bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrative Review for Patients With Bilateral Total Knee Replacement
Authors: Pietsch Theresa , David Jonathan , Vergara Franz
Published: July 2018

BACKGROUND:

The aim of this joint project between the National Association of Orthopaedic Nurses and the Association of Rehabilitation Nurses was to develop nursing practice guidelines for patients who experience bilateral knee arthroplasty (BTKA) across the continuum of care. No guidelines existed and an integrative review was completed to address this gap.

METHODS:

An integrative review of refereed quantitative and qualitative research in published and gray literature was completed to answer the clinical questions: (1) What is the scope of evidence-based nursing interventions for patients undergoing BTKA? (2) What are patients' experiences with BTKA across the care continuum? The scope of the literature search was patients with bilateral and unilateral total knee arthroplasty. An evidence-based system was used to rate the strength of studies that met the criteria for inclusion in this review.

RESULTS:

The search method identified 588 potential titles but the analysis of the abstracts supported only 128 studies for possible inclusion in this project. The authors independently reviewed these studies and concluded that 126 studies did not meet the inclusion criteria and 2 quantitative studies were eligible for inclusion.

CONCLUSIONS:

Understanding which interventions are most effective for pain management, functional gains, quality of life, and other nurse-sensitive outcomes is best derived from empirical studies. Most likely, BTKA nursing care is being guided by clinical experts and not by empirical nursing evidence. In the absence of empirical evidence, it is feasible that nurses can extrapolate findings from other studies to guide and support the care of BTKA patients. Research recommendations include the exploration of early mobilization interventions, development of nursing care bundles, and evaluation of patient-centered outcomes at the points of transitional care.
The Effect of Functional Disability and Quality of Life on Decision to Have Surgery in Patients With Lumbar Disc Herniation
Authors: Yılmaz Emel , Çıkrıkçıoğlu H. Yağmur , Baydur Hakan
Published: July 2018

BACKGROUND/PURPOSE:

This study aimed to determine the effect of functional disability and quality of life (QoL) on the decision to have surgery in patients with lumbar disc herniation (LDH).

METHOD/DESIGN:

This is descriptive and cross-sectional survey. A total of 239 patients were included in the study. Data were collected using a personal information form, Surgical Belief and Attitudes Questionnaire (SBAQ), Visual Analog Scale (VAS), Oswestry Disability Index (ODI), Roland–Morris Disability Questionnaire (RMDQ) and Short Form-36 (SF-36). The data analysis was undertaken using Mann–Whitney U test, χ2 test, and logistic regression model.

RESULTS:

Patients were found to have low mean scores in the SF-36 subscales and SBAQ and high mean scores in ODI, RMDQ, and VAS. Six weeks after the first interview, 48.1% of patients decided to undergo surgery. A statistically significant difference was found between a decision to have surgery and the ODI, RMDQ, VAS, SBAQ scores and 6 of the 8 SF-36 subscales (except for role physical and general health; p < .05). Patients who had higher functional disability, pain intensity, and SBAQ score and those with lower QoL were more likely to decide to undergo surgery.

CONCLUSIONS:

The results of the study showed that patients with LDH who have been referred for surgery experience high functional disability and pain and a poor QoL, and that these factors have an impact on their decision to have surgery process.
Urologic Diseases Germane to the Medical Renal Biopsy: Review of a Large Diagnostic Experience in the Context of the Renal Architecture and Its Environs
Authors: Bonsib Stephen M.
Published: July 2018

The kidney is one of the most complicated organs in development and is susceptible to more types of diseases than other organs. The disease spectrum includes developmental and cystic diseases, involvement by systemic diseases, iatrogenic complications, ascending infections and urinary tract obstruction, and neoplastic diseases. The diagnosis of kidney disease is unique involving 2 subspecialties, urologic pathology and renal pathology. Both renal and urologic pathologists employ the renal biopsy as a diagnostic modality. However, urologic pathologists commonly have a generous specimen in the form of a nephrectomy or partial nephrectomy while a renal pathologist requires ancillary modalities of immunofluorescence and electron microscopy. The 2 subspecialties differ in the disease spectrum they diagnose. This separation is not absolute as diseases of one subspecialty not infrequently appear in the diagnostic materials of the other. The presence of medical renal diseases in a nephrectomy specimen is well described and recommendations for reporting these findings have been formalized. However, urologic diseases appearing in a medical renal biopsy have received less attention. This review attempts to fill that gap by first reviewing the perirenal anatomy to illustrate why inadvertent biopsy of adjacent organs occurs and determine its incidence in renal biopsies followed by a discussion of gross anatomic features relevant to the microscopic domain of the medical renal biopsy. Unsuspected neoplasms and renal cysts and cystic kidney diseases will then be discussed as they create a diagnostic challenge for the renal pathologist who often has limited training and experience in these diseases.
Etoposide and Corticosteroid Combination Therapy Improves Acute Respiratory Distress Syndrome in Mice
Authors: Aoyagi Tetsuji , Sato Yukio , Toyama Masahiko , Oshima Kengo , Kawakami Kazuyoshi , Kaku Mistuo
Published: July 2018

Excessive inflammation reactions with a cytokine storm in the lungs have historically been thought as the primary cause of fatal acute respiratory distress syndrome (ARDS). However, interruption of inflammatory cytokine activation failed to attenuate ARDS, suggesting that other therapies are required to treat this illness and improve survival. Etoposide (ET), a cytotoxic agent, and prednisolone (PSL), a corticosteroid with strong anti-inflammatory activity, have been used to treat other disease involving similar cytokine-activated macrophages and hemophagocytic activity. However, they have not been previously tested as ARDS therapeutics alone or in combination. In the present study, we used a fatal ARDS mouse model induced via administration of α-galactosylceramide and lipopolysaccharide, which resulted in the development of severe lung injury with hypercytokinemia and hemophagocytosis, all of which were observed in ARDS patients infected with highly pathogenic respiratory viruses. The ET and PSL combination therapy, but not ET or PSL alone, reduced the recruitment and activation of inflammatory cells including macrophages, natural killer T cells, and neutrophils, and significantly improved the survival rate in this model. Furthermore, whereas ET alone improved lung edema, it did not increase the survival rate, indicating the necessity of PSL in the treatment of ARDS. Surprisingly, combination therapy did not reduce the production of cytokines and chemokines in the lungs, demonstrating that inflammatory cells, rather than hypercytokinemia, are the direct target of these compounds and primary cause of ARDS-related death. Thus, combination therapy with ET and PSL that targets inflammatory cells has the potential to attenuate fatal ARDS.
Transplant-free Survival in Chronic Liver Disease Presenting as Acute Liver Failure in Childhood
Authors: Di Giorgio Angelo , Nicastro Emanuele , Dalla Rosa Davide , Nebbia Gabriella , Sonzogni Aurelio , D’Antiga Lorenzo
Published: July 2018

Background.

In adults, the absence of a preexisting chronic liver disease (CLD) is required to diagnose acute liver failure (ALF). The pediatric classification does not consider this aspect, thus previous studies pooled together children with ALF and children with unknown CLD presenting with acute hepatic decompensation (ALF-CLD). We aimed to compare prevalence, features, and outcome of children with ALF-CLD to those with a proper ALF.

Methods.

Patients admitted between 1996 and 2017 because of ALF defined by Pediatric Acute Liver Failure criteria (raised transaminases, International Normal Ratio ≥2.0, no history of liver disease) were classified as ALF-CLD if diagnosed with autoimmune hepatitis, Wilson disease, Budd-Chiari syndrome, hepatitis B virus reactivation, inborn errors of metabolism. The others were classified as ALF.

Results.

Seventy-four children (median age, 4 years; 1.0–8.8; male/female, 36/38] with ALF were found; 18 of <1 year of age were excluded. Fifty-six (median age, 6.6 years; 2.7–11.7; male/female, 23/33], 22 with ALF-CLD (autoimmune hepatitis, n = 14; Wilson disease, n = 6; inborn errors of metabolism, n = 2) and 34 with ALF (paracetamol overdose, n = 6; viral infections, n = 3; mushroom poisoning, n = 5; indeterminate, n = 20) were compared. In ALF-CLD, the median age at onset was higher, alanine aminotransferase, albumin, and International Normal Ratio levels were lower, splenomegaly, ascites, and cirrhosis were more common (all P < 0.01). On multivariate analysis, the diagnosis of ALF-CLD was an independent predictor of transplant-free survival (P = 0.006).

Conclusions.

In children, ALF-CLD is common, has peculiar features, and is associated with a favorable outcome. This study suggests the need to distinguish this entity from other forms of ALF in children.
NF-Y controls fidelity of transcription initiation at gene promoters through maintenance of the nucleosome-depleted region
Authors: Oldfield Andrew J , Henriques Telmo , Kumar Dhirendra , Burkholder Adam B. , Cinghu Senthilkumar , Paulet Damien , Bennett Brian , Yang Pengyi , Scruggs Benjamin S. , Lavender Christopher A. , Rivals Eric , Adelman Karen , Jothi Raja
Published: July 2018

Faithful transcription initiation is critical for accurate gene expression, yet the mechanisms underlying specific transcription start site (TSS) selection in mammals remain unclear. Here, we show that the histone-fold domain protein NF-Y, a ubiquitously expressed transcription factor, controls the fidelity of transcription initiation at gene promoters. We report that NF-Y maintains the region upstream of TSSs in a nucleosome-depleted state while simultaneously protecting this accessible region against aberrant and/or ectopic transcription initiation. We find that loss of NF-Y binding in mammalian cells disrupts the promoter chromatin landscape, leading to nucleosomal encroachment over the canonical TSS. Importantly, this chromatin rearrangement is accompanied by upstream relocation of the transcription preinitiation complex and ectopic transcription initiation. Further, this phenomenon generates aberrant extended transcripts that undergo translation, disrupting gene expression profiles. These results establish NF-Y as a central player in TSS selection in metazoans and highlight the deleterious consequences of inaccurate transcription initiation.
Hybrid misexpression in multiple developing tissues within a recent adaptive radiation ofCyprinodonpupfishes
Authors: McGirr Joseph A. , Martin Christopher H.
Published: July 2018

Genetic incompatibilities constitute the final stages of reproductive isolation and speciation, but little is known about incompatibilities that occur within recent adaptive radiations among closely related diverging populations. Crossing divergent species to form hybrids can break up coadapted variation, resulting in genetic incompatibilities within developmental networks shaping adaptive traits. We crossed two closely related sympatricCyprinodonpupfish species – a dietary generalist and a specialized molluscivore – and measured expression levels in their F1hybrids to identify regulatory variation underlying the novel craniofacial morphology found in this recent microendemic adaptive radiation. We extracted mRNA from eight day old whole-larvae tissue and from craniofacial tissues dissected from 17-20 day old larvae to compare gene expression between a total of seven F1hybrids and 24 individuals from parental species populations. We found 3.9% of genes differentially expressed between generalists and molluscivores in whole-larvae tissues and 0.6% of genes differentially expressed in craniofacial tissue. We found that 2.1% of genes were misexpressed in whole-larvae hybrids at 8 dpf whereas 19.1% of genes were misexpressed in hybrid craniofacial tissue at 17-20 dpf, after correcting for sequencing biases. We also measured allele specific expression across 15,429 phased heterozygous sites to identify regulatory mechanisms underlying differential expression between generalists and molluscivores. Together, our results highlight the importance of considering misexpression as an early indicator of genetic incompatibilities in the context of rapidly diverged morphology and suggests that wide-spread compensatory regulatory divergence drives hybrid misexpression in developing tissues that give rise to novel craniofacial traits.
Short hairpin RNAs artifactually impair cell growth and suppress clustered microRNA expression
Authors: Powers JT , da Rocha EL , Pearson DS , Missios P , de Soysa TY , Barragan J , Cahan P , Daley GQ
Published: July 2018

Functional gene disruption is a central tenet of cancer research, where novel drug targets are often identified and validated through cell-growth based knockdown studies or screens. Short hairpin RNA (shRNA)-mediated mRNA knockdown is widely used in both academic and pharmaceutical settings. However, off-target effects of shRNAs as well as interference with endogenous small RNA processing have been reported. We show here that lentiviral delivery of both gene-specific and non-targeting control shRNAs impair in vitro cell growth in a sequence independent manner. In addition, exogenous shRNAs induce a depressed cell-cycle-gene expression signature that is also shRNA-sequence independent and present across several studies. Further, we observe an shRNA mediated general repression of microRNAs belonging to polycistronic genetic clusters, including microRNAs from established oncogenic microRNA clusters. The collective impact of these observations is particularly relevant for cancer research, given the widespread historical use of shRNAs and the common goal of interrogating genes that regulate proliferation. We therefore recommend that when employing shRNA for target validation, care be taken to titrate shRNA dose, use hairpin-expressing controls, perform gene-of-interest rescue experiments and/or corroborate shRNA-derived results by small interfering RNA (siRNA) knockdown or CRISPR/Cas9-mediated genetic knockout. Minimizing these deleterious sequence independent effects will improve research fidelity and help address reported challenges in experimental reproducibility.
Glycolytic flux inSaccharomyces cerevisiaeis dependent on RNA polymerase III and its negative regulator Maf1
Authors: Szatkowska Róża , Garcia-Albornoz Manuel , Roszkowska Katarzyna , Holman Stephen , Hubbard Simon , Beynon Robert , Adamczyk Malgorzata
Published: July 2018

Protein biosynthesis is energetically costly, is tightly regulated and is coupled to stress conditions including glucose deprivation. RNA polymerase III (RNAP III) driven transcription of tDNA genes for production of tRNAs is a key element in efficient protein biosynthesis. Here we present an analysis of the effects of altered RNAP III activity on theSaccharomyces cerevisiaeproteome and metabolism under glucose rich conditions. We show for the first time that RNAP III is tightly coupled to the glycolytic system at the molecular systems level. Decreased RNAP III activity or the absence of the RNAP III negative regulator, Maf1 elicit broad changes in the abundance profiles of enzymes engaged in fundamental metabolism inS. cerevisiae.In a mutant compromised in RNAP III activity there is a repartitioning towards amino acids synthesisde novoat the expense of glycolytic throughput. Conversely, cells lacking Maf1 protein have greater potential for glycolytic flux.
The interplay of structural and cellular biophysics controls clustering of multivalent molecules
Authors: Chattaraj A. , Youngstrom M. , Loew L. M.
Published: July 2018

Dynamic molecular clusters are assembled through weak multivalent interactions and are platforms for cellular functions, especially receptor-mediated signaling. Clustering is also a prerequisite for liquid-liquid phase separation. But it is not well understood how molecular structure and cellular organization control clustering. Using coarse-grain kinetic Langevin dynamics, we performed computational experiments on a prototypical ternary system modeled after membrane-bound nephrin, the adaptor Nck1 and the actin nucleation promoting factor NWASP. Steady state cluster size distributions favored stoichiometries that optimized binding (stoichiometry matching), but still were quite broad. At high concentrations, the system can be driven beyond the saturation boundary such that cluster size is limited only by the number of available molecules. This behavior would be predictive of phase separation. Domains close to binding sites sterically inhibited clustering much less than terminal domains because the latter effectively restrict access to the cluster interior. Increased flexibility of interacting molecules diminished clustering by shielding binding sites within compact conformations. Membrane association of nephrin increased the cluster size distribution in a density-dependent manner. These properties provide insights into how molecular ensembles function to localize and amplify cell signaling.
Native RNA sequencing on nanopore arrays redefines the transcriptional complexity of a viral pathogen
Authors: Depledge Daniel P. , Srinivas Kalanghad Puthankalam , Sadaoka Tomohiko , Bready Devin , Mori Yasuko , Placantonakis Dimitris G. , Mohr Ian , Wilson Angus C
Published: July 2018

Viral genomes exhibit a higher gene density and more diversified transcriptome than the host cell. Coding potential is maximized through the use of multiple reading frames, placement of genes on opposing strands, inefficient or modified use of termination signals, and the deployment of complex alternative splicing patterns. As a consequence, detailed characterization of viral transcriptomes by conventional methods can be challenging. Full length native RNA sequencing (nRNA-seq) using nanopore arrays offers an exciting alternative. Individual transcripts are sequenced directly, without the biases inherent to the recoding or amplification steps included in other sequencing methodologies. nRNA-seq simplifies the detection of variation brought about by RNA splicing, use of alternative transcription initiation and termination sites, and other RNA modifications. Here we use nRNA-seq to profile the herpes simplex virus type 1 transcriptome during early and late stages of productive infection of primary cells. We demonstrate the effectiveness of the approach and identify a novel class of intergenic transcripts, including an mRNA that accumulates late in infection that codes for a novel fusion of the viral E3 ubiquitin ligase ICP0 and viral membrane glycoprotein L.
The prokaryotic SPHINX 1.8 REP protein is tissue-specific and expressed in human germline cells
Authors: Manuelidis Laura
Published: July 2018

Small circular DNAs of 1.8 and 2.4kb were initially discovered in highly infectious CJD and scrapie particles from mammalian brain and cultured cells. Surprisingly, these protected cytoplasmic "SPHINX" DNAs contained replication (REP) initiation sequences resembling those of Acinetobacter phage viruses. An antibody was generated against a REP peptide encoded by the SPHINX 1.8 ORF that was not present in mammals. It bound to a 41kd "spx1" protein on Western blots. Cytologically, spx1 concentrated in spinal cord synapses and pancreatic islet, but not exocrine cells. We hypothesized that circular SPHINX DNAs are ancient symbiotic elements that can participate in functional differentiation and neurodegeneration. Cell and tissue specific patterns of spx1 expression shown below implicate somatic cell-to-cell communication and differentiation functions that would favor conservation of SPHINX 1.8 in evolution. Remarkably, primary human oocytes and spermatogonia, but not mature sperm, displayed intense cytoplasmic spx1 signals that underscore the maternal inheritance of SPHINX 1.8. These findings should encourage investigations of unexplored networks of incorporated environmental infectious agents that can be key actors in progressive neurodegeneration, immunity and cancer.
Tris(4-methoxyphenyl)stibine
Authors: Böhm Marvin J. , Golz Christopher , Alcarazo Manuel
Published: July 2018

The C
3-symmetrical molecule, tris(4-methoxyphenyl)stibine, C21H21O3Sb, crystallizes with one third of the molecule in the asymmetric unit. Bond lengths and angles of the Sb—C bonds lie in between those of the isostructural homologues C21H21O3Bi and C21H21O3As. The formation of dimers via six weak C—H...π interactions is considered.
Distribution of alpha‐neoendorphin, ACTH (18–39) and beta‐endorphin (1–27) in the alpaca brainstem
Authors: Sánchez Manuel L. , de Souza Eliana , Aguilar Luis A. , Coveñas Rafael
Published: July 2018

Using an immunocytochemical technique, we have studied in the alpaca brainstem the distribution of immunoreactive structures containing prodynorphin (alpha‐neoendorphin)‐ and pro‐opiomelanocortin (adrenocorticotrophin hormone (18–39) (ACTH), beta‐endorphin (1–27))‐derived peptides. No peptidergic‐immunoreactive cell body was observed. Immunoreactive fibres were widely distributed, although in most of the brainstem nuclei the density of the peptidergic fibres was low or very low. In general, the distribution of the immunoreactive fibres containing the peptides studied was very similar. A close anatomical relationship occurred among the fibres containing alpha‐neoendorphin, ACTH or beta‐endorphin (1–27), suggesting a functional interaction among the three peptides in many of the brainstem nuclei. The number of fibres belonging to the prodynorphin system was higher than that of the pro‐opiomelanocortin system. A moderate/low density of immunoreactive fibres was observed in 65.11% (for alpha‐neoendorphin (1–27)), 18.18% (for ACTH) and 13.95% (for beta‐endorphin) of the brainstem nuclei/tracts. In the alpaca brainstem, a high density of immunoreactive fibres was not observed. The neuroanatomical distribution of the immunoreactive fibres suggests that the peptides studied are involved in auditory, motor, gastric, feeding, vigilance, stress, respiratory and cardiovascular mechanisms, taste response, sleep‐waking cycle and the control of pain transmission.
Developmental defects of enamel increase caries susceptibility in Chinese preschool children
Authors: Li Yihong , Chen Xi , Chen Shuli , Janal Malvin N. , Sarnat Haim
Published: July 2018

Objectives

The present epidemiological study aimed to compare the prevalence and severity of developmental defects of enamel (DDE) and dental caries between urban and suburban Chinese preschool children.

Methods

A total of 1351 3‐ to 6‐year‐old children were invited to participate in this study and received dental examinations. A modified DDE index was used to assess the prevalence and severity of DDE. The dental caries diagnosis was based on the World Health Organization (WHO) health survey methods for field studies and was recorded using the decayed, missing and filled tooth (dmft) index. The caries status was further classified as caries or severe caries according to a modification of the American Academy of Pediatric Dentistry definition.

Results

Overall, the DDE prevalence was 48.3% among the 1351 preschool children. The DDE prevalence was higher in innercity children (54.1%) than in suburban children (42.0%; P < 0.001). In contrast, the suburban children had a higher prevalence of dental caries (65.2% vs 57.5%; P = 0.004) and a higher mean dmft score (3.5 ± 4.2 vs 2.9 ± 3.8; P = 0.005) than the innercity children. Only 23.9% of the children were free of both DDE and caries. The caries risk increased significantly and independently as DDE severity increased (linear trend, 95% confidence interval = [1.32, 1.69], age [1.60, 1.88], urban residence [1.18, 2.15] and breastfeeding experience [1.04, 1.60]) after controlling for other demographic risk factors.

Conclusions

The study provides new evidence that DDE is a significant contributing factor for the highly prevalent and progressive dental caries observed in Chinese preschool children. These results highlight the importance of including DDE in caries risk assessments.
Understanding child neglect in Aboriginal families and communities in the context of trauma
Authors: Newton BJ
Published: July 2018

Child neglect is a significant concern for Aboriginal families and communities both in Australia and internationally. Service responses to child neglect are largely informed by child neglect theories, which explain the nature and causes of child neglect. However, child neglect is a problem that is worsening for Aboriginal children, suggesting that these theories are not appropriate. This paper argues that to meet the needs of Aboriginal families and communities where there is child neglect, policy and practice needs to acknowledge and address the impact of trauma in shaping the lived experiences of Aboriginal people.

International literature discusses the impact and consequence of historical trauma within Indigenous families and communities, and separately, child maltreatment theorists have discussed the ecological nature of child neglect. However, the literature and evidence‐base linking the two, child neglect and historical trauma in Indigenous contexts, are very scant. This paper aims to fill this gap and emphasize the importance of addressing child neglect within Aboriginal families and communities in the context of historical trauma. Although this paper focuses on the post‐colonial experiences of Aboriginal people in Australia, the arguments can extend to many Indigenous cultures universally where child welfare interventions have resulted in significant and ongoing trauma.
Distal renal tubular acidosis caused by tryptophan‐aspartate repeat domain 72 (WDR72) mutations
Authors: Rungroj N. , Nettuwakul C. , Sawasdee N. , Sangnual S. , Deejai N. , Misgar R.A. , Pasena A. , Khositseth S. , Kirdpon S. , Sritippayawan S. , Vasuvattakul S. , Yenchitsomanus PT.
Published: July 2018

Hereditary distal renal tubular acidosis (dRTA) is a rare genetic disease that is caused by mutations in SLC4A1, ATP6V1B1, or ATP6V0A4. However, there are many families with hereditary dRTA in whom the disease‐causing genes are unknown. Accordingly, we performed whole exome sequencing and genetic studies of the members of a family with autosomal recessive dRTA of an unknown genetic etiology. Here, we report compound heterozygous pathogenic variations in tryptophan‐aspartate repeat domain 72 (WDR72) (c.1777A>G [p.R593G] and c.2522T>A [p.L841Q]) in three affected siblings of a family with dRTA. Both variants segregated with dRTA in the family and were not observed in normal control subjects. Homologous modeling and in silico mutagenesis indicated that R593G and L841Q alter the H‐bond formations in the nearby residues, affecting the WDR72 protein structure. All these evidences indicate that the identified WDR72 variations were probably to have caused hereditary dRTA in the reported family. In addition, homozygous nonsense mutation (c.2686C>T [p.R896X]) was identified in another family, strongly supporting the causal role of WDR72 in dRTA. Based on our literature review, WDR72 mutations associated with dRTA have not been previously described. This is the first identification of pathogenic variations in WDR72 as a cause of hereditary dRTA.
Runtime Shader Simplification via Instant Search in Reduced Optimization Space
Authors: Yuan Yazhen , Wang Rui , Hu Tianlei , Bao Hujun
Published: July 2018

Traditional automatic shader simplification simplifies shaders in an offline process, which is typically carried out in a context‐oblivious manner or with the use of some example contexts, e.g., certain hardware platforms, scenes, and uniform parameters, etc. As a result, these pre‐simplified shaders may fail at adapting to runtime changes of the rendering context that were not considered in the simplification process. In this paper, we propose a new automatic shader simplification technique, which explores two key aspects of a runtime simplification framework: the optimization space and the instant search for optimal simplified shaders with runtime context. The proposed technique still requires a preprocess stage to process the original shader. However, instead of directly computing optimal simplified shaders, the proposed preprocess generates a reduced shader optimization space. In particular, two heuristic estimates of the quality and performance of simplified shaders are presented to group similar variants into representative ones, which serve as basic graph nodes of the simplification dependency graph (SDG), a new representation of the optimization space. At the runtime simplification stage, a parallel discrete optimization algorithm is employed to instantly search in the SDG for optimal simplified shaders. New data‐driven cost models are proposed to predict the runtime quality and performance of simplified shaders on the basis of data collected during runtime. Results show that the selected simplifications of complex shaders achieve 1.6 to 2.5 times speedup and still retain high rendering quality.
Comparison of clinical and radiographic peri‐implant parameters among obese and non‐obese patients: A 5‐year study
Authors: Alkhudhairy Fahad , Vohra Fahim , Al‐Kheraif Abdulaziz A. , Akram Zohaib
Published: July 2018

Background

It is postulated that peri‐implant parameters are worse in obese individuals as compared to nonobese.

Objective

The aim of the present 5‐year longitudinal study was to analyze and compare the changes in clinical and radiographic peri‐implant parameters among obese and non‐obese patients.

Materials and methods

Twenty patients with body mass index ≥ 27.5 kg/m2 and 18 non‐obese controls were included. All patients were indicated for single tooth maxillary or mandibular molar replacement with the adjacent teeth intact. Peri‐implant clinical (plaque index [PI], bleeding on probing [BOP], probing depth [PD]) and radiographic (marginal bone loss [MBL]) parameters were measured at 12, 24, and 60 months of follow‐up.

Results

All peri‐implant parameters showed statistically significant difference between obese and non‐obese individuals. Obese group recorded significant higher BOP, PD, and MBL at different observation times. Probing depth and MBL increased significantly with advance of time in both groups. After 60 months of follow‐up period, greater PI and BOP was observed in obese patients (P < 0.01). At 60 months follow‐up period, obese patients showed significant increased PD (3.69 mm) as compared to non‐obese individuals (2.46 mm). Marginal bone loss in non‐obese individuals varied from 0.30 mm after 12 months, reaching 0.55 mm after 60 months of follow‐up period, while in obese patients MBL values went from 0.36 mm after 12 months to 0.91 mm at 60 months follow‐up (P < 0.01).

Conclusions

Patients with obesity are at risk of increased localized peri‐implant soft and hard tissue inflammation. It is recommended that clinicians should educate obese patients about risk of increased peri‐implant tissue inflammation and susceptibility to bone loss and stipulate stringent oral hygiene care for ideal peri‐implant health.
Prevention and treatment of parastomal hernia: a position statement on behalf of the Association of Coloproctology of Great Britain and Ireland
Authors:   ACPGBI Parastomal Hernia Group
Published: July 2018

Aim

The Association of Coloproctology of Great Britain and Ireland (ACPGBI) Delphi process identified prevention and treatment of parastomal hernia (PSH) as the second highest priority non‐cancer related colorectal pathology. This position statement aims to summarize the current evidence base.

Methods

Four broad themes were identified (prevention, diagnosis/classification, management and operative repair). Guidelines are based on evidence from an extensive literature review using organized searches on the PubMed, MEDLINE, Embase and Cochrane databases. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was adhered to for classifying the quality of evidence and reporting the strength of recommendations.

Results

The suture repair of PSH other than for patients in extremis is not recommended. Synthetic non‐absorbable mesh can be used safely in the short term in the construction of colostomies post rectal surgery, but longer‐term follow‐up is needed. Other broad recommendations are made around access to stoma care nurses, prevention classification and management.

Conclusion

There is a lack of high quality evidence for many domains in the prevention and treatment of PSH but the results of several studies are awaited.

What does this paper add to the literature?

Parastomal hernias are a common and debilitating condition following stoma formation. This position statement from ACPGBI details the current evidence base and ongoing research for the prevention, diagnosis and management of parastomal hernias.
The importance of early life experience and animal cultures in reintroductions
Authors: Teitelbaum Claire S. , Converse Sarah J. , Mueller Thomas
Published: July 2018

Even within a single population, individuals can display striking differences in behavior, with consequences for their survival and fitness. In reintroduced populations, managers often attempt to promote adaptive behaviors by controlling the early life experiences of individuals, but it remains largely unknown whether this early life training has lasting effects on behavior. We investigated the behavior of reintroduced whooping cranes (Grus americana) trained to migrate using two different methods to see whether their migration behavior remained different or converged over time. We found that the behavior of the two groups converged relatively rapidly, indicating that early life training may not produce lasting effects, especially in species that display lifelong learning and behavioral adaptation. In some cases, managers may consider continual behavioral interventions after release if desired behaviors are not present. Understanding the roles early life experience and animal cultures play in determining behavior is crucial for successful reintroduction programs.
Contactin‐associated protein‐like 2, a protein of the neurexin family involved in several human diseases
Authors: Saint‐Martin Margaux , Joubert Bastien , Pellier‐Monnin Véronique , Pascual Olivier , Noraz Nelly , Honnorat Jérôme
Published: July 2018

Contactin‐associated protein‐like 2 (CASPR2) is a cell adhesion protein of the neurexin family. Proteins of this family have been shown to play a role in the development of the nervous system, in synaptic functions, and in neurological diseases. Over recent years, CASPR2 function has gained an increasing interest as demonstrated by the growing number of publications. Here, we gather published data to comprehensively review CASPR2 functions within the nervous system in relation to CASPR2‐related diseases in humans. On the one hand, studies on Cntnap2 (coding for CASPR2) knockout mice revealed its role during development, especially, in setting‐up the inhibitory network. Consistent with this result, mutations in the CNTNAP2 gene coding for CASPR2 in human have been identified in neurodevelopmental disorders such as autism, intellectual disability, and epilepsy. On the other hand, CASPR2 was shown to play a role beyond development, in the localization of voltage‐gated potassium channel (VGKC) complex that is composed of TAG‐1, Kv1.1, and Kv1.2. This complex was found in several subcellular compartments essential for action potential propagation: the node of Ranvier, the axon initial segment, and the synapse. In line with a role of CASPR2 in the mature nervous system, neurological autoimmune diseases have been described in patients without neurodevelopmental disorders but with antibodies directed against CASPR2. These autoimmune diseases were of two types: central with memory disorders and temporal lobe seizures, or peripheral with muscular hyperactivity. Overall, we review the up‐to‐date knowledge on CASPR2 function and pinpoint confused or lacking information that will need further investigation.
A dipeptidyl peptidase‐4 inhibitor promotes wound healing in normoglycemic mice by modulating keratinocyte activity
Authors: Shih Chun‐Ming , Huang Chun‐Yao , Huang Chien‐Yu , Wang Kuo‐Hsien , Wei Po‐Li , Chang Yu‐Jia , Fong Tsorng‐Harn , Pan Jun‐Liang , Lee Ai‐Wei
Published: July 2018

Dipeptidyl peptidase‐4 (DPP‐4) inhibitors are a well‐known and novel class of oral antihyperglycaemic drugs. DPP‐4 inhibition facilitates ulcer healing in patients with diabetes. However, the actual mechanisms, which are independent of lower blood glucose levels, are still unknown. Therefore, the aim of this study was to analyse the effect of the DPP‐4 inhibitor sitagliptin on wound healing through a glucose‐independent pathway. In this study, DPP‐4 inhibitors facilitate keratinocyte differentiation and the proliferation, increase blood flow in the cutaneous of wounds in healthy C57BL/6 mice. Additionally, the administration of the DPP‐4 inhibitor ameliorates wound healing and enhances adiponectin expression in healthy C57BL/6 mice. Taken together, our results reveal a protective role for the DPP‐4 inhibitor sitagliptin in wound healing by regulating adiponectin and phospho‐eNOS levels in keratinocytes. Based on these results, the DPP‐4 inhibitor may have therapeutic potential for healing wounds through a diabetes‐independent mechanism.
Relationships between ecological niche and expected shifts in elevation and latitude due to climate change in South American temperate forest plants
Authors: Alarcón Diego , Cavieres Lohengrin A.
Published: July 2018

Aim

Niche properties, such as breadth and position along environmental gradients, are hypothesized to determine plant responses to climate change. We explored the properties of different plant niches in a biodiversity hotspot, over a wide span of elevational and latitudinal ranges, to assess the relationship between niche characteristics and the modelled distributional shifts due to climate change.

Location

South American temperate forests.

Methods

We assessed the niche breadth and position of 118 plant species of South American temperate forests, using an Outlying Mean Index (OMI). Bioclimatic information was gathered for each species from WorldClim, and both present and future distributions were modelled using BIOMOD, considering migration constraints with MIGCLIM. The relationships between niche properties and shifts in elevational and latitudinal distributions were explored using linear regressions.

Results

Niche differences among species were related to two bioclimatic dimensions: the first one correlated with the mean diurnal temperature range and precipitation seasonality following the mediterranean—temperate—sub‐Antarctic climatic gradient; the second one correlated with minimum winter temperature along a gradient from oceanic‐influenced habitats to cold tree line habitats. The projected elevational shifts were inversely related to niche breadth and the forecast latitudinal shifts were directly related to niche breadth. The shifts in elevation and latitude for understorey plants were not consistent with the shifts of dominant trees.

Main conclusions

The plant niches were successfully discerned by OMI analyses and they were associated with specific morphological or physiological traits. South American temperate forest plants showed an inverse relationship between niche breadth and elevational shifts, but a positive relationship regarding expected latitudinal shifts. This may be related to the fact that niche drivers followed a latitudinal orientation and the species showed the Rapoport's effect. Thus, the niche breadth and latitudinal position of the species should be considered in climatic change studies.
Time trends regarding the etiology of renal artery stenosis: 18 years’ experience from the China Center for Cardiovascular Disease
Authors: Xiong Hong‐liang , Peng Meng , Jiang Xiong‐jing , Che Wu‐qiang , Dong Hui , Chen Yang , Zou Yu‐bao , Gao Run‐lin , Liu Li-sheng
Published: July 2018

The time trends regarding the etiology of renal artery stenosis (RAS) are changing, but few investigations have focused on these issues. This study aimed to analyze the time trends regarding the etiology of RAS in a large patient sample from the China Center for Cardiovascular Disease. Consecutive inpatients with RAS from January 1999 to December 2016 were enrolled in this study. The etiologic diagnosis of RAS was based on established criteria. We retrospectively analyzed the time trends regarding the etiology of RAS during an 18‐year period. A total of 2905 patients with RAS were enrolled. There were 2393 (82.4%) patients with atherosclerosis (AS), 345 (11.9%) with Takayasu arteritis (TA), 126 (4.3%) with fibromuscular dysplasia (FMD), and 41 (1.4%) with other causes. Among all patients (n = 2905), patients aged ≤ 40 years (n = 450), patients aged >40 years (n = 2455), female patients (n = 1097), male patients (n = 1808), female patients aged >40 years (n = 808), and male patients aged >40 years (n = 1647), there were a gradual increase in the proportion of atherosclerotic RAS (P < 0.05), a gradual decrease in the proportion of RAS caused by TA (P < 0.05), and almost no change in the proportion of RAS caused by FMD during the 18‐year period (P > 0.05). The data show that the primary causes of RAS are AS, TA, and FMD. The proportion of RAS caused by AS and TA gradually increased and decreased, respectively, over time, and the proportion of RAS caused by FMD showed no significant change.
Tracking pressure injuries as adverse events: National use of the Global Trigger Tool over a 4‐year period
Authors: Gunningberg Lena , Sving Eva , Hommel Ami , Ålenius Carina , Wiger Per , Bååth Carina
Published: July 2018

Aim

To examine the frequency, preventability, and consequences of hospital acquired pressure injuries in acute care hospitals over a 4‐year period.

Method

A retrospective record review was performed using the Swedish version of the Global Trigger Tool (GTT). A total of 64 917 hospital admissions were reviewed. Data were collected between 2013 and 2016 from all 63 Swedish acute care hospitals.

Results

The prevalence of pressure injuries (category 2‐4) was 1%. Older patients, “satellite patients”, and patients with acute admissions had more pressure injuries. Most pressure injuries (91%) were determined to be preventable. The mean extended length of hospital stay was 15.8 days for patients who developed pressure injuries during hospitalization.

Conclusion

The GTT provides a useful and complementary national perspective on hospital acquired pressure injuries across hospitals, informing health care providers on safety priorities to reduce patient harm. Clinical leaders can use information on the preventability and the consequences of pressure injuries, as well as evidence‐based arguments for improving the health care organization.
The mGluR5 positive allosteric modulator VU0409551 improves synaptic plasticity and memory of a mouse model of Huntington's disease
Authors: Doria Juliana G. , de Souza Jessica M. , Silva Flavia R. , Olmo Isabella G. , Carvalho Toniana G. , Alves‐Silva Juliana , Ferreira‐Vieira Talita H. , Santos Jessica T. , Xavier Claudymara Q. S. , Silva Nathalia C. , Maciel Esther M. A. , Conn Peter Jeffrey , Ribeiro Fabiola M.
Published: July 2018

Huntington's Disease (HD) is an autosomal‐dominant neurodegenerative disorder, characterized by involuntary body movements, cognitive impairment, and psychiatric disorder. The metabotropic glutamate receptor 5 (mGluR5) plays an important role in HD and we have recently demonstrated that mGluR5‐positive allosteric modulators (PAMs) can ameliorate pathology and the phenotypic signs of a mouse model of HD. In this study, we investigated the molecular mechanisms involved in mGluR5 PAMs effect on memory. Our results demonstrate that subchronic treatment with the mGluR5 PAM VU0409551 was effective in reversing the memory deficits exhibited by BACHD mice, a mouse model for HD. Moreover, VU0409551 treatment stabilized mGluR5 at the cellular plasma membrane of BACHD mice, increasing the expression of several genes important for synaptic plasticity, including c‐Fos, brain‐derived neurotrophic factor, Arc/Arg3.1, syntaxin 1A, and post‐synaptic density‐95. In addition, VU0409551 treatment also increased dendritic spine density and maturation and augmented the number of pre‐synaptic sites. In conclusion, our results demonstrate that VU0409551 triggered the activation of cell signaling pathways important for synaptic plasticity, enhancing the level of dendritic spine maturation and rescuing BACHD memory impairment.

Open Practices

Open Science: This manuscript was awarded with the Open Materials Badge.

For more information see: https://cos.io/our-services/open-science-badges/

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Novel insights into the spatial and temporal complexity of hypothalamic organization through precision methods allowing nanoscale resolution
Authors: Alpár A. , Harkany T.
Published: July 2018

The mammalian hypothalamus contains an astounding heterogeneity of neurons to achieve its role in coordinating central responses to virtually any environmental stressor over the life‐span of an individual. Therefore, while core features of intrahypothalamic neuronal modalities and wiring patterns are stable during vertebrate evolution, integration of the hypothalamus into hierarchical brain‐wide networks evolved to coordinate its output with emotionality, cognition and conscious decision‐making. The advent of single‐cell technologies represents a recent milestone in the study of hypothalamic organization by allowing the dissection of cellular heterogeneity and establishing causality between opto‐ and chemogenetic activity modulation of molecularly‐resolved neuronal contingents and specific behaviours. Thus, organizational rules to accumulate an unprecedented variety of hierarchical neuroendocrine command networks into a minimal brain volume are being unravelled. Here, we review recent understanding at nanoscale resolution on how neuronal heterogeneity in the mammalian hypothalamus underpins the diversification of hormonal and synaptic output and keeps those sufficiently labile for continuous adaptation to meet environmental demands. Particular emphasis is directed towards the dissection of neuronal circuitry for aggression and food intake. Mechanistic data encompass cell identities, synaptic connectivity within and outside the hypothalamus to link vegetative and conscious levels of innate behaviours, and context‐ and circadian rhythm‐dependent rules of synaptic neurophysiology to distinguish hypothalamic foci that either tune the body's metabolic set‐point or specify behaviours. Consequently, novel insights emerge to explain the evolutionary advantages of non‐laminar organization for neuroendocrine circuits coincidently using fast neurotransmitters and neuropeptides. These are then accrued into novel therapeutic principles that meet therapeutic criteria for human metabolic diseases.