bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduction of Zika virus infectivity in platelet concentrates after treatment with ultraviolet C light and in plasma after treatment with methylene blue and visible light
Authors: Fryk Jesse J. , Marks Denese C. , Hobson‐Peters Jody , Watterson Daniel , Hall Roy A. , Young Paul R. , Reichenberg Stefan , Tolksdorf Frank , Sumian Chryslain , Gravemann Ute , Seltsam Axel , Faddy Helen M. 
Published: July 2017

BACKGROUNDZika virus (ZIKV) has emerged as a potential threat to transfusion safety worldwide. Pathogen inactivation is one approach to manage this risk. In this study, the efficacy of the THERAFLEX UV‐Platelets system and THERAFLEX MB‐Plasma system to inactivate ZIKV in platelet concentrates (PCs) and plasma was investigated.STUDY DESIGN AND METHODSPCs spiked with ZIKV were treated with the THERAFLEX UV‐Platelets system at 0.05, 0.10, 0.15, and 0.20 J/cm2 UVC. Plasma spiked with ZIKV was treated with the THERAFLEX MB‐Plasma system at 20, 40, 60, and 120 J/cm2 light at 630 nm with at least 0.8 µmol/L methylene blue (MB). Samples were taken before the first and after each illumination dose and tested for residual virus. For each system the level of viral reduction was determined.RESULTSTreatment of PCs with THERAFLEX UV‐Platelets system resulted in a mean of 5 log reduction in ZIKV infectivity at the standard UVC dose (0.20 J/cm2), with dose dependency observed with increasing UVC dose. For plasma treated with MB and visible light, ZIKV infectivity was reduced by a mean of at least 5.68 log, with residual viral infectivity reaching the detection limit of the assay at 40 J/cm2 (one‐third the standard dose).CONCLUSIONSOur study demonstrates that the THERAFLEX UV‐Platelets system and THERAFLEX MB‐Plasma system can reduce ZIKV infectivity in PCs and pooled plasma to the detection limit of the assays used. These findings suggest both systems have the capacity to be an effective option to manage potential ZIKV transfusion transmission risk.
Mitochondrial proteostasis as a shared characteristic of slowed aging: the importance of considering cell proliferation
Authors: Hamilton Karyn L. , Miller Benjamin F. 
Published: July 2017

AbstractProteostasis is one of the seven “pillars of aging research” identified by the Trans‐NIH Geroscience Initiative and loss of proteostasis is associated with aging and age‐related chronic disease. Accumulated protein damage and resultant cellular dysfunction are consequences of limited protein repair systems and slowed protein turnover. When relatively high rates of protein turnover are maintained despite advancing age, damaged proteins are more quickly degraded and replaced, maintaining proteome fidelity. Therefore, maintenance of protein turnover represents an important proteostatic mechanism. However, measurement of protein synthesis without consideration for cell proliferation can result in an incomplete picture, devoid of information about how new proteins are being allocated. Simultaneous measurement of protein and DNA synthesis provides necessary mechanistic insight about proteins apportioned for newly proliferating cells versus for somatic maintenance. Using this approach with a number of murine models of slowed aging shows that, compared to controls, energetic resources are directed more toward somatic maintenance and proteostasis, and away from cell growth and proliferation. In particular, slowed aging models are associated with heightened mechanisms of mitochondrial proteostatic maintenance. Taking cell proliferation into account may explain the paradoxical findings that aging itself and slowed aging interventions can both be characterized by slower rates of protein synthesis.
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The Norepinephrine Metabolite 3,4-Dihydroxymandelic Acid Is Produced by the Commensal Microbiota and Promotes Chemotaxis and Virulence Gene Expression in Enterohemorrhagic Escherichia coli
Authors: Sule Nitesh , Pasupuleti Sasi , Kohli Nandita , Menon Rani , Dangott Lawrence J. , Manson Michael D. , Jayaraman Arul 
Published: July 2017

ABSTRACT

Enterohemorrhagic
Escherichia coli
(EHEC) is a commonly occurring foodborne pathogen responsible for numerous multistate outbreaks in the United States. It is known to infect the host gastrointestinal tract, specifically, in locations associated with lymphoid tissue. These niches serve as sources of enteric neurotransmitters, such as epinephrine and norepinephrine, that are known to increase virulence in several pathogens, including enterohemorrhagic
E. coli
. The mechanisms that allow pathogens to target these niches are poorly understood. We previously reported that 3,4-dihydroxymandelic acid (DHMA), a metabolite of norepinephrine produced by
E. coli
, is a chemoattractant for the nonpathogenic
E. coli
RP437 strain. Here we report that DHMA is also a chemoattractant for EHEC. In addition, DHMA induces the expression of EHEC virulence genes and increases attachment to intestinal epithelial cells
in vitro
in a QseC-dependent manner. We also show that DHMA is present in murine gut fecal contents and that its production requires the presence of the commensal microbiota. On the basis of its ability to both attract and induce virulence gene expression in EHEC, we propose that DHMA acts as a molecular beacon to target pathogens to their preferred sites of infection
in vivo
.
Rifaximin versus norfloxacin for prevention of spontaneous bacterial peritonitis: a systematic review
Authors: Sidhu Gurpartap S , Go Andrew , Attar Bashar M , Mutneja Hemant R , Arora Shilpa , Patel Sanjay A 
Published: July 2017

AimThe aim of this systematic review is to evaluate the efficacy and safety of rifaximin in the prophylaxis of spontaneous bacterial peritonitis (SBP) as compared with norfloxacin.MethodsWe searched MEDLINE, CINAHL, Google Scholar and Cochrane databases from inception to January 2017. Reference lists of articles as well as conference proceedings were manually screened. We included studies that recruited patients with cirrhosis and ascites who met the criteria for primary or secondary SBP prophylaxis as defined by the European Association for the Study of the Liver and American Association for the Study of Liver Diseases. Two independent investigators reviewed the studies for eligibility, extracted the data and assessed study quality using the Cochrane risk of bias tool. The primary outcome was occurrence of SBP. Secondary outcomes included mortality and adverse events with therapy.ResultsOf the 435 studies identified, a total of five were included for full-text review. Four studies were eligible for the systematic review, three of which were randomised controlled trials and one was a prospective observational study. The population examined in majority of studies was primarily hepatitis C cirrhosis. The results of individual studies indicated either superior efficacy of rifaximin or no statistical difference between rifaximin and norfloxacin for SBP prophylaxis.ConclusionsModerate-quality evidence shows that long-term use of rifaximin appears to be a reasonable alternative to norfloxacin for SBP prevention in hepatitis C cirrhosis.
MCPIP1 Downregulation in Clear Cell Renal Cell Carcinoma Promotes Vascularization and Metastatic Progression
Authors: Marona Paulina , Górka Judyta , Mazurek Zofia , Wilk Waclaw , Rys Janusz , Majka Marcin , Jura Jolanta , Miekus Katarzyna 
Published: July 2017

Abstract
Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer and it forms highly vascularized tumors. The monocyte endoribonuclease MCPIP1 negatively regulates inflammation by degrading mRNA encoding proinflammatory cytokines, such as IL6, IL1, and IL12. MCPIP1 is also a negative regulator of NFκB and AP1 activity and it influences a broad range of miRNA activities. Here we report that MCPIP1 protein levels are decreased during renal cancer progression. In patient-derived tumors and xenografts established in NOD-SCID or nude mice, low MCPIP1 levels correlated strongly with increased proliferation, tumor outgrowth, and vascularity. MCPIP1 activity regulated secretion of VEGF, IL8, and CXCL12 leading to chemotaxis of microvascular endothelial cells, phosphorylation of VE-cadherin, and increased vascular permeability. Mechanistic investigations showed that MCPIP1 regulated ccRCC cell motility, lung metastasis, and mesenchymal phenotype by regulating key elements in the EMT signaling axis. Overall, our results illuminate how MCPIP1 serves as a key nodal point in coordinating tumor growth, angiogenesis, and metastatic spread in ccRCC. Cancer Res; 77(18); 4905–20. ©2017 AACR.
PI3Kγ/δ and NOTCH1 Cross-Regulate Pathways That Define the T-cell Acute Lymphoblastic Leukemia Disease Signature
Authors: Efimenko Evgeni , Davé Utpal P. , Lebedeva Irina V. , Shen Yao , Sanchez-Quintero Maria J. , Diolaiti Daniel , Kung Andrew , Lannutti Brian J. , Chen Jianchung , Realubit Ronald , Niatsetskaya Zoya , Ten Vadim , Karan Charles , Chen Xi , Califano Andrea , Diacovo Thomas G. 
Published: July 2017

AbstractPI3K/AKT and NOTCH1 signaling pathways are frequently dysregulated in T-cell acute lymphoblastic leukemias (T-ALL). Although we have shown that the combined activities of the class I PI3K isoforms p110γ and p110δ play a major role in the development and progression of PTEN-null T-ALL, it has yet to be determined whether their contribution to leukemogenic programing is unique from that associated with NOTCH1 activation. Using an Lmo2-driven mouse model of T-ALL in which both the PI3K/AKT and NOTCH1 pathways are aberrantly upregulated, we now demonstrate that the combined activities of PI3Kγ/δ have both overlapping and distinct roles from NOTCH1 in generating T-ALL disease signature and in promoting tumor cell growth. Treatment of diseased animals with either a dual PI3Kγ/δ or a γ-secretase inhibitor reduced tumor burden, prolonged survival, and induced proapoptotic pathways. Consistent with their similar biological effects, both inhibitors downregulated genes involved in cMYC-dependent metabolism in gene set enrichment analyses. Furthermore, overexpression of cMYC in mice or T-ALL cell lines conferred resistance to both inhibitors, suggesting a point of pathway convergence. Of note, interrogation of transcriptional regulators and analysis of mitochondrial function showed that PI3Kγ/δ activity played a greater role in supporting the disease signature and critical bioenergetic pathways. Results provide insight into the interrelationship between T-ALL oncogenic networks and the therapeutic efficacy of dual PI3Kγ/δ inhibition in the context of NOTCH1 and cMYC signaling. Mol Cancer Ther; 16(10); 2069–82. ©2017 AACR.
Relationship between Vascular Resistance and Sympathetic Nerve Fiber Density in Arterial Vessels in Children With Sleep Disordered Breathing
Authors: Kontos Anna , Lushington Kurt , Martin James , Schwarz Quenten , Green Ryan , Wabnitz David , Xu Xiangjun , M. Sokoya Elke , Willoughby Scott , Baumert Mathias , Ferrante Antonio , La Forgia Melissa , Kennedy Declan 
Published: July 2017

Background
Sleep disordered breathing in children is associated with increased blood flow velocity and sympathetic overactivity. Sympathetic overactivity results in peripheral vasoconstriction and reduced systemic vascular compliance, which increases blood flow velocity during systole. Augmented blood flow velocity is recognized to promote vascular remodeling. Importantly, increased vascular sympathetic nerve fiber density and innervation in early life plays a key role in the development of early‐onset hypertension in animal models. Examination of sympathetic nerve fiber density of the tonsillar arteries in children undergoing adenotonsillectomy for Sleep disordered breathing will address this question in humans.

Methods and Results

Thirteen children scheduled for adenotonsillectomy to treat sleep disordered breathing underwent pupillometry, polysomnography, flow‐mediated dilation, resting brachial artery blood flow velocity (velocity time integral), and platelet aggregation. The dorsal lingual artery (tonsil) was stained and immunofluorescence techniques used to determine sympathetic nerve fiber density. Sympathetic nerve fiber density was correlated with increased resting velocity time integral (
r
=0.63;
P
<0.05) and a lower Neuronal Pupillary Index (
r
=−0.71,
P
<0.01), as well as a slower mean pupillary constriction velocity (mean,
r
=−0.64;
P
<0.05). A faster resting velocity time integral was associated with a slower peak pupillary constriction velocity (
r
=−0.77;
P
<0.01) and higher platelet aggregation to collagen antigen (
r
=0.64;
P
<0.05). Slower mean and peak pupillary constriction velocity were associated with higher platelet aggregation scores (
P
<0.05;
P
<0.01, respectively).

Conclusions
These results indicate that sympathetic activity is associated with change in both the function and structure of systemic vasculature in children with sleep disordered breathing.
Blood Biomarkers for the Early Diagnosis of Stroke
Authors: Bustamante Alejandro , López-Cancio Elena , Pich Sara , Penalba Anna , Giralt Dolors , García-Berrocoso Teresa , Ferrer-Costa Carles , Gasull Teresa , Hernández-Pérez María , Millan Mónica , Rubiera Marta , Cardona Pedro , Cano Luis , Quesada Helena , Terceño Mikel , Silva Yolanda , Castellanos Mar , Garces Moisés , Reverté Silvia , Ustrell Xavier , Marés Rafael , Baiges Joan Josep , Serena Joaquín , Rubio Francisco , Salas Eduardo , Dávalos Antoni , Montaner Joan 
Published: July 2017

Background and Purpose—
Stroke diagnosis could be challenging in the acute phase. We aimed to develop a blood-based diagnostic tool to differentiate between real strokes and stroke mimics and between ischemic and hemorrhagic strokes in the hyperacute phase.

Methods—
The Stroke-Chip was a prospective, observational, multicenter study, conducted at 6 Stroke Centers in Catalonia. Consecutive patients with suspected stroke were enrolled within the first 6 hours after symptom onset, and blood samples were drawn immediately after admission. A 21-biomarker panel selected among previous results and from the literature was measured by immunoassays. Outcomes were differentiation between real strokes and stroke mimics and between ischemic and hemorrhagic strokes. Predictive models were developed by combining biomarkers and clinical variables in logistic regression models. Accuracy was evaluated with receiver operating characteristic curves.

Results—

From August 2012 to December 2013, 1308 patients were included (71.9% ischemic, 14.8% stroke mimics, and 13.3% hemorrhagic). For stroke versus stroke mimics comparison, no biomarker resulted included in the logistic regression model, but it was only integrated by clinical variables, with a predictive accuracy of 80.8%. For ischemic versus hemorrhagic strokes comparison, NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) >4.9 (odds ratio, 2.40; 95% confidence interval, 1.55–3.71;
P
<0.0001) and endostatin >4.7 (odds ratio, 2.02; 95% confidence interval, 1.19–3.45;
P
=0.010), together with age, sex, blood pressure, stroke severity, atrial fibrillation, and hypertension, were included in the model. Predictive accuracy was 80.6%.

Conclusions—
The studied biomarkers were not sufficient for an accurate differential diagnosis of stroke in the hyperacute setting. Additional discovery of new biomarkers and improvement on laboratory techniques seem necessary for achieving a molecular diagnosis of stroke.
Systematic Review of the Cost and Cost-Effectiveness of Rapid Endovascular Therapy for Acute Ischemic Stroke
Authors: Sevick Laura K. , Ghali Sarah , Hill Michael D. , Danthurebandara Vishva , Lorenzetti Diane L. , Noseworthy Tom , Spackman Eldon , Clement Fiona 
Published: July 2017

Background and Purpose—
Rapid endovascular therapy (EVT) is an emerging treatment option for acute ischemic stroke. Several economic evaluations have been published examining the cost-effectiveness of EVT, and many international bodies are currently making adoption decisions. The objective of this study was to establish the cost-effectiveness of EVT for ischemic stroke patients and to synthesize all the publicly available economic literature.

Methods—
A systematic review of the published literature was conducted to identify economic evaluations and cost analyses of EVT for acute ischemic stroke patients. Systematic review best practices were followed, and study quality was assessed.

Results—
Four-hundred sixty-three articles were identified from electronic databases. After deduplication, abstract review, and full-text review, 17 studies were included. Seven of the studies were cost analyses, and 10 were cost-effectiveness studies. Generally, the cost analyses reported on the cost of the approach/procedure or the hospitalization costs associated with EVT. All of the cost-effectiveness studies reported a cost per quality-adjusted life year as the primary outcomes. Studies varied in regards to the costs considered, the perspective adopted, and the time horizon used. All the studies reported a cost per quality-adjusted life year of <$50 000 as the primary outcome.

Conclusions—
There is a robust body of evidence for the cost and cost-effectiveness of EVT. The cost analyses suggested that although EVT was associated with higher costs, it also resulted in improved patient outcomes. From the cost-effectiveness studies, EVT seems to be good value for money when a threshold of $50 000 per quality-adjusted life year gained is adopted.
Real-World Setting Comparison of Nonvitamin-K Antagonist Oral Anticoagulants Versus Vitamin-K Antagonists for Stroke Prevention in Atrial Fibrillation
Authors: Ntaios George , Papavasileiou Vasileios , Makaritsis Konstantinos , Vemmos Konstantinos , Michel Patrik , Lip Gregory Y.H. 
Published: July 2017

Background and Purpose—
Evidence from the real-world setting complements evidence coming from randomized controlled trials. We aimed to summarize all available evidence from high-quality real-world observational studies about efficacy and safety of nonvitamin-K oral anticoagulants compared with vitamin-K antagonists in patients with atrial fibrillation.

Methods—
We searched PubMed and Web of Science until January 7, 2017 for observational nationwide or health insurance databases reporting matched or adjusted results comparing nonvitamin-K oral anticoagulants versus vitamin-K antagonists in patients with atrial fibrillation. Outcomes assessed included ischemic stroke, ischemic stroke or systemic embolism, any stroke or systemic embolism, myocardial infarction, intracranial hemorrhage, major hemorrhage, gastrointestinal hemorrhage, and death.

Results—
In 28 included studies of dabigatran, rivaroxaban, and apixaban compared with vitamin-K antagonists, all 3 nonvitamin-K oral anticoagulants were associated with a large reduction of intracranial hemorrhage (apixaban hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.31–0.63; dabigatran HR, 0.42; 95% CI, 0.37–0.49; rivaroxaban HR, 0.64; 95% CI, 0.47–0.86); similar rates of ischemic stroke and ischemic stroke or systemic embolism (apixaban HR, 1.05; 95% CI, 0.75–1.19 and HR, 1.08; 95% CI, 0.95–1.22 / dabigatran HR, 0.96; 95% CI, 0.80–1.16 and HR, 1.17; 95% CI, 0.92–1.50 / rivaroxaban HR, 0.89; 95% CI, 0.76–1.04 and HR, 0.73; 95% CI, 0.52–1.04, respectively); apixaban and dabigatran with lower mortality (HR, 0.65; 95% CI, 0.56–0.75 and HR, 0.63; 95% CI, 0.53–0.75, respectively); apixaban with fewer gastrointestinal (HR, 0.63; 95% CI, 0.42–0.95) and major hemorrhages (HR, 0.55; 95% CI, 0.48–0.63); dabigatran and rivaroxaban with more gastrointestinal hemorrhages (HR, 1.20; 95% CI, 1.06–1.36 and HR, 1.24; 95% CI, 1.08–1.41, respectively); dabigatran and rivaroxaban with similar rate of myocardial infarction (HR, 0.96; 95% CI, 0.77–1.21 and HR, 1.02; 95% CI, 0.54–1.89, respectively).

Conclusions—
This meta-analysis confirms the main findings of the randomized controlled trials of dabigatran, rivaroxaban, and apixaban in the real-world setting and, hence, strengthens their validity.
Diverse Characteristics of U.S. Summer Heat Waves
Authors: Lyon Bradfield , Barnston Anthony G. 
Published: July 2017

Abstract
Heat waves are climate extremes having significant environmental and social impacts. However, there is no universally accepted definition of a heat wave. The major goal of this study is to compare characteristics of continental U.S. warm season (May–September) heat waves defined using four different variables—temperature itself and three variables incorporating atmospheric moisture—all for differing intensity and duration requirements. To normalize across different locations and climates, daily intensity is defined using percentiles computed over the 1979–2013 period. The primary data source is the U.S. Historical Climatological Network (USHCN), with humidity data from the North American Regional Reanalysis (NARR) also tested and utilized. The results indicate that heat waves defined using daily maximum temperatures are more frequent and persistent than when based on minimum temperatures, with substantial regional variations in behavior. For all four temperature variables, heat waves based on daily minimum values have greater spatial coherency than for daily maximum values. Regionally, statistically significant upward trends (1979–2013) in heat wave frequency are identified, largest when based on daily minimum values, across variables. Other notable differences in behavior include a higher frequency of heat waves based on maximum temperature itself than for variables that include humidity, while daily minimum temperatures show greater similarity across all variables in this regard. Overall, the study provides a baseline to compare with results from climate model simulations and projections, for examining differing regional and large-scale circulation patterns associated with U.S. summer heat waves and for examining the role of land surface conditions in modulating regional variations in heat wave behavior.
The Chiricahua Gap and the Role of Easterly Water Vapor Transport in Southeastern Arizona Monsoon Precipitation
Authors: Ralph F. Martin , Galarneau Thomas J. 
Published: July 2017

Abstract
Between North America’s Sierra Madre and Rocky Mountains exists a little-recognized terrain “gap.” This study defines the gap, introduces the term “Chiricahua Gap,” and documents the role of easterly transport of water vapor through the gap in modulating summer monsoon precipitation in southeastern Arizona. The gap is near the Arizona–New Mexico border north of Mexico and is approximately 250 km wide by 1 km deep. It is the lowest section along a 3000-km length of the Continental Divide from 16° to 45°N and represents 80% of the total cross-sectional area below 2.5 km MSL open to horizontal water vapor transport in that region. This study uses reanalyses and unique upper-air observations in a case study and a 15-yr climatology to show that 72% (76%) of the top-quartile (decile) monsoon precipitation days in southeast Arizona during 2002–16 occurred in conditions with easterly water vapor transport through the Chiricahua Gap on the previous day.