bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computer vision‐based diameter maps to study fluoroscopic recordings of small intestinal motility from conscious experimental animals
Authors: Ramírez I. , Pantrigo J. J. , Montemayor A. S. , López‐Pérez A. E. , Martín‐Fontelles M. I. , Brookes S. J. H. , Abalo R. 
Published: March 2017

AbstractBackgroundWhen available, fluoroscopic recordings are a relatively cheap, non‐invasive and technically straightforward way to study gastrointestinal motility. Spatiotemporal maps have been used to characterize motility of intestinal preparations in vitro, or in anesthetized animals in vivo. Here, a new automated computer‐based method was used to construct spatiotemporal motility maps from fluoroscopic recordings obtained in conscious rats.MethodsConscious, non‐fasted, adult, male Wistar rats (n=8) received intragastric administration of barium contrast, and 1‐2 hours later, when several loops of the small intestine were well‐defined, a 2 minutes‐fluoroscopic recording was obtained. Spatiotemporal diameter maps (Dmaps) were automatically calculated from the recordings. Three recordings were also manually analyzed for comparison. Frequency analysis was performed in order to calculate relevant motility parameters.Key ResultsIn each conscious rat, a stable recording (17‐20 seconds) was analyzed. The Dmaps manually and automatically obtained from the same recording were comparable, but the automated process was faster and provided higher resolution. Two frequencies of motor activity dominated; lower frequency contractions (15.2±0.9 cpm) had an amplitude approximately five times greater than higher frequency events (32.8±0.7 cpm).Conclusions & InferencesThe automated method developed here needed little investigator input, provided high‐resolution results with short computing times, and automatically compensated for breathing and other small movements, allowing recordings to be made without anesthesia. Although slow and/or infrequent events could not be detected in the short recording periods analyzed to date (17‐20 seconds), this novel system enhances the analysis of in vivo motility in conscious animals.
Age at onset and persistence of eczema are related to subsequent risk of asthma and hay fever from birth to 18 years of age
Authors: Lowe Adrian J. , Angelica Bianca , Su John , Lodge Caroline J. , Hill David J. , Erbas Bircan , Bennett Catherine M. , Gurrin Lyle C. , Axelrad Christine , Abramson Michael J. , Allen Katrina J. , Dharmage Shyamali C. 
Published: March 2017

AbstractBackgroundFew studies have simultaneously addressed the importance of age of onset and persistence of eczema for the subsequent development of asthma and hay fever, particularly into early adulthood.MethodsA high‐risk birth cohort was recruited comprising 620 infants, who were then followed up frequently until 2 years of age, annually from age 3 to 7, then at 12 and 18 years, to document any episodes of eczema, current asthma, and hay fever. The generalized estimation equation technique was used to examine asthma and hay fever outcomes at 6 (n = 325), 12 (n = 248) and 18 (n = 240) years, when there was consistency of associations across the follow‐ups.ResultsVery early‐onset persistent (onset <6 months, still present from 2 to 5 years) eczema was related to current asthma (adjusted OR = 3.2 [95% CI = 1.7–6.1]), as was very early‐onset remitting eczema (onset <6 months but not present from 2–5 years, OR = 2.7, 95% CI = 1.0–7.2) and early‐onset persistent eczema (onset from 6–24 months, OR = 2.3, 95% CI = 1.2–4.7). Late‐onset eczema (commenced from 2–5 years) was associated with increased risk of asthma at 12 years (OR = 3.0, 95% CI=1.1–8.2) but not at age 6 years. Only very early‐onset persistent eczema was associated with increased risk of hay fever (aOR = 2.4, 95% CI = 1.4–4.1).Conclusion and clinical relevanceEczema which commences in early infancy and persists into toddler years is strongly associated with asthma, and to a lesser extent hay fever, in high‐risk children. If these associations are causal, prevention of early‐life eczema might reduce the risk of respiratory allergy.
Is behavioural activation effective in the treatment of depression in young people? A systematic review and meta‐analysis
Authors: Tindall Lucy , Mikocka‐Walus Antonina , McMillan Dean , Wright Barry , Hewitt Catherine , Gascoyne Samantha 
Published: March 2017

PurposeDepression is currently the leading cause of illness and disability in young people. Evidence suggests that behavioural activation (BA) is an effective treatment for depression in adults but less research focuses on its application with young people. This review therefore examined whether BA is effective in the treatment of depression in young people.MethodsA systematic review (International Prospective Register of Systematic Reviews reference: CRD42015020453), following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines, was conducted to examine studies that had explored behavioural interventions for young people with depression. The electronic databases searched included the Cochrane Library, EMBASE, MEDLINE, CINAHL Plus, PsychINFO, and Scopus. A meta‐analysis employing a generic inverse variance, random‐effects model was conducted on the included randomized controlled trials (RCTs) to examine whether there were overall effects of BA on the Children's Depression Rating Scale – Revised.ResultsTen studies met inclusion criteria: three RCTs and seven within‐participant designs (total n = 170). The review showed that BA may be effective in the treatment of depression in young people. The Cochrane risk of bias tool and the Moncrieff scale used to assess the quality of the included studies revealed a variety of limitations within each.ConclusionsDespite demonstrating that BA may be effective in the treatment of depression in young people, the review indicated a number of methodological problems in the included studies meaning that the results and conclusions should be treated with caution. Furthermore, the paucity of studies in this area highlights the need for further research.Practitioner points

Currently BA is included within National Institute for Health and Clinical Excellence (NICE, 2009) guidelines as an evidence‐based treatment for depression in adults with extensive research supporting its effectiveness. It is important to investigate whether it may also be effective in treating young people.

Included studies reported reductions in depression scores across a range of measures following BA.

BA may be an effective treatment of depression in young people.
Asymptotic Optimality of Sparse Linear Discriminant Analysis with Arbitrary Number of Classes
Authors: Luo Ruiyan , Qi Xin 
Published: March 2017

AbstractMany sparse linear discriminant analysis (LDA) methods have been proposed to overcome the major problems of the classic LDA in high‐dimensional settings. However, the asymptotic optimality results are limited to the case with only two classes. When there are more than two classes, the classification boundary is complicated and no explicit formulas for the classification errors exist. We consider the asymptotic optimality in the high‐dimensional settings for a large family of linear classification rules with arbitrary number of classes. Our main theorem provides easy‐to‐check criteria for the asymptotic optimality of a general classification rule in this family as dimensionality and sample size both go to infinity and the number of classes is arbitrary. We establish the corresponding convergence rates. The general theory is applied to the classic LDA and the extensions of two recently proposed sparse LDA methods to obtain the asymptotic optimality.
Blood transfusion knowledge of surgical residents: is an educational intervention effective?
Authors: Champion Caitlin , Saidenberg Elianna , Lampron Jacinthe , Pugh Debra 
Published: March 2017

BACKGROUNDEvidence‐based transfusion education for surgical residents is crucial to improving practice. A pilot study was undertaken to assess the effectiveness of an education module for improving transfusion knowledge among surgical residents.METHODSModules were developed and delivered by experts in surgery and transfusion medicine. They were delivered to residents in their first 2 years of training (Surgical Foundations), and to General Surgery residents across all years of training. Premodule and postmodule and retention knowledge assessments were used to assess efficacy. Median assessment scores for each group were compared using a two‐sample Wilcoxon rank‐sum analysis. Chi‐square tests were used to compare each group's correct response rates for each question across the three tests.RESULTSMedian assessment scores of residents in the Surgical Foundations program improved from a mean of 60% premodule to 80% postmodule and remained at 80% in the retention assessment (p < 0.01). Improvements were seen in the areas of transfusion dose, preoperative blood management, management of reactions, and informed consent (p < 0.01). Assessment scores of General Surgery residents also improved from 59%, to 73%, and to 82%, with significant improvement (p < 0.01) between premodule and postmodule scores. Improvements in correct response rates were seen in the areas of management of anemia and permissive hypotension in trauma (p < 0.01).CONCLUSIONSTransfusion knowledge of surgical residents was improved by a collaborative educational initiative. This could serve as a model for other training programs to improve resident knowledge of evidence‐based transfusion practices. The efficacy of such interventions in changing practice remains untested.
Applications of Digital PCR for Clinical Microbiology
Authors: Kuypers Jane , Jerome Keith R. 
Published: March 2017

ABSTRACT
Digital PCR (dPCR) is an important new tool for use in the clinical microbiology laboratory. Its advantages over quantitative PCR (qPCR), including absolute quantification without a standard curve, improved precision, improved accuracy in the presence of inhibitors, and more accurate quantitation when amplification efficiency is low, make dPCR the assay of choice for several specimen testing applications. This minireview will discuss the advantages and disadvantages of dPCR compared to qPCR, its applications in clinical microbiology, and considerations for implementation of the method in a clinical laboratory.
Evaluation of Altona Diagnostics RealStar Zika Virus Reverse Transcription-PCR Test Kit for Zika Virus PCR Testing
Authors: L'Huillier Arnaud G. , Lombos Ernesto , Tang Elaine , Perusini Stephen , Eshaghi Alireza , Nagra Sandeep , Frantz Christine , Olsha Romy , Kristjanson Erik , Dimitrova Kristina , Safronetz David , Drebot Mike , Gubbay Jonathan B. 
Published: March 2017

ABSTRACT
With the emerging Zika virus (ZIKV) epidemic, accessible real-time reverse transcription-PCR (rRT-PCR) assays are needed to streamline testing. The commercial Altona Diagnostics RealStar ZIKV rRT-PCR test kit (Altona PCR) has been approved for emergency use authorization by the U.S. FDA. Our aim was to verify the Altona PCR by comparing it to the CDC-designed dual-target ZIKV rRT-PCR reference assay (reference PCR) and describe the demographics of patients tested for ZIKV by rRT-PCR in Ontario, Canada. A large set of clinical specimens was tested for ZIKV by the Altona PCR and the reference PCR. Positive or equivocal specimens underwent PCR and Sanger sequencing targeting the ZIKV NS5 gene. A total of 671 serum specimens were tested by the reference PCR: 58 (8.6%) were positive, 193 (28.8%) were equivocal, and 420 (62.6%) were negative. Ninety percent of the reference PCR-positive patients were tested in the first 5 days after symptom onset. The Altona PCR was performed on 284/671 specimens tested by the reference PCR. The Altona PCR was positive for 53/58 (91%) reference PCR-positive specimens and 16/193 (8%) reference PCR-equivocal specimens; the ZIKV NS5 PCR was positive for all 68 Altona PCR-positive specimens and negative for all 181 Altona PCR-negative specimens that underwent the NS5 PCR. The Altona PCR has very good sensitivity (91%) and specificity (97%) compared to the reference PCR. The Altona PCR can be used for ZIKV diagnostic testing and has less extensive verification requirements than a laboratory-developed test.
Dengue Virus Activates the AMP Kinase-mTOR Axis To Stimulate a Proviral Lipophagy
Authors: Jordan Tristan X. , Randall Glenn 
Published: March 2017

ABSTRACT
Robust dengue virus (DENV) replication requires lipophagy, a selective autophagy that targets lipid droplets. The autophagic mobilization of lipids leads to increased β-oxidation in DENV-infected cells. The mechanism by which DENV induces lipophagy is unknown. Here, we show that infection with DENV activates the metabolic regulator 5′ adenosine-monophosphate activated kinase (AMPK), and that the silencing or pharmacological inhibition of AMPK activity decreases DENV replication and the induction of lipophagy. The activity of the mechanistic target of rapamycin complex 1 (mTORC1) decreases in DENV-infected cells and is inversely correlated with lipophagy induction. Constitutive activation of mTORC1 by depletion of tuberous sclerosis complex 2 (TSC2) inhibits lipophagy induction in DENV-infected cells and decreases viral replication. While AMPK normally stimulates TSC2-dependent inactivation of mTORC1 signaling, mTORC1 inactivation is independent of AMPK activation during DENV infection. Thus, DENV stimulates and requires AMPK signaling as well as AMPK-independent suppression of mTORC1 activity for proviral lipophagy.

IMPORTANCE
Dengue virus alters host cell lipid metabolism to promote its infection. One mechanism for altered metabolism is the induction of a selective autophagy that targets lipid droplets, termed lipophagy. Lipophagy mobilizes lipid stores, resulting in enhanced β-oxidation and viral replication. We show here that DENV infection activates and requires the central metabolic regulator AMPK for its replication and the induction of lipophagy. This is required for the induction of lipophagy, but not basal autophagy, in DENV-infected cells.
Human Herpesvirus 6B Induces Hypomethylation on Chromosome 17p13.3, Correlating with Increased Gene Expression and Virus Integration
Authors: Engdahl Elin , Dunn Nicky , Niehusmann Pitt , Wideman Sarah , Wipfler Peter , Becker Albert J. , Ekström Tomas J. , Almgren Malin , Fogdell-Hahn Anna 
Published: March 2017

ABSTRACT

Human herpesvirus 6B (HHV-6B) is a neurotropic betaherpesvirus that achieves latency by integrating its genome into host cell chromosomes. Several viruses can induce epigenetic modifications in their host cells, but no study has investigated the epigenetic modifications induced by HHV-6B. This study analyzed methylation with an Illumina 450K array, comparing HHV-6B-infected and uninfected Molt-3 T cells 3 days postinfection. Bisulfite pyrosequencing was used to validate the Illumina results and to investigate methylation over time
in vitro
. Expression of genes was investigated using quantitative PCR (qPCR), and virus integration was investigated with PCR. A total of 406 CpG sites showed a significant HHV-6B-induced change in methylation
in vitro
. Remarkably, 86% (351/406) of these CpGs were located <1 Mb from chromosomal ends and were all hypomethylated in virus-infected cells. This was most evident at chromosome 17p13.3, where HHV-6B had induced CpG hypomethylation after 2 days of infection, possibly through TET2, which was found to be upregulated by the virus. In addition, virus-induced cytosine hydroxymethylation was observed. Genes located in the hypomethylated region at 17p13.3 showed significantly upregulated expression in HHV-6B-infected cells. A temporal experiment revealed HHV-6B integration in Molt-3 cell DNA 3 days after infection. The telomere at 17p has repeatedly been described as an integration site for HHV-6B, and we show for the first time that HHV-6B induces hypomethylation in this region during acute infection, which may play a role in the integration process, possibly by making the DNA more accessible.

IMPORTANCE
The ability to establish latency in the host is a hallmark of herpesviruses, but the mechanisms differ. Human herpesvirus 6B (HHV-6B) is known to establish latency through integration of its genome into the telomeric regions of host cells, with the ability to reactivate. Our study is the first to show that HHV-6B specifically induces hypomethylated regions close to the telomeres and that integrating viruses may use the host methylation machinery to facilitate their integration process. The results from this study contribute to knowledge of HHV-6B biology and virus-host interaction. This in turn will lead to further progress in our understanding of the underlying mechanisms by which HHV-6B contributes to pathological processes and may have important implications in both disease prevention and treatment.
CXCR5-Dependent Entry of CD8 T Cells into Rhesus Macaque B-Cell Follicles Achieved through T-Cell Engineering
Authors: Ayala Victor I. , Deleage Claire , Trivett Matthew T. , Jain Sumiti , Coren Lori V. , Breed Matthew W. , Kramer Joshua A. , Thomas James A. , Estes Jacob D. , Lifson Jeffrey D. , Ott David E. 
Published: March 2017

ABSTRACT

Follicular helper CD4 T cells, T
FH
, residing in B-cell follicles within secondary lymphoid tissues, are readily infected by AIDS viruses and are a major source of persistent virus despite relative control of viral replication. This persistence is due at least in part to a relative exclusion of effective antiviral CD8 T cells from B-cell follicles. To determine whether CD8 T cells could be engineered to enter B-cell follicles, we genetically modified unselected CD8 T cells to express CXC chemokine receptor 5 (CXCR5), the chemokine receptor implicated in cellular entry into B-cell follicles. Engineered CD8 T cells expressing human CXCR5 (CD8
hCXCR5
) exhibited ligand-specific signaling and chemotaxis
in vitro
. Six infected rhesus macaques were infused with differentially fluorescent dye-labeled autologous CD8
hCXCR5
and untransduced CD8 T cells and necropsied 48 h later. Flow cytometry of both spleen and lymph node samples revealed higher frequencies of CD8
hCXCR5
than untransduced cells, consistent with preferential trafficking to B-cell follicle-containing tissues. Confocal fluorescence microscopy of thin-sectioned lymphoid tissues demonstrated strong preferential localization of CD8
hCXCR5
T cells within B-cell follicles with only rare cells in extrafollicular locations. CD8
hCXCR5
T cells were present throughout the follicles with some observed near infected T
FH
. In contrast, untransduced CD8 T cells were found in the extrafollicular T-cell zone. Our ability to direct localization of unselected CD8 T cells into B-cell follicles using CXCR5 expression provides a strategy to place highly effective virus-specific CD8 T cells into these AIDS virus sanctuaries and potentially suppress residual viral replication.

IMPORTANCE
AIDS virus persistence in individuals under effective drug therapy or those who spontaneously control viremia remains an obstacle to definitive treatment. Infected follicular helper CD4 T cells, T
FH
, present inside B-cell follicles represent a major source of this residual virus. While effective CD8 T-cell responses can control viral replication in conjunction with drug therapy or in rare cases spontaneously, most antiviral CD8 T cells do not enter B-cell follicles, and those that do fail to robustly control viral replication in the T
FH
population. Thus, these sites are a sanctuary and a reservoir for replicating AIDS viruses. Here, we demonstrate that engineering unselected CD8 T cells to express CXCR5, a chemokine receptor on T
FH
associated with B-cell follicle localization, redirects them into B-cell follicles. These proof of principle results open a pathway for directing engineered antiviral T cells into these viral sanctuaries to help eliminate this source of persistent virus.
Determinants of reflux-induced chronic cough
Authors: Herregods Thomas V K , Pauwels Ans , Jafari Jafar , Sifrim Daniel , Bredenoord Albert J , Tack Jan , Smout André J P M 
Published: March 2017

ObjectiveGastro-oesophageal reflux is considered to be an important contributing factor in chronic unexplained cough. It remains unclear why some reflux episodes in the same patient causes cough while others do not. To understand more about the mechanism by which reflux induces cough, we aimed to identify factors which are important in triggering cough.DesignIn this multicentre study, 49 patients with reflux-associated chronic cough were analysed using 24-hour pH-impedance-pressure monitoring. The characteristics of reflux episodes that were followed by cough were compared with reflux episodes not associated with cough.ResultsThe majority (72.4%) of the reflux episodes were acidic (pH<4). Compared with reflux episodes that were not followed by cough, reflux episodes that were followed by a cough burst were associated with a higher proximal extent (p=0.0001), a higher volume clearance time (p=0.002) and a higher acid burden in the preceding 15 min window (p=0.019) and higher reflux burden in the preceding 30 min window (p=0.044). No significant difference was found between the two groups when looking at the nadir pH, the pH drop, the acid clearance time or the percentage of reflux episodes which were acidic.ConclusionsThe presence of a larger volume of refluxate and oesophageal exposure to reflux for a longer period of time seems to play an important role in inducing cough, while the acidity of the refluxate seems to be less relevant. This helps explain the observation that most patients with chronic cough tend not to benefit from acid inhibitory treatment.
Reliability-Based Design of Tuned Mass Damper Using Monte Carlo Simulation Under Artificial Earthquake Records
Authors: Gholizad Amin , Ojaghzadeh Mohammadi Seyyed Davood 
Published: March 2017

Displacement- and reliability-based designs of tuned mass damper (TMD) for a shear building are studied herein. Different sources of uncertainties such as earthquake records and their peak ground accelerations (PGA), masses of floors, cross-sectional dimensions of structural members, damping of the structure and modulus of elasticity are considered. Monte Carlo simulation (MCS) is used for evaluating the performance of the designed TMD. A method for generating artificial earthquake record by using wavelet packet transform (WPT) and particle swarm optimization (PSO) is proposed to generate artificial records for areas without sufficient strong ground motion records. An illustrative example is used to study the displacement- and reliability-based designs of TMD, which are related to minimizing the structural displacement and maximizing the performance of TMD, respectively. In addition, the performance of TMD on mitigating the response of structure and its reliability under uncertain parameters of loading and structural properties are investigated. The results show that a displacement-based designed TMD could reduce the lateral displacement of a structure. Furthermore, it illustrates that the reliability-based designed TMD has a better performance in real condition of loading and structural parameters.