bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Renal Impairment on the Pharmacokinetics of Morinidazole: Uptake Transporter-Mediated Renal Clearance of the Conjugated Metabolites
Authors: Zhong Kan , Li Xiuli , Xie Cen , Zhang Yifan , Zhong Dafang , Chen Xiaoyan 
Published: May 2014

ABSTRACT

Morinidazole is a novel 5-nitroimidazole antimicrobial drug that undergoes extensive metabolism in humans via
N
+
-glucuronidation (
N
+
-glucuronide of
S
-morinidazole [M8-1] and
N
+
-glucuronide of
R
-morinidazole [M8-2]) and sulfation (sulfate conjugate of morinidazole [M7]). Our objectives were to assess the effects of renal impairment on the pharmacokinetics (PK) of morinidazole and to elucidate the potential mechanisms. In this parallel-group study, healthy subjects and patients with severe renal impairment received an intravenous infusion of 500 mg of morinidazole. Plasma and urine samples were collected and analyzed. The areas under the plasma concentration-time curves (AUC) for M7, M8-1, and M8-2 were 15.1, 20.4, and 17.4 times higher, respectively, in patients with severe renal impairment than in healthy subjects, while the AUC for morinidazole was 1.5 times higher. The urinary recovery of the major metabolites was not significantly different between the two groups over 0 to 48 h, but the renal clearances of M7, M8-1, and M8-2 in patients were 85.3%, 92.5%, and 92.2% lower, respectively.
In vitro
transporter studies revealed that M7 is a substrate for organic anion transporter 1 (OAT1) and OAT3 (

K
m

= 28.6 and 54.0 μM, respectively). Only OAT3 transported M8-1 and M8-2. Morinidazole was not a substrate for the transporter-transfected cells examined. These results revealed that the function or activity of renal uptake transporters might be impaired in patients with severe renal impairment, which accounted for dramatically increased plasma exposure and reduced renal clearance of the conjugated metabolites of morinidazole, the substrates of renal transporters in patients. It will help clinicians to adjust the dose in patients with severe renal impairment and to predict possible transporter-based drug-drug interactions.
Immunomodulatory Effect of Linezolid on Methicillin-Resistant Staphylococcus aureus Supernatant-Induced MUC5AC Overexpression in Human Airway Epithelial Cells
Authors: Kaku Norihito , Yanagihara Katsunori , Morinaga Yoshitomo , Yamada Koichi , Harada Yosuke , Migiyama Yohei , Nagaoka Kentaro , Nakamura Shigeki , Izumikawa Koichi , Kohno Shigeru 
Published: May 2014

ABSTRACT

Linezolid is the first member of the oxazolidinones and is active against drug-resistant Gram-positive pathogens, such as methicillin-resistant
Staphylococcus aureus
(MRSA). Additionally, linezolid shows an immunomodulatory effect, such as inhibition of inflammatory cytokine production. In this study, we examined the effect of linezolid on MRSA-induced MUC5AC overexpression in airway epithelial cells. In this study, an MRSA supernatant was used to avoid the direct effect of linezolid on MRSA. MUC5AC protein production was significantly increased with a 40-fold dilution of MRSA supernatant. At the mRNA level, MUC5AC gene expression was significantly increased 6 and 9 h after stimulation. In an inhibition study, linezolid significantly reduced MRSA-induced MUC5AC protein and mRNA overexpression at concentrations of 5 and 20 μg/ml, which were the same as the trough and peak concentrations in human epithelial lining fluid. In an analysis of cell signaling, among the mitogen-activated protein kinase inhibitors, only the extracellular signal-regulated protein kinase 1/2 (ERK1/2) inhibitor reduced the MUC5AC protein production to the same level as that of the control; on Western blot analysis, only ERK1/2 was phosphorylated by the MRSA supernatant. In addition, the ERK1/2 phosphorylation was inhibited by linezolid. MUC5AC and MUC5B are the major barrier that traps inhaled microbial organisms, particulates, and foreign irritants. However, in patients with chronic respiratory diseases, pathogen-induced MUC5AC overexpression causes many problems, and control of the overexpression is important. Thus, this study revealed that linezolid showed a direct immunomodulatory effect in airway epithelial cells.
PaTH: towards a learning health system in the Mid-Atlantic region
Authors: Amin Waqas , Tsui Fuchiang (Rich) , Borromeo Charles , Chuang Cynthia H , Espino Jessi , Ford Daniel , Hwang Wenke , Kapoor Wishwa , Lehmann Harold , Martich G Daniel , Morton Sally , Paranjape Anuradha , Shirey William , Sorensen Aaron , Becich Michael J , Hess Rachel ,   the PaTH network team, Docimo Anne Boland , Gibson Kevin , Heinrich Theresa A , Jain Sandeep , Kahn Jeremy , Khorey Lisa , Lindell Kathleen , McTigue Kathleen , Mueller Mary , Ryan Chris , Clark Jeanne , Danoff Sonye , Gumas Diana , Meiselman Sam , Nazarian Saman , Oberteuffer Robert , Wang Nae-Yuh , Abendroth Thomas , Bascom Rebecca , Berg Arthur , Dimmock Anne , Dzomba Bari , Kraschnewski Jennifer , Naccarelli Gerald , Notterman Daniel , Paz Harold , Rauscher Richard , Sciamanna Christopher , Cheung Joseph , Cordova Francis , Feldman Art , Frank Erdlen , Jacobs Mike , Mohan Kruti , Parker Mitch , Pettengill Chad , Valentin Maribel , Weiner Mark 
Published: May 2014

Abstract
The PaTH (University of Pittsburgh/UPMC, Penn State College of Medicine, Temple University Hospital, and Johns Hopkins University) clinical data research network initiative is a collaborative effort among four academic health centers in the Mid-Atlantic region. PaTH will provide robust infrastructure to conduct research, explore clinical outcomes, link with biospecimens, and improve methods for sharing and analyzing data across our diverse populations. Our disease foci are idiopathic pulmonary fibrosis, atrial fibrillation, and obesity. The four network sites have extensive experience in using data from electronic health records and have devised robust methods for patient outreach and recruitment. The network will adopt best practices by using the open-source data-sharing tool, Informatics for Integrating Biology and the Bedside (i2b2), at each site to enhance data sharing using centrally defined common data elements, and will use the Shared Health Research Information Network (SHRINE) for distributed queries across the network.
Adjunctive value of intra-arterial cone beam CT angiography relative to DSA in the evaluation of cranial and spinal arteriovenous fistulas
Authors: Honarmand Amir R , Gemmete Joseph J , Hurley Michael C , Shaibani Ali , Chaudhary Neeraj , Pandey Aditya S , Bendok Bernard R , Ansari Sameer A 
Published: May 2014

ObjectiveTo assess the adjunctive diagnostic value of intra-arterial cone-beam CT angiography (IA-CBCTA) relative to digital subtraction angiography (DSA) in the anatomic identification/localization of intracranial/spinal arteriovenous fistulas (AVFs) and utility for surgical/endovascular treatment planning.MethodsRetrospectively, two blinded observers scored DSA and IA-CBCTA images of 32 patients with intracranial/spinal AVFs based on a qualitative scale. The following parameters were scored: arterial feeders, venous drainers and course, fistula site, and adjacent anatomic landmarks for cross-sectional localization. The total score was defined as the overall diagnostic value. Differences between IA-CBCTA and DSA scores were defined as the IA-CBCTA efficacy value. Observers described the treatment strategy at the end of DSA and IA-CBCTA grading, respectively. Mann–Whitney U test, Wilcoxon's signed rank test, and Kendall’s tau (τ) coefficient were used for statistical analysis.ResultsInterobserver agreement of overall diagnostic value for IA-CBCTA was good (τ=0.59, p=0.001) with no significant variance between the two observers' IA-CBCTA efficacy values (p=0.2). Significantly higher scores were assigned to IA-CBCTA for overall diagnostic value (both observers: p<0.0001), delineation of fistula site (observer 1: p<0.0001, observer 2: p=0.0003), and adjacent anatomic landmarks (both observers: p<0.0001). Observers found IA-CBCTA helpful, enabling a more confident treatment approach in 30 and 29 cases for observer 1 and observer 2, respectively. Both observers altered the treatment plan in two cases based on IA-CBCTA findings.ConclusionsIA-CBCTA as an adjunctive technique to DSA improves the anatomic delineation of AVFs, particularly for the fistula site and cross-sectional localization, and has the potential to improve treatment planning.
Ecologies, Post-Modern Urbanisms, and Symbolic Economies: A Comparative Assessment of American Urban Sociology
Authors: Hunter Marcus Anthony 
Published: May 2014

AbstractThe field of urban sociology has been significantly linked to particular cities, with cities such as Chicago (il), Los Angeles (ca), and New York City (ny) have become hallmarks reflecting both the possibilities and the limitations of the urban sociological imagination. Using what have been three major foci in American urban sociology – 1) Organization of the City, 2) Ethnography and 3) Neighborhoods – using a comparative assessment of the field this paper seeks to apprehend the larger understandings, trends and methods in the field. Comparing urban sociological methods and theories through sections focusing on the three aforementioned themes, this article underscores paths taken in the field whilst highlighting potential new directions.
Women affiliated with Muslims Against Crusaders and Women4Shariah
Authors: Ilyas Mohammed 
Published: May 2014

Abstract
Over the last few years we have seen a number of Muslim women being convicted of terrorism such as Roshonara Choudhry for stabbing MP Stephen Timms in 2010 and Shasta Khan for bomb making in 2012. These cases demonstrate that Muslim women, like their male counterparts are also targets for radicalization and recruitment from political and violent Islamist groups in the uk. Although it is important to explore the acquisition of extreme ideas and the move to violence but access to such individuals is very difficult. Access to women involved in Islamist groups is possible but is fraught with problems. This paper is based on preliminary findings from interviews carried out with Muslim women that were affiliated with political Islamist groups Muslim Against Crusaders (proscribed in 2011) and Women4Shariah. It explores how they become affiliated with the groups, and what impact this has had on their lives.
Development of a High-Resolution Gridded Daily Meteorological Dataset over Sub-Saharan Africa: Spatial Analysis of Trends in Climate Extremes
Authors: Chaney Nathaniel W. , Sheffield Justin , Villarini Gabriele , Wood Eric F. 
Published: May 2014

Abstract
Assessing changes in the frequency and intensity of extreme meteorological events and their impact on water resources, agriculture, and infrastructure is necessary to adequately prepare and adapt to future change. This is a challenge in data-sparse regions such as sub-Saharan Africa, where a lack of high-density and temporally consistent long-term in situ measurements complicates the analysis. To address this, a temporally homogenous and high-temporal- and high-spatial-resolution meteorological dataset is developed over sub-Saharan Africa (5°S–25°N), covering the time period between 1979 and 2005. It is developed by spatially downscaling the National Centers for Environmental Prediction–National Center for Atmospheric Research (NCEP–NCAR) reanalysis to a 0.1° spatial resolution, detecting and correcting for temporal inhomogeneities, and by removing random errors and biases by assimilating quality-controlled and gap-filled Global Summary of the Day (GSOD) in situ measurements. The dataset is then used to determine the statistical significance and magnitude of changes in climate extremes between 1979 and 2005. The results suggest a shift in the distribution of daily maximum and minimum temperatures toward a warmer mean with a faster increase in warm than cold events. Changes in the mean annual precipitation and heavy rainfall events are significant only in regions affected by the Sahel droughts of the 1970s and 1980s.
Summer Soil Moisture Spatiotemporal Variability in Southeastern Arizona
Authors: Stillman Susan , Ninneman Jason , Zeng Xubin , Franz Trenton , Scott Russell L. , Shuttleworth William J. , Cummins Ken 
Published: May 2014

Abstract
Soil moisture is important for many applications, but its measurements are lacking globally and even regionally. The Walnut Gulch Experimental Watershed (WGEW) in southeastern Arizona has measured near-surface 5-cm soil moisture with 19 in situ probes since 2002 within its 150 km2 area. Using various criteria to identify erroneous data, it is found that in any given period from 1 July to 30 September from 2002 to 2011, 13–17 of these probes were producing reasonable data, and this is sufficient to estimate area-averaged seasonal soil moisture. A soil water balance model is then developed using rainfall as its only input to spatially extrapolate soil moisture estimates to the 88 rain gauges located within the watershed and to extend the measurement period to 56 years. The model is calibrated from 2002 to 2011 so that the daily in situ and modeled soil moisture time series have a high average correlation of 0.89 and a root-mean-square deviation of 0.032 m3 m−3. By interpolating modeled soil moisture from the 88 rain gauges to a 100-m gridded domain over WGEW, it is found that spatial variability often increases when 88 (rather than 13–17) estimates are taken. While no trend in the spatial average surface soil moisture is found, large variability in the spatial average soil moisture from 1 July to 30 September is observed from year to year, ranging from 0.05 to 0.09 m3 m−3. In addition to spatiotemporal analysis of WGEW, this gridded soil moisture product from 1956 to 2011 can be used for validation of satellite-based and reanalysis products and land surface models.
Cloud Initialization in the Rapid Update Cycle of HIRLAM
Authors: de Haan Siebren , van der Veen Siebe H. 
Published: May 2014

Abstract
The Nowcasting Satellite Application Facility (NWC SAF) cloud mask from the Meteosat Second Generation (MSG) satellite is introduced in the initialization step of an hourly Rapid Update Cycle (RUC) of the High Resolution Limited Area Model (HIRLAM). MSG cloud-top temperatures and synoptic cloud-base height information are combined at analysis time. This cloud initialization scheme is applied to an experimental run, which is a copy of the operational Royal Netherlands Meteorological Institute [Koninklijk Nederlands Meteorologisch Instituut (KNMI)] RUC model. The experimental run was employed during the period June–December 2011. The RUC model has a forecast length of 6 h. Cloud cover forecasts are verified against MSG cloud cover information and synoptic observations. Forecasts of precipitation, surface pressure, 2-m temperature, and upper-air temperature are verified against synoptic observations and aircraft temperature observations. It is shown that including MSG cloud information in the RUC considerably improves the forecasts of most of these model fields, when compared to the operational control RUC. Both the bias and standard deviation of the errors of the cloud cover forecast are reduced substantially. Forecasts of light precipitation show a slight negative impact, but forecasts of heavy precipitation become better. The bias in 3D temperature fields disappears nearly completely. The error bias of 2-m temperatures has become larger. Two case studies are presented. The first case study had very good forecast performance with respect to low clouds when compared to the reference run. The second case study shows an ambiguous impact; there are still some deficiencies in the cloud initialization and cloud forecast when focusing on a single location.
Multiple transcription factors directly regulate Hox gene lin-39 expression in ventral hypodermal cells of the C. elegans embryo and larva, including the hypodermal fate regulators LIN-26 and ELT-6
Authors: Liu Wan-Ju , Reece-Hoyes John S , Walhout Albertha JM , Eisenmann David M 
Published: May 2014

AbstractBackgroundHox genes encode master regulators of regional fate specification during early metazoan development. Much is known about the initiation and regulation of Hox gene expression in Drosophila and vertebrates, but less is known in the non-arthropod invertebrate model system,C. elegans. TheC. elegansHox genelin-39is required for correct fate specification in the midbody region, including the Vulval Precursor Cells (VPCs). To better understandlin-39regulation and function, we aimed to identify transcription factors necessary forlin-39expression in the VPCs, and in particular sought factors that initiatelin-39expression in the embryo.ResultsWe used the yeast one-hybrid (Y1H) method to screen for factors that bound to 13 fragments from thelin-39region: twelve fragments contained sequences conserved betweenC. elegansand two other nematode species, while one fragment was known to drive reporter gene expression in the early embryo in cells that generate the VPCs. Sixteen transcription factors that bind to eightlin-39genomic fragments were identified in yeast, and we characterized several factors by verifying their physical interactionsin vitro, and showing that reduction of their function leads to alterations inlin-39levels andlin-39::GFPreporter expressionin vivo. Three factors, the orphan nuclear hormone receptor NHR-43, the hypodermal fate regulator LIN-26, and the GATA factor ELT-6 positively regulatelin-39expression in the embryonic precursors to the VPCs. In particular, ELT-6 interacts with an enhancer that drives GFP expression in the early embryo, and the ELT-6 site we identified is necessary for proper embryonic expression. These three factors, along with the factors ZTF-17, BED-3 and TBX-9, also positively regulatelin-39expression in the larval VPCs.ConclusionsThese results significantly expand the number of factors known to directly bind and regulatelin-39expression, identify the first factors required forlin-39expression in the embryo, and hint at a positive feedback mechanism involving GATA factors that maintainslin-39expression in the vulval lineage. This work indicates that, as in other organisms, the regulation of Hox gene expression inC. elegansis complicated, redundant and robust.
Pharmacokinetics of tramadol after subcutaneous administration in a critically ill population and in a healthy cohort
Authors: Dooney Neil M , Sundararajan Krishnaswamy , Ramkumar Tharapriya , Somogyi Andrew A , Upton Richard N , Ong Jennifer , O’Connor Stephanie N , Chapman Marianne J , Ludbrook Guy L 
Published: May 2014

Abstract

Background
Tramadol is an atypical centrally acting analgesic agent available as both oral and parenteral preparations. For patients who are unable to take tramadol orally, the subcutaneous route of administration offers an easy alternative to intravenous or intramuscular routes. This study aimed to characterise the absorption pharmacokinetics of a single subcutaneous dose of tramadol in severely ill patients and in healthy subjects.

Methods/design
Blood samples (5 ml) taken at intervals from 2 minutes to 24 hours after a subcutaneous dose of tramadol (50 mg) in 15 patients (13 male, two female) and eight healthy male subjects were assayed using high performance liquid chromatography. Pharmacokinetic parameters were derived using a non-compartmental approach.

Results
There were no statistically significant differences between the two groups in the following parameters (mean ± SD): maximum venous concentration 0.44 ± 0.18 (patients) vs. 0.47 ± 0.13 (healthy volunteers) mcg/ml (p = 0.67); area under the plasma concentration-time curve 177 ± 109 (patients) vs. 175 ± 75 (healthy volunteers) mcg/ml*min (p = 0.96); time to maximum venous concentration 23.3 ± 2 (patients) vs. 20.6 ± 18.8 (healthy volunteers) minutes (p = 0.73) and mean residence time 463 ± 233 (patients) vs. 466 ± 224 (healthy volunteers) minutes (p = 0.97).

Conclusions
The similar time to maximum venous concentration and mean residence time suggest similar absorption rates between the two groups. These results indicate that the same dosing regimens for subcutaneous tramadol administration may therefore be used in both healthy subjects and severely ill patients.

Trial registration

ACTRN12611001018909
Knowledge, attitudes, beliefs and behaviours of older adults about pneumococcal immunization, a Public Health Agency of Canada/Canadian Institutes of Health Research Influenza Research Network (PCIRN) investigation
Authors: Schneeberg Amy , Bettinger Julie A , McNeil Shelly , Ward Brian J , Dionne Marc , Cooper Curtis , Coleman Brenda , Loeb Mark , Rubinstein Ethan , McElhaney Janet , Scheifele David W , Halperin Scott A 
Published: May 2014

Abstract

Background
Fewer Canadian seniors are vaccinated against pneumococcal disease than receive the influenza vaccine annually. Improved understanding of factors influencing pneumococcal vaccination among older adults is needed to improve vaccine uptake.

Methods
A self-administered survey measuring knowledge, attitudes, beliefs and behaviours about pneumococcal vaccination was administered to a cohort of seniors participating in a clinical trial of seasonal influenza vaccines at eight centers across Canada. Eligible participants were ambulatory adults 65 years of age or older, in good health or with stable health conditions, previously given influenza vaccine. The primary outcome was self-reported receipt of pneumococcal vaccination. Multi-variable logistic regression was used to determine factors significantly associated with pneumococcal vaccine receipt.

Results
A total of 863 participants completed questionnaires (response rate 92%); 58% indicated they had received the pneumococcal vaccine. Being offered the vaccine by a health care provider had the strongest relationship with vaccine receipt (AOR 23.4 (95% CI 13.4-40.7)). Other variables that remained significantly associated with vaccine receipt in the multivariable model included having heard of the vaccine (AOR 10.1(95% CI 4.7-21.7)), and strongly agreeing that it is important for adults > 65 to be vaccinated against pneumococcus (AOR 3.3 (95% CI 1.2-9.2)). Participants who were < 70 years of age were less likely to be vaccinated.

Conclusions
These results indicate healthcare recommendation significantly influenced vaccine uptake in this population of older adults. Measures to encourage healthcare providers to offer the vaccine may help increase coverage.
Proof by synthesis of Tobacco mosaic virus
Authors: Cooper Bret 
Published: May 2014

Abstract
Background
Synthetic biology is a discipline that includes making life forms artificially from chemicals. Here, a DNA molecule was enzymatically synthesized in vitro from DNA templates made from oligonucleotides representing the text of the first Tobacco mosaic virus (TMV) sequence elucidated in 1982. No infectious DNA molecule of that seminal reference sequence exists, so the goal was to synthesize it and then build viral chimeras.

Results
RNA was transcribed from synthetic DNA and encapsidated with capsid protein in vitro to make synthetic virions. Plants inoculated with the virions did not develop symptoms. When two nucleotide mutations present in the original sequence, but not present in most other TMV sequences in GenBank, were altered to reflect the consensus, the derivative synthetic virions produced classic TMV symptoms. Chimeras were then made by exchanging TMV capsid protein DNA with Tomato mosaic virus (ToMV) and Barley stripe mosaic virus (BSMV) capsid protein DNA. Virus expressing ToMV capsid protein exhibited altered, ToMV-like symptoms in Nicotiana sylvestris. A hybrid ORF6 protein unknown to nature, created by substituting the capsid protein genes in the virus, was found to be a major symptom determinant in Nicotiana benthamiana. Virus expressing BSMV capsid protein did not have an extended host range to barley, but did produce novel symptoms in N. benthamiana.

Conclusions
This first report of the chemical synthesis and artificial assembly of a plant virus corrects a long-standing error in the TMV reference genome sequence and reveals that unnatural hybrid virus proteins can alter symptoms unexpectedly.