Miracle-dz/UniFAR-FTUs huggingface dataset:
The Tissue-Engineered Human Psoriatic Skin Substitute: A Valuable In Vitro Model to Identify Genes with Altered Expression in Lesional Psoriasis

Psoriasis is a chronic inflammatory skin disease for which no cure has emerged. Its complex etiology requires the development of an in vitro model representative of the pathology. In this study, we exploited gene profiling analyses on microarray in order to characterize and further optimize the production of a human psoriatic skin model representative of this in vivo skin disease. Various skin substitutes were produced by tissue-engineering using biopsies from normal, healthy donors, or from lesional or non-lesional skin samples from patients with psoriasis, and their gene expression profiles were examined by DNA microarray. We demonstrated that more than 3540 and 1088 genes (two-fold change) were deregulated between healthy/lesional and lesional/non-lesional psoriatic substitutes, respectively. Moreover, several genes related to lipid metabolism, such as PLA2G4E and PLA2G4C, were identified as repressed in the lesional substitutes. In conclusion, gene profiling analyses identified a list of deregulated candidate genes associated with various metabolic pathways that may contribute to the progression of psoriasis.
Small RNA sequencing of sessile serrated polyps identifies microRNA profile associated with colon cancer

Sessile serrated adenoma/polyps (SSA/Ps) of the colon account for 20–30% of all colon cancers. Small non‐coding RNAs, including microRNAs (miRNAs), may function as oncogenes or tumor suppressor genes involved in cancer development. Small RNA sequencing (RNA‐seq) was used to characterize miRNA profiles in SSA/Ps, hyperplastic polyps (HPs), adenomatous polyps and paired uninvolved colon. Our 108 small RNA‐seq samples' results were compared to small RNA‐seq data from 212 colon cancers from the Cancer Genome Atlas. Twenty‐three and six miRNAs were differentially expressed in SSA/Ps compared to paired uninvolved colon and HPs, respectively. Differential expression of MIR31‐5p, MIR135B‐5p and MIR378A‐5p was confirmed by RT‐qPCR. SSA/P‐specific miRNAs are similarly expressed in colon cancers containing genomic aberrations described in serrated cancers. Correlation of miRNA expression with consensus molecular subtypes suggests more than one subtype is associated with the serrated neoplasia pathway. Canonical pathway analysis suggests many of these miRNAs target growth factor signaling pathways.
Specific Volumetric Weight-Driven Shift in Microbiota Compositions With Saccharifying Activity Change in Starter for Chinese Baijiu Fermentation

Chinese starter Jiuqu, traditionally produced by spontaneous fermentation and always squeezed into bricks, serves as a vital saccharifying agent for simultaneous saccharification and fermentation of Chinese Baijiu. It is important to reveal the key saccharifying microbiota and the driving force to improve the quality of Jiuqu. Here we studied the compositions of the microbiota by high-throughput amplicons sequencing analysis in Jiuqu, and revealed eight bacterial and seven fungal genera as the dominant community members. Among them, Lactobacillus, Aspergillus, Pichia, Saccharomyces, Rhizopus were the main contributors of proteins by metaproteomics analysis. Whereas, only Lactobacillus, Pichia, Rhizopus appeared as key actors for saccharification by secreting three glycosidases and two glycosyltransferases, and it indicated they were the key saccharifying microbiota in Jiuqu. Especially, Rhizopus secreted the most abundant glucoamylase. Interestingly, these three active genera significantly decreased and the key saccharifying enzymes were down-expressed, when Jiuqu was produced in diffused shape with a low volumetric weight. Rhizopus microsporus, the main producer of glucoamylase, was positively correlated with volumetric weight of Jiuqu. It indicated volumetric weight was the major driving force of the key saccharifying microbiota in Jiuqu. This work provides deep insights of key saccharifying microbiota, and indicates the main driving force for the key microbe. Furthermore, this finding can contribute to the improvement of saccharifying agent for food fermentation.
SGLT-2 Inhibitors and DPP-4 Inhibitors as Second-Line Drugs in Patients with Type 2 Diabetes: A Meta-Analysis of Randomized Clinical Trials

Abstract Sodium-glucose co-transporter 2 (SGLT-2) inhibitors and dipeptidyl peptidase 4 (DPP-4) inhibitors are both novel and second-line therapies in type 2 diabetes mellitus, yet no well-rounded comparison of these two drugs has been published. Upon searching randomized controlled trials in databases from inception to July 2018, we collected studies on the efficacy or safety of SGLT-2 inhibitors compared with those of DPP-4 inhibitors for the treatment of type 2 diabetes mellitus. A total of 12 randomized controlled studies including 4342 patients were included in this meta-analysis. Compared with DPP-4 inhibitors, SGLT-2 inhibitors achieved greater reductions in HbA1c (SMD –0.22; 95% CI: –0.30, –0.14; p=0.000) and fasting plasma glucose (SMD –0.48; 95% CI: –0.56, –0.41; p=0.000). In addition, these reductions increased with a prolonged treatment duration from 12 to 78 weeks. Geographically, significant reductions of SGLT-2 inhibitors in HbA1c and FPG were found in North America and Europe, but not in Asia. Furthermore, SGLT-2 inhibitors showed greater reductions in body weight (SMD −0.72; 95% CI: –0.81, –0.63; p=0.000) from baseline, with an increased incidence of genital infections (OR 4.49; 95% CI: 2.96, 6.83; p=0.000) and pollakiuria (OR 2.24; 95% CI: 1.05, 4.79; p=0.037) and a decreased incidence of hypertension and hyperglycemia. Overall, the current meta-analysis demonstrated that compared to DPP-4 inhibitors, SGLT-2 inhibitors have beneficial effects on HbA1c, FPG, body weight, SBP, DBP, and HDL-cholesterol in patients with type 2 diabetes. However, SGLT-2 inhibitors are associated with increased total cholesterol and LDL-cholesterol and a higher incidence of genital infections and pollakiuria.
Synthetic-to-Natural Speech Waveform Conversion Using Cycle-Consistent Adversarial Networks

We propose a learning-based filter that allows us to directly modify a synthetic speech waveform into a natural speech waveform. Speech-processing systems using a vocoder framework such as statistical parametric speech synthesis and voice conversion are convenient especially for a limited number of data because it is possible to represent and process interpretable acoustic features over a compact space, such as the fundamental frequency (F0) and mel-cepstrum. However, a well-known problem that leads to the quality degradation of generated speech is an over-smoothing effect that eliminates some detailed structure of generated/converted acoustic features. To address this issue, we propose a synthetic-to-natural speech waveform conversion technique that uses cycle-consistent adversarial networks and which does not require any explicit assumption about speech waveform in adversarial learning. In contrast to current techniques, since our modification is performed at the waveform level, we expect that the proposed method will also make it possible to generate “vocoder-less” sounding speech even if the input speech is synthesized using a vocoder framework. The experimental results demonstrate that our proposed method can 1) alleviate the over-smoothing effect of the acoustic features despite the direct modification method used for the waveform and 2) greatly improve the naturalness of the generated speech sounds.
CRISPR/Cas9-mediated knockout of Populus BRANCHED1 and BRANCHED2 orthologs reveals a major function in bud outgrowth control

The TCP-type transcription factors BRANCHED1 and BRANCHED2 shape plant architecture by suppressing bud outgrowth, with BRANCHED2 only playing a minor role in Arabidopsis. Here, we investigated the function of orthologs of these genes in the model tree Populus. We used CRISPR/Cas9 to generate loss-of-function mutants of previously identified Populus BRANCHED1-1 and BRANCHED2-1 candidate genes. BRANCHED1-1 mutants exhibited strongly enhanced bud outgrowth. BRANCHED2-1 mutants had an extreme bud outgrowth phenotype and possessed two ectopic leaves at each node. While BRANCHED1 function is conserved in poplar, BRANCHED2, in contrast to its Arabidopsis counterpart, plays an even more critical role in bud outgrowth regulation. In addition, we identified a new, not yet reported association of this gene to leaf development.
A Worst Case Performance Analysis of Approximated Zero Forcing Vectoring for DSL Systems

In this paper we introduce a Gaussian approximation for the achievable downstream bit rate per user in modern broadband and ultra-broadband digital subscriber loop-based access systems. The considered formulation allows one to account for the main characteristics of the interference scenario (e.g., number and positions of interferers along the cable), the far-end crosstalk (FEXT) fluctuations, bit loading limitation per sub-carrier, and approximated zero forcing in vectoring pre-coding. Formulas are obtained assuming log-normal statistics for the signal-to-interference plus noise ratio per sub-carrier. The validity of the considered approximation has been assessed by computer calculation. A very good agreement between the exact and the approximated bit rates is obtained. The bit rate approximation is then used to analyze the performance of a very high-speed digital subscriber line type 2 (VDSL2, Profile 35b) with vectoring and used to assess G.fast performance degradation when approximated zero forcing in vectoring pre-coding is applied. It is observed for G.fast performance that degradation due to residual FEXT after vectoring pre-coding can be relevant. A significant performance improvement can be achieved at the expense of increased computational complexity of the vectoring pre-coding.
Ageing, Cellular Senescence and Neurodegenerative Disease

Ageing is a major risk factor for developing many neurodegenerative diseases. Cellular senescence is a homeostatic biological process that has a key role in driving ageing. There is evidence that senescent cells accumulate in the nervous system with ageing and neurodegenerative disease and may predispose a person to the appearance of a neurodegenerative condition or may aggravate its course. Research into senescence has long been hindered by its variable and cell-type specific features and the lack of a universal marker to unequivocally detect senescent cells. Recent advances in senescence markers and genetically modified animal models have boosted our knowledge on the role of cellular senescence in ageing and age-related disease. The aim now is to fully elucidate its role in neurodegeneration in order to efficiently and safely exploit cellular senescence as a therapeutic target. Here, we review evidence of cellular senescence in neurons and glial cells and we discuss its putative role in Alzheimer’s disease, Parkinson’s disease and multiple sclerosis and we provide, for the first time, evidence of senescence in neurons and glia in multiple sclerosis, using the novel GL13 lipofuscin stain as a marker of cellular senescence.
An Improved Genetic Algorithm with a New Initialization Mechanism Based on Regression Techniques

Genetic algorithm (GA) is one of the well-known techniques from the area of evolutionary computation that plays a significant role in obtaining meaningful solutions to complex problems with large search space. GAs involve three fundamental operations after creating an initial population, namely selection, crossover, and mutation. The first task in GAs is to create an appropriate initial population. Traditionally GAs with randomly selected population is widely used as it is simple and efficient; however, the generated population may contain poor fitness. Low quality or poor fitness of individuals may lead to take long time to converge to an optimal (or near-optimal) solution. Therefore, the fitness or quality of initial population of individuals plays a significant role in determining an optimal or near-optimal solution. In this work, we propose a new method for the initial population seeding based on linear regression analysis of the problem tackled by the GA; in this paper, the traveling salesman problem (TSP). The proposed Regression-based technique divides a given large scale TSP problem into smaller sub-problems. This is done using the regression line and its perpendicular line, which allow for clustering the cities into four sub-problems repeatedly, the location of each city determines which category/cluster the city belongs to, the algorithm works repeatedly until the size of the subproblem becomes very small, four cities or less for instance, these cities are more likely neighboring each other, so connecting them to each other creates a somehow good solution to start with, this solution is mutated several times to form the initial population. We analyze the performance of the GA when using traditional population seeding techniques, such as the random and nearest neighbors, along with the proposed regression-based technique. The experiments are carried out using some of the well-known TSP instances obtained from the TSPLIB, which is the standard library for TSP problems. Quantitative analysis is carried out using the statistical test tools: analysis of variance (ANOVA), Duncan multiple range test (DMRT), and least significant difference (LSD). The experimental results show that the performance of the GA that uses the proposed regression-based technique for population seeding outperforms other GAs that uses traditional population seeding techniques such as the random and the nearest neighbor based techniques in terms of error rate, and average convergence.
Design Thinking in Health Care

Introduction Applying Design Thinking to health care could enhance innovation, efficiency, and effectiveness by increasing focus on patient and provider needs. The objective of this review is to determine how Design Thinking has been used in health care and whether it is effective. Methods We searched online databases (PubMed, Medline, Web of Science, CINAHL, and PyscINFO) for articles published through March 31, 2017, using the terms “health,” “health care,” or “healthcare”; and “Design Thinking,” “design science,” “design approach,” “user centered design,” or “human centered design. ” Studies were included if they were written in English, were published in a peer-reviewed journal, provided outcome data on a health-related intervention, and used Design Thinking in intervention development, implementation, or both. Data were collected on target users, health conditions, intervention, Design Thinking approach, study design or sample, and health outcomes. Studies were categorized as being successful (all outcomes improved), having mixed success (at least one outcome improved), or being not successful (no outcomes improved). Results Twenty-four studies using Design Thinking were included across 19 physical health conditions, 2 mental health conditions, and 3 systems processes. Twelve were successful, 11 reported mixed success, and one was not successful. All 4 studies comparing Design Thinking interventions to traditional interventions showed greater satisfaction, usability, and effectiveness. Conclusion Design Thinking is being used in varied health care settings and conditions, although application varies. Design Thinking may result in usable, acceptable, and effective interventions, although there are methodological and quality limitations. More research is needed, including studies to isolate critical components of Design Thinking and compare Design Thinking–based interventions with traditionally developed interventions.
Genome-Wide Chromatin Structure Changes During Adipogenesis and Myogenesis

The recently developed high-throughput chromatin conformation capture (Hi-C) technology enables us to explore the spatial architecture of genomes, which is increasingly considered an important regulator of gene expression. To investigate the changes in three-dimensional (3D) chromatin structure and its mediated gene expression during adipogenesis and myogenesis, we comprehensively mapped 3D chromatin organization for four cell types (3T3-L1 pre-adipocytes, 3T3-L1-D adipocytes, C2C12 myoblasts, and C2C12-D myotubes). We demonstrate that the dynamic spatial genome architecture affected gene expression during cell differentiation. A considerable proportion (~22%) of the mouse genome underwent compartment A/B rearrangement during adipogenic and myogenic differentiation, and most (~80%) upregulated marker genes exhibited an active chromatin state with B to A switch or stable A compartment. More than half (65.4%-73.2%) of the topologically associating domains (TADs) are dynamic. The newly formed TAD and intensified local interactions in the Fabp gene cluster indicated more precise structural regulation of the expression of pro-differentiation genes during adipogenesis. About half (32.39%-59.04%) of the differential chromatin interactions (DCIs) during differentiation are promoter interactions, although these DCIs only account for a small proportion of genome-wide interactions (~9.67% in adipogenesis and ~4.24% in myogenesis). These differential promoter interactions were enriched with promoter-enhancer interactions (PEIs), which were mediated by typical adipogenic and myogenic transcription factors. Differential promoter interactions also included more differentially expressed genes than nonpromoter interactions. Our results provide a global view of dynamic chromatin interactions during adipogenesis and myogenesis and are a resource for studying long-range chromatin interactions mediating the expression of pro-differentiation genes.
Provider general attitudes versus specific perceptions of evidence-based psychotherapies for PTSD.

This study examined the role of attitudes toward evidence-based psychotherapies (EBPs) in predicting use of prolonged exposure (PE) and cognitive processing therapy (CPT), two EBPs for posttraumatic stress disorder (PTSD) among PTSD treatment providers within the Department of Veterans Affairs. Providers' general attitudes toward EBPs, as well as their specific perceptions of PE and CPT, were examined as potential predictors of use. One hundred fifty-nine providers from 38 Department of Veterans Affairs' residential PTSD programs across the United States completed an online survey that included the predictors listed as well as self-reported use of PE on an individual basis and CPT on an individual and on a group basis. Although general attitudes toward EBPs were related to use of individually administered CPT, they were not related to use of PE or group-administered CPT. For each of the 3 treatments, however, specific positive perceptions were related to use. In examination of other training, skill, and delivery-related variables, general attitudes appear more in line with perceptions and delivery of CPT than PE. Perhaps this is because of the unique exposure component of PE. Assessing provider perceptions of specific EBPs may help providers in guiding their own practice as well as aid treatment developers, trainers, and administrators to more effectively tailor dissemination and implementation efforts. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
Genetic Influences on Delayed Reward Discounting: A Genome-Wide Prioritized Subset Approach

Delayed reward discounting (DRD) is a behavioral economic measure of impulsivity that has been consistently associated with addiction. It has also been identified as a promising addiction endophenotype, linking specific sources of genetic variation to individual risk. A challenge in the studies to date is that levels of DRD are often confounded with prior drug use, and previous studies have also had limited genomic scope. The current investigation sought to address these issues by studying DRD in healthy young adults with low levels of substance use (N = 986; 62% female, 100% European ancestry) and investigating genetic variation genome-wide. The genome-wide approach used a prioritized subset design, organizing the tests into theoretically and empirically informed categories and apportioning power accordingly. Three subsets were used: (a) a priori loci implicated by previous studies; (b) high-value addiction (HVA) markers from the recently developed SmokeScreen array; and (c) an atheoretical genome-wide scan. Among a priori loci, a nominally significant association was present between DRD and rs521674 in ADRA2A. No significant HVA loci were detected. One statistically significant genome-wide association was detected (rs13395777, p = 2.8 × 10−8), albeit in an intergenic region of unknown function. These findings are generally not supportive of the previous candidate gene studies and suggest that DRD has a complex genetic architecture that will require considerably larger samples to identify genetic associations more definitively.
Protein Kinase A Signaling Inhibits Iridophore Differentiation in Zebrafish

In zebrafish (Danio rerio), iridophores are specified from neural crest cells and represent a tractable system for examining mechanisms of cell fate and differentiation. Using this system, we have investigated the role of cAMP protein kinase A (PKA) signaling in pigment cell differentiation. Activation of PKA with the adenylyl cyclase activator forskolin reduces the number of differentiated iridophores in wildtype larvae, with insignificant changes to melanophore number. Inhibition of PKA with H89 significantly increases iridophore number, supporting a specific role for PKA during iridophore development. To determine the effects of altering PKA activity on iridophore and melanophore gene expression, we examined expression of iridophore marker pnp4a, melanophore marker mitfa, and the mitfa repressor foxd3. Consistent with our cell counts, forskolin significantly decreased pnp4a expression as detected by in situ hybridization and quantification of pnp4a+ cells. Forskolin had the opposite effect on mitfa and foxd3 gene activity, increasing the area of expression. As mitfa/nacre mutants have extra iridophores as compared to wildtype larvae, we examined the function of mitfa during PKA-sensitive iridophore development. Forskolin treatment of mitfa/nacre mutants did significantly reduce the number of iridophores but to a lesser extent than that observed in treated wildtype larvae. Taken together, our data suggests that PKA inhibits iridophore development in a subset of iridophore precursors, potentially via a foxd3-independent pathway.
A Survey of System Level Power Management Schemes in the Dark-Silicon Era for Many-Core Architectures

Power consumption in Complementary Metal Oxide Semiconductor (CMOS) technology has escalated to a point that only a fractional part of many-core chips can be powered-on at a time. Fortunately, this fraction can be increased at the expense of performance through the dark-silicon solution. However, with many-core integration set to be heading towards its thousands, power consumption and temperature increases per time, meaning the number of active nodes must be reduced drastically. Therefore, optimized techniques are demanded for continuous advancement in technology. Existing eﬀorts try to overcome this challenge by activating nodes from diﬀerent parts of the chip at the expense of communication latency. Other eﬀorts on the other hand employ run-time power management techniques to manage the power performance of the cores trading-oﬀ performance for power. We found out that, for a signiﬁcant amount of power to saved and high temperature to be avoided, focus should be on reducing the power consumption of all the on-chip components. Especially, the memory hierarchy and the interconnect. Power consumption can be minimized by, reducing the size of high leakage power dissipating elements, turning-oﬀ idle resources and integrating power saving materials.