bluuebunny/crossref_metadata_2025 huggingface dataset:
FQC Dashboard: integrates FastQC results into a web-based, interactive, and extensible FASTQ quality control tool
Authors: Brown Joseph , Pirrung Meg , McCue Lee Ann
Published: June 2017

FQC is software that facilitates quality control of FASTQ files by carrying out a QC protocol using FastQC, parsing results, and aggregating quality metrics into an interactive dashboard designed to richly summarize individual sequencing runs. The dashboard groups samples in dropdowns for navigation among the data sets, utilizes human-readable configuration files to manipulate the pages and tabs, and is extensible with CSV data.

Availability and implementation

FQC is implemented in Python 3 and Javascript, and is maintained under an MIT license. Documentation and source code is available at: https://github.com/pnnl/fqc.
The relationship between the continental shelf regime and a new international instrument for protecting marine biodiversity in areas beyond national jurisdiction
Authors: Mossop Joanna
Published: June 2017

States have acknowledged that the new internationally legally binding instrument (ILBI) for the conservation and sustainable use of marine biodiversity beyond national jurisdiction must take account of the interests of coastal states with continental shelves that extend beyond 200 nautical miles. This article argues that the ILBI should go beyond repeating the existing legal position as set out in international treaties and customary international law. In particular, the concept of sedentary species is unhelpful in the context of a legal regime governing the use of marine genetic resources. The article makes a number of suggestions for possible inclusions in the ILBI to clarify the relationship between the continental shelf regime and the regime for biodiversity beyond national jurisdiction.
Aspirin challenge and desensitization: how, when and why
Authors: Cortellini Gabriele , Caruso Cristiano , Romano Antonino
Published: June 2017

Purpose of review

To investigate the current approach to aspirin challenge (drug provocation) and/or desensitization in patients with histories of hypersensitivity reactions to it, particularly in those with cardiovascular diseases.

Recent findings

The literature indicates that patients with coronary artery disease (CAD), including those with an acute coronary syndrome, may safely undergo low-dose aspirin challenge and/or desensitization. Recently, flowcharts regarding challenge/desensitization procedures with aspirin in patients with CAD and histories of aspirin hypersensitivity reactions have become available. Aspirin desensitization and continuous aspirin therapy constitute an effective option in patients with nonsteroidal anti-inflammatory drug-exacerbated respiratory diseases (NERD) who have suboptimally controlled asthma or rhinosinusitis, or require multiple revision polypectomies.

The use of aspirin has proven to reduce morbidity and mortality associated with CAD. There is a general consensus on aspirin's effectiveness in secondary prevention of CAD. Therefore, aspirin desensitization is necessary in patients with CAD and histories of hypersensitivity reactions to it. The effectiveness of aspirin desensitization and continuous therapy in patients with NERD has been shown in numerous studies. However, shared selection criteria of candidates for aspirin challenge/desensitization procedures, and simple and homogeneous protocols are necessary. Moreover, preventive safety measures are still needed in order to reduce the potential risks of these procedures.
Muscle Pain Induces a Shift of the Spatial Distribution of Upper Trapezius Muscle Activity During a Repetitive Task
Authors: Falla Deborah , Cescon Corrado , Lindstroem Rene , Barbero Marco
Published: June 2017

Objective:

An association exists between repetitive movements and the development or perpetuation of neck-shoulder muscle pain. The mechanisms underlying this association remain unclear. This observational study investigated the effect of upper trapezius muscle pain on the distribution of upper trapezius activity during repetitive lifting. It was hypothesized that nociception would change the distribution of activity resulting in activation of muscle regions which would not normally be active during the task.

Materials and Methods:

Healthy men repeatedly lifted a box with a cycle time of 3 seconds for 50 cycles, at baseline, following injection of isotonic and hypertonic saline into the upper trapezius muscle and 15 minutes after the last injection. High-density surface electromyography (EMG) was recorded from the upper trapezius using a grid of 64 electrodes. The EMG amplitude was computed for each location to form a map of the EMG amplitude distribution.

Results:

During the painful condition, the overall EMG amplitude was lower compared with all other conditions (P<0.05) and in addition, the center of upper trapezius activity was shifted toward the caudal region of the muscle (P<0.01), a region not normally active during the task. The described alterations of muscle activity likely play an important role in the perpetuation of pain during repetitive activity.

Discussion:

Novel mapping of the spatial distribution of upper trapezius muscle activity showed that nociception induced a redistribution of activity during repetitive lifting. This knowledge provides new insights into the mechanisms underlying the perpetuation of pain with repetitive activity.
Dexamethasone Injected Perineurally is More Effective than Administered Intravenously for Peripheral Nerve Blocks
Authors: Zorrilla-Vaca Andres , Li Jinlei
Published: June 2017

Introduction:

Peripheral nerve blocks (PNBs) are widely and increasingly used for better acute perioperative pain control for a variety of procedures. Clinically preservative-free dexamethasone is arguably the most commonly used adjuvant and offers the most optimization effects on PNBs yet with the least side-effects noted. Our aim was to compare the effectiveness of intravenous versus perineural dexamethasone on the effectiveness and safety of PNBs.

Methods:

Major databases (PubMed, EMBASE, Cochrane library, ISI Web of Science, Google Scholar) were systematically searched for randomized controlled trials comparing the effectiveness of intravenous versus perineural dexamethasone on PNBs. Study characteristics, intraoperative events, and postoperative outcomes including duration of analgesia, duration of sensory block, duration of motor block, pain score at 24 hours, opioid consumption, and postoperative nausea and vomiting, were extracted from the articles. Meta-analysis was performed using random-effect models.

Results:

Thirteen randomized controlled trials comprising a total of 937 patients (intravenous: 464 patients; perineural: 473 patients) were included in this meta-analysis. Perineural dexamethasone significantly prolonged the duration of analgesia (standardized mean difference [SMD], 0.48 h; 95% confidence interval [CI], 0.18-0.79) and sensory block (SMD, 0.74; 95% CI, 0.53-0.94). In subgroup of studies that used 4 to 5 mg we found that perineural dexamethasone was universally more effective to prolong analgesia as compared with intravenous dexamethasone (SMD, 0.48 h; 95% CI, 0.24-0.72), but there was no significant difference between intravenous versus perineural dexamethasone when using a dose of dexamethasone ≥8 mg (SMD, 0.33 h; 95% CI, −0.11 to 0.77). Perineural dexamethasone had similarly more benefits in terms of prolongation of motor block duration, decreasing pain score, reducing opioid consumption, and less postoperative nausea and vomiting.

Conclusions:

This investigation not only confirmed the better analgesic effects of perineurally administered dexamethasone as compared with its intravenous injection, but also implicitly supported the hypothesis of local interaction between dexamethasone and the nerve as one of the pain modulation mechanisms of dexamethasone, because systemic absorption alone could not explain the superior quality of PNBs.
Adverse Events With Sustained-Release Donepezil in Alzheimer Disease
Authors: Lee Chunsoo , Lee Kyungsang , Yu Hyewon , Ryu Seung-Ho , Moon Seok Woo , Han Changsu , Lee Jun-Young , Lee Young Min , Kim Shin-Gyeom , Kim Ki Woong , Lee Dong Woo , Kim Seong Yoon , Lee Sang-Yeol , Bae Jae Nam , Jung Young-Eun , Kim Jeong Lan , Kim Byung-Soo , Shin Il-Seon , Kim Young Hoon , Kim Bong Jo , Kang Hyo Shin , Myung Woojae , Carroll Bernard J. , Kim Doh Kwan
Published: June 2017

Purpose/Background

Sustained-release, high-dose (23 mg/d) donepezil has been approved for treatment of moderate to severe Alzheimer disease (AD). Based on a previous clinical trial, body weight of less than 55 kg is a risk factor for adverse events with donepezil 23 mg/d treatment in global population.

Methods/Procedures

To clarify whether this finding is consistent across ethnic groups that vary in absolute body mass, we recruited Korean patients aged 45 to 90 years with moderate to severe AD who had been receiving standard donepezil immediate release 10 mg/d for at least 3 months. After screening, we analyzed a final cohort of 166 patients who received donepezil 23 mg/d for 24 weeks to compare the occurrence of treatment-emergent adverse events (TEAEs) between patients with high versus low body mass index (BMI) based on the World Health Organization overweight criteria for Asian populations (23 kg/m2).

Findings/Results

Treatment-emergent adverse events were reported by 79.45% of patients in the lower BMI group and 58.06% of patients in the higher BMI group (odds ratio, 2.79; 95% confidence interval, 1.39–5.63; χ2= 7.58,P= 0.006). In a multivariable survival analysis, the group with lower BMI showed a higher occurrence of TEAEs (hazard ratio, 1.83; 95% confidence interval, 1.25–2.68;P= 0.002).

Implications/Conclusions

In Korean patients with moderate to severe AD receiving high-dose donepezil over 24 weeks, TEAEs were significantly more common in those with lower BMI (not clinically overweight), especially nausea. This finding may inform clinical practice for Asian patients.
Is There a Relationship Between Treatment With Direct Antiviral Agents for HCV Infection and the Development of Malignancies?
Authors: Saadi Tarek , Khoury Johad
Published: June 2017

Background and Aims:

Direct antiviral agents (DAAs) have become the treatment of choice for patients with chronic hepatitis C virus (HCV) infection. As these drugs are new, it is important to learn the adverse events of these drugs in the short and long terms. We report on 7 patients who developed malignancies during treatment with DAAs or a short time after finishing treatment.

Methods:

We treated 133 patients with DAAs in our unit between January 2015 and June 2016, 100 (75%) of whom were treated with the combination of paritaprevir/ritonavir/ombitasvir with/without dasabuvir (PrOD). The distribution of HCV genotypes was as follow: G1b 114 (85.7%), G1a 3 (2.2%), G2 3 (2.2%), G3 10 (7.5%), G4 2 (1.5%). One hundred ten (82.7%) patients finished treatment. Adverse events were recorded during treatment and after finishing treatment. Efficacy was determined by assessment of serum HCV RNA.

Results:

We observed malignancies in 7 patients: 1 developed laryngeal carcinoma, 1 developed pancreatic adenocarcinoma, 1 developed oropharyngeal lymphoma, 1 developed recurrent aggressive transitional cell carcinoma of the urinary bladder, 1 developed recurrent aggressive hepatocellular carcinoma, and 2 patients developed de novo hepatocellular carcinoma. All of these patients had advanced liver disease.

Conclusions:

This report raises questions about DAAs and the possible development of malignancies. It will be important to look at large clinical trial data and real-world experience to determine if this relationship is real.
Zoonoses, One Health and complexity: wicked problems and constructive conflict
Authors: Waltner-Toews David
Published: June 2017

Infectious zoonoses emerge from complex interactions among social and ecological systems. Understanding this complexity requires the accommodation of multiple, often conflicting, perspectives and narratives, rooted in different value systems and temporal–spatial scales. Therefore, to be adaptive, successful and sustainable, One Health approaches necessarily entail conflicts among observers, practitioners and scholars. Nevertheless, these integrative approaches have, both implicitly and explicitly, tended to marginalize some perspectives and prioritize others, resulting in a kind of technocratic tyranny. An important function of One Health approaches should be to facilitate and manage those conflicts, rather than to impose solutions.

This article is part of the themed issue ‘One Health for a changing world: zoonoses, ecosystems and human well-being’.
Proteomics of phosphorylation and protein dynamics during fertilization and meiotic exit in theXenopusegg
Authors: Presler Marc , Van Itallie Elizabeth , Klein Allon M. , Kunz Ryan , Coughlin Margaret L. , Peshkin Leonid , Gygi Steven P. , Wühr Martin , Kirschner Marc W.
Published: June 2017

Fertilization triggers release from meiotic arrest and initiates events that prepare for the ensuing developmental program. Protein degradation and phosphorylation are known to regulate protein activity during this process. However, the full extent of protein loss and phospho-regulation is still unknown. We examined absolute protein and phospho-site dynamics after fertilization by mass spectrometry-based proteomics. To do this, we developed a new approach for calculating the stoichiometry of phospho-sites from multiplexed proteomics that is compatible with dynamic, stable and multi-site phosphorylation. Overall, the data suggest that degradation is limited to a few low abundance proteins. However, this degradation promotes extensive dephosphorylation that occurs over a wide range of abundances during meiotic exit. We also show that eggs release a large amount of protein into the medium just after fertilization, most likely related to the blocks to polyspermy. Concomitantly, there is a substantial increase in phosphorylation likely tied to calcium activated kinases. We identify putative degradation targets as well as new components of the block to polyspermy. The analytical approaches demonstrated here are broadly applicable to studies of dynamic biological systems.

Significance Statement

Protein phosphorylation and degradation drive critical events in early embryogenesis and the cell cycle; however, comprehensive and accurate analysis of these changes is currently difficult. Using a mass spectrometric approach, we present a quantitative view of the protein and posttranslational economy of the fertilization response in the frog egg. Protein degradation affects a small but very important class of proteins, while regulatory phosphorylation and protein release occur on a far larger scale. We have developed new, broadly applicable analytical methods for phosphorylation that provide absolute quantification with confidence intervals for improved interpretability of post-translational modification analysis.
Clarinet (CLA-1), a novel active zone protein required for synaptic vesicle clustering and release
Authors: Xuan Zhao , Manning Laura , Nelson Jessica , Richmond Janet E. , Colón-Ramos Daniel , Shen Kang , Kurshan Peri T.
Published: June 2017

Active zone proteins cluster synaptic vesicles at presynaptic terminals and coordinate their release. In forward genetic screens we isolated a novelC. elegansactive zone gene,clarinet (cla-1). cla-1mutants exhibit defects in synaptic vesicle clustering, reduced spontaneous neurotransmitter release, increased synaptic depression and reduced synapse number. Ultrastructurally,cla-1mutants have fewer synaptic vesicles adjacent to the dense projection and an increased number of docked vesicles.Cla-1encodes 3 isoforms containing common C-terminal PDZ and C2 domains with homology to vertebrate active zone proteins Piccolo and RIM. The short isoform localizes exclusively to the active zone while a longer ~9000 amino acid isoform colocalizes with synaptic vesicles. Specific loss of CLA-1L results in synaptic vesicle clustering defects and increased synaptic depression, but not in reduced synapse number or mini frequency. Together our data indicate that specific isoformsof clarinetserve distinct functions, regulating synapse development, synaptic vesicle clustering and release.
The collective influence of 1, 25-dihydroxyvitamin D3with physiological fluid shear stress on osteoblasts
Authors: Li Yan , Yuan Jiafeng , Wang Qianwen , Sun Lijie , Sha Yunying , Li Yanxiang , Wang Lizhong , Wang Zhonghua
Published: June 2017

1, 25-dihydroxyvitamin D3(1, 25 (OH)2D3) and mechanical stimuli in physiological environment play an important role in the pathogenesis of osteoporosis. The effects of 1, 25-dihydroxyvitamin D3alone and mechanical stimuli alone on osteoblasts have been widely investigated. This study reports the collective influences of 1, 25-dihydroxyvitamin D3and flow shear stress (FSS) on biological functions of osteoblasts. 1, 25 (OH)2D3were constructed in various kinds of concentration (0, 1, 10, 100 nmmol/L), while physiological fluid shear stress (12 dynes/cm2) were produced by using a parallel-plate fluid flow system. 1, 25 (OH)2D3affects the responses of ROBs to FSS, including the inhibition of NO releases and cell proliferation as well as the promotion of PGE2releases and cell differentiation. These findings provide a possible mechanism by which 1, 25(OH)2D3influences osteoblasts responses to FSS and may provide guidance for the selection of 1, 25(OH)2D3concentration and mechanical loading in order toin vitroproduce functional bone tissues.
MEA Viewer: a High-performance Interactive Application for Visualizing Electrophysiological Data
Authors: Bridges Daniel C. , Tovar Kenneth R. , Wu Bian , Hansma Paul K. , Kosik Kenneth S.
Published: June 2017

Multi-electrode arrays (MEAs) have been used for many years to measure electrical activity in ensembles of many hundreds of neurons, and are used in research areas as diverse as neuronal connectivity and drug discovery. A high sampling frequency is required to adequately capture action potentials, also known as spikes, the primary electrical event associated with neuronal activity, and the resulting raw data files are large and difficult to visualize with traditional plotting tools. Many common approaches to deal with this issue, such as extracting spikes times and solely performing spike train analysis, significantly reduce data dimensionality. Unbiased data exploration benefits from the use of tools that minimize data transforms and such tools enable the development of heuristic perspective from data prior to any subsequent processing. Here we introduce MEA Viewer, a high-performance interactive application for the direct visualization of multi-channel electrophysiological data. MEA Viewer provides many high-performance visualizations of electrophysiological data, including an easily navigable overview of all recorded extracellular signals overlaid with spike timestamp data and an interactive raster plot. Beyond the fundamental data displays, MEA Viewer can signal average and spatially overlay the extent of action potential propagation within single neurons. This view extracts information below the spike detection threshold to directly visualize the propagation of action potentials across the plane of the MEA. This entirely new method of using MEAs opens up new and novel research applications for medium density arrays. MEA Viewer is licensed under the General Public License version 3, GPLv3, and is available athttp://github.com/dbridges/mea-tools.
Type 4 pili are dispensable for biofilm development in the cyanobacterium Synechococcus elongatus
Authors: Nagar Elad , Zilberman Shaul , Sendersky Eleonora , Simkovsky Ryan , Shimoni Eyal , Gershtein Diana , Herzberg Moshe , Golden Susan S. , Schwarz Rakefet
Published: June 2017

The hair‐like cell appendages denoted as type IV pili are crucial for biofilm formation in diverse eubacteria. The protein complex responsible for type IV pilus assembly is homologous with the type II protein secretion complex. In the cyanobacterium Synechococcus elongatus PCC 7942, the gene Synpcc7942_2071 encodes an ATPase homologue of type II/type IV systems. Here, we report that inactivation of Synpcc7942_2071 strongly affected the suite of proteins present in the extracellular milieu (exo‐proteome) and eliminated pili observable by electron microscopy. These results support a role for this gene product in protein secretion as well as in pili formation. As we previously reported, inactivation of Synpcc7942_2071 enables biofilm formation and suppresses the planktonic growth of S. elongatus. Thus, pili are dispensable for biofilm development in this cyanobacterium, in contrast to their biofilm‐promoting function in type IV pili‐producing heterotrophic bacteria. Nevertheless, pili removal is not required for biofilm formation as evident by a piliated mutant of S. elongatus that develops biofilms. We show that adhesion and timing of biofilm development differ between the piliated and non‐piliated strains. The study demonstrates key differences in the process of biofilm formation between cyanobacteria and well‐studied type IV pili‐producing heterotrophic bacteria.
Rethinking Organic Farming in the Post‐Socialist Context: Lessons from Bulgaria
Authors: Moschitz Heidrun , Stoeva Svetla , Slavova Petya , Pickard Dona , Georgieva Zdravka , Stolze Matthias
Published: June 2017

On the basis of an in‐depth qualitative study, this article discusses the case of Bulgaria as an example of a new EU Member State that implemented EU organic farming policies in a top‐down process during EU accession. We explore the difficulties in transposing a concept originating in Western Europe to post‐Socialist countries, and particularly ask what this transposing of an alien concept means for long‐term development of the organic sector. We found that the top‐down agenda‐setting for organic farming in Bulgaria resulted in inefficient policies that inhibited an orientation of producers towards the market's needs. Tacit assumptions underlying the concept of organic farming in Western Europe, such as the relevance of social capital could not be sustained in Bulgaria, which added to the challenges of policy implementation. To increase policy efficiency, we recommend a policy process that involves the expertise of all organic sector actors, including organic operators, but also policymakers, organic organisations, consumers and academic experts. Expertise and knowledge requirements are diverse, touching policy, market, collective action and practice‐oriented skills. Integrating these skills could maximise success in finding the best solution for implementing – and adjusting – a foreign concept meaningfully in a particular local context.
Functional and phenotypic analysis of basophils allows determining distinct subtypes in patients with chronic urticaria
Authors: Rauber M. M. , Pickert J. , Holiangu L. , Möbs C. , Pfützner W.
Published: June 2017

Background

Chronic urticaria (CU) is a frequent skin disease characterized by relapsing appearance of pruritic hives. While clinical symptoms are due to the release of histamine by cutaneous mast cells, the underlying pathophysiology is still unknown. However, previous studies indicate that basophils might be of relevance. Besides, the occurrence of autoantibodies against IgE or its receptor, FcεRI, and the therapeutic efficacy of anti‐IgE antibodies imply that IgE‐mediated mechanisms also play an important role in CU.

Methods

Reactivity of CU patients’ peripheral blood basophils (n=60) to specific anti‐FcεRI and IgE‐independent fMLP stimulation was determined by basophil activation test in comparison with patients suffering from IgE‐mediated allergic rhinitis (n=10) and healthy controls (n=10). In addition, immunoglobulin receptor (FcεRI, FcγRII) expression and surface bound antibodies (IgE, IgG) were quantified on basophils. Furthermore, the autoreactive capacity of CU sera was evaluated and urticaria‐related symptoms were assessed by both UCT and CU‐Q2oL.

Results

Stimulating CU patients’ basophils via FcεRI, we identified three distinct immunologic phenotypes. One subgroup of patients’ basophils reacted to FcεRI stimulation, whereas the others had anti‐FcεRI nonreactive basophils. Among the latter, a subgroup with pronounced basopenia was identified. Of note, this group was characterized by augmented serum‐induced basophil activation, increased levels of autoantibodies against thyroid peroxidase, and also exhibited the strongest disease impact on their quality of life.

Conclusions

Patients with CU can be categorized into three immunologic subgroups based on their basophil reactivity and frequency. These phenotypes are associated with different clinical characteristics, pointing to basophils as important players in CU pathophysiology.
TFE3‐rearranged hepatic epithelioid hemangioendothelioma—a case report with immunohistochemical and molecular study
Authors: Kuo Fang‐Ying , Huang Hsuan‐Ying , Chen Chao‐Long , Eng Hock‐Liew , Huang Chao‐Cheng
Published: June 2017

A recurrent YAP1‐TFE3 gene fusion has been identified in WWTR1‐CAMTA1‐negative epithelioid hemangioendotheliomas arising in soft tissue, bone, and lung, but not in liver. We present the first case of TFE3‐rearranged hepatic epithelioid hemangioendothelioma in a 39‐year‐old Taiwanese woman. Computed tomography scan revealed multifocal, ill‐defined nodules involving both hepatic lobes. She then underwent deceased donor liver transplantation. Histologically, the tumors in the liver explant showed a biphasic growth pattern. One component was composed of dilated and well‐formed blood vessels lined by epithelioid cells with abundant eosinophilic cytoplasm, mimicking an alveolar pattern, whereas the other component was composed of cords and single cells, featuring intracytoplasmic vacuoles, separated by a myxoid stroma. The tumor cells showed vesicular nuclei and small indistinct nucleoli with mild to moderate cytologic atypia. Most tumor cells showed factor VIII, CD34, CD31, and TFE3 positivity in immunohistochemical study. Fluorescence in situ hybridization analysis for the tumor cells exhibited TFE3 gene rearrangement. The patient is currently alive, and no post‐operative tumor recurrence developed during a 13‐year follow‐up. Awareness of this rare vasoformative variant and identification of the gene rearrangement would be helpful on differential diagnosis with other high‐grade carcinoma and angiosarcoma of liver.
Laboratory parameter‐based machine learning model for excluding non‐alcoholic fatty liver disease (NAFLD) in the general population
Authors: Yip T. C.‐F. , Ma A. J. , Wong V. W.‐S. , Tse Y.‐K. , Chan H. L.‐Y. , Yuen P.‐C. , Wong G. L.‐H.
Published: June 2017

Background

Non‐alcoholic fatty liver disease (NAFLD) affects 20%‐40% of the general population in developed countries and is an increasingly important cause of hepatocellular carcinoma. Electronic medical records facilitate large‐scale epidemiological studies, existing NAFLD scores often require clinical and anthropometric parameters that may not be captured in those databases.

Aim

To develop and validate a laboratory parameter‐based machine learning model to detect NAFLD for the general population.

Methods

We randomly divided 922 subjects from a population screening study into training and validation groups; NAFLD was diagnosed by proton‐magnetic resonance spectroscopy. On the basis of machine learning from 23 routine clinical and laboratory parameters after elastic net regulation, we evaluated the logistic regression, ridge regression, AdaBoost and decision tree models. The areas under receiver‐operating characteristic curve (AUROC) of models in validation group were compared.

Results

Six predictors including alanine aminotransferase, high‐density lipoprotein cholesterol, triglyceride, haemoglobin A1c, white blood cell count and the presence of hypertension were selected. The NAFLD ridge score achieved AUROC of 0.87 (95% CI 0.83‐0.90) and 0.88 (0.84‐0.91) in the training and validation groups respectively. Using dual cut‐offs of 0.24 and 0.44, NAFLD ridge score achieved 92% (86%‐96%) sensitivity and 90% (86%‐93%) specificity with corresponding negative and positive predictive values of 96% (91%‐98%) and 69% (59%‐78%), and 87% of overall accuracy among 70% of classifiable subjects in the validation group; 30% of subjects remained indeterminate.

Conclusions

NAFLD ridge score is a simple and robust reference comparable to existing NAFLD scores to exclude NAFLD patients in epidemiological studies.
Astrocytes in a dish: Using pluripotent stem cells to model neurodegenerative and neurodevelopmental disorders
Authors: Crompton Lucy A. , Cordero‐Llana Oscar , Caldwell Maeve A.
Published: June 2017

Neuroscience and Neurobiology have historically been neuron biased, yet up to 40% of the cells in the brain are astrocytes. These cells are heterogeneous and regionally diverse but universally essential for brain homeostasis. Astrocytes regulate synaptic transmission as part of the tripartite synapse, provide metabolic and neurotrophic support, recycle neurotransmitters, modulate blood flow and brain blood barrier permeability and are implicated in the mechanisms of neurodegeneration. Using pluripotent stem cells (PSC), it is now possible to study regionalised human astrocytes in a dish and to model their contribution to neurodevelopmental and neurodegenerative disorders. The evidence challenging the traditional neuron‐centric view of degeneration within the CNS is reviewed here, with focus on recent findings and disease phenotypes from human PSC‐derived astrocytes. In addition we compare current protocols for the generation of regionalised astrocytes and how these can be further refined by our growing knowledge of neurodevelopment. We conclude by proposing a functional and phenotypical characterisation of PSC‐derived astrocytic cultures that is critical for reproducible and robust disease modelling.
Partial‐mouth periodontal examination protocols for the determination of the prevalence and extent of gingival bleeding in adolescents
Authors: Machado Michely Ediani , Tomazoni Fernanda , Casarin Maísa , Ardenghi Thiago M. , Zanatta Fabricio Batistin
Published: June 2017

Objective

To compare the performance of partial‐mouth periodontal examination (PMPE) protocols with different cut‐off points to the full‐mouth examination (FME) in the assessment of the prevalence and extent of gingival bleeding in adolescents.

Methods

A cross‐sectional study was conducted involving 12‐year‐old adolescents. Following a systematic two‐stage cluster sampling process, 1134 individuals were evaluated. Different PMPE protocols were compared to the FME with six sites per tooth. Sensitivity, specificity, area under the ROC curve (AUC), intraclass correlation coefficient (ICC), relative and absolute biases and the inflation factor were assessed for each PMPE protocol with different cut‐off points for the severity of gingival bleeding.

Results

The highest AUC values were found for the six‐site two‐diagonal quadrant (2‐4) (0.97), six‐site random half‐mouth (0.95) and Community Periodontal Index (0.95) protocols. The assessment of three sites [mesiobuccal (MB), buccal (B) and distolingual (DL)] in two diagonal quadrants and the random half‐mouth protocol had higher sensitivity and lower specificity than the same protocols with distobuccal (DB) sites. However, the use of DB sites led to better specificity and improved the balance between sensitivity and specificity, except for the two‐diagonal quadrant (1‐3) protocol. The ≥1 cut‐off point led to the most discrepant results from the FME.

Conclusion

Six‐site two‐diagonal quadrant (2‐4) and random half‐mouth assessments perform better in the evaluation of gingival bleeding in adolescents. However, when a faster protocol is needed, a two‐diagonal quadrant assessment using only MB, B and DL sites can be used with no important loss of information.
Enrichment of IL-17A+IFN-γ+ and IL-22+IFN-γ+ T cell subsets is associated with reduction of NKp44+ILC3s in the terminal ileum of Crohn's disease patients
Authors: Li J , Doty A L , Tang Y , Berrie D , Iqbal A , Tan S A , Clare-Salzler M J , Wallet S M , Glover S C
Published: June 2017

Crohn's disease (CD) is a chronic inflammatory condition of the human gastrointestinal tract whose aetiology remains largely unknown. Dysregulated adaptive immune responses and defective innate immunity both contribute to this process. In this study, we demonstrated that the interleukin (IL)-17A+interferon (IFN)-γ+ and IL-22+IFN-γ+ T cell subsets accumulated specifically in the inflamed terminal ileum of CD patients. These cells had higher expression of Ki-67 and were active cytokine producers. In addition, their proportions within both the IL-17A-producer and IL-22-producer populations were increased significantly. These data suggest that IL-17A+IFN-γ+ and IL-22+IFN-γ+ T cell subsets might represent the pathogenic T helper type 17 (Th17) population in the context of intestinal inflammation for CD patients. In the innate immunity compartment we detected a dramatic alteration of both phenotype and function of the intestinal innate lymphoid cells (ILCs), that play an important role in the maintenance of mucosal homeostasis. In the inflamed gut the frequency of the NKp44–CD117–ILC1s subset was increased significantly, while the frequency of NKp44+ILC3s was reduced. Furthermore, the frequency of human leucocyte antigen D-related (HLA-DR)-expressing-NKp44+ILC3s was also reduced significantly. Interestingly, the decrease in the NKp44+ILC3s population was associated with an increase of pathogenic IL-17A+IFN-γ+ and IL-22+IFN-γ+ T cell subsets in the adaptive compartment. This might suggest a potential link between NKp44+ILC3s and the IL-17A+IFN-γ+ and IL-22+IFN-γ+ T cell subsets in the terminal ileum of CD patients.
A meta‐analysis of intraoperative neuromonitoring of recurrent laryngeal nerve palsy during thyroid reoperations
Authors: Sun Wei , Liu Jinhao , Zhang Hao , Zhang Ping , Wang Zhihong , Dong Wenwu , He Liang , Zhang Ting
Published: June 2017

Background

The rate of recurrent laryngeal nerve (RLN) palsy, a common complication of thyroid surgery, is especially high in thyroid reoperations. The present meta‐analysis assesses whether intraoperative neuromonitoring (IONM) reduces the prevalence of RLN palsy in thyroid reoperations.

Design and methods

A systematic literature search was conducted in the PubMed, SCIE and Wan Fang databases for studies published up to 31 August 2016. All data were analysed using STATA (version 11) software. Publication bias was assessed using Begg's funnel plot and Egger's test, and sensitivity analysis was performed.

Results

Nine studies including 2436 at‐risk nerves met the inclusion criteria. The results were presented as pooled relative risks (RRs) with 95% confidence intervals (CI). The overall RLN palsy rate was significantly lower in reoperations conducted with IONM than in those conducted without IONM (RR=0.434, 95% CI=0.206‐0.916, P=.029). High heterogeneity was found (I2=70.2%, P=.001). The rates of transient RLN palsy with and without IONM did not differ significantly (RR=0.607, 95% CI=0.270‐1.366, P=.227). The heterogeneity was high (I2=67.4%, P=.005). However, IONM was significantly associated with a reduction in permanent RLN palsy (RR=0.426, 95% CI=0.196‐0.925, P=.031). No significant heterogeneity was found (I2=13.7%, P=.325). Funnel plots for overall and transient RLN palsy showed a possible publication bias.

Conclusions

Intraoperative neuromonitoring (IONM) is associated with a reduction in overall and permanent RLN palsy in thyroid reoperations. However, given the limited sample size and heterogeneity in this meta‐analysis, further studies are required to confirm our preliminary findings.
Spinal cord multi‐parametric magnetic resonance imaging for survival prediction in amyotrophic lateral sclerosis
Authors: Querin G. , El Mendili M. M. , Lenglet T. , Delphine S. , Marchand‐Pauvert V. , Benali H. , Pradat P.‐F.
Published: June 2017

Background and purpose

Assessing survival is a critical issue in patients with amyotrophic lateral sclerosis (ALS). Neuroimaging seems to be promising in the assessment of disease severity and several studies also suggest a strong relationship between spinal cord (SC) atrophy described by magnetic resonance imaging (MRI) and disease progression. The aim of the study was to determine the predictive added value of multimodal SC MRI on survival.

Methods

Forty‐nine ALS patients were recruited and clinical data were collected. Patients were scored on the Revised ALS Functional Rating Scale and manual muscle testing. They were followed longitudinally to assess survival. The cervical SC was imaged using the 3 T MRI system. Cord volume and cross‐sectional area (CSA) at each vertebral level were computed. Diffusion tensor imaging metrics were measured. Imaging metrics and clinical variables were used as inputs for a multivariate Cox regression survival model.

Results

On building a multivariate Cox regression model with clinical and MRI parameters, fractional anisotropy, magnetization transfer ratio and CSA at C2–C3, C4–C5, C5–C6 and C6–C7 vertebral levels were significant. Moreover, the hazard ratio calculated for CSA at the C3–C4 and C5–C6 levels indicated an increased risk for patients with SC atrophy (respectively 0.66 and 0.68). In our cohort, MRI parameters seem to be more predictive than clinical variables, which had a hazard ratio very close to 1.

Conclusions

It is suggested that multimodal SC MRI could be a useful tool in survival prediction especially if used at the beginning of the disease and when combined with clinical variables. To validate it as a biomarker, confirmation of the results in bigger independent cohorts of patients is warranted.
Continental impacts of water development on waterbirds, contrasting two Australian river basins: Global implications for sustainable water use
Authors: Kingsford Richard T. , Bino Gilad , Porter John L.
Published: June 2017

The world's freshwater biotas are declining in diversity, range and abundance, more than in other realms, with human appropriation of water. Despite considerable data on the distribution of dams and their hydrological effects on river systems, there are few expansive and long analyses of impacts on freshwater biota. We investigated trends in waterbird communities over 32 years, (1983–2014), at three spatial scales in two similarly sized large river basins, with contrasting levels of water resource development, representing almost a third (29%) of Australia: the Murray–Darling Basin and the Lake Eyre Basin. The Murray–Darling Basin is Australia's most developed river basin (240 dams storing 29,893 GL) while the Lake Eyre Basin is one of the less developed basins (1 dam storing 14 GL). We compared the long‐term responses of waterbird communities in the two river basins at river basin, catchment and major wetland scales. Waterbird abundances were strongly related to river flows and rainfall. For the developed Murray–Darling Basin, we identified significant long‐term declines in total abundances, functional response groups (e.g., piscivores) and individual species of waterbird (n = 50), associated with reductions in cumulative annual flow. These trends indicated ecosystem level changes. Contrastingly, we found no evidence of waterbird declines in the undeveloped Lake Eyre Basin. We also modelled the effects of the Australian Government buying up water rights and returning these to the riverine environment, at a substantial cost (>3.1 AUD billion) which were projected to partly (18% improvement) restore waterbird abundances, but projected climate change effects could reduce these benefits considerably to only a 1% or 4% improvement, with respective annual recovery of environmental flows of 2,800 GL or 3,200 GL. Our unique large temporal and spatial scale analyses demonstrated severe long‐term ecological impact of water resource development on prominent freshwater animals, with implications for global management of water resources.
The deep fascia and retinacula of the equine forelimb – structure and innervation
Authors: Skalec Aleksandra , Egerbacher Monika
Published: June 2017

Recent advances in human fascia research have shed new light on the role of the fascial network in movement perception and coordination, transmission of muscle force, and integrative function in body biomechanics. Evolutionary adaptations of equine musculoskeletal apparatus that assure effective terrestrial locomotion are employed in equestrianism, resulting in the wide variety of movements in performing horses, from sophisticated dressage to jumping and high‐speed racing. The high importance of horse motion efficiency in the present‐day equine industry indicates the significance of scientific knowledge of the structure and physiology of equine fasciae. In this study, we investigated the structure and innervation of the deep fascia of the equine forelimb by means of anatomical dissection, histology and immunohistochemistry. Macroscopically, the deep fascia appears as a dense, glossy and whitish lamina of connective tissue continuous with its fibrous reinforcements represented by extensor and flexor retinacula. According to the results of our histological examination, the general structure of the equine forelimb fascia corresponds to the characteristics of the human deep fasciae of the limbs. Although we did find specific features in all sample types, the general composition of all examined fascial tissues follows roughly the same scheme. It is composed of dense, closely packed collagen fibers organized in layers of thick fibrous bundles with sparse elastic fibers. This compact tissue is covered from both internal and external sides by loosely woven laminae of areolar connective tissue where elastic fibers are mixed with collagen. Numerous blood vessels running within the loose connective tissue contribute to the formation of regular vascular network throughout the compact layer of the deep fascia and retinacula. We found nerve fibers of different calibers in all samples analyzed. The fibers are numerous in the areolar connective tissue and near the blood vessels but scarce in the compact layers of collagen. We did not observe any Ruffini, Pacini or Golgi‐Mazzoni corpuscles. In conclusion, the multilayered composition of compact bundles of collagen, sparse elastic fibers in the deep fascia and continuous transition into retinacula probably facilitate resistance to gravitational forces and volume changes during muscle contraction as well as transmission of muscle force during movement. However, further research focused on innervation is needed to clarify whether the deep fascia of the equine forelimb plays a role in proprioception and movement coordination.
Pulmonary artery: A pivotal site for catheter ablation in idiopathic RVOT ventricular arrhythmias
Authors: Wang Chunmiao , Zhang Yawen , Hong Fangde , Huang Ying
Published: June 2017

In patients without associated myocardial diseases, characterized by left bundle branch block and inferior axis morphologies, repetitive idiopathic right ventricular tachycardias and ventricular premature contractions typically arise from right ventricular outflow tract (RVOT). Accumulated evidences have shown that radiofrequency catheter ablation is a useful treatment for patients with RVOT ventricular arrhythmias (VAs). Interestingly, several medical centers have shown that pulmonary artery (PA) is a potential novel site for catheter ablation in RVOT‐like VAs, particularly in patients where termination of RVOT VAs at the usual site fails. In this review, we comprehensively demonstrated that RVOT VAs were successfully terminated at the site of PA, analyzed the characteristics of surface electrocardiogram and endocardial potentials, and explored the underlying mechanisms for these cases.
Extracting spatial patterns in bicycle routes from crowdsourced data
Authors: Sultan Jody , Ben‐Haim Gev , Haunert Jan‐Henrik , Dalyot Sagi
Published: June 2017

Much is done nowadays to provide cyclists with safe and sustainable road infrastructure. Its development requires the investigation of road usage and interactions between traffic commuters. This article is focused on exploiting crowdsourced user‐generated data, namely GPS trajectories collected by cyclists and road network infrastructure generated by citizens, to extract and analyze spatial patterns and road‐type use of cyclists in urban environments. Since user‐generated data shows data‐deficiencies, we introduce tailored spatial data‐handling processes for which several algorithms are developed and implemented. These include data filtering and segmentation, map‐matching and spatial arrangement of GPS trajectories with the road network. A spatial analysis and a characterization of road‐type use are then carried out to investigate and identify specific spatial patterns of cycle routes. The proposed analysis was applied to the cities of Amsterdam (The Netherlands) and Osnabrück (Germany), proving its feasibility and reliability in mining road‐type use and extracting pattern information and preferences. This information can help users who wish to explore friendlier and more interesting cycle patterns, based on collective usage, as well as city planners and transportation experts wishing to pinpoint areas most in need of further development and planning.
Ultramicronized palmitoylethanolamide counteracts the effects of compound 48/80 in a canine skin organ culture model
Authors: Abramo Francesca , Lazzarini Giulia , Pirone Andrea , Lenzi Carla , Albertini Sonia , della Valle M. Frederica , Schievano Carlo , Vannozzi Iacopo , Miragliotta Vincenzo
Published: June 2017

Background

Ultramicronized palmitoylethanolamide (PEA‐um) has been reported to reduce pruritus and skin lesions in dogs with moderate atopic dermatitis and pruritus.

Hypothesis/Objectives

A canine ex vivo skin model was used to investigate the ability of PEA‐um to counteract changes induced by compound 48/80, a well‐known secretagogue that causes mast cell degranulation.

Animals

Normal skin was obtained from three donor dogs subjected to surgery for reasons unrelated to the study.

Methods

Cultured skin biopsy samples in triplicate were treated with 10 and 100 μg/mL compound 48/80, without or with 30 μM PEA‐um. Mast cell (MC) degranulation, histamine release into the culture medium, local microvascular dilatation, epidermal thickness, keratinocyte proliferation and epidermal differentiation markers were evaluated.

Results

Exposure of the skin organ culture to PEA‐um 24 h before and 72 h concomitantly to compound 48/80 resulted in a significant decrease of degranulating MCs. PEA‐um also reduced the histamine content in the culture medium by half, although the effect did not reach statistical significance. PEA‐um significantly counteracted vasodilation induced by 100 μg/mL compound 48/80. Finally, PEA‐um alone did not induce changes in epidermal thickness, differentiation markers, keratinocyte proliferation, MC density and/or degranulation.

Conclusions and clinical importance

Collectively, these results support the protective action PEA‐um on the skin of dogs undergoing allergic changes.
Evaluation of a first‐flush capture and detention tank receiving runoff from an asphalt‐paved road
Authors: Cheng Jing , Yuan Qingke , Youngchul Kim
Published: June 2017

In this article, we propose and examine a first‐flush capture and detention tank (FCDT) working as a first flush capture device and pretreatment unit receiving stormwater runoff from an asphalt‐paved road. We design the FCDT to completely capture all the stormwater including a first flush generated by an initial 5 mm effective rainfall depth, and to bypass the exceeding part. According to our analysis based on the data from field monitoring and SWMM simulation for 27 events from April to June, 2015, the tank captured 35% of total runoff, which resulted in catching 74% of the TSS load. The TSS mass detention attained in this study by capturing the first 35% of the total runoff is close to the typical definition of a first flush, and also justifies the need for a first‐flush friendly treatment.