Miracle-dz/UniFAR-FTUs huggingface dataset:
Investigation of a two‐step device implementing magnetophoresis and dielectrophoresis for separation of circulating tumor cells from blood cells

Identifying tumor cells from a pool of other cells has always been an appealing topic for different purposes. The objective of this study is to discriminate circulating tumor cells (CTCs) from blood cells for diagnostic purposes in a novel microfluidic device using two active methods: magnetophoresis and dielectrophoresis. The most specific feature of this device is the differentiation of CTCs without labeling them in order to achieve a more reliable and less complicated method. This device was analyzed and evaluated using finite element method. Four cell lines are separated in this device containing red blood cells, platelets, white blood cells, and CTCs. Primarily, red blood cells and platelets, which constitute the largest part of a blood sample, are removed in the magnetophoresis section. Remaining cells enter the dielectrophoresis part and based on their inherent dielectric properties and diameters, final separation occurs. In each step, different parameters are examined to obtain the maximum purification. The results demonstrate the potential of different CTCs separation by changing the effective parameters in the designed device based on the inherent properties of the cells.
α-hederin induces autophagic cell death in colorectal cancer cells through reactive oxygen species dependent AMPK/mTOR signaling pathway activation

α-hederin, a monodesmosidic triterpenoid saponin, had previously demonstrated strong anticancer effects. In the current study, the pharmacological mechanism of autophagic cell death induced by α-hederin was investigated in human colorectal cancer cells. First, through cell counting kit-8 and colony formation assays, it was demonstrated that α-hederin could inhibit the proliferation of HCT116 and HCT8 cell. Results of flow cytometry using fluorescein isothiocyanate Annexin V/propidium iodide and Hoechst 33258 staining indicated that α-hederin could induce apoptosis. Western blotting demonstrated that α-hederin could activate mitochondrial apoptosis signal pathway. Then, using light chain 3 lentiviral and electron microscope assay, it was demonstrated that α-hederin could induce autophagy in colorectal cancer cells. In addition, immunohistochemistry results from in vivo experiments also demonstrated that α-hederin could induce autophagy. AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR) signaling was demonstrated to be activated by α-hederin, which could be blocked by reactive oxygen species (ROS) inhibitor NAC. Furthermore, NAC could inhibit apoptosis and autophagy induced by α-hederin. Finally, 3-MA (autophagy inhibitor) reduced the inhibition of α-hederin on cell activity, but it had no significant effect on apoptosis. In conclusion, α-hederin triggered apoptosis through ROS-activated mitochondrial signaling pathway and autophagic cell death through ROS dependent AMPK/mTOR signaling pathway activation in colorectal cancer cells.
Multi-Level, Multi-Scale Modeling and Predictive Mapping for Jaguars in the Brazilian Pantanal.

Background Machine learning (ML) methods and remote sensing data were used to build multi-level multi-scale resource selection models and predictive maps onto the extended landscape for jaguars (Panthera onca) in the Brazilian Pantanal. Objectives were to compare multiple predictive modeling and exploratory modeling approaches. Included in the analysis, multi-scale raster grains (30m, 90m, 180m, 360m, 720m, 1440m), GPS collaring temporal levels (point, path, and step) and model data structural levels (group, individual, case-control). Methods Multi-scale multi-level data subsets were fit with explanatory and predictive statistical methods. Conditional logistic regression, generalized additive modeling (GAM), and classification regression trees, such as random forests (RF) and gradient boosted regression tree (GBM) were compared for their utility to the study. Model evaluation, using training and testing data in a k-fold cross-validation approach, determined the AUC, Kappa, and TSS for model evaluation and comparison. · Results Results indicated that the multi-level, multi-scale techniques improved model outputs. Overall, larger level models and those that used multi-scale raster grains showed the best model evaluation. The highest-ranked model was the multi-scale path selection function GBM and was one of the broadest levels of data. ·Conclusions Results indicated that multi-level, multi-scale models produced mixed results of applicability across models and levels. The identification of the appropriate temporal scale and statistical model needs careful consideration in predictive mapping efforts.
Transcriptome profiling reveals association of peripheral adipose tissue pathology with type-2 diabetes in Asian Indians

ABSTRACT Type 2 diabetes (T2D) is a complex disease with an elusive link between its molecular aetiology and clinical presentation. Although, the role of visceral adipose tissue in insulin-resistance and T2D is known, limited information is available on the role of peripheral-subcutaneous adipose tissue especially in Asian Indians. In this microarray-based study of diabetic and normal glucose tolerant Asian Indians, we generated the transcriptome of their thigh adipose tissue and analyzed differentially expressed genes (DEGs) using weighted gene co-expression network analysis; further we identified perturbed pathways implicated by these DEGs in relevant co-expression modules. We also attempted to link these pathways with known aspects of T2D pathophysiology in terms of their association with some of their intermediate traits, namely; adipocyte size, HOMA-B, HOMA-R, Hb1Ac, insulin, glucose-level, TNF-α, IL-6, VLDLs, LDLs, HDLs, and NEFAs. It was observed that several modules of co-expressed genes show an association with diabetes and some of its intermediate phenotypic traits mentioned above. Therefore, these findings suggest a role of peripheral subcutaneous adipose tissue in the pathophsiology of T2D in Asian Indians. Additionally, our study indicated that the peripheral subcutaneous adipose tissue in diabetics shows pathologic changes characterized by adipocyte hypertrophy and up-regulation of inflammation-related pathways. Graphical abstract
Link prediction with hyperbolic geometry

Link prediction is a paradigmatic problem in network science with a variety of applications. In latent space network models this problem boils down to ranking pairs of nodes in the order of increasing latent distances between them. The network model with hyperbolic latent spaces has a number of attractive properties suggesting it must be a powerful tool to predict links, but the past work in this direction reported mixed results. Here we perform systematic investigation of the utility of latent hyperbolic geometry for link prediction in networks. We first show that some measures of link prediction accuracy are extremely sensitive with respect to inaccuracies in the inference of latent hyperbolic coordinates of nodes, so that we develop a new coordinate inference method that maximizes the accuracy of such inference. Applying this method to synthetic and real networks, we then find that while there exists a multitude of competitive methods to predict obvious easy-to-predict links, among which hyperbolic link prediction is rarely the best but often competitive, it is the best, often by far, when the task is to predict less obvious missing links that are really hard to predict. These links include missing links in incomplete networks with large fractions of missing links, missing links between nodes that do not have any common neighbors, and missing links between dissimilar nodes at large latent distances. Overall these results suggest that the harder a specific link prediction task is, the more seriously one should consider using hyperbolic geometry.
Hydraulic Model Calibration and Performance Assessment of Pressure Managed Areas with Multiple Inlets

Pressure management is a widely adopted technique in the toolset of drinking water distribution system operators. It has multiple benefits, like reducing physical losses in pipe networks with excessive leakage, prolong the expected lifetime of the pipes and protecting home appliances from unacceptably high pressure. In some cases, even legislation compliance can be the motivation behind pressure management: It is mandatory to supply water at the customer’s connection between 1.5 and 6.0 bar in Hungary since 2011. Diaphragm pressure reducing valves are widespread in the drinking water distribution networks. Although, their sensitivity for gas pocket accumulation in the valve house makes hydraulic calibration of these pressure managed areas a challenging task for hydraulic modelers and network operators. This is especially true when more than one inlet is used to supply the same area in order to increase resilience and flow capacity. This paper investigates the hydraulic properties of pressure reduced areas with multiple inlet points. Model calibration using a single valve and minor loss was found insufficient because the additional pressure loss referenced to the pressure setting has a nonquadratic relationship with flow-rate on the discharge side under real-life circumstances. This phenomenon can be handled by using a PRV (pressure reducing valve) + GPV (general purpose valve) in series.
Antibiotic Resistance in Pacific Island Countries and Territories: A Systematic Scoping Review

Several studies have investigated antimicrobial resistance in low- and middle-income countries, but to date little attention has been paid to the Pacific Islands Countries and Territories (PICTs). This study aims to review the literature on antibiotic resistance (ABR) in healthcare settings in PICTs to inform further research and future policy development for the region. Following the PRISMA-ScR checklist health databases and grey literature sources were searched. Three reviewers independently screened the literature for inclusion, data was extracted using a charting tool and the results were described and synthesised. Sixty-five studies about ABR in PICTs were identified and these are primarily about New Caledonia, Fiji and Papua New Guinea. Ten PICTs contributed the remaining 21 studies and nine PICTs were not represented. The predominant gram-positive pathogen reported was community-acquired methicillin resistant S. aureus and the rates of resistance ranged widely (>50% to <20%). Resistance reported in gram-negative pathogens was mainly associated with healthcare-associated infections (HCAIs). Extended spectrum beta-lactamase (ESBL) producing K. pneumoniae isolates were reported in New Caledonia (3.4%) and Fiji (22%) and carbapenem resistant A. baumannii (CR-ab) isolates in the French Territories (24.8%). ABR is a problem in the PICTs, but the epidemiology requires further characterisation. Action on strengthening surveillance in PICTs needs to be prioritised so strategies to contain ABR can be fully realised.
PKA17—A Coarse‐Grain Grid‐Based Methodology and Web‐Based Software for Predicting Protein pK
a Shifts

We have developed and tested PKA17, a coarse‐grain grid‐based model for predicting protein pK a shifts. Our pK a predictor is currently deployed via a website interface. We have carried out parameter fitting using 442 Asp, Glu, His, Lys, and Arg residues for which experimental results are available in the literature. PROPKA software has been used for benchmarking. The average unsigned error and root‐mean‐square deviation (RMSD) have been found to be 0.628 and 0.831 pH units, respectively, for PKA17. The corresponding results with PROPKA are 0.761 and 1.063 units. We have assessed the robustness of the developed PKA17 methodology with a number of tests and have also explored the possibility of using a combination of PROPKA and PKA17 calculations in order to improve the accuracy of predicted pK a values for protein residues. We have also once again confirmed that protein acidity constants are influenced almost entirely by residues in the immediate spatial proximity of the ionizable amino acids. The resulting PKA17 software has been deployed online with a web‐based interface at http://users.wpi. edu/~jpcvitkovic/pka_calc. html. © 2019 Wiley Periodicals, Inc.
Structural analysis of a plant fatty acid amide hydrolase provides insights into the evolutionary diversity of bioactive acylethanolamides

N-Acylethanolamines (NAEs) are fatty acid derivatives that in animal systems include the well-known bioactive metabolites of the endocannabinoid signaling pathway. Plants use NAE signaling as well, and these bioactive molecules often have oxygenated acyl moieties. Here, we report the three-dimensional crystal structures of the signal-terminating enzyme fatty acid amide hydrolase (FAAH) from Arabidopsis in its apo and ligand-bound forms at 2.1- and 3.2-Å resolutions, respectively. This plant FAAH structure revealed features distinct from those of the only other available FAAH structure (rat). The structures disclosed that although catalytic residues are conserved with the mammalian enzyme, AtFAAH has a more open substrate-binding pocket that is partially lined with polar residues. Fundamental differences in the organization of the membrane-binding “cap” and the membrane access channel also were evident. In accordance with the observed structural features of the substrate-binding pocket, kinetic analysis showed that AtFAAH efficiently uses both unsubstituted and oxygenated acylethanolamides as substrates. Moreover, comparison of the apo and ligand-bound AtFAAH structures identified three discrete sets of conformational changes that accompany ligand binding, suggesting a unique “squeeze and lock” substrate-binding mechanism. Using molecular dynamics simulations, we evaluated these conformational changes further and noted a partial unfolding of a random-coil helix within the region 531–537 in the apo structure but not in the ligand-bound form, indicating that this region likely confers plasticity to the substrate-binding pocket. We conclude that the structural divergence in bioactive acylethanolamides in plants is reflected in part in the structural and functional properties of plant FAAHs.
The Structure and Occurrence of a Velum in Utricularia Traps (Lentibulariaceae)

Bladderworts (Utricularia, Lentibulariaceae, Lamiales) are carnivorous plants that form small suction traps (bladders) for catching invertebrates. The velum is a cuticle structure that is produced by specialized trichomes of the threshold pavement epithelium. It is believed that the velum together with the mucilage seals the free edge of the trap door and that it is necessary for correct functioning of the trap. However, recently, some authors have questioned the occurrence of a velum in the traps of the Utricularia from the various sections. The main aim of this study was to confirm whether velum occurs in the traps of the Utricularia species from the subgenera Polypompholyx, Bivalvaria, and Utricularia. The 15 species were examined from subg. Polypompholyx, subg. Bivalvaria, and subg. Utricularia. A velum was found in all examined Utricularia species. In the traps of the members of section Pleiochasia, there was an outer velum (forming a complete ring) and an inner velum. In the traps of Utricularia uniflora (Lasiocaules), there was only an inner velum. In these species, the formation of the velum was accompanied by intensive mucilage production, and as a result, when door was closed (set position), the mucilage and the velum touched the surface of the door. In members of both sections of Pleiochasia and Lasiocaules, the pavement epithelium had a more complicated structure (four to five zones) than in the members of the subgenera Bivalvaria and Utricularia in which three distinct zones occurred (an outer with a velum, a middle and an internal with the mucilage trichomes). Even in U. purpurea, where the threshold was a reduced pavement epithelium, it consisted of three functional zones and the presence of a velum. Two main types of velum have been proposed. A velum was present in Utricularia traps regardless of the trap type or the habitat (aquatic, epiphytic, and terrestrial species). We proposed broad definition of velum as cuticle membranes covered by mucilage; from a functional point of view, this definition is more useful and more reflects complexity of this structure.
Standardised electronic algorithms for monitoring prophylaxis of postoperative nausea and vomiting

Introduction Despite comprehensive guidelines with high-grade evidence, postoperative nausea and vomiting (PONV) remains a frequent problem in anaesthesia care. Anaesthesia information management systems (AIMS) may aid clinicians in PONV prevention, but their benefit is critically dependent on the details of implementation into practice. This study aimed to examine strengths and weaknesses of the local AIMS-based algorithm in prevention of PONV. Material and methods This retrospective study was conducted in the post-anaesthesia care unit (PACU) of a university hospital and included 10 604 patients aged 18 or older who were followed up in the PACU (intracranial, obstetrical or cardiothoracic surgery excluded) from March 2013 until March 2014. The PONV incidence in PACU and AIMS data validity were analysed. Results Adherence to PONV guideline recommendations was considerably low, with only 5749 (54%) of the patients receiving correct PONV prophylaxis. Two thousand seven hundred sixty-six (26%) of the patients received an insufficient PONV prophylaxis, which was associated with an excess PONV incidence (11% vs. 4% with correct prophylaxis, p < 0.001) in the PACU. Two thousand four hundred forty-nine (23%) of all patients were discharged from the PACU with an insufficient PONV prophylaxis despite perioperative digital PONV prevention algorithms. Conclusions Adherence to PONV prophylaxis guidelines in the era of AIMS software and decision support is still remarkably low. The AIMS data usefulness depends on the user, the type of data input and the configuration of the software. Adherence to correct PONV prophylaxis should be re-evaluated systematically before discharge from PACU.
Automatic identification and description of software developers tasks

A software developer works on many tasks per day, frequently switching back and forth between their tasks. This constant churn of tasks makes it difficult for a developer to know the specifics of what tasks they worked on, and when they worked on them. Consequently, activities such as task resumption, planning, retrospection, and reporting become complicated. To help a developer determine which tasks they worked on and when these tasks were performed, we introduce two novel approaches. First, an approach that captures the contents of a developer’s active window at regular intervals to create vector and visual representations of the work in a particular time interval. Second, an approach that automatically detects the times at which developers switch tasks, as well as coarse grained information about the type of the task. To evaluate the first approach, we created a data set with multiple developers working on the same set of six information seeking tasks. To evaluate the second approach, we conducted two field studies, collecting data from a total of 25 professional developers. Our analyses show that our approaches enable: 1) segments of a developer’s work to be automatically associated with a task from a known set of tasks with average accuracy of 70.6%, 2) a visual representation of a segment of work performed such that a developer can recognize the task with average accuracy of 67.9%, 3) the boundaries of a developer’s task to be detected with an accuracy as high as 84%, and 4) the coarse grained type of a task that a developer works on to be detected with 61% accuracy.
Ethical Principles in Patient-Centered Medical Care to Support Quality of Life in Amyotrophic Lateral Sclerosis

It is one of the primary goals of medical care to secure good quality of life (QoL) while prolonging survival. This is a major challenge in severe medical conditions with a prognosis such as amyotrophic lateral sclerosis (ALS). Further, the definition of QoL and the question whether survival in this severe condition is compatible with a good QoL is a matter of subjective and culture-specific debate. Some people without neurodegenerative conditions believe that physical decline is incompatible with satisfactory QoL. Current data provide extensive evidence that psychosocial adaptation in ALS is possible, indicated by a satisfactory QoL. Thus, there is no fatalistic link of loss of QoL when physical health declines. There are intrinsic and extrinsic factors that have been shown to successfully facilitate and secure QoL in ALS which will be reviewed in the following article following the four ethical principles (1) Beneficence, (2) Non-maleficence, (3) Autonomy and (4) Justice, which are regarded as key elements of patient centered medical care according to Beauchamp and Childress. This is a JPND-funded work to summarize findings of the project NEEDSinALS (www.NEEDSinALS.com) which highlights subjective perspectives and preferences in medical decision making in ALS.
Association of Human FOS Promoter Variants with the Occurrence of Knee-Osteoarthritis in a Case Control Association Study

Our aim was to analyse (i) the presence of single nucleotide polymorphisms (SNPs) in the JUN and FOS core promoters in patients with rheumatoid arthritis (RA), knee-osteoarthritis (OA), and normal controls (NC); (ii) their functional influence on JUN/FOS transcription levels; and (iii) their associations with the occurrence of RA or knee-OA. JUN and FOS promoter SNPs were identified in an initial screening population using the Non-Isotopic RNase Cleavage Assay (NIRCA); their functional influence was analysed using reporter gene assays. Genotyping was done in RA (n = 298), knee-OA (n = 277), and NC (n = 484) samples. For replication, significant associations were validated in a Finnish cohort (OA: n = 72, NC: n = 548). Initially, two SNPs were detected in the JUN promoter and two additional SNPs in the FOS promoter in perfect linkage disequilibrium (LD). JUN promoter SNP rs4647009 caused significant downregulation of reporter gene expression, whereas reporter gene expression was significantly upregulated in the presence of the FOS promoter SNPs. The homozygous genotype of FOS promoter SNPs showed an association with the susceptibility for knee-OA (odds ratio (OR) 2.12, 95% confidence interval (CI) 1.2–3.7, p = 0.0086). This association was successfully replicated in the Finnish Health 2000 study cohort (allelic OR 1.72, 95% CI 1.2–2.5, p = 0.006). FOS Promoter variants may represent relevant susceptibility markers for knee-OA.
Fibroblast growth factor 21 controls mitophagy and muscle mass

Skeletal muscle is a plastic tissue that adapts to changes in exercise, nutrition, and stress by secreting myokines and myometabolites. These muscle‐secreted factors have autocrine, paracrine, and endocrine effects, contributing to whole body homeostasis. Muscle dysfunction in aging sarcopenia, cancer cachexia, and diabetes is tightly correlated with the disruption of the physiological homeostasis at the whole body level. The expression levels of the myokine fibroblast growth factor 21 (FGF21) are very low in normal healthy muscles. However, fasting, ER stress, mitochondrial myopathies, and metabolic disorders induce its release from muscles. Although our understanding of the systemic effects of muscle‐derived FGF21 is exponentially increasing, the direct contribution of FGF21 to muscle function has not been investigated yet.