tbuckley/cabot-search huggingface dataset:
Abstract 13399: Variable Exposure to Echocardiography Pathology and Core Competencies Among Cardiology Fellows-in-training
Authors: Matthew Bierowski, Umer Qureshi, Shayann Ramedani, Simran Grewal, Ravi Shah, Robert Park, Brandon R Peterson
Journal: Circulation (2020)

Introduction: Current guidelines recommend interpretation of at least 300 echocardiograms to achieve competency in echocardiography for independent practice (level II COCATS). Recommended core competencies in echocardiography include proficiency in evaluating native and prosthetic valve diseases, pulmonary hypertension and right heart dysfunction, and suspected cardiac masses or endocarditis, among others. Whether the recommended number of cases allows for adequate exposure to the various core competencies, however, is unclear. Hypothesis: We investigated whether certain core competencies are less commonly encountered when using the recommended case numbers by current guidelines. Methods: We reviewed echocardiograms interpreted by 10 of our cardiology fellows (2 per year) who began training from July 2015 through July 2019. We recorded core competency measures encountered in the first 300 echocardiograms interpreted by each fellow, including measures of left and right ventricular dysfunction, valvular diseases, cardiac masses, aortic disease, and pericardial disease. Paired T-test was used to compare the mean occurrence between different core competencies. Results: Among the 3000 echocardiograms reviewed, abnormal wall motion was the most common pathology encountered, whereas each other core competency was relatively less common (p&lt;0.05 for all comparisons, see plots below). Deficiencies in core competencies included: 9/10 fellows had no cases of aortic dissection, 3/10 had no cases of valvular mass, 2/10 had no cases of cardiac chamber mass, 2/10 had no cases of cardiac tamponade, and 1/10 had no cases of prosthetic valve dysfunction. Conclusions: The recommend number of echocardiograms in current guidelines does not ensure adequate exposure to all areas of echocardiography core competency. Educators should consider strategies to supplement learning in these areas to ensure experience in all areas of echocardiography core competency.
Correction: Treatment of Triple-Negative Breast Cancer with TORC1/2 Inhibitors Sustains a Drug-Resistant and Notch-Dependent Cancer Stem Cell Population
Authors: Neil E. Bhola, Valerie M. Jansen, James P. Koch, Hua Li, Luigi Formisano, Janice A. Williams, Jennifer R. Grandis, Carlos L. Arteaga
Journal: Cancer Research (2019)

In the original version of this article (1), the stated disclosure of the author Carlos L. Arteaga is incorrect. The error has been corrected in the latest online HTML and PDF versions of the article. The authors regret this error.
Back from the Brink: EGFR Inhibition in Gastroesophageal Cancer
Authors: Mark R. Openshaw, David J. Pinato, Nicola Valeri
Journal: Clinical Cancer Research (2021)

Abstract Gastroesophageal adenocarcinomas (GEA) remain difficult to treat with limited targeted therapeutics. Negative results from randomized trials of EGFR inhibitors (EGFRi) in patients with molecularly unselected GEA have hampered the development of EGFRi in the gastroesophageal cancer space. A recent study reopens the game. See related article by Corso et al., p. 3126
Leishmania donovani hybridisation and introgression in nature: a comparative genomic investigation
Authors: Patrick Lypaczewski, Greg Matlashewski
Journal: The Lancet Microbe (2021)

Leishmaniasis is a neglected tropical disease transmitted by infected sandflies that results in diverse human pathologies contingent on the species of Leishmania. Leishmania donovani causes highly virulent fatal visceral leishmaniasis, whereas Leishmania major and Leishmania tropica cause less virulent, cutaneous leishmaniasis, in which the infection remains in the skin at the site of the sandfly bite. The aim of this study was to investigate the genetic basis for the emergence of L donovani strains that cause cutaneous leishmaniasis instead of visceral leishmaniasis in Sri Lanka.All available sequencing data for L donovani samples from Asia and Africa in GenBank and the Sequence Read Archive were retrieved and filtered to select for paired-end Illumina sequencing reads with no region bias and coverage of the entire reference genome. These data were used for sequence alignments against the reference L donovani genome from Sri Lanka, and sequence analysis was used to assess the presence of genomic recombination markers and the presence of foreign genetic sequences in the genomes of L donovani isolates associated with cutaneous leishmaniasis in Sri Lanka. BLAST analysis was used to compare the genetic sequences from the Sri Lankan isolates to all genomes of Leishmania species from the Old World available in TriTrypDB, including L major and L tropica.After filtering of the 1238 existing sequencing records, 684 high-quality records were used to show that 12 L donovani strains from Sri Lanka form three phylogenetic groups. In one group, the density of heterozygous variants is higher than in previously characterised Leishmania hybrid strains. BLAST analysis showed this group contains gene polymorphisms homologous with L major and L tropica genomes for 22% (2160 of 9757) to 78% (7671 of 9757) of all genes analysed. Analysis by phylogeny and BLAST showed that the L donovani-L major and L donovani-L tropica hybrid strains originated from Africa and are phylogenetically distinct from the L donovani strains in neighbouring India.Novel L donovani strains might arise in new environments through the integration of genes from another species. On the basis of the findings of this study, we hypothesise that hybridisation with genomes from L major and L tropica, followed by recombination and introgression, contributed to the emergence of L donovani offspring capable of causing cutaneous leishmaniasis in Sri Lanka.Canadian Institutes of Health Research, Fonds de recherche du Québec-Santé.
MA10.04 A New Predictive Score for Venous Thromboembolism Associated with Advanced Lung Cancer: A Multicenter, Prospective Study (Rising-VTE/NEJ037)
Authors: Y. Tsubata, H. Ohtsu, T. Hotta, M. Yamasaki, N. Ishikawa, K. Fujitaka, T. Kubota, K. Kobayashi, T. Isobe
Journal: Journal of Thoracic Oncology (2021)
P14.27 Pathogenic Genomic Alterations of CDKN2A Predict Immunotherapy Resistance in NSCLC
Authors: S. Gutiontov, W. Turchan, S. Rouhani, C. Soto Chervin, J. Segal, C. Bestvina, J. Donington, P. Hoffman, S. Chmura, P. Connell, A. Juloori, R. Malik, M. Ferguson, J. Patel, E. Vokes, R. Weichselbaum, S. Pitroda
Journal: Journal of Thoracic Oncology (2021)
Abstract S03-04: Spatial profiling of lung SARS-CoV-2 and influenza virus infection identifies virus specific host responses and gene signatures
Authors: Arutha Kulasinghe
Journal: Clinical Cancer Research (2021)

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged in late 2019 has spread globally, causing a pandemic of respiratory illness designated coronavirus disease 2019 (COVID-19). Robust blood biomarkers that reflect tissue damage are urgently needed to better stratify and triage infected patients. Here, we use spatial transcriptomics to generate an in-depth picture of the pulmonary transcriptional landscape of COVID-19 (10 patients), pandemic H1N1 (pH1N1) influenza (5) and uninfected control patients (4). Host transcriptomics showed a significant upregulation of genes associated with inflammation, type I interferon production, coagulation and angiogenesis in the lungs of COVID-19 patients compared to non-infected controls. SARS-CoV-2 was non-uniformly distributed in lungs with few areas of high viral load and these were largely only associated with an increased type I interferon response. A very limited number of genes were differentially expressed between the lungs of influenza and COVID-19 patients. Specific interferon-associated genes (including IFI27) were identified as candidate novel biomarkers for COVID-19 differentiating this COVID-19 from influenza. Collectively, these data demonstrate that spatial transcriptomics is a powerful tool to identify novel gene signatures within tissues, offering new insights into the pathogenesis of SARS-COV-2 to aid in patient triage and treatment. Citation Format: Arutha Kulasinghe. Spatial profiling of lung SARS-CoV-2 and influenza virus infection identifies virus specific host responses and gene signatures [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2021 Feb 3-5. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(6_Suppl):Abstract nr S03-04.
Targeted next-generation sequencing: a Swiss army knife for mycobacterial diagnostics?
Authors: Sagal Mohamed, Claudio U. Köser, Max Salfinger, Wladimir Sougakoff, Scott K. Heysell
Journal: European Respiratory Journal (2021)

<b>Like a multifunctional Swiss army knife, Deeplex offers unprecedented versatility directly from the clinical sample and represents a welcome addition to the diagnostic and epidemiological toolbox</b>https://bit.ly/38s6ukF
Risk factors for SARS-CoV-2 infection and course of COVID-19 disease in patients with IBD in the Veterans Affair Healthcare System
Authors: Nabeel Khan, Nadim Mahmud, Chinmay Trivedi, Walter Reinisch, James D Lewis
Journal: Gut (2021)

Objective Our aim was to explore the risk of infection with all classes of inflammatory bowel disease (IBD) medications and the impact of these medications on the disease course in a nationwide cohort of patients with IBD. Design This was a retrospective national cohort study of patients with IBD in the Veterans Affairs Healthcare System. We categorised IBD medication use immediately prior to the COVID-19 pandemic and used survival analysis methods to study associations with SARS-CoV-2 infection, as well as a combined secondary outcome of COVID-19 hospitalisation or COVID-19-related mortality. Results The analytical cohort of 30 911 patients was primarily male (90.9%), white (78.6%) and with ulcerative colitis (58.8%). Over a median follow-up of 10.7 months, 649 patients (2.1%) were diagnosed with SARS-CoV-2 infection and 149 (0.5%) met the combined secondary outcome. In adjusted models, vedolizumab (VDZ) use was significantly associated with infection relative to mesalazine alone (HR 1.70, 95% CI 1.16 to 2.48, p=0.006). Patients on no IBD medications had increased risk of the combined secondary outcome relative to mesalazine alone (sub-HR 1.64, 95% CI 1.12 to 2.42, p=0.01), however, no other IBD medication categories were significantly associated with this outcome, relative to mesalazine alone (each p&gt;0.05). Corticosteroid use was independently associated with both SARS-CoV-2 infection (HR 1.60, 95% CI 1.23 to 2.09, p=0.001) and the combined secondary outcome (sub-HR 1.90, 95% CI 1.14 to 3.17, p=0.01). Conclusion VDZ and corticosteroid were associated with an increased risk of SARS-CoV-2 infection. Except for corticosteroids no medications including mesalazine were associated with an increased risk of severe COVID-19.
Perfect as the enemy of good: tracing transmissions with low-sensitivity tests to mitigate SARS-CoV-2 outbreaks
Authors: Lee Kennedy-Shaffer, Michael Baym, William P Hanage
Journal: The Lancet Microbe (2021)

Throughout the COVID-19 pandemic, governments and individuals have attempted a wide variety of strategies to limit the damage of the pandemic on human lives, population health, and economies. Contact tracing has been a commonly used strategy, and various approaches have been proposed and attempted. We summarise some methods of contact tracing and testing, considering the resources demanded by each and how features of SARS-CoV-2 transmission affect their effectiveness. We also propose an approach focusing on tracing transmission events, which can be particularly effective when superspreading events play a large role in transmission. Accounting for the best available evidence on a pathogen and for the availability of resources can make control strategies more effective, even if they are not perfect.
Effective and safe delivery of GLP-1AR and FGF-21 plasmids using amino-functionalized dual-mesoporous silica nanoparticles in vitro and in vivo
Authors: Shan Geng, Limei Qin, Yirui He, Xinrun Li, Mengliu Yang, Ling Li, Dongfang Liu, Yongsheng Li, Dechao Niu, Gangyi Yang
Journal: Biomaterials (2021)
Hyperprogression in Patients With Cancer Receiving Immune Checkpoint Inhibitors
Authors: Kartik Sehgal
Journal: JAMA Network Open (2021)

Hyo Jung Park, MD, PhD; Kyung Won Kim, MD, PhD; Sang Eun Won, MS; Shinkyo Yoon, MD; Young Kwang Chae, MD; Sree Harsha Tirumani, MD; Nikhil H. Ramaiya, MD
The mRNA–miRNA–lncRNA Regulatory Network and Factors Associated with Prognosis Prediction of Hepatocellular Carcinoma
Authors: Bo Hu, Xiaolu Ma, Peiyao Fu, Qiman Sun, Weiguo Tang, Haixiang Sun, Zhangfu Yang, Mincheng Yu, Jian Zhou, Jia Fan, Yang Xu
Journal: Genomics Proteomics & Bioinformatics (2021)

Abstract The aim of this study was to identify novel prognostic mRNA and microRNA (miRNA) biomarkers for hepatocellular carcinoma (HCC) using methods in systems biology. Differentially expressed mRNAs, miRNAs, and long non-coding RNAs (lncRNAs) were compared between HCC tumor tissues and normal liver tissues in The Cancer Genome Atlas (TCGA) database. Subsequently, a prognosis-associated mRNA co-expression network, an mRNA–miRNA regulatory network, and an mRNA–miRNA–lncRNA regulatory network were constructed to identify prognostic biomarkers for HCC through Cox survival analysis. Seven prognosis-associated mRNA co-expression modules were obtained by analyzing these differentially expressed mRNAs. An expression module including 120 mRNAs was significantly correlated with HCC patient survival. Combined with patient survival data, several mRNAs and miRNAs, including CHST4, SLC22A8, STC2, hsa-miR-326, and hsa-miR-21 were identified from the network to predict HCC patient prognosis. Clinical significance was investigated using tissue microarray analysis of samples from 258 patients with HCC. Functional annotation of hsa-miR-326 and hsa-miR-21-5p indicated specific associations with several cancer-related pathways. The present study provides a bioinformatics method for biomarker screening, leading to the identification of an integrated mRNA–miRNA–lncRNA regulatory network and their co-expression patterns in relation to predicting HCC patient survival.
Value of Discharging Heart Failure Patients Home—Reply
Authors: Jose F. Figueroa, Rishi K. Wadhera, Karen Joynt Maddox
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
CACTUS: integrating clonal architecture with genomic clustering and transcriptome profiling of single tumor cells
Authors: Shadi Darvish Shafighi, Szymon M. Kiełbasa, Julieta Sepúlveda-Yáñez, Ramin Monajemi, Davy Cats, Hailiang Mei, Roberta Menafra, Susan Kloet, Hendrik Veelken, Cornelis A.M. van Bergen, Ewa Szczurek
Journal: Genome Medicine (2021)

Drawing genotype-to-phenotype maps in tumors is of paramount importance for understanding tumor heterogeneity. Assignment of single cells to their tumor clones of origin can be approached by matching the genotypes of the clones to the mutations found in RNA sequencing of the cells. The confidence of the cell-to-clone mapping can be increased by accounting for additional measurements. Follicular lymphoma, a malignancy of mature B cells that continuously acquire mutations in parallel in the exome and in B cell receptor loci, presents a unique opportunity to join exome-derived mutations with B cell receptor sequences as independent sources of evidence for clonal evolution. Here, we propose CACTUS, a probabilistic model that leverages the information from an independent genomic clustering of cells and exploits the scarce single cell RNA sequencing data to map single cells to given imperfect genotypes of tumor clones. We apply CACTUS to two follicular lymphoma patient samples, integrating three measurements: whole exome, single-cell RNA, and B cell receptor sequencing. CACTUS outperforms a predecessor model by confidently assigning cells and B cell receptor-based clusters to the tumor clones. The integration of independent measurements increases model certainty and is the key to improving model performance in the challenging task of charting the genotype-to-phenotype maps in tumors. CACTUS opens the avenue to study the functional implications of tumor heterogeneity, and origins of resistance to targeted therapies. CACTUS is written in R and source code, along with all supporting files, are available on GitHub ( https://github.com/LUMC/CACTUS ).
SIRT2 ablation inhibits glucose-stimulated insulin secretion through decreasing glycolytic flux
Authors: Feiye Zhou, Linlin Zhang, Kecheng Zhu, Mengyao Bai, Yuqing Zhang, Qin Zhu, Shushu Wang, Chunxiang Sheng, Miaomiao Yuan, Yun Liu, Jieli Lu, Li Shao, Xiao Wang, Libin Zhou
Journal: Theranostics (2021)

Rationale: Sirtuins are NAD+-dependent protein deacylases known to have protective effects against age-related diseases such as diabetes, cancer, and neurodegenerative disease. SIRT2 is the only primarily cytoplasmic isoform and its overall role in glucose homeostasis remains uncertain. Methods: SIRT2-knockout (KO) rats were constructed to evaluate the role of SIRT2 in glucose homeostasis. The effect of SIRT2 on β-cell function was detected by investigating the morphology, insulin secretion, and metabolomic state of islets. The deacetylation and stabilization of GKRP in β-cells by SIRT2 were determined by western blot, adenoviral infection, and immunoprecipitation. Results: SIRT2-KO rats exhibited impaired glucose tolerance and glucose-stimulated insulin secretion (GSIS), without change in insulin sensitivity. SIRT2 deficiency or inhibition by AGK2 decreased GSIS in isolated rat islets, with lowered oxygen consumption rate. Adenovirus-mediated overexpression of SIRT2 enhanced insulin secretion from rat islets. Metabolomics analysis revealed a decrease in metabolites of glycolysis and tricarboxylic acid cycle in SIRT2-KO islets compared with control islets. Our study further demonstrated that glucokinase regulatory protein (GKRP), an endogenous inhibitor of glucokinase (GCK), was expressed in rat islets. SIRT2 overexpression deacetylated GKRP in INS-1 β-cells. SIRT2 knockout or inhibition elevated GKRP protein stability in islet β-cells, leading to an increase in the interaction of GKRP and GCK. On the contrary, SIRT2 inhibition promoted the protein degradation of ALDOA, a glycolytic enzyme. Conclusions: SIRT2 ablation inhibits GSIS through blocking GKRP protein degradation and promoting ALDOA protein degradation, resulting in a decrease in glycolytic flux.
母体ω3ドコサペンタエン酸は,マウスにおけるTRAIL発現形質細胞様樹状細胞を介して乳児アレルギー性皮膚炎を阻害する【JST・京大機械翻訳】
Authors: Hirata So-ichiro, Nagatake Takahiro, Sawane Kento, Hosomi Koji, Honda Tetsuya, Ono Sachiko, Shibuya Noriko, Saito Emiko, Adachi Jun, Abe Yuichi, Isoyama Junko, Suzuki Hidehiko, Matsunaga Ayu, Tomonaga Takeshi, Kiyono Hiroshi, Kabashima Kenji, Arita Makoto, Kunisawa Jun
Journal: Allergy (2020)
Age-dependent decline in remyelination capacity is mediated by apelin–APJ signaling
Authors: Masumi Ito, Rieko Muramatsu, Yuki Kato, Bikram Sharma, Akiko Uyeda, Shogo Tanabe, Harutoshi Fujimura, Hiroyasu Kidoya, Nobuyuki Takakura, Yukio Kawahara, Masaki Takao, Hideki Mochizuki, Akiyoshi Fukamizu, Toshihide Yamashita
Journal: Nature Aging (2021)
FP07.11 Circulating Tumor DNA (ctDNA) Clearance as a Biomarker in Patients With Locally Advanced NSCLC Following Chemoradiation
Authors: B. Knapp, L. Mezquita, S. Devarakonda, M. Aldea, S. Waqar, K. Pepin, J. Ward, A. Botticella, K. Howarth, C. Knape, C. Morris, R. Govindan, B. Besse, D. Morgensztern
Journal: Journal of Thoracic Oncology (2021)
Covid-19: Italy reimposes widespread lockdown as transmission rate rises again
Authors: Michael Day
Journal: BMJ (2021)

Covid-19: Italy reimposes widespread lockdown as transmission rate rises again Michael DayItaly has once again emerged as Europe's covid-19 hotspot, with half the country forced into the tightest tier of lockdown as virus transmission rates continue to rise and intensive care wards again buckle under the strain of new cases.Rome's decision on 15 March to suspend use of the AstraZeneca vaccine, along with France, Germany, and Spain, has exacerbated the already difficult situation.
Comparative Study of Oral Anticoagulation in Left Ventricular Thrombi (No-LVT Trial)
Authors: Mahmoud Abdelnabi, Yehia Saleh, Ahmed Fareed, Alexander Nossikof, Ling Wang, Mahmoud Morsi, Nouran Eshak, Ola Abdelkarim, Haitham Badran, Abdallah Almaghraby
Journal: Journal of the American College of Cardiology (2021)
GMPPA defects cause a neuromuscular disorder with α-dystroglycan hyperglycosylation
Authors: Patricia Franzka, Henriette Henze, M. Juliane Jung, Svenja Caren Schüler, Sonnhild Mittag, Karina Biskup, Lutz Liebmann, Takfarinas Kentache, José Morales, Braulio Martínez, Istvan Katona, Tanja Herrmann, Antje-Kathrin Huebner, J. Christopher Hennings, Susann Groth, Lennart Gresing, Rüdiger Horstkorte, Thorsten Marquardt, Joachim Weis, Christoph Kaether, Osvaldo M. Mutchinick, Alessandro Ori, Otmar Huber, Véronique Blanchard, Julia von Maltzahn, Christian A. Hübner
Journal: Journal of Clinical Investigation (2021)

GDP-mannose-pyrophosphorylase-B (GMPPB) facilitates the generation of GDP-mannose, a sugar donor required for glycosylation. GMPPB defects cause muscle disease due to hypoglycosylation of α-dystroglycan (α-DG). Alpha-DG is part of a protein complex, which links the extracellular matrix with the cytoskeleton, thus stabilizing myofibers. Mutations of the catalytically inactive homolog GMPPA cause alacrima, achalasia, and mental retardation syndrome (AAMR syndrome), which also involves muscle weakness. Here, we showed that Gmppa-KO mice recapitulated cognitive and motor deficits. As structural correlates, we found cortical layering defects, progressive neuron loss, and myopathic alterations. Increased GDP-mannose levels in skeletal muscle and in vitro assays identified GMPPA as an allosteric feedback inhibitor of GMPPB. Thus, its disruption enhanced mannose incorporation into glycoproteins, including α-DG in mice and humans. This increased α-DG turnover and thereby lowered α-DG abundance. In mice, dietary mannose restriction beginning after weaning corrected α-DG hyperglycosylation and abundance, normalized skeletal muscle morphology, and prevented neuron degeneration and the development of motor deficits. Cortical layering and cognitive performance, however, were not improved. We thus identified GMPPA defects as the first congenital disorder of glycosylation characterized by α-DG hyperglycosylation, to our knowledge, and we have unraveled underlying disease mechanisms and identified potential dietary treatment options.
MA03.08 Impact of COVID-19 Pandemic in the Diagnosis and Prognosis of Lung Cancer
Authors: R. Reyes, R. López-Castro, E. Auclin, T. García, M.J. Chourio, A. Rodriguez, L. López, J.C. Laguna, C. Lucena, L. Molins, D. Martínez, F. Casas, M. Mayoral, C. Teixidó, A. Prat, N. Viñolas, N. Reguart, L. Mezquita
Journal: Journal of Thoracic Oncology (2021)