bluuebunny/crossref_metadata_2025 huggingface dataset:
Platelet-Rich Plasma and Its Utilities in Alopecia: A Systematic Review
Authors: Hesseler Michael J. , Shyam Nikhil
Published: June 2019

BACKGROUND

The use of platelet-rich plasma is becoming more prevalent in the field of dermatology. Variable preparation techniques and treatment methods have been described with reported success in alopecia.

OBJECTIVE

To consolidate the available evidence of platelet-rich plasma and its utility in the treatment of alopecia for the practicing dermatologist.

METHODS

Evaluating the available evidence up to May 31, 2018, a search was conducted in the PubMed database for “platelet rich plasma” or “platelet releasate” or “platelet gel” or “PRP” and “dermatology” or “skin” or “hair” or “cutaneous.”

RESULTS

Nineteen articles met the inclusion criteria for analysis including 3 alopecia areata studies with a total of 71 patients and 16 androgenetic alopecia studies with a total of 389 patients. Although the heterogeneity of the studies prevented direct comparisons and subsequent statistical analysis, the majority demonstrated that platelet-rich plasma produced successful hair growth in androgenetic alopecia and alopecia areata.

CONCLUSION

This review advocates for the use of platelet-rich plasma in 3 to 4 monthly sessions for the treatment of alopecia. Future studies should include a detailed description of the platelet-rich plasma isolation process to allow for comparison among studies, provide reproducibility, and generate a standardized treatment protocol.
Preoperative Blood Management Strategy for Elective Hip and Knee Arthroplasty
Authors: Kurian Dinesh J. , Guinn Nicole R. , Hunting John , Gamble John F. , Hopkins Thomas J. , Grimsley Aime , Guercio Jason R. , Bolognesi Michael P. , Schroeder Rebecca , Aronson Solomon ,   on behalf of the Duke Perioperative Enhancement Team (POET)
Published: June 2019

To improve quality and outcomes, a preoperative anemia clinic (PAC) was established to screen, evaluate, and manage preoperative anemia. A retrospective review of primary and revision hip and knee arthroplasty patients from August 2013 to September 2017 was conducted. Patients at “high risk” for transfusion were referred to PAC for treatment with iron, erythropoietin, or both based on anemia type. Preoperative anemia clinic referred patients were compared with a 1:3 historic propensity-matched control set of patients to help determine impact of PAC. Forty PAC patients were compared with 120 control patients. Among PAC patients, 26 (63.41%) received iron only, 3 (7.32%) received erythropoietin (EPO) only, and 12 (29.27%) received both. Preoperative hemoglobin significantly increased in the treatment group (median [interquartile range] 10.9 g/dl [10.3–11.2] vs. 12.0 g/dl [11.2–12.7];p< .001). Four PAC patients (10.00%) received red blood cell transfusions compared with 29 (24.17%) from matched controls (p= .055). In addition, the PAC cohort had higher postoperative nadir hemoglobin levels (mean [SD] 9.7 g/dl [1.31] vs. 8.7 g/dl [1.25];p< .001). High-risk patients appropriately treated with iron and/or EPO before surgery demonstrate a significant increase in preoperative hemoglobin, trend toward decrease perioperative transfusion, and increased hemoglobin levels postoperatively compared with matched controls.
Budesonide treatment for microscopic colitis: systematic review and meta-analysis
Authors: Sebastian Shaji , Wilhelm Annika , Jessica Lisle , Myers Sally , Veysey Martin
Published: June 2019

Microscopic colitis (MC), encompassing lymphocytic and collagenous colitis, is a common cause for chronic nonbloody diarrhoea, which impacts significantly on the quality of life for patients. Despite increasing awareness of the condition and its treatment, there is considerable variation in therapeutic approaches. To conduct a systematic review and meta-analysis on the efficacy and safety of budesonide in the treatment of MC. We searched Medline, Embase and Central databases using predefined search methodology for randomised trials using budesonide in the treatment of MC. We extracted data, on the efficacy and safety of budesonide, from studies identified that met the feasibility for analysis criteria. These data were pooled with a fixed effects model. Nine studies met the inclusion criteria for analysis. The pooled odds ratios (ORs) for a response to budesonide therapy at induction and maintenance were 7.34 [95% confidence interval (CI): 4.08–13.19] and 8.35 (95% CI: 4.14–16.85) respectively. Histological response rates were superior in budesonide-treated patients compared to placebo following induction (OR: 11.52; 95% CI: 5.67–23.40) and maintenance treatment (OR: 5.88; 95% CI: 1.90–18.17). There was no difference in adverse events. Significant relapse rates (>50%) were observed following treatment cessation with no difference noted between the budesonide or the placebo-treated patients. Budesonide is an effective treatment option for MC for achieving induction and maintenance of both clinical and histological response. High relapse rates on treatment cessation were observed.
A proposal for a useful algorithm to diagnose small hepatocellular carcinoma on MRI
Authors: Coty Jean-Baptiste , Paisant Anita , Esvan Maxime , Lonjon Julie , Seror Olivier , Rode Agnès , Ronot Maxime , Lebigot Jérôme , Vilgrain Valérie , Aubé Christophe
Published: June 2019

Objective

To assess MRI features for the diagnosis of small hepatocellular carcinomas (HCCs) and especially for nodules not showing both of the typical hallmarks.

Patients and methods

Three hundred and sixty-four cirrhotic patients underwent liver MRI for 10–30 mm nodules suggestive of HCC. The diagnostic performances of MRI features [T1, T2; diffusion-weighted (DW) imaging signal, enhancement, capsule, fat content] were tested, both individually and in association with both typical hallmarks and as substitutions for one hallmark. The diagnostic reference was obtained using a multifactorial algorithm ensuring high specificity (Sp).

Results

Four hundred and ninety-three nodules were analyzed. No alternative features, associations or substitutions outperformed the typical hallmarks for the diagnosis of HCC. For 10–20 mm nodules not displaying one of the typical hallmarks, hyperintensity on DW images was the most accurate substitutive sign, providing a sensitivity of 71.4% and Sp of 75% for nodules without arterial enhancement and sensitivity = 65.2% and Sp = 66% for nodules without washout on the portal or delayed phases. A new diagnostic algorithm, including typical hallmarks as a first step then the best-performing substitutive signs (capsule presence or DW hyperintensity) in combination with the nonmissing typical hallmark as a second step, enabled the correct classification of 77.7% of all nodules, regardless of size.

Conclusion

Using MRI, the typical hallmarks remain the best criteria for the diagnosis of small HCCs. However, by incorporating other MRI features, it is possible to build a simple algorithm enabling the noninvasive diagnosis of HCCs displaying both or only one of the typical hallmarks.
Rotavirus A Infections in Community Childhood Diarrhea in the Brazilian Semiarid Region During Postvaccination Era
Authors: Pankov Rafaela C. , Gondim Rafhaella N.D.G. , Prata Mara M.G. , Medeiros Pedro H.Q.S. , Veras Herlice N. , Santos Ana K.S. , Havt Alexandre , da Silva Marcelle F.M. , Fumian Tulio M. , Miagostovich Marize P. , Leite José P.G. , Lima Aldo A.M.
Published: June 2019

Background:

Rotavirus A (RVA) is one of the leading causes of acute gastroenteritis worldwide; however, few studies assessed RVA genetics with community surveillance.

Objectives:

This study aimed to investigate clinical data, genetic diversity, and coinfection patterns of RVA infections in children from 2 to 36 months old with or without community childhood diarrhea in the Brazilian semiarid region during postvaccination era.

Methods:

We enrolled and collected socioeconomic/clinical information using a standardized questionnaire and fecal samples from 291 children. Viral RNA samples were extracted and analyzed using quantitative reverse transcription polymerase chain reaction to establish the diagnosis of RVA. Sequencing of VP7 and VP4 (VP8*) regions and phylogenetic analysis were performed.

Results:

RVA‐negative diagnosis was associated with children 24 to 36 months old with complete vaccination schedule. Genotype G1P[8] was the most prevalent (57%), whereas unusual genotypes including G1P[4], G2P[8], and G3P[9] were also detected. G1‐ and P[8]‐positive samples showed high degrees of similarity with the vaccine strain. RVA coinfections were frequently observed, and enteroaggregative Escherichia coli was the most prevalent copathogen.

Conclusions:

These results demonstrate that genotype G1P[8] is the most prevalent strain. VP7 and/or VP8* gene segments arising from RV1 vaccine strain were documented in these children, suggesting shedding or herd vaccination. Moreover, our study indicates full vaccination is important for protection against RVA infections.
The Risk of Autoimmune Disorders in Treated Celiac Disease Patients in Olmsted County, Minnesota
Authors: Khan Muhammad R. , Nellikkal Shilpa S. , Barazi Ahmed , Larson Joseph J. , Murray Joseph A. , Absah Imad
Published: June 2019

Background:

Patients with autoimmune disorders (ADs) are at increased risk for celiac disease (CD), but data are conflicting on the risk of ADs in treated patients with CD. We aimed to assess the incidence of ADs in treated patients with CD.

Methods:

Using the Rochester Epidemiology Project, we retrospectively searched for the medical records at Mayo Clinic and Olmsted Medical Center from January 1997 to December 2015 for patients with CD who met accepted diagnostic criteria. For each patient with CD, we identified 2 age and sex‐matched controls during the same study period. The incidence rate of AD diagnosis 5 years after index date was calculated using Kaplan‐Meier analysis for the CD cases and controls and compared using the log‐rank test.

Results:

We identified 249 treated patients with CD during the study period and 498 matched controls, with mean (standard deviation) ages of 32 (22) years and 33 (22) years, respectively. One third of patients (n = 85) and controls (n = 170) were boys. Five years after the index date, 5.0% of patients with CD and 1.3% of controls had a de novo AD diagnosis (P = 0.006). In the presence of a prior AD, the cumulative risk of a de novo or additional AD was significantly higher in the CD group compared with controls (P < 0.001). Children had a significantly higher risk of AD development compared with adults (P = 0.010).

Conclusions:

Treated patients with CD are at higher risk for the development of ADs. The risk of a new AD is higher in children, especially when >1 AD diagnosis exists.
Regulation of Ascorbic acid by gonadotropins in rat Ovary
Authors: Hussain Shah Saddad , Arora Taruna , Chaturvedi Madan Mohan , Basu-Modak Sharmila , Chaudhary Rajesh , Muralidhar Kambadur
Published: June 2019

The dose dependent depletion of ovarian Ascorbic acid (AA) in rat ovaries, has been used as a bioassay for measurement of Luteinizing Hormone (LH). However, the mechanism of action of gonadotropin (LH, FSH) on ascorbic acid depletion is not completely clear in biochemical terms. To elucidate the mechanism, we looked for the pathways; one, where L-GulonateDehydrogenase (L-GuDH) catalyzes the conversion of L-Gulonic acid (L-GuA) to L-Xylulose, and, in the second the pathway conversion of L-GuA to AA, in a cats, dogs and Rats. Kinetic analysis of the enzyme L-GuDHin vitroshowed the inhibitory effect of AA on L-GuDH. Therefore, we hypothesized that gonadotropins (FSH and LH) may regulate the L-GuDH maintain level of AA in ovary. LH administration to super-ovulated immature female rats caused depletion of ovarian AA but did not result in any change in the specific activity of the ovarian L-GuDH. Further, we administrated a surrogate FSH like hormone (PMSG) to immature female rats which, resulted in increased specific activity of ovarian L-GuDH. However, microarray data on RNA from ovaries exposed to FSH like hormone such as Pregnant Mare serum Gonadotropin (PMSG) did not reveal any increased expression of L-GuDH transcript. It is therefore concluded from the results obtained that; that neither LH, in decreasing the ovarian AA, nor FSH, in increasing the ovarian AA do so by regulating the activity of enzyme L-GuDH at transcriptional level. The results obtained have also been discussed by giving emphasis on the mechanism of ovarian ascorbic acid regulation of LH and FSH.
Single-cell analysis of the muscle stem cell hierarchy identifies heterotypic communication signals involved in skeletal muscle regeneration
Authors: De Micheli Andrea J. , Fraczek Paula , Soueid-Baumgarten Sharon , Ravichandran Hiranmayi , De Vlaminck Iwijn , Elemento Olivier , Cosgrove Benjamin D.
Published: June 2019

Muscle stem cells (MuSCs) are an essential adult stem cell population with the capacity to self-renew and regenerate muscle tissue. Functionally heterogeneous subpopulations of MuSCs have been identified based on their expression of myogenic regulatory factors and surface markers. However, a unified organization of muscle stem and progenitor cells and their subpopulations remains unresolved. Here, we performed temporal analysis of skeletal muscle regeneration using single-cell RNA-sequencing (scRNA-seq) of myotoxin-injured adult mouse hindlimb muscles. We generated over 34,000 single-cell transcriptomes spanning four muscle regeneration time-points and identified 15 distinct cell types, including a heterogeneous population of MuSCs and progenitor cells. Our analysis provides a hierarchical map of myogenic cell populations and identifies stage-specific regulatory programs that govern their contributions to muscle regeneration. In this transcriptomic atlas, we observed cell type-specific regenerative dynamics, exemplified by waves of transient amplification and diversification of multiple immune cell types and, subsequently, myogenic cells. Unbiased trajectory inference organized the myogenic cell populations within the atlas into a continuum, consisting of a hierarchy of quiescent MuSCs, cycling progenitors, committed myoblasts, and terminally differentiated myocytes. This myogenic trajectory matched prior understanding and also revealed that MuSC stages are defined by synchronous changes in regulatory factors, cell cycle-associated, and surface receptor gene expression. Lastly, we analyzed the transcriptomic atlas to identify over 100 candidate heterotypic communication signals between myogenic and non-myogenic cell populations, including many involving the fibroblast growth factor (FGF), Notch, and Syndecan receptor families and their associated ligands. Syndecan receptors were implicated in a large fraction of these cell communication interactions and were observed to exhibit transcriptional heterogeneity within the myogenic continuum. Using multiparameter mass cytometry (CyTOF), we confirmed that cycling MuSCs exhibit diversified Syndecan-1/2 expression, which suggests that dynamic alterations in Syndecan signaling interactions may coordinate stage-specific myogenic cell fate regulation. This scRNA-seq reference atlas provides a resolved hierarchical organization of myogenic subpopulations as a resource to investigate cell-cell interactions that regulate myogenic stem and progenitor cell fates in muscle regeneration.
Mass Spectrometry based Metabolomics Deciphered Metabolic Reprogramming That Was Required for Biofilm formation in UropathogenicEscherichia coli
Authors: Lu Haitao , Que Yumei , Wu Xia , Guan Tianbing , Guo Hao
Published: June 2019

Biofilm formation plays a key role in many bacteria causing infections, which mostly accounts for high-frequency infectious recurrence and antibiotics resistance. In this study, we sought to compare modified metabolism of biofilm and planktonic populations with UIT89, a predominant agent of urinary tract infection, by combining mass spectrometry based untargeted and targeted metabolomics methods, as well as cytological visualization, which enable us to identify the driven metabolites and associated metabolic pathways underlying biofilm formation. Surprisingly, our finding revealed distinct differences in both phenotypic morphology and metabolism between two patterns. Furthermore, we identified and characterized 38 differential metabolites and associated three metabolic pathways involving glycerolipid metabolism, amino acid metabolism and carbohydrate metabolism that were altered mostly during biofilm formation. This discovery in metabolic phenotyping permitted biofilm formation shall provide us a novel insight into the desperation of biofilm, which enable to develop novel biofilm based treatments against pathogen causing infections, with lower antibiotic resistance.
The repertoire of serous ovarian cancer non-genetic heterogeneity revealed by single-cell sequencing of normal fallopian tube epithelial cells
Authors: Hu Zhiyuan , Artibani Mara , Alsaadi Abdulkhaliq , Wietek Nina , Morotti Matteo , Gonzalez Laura Santana , El-Sahhar Salma , KaramiNejadRanjbar Mohammad , Mallett Garry , Shi Tingyan , Masuda Kenta , Zheng Yiyan , Chong Kay , Damato Stephen , Dhar Sunanda , Campanile Riccardo Garruto , majd Hooman Soleymani , Cerundolo Vincenzo , Sauka-Spengler Tatjana , Yau Christopher , Ahmed Ahmed A.
Published: June 2019

The inter-differentiation between cell states promotes cancer cell survival under stress and fosters non-genetic heterogeneity (NGH). NGH is, therefore, a surrogate of tumor resilience but its quantification is confounded by genetic heterogeneity. Here we show that NGH can be accurately measured when informed by the molecular signatures of the normal cells of origin. We surveyed the transcriptomes of ∼ 4000 normal fallopian tube epithelial (FTE) cells, the cells of origin of serous ovarian cancer (SOC), and identified six FTE subtypes. We used subtype signatures to deconvolute SOC expression data and found substantial intra-tumor NGH that was previously unrecognized. Importantly, NGH-based stratification of ∼1700 tumors robustly predicted survival. Our findings lay the foundation for accurate prognostic and therapeutic stratification of SOC.

Highlights

The projection of FTE subtypes refines the molecular classification of serous OC

Comprehensive single-cell profiling of FTE cells identifies 6 molecular subtypes

Substantial non-genetic heterogeneity of HGSOC identified in 1700 tumors

A mesenchymal-high HGSOC subtype is robustly correlated with poor prognosis
CRISPR-assisted targeted enrichment-sequencing (CATE-seq)
Authors: Xu Xinhui , Xia Qiang , Zhang Shuyan , Gao Jinliang , Dai Wei , Wu Jian , Wang Jinke
Published: June 2019

The current targeted sequencing of genome is mainly dependent on various hybridization-based methods. However, the hybridization-based methods are still limited by the intrinsic shortcomings of nucleic acid hybridization. This study developed a new CRISPR-based targeted sequencing technique, CRISPR-assisted targeted enrichment-sequencing (CATE-seq). In this technique, the input genomic DNA (gDNA) was firstly bound by a complex of dCas9 and capture sgRNA (csgRNA). The DNA-dCas9-csgRNA complex was then captured on magnetic beads through an easy room-temperature annealing between a short universal capture sequence (24 bp) at the 3′ end of csgRNA and capture oligonucleotide coupled on magnetic beads. The enriched DNAs were finally analyzed by next generation sequencing. Using this technique, three different scales of targeted enrichments were successfully performed, including enriching 35 target exons of 6 genes from 6 gDNA samples with 54 csgRNAs, 339 target exons of 186 genes from 9 gDNA samples with 367 csgRNAs, and 2031 target exons of 451 genes from 2 gDNA samples with 2302 csgRNAs. This technique has several significant advantages over the current hybridization-based methods, including high simplicity, specificity, sensitivity, throughput, and scalability.
Controlled dehydration, structural flexibility, and Gadolinium MRI contrast compound binding in human plasma glycoprotein afamin
Authors: Naschberger Andreas , Juyoux Pauline , von Velsen Jill , Rupp Bernhard , Bowler Matthew W.
Published: June 2019

Afamin, a human blood plasma glycoprotein, a putative multi-functional transporter of hydrophobic molecules and a marker for metabolic syndrome, poses multiple challenges for crystallographic structure determination, both practically and in analysis of the models. Several hundred crystals were analysed, and unusual variability in cell volume and difficulty solving the structure despite a ~34% sequence identity with non-glycosylated human serum albumin indicated that the molecule exhibits variable and context-sensitive packing, despite greatly simplified glycosylation in insect cell expressed recombinant afamin. Controlled dehydration of the crystals was able to stabilise the orthorhombic crystal form reducing the number of molecules in the asymmetric unit from the monoclinic form and changing the conformational states of the protein. An iterative strategy, using fully automatic experiments available on MASSIF-1, was used to quickly determine the optimal protocol to achieve the phase transition that should be readily applicable to many types of sample. The study also highlights the drawback of using a single crystallographic structure model for computation modelling purposes given that conformational state of the binding sites and electron density in the binding site, likely resulting from PEGs, greatly varies between models. This also holds for the analysis of unspecific low-affinity ligands, where often a variety fragments with similar uncertainty can be modelled, inviting interpretative bias. As a promiscuous transporter, afamin also seems to bind Gadoteridol, a magnetic resonance imaging contrast compound, in at least two sites. One pair of Gadoteridol molecules is located near the human albumin Sudlow-site, and a second Gadoteridol at an intermolecular site in proximity of domain IA. The data from the co-crystals provide an opportunity to evaluate modern metrics of data quality in the context of the information that can be gleaned from data sets that would be abandoned on classical measures.

Synopsis

Controlled dehydration experiments have revealed a new crystal form of afamin, a human blood plasma glycoprotein and transporter of hydrophobic molecules. The comparison shows substantial molecular plasticity and amplifies the necessity to examine multiple crystal forms and to refine multiple models, while at the same time the new structure cautions against interpretation of fatty acid ligand density in crystals derived from PEG as major precipitants. An isomorphic low-resolution structure model suggests that afamin is capable of transporting Gadolinium-DO3A, a magnetic resonance imaging compound.
The multiple population genetic and demographic routes to islands of genomic divergence
Authors: Quilodrán Claudio S. , Ruegg Kristen , Sendell-Price Ashley T. , Anderson Eric , Coulson Tim , Clegg Sonya
Published: June 2019

1. The way that organisms diverge into reproductively isolated species is a major question in biology. The recent accumulation of genomic data provides promising opportunities to understand the genomic landscape of divergence, which describes the distribution of differences across genomes. Genomic areas of unusually high differentiation have been called genomic islands of divergence. Their formation has been attributed to a variety of mechanisms, but a prominent hypothesis is that they result from divergent selection over a small portion of the genome, with surrounding areas homogenised by gene flow. Such islands have often been interpreted as being associated with divergence with gene flow. However other mechanisms related to genetic architecture and population history can also contribute to the formation of genomic islands of divergence.

2. We currently lack a quantitative framework to examine the dynamics of genomic landscapes under the complex and nuanced conditions that are found in natural systems. Here, we develop an individual-based simulation to explore the dynamics of diverging genomes under various scenarios of gene flow, selection and genotype-phenotype maps.

3. Our modelling results are consistent with empirical observations demonstrating the formation of genomic islands under genetic isolation. Importantly, we have quantified the range of conditions that produce genomic islands. We demonstrate that the initial level of genetic diversity, drift, time since divergence, linkage disequilibrium, strength of selection and gene flow are all important factors that can influence the formation of genomic islands. Because the accumulation of genomic differentiation over time tends to erode the signal of genomic islands, genomic islands are more likely to be observed in recently divergent taxa, although not all recently diverged taxa will necessarily exhibit islands of genomic divergence. Gene flow primarily slows the swamping of islands of divergence with time.

4. By using this framework, further studies may explore the relative influence of particular suites of events that contribute to the emergence of genomic islands under sympatric, parapatric and allopatric conditions. This approach represents a novel tool to explore quantitative expectations of the speciation process, and should prove useful in elucidating past and projecting future genomic evolution of any taxa.
Photodamage repair pathways contribute to the accurate maintenance of the DNA methylome landscape upon UV exposure
Authors: Graindorge Stéfanie , Cognat Valérie , Johann to Berens Philippe , Mutterer Jérôme , Molinier Jean
Published: June 2019

Plants are exposed to the damaging effect of sunlight that induces DNA photolesions. In order to maintain genome integrity, specific DNA repair pathways are mobilized. Upon removal of UV-induced DNA lesions, the accurate re-establishment of epigenome landscape is expected to be a prominent step of these DNA repair pathways. However, it remains poorly documented whether DNA methylation is accurately maintained at photodamaged sites and how photodamage repair pathways contribute to the maintenance of genome/methylome integrities. Using genome wide approaches, we report that UV-C irradiation leads to asymmetric DNA methylation changes. We identified that the specific DNA repair pathways involved in the repair of UV-induced DNA lesions, Direct Repair (DR) and Global Genome Repair (GGR), prevent the excessive alterations of DNA methylation landscape. Moreover, we identified that UV-C irradiation induced chromocenter reorganization and that photodamage repair factors control this dynamics. The methylome changes rely on misregulation of maintenance, de novo and active DNA demethylation pathways highlighting that molecular processes related to genome and methylome integrities are closely interconnected. Importantly, we identified that photolesions are sources of DNA methylation changes in both, constitutive and facultative heterochromatin. This study unveils that DNA repair factors, together with small RNA, act to accurately maintain both genome and methylome integrities at photodamaged silent genomic regions, strengthening the idea that plants have evolved sophisticated interplays between DNA methylation dynamics and DNA repair.
Chronic Stability of Single-Channel Neurophysiological Correlates of Gross and Fine Reaching Movements in the Rat
Authors: Bundy David T. , Guggenmos David J , Murphy Maxwell D , Nudo Randolph J.
Published: June 2019

Following injury to motor cortex, reorganization occurs throughout spared brain regions and is thought to underlie motor recovery. Unfortunately, the standard neurophysiological and neuroanatomical measures of post-lesion plasticity are only indirectly related to observed changes in motor execution. While substantial task-related neural activity has been observed during motor tasks in rodent primary motor cortex and premotor cortex, the long-term stability of these responses in healthy rats is uncertain, limiting the interpretability of longitudinal changes in the specific patterns of neural activity during motor recovery following injury. This study examined the stability of task-related neural activity associated with execution of reaching movements in healthy rodents. Rats were trained to perform a novel reaching task combining a ‘gross’ lever press and a ‘fine’ pellet retrieval. In each animal, two chronic microelectrode arrays were implanted in motor cortex spanning the caudal forelimb area (rodent primary motor cortex) and the rostral forelimb area (rodent premotor cortex). We recorded multiunit spiking and local field potential activity from 10 days to 7-10 weeks post-implantation to characterize the patterns of neural activity observed during each task component and analyzed the consistency of channel-specific task-related neural activity. Task-related changes in neural activity were observed on the majority of channels. While the task-related changes in multi-unit spiking and local field potential spectral power were consistent over several weeks, spectral power changes were more stable, despite the trade-off of decreased spatial and temporal resolution. These results show that rodent primary and premotor cortex are both involved in reaching movements with stable patterns of task-related activity across time, establishing the relevance of the rodent for future studies designed to examine changes in task-related neural activity during recovery from focal cortical lesions.
Nav1.5 single-molecule localization reveals different reorganization modes at cardiomyocyte domains
Authors: Vermij Sarah H. , Rougier Jean-Sébastien , Agulló-Pascual Esperanza , Rothenberg Eli , Delmar Mario , Abriel Hugues
Published: June 2019

Mutations in the gene encoding the sodium channel Nav1.5 cause various cardiac arrhythmias. This variety may arise from different determinants of Nav1.5 expression between cardiomyocyte domains. At the lateral membrane and T-tubules, Nav1.5 localization and function remain insufficiently characterized. We used novel single-molecule localization microscopy (SMLM) and modeling to define nanoscale features of Nav1.5 localization and distribution at the lateral membrane, groove, and T-tubules in wild-type, dystrophin-deficient (mdx) mice, and mice expressing C-terminally truncated Nav1.5 (ΔSIV). We show that Nav1.5 organizes as distinct clusters in the groove and T-tubules which density and distribution partially depend on SIV and dystrophin. We found that overall reduction in Nav1.5 expression in mdx and ΔSIV cells results in a non-uniform redistribution with Nav1.5 being specifically reduced at the groove of ΔSIV and increased in T-tubules of mdx cardiomyocytes. Nav1.5 mutations may therefore site-specifically affect Nav1.5 localization and distribution depending on site-specific interacting proteins.
perfectphyloR: An R package for reconstructing perfect phylogenies
Authors: Karunarathna Charith Bhagya , Graham Jinko
Published: June 2019

Background

A perfect phylogeny is a rooted binary tree that recursively partitions sequences. The nested partitions of a perfect phylogeny provide insight into the pattern of ancestry of genetic sequence data. For example, sequences may cluster together in a partition indicating that they arise from a common ancestral haplotype.

Results

We present an R packageperfectphyloRto reconstruct the local perfect phylogenies underlying a sample of binary sequences. The package enables users to associate the reconstructed partitions with a user-defined partition. We describe and demonstrate the major functionality of the package.

Conclusion

TheperfectphyloRpackage should be of use to researchers seeking insight into the ancestral structure of their sequence data. The reconstructed partitions have many applications, including the mapping of trait-influencing variants.
Non-Genetic Reprogramming of Monocytes via Microparticle Phagocytosis for Sustained Modulation of Macrophage Phenotype
Authors: Wofford Kathryn L. , Singh Bhavani S. , Cullen D. Kacy , Spiller Kara L.
Published: June 2019

Monocyte-derived macrophages orchestrate tissue regeneration by homing to sites of injury, phagocytosing pathological debris, and stimulating other cell types to repair the tissue. Accordingly, monocytes have been investigated as a translational and potent source for cell therapy, but their utility has been hampered by their rapid acquisition of a pro-inflammatory phenotype in response to the inflammatory injury microenvironment. To overcome this problem, we designed a cell therapy strategy where we collect and exogenously reprogram monocytes by intracellularly loading the cells with biodegradable microparticles containing an anti-inflammatory drug in order to modulate and maintain an anti-inflammatory phenotype over time. To test this concept, poly(lactic-co-glycolic) acid microparticles were loaded with the anti-inflammatory drug dexamethasone (Dex) and administered to primary human monocytes for four hours to facilitate phagocytic uptake. After removal of non-phagocytosed microparticles, microparticle-loaded monocytes differentiated into macrophages and stored the microparticles intracellularly for several weeksin vitro, releasing drug into the extracellular environment over time. Cells loaded with intracellular Dex microparticles showed decreased expression and secretion of inflammatory factors even in the presence of pro-inflammatory stimuli up to 7 days after microparticle uptake compared to untreated cells or cells loaded with blank microparticles. This study represents a new strategy for long-term maintenance of anti-inflammatory macrophage phenotype using a translational monocyte-based cell therapy strategy without the use of genetic modification. Because of the ubiquitous nature of monocyte-derived macrophage involvement in pathology and regeneration, this strategy holds potential as a treatment for a vast number of diseases and disorders.
Critical role for P53 in regulating the cell cycle of ground state embryonic stem cells
Authors: ter Huurne Menno , Peng Tianran , Yi Guoqiang , van Mierlo Guido , Marks Hendrik , Stunnenberg Hendrik G.
Published: June 2019

Mouse Embryonic Stem Cells (ESCs) grown in serum-supplemented conditions are characterized by an extremely short G1-phase due to the lack of G1-phase control. Concordantly, the G1-phase-specific P53-P21 pathway is compromised in serum ESCs. Here we provide evidence that P53 is activated upon transition of serum ESCs to their pluripotent ground state using serum-free 2i conditions and modulates G1-phase progression. Our data shows that the elongated G1-phase characteristic of ground state ESCs is dependent on P53. RNA-seq and ChIP-seq analyses reveal that P53 directly regulates the expression of the Retinoblastoma (RB) protein and that the hypo-phosphorylated, active RB protein plays a key role in G1-phase control. Our findings suggest that the P53-P21 pathway is active in ground state 2i ESCs and that its role in the G1-checkpoint is abolished in serum ESCs. Taken together, the data reveals a mechanism by which inactivation of P53 can lead to loss of RB and uncontrolled cell proliferation.
A real-time phase-space beam emittance monitoring system
Authors: Samadi Nazanin , Shi Xianbo , Dallin Les , Chapman Dean
Published: June 2019

An electron beam position and angle monitoring system, ps-BPM, has been shown to be able to measure the electron source position and angle at a single location in a beamline at a synchrotron source. This system uses a monochromator to prepare a photon beam whose energy is at that of the K-edge of an absorber filter. The divergence of the beam from the source gives an energy range that will encompass the K-edge of the filter. A measurement of the centre of the monochromatic beam and the K-edge location through the absorber filter gives the position and angle of the electron source. Here, it is shown that this system is also capable of measuring the source size and divergence at the same time. This capability is validated by measurement as the beam size in the storage ring was changed and by ray-tracing simulations. The system operates by measuring the photon beam spatial distribution as well as a K-edge filtered beam distribution. These additional measurements result in the ability to also determine the electron source size and divergence.
Hard X-ray self-seeding commissioning at PAL-XFEL
Authors: Min Chang-Ki , Nam Inhyuk , Yang Haeryong , Kim Gyujin , Shim Chi Hyun , Ko Jun Ho , Cho Myung-Hoon , Heo Hoon , Oh Bonggi , Suh Young Jin , Kim Min Jae , Na Donghyun , Kim Changbum , Kim Yongsam , Chun Sae Hwan , Lee Jae Hyuk , Kim Jangwoo , Kim Sunam , Eom Intae , Kim Seung Nam , Koo Tae-Yeong , Rah Seungyu , Shvyd'ko Yuri , Shu Deming , Kim Kwang-Je , Terentyev Sergey , Blank Vladimir , Kang Heung-Sik
Published: June 2019

A wake monochromator based on a large-area diamond single crystal for hard X-ray self-seeding has been successfully installed and commissioned in the hard X-ray free-electron laser (FEL) at the Pohang Accelerator Laboratory with international collaboration. For this commissioning, the self-seeding was demonstrated with a low bunch charge (40 pC) and the nominal bunch charge (180 pC) of self-amplified spontaneous emission (SASE) operation. The FEL pulse lengths were estimated as 7 fs and 29.5 fs, respectively. In both cases, the average spectral brightness increased by more than three times compared with the SASE mode. The self-seeding experiment was demonstrated for the first time using a crystal with a thickness of 30 µm, and a narrow bandwidth of 0.22 eV (full width at half-maximum) was obtained at 8.3 keV, which confirmed the functionality of a crystal with such a small thickness. In the nominal bunch-charge self-seeding experiment, the histogram of the intensity integrated over a 1 eV bandwidth showed a well defined Gaussian profile, which is evidence of the saturated FEL and a minimal electron-energy jitter (∼1.2 × 10−4) effect. The corresponding low photon-energy jitter (∼2.4 × 10−4) of the SASE FEL pulse, which is two times lower than the Pierce parameter, enabled the seeding power to be maximized by maintaining the spectral overlap between SASE FEL gain and the monochromator.
Social capital and export performance of SMEs in Ghana: the role of firm capabilities
Authors: Easmon Roseline Barbara , Kastner Adelaide Naa Amerley , Blankson Charles , Mahmoud Mahmoud Abdulai
Published: June 2019

Purpose

The purpose of this paper is to understand the direct impact of social capital and the influence of market-based capabilities as intervening variables on the export performance of small and medium-sized enterprises (SMEs) in Ghana.

Design/methodology/approach

Questionnaire-based survey was used to collect data from top executives and senior managers of exporting companies in Ghana. Data obtained were analysed using the structural equation modelling.

Findings

The findings revealed that social capital of SMEs exert the greatest influence on their export performance. Innovation and marketing capabilities are also key drivers of export performance among SMEs as they fully mediate the social capital–export performance relationship. Notwithstanding, marketing capabilities appear to exert a greater influence than innovation capabilities on the export performance of SMEs.

Research limitations/implications

The study used perceptual measures of international performance by managers of SMEs in the Ghanaian exporting sector making it difficult to determine respondent bias.

Practical implications

Managers of exporting firms should build stronger relationships with their customers and suppliers who contribute significantly to their export performance. SMEs would also have to hone their innovation and marketing skills as strategic components in enhancing their export performance.

Social implications

Market-based resources such as marketing and innovation should not be taken for granted by SMEs in the export business.

Originality/value

The study offers some lessons on how small firms can sharpen their marketing and innovation capabilities to derive export performance benefits from social capital. Theoretically, while the findings offer strong evidence reinforcing the DC theory, an exploration of the nexus of the theories brings to the fore the need to reassess the resource-based view and SC theories.
Exploring adaptive information sharing from the perspective of cognitive switching
Authors: Zha Xianjin , Yang Haijuan , Yan Yalan , Yan Guanxiang , Huang Chengsong , Liu Kunfeng
Published: June 2019

Purpose

Microblogging as one kind of social media application provides an important information sharing platform. Adaptive information sharing is the combination of adaptive information technologies (IT) use behavior and information sharing behavior and subsequently refers to adaptive use of IT oriented to information sharing. The purpose of this paper is to understand adaptive information sharing in the context of microblogging from the perspective of cognitive switching.

Design/methodology/approach

A research model was developed and survey data were collected. The partial least squares structural equation modeling was employed to verify the research model.

Findings

Adaptive information sharing is positively impacted by other people’s use, discrepancies and deliberate initiatives among which other people’s use is the key determinant. Meanwhile, task self-efficacy positively moderates the effect of other people’s use on adaptive information sharing.

Practical implications

Developers of microblogging should as far as possible create learning atmosphere and learning culture. With learning atmosphere and culture, more and more users could keep on learning from observing other people. Consequently, more and more users would be willing to try new features of microblogging to share information.

Originality/value

This study examines adaptive information sharing by extending adaptive IT use behavior from the levels of technology, system and feature to the information level, presenting a new lens for adaptive IT use and information sharing alike.
Modeling the interplay of information seeking and information sharing
Authors: Savolainen Reijo
Published: June 2019

Purpose

The purpose of this paper is to contribute to the creation of a holistic picture of information behavior by examining the connections between information seeking and sharing.

Design/methodology/approach

Conceptual analysis is used to focus on the ways in which the researchers have modeled the interplay of information seeking and sharing. The study draws on conceptual analysis of 27 key studies examining the above issue, with a focus on the scrutiny of six major models for information behavior.

Findings

Researchers have employed three main approaches to model the relationships between information seeking and sharing. The indirect approach conceptualizes information seeking and sharing as discrete activities connected by an intermediating factor, for example, information need. The sequential approach assumes that information seeking precedes information sharing. From the viewpoint of the interactive approach, information seeking and sharing appear as mutually related activities shaping each other iteratively or in a cyclical manner. The interactive approach provides the most sophisticated research perspective on the relationships of information seeking and sharing and contributes to holistic understanding of human information behavior.

Research limitations/implications

As the study focuses on information seeking and sharing, no attention is devoted to other activities constitutive of information behavior, for example, information use.

Originality/value

The study pioneers by providing an in-depth analysis of the connections of information seeking and information sharing.
Development of an alcohol withdrawal risk stratification tool based on patients referred to an addiction liaison nursing service in Glasgow
Authors: Benson George , McPherson Andrew , McCallum Jacqueline , Roberts Nicola
Published: June 2019

Purpose

The purpose of this paper is to develop an alcohol withdrawal syndrome risk stratification tool that could support the safe discharge of low risk patients from the emergency department.

Design/methodology/approach

A retrospective cohort study that included all patients referred to the acute addiction liaison nursing service over one calendar month (n=400, 1–30 April 2016) was undertaken. Bivariate and multivariate modelling identified the significant variables that supported the prediction of severe alcohol withdrawal syndrome (SAWS) in the cohort population.

Findings

The Glasgow Modified Alcohol Withdrawal Scale (GMAWS), hours since last drink, fast alcohol screening test (FAST) and systolic blood pressure correctly identified 89 per cent of patients who developed SAWS and 84 per cent of patients that did not. Increasing each component by a score of one is associated with an increase in the odds of SAWS by a factor of 2.76 (95% CI 2.21, 3.45), 1.31 (95% CI 1.24, 1.37), 1.30 (95% CI 1.08, 1.57) and 1.22 (95% CI 1.10, 1.34), respectively.

Research limitations/implications

The research was conducted in a single healthcare system that had a high prevalence of alcohol dependence syndrome (ADS). Second, the developed risk stratification tool was unable to guarantee no risk and lastly, the FAST score previously aligned to severe ADS may have influenced the patients highest GMAWS score.

Practical implications

The tool could help redesign the care pathway for patients who attend the emergency department at risk of SAWS and link low risk patients with community alcohol services better equipped to deal with their physical and psychological needs short and long term supporting engagement, abstinence and prolongation of life.

Originality/value

The tool could help redesign the care pathway for emergency department patients at low risk of SAWS and link them with community alcohol services better equipped to deal with their physical and psychological needs, short and long term, supporting engagement, abstinence and prolongation of life.
Learning from defects in the UK housing sector using action research
Authors: Hopkin Tony , Lu Shu-Ling , Sexton Martin , Rogers Phil
Published: June 2019

Purpose

Maximising the benefit of learning from defects is regarded by UK housing associations (HAs) as a key opportunity to meet their challenges of building more homes with reduced government funding and rent incomes. Despite learning from defects being a frequent recommendation to reduce defects in the construction literature, there is scarce empirical evidence into how HAs actually learn from defects. The purpose of this paper is to better understand how HAs learn from past defects and induce change to reduce defects.

Design/methodology/approach

Guided by organisational learning (OL) as the theoretical lens, a 21-month action research (AR) project explored one HA’s defects management and learning processes.

Findings

OL has the potential to reduce defects in new homes but is a secondary task which is reliant on a defects management team analysing defect data to identify priority areas. As such, learning from defects can be reduced due to peaks in workload if data analysis is a manual process. Furthermore, a dual learning approach plays a significant role for HA’s learning consisting of designing out defects (codification) supported by networking (personalisation) to tackle issues of workmanship on site and those defects that cannot be designed out.

Originality/value

This study demonstrates OL has the potential to reduce defects in new homes but is a secondary task in HA’s practice; and highlights the practical challenges of academia and industry co-production in AR in construction.