Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of costs and outcomes of dapagliflozin with other glucose-lowering therapy classes added to metformin using a short-term cost-effectiveness model in the US setting

Abstract Objective: To compare 1-year costs and benefits of dapagliflozin (DAPA), a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, with those of other treatments for type 2 diabetes (T2D), such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), sulfonylureas (SUs), thiazolidinediones (TZDs), and dipeptidyl peptidase-4 inhibitors (DPP-4i), all combined with metformin. Methods: A short-term decision-analytic model with a 1-year time horizon was developed from a payer’s perspective in the United States setting. Costs and benefits associated with four clinical end-points (glycated hemoglobin [A1C], body weight, systolic blood pressure [SBP], and risk of hypoglycemia) were evaluated in the analysis. The impact of DAPA and other glucose-lowering therapy classes on these clinical end-points was estimated from a network meta-analysis (NMA). Data for costs and quality-adjusted life-years (QALYs) associated with a per-unit change in these clinical end-points were taken from published literature. Drug prices were taken from an annual wholesale price list. All costs were inflation-adjusted to December 2016 costs using the medical care component of the consumer price index. Total costs (both medical and drug costs), total QALYs, and incremental cost-effectiveness ratios (ICERs) were estimated. Sensitivity analyses (SA) were performed to explore uncertainty in the inputs. To assess face validity, results from the short-term model were compared with long-term models published for these drugs. Results: The total annual medical cost for DAPA was less than that for GLP-1RA ($186 less), DPP-4i ($1,142 less), SU ($2,474 less), and TZD ($1,640 less). Treatment with DAPA resulted in an average QALY gain of 0.0107, 0.0587, 0.1137, and 0.0715 per treated patient when compared with GLP-1RA, DPP-4i, SU, and TZD, respectively. ICERs for DAPA vs SU and TZD were $19,005 and $25,835, respectively. DAPA was a cost-saving option when compared with GLP-1RAs and DPP-4is. Among all four clinical end-points, change in weight had the greatest impact on total annual costs and ICERS. Sensitivity analysis showed that results were robust, and results from the short-term model were found to be similar to those of published long-term models. Conclusion: This analysis showed that DAPA was cost-saving compared with GLP-1RA and DPP-4i, and cost-effective compared with SU and TZD in the US setting over 1 year. Furthermore, the results suggest that, among the four composite clinical end-points, change in weight and SBP had an impact on cost-effectiveness results.
Morphology and Morphometry of the Ovaries and Uteri of the Amazonian Freshwater Stingrays (Potamotrygonidae: Elasmobranchii)

The reproductive biology of South American freshwater stingrays (family Potamotrygonidae) is still poorly studied compared to other marine species. In the present study, we examined the gross anatomy and histology of six species of potamotrygonids from the Amazon basin and described the structural asymmetry of the ovaries and their relationship between ovarian and uterine fecundities. Stereological techniques were used to quantify the volume of ovarian and epigonal organ tissue associated with the left and right sides of the Potamotrygon wallacei, a recently described species, locally known as the cururu ray. This species presented ovarian asymmetry; the left epigonal organ‐ovary complex was 55 times larger than the right side. The right side was composed of, volumetrically, 7.3% ovarian tissue and 92.7% epigonal organ tissue whereas the left side was 51.2% of ovarian tissue and 48.8% epigonal organ tissue. In all species, six types of follicles were identified in both right and left ovaries. Uteri were symmetrical and the fecundity ratio between the right and left sides was 0.9:1.1, respectively. Despite the volumetric difference of ovarian tissue between the two sides, the uterine fecundity shows that both ovaries are functional and that ovarian fecundity alone is not an accurate measure to determine the reproductive potential of freshwater stingrays. Anat Rec, 300:265–276, 2017. © 2016 Wiley Periodicals, Inc.
An isogenic blood–brain barrier model comprising brain endothelial cells, astrocytes, and neurons derived from human induced pluripotent stem cells

The blood–brain barrier (BBB) is critical in maintaining a physical and metabolic barrier between the blood and the brain. The BBB consists of brain microvascular endothelial cells (BMECs) that line the brain vasculature and combine with astrocytes, neurons and pericytes to form the neurovascular unit. We hypothesized that astrocytes and neurons generated from human‐induced pluripotent stem cells (iPSCs) could induce BBB phenotypes in iPSC‐derived BMECs, creating a robust multicellular human BBB model. To this end, iPSCs were used to form neural progenitor‐like EZ‐spheres, which were in turn differentiated to neurons and astrocytes, enabling facile neural cell generation. The iPSC‐derived astrocytes and neurons induced barrier tightening in primary rat BMECs indicating their BBB inductive capacity. When co‐cultured with human iPSC‐derived BMECs, the iPSC‐derived neurons and astrocytes significantly elevated trans‐endothelial electrical resistance, reduced passive permeability, and improved tight junction continuity in the BMEC cell population, while p‐glycoprotein efflux transporter activity was unchanged. A physiologically relevant neural cell mixture of one neuron: three astrocytes yielded optimal BMEC induction properties. Finally, an isogenic multicellular BBB model was successfully demonstrated employing BMECs, astrocytes, and neurons from the same donor iPSC source. It is anticipated that such an isogenic facsimile of the human BBB could have applications in furthering understanding the cellular interplay of the neurovascular unit in both healthy and diseased humans.
The effect of flat and textured insoles on the balance of primary care elderly people: a randomized controlled clinical trial

Background Aging is associated with reduced postural stability and increased fall risk. Foot orthoses have been reported as an adjuvant intervention to improve balance by stimulating foot plantar mechanical receptors and thus increasing somatosensory input. Purpose The aim of this study is to evaluate the effect of flat and textured insoles on the balance of primary care elderly people. Design Prospective, parallel, randomized, and single-blind trial. Methods A total of 100 subjects from a primary care unit, aged ≥65 years, were randomly assigned to intervention groups with flat insoles (n=33), textured insoles (n=33), or control group (n=34) without insoles. The Berg Balance Scale and the Timed Up and Go test were assessed at baseline and after 4 weeks. Results Improvements in the Berg Balance Scale and the Timed Up and Go test were noted only in intervention groups with insoles but not in control group. No significant difference was found between flat and textured insoles. Minor adverse effects were noted only in the group with textured insoles. Conclusion The results suggest that foot orthoses (both flat and textured insoles) are effective in improving balance in primary care elderly people. They may represent a low-cost and high-availability adjuvant strategy to improve balance and prevent falls in this population.
Aneustat (OMN54) has aerobic glycolysis‐inhibitory activity and also immunomodulatory activity as indicated by a first‐generation PDX prostate cancer model

Aneustat (OMN54) is a multivalent, botanical anticancer candidate therapeutic. A recent Phase‐I clinical trial has indicated that it is well tolerated by patients and has immunomodulatory activity. In our study, using in vitro and in vivo prostate cancer models, we investigated Aneustat with regard to effects on (i) cancer‐generated immunosuppression based on aerobic glycolysis leading to acidification of the tumor microenvironment, and (ii) immune‐related processes such as macrophage differentiation and shifts in the intratumoral levels of host immune cells. Aneustat markedly reduced glucose consumption, lactic acid secretion, glycolysis‐related gene expressions and proliferation of human LNCaP prostate cancer cells. In addition, Aneustat induced differentiation of RAW264.7 macrophages to the M1 anticancer phenotype. Treatment of LNCaP xenografts and first‐generation patient‐derived prostate cancer tissue xenografts with Aneustat in both cases led to a marked shift in intratumoral host (mouse/patient) immune cell levels: a higher ratio of cytotoxic CD8+ T/Treg cells, higher numbers of NK cells, lower numbers of Treg cells and MDSCs, i.e. changes favoring the host anticancer immune response. Taken together, the data indicate that Aneustat has immunomodulatory activity based on inhibition of aerobic glycolysis which in patients may lead to reduction of cancer‐induced immunosuppression. Furthermore, first‐generation patient‐derived cancer tissue xenograft models may be used for screening compounds for immunomodulatory activity.
Memory and Performance Isolation for a Multi-tenant Function-based Dataplane

Existing software dataplanes that run network functions inside VMs or containers can provide either performance (by dedicating CPU cores) or multiplexing (by context switching), but not both at once. Function-based dataplane architectures that avoid context switching by replacing VMs and containers with function calls to packet processing functions promise to achieve both multiplexing and performance at the same time. However, they compromise memory isolation between tenants by forcing them to use a shared memory address space. In this paper, we show that an operating system-like management layer for modules in a function-based data plane can offer OS-like constructs such as performance and memory isolation. We are applying these insights in developing FastPaas, a function-based data plane for multi-tenant environments. To provide memory isolation, FastPaas leverages new Intel CPU extensions (MPX) to create coarse-grained heap and stack protection even for legacy code written in unsafe native languages such as C. In addition, FastPaas uses programmable NIC offloads to distribute load across cores as well as to prevent batch fragmentation when processing complex service graphs. Our preliminary evaluation shows the limitations of existing techniques that require heavy weight memory isolation or incur cross-core overheads.
Walking Like Dinosaurs: Chickens with Artificial Tails Provide Clues about Non-Avian Theropod Locomotion

Birds still share many traits with their dinosaur ancestors, making them the best living group to reconstruct certain aspects of non-avian theropod biology. Bipedal, digitigrade locomotion and parasagittal hindlimb movement are some of those inherited traits. Living birds, however, maintain an unusually crouched hindlimb posture and locomotion powered by knee flexion, in contrast to the inferred primitive condition of non-avian theropods: more upright posture and limb movement powered by femur retraction. Such functional differences, which are associated with a gradual, anterior shift of the centre of mass in theropods along the bird line, make the use of extant birds to study non-avian theropod locomotion problematic. Here we show that, by experimentally manipulating the location of the centre of mass in living birds, it is possible to recreate limb posture and kinematics inferred for extinct bipedal dinosaurs. Chickens raised wearing artificial tails, and consequently with more posteriorly located centre of mass, showed a more vertical orientation of the femur during standing and increased femoral displacement during locomotion. Our results support the hypothesis that gradual changes in the location of the centre of mass resulted in more crouched hindlimb postures and a shift from hip-driven to knee-driven limb movements through theropod evolution. This study suggests that, through careful experimental manipulations during the growth phase of ontogeny, extant birds can potentially be used to gain important insights into previously unexplored aspects of bipedal non-avian theropod locomotion.
DRUNET: A Dilated-Residual U-Net Deep Learning Network to Digitally Stain Optic Nerve Head Tissues in Optical Coherence Tomography Images

Given that the neural and connective tissues of the optic nerve head (ONH) exhibit complex morphological changes with the development and progression of glaucoma, their simultaneous isolation from optical coherence tomography (OCT) images may be of great interest for the clinical diagnosis and management of this pathology. A deep learning algorithm was designed and trained to digitally stain (i.e. highlight) 6 ONH tissue layers by capturing both the local (tissue texture) and contextual information (spatial arrangement of tissues). The overall dice coefficient (mean of all tissues) was $0.91 \pm 0.05$ when assessed against manual segmentations performed by an expert observer. We offer here a robust segmentation framework that could be extended for the automated parametric study of the ONH tissues.
Conserved binding of GCAC motifs by MEC-8, couch potato, and the RBPMS protein family

Precise regulation of mRNA processing, translation, localization, and stability relies on specific interactions with RNA-binding proteins whose biological function and target preference are dictated by their preferred RNA motifs. The RBPMS family of RNA-binding proteins is defined by a conserved RNA recognition motif (RRM) domain found in metazoan RBPMS/Hermes and RBPMS2, Drosophila couch potato, and MEC-8 from Caenorhabditis elegans. In order to determine the parameters of RNA sequence recognition by the RBPMS family, we have first used the N-terminal domain from MEC-8 in binding assays and have demonstrated a preference for two GCAC motifs optimally separated by >6 nucleotides (nt). We have also determined the crystal structure of the dimeric N-terminal RRM domain from MEC-8 in the unbound form, and in complex with an oligonucleotide harboring two copies of the optimal GCAC motif. The atomic details reveal the molecular network that provides specificity to all four bases in the motif, including multiple hydrogen bonds to the initial guanine. Further studies with human RBPMS, as well as Drosophila couch potato, confirm a general preference for this double GCAC motif by other members of the protein family and the presence of this motif in known targets.
Portuguese version of a stress and well-being evaluation tool (ASSET)at the workplace: validation of the psychometric properties

Objective The main objective of this work was to translate the English version of ASSET (A Shortened Stress Evaluation Tool) into the Portuguese version and to validate its psychometric properties. Additionally, this work tested the convergent validity of the instrument. Methods The translation and retroversion were conducted by experts and submitted to the authors for approval. Within an observational, cross-sectional study, regarding mental health at the workplace, ASSET together with other scales was applied to a sample of 405 participants. The psychometric validity of the subscales was studied using confirmatory factorial analysis. Results The factorial structure of ASSET is globally supported by the results, with the Perceptions of Your Job and Attitudes Towards your Organisation subscales requiring slight adjustments in the item structure and the Your Health subscales replicating the original structure. The convergent validity also supports the ASSET, showing that all subscales are significantly correlated with variables used to test convergence. Conclusions Globally, the results constitute an important contribution to ASSET and open the possibility of its usage among Portuguese-speaking countries. The results provide an evidence on the validity of the instrument and, in particular, of the mental and physical health subscales.
Nucleus Decompositions for Identifying Hierarchy of Dense Subgraphs

Finding dense substructures in a graph is a fundamental graph mining operation, with applications in bioinformatics, social networks, and visualization to name a few. Yet most standard formulations of this problem (like clique, quasi-clique, densest at-least-k subgraph) are NP-hard. Furthermore, the goal is rarely to find the “true optimum” but to identify many (if not all) dense substructures, understand their distribution in the graph, and ideally determine relationships among them. Current dense subgraph finding algorithms usually optimize some objective and only find a few such subgraphs without providing any structural relations. We define the nucleus decomposition of a graph, which represents the graph as a forest of nuclei. Each nucleus is a subgraph where smaller cliques are present in many larger cliques. The forest of nuclei is a hierarchy by containment, where the edge density increases as we proceed towards leaf nuclei. Sibling nuclei can have limited intersections, which enables discovering overlapping dense subgraphs. With the right parameters, the nucleus decomposition generalizes the classic notions of k-core and k-truss decompositions. We present practical algorithms for nucleus decompositions and empirically evaluate their behavior in a variety of real graphs. The tree of nuclei consistently gives a global, hierarchical snapshot of dense substructures and outputs dense subgraphs of comparable quality with the state-of-the-art solutions that are dense and have non-trivial sizes. Our algorithms can process real-world graphs with tens of millions of edges in less than an hour. We demonstrate how proposed algorithms can be utilized on a citation network. Our analysis showed that dense units identified by our algorithms correspond to coherent articles on a specific area. Our experiments also show that we can identify dense structures that are lost within larger structures by other methods and find further finer grain structure within dense groups.
Absorption Based Characterization Method for Fluid Properties Using Electrowetting-on-Dielectric Forces: Modeling and Fabrication

Electrowetting-on-Dielectrics (EWOD) can be used to build a device, where a polar fluid droplet gets actuated between two EWOD electrodes. In our setup, each electrode is located between a laser diode and an oppositely arranged photo diode. In that manner, the presence of a fluid droplet located above one certain electrode can be optically detected by means of this transmission setup. The droplet’s viscosity dependent switching time, i.e., the time it takes to move the droplet between these two electrodes can be obtained by a time difference measurement of both transmission signals. CFD simulations of the switching time, which depends on the droplet’s viscosity, and furthermore absorption simulations according to the Beer Lambert law have been carried out with DI water as a sample fluid. A low-cost and rapid fabrication method of the so called absorption EWOD (aEWOD) switch is reported and the fabricated EWOD stack is characterized with the aid of surface profilometry.
Cascade classification of endocytoscopic images of colorectal lesions for automated pathological diagnosis

This paper presents a new classification method for endocytoscopic images. Endocytoscopy is a new endoscope that enables us to perform conventional endoscopic observation and ultramagnified observation of cell level. This ultramagnified views (endocytoscopic images) make possible to perform pathological diagnosis only on endo-scopic views of polyps during colonoscopy. However, endocytoscopic image diagnosis requires higher experiences for physicians. An automated pathological diagnosis system is required to prevent the overlooking of neoplastic lesions in endocytoscopy. For this purpose, we propose a new automated endocytoscopic image classification method that classifies neoplastic and non-neoplastic endocytoscopic images. This method consists of two classification steps. At the first step, we classify an input image by support vector machine. We forward the image to the second step if the confidence of the first classification is low. At the second step, we classify the forwarded image by convolutional neural network. We reject the input image if the confidence of the second classification is also low. We experimentally evaluate the classification performance of the proposed method. In this experiment, we use about 16,000 and 4,000 colorectal endocytoscopic images as training and test data, respectively. The results show that the proposed method achieves high sensitivity 93.4% with small rejection rate 9.3% even for difficult test data.
biological Properties of Regenerated silk Fibroin Films

Lomonosov Moscow State university, 1 Leninskiye gory, Moscow, 119991, Russian FederationThe aim of the investigation was to study the biological and mechanical properties of silk fibroin films and composite silk fibroin films containing 30% collagen by weight.Materials and Methods. All films were prepared by casting method using water and formic acid as solvents. Scanning electron microscopy and atomic force microscopy were applied. Human hepatoblastoma cell line Hep-g
Influence of silane coupling agent on interface interaction and properties of nano-silica / silicone rubber composites

The nano-silica was surface modified by single functional coupling agent,hexamethyldisilazane( HMDS) and bifunctional coupling agent,γ-methacryloxypropyltrimethoxysilane( KH-570) respectively,the modified silica / methyl vinyl silicone rubber( MVQ) composites were prepared,the modification effect of coupling agents and dispersion of modified silica in MVQ were studied and characterized,and the influence of coupling agents on bound rubber,dynamic mechanical properties,crosslinking density and tensile properties was investigated. The results showed that HMDS and KH-570 had been grafted onto silica respectively,and both modified silicas had the same mole grafting ratio. A certain amount of HMDS modified silica aggregated when it was dispersed in rubber,but KH-570 modified silica dispersed well and part of it dispersed in primary level,which indicated better compatibility between particles and matrix. At lower strain,the storage modulus( G') and loss factor( tan δ) of the modified silica filled composites decreased,G' of KH-570 modified silica filled composites was lower than that of HMDS modified system,but tan δ higher. At higher strain,the G' of composites filled with silica or modified silica tended to be consistent,and tan δof KH-570 modified composites was lower than that of HMDS modified system. Modified silica filled composites had higher crosslinking density and tensile properties,the crosslinking density and tensile properties of the KH-570 modified system was higher than those of HMDS modified system.