bluuebunny/crossref_metadata_2025 huggingface dataset:
Self-consistency test reveals systematic bias in programs for prediction change of stability upon mutation
Authors: Usmanova Dinara R , Bogatyreva Natalya S , Ariño Bernad Joan , Eremina Aleksandra A , Gorshkova Anastasiya A , Kanevskiy German M , Lonishin Lyubov R , Meister Alexander V , Yakupova Alisa G , Kondrashov Fyodor A , Ivankov Dmitry N
Published: April 2018

Motivation

Computational prediction of the effect of mutations on protein stability is used by researchers in many fields. The utility of the prediction methods is affected by their accuracy and bias. Bias, a systematic shift of the predicted change of stability, has been noted as an issue for several methods, but has not been investigated systematically. Presence of the bias may lead to misleading results especially when exploring the effects of combination of different mutations.

Results

Here we use a protocol to measure the bias as a function of the number of introduced mutations. It is based on a self-consistency test of the reciprocity the effect of a mutation. An advantage of the used approach is that it relies solely on crystal structures without experimentally measured stability values. We applied the protocol to four popular algorithms predicting change of protein stability upon mutation, FoldX, Eris, Rosetta and I-Mutant, and found an inherent bias. For one program, FoldX, we manage to substantially reduce the bias using additional relaxation by Modeller. Authors using algorithms for predicting effects of mutations should be aware of the bias described here.

Availability and implementation

All calculations were implemented by in-house PERL scripts.

Supplementary information

Supplementary data are available at Bioinformatics online.

Note

The article 10.1093/bioinformatics/bty348, published alongside this paper, also addresses the problem of biases in protein stability change predictions.
Applying graph theory to protein structures: an Atlas of coiled coils
Authors: Heal Jack W , Bartlett Gail J , Wood Christopher W , Thomson Andrew R , Woolfson Derek N
Published: April 2018

Motivation

To understand protein structure, folding and function fully and to design proteins de novo reliably, we must learn from natural protein structures that have been characterized experimentally. The number of protein structures available is large and growing exponentially, which makes this task challenging. Indeed, computational resources are becoming increasingly important for classifying and analyzing this resource. Here, we use tools from graph theory to define an Atlas classification scheme for automatically categorizing certain protein substructures.

Results

Focusing on the α-helical coiled coils, which are ubiquitous protein-structure and protein–protein interaction motifs, we present a suite of computational resources designed for analyzing these assemblies. iSOCKET enables interactive analysis of side-chain packing within proteins to identify coiled coils automatically and with considerable user control. Applying a graph theory-based Atlas classification scheme to structures identified by iSOCKET gives the Atlas of Coiled Coils, a fully automated, updated overview of extant coiled coils. The utility of this approach is illustrated with the first formal classification of an emerging subclass of coiled coils called α-helical barrels. Furthermore, in the Atlas, the known coiled-coil universe is presented alongside a partial enumeration of the ‘dark matter’ of coiled-coil structures; i.e. those coiled-coil architectures that are theoretically possible but have not been observed to date, and thus present defined targets for protein design.

Availability and implementation

iSOCKET is available as part of the open-source GitHub repository associated with this work (https://github.com/woolfson-group/isocket). This repository also contains all the data generated when classifying the protein graphs. The Atlas of Coiled Coils is available at: http://coiledcoils.chm.bris.ac.uk/atlas/app.
PBRpredict-Suite: a suite of models to predict peptide-recognition domain residues from protein sequence
Authors: Iqbal Sumaiya , Hoque Md Tamjidul
Published: April 2018

Motivation

Machine learning plays a substantial role in bioscience owing to the explosive growth in sequence data and the challenging application of computational methods. Peptide-recognition domains (PRDs) are critical as they promote coupled-binding with short peptide-motifs of functional importance through transient interactions. It is challenging to build a reliable predictor of peptide-binding residue in proteins with diverse types of PRDs from protein sequence alone. On the other hand, it is vital to cope up with the sequencing speed and to broaden the scope of study.

Results

In this paper, we propose a machine-learning-based tool, named PBRpredict, to predict residues in peptide-binding domains from protein sequence alone. To develop a generic predictor, we train the models on peptide-binding residues of diverse types of domains. As inputs to the models, we use a high-dimensional feature set of chemical, structural and evolutionary information extracted from protein sequence. We carefully investigate six different state-of-the-art classification algorithms for this application. Finally, we use the stacked generalization approach to non-linearly combine a set of complementary base-level learners using a meta-level learner which outperformed the winner-takes-all approach. The proposed predictor is found competitive based on statistical evaluation.

Availability and implementation

PBRpredict-Suite software: http://cs.uno.edu/~tamjid/Software/PBRpredict/pbrpredict-suite.zip.

Supplementary information

Supplementary data are available at Bioinformatics online.
Strangers in the Frame: Inside and Outside the
Cent Nouvelles nouvelles
Authors: Emerson Catherine
Published: April 2018

This article examines the way in which tales of the Burgundian
Cent Nouvelles nouvelles
are interpreted differently by different reading publics. Taking a neglected tale in the corpus,
nouvelle
66, as a starting point, the article argues that this
nouvelle
exemplifies tendencies observable throughout the collection, particularly in regard to surprising physical characteristics of outgroup members such as women and clerics. Viewed in the context of the tales’ original readership, such stories cement ingroup solidarity amongst a group of elite men who, whilst sharing some characteristics, were reasonably diverse in a number of ways. However, the original reading context is not fully reconstructable because it is unclear as to what the narrative frame actually represents. Once the tales move beyond this frame, the court of Philippe le Bon becomes a spectacle itself, and this is reflected in a number of readings which censure the original audience. The article argues that this reaction is present in the very first edition and is indeed inherent in the narrative frame of the
Cent Nouvelles nouvelles
.
Confucian Values as a Buffer Against Age-Based Stereotype Threat for Chinese Older Adults
Authors: Tan Shyuan Ching , Barber Sarah J
Published: April 2018

Objectives

Research has shown that stereotype threat can impair older adults’ memory in Western cultures. We tested whether this also occurs for older adults from the East Asian Chinese culture. We also tested whether an intervention that highlighted Confucian principles would protect Chinese older adults from stereotype threat’s detrimental effects.

Method

Culturally-Chinese older adults residing in the United States completed a memory test either under age-based stereotype threat about cognitive decline or not. Prior to this, some participants were also reminded of Confucian traditions of filial piety and were assured these values had been transmitted to the younger generation.

Results

Stereotype threat impaired Chinese older adults’ memory performance. However, our intervention was effective in eliminating this deficit. When the Chinese participants were reminded of the Confucian principle of filial piety they did not exhibit stereotype threat effects.

Discussion

Confirming that younger adults have an obligation to respect their elders can eliminate the social-evaluative pressure of stereotype threat for Chinese older adults. These findings are noteworthy since population aging is happening at an unprecedented pace in East Asia. Although our results suggest that stereotype threat can adversely affect older adults’ cognitive performance in these societies, we also identify a culturally-based intervention to alleviate this impairment.
Mincle: 20 years of a versatile sensor of insults
Authors: Lu Xiuyuan , Nagata Masahiro , Yamasaki Sho
Published: April 2018

Macrophage-inducible C-type lectin, better known as Mincle, is a member of the C-type lectin receptor family and is encoded by Clec4e. Mincle was an orphan receptor for a long time after having been discovered as a lipopolysaccharide-induced protein, yet later an adjuvant glycolipid in mycobacteria—trehalose dimycolate—was identified as a ligand. Ligands for Mincle were also found existing in bacteria, fungi and even mammals. When confronted with foreign elements, Mincle can recognize characteristic pathogen-associated molecular patterns, mostly glycolipids, from Mycobacterium tuberculosis and other pathogens, and thus induce immune responses against infection. To maintain self-homeostasis, Mincle can recognize lipid-based damage-associated molecular patterns, thereby monitoring the internal environment. The mechanism by which Mincle functions in the immune system is also becoming more clear along with the identification of its ligands. Being expressed widely on antigen-presenting cells, Mincle activation leads to the production of cytokines and chemokines, neutrophil infiltration and other inflammatory responses. Besides, Mincle can induce acquired immunity such as antigen-specific T-cell responses and antibody production as an adjuvant receptor. In this review, we will retrospectively sketch the discovery and study of Mincle, and outline some current work on this receptor.
High particulate matter 2.5 levels and ambient temperature are associated with acute lung edema in patients with nondialysis Stage 5 chronic kidney disease
Authors: Chiu Ping-Fang , Chang Chin-Hua , Wu Chia-Lin , Chang Teng-Hsiang , Tsai Chun-Chieh , Kor Chew-Teng , Li Jhao-Rong , Kuo Cheng-Ling , Huang Ching-Shan , Chu Cheng Chung , Chang Chia-Chu
Published: April 2018

Background

Numerous studies have shown that exposure to air pollution, especially particulate matter (PM) with a diameter <2.5 μm (PM2.5), was associated with various diseases. We tried to determine the impact of PM2.5 and other weather factors on acute lung edema in patients with Stage 5 nondialysis chronic kidney disease (CKD Stage 5-ND).

Methods

In total, 317 CKD Stage 5-ND (estimated glomerular filtration rate 6.79 ± 4.56 mL/min) patients residing in central Taiwan who developed acute lung edema and initiated long-term dialysis were included in this case-crossover study. Pearson’s correlation test was used to examine the relationship of acute lung edema cases with PM2.5 levels and ambient temperature separately.

Results

The average PM2.5 level within the 7-day period correlated with acute lung edema incidence in the fall [adjusted odds ratio (OR) 3.23, P = 0.047] and winter (adjusted OR 1.99, P < 0.001). In winter, even a 3-day exposure to PM2.5 was associated with increased risk (adjusted OR 1.55, P < 0.001). The average temperatures within 3 days in spring and summer were correlated positively with the risk (adjusted OR 2.77 P < 0.001 and adjusted OR 2.72, P < 0.001, respectively). In the fall and winter, temperatures were correlated negatively with the risk (adjusted OR 0.36, P < 0.001 and adjusted OR 0.54, P < 0.001, respectively).

Conclusions

A high PM2.5 level was associated with an increased risk of acute lung edema. High ambient temperature in hot seasons and low ambient temperature in cold seasons were also associated with increased risk. It is essential to educate these patients to avoid areas with severe air pollution and extreme ambient temperature.
Iterative Surgical Resections of Diffuse Glioma With Awake Mapping: How to Deal With Cortical Plasticity and Connectomal Constraints?
Authors: Picart Thiébaud , Herbet Guillaume , Moritz-Gasser Sylvie , Duffau Hugues
Published: April 2018

BACKGROUND

In diffuse glioma, a multistage approach with iterative tailored surgical resections can be considered.

OBJECTIVE

To compare results of iterative intrasurgical brain mappings to investigate the potential and limitation of neuroplasticity at the individual stage, and to highlight to what extent it can influence the therapeutic strategy.

METHODS

Glioma patients who underwent 2 consecutive awake surgeries with cortical and subcortical stimulation were classified into group 1 (n = 23) if cortical mappings exhibited high level of plasticity (displacement of ≥2 sites) or into group 2 (n = 19) with low level of plasticity.

RESULTS

Clinical characteristics did not differ significantly between both groups. The borders of the tumors were mostly sharp in group 1 (82.6%) and rather indistinct in group 2 (84.2%), (P = .00001). Tumor remnants were more often cortical (± subcortical) in group 1 (39.1%) and more often purely subcortical in group 2 (68.4%; P = .009). In group 1, the time needed to recover independence was significantly shorter at reoperation (37.6 h vs 78.3 h after the first surgery, P = .00003) while this difference was not significant in group 2. The iterative extents of resection (EOR) remain comparable in group 1 (94% vs 92%, P = .40) but were significantly smaller in group 2 at reoperation (94% vs 88%, P = .05).

CONCLUSION

More efficient plasticity mechanisms are facilitated by cortical tumors with sharp borders, are associated with an increase of EOR at reoperation and with earlier functional recovery. Tumoral invasion of the white matter tracts represents the main limitation of neuroplasticity: this connectomal constraint limits EOR during second surgery.
A Recurrent Neural Network Approach for Automated Neural Tracing in Multispectral 3D Images
Authors: Yan Yan , Roossien Douglas H. , Sadis Benjamin V. , Corso Jason J. , Cai Dawen
Published: April 2018

Neuronal morphology reconstruction in fluorescence microscopy 3D images is essential for analyzing neuronal cell type and connectivity. Manual tracing of neurons in these images is time consuming and subjective. Automated tracing is highly desired yet is one of the foremost challenges in computational neuroscience. The multispectral labeling technique, Brainbow utilizes high dimensional spectral information to distinguish intermingled neuronal processes. It is particular interesting to develop new algorithms to include the spectral information into the tracing process. Recently, deep learning approaches achieved state-of-the-art in different computer vision and medical imaging applications. To benefit from the power of deep learning, in this paper, we propose an automated neural tracing approach in multispectral 3D Brainbow images based on recurrent neural net-work. We first adopt VBM4D approach to denoise multispectral 3D images. Then we generate cubes as training samples along the ground truth, manually traced paths. These cubes are the input to the recur-rent neural network. The proposed approach is simple and effective. The approach can be implemented with the deep learning toolbox ‘Keras’ in 100 lines. Finally, to evaluate our approach, we computed the average and standard deviation of DIADEM metric from the ground truth results to our tracing results, and from our tracing results to the ground truth results. Extensive experimental results on the collected dataset demonstrate that the proposed approach performs well in Brainbow labeled mouse brain images.
Identification of Polynucleotide Phosphorylase (PNPase) in Escherichia coli Involved in Persister Formation
Authors: Wu Nan , Zhang Yumeng , Zhang Shanshan , Yuan Youhua , Liu Shuang , Cui Peng , Zhang Wenhong , Zhang Ying
Published: April 2018

Despite the identification of many genes and pathways involved in the persistence phenomenon of bacteria, the mechanisms of persistence are not well understood. Here, using Escherichia coli as a model, we identified polynucleotide phosphorylase (PNPase) as a key regulator in persister formation. We successfully constructed pnp knockout mutant strain and its complemented strain, and exposed the pnp knockout mutant and complemented strain to antibiotics and stress conditions. The results showed that, compared with the wild-type W3110, the pnp knockout strain had defect in persistence to antibiotics and stress conditions, and the persistence to antibiotics and stresses was restored upon complementation. RNA-Seq was performed to identify the transcriptome profile in the pnp knockout strain compared with wild-type strain W3110, and the data revealed that 242 (166 up-regulated, and 76 down-regulated) genes were differentially expressed in the pnp knockout mutant strain. KEGG pathway analysis of the up-regulated genes showed that they were mostly mapped to metabolism and virulence pathways, most of which are positively regulated by the global regulator cyclic AMP receptor protein (CRP). Similarly, the transcription level of the crp gene in the pnp-deletion strain increased 3.22-fold in the early stationary phase. We further explored the indicators of cellular metabolism of the pnp-deletion strain, the persistence phenotype of the pnp and crp double-deletion mutant, and the transcriptional activity of crp gene. Our results indicate that PNPase controls cellular metabolism by negatively regulating the crp operon at the post-transcriptional level by targeting the 5’- Untranslated Region (UTR) of the crp transcript. This study offers new insight about the persister mechanisms and provides new targets for development of new drugs against persisters for more effective treatment of persistent bacterial infections.
A systematic survey of human tissue-specific gene expression and splicing reveals new opportunities for therapeutic target identification and evaluation
Authors: Yang Robert Y. , Quan Jie , Sodaei Reza , Aguet Francois , Segrè Ayellet V. , Allen John A. , Lanz Thomas A. , Reinhart Veronica , Crawford Matthew , Hasson Samuel ,   GTEx Consortium, Ardlie Kristin G. , Guigó Roderic , Xi Hualin S.
Published: April 2018

Differences in the expression of genes and their splice isoforms across human tissues are fundamental factors to consider for therapeutic target evaluation. To this end, we conducted a transcriptome-wide survey of tissue-specific gene expression and splicing events in the unprecedented collection of 8527 high-quality RNA-seq samples from the GTEx project, covering 36 human peripheral tissues and 13 brain subregions. We derived a weighted tissue-specificity scoring scheme accounting for the similarity of related tissues and inherent variability across individual samples. We showed that ~50.6% of all annotated human genes show tissue-specific expression, including many low abundance transcripts vastly underestimated by previous array-based expression atlases. As utilities for drug discovery, we demonstrated that tissue-specificity is a highly desirable attribute of validated drug targets and tissue-specificity can be used to prioritize disease-associated genes from genome-wide association studies (GWAS). Using brain striatum-specific gene expression as an example, we provided a template to leverage tissue-specific gene expression to identify novel therapeutic targets. Mining of tissue-specific splicing further reveals new opportunities for tissue-specific targeting. Thus, the high quality transcriptome atlas provided by the GTEx is an invaluable resource for drug discovery and systematic analysis anchored on the human tissue specific gene expression provides a promising avenue to identify novel therapeutic target hypotheses.
Arrayed CRISPR screen with image-based assay reliably uncovers host genes required for coxsackievirus infection
Authors: Kim Heon Seok , Lee Kyungjin , Kim Seong-Jun , Cho Sungchan , Shin Hye Jin , Kim Chonsaeng , Kim Jin-Soo
Published: April 2018

Pooled CRISPR screens based on lentiviral systems have been widely applied to identify the effect of gene knockout on cellular phenotype. Although many screens were successful, they also have the limitation that genes conferring mild phenotypes or those essential for growth can be overlooked, as every genetic perturbation is incorporated in the same population. Arrayed screens, on the other hand, incorporate a single genetic perturbation in each well and could overcome these limitations. However, arrayed screens based on siRNA-mediated knockdown were recently criticized for low reproducibility caused by incomplete inhibition of gene expression. To overcome these limitations, we developed a novel arrayed CRISPR screen based on a plasmid library expressing a single guide RNA (sgRNA) and disrupted 1514 genes, encoding kinases, proteins related to endocytosis, and Golgi-localized proteins, individually using 4542 sgRNAs (three sgRNAs per gene). This screen revealed host factors required for infection by coxsackievirus B3 (CVB3) from Picornaviridae, which includes human pathogens causing diverse diseases. Many host factors that had been overlooked in a conventional pooled screen were identified for CVB3 infection, including entry-related factors, translational initiation factors, and several replication factors with different functions, demonstrating the advantage of the arrayed screen. This screen was quite reliable and reproducible, as most genes identified in the primary screen were confirmed in secondary screens. Moreover, ACBD3, whose phenotype was not affected by siRNA-mediated knockdown, was reliably identified. We propose that arrayed CRISPR screens based on sgRNA plasmid libraries are powerful tools for arrayed genetic screening and applicable to larger-scale screens.
Heterogeneous local order in self-assembled nanoparticle films revealed by X-ray cross-correlations
Authors: Lehmkühler Felix , Schulz Florian , Schroer Martin A. , Frenzel Lara , Lange Holger , Grübel Gerhard
Published: April 2018

We report on the self-assembly of gold nanoparticles coated with a soft poly(ethylene glycol) shell studied by X-ray cross-correlation analysis. Depending on the initial concentration of gold nanoparticles used, structurally heterogeneous films were formed. The films feature hot spots of dominating four- and sixfold local order with patch sizes of a few micrometres, containing 104–105 particles. The amplitude of the order parameters suggested that a minimum sample amount was necessary to form well ordered local structures. Furthermore, the increasing variation in order parameters with sample thickness demonstrated a high degree of structural heterogeneity. This wealth of information cannot be obtained by the conventional microscopy techniques that are commonly used to study nanocrystal superstructures, as illustrated by complementary scanning electron microscopy measurements.
How can leaders and managers in the Police support the learning of others and at the same time, support their own?
Authors: Jones Jenni
Published: April 2018

Purpose

The purpose of this paper is to attempt to demonstrate that formal mentoring is a helpful tool to develop managers within the changing context of the UK Police, and to highlight how managers can have an influence on mentoring programmes and the learning within them.

Design/methodology/approach

A longitudinal qualitative case study approach was chosen and semi-structured interviews were conducted alongside focus groups.

Findings

The findings showed that both mentees and mentors perceived they were learning within the mentoring relationship. Also, despite some common themes in relation to the key moderating factors, managers were seen as both facilitating and hindering these mentoring relationships.

Research limitations/implications

It was recognised that although interesting to compare and contrast the findings between the two different case study organisations, the findings drawn from this study may not be directly applicable to other mentoring programmes beyond these UK Police Forces. More could have been explored in the focus groups and information could have been collected from those that did not attend the interviews or the focus groups.

Originality/value

This research adds value as there is little written about the mentoring and managers, within the interesting changing context of the UK Police force. The insights from this mentoring research suggest that there is much learning to be gained by both parties through mentoring and that line managers need to be encouraged away from the day to day reactive approach towards being more proactive with supporting the personal development of their team members (and themselves) into the future. If they are more involved and supportive of learning and development interventions, then they and their team members will gain more from the experience and this will ultimately help them to make a more positive difference within their role.
Habitat management alters thermal opportunity
Authors: Neel Lauren K. , McBrayer Lance D.
Published: April 2018

Ectotherms engage in behavioral thermoregulation to optimize body temperatures, however, thermoregulatory effort varies across species, over time, and among habitats. Classic cost‐benefit models of ectothermic thermoregulation postulate that ectotherms should increase thermoregulatory effort when the benefits of thermoregulatory behavior outweigh the costs (Huey and Slatkin, 1976). However, alteration of habitat via land management may lead to unforeseen shifts in microclimate that change associated costs and benefits. In light of anthropogenic impacts on natural habitats, thermoregulatory effort should be examined in cases where land management results in environmental temperatures that deviate from the preferred temperature range of a given species.

We examined how habitat management alters microclimates and influences activity time, thermoregulatory behavior, and thermal physiology in a lizard (Sceloporus woodi) whose range has been significantly reduced due to habitat loss. We compared populations from two ecologically distinct habitats: longleaf pine and sand pine scrub, which have very different management histories. Daily surveys were conducted in each habitat type while environmental temperatures were recorded simultaneously with biophysical models.

Thermal performance curves differed between populations such that physiological performance was optimized in each environment. Longleaf pine habitat had greater thermal opportunity because cooler microclimates were available on arboreal perches. In longleaf pine habitat, lizards were able to stay active longer and thermoregulate more effectively. Regardless of habitat, thermoregulatory effort ofS. woodiincreased when thermal quality of habitat was low. However, when unfavorably high temperatures were experienced, the thermoregulatory effort increased significantly.

Our results demonstrate that ectotherms can afford to imprecisely thermoregulate when habitat thermal quality is poor due to cooler environmental temperatures. However under unfavorably hot environmental temperatures, lizards must precisely regulate body temperature in spite of any costs. These results further demonstrate that habitat management has major implications on species‐specific thermal opportunity, thermoregulatory behavior, and thermal physiology, such that shifts in thermoregulatory behavior may lead to higher energetic costs, enhanced predation risk, and constrained activity times.

Aplain language summaryis available for this article.
Association between Parathyroid Hormone and Cardiovascular Disease
Authors: Fujii Hideki
Published: April 2018

Although parathyroid hormone is known to be related with calcium and phosphate metabolism, it has been also reported to have several effects on the cardiovascular system including heart and vessels. However, the detailed pathophysiological mechanisms remain unclear. Clinical studies have indicated that parathyroid hormone is associated with cardiovascular events and mortality not only in patients with chronic kidney disease but also in those without chronic kidney disease. As a possible mechanism, it is thought that parathyroid hormone is associated with the renin‐angiotensin‐aldosterone system and has direct effects on the cardiovascular system. Therefore, we should pay attention to not only the control of serum phosphate and calcium levels but also the control of serum parathyroid hormone levels, especially in patients with chronic kidney disease.
Dietitians’ opinions regarding refeeding syndrome, clinical guidelines and extended scope of practice
Authors: Matthews Kylie L. , Palmer Michelle A. , Capra Sandra M.
Published: April 2018

Aim

Refeeding syndrome (RFS) prevalence rates vary across studies depending on the criteria used for assessment and identification. For registered dietitians, the assessment and management of RFS is highly reliant on daily serum electrolyte values; however, registered dietitians working within Australia do not currently possess laboratory test ordering privileges. We aimed to examine the opinions of registered dietitians regarding RFS identification, management and guidelines and the option of using extended scope of practice to order electrolyte monitoring autonomously.

Methods

A multi‐method action research approach was used, incorporating two projects. The first was a survey examining Australian registered dietitians’ (n = 187) opinions regarding RFS identification, management and guidelines, and autonomous electrolyte monitoring. To establish if results were similar internationally, an interview was conducted with 22 registered dietitians working within 10 different countries. Data were analysed using chi‐square tests and thematic analysis.

Results

Australian registered dietitians (75%) identify patients at risk of RFS at a high rate of more than once per fortnight, with 74% reporting that they have previously worked with a patient diagnosed with RFS. Results varied internationally, with respondents from eight countries reporting that RFS is a problem within acute care versus respondents from five countries having never treated a patient with RFS. The majority (≥89%) of registered dietitians desire new guidelines and the option to order patient electrolyte monitoring autonomously.

Conclusions

Our findings suggest that more stringent tools for the identification of RFS are necessary. There was limited uniformity across countries, and updated practice guidelines are needed.
Detecting signatures of a sponge‐associated lifestyle in bacterial genomes
Authors: Díez‐Vives Cristina , Esteves Ana I. S. , Costa Rodrigo , Nielsen Shaun , Thomas Torsten
Published: April 2018

Sponges interact with diverse and rich communities of bacteria that are phylogenetically often distinct from their free‐living counterparts. Recent genomics and metagenomic studies have indicated that bacterial sponge symbionts also have distinct functional features from free‐living bacteria; however, it is unclear, if such genome‐derived functional signatures are common and present in different symbiont taxa. We therefore compared here a large set of genomes from cultured (Pseudovibrio, Ruegeria and Aquimarina) and yet‐uncultivated (Synechococcus) bacteria found in either sponge‐associated or free‐living sources. Our analysis revealed only very few genera‐specific functions that could be correlated with a sponge‐associated lifestyle. Using different sets of sponge‐associated and free‐living bacteria for each genus, we could however show that the functions identified as ‘sponge‐associated’ are dependent on the reference comparison being made. Using simulation approaches, we show how this influences the robustness of identifying functional signatures and how evolutionary divergence and genomic adaptation can be distinguished. Our results highlight the future need for robust comparative analyses to define genomic signatures of symbiotic lifestyles, whether it is for symbionts of sponges or other host organisms.
Knockout of the Gsta4 Gene in Male Mice Leads to an Altered Pattern of Hepatic Protein Carbonylation and Enhanced Inflammation Following Chronic Consumption of an Ethanol Diet
Authors: Shearn Colin T. , Pulliam Casey F. , Pedersen Kim , Meredith Kyle , Mercer Kelly E. , Saba Laura M. , Orlicky David J. , Ronis Martin J. , Petersen Dennis R.
Published: April 2018

Background

Glutathione S‐transferase A4‐4 (GSTA4) is a key enzyme for removal of toxic lipid peroxidation products such as 4‐hydroxynonenal (4‐HNE). In this study, we examined the potential role of GSTA4 on protein carbonylation and progression of alcoholic liver disease by examining the development of liver injury in male wild‐type (WT) SV/J mice and SV/J mice lacking functional GSTA4 (GSTA4−/− mice).

Methods

Adult male WT and GSTA4−/− mice were fed chow (N = 10 to 12) or high‐fat Lieber‐DeCarli liquid diets containing up to 28% calories as ethanol (EtOH) (N = 18 to 20) for 116 days. At the end of the study, half of the EtOH‐fed mice were acutely challenged with an EtOH binge (3 g/kg given intragastrically) 12 hours before sacrifice. Carbonylation of liver proteins was assessed by immunohistochemical staining for 4‐HNE adduction and by comprehensive liquid chromatography–tandem mass spectrometry (LC‐MS/MS) of purified carbonylated proteins.

Results

Chronic EtOH intake significantly increased hepatic 4‐HNE adduction and protein carbonylation, including carbonylation of ribosomal proteins. EtOH intake also resulted in steatosis and increased serum alanine aminotransferase. Hepatic infiltration with B cells, T cells, and neutrophils and mRNA expression of pro‐inflammatory cytokines tumor necrosis factor (TNF)α and interferon (IFN)γ was modest in WT mice. However, an EtOH binge increased hepatic necrosis, hepatic cell proliferation, and expression of TNFα mRNA (p < 0.05). EtOH treatment of GSTA4−/− mice increased B‐cell infiltration and increased mRNA expression of TNFα and IFNγ and of matrix remodeling markers MMP9, MMP13, and Col1A1 (p < 0.05). GSTA4−/− mice exhibited panlobular rather than periportal distribution of 4‐HNE‐adducted proteins and increased overall 4‐HNE staining after EtOH binge. Comprehensive LC‐MS of carbonylated proteins identified 1,022 proteins of which 189 were unique to the GSTA4−/− group.

Conclusions

These data suggest long‐term adaptation to EtOH in WT mice does not occur in GSTA4−/− mice. Products of lipid peroxidation appear to play a role in inflammatory responses due to EtOH. And EtOH effects on B‐cell infiltration and autoimmune responses may be secondary to formation of carbonyl adducts.
Chinese Proverb Scale: Development and validation of an indigenous measure of Chinese traditional values
Authors: Ye Shengquan , Ng Ting Kin , Lu Erin Yiqing , Ma Zewei
Published: April 2018

The aim of this study was to develop and validate an indigenous measure of Chinese traditional values using Chinese proverbs. A sample of 363 Mainland Chinese undergraduates participated in Study 1, in which a 26‐item Chinese Proverb Scale (CPS) was developed through factor analysis on an initial pool of 118 Chinese proverbs. Four factors were clearly identified: (a) Diligence, (b) Integrity, (c) Self‐Preservation, and (d) Self‐Interest. TheCPSshowed satisfactory convergent validity with personal values (S. H. Schwartz, 1992,Advances In Experimental Social Psychology, San Diego, Academic Press) and social axioms (K. Leung et al., 2002,Journal of Cross‐Cultural Psychology, 33, p. 286). For incremental validity, theCPSpredicted life satisfaction beyond the Big Five personality, personal values, and social axioms. In Study 2, a sample of 239 Mainland Chinese participants completed theCPSacross two measurement occasions with an interval of 6 months. Longitudinal structural equation modeling (SEM) revealed the structure of theCPSwas robust and invariant over time. In Study 3, a sample of 167 Chinese undergraduates from Hong Kong responded to an adapted version of theCPS. MultigroupSEMshowed structural equivalence of the scale across the mainland and Hong Kong samples. The cultural origins of the factors in theCPSand future applications of the scale in various research areas are discussed.
Review shows that parental reassurance and nutritional advice help to optimise the management of functional gastrointestinal disorders in infants
Authors: Salvatore Silvia , Abkari Abdelhak , Cai Wei , Catto‐Smith Anthony , Cruchet Sylvia , Gottrand Frederic , Hegar Badriul , Lifschitz Carlos , Ludwig Thomas , Shah Neil , Staiano Annamaria , Szajewska Hania , Treepongkaruna Suporn , Vandenplas Yvan
Published: April 2018

Aim

Regurgitation, infantile colic and functional constipation are common functional gastrointestinal disorders (FGIDs) during infancy. Our aim was to carry out a concise review of the literature, evaluate the impact of these common FGIDs on infants and their families, and provide an overview of national and international guidelines and peer‐reviewed expert recommendations on their management.

Methods

National and international guidelines and peer‐reviewed expert recommendations on the management of regurgitation, infantile colic and functional constipation were examined and summarised.

Results

Regurgitation, infantile colic and functional constipation cause frequent parental concerns, lead to heavy personal and economic costs for families and impose a financial burden on public healthcare systems. Guidelines emphasise that the first‐line management of these common FGIDs should focus on parental education, reassurance and nutritional advice. Nutritional advice should stress the benefits of continuing breastfeeding, while special infant formulas may be considered for non‐breastfed infants with common FGIDs. Drug treatment is seldom required, with the exception of functional constipation.

Conclusion

By providing complete and updated parental education, reassurance and nutritional advice, healthcare professionals can optimise the management of FGIDs and related symptoms and reduce the inappropriate use of medication or dietary interventions.
Impact of duration of induction therapy on survival in newly diagnosed multiple myeloma patients undergoing upfront autologous stem cell transplantation
Authors: Chakraborty Rajshekhar , Muchtar Eli , Kumar Shaji K. , Buadi Francis K. , Dingli David , Dispenzieri Angela , Hayman Suzanne R. , Hogan William J. , Kapoor Prashant , Lacy Martha Q. , Leung Nelson , Warsame Rahma , Kourelis Taxiarchis , Gonsalves Wilson , Gertz Morie A.
Published: April 2018

The optimal duration of induction therapy (IT) in transplant‐eligible multiple myeloma (MM) patients in not well defined, resulting in a wide variation in clinical practice. The objective of our study was to determine whether the duration of IT in patients undergoing upfront autologous stem cell transplantation (ASCT) has an impact on progression‐free survival (PFS) in the era of proteasome inhibitors and immunomodulatory drugs. A total of 596 patients who underwent ASCT at Mayo Clinic between 2007 and 2014 were included. The patients were divided into two cohorts based on the duration of IT: IT ≤ 4 and IT > 4 months. At a median follow‐up of 54·5 months from ASCT, the median PFS in the IT ≤ 4 group was 28 months [95% confidence interval (CI), 25–33], compared to 26 months in the IT > 4 group (95% CI, 24–31) [P = 0·605]. There was no significant difference in overall survival (OS) in the two groups (P = 0·904). The lack of impact of IT duration on PFS and OS was consistent in subgroups with high‐risk features at diagnosis (International Staging System III or high‐risk cytogenetics) and different depths of pre‐transplant response [≥very good partial response (VGPR) and <VGPR]. In conclusion, prolonging the duration of IT beyond 4 months does not impact survival in patients with newly diagnosed MM who complete a single line of IT followed by consolidation with ASCT.
Early‐stage Hodgkin lymphoma in the modern era: simulation modelling to delineate long‐term patient outcomes
Authors: Parsons Susan K. , Kelly Michael J. , Cohen Joshua T. , Castellino Sharon M. , Henderson Tara O. , Kelly Kara M. , Keller Frank G. , Henzer Tobi J. , Kumar Anita J. , Johnson Peter , Meyer Ralph M. , Radford John , Raemaekers John , Hodgson David C. , Evens Andrew M.
Published: April 2018

We developed a novel simulation model integrating multiple data sets to project long‐term outcomes with contemporary therapy for early‐stage Hodgkin lymphoma (ESHL), namely combined modality therapy (CMT) versus chemotherapy alone (CA) via 18F‐fluorodeoxyglucose positron emission tomography response‐adaption. The model incorporated 3‐year progression‐free survival (PFS), probability of cure with/without relapse, frequency of severe late effects (LEs), and 35‐year probability of LEs. Furthermore, we generated estimates for quality‐adjusted life years (QALYs) and unadjusted survival (life years, LY) and used model projections to compare outcomes for CMTversusCA for two index patients. Patient 1: a 25‐year‐old male with favourable ESHL (stage IA); Patient 2: a 25‐year‐old female with unfavourable ESHL (stage IIB). Sensitivity analyses assessed the impact of alternative assumptions for LE probabilities. For Patient 1, CMT was superior to CA (CMT incremental gain = 0·11 QALYs, 0·21 LYs). For Patient 2, CA was superior to CMT (CA incremental gain = 0·37 QALYs, 0·92 LYs). For Patient 1, the advantage of CMT changed minimally when the proportion of severe LEs was reduced from 20% to 5% (0·15 QALYs, 0·43 LYs), whereas increasing the severity proportion for Patient 2's LEs from 20% to 80% enhanced the advantage of CA (1·1 QALYs, 6·5 LYs). Collectively, this detailed simulation model quantified the long‐term impact that varied host factors and alternative contemporary treatments have in ESHL.
New plate kinematic model and tectono‐stratigraphic history of the East African and West Madagascan Margins
Authors: Tuck‐Martin Amy , Adam Jürgen , Eagles Graeme
Published: April 2018

The continental margins of East Africa and West Madagascar are a frontier for hydrocarbon exploration. However, the links between the regional tectonic history of sedimentary basins and margin evolution are relatively poorly understood. We use a plate kinematic model built by joint inversion of seafloor spreading data as a starting point to analyse the evolution of conjugate margin segments and corresponding sedimentary basins. By correlating megasequences in the basins to the plate model we produce a margin‐scale tectono‐stratigraphic framework comprising four phases of tectonic development. During Phase 1 (183–133 Ma) Madagascar/India/Antarctica separated from Africa, first by rifting and later, after breakup (at ca. 170–165 Ma), by seafloor spreading in the West Somali and Mozambique basins and dextral strike‐slip movement on the Davie Fracture Zone. Mixed continental/marine syn‐rift megasequences were deposited in rift basins followed by shallow‐marine early postrift sequences. In Phase 2 (133–89 Ma) spreading ceased in the West Somali basin and Madagascar became fixed to the African plate. However, spreading continued between the African and Antarctic plates and deposition of the early postrift megasequence continued. The onset of spreading on the Mascarene Ridge separated India from Madagascar in Phase 3 (89–60 Ma). Phase 3 was characterized by the onset of deposition of the late postrift megasequence with continued deep marine sedimentation. At the onset of Phase 4 (60 Ma onward) spreading on the Mascarene ridge ceased and the Carlsberg Ridge propagated south to form the Central Indian Ridge, separating India from the Seychelles and the Mascarene Plateau. Late postrift deposition continued until a major unconformity linked to the development of the East African Rift System marked the change to deposition of the modern margin megasequence.
Maternal Language and Child Vocabulary Mediate Relations Between Socioeconomic Status and Executive Function During Early Childhood
Authors: Daneri M. Paula , Blair Clancy , Kuhn Laura J. ,   FLP Key Investigators
Published: April 2018

This article examined longitudinal relations among socioeconomic risk, maternal language input, child vocabulary, and child executive function (EF) in a large sample (N = 1,009) recruited for a prospective longitudinal study. Two measures of maternal language input derived from a parent–child picture book task, vocabulary diversity (VOCD), and language complexity, showed variation by socioeconomic risk at child ages 15, 24, and 36 months. Maternal VOCD at child age 24 months and maternal language complexity at child age 36 months mediated the relation between socioeconomic risk and 48‐month child EF, independent of parenting sensitivity. Moreover, 36‐month child vocabulary mediated the relation between maternal language input and child EF. These findings provide novel evidence about mechanisms linking socioeconomic risk and child executive function.
Universality and prediction in business rules
Authors: Wang Olivier , de Sainte Marie Christian , Ke Changhai , Liberti Leo
Published: April 2018

Business rules (BR) have the form ⟨if condition then action⟩. A BR program, which can be executed by means of an interpreter, is a sequence of business rules. Motivated by International Business Machines use cases, we look at the problem of setting parameter values in a given BR program so it will achieve a given average goal over all possible instances. We explore the following fundamental question: Is there a general learning algorithm, which addresses this issue? We prove the answer is negative. On the positive side, we derive operational semantics for BR programs. As a proof of concept, we show empirically that these can be used to detect potential nontermination situations.
Effectiveness of protected areas for bird conservation depends on guild
Authors: Duckworth Gregory D. , Altwegg Res
Published: April 2018

Aim

Protected areas are key conservation tools intended to increase biodiversity and reduce extinction risks of species and populations. However, the degree to which protected areas achieve their conservation goals is generally unknown for many protected areas worldwide. We assess the effect of protected areas on the abundance of 196 common, resident bird species. If protected areas were beneficial to avian biodiversity, we expect landscapes with a higher proportion of protected areas will have higher densities of species compared to landscapes with no protection.

Location

Greater Gauteng region, South Africa.

Methods

We analysed bird survey data collected over regular grid cells across the study area. We estimated bird abundance in relation to the proportion of a grid cell that was protected with the Royle–Nichols model and fitted the model once for each of the species. We examined variation in estimated abundance as a function of avian guild (defined by the type of food a species preferentially ate and its foraging mode) with a regression tree analysis.

Results

Abundance was significantly positively related to the proportion of protected areas in grid cells for 26% of the species, significantly negatively related in 15%, and not significantly related in 59% species. We found three distinct guild groups which differed in their average abundance, after accounting for associated variance. Group 1 consisted of guilds frugivores, ground‐feeders, hawkers, predators, and vegivores and average abundance was strongly positively related to the proportion of protected areas. Group 2 included granivores, and average abundance was strongly negatively related to proportion of protected areas. Group 3 included gleaners only, and average abundance was not related to proportion of protected areas.

Main conclusion

We conclude that the network of protected areas within the greater Gauteng region sustained relatively higher abundances of common birds and thus perform an important conservation role.