-specific genetic regulation of gene expression
Authors: Yuan He, Surya B. Chhetri, Marios Arvanitis, Kaushik Srinivasan, François Aguet, Kristin G. Ardlie, Alvaro N. Barbeira, Rodrigo Bonazzola, Hae Kyung Im, Christopher D. Brown, Alexis Battle
Journal: Genome biology (2020)

Abstract Genetic regulation of gene expression, revealed by expression quantitative trait loci (eQTLs), exhibits complex patterns of tissue-specific effects. Characterization of these patterns may allow us to better understand mechanisms of gene regulation and disease etiology. We develop a constrained matrix factorization model, sn-spMF, to learn patterns of tissue-sharing and apply it to 49 human tissues from the Genotype-Tissue Expression (GTEx) project. The learned factors reflect tissues with known biological similarity and identify transcription factors that may mediate tissue-specific effects. sn-spMF, available at https://github.com/heyuan7676/ts_eQTLs , can be applied to learn biologically interpretable patterns of eQTL tissue-specificity and generate testable mechanistic hypotheses.
FRI0210 Cardiac involvement in systemic sclerosis (ssc) – doppler echorardiography studies in 100 ssc patients
Authors: AV Volkov, GP Kotelnikova, ES Match
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Cardiac involvement is a relatively common occurrence in systemic sclerosis. When this complication is clinically recognisable, the prognosis is usually poor. However, heart abnormalities is frequently asymptomatic and they can only be diagnosed by Doppler- echocardiography. <h3>Objectives</h3> The aim of this study is to find out the frequency of different variants of cardiac involvements in SSc pts and connexion with other SSc manifestation. <h3>Methods</h3> 100 SSc pts (18 male and 82 women, mean age ± SD 51,8 ± 14,1 years, ranging from 15 to 83 years, mean duration of disease ± SD 10,11 ± 9,22 years). All of the pts were clinically studied with Doppler Ehocardiography. <h3>Results</h3> According to the Doppler Ehocardiography studies cardiac involvement was found in 82% occurences, and was the most frequent symptoms of internal organ damage. Pericard, myocard and endocard were involved. Pericarditis was found in 30% pts, higher frequency (25%) in limited cutaneous SSc, and correlated with disease duration. Pericardit pts have more frequently interstitial lung disease, pulmonary hypertension. The microcirculation changies such as tendency to decreasing of basal digital blood flow and the reduction of capillar loops density were noted in the pericardit patients. The changes in the size of left ventricular were more frequent in pts with diffuse cutaneous SSc, shorter duration of the disease and artherial hypertension, the latter does not exclude the influence of age factors in evolution of these changes. Diastolic disfunction was found in 25% and most frequently in the elderly pts with arterial hypertension. However, the fact of the correlation between diastolic disfunction and high level of ESR (r = 0,364, p &lt; 0,05) as well as fibrinogen concentration (r = 0,325, p &lt; 0,05) and reduction of capillary loops do not exclude the influence of sclerodermic fibrosis on these abnormalities. Mitral (22%) and aortal (5%) regurgitations were the most frequent indication of endocard damage, however, there was no significant difference between these abnormalities and other clinical manifestations of SSc. Fifty one out of 100 pts (51%) were diagnosed as having pulmonary hypertension (PH), including 15 pts having isolated PH without other antecedent pulmonary or cardiac conditions. Correlations were found between PH and age of pts, high level of ESR and fibrinogen concentration. Twenty-six pts out of 100 did not complain on cardiac problem, but Doppler Ehocardiography studies showed pericarditis in two cases, diastolic abnormality in three cases, mitral regurgitation in four cases and pulmonary hypertension also in four cases. <h3>Conclusion</h3> Doppler Ehocardiography is an important method in diagnosis of cardial involvement in SSc pts including those without any symptoms of sclerodermic cardiac disease.
Sacubitril/Valsartan and Sudden Cardiac Death According to Implantable Cardioverter-Defibrillator Use and Heart Failure Cause
Authors: Luis E. Rohde, Neal A. Chatterjee, Muthiah Vaduganathan, Brian Claggett, Milton Packer, Akshay S. Desai, Michael Zile, Jean Rouleau, Karl Swedberg, Martin Lefkowitz, Victor Shi, John J.V. McMurray, Scott D. Solomon
Journal: JACC Heart Failure (2020)
hNaa10p/Human arrest-defective 1 contributes to tumorigenesis by facilitating DNMT1-mediated tumor suppressor gene silencing
Authors: Chung-Fan Lee, Derick S. C. Ou, Sung-Bau Lee, Liang-Hao Chang, Ruo-Kai Lin, Ying-Shiuan Li, Anup K. Upadhyay, Xiaodong Cheng, Yi-Ching Wang, Han-Shui Hsu, Michael Hsiao, Cheng-Wen Wu, Li-Jung Juan
Journal: Journal of Clinical Investigation (2010)
Video-Based Feedback for the Improvement of Surgical Technique
Authors: Cary Jo R. Schlick, Karl Y. Bilimoria, Jonah J. Stulberg
Journal: JAMA Surgery (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery 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 Surgery journal
Testing for SARS-CoV-2 antibodies
Authors: Jessica Watson, Alex Richter, Jonathan Deeks
Journal: BMJ (2020)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Testing for SARS-CoV-2 antibodies Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Transmission of SARS-CoV-2 in children aged 0 to 19 years in childcare facilities and schools after their reopening in May 2020, Baden-Württemberg, Germany
Authors: J Ehrhardt, A Ekinci, H Krehl, M Meincke, I Finci, J Klein, B Geisel, C Wagner-Wiening, M Eichner, SO Brockmann
Journal: Eurosurveillance (2020)

We investigated data from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected 0-19 year olds, who attended schools/childcare facilities, to assess their role in SARS-CoV-2 transmission after these establishments' reopening in May 2020 in Baden-Württemberg, Germany. Child-to-child transmission in schools/childcare facilities appeared very uncommon. We anticipate that, with face mask use and frequent ventilation of rooms, transmission rates in schools/childcare facilities would remain low in the next term, even if classes' group sizes were increased.
COVID-19 herd immunity: where are we?
Authors: Arnaud Fontanet, Simon Cauchemez
Journal: Nature reviews. Immunology (2020)

Herd immunity is a key concept for epidemic control. It states that only a proportion of a population needs to be immune (through overcoming natural infection or through vaccination) to an infectious agent for it to stop generating large outbreaks. A key question in the current COVID-19 pandemic is how and when herd immunity can be achieved and at what cost. During the current COVID-19 pandemic, the concept of herd immunity has become a topic of much debate. This Comment examines the factors that determine it, discusses how far we have come and considers what it will take to reach herd immunity safely.
Projected health-care resource needs for an effective response to COVID-19 in 73 low-income and middle-income countries: a modelling study
Authors: Tessa Tan-Torres Edejer, Odd Hanssen, Andrew Mirelman, Paul Verboom, Glenn Lolong, Oliver John Watson, Lucy Linda Boulanger, Agnès Soucat
Journal: The Lancet Global Health (2020)

Since WHO declared the COVID-19 pandemic a Public Health Emergency of International Concern, more than 20 million cases have been reported, as of Aug 24, 2020. This study aimed to identify what the additional health-care costs of a strategic preparedness and response plan (SPRP) would be if current transmission levels are maintained in a status quo scenario, or under scenarios where transmission is increased or decreased by 50%.
Chikungunya Virus–Like Particle Vaccine
Authors: Nishant Jaiswal, Shreya Singh, Meenu Singh
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA 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
A Learning Health Care System–Based Approach for Improving Quality of Care Among Patients With Transient Ischemic Attack
Authors: Farhaan S. Vahidy
Journal: JAMA Network Open (2020)

Dawn M. Bravata, MD; Laura J. Myers, PhD; Anthony J. Perkins, MS; Ying Zhang, PhD; Edward J. Miech, EdD; Nicholas A. Rattray, PhD; Lauren S. Penney, PhD; Deborah Levine, MD; Jason J. Sico, MD; Eric M. Cheng, MD, MS; Teresa M. Damush, PhD
Germline Genetic Risk Stratification in ALL? GATA Get More Information
Authors: Logan G Spector, Lucie M Turcotte
Journal: JNCI Journal of the National Cancer Institute (2020)

Over the past several decades, outcomes for pediatric acute lymphoblastic leukemia (ALL) have improved dramatically ( 1), yet 10%-20% of patients still relapse in some subsets of disease (2,3).Relapsed disease is difficult to treat, and mortality reaches nearly 50% even in the modern era.Thus, predicting relapse has become an important goal to stratify patients by risk and potentially to modify therapy.Long-established risk factors for relapse include age at diagnosis, white blood cell count at diagnosis, and DNA index.More recently, minimal residual disease (MRD) assessed by flow cytometry or polymerase chain reaction at the end of induction has emerged as a strong predictor of relapse.To this, the current study by Zhang et al. ( 4) adds host germline genetics, which predicted suboptimal response to induction (ie, high MRD) and relapse independently of most baseline risk factors in a large genome-wide association study (GWAS) of high-risk pediatric B-ALL patients.The study featured high-quality data, having consisted of more than 3000 patients on Children's Oncology Group trials with MRD assessed by standardized flow cytometry and relapse determined by consistent criteria across participating sites.Appropriate statistical methods for GWAS were applied, with MRD construed as either a dichotomous or ordinal variable.Reassuringly, the top variant to appear, rs3824662, remained statistically significant in multivariable analyses with both MRD and relapse as the outcomes, although, as discussed below, in the analysis adjusting for cytogenetic subtypes the statistical association dissipated.Aside from the statistical evidence, there is strong prior evidence supporting the function of rs3824662.The variant is located in the GATA3 gene, which encodes a transcription factor that influences lymphopoiesis (5).Perhaps more important, the authors have previously linked the variant to development of B-ALL, particularly Ph-like ALL, in an earlier GWAS (6).This association was particularly notable for its strength, with an odds ratio of 3.85 per allele (95% confidence interval ¼ 2.71 to 5.47).Given the diminishing association of rs3824662 with MRD when controlling for Ph-like ALL, the authors speculated that some of