Miracle-dz/UniFAR-FTUs huggingface dataset:
Yersinia pseudotuberculosis YopH targets SKAP2-dependent and independent signaling pathways to block neutrophil antimicrobial mechanisms during infection

Yersinia suppress neutrophil responses by using a type 3 secretion system (T3SS) to inject 6–7 Yersinia effector proteins (Yops) effectors into their cytoplasm. YopH is a tyrosine phosphatase that causes dephosphorylation of the adaptor protein SKAP2, among other targets in neutrophils. SKAP2 functions in reactive oxygen species (ROS) production, phagocytosis, and integrin-mediated migration by neutrophils. Here we identify essential neutrophil functions targeted by YopH, and investigate how the interaction between YopH and SKAP2 influence Yersinia pseudotuberculosis (Yptb) survival in tissues. The growth defect of a ΔyopH mutant was restored in mice defective in the NADPH oxidase complex, demonstrating that YopH is critical for protecting Yptb from ROS during infection. The growth of a ΔyopH mutant was partially restored in Skap2-deficient (Skap2KO) mice compared to wild-type (WT) mice, while induction of neutropenia further enhanced the growth of the ΔyopH mutant in both WT and Skap2KO mice. YopH inhibited both ROS production and degranulation triggered via integrin receptor, G-protein coupled receptor (GPCR), and Fcγ receptor (FcγR) stimulation. SKAP2 was required for integrin receptor and GPCR-mediated ROS production, but dispensable for degranulation under all conditions tested. YopH blocked SKAP2-independent FcγR-stimulated phosphorylation of the proximal signaling proteins Syk, SLP-76, and PLCγ2, and the more distal signaling protein ERK1/2, while only ERK1/2 phosphorylation was dependent on SKAP2 following integrin receptor activation. These findings reveal that YopH prevents activation of both SKAP2-dependent and -independent neutrophilic defenses, uncouple integrin- and GPCR-dependent ROS production from FcγR responses based on their SKAP2 dependency, and show that SKAP2 is not required for degranulation.
Convergence Analysis of Single Latent Factor-Dependent, Nonnegative, and Multiplicative Update-Based Nonnegative Latent Factor Models

A single latent factor (LF)-dependent, nonnegative, and multiplicative update (SLF-NMU) learning algorithm is highly efficient in building a nonnegative LF (NLF) model defined on a high-dimensional and sparse (HiDS) matrix. However, convergence characteristics of such NLF models are never justified in theory. To address this issue, this study conducts rigorous convergence analysis for an SLF-NMU-based NLF model. The main idea is twofold: 1) proving that its learning objective keeps nonincreasing with its SLF-NMU-based learning rules via constructing specific auxiliary functions; and 2) proving that it converges to a stable equilibrium point with its SLF-NMU-based learning rules via analyzing the Karush–Kuhn–Tucker (KKT) conditions of its learning objective. Experimental results on ten HiDS matrices from real applications provide numerical evidence that indicates the correctness of the achieved proof.
A mammalian Wnt5a–Ror2–Vangl2 axis controls the cytoskeleton and confers cellular properties required for alveologenesis

Alveolar formation increases the surface area for gas-exchange and is key to the physiological function of the lung. Alveolar epithelial cells, myofibroblasts and endothelial cells undergo coordinated morphogenesis to generate epithelial folds (secondary septa) to form alveoli. A mechanistic understanding of alveologenesis remains incomplete. We found that the planar cell polarity (PCP) pathway is required in alveolar epithelial cells and myofibroblasts for alveologenesis in mammals. Our studies uncovered a Wnt5a–Ror2–Vangl2 cascade that endows cellular properties and novel mechanisms of alveologenesis. This includes PDGF secretion from alveolar type I and type II cells, cell shape changes of type I cells and migration of myofibroblasts. All these cellular properties are conferred by changes in the cytoskeleton and represent a new facet of PCP function. These results extend our current model of PCP signaling from polarizing a field of epithelial cells to conferring new properties at subcellular levels to regulate collective cell behavior.
Electrospun metronidazole-loaded nanofibers for vaginal drug delivery

Abstract Objective: To develop and characterize innovative vaginal dosage forms for the treatment of bacterial vaginosis (BV). Significance: This study is the first comparative evaluation of the metronidazole (MET)-loaded polyvinylpyrrolidone (PVP) nanofiber formulations on BV treatment. Vaginal nanofibers are one of the potential innovative dosage forms for BV treatment because of their flexible, mucoadhesive, and easy application in vaginal application which can be applied by the mucosal route. Methods: Blank and MET-loaded PVP solutions were prepared at three different concentrations (10, 12.5, 15%) for produce nanofiber. The suitability of the viscosities, surface tensions, and conductivity values of the solutions used to produce nanofibers for the electrospinning process has been evaluated. Scanning electron microscopy, mucoadhesion, permeability, Fourier transform infrared spectroscopy, differential scanning calorimetry, and drug release tests were performed to reveal the physical, chemical, and pharmaceutical properties of the nanofibers. Mechanical properties, and contact angle of the fibers were also determined. Gel and solution formulations containing MET were prepared for comparative studies. Results: All polymer solutions were found to be suitable for electrospinning process. PVP concentration directly affected nanofiber diameter, mechanical, and mucoadhesion properties of nanofibers. The release profiles of the drug from the nanofibers were similar for all concentration of PVP and release from the fibers was rapid. The permeability coefficient of MET from nanofibers was increased more than gel and solution formulations. Conclusions: Vaginal use of MET-loaded nanofibers has been shown to be a potential drug delivery system for the treatment of BV.
Strategies to change body composition in older adults: do type of exercise and dose distribution matter?

BACKGROUND This study aims to analyze changes in sedentary elderlies' body composition, comparing the impact of two dose distributions: continuous (60 min/session) vs. accumulated (30 min/session in the morning and 30 min/session in the afternoon), on two types of physical exercise programs (multicomponent-training [MCT] vs. walking interval-training [WIT]). METHODS Forty-six sedentary overweight elderly (71.3±4.3 years) were evaluated by bioimpedance with a pre-post 2x2 factorial design. Participants were distributed in four homogeneous groups, considering gait and health parameters. RESULTS The overall sample showed significant improvements in fat mass (% and kg) and fat-free mass (kg) following 15 weeks of training. There was a main effect of "type of exercise" and a moderating effect of "dose distribution" reflected in the interaction of both factors. Bonferroni analyses of the type*dose interaction revealed significant improvements in all groups, except for MCT-accumulated, on both body composition compartments. CONCLUSIONS Starting exercise training, properly periodized and supervised by physical-education trainers, improves body composition of sedentary elderlies regardless of the type of exercise. Accumulated strategies were beneficial only when applied to WIT. Although MCT training improves body composition with only 2 days/week, WIT-accumulated could be a key element in the design of weight control policies looking for breaking sedentary behaviors.
Quantitative analysis of the effect of fraction of inspired oxygen on peripheral oxygen saturation in healthy volunteers

Background The international organization for standardization (ISO) 80601-2-61 dictates that the accuracy of a pulse oximeter should be assessed by a controlled desaturation study. We aimed to characterize the relationship between the fraction of inspired oxygen (FiO2) and peripheral oxygen saturation (SpO2) using a turnover model by retrospectively analyzing the data obtained from previous controlled desaturation studies. Materials and Methods Each volunteer was placed in a semi-Fowler's position and connected to a breathing circuit to administer the hypoxic gas mixture containing medical air, oxygen, nitrogen, and carbon dioxide. Volunteers were exposed to various levels of induced hypoxia over 70–100% arterial oxygen saturation (SaO2). The study period consisted of two rounds of hypoxia and the volunteers were maintained in room air between each round. FiO2 and SpO2 were recorded continuously during the study period. A population pharmacodynamic analysis was performed with the NONMEM VII level 4 (ICON Development Solutions, Ellicott City, MD, USA). Results In total, 2899 SpO2 data points obtained from 20 volunteers were used to determine the pharmacodynamic characteristics. The pharmacodynamic parameters were as follows: kout = 0.942 1/min, Imax = 0.802, IC50 = 85.3%, γ = 27.3. Conclusion The changes in SpO2 due to decreases in FiO2 well explained by the turnover model with inhibitory function as a sigmoidal model.
RESTful API for iPTMnet: a resource for protein post-translational modification network discovery

Abstract iPTMnet is a bioinformatics resource that integrates protein post-translational modification (PTM) data from text mining and curated databases and ontologies to aid in knowledge discovery and scientific study. The current iPTMnet website can be used for querying and browsing rich PTM information but does not support automated iPTMnet data integration with other tools. Hence, we have developed a RESTful API utilizing the latest developments in cloud technologies to facilitate the integration of iPTMnet into existing tools and pipelines. We have packaged iPTMnet API software in Docker containers and published it on DockerHub for easy redistribution. We have also developed Python and R packages that allow users to integrate iPTMnet for scientific discovery, as demonstrated in a use case that connects PTM sites to kinase signaling pathways.
Resting‐state and task‐based centrality of dorsolateral prefrontal cortex predict resilience to 1 Hz repetitive transcranial magnetic stimulation

Repetitive transcranial magnetic stimulation (rTMS) is used to investigate normal brain function in healthy participants and as a treatment for brain disorders. Various subject factors can influence individual response to rTMS, including brain network properties. A previous study by our group showed that “virtually lesioning” the left dorsolateral prefrontal cortex (dlPFC; important for cognitive flexibility) using 1 Hz rTMS reduced performance on a set‐shifting task. We aimed to determine whether this behavioural response was related to topological features of pre‐TMS resting‐state and task‐based functional networks. 1 Hz (inhibitory) rTMS was applied to the left dlPFC in 16 healthy participants, and to the vertex in 17 participants as a control condition. Participants performed a set‐shifting task during fMRI at baseline and directly after a single rTMS session 1–2 weeks later. Functional network topology measures were calculated from resting‐state and task‐based fMRI scans using graph theoretical analysis. The dlPFC‐stimulated group, but not the vertex group, showed reduced setshifting performance after rTMS, associated with lower task‐based betweenness centrality (BC) of the dlPFC at baseline (p = .030) and a smaller reduction in task‐based BC after rTMS (p = .024). Reduced repeat trial accuracy after rTMS was associated with higher baseline resting state node strength of the dlPFC (p = .017). Our results suggest that behavioural response to 1 Hz rTMS to the dlPFC is dependent on baseline functional network features. Individuals with more globally integrated stimulated regions show greater resilience to rTMS effects, while individuals with more locally well‐connected regions show greater vulnerability.
Role of the gut microbiome in mediating standard metabolic rate after dietary shifts in the viviparous cockroach, Diploptera punctata

ABSTRACT Diet may be a significant determinant of insect gut microbiome composition. However, the extent to which dietary shifts shape both the composition and relevant functions of insect gut microbiomes, and ultimately impact host energy balance (i.e. metabolic phenotype), is not well understood. We investigated the impacts of diet switching on Diploptera punctata females maintained on a dog food (DF) diet relative to those fed a comparatively sub-optimal cellulose-amended dog food (CADF) diet for 4 weeks. After this period, dietary shift resulted in a significantly higher average mass-specific standard metabolic rate (SMR) in CADF-fed females compared with DF-fed females. We also uncovered significant 13C-enrichment in DF-fed insect samples relative to CADF-fed insect samples and lowered bacterial essential amino acid (EAA) provisioning in CADF-fed samples. Differences in SMR and EAA provisioning were not accompanied by significant differences in overall microbiome composition between the two groups. However, cellulolytic and nitrogen-fixing bacterial families dominant in wild omnivorous cockroaches and wood-feeding termites were significantly enriched in CADF-fed females than in DF-fed females, at the end of the study. We propose that these changes in microbiome composition after dietary shifts are associated with changes in EAA provisioning and possibly SMR. Further studies are needed to comprehensively understand the relative importance of gut microbial functions among the complexity of factors known to underscore SMR responses in insects under varying dietary conditions. Summary: Dietary shifts resulted in differential emergences of microbial taxa in the gut microbiomes of Diploptera punctata, impacting microbial essential amino acid provisioning functions that may underlie differences in determined host metabolic phenotypes, measured as standard metabolic rate.
Genotypic and environmental variation in bulb composition of New Zealand adapted onion (Allium cepa) germplasm

Abstract Bulb pungency, soluble solids content, and storage quality of 154 lines from the New Zealand Institute of Crop & Food Research Limited onion (Allium cepa L.) breeding programme were evaluated at Pukekohe and Lincoln, New Zealand in the 1998/99 season. Within‐site variation was controlled by an experimental design incorporating systematically allocated mild and pungent check lines rather than blocking. Spatial trends in bulb composition were detected and adjustments made to models accordingly, suggesting that this is an appropriate and efficient means of compensating for within‐site variation in onion trials. The lines surveyed included many that were early, but few that were mild and/or had low soluble solids. Correlation between soluble solids content and storage loss was observed at both sites. The correlation observed between maturity date and frequency of rots at Pukekohe was probably the result of greater impacts of onion thrip damage and wet weather on late‐maturing lines. We conclude that although selection for storage and earliness in this programme have been effective lower pungency may have been lost from mild introductions through lack of deliberate selection.
Electrophilic Vinylation of Thiols under Mild and Transition Metal‐Free Conditions

Abstract The iodine(III) reagents vinylbenziodoxolones (VBX) were employed to vinylate a series of aliphatic and aromatic thiols, providing E‐alkenyl sulfides with complete chemo‐ and regioselectivity, as well as excellent stereoselectivity. The methodology displays high functional group tolerance and proceeds under mild and transition metal‐free conditions without the need for excess substrate or reagents. Mercaptothiazoles could be vinylated under modified conditions, resulting in opposite stereoselectivity compared to previous reactions with vinyliodonium salts. Novel VBX reagents with substituted benziodoxolone cores were prepared, and improved reactivity was discovered with a dimethyl‐substituted core.
Common Atopic Dermatitis Rating Scales: A Practical Approach and Brief Review

Atopic dermatitis (AD) severity measurement scales are important in clinical trials as objective outcome measures and are often required for government and private insurance plans. These scales are sometimes underused by clinicians due to a variety of factors including time constraints and lack familiarity. We conducted a literature review on the most commonly used AD measurement scales and provide succinct user guides and scoring explanations, advantages and disadvantages, and interscale comparisons.
Color Preference of Three Parasitoids Imported to the Americas for the Biological Control of the Coffee Berry Borer (Curculionidae: Scolytinae)

Abstract The African parasitoids Cephalonomia stephanoderis Waterston (Bethylidae: Hymenoptera), Prorops nasuta Betrem (Bethylidae: Hymenoptera), and Phymastichus coffea LaSalle (Eulophidae: Hymenoptera) are biological control agents of the coffee berry borer (Coleoptera: Curculionidae). In this study, we investigated in laboratory the female behavioral responses of these parasitoids to 14 different wavelengths (340–670 nm) against a control (570 nm, yellow). When nonchooser females were included in the analysis, none parasitoids species showed a preference between 340, 350, 370, 460, 490, 520, 540, 590, 640, and 650 nm with respect to the control wavelength. In contrast, the three species of parasitoids were more attracted to wavelengths of 380, 400, and 420 nm than the control wavelength. Phymastichus coffea and P. nasuta were more attracted to the wavelength of 400 and 420 nm compared to C. stephanoderis. At 380 nm, P. coffea and C. stephanoderis wasps showed the higher responses in comparison to P. nasuta females. When nonchooser wasps were excluded from the analysis, we observed other differences among the parasitoid species. For instance, P. coffea were more attracted to 490–540 nm than to 570 nm, whereas the bethylids did not discriminate between 490–540 nm or 570 nm. Our results are discussed in relation to possible implications associated with the vision of these parasitoid species.
Reaction Force Mapping by 3-Axis Tactile Sensing With Arbitrary Angles for Tissue Hard-Inclusion Localization

Although robot-assisted diagnosis and minimally invasive surgery (MIS) brings distinct benefits, deficient multi-dimensional force feedback remains a noteworthy limitation and challenge in MIS. Aiming for a comprehensive high-fidelity perception of tissue-instrument interactions, we present a Fiber Bragg Grating (FBG)-based 3-axis tactile sensing for surface reaction force mapping, identification and localization of tissue hard-inclusion. The tactile sensing probe consists of five optical fibers inscribed with FBGs and a force-sensitive 3D printed deformable body. All fibers are suspended inside the deformable body in a parallel manner, leading to the direct compression or tension of each FBG. Such configuration can effectively avoid the chirping failure of FBG compared with the pasting FBG-based sensors. A linearized difference model is proposed to calibrate the 3-axis force detection and enhance the resistance to nonlinear interferences. Hard-inclusion identification experiments with varied hard-inclusion sizes and depths have been implemented through discrete palpation and dragging palpation modes. Results indicate that the probe can effectively identify the presence and location of these small hard-inclusions from the force mapping. Furthermore, lengthy vessels embedded in the phantom can be accurately identified through dragging palpation with an arbitrary contact angle. Another novelty of the probe is the reconstruction of the surface profile of a non-planar tissue, which further allows hard-inclusion identification and 3D localization. Ex-vivo tissue palpation on a porcine kidney further validates the effectiveness and feasibility of the probe to map surface reaction forces and localize the hard-inclusions intraoperatively.
A Data-informed Public Health Policy-Makers Platform

Hearing loss is a disease exhibiting a growing trend due to a number of factors, including but not limited to the mundane exposure to the noise and ever-increasing size of the older population. In the framework of a public health policymaking process, modeling of the hearing loss disease based on data is a key factor in alleviating the issues related to the disease and in issuing effective public health policies. First, the paper describes the steps of the data-driven policymaking process. Afterward, a scenario along with the part of the proposed platform responsible for supporting policymaking are presented. With the aim of demonstrating the capabilities and usability of the platform for the policy-makers, some initial results of preliminary analytics are presented in the framework of a policy-making process. Ultimately, the utility of the approach is validated throughout the results of the survey which was presented to the health system policy-makers involved in the policy development process in Croatia.
Selection of biological prosthesis for abdominal wall repair on the basis of in vitro biocompatibility determination

Research on prostheses for repairing abdominal wall defects has progressed through past decades for developing an ideal prosthesis. The study was designed to compare different extracellular matrix (ECM) derived biological prostheses as alternate to conventional synthetic polymeric prostheses for the repair of full thickness abdominal wall defects. Five biological scaffolds derived from bovine diaphragm, bovine aorta, bovine gall bladder, porcine gall bladder, and rabbit skin were prepared and screened for their in vitro biocompatibility. Decellularized ECMs were subjected to various biocompatibility analyses, namely, water absorption potential, matrix degradation analysis, biomechanical testing, and cytocompatibility analysis. Though the rabbit skin displayed maximum biomechanical strength, due to its rapid degradation, it failed to fulfill the criteria of an ideal prosthesis. ECMs derived from bovine diaphragm and aorta were found to be superior than others based upon hydration and matrix degradation analysis, with best scores for bovine diaphragm followed by bovine aorta. The bovine diaphragm and aorta also displayed sufficient biomechanical strength, with diaphragm being the second highest (next to rabbit skin), in biomechanical strength followed by aorta. None of the biological prosthesis revealed any cytotoxicity. Thus, bovine diaphragm and aorta derived ECM fulfill the necessary criteria for their use as biological prosthesis. Because these prostheses are biocompatible, apart from their low cost, ease of availability, and simple preparation, they present a potential alternative to synthetic prosthesis for repair of abdominal wall defects, especially in veterinary patients.