tbuckley/cabot-search huggingface dataset:
Screening the Blood Supply for Zika Virus in the 50 U.S. States and Puerto Rico
Authors: W. Alton Russell, Susan L. Stramer, Michael P. Busch, Brian Custer
Journal: Annals of Internal Medicine (2019)

In 2016, universal individual donation nucleic acid testing (ID-NAT) of donated blood for Zika virus began in U.S. states and territories.To assess the cost-effectiveness of universal ID-NAT in the first year of screening compared with alternatives for the 50 states and separately for Puerto Rico.Microsimulation that captured Zika-related harms to transfusion recipients, sexual partners, and their infants.National testing results compiled by AABB and costs, utilities, and outcome probabilities estimated from the literature.Transfusion recipients.Lifetime.Societal.Universal ID-NAT, universal mini-pool NAT (MP-NAT), and ID-NAT exclusively for components transfused to women of childbearing age. Seasonally targeted strategies in Puerto Rico and geographically targeted strategies in the 50 states were also considered.Costs, quality-adjusted life-years (QALYs), and outcomes.In Puerto Rico, MP-NAT exclusively during high mosquito season was cost-effective at $81 123 per QALY (95% CI, -$49 138 to $978 242 per QALY). No screening policy was cost-effective in the 50 states. Universal ID-NAT cost $341 million per QALY (CI, $125 million to $2.90 billion per QALY) compared with no screening in the 50 states.In Puerto Rico, MP-NAT only during the season of high mosquito activity was most cost-effective in 64% of probabilistic sensitivity analysis iterations. In the 50 states, no intervention was cost-effective in 99.99% of iterations. Cost-effectiveness was highly dependent on the rate of assumed infectious donations.Data were limited on the component-specific transmissibility of Zika and long-term sequelae of infection.Screening was cost-effective only in the high mosquito season in Puerto Rico, and no evaluated screening policy was cost-effective in the 50 states. During periods with lower rates of Zika-infectious donations, the cost-effectiveness of screening will be even less favorable.None.
Earth Observation: Investigating Noncommunicable Diseases from Space
Authors: Peng Jia, Alfred Stein, Peter James, Ross C. Brownson, Tong Wu, Qian Xiao, Limin Wang, Clive E. Sabel, Youfa Wang
Journal: Annual Review of Public Health (2019)

The United Nations has called on all nations to take immediate actions to fight noncommunicable diseases (NCDs), which have become an increasingly significant burden to public health systems around the world. NCDs tend to be more common in developed countries but are also becoming of growing concern in low- and middle-income countries. Earth observation (EO) technologies have been used in many infectious disease studies but have been less commonly employed in NCD studies. This review discusses the roles that EO data and technologies can play in NCD research, including ( a) integrating natural and built environment factors into NCD research, ( b) explaining individual-environment interactions, ( c) scaling up local studies and interventions, ( d) providing repeated measurements for longitudinal studies including cohorts, and ( e) advancing methodologies in NCD research. Such extensions hold great potential for overcoming the challenges of inaccurate and infrequent measurements of environmental exposure at the level of both the individual and the population, which is of great importance to NCD research, practice, and policy.
Abstract 12582: The Origin of Hypertension and Sympathetic Regulation in Diet Induced Obesity
Authors: Kyungjoon Lim, Benjie Barzel, Sandra L Burke, Geoffrey A Head
Journal: Circulation (2015)

Obesity is closely associated with a greater risk of developing hypertension and there is a strong link between bodyweight gain and greater blood pressure (BP). Plasma leptin levels correlate with BP and renal sympathetic nerve activity (RSNA). The central effects of leptin are mediated primarily through the arcuate (ARC) nucleus of the hypothalamus from which peripheral signals are relayed downstream, to other hypothalamic nuclei, via a network of second order neurons. Dense projections of both Neuropeptide Y (NPY) and alpha-melanocyte stimulating hormone (α-MSH) containing neurons ascend from the ARC and terminate in several hypothalamic nuclei such as the ventromedial hypothalamus (VMH) which are the key centres of energy homeostasis, hemodynamics and sympathetic tone to brown adipose and renal vasculature. It is therefore possible that a change in the activity of either POMC or, NPY neurons or both may underlie the mechanism by which sympathetic output is increased in obesity, leading to hypertension. In the present study we assessed the contribution of α-MSH and NPY neurons in the VMH on development of diet-induced neurogenic hypertension. New Zealand White rabbits were instrumented with a VMH cannula and a renal sympathetic nerve electrode. Blood pressure (BP) was measured by means of an intra-arterial catheter. Rabbits were injected with α-MSH, SHU9119 (MC3/4R antagonist), NPY or Leptin receptor antagonist into the VMH, 60 minutes apart using an injector. Following 3 weeks of a high fat diet (HFD, 13.5% fat), conscious rabbits had higher BP (+7.6 ± 0.5mmHg, P&lt;0.001) and RSNA (+4.6 ± 0.4nu, P&lt;0.001) compared to control group (3.5% fat). α-MSH injection into the VMH increased BP (+7%) and RSNA (+35%) (P&lt;0.001) and SHU9119 injection showed reduction (P&lt;0.05) in BP (-7%), HR (-5%) and RSNA (-23%) in HFD rabbits. Leptin antagonist or NPY injection showed dose dependant reduction in BP (-7%), HR (-5%) and RSNA (-11%) (P&lt;0.05) when given to HFD rabbits. NPY injection reduced BP in all groups. We conclude that the HFD feeding may induce pathway-specific changes in the VMH and VMH is the likely origin of leptin-mediated sympathoexcitation, α-MSH hypersensitivity and altered central responsiveness to NPY.
Interim Results from Fight-203, a Phase 2, Open-Label, Multicenter Study Evaluating the Efficacy and Safety of Pemigatinib (INCB054828) in Patients with Myeloid/Lymphoid Neoplasms with Rearrangement of Fibroblast Growth Factor Receptor 1 (FGFR1)
Authors: Srdan Verstovsek, Alessandro M. Vannucchi, Alessandro Rambaldi, Jason R. Gotlib, Adam J. Mead, Andreas Hochhaus, Jean-Jacques Kiladjian, Juan Carlos Hernandez Boluda, Ekaterine Asatiani, Christine Lihou, Huiling Zhen, Andreas Reiter
Journal: Blood (2018)
The Emergence and Functional Fitness of Memory CD4+ T Cells Require the Transcription Factor Thpok
Authors: Thomas Ciucci, Melanie S. Vacchio, Yayi Gao, Francesco Tomassoni Ardori, Julian Candia, Monika Mehta, Yongmei Zhao, Bao Tran, Marion Pepper, Lino Tessarollo, Dorian B. McGavern, Rémy Bosselut
Journal: Immunity (2019)
Altered Epigenetic Maturation in Early Erythroid Cells from Diamond Blackfan Anemia Patients Treated with Transfusions, Corticosteroids, or in Remission
Authors: Jason E. Farrar, Jessica Kang, Nancy Seidel, Jens Lichtenberg, Evangelia Atsidaftos, Jeffrey M Lipton, Adrianna Vlachos, David M. Bodine
Journal: Blood (2018)
AB1256 Development of a national service for biologic drug monitoring
Authors: M.E. Perry
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Monitoring serum levels of biological drugs has well recognised benefits for patients and health services. These include appropriate dosing, avoidance of overtreatment, identification of drug failure due to immunogenicity, cost and facilitation of switching therapy.<sup>1</sup> <h3>Objectives</h3> To establish a national service for monitoring serum levels of biological drugs. <h3>Methods</h3> National Services Scotland established a working group comprised of clinicians, lead pharmacist and Director of Public Health to help optimise biological drug prescribing. (Effective Prescribing Programme Biologics -EPPB). It was recognised that ad-hoc biologic drug monitoring (BM) posed a risk of variation in standards and inequity of access. Existing test volume and cost was established and a business case submitted to the CEO’s of each Health Board in Scotland for a national service, testing adalimumab and infliximab twice yearly in 2265 patients. Potential cost savings based on drug withdrawl of 2.5%, 5%, 10%, and 15% in gastroenterology patients ranged from 400,000Euro to 3.5 million Euro. Additional savings for dose reduction in rheumatology patients were not costed but likely to incur further financial advantage. <h3>Results</h3> The case was accepted and service tendered. A single site in Glasgow will run the assays (purchased from Grifols) commencing December 2017. The cost modelling predicts a 50% reduction in cost per test compared to existing arrangements. Cost for the whole service will be divided between the commissioning Health Boards with outlay proportional to patient population. The EPPB developed specialty specific advice and an ordercomm with minimum dataset accessible from all Health Boards with the option of retrospective interrogation. A national educational event is scheduled to improve clinician confidence and awareness. <h3>Conclusions</h3> To our knowledge this is the first national fully funded biologic drug monitoring service with access to all users of biological drugs. Its introduction will: 1. Support the implementation of national standards of care to ensure the effective and cost effective use of biologic medicines 2. Ensure equity of access to BM across Health Boards. 3. Provide a stronger position for procurement of biologic drugs (uncomplicated by additional service offerings) 4. Provide a sustainable service for Scotland, independent of the drug manufacturer. <h3>Reference</h3> [1] Jani, et al. Clinical Utility of Random Anti-Tumor Necrosis Factor Drug Level Testing and Measurement of Antidrug Antibodies on the Long-Term Treatment Response in Rheumatoid Arthritis. Arthritis and Rheumatology 67:8;(2015) p2011–2019. <h3>Disclosure of Interest</h3> None declared
Urinary Cross-Linked Carboxyterminal Telopeptide Decreases with Resolution of Painful Vaso-Occlusive Crises in Adults with Sickle Cell Disease - Results from the Sickle Cell Pain Markers (SCPM) Study
Authors: Oyebimpe O. Adesina, Isaac C. Jenkins, Qian V. Wu, Ellen B. Fung, Kanika Mahajan, Rebecca Kruse-Jarres
Journal: Blood (2018)
Development of a Human Antibody Cocktail that Deploys Multiple Functions to Confer Pan-Ebolavirus Protection
Authors: Anna Z. Wec, Zachary A. Bornholdt, Shihua He, Andrew S. Herbert, Eileen Goodwin, Ariel S. Wirchnianski, Bronwyn M. Gunn, Zirui Zhang, Wenjun Zhu, Guodong Liu, Dafna M. Abelson, Crystal L. Moyer, Rohit K. Jangra, Rebekah M. James, Russell R. Bakken, Natasha Bohorova, Ognian Bohorov, Do H. Kim, Michael H. Pauly, Jesus Velasco, Robert H. Bortz, Kevin J. Whaley, Tracey Goldstein, Simon J. Anthony, Galit Alter, Laura M. Walker, John M. Dye, Larry Zeitlin, Xiangguo Qiu, Kartik Chandran
Journal: Cell Host & Microbe (2019)
SP0065 To taper or not to taper non biological dmards in ra remission?
Authors: K.F. Baker, J.D. Isaacs
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> Remission is now a realistic goal in rheumatoid arthritis (RA), with a third of patients achieving sustained remission through the use of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) in modern treat-to-target strategies. Nevertheless, csDMARDs pose a risk of severe side-effects and require regular blood safety monitoring, which is both intrusive for patients and expensive for healthcare systems. This poses a therapeutic challenge – when is it appropriate to withdraw csDMARDs from patients with RA in sustained disease remission? In the first part of this presentation we will use case histories to contrast the possible outcomes following withdrawal of csDMARDs from patients in sustained remission, highlighting the uncertainty facing patients and their clinicians in this scenario (presented by Dr Kenneth Baker). In the second section of this lecture (presented by Prof John Isaacs) we will discuss the criteria to consider when stopping csDMARDs, any potential risks to the strategy, and the potential to identify informative biomarkers to help guide management of the patient in remission. <h3>Disclosure of Interest</h3> None declared
AB0664 Life expectancy in patient with giant cell arteritis (GCA): impact of vision loss
Authors: G.S. Breuer, V. Poltorak, R. Nesher, G. Nesher
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background and purpose</h3> Several epidemiologic studies reported increased mortality in patients with GCA, while others found that the overall survival was essentially identical to that of the general population. Those studies used different methods to calculate the mortality rates. <h3>Objectives</h3> In this retrospective study we evaluated longevity in a group of GCA patients using specific gender and age-matched life expectancy tables. <h3>Methods</h3> Medical records of patients diagnosed with GCA in one Medical Centre between 1980–1999 were reviewed for clinical parameters at the time of diagnosis and during the first year of treatment, and for time of death and cause of death. All patients diagnosed as GCA during that time period have already passed away. For each patient the observed survival was compared with the specific age and gender-matched life expectancy in the general population, based on life expectancy tables of the Israel Central Bureau of Statistics. <h3>Results</h3> 87 patients (51 females, 36 males) were included, their mean age at the time of GCA diagnosis was 73.9±8.4 and 75±8.1 years, respectively. The calculated mean life expectancy for this group of patients, from the time of diagnosis, was 14.1±6 years for females and 12±5.2 for males. However, the actual survival was significantly shorter, 7.5±6.2 years (p&lt;0.001) in females, and 7.7±7.3 years (p=0.005) in males. Survival was not significantly affected by the intensity of inflammation at the time of diagnosis (based on the presence of fever, anaemia, sedimentation rate above 100 mm/h, thrombocytosis and leukocytosis), by the daily dose of prednisone at 1 year, or by the use of low-dose aspirin during the first year. However, vision loss at the time of presentation (n=13), was associated with further decrease in survival, 4.1±4.4 years compared to 8.3±6.8 years in GCA patients with no vision loss (p=0.035). Causes of death were defined in 54 patients. The leading causes of death were cardiovascular/cerebrovascular diseases, in 43% of the patients, slightly exceeding the respective rate in the age-matched general population (40%, p=0. 8), and infectious diseases, in 37% of the patients, significantly exceeding the respective rate in the age-matched general population (22%, p=0.015). <h3>Conclusion</h3> Infectious diseases were often the cause of mortality In this group of GCA patients, relative to the background population. Survival following GCA diagnosis was significantly shorter than expected, especially in patients presenting with vision loss. <h3>Disclosure of Interest</h3> None declared
A phase II trial of second-line erlotinib in combination with stereotactic body radiation therapy (SBRT) for patients with metastatic non-small cell lung cancer (NSCLC).
Authors: Puneeth Iyengar, Brian D. Kavanagh, Irma Smith, Chul Ahn, David E. Gerber, Johnathan Dowell, Randall S. Hughes, Ramzi Abdulrahman, D. Ross Camidge, Laurie E. Gaspar, Robert Charles Doebele, Paul A. Bunn, Hak Choy, Robert D. Timmerman
Journal: Journal of Clinical Oncology (2013)

8074 Background: Stage IV NSCLC patients who progress through first-line therapy have poor progression-free survival (PFS) and overall survival (OS), most commonly failing in existing sites of gross disease after systemic therapy. Cytoreduction with SBRT may aid systemic agents in prolonging survival. We decided to test this hypothesis in a multi-institutional phase II study with SBRT and erlotinib. Methods: Stage IV NSCLC patients with ≤ 6 sites of extracranial disease who failed first-line systemic therapy were eligible to receive SBRT to all sites of clinically apparent disease, utilizing equipotent fractionation schemes based on location of disease and risk of toxicity to critical normal structures, and erlotinib given daily (150 mg OD) until disease progression. Frequent SBRT fractionation schemes used included 33 Gy in 11 Gy fractions and 40 Gy in 8 Gy fractions. Safety and clinical endpoints were evaluated. Results: 23 patients (12 M: 11 F) with a median age of 67 (56-86) were enrolled in this trial with median follow-up of 14.7 months. All patients progressed through platinum-based chemotherapy, 14 with paclitaxel and 7 with pemetrexed as part of the doublet regimen. 20/23 patients received SBRT to 3 or fewer sites. Lung parenchyma and mediastinal lymph nodes represented most common sites of irradiation. Median PFS was 10.7 months and median OS was 20.8 months.A majority of patients progressed in new sites with only 4 patients failing locally. Most distant failures manifested in the liver. Only one grade 3 toxicity, pneumonitis, was radiation-related. The trial commenced before molecular profiling became standard; 5/10 patient tumors tested, however, had EGFR alterations by IHC/FISH, 0/10 were positive for an EGFR mutation. Conclusions: Use of SBRT with erlotinib for unselected stage IV NSCLC patients as a second-line therapy was well tolerated and resulted in significant PFS and OS, substantially greater than historical values for patients who only received second-line systemic agents. Debulking gross disease with local therapy results in a median PFS of nearly a year with patients relapsing most commonly in new rather than existing sites. Clinical trial information: NCT00547105.
SAT0725-HPR Comparative analyses of responsiveness between the rheumatoid arthritis impact of disease (RAID) score, other patient reported outcomes and disease activity measures: secondary analyses from the arctic study
Authors: K. Holten, J. Sexton, T.K. Kvien, E.A. Haavardsholm, A.-B. Aga
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The RAID score is a patient-derived patient reported outcome measure (PROM), developed by a EULAR task force, that assesses the impact of RA on seven important domains. Responsiveness of the RAID score was assessed in the preliminary validation,<sup>1</sup> but more data is needed on the sensitivity to change, especially compared to other PROMs and other conventional outcome measures. <h3>Objectives</h3> The objective of this study was to assess the changes in the RAID score in patients with early RA during the first six months of intensive DMARD treatment, and to evaluate the responsiveness of RAID after 3 months compared to other PROMs and conventional measures of disease activity. <h3>Methods</h3> RA patients with short disease duration were followed in the 24 month treat-to-target strategy ARCTIC trial.<sup>2</sup> The responsiveness of the RAID score was evaluated by calculating the Standardised Response Mean (SRM) followed by the Relative Efficiency (RE) with respect to the Ritchie Articular Index. SRMs and RE were also calculated for other PROMs and clinical outcome measures. An SRM with absolute value above 0.80 was considered high. <h3>Results</h3> 230 RA patients were included. The mean symptom duration was 7.09±5.40 (±SD) months, the baseline mean RAID score was 4.49±2.14. At the 3 month follow-up, the mean change score for RAID was −2.25±1.98 and the SRM was −1.13 (-1.33 to −0.96) (table 1). The RAID score was more efficient in detecting change than the Ritchie Articular Index and also demonstrated relatively high efficiency in detecting change compared to other PROMs and clinical outcome measures (figure 1). <h3>Conclusions</h3> The RAID score proved to be highly responsive to change in RA patients with short disease duration who followed a treat-to-target strategy. The RAID score was efficient in detecting change compared to other PROMs and conventional disease activity measures. <h3>References</h3> [1] Gossec, et al. ARD2011;70:935–42. [2] Haavardsholm, et al. BMJ2016;354:i4205, 2016. <h3>Disclosure of Interest</h3> K. Holten: None declared, J. Sexton: None declared, T. K. Kvien: None declared, E. A. Haavardsholm Grant/research support from: Pfizer, UCB, Roche, MSD and AbbVie, A.-B. Aga: None declared
Abstract 14936: Activation of Cardiomyocyte Proliferation via Targeting Mir-128 in Infarcted Heart
Authors: Wei Huang, Jialiang Liang, Lin Jiang, Wenfeng Cai, Paul Christian, Meifeng Xu, Yigang Wang
Journal: Circulation (2016)

Background: In contrast to neonatal hearts, adult mouse cardiac regeneration ability is limited due to the ineffective reactivation of cardiomyocyte (CM) proliferation following injury. However, it is unclear whether the underlying mechanism employed during the neonatal period can be manipulated in the adult heart to activate endogenous CM proliferation and facilitate cardiac regeneration. Methods and Results: Mouse hearts were harvested at postnatal days 1, 7, and 28 (P1, P7, and P28) and analyzed to screen the miRNA involved in postnatal CM proliferation. The percentage of proliferative CM (Ki67+) in mouse hearts was significantly decreased between P7 and P28, whereas expression of miR128 progressively increased. Gain- and loss-of-function approaches using genetic mouse models were then developed to delineate the functional effects and mechanisms that involved in miR128-regulated CM proliferation. Cell dedifferentiation, DNA synthesis, mitosis, and cytokinesis were analyzed by immunostaining. Cell cycle...
Heterozygous <i>Tbk1</i> loss has opposing effects in early and late stages of ALS in mice
Authors: David Brenner, Kirsten Sieverding, Clara Bruno, Patrick Lüningschrör, Eva Buck, Simon Mungwa, Lena Fischer, Sarah J. Brockmann, Johannes Ulmer, Corinna Bliederhäuser, Clémentine E. Philibert, Takashi Satoh, Shizuo Akira, Séverine Boillée, Benjamin Mayer, Michael Sendtner, Albert C. Ludolph, Karin M. Danzer, Christian S. Lobsiger, Axel Freischmidt, Jochen H. Weishaupt
Journal: The Journal of Experimental Medicine (2019)

Heterozygous loss-of-function mutations of TANK-binding kinase 1 (TBK1) cause familial ALS, yet downstream mechanisms of TBK1 mutations remained elusive. TBK1 is a pleiotropic kinase involved in the regulation of selective autophagy and inflammation. We show that heterozygous Tbk1 deletion alone does not lead to signs of motoneuron degeneration or disturbed autophagy in mice during a 200-d observation period. Surprisingly, however, hemizygous deletion of Tbk1 inversely modulates early and late disease phases in mice additionally overexpressing ALS-linked SOD1G93A, which represents a “second hit” that induces both neuroinflammation and proteostatic dysregulation. At the early stage, heterozygous Tbk1 deletion impairs autophagy in motoneurons and prepones both the clinical onset and muscular denervation in SOD1G93A/Tbk1+/− mice. At the late disease stage, however, it significantly alleviates microglial neuroinflammation, decelerates disease progression, and extends survival. Our results indicate a profound effect of TBK1 on brain inflammatory cells under pro-inflammatory conditions and point to a complex, two-edged role of TBK1 in SOD1-linked ALS.
ACOT12-Dependent Alteration of Acetyl-CoA Drives Hepatocellular Carcinoma Metastasis by Epigenetic Induction of Epithelial-Mesenchymal Transition
Authors: Ming Lu, Wen-Wei Zhu, Xuan Wang, Jing-Jie Tang, Kai-Li Zhang, Guang-Yang Yu, Wei-Qing Shao, Zhi-Fei Lin, Sheng-Hao Wang, Lu Lu, Jian Zhou, Lian-Xin Wang, Hu-Liang Jia, Qiong-Zhu Dong, Jin-Hong Chen, Jian-Quan Lu, Lun-Xiu Qin
Journal: Cell Metabolism (2019)