tbuckley/cabot-search huggingface dataset:
Abstract 10654: Ultrasound Ultrafast Imaging of the Carotid Artery Pulse Wave Velocity: Is the Surrogate of Regional Artery Stiffness?
Authors: Li Zhang, Lingyun Fang, Dan Zhang, Feixiang Xiang, Yue Song, Mingxing Xie
Journal: Circulation (2019)

Background: Arterial stiffness could be a strongest predictor for coronary heart disease and stroke. Pulsed wave velocity(PWV) is “the most hallowed and still probably the best” measure of arterial...
OP0034 Inflammation-inducible intra-articular production of human il-1 receptor antagonist results in more efficient inhibition of collagen-induced arthritis than does constitutive local expression of the same transgene
Authors: FA Van de Loo, AC Bakker, LA Joosten, OJ Arntz, AW Varley, RS Munford, WB Van den Berg
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Achieving biologically effective yet safe levels of recombinant anti-inflammatory proteins by gene therapy may require three regulatory features: 1) a basal level that is sufficiently low to avoid or minimise chronic immunosuppression 2) transcriptional regulation over a wide dynamic range, and 3) induced expression levels that are sufficiently high to achieve the desired biological effects. The C3-Tat/HIV promoter construct seems to have these properties.<sup>1</sup> In this two-component expression system the complement factor 3 (C3) promoter regulates production of the HIV transactivator of transcription, and the Tat protein then stimulates expression of the desired transgene, which is regulated by the HIV-LTR promoter. Both C3 and HIV LTR promoters are inducible by proinflammatory cytokines. <h3>Objectives</h3> To achieve disease-inducible expression of recombinant anti-inflammatory proteins in order to allow autoregulation of drug dose by natural homeostatic mechanisms. <h3>Methods</h3> We compared a disease-inducible, two component expression system (C3-Tat/HIV) with the constitutive immediate early cytomegalovirus (ieCMV) promoter in the polyarticular Collagen-Induced Arthritis (CIA) model in mice. DBA/I mice were immunised with bovine type II collagen and boostered on day 22. On day 22, mice without any clinical signs of arthritis were selected and adenoviral vectors (Ad. CMV-Luc, Ad. CMV-IL-1Ra, or Ad. C3-Tat/HIV-IL-1Ra) that contained luciferase or the human IL-1Ra gene under control of one of the two promoters were used to transfect the synovial lining of both knees. The injected knee joints and ipsilateral paws were then scored for signs of arthritis and at the end histology was taken. <h3>Results</h3> Inducible promoter-driven IL-1Ra expression resulted in significantly improved inhibition of CIA than did CMV-driven IL-1Ra production. Moreover, overexpression of IL-1Ra in the knee joints also prevented CIA in the ipsilateral paws. <h3>Conclusion</h3> Our data (1) demonstrate the feasibility of an inducible expression system for producing a recombinant transgene for treatment of arthritis and (2) show that this system is more effective than strong, constitutive transgene expression for preventing collagen-induced arthritis in mice. <h3>Reference</h3> Varley AW, Geiszler SM, Gaynor RB, Munford RS. A two-component expression system that responds to inflammatory stimuli <i>in vivo</i>in vivo. Nat Biotechnol. 1997;15(10):1002–6
COVID-19 post-discharge mortality rate in a London district general hospital
Authors: J. Navvas, R. Varghese, B. Selvakannan, Y. Narayan, O. Newman, M. Butt, R. Ragatha, C. Freer, S. Kuckreja, S. Naik, U. Ekeowa, K. Nawaz, K. Khurum, P. Russell, M. S. Anwar, N. Surendraraj
Journal: Gut (2021)

Introduction Due to the novelty of COVID-19, uncertainty about the factors contributing to mortality, unavailability of definitive treatment options, limited access to medical, social support and rehabilitation in the community during the COVID-19 peak;compounded with anxiety and reluctance to seek medical help in timely manner, it was anticipated that vulnerable patients would be affected the worst  We report post-discharge mortality and the associated risk factors  Method This is a retrospective study of all the patients admitted at a busy district general hospital during the peak period of the COVID-19 pandemic i e  1st March to 20 June 2020  We included all patients aged 18 and above in data analysis  Results A total of 628 patients were admitted during the study period with 481 having positive swab PCR  Of these, 389 (62%) patients had two or more comorbidities, 311 (49 5%) hypertensive and 166 (26 4%) diabetic  In-hospital mortality: 226/628 (35 9%) patient died in hospital, of which 194 (85 8%) had a positive Coronavirus nasopharyngeal swab  This was statistically significant with p-value of 0 001  Post-discharge mortality of patients: 54/402 (13 4%) of those patients discharged home following hospitalisation died within 28 days of discharge  42/54 (77 7%) were swab positive  Swab positive patients 42/54 (77 8%) had a higher risk of death  Two thirds of swab positive patient were older than 75 years and 81% had two or more pre-existing comorbidities  There was no difference in length of stay between the survivors and non-survivors  Conclusion As expected, age, male gender, COVID-19 PCRpositivity, multiple comorbidities, high BMI and raised CRP were associated with higher in-hospital and post-discharge mortality  It is unsurprising that antibiotic treatment without bacterial infection was associated with higher but statistically insignificant mortality rate, while therapeutic anticoagulation and steroids were associated with better outcomes  There is an urgent need for further analysis of root cause to mitigate the modifiable factors and devise a robust post-discharge management plan in collaboration with all stakeholders
Positive selection of IgG+ over IgM+ B cells in the germinal center reaction
Authors: Christopher Sundling, Angelica W.Y. Lau, Katherine Bourne, Clara Young, Candy Laurianto, Jana R. Hermes, Rosemary J. Menzies, Danyal Butt, Nike J. Kräutler, David Zahra, Dan Suan, Robert Brink
Journal: Immunity (2021)
Abstract PO-026: DNA damage response and repair characterization in <i>CHK2</i>-deficient cancers
Authors: Carmen Muñoz-Maldonado, Aurélie Quintin, Daniel M. Aebersold, Yitzhak Zimmer, Michaela Medová
Journal: Clinical Cancer Research (2021)

Abstract Double strand breaks (DSBs) are the most lethal DNA lesions as they can result in chromosomal rearrangements or loss of genetic material. To detect and repair DNA, cells have developed the DNA damage response, a cascade of proteins in which the checkpoint kinase 2 (CHK2) is involved. CHK2-deficient cancers, such as breast, prostate or colon, might have a compromised response to ionizing radiation (IR), arresting cell cycle at checkpoints or inducing apoptosis in presence of irreparable damage. To understand how the lack of CHK2 is affecting DNA damage response and repair, the human isogenic HCT116 colorectal cancer cell lines proficient (CHK2 WT) and deficient (CHK2 KO) for CHK2 have been characterized. Cell cycle distribution and γH2AX foci formation were assessed by flow cytometry and immunofluorescence, respectively, to determine the differences in cell cycle checkpoints and DSBs infliction and resolution upon IR. Traffic Light Reporter, complemented by immunofluorescence of RAD51 foci, was employed in both CHK2 WT and KO cell lines to identify the preferred DSB repair pathway. Our results indicate that CHK2-proficient and -deficient cell lines do not exhibit significant differences in cell cycle distribution upon IR. On the other hand, CHK2 KO cells display a significant increase in γH2AX foci per cell compared to the CHK2 WT. Upon 1Gy of IR, cells lacking CHK2 increment the number of foci per cell, indicating that DSBs detection occurs independently of the CHK2 status. Furthermore, the Traffic Light Reporter revealed higher homologous recombination (HR) to non-homologous end-joining (NHEJ) ratio in the CHK2 KO cells as compared to their CHK2 WT counterparts, suggesting that the lack of CHK2 stimulates a shift in the DSBs repair pathway choice. These results contrast with the RAD51 foci formation, which seems to be compromised in the CHK2 KO cells in both treated and untreated conditions as compared to the CHK2-proficient cells. Our results suggest that CHK2 status considerably affects cellular DNA damage response and these differences in execution of DNA repair could be exploited in CHK2-deficient cancers. Citation Format: Carmen Muñoz-Maldonado, Aurélie Quintin, Daniel M. Aebersold, Yitzhak Zimmer, Michaela Medová. DNA damage response and repair characterization in CHK2-deficient cancers [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PO-026.
Tacrolimus Pharmacogenetics and Steady State Drug Concentrations in Cancer Patients Undergoing Allogeneic Stem Cell Transplantation
Authors: Issam Hamadeh, Qing Zhang, Nury M Steuerwald, Alicia Hamilton, Lawrence J Druhan, Yordanis Diez, Stephanie Rusin, Yimei Han, James Symanowski, Jigar Trivedi, Michael Richard Grunwald, Nilanjan Ghosh, Belinda Rene Avalos, Edward A Copelan, Jai N Patel
Journal: Blood (2017)
Investigation of Outcomes Using Immunophenotiping of Elderly Patients with Acute Myeloid Leukemia from Rio Grande Do Norte State, Brazil
Authors: Leonardo Lima Fernandes, Aldair Paiva, Gabriela Va Alves, Gilena Dantas Brito, Carolina Colaço Vilarim, Marcos Dias Leão, Rodrigo Villar Freitas, Andre Aleixo P. H. Dantas, Marcelo Rocha Barbosa, Geraldo Barroso Cavalcanti, Hugo Diogenes De Oliveira Paiva
Journal: Blood (2017)
Rapid spread and high impact of the variant of concern P.1 in the largest city of Brazil
Authors: Gabriela Rodrigues Barbosa, Luiz Vinicius Leão Moreira, Alberto Fernando Oliveira Justo, Ana Helena Perosa, Luciano Kleber de Souza Luna, Ana Paula Cunha Chaves, Mariana Sardinha Bueno, Danielle Dias Conte, Joseane Mayara Almeida Carvalho, Janesly Prates, Patricia Sousa Dantas, Klinger Soares Faico-Filho, Clarice Camargo, Paola Cristina Resende, Marilda Mendonça Siqueira, Nancy Bellei
Journal: Journal of Infection (2021)
Performance Evaluation of a Deep Learning System for Differential Diagnosis of Lung Cancer With Conventional CT and FDG PET/CT Using Transfer Learning and Metadata
Authors: Yong-Jin Park, Dongmin Choi, Joon Young Choi, Seung Hyup Hyun
Journal: Clinical Nuclear Medicine (2021)

Purpose We aimed to evaluate the performance of a deep learning system for differential diagnosis of lung cancer with conventional CT and FDG PET/CT using transfer learning (TL) and metadata. Methods A total of 359 patients with a lung mass or nodule who underwent noncontrast chest CT and FDG PET/CT prior to treatment were enrolled retrospectively. All pulmonary lesions were classified by pathology (257 malignant, 102 benign). Deep learning classification models based on ResNet-18 were developed using the pretrained weights obtained from ImageNet data set. We propose a deep TL model for differential diagnosis of lung cancer using CT imaging data and metadata with SUVmax and lesion size derived from PET/CT. The area under the receiver operating characteristic curve (AUC) of the deep learning model was measured as a performance metric and verified by 5-fold cross-validation. Results The performance metrics of the conventional CT model were generally better than those of the CT of PET/CT model. Introducing metadata with SUVmax and lesion size derived from PET/CT into baseline CT models improved the diagnostic performance of the CT of PET/CT model (AUC = 0.837 vs 0.762) and the conventional CT model (AUC = 0.877 vs 0.817). Conclusions Deep TL models with CT imaging data provide good diagnostic performance for lung cancer, and the conventional CT model showed overall better performance than the CT of PET/CT model. Metadata information derived from PET/CT can improve the performance of deep learning systems.
Patient-centred outcomes and effect of disease progression on health status in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation receiving maintenance olaparib or placebo (SOLO1): a randomised, phase 3 trial
Authors: Michael Friedlander, Kathleen N Moore, Nicoletta Colombo, Giovanni Scambia, Byoung-Gie Kim, Ana Oaknin, Alla Lisyanskaya, Gabe S Sonke, Charlie Gourley, Susana Banerjee, Amit Oza, Antonio González-Martín, Carol Aghajanian, William H Bradley, Joyce Liu, Cara Mathews, Frédéric Selle, Alain Lortholary, Elizabeth S Lowe, Robert Hettle, Emuella Flood, Elena Parkhomenko, Paul DiSilvestro
Journal: The Lancet Oncology (2021)
Quantifying the Effect of Lower vs Higher Positive End-Expiratory Pressure on Ventilator-Free Survival in ICU Patients
Authors: Zachary R. McCaw, Lu Tian, Lee-Jen Wei
Journal: JAMA (2021)

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Interfacing Biomaterials with Synthetic T Cell Immunity
Authors: Fang‐Yi Su, Quoc D. Mac, Anirudh Sivakumar, Gabriel A. Kwong
Journal: Advanced Healthcare Materials (2021)

The clinical success of cancer immunotherapy is providing exciting opportunities for the development of new methods to detect and treat cancer more effectively. A new generation of biomaterials is being developed to interface with molecular and cellular features of immunity and ultimately shape or control anti-tumor responses. Recent advances that are supporting the advancement of engineered T cells are focused here. This class of cancer therapy has the potential to cure disease in subsets of patients, yet there remain challenges such as the need to improve response rates and safety while lowering costs to expand their use. To provide a focused overview, recent strategies in three areas of biomaterials research are highlighted: low-cost cell manufacturing to broaden patient access, noninvasive diagnostics for predictive monitoring of immune responses, and strategies for in vivo control that enhance anti-tumor immunity. These research efforts shed light on some of the challenges associated with T cell immunotherapy and how engineered biomaterials that interface with synthetic immunity are gaining traction to solve these challenges.
Abstract 14714: Implementing a Multidimensional Model of Medical Adherence to Improve Outcomes in Blood Pressure Control
Authors: Masood A Shariff, Aaiza Aamer, Rakeshkumar Mistry, Humberto G Mendoza, Zerremi Cagaanan, Zeus Castro, Balavenkatesh Kanna, Maria Espejo
Journal: Circulation (2018)

Introduction: Hypertension (HTN) is a significant public health problem in the nation with half of the population unable to keep blood pressure (BP) under control. Uncontrolled hypertension leads t...
Personalized genome structure via single gamete sequencing
Authors: Ruqian Lyu, Vanessa Tsui, Davis J. McCarthy, Wayne Crismani
Journal: Genome biology (2021)

Abstract Genetic maps have been fundamental to building our understanding of disease genetics and evolutionary processes. The gametes of an individual contain all of the information required to perform a de novo chromosome-scale assembly of an individual’s genome, which historically has been performed with populations and pedigrees. Here, we discuss how single-cell gamete sequencing offers the potential to merge the advantages of short-read sequencing with the ability to build personalized genetic maps and open up an entirely new space in personalized genetics.
A cross-sectional seroepidemiology study of seven major enteroviruses causing HFMD in Guangdong, China
Authors: Fan Gao, Lian-lian Bian, Lei Chen, Yan-ping Zhou, Gui-fan Li, Qun-ying Mao, Qian He, Xing Wu, Shan-shan Yao, Xiao-ming Yang, Zheng-lun Liang
Journal: Journal of Infection (2021)
Recombinant GII.P16 genotype challenges RT-PCR-based typing in region A of norovirus genome
Authors: Floriana Bonura, Noemi Urone, Celestino Bonura, Leonardo Mangiaracina, Chiara Filizzolo, Giuseppa Sciortino, Giuseppa L. Sanfilippo, Vito Martella, Giovanni M. Giammanco, Simona De Grazia
Journal: Journal of Infection (2021)
Day 90 Post-Allogeneic Hematopoietic Cell Transplantation T Cell Receptor Diversity Level Correlates with Risk of Relapse in Patients with Multiple Myeloma
Authors: Robert Korngold, Kira Goldgirsh, Themba Nyirenda, Phyllis McKiernan, Ryan Emerson, Marissa Vignali, Julie Rubinstein, Harlan Robins, David Siegel, Michele L. Donato
Journal: Blood (2017)
Association of Oral Corticosteroid Bursts With Severe Adverse Events in Children
Authors: Tsung-Chieh Yao, Jiu-Yao Wang, Sheng-Mao Chang, Yen-Chen Chang, Yi-Fen Tsai, Ann Chen Wu, Jing-Long Huang, Hui-Ju Tsai
Journal: JAMA Pediatrics (2021)

<h3>Importance</h3> The adverse effects from the long-term use of oral corticosteroids are known, but, to our knowledge, few studies have reported the risk of corticosteroid bursts, particularly among children. <h3>Objective</h3> To quantify the associations of corticosteroid bursts with severe adverse events, including gastrointestinal (GI) bleeding, sepsis, pneumonia, and glaucoma, in children. <h3>Design, Setting, and Participants</h3> This study used data derived from the National Health Insurance Research Database in Taiwan from January 1, 2013, to December 31, 2017, on children younger than 18 years of age and used a self-controlled case series design. Data were analyzed from January 1 to July 30, 2020. <h3>Exposure</h3> Oral corticosteroid bursts (defined as oral corticosteroid use for ≤14 days). <h3>Main Outcomes and Measures</h3> Incidence rates were calculated of 4 severe adverse events (GI bleeding, sepsis, pneumonia, and glaucoma) in children who did or did not receive corticosteroid bursts. Conditional fixed-effect Poisson regression was used to estimate incidence rate ratios (IRRs) of severe adverse events within 5 to 30 days and 31 to 90 days after initiation of corticosteroid bursts. <h3>Results</h3> Among 4 542 623 children, 23% (1 064 587; 544 268 boys [51.1%]; mean [SD] age, 9.7 [5.8] years) were prescribed a single corticosteroid burst. The most common indications were acute respiratory tract infections and allergic diseases. The incidence rate differences per 1000 person-years between children administered a single corticosteroid burst and those not prescribed corticosteroids were 0.60 (95% CI, 0.55-0.64) for GI bleeding, 0.03 (95% CI, 0.02-0.05) for sepsis, 9.35 (95% CI, 9.19-9.51) for pneumonia, and 0.01 (95% CI, 0.01-0.03) for glaucoma. The IRRs within 5 to 30 days after initiating corticosteroid bursts were 1.41 (95% CI, 1.27-1.57) for GI bleeding, 2.02 (95% CI, 1.55-2.64) for sepsis, 2.19 (95% CI, 2.13-2.25) for pneumonia, and 0.98 (95% CI, 0.85-1.13) for glaucoma; the IRRs within the subsequent 31 to 90 days were 1.10 (95% CI, 1.02-1.19) for GI bleeding, 1.08 (95% CI, 0.88-1.32) for sepsis, 1.09 (95% CI, 1.07-1.11) for pneumonia, and 0.95 (95% CI, 0.85-1.06) for glaucoma. <h3>Conclusions and Relevance</h3> This study suggests that corticosteroid bursts, which are commonly prescribed for children with respiratory and allergic conditions, are associated with a 1.4- to 2.2-fold increased risk of GI bleeding, sepsis, and pneumonia within the first month after initiation of corticosteroid therapy that is attenuated during the subsequent 31 to 90 days.
Evaluation of Publication of Pediatric Drug Trials
Authors: Ananya Srivastava, Florence T. Bourgeois
Journal: JAMA Network Open (2021)

MethodsWe performed a cross-sectional evaluation of pediatric trials registered in ClinicalTrials.gov.Trials were included if they examined a drug intervention in children younger than 18 years; had a randomized trial design; were registered between January 1, 2014, and June 30, 2016; and were completed or discontinued by June 30, 2018. 3 This date was selected to allow a minimum of 2 years from trial end to publication of trial findings.The study was deemed exempt from institutional review board approval by the institutional review board at
Prognostic Value of Feature-Tracking Right Ventricular Longitudinal Strain in Severe Functional Tricuspid Regurgitation
Authors: Simone Romano, Davide Dell'atti, Robert M Judd, Raymond J Kim, Jonathan W Weinsaft, Jiwon Kim, John F Heitner, Rebecca T Hahn, Afshin Farzaneh-Far
Journal: JACC. Cardiovascular imaging (2021)
The Association of Mitochondrial Copy Number With Sarcopenia in Adult Survivors of Childhood Cancer
Authors: Kelly McCastlain, Carrie R Howell, Catherine E Welsh, Zhaoming Wang, Carmen L Wilson, Heather L Mulder, John Easton, Ann C Mertens, Jinghui Zhang, Yutaka Yasui, Melissa M Hudson, Leslie L Robison, Mondira Kundu, Kirsten K Ness
Journal: JNCI Journal of the National Cancer Institute (2021)

Abstract Background Adult childhood cancer survivors are at risk for frailty, including low muscle mass and weakness (sarcopenia). Using peripheral blood mitochondrial DNA copy number (mtDNAcn) as a proxy for functional mitochondria, this study describes cross-sectional associations between mtDNAcn and sarcopenia among survivors. Methods Among 1762 adult childhood cancer survivors (51.6% male; median age = 29.4 years, interquartile range [IQR] = 23.3-36.8), with a median of 20.6 years from diagnosis (IQR = 15.2-28.2), mtDNAcn estimates were derived from whole-genome sequencing. A subset was validated by quantitative polymerase chain reaction and evaluated cross-sectionally using multivariable logistic regression for their association with sarcopenia, defined by race-, age-, and sex-specific low lean muscle mass or weak grip strength. All statistical tests were 2-sided. Results The prevalence of sarcopenia was 27.0%, higher among female than male survivors (31.5% vs 22.9%; P &amp;lt; .001) and associated with age at diagnosis; 51.7% of survivors with sarcopenia were diagnosed ages 4-13 years (P = .01). Sarcopenia was most prevalent (39.0%) among central nervous system tumor survivors. Cranial radiation (odds ratio [OR] = 1.84, 95% confidence interval [CI] = 1.32 to 2.59) and alkylating agents (OR = 1.34, 95% CI = 1.04 to 1.72) increased, whereas glucocorticoids decreased odds (OR = 0.72, 95% CI = 0.56 to 0.93) of sarcopenia. mtDNAcn decreased with age (β = −0.81, P = .002) and was higher among female survivors (β = 9.23, P = .01) and among survivors with a C allele at mt.204 (β = −17.9, P = .02). In adjusted models, every standard deviation decrease in mtDNAcn increased the odds of sarcopenia 20% (OR = 1.20, 95% CI = 1.07 to 1.34). Conclusions A growing body of evidence supports peripheral blood mtDNAcn as a biomarker for adverse health outcomes; however, this study is the first to report an association between mtDNAcn and sarcopenia among childhood cancer survivors.