tbuckley/cabot-search huggingface dataset:
Covid-19: Rapid test missed over 50% of positive cases in Manchester pilot
Authors: Gareth Iacobucci
Journal: BMJ (2020)

A rapid covid-19 test due to be rolled out to healthcare staff in Liverpool next week missed more than 50% of positive cases in a pilot in Greater Manchester, it has emerged.The government has spent £323m (€358m; $425m) on securing the technology to deliver 20 minute saliva tests to give to asymptomatic staff at hospitals and care homes as part of its Operation Moonshot mass testing programme. 1 But a letter seen by the Guardian newspaper 2 reported concerns from scientists in Greater Manchester about the accuracy and sensitivity of the OptiGene Direct RT-LAMP (loop mediated isothermal amplification) tests, which identified only 46.7% of infections during a pilot last month.The Department of Health and Social Care said that the results of the Greater Manchester pilot differed from successful trials at three other labs, which had validated the test's effectiveness.Mark Wilcox, co-chair of the department's Technical Validation Group, said, "The direct LAMP tests used in Manchester have been validated in other laboratories and in real world testing for use in different settings."It is incorrect to claim the tests have a low sensitivity, with a recent pilot showing overall technical sensitivity of nearly 80% rising to over 96% in individuals with a higher viral load, making it important for detecting individuals in the infectious stage.The challenge now is to understand the reasons for the difference in claimed sensitivity in one evaluation versus those in multiple others."The OptiGene RT-LAMP assay has two formats.The rapid Direct RT LAMP tests saliva for presence of the virus and does not require RNA to be extracted, while RNA RT-LAMP takes longer because RNA must be extracted first from nose and throat swabs.In June the department launched a pilot of OptiGene's saliva tests in Southampton, 3 but it has yet to publish the results of this trial.The department said that small volumes of the rapid tests would be given to NHS staff in Liverpool hospitals from next week as part of the UK's first city-wide mass testing initiative. 41
Abstract 221: Tannic Acid Coated Nanoparticles for Cardiac Regeneration
Authors: Giulia Torrieri, Mónica P Ferreira, Mohammad-Ali Shahbazi, Virpi Talman, Cláudia Carvalho, Tuuli Karhu, João F Pinto, Jouni Hirvonen, Heikki J Ruskoaho, Vimalkumar Balasubramanian, Hélder A Santos
Journal: Circulation Research (2020)

The advance of nanomedicines has recently offered novel approaches to tackle cardiovascular diseases and, in particular, myocardial infarction (MI). However, the constant pumping of the heart and the still poor knowledge of targetable moieties, prevented the application of nanomedicines in the cardiovascular field to rise. Tannic acid, a polyphenol derived from plants, has showed affinity for components of the extracellular matrix, in particular elastin, allowing the retention of protein aggregates in the cardiac tissue. Here, we explored the heart targeting abilities of tannic acid by using it to coat spermine modified-acetalated dextran (AcDXSp) nanoparticles (NPs). Briefly, particles were prepared by single emulsion technique and then coated with tannic acid by complexation of the polyphenol with Fe 3+ ions, resulting in the formation of a capsule around the AcDXSp NPs. The nanoparticles were loaded with two small hydrophobic compounds, CHIR99021 and SB431542, which were both proven to increase the efficiency of direct reprogramming of fibroblasts into cardiomyocytes. The biocompatibility of the nanosystem and cellular uptake were performed on both primary rat cardiomyocytes and fibroblasts. The nanoparticles were taken-up by both the cell types and were safe towards primary cardiomyocytes, while the tannic acid coating showed anti-fibrotic effects on primary fibroblasts. Anti-fibrotic effect was further confirmed by RT-qPCR and the effect of the loaded compounds was assessed by β-catenin and Smad3 immunostainings, which demonstrated the ability of the system to induce direct reprogramming of fibroblasts into cardiomyocytes. In particular, the system stabilized β-catenin and prevented the translocation of Smad3 to the nucleus of myo(fibroblasts). In conclusion this nanosystems exhibited potential to tackle the negative fibrosis process occurring after myocardial infarction by both contrasting it, due to the anti-fibrotic effects showed by the tannic acid coating and by potentially regenerating the cardiac tissue, due to the efficient direct reprogramming of fibroblasts into cardiomyocytes exerted by the loaded drugs.
Phase II Study of Venetoclax Added to Cladribine + Low Dose AraC (LDAC) Alternating with 5-Azacytidine Demonstrates High Rates of Minimal Residual Disease (MRD) Negative Complete Remissions (CR) and Excellent Tolerability in Older Patients with Newly Diagnosed Acute Myeloid Leukemia (AML)
Authors: Tapan M. Kadia, Gautam Borthakur, Naveen Pemmaraju, Naval Daver, Courtney D. DiNardo, Koji Sasaki, Ghayas C. Issa, Maro Ohanian, Guillermo Montalban Bravo, Nicholas J. Short, Nitin Jain, Alessandra Ferrajoli, Kapil N. Bhalla, Elias Jabbour, Rashmi Kanagal-Shamanna, Koichi Takahashi, Rashmi Malla, Kelly Marek, Mark Brandt, Uday R. Popat, Michael Andreeff, Jorge E. Cortes, Guillermo Garcia-Manero, Marina Konopleva, Farhad Ravandi, Hagop M. Kantarjian
Journal: Blood (2020)
Anti-CD19 Chimeric Antigen Receptor T Cell Treatment of Relapsed /Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Resistant to Bruton's Tyrosine Kinase (BTK) Inhibitor
Authors: Weihong Chen, Xin Du, Wenyujing Zhou, Changru Luo, Xiaoqing LI
Journal: Blood (2020)
Abstract IA23: Impact of metastatic prostate cancer on human bone marrow
Authors: Ninib Baryawno, Youmna Kfoury, Nicolas Severe, Shenglin Mei, Karin Gustafsson, Taghreed Hirz, Thomas Brouse, Elizabeth W. Scadden, Anna A. Igolkina, Bryan D. Choi, Nikolas Barkas, John H. Shin, Philip J. Saylor, David T. Scadden, David B. Sykes, Peter V. Kharchenko
Journal: Cancer Research (2020)

Abstract Cancer-related mortality due to solid tumor malignancies is overwhelmingly due to the development and progression of metastases. In advanced prostate cancer, metastases most often involve the bone and generally represent incurable disease. It remains unclear what aspects of the bone marrow microenvironment make it hospitable to metastatic dissemination. Similarly, the impact of the metastatic tumor on hematopoiesis and the marrow immune response is poorly understood. We took advantage of rare spinal cord decompression surgeries to profile marrow and metastatic tumors from men with advanced prostate cancer at single-cell resolution. Our analysis contrasts the cellular composition and transcriptional states in matched samples of tumor and liquid bone marrow collected at adjacent vertebral body levels, as well as bone marrow of orthopedic patients without malignancy. Metastatic prostate cancer was associated with hematopoietic suppression and multifaceted immune distortion. There was exhaustion of specific T cell subsets, appearance of inflammatory monocytes and macrophages, and alteration of cytokine profiles. Computational analysis showed association between the presence of specific myeloid subsets and the level of T lymphocyte dysfunction in the tumor fraction. We screened for potential signaling axes that may underlie this interaction. Among them was chemokine CCL20, notably overexpressed by myeloid cells, as was its cognate CCR6 receptor, expressed on T cells. We developed a syngeneic mouse model of bone-metastatic prostate cancer to explore this observation, and demonstrated that disruption of the CCL20-CCR6 axis from either side resulted in significant prolongation of survival. Our results further indicated that this dual overexpression was associated with repressed immune responses. Overall, comparative high-resolution analysis of bone marrow reveals distinct alterations associated with prostate cancer bone metastases that may be amenable to therapeutic targeting with the goal of altering cancer progression. Citation Format: Ninib Baryawno, Youmna Kfoury, Nicolas Severe, Shenglin Mei, Karin Gustafsson, Taghreed Hirz, Thomas Brouse, Elizabeth W. Scadden, Anna A. Igolkina, Bryan D. Choi, Nikolas Barkas, John H. Shin, Philip J. Saylor, David T. Scadden, David B. Sykes, Peter V. Kharchenko, as part of the Boston Bone Metastasis Consortium. Impact of metastatic prostate cancer on human bone marrow [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr IA23.
Aplastic Anemia in Thailand: Incidence and Treatment Outcome from a Prospective Nationwide Population-Based Study
Authors: Lalita Norasetthada, Somchai Wongkhantee, Jindaratn Chaipokam, Kanyaporn Charoenprasert, Suporn Chuncharunee, Ponlapat Rojnuckarin, Chittima Sirijerachai, Wanchai Wanachiwanawin, Surapol Issaragrisil
Journal: Blood (2020)
Edoxaban Vs. Low Molecular Weight Heparin As Anticoagulant Therapy in Hospitalized Patients with Atrial Fibrillation and COVID-19 Infection
Authors: Pável E Olivera, Desiree Campoy, César A Velasquez, Katia Flores, Tania Canals, Erik A Johansson, Laia Martinez, Jorge Sierra, Juan Jose Cerezo, Ramón Salinas
Journal: Blood (2020)
<i>PTPN11</i> Mutations Are Associated with Poor Outcomes across Myeloid Malignancies
Authors: David M Swoboda, Najla E. Al Ali, Eric Padron, Andrew T. Kuykendall, Jinming Song, Mohammad O Hussaini, Jeffrey E. Lancet, Kendra L. Sweet, David A. Sallman, Rami Komrokji
Journal: Blood (2020)
DISC-0974, a Novel, First-in-Class, Anti-Hemojuvelin Monoclonal Antibody Is Predicted to be Efficacious at Low Doses in Humans As Determined By Pharmacokinetic/Pharmacodynamic (PK/PD) Modeling in Non-Clinical Studies
Authors: Mark Hixon, Cecile Blaustein, Christopher King, Sophia Nguyen, Will Savage, Maria G. Beconi
Journal: Blood (2020)
Syncope in a Young Woman
Authors: Catherine E. Lowe, Michael D. Winniford, Tanyanan Tanawuttiwat
Journal: JAMA Cardiology (2020)

A 27-year-old woman with a history of heroin use presented with syncope but denied chest pain, shortness of breath, palpitations, or recent illicit drug use. Results of imaging tests were unremarkable, and electrocardiography was ordered. What would you do next?
Assessing United States County-Level Exposure for Research on Tropical Cyclones and Human Health
Authors: G. Brooke Anderson, Joshua Ferreri, Mohammad Al-Hamdan, William Crosson, Andrea Schumacher, Seth Guikema, Steven Quiring, Dirk Eddelbuettel, Meilin Yan, Roger D. Peng
Journal: Environmental Health Perspectives (2020)

Tropical cyclone epidemiology can be advanced through exposure assessment methods that are comprehensive and consistent across space and time, as these facilitate multiyear, multistorm studies. Further, an understanding of patterns in and between exposure metrics that are based on specific hazards of the storm can help in designing tropical cyclone epidemiological research. a) Provide an open-source data set for tropical cyclone exposure assessment for epidemiological research; and b) investigate patterns and agreement between county-level assessments of tropical cyclone exposure based on different storm hazards. We created an open-source data set with data at the county level on exposure to four tropical cyclone hazards: peak sustained wind, rainfall, flooding, and tornadoes. The data cover all eastern U.S. counties for all land-falling or near-land Atlantic basin storms, covering 1996-2011 for all metrics and up to 1988-2018 for specific metrics. We validated measurements against other data sources and investigated patterns and agreement among binary exposure classifications based on these metrics, as well as compared them to use of distance from the storm's track, which has been used as a proxy for exposure in some epidemiological studies. Our open-source data set was typically consistent with data from other sources, and we present and discuss areas of disagreement and other caveats. Over the study period and area, tropical cyclones typically brought different hazards to different counties. Therefore, when comparing exposure assessment between different hazard-specific metrics, agreement was usually low, as it also was when comparing exposure assessment based on a distance-based proxy measurement and any of the hazard-specific metrics. Our results provide a multihazard data set that can be leveraged for epidemiological research on tropical cyclones, as well as insights that can inform the design and analysis for tropical cyclone epidemiological research. https://doi.org/10.1289/EHP6976.
Dartumumab in Pretreated AL Amyloidosis: A Systematic Review
Authors: Iqraa Ansar, Karun Neupane, Hamid Ehsan, Muhammad Yasir Anwar, Hassaan Imtiaz, Ali Younas Khan, Anum Javaid, Muhammad Aadil Rahman, Hafiz Muhammad Haroon Afzal, Kanza Noor Butt, Muhammad Salman Faisal, Ahsan Wahab, Sadia Ansar, Faiz Anwer
Journal: Blood (2020)
Transcriptomic Landscape of Umbilical Cord Blood Mononuclear Cells after Genetic Modification
Authors: Ilnur I. Salafutdinov, Dilara Z Gatina, Мaria I Markelova, Ekaterina E Garanina, Sergey Yu Malanin, Ilnaz M Gazizov, Svetlana Khaiboullina, Albert A Rizvanov, Rustem I. Islamov
Journal: Blood (2020)
Health-Related Quality of Life Outcomes in Patients with Myelodysplastic Syndromes with Ring Sideroblasts Treated with Luspatercept in the Medalist Study
Authors: Esther Natalie Oliva, Uwe Platzbecker, Guillermo Garcia-Manero, Ghulam J. Mufti, Valeria Santini, Mikkael A. Sekeres, Rami S. Komrokji, Jeevan K. Shetty, Derek Tang, Shien Guo, Weiqin Liao, George Zhang, Xianwei Ha, Rodrigo Ito, Jennifer Lord-Bessen, Jay T. Backstrom, Pierre Fenaux
Journal: Blood (2020)
Preclinical Development of Inducible MyD88/CD40 (iMC)-Enhanced Chimeric Antigen Receptor Natural Killer (GoCAR-NK) Cells to Target BCMA+ Tumors
Authors: Xiaomei Wang, MyLinh T Duong, Alan D. Guerrero, Aruna Mahendravada, Kelly L Sharp, Mary E. Brandt, Christine Gagliardi, Aaron E. Foster, J. Henri Bayle
Journal: Blood (2020)
Genetic Variants That Influence Fetal Hemoglobin Expression from Hydroxyurea Treatment
Authors: Anu Marahatta, Jonathan M. Flanagan, Thad A. Howard, Nicole Mortier, William Schultz, Kathryn L McElhinney, Leon Tshilolo, Thomas N. Williams, Peter Olupot-Olupot, Brigida Santos, Chandy C. John, Robert Opoka, Rosa M. Nieves, Rafael Mena, Marvin E Reid, Angela Rankine-Mullings, Jasmine Baker, Patrick T. McGann, Banu Aygun, Adam Lane, George A. Tomlinson, Teresa Latham, Susan E. Stuber, Russell E. Ware
Journal: Blood (2020)
A Phase 1a/b Dose Escalation Study of the MYC Repressor Apto-253 in Patients with Relapsed or Refractory AML or High-Risk MDS
Authors: Rafael Bejar, Hongying Zhang, Nasrin Rastgoo, Khalid Benbatoul, Yuying Jin, Matthew Thayer, Susan Sheng, Gregory k Chow, Victor Montalvo-Lugo, Jotin Marango, Stephen B Howell, William G Rice
Journal: Blood (2020)
Carrying Capacity of Spatially Distributed Metapopulations
Authors: Bo Zhang, Donald L. DeAngelis, Wei-Ming Ni
Journal: Trends in Ecology & Evolution (2020)

Carrying capacity is a key concept in ecology. A body of theory, based on the logistic equation, has extended predictions of carrying capacity to spatially distributed, dispersing populations. However, this theory has only recently been tested empirically. The experimental results disagree with some theoretical predictions of when they are extended to a population dispersing randomly in a two-patch system. However, they are consistent with a mechanistic model of consumption on an exploitable resource (consumer-resource model). We argue that carrying capacity, defined as the total equilibrium population, is not a fundamental property of ecological systems, at least in the context of spatial heterogeneity. Instead, it is an emergent property that depends on the population's intrinsic growth and dispersal rates.
Abstract 244: Post- But Not Pre-menopausal Female Smoothelin-like 1 Deficient Mice Develop Diastolic Dysfunction Unlike Their Male Counterparts
Authors: Megha Murali, Darrell D Belke, William C Cole, Justin A MacDonald
Journal: Circulation Research (2020)

Diastolic dysfunction is a core characteristic of heart failure with preserved ejection fraction (HFpEF), which accounts for half of all HF cases. Our group revealed a novel impact of the smoothelin-like 1 (SMTNL1) protein which when subjected to genetic deletion drives alterations in endothelial and cardiovascular performances. Of note, previous cardiac hemodynamic profiling showed that young male SMTNL1 knockout (KO) mice developed diastolic dysfunction as evidenced by increased end diastolic pressure (EDP), left ventricular relaxation time constant (Tau) and steeper end diastolic pressure-volume relationship (EDPVR). A majority of HFpEF patients are post-menopausal women, so this study examined the impact of SMTNL1 silencing on endothelial and cardiac function with increasing age in a novel female murine model. The cardiac function of SMTNL1 global KO mice (3-, 12- and 18-month old, male and female) was assessed by echocardiography and pressure-volume loop. Unlike young males, 3-month old female KO mice did not develop diastolic dysfunction. However, ageing provided progressive impairment of diastolic function in female KO mice with increased EDP (8.4±1.1 vs 12.2±0.8 mmHg, p&lt;0.02) and EDPVR (0.22±0.05 vs 0.51±0.05, p=0.02) at 18 months; an elevated E/E′ (20.8±1.6 vs 28.3±2.2, p=0.02) and decreased E′/A′ (1.49±0.19 vs 0.97±0.14, p&lt;0.05) at 12 months in comparison to their WT counterparts, along with a normal ejection fraction (&gt;60%) for all age groups. Furthermore, while flow-mediated dilation was continuously impaired in male KO cohorts from 3-month age, female KO showed impairment only at 12-months. Aging was also associated with altered cardiac morphology and fibrotic levels in the aged female KO cohort. Taken together, we have identified pathophysiologic effects of SMTNL1 silencing on vascular and cardiac function with ageing in female mice. The SMTNL1 KO model for the first time recapitulates the sex dimorphic onset of diastolic dysfunction that is central to HFpEF clinical phenotypes and represents a novel preclinical model to study the etiology of the HFpEF condition. Furthermore, the absence of diastolic dysfunction in KO female mice until post-menopausal age reveals a protective role of female sex hormones and warrants further study.
Standalone performance of artificial intelligence for upper GI neoplasia: a meta-analysis
Authors: Julia Arribas, Giulio Antonelli, Leonardo Frazzoni, Lorenzo Fuccio, Alanna Ebigbo, Fons van der Sommen, Noha Ghatwary, Christoph Palm, Miguel Coimbra, Francesco Renna, J J G H M Bergman, Prateek Sharma, Helmut Messmann, Cesare Hassan, Mario J Dinis-Ribeiro
Journal: Gut (2020)

Objective Artificial intelligence (AI) may reduce underdiagnosed or overlooked upper GI (UGI) neoplastic and preneoplastic conditions, due to subtle appearance and low disease prevalence. Only disease-specific AI performances have been reported, generating uncertainty on its clinical value. Design We searched PubMed, Embase and Scopus until July 2020, for studies on the diagnostic performance of AI in detection and characterisation of UGI lesions. Primary outcomes were pooled diagnostic accuracy, sensitivity and specificity of AI. Secondary outcomes were pooled positive (PPV) and negative (NPV) predictive values. We calculated pooled proportion rates (%), designed summary receiving operating characteristic curves with respective area under the curves (AUCs) and performed metaregression and sensitivity analysis. Results Overall, 19 studies on detection of oesophageal squamous cell neoplasia (ESCN) or Barrett's esophagus-related neoplasia (BERN) or gastric adenocarcinoma (GCA) were included with 218, 445, 453 patients and 7976, 2340, 13 562 images, respectively. AI-sensitivity/specificity/PPV/NPV/positive likelihood ratio/negative likelihood ratio for UGI neoplasia detection were 90% (CI 85% to 94%)/89% (CI 85% to 92%)/87% (CI 83% to 91%)/91% (CI 87% to 94%)/8.2 (CI 5.7 to 11.7)/0.111 (CI 0.071 to 0.175), respectively, with an overall AUC of 0.95 (CI 0.93 to 0.97). No difference in AI performance across ESCN, BERN and GCA was found, AUC being 0.94 (CI 0.52 to 0.99), 0.96 (CI 0.95 to 0.98), 0.93 (CI 0.83 to 0.99), respectively. Overall, study quality was low, with high risk of selection bias. No significant publication bias was found. Conclusion We found a high overall AI accuracy for the diagnosis of any neoplastic lesion of the UGI tract that was independent of the underlying condition. This may be expected to substantially reduce the miss rate of precancerous lesions and early cancer when implemented in clinical practice.
FRI0085 Anti-beta-2- glycoprotein i antibodies in systemic lupus erythematosus patients
Authors: AG Borodin, EL Nassonov, AA Baranov, NG Klukvina
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> <h3>Methods</h3> Anticardiolipin antibodies (aCL) react with negatively charged phospholipids, which may often be complexed with a protein cofactor such as beta-2-glycoprotein I. <h3>Results</h3> To obtain information about the prevalence and levels of IgG anti-â2-GPI, IgG- and IgM-aCL in systemic lupus erythematosus (SLE) patients (pts) these antibodies were measured, by an enzyme linked immunosorbent assay, in sera from 147 pts with SLE (70 men and 77 women). The results were compared with 20 healthy subjects. Anti-â2-GPI were found positive (more than 3s.d. above the mean in normal controls) in 15 females (19,4%), 14 males (20%) in pts with SLE compared to 1 person (5%) in normal controls. 48,3% of pts with anti-â2-GPI had the history of thrombosis, compared with 11,02% of pts without anti-â2-GPI (p &lt; 0,001). 35,7% of females with anti-â2-GPI had the history of fetal loss, in comparison with 6,56% of anti-â2-GPI negative pts. APS was diagnosed in 16 (69,56%) anti-â2-GPI (+)-aCL(+) pts (n = 23) and in 15 (37,5%) anti-â2-GPI (-)-aCL(+) pts (n = 40) (p &lt; 0,01). Anti-â2-GPI(+)-aCL(+) pts had a history of thrombosis more frequently (n = 14, 60,86%) than anti-â2-GPI (+)-aCL(-) (n = 6) (n = 0, 0%, p &lt; 0,002). Our data show that the presence of anti-â2-GPI simultaneously with aCL is strong associated with APS in SLE. <h3>Conclusion</h3>
Ponatinib and Chemotherapy in Young Adults with <i>De Novo</i> Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia. Results of Ponalfil Clinical Trial after Completion of Recruitment
Authors: Josep-Maria Ribera, Olga García, Pau Montesinos, Pilar Martinez, Jordi Esteve, Daniel Esteban, María José Moreno, Natalia Alonso, José González-Campos, Arancha Bermúdez, Anna Torrent, Joaquin Martinez-Lopez, Santiago Mercadal, Ramon Garcia-Sanz
Journal: Blood (2020)
Characteristics and Prognostic Effects of IDH Mutations across the Age Spectrum in AML: A Collaborative Analysis from COG, SWOG, and ECOG
Authors: Sara Zarnegar-Lumley, Todd A. Alonzo, Megan Othus, Zhuoxin Sun, Rhonda E. Ries, Yi-Cheng Wang, Amanda R. Leonti, Matthew A. Kutny, Derek Stirewalt, Jerald P. Radich, Frederick R. Appelbaum, Era L Pogosova-Agadjanyan, Kristen Marie O'Dwyer, Harry P. Erba, Omar Abdel-Wahab, Martin S. Tallman, Mark Litzow, Ehab L. Atallah, Selina M. Luger, Ross L. Levine, Todd M. Cooper, Alan S. Gamis, Richard Aplenc, Anders E. Kolb, Soheil Meshinchi, Katherine Tarlock
Journal: Blood (2020)
Re: Andrew Vickers, Sigrid V. Carlsson, Matthew Cooperberg. Routine Use of Magnetic Resonance Imaging for Early Detection of Prostate Cancer Is Not Justified by the Clinical Trial Evidence. Eur Urol 2020;78:304–6
Authors: Yi Sun, Fengxiang Sun, Qiang Wei, Jin Huang, Ruiqi Duan
Journal: European Urology (2020)