bluuebunny/crossref_metadata_2025 huggingface dataset:
Dr.seq2: a quality control and analysis pipeline for parallel single cell transcriptome and epigenome data
Authors: Zhao Chengchen , Hu Sheng’en , Huo Xiao , Zhang Yong
Published: May 2017

An increasing number of single cell transcriptome and epigenome technologies, including single cell ATAC-seq (scATAC-seq), have been recently developed as powerful tools to analyze the features of many individual cells simultaneously. However, the methods and software were designed for one certain data type and only for single cell transcriptome data. A systematic approach for epigenome data and multiple types of transcriptome data is needed to control data quality and to perform cell-to-cell heterogeneity analysis on these ultra-high-dimensional transcriptome and epigenome datasets. Here we developed Dr.seq2, a Quality Control (QC) and analysis pipeline for multiple types of single cell transcriptome and epigenome data, including scATAC-seq and Drop-ChIP data. Application of this pipeline provides four groups of QC measurements and different analyses, including cell heterogeneity analysis. Dr.seq2 produced reliable results on published single cell transcriptome and epigenome datasets. Overall, Dr.seq2 is a systematic and comprehensive QC and analysis pipeline designed for parallel single cell transcriptome and epigenome data. Dr.seq2 is freely available at:http://www.tongji.edu.cn/~zhanglab/drseq2/andhttps://github.com/ChengchenZhao/DrSeq2.
Bias, robustness and scalability in differential expression analysis of single-cell RNA-seq data
Authors: Soneson Charlotte , Robinson Mark D.
Published: May 2017

Background

As single-cell RNA-seq (scRNA-seq) is becoming increasingly common, the amount of publicly available data grows rapidly, generating a useful resource for computational method development and extension of published results. Although processed data matrices are typically made available in public repositories, the procedure to obtain these varies widely between data sets, which may complicate reuse and cross-data set comparison. Moreover, while many statistical methods for performing differential expression analysis of scRNA-seq data are becoming available, their relative merits and the performance compared to methods developed for bulk RNA-seq data are not sufficiently well understood.

Results

We presentconquer, a collection of consistently processed, analysis-ready public single-cell RNA-seq data sets. Each data set has count and transcripts per million (TPM) estimates for genes and transcripts, as well as quality control and exploratory analysis reports. We use a subset of the data sets available inconquerto perform an extensive evaluation of the performance and characteristics of statistical methods for differential gene expression analysis, evaluating a total of 30 statistical approaches on both experimental and simulated scRNA-seq data.

Conclusions

Considerable differences are found between the methods in terms of the number and characteristics of the genes that are called differentially expressed. Pre-filtering of lowly expressed genes can have important effects on the results, particularly for some of the methods originally developed for analysis of bulk RNA-seq data. Generally, however, methods developed for bulk RNA-seq analysis do not perform notably worse than those developed specifically for scRNA-seq.
Improving tauG-control of action in PD
Authors: Schögler Benjaman , Polokoff Rachel , Pepping Gert-Jan , Perkins Jon , Lee David N
Published: May 2017

A theory of action control (General Tau Theory) is applied to analyzing normal and abnormal movements in PD; and to designing and testing the efficacy of a sonic aid for PD. A central aspect of the theory, which is supported by experimental evidence across a variety of actions and species, is that the trajectories of competent skilled actions follow a particular temporal pattern, which is described by the mathematical function, tauG. Since tauG-control of actions can be largely deficient in PD, we designed a device that generates whoop-like sounds, where the fundamental frequency of the sound follows the tauG pattern. Our hypothesis was that by listening to these sounds the nervous system of someone with PD might be helped subsequently to self-generate tauG patterns in their nervous system, which might facilitate movement control in different situations. Five adults with PD, and five age-matched controls, took part in the study. They each listened to the sounds under two conditions: (a) experimental - turning a handle for 5 minutes while the sounds were played (b) control - turning the handle without the sounds. Before and after each condition, the tauG-control of lateral body sway while standing was measured (without the sounds playing), using force-plates, on two tasks: (i) keeping the feet down, (ii) lifting the trailing foot. The number of participants out of five, who showed greater ratio improvement following practice with whoop sounds compared to without sounds, was, on each task, high for the PDs compared with the age-matched controls (4 vs 2 or 3). Thus, for the PDs, listening to the tauG whoop-like sounds while performing one action (handle turning) improved subsequent tauG-control on a different task (body-swaying).
SpatialDE - Identification of spatially variable genes
Authors: Svensson Valentine , Teichmann Sarah A , Stegle Oliver
Published: May 2017

Technological advances have enabled low-input RNA-sequencing, paving the way for assaying transcriptome variation in spatial contexts, including in tissues. While the generation of spatially resolved transcriptome maps is increasingly feasible, computational methods for analysing the resulting data are not established. Existing analysis strategies either ignore the spatial component of gene expression variation, or require discretization of the cells into coarse grained groups.

To address this, we have developed SpatialDE, a computational framework for identifying and characterizing spatially variable genes. Our method generalizes variable gene selection, as used in population-and single-cell studies, to spatial expression profiles. To illustrate the broad utility of our approach, we apply SpatialDE to spatial transcriptomics data, and to data from single cell methods based on multiplexedin situhybridisation (SeqFISH and MERFISH). SpatialDE enables the statistically robust identification of spatially variable genes, thereby identifying genes with known disease implications, several of which are missed by conventional variable gene selection. Additionally, to enable gene-expressed based histology, SpatialDE implements a spatial gene clustering model which we call “automatic expression histology,” allowing to classify genes into groups with distinct spatial patterns.
Effects of Sika Deer (Cervus nippon) and Dwarf Bamboo (Sasa senanensis) on TrilliumPopulations in Akan National Park, Eastern Hokkaido, Japan
Authors: Inatomi Yoshihiro , Uno Hiroyuki , Iijima Hayato
Published: May 2017

The competition between Trillium spp. and other species could modify the utility of Trillium spp. as indicators of the impact of deer on forest vegetation. To evaluate whether Trillium spp. (T. camschatcense and T. tschonoskii) are appropriate indicators of the impact of sika deer (Cervus nippon) in the presence of dwarf bamboo (Sasa senanensis), which competes with Trillium populations, we examined the size class of large‐growth‐stage Trillium plants, the frequency of the presence of deer pellets and the coverage of S. senanensis in deer‐excluded sites (where deer have been eliminated since 1995) and unfenced control sites in Akan National Park, eastern Hokkaido, Japan. The result of a cumulative link mixed model (CLMM) suggests that size class at deer‐excluded sites is influenced by competitive understory species, even without deer grazing. The CLMM result for unfenced control sites suggests that C. nippon negatively influences the size class of Trillium populations; however, the negative effect weakened with increasing S. senanensis coverage. Thus, S. senanensis can function as an unpalatable neighbor that makes it difficult for C. nippon to detect Trillium plants. We conclude that the size class structure of Trillium spp. can be a useful index of C. nippon usage under sparse or medium S. senanensis understories; however, it is difficult to use these indices under dense S. senanensis understories because of the weakened negative effect of C. nippon grazing.
Post‐Fordist reconfigurations of gender, work and life: theory and practice
Authors: Gray Breda , Ciolfi Luigina , de Carvalho Aparecido Fabiano Pinatti , D'Andrea Anthony , Wixted Lisa
Published: May 2017

Based on an in‐depth study with 56 informants (25 women and 31 men), across the ICT (information and communication technology), creative and academic sectors in one city/regional hub in Ireland, this article investigates the so‐called revolution in work/life practices associated with the post‐Fordist labour processes of the Knowledge Economy from the perspectives of workers themselves. Recent theorizations of post‐Fordist work patterns emphasize a rearranging of work and life place boundaries; a reconfiguring of work and life time boundaries; and a dissolving of the gendered boundaries of work and life (production and social reproduction) (Adkins and Dever ; Morini and Fumagalli ; Gill and Pratt ; Weeks ; Hardt and Negri ). Our findings suggest that, instead of dissolving boundaries, workers constantly struggle to draw boundaries between what counts as work and as life, and that this varies primarily in relation to gender and stage in a gendered life trajectory. Work extensification is compensated for via a perceived freedom to shape one's own life, which is articulated in terms of individualized boundary‐drawing. While younger men embraced ‘always on’ work, they also articulated anxieties about how these work habits might interfere with family aspirations. This was also true for younger women who also struggled to make time for life in the present. For mothers, boundary drawing was articulated as a necessity but was framed more in terms of personal choice by fathers. Although all participants distinguished between paid work and life as distinct sites of value, boundaries were individually drawn and resist any easy mapping of masculinity and femininity onto the domains of work and life. Instead, we argue that it is the process of boundary drawing that reveals gendered patterns. The personalized struggles of these relatively privileged middle‐class workers centre on improving the quality of their lives, but raise important questions about the political possibilities within and beyond the world of post‐Fordist labour.
Mind the gap: financial London and the regional class pay gap
Authors: Friedman Sam , Laurison Daniel
Published: May 2017

The hidden barriers, or ‘gender pay gap’, preventing women from earning equivalent incomes to men is well documented. Yet recent research has uncovered that, in Britain, there is also a comparable class‐origin pay gap in higher professional and managerial occupations. So far this analysis has only been conducted at the national level and it is not known whether there are regional differences within the UK. This paper uses pooled data from the 2014 and 2015 Labour Force Survey (N = 7,534) to stage a more spatially sensitive analysis that examines regional variation in the class pay gap. We find that this ‘class ceiling’ is not evenly spatially distributed. Instead it is particularly marked in Central London, where those in high‐status occupations who are from working‐class backgrounds earn, on average, £10,660 less per year than those whose parents were in higher professional and managerial employment. Finally, we inspect the Capital further to reveal that the class pay gap is largest within Central London's banking and finance sector. Challenging policy conceptions of London as the ‘engine room’ of social mobility, these findings suggest that class disadvantage within high‐status occupations is particularly acute in the Capital. The findings also underline the value of investigating regional differences in social mobility, and demonstrate how such analysis can unravel important and previously unrecognized spatial dimensions of class inequality.
Simultaneous fermentation of cellulose and current production with an enriched mixed culture of thermophilic bacteria in a microbial electrolysis cell
Authors: Lusk Bradley G. , Colin Alexandra , Parameswaran Prathap , Rittmann Bruce E. , Torres Cesar I.
Published: May 2017

An enriched mixed culture of thermophilic (60°C) bacteria was assembled for the purpose of using cellulose to produce current in thermophilic microbial electrolysis cells (MECs). Cellulose was fermented into sugars and acids before being consumed by anode‐respiring bacteria (ARB) for current production. Current densities (j) were sustained at 6.5 ± 0.2 A m−2 in duplicate reactors with a coulombic efficiency (CE) of 84 ± 0.3%, a coulombic recovery (CR) of 54 ± 11% and without production of CH4. Low‐scan rate cyclic voltammetry (LSCV) revealed a mid‐point potential (Eka) of −0.17 V versus SHE. Pyrosequencing analysis of the V4 hypervariable region of 16S rDNA and scanning electron microscopy present an enriched thermophilic microbial community consisting mainly of the phylum Firmicutes with the Thermoanaerobacter (46 ± 13%) and Thermincola (28 ± 14%) genera occupying the biofilm anode in high relative abundance and Tepidmicrobium (38 ± 6%) and Moorella (11 ± 8%) genera present in high relative abundance in the bulk medium. The Thermoanaerobacter (15 ± 16%) and Brevibacillus (21 ± 30%) genera were also present in the bulk medium; however, their relative abundance varied by reactor. This study indicates that thermophilic consortia can obtain high CE and CR, while sustaining high current densities from cellulose in MECs.
Efficacy between high and medium doses of glucocorticoid therapy in remission induction of IgG4‐related diseases: a preliminary randomized controlled trial
Authors: Wu Qingjun , Chang Jie , Chen Hua , Chen Yu , Yang Hongxian , Fei Yunyun , Zhang Panpan , Zeng Xiaofeng , Zhang Fengchun , Zhang Wen
Published: May 2017

Aim

In order to evaluate the efficacy and safety of high versus medium doses of glucocorticoid therapy in remission induction of immunoglobulin G4‐related disease (IgG4‐RD), we set up a randomized controlled study.

Method

Newly diagnosed IgG4‐RD patients were randomly assigned to two groups: high doses of prednisone (0.8–1.0 mg/kg/day) and medium doses (0.5–0.6 mg/kg/day). Patients were assessed at weeks 0, 4, 12 and 24. The primary outcome was the remission rate at week 24. The secondary endpoints included IgG4‐RD responder index (IgG4‐RD RI), IgG and IgG4 levels.

Results

Twenty cases in each group finished the study. At week 24, the total response rates were 95% and 80% in high and medium dose groups, respectively. There was no significant difference between the two groups. IgG4‐RD RI reduced from 14.9 to 3.0 in the high dose group, while in the medium dose group it was from 13.1 to 3.2. At week 24, the average level of IgG4 reduced from 1576 to 324 mg/dL and from 1445 to 684 mg/dL in the two groups, respectively. Relapsed patients had higher baseline IgG4‐RD RI. There was no severe adverse effect shown in both groups.

Conclusion

The effect of remission induction was similar in high and medium glucocorticoid groups. However, patients with more organs involved and higher IgG4‐RD RI score at baseline might get more benefit with high dose glucocorticoid for remission induction.
Evaluation of sleep quality in patients with ankylosing spondylitis and efficacy of anti‐TNF‐α therapy on sleep problems: A polisomnographic study
Authors: Karatas Gulsah , Bal Ajda , Yuceege Melike , Firat Hikmet , Gurcay Eda , Ardic Sadik , Cakci Fatma Aytul
Published: May 2017

Introduction

This study was conducted to investigate the relationship between sleep quality (SQ) and disease activity (DA) in patients with ankylosing spondylitis (AS) and to evaluate the response to anti‐tumor necrosis factor α (anti‐TNF‐α) therapy on sleep disorders.

Materials and Methods

A total of 34 patients who met the modified New York classification criteria for AS were included in this prospective study. Patients were divided into two groups as follows: Group I (n = 15) with high DA and receiving anti‐TNF‐α therapy, and Group II (n = 19) in remission. DA was assessed by the Bath AS Disease Activity Index. Pittsburgh Sleep Quality Index (PSQI) and polysomnography (PSG) were used to determine disorders and patterns of sleep, respectively, in both groups at baseline as well as at the third month of anti‐TNF‐α therapy in Group I.

Results

Baseline evaluation revealed impaired SQ in 57.9% of all patients. PSG demonstrated obstructive sleep apnea syndrome, snoring and periodic leg movements in 73.7%, 74.4% and 26.3% of patients, respectively. Prior to anti‐TNF‐α therapy, PSQI and snoring score were significantly higher in Group I (P = 0.0001, P = 0.012, respectively). Although there was a significant reduction in PSQI scores in Group I (P = 0.005) at the third month of anti‐TNF‐α therapy, no change was observed in PSG parameters (P > 0.05).

Conclusion

Sleep disorders increase in AS, particularly in patients with high DA. Anti‐TNF‐α therapy has improved SQ without any improvement in PSG. Therefore, it may be concluded that PSG parameters might be more associated with disease pathogenesis rather than DA in patients with AS.
Discovery of ectosymbiotic Endomicrobium lineages associated with protists in the gut of stolotermitid termites
Authors: Izawa Kazuki , Kuwahara Hirokazu , Sugaya Kaito , Lo Nathan , Ohkuma Moriya , Hongoh Yuichi
Published: May 2017

The genus Endomicrobium is a dominant bacterial group in the gut of lower termites, and most phylotypes are intracellular symbionts of gut protists. Here we report the discovery of Endomicrobium ectosymbionts of termite gut protists. We found that bristle‐like Endomicrobium cells attached to the surface of spirotrichosomid protist cells inhabiting the termite Stolotermes victoriensis. Transmission electron microscopy revealed that a putative Endomicrobium cell likely attached to the protist surface via a protrusion from the tip of the bacterium. A phylotype, sharing 98.9% 16S rRNA sequence identity with the Endomicrobium ectosymbionts of the spirotrichosomid protists, was also found on the cell surface of the protist Trichonympha magna in the gut of the termite Porotermes adamsoni. We propose the novel species ‘Candidatus Endomicrobium superficiale’ for these bacteria. T. magna simultaneously harboured another Endomicrobium ectosymbiont that shared 93.5–94.2% 16S rRNA sequence identities with ‘Ca. Endomicrobium superficiale’. Furthermore, Spirotrichonympha‐like protists in P. adamsoni guts were associated with an Endomicrobium phylotype that possibly attached to the host flagella. A phylogenetic analysis suggested that these ectosymbiotic lineages have evolved multiple times from free‐living Endomicrobium lineages and are relatively distant from the endosymbionts. Our results provide novel insights into the ecology and evolution of the Endomicrobium.
Using taxonomic consistency with semi‐automated data pre‐processing for high quality DNA barcodes
Authors: Rulik Björn , Eberle Jonas , von der Mark Laura , Thormann Jana , Jung Manfred , Köhler Frank , Apfel Wolfgang , Weigel Andreas , Kopetz Andreas , Köhler Jonas , Fritzlar Frank , Hartmann Matthias , Hadulla Karl , Schmidt Joachim , Hörren Thomas , Krebs Detlef , Theves Florian , Eulitz Ute , Skale André , Rohwedder Dirk , Kleeberg Andreas , Astrin Jonas J. , Geiger Matthias F. , Wägele J. Wolfgang , Grobe Peter , Ahrens Dirk
Published: May 2017

In recent years, large‐scale DNA barcoding campaigns have generated an enormous amount of COI barcodes, which are usually stored in NCBI's GenBank and the official Barcode of Life database (BOLD). BOLD data are generally associated with more detailed and better curated meta‐data, because a great proportion is based on expert‐verified and vouchered material, accessible in public collections. In the course of the initiative German Barcode of Life data were generated for the reference library of 2,846 species of Coleoptera from 13,516 individuals.

Confronted with the high effort associated with the identification, verification and data validation, a bioinformatic pipeline, “TaxCI” was developed that (1) identifies taxonomic inconsistencies in a given tree topology (optionally including a reference dataset), (2) discriminates between different cases of incongruence in order to identify contamination or misidentified specimens, (3) graphically marks those cases in the tree, which finally can be checked again and, if needed, corrected or removed from the dataset. For this, “TaxCI” may use DNA‐based species delimitations from other approaches (e.g. mPTP) or may perform implemented threshold‐based clustering.

The data‐processing pipeline was tested on a newly generated set of barcodes, using the available BOLD records as a reference. A data revision based on the first run of the TaxCI tool resulted in the second TaxCI analysis in a taxonomic match ratio very similar to the one recorded from the reference set (92% vs. 94%). The revised dataset improved by nearly 20% through this procedure compared to the original, uncorrected one.

Overall, the new processing pipeline for DNA barcode data allows for the rapid and easy identification of inconsistencies in large datasets, which can be dealt with before submitting them to public data repositories like BOLD or GenBank. Ultimately, this will increase the quality of submitted data and the speed of data submission, while primarily avoiding the deterioration of the accuracy of the data repositories due to ambiguously identified or contaminated specimens.
Statistical design and analysis for plant cover studies with multiple sources of observation errors
Authors: Wright Wilson J. , Irvine Kathryn M. , Warren Jeffrey M. , Barnett Jenny K.
Published: May 2017

Effective wildlife habitat management and conservation requires understanding the factors influencing distribution and abundance of plant species. Field studies, however, have documented observation errors in visually estimated plant cover including measurements which differ from the true value (measurement error) and not observing a species that is present within a plot (detection error). Unlike the rapid expansion of occupancy and N‐mixture models for analysing wildlife surveys, development of statistical models accounting for observation error in plants has not progressed quickly. Our work informs development of a monitoring protocol for managed wetlands within the National Wildlife Refuge System.

Zero‐augmented beta (ZAB) regression is the most suitable method for analysing areal plant cover recorded as a continuous proportion but assumes no observation errors. We present a model extension that explicitly includes the observation process thereby accounting for both measurement and detection errors. Using simulations, we compare our approach to a ZAB regression that ignores observation errors (naïve model) and an “ad hoc” approach using a composite of multiple observations per plot within the naïve model. We explore how sample size and within‐season revisit design affect the ability to detect a change in mean plant cover between 2 years using our model.

Explicitly modelling the observation process within our framework produced unbiased estimates and nominal coverage of model parameters. The naïve and “ad hoc” approaches resulted in underestimation of occurrence and overestimation of mean cover. The degree of bias was primarily driven by imperfect detection and its relationship with cover within a plot. Conversely, measurement error had minimal impacts on inferences. We found >30 plots with at least three within‐season revisits achieved reasonable posterior probabilities for assessing change in mean plant cover.

For rapid adoption and application, code for Bayesian estimation of our single‐species ZAB with errors model is included. Practitioners utilizing our R‐based simulation code can explore trade‐offs among different survey efforts and parameter values, as we did, but tuned to their own investigation. Less abundant plant species of high ecological interest may warrant the additional cost of gathering multiple independent observations in order to guard against erroneous conclusions.
Sustained NFκB inhibition improves insulin sensitivity but is detrimental to muscle health
Authors: Zhang Ning , Valentine Joseph M. , Zhou You , Li Mengyao E. , Zhang Yiqiang , Bhattacharya Arunabh , Walsh Michael E. , Fischer Katherine E. , Austad Steven N. , Osmulski Pawel , Gaczynska Maria , Shoelson Steven E. , Van Remmen Holly , Chen Hung I. , Chen Yidong , Liang Hanyu , Musi Nicolas
Published: May 2017

Older adults universally suffer from sarcopenia and approximately 60–70% are diabetic or prediabetic. Nonetheless, the mechanisms underlying these aging‐related metabolic disorders are unknown. NFκB has been implicated in the pathogenesis of several aging‐related pathologies including sarcopenia and type 2 diabetes and has been proposed as a target against them. NFκB also is thought to mediate muscle wasting seen with disuse, denervation, and some systemic diseases (e.g., cancer, sepsis). We tested the hypothesis that lifelong inhibition of the classical NFκB pathway would protect against aging‐related sarcopenia and insulin resistance. Aged mice with muscle‐specific overexpression of a super‐repressor IκBα mutant (MISR) were protected from insulin resistance. However, MISR mice were not protected from sarcopenia; to the contrary, these mice had decreases in muscle mass and strength compared to wild‐type mice. In MISR mice, NFκB suppression also led to an increase in proteasome activity and alterations in several genes and pathways involved in muscle growth and atrophy (e.g., myostatin). We conclude that the mechanism behind aging‐induced sarcopenia is NFκB independent and differs from muscle wasting due to pathologic conditions. Our findings also indicate that, while suppressing NFκB improves insulin sensitivity in aged mice, this transcription factor is important for normal muscle mass maintenance and its sustained inhibition is detrimental to muscle function.
Sarcopenia in Alcoholic Liver Disease: Clinical and Molecular Advances
Authors: Dasarathy Jaividhya , McCullough Arthur J. , Dasarathy Srinivasan
Published: May 2017

Despite advances in treatment of alcohol use disorders that focus on increasing abstinence and reducing recidivism, alcoholic liver disease (ALD) is projected to be the major cause of cirrhosis and its complications. Malnutrition is recognized as the most frequent complication in ALD, and despite the high clinical significance, there are no effective therapies to reverse malnutrition in ALD. Malnutrition is a relatively imprecise term, and sarcopenia or skeletal muscle loss, the major component of malnutrition, is primarily responsible for the adverse clinical consequences in patients with liver disease. It is, therefore, critical to define the specific abnormality (sarcopenia) rather than malnutrition in ALD, so that therapies targeting sarcopenia can be developed. Skeletal muscle mass is maintained by a balance between protein synthesis and proteolysis. Both direct effects of ethanol (EtOH) and its metabolites on the skeletal muscle and the consequences of liver disease result in disturbed proteostasis (protein homeostasis) and consequent sarcopenia. Once cirrhosis develops in patients with ALD, abstinence is unlikely to be effective in completely reversing sarcopenia, as other contributors including hyperammonemia, hormonal, and cytokine abnormalities aggravate sarcopenia and maintain a state of anabolic resistance initiated by EtOH. Cirrhosis is also a state of accelerated starvation, with increased gluconeogenesis that requires amino acid diversion from signaling and substrate functions. Novel therapeutic options are being recognized that are likely to supplant the current “deficiency replacement” approach and instead focus on specific molecular perturbations, given the increasing availability of small molecules that can target specific signaling components. Myostatin antagonists, leucine supplementation, and mitochondrial protective agents are currently in various stages of evaluation in preclinical studies to prevent and reverse sarcopenia, in cirrhosis in general, and ALD, specifically. Translation of these data to human studies and clinical application requires priority for allocation of resources.
Two‐year functional and anatomical results after converting treatment resistant eyes with exudative age‐related macular degeneration to aflibercept in accordance with a treat and extend protocol
Authors: Jørstad Øystein Kalsnes , Faber Rowan Thomas , Moe Morten Carstens
Published: May 2017

Purpose

To study the effects of converting to aflibercept in accordance with a treat and extend (T&E) strategy in eyes with treatment resistant exudative age‐related macular degeneration (AMD).

Methods

Two‐year prospective study of eyes with exudative AMD and persistent macular fluid despite monthly treatment with ranibizumab or bevacizumab. Eyes were converted to 2.0 mg aflibercept in accordance with a T&E protocol.

Results

Fifty eyes from 47 patients were included. At baseline, the mean central retinal thickness (CRT) was 273 μm and mean best‐corrected visual acuity (BCVA) 0.25 logarithm of the minimal angle of resolution (logMAR). The mean number of aflibercept injections the first year was 9.2. After 1 year, there was a reduction in mean CRT to 228 μm (p < 0.001); 22 eyes (44%) had a dry macula; and the mean BCVA was 0.24 logMAR (p = 0.531). The mean number of aflibercept injections the second year was 8.0 (p = 0.013 compared to first year). After 2 years, 24 eyes (48%) received treatment more frequently than every eighth week. The mean CRT was 225 μm (p < 0.001 compared to baseline); 31 eyes (62%) had a dry macula; and mean BCVA was 0.32 logMAR (p = 0.005 compared to baseline). Five eyes did not complete 2 years of aflibercept treatment after failing to improve.

Conclusion

A majority of eyes showed improved anatomic outcomes. There was a small decrease in mean BCVA after the second year of treatment. About half of the eyes required treatment more frequently than the recommended aflibercept label of an 8‐week interval.
Evaluation of clinical validity of the Rabin cone contrast test in normal phakic or pseudophakic eyes and severely dichromatic eyes
Authors: Fujikawa Masato , Muraki Sanae , Niwa Yuichi , Ohji Masahito
Published: May 2017

Purpose

To evaluate the clinical validity of the Rabin cone contrast test (RCCT; Innova Systems, Inc.) in patients with normal phakic/pseudophakic eyes and severe dichromatic colour vision deficiency (CVD).

Methods

We evaluated age‐related changes in the RCCT scores in 166 phakic eyes and 34 pseudophakic eyes and the RCCT sensitivity and specificity in 28 men with severe dichromatic CVD (10 with protanopia, 18 with deutanopia) and nine age‐matched controls. All participants had 20/20 or better Snellen best‐corrected visual acuity (BCVA). The RCCT was used to measure the L, M and S‐CCT scores (range, 0–100).

Results

In normal phakic eyes, the mean L, M and S‐CCT scores decreased gradually with ageing, with normal levels in patients in the second to seventh decades of life and some below normal in the eighth and ninth decades of life. In normal pseudophakic eyes, the mean L, M and S‐CCT scores were normal in patients in the seventh to ninth decades of life. In eyes with severe CVD, the mean L, M and S‐CCT scores were, respectively, 31.5 ± 18.3, 86.0 ± 12.6 and 98.0 ± 6.3 in patients with protanopia; 92.8 ± 10.5, 50.8 ± 19.6 and 97.8 ± 5.2 in patients with deutanopia; and 99.4 ± 1.7, 98.3 ± 5.0 and 99.4 ± 1.7 in controls. The RCCT sensitivity and specificity were 100% for diagnosing the CVD type.

Conclusion

The RCCT can be used in non‐visually impaired patients up to the seventh decade of life and after cataract surgery in elderly patients. The RCCT is available for CVD screening and typing and the score has a wide distribution range even in patients with severe CVD.
Hypothalamic dopamine is required for salsolinol‐induced prolactin secretion in goats
Authors: Hashizume Tsutomu , Watanabe Ryunosuke , Inaba Yuki , Sawai Ken , Fülöp Ferenc , Nagy György Miklos
Published: May 2017

The aim of the present study was to clarify the relationship between hypothalamic dopamine (DA) and salsolinol (SAL) for the secretion of prolactin (PRL) in goats.SALor thyrotropin‐releasing hormone (TRH) was intravenously injected into female goats treated with or without the D2DAreceptor antagonist haloperidol (Hal), which crosses the blood‐brain barrier, and thePRL‐releasing response toSALwas compared with that toTRH.PRL‐releasing responses toSAL, Hal, and Hal plusSALwere also examined after a pretreatment to augment centralDAusing carbidopa (Carbi) and L‐dopa. ThePRL‐releasing response to Hal alone was greater than that toSALorTRHalone. ThePRL‐releasing response to Hal plusSALwas similar to that of Hal alone. In contrast, thePRL‐releasing response to Hal plusTRHwas greater than that toTRHor Hal alone. The treatment with Carbi plus L‐dopa inhibitedSAL‐ and Hal‐inducedPRLsecretion. The inhibition of thePRL‐releasing response toSALdisappeared whenSALwas injected with Hal. These results indicate that the mechanisms underlying theSAL‐inducedPRLresponse differ from those ofTRH, and suggest that hypothalamicDAand its synthesis is associated in part withSAL‐inducedPRLsecretion in goats.
The Impact of Audit Committee Characteristics on CSR Disclosure: An Analysis of Australian Firms
Authors: Appuhami Ranjith , Tashakor Shamim
Published: May 2017

This study examines the influence of audit committee (AC) characteristics on voluntary corporate social responsibility (CSR) disclosure in the corporate annual reports of Australian listed firms. It develops hypotheses about the relationship between voluntary CSR disclosure and AC characteristics such as size, frequency of meetings, independence, independent chair, financial expertise and gender diversity. Using multiple regression analysis on data collected from the corporate annual reports of 300 listed firms, the study finds that AC characteristics such as size, frequency of meetings, committee independence and gender diversity have a significant positive influence on the level of CSR disclosure. However, there is no evidence that AC characteristics such as independent chair and members’ financial expertise affect CSR disclosure in Australian firms. Based on an additional analysis, the study also sheds some light on the effect of AC characteristics on environmental disclosure. The findings of this study may be of particular interest to regulators, shareholders, investment analysts and managers in assessing CSR disclosure in annual reports, and in strengthening the monitoring and oversight role of ACs.
Can bottom‐up processes of attention be a source of ‘interference’ in situations where top‐down control of attention is crucial?
Authors: Nikolla Dritan , Edgar Graham , Catherwood Dianne , Matthews Tristan
Published: May 2017

In this study, we investigate whether emotionally engaged bottom‐up processes of attention can be a source of ‘interference’ in situations where top‐down control of attention is necessary. Participants were asked to monitor and report on a video of a war scenario showing a developing battle in two conditions: emotionally positive and emotionally negative. Half of the participants (n = 15) were exposed to task‐irrelevant pictures of positive emotional valence embedded within the scenario; the other half were exposed to task‐irrelevant pictures of negative emotional valence. Sensitivity and Bias scores were calculated using signal detection theory. Overall, task accuracy scores were dependent upon the valence; negative pictures had an adverse effect on performance, whereas positive pictures improved performance. We concluded that negative emotional pictures interfered with top‐down control of attention by attracting competing bottom‐up processes of attention. We found the opposite effect for positive emotional stimuli.
Attachment Security and Developmental Patterns of Growth in Executive Functioning During Early Elementary School
Authors: Matte‐Gagné Célia , Bernier Annie , Sirois Marie‐Soleil , Lalonde Gabrielle , Hertz Sarah
Published: May 2017

Despite the extensive research demonstrating the importance of child executive functioning (EF) for school adjustment, little longitudinal work has formally examined developmental change in EF during the early school years. Based on a sample of 106 mother–child dyads, the current longitudinal study investigated patterns of growth in child performance on three executive tasks between kindergarten (Mage = 6 years) and Grade 3 (Mage = 9 years), and the predictive role of earlier mother–child attachment security in these patterns. The results suggest that early elementary school is a period of significant developmental improvement in child EF, although child performance on different EF tasks follows distinct trajectories across time. The study also provides evidence for a sustained relation between children's early attachment security and their ongoing acquisition of executive skills.
Dimensional alterations following vertical ridge augmentation using collagen membrane and three types of bone grafting materials: A retrospective observational study
Authors: Park Yun‐Ho , Choi Seong‐Ho , Cho Kyoo‐Sung , Lee Jung‐Seok
Published: May 2017

Background

Various biomaterials have been introduced for vertical ridge augmentation to replace autogenous block bone grafting.

Purpose

This retrospective study radiographically evaluated dimensional alterations of the vertically augmented alveolar ridge using collagen membrane and 3 types of materials: autogenous bone block, allogenous bone block, and particulated bone substitute.

Materials and methods

The electronic medical records of 32 patients who received vertical ridge augmentation using 3 types of materials were searched: 9 for autogenous bone block, 12 for allogenous bone block, and 11 for particulated bone substitutes. The vertical bone gain, progression of bone resorption, and peri‐implant marginal bone loss after prosthetic loading were measured on follow‐up radiographs.

Results

The alveolar ridge was vertically augmented by 5.13 ± 1.61, 4.54 ± 2.48, and 3.90 ± 0.85 mm (mean ± standard deviation) after grafting with autogenous bone block, allogenous bone block, and particulated bone substitute, respectively. The radiographic vertical height of the augmented ridge that received autogenous bone block reduced continuously during the first year but was stable thereafter. Sites that received allogenous bone block or particulated bone substitute exhibited dimensional shrinkage for up to 1.5 years postsurgery. However, the peri‐implant marginal bone loss did not exceed 1 mm throughout the observational periods in all groups.

Conclusions

The clinical findings of this study suggest that the alveolar ridge can be vertically augmented using either allogenous bone block or particulated bone substitute. However, they require a longer healing period to ensure dimensional stability compared to the autogenous bone block.
Pituicytoma—An outlook on possible targeted therapies
Authors: Mende Klaus Christian , Matschke Jakob , Burkhardt Till , Saeger Wolfgang , Buslei Rolf , Buchfelder Michael , Fahlbusch Rudolf , Westphal Manfred , Flitsch Jörg
Published: May 2017

Introduction

Pituicytoma is a rare neoplasm of the sella region. Tumor resection is the primary treatment option, but remains subtotal due to excessive bleeding in many cases. The search for alternative or additional treatment regimens is necessary.

Aims

We aimed to determine the receptor expression of pituicytoma to find alternatives or supplements to surgical therapy in the use of targeted therapies.

Methods

Pituicytoma samples were collected from three institutions between 2006 and 2015 and were stained for vascular endothelial growth factors (VEGF), thyroid transcription factor (TTF1), and somatostatin receptors (SSTR 2/3/5). The stains were classified from 0=no staining to +++=strong staining. A complementary retrospective analysis of the patient charts regarding sex, age, and primary symptoms, pituitary function, and perioperative complications was performed.

Results

Ten samples were analyzed; mean patient age was 57.8 years SD 16.3 years. Seven samples were acquired from male patients (one relapse) and three from female. All tumors stained strongly positive (+++) for VEGF‐R. Six samples stained positive for TTF1. As for somatostatin receptors, three samples were slightly positive for SSTR 2; seven were negative. SSTR 3 was + in one, three were ++, three were +++, and three were 0. SSTR 5 stained +++ in 1, ++ in 5, + in 1, and 0 in three patients.

Conclusions

Pituicytomas were generally positive for VEGFR and showed regular expression of SSTR 3 and 5 indicating a possible treatment option through targeted therapies in cases where resection remains insufficient. Further research is necessary as to whether tumor growth can be inhibited using these pathways.
Psychological impact of a genetic diagnosis on hearing impairment—An exploratory study
Authors: Oonk A.M.M. , Ariens S. , Kunst H.P.M. , Admiraal R.J.C. , Kremer H. , Pennings R.J.E.
Published: May 2017

Objective

Genetic testing for hereditary hearing impairment has become more routinely available as a diagnostic tool in the outpatient clinic. However, little is known about the psychological impact of a genetic diagnosis. To evaluate this impact, an exploratory study was conducted.

Design

Prospectively, 48 individuals who underwent genetic testing for hereditary hearing impairment were included in this study. Study participants were asked to fill out the following questionnaires: Hospital Anxiety Depression Scale, Impact of Event Scale, Self‐Efficacy 24, Illness Cognition Questionnaire and the Inventory for Social Reliance. Questionnaires were filled out on three occasions: before genetic testing, directly after counselling on either positive or negative test results, and six weeks thereafter.

Results

No significant differences were found between the group that received a genetic diagnosis for their hearing impairment and the group that did not.

Conclusion

This study did not demonstrate differences between receiving a genetic diagnosis or not; however, special attention to psychological well‐being should be offered to hearing‐impaired patients who seek a genetic diagnosis for their hearing impairment. Additionally, the psychological impact of sensorineural hearing impairment might be greater than the impact of a genetic diagnosis itself. Based on the current exploratory study, there are no psychological reasons in favour of or against genetic testing for hereditary hearing impairment.
G‐CSF Indirectly Induces Apoptosis of Osteoblasts During Hematopoietic Stem Cell Mobilization
Authors: Li S‐D , Chen Y‐B , Qiu L‐G , Qin M‐Q
Published: May 2017

The objective of this study was to explore the mechanism underlying osteoblast suppression in the process of hematopoietic stem cells mobilization induced by granulocyte colony‐stimulating factor (G‐CSF). The apoptosis of human and mouse osteoblasts was examined by detecting caspase 3. The levels of serum DKK1 and osteocalcin in the supernatant of co‐culture of mouse osteoblasts and mouse bone marrow nucleated cells were measured. The number of mouse osteoblasts co‐cultured with mouse bone marrow nucleated cells was measured and the osteocalcin mRNA level was also measured. The G‐CSF‐induced decrease in osteoblast function was partly due to the apoptosis of osteoblasts. There was no significant difference in the level of serum DKK1 in healthy donors before and 5 days after mobilization. The osteocalcin gene and protein expression was significantly different in co‐cultured osteoblasts with bone marrow nucleated cells treated with and without G‐CSF. Osteoblasts undergo apoptosis during mobilization and G‐CSF affects osteoblasts through bone marrow nucleated cells.
Hereditary progressive mucinous histiocytosis: 3 different phenotypes in 3 family members
Authors: Requena Celia , Requena Luis , Traves Victor , Sanmartín Onofre
Published: May 2017

We describe 3 cases of multiple histiocytic cutaneous tumors that began in childhood and affected 3 members from 2 generations of the same family: a mother, a daughter and a nephew. The lesions were mostly skin‐colored papules distributed symmetrically on the dorsum of the forearms and hands and on the face and thighs. There were no signs of spontaneous regression. The clinical and histopathological features were consistent with a diagnosis of hereditary progressive mucinous histiocytosis (HPMH), but phenotypic expression varied somewhat between the 3 patients. HPMH has only been described in 8 families to date, and just one of the reports included 3 well‐documented cases. Our cases confirm that HPMH can affect males and expands the clinical spectrum of skin lesions in this disease.
Expression patterns of Sema3A in developing amniote limbs: With reference to the diversification of peripheral nerve innervation
Authors: Noguchi Kanami , Ishikawa Ryota , Kawaguchi Masahumi , Miyoshi Kanako , Kawasaki Takahiko , Hirata Tatsumi , Fukui Makiko , Kuratani Shigeru , Tanaka Mikiko , Murakami Yasunori
Published: May 2017

Paired limbs were acquired in the ancestor of tetrapods and their morphology has been highly diversified in amniotes in relation to the adaptive radiation to the terrestrial environment. These morphological changes may have been induced by modification of the developmental program of the skeletal or muscular system. To complete limb modification, it is also important to change the neuronal framework, because the functions of the limbs rely on neural circuits that involve coordinated movement. Previous studies have shown that class 3 semaphorins (Sema3 semaphorins), which act as repulsive axonal guidance cues, play a crucial role in the formation of the peripheral nerves in mice. Here, we studied the expression pattern of Sema3A orthologues in embryos of developing amniotes, including mouse, chick, soft‐shelled turtle, and ocelot gecko. Sema3A transcripts were expressed in restricted mesenchymal parts of the developing limb primordium in all animals studied, and developing spinal nerves appeared to extend through Sema3A‐negative regions. These results suggest that a Sema3A‐dependent guidance system plays a key role in neuronal circuit formation in amniote limbs. We also found that Sema3A partially overlapped with the distribution of cartilage precursor cells. Based on these results, we propose a model in which axon guidance and skeletogenesis are linked by Sema3A; such mechanisms may underlie functional neuron rearrangement during limb diversification.
The value of a comprehensive natural history in late infantile CLN5 disease
Authors: Mole Sara E
Published: May 2017

This commentary is on the original article by Simonati et al. on pages 815–821 of this issue.
Pain in cerebral palsy: a neglected comorbidity
Authors: Fehlings Darcy
Published: May 2017

This commentary is on the original article by Westbom et al. on pages 858–863 of this issue.
A new player in the international development community? Chile as an emerging donor
Authors: Gutiérrez Alexis , Jaimovich Dany
Published: May 2017

In recent years a series of non‐traditional donors have gained relevance as providers of Official Development Assistance (ODA). In the present study we analyze the case of Chile, one of these emerging donors. Our estimates indicate that Chile's ODA was roughly 0.01% of gross domestic product (GDP) in the period from 2006 to 2012. Even though this magnitude was far below that of other emerging donors, Chile has become one of the main regional donors within Latin America. We show that the Chilean approach to international co‐operation has been a mix of emergency aid and technical assistance for social policies, often in response to diplomatic affairs. As such, Chilean ODA has been mainly an instrument of soft power diplomacy.