bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of lumpfish for sea‐lice control in salmon farming: challenges and opportunities
Authors: Powell Adam , Treasurer Jim W. , Pooley Craig L. , Keay Alex J. , Lloyd Richard , Imsland Albert K. , Garcia de Leaniz Carlos 
Published: March 2017

AbstractEfficient sea‐lice control remains one of the most important challenges for the salmon farming industry. The use of wrasse (Labridae) as cleaner fish offers an alternative to medicines for sea‐lice control, but wrasse tend to become inactive in winter. Lumpfish (Cyclopterus lumpus) continue to feed on sea‐lice at low temperatures, and commercial production has escalated from thousands of fish in 2010 to well over 30 million juveniles deployed in 2016. However, production still relies on the capture of wild broodstock, which may not be sustainable. To meet global industry needs, lumpfish production needs to increase to reach c. 50 million fish annually and this can only come from aquaculture. We review current production methods and the use of lumpfish in sea cages and identify some of the main challenges and bottlenecks facing lumpfish intensification. Our gap analysis indicates that the areas in most need of research include better control of maturation for year‐round production; formulation of appropriate diets; artificial selection of elite lines with desirable traits; and development of vaccines for certified, disease‐free juvenile production. The welfare of farmed lumpfish also needs to be better quantified, and more information is needed on optimal densities and tank design. Finally, the risk of farmed lumpfish escaping from net pens needs to be critically assessed, and we argue that it might be beneficial to recover cleaner fish from salmon cages after the production cycle, perhaps using them as broodstock, for export to the Asian food markets or for the production of animal feeds.
Progranulin protects lung epithelial cells from cigarette smoking‐induced apoptosis
Authors: Lee Kyoung Young , Park So‐Young , Park Sunjoo , Hong Gyong Hwa , Moon Keun‐Ai , Kim You‐Sun , Oh Yeon‐Mok , Kwon Hyouk‐Soo , Kim Tae‐Bum , Moon Hee‐Bom , Cho You Sook 
Published: March 2017

ABSTRACT
Background and objectiveEmphysema is characterized by irreversible destruction of alveolar walls with distal air space enlargement. Cigarette smoke (CS) is considered a major risk factor for emphysematous changes in COPD. Progranulin (PGRN), a glycoprotein induced by CS, has been reported to participate in apoptosis. However, the precise role of PGRN in emphysema is currently unknown. This study aimed to evaluate the role of PGRN in human alveolar epithelial cells (AECs) in response to CS.MethodsFirst, PGRN expression was assessed in a mouse model of CS‐induced emphysema and in AECs after exposure to CS extract (CSE). Then, the effect of PGRN on CSE‐mediated apoptosis was determined under PGRN silencing or overexpressing conditions. To investigate the functional mechanism of PGRN, endoplasmic reticulum (ER) stress markers and the mitogen‐activated protein kinase (MAPK) pathway were also evaluated in the CSE‐exposed cells. Finally, PGRN expression levels in sera and peripheral blood mononuclear cells (PBMCs) were measured and compared between patients with COPD and healthy subjects.ResultsOur results revealed that PGRN expression was elevated in CS‐exposed mouse lungs and CSE‐treated AECs. CSE‐induced cellular apoptosis was significantly increased in PGRN‐knockdown AECs and decreased in PGRN‐overexpression cells. The activation of ER stress‐associated molecules correlated with PGRN expression levels. Compared with healthy controls, COPD patients exhibited significantly lower PGRN serum levels and higher PBMC intracellular PGRN levels.Conclusion
PGRN in airway epithelial cells may regulate CS‐induced AEC apoptosis and may be involved in the development of COPD.
Partial polygon pruning of hydrographic features in automated generalization
Authors: Stum Alexander K. , Buttenfield Barbara P. , Stanislawski Lawrence V. 
Published: March 2017

AbstractThis article demonstrates a working method to automatically detect and prune portions of waterbody polygons to support creation of a multi‐scale hydrographic database. Water features are sensitive to scale change, therefore multiple representations are required to maintain visual and geographic logic at smaller scales. Partial pruning of polygonal features – such as long, sinuous reservoir arms, stream channels too narrow at the target scale, and islands that begin to coalesce – entails concurrent management of the length and width of polygonal features as well as integrating pruned polygons with other generalized point and linear hydrographic features to maintain stream network connectivity. The implementation follows data representation standards developed by the US Geological Survey (USGS) for the National Hydrography Dataset (NHD). Portions of polygonal rivers, streams, and canals are automatically characterized for width, length, and connectivity. This article describes an algorithm for automatic detection and subsequent processing, and shows results for a sample of NHD subbasins in different landscape conditions in the US.
Mobile phone‐based interactive voice response as a tool for improving access to healthcare in remote areas in Ghana – an evaluation of user experiences
Authors: Brinkel J. , May J. , Krumkamp R. , Lamshöft M. , Kreuels B. , Owusu‐Dabo E. , Mohammed A. , Bonacic Marinovic A. , Dako‐Gyeke P. , Krämer A. , Fobil J. N. 
Published: March 2017

AbstractObjectivesTo investigate and determine the factors that enhanced or constituted barriers to the acceptance of an mHealth system which was piloted in Asante‐Akim North District of Ghana to support healthcare of children.MethodsFour semi‐structured focus group discussions were conducted with a total of 37 mothers. Participants were selected from a study population of mothers who subscribed to a pilot mHealth system which used an interactive voice response (IVR) for its operations. Data were evaluated using qualitative content analysis methods. In addition, a short quantitative questionnaire assessed system's usability (SUS).ResultsResults revealed 10 categories of factors that facilitated user acceptance of the IVR system including quality‐of‐care experience, health education and empowerment of women. The eight categories of factors identified as barriers to user acceptance included the lack of human interaction, lack of update and training on the electronic advices provided and lack of social integration of the system into the community. The usability (SUS median: 79.3; range: 65–97.5) of the system was rated acceptable.ConclusionsThe principles of the tested mHealth system could be of interest during infectious disease outbreaks, such as Ebola or Lassa fever, when there might be a special need for disease‐specific health information within populations.
Stress‐sensitive arterial hypertension, haemodynamic changes and brain metabolites in hypertensive ISIAH rats: MRI investigation
Authors: Seryapina A. A. , Shevelev O. B. , Moshkin M. P. , Markel A. L. , Akulov A. E. 
Published: March 2017

New Findings
What is the central question of this study?
Stress‐sensitive arterial hypertension is considered to be controlled by changes in central and peripheral sympathetic regulating mechanisms, which eventually result in haemodynamic alterations and blood pressure elevation. Therefore, study of the early stages of development of hypertension is of particular interest, because it helps in understanding the aetiology of the disease.

What is the main finding and its importance?
Non‐invasive in vivo investigation in ISIAH rats demonstrated that establishment of sustainable stress‐sensitive hypertension is accompanied by a decrease in prefrontal cortex activity and mobilization of hypothalamic processes, with considerable correlations between haemodynamic parameters and individual metabolite ratios.

The study of early development of arterial hypertension in association with emotional stress is of great importance for better understanding of the aetiology and pathogenesis of the hypertensive disease. Magnetic resonance imaging (MRI) was applied to evaluate the changes in haemodynamics and brain metabolites in 1‐ and 3‐month‐old inherited stress‐induced arterial hypertension (ISIAH) rats (10 male rats) with stress‐sensitive arterial hypertension and in control normotensive Wistar Albino Glaxo (WAG) rats (eight male rats). In the 3‐month‐old ISIAH rats, the age‐dependent increase in blood pressure was associated with increased blood flow through the renal arteries and decreased blood flow in the lower part of the abdominal aorta. The renal vascular resistance in the ISIAH rats decreased during ageing, although at both ages it remained higher than the renal vascular resistance in WAG rats. An integral metabolome portrait demonstrated that development of hypertension in the ISIAH rats was associated with an attenuation of the excitatory and energetic activity in the prefrontal cortex, whereas in the WAG rats the opposite age‐dependent changes were observed. In contrast, in the hypothalamus of 3‐month‐old ISIAH rats, an increase in energetic activity and prevalence of excitatory over inhibitory neurotransmitters was noticed. The blood flow through the main arteries showed a positive correlation with glutamate and glutamine levels in the hypothalamus and a negative correlation with the hypothalamic GABA level. The blood pressure values were positively correlated with hypothalamic choline levels. Thus, the early development of stress‐sensitive hypertension in the ISIAH rats is accompanied by considerable changes both in brain metabolite ratios and in the parameters of blood flow through the main arteries.
Polymyxins: Antibacterial Activity, Susceptibility Testing, and Resistance Mechanisms Encoded by Plasmids or Chromosomes
Authors: Poirel Laurent , Jayol Aurélie , Nordmann Patrice 
Published: March 2017

SUMMARY
Polymyxins are well-established antibiotics that have recently regained significant interest as a consequence of the increasing incidence of infections due to multidrug-resistant Gram-negative bacteria. Colistin and polymyxin B are being seriously reconsidered as last-resort antibiotics in many areas where multidrug resistance is observed in clinical medicine. In parallel, the heavy use of polymyxins in veterinary medicine is currently being reconsidered due to increased reports of polymyxin-resistant bacteria. Susceptibility testing is challenging with polymyxins, and currently available techniques are presented here. Genotypic and phenotypic methods that provide relevant information for diagnostic laboratories are presented. This review also presents recent works in relation to recently identified mechanisms of polymyxin resistance, including chromosomally encoded resistance traits as well as the recently identified plasmid-encoded polymyxin resistance determinant MCR-1. Epidemiological features summarizing the current knowledge in that field are presented.
Mass Spectrometry Approaches for Identification and Quantitation of Therapeutic Monoclonal Antibodies in the Clinical Laboratory
Authors: Ladwig Paula M. , Barnidge David R. , Willrich Maria A. V. 
Published: March 2017

ABSTRACTTherapeutic monoclonal antibodies (MAbs) are an important class of drugs used to treat diseases ranging from autoimmune disorders to B cell lymphomas to other rare conditions thought to be untreatable in the past. Many advances have been made in the characterization of immunoglobulins as a result of pharmaceutical companies investing in technologies that allow them to better understand MAbs during the development phase. Mass spectrometry is one of the new advancements utilized extensively by pharma to analyze MAbs and is now beginning to be applied in the clinical laboratory setting. The rise in the use of therapeutic MAbs has opened up new challenges for the development of assays for monitoring this class of drugs. MAbs are larger and more complex than typical small-molecule therapeutic drugs routinely analyzed by mass spectrometry. In addition, they must be quantified in samples that contain endogenous immunoglobulins with nearly identical structures. In contrast to an enzyme-linked immunosorbent assay (ELISA) for quantifying MAbs, mass spectrometry-based assays do not rely on MAb-specific reagents such as recombinant antigens and/or anti-idiotypic antibodies, and time for development is usually shorter. Furthermore, using molecular mass as a measurement tool provides increased specificity since it is a first-order principle unique to each MAb. This enables rapid quantification of MAbs and multiplexing. This review describes how mass spectrometry can become an important tool for clinical chemists and especially immunologists, who are starting to develop assays for MAbs in the clinical laboratory and are considering mass spectrometry as a versatile platform for the task.
Laboratory Diagnostics for Histoplasmosis
Authors: Azar Marwan M. , Hage Chadi A. 
Published: March 2017

ABSTRACT
The diagnosis of histoplasmosis is based on a multifaceted approach that includes clinical, radiographic, and laboratory evidence of disease. The gold standards for laboratory diagnosis include demonstration of yeast on pathological examination of tissue and isolation of the mold in the culture of clinical specimens; however, antigen detection has provided a rapid, noninvasive, and highly sensitive method for diagnosis and is a useful marker of treatment response. Molecular methods with improved sensitivity on clinical specimens are being developed but are not yet ready for widespread clinical use. This review synthesizes currently available laboratory diagnostics for histoplasmosis, with an emphasis on complexities of testing and performance in various clinical contexts.
Multicenter Evaluation of the Cepheid Xpert Hepatitis C Virus Viral Load Assay
Authors: McHugh M. P. , Wu A. H. B. , Chevaliez S. , Pawlotsky J. M. , Hallin M. , Templeton K. E. 
Published: March 2017

ABSTRACT

Viral load monitoring for hepatitis C virus (HCV) is necessary to diagnose infection and monitor response to therapy, but the tests involved are currently confined to specialist institutions. There is a need for a fast, accurate assay with limited operator input to enhance the access to viral load monitoring. We evaluated the quantification of HCV RNA in serum and plasma by the Cepheid Xpert HCV Viral Load assay in comparison to the Abbott RealTi
m
e HCV assay. Serum and plasma samples were gathered from HCV-infected individuals at four international sites. These were tested with the Xpert HCV Viral Load assay, and results were compared to quantification by the Abbott RealTi
m
e HCV assay. An external quality assessment panel of eight samples was also tested. In total, 614 samples were analyzed in the study, and the qualitative results agreed on the two platforms for 588 (95.8%) samples. Further analysis of 396 samples quantified by both tests showed strong correlation (correlation coefficient
r
= 0.99) across the quantifiable range, with Bland-Altman plot data showing a mean difference (±1.96 standard deviation) of 0.03 ± 0.44 log
10
IU/ml. In the external quality assessment panel, the Xpert HCV Viral Load assay results (quantified in log
10
IU per milliliter) were within 1 standard deviation of the target value for all but one sample, which was also similarly misquantified by the Abbott RealTime HCV assay. The Xpert HCV Viral Load assay performs well compared to a market-leading HCV viral load test and should be considered for instances where rapid near-to-patient testing is required.
Impact of a Rapid Herpes Simplex Virus PCR Assay on Duration of Acyclovir Therapy
Authors: Van Tam T. , Mongkolrattanothai Kanokporn , Arevalo Melissa , Lustestica Maryann , Dien Bard Jennifer 
Published: March 2017

ABSTRACT

Herpes simplex virus (HSV) infections of the central nervous system (CNS) are associated with significant morbidity and mortality rates in children. This study assessed the impact of a direct HSV (dHSV) PCR assay on the time to result reporting and the duration of acyclovir therapy for children with signs and symptoms of meningitis and encephalitis. A total of 363 patients with HSV PCR results from cerebrospinal fluid (CSF) samples were included in this retrospective analysis, divided into preimplementation and postimplementation groups. For the preimplementation group, CSF testing was performed using a laboratory-developed real-time PCR assay; for the postimplementation group, CSF samples were tested using a direct sample-to-answer assay. All CSF samples were negative for HSV. Over 60% of patients from both groups were prescribed acyclovir. The average HSV PCR test turnaround time for the postimplementation group was reduced by 14.5 h (23.6 h versus 9.1 h;
P
< 0.001). Furthermore, 79 patients (43.6%) in the postimplementation group had dHSV PCR results reported <4 h after specimen collection. The mean time from specimen collection to acyclovir discontinuation was 17.1 h shorter in the postimplementation group (31.1 h versus 14 h;
P
< 0.001). The median duration of acyclovir therapy was also significantly reduced in the postimplementation group (29.2 h versus 14.3 h;
P
= 0.01). Our investigation suggests that implementation of rapid HSV PCR testing can decrease turnaround times and the duration of unnecessary acyclovir therapy.
The Deacetylase SIRT1 Regulates the Replication Properties of Human Papillomavirus 16 E1 and E2
Authors: Das Dipon , Smith Nathan , Wang Xu , Morgan Iain M. 
Published: March 2017

ABSTRACT
Human papillomaviruses (HPV) replicate their genomes in differentiating epithelium using the viral proteins E1 and E2 in association with host proteins. While the roles of E1 and E2 in this process are understood, the host factors involved and how they interact with and regulate E1-E2 are not. Our previous work identified the host replication and repair factor TopBP1 as an E2 partner protein essential for optimal E1-E2 replication and for the viral life cycle. The role of TopBP1 in host DNA replication is regulated by the class III deacetylase SIRT1; activation of the DNA damage response prevents SIRT1 deacetylation of TopBP1, resulting in a switch from DNA replication to repair functions for this protein and cell cycle arrest. Others have demonstrated an essential role for SIRT1 in regulation of the HPV31 life cycle; here, we report that SIRT1 can directly regulate HPV16 E1-E2-mediated DNA replication. SIRT1 is part of the E1-E2 DNA replication complex and is recruited to the viral origin of replication in an E1-E2-dependent manner. CRISPR/Cas9 was used to generate C33a clones with undetectable SIRT1 expression and lack of SIRT1 elevated E1-E2 DNA replication, in part due to increased acetylation and stabilization of the E2 protein in the absence of SIRT1. The results demonstrate that SIRT1 is a member of, and can regulate, the HPV16 replication complex. We discuss the potential role of this protein in the viral life cycle.

IMPORTANCE
HPV are causative agents in a number of human diseases, and currently only the symptoms of these diseases are treated. To identify novel therapeutic approaches for combating these diseases, the viral life cycle must be understood in more detail. This report demonstrates that a cellular enzyme, SIRT1, is part of the HPV16 DNA replication complex and is brought to the viral genome by the viral proteins E1 and E2. Using gene editing technology (CRISPR/Cas9), the SIRT1 gene was removed from cervical cancer cells. The consequence of this was that viral replication was elevated, probably due to a stabilization of the viral replication factor E2. The overall results demonstrate that an enzyme with known inhibitors, SIRT1, plays an important role in controlling how HPV16 makes copies of itself. Targeting this enzyme could be a new therapeutic approach for combating HPV spread and disease.
The Product of the Herpes Simplex Virus 2 UL16 Gene Is Critical for the Egress of Capsids from the Nuclei of Infected Cells
Authors: Gao Jie , Hay Thomas J. M. , Banfield Bruce W. 
Published: March 2017

ABSTRACT

The herpes simplex virus (HSV)
UL16
gene is conserved throughout the
Herpesviridae
and encodes a poorly understood tegument protein. The HSV-1 UL16 protein forms complexes with several viral proteins, including UL11, gE, VP22, and UL21. We previously demonstrated that HSV-2
UL21
was essential for virus propagation due to the failure of DNA-containing capsids (C capsids) to exit the nucleus. We hypothesized that if a UL16/UL21 complex was required for nuclear egress, HSV-2 lacking UL16 would have a phenotype similar to that of HSV-2 lacking UL21. Deletion of HSV-2
UL16
(Δ16) resulted in a 950-fold reduction in virus propagation in mouse L cell fibroblasts and a 200-fold reduction in virus propagation in Vero cells that was fully reversed upon the repair of Δ16 (Δ16R) and partially reversed by infecting UL16-expressing cells with Δ16. The kinetics of viral gene expression in cells infected with Δ16 were indistinguishable from those of cells infected with Δ16R or the parental virus. Additionally, similar numbers of capsids were isolated from the nuclei of cells infected with Δ16 and the parental virus. However, transmission electron microscopy, fluorescence
in situ
hybridization experiments, and fluorescent capsid localization assays all indicated a reduction in the ability of Δ16 C capsids to exit the nucleus of infected cells. Taken together, these data indicate that, like
UL21
,
UL16
is critical for HSV-2 propagation and suggest that the UL16 and UL21 proteins may function together to facilitate the nuclear egress of capsids.

IMPORTANCE
HSV-2 is a highly prevalent sexually transmitted human pathogen that is the main cause of genital herpes infections and is fueling the epidemic transmission of HIV in sub-Saharan Africa. Despite important differences in the pathological features of HSV-1 and HSV-2 infections, HSV-2 is understudied compared to HSV-1. Here we demonstrate that a deletion of the HSV-2
UL16
gene results in a substantial inhibition of virus replication due to a reduction in the ability of DNA-containing capsids to exit the nucleus of infected cells. The phenotype of this
UL16
mutant resembles that of an HSV-2
UL21
mutant described previously by our laboratory. Because UL16 and UL21 interact, these findings suggest that a complex containing both proteins may function together in nuclear egress.