tbuckley/cabot-search huggingface dataset:
Restoring the natural tropism of AAV2 vectors for human liver
Authors: Marti Cabanes-Creus, Claus V. Hallwirth, Adrian Westhaus, Boaz H. Ng, Sophia H.Y. Liao, Erhua Zhu, Renina Gale Navarro, Grober Baltazar, Matthieu Drouyer, Suzanne Scott, Grant J. Logan, Giorgia Santilli, Antonette Bennett, Samantha L. Ginn, Geoff McCaughan, Adrian J. Thrasher, Mavis Agbandje-McKenna, Ian E. Alexander, Leszek Lisowski
Journal: Science Translational Medicine (2020)

AAVs isolated from human liver are tropic for human hepatocytes in vivo, but this phenotype becomes attenuated after passage in culture.
Access and Care Disparities in Ambulatory Surgery Centers
Authors: Marie Crandall
Journal: JAMA Surgery (2020)

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Use of imaging techniques for non-invasive assessment in the diagnosis and staging of non-alcoholic fatty liver disease
Authors: Luca Miele, Maria A. Zocco, Fabrizio Pizzolante, Nicoletta De Matthaeis, Maria E. Ainora, Antonio Liguori, Antonio Gasbarrini, Antonio Grieco, Gianludovico Rapaccini
Journal: Metabolism (2020)
A feedforward circuit shaped by ECT2 and USP7 contributes to breast carcinogenesis
Authors: Qi Zhang, Cheng Cao, Wenchen Gong, Kaiwen Bao, Qian Wang, Yuejiao Wang, Liyuan Bi, Shuai Ma, Jiao Zhao, Ling Liu, Shanshan Tian, Kai Zhang, Jie Yang, Zhi Yao, Nan Song, Lei Shi
Journal: Theranostics (2020)

Rationale: A number of guanine nucleotide exchange factors (GEFs) including epithelial cell transforming factor ECT2 are believed to drive carcinogenesis through activating distinct oncogenic GTPases. Yet, whether GEF-independent activity of ECT2 also plays a role in tumorigenesis remains unclear. Methods: Immunohistochemical (IHC) staining, colony formation and xenograft assays were used to examine the role of ECT2 in breast carcinogenesis. Co-immunoprecipitation, immunofluorescent stainings, in vivo deubiquitination and in vitro deubiquitination experiments were performed to examine the physical and functional interaction between ECT2 and ubiquitin-specific protease USP7. High-throughput RNA sequencing, quantitative reverse transcription-PCR and Western blotting were employed to investigate the biological significance of the interplay between ECT2 and USP7. Results: We report that ECT2 plays a tumor-promoting role in breast cancer, and GEF activity-deficient ECT2 is able to alleviate ECT2 depletion associated growth defects in breast cancer cells. Mechanistically, we demonstrated that ECT2 physically interacts with ubiquitin-specific protease USP7 and functionally facilitates USP7 intermolecular self-association, -deubiquitination and -stabilization in a GEF activity-independent manner. USP7 in turn, deubiquitinates and stabilizes ECT2, resulting in a feedforward regulatory circuit that ultimately sustains the expression of oncogenic protein MDM2. Conclusion: Our study uncovers a GEF-independent role of ECT2 in promoting survival of breast cancer cells, provides a molecular insight for the reciprocal regulation of ECT2 and USP7, and supports the pursuit of ECT2/USP7 as potential targets for breast cancer intervention.
Association between high blood pressure and long term cardiovascular events in young adults: systematic review and meta-analysis
Authors: Dongling Luo, Yunjiu Cheng, Haifeng Zhang, Mingchuan Ba, Pengyuan Chen, Hezhi Li, Kequan Chen, Weihong Sha, Caojin Zhang, Hao Chen
Journal: BMJ (2020)

Abstract Objective To evaluate and quantify the future risk of cardiovascular events in young adults with high blood pressure. Design Systematic review and meta-analysis. Data sources Medline, Embase, and Web of Science were searched from inception to 6 March 2020. Relative risks were pooled using a random effects model and expressed with 95% confidence intervals. Absolute risk difference was calculated. Dose-response relations between blood pressure and individual outcomes were assessed by a restricted cubic spline model. Eligibility criteria for selecting studies Studies were selected that investigated the adverse outcomes of adults aged 18-45 with raised blood pressure. The primary study outcome was a composite of total cardiovascular events. Coronary heart disease, stroke, and all cause mortality were examined as secondary outcomes. Results Seventeen observational cohorts consisting of approximately 4.5 million young adults were included in the analysis. The average follow-up was 14.7 years. Young adults with normal blood pressure had increased risk of cardiovascular events compared with those with optimal blood pressure (relative risk 1.19, 95% confidence interval 1.08 to 1.31; risk difference 0.37, 95% confidence interval 0.16 to 0.61 per 1000 person years). A graded, progressive association was found between blood pressure categories and increased risk of cardiovascular events (high normal blood pressure: relative risk 1.35, 95% confidence interval 1.22 to 1.49; risk difference 0.69, 95% confidence interval 0.43 to 0.97 per 1000 person years; grade 1 hypertension: 1.92, 1.68 to 2.19; 1.81, 1.34 to 2.34; grade 2 hypertension: 3.15, 2.31 to 4.29; 4.24, 2.58 to 6.48). Similar results were observed for coronary heart disease and stroke. Generally, the population attributable fraction for cardiovascular events associated with raised blood pressure was 23.8% (95% confidence interval 17.9% to 28.8%). The number needed to treat for one year to prevent one cardiovascular event was estimated at 2672 (95% confidence interval 1639 to 6250) for participants with normal blood pressure, 1450 (1031 to 2326) for those with high normal blood pressure, 552 (427 to 746) for those with grade 1 hypertension, and 236 (154 to 388) for those with grade 2 hypertension. Conclusions Young adults with raised blood pressure might have a slightly increased risk of cardiovascular events in later life. Because the evidence for blood pressure lowering is limited, active interventions should be cautious and warrant further investigation.
OP0072 Increased calreticulin expression on surface membranes of monocytes and neutrophils in systemic lupus erythematosus: relevance to apoptotic cell clearance
Authors: AP Cairns, AD Crockard, AL Bell
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Increased numbers of apoptotic leukocytes<sup>1</sup> and impaired clearance of apoptotic cells<sup>2</sup> have been demonstrated in SLE. Patients with C1q deficiency almost invariably develop SLE, probably because C1q is important in the clearance of apoptotic cells by monocyte/macrophages.<sup>3</sup> Calreticulin has been shown to bind to the early complement component C1q, and interfere with complement-mediated immune processes. Patients with systemic lupus erythematosus (SLE) have increased serum levels of calreticulin.<sup>4</sup> C-reactive protein (CRP) facilitates the clearance of apoptotic cells in the presence of C1q,<sup>5</sup> but CRP levels are inappropriately low in SLE. <h3>Objectives</h3> To measure the expression of calreticulin on the surface of peripheral blood monocytes and neutrophils in SLE patients compared to normal and rheumatoid arthritis (RA) subjects, and correlate these with disease activity. <h3>Methods</h3> Peripheral blood was sampled from 28 SLE, 17 normal, and 19 RA subjects. Calreticulin expression on monocytes and neutrophils was measured by immunofluorescence labelling and flow cytometry, and the density of surface expression of calreticulin expressed as mean channel fluorescence (MCF) values. <h3>Results</h3> Calreticulin was expressed on the surface of over 90% of monocyes and neutrophils in all three groups. No differences in the percentage of cells expressing calreticulin were seen when the three groups were compared. The density of surface expression of calreticulin on monocytes was significantly higher in SLE (median MCF = 4.45) compared with normal subjects (median MCF = 3.25, p = 0.014). Density of surface expression of calreticulin on neutrophils was also higher in SLE (median MCF = 19.6) compared with normal subjects (median MCF = 14.50, p = 0.002). Calreticulin expression did not correlate with SLAM or BILAG scores. There were trends towards higher surface calreticulin expression on monocytes and neutrophils in SLE compared with RA, but these did not reach statistical significance. <h3>Conclusion</h3> Calreticulin expression is increased on monocyte and neutrophil cell surface membranes in SLE. The combination of increased monocyte and neutrophil surface calreticulin expression (which can interfere with C1q-mediated clearance), and inappropriately low levels of serum CRP and/or C1q (which facilitate this clearance), may contribute to the increased circulating apoptotic leukocytes seen in SLE. <h3>References</h3> Courtney PA, Crockard AD, Williamson K, Irvine AE, Kennedy RJ, Bell AL. Ann Rheum Dis. 1999;58(5):309–14 Herrmann M, Voll RE, Zoller OM, Hagenhofer M, Ponner BB, Kalden JR. Arthritis Rheum. 1998;41(7):1241–50 Walport MJ, Davies KA, Botto M. Immunobiology 1998;199(2):265–85 Eggleton P, Reid KB, Kishore U, Sontheimer RD. Lupus 1997;6(7):564–71 Gershov D, Kim S, Brot N, Elkon KB. J Exp Med. 2000;192(9):1353–64
THU0153 Open-label evaluation of the quality of life of patients treated with etanercept in common rheumatology usage (ecru)
Authors: J Hermann, A Aytekin, J Bröll, A Dunky, J Nowak, F Singer, J Smolen
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Tumour Necrosis Factor-alpha (TNFα) plays an important role in the inflammatory processes of RA and the resulting joint pathology. Etanercept is a dimeric fusion protein consisting of two p75 TNFα receptors linked to the Fc portion of the human IgG1. This protein can bind and inactivate up to two free molecules of TNFα. The safety and efficacy of etanercept has been demonstrated in human clinical trials of early RA and active RA. <h3>Objectives</h3> This current study was designed to further evaluate safety and efficacy of etanercept. One of the objectives was also to evaluate quality of life of patients treated with this substance by means of SF-36. <h3>Methods</h3> This study was conducted in 55 Austrian outpatients with active RA who have failed at least one disease-modifying anti-rheumatic drug (DMARD). Each patient received twice-weekly subcutaneous injections of etanercept 25 mg administered over a treatment period of 16 weeks. Stable doses of methotrexate (MTX) and steroids were permitted. For SF-36 interpretation the normal rages of the most recent published Canadian data and SF-36 Manual were used. <h3>Results</h3> At baseline, all 8 domains revealed substantially lower score than observed in healthy subjects. Five of them indicated level of disability of 50% or more. At week 16, all domains improved. Observed improvements ranged from 15 (general health perceptions) to 42,1 points (role function limited by physical problems). All were clinically significant (more than 5 points improvement). Two domains reached almost level characteristic for a healthy population: social functioning (97% of normal) and mental health (92% of normal). <h3>Conclusion</h3> In general, study patients at baseline demonstrated poor functioning in all domains of SF-36 QoL assessment; in five domains their functioning was at least 50% worse than in healthy subjects. The study was conducted in a heavily pretreated population. In spite of that, substantial improvement in the course of the study was observed. Improvement in all domains could be observed already after one week of treatment. At week 16, substantial improvement in all 8 domains was recorded, in two of them reaching almost normal ranges. The significant improvement in Physical Function and Bodily Pain also suggest that work-difficulty may be delayed or prevented in patients treated with etanercept.
Tumor immune profiles noninvasively estimated by FDG PET with deep learning correlate with immunotherapy response in lung adenocarcinoma
Authors: Changhee Park, Kwon Joong Na, Hongyoon Choi, Chan-Young Ock, Seunggyun Ha, Miso Kim, Samina Park, Bhumsuk Keam, Tae Min Kim, Jin Chul Paeng, In Kyu Park, Chang Hyun Kang, Dong-Wan Kim, Gi-Jeong Cheon, Keon Wook Kang, Young Tae Kim, Dae Seog Heo
Journal: Theranostics (2020)

Rationale:The clinical application of biomarkers reflecting tumor immune microenvironment is hurdled by the invasiveness of obtaining tissues despite its importance in immunotherapy.We developed a deep learning-based biomarker which noninvasively estimates a tumor immune profile with fluorodeoxyglucose positron emission tomography (FDG-PET) in lung adenocarcinoma (LUAD).Methods: A deep learning model to predict cytolytic activity score (CytAct) using semi-automatically segmented tumors on FDG-PET trained by a publicly available dataset paired with tissue RNA sequencing (n = 93).This model was validated in two independent cohorts of LUAD: SNUH (n = 43) and The Cancer Genome Atlas (TCGA) cohort (n = 16).The model was applied to the immune checkpoint blockade (ICB) cohort, which consists of patients with metastatic LUAD who underwent ICB treatment (n = 29).Results: The predicted CytAct showed a positive correlation with CytAct of RNA sequencing in validation cohorts (Spearman rho = 0.32, p = 0.04 in SNUH cohort; spearman rho = 0.47, p = 0.07 in TCGA cohort).In ICB cohort, the higher predicted CytAct of individual lesion was associated with more decrement in tumor size after ICB treatment (Spearman rho = -0.54,p < 0.001).Higher minimum predicted CytAct in each patient associated with significantly prolonged progression free survival and overall survival (Hazard ratio 0.25, p = 0.001 and 0.18, p = 0.004, respectively).In patients with multiple lesions, ICB responders had significantly lower variance of predicted CytActs (p = 0.005). Conclusion:The deep learning model that predicts CytAct using FDG-PET of LUAD was validated in independent cohorts.Our approach may be used to noninvasively assess an immune profile and predict outcomes of LUAD patients treated with ICB.
Response by Zelniker et al to Letter Regarding Article, “Effect of Dapagliflozin on Atrial Fibrillation in Patients With Type 2 Diabetes Mellitus: Insights From the DECLARE-TIMI 58 Trial”
Authors: Thomas A. Zelniker, Itamar Raz, Marc S. Sabatine, Stephen D. Wiviott
Journal: Circulation (2020)
Incidence of Nosocomial COVID-19 in Patients Hospitalized at a Large US Academic Medical Center
Authors: Chanu Rhee, Meghan Baker, Vineeta Vaidya, Robert Tucker, Andrew Resnick, Charles A. Morris, Michael Klompas
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Some patients are avoiding essential care for fear of contracting coronavirus disease 2019 (COVID-19) in hospitals. There are few data, however, on the risk of acquiring COVID-19 in US hospitals. <h3>Objective</h3> To assess the incidence of COVID-19 among patients hospitalized at a large US academic medical center in the 12 weeks after the first inpatient case was identified. <h3>Design, Setting, and Participants</h3> This cohort study included all patients admitted to Brigham and Women's Hospital (Boston, Massachusetts) between March 7 and May 30, 2020. Follow-up occurred through June 17, 2020. Medical records for all patients who first tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse-transcription polymerase chain reaction (RT-PCR) on hospital day 3 or later or within 14 days of discharge were reviewed. <h3>Exposures</h3> A comprehensive infection control program was implemented that included dedicated COVID-19 units with airborne infection isolation rooms, personal protective equipment in accordance with US Centers for Disease Control and Prevention recommendations, personal protective equipment donning and doffing monitors, universal masking, restriction of visitors, and liberal RT-PCR testing of symptomatic and asymptomatic patients. <h3>Main Outcomes and Measures</h3> Whether infection was community or hospital acquired based on timing of tests, clinical course, and exposures. <h3>Results</h3> Over the 12-week period, 9149 patients (mean [SD] age, 46.1 [26.4] years; median [IQR] age, 51 years [30-67 years]; 5243 female [57.3%]) were admitted to the hospital, for whom 7394 SARS-CoV-2 RT-PCR tests were performed; 697 COVID-19 cases were confirmed, translating into 8656 days of COVID-19–related care. Twelve of the 697 hospitalized patients with COVID-19 (1.7%) first tested positive on hospital day 3 or later (median, 4 days; range, 3-15 days). Of these, only 1 case was deemed to be hospital acquired, most likely from a presymptomatic spouse who was visiting daily and diagnosed with COVID-19 before visitor restrictions and masking were implemented. Among 8370 patients with non–COVID-19–related hospitalizations discharged through June 17, 11 (0.1%) tested positive within 14 days (median time to diagnosis, 6 days; range, 1-14 days). Only 1 case was deemed likely to be hospital acquired, albeit with no known exposures. <h3>Conclusions and Relevance</h3> In this cohort study of patients in a large academic medical center with rigorous infection control measures, nosocomial COVID-19 was rare during the height of the pandemic in the region. These findings may inform practices in other institutions and provide reassurance to patients concerned about contracting COVID-19 in hospitals.
What do people hospitalised with covid-19 think about the care they received?
Authors: Meng-San Wu, Fatima Hayat, Libuse Ratcliffe, Mike B J Beadsworth, Sylviane Defres, Tom Wingfield
Journal: BMJ (2020)

Since the start of the covid-19 pandemic, an inordinate mass of variable quality evidence concerning clinical presentation, diagnostic assays, novel treatments, and vaccines has accumulated. As Michie and colleagues note,1 beyond modelling, practical evidence of social, environmental, behavioural, and systems interventions against covid-19 has received little attention. This is despite such complex interventions forming a cornerstone of the public health response of …
Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study
Authors: Aurélien Marabelle, Marwan Fakih, Juanita Lopez, Manisha Shah, Ronnie Shapira-Frommer, Kazuhiko Nakagawa, Hyun Cheol Chung, Hedy L Kindler, Jose A Lopez-Martin, Wilson H Miller, Antoine Italiano, Steven Kao, Sarina A Piha-Paul, Jean-Pierre Delord, Robert R McWilliams, David A Fabrizio, Deepti Aurora-Garg, Lei Xu, Fan Jin, Kevin Norwood, Yung-Jue Bang
Journal: The Lancet Oncology (2020)
Safety, Efficacy, and Pharmacokinetics of Almonertinib (HS-10296) in Pretreated Patients With EGFR-Mutated Advanced NSCLC: A Multicenter, Open-label, Phase 1 Trial
Authors: James Chih-Hsin Yang, D. Ross Camidge, Cheng-Ta Yang, Jianying Zhou, Renhua Guo, Chao-Hua Chiu, Gee-Chen Chang, Her-Shyong Shiah, Yuan Chen, Chin-Chou Wang, David Berz, Wu-Chou Su, Nong Yang, Ziping Wang, Jian Fang, Jianhua Chen, Petros Nikolinakos, You Lu, Hongming Pan, Ajit Maniam, Lyudmila Bazhenova, Keisuke Shirai, Mohammad Jahanzeb, Maurice Willis, Nehal Masood, Naveed Chowhan, Te-Chun Hsia, Hong Jian, Shun Lu
Journal: Journal of Thoracic Oncology (2020)
Volatile organic compounds in bile can distinguish pancreatic cancer from chronic pancreatitis: a prospective observational study
Authors: Udayakumar Navaneethan, Chad Spencer, Xiang Zhu, John J. Vargo, David Grove, Raed A. Dweik
Journal: Endoscopy (2020)

Abstract Background Early and accurate diagnosis of pancreatic cancer is important. Our aim was to identify potential volatile organic compounds (VOCs) in the bile that can help distinguish pancreatic cancer from chronic pancreatitis. Methods In this prospective observational study, bile was aspirated from patients undergoing endoscopic retrograde cholangiopancreatography for chronic pancreatitis and pancreatic cancer, and the gaseous headspace was analyzed using mass spectrometry. Results The study included a discovery cohort of 57 patients (46 pancreatic cancer, 11 chronic pancreatitis) and a validation cohort of 31 patients (19 and 12, respectively). Using logistic regression analysis, the model [0.158 × age + 9.747 × log (ammonia) – 3.994 × log (acetonitrile) + 5.044 × log (trimethylamine) – 30.23] successfully identified patients with pancreatic cancer with a sensitivity of 93.5 % and specificity of 100 % (likelihood ratio 40.9, area under the curve 0.98, 95 % confidence interval 0.95 – 1.00). The diagnostic accuracy of this model was confirmed in the second independent validation cohort. Conclusion The measurement of VOCs in bile helped to accurately distinguish pancreatic cancer from chronic pancreatitis.
Cavitation‐Inducible Mesoporous Silica–Titania Nanoparticles for Cancer Sonotheranostics
Authors: Jeongjin Lee, Jae‐Hyun Kim, Dong Gil You, Sohyun Kim, Wooram Um, Jueun Jeon, Chan Ho Kim, Hyeyeon Joo, Gi‐Ra Yi, Jae Hyung Park
Journal: Advanced Healthcare Materials (2020)

Sonodynamic therapy has received increasing attention for cancer treatments as an alternative to photodynamic therapy. However, its clinical applications have been limited by the lack of a sonosensitizer that is capable of producing sufficient amounts of reactive oxygen species (ROS) in response to ultrasound (US) exposure. Herein, PEGylated mesoporous silica-titania nanoparticles (P-MSTNs) are prepared and used as US-responsive nanocarriers for cancer sonotheranostics. Perfluorohexane (PFH), which is chosen as the gas precursor, is physically encapsulated into P-MSTNs using the oil-in-water emulsion method. Owing to the vaporization of the gas precursor, PFH@P-MSTNs (137 nm in diameter) exhibit a strong photoacoustic signal in vivo for at least 6 h. Compared to P-MSTNs, PFH@P-MSTNs generate significantly higher amounts of ROS due to the nanobubble-induced cavitation in the presence of US. When systemically administered to tumor-bearing mice, PFH@P-MSTNs effectively accumulate in the tumor site due to the passive targeting mechanism. Consequently, PFH@P-MSTNs show much higher antitumor efficacy than P-MSTNs due to the enhanced cavitation-mediated ROS generation in response to US exposure. It is considered that PFH@P-MSTNs may hold significant potential for cancer sonotheranostics.
Abstract 973: Angiotensin II Up-Regulates Soluble Epoxide Hydrolase in Vascular Endothelial Cells
Authors: Ding Ai, Deliang Guo, John Y Shyy, Yi Zhu
Journal: Circulation (2006)

Epoxyeicosatrienoic acids (EETs) can hyperpolarize vascular smooth muscle, induce dilation of coronary arteries, and decrease the expression of adhesion molecules, thus, may be endogenous mediators...