bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and drug treatment practices of inflammatory bowel diseases in Poland in the years 2012–2014: an analysis of nationwide databases
Authors: Holko Przemysław , Kawalec Paweł , Stawowczyk Ewa
Published: December 2017

Background

Inflammatory bowel diseases (IBDs) such as ulcerative colitis (UC) and Crohn’s disease (CD) are chronic autoimmune disorders that constitute a major societal and economic burden for individual patients, their families and the society. The aim of this study was to assess the current prevalence and treatment patterns of IBD in Poland.

Patients and methods

We carried out a retrospective analysis of the nationwide databases of the National Health Fund for the years from 2012 to 2014 to obtain data on the prevalence and treatment patterns of IBD. Patients with IBD were identified according to the ICD-10 codes indicated in medical records and the type of medical resource utilized during the study. Pharmacotherapy for IBD by age group, sex and IBD types was presented.

Results

The prevalence of IBDs was 157/100 000 individuals, including 35 patients with CD per 100 000 individuals. The use of drugs differed by age and diagnosis (P<0.001). Biologics, steroids and immunosuppressants were used more often by patients with CD than those with UC (13.2 vs. 0.3%, 54.5 vs. 37.5%, and 44.8 vs. 15.1%, respectively). Aminosalicylates were used more often by patients with UC than those with CD. Biologics were used most often by the youngest patients (≤18 years) and seldom by patients aged 65 years or older (7.7 and 0.1%, respectively).

Conclusion

Our study showed a moderate prevalence of IBD in Poland. Treatment patterns depended on the patient’s age and IBD type. The use of biologics was higher among young patients with CD than among older patients with other IBDs. Although not recommended, aminosalicylates were still commonly used in patients with CD, even during biologic and/or immunosuppressive treatment.
Self-Reported Cognitive Biases Are Equally Present in Patients Diagnosed With Psychotic Versus Nonpsychotic Disorders
Authors: Bastiaens Tim , Claes Laurence , Smits Dirk , Vanwalleghem Dominique , De Hert Marc
Published: December 2017

We investigated the relation between subjective cognitive biases measured with the Dutch Davos Assessment of Cognitive Biases (DACOBS-NL) and (1) the presence of a psychotic versus nonpsychotic psychiatric disorder, (2) the current dose of antipsychotic medication and current psychotic symptoms, and (3) the Personality Inventory for the DSM-5 (PID-5) Psychoticism personality trait. Results showed that DACOBS-NL subjective cognitive biases (1) were equally present in patients diagnosed with nonpsychotic disorders compared with patients with a psychotic disorder, (2) could not be explained by the current dose of antipsychotic medication, nor by current psychotic symptoms, and (3) significantly correlated with all PID-5 Personality domains. Moreover, in predicting membership of the psychotic versus nonpsychotic psychiatric disorder group, the addition of the PID-5 domains in step 2 rendered the contribution of the DACOBS-NL subjective cognitive biases in step 1 nonsignificant. Further research is needed to clarify the interplay between cognitive biases and aberrant salience in the prediction of psychotic disorders.
The Spectrum of Morphologic Alterations Associated With Infarction in Endometrial Polyps: A Report of 41 Cases
Authors: Fadare Oluwole , Renshaw Idris L. , Parkash Vinita
Published: December 2017

The authors describe the clinicopathologic features of a group of endometrial polyps that exhibited large areas of infarction, to highlight the spectrum of morphologic alterations that may occur in this setting, including moderate cytologic atypia in a subset. Forty-one infarcted endometrial polyps, classified as such based on the presence therein of confluent zones of stromal necrosis and/or sharply demarcated zones of paucicellular to acellular stromal hyalinization, were assembled from multiple institutions. All were diagnosed in biopsies, polypectomies, or curettages. The morphologic profile of the epithelium associated with the infarcted zones was compared with those of a control group of 40 consecutive noninfarcted polyps. The patients with infarcted polyps ranged in age from 23 to 94 yr and were significantly older than the control group patients (mean ages, 60.8 vs. 49 yr respectively; P=0.02). The most common architectural alteration in infarcted polyps was a distinctive cellular tufting or pseudopapillary change, possibly representing an exuberant iteration of papillary syncytial change, which was seen in 39% of cases. Among the features that were significantly more prevalent in infarcted polyps than the control group were grade 2 pleomorphism (i.e., a 2–3-fold variation in nuclear size and/or shape) (37% vs. 2.5%, respectively; P=0.00029), cellular syncytia (44% vs. 15%; P=0.069), vesicular chromatin greater than background glands (56% vs. 7.5%; P <0.0001), hobnail cells (27% vs. 0%; P=0.0004), clear cells (12% vs. 0%; P=0.055), and eosinophilic cells (56% vs. 15%; P=0.000115). The 2 groups were not significantly different regarding mitotic index and a variety of other morphologic variables. Irrespective of morphology, epithelia within the infarcted zones at least focally showed a core immunophenotype (p53-wild type, p16-diffusely positive; low proliferative index) that was essentially identical to the phenotype displayed by foci of papillary syncytial metaplasia unassociated with polyps in a 10-case comparison group. None of the 34 patients with follow-up information has subsequently been diagnosed with a uterine neoplasm. In summary, infarcted endometrial polyps frequently display a spectrum of cytoarchitecturally atypical epithelial changes. These pseudoneoplastic alterations are most likely degenerative and/or metaplastic in nature.
Is There a Limit? A Risk Assessment Model of Liposuction and Lipoaspirate Volume on Complications in Abdominoplasty
Authors: Vieira Brittany L. , Chow Ian , Sinno Sammy , Dorfman Robert G. , Hanwright Philip , Gutowski Karol A.
Published: December 2017

Background:

Combining liposuction and abdominoplasty is controversial because of concerns for increased complications and potential for vascular compromise of the abdominoplasty flap. Also, the lipoaspirate volume in abdominoplasty is regulated in some areas to as little as 500 ml when performed with abdominoplasty. This study measures abdominoplasty complication rates when performed with and without trunk liposuction, and evaluates the effect of lipoaspirate volume on complications.

Methods:

Abdominoplasty and liposuction of the trunk procedures were identified in the Tracking Operations and Outcomes for Plastic Surgeons database. Multivariate regression models determined the effect of liposuction with abdominoplasty on complications compared with abdominoplasty alone and determined the effect of liposuction volume on complications.

Results:

Eleven thousand one hundred ninety-one patients were identified: 9638 (86.1 percent) having abdominoplasty with truncal liposuction and 1553 (13.9 percent) having abdominoplasty alone. Overall complication rates were 10.5 percent and 13.0 percent, respectively. Combined liposuction and abdominoplasty was independently associated with a reduced risk of both overall complications (p = 0.046) and seroma (p = 0.030). Given existing laws limiting liposuction volume to 500 or 1000 ml in combination with abdominoplasty, each of these thresholds was evaluated, with no effect on complications. Surprisingly, increasing liposuction volume was not independently associated with an increased risk of any complication.

Conclusions:

When done by board-certified plastic surgeons, abdominoplasty with truncal liposuction is safe, with fewer complications than abdominoplasty alone. Regulations governing liposuction volumes in abdominoplasty are arbitrary and do not reflect valid thresholds for increased complications.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Objective Assessment of the Unilateral Cleft Lip Nasal Deformity Using Three-Dimensional Stereophotogrammetry: Severity and Outcome
Authors: Mercan Ezgi , Oestreich Makinna , Fisher David M. , Allori Alexander C. , Beals Stephen P. , Samson Thomas D. , Sitzman Thomas J. , Matic Damir B. , Siebold Babette S. , Tse Raymond W.
Published: December 2017

Background:

Optimization of care to correct the unilateral cleft lip nasal deformity is hampered by lack of objective measures to quantify preoperative severity and outcome. The purpose of this study was to develop a consensus standard of nasal appearance using three-dimensional stereophotogrammetry; determine whether anthropometric measurements could be used to quantify severity and outcome; and determine whether preoperative severity predicts postoperative outcome.

Methods:

The authors collected facial three-dimensional images of 100 subjects in three groups: 45 infants before cleft lip repair; the same 45 infants after cleft lip repair; and 45 children aged 8 to 10 years with previous repairs. Five additional age-matched unaffected control subjects were included in each group. Seven expert surgeons ranked images in each group according to nasal appearance. The rank sum score was used as consensus standard. Anthropometric analysis was performed on each image and compared to the rank sum score. Preoperative rank and anthropometric measurements were compared to postoperative rank.

Results:

Interrater and intrarater reliability was excellent (intraclass correlation coefficient, >0.76; Pearson correlation, >0.75) on each of the three image sets. Columellar angle, nostril width ratio, and lateral lip height ratio were highly correlated with preoperative severity and moderately correlated with postoperative nasal appearance. Postoperative outcome was associated with preoperative severity (rank and anthropometric measurement).

Conclusions:

Consensus ranking of preoperative severity and postoperative outcome can be achieved on three-dimensional images. Preoperative severity predicts postoperative outcomes. Columellar angle, nostril width ratio, and lateral lip height ratio are objective measures that correlate with consensus ratings by surgeons at multiple ages.
The first seizure as an indicator of epilepsy
Authors: Kunze Albrecht , Reuber Markus
Published: December 2017

Purpose of review

Optimal treatment of a possible first seizure depends on the determination if the paroxysmal event was an epileptic seizure and was on an accurate assessment of the recurrence risk. This review summarizes evidence from the last 5 years addressing the following questions: Is it an epileptic seizure? Is it a first seizure? When does a first seizure indicate epilepsy?

Recent findings

The acts of taking and interpreting the history from patients and witnesses continue to be the most important tools in the diagnosis of first seizures. Assessment tools based on factual questions and the observation of patients’ conversational behaviour can contribute to the differentiation of patients with epileptic seizures from those who have experienced other types of transient loss of consciousness (TLOC). At present, only about 40% of patients are seen after their very first seizure. Tests have a limited role in the initial diagnosis of a seizure but help to determine the recurrence risk based on the cause. A remote symptomatic cause and detection of epileptiform discharges are associated with a recurrence risk of at least 60% and allow a diagnosis of epilepsy after a first seizure. The risk of recurrence after an acute symptomatic first seizure is well below 60%.

Expert history-taking continues to be the most important tool in the diagnosis of a first seizure. Cause is the most important determinant of the recurrence risk. Unfortunately, there is currently no formula enabling a precise calculation of an individualized recurrence risk.
Semantic Feature Disturbance in Alzheimer Disease: Evidence from an Object Decision Task
Authors: Flanagan Kieran J. , Copland David A. , Chenery Helen J. , Byrne Gerard J. , Angwin Anthony J.
Published: December 2017

Background and Objective:

It is widely held that semantic disturbance in Alzheimer disease (AD) involves the loss of distinctive features but the relative sparing of nondistinctive features. Many previous studies of semantic feature disturbance have used cognitively challenging tasks with verbal stimuli that allow for potential cognitive confounds. Our objective was to use a task with lower memory demands to investigate distinctive feature disturbance in AD.

Methods:

We used an object decision task to compare the processing of distinctive and nondistinctive semantic features in people with AD and age-matched controls. The task included six conditions based on the relationship between each prime and target object. We tested the processing of distinctive and nondistinctive features by selectively altering distinctive and nondistinctive semantic features between prime and target pairs.

Results:

Performance accuracy was significantly lower for participants with AD than for age-matched controls when distinctive features were manipulated, but no difference was found when nondistinctive features were manipulated.

Conclusions:

Our results provide evidence of semantic content disturbance in AD in the context of a task with low cognitive demands.
AP-4 vesicles contribute to spatial control of autophagy via RUSC-dependent peripheral delivery of ATG9A
Authors: Davies Alexandra K. , Itzhak Daniel N. , Edgar James R. , Archuleta Tara L. , Hirst Jennifer , Jackson Lauren P. , Robinson Margaret S. , Borner Georg H. H.
Published: December 2017

Adaptor protein 4 (AP-4) is an ancient membrane trafficking complex, whose function has largely remained elusive. In humans, AP-4 deficiency causes a severe neurological disorder of unknown aetiology. We apply unbiased proteomic methods, including ‘Dynamic Organellar Maps’, to find proteins whose subcellular localisation depends on AP-4. We identify three transmembrane cargo proteins, ATG9A, SERINC1 and SERINC3, and two AP-4 accessory proteins, RUSC1 and RUSC2. We demonstrate that AP-4 deficiency causes missorting of ATG9A in diverse cell types, including patient-derived cells, as well as dysregulation of autophagy. RUSC2 facilitates the transport of AP-4-derived, ATG9A-positive vesicles from the TGN to the cell periphery. These vesicles cluster in close association with autophagosomes, suggesting they are the “ATG9A reservoir” required for autophagosome biogenesis. Our study uncovers ATG9A trafficking as a ubiquitous function of the AP-4 pathway. Furthermore, it provides a potential molecular pathomechanism of AP-4 deficiency, through dysregulated spatial control of autophagy.
Measures of time series coupling based on generalized weighted multiple regression
Authors: Pascual-Marqui Roberto D. , Biscay Rolando J. , Bosch-Bayard Jorge , Faber Pascal , Kinoshita Toshihiko , Kochi Kieko , Milz Patricia , Nishida Keiichiro , Yoshimura Masafumi
Published: December 2017

1.

The sharing and the transmission of information between cortical brain regions is carried out by mechanisms that are still not fully understood. A deeper understanding should shed light on how consciousness and cognition are implemented in the brain. Research activity in this field has recently been focusing on the discovery of non-conventional coupling mechanisms, such as all forms of cross-frequency couplings between diverse combinations of amplitudes and phases, applied to measured or estimated cortical signals of electric neuronal activity. However, all coupling measures that involve phase computation have poor statistical properties. In this work, the conventional estimators for the well-known phase-phase (phase synchronization or locking), phase-amplitude, and phaseamplitude-amplitude couplings are generalized by means of the weighted multiple regression model. The choice of appropriate weights produces estimators that bypass the need for computing the complex-valued phase. In addition, a new coupling, denoted as the inhibitory coupling (InhCo), is introduced and defined as the dependence of one complex-valued variable on the inverse and on the conjugate inverse of another complex-valued variable. A weighted version denoted as wInhCo is also introduced, bypassing the need for computing the inverse of a complex variable, which has very poor statistical properties. The importance of this form of inhibitory coupling is that it may capture well- known processes, such as the observed inverse alpha/gamma relation within the same cortical region, or the inverse alpha/alpha relation between distant cortical regions.
Parallel Likelihood Calculation for Phylogenetic Comparative Models: the SPLITT C++ Library
Authors: Mitov Venelin , Stadler Tanja
Published: December 2017

Phylogenetic comparative models (PCMs) have been used to study macroevolutionary patterns, to characterize adaptive phenotypic landscapes, to quantify rates of evolution, to measure the heritability of traits, and to test various evolutionary hypotheses. A major obstacle to applying these models has been the complexity of evaluating their likelihood function. Recent works have shown that for many PCMs, the likelihood can be obtained in time proportional to the size of the tree based on post-order tree traversal, also known as pruning. Despite this progress, inferring complex multi-trait PCMs on large trees remains a time-intensive task. Here, we study parallelizing the pruning algorithm as a generic technique for speeding-up PCM-inference.

We implement several parallel traversal algorithms in the form of a generic C++ library for Serial and Parallel LIneage Traversal of Trees (SPLITT). Based on SPLITT, we provide examples of parallel likelihood evaluation for several popular PCMs, ranging from a single-trait Brownian motion model to complex multi-trait Ornstein-Uhlenbeck and mixed Gaussian phylogenetic models.

Using the phylogenetic Ornstein-Uhlenbeck mixed model (POUMM) as a showcase, we run benchmarks on up to 24 CPU cores, reporting up to an order of magnitude parallel speed-up on simulated balanced and unbalanced trees of up to 100,000 tips with up to 16 traits. Noticing that the parallel speed-up depends on multiple factors, the SPLITT library is capable to automatically select the fastest traversal strategy for a given hardware, tree-topology, and data. Combining SPLITT likelihood calculation with adaptive Metropolis sampling on real data, we show that the time for Bayesian POUMM inference on a tree of 10,000 tips can be reduced from several days to minutes.

We conclude that parallel pruning effectively accelerates the likelihood calculation and, thus, the statistical inference of Gaussian phylogenetic models. For time-intensive Bayesian inferences, we recommend combining this technique with adaptive Metropolis sampling. Beyond Gaussian models, the parallel tree traversal can be applied to numerous other models, including discrete trait and birth-death population dynamics models. Currently, SPLITT supports multi-core shared memory architectures, but can be extended to distributed memory architectures as well as graphical processing units.
Mutations alter RNA-mediated conversion of human prions
Authors: Alred Erik J. , Lodangco Izra D. , Gallaher Jennifer , Hansmann Ulrich
Published: December 2017

Prion diseases are connected with self-replication and self-propagation of mis-folded proteins. The rate-limiting factor is the formation of the initial seed. We have recently studied early stages in the conversion between functional PrPC and the infectious scrapie PrPSC form, triggered by the binding of RNA. Here, we study how this process is modulated by the prion sequence. We focus on residues 129 and 178, which are connected to the hereditary neurodegenerative disease Fatal Familial Insomnia.
Fitness traits of deoxynivalenol and nivalenol-producing Fusarium graminearum species complex strains from wheat
Authors: Nicolli C.P. , Machado F.J. , Spolti P. , Del Ponte E.M.
Published: December 2017

Fusarium graminearum of the 15-acetyl(A)deoxynivalenol(D0N) chemotype is the main cause of Fusarium head blight (FHB) of wheat in south of Brazil. However, 3-ADON and nivalenol(NIV) chemotypes have been found in other members of the species complex causing FHB in wheat. To improve our understanding of the pathogen ecology, we assessed a range of fitness-related traits in a sample of 30 strains representatives of 15-ADON (F. graminearum), 3-ADON (F. cortaderiae and F. austroamericanum) and NIV (F. meridionale and F. cortaderiae). These included: perithecia formation on three cereal-based substrates, mycelial growth at two suboptimal temperatures, sporulation and germination, pathogenicity towards a susceptible and a moderately resistant cultivar and sensitivity to tebuconazole. The most important trait favoring F. graminearum was its 2x higher sexual fertility (> 40% PPI = perithecia production index) than the other species (< 30% PPI); PPI varied among substrates (maize > rice > wheat). In addition, sensitivity to tebuconazole appeared lower in F. graminearum which had the only strain with EC50 > 1 ppm. In the pathogenicity assays, the DON-producers were generally more aggressive (1.5 to 2x higher final severity) towards the two cultivars, with 3-ADON or 15-ADON leading to higher area under the severity curve than the NIV strains in the susceptible and moderately resistant cv., respectively. There was significant variation among strains of a same species with regards asexual fertility (mycelial growth, macroconidia production and germination), which suggest a strain-rather than a species-specific differences. These results contribute new knowledge to improve our understanding of the pathogen-related traits that may explain the dominance of certain members of the species complex in specific wheat agroecosystems.
Hi-TOM: a platform for high-throughput tracking of mutations induced by CRISPR/Cas systems
Authors: Liu Qing , Wang Chun , Jiao Xiaozhen , Zhang Huawei , Song Lili , Li Yanxin , Gao Caixia , Wang Kejian
Published: December 2017

The CRISPR/Cas system has been extensively applied to make precise genetic modifications in various organisms. Despite its importance and widespread use, large-scale mutation screening remains time-consuming, labour-intensive and costly. Here, we describe a cheap, practicable and high-throughput screening strategy that allows parallel screening of 96 × N (N denotes the number of targets) genome-modified sites. The strategy simplified and streamlined the process of next-generation sequencing (NGS) library construction by fixing the bridge sequences and barcoding primers. We also developed Hi-TOM (available at http://www.hi-tom.net/hi-tom/), an online tool to track the mutations with precise percentage. Analysis of the samples from rice, hexaploid wheat and human cells reveals that the Hi-TOM tool has high reliability and sensitivity in tracking various mutations, especially complex chimeric mutations that frequently induced by genome editing. Hi-TOM does not require specially design of barcode primers, cumbersome parameter configuration or additional data analysis. Thus, the streamlined NGS library construction and comprehensive result output make Hi-TOM particularly suitable for high-throughput identification of all types of mutations induced by CRISPR/Cas systems.
Linkage Disequilibrium Estimation in Low Coverage High-Throughput Sequencing Data
Authors: Bilton Timothy P. , McEwan John C. , Clarke Shannon M. , Brauning Rudiger , van Stijn Tracey C. , Rowe Suzanne J. , Dodds Ken G.
Published: December 2017

High-throughput sequencing methods that multiplex a large number of individuals have provided a cost-effective approach for discovering genome-wide genetic variation in large populations. These sequencing methods are increasingly being utilized in population genetic studies across a diverse range of species. One side-effect of these methods, however, is that one or more alleles at a particular locus may not be sequenced, particularly when the sequencing depth is low, resulting in some heterozygous genotypes being called as homozygous. Under-called heterozygous genotypes have a profound effect on the estimation of linkage disequilibrium and, if not taken into account, leads to inaccurate estimates. We developed a new likelihood method, GUS-LD, to estimate pairwise linkage disequilibrium using low coverage sequencing data that accounts for under-called heterozygous genotypes. Our findings show that accurate estimates were obtained using GUS-LD on low coverage sequencing data, whereas underestimation of linkage disequilibrium results if no adjustment is made for under-called heterozygotes.
Mushroom body-specific profiling of gene expression identifies regulators of long-term memory inDrosophila
Authors: Widmer Yves F , Bilican Adem , Bruggmann Rémy , Sprecher Simon G
Published: December 2017

Memory formation is achieved by genetically tightly controlled molecular pathways that result in a change of synaptic strength and synapse organization. While for short-term memory traces rapidly acting biochemical pathways are in place, the formation of long-lasting memories requires changes in the transcriptional program of a cell. Although many genes involved in learning and memory formation have been identified, little is known about the genetic mechanisms required for changing the transcriptional program during different phases of long-term memory formation. WithDrosophila melanogasteras a model system we profiled transcriptomic changes in the mushroom body, a memory center in the fly brain, at distinct time intervals during long-term memory formation using the targeted DamID technique. We describe the gene expression profiles during these phases and tested 33 selected candidate genes for deficits in long-term memory formation using RNAi knockdown. We identified 10 genes that enhance or decrease memory when knocked-down in the mushroom body. Forvajk-1andhacd1, the two strongest hits, we gained further support for their crucial role in learning and forgetting. These findings show that profiling gene expression changes in specific cell-types harboring memory traces provides a powerful entry point to identify new genes involved in learning and memory. The presented transcriptomic data may further be used as resource to study genes acting at different memory phases.
Random Forest Feature Selection, Fusion and Ensemble Strategy: Combining Multiple Morphological MRI Measures to Discriminate among healthy elderly, MCI, cMCI and Alzheimer's disease patients: from the Alzheimer’s disease neuroimaging initiative (ADNI) database
Authors: Dimitriadis S.I. , Liparas D. , Tsolaki Magda N.
Published: December 2017

Background

In the era of computer-assisted diagnostic tools for various brain diseases, Alzheimer’s disease (AD) covers a large percentage of neuroimaging research, with the main scope being its use in daily practice. However, there has been no study attempting to simultaneously discriminate among Healthy Controls (HC), early mild cognitive impairment (MCI), late MCI (cMCI) and stable AD, using features derived from a single modality, namely MRI.

New Method

Based on preprocessed MRI images from the organizers of a neuroimaging challenge2, we attempted to quantify the prediction accuracy of multiple morphological MRI features to simultaneously discriminate among HC, MCI, cMCI and AD. We explored the efficacy of a novel scheme that includes multiple feature selections via Random Forest from subsets of the whole set of features (e.g. whole set, left/right hemisphere etc.), Random Forest classification using a fusion approach and ensemble classification via majority voting.

From the ADNI database, 60 HC, 60 MCI, 60 cMCI and 60 AD were used as a training set with known labels. An extra dataset of 160 subjects (HC: 40, MCI: 40, cMCI: 40 and AD: 40) was used as an external blind validation dataset to evaluate the proposed machine learning scheme.

Results

In the second blind dataset, we succeeded in a four-class classification of 61.9% by combining MRI-based features with a Random Forest-based Ensemble Strategy. We achieved the best classification accuracy of all teams that participated in this neuroimaging competition.

Comparison with Existing Method(s)

The results demonstrate the effectiveness of the proposed scheme to simultaneously discriminate among four groups using morphological MRI features for the very first time in the literature.

Conclusions

Hence, the proposed machine learning scheme can be used to define single and multi-modal biomarkers for AD.

HIGHLIGHTS

1stplace in International Challenge for Automated Prediction of MCI from MRI Data

Multi-class classification of normal control, MCI, converting MCI, and Alzheimer’s disease

Morphometric measures from 3D T1 brain MRI images have been analysed (ADNI1 cohort).

ARandom Forest Feature Selection, Fusion and Ensemble Strategywas applied to classification and prediction of AD.

Accuracy and robustness have been assessed in a blind dataset
Computational Model for Simulating Drug-Induced Arrhythmia Sensitivity of Human iPSC-derived Cardiomyocytes
Authors: Gao Xin , Yin Yue , Daily Neil , Engel Tyler , Pang Li , Carlson Brian E. , Wakatsuki Tetsuro
Published: December 2017

A mathematical model describing the electrophysiology and ion handling of cardiomyocytes is a complement to experimental analysis predicting drug-induced proarrhythmic potential in humans as proposed by Comprehensive in vitro Proarrhythmia Assay (CiPA). While CiPA endorses the use of the O’Hara Rudy (ORd) model, which was developed to simulate electrophysiology of human adult ventricular cardiomyocytes (hAVCMs), to predict drug-induced proarrhythmias; the human induced pluripotent stem cell derived-cardiomyocytes (hiPSC-CMs) was proposed for experimental verifications. The hiPSC-CMs, especially cultured in 2D culture dishes, are inherently different from hAVCMs exhibiting different ion channel density and an immature sarcoplasmic reticulum function. To reconcile this mismatch, we have developed a mathematical electrophysiology model of an hiPSC-CM by incorporating differences in gene expressions of ion channels, pumps and receptors in hiPSC-CMs against those found in hAVCMs. This model can be used to model any hiPSC-CM cell line where expression data has been obtained and replaces the background currents for K+ and Na+ in the ORd model with the known ultra-rapid K+ channel and hyperpolarization activated K+/Na+ channel currents. With this new model, three batches each from two different hiPSC-CM cell lines are compared to experimental data of action potential duration. This mathematical model recapitulates a ventricular-like action potential morphology with a Phase 2 plateau lasting a few hundred milliseconds. However, the resting membrane potential is not as depolarized (−65 to −70 mV) as that of hAVCM (-80 mV). The elevated resting membrane potential matches experimental data previously and is thought to keep rapid sodium channels from triggering membrane depolarization instead being replaced by an overexpression of L-Type Ca2+ channel current. This model is a key step in identifying the variability between different hiPSC-CM lines and even batches of the same line, opening the door to realizing analysis of patient specific preparations in the future.
Two sets of wing homologs in the crustacean,Parhyale hawaiensis
Authors: Clark-Hachtel Courtney M. , Tomoyasu Yoshinori
Published: December 2017

The origin of insect wings is a biological mystery that has fascinated scientists for centuries. Through extensive investigations performed across various fields, two possible wing origin tissues have been identified; a lateral outgrowth of the dorsal body wall (tergum) and ancestral proximal leg structures1,2. With each idea offering both strengths and weaknesses, these two schools of thought have been in an intellectual battle for decades without reaching a consensus3. Identification of tissues homologous to insect wings from linages outside of Insecta will provide pivotal information to resolve this conundrum. Here, through expression analyses and CRISPR/Cas9-based genome-editing in the crustacean,Parhyale hawaiensis, we show that a wing-like gene regulatory network (GRN) operates both in the crustacean terga and in the proximal leg segments, suggesting that (i) the evolution of a wing-like GRN precedes the emergence of insect wings, and (ii) that both of these tissues are equally likely to be crustacean wing homologs. Interestingly, the presence of two sets of wing homologs parallels previous findings in some wingless segments of insects, where wing serial homologs are maintained as two separate tissues4–7. This similarity provides crucial support for the idea that the wingless segments of insects indeed reflect an ancestral state for the tissues that gave rise to the insect wing, while the true insect wing represents a derived state that depends upon the contribution of two distinct tissues. These outcomes point toward a dual origin of insect wings, and thus provide a crucial opportunity to unify the two historically competing hypotheses on the origin of this evolutionarily monumental structure.
Landscape of gene transposition-duplication within the Brassicaceae family
Authors: Oh Dong-Ha , Dassanayake Maheshi
Published: December 2017

We developed the CLfinder-OrthNet pipeline that detects co-linearity in gene arrangement among multiple closely related genomes; find ortholog groups; and encodes the evolutionary history of each ortholog group into a representative network (OrthNet). Using a search based on network topology, out of a total of 17,432 OrthNets in six Brassicaceae genomes, we identified 1,394 that included gene transposition-duplication (tr-d) events in one or more genomes. Occurrences of tr-d shared by subsets of Brassicaceae genomes mirrored the divergence times between the genomes and their repeat contents. The majority of tr-d events resulted in truncated open reading frames (ORFs) in the duplicated loci. However, the duplicates with complete ORFs were significantly more frequent than expected from random events. They also had a higher chance of being expressed and derived from older tr-d events. We also found an enrichment, compared to random chance, of tr-d events with complete loss of intergenic sequence conservation between the original and duplicated loci. Finally, we identified tr-d events uniquely found in two extremophytes among the six Brassicaceae genomes, including tr-d of SALT TOLERANCE 32 and ZINC TRANSPORTER 3. The CLfinder-OrthNet pipeline provides a flexible and a modular toolkit to compare gene order, encode and visualize evolutionary paths among orthologs as networks, and identify all gene loci that share the same evolutionary history using network topology searches.

Funding source: This work was supported by National Science Foundation (MCB 1616827) and the Next Generation BioGreen21 Program (PJ011379) of the Rural Development Administration, Republic of Korea.

Online-only Supplementary materials includes supplementary text (S1-S10), methods (M1-M4), figures (S1-S7), and tables (S1-S3), in two PDF files, one for text and methods and the other for figures and tables. Additionally, Supplementary Dataset S1 is available at the Figshare repository (https://doi.org/10.6084/m9.figshare.5825937) and Dataset S2 and S3 as separate Excel files.
Large-scale discovery of mouse transgenic integration sites reveals frequent structural variation and insertional mutagenesis
Authors: Goodwin Leslie O. , Splinter Erik , Davis Tiffany L. , Urban Rachel , He Hao , Braun Robert E. , Chesler Elissa J. , Kumar Vivek , van Min Max , Ndukum Juliet , Philip Vivek M. , Reinholdt Laura G. , Svenson Karen , White Jacqueline K. , Sasner Michael , Lutz Cathleen , Murray Stephen A.
Published: December 2017

Transgenesis has been a mainstay of mouse genetics for over 30 years, providing numerous models of human disease and critical genetic tools in widespread use today. Generated through the random integration of DNA fragments into the host genome, transgenesis can lead to insertional mutagenesis if a coding gene or essential element is disrupted, and there is evidence that larger scale structural variation can accompany the integration. The insertion sites of only a tiny fraction of the thousands of transgenic lines in existence have been discovered and reported due in part to limitations in the discovery tools. Targeted Locus Amplification (TLA) provides a robust and efficient means to identify both the insertion site and content of transgenes through deep sequencing of genomic loci linked to specific known transgene cassettes. Here, we report the first large-scale analysis of transgene insertion sites from 40 highly used transgenic mouse lines. We show that the transgenes disrupt the coding sequence of endogenous genes in half of the lines, frequently involving large deletions and/or structural variations at the insertion site. Furthermore, we identify a number of unexpected sequences in some of the transgenes, including undocumented cassettes and contaminating DNA fragments. We demonstrate that these transgene insertions can have phenotypic consequences, which could confound certain experiments, emphasizing the need for careful attention to control strategies. Together, these data show that transgenic alleles display a high rate of potentially confounding genetic events, and highlight the need for careful characterization of each line to assure interpretable and reproducible experiments.
Anomalous Diffusion as a Descriptive Model of Cell Migration
Authors: Luzhanskey Igor D. , MacMunn John P. , Cohen Joshua D. , Barney Lauren E. , Jansen Lauren E. , Schwartz Alyssa D. , Peyton Shelly R.
Published: December 2017

Appropriately chosen descriptive models of cell migration in biomaterials will allow researchers to characterize and ultimately predict the movement of cells in engineered systems for a variety of applications in tissue engineering. The persistent random walk (PRW) model accurately describes cell migration on two-dimensional (2D) substrates. However, this model inherently cannot describe subdiffusive cell movement, i.e. migration paths in which the root mean square displacement increases more slowly than the square root of the time interval. Subdiffusivity is a common characteristic of cells moving in confined environments, such as three-dimensional (3D) porous scaffolds, hydrogel networks, and in vivo tissues. We demonstrate that a generalized anomalous diffusion (AD) model, which uses a simple power law to relate the mean square displacement (MSD) to time, more accurately captures individual cell migration paths across a range of engineered 2D and 3D environments than does the more commonly used PRW model. We used the AD model parameters to distinguish cell movement profiles on substrates with different chemokinetic factors, geometries (2D vs 3D), substrate adhesivities, and compliances. Although the two models performed with equal precision for superdiffusive cells, we suggest a simple AD model, in lieu of PRW, to describe cell trajectories in populations with a significant subdiffusive fraction, such as cells in confined, 3D environments.
Decoupling from yolk sac is required for extraembryonic tissue spreading in the scuttle fly Megaselia abdita
Authors: Caroti Francesca , Avalos Everardo González , Noeske Viola , Avalos Paula González , Kromm Dimitri , Wosch Maike , Schütz Lucas , Hufnagel Lars , Lemke Steffen
Published: December 2017

Extraembryonic tissues contribute to animal development, which often entails spreading over embryo or yolk. Apart from changes in cell shape, the requirements for this tissue spreading are not well understood. Here we analyze spreading of the extraembryonic serosa in the scuttle fly Megaselia abdita. The serosa forms from a columnar blastoderm anlage, becomes a squamous epithelium, and eventually spreads over the embryo proper. We describe the dynamics of this process in long-term, whole-embryo time-lapse recordings, demonstrating that free serosa spreading is preceded by a prolonged pause in tissue expansion. Closer examination of this pause reveals mechanical coupling to the underlying yolk sac, which is later released. We find mechanical coupling prolonged and serosa spreading impaired after knockdown of M. abdita Matrix metalloprotease 1. We conclude that tissue-tissue interactions provide a critical functional element to constrain spreading epithelia.

Impact Statement

Extraembryonic tissue spreading in the scuttle fly Megaselia abdita requires mechanical decoupling from the underlying yolk sac.
Crystal structure of 5,15-bis(4-methylphenyl)-10,20-bis(4-nitrophenyl)porphyrin nitrobenzene disolvate
Authors: Baptayev Bakhytzhan , Adilov Salimgerey
Published: December 2017

The whole molecule of the title porphyrin, C46H32N6O4·2C6H5NO2, which crystallized as a nitrobenzene disolvate, is generated by inversion symmetry. The porphyrin macrocycle is almost planar, the maximum deviation from the mean plane of the non-hydrogen atoms is 0.097 (2) Å. The aryl rings at themesopositions are inclined to this mean plane by 74.84 (6)° for the nitrophenyl rings and 73.37 (7)° for the tolyl rings. In the crystal, the porphyrin molecules are linked by C—H...O hydrogen bonds, forming chains along [100]. The solvent molecules are also linked by C—H...O hydrogen bonds, forming chains along [100]. Interdigitation of thep-tolyl groups along thecaxis creates rectangular channels in which the solvent molecules are located.
Exploring FM’s dominant logics
Authors: Price Ilfryn
Published: December 2017

Purpose

This paper aims to investigate the service ecosystem of facility/facilities management (FM) against the Vargo and Lusch framework of service-dominant logic (S-D Logic).

Design/methodology/approach

A theoretical argument guided by previous research into service excellence in FM.

Findings

In the paper, two arguments are made. First, FM is still dominated by a contractual logic grounded in the tangible world of buildings and bills of quantities. Second, the reciprocal flow of services inherent in the S-D Logic offers a powerful tool for appreciating real service excellence and a business contribution from FM.

Research limitations/implications

The S-D Logic framework is theoretical but, it is argued, has profound implications for the practical delivery of FM and the addition of both business and social value.

Originality/value

The reciprocal flow of service (as recognition, involvement and development) to FM’s “shop-floor” staff – the actual fee earners – may be the cornerstone of the co-creation and partnership, much espoused but less frequently practiced.
Failing to plan – planning to fail
Authors: Boge Knut , Salaj AlenkaTemeljotov , Bjørberg Svein , Larssen Anne Kathrine
Published: December 2017

Purpose

The purpose of this paper is to know how do early-phase planning of real estate (RE) and facilities management (FM) create value for owners and users of commercial and public sector buildings.

Design/methodology/approach

The data were collected in Norway in 2015 through a national online survey (N = 837). The sample gives a good picture of Norwegian owners’ and even users on tactical-level (customer) perspectives on RE and FM. The data have been analysed through descriptive statistics and exploratory factor analysis. The hypotheses have been tested through analyses of correlations and ordinary least square (OLS) linear regressions.

Findings

Exploratory factor analysis made it possible to establish seven composite variables (constructs). Based on these seven constructs, six hypotheses were derived and tested. Obstacles and financials have no significant effect on buildings’ perceived usability. The most important factors during early-phase planning that influence buildings’ perceived usability and lifetime value creation are measures promoting environment and life-cycle costs (LCC), FM, adaptability and image.

Research limitations/implications

Further empirical and preferably, comparative studies are needed to establish whether the findings can be generalized. The study has shown that a building’s usability and lifetime value creation is largely determined by decisions made during early phase planning.

Practical implications

Well-founded early-phase planning of RE and FM may actually provide very high return on the investments and significantly improve the buildings’ lifetime value creation for owners and users. Early-phase planning is also of great importance both for buildings’ physical design, as well as for successful FM during the buildings’ use phase, and may prevent irreversible blunders.

Originality/value

This is a large N empirical study in Norway. The findings indicate what owner and users of buildings should emphasize during early phase planning.
Moderation effect on Islamic banking preferences in UAE
Authors: Warsame Mohammed Hersi , Ireri Edward Mugambi
Published: December 2017

Purpose

The purpose of this paper is to examine the direct and indirect moderation effects of demographic and socio-economic(s) factors on the adoption of Islamic banking in UAE.

Design/methodology/approach

Convenience sampling was done on the residents of Sharjah, Dubai, and Abu Dhabi. A closed-ended questionnaire with 30 items was designed and pre-tested before the start of the study. Path analysis and moderation testing were the main analytical approach. A total of 320 respondents completed the survey.

Findings

The research revealed that demographic and socio-economic(s) moderators may have direct and indirect moderation effects on the adoption of the Islamic banking in the UAE, which indicates the importance of these factors in the provision of Islamic banking products and services in the UAE.

Practical implications

This study further revealed that these moderators have huge practical implications for Islamic bank managers and marketers as they can exploit these demographics to enhance their market share in the UAE.

Social implications

In UAE, minimal attention has been directed toward the role moderators would play in the criterion that individual investors would use in the adoption of Islamic banking products and services in a cosmopolitan environment that is experiencing competition from conventional banks.

Originality/value

An extensive review of the existing literature on the adoption of Islamic banking reveals that no empirical research has been undertaken to explore the role played by demographic and socio-economic(s) moderators in the adoption of Islamic banking in UAE and internationally. This study attempts to fill this gap.
Lessons from Thailand: universal healthcare achievements and challenges
Authors: Nonkhuntod Ravikan , Yu Suchuan
Published: December 2017

Purpose

The purpose of this paper is to discuss the successes of Thailand’s healthcare system along with challenges it is facing, examining documents and policies used by those charged with developing and implementing health services.

Design/methodology/approach

The search pool comprised PubMed and Google Scholar from the period 2001-2015. Selection criterion for inclusion was sources dealing with out-of-pocket (OOP) expenditure and healthcare utilization in Thailand. In total, 33 studies met the criterion of containing sufficient data to be included in the meta-analysis.

Findings

The authors found a small positive effect size on OOP expenditure and healthcare utilization, obtaining values of 0.1604 (95% CI 0.1320-0.1888, p<0.0001) and 0.2788 (95% CI 0.0917-0.4659, p=0.0035), respectively.

Originality/value

To review and meta-analyze the literature dealing with the outcomes of Thailand’s healthcare system to understand whether Thailand’s healthcare system is achieving its mandate or not. The results of this paper can help policy makers to understand and evaluate Thailand’s healthcare system.