Miracle-dz/UniFAR-FTUs huggingface dataset:
Göttingen Minipig is not a Suitable Animal Model for in Vivo Testing of Tissue-Engineered Corneal Endothelial Cell-Carrier Sheets and for Endothelial Keratoplasty

ABSTRACT Aim: To test the feasibility of implanting human anterior lens capsules (HALCs) with porcine corneal endothelial cells (pCEC) in vivo in Göttingen minipigs and at the same time test the suitability of Göttingen minipig as model for endothelial keratoplasty. Materials and Methods: Cell-carrier constructs of decellularized HALC with cultured (pCEC) were created for implementation in vivo. Eight Göttingen minipigs (6 months old) underwent surgery with descemetorhexis or removal of endothelium by scraping and implementation of HALC without (animal 1–4) and with (animal 5–8) pCEC. Follow-up examinations included optical coherence tomography (OCT) imaging (1,2 and 3 months) and slit-lamp examination (<1 week as well as 1,2 and 3 months). Results: Intraoperative challenges included difficulties in maintaining an anterior chamber due to soft tissue and vitreous pressure, development of corneal edema and difficulties removing Descemet’s membrane because of strong adhesion to stroma. Therefore, descemetorhexis was replaced by mechanical scraping of the endothelium in animal 4–8. HALCs without pCEC were implanted in animal 1–4. Apposition to the back surface was not achieved in animal 1 and 3 because of corneal edema and poor visibility. Animal 5 was sacrificed because of a lens capsule tear. HALCs with pCEC were implanted in animal 6–8. Slit-lamp examination the first week revealed corneal edema in all animals, although mild in animals 4. One-month examination showed retrocorneal membranes with overlying corneal edema in all animals. Histology showed fibrosis in the AC and on the back surface of the cornea, compatible with the clinical diagnosis of retrocorneal membrane. Conclusions: In conclusion, the minipig is not suitable for corneal transplantation studies in vivo because of intraoperative challenges and development of retrocorneal membrane postoperatively. For in vivo testing of the surgical handling and the therapeutic potential of tissue-engineered endothelial cell-carrier constructs other animal models are required.
Evaluating the combination of a Brief Motivational Intervention plus Cognitive Behavioral Therapy for Depression and heavy episodic drinking in college students.

Heavy episodic drinking (HED) and depressive symptoms often co-occur among college students and are associated with significant impairment. However, evidence-based treatments for these common co-occurring conditions are not available for college students. The current study compared the effectiveness of a treatment combining Cognitive-Behavioral Therapy for Depression and Brief Motivational Interviewing (CBT-D + BMI) versus Cognitive-Behavioral Therapy for Depression (CBT-D) alone among 94 college students with HED and depressive symptoms. Both treatment programs were associated with significant reductions of similar magnitude in HED, alcohol-related problems (ARP), and depressive symptoms at the end of treatment and at the 1-month follow-up assessment. Moderation analyses indicated that, among college students with fewer depressive symptoms at baseline, CBT-D was associated with greater sustained reduction in heavy drinking relative to CBT-D + BMI at the 1-month follow-up. Although the study did not include a no-treatment condition, the magnitude of improvement during treatment in both groups was greater than what is expected with passage of time. Although clinicians in college counseling centers may lack specialty training for co-occurring conditions, CBT-D is widely implemented in college settings. Our findings suggest that CBT-D may reduce both depressive symptoms and HED in college students and may be used to address a significant public health problem. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Lifestyle interventions and quality of life for women with polycystic ovary syndrome

Abstract Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. PCOS has a significant negative impact on the health-related quality of life (HRQoL) and psychological function of women, of which there are reports of high levels of depression in women with PCOS compared to those without PCOS. However, the evidence surrounding the effects of exercise and/or dietary intervention participation on the HRQoL of women with PCOS is limited. Therefore, our objective is to examine the effects of lifestyle interventions (definition include exercise-only, diet-only, exercise + diet and behavioral or combined) on health-related quality of life or general quality of life in women with PCOS. Methods: We will conduct an update of systematic review and we will follow the recommendations and guidelines of the Cochrane handbook for systematic reviews and Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol (PRISMA-P). We will search the studies in the following databases: MEDLINE. PubMed, PsychINFO, Embase, SportDiscus, Web of Science, Cochrane Database (via Cochrane library), Cochrane Controlled Register of Trials (CENTRAL), and Google Scholar (advance). Manual search of the reference list of identified works, without language and year restrictions. The process of study selection and data extraction will be performed independently by 2 reviewers, with a third reviewer being responsible for the final decision in case of disagreement between the first two. We will use Egger funnel chart to evaluate possible publication biases, in addition, when possible we will perform a subgroup/meta-regression analysis. The strength of the evidence will be assessed according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Protocol registry: PROSPERO number: CRD42019124176.
Emergence of extended-spectrum β-lactamase (ESBL) and/or carbapenemase producing Enterobacteriaceae (CPE) and their antimicrobial resistance.

OBJECTIVES We focused on detecting the most frequent resistance mechanisms in selected multidrug-resistant (MDR) strains and determining their antimicrobial resistance. BACKGROUND MDR pathogens pose urgent public health threat due to limited treatment options, rigorous control measures and significant mortality. METHODS We confirmed extended-spectrum β-lactamase (ESBL) and carbapenemase producing Enterobacteriaceae through guidelines, as well following β-lactamases: AmpC by cloxacillin, class A carbapenemase with phenylboronic acid, class B metallo-β-lactamase with ethylenediaminetetraacetic acid. Multilocus sequence typing was used to investigate 20 Escherichia coli strains. RESULTS Overall 205 mostly ESBL Escherichia coli demonstrated resistance against amikacin (4.7 %), tigecycline (1.2 %), and no resistance to ceftazidime/avibactam, meropenem, nitrofurantoin and fosfomycin. Out of 41 Klebsiella species (spp.), 37 (90.2 %) showed carbapenemase activity, 13 (35.1 %) of class A and 24 (64.9 %) of class B. Resistance was following: meropenem 66.7 %, tigecyclin 10.2 % and colistin 0 %. From Enterobacter spp. 21 strains, 14 (66.7 %) were ESBL, 5 produced ESBL and/or AmpC and 2 were MDR. We ascertained 14 (70 %) E. coli sequence type - ST131. CONCLUSIONS The study revealed various resistance mechanisms in concert with different agents and association of specific ST131 within E. coli. These characteristics considerably contribute to emergence of antimicrobial resistance (Tab. 4, Ref. 30).
Integrative analyses of noncoding RNAs reveal the potential mechanisms augmenting tumor malignancy in lung adenocarcinoma

Abstract Precise noncoding RNA (ncRNA)-based network prediction is necessary to reveal ncRNA functions and pathological mechanisms. Here, we established a systemic pipeline to identify prognostic ncRNAs, predict their functions and explore their pathological mechanisms in lung adenocarcinoma (LUAD). After in silico and experimental validation based on evaluations of prognostic value in multiple LUAD cohorts, we selected the PTTG3P pseudogene from among other prognostic ncRNAs (MIR497HG, HSP078, TBX5-AS1, LOC100506990 and C14orf64) for mechanistic studies. PTTG3P upregulation in LUAD cells shortens the metaphase to anaphase transition in mitosis, increases cell viability after cisplatin or paclitaxel treatment, facilitates tumor growth that leads to poor survival in orthotopic lung models, and is associated with a poor survival rate in LUAD patients in the TCGA cohort who received chemotherapy. Mechanistically, PTTG3P acts as an ncRNA that interacts with the transcription factor FOXM1 to regulate the transcriptional activation of the mitotic checkpoint kinase BUB1B, which augments tumor growth and chemoresistance and leads to poor outcomes for LUAD patients. Overall, we established a systematic strategy to uncover prognostic ncRNAs with functional prediction methods suitable for pan-cancer studies. Moreover, we revealed that PTTG3P, due to its upregulation of the PTTG3P/FOXM1/BUB1B axis, could be a therapeutic target for LUAD patients.
Across‐vendor standardization of semi‐LASER for single‐voxel MRS at 3T

The semi‐adiabatic localization by adiabatic selective refocusing (sLASER) sequence provides single‐shot full intensity signal with clean localization and minimal chemical shift displacement error and was recommended by the international MRS Consensus Group as the preferred localization sequence at high‐ and ultra‐high fields. Across‐vendor standardization of the sLASER sequence at 3 tesla has been challenging due to the B1 requirements of the adiabatic inversion pulses and maximum B1 limitations on some platforms. The aims of this study were to design a short‐echo sLASER sequence that can be executed within a B1 limit of 15 μT by taking advantage of gradient‐modulated RF pulses, to implement it on three major platforms and to evaluate the between‐vendor reproducibility of its perfomance with phantoms and in vivo. In addition, voxel‐based first and second order B0 shimming and voxel‐based B1 adjustments of RF pulses were implemented on all platforms. Amongst the gradient‐modulated pulses considered (GOIA, FOCI and BASSI), GOIA‐WURST was identified as the optimal refocusing pulse that provides good voxel selection within a maximum B1 of 15 μT based on localization efficiency, contamination error and ripple artifacts of the inversion profile. An sLASER sequence (30 ms echo time) that incorporates VAPOR water suppression and 3D outer volume suppression was implemented with identical parameters (RF pulse type and duration, spoiler gradients and inter‐pulse delays) on GE, Philips and Siemens and generated identical spectra on the GE ‘Braino’ phantom between vendors. High‐quality spectra were consistently obtained in multiple regions (cerebellar white matter, hippocampus, pons, posterior cingulate cortex and putamen) in the human brain across vendors (5 subjects scanned per vendor per region; mean signal‐to‐noise ratio > 33; mean water linewidth between 6.5 Hz to 11.4 Hz). The harmonized sLASER protocol is expected to produce high reproducibility of MRS across sites thereby allowing large multi‐site studies with clinical cohorts.
Gastroenteric parasite of wild Galliformes in the Italian Alps: implication for conservation management

Abstract This study provides insights about the diversity, prevalence and distribution of alpine wild galliformes gastrointestinal parasite community, trying to fill a gap in the scientific information currently available in scientific literature. The analysis included three host species: 77 rock partridge (Alectoris graeca saxatilis), 83 black grouse (Tetrao tetrix tetrix) and 26 rock ptarmigan (Lagopus muta helveticus) shot during the hunting seasons 2008–2015. Parasites isolated were Ascaridia compar, Capillaria caudinflata and cestodes. The rock ptarmigan was free from gastrointestinal parasites, whereas the most prevalent helminth (37%) was A. compar in both black grouse and rock partridge. C. caudinflata occurrence was significantly higher in black grouse (prevalence = 10%, mean abundance = 0.6 parasites/sampled animal) than in rock partridge (prevalence = 1.20%, mean abundance = 0.01 parasites/sampled animal). Significant differences were detected among hunting districts. A. compar was found with a significant higher degree of infestation in the hunting districts in the northern part of the study area whereas cestodes abundance was higher in Lanzo Valley. Quantitative analysis of risk factors was carried out using a generalized linear model (GLM) only on the most common parasite (A. compar). Latitude was the only factors associated with infestation risk (OR = 52.4). This study provides information on the composition and variability of the parasite community in the alpine Galliformes species.
Neutrophils Enhance Their Own Influx to Sites of Bacterial Infection via Endosomal TLR-Dependent Cxcl2 Production

Key Points Neutrophils produce high levels of Cxcl2 in response to whole bacteria. Cxcl2 production depends on sensing of bacterial nucleic acids by TLR7, 9, and 13. Cxcl2 acts autocrinously to enhance antibacterial activities and its own production. Visual Abstract The influx of neutrophils to infection sites is a fundamental step in host defenses against the frequent human pathogen group B Streptococcus (GBS) and other extracellular bacteria. Using a mouse model of GBS-induced peritonitis, we show in this study that the chemokines Cxcl1 and Cxcl2 play distinctive roles in enhancing the recruitment and the antibacterial activities of neutrophils in a manner that is linked to differences in the cellular sources of these mediators. Cell depletion experiments demonstrated that neutrophils make a significant contribution to the in vivo production of Cxcl2 but not Cxcl1. In vitro, neutrophils responded weakly to LPS but released high levels of Cxcl2 after stimulation with GBS or other bacteria. Neutrophil-derived Cxcl2 acted in an autocrinous manner to increase its own production and to enhance antibacterial activities, including the release of oxygen radicals. In both neutrophils and macrophages, the production of Cxcl1/2 largely required the presence of functional UNC93B1, a chaperone protein involved in signaling by endosomal TLRs. Moreover, the phenotype of UNC93B1-defective phagocytes could be recapitulated by the simultaneous absence of TLR7, 9, and 13 but not by the absence of individual TLRs. Collectively, our data show that neutrophils recognize Gram-positive and Gram-negative bacteria by means of multiple phagosomal TLRs, resulting in de novo synthesis of Cxcl2, amplification of neutrophil recruitment, and potentiation of their antibacterial activities. These data may be useful to devise alternative therapeutic strategies aimed at enhancing the recruitment and the functional activities of polymorphonuclear leukocytes during infections caused by antibiotic-resistant bacteria.
Isothiocyanate groups of 4,4′‐diisothiocyanatostilbene‐2,2′‐disulfonate (DIDS) inhibit cell penetration of octa‐arginine (R8)–fused peptides

Delivering biomolecules, such as antibodies, proteins, and peptides, to the cytosol is an important and challenging aspect of drug development and chemical biology. Polyarginine—a well‐known cell‐penetrating peptide (CPP)—is capable of exploiting its positive charge and guanidium groups to carry a fused cargo into the cytosol. However, the precise mechanism by which this occurs remains ambiguous. In the present study, we established a new method of quantitatively assessing cell penetration. The method involves inducing cell death by using a polyarginine (R8) to deliver a peptide—ie, mitochondrial targeting domain (MTD)—to the cytosol. We found that 4,4′‐diisothiocyanatostilbene‐2,2′‐di‐sulfonate (DIDS)—an anion channel blocker—inhibited the ability of octa‐arginine (R8)–fused MTD to penetrate cells. Other anion channel blockers did not inhibit the penetration of peptides fused with R8. Comparison of DIDS with other structurally similar chemicals revealed that the isothiocyanate group of DIDS may be primarily responsible for the inhibitory effect than its stilbene di‐sulfonate backbone. These results imply that the inhibitory effect of DIDS may not be derived from the interaction between stilbene di‐sulfonate and the anion channels, but from the interaction between the isothiocyanate groups and the cell membrane. Our new MTD method enables the quantitative assessment of cell penetration. Moreover, further studies on the inhibition of CPPs by DIDS may help clarify the mechanism by which penetration occurs and facilitate the design of new penetrative biomolecules.
Implementation of Automatic Lift Axle System for Trucks with Mechanical Suspension

The aim of an automatic lift axle auto-drop system is to drop the appropriate liftable axle of a truck automatically based on the loading condition, instead of being manually controlled by the driver. In this paper, addition to previous studies, experimental implementation of an AutoDrop system to a truck suspended with compensating arm type mechanical suspension is told. Weight estimation for compensating arm type suspension has challenge because of articulation working and huge hysteresis characteristic. An approach is brought and analyzed for weight estimation for the axles with compensating arm using height sensors resulting higher accuracy. An improved algorithm is developed and lift axle system becomes automatized to satisfy the rules mentioned in EU Directive 1230/2012 EEC. An algorithm is achieved by Coding and implementing the software using Electronic Control Unit mounted in Cab.
Towards the automated high-throughput characterization of immobilized enzymes

Here we propose an automated high-throughput technique that allows quick and thorough characterization of the effects on the activity of immobilized 6xHis-tag enzymes using magnetic beads as a support in different reaction conditions. The enzyme used was E. coli transketolase (TK) (pQR412). The adopted immobilization technique made use of Ni-NTA magnetic agarose beads. It was tested and characterized regarding the amount of TK immobilized after incubation with the magnetic beads as well the biocatalyst distribution during the various immobilization steps. Afterwards the immobilization technique was used in manually conducted experiments aimed at determining the most appropriate buffer and the optimal biocatalyst amount. Tris-HCl proved to be the optimal buffer tested while a 1:5 (v/v) ratio of bead/TK solutions proved optimal. Finally, this technique was implemented and optimized in an automated robotic platform. After succeeding obtaining activity in automated runs, a comparison between automatically and manually immobilized TK activities was made. A considerable difference between both results was verified and the possible reasons for this explored. A competitive/inhibitory effect of Imidazole was the most coherent hypothesis raised to explain these discrepancies.
Search for new decays of the Λ0b baryon at the LHCb experiment

High statistics collected by the LHCb experiment between 2011 and 2018 in proton-proton (pp) collisions at the Large Hadron Colllider (LHC), jointly with the large cross-section of bb− pairs production provides unique possibility for the search and study new decays of beauty hadrons. The results of search for new decays of the Λ0b baryons are presented. In particular the decays Λ0b → Λ+c pp−π−, Λ0b → J/ψΛ, Λ0b → ψ(2S)Λ, Λ0b → ψ(2S)pπ−, Λ0b → χc1(3872)pK− and Λ0b → Λγ are found and branching fraction ratios measurement for these decays are done. Also the study of the Λ0bπ+π− systems led to the observation of two new excited Λ0b states, denoted as Λb(6146)0 and Λb(6152)0, are found.
Measuring B-cell function in vivo to understand the pathophysiology of type 2 diabetes

Diabetes arises when insulin secretion is inadequate for the prevailing metabolic conditions. As such appropriate measurement of B-cell function is necessary for a better understanding of the pathophysiology of prediabetes and diabetes. Unfortunately this is not a straightforward process and requires utilization of mathematical modelling to best appreciate its complexities. This is because insulin concentrations in the plasma represent a balance between the processes of secretion, hepatic extraction and clearance. In isolation such simple measures reveal very little about B-cell function. Moreover, since insulin lowers glucose accounting for the effect of the former on the latter it is a key part of understanding insulin action. The development of the minimal model has allowed simultaneous measurement of the dynamic relationship between insulin secretion and insulin action and produces a quantitative number – the Disposition Index – which quantifies B-cell function. At present this remains the best functional measure of islet health, however, it may not capture other phenotypes such as B-cell senescence or the effect of incretin hormones on B-cell function. Future ongoing development and interaction with other technologies, such as functional imaging, should enhance the contribution of this functional testing to the prevention, treatment and understanding of type 2 diabetes.
E-LEARNING A VÝZNAM PŘEDÁVÁNÍ INFORMACE STUDENTŮM A PACIENTŮM V MNOHOJAZYČNÉM PROSTŘEDÍ (CZE) E-LEARNING AND THE IMPACT OF INFORMATION DELIVERY TO STUDENTS AND PATIENTS IN MULTILINGUAL SETTING (ENG)

Particularly important in educational programmes and knowledge dissemination is the role of the Internet. We show several approaches how to use Internet and Web 2.0 based e-learning tools in doctoral and lifelong education. Within the fields of health and medicine there are three main areas, where the e-learning approach has been applied: medical training, research translation and health literacy. We show some e-learning tools, especially interactive books, interactive programs and system ExaMe, using examples from the field of dentistry. We also concern with problem of transferring knowledge in different languages using Internet based European Journal for Biomedical Informatics.
A Flexible Sampling-Based Approach to Task and Motion Planning

Generalized robot autonomy requires robots to plan solutions for complex and varied tasks involving interaction with the physical world. Traditionally, the (continuous) geometric and (discrete) symbolic aspects of the problem are studied independently; motion planners solve geometric problems, whereas task planners solve symbolic problems. Integrated Task and Motion Planning (TAMP) seeks to unify the planning problem using information from each component to ease the solution of the other. Most TAMP approaches focus on information flow between task and motion planners; the majority of these approaches integrate the motion planning layer into the task planning layer as a source of constraints and/or a validator for task plans [1, 2, 5, 8]. Validating task plans with a motion planner may require repeated expensive executions of both planners. Getting constraints from the motion planner is more efficient but is often limited by the manual selection of a restricted subset of motion constraints to integrate in the task layer. Both of these issues affect not only the efficacy of a planner but also its robustness — planning for or responding to action failures and uncertainty is difficult if doing so is computationally heavy or if the system does not capture all reasons for action failure. We present a novel approach to TAMP that fully embeds a symbolic abstraction of a planning problem into the continuous representation of the problem. This fused representation allows a single sampling-based motion planner to solve both problems simultaneously and efficiently in a single invocation while implicitly capturing all geometric/kinematic constraints on actions. To make this process efficient, we contribute methods for: 1) a continuous semantics for logical formulae in configuration space, 2) a factorization of the sampling problem to mitigate a dimensional explosion, and 3) the use of standard task planning heuristics as sampling biases. Our approach lends itself to efficient replanning in the face of failure, which we discuss as a possible extension to the technique.