bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlations between physiological parameters related with kidney function and minute‐by‐minute urine output
Authors: Otero Abraham , Cardinal‐Fernández Pablo , Nin Nicolás , Rojas Yeny , Oteiza Lorena , Garcia‐Carmona Rodrigo , Caffarena Gabriel , Lorente José A. 
Published: December 2015

AbstractAimRecently, devices capable of measuring minute‐by‐minute urine output (UOm) have become available. It is not known how UOm correlates with physiological parameters in normal conditions and in disease states characterized by vascular dysfunction. This paper analyzes correlations between UOm and physiological parameters related to kidney perfusion to provide some insight about UOm pathophysiological interpretation and its relationship with renal blood flow.MethodsWe studied 14 male pigs were anesthetized, tracheostomized, and mechanically ventilated. Mean systemic blood pressure (PART), mean pulmonary artery blood pressure (PPA), carotid artery blood flow (QCA), as well as total (QREN), cortical (QCOR) and medullary (QMED) renal blood flows, and the renal resistive index (RRI) were measured or calculated. Animals received an intravenous dose of live E. coli for the induction of sepsis (septic group), or an equivalent amount of normal saline (nonseptic group). Three groups were studied: nonseptic (n = 6) and septic (n = 4), both receiving for resuscitation NaCl 0.9% at 4 mL/kg per h; and septic (n = 4), receiving for resuscitation NaCl 0.9% at 17 mL/kg per h. Animals were monitored for 5 h after the induction of sepsis.ResultsIn septic animals, UOm was strongly positively correlated with QREN (Kendall's τ = 0.770, P < 0.05), QCOR (τ = –0.566, P < 0.05) and QMED (τ = 0.632, P < 0.05); and negatively correlated with PPA (τ = –0.524, P < 0.05) and RRI (τ = –0.672, P < 0.05). Control animals exhibited weaker correlations.ConclusionUOm is a good physiological surrogate marker of total and regional renal blood flows and vascular resistance, particularly under septic conditions, probably reflecting glomerulo‐tubular dysfunction in sepsis.
Progression and outcomes of non‐dialysis dependent chronic kidney disease patients: A single center longitudinal follow‐up study
Authors: Khan Yusra Habib , Sarriff Azmi , Adnan Azreen Syazril , Khan Amer Hayat , Mallhi Tauqeer Hussain , Jummaat Fauziah 
Published: December 2015

AbstractAimDespite increase global prevalence of End stage renal disease (ESRD) and subsequent need for renal replacement therapy (RRT), relatively little is known about disease progression and prognosis of earlier stages of CKD. Current study was conducted to examine rate of CKD progression, predictors of ESRD and death.MethodsA total 621 patients with estimated glomerular filtration rate (eGFR) of 15‐59ml/min/1.73m2 (CKD stage 3 & 4) were selected and followed up for 10 years or until ESRD or death, whichever occurred first. Subjects who did not meet inclusion criteria were excluded (n=1474).ResultsAnnual cumulative decline in eGFR was 3.01±0.40 ml/min/1.73m2. Overall disease progression was observed in 60% patients while 18% died. Among patients with CKD stage 3, 21% progressed to stage 4, 10% to stage 5ND (non‐dialysis) and 31% to RRT while mortality was observed in 16% patients. On the other hand, 8% patients with CKD stage 4 progressed to stage 5ND, 31% to RRT and mortality was observed in 24% cases. Patients with CVD, higher systolic blood pressure, elevated phosphate levels, heavy proteinuria, microscopic hematuria and use of diuretics were more likely to develop ESRD. Advancing age, low eGFR, low systolic blood pressure, low hemoglobin and baseline diabetes were found to be significant predictors of mortality while being female reduced risk of mortality.ConclusionOur data suggest that, in this CKD cohort, patients were more likely to develop ESRD than death. Prime importance should be given to mild forms of CKD to retard and even reverse CKD progression.
Genome‐wide recombination dynamics are associated with phenotypic variation in maize
Authors: Pan Qingchun , Li Lin , Yang Xiaohong , Tong Hao , Xu Shutu , Li Zhigang , Li Weiya , Muehlbauer Gary J. , Li Jiansheng , Yan Jianbing 
Published: December 2015

Summary

Meiotic recombination is a major driver of genetic diversity, species evolution, and agricultural improvement. Thus, an understanding of the genetic recombination landscape across the maize (Zea mays) genome will provide insight and tools for further study of maize evolution and improvement.

Here, we used c. 50 000 single nucleotide polymorphisms to precisely map recombination events in 12 artificial maize segregating populations. We observed substantial variation in the recombination frequency and distribution along the ten maize chromosomes among the 12 populations and identified 143 recombination hot regions.

Recombination breakpoints were partitioned into intragenic and intergenic events. Interestingly, an increase in the number of genes containing recombination events was accompanied by a decrease in the number of recombination events per gene. This kept the overall number of intragenic recombination events nearly invariable in a given population, suggesting that the recombination variation observed among populations was largely attributed to intergenic recombination. However, significant associations between intragenic recombination events and variation in gene expression and agronomic traits were observed, suggesting potential roles for intragenic recombination in plant phenotypic diversity.

Our results provide a comprehensive view of the maize recombination landscape, and show an association between recombination, gene expression and phenotypic variation, which may enhance crop genetic improvement.
YouTube as a source of information on mouth (oral) cancer
Authors: Hassona Y , Taimeh D , Marahleh A , Scully C 
Published: December 2015

ObjectivesWe examined the content of YouTube™ videos on mouth (oral) cancer and evaluated their usefulness in promoting early detection of oral cancer.Materials and MethodsA systematic search of YouTube™ for videos containing information on mouth cancer was conducted using the keywords ‘mouth cancer’ and ‘oral cancer’. Demographics of videos, including type, source, length, and viewers’ interaction, were evaluated, and three researchers independently assessed the videos for usefulness in promoting early detection of oral cancer.ResultsA total of 188 YouTube™ videos (152 patient‐oriented educational videos and 36 testimonial videos) were analyzed. The overall usefulness score ranged from 0 to 10 (mean = 3.56 ± 2.44). The most useful videos ranked late on the viewing list, and there was no significant correlation between video usefulness and viewing rate, viewers’ interaction, and video length. Videos uploaded by individual users were less useful compared with videos uploaded by professional organizations or by healthcare professionals.ConclusionHealthcare professionals, academic institutions, and professional organizations have a responsibility for improving the content of YouTube™ about mouth cancer by uploading useful videos, and directing patients to reliable information sources.
hERG quality control and the long QT syndrome
Authors: Foo Brian , Williamson Brittany , Young Jason C. , Lukacs Gergely , Shrier Alvin 
Published: December 2015

AbstractLong‐QT syndrome type‐2 (LQT2) is characterized by reduced functional expression of the human ether‐à‐go‐go related (hERG) gene product, resulting in impaired cardiac repolarization and predisposition to fatal arrhythmia. Previous studies have implicated abnormal trafficking of misfolded hERG as the primary mechanism of LQT2, with misfolding being caused by mutations in the hERG gene (inherited) or drug treatment (acquired). More generally, environmental and metabolic stresses present a constant challenge to the folding of proteins, including hERG, and must be countered by robust protein quality control (QC) systems. Disposal of partially unfolded yet functional plasma membrane (PM) proteins by protein QC contributes to the loss‐of‐function phenotype in various conformational diseases including cystic fibrosis (CF) and long‐QT syndrome type‐2 (LQT2). The prevalent view has been that the loss of PM expression of hERG is attributed to biosynthetic block by endoplasmic reticulum (ER) QC pathways. However, there is a growing appreciation for protein QC pathways acting at post‐ER cellular compartments, which may contribute to conformational disease pathogenesis. This article will provide a background on the structure and cellular trafficking of hERG as well as inherited and acquired LQT2. We will review previous work on hERG ER QC and introduce the more novel view that there is a significant peripheral QC at the PM and peripheral cellular compartments. Particular attention is drawn to the unique role of the peripheral QC system in acquired LQT2. Understanding the QC process and players may provide targets for therapeutic intervention in dealing with LQT2.
image
Structure of the Sec61 channel opened by a signal sequence
Authors: Voorhees Rebecca M. , Hegde Ramanujan S. 
Published: December 2015

Seeing the signal sequence in action
Protein translocation across the endoplasmic reticulum (ER) involves the interaction of a signal sequence with the protein translocation channel. Although much work has looked at the details of protein translocation, questions remain. Voorhees and Hegde present a single-particle cryoelectron microscopy study of the mammalian ER translocation apparatus at the point in which the signal sequence is engaging the translocation pore.

Science
, this issue p.
88
Clinafloxacin for Treatment of Burkholderia cenocepacia Infection in a Cystic Fibrosis Patient
Authors: Balwan Akshu , Nicolau David P. , Wungwattana Minkey , Zuckerman Jonathan B. , Waters Valerie 
Published: December 2015

ABSTRACT

Respiratory infection with
Burkholderia cenocepacia
is associated with accelerated decline in lung function and increased mortality in cystic fibrosis (CF) patients (A. M. Jones, M. E. Dodd, J. R. W. Govan, V. Barcus, C. J. Doherty, J. Morris, and A. K. Webb, Thorax 59:948–951, 2004,
http://dx.doi.org/10.1136/thx.2003.017210
).
B. cenocepacia
often possesses innate resistance to multiple antimicrobial classes, making eradication uncommon in established infection (P. B. Davis, Am J Respir Crit Care Med 173:475–482, 2006,
http://dx.doi.org/10.1164/rccm.200505-840OE
). We report the use of clinafloxacin in a CF patient with advanced
B. cenocepacia
infection, present pharmacokinetic (PK) data, and discuss the potential therapeutic role of clinafloxacin in patients with this condition.
Oral Immunization with Recombinant Vaccinia Virus Prime and Intramuscular Protein Boost Provides Protection against Intrarectal Simian-Human Immunodeficiency Virus Challenge in Macaques
Authors: Thippeshappa Rajesh , Tian Baoping , Cleveland Brad , Guo Wenjin , Polacino Patricia , Hu Shiu-Lok 
Published: December 2015

ABSTRACT

Human immunodeficiency virus type 1 (HIV-1) acquisition occurs predominantly through mucosal transmission. We hypothesized that greater mucosal immune responses and protective efficacy against mucosal HIV-1 infection may be achieved by prime-boost immunization at mucosal sites. We used a macaque model to determine the safety, immunogenicity, and protective efficacy of orally delivered, replication-competent but attenuated recombinant vaccinia viruses expressing full-length HIV-1 SF162 envelope (Env) or simian immunodeficiency virus (SIV) Gag-Pol proteins. We examined the dose and route that are suitable for oral immunization with recombinant vaccinia viruses. We showed that sublingual inoculation of two vaccinia virus-naive pigtailed macaques with 5 × 10
8
PFU of recombinant vaccinia viruses was safe. However, sublingual inoculation with a higher dose or tonsillar inoculation resulted in secondary oral lesions, indicating the need to optimize the dose and route for oral immunization with replication-competent vaccinia virus vectors. Oral priming alone elicited antibody responses to vaccinia virus and to the SF162 Env protein. Intramuscular immunization with the SF162 gp120 protein at either 20 or 21 weeks postpriming resulted in a significant boost in antibody responses in both systemic and mucosal compartments. Furthermore, we showed that immune responses induced by recombinant vaccinia virus priming and intramuscular protein boosting provided protection against intrarectal challenge with the simian-human immunodeficiency virus SHIV-SF162-P4.
The “3 in 1” Study: Pooling Self-Taken Pharyngeal, Urethral, and Rectal Samples into a Single Sample for Analysis for Detection of Neisseria gonorrhoeae and Chlamydia trachomatis in Men Who Have Sex with Men
Authors: Sultan B. , White J. A. , Fish R. , Carrick G. , Brima N. , Copas A. , Robinson A. , Gilson R. , Mercey D. , Benn P. 
Published: December 2015

ABSTRACT

Triple-site testing (using pharyngeal, rectal, and urethral/first-void urine samples) for
Neisseria gonorrhoeae
and
Chlamydia trachomatis
using nucleic acid amplification tests detects greater numbers of infections among men who have sex with men (MSM). However, triple-site testing represents a cost pressure for services. MSM over 18 years of age were eligible if they requested testing for sexually transmitted infections (STIs), reported recent sexual contact with either
C. trachomatis
or
N. gonorrhoeae
, or had symptoms of an STI. Each patient underwent standard-of-care (SOC) triple-site testing, and swabs were taken to form a pooled sample (PS) (pharyngeal, rectal, and urine specimens). The PS was created using two methods during different periods at one clinic, but we analyzed the data in combination because the sensitivity of the two methods did not differ significantly for
C. trachomatis
(
P
= 0.774) or
N. gonorrhoeae
(
P
= 0.163). The sensitivity of PS testing (92%) was slightly lower than that of SOC testing (96%) for detecting
C. trachomatis
(
P
= 0.167). For
N. gonorrhoeae
, the sensitivity of PS testing (90%) was significantly lower than that of SOC testing (99%) (
P
< 0.001). When pharynx-only infections were excluded, the sensitivity of PS testing to detect
N. gonorrhoeae
infections increased to 94%. Our findings show that pooling of self-taken samples could be an effective and cost-saving method, with high negative predictive values. (Interim results of this study were presented at the BASHH 2013 summer meeting.)
Flow Cytometry To Assess Cerebrospinal Fluid Fungal Burden in Cryptococcal Meningitis
Authors: Scriven James E. , Graham Lisa M. , Schutz Charlotte , Scriba Thomas J. , Wilkinson Robert J. , Boulware David R. , Meintjes Graeme , Lalloo David G. , Urban Britta C. 
Published: December 2015

ABSTRACT
Fungal burden in the cerebrospinal fluid is an important determinant of mortality in cryptococcal meningitis, but its use in aiding clinical decision making is hampered by the time involved to perform quantitative cultures. Here, we demonstrate the potential of flow cytometry as a novel and rapid technique to address this issue.
Multilaboratory Evaluation of
In Vitro
Antifungal Susceptibility Testing of Dermatophytes for ME1111
Authors: Ghannoum M. , Chaturvedi V. , Diekema D. , Ostrosky-Zeichner L. , Rennie R. , Walsh T. , Wengenack N. , Fothergill A. , Wiederhold N. 
Published: December 2015

ABSTRACT

ME1111 is a novel small molecule antifungal agent under development for the topical treatment of onychomycosis. Standardization of the susceptibility testing method for this candidate antifungal is needed. Toward this end, 8 independent laboratories determined the interlaboratory reproducibility of ME1111 susceptibility testing. In addition, we subsequently identified 2 strains as quality control (QC) isolates for the method. In the reproducibility study, 5 blinded clinical strains each of
Trichophyton rubrum
,
Trichophyton mentagrophytes
, and
Epidermophyton floccosum
were tested, while the QC study tested 6 blinded
T. rubrum
or
T. mentagrophytes
ATCC strains. Testing was performed in frozen microtiter panels according to the Clinical and Laboratory Standards Institute (CLSI) M38-A2 methodology. In the reproducibility study, 9 of 15 clinical strains showed interlaboratory agreement of >90% at the 80% inhibition endpoint, with a range of agreement of 76.2% to 100%. In the QC study, 4 of the 6 ATCC strains showed interlaboratory agreement of >90%. ME1111 demonstrated excellent interlaboratory agreement when tested against dermatophytes. Based on this data, the CLSI Subcommittee on Antifungal Susceptibility Tests approved the susceptibility testing of ME1111 against dermatophytes according to M38-A2 methodology, which stipulates RPMI 1640 as the test medium, an inoculum size of 1 to 3 × 10
3
CFU/ml, and an incubation time and temperature of 96 h at 35°C. The MIC endpoint should be 80% inhibition compared with the growth control.
T. rubrum
ATCC MYA-4438 and
T. mentagrophytes
ATCC 28185 were selected as QC isolates, with an acceptable range of 0.12 to 1 μg/ml for the two strains.
Epstein-Barr Virus Nuclear Antigen 3 (EBNA3) Proteins Regulate EBNA2 Binding to Distinct RBPJ Genomic Sites
Authors: Wang Anqi , Welch Rene , Zhao Bo , Ta Tram , Keleş Sündüz , Johannsen Eric 
Published: December 2015

ABSTRACT

Latent infection of B lymphocytes by Epstein-Barr virus (EBV)
in vitro
results in their immortalization into lymphoblastoid cell lines (LCLs); this latency program is controlled by the EBNA2 viral transcriptional activator, which targets promoters via RBPJ, a DNA binding protein in the Notch signaling pathway. Three other EBNA3 proteins (EBNA3A, EBNA3B, and EBNA3C) interact with RBPJ to regulate cell gene expression. The mechanism by which EBNAs regulate different genes via RBPJ remains unclear. Our chromatin immunoprecipitation with deep sequencing (ChIP-seq) analysis of the EBNA3 proteins analyzed in concert with prior EBNA2 and RBPJ data demonstrated that EBNA3A, EBNA3B, and EBNA3C bind to distinct, partially overlapping genomic locations. Although RBPJ interaction is critical for EBNA3A and EBNA3C growth effects, only 30 to 40% of EBNA3-bound sites colocalize with RBPJ. Using LCLs conditional for EBNA3A or EBNA3C activity, we demonstrate that EBNA2 binding at sites near EBNA3A- or EBNA3C-regulated genes is specifically regulated by the respective EBNA3. To investigate EBNA3 binding specificity, we identified sequences and transcription factors enriched at EBNA3A-, EBNA3B-, and EBNA3C-bound sites. This confirmed the prior observation that IRF4 is enriched at EBNA3A- and EBNA3C-bound sites and revealed IRF4 enrichment at EBNA3B-bound sites. Using IRF4-negative BJAB cells, we demonstrate that IRF4 is essential for EBNA3C, but not EBNA3A or EBNA3B, binding to specific sites. These results support a model in which EBNA2 and EBNA3s compete for distinct subsets of RBPJ sites to regulate cell genes and where EBNA3 subset specificity is determined by interactions with other cell transcription factors.

IMPORTANCE
Epstein-Barr virus (EBV) latent gene products cause human cancers and transform B lymphocytes into immortalized lymphoblastoid cell lines
in vitro
. EBV nuclear antigens (EBNAs) and membrane proteins constitutively activate pathways important for lymphocyte growth and survival. An important unresolved question is how four different EBNAs (EBNA2, -3A, -3B, and -3C) exert unique effects via a single transcription factor, RBPJ. Here, we report that each EBNA binds to distinct but partially overlapping sets of genomic sites. EBNA3A and EBNA3C specifically regulate EBNA2's access to different RBPJ sites, providing a mechanism by which each EBNA can regulate distinct cell genes. We show that IRF4, an essential regulator of B cell differentiation, is critical for EBNA3C binding specificity; EBNA3A and EBNA3B specificities are likely due to interactions with other cell transcription factors. EBNA3 titration of EBNA2 transcriptional function at distinct sites likely limits cell defenses that would be triggered by unchecked EBNA2 prooncogenic activity.
Identification of Stabilizing Mutations in an H5 Hemagglutinin Influenza Virus Protein
Authors: Hanson Anthony , Imai Masaki , Hatta Masato , McBride Ryan , Imai Hirotaka , Taft Andrew , Zhong Gongxun , Watanabe Tokiko , Suzuki Yasuo , Neumann Gabriele , Paulson James C. , Kawaoka Yoshihiro 
Published: December 2015

ABSTRACT
Highly pathogenic avian influenza viruses of the H5N1 subtype continue to circulate in poultry in Asia, Africa, and the Middle East. Recently, outbreaks of novel reassortant H5 viruses have also occurred in North America. Although the number of human infections with highly pathogenic H5N1 influenza viruses continues to rise, these viruses remain unable to efficiently transmit between humans. However, we and others have identified H5 viruses capable of respiratory droplet transmission in ferrets. Two experimentally introduced mutations in the viral hemagglutinin (HA) receptor-binding domain conferred binding to human-type receptors but reduced HA stability. Compensatory mutations in HA (acquired during virus replication in ferrets) were essential to restore HA stability. These stabilizing mutations in HA also affected the pH at which HA undergoes an irreversible switch to its fusogenic form in host endosomes, a crucial step for virus infectivity. To identify additional stabilizing mutations in an H5 HA, we subjected a virus library possessing random mutations in the ectodomain of an H5 HA (altered to bind human-type receptors) to three rounds of treatment at 50°C. We isolated several mutants that maintained their human-type receptor-binding preference but acquired an appreciable increase in heat stability and underwent membrane fusion at a lower pH; collectively, these properties may aid H5 virus respiratory droplet transmission in mammals.

IMPORTANCE
We have identified mutations in HA that increase its heat stability and affect the pH that triggers an irreversible conformational change (a prerequisite for virus infectivity). These mutations were identified in the genetic background of an H5 HA protein that was mutated to bind to human cells. The ability to bind to human-type receptors, together with physical stability and an altered pH threshold for HA conformational change, may facilitate avian influenza virus transmission via respiratory droplets in mammals.