tbuckley/cabot-search huggingface dataset:
Development of a public health emergency preparedness competency model for European Union countries
Authors: Michael A. Stoto, Elena Savoia, Christopher Nelson, Rachael Piltch-Loeb, Stefano Guicciardi, Judit Takacs, Carmen Varela Santos, Massimo Ciotti
Journal: Eurosurveillance (2018)

In 2017, the European Centre for Disease Prevention and Control (ECDC) developed a competency model for individuals who work in public health emergency preparedness (PHEP) in European Union (EU) countries. The model serves as the basis for developing competency-based training programmes to support professionals in PHEP efforts at the country level. The competency model describes the knowledge and skills professionals need when working in national-level PHEP, such as preparedness committee members or their equivalents. In order to develop the model, existing competency statements were reviewed, as well as case studies and reports. Fifty-three professionals from the EU and other countries provided feedback to the model by participating in a three-stage consultation process. The model includes 102 competency, 100 knowledge and 158 skill statements. In addition to specifying the appropriate content for training programmes, the proposed common competency model can help to standardise terminology and approaches to PHEP training.
Upregulation of CD81 in trophoblasts induces an imbalance of Treg/Th17 cells by promoting IL-6 expression in preeclampsia
Authors: Hailin Ding, Yimin Dai, Yi Lei, Zhiyin Wang, Dan Liu, Ruotian Li, Li Shen, Ning Gu, Mingming Zheng, Xiangyu Zhu, Guangfeng Zhao, Yali Hu
Journal: Cellular and Molecular Immunology (2018)
CD44ICD promotes breast cancer stemness via PFKFB4-mediated glucose metabolism
Authors: Ruifang Gao, Dan Li, Jing Xun, Wei Zhou, Jun Li, Juan Wang, Chen Liu, Xiru Li, Wenzhi Shen, Huan Qiao, Dwayne G. Stupack, Na Luo
Journal: Theranostics (2018)

CD44 is a single-pass cell surface glycoprotein that is distinguished as the first molecule used to identify cancer stem cells in solid tumors based on its expression.In this regard, the CD44 high cell population demonstrates not only the ability to regenerate a heterogeneous tumor, but also the ability to self-regenerate when transplanted into immune-deficient mice.However, the exact role of CD44 in cancer stem cells remains unclear in part because CD44 exists in various isoforms due to alternative splicing.Methods: Gain-and loss-of-function methods in different models were used to investigate the effects of CD44 on breast cancer stemness.Cancer stemness was analyzed by detecting SOX2, OCT4 and NANOG expression, ALDH activity, side population (SP) and sphere formation.Glucose consumption, lactate secretion and reactive oxygen species (ROS) levels were detected to assess glycolysis.Western blot, immunohistochemical staining, ELISA and TCGA dataset analysis were performed to determine the association of CD44ICD and PFKFB4 with clinical cases.A PFKFB4 inhibitor, 5MPN, was used in a xenograft model to inhibit breast cancer development.Results: In this report, we found that the shortest CD44 isoform (CD44s) inhibits breast cancer stemness, whereas the cleaved product of CD44 (CD44ICD) promotes breast cancer stemness.Furthermore, CD44ICD interacts with CREB and binds to the promoter region of PFKFB4, thereby regulating PFKFB4 transcription and expression.The resultant PFKFB4 expression facilitates the glycolysis pathway (vis-à-vis oxidative phosphorylation) and promotes stemness of breast cancer.In addition, we found that CD44ICD and PFKFB4 expressions are generally up-regulated in the tumor portion of breast cancer patient samples.Most importantly, we found that 5MPN (a selective inhibitor of PFKFB4) suppresses CD44ICD-induced tumor development.Conclusion: CD44ICD promotes breast cancer stemness via PFKFB4-mediated glycolysis, and therapies that target PFKFB4 (e.g., 5MPN therapy) may lead to improved outcomes for cancer patients.
Pregnant Women and the Ebola Crisis
Authors: Lisa B. Haddad, Denise J. Jamieson, Sonja A. Rasmussen
Journal: New England Journal of Medicine (2018)

Pregnant Women and the Ebola Crisis Ebola prevention and control measures in the current outbreak in the Democratic Republic of Congo have benefited from lessons learned from past outbreaks. Yet issues related to pregnant women have been largely ignored in these efforts.
Glycyrrhetinic acid binds to the conserved P-loop region and interferes with the interaction of RAS-effector proteins
Authors: Yuan Zhang, Zhihua Wang, Xiaoyao Ma, Shengnan Yang, Xueyan Hu, Jin Tao, Yuanyuan Hou, Gang Bai
Journal: Acta Pharmaceutica Sinica B (2018)

Members of the RAS proto-oncogene superfamily are indispensable molecular switches that play critical roles in cell proliferation, differentiation, and cell survival. Recent studies have attempted to prevent the interaction of RAS/GTP with RAS guanine nucleotide exchange factors (GEFs), impair RAS-effector interactions, and suppress RAS localization to prevent oncogenic signalling. The present study aimed to investigate the effect of the natural triterpenoic acid inhibitor glycyrrhetinic acid, which is isolated from the roots of Glycyrrhiza plant species, on RAS stability. We found that glycyrrhetinic acid may bind to the P-loop of RAS and alter its stability. Based on our biochemical tests and structural analysis results, glycyrrhetinic acid induced a conformational change in RAS. Meanwhile, glycyrrhetinic acid abolishes the function of RAS by interfering with the effector protein RAF kinase activation and RAS/MAPK signalling.
Overcoming the Barrier
Authors: Rabih M. Geha, Gurpreet Dhaliwal, Lisa G. Winston, Thomas S. Kickler, Reza Manesh
Journal: New England Journal of Medicine (2018)

A 74-year-old man presented to the emergency department with jaundice. Three days earlier, his wife had noted yellow discoloration of his eyes and skin, followed by progressive lethargy and confusion.
Analgesic efficacy and safety of morphine in the Procedural Pain in Premature Infants (Poppi) study: randomised placebo-controlled trial
Authors: Caroline Hartley, Fiona Moultrie, Amy Hoskin, Gabrielle Green, Vaneesha Monk, Jennifer L Bell, Andrew R King, Miranda Buckle, Marianne van der Vaart, Deniz Gursul, Sezgi Goksan, Edmund Juszczak, Jane E Norman, Richard Rogers, Chetan Patel, Eleri Adams, Rebeccah Slater
Journal: The Lancet (2018)

BackgroundInfant pain has immediate and long-term effects but is undertreated because of a paucity of evidence-based analgesics. Although morphine is often used to sedate ventilated infants, its analgesic efficacy is unclear. We aimed to establish whether oral morphine could provide effective and safe analgesia in non-ventilated premature infants for acute procedural pain.MethodsIn this single-centre masked trial, 31 infants at the John Radcliffe Hospital, Oxford, UK, were randomly allocated using a web-based facility with a minimisation algorithm to either 100 μg/kg oral morphine sulphate or placebo 1 h before a clinically required heel lance and retinopathy of prematurity screening examination, on the same occasion. Eligible infants were born prematurely at less than 32 weeks' gestation or with a birthweight lower than 1501 g and had a gestational age of 34–42 weeks at the time of the study. The co-primary outcome measures were the Premature Infant Pain Profile–Revised (PIPP-R) score after retinopathy of prematurity screening and the magnitude of noxious-evoked brain activity after heel lancing. Secondary outcome measures assessed physiological stability and safety. This trial is registered with the European Clinical Trials Database (number 2014-003237-25).FindingsBetween Oct 30, 2016, and Nov 17, 2017, 15 infants were randomly allocated to morphine and 16 to placebo; one infant assigned placebo was withdrawn from the study before monitoring began. The predefined stopping boundary was crossed, and trial recruitment stopped because of profound respiratory adverse effects of morphine without suggestion of analgesic efficacy. None of the co-primary outcome measures differed significantly between groups. PIPP-R score after retinopathy of prematurity screening was mean 11·1 (SD 3·2) with morphine and 10·5 (3·4) with placebo (mean difference 0·5, 95% CI −2·0 to 3·0; p=0·66). Noxious-evoked brain activity after heel lancing was median 0·99 (IQR 0·40–1·56) with morphine and 0·75 (0·33–1·22) with placebo (median difference 0·25, 95% CI −0·16 to 0·80; p=0·25).InterpretationAdministration of oral morphine (100 μg/kg) to non-ventilated premature infants has the potential for harm without analgesic efficacy. We do not recommend oral morphine for retinopathy of prematurity screening and strongly advise caution if considering its use for other acute painful procedures in non-ventilated premature infants.FundingWellcome Trust and National Institute for Health Research.
Ibrutinib and Obinutuzumab in CLL: Improved MRD Response Rates with Substantially Enhanced MRD Depletion for Patients with &gt;1 Year Prior Ibrutinib Exposure
Authors: Andy Rawstron, Talha Munir, Kristian Brock, Nichola Webster, Samuel Munoz Vicente, Francesca Yates, Sophie Cramp, Rebecca Bishop, Surita Dalal, Ruth M De Tute, Oonagh Sheehy, Andrew Pettitt, Christopher P. Fox, Stephen Devereux, Christopher Fegan, Donald MacDonald, Adrian Bloor, Peter Hillmen
Journal: Blood (2018)
Abstract 9598: Continuous Positive Airway Pressure Therapy and Rate of Stroke in Patients With Atrial Fibrillation
Authors: Dmitry Yaranov, Athanasios Smyrlis, Natalia Usatii, Amber Butler, Joann Petrini, Jose Mendez, Mark Warshofsky
Journal: Circulation (2014)

Introduction: Obstructive sleep apnea (OSA) has been proven to be an independent risk factor for ischemic stroke (CVA) and may increase the risk of the latter in patients with atrial fibrillation (...
An Economic Evaluation of Stopping Versus Continuing Tumor Necrosis Factor Inhibitor Treatment in Rheumatoid Arthritis Patients With Disease Remission or Low Disease Activity
Authors: An Tran‐Duy, Marjan Ghiti Moghadam, Martijn A. H. Oude Voshaar, Harald E. Vonkeman, Annelies Boonen, Philip Clarke, Geoff McColl, Peter M. ten Klooster, T. R. Zijlstra, Willem F. Lems, N. Riyazi, E. N. Griep, J. M. W. Hazes, Robert Landewé, Hein J. Bernelot Moens, Piet L. C. M. van Riel, Mart A. F. J. van de Laar, T. L. Jansen
Journal: Arthritis & Rheumatology (2018)

Objective To evaluate, from a societal perspective, the incremental cost‐effectiveness of withdrawing tumor necrosis factor inhibitor ( TNF i) treatment compared to continuation of these drugs within a 1‐year, randomized trial among rheumatoid arthritis patients with longstanding, stable disease activity or remission. Methods Data were collected from a pragmatic, open‐label trial. Cost‐utility analysis was performed using the nonparametric bootstrapping method, and a cost‐effectiveness acceptability curve was constructed using the net‐monetary benefit framework, where a willingness‐to‐accept threshold ( WTA ) was defined as the minimal cost saved that a patient accepted for each quality‐adjusted life year ( QALY ) lost. Results A total of 531 patients were randomized to the stop group and 286 patients to the continuation group. Withdrawal of TNF i treatment resulted in a &gt;60% reduction of the total drug cost, but led to an increase of ∼30% in other health care expenditures. Compared to continuation, stopping TNF i resulted in a mean yearly cost saving of €7,133 (95% confidence interval [95% CI ] €6,071, €8,234]) and was associated with a mean loss of QALY s of 0.02 (95% CI 0.002, 0.040). Mean saved cost per QALY lost and per extra flare incurred in the stop group compared to the continuation group was €368,269 (95% CI €155,132, €1,675,909) and €17,670 (95% CI €13,650, €22,721), respectively. At a WTA of €98,438 per QALY lost, the probability that stopping TNF i treatment is cost‐effective was 100%. Conclusion Although an official WTA is not defined, the mean saved cost of €368,269 per QALY lost seems acceptable in The Netherlands, given existing data on willingness to pay.
Iron, erythropoietin, and inflammation regulate hepcidin in <i>Bmp2</i>‐deficient mice, but serum iron fails to induce hepcidin in <i>Bmp6</i>‐deficient mice
Authors: Chia‐Yu Wang, Susanna Canali, Abraham Bayer, Som Dev, Aneesh Agarwal, Jodie L. Babitt
Journal: American Journal of Hematology (2018)

Abstract The bone morphogenetic protein (BMP)‐SMAD signaling pathway is a key transcriptional regulator of hepcidin in response to tissue iron stores, serum iron, erythropoietic drive and inflammation to increase the iron supply when needed for erythropoiesis, but to prevent the toxicity of iron excess. Recently, BMP2 was reported to play a non‐redundant role in hepcidin regulation in addition to BMP6. Here, we used a newly validated BMP2 ELISA assay and mice with a global or endothelial conditional knockout (CKO) of Bmp2 or Bmp6 to examine how BMP2 is regulated and functionally contributes to hepcidin regulation by its major stimuli. Erythropoietin (EPO) did not influence BMP2 expression in control mice, and still suppressed hepcidin in Bmp2 CKO mice. Lipopolysaccharide (LPS) reduced BMP2 expression in control mice, but still induced hepcidin in Bmp2 CKO mice. Chronic dietary iron loading that increased liver iron induced BMP2 expression, whereas acute oral iron gavage that increased serum iron without influencing liver iron did not impact BMP2. However, hepcidin was still induced by both iron loading methods in Bmp2 CKO mice, although the degree of hepcidin induction was blunted relative to control mice. Conversely, acute oral iron gavage failed to induce hepcidin in Bmp6 −/− or CKO mice. Thus, BMP2 has at least a partially redundant role in hepcidin regulation by serum iron, tissue iron, inflammation and erythropoietic drive. In contrast, BMP6 is absolutely required for hepcidin regulation by serum iron.
Cost-effectiveness Analysis of Routine Screening Using Massively Parallel Sequencing for Maturity-Onset Diabetes of the Young in a Pediatric Diabetes Cohort: Reduced Health System Costs and Improved Patient Quality of Life
Authors: Stephanie R. Johnson, Hannah E. Carter, Paul Leo, Samantha A. Hollingworth, Elizabeth A. Davis, Timothy W. Jones, Louise S. Conwell, Mark Harris, Matthew A. Brown, Nicholas Graves, Emma L. Duncan
Journal: Diabetes Care (2018)

OBJECTIVE Maturity-onset diabetes of the young (MODY) is an autosomal dominant form of diabetes, with multiple causative genes. Some MODY subtypes can be treated with sulfonylureas instead of insulin, improving glycemic control, complication rates, quality of life (QoL), and costs. Using massively parallel sequencing (MPS), we recently determined the prevalence of pathogenic/likely pathogenic MODY variants in an Australian pediatric diabetes cohort. Here, these data are used to estimate cost-effectiveness of using MPS for MODY in all pediatric diabetes cases compared with standard practice (sequencing limited to individuals with specific clinical features). RESEARCH DESIGN AND METHODS A Markov decision model was developed to estimate incremental costs and quality-adjusted life-years (QALYs) of MPS screening, modeled over 30 years. We used our observed prevalence of 2.14% compared with 0.7% for standard practice, based on published data. The probabilities and utility weightings of long-term diabetes complications were based on HbA1c and estimated from published data. A series of one-way sensitivity analyses were performed using the net monetary benefit framework. RESULTS Routine MPS screening for MODY was more effective and less costly than standard care screening, with 26 QALYs gained and 1,016,000 AUD (782,000 USD) saved per 1,000 patients. Cost of screening was fully offset within 10 years. Routine MPS screening remained dominant until MODY prevalence fell to &amp;lt;1.1%. CONCLUSIONS Routine MPS screening for MODY in the pediatric population with diabetes could reduce health system costs and improve patient QoL. Our results make a compelling argument for routine genetic screening in all children with presumed type 1 diabetes mellitus.
Abstract 17771: The Effect of Utilization of Non-vitamin K Antagonist Oral Anticoagulants on Time-Trends In Mortality and Hospitalization Rates for Atrial Fibrillation: A Nationwide Study Using the Korean National Health Insurance Data
Authors: Hee Tae Yu, Pil-Sung Yang, Jinseub Hwang, Soorack Ryu, Tae-Hoon Kim, Jae-Sun Uhm, Jong-Youn Kim, Hui-Nam Pak, Moon-Hyoung Lee, Boyoung Joung, Gregory Y Lip
Journal: Circulation (2017)

Introduction: The nationwide effect of significant changes in the rate of oral anticoagulation (OAC) on the mortality and admission rate of atrial fibrillation (AF) patients in the recent years is ...
Prediction of personalised prognosis in patients with amyotrophic lateral sclerosis: development and validation of a prediction model
Authors: H J Westeneng, Debray Tpa., A E Visser, van Eijk Rpa., Rooney Jpk., A Calvo, S Martin, C J McDermott, A G Thompson, S Pinto, X Koboleva, A Rosenbohm, B Stubendorff, H Sommer, B M Middelkoop, A M Dekker, van Vugt Jfa., W van Rheenen, A Vajda, M Heverin, M Kazoka, H Hollinger, M Gromicho, S Körner, T M Ringer, A Rödiger, A Gunkel, C E Shaw, A L Bredenoord, M A van Es, P Corcia, P Couratier, M Weber, J Grosskreutz, A C Ludolph, S Petri, M de Carvalho, P Van Damme, K Talbot, M R Turner, P J Shaw, A Al-Chalabi, A Chiò, O Hardiman, Moons Kgm., J H Veldink, L H van den Berg
Journal: The Lancet Neurology (2018)
Bystander Proliferation of Piga-Mutated Hematopoietic Progenitor Cells in Acquired Aplastic Anemia Patients Possessing HLA Class I Allele-Lacking Leukocytes
Authors: Takeshi Yoroidaka, Kohei Hosokawa, Tatsuya Imi, Takamasa Katagiri, Fumihiro Azuma, Shinji Nakao
Journal: Blood (2018)
Oncolytic virus immunotherapy: future prospects for oncology
Authors: Junaid Raja, Johannes M. Ludwig, Scott N. Gettinger, Kurt A. Schalper, Hyun S. Kim
Journal: Journal for ImmunoTherapy of Cancer (2018)

Immunotherapy is at the forefront of modern oncologic care. Various novel therapies have targeted all three layers of tumor biology: tumor, niche, and immune system with a range of promising results. One emerging class in both primary and salvage therapy is oncolytic viruses. This therapy offers a multimodal approach to specifically and effectively target and destroy malignant cells, though a barrier oncoviral therapies have faced is a limited therapeutic response to currently delivery techniques.
Hydroxyurea for Children with Sickle Cell Anemia in Sub-Saharan Africa
Authors: Léon Tshilolo, George Tomlinson, Thomas N. Williams, Brígida Santos, Peter Olupot-Olupot, Adam Lane, Banu Aygun, Susan E. Stuber, Teresa S. Latham, Patrick T. McGann, Russell E. Ware
Journal: New England Journal of Medicine (2018)

Hydroxyurea is an effective treatment for sickle cell anemia, but few studies have been conducted in sub-Saharan Africa, where the burden is greatest. Coexisting conditions such as malnutrition and malaria may affect the feasibility, safety, and benefits of hydroxyurea in low-resource settings.
Abstract P007: Arterial Stiffness is Associated With Increased Risk of Incident Dementia in the Older Elderly: The Cardiovascular Health Study Cognition Study
Authors: Chendi Cui, Akira Sekikawa, Lewis Kuller, Oscar Lopez, Anne Newman, Allison Kuipers, Rachel Mackey
Journal: Circulation (2018)

Introduction: Arterial stiffness is related to aging, hypertension, and obesity, and higher carotid-femoral pulse wave velocity (PWV) is associated with brain amyloid deposition. We hypothesized that higher cfPWV was associated with incident dementia in older adults (mean age 78) of the Cardiovascular Health Study Cognition Study (CHS-CS). Methods: Pittsburgh CHS-CS participants (n=532) without dementia at baseline (1998-99) had annual cognitive exams through 2013. CfPWV (m/sec) was measured from pulse velocity waveforms on 356 participants between 1996-2000, who were slightly younger, more educated, with less mild cognitive impairment (MCI) than those not included. Associations of cfPWV [continuous (transformed: -1/cfPWV) and quartile] with time-to-event [cfPWV measurement to dementia or death (competing event), or end of follow-up] were assessed in Cox proportional hazards model with competing risk of death. Results: Over 15-year follow-up, 212 (59.6%) dementia cases (median onset time=4 years) and 87 (24.4%) deaths occurred prior to dementia diagnosis. Adjusted for age and sex, incident dementia was related to higher cfPWV [hazard ratio (HR)=1.52 per -1/cfPWV, 95%CI=1.04, 2.24] (Table). Results were similar when further adjusted for education, race, ApoE4 , hypertension, diabetes, MCI, and abnormal white matter (WMG) or ventricular grade (VG). Results persisted in separate models that excluded those with ApoE4 + (n=79), diabetes (n=40), MCI (n=65) or abnormal WMG or VG (n=136). In stratified models, results were stronger for age ≥80 vs. &lt;80 and for hypertension vs. no hypertension. Pulse pressure (PP), another index of arterial stiffness, was not associated with incident dementia (age- and sex-adjusted HR=1.01 per mmHg PP, 95%CI=0.99, 1.01). Conclusions: Higher cfPWV, but not higher PP, was significantly associated with incident dementia in the older adults. Interventions to slow arterial stiffness with aging may reduce the risk of dementia among older individuals.
Overlooked Implications of Disturbed Sleep in Traumatic Brain Injury
Authors: Miranda M. Lim, Vincent Mysliwiec
Journal: JAMA Neurology (2018)

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