tbuckley/cabot-search huggingface dataset:
Automated Expansion of Primary Human T Cells in Scalable and Cell‐Friendly Hydrogel Microtubes for Adoptive Immunotherapy
Authors: Haishuang Lin, Qiang Li, Ou Wang, Jack Rauch, Braden Harm, Hendrik J. Viljoen, Chi Zhang, Erika Van Wyk, Chi Zhang, Yuguo Lei
Journal: Advanced Healthcare Materials (2018)

Adoptive immunotherapy is a highly effective strategy for treating many human cancers, such as melanoma, cervical cancer, lymphoma, and leukemia. Here, a novel cell culture technology is reported for expanding primary human T cells for adoptive immunotherapy. T cells are suspended and cultured in microscale alginate hydrogel tubes (AlgTubes) that are suspended in the cell culture medium in a culture vessel. The hydrogel tubes protect cells from hydrodynamic stresses and confine the cell mass less than 400 µm (in radial diameter) to ensure efficient mass transport, creating a cell-friendly microenvironment for growing T cells. This system is simple, scalable, highly efficient, defined, cost-effective, and compatible with current good manufacturing practices. Under optimized culture conditions, the AlgTubes enable culturing T cells with high cell viability, low DNA damage, high growth rate (≈320-fold expansion over 14 days), high purity (≈98% CD3+), and high yield (≈3.2 × 108 cells mL-1 hydrogel). All offer considerable advantages compared to current T cell culturing approaches. This new culture technology can significantly reduce the culture volume, time, and cost, while increasing the production.
The 100 000 Genomes Project: bringing whole genome sequencing to the NHS
Authors: Clare Turnbull, Richard H Scott, Ellen Thomas, Louise Jones, Nirupa Murugaesu, Freya Boardman Pretty, Dina Halai, Emma Baple, Clare Craig, Angela Hamblin, Shirley Henderson, Christine Patch, Amanda O’Neill, Andrew Devereau, Katherine Smith, Antonio Rueda Martin, Alona Sosinsky, Ellen M McDonagh, Razvan Sultana, Michael Mueller, Damian Smedley, Adam Toms, Lisa Dinh, Tom Fowler, Mark Bale, Tim Hubbard, Augusto Rendon, Sue Hill, Mark J Caulfield
Journal: BMJ (2018)

In partnership with NHS England, Genomics England's ambitious plans to embed genomic medicine into routine patient care are well underway. <b>Clare Turnbull and colleagues</b> discuss its progress
Abstract 18690: Recombinant Human Relaxin-2 (Serelaxin) Attenuates Ischemic Cardiomyopathy and Improves Left Ventricular Function in Mice
Authors: Juan Valle Raleigh, Adolfo G Mauro, Jun He, Stefano Toldo, Antonio Abbate, Fadi N Salloum
Journal: Circulation (2016)

Background:  In the RELAX-AHF trial, 48-hour infusion of recombinant human relaxin-2 (serelaxin; SRLX) reduced post-discharge mortality at 180 days in selected patients with acute heart failure. However, the underlying mechanisms remain under investigation. Therefore, we studied the effect of SRLX on attenuation of left ventricular (LV) adverse remodeling following infarction in a mouse model of ischemic cardiomyopathy.   Methods and Results:  48 adult male CD-1 mice underwent myocardial infarction (MI) by permanent ligation of the left anterior descending coronary artery and were treated with SRLX (10 μg/Kg/day;  sc  via osmotic mini-pump) or saline for 4 weeks. Survival at 28 days was 90% in the SRLX group vs. 52% in the saline group (Fig. A). The fibrotic area (% of LV), assessed by Masson’s trichrome staining was reduced to 12.6±1.0% with SRLX as compared to 23.7±3.0% with saline at 28 days post MI (Fig. B). The apoptotic index, measured by TUNEL assay, was 4-fold higher in the saline group vs. SRLX group on day 28 post MI (Fig. C). Fractional shortening (FS) measured using echocardiography on days 7 and 28 post-MI revealed significant LV dysfunction in saline-treated group; however, SRLX markedly preserved FS at both time points (Fig. D). Baseline FS was 43 ± 2%. Although the difference in caveolin-1 expression as assessed by immunofluorescence did not reach statistical significance (P=0.06, not shown) between the groups, there was a promising trend favoring increased capillary density with SRLX at 28 days in the post-infarcted heart. SRLX plasma levels were assessed 7 days after pump implantation using ELISA and the results demonstrate therapeutic levels comparable to plasma relaxin during the first trimester of pregnancy (Fig. E).   Conclusion:  SRLX improves survival and attenuates cardiomyocyte death and adverse LV remodeling at 28 days post MI. We propose that prolonged SRLX therapy can be explored for treatment of chronic ischemic heart failure in patients.
Trends in tuberculosis in the UK
Authors: Philippe Glaziou, Katherine Floyd, Mario Raviglione
Journal: Thorax (2018)

The industrial revolution, starting in the 18th-century England and coupled with poverty, urbanisation and squalor, created an optimal environment for the propagation of TB.1 One in four deaths were due to TB by the early 19th century.2 Since then, the remarkable decline in the burden of TB at an average annual rate of 3.3% between 1913 and 1940, documented in one of the longest ever recorded time series of data on the burden of TB (figure 1), a notifiable disease in the UK since 1912, was only interrupted by the two world wars. During those years, the temporary peaks in both incidence and mortality were linked to impoverishment of the population and poorer nutrition. In the years following the Second World War, as in other Western European countries, the fall in TB burden significantly accelerated to an average annual decline of 10% between 1955 and 1960 following the advent of modern chemotherapy. This allowed a reduction in transmission and drastically improved the prognosis of the disease, with a case fatality ratio (approximated as the ratio of mortality over incidence) of about 50% in the prechemotherapy era dropping to less than 10% within a decade of the introduction of chemotherapy. A decline in the effective contact rate3 and low TB rates have also been achieved in other settings that have in common a combination of near-universal access to …
TCTAP A-048 Immediate and Long-term Results of Left Main Percutaneous Coronary Interventions: Single Centre Registry
Authors: Valeri Gelev, Ivayla Zhivkova Zheleva-Kyuchukova, Rumyana Radoslavova, Lilyana Zolumova, Vyara Mihaylova Konstantinova
Journal: Journal of the American College of Cardiology (2018)
A Survey of Interventional Cardiologists’ Attitudes and Beliefs About Public Reporting of Percutaneous Coronary Intervention
Authors: Daniel M. Blumenthal, Linda R. Valsdottir, Yuansong Zhao, Changyu Shen, Ajay J. Kirtane, Duane S. Pinto, Fred S. Resnic, Karen E. Joynt Maddox, Jason H. Wasfy, Roxana Mehran, Ken Rosenfield, Robert W. Yeh
Journal: JAMA Cardiology (2018)

Public reporting of procedural outcomes has been associated with lower rates of percutaneous coronary intervention (PCI) and worse outcomes after myocardial infarction. Contemporary data are limited on the influence of public reporting on interventional cardiologists' clinical decision making.To survey a contemporary cohort of interventional cardiologists in Massachusetts and New York about how public reporting of PCI outcomes influences clinical decision making.An online survey was developed with public reporting experts and administered electronically to eligible physicians in Massachusetts and New York who were identified by Doximity (an online physician networking site) and 2014 Medicare fee-for-service claims for PCI procedures. The personal and hospital characteristics of participants were ascertained via a comprehensive database from Doximity and the American Hospital Association annual surveys of US hospitals (2012 and 2013) and linked to survey responses. Associations between survey responses and characteristics of participants were evaluated in univariable and multivariable analyses.Reported rate of avoidance of performing PCIs in high-risk patients and of perception of pressure from colleagues to avoid performing PCIs.Of the 456 physicians approached, 149 (32.7%) responded, including 67 of 129 (51.9%) in Massachusetts and 82 of 327 (25.1%) in New York. The mean (SD) age was 49 (9.2) years; 141 of 149 participants (94.6%) were men. Most participants reported practicing at medium to large, nonprofit hospitals with high-volume cardiac catheterization laboratories and cardiothoracic surgery capabilities. In 2014, participants had higher annual PCI volumes among Medicare patients than nonparticipants did (median, 31; interquartile range [IQR], 13-47 vs median, 17; IQR, 0-41; P < .001). Among participants, 65% reported avoiding PCIs on at least 2 occasions becase of concern that a bad outcome would negatively impact their publicly reported outcomes; 59% reported sometimes or often being pressured by colleagues to avoid performing PCIs because of a concern about the patient's risk of death. After multivariable adjustment, more years of experience practicing interventional cardiology was associated with lower odds of PCI avoidance. The state of practice was not associated with survey responses.Current PCI public reporting programs can foster risk-averse clinical practice patterns, which do not vary significantly between interventional cardiologists in New York and Massachusetts. Coordinated efforts by policy makers, health systems leadership, and the interventional cardiology community are needed to mitigate these unintended consequences.
RO7020531, a novel prodrug of a toll-like receptor 7 agonist, is safe, well tolerated and activates TLR signaling in healthy volunteers
Authors: E. Gane, I. Folitar, C. Schwabe, I. Rodriguez, L. Gao, E. Calleja, R. Upmanyu, T. Racek, E. Coakley, J. Grippo
Journal: Journal of Hepatology (2018)
The Impact of Staging by Positron-Emission Tomography on Overall Survival and Progression-Free Survival in Patients With Locally Advanced NSCLC
Authors: Everett E. Vokes, Ramaswamy Govindan, Neill Iscoe, Anwar M. Hossain, Belen San Antonio, Nadia Chouaki, Marianna Koczywas, Suresh Senan
Journal: Journal of Thoracic Oncology (2018)
EDP-305, a highly selective and potent farnesoid X receptor agonist, favorably regulates the expression of key fibrogenic genes in vitro and in vivo
Authors: Y. Li, J. Shang, M. Chau, M. Roqueta-Riverta, K. Garlick, P. An, K. Vaid, Y. Popov, Y.S. Or, L. Jiang
Journal: Journal of Hepatology (2018)
A pilot study of galunisertib (LY2157299) plus stereotactic body radiotherapy (SBRT) in advanced hepatocellular carcinoma (HCC).
Authors: Kim Anna Reiss, Edgar Ben-Josef, Nevena Damjanov, Maarouf Hoteit, Mark H. O'Hara, Thomas Benjamin Karasic, Ursina R. Teitelbaum, Charles Schneider, Peter J. O'Dwyer, Erica L. Carpenter, Rosemarie Mick, Robert H. Vonderheide
Journal: Journal of Clinical Oncology (2018)

TPS528 Background: Hepatocellular carcinoma (HCC) is a common and lethal malignancy with few effective treatment options. Inherently aggressive disease biology combined with the immunosuppressive hepatic microenvironment creates a unique therapeutic challenge. TGF-β, the strongest known immunosuppressive cytokine [1, 2], modulates the hepatic immune response to various antigens and to ionizing radiation [3, 4]. TGF-β is constitutively released by liver cells and plays a key role in the early and late pathogenesis of HCC [5-7] by dampening the local T-cell response to the oncogenic hepatitis B and –C viruses [4, 8-11]. TGF-β is activated by ionizing radiation, where it blocks the effector T-cell response to cellular destruction and the release of tumor-specific antigens [4]. Preclinical data demonstrate that neutralizing TGF-β during radiation therapy effectively generates a CD8+ T-cell response to multiple endogenous tumor antigens [4], thereby generating an in-situ vaccine against a tumor [12-17]. We hypothesize that the combination of TGF-β receptor inhibition plus radiation therapy will produce a potent and clinically effective antitumor immune response against HCC. Methods: We have enrolled 9 of 15 planned patients on study NCT02906397. Eligibility criteria include inoperable HCC, Childs Pugh score of ≤7, and either failure of or refusal to take sorafenib. Patients must be 4 weeks from prior therapy and may not be taking immunosuppressants. Patients with major cardiac disease or abnormalities or a predisposition toward aneurysm development are excluded. Patients receive galunisertib on days 1-14 of 28 day cycles. SBRT will be delivered in a single fraction of 18 Gy between days 15-28 of C1. Pre-treatment and on-treatment biopsies are obtained, as well as serial blood collections for circulating tumor material. Immunologic evaluation will include TCR deep sequencing to track T-cell receptor clones, analysis of serum inflammatory cytokines, analysis of myeloid and B cell activation, multiplex flow cytometry of PBMCs to measure percentages and absolute counts of T-cell subsets and tissue assessment of immune markers. Peripheral and tissue levels of TGF-β will be assessed. Clinical trial information: NCT02906397.
Retinopathy Regression with Treat and Extend Ranibizumab for Diabetic Macular Edema
Authors: John F. Payne, W. Lloyd Clark, Beau B. Bruce, Charles C. Wykoff, David M. Brown, Brandon M. Menke, Shawn M. Iverson, Keri F. Allen, David S. Boyer, John F. Payne, W. Lloyd Clark, John A. Wells, David L. Johnson, Charles C. Wykoff, David M. Brown, Matthew Benz, Eric Chen, Richard H. Fish, Rosa Y. Kim, James C. Major, Ronan E. O’Malley, Amy C. Schefler, Ankoor R. Shah, Tien P. Wong, David S. Boyer, Roger L. Novack, Thomas G. Chu, Firas Rahhal, Homayoun Tabandeh, Richard H. Roe, Pouya N. Dayani, David Liao, Alexander Walsh, Daniel D. Esmaili
Journal: Ophthalmology (2018)
Abstract 16926: Phenotypically Heterogeneous Podoplanin-expressing Populations are Associated With Lymphatic Vessel Growth and Fibrogenic Responses in the Acutely and Chronically Infarcted Myocardium
Authors: Maria Cimini, Antonio Cannata, Calum A MacRae, Marcello Rota, Polina Goichberg
Journal: Circulation (2016)

Introduction: The cardiac lymphatic system is crucial for the control of intra-myocardial pressure and prevention of edema, lipid metabolism, and balanced regulation of tissue inflammation. Cardiac...
Bronchial mucosal IFN-α/β and pattern recognition receptor expression in patients with experimental rhinovirus-induced asthma exacerbations
Authors: Jie Zhu, Simon D. Message, Patrick Mallia, Tatiana Kebadze, Marco Contoli, Christine K. Ward, Elliot S. Barnathan, Mary Ann Mascelli, Onn M. Kon, Alberto Papi, Luminita A. Stanciu, Michael R. Edwards, Peter K. Jeffery, Sebastian L. Johnston
Journal: Journal of Allergy and Clinical Immunology (2018)

The innate immune system senses viral infection through pattern recognition receptors (PRRs), leading to type I interferon production. The role of type I interferon and PPRs in rhinovirus-induced asthma exacerbations in vivo are uncertain.We sought to compare bronchial mucosal type I interferon and PRR expression at baseline and after rhinovirus infection in atopic asthmatic patients and control subjects.Immunohistochemistry was used to detect expression of IFN-α, IFN-β, and the PRRs: Toll-like receptor 3, melanoma differentiation-associated gene 5, and retinoic acid-inducible protein I in bronchial biopsy specimens from 10 atopic asthmatic patients and 15 nonasthmatic nonatopic control subjects at baseline and on day 4 and 6 weeks after rhinovirus infection.We observed IFN-α/β deficiency in the bronchial epithelium at 3 time points in asthmatic patients in vivo. Lower epithelial IFN-α/β expression was related to greater viral load, worse airway symptoms, airway hyperresponsiveness, and reductions in lung function during rhinovirus infection. We found lower frequencies of bronchial subepithelial monocytes/macrophages expressing IFN-α/β in asthmatic patients during infection. Interferon deficiency at baseline was not accompanied by deficient PRR expression in asthmatic patients. Both epithelial and subepithelial PRR expression were induced during rhinovirus infection. Rhinovirus infection-increased numbers of subepithelial interferon/PRR-expressing inflammatory cells were related to greater viral load, airway hyperresponsiveness, and reductions in lung function.Bronchial epithelial IFN-α/β expression and numbers of subepithelial IFN-α/β-expressing monocytes/macrophages during infection were both deficient in asthmatic patients. Lower epithelial IFN-α/β expression was associated with adverse clinical outcomes after rhinovirus infection in vivo. Increases in numbers of subepithelial cells expressing interferon/PRRs during infection were also related to greater viral load/illness severity.
Early-Life Antibiotic-Driven Dysbiosis Leads to Dysregulated Vaccine Immune Responses in Mice
Authors: Miriam Anne Lynn, Damon John Tumes, Jocelyn Mei Choo, Anastasia Sribnaia, Stephen James Blake, Lex Ee Xiang Leong, Graeme Paul Young, Helen Siobhan Marshall, Steve Lodewijk Wesselingh, Geraint Berian Rogers, David John Lynn
Journal: Cell Host & Microbe (2018)
P157Reversing adrenoceptor dysfunction in obese perivascular adipose tissue using exercise
Authors: S Saxton, R G Aldous, S B Withers, J Ohanian, A M Heagerty
Journal: Cardiovascular Research (2018)

genotypes of hemostatic system.One patient (2,3%) had unfavorable heterozygous genotypes according to 5 studied variants predisposing to the development of thrombophilia; 8 (18%) had heterozygous genotypes of 4 SNP, 14 (32%) had heterozygous genotypes of 3 SNP, 14 (32%) had 2 SNPs, 4 (9% ) -1 SNP; only three (7%) individuals did not have adverse heterozygous alleles.The frequency of registration of genotypes predisposing to thromboses shown in table.At the same time, data are available on the prevalence of alleles 5G and 4G polymorphic variant of the PAI-1 gene in healthy adolescents in Russia.In particular, heterozygous genotypes of homozygotes both at the 5G allele and 4G allele are less frequently detected in patients with NOCA, and 5G / 4G are more often detected. Conclusion:The proportion of patients with NOCA among patients with ACS in 2015-2016 was 4.8%.The frequency of adverse allelic variants hemostatic gene polymorphisms associated with risk of thrombophilia in patients with ACS and NOCA was 98%.
P112Epithelial-to-mesenchymal transition is required for a therapeutic effect of epicardial-derived cells after myocardial infarction
Authors: A M Smits, AMD Vegh, T Van Herwaarden, M J Goumans
Journal: Cardiovascular Research (2018)

after, and 24h post cell delivery.In vitro bioluminescence signal was used to identify tissue samples containing GFP-Luc-MSCs.Myocardial tissue matrix metalloproteinase 2 (MMP2) (index of ischemic/oxidative stress) and CXCR4 receptor expression (index of homing signal) were measured in bioluminescence positive and negative myocardial areas one day post cell transfer.Biodistribution of the implanted cells was quantified by using Luciferase assay and confirmed by fluorescence immunochemistry.Global left ventricular ejection fraction (LVEF) was measured at baseline and one month post cell therapy using MRI.Results: AMF decreased immediately after intracoronary cell delivery, while no change in tissue perfusion was found in the IM group.Intracoronary delivery led to a significant increase in myocardial MMP2 expression and decreased expression of CXCR4.Fluorescence immunochemistry indicated a higher expression level of a variety of homing (tenascin and cadherin) and angiogenic factor (FGF-2 and VEGF) in the IM group.LVEF increase was also significantly higher in IM group at the 1-month follow up.Conclusions: Intracoronary stem cell delivery decreased AMF, increased myocardial expression of MMP2, and lead to reduced CXCR4 expression with enhanced biodistribution and diminished functional recovery post-infarction.
Response to: ’Unending story of the indirect immunofluorescence assay on HEp-2 cells: old problems and new solutions?' by Meroni <i>et al</i>
Authors: David S Pisetsky, Diane M Spencer, Peter E Lipsky, Brad H Rovin
Journal: Annals of the Rheumatic Diseases (2018)

We would like to thank Professor Meroni and colleagues for their comments1 regarding our paper2 on testing for antinuclear antibodies (ANAs) in patients with systemic lupus erythematosus (SLE) and the very thoughtful discussion of the approaches for serological determinations. This letter provides a further perspective on ANA assays that were also discussed in a letter to this journal by Dr M Mahler.3 With respect to approaches to serological testing beyond immunofluorescence assays (IFA), we fully agree that solid phase assays (SPA) can provide a useful adjunctive approach and, indeed, we provided data on an ANA ELISA in our paper. In our study, the SPA kit that we assessed did not perform better than the IFA tests (11.7% ANA negative for the …
Multiple-Institution Comparison of Resident and Faculty Perceptions of Burnout and Depression During Surgical Training
Authors: Michael L. Williford, Sara Scarlet, Michael O. Meyers, Daniel J. Luckett, Jason P. Fine, Claudia E. Goettler, John M. Green, Thomas V. Clancy, Amy N. Hildreth, Samantha E. Meltzer-Brody, Timothy M. Farrell
Journal: JAMA Surgery (2018)

Prior studies demonstrate a high prevalence of burnout and depression among surgeons. Limited data exist regarding how these conditions are perceived by the surgical community.To measure prevalence of burnout and depression among general surgery trainees and to characterize how residents and attendings perceive these conditions.This cross-sectional study used unique, anonymous surveys for residents and attendings that were administered via a web-based platform from November 1, 2016, through March 31, 2017. All residents and attendings in the 6 general surgery training programs in North Carolina were invited to participate.The prevalence of burnout and depression among residents was assessed using validated tools. Burnout was defined by high emotional exhaustion or depersonalization on the Maslach Burnout Inventory. Depression was defined by a score of 10 or greater on the Patient Health Questionnaire-9. Linear and logistic regression models were used to assess predictive factors for burnout and depression. Residents' and attendings' perceptions of these conditions were analyzed for significant similarities and differences.In this study, a total of 92 residents and 55 attendings responded. Fifty-eight of 77 residents with complete responses (75%) met criteria for burnout, and 30 of 76 (39%) met criteria for depression. Of those with burnout, 28 of 58 (48%) were at elevated risk of depression (P = .03). Nine of 77 residents (12%) had suicidal ideation in the past 2 weeks. Most residents (40 of 76 [53%]) correctly estimated that more than 50% of residents had burnout, whereas only 13 of 56 attendings (23%) correctly estimated this prevalence (P < .001). Forty-two of 83 residents (51%) and 42 of 56 attendings (75%) underestimated the true prevalence of depression (P = .002). Sixty-six of 73 residents (90%) and 40 of 51 attendings (78%) identified the same top 3 barriers to seeking care for burnout: inability to take time off to seek treatment, avoidance or denial of the problem, and negative stigma toward those seeking care.The prevalence of burnout and depression was high among general surgery residents in this study. Attendings and residents underestimated the prevalence of these conditions but acknowledged common barriers to seeking care. Discrepancies in actual and perceived levels of burnout and depression may hinder wellness interventions. Increasing understanding of these perceptions offers an opportunity to develop practical solutions.