Miracle-dz/UniFAR-FTUs huggingface dataset:
On the Enhanced Accuracy of Kinetic Curve Building in Supercritical Fluid Extraction from Aroma Plants Using a New 3D-Printed Extract Collection Device

Accurate collection of extracted material represents a technical problem in supercritical fluid extraction because trapping should be performed in severe conditions of rapidly moving and freezing expanded fluid. We have developed a simple device for effective sample collection in analytical-scale supercritical fluid extraction. The device consists of a cyclone separator equipped with a spray trap and a heated check valve. The cyclone separator and spray trap are manufactured from a light polymer via 3D printing and are quick-detachable, which encourages its use in applications where mass yield measurements are required. The device was compared to a standard tubing-and-vial approach in the task of building kinetic curves for the extraction from two aroma plants, namely, laurel and rosemary. The new device showed almost two-fold increase in extraction trapping, most probably due to better collection of volatile compounds. A curious effect of the number of mass measurement points per curve on apparent yield was observed. An increase in the number of points led to an increase in yield, probably due to the effect of the static–dynamic extract regime posed by the manner in which the device is used.
Microtubule Retrograde Motors and Their Role in Retroviral Transport

Following entry into the host cell, retroviruses generate a dsDNA copy of their genomes via reverse transcription, and this viral DNA is subsequently integrated into the chromosomal DNA of the host cell. Before integration can occur, however, retroviral DNA must be transported to the nucleus as part of a ‘preintegration complex’ (PIC). Transporting the PIC through the crowded environment of the cytoplasm is challenging, and retroviruses have evolved different mechanisms to accomplish this feat. Within a eukaryotic cell, microtubules act as the roads, while the microtubule-associated proteins dynein and kinesin are the vehicles that viruses exploit to achieve retrograde and anterograde trafficking. This review will examine the various mechanisms retroviruses have evolved in order to achieve retrograde trafficking, confirming that each retrovirus has its own strategy to functionally subvert microtubule associated proteins.
Interspecies comparison of alveolar bone biology: Tooth extraction socket healing in mini pigs and mice.

BACKGROUND in an effort to identify and validate which animal models are best suited for dental implant research, we used multiscale analyses to examine tooth extraction wound healing in a well-accepted model, the Yucatan mini pig and a more controversial model, the laboratory mouse. METHODS first molar extractions were performed in adult, skeletally mature mini pigs and mice. Alveolar bone repair was evaluated at early, intermediate and late timepoints using quantitative micro-computed tomographic (μCT) imaging, histology, molecular, and cellular assays. Vital dye labeling was employed to quantify mineral apposition rates (MAR) in both species. RESULTS Despite a 3000-fold difference in weight, the relative proportions of the mini pig and murine maxillae and are equivalent. Quantitative μCT demonstrated that within the posterior alveolar bone, the volume of mineralized bone was lower in mini pig than in the mice; during healing, however, the bone volume fraction was equivalent. The histologic appearance of healing sites was also comparable, and alkaline phosphatase (ALP) and tartrate resistant acid phosphatase (TRAP) staining showed a similar temporal and spatial distribution of bone remodeling. Vital dye labeling indicated equivalent MAR between the species. The absolute duration of the healing period differed: In mice, complete healing was accomplished in ∼21 days. In mini pigs, the same process took four times longer. CONCLUSIONS Extraction socket healing is histologically equivalent between mini pigs and mice, supporting the hypothesis that the underlying mechanisms of alveolar bone healing are conserved amongst species. This article is protected by copyright. All rights reserved.
Is Antimicrobial Treatment Effective During Therapeutic Plasma Exchange? Investigating the Role of Possible Interactions

Antimicrobial treatment during therapeutic plasma exchange (TPE) remains a complex issue. Recommendations based on a limited number of experimental studies should be implemented in clinical practice with caution. Effective management of infections due to plasma or albumin-related interactions, as well as impaired pharmacokinetics, in critical illness is difficult. Knowing the pharmacokinetics of the drugs concerned and the procedural aspects of plasmapheresis should be helpful in planning personalized treatment. In general, possessing a low distribution volume, a high protein-binding affinity, a low endogenous clearance rate, and long distribution and elimination half-lives make a drug more prone to elimination during TPE. A high frequency and longer duration of the procedure may also contribute to altering a drug’s concentration. The safest choice would be to start and finish TPE before antimicrobial agent infusion. If this not feasible, a reasonable alternative is to avoid administering the drug just before TPE and to delay the procedure for the time of the administered drug’s distributive phase. Ultimately, if plasma exchange must be performed urgently or the drug has a very narrow therapeutic index, monitoring its plasma concentration is advised.
Rabacfosadine for naïve canine intermediate to large cell lymphoma: Efficacy and adverse event profile across three prospective clinical trials

Abstract While current lymphoma therapies induce remission in most dogs, drug‐resistant relapse is common, creating a need for novel agents. Rabacfosadine (RAB), a double prodrug of the acyclic nucleotide phosphonate 9‐(2‐phosphonylmethoxyethel) guanine (PMEG), preferentially targets lymphoma cells with reduced systemic toxicity compared with PMEG. Previous studies evaluating RAB administered every 21 days have suggested efficacy in both naïve and relapsed subjects; however, no large studies of RAB as a single agent have been reported in previously untreated dogs with intermediate to large cell lymphoma. The purpose of this study was to evaluate the safety and efficacy of RAB in dogs with previously untreated (excluding corticosteroids) lymphoma. Sixty‐three dogs received up to five RAB treatments every 21 days (16 at 0.82 mg/kg and 47 at 1.0 mg/kg) as a 30 minutes intravenous infusion, with (n = 23) or without (n = 40) concurrent corticosteroids. Response assessment and adverse event (Ae) evaluation were performed every 21 days via Veterinary Cooperative Oncology Group (VCOG) criteria. The overall response rate was 87% (52% CR, 35% PR). The overall median progression free interval was 122 days (199 for CR, 89 for PR and 153 days for all responders). T‐cell immunophenotype and corticosteroid pre‐treatment were predictive of inferior outcomes on multivariate analysis. AEs were most commonly of gastrointestinal origin (hyporexia/diarrhoea) and generally resolved with supportive treatment and/or dosage adjustment. Three dogs experienced VCOG‐CTCAE grade 5 delayed pulmonary fibrosis. In conclusion, RAB administered every 3 weeks is generally well tolerated and demonstrates substantial antitumour activity in dogs with previously untreated intermediate to large cell lymphoma.
Structure‐based discovery of CZL80, a caspase‐1 inhibitor with therapeutic potential for febrile seizures and later enhanced epileptogenic susceptibility

Febrile seizures (FS), the most common seizures in childhood and often accompanied by later epileptogenesis, are not well controlled. Inflammatory processes have been implicated in the pathophysiology of epilepsy. However, whether caspase‐1 is involved in FS generation and could be a target for the treatment of FS is still unclear.
A DSG1 Frameshift Variant in a Rottweiler Dog with Footpad Hyperkeratosis

A single male Rottweiler dog with severe footpad hyperkeratosis starting at an age of eight weeks was investigated. The hyperkeratosis was initially restricted to the footpads. The footpad lesions caused severe discomfort to the dog and had to be trimmed under anesthesia every 8–10 weeks. Histologically, the epidermis showed papillated villous projections of dense keratin in the stratum corneum. Starting at eight months of age, the patient additionally developed signs consistent with atopic dermatitis and recurrent bacterial skin and ear infections. Crusted hyperkeratotic plaques developed at sites of infection. We sequenced the genome of the affected dog and compared the data to 655 control genomes. A search for variants in 32 candidate genes associated with human palmoplantar keratoderma (PPK) revealed a single private protein-changing variant in the affected dog. This was located in the DSG1 gene encoding desmoglein 1. Heterozygous monoallelic DSG1 variants have been reported in human patients with striate palmoplantar keratoderma I (SPPK1), while biallelic DSG1 loss of function variants in humans lead to a more pronounced condition termed severe dermatitis, multiple allergies, and metabolic wasting (SAM) syndrome. The identified canine variant, DSG1:c. 2541_2545delGGGCT, leads to a frameshift and truncates about 20% of the coding sequence. The affected dog was homozygous for the mutant allele. The comparative data on desmoglein 1 function in humans suggest that the identified DSG1 variant may have caused the footpad hyperkeratosis and predisposition for allergies and skin infections in the affected dog.
Data Offloading in UAV-Assisted Multi-Access Edge Computing Systems: A Resource-Based Pricing and User Risk-Awareness Approach

Unmanned Aerial Vehicle (UAV)-assisted Multi-access Edge Computing (MEC) systems have emerged recently as a flexible and dynamic computing environment, providing task offloading service to the users. In order for such a paradigm to be viable, the operator of a UAV-mounted MEC server should enjoy some form of profit by offering its computing capabilities to the end users. To deal with this issue in this paper, we apply a usage-based pricing policy for allowing the exploitation of the servers’ computing resources. The proposed pricing mechanism implicitly introduces a more social behavior to the users with respect to competing for the UAV-mounted MEC servers’ computation resources. In order to properly model the users’ risk-aware behavior within the overall data offloading decision-making process the principles of Prospect Theory are adopted, while the exploitation of the available computation resources is considered based on the theory of the Tragedy of the Commons. Initially, the user’s prospect-theoretic utility function is formulated by quantifying the user’s risk seeking and loss aversion behavior, while taking into account the pricing mechanism. Accordingly, the users’ pricing and risk-aware data offloading problem is formulated as a distributed maximization problem of each user’s expected prospect-theoretic utility function and addressed as a non-cooperative game among the users. The existence of a Pure Nash Equilibrium (PNE) for the formulated non-cooperative game is shown based on the theory of submodular games. An iterative and distributed algorithm is introduced which converges to the PNE, following the learning rule of the best response dynamics. The performance evaluation of the proposed approach is achieved via modeling and simulation, and detailed numerical results are presented highlighting its key operation features and benefits.
CRISPR/Cas9 gene editing: A new therapeutic approach in the treatment of infection and autoimmunity

CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR‐associated protein9) may be viewed as an adaptive bacterial immune system. When a virus infects a bacterium, a fragment of the virus genome is inserted into the CRISPR sequence of the bacterial genome as a memory. When the bacterium becomes infected again with the same virus, an RNA molecule that is a transcript of the memory sequence, directs Cas9, an endonuclease, to the complementary region of the virus genome, and Cas9 disables the virus by a double‐strand break. In recent years, studies have shown that by designing synthetic RNA molecules and delivering them along with Cas9 into eukaryotic cells, different regions of the cell's genome can be targeted and manipulated. These findings have drawn much attention to this new technology and it has been shown that CRISPR/Cas9 gene editing can be used to treat some human diseases. These include infectious diseases and autoimmune diseases. In this review article, in addition to a brief overview of the biology of the CRISPR/Cas9 system, we collected the most recent findings on the applications of CRISPR/Cas9 technology for better investigation of the pathogenesis and treatment of viral infections (human immunodeficiency virus infection, hepatitis virus infections, and onco‐virus infections), non‐viral infections (parasitic, fungal, and bacterial infections), and autoimmune diseases.
Comparing Cone Structure and Function in RHO- and RPGR-Associated Retinitis Pigmentosa

Purpose To study cone structure and function in patients with retinitis pigmentosa (RP) owing to mutations in rhodopsin (RHO), expressed in rod outer segments, and mutations in the RP-GTPase regulator (RPGR) gene, expressed in the connecting cilium of rods and cones. Methods Four eyes of 4 patients with RHO mutations, 5 eyes of 5 patients with RPGR mutations, and 4 eyes of 4 normal subjects were studied. Cone structure was studied with confocal and split-detector adaptive optics scanning laser ophthalmoscopy (AOSLO) and spectral-domain optical coherence tomography. Retinal function was measured using a 543-nm AOSLO-mediated adaptive optics microperimetry (AOMP) stimulus. The ratio of sensitivity to cone density was compared between groups using the Wilcoxon rank-sum test. Results AOMP sensitivity/cone density in patients with RPGR mutations was significantly lower than normal (P < 0.001) and lower than patients with RHO mutations (P < 0.015), whereas patients with RHO mutations were similar to normal (P > 0.9). Conclusions Retinal sensitivity/cone density was lower in patients with RPGR mutations than normal and lower than patients with RHO mutations, perhaps because cones express RPGR and degenerate primarily, whereas cones in eyes with RHO mutations die secondary to rod degeneration. High-resolution microperimetry can reveal differences in cone degeneration in patients with different forms of RP.
Chitosan Coated Microparticles Enhance Simvastatin Colon Targeting and Pro-Apoptotic Activity

This work aimed at improving the targeting and cytotoxicity of simvastatin (SMV) against colon cancer cells. SMV was encapsulated in chitosan polymers, followed by eudragit S100 microparticles. The release of SMV double coated microparticles was dependent on time and pH. At pH 7.4 maximum release was observed for 6 h. The efficiency of the double coat to target colonic tissues was confirmed using real-time X-ray radiography of iohexol dye. Entrapment efficiency and particle size were used in the characterization of the formula. Cytotoxicity of SMV microparticles against HCT-116 colon cancer cells was significantly improved as compared to raw SMV. Cell cycle analysis by flow cytomeric technique indicated enhanced accumulation of colon cancer cells in the G2/M phase. Additionally, a significantly higher cell fraction was observed in the pre-G phase, which highlighted enhancement of the proapoptotic activity of SMV prepared in the double coat formula. Assessment of annexin V staining was used for confirmation. Cell fraction in early, late and total cell death were significantly elevated. This was accompanied by a significant elevation of cellular caspase 3 activity. In conclusion, SMV-loaded chitosan coated with eudragit S100 formula exhibited improved colon targeting and enhanced cytotoxicity and proapoptotic activity against HCT-116 colon cancer cells.
Excessively activated plasminogen in human plasma cleaves VWF multimers and reduces collagen-binding activity.

Plasmin (Pm) is a serine protease that can dissolve fibrin clots. Several possible functions of Pm in blood other than fibrinolysis have been proposed. To explore the effects of Pm on primary hemostasis, we evaluated the cleavage of von Willebrand factor multimers (VWFMs) in human plasma by streptokinase (SK)-activated plasminogen (Pg) and the binding ability of the digested VWFMs to collagen. SK-activated Pg and ADAMTS13 (a VWF-cleaving enzyme) in human plasma cleaved VWFMs in conformation-dependent manners through dialysis to the urea-containing buffer. However, VWFMs in human plasma under vortex-based shear stress were cleaved by SK-activated Pg but not by ADAMTS13. These results suggested that the VWFM cleavage sites in human plasma are exposed to some extent by vortex-based shear stress for Pm but not for ADAMTS13. Additionally, we revealed that cleavage by SK-activated Pg reduced VWFMs' binding ability to collagen, and VWFMs in human plasma were cleaved by Pm at several sites. These results suggest that SK-activated Pg degrades VWFMs, reduces their binding abilities to collagen, and affects primary hemostasis. Because excessive Pg activation can degrade fibrinogen/fibrin, we propose that SK-activated Pg in blood may cause impaired primary and secondary hemostasis.
ER stress response regulates the fate of myeloid-derived suppressor cells through TRAIL receptors mediated apoptosis (TUM4P.907)

We studied the fate of myeloid-derived suppressor cells (MDSC) in cancer. Unexpectedly, MDSC had lower viability and a shorter half-life than their control counterparts neutrophils and monocytes. This effect was due to increased apoptosis mediated by the changes in TRAIL receptors (TRAIL-R) expression. Targeting TRAIL-R did not affect myeloid cells from naïve mice, but dramatically reduced the presence of MDSC and improved the immune responses in tumor-bearing mice. Pro-inflammatory cytokines did not affect TRAIL-R expression. However, induction of ER stress recapitulated changes in TRAIL-R expression observed in tumor-bearing hosts. ER stress response was detected in MDSC isolated from cancer patients and tumor-bearing mice, but not in control neutrophils or monocytes. Block of ER stress abrogated changes in TRAIL-R. Thus, MDSC pathophysiology is linked to ER stress, which shortens their lifespan in the periphery and promotes their expansion in bone marrow. In conclusion, TRAIL-R can be considered for selective targeting of MDSC.
Second Cancer in a Patient With Breast Cancer

of the cases occur sporadically and less common form of osteoma can arise with Gardner syndrome. We present a patient with evident proptosis and diplopia due to massive orbital ivory osteoma. A 42 year-old man who had been diagnosed with ivory osteoma was admitted to our clinic. There was a palpable, smooth, and dense mass on right lateral orbital wall (Fig. 1). Proptosis and diplopia were observed during opthalmologic examination. Eye movement restriction, pupillary edema, and optic nerve compression were not observed; fundus examination and pupillary reflexes were normal. A 5 3 cm hyperdense, pedunculated lesion was detected on the right lateral orbital wall by using computed tomography (Fig. 1). Bicoronal incision was performed while patient was under general anesthesia. Subgaleal plane was dissected gently. Temporal muscle was incised and subperiostal dissection was performed toward the lateral orbital wall. Pedinculated mass and partial lateral orbital wall were excised. Incision was closed properly. There were no complications on postoperative 2-year period (Fig. 2). Proptosis and diplopia complaints regressed totally. Although the orbital ivory osteomas are rare, they may cause serious complaints such as proptosis and diplopia. The craniofacial surgeon should give importance to the management of these tumors.
Exploring Deep Learning Based Approaches for Endoscopic Artefact Detection and Segmentation

The Endoscopic Artefact Detection challenge comprises tasks for detection and segmentation of artefacts found in endoscopic imaging, with a speciﬁc task for evaluating the generalization capacity of detection algorithms on external data. For the detection of artefacts, we train RetinaNet and Faster-RCNN models. To segment artefacts from the endoscopic images, we train a Deeplab v3 model and a U-Net model and also implement post-processing techniques such as the usage of an EAST text detector for detection of text artefacts and pixel-wise voting ensemble after applying test time augmentation. We observe that the RetinaNet model with a ResNet-101 feature extractor is the best performing model across all object detection tasks, while the U-Net performs best in the segmentation tasks. We also implement a model agnostic object tracking pipeline utilizing image correlation-based trackers to reduce the inference time of object detection models. We believe that this pipeline can enable real-time analysis of endoscopic images in systems with processing constraints.
HT-based Recognition of Patterns on 3D Shapes Using a Dictionary of Mathematical Curves

Characteristic curves play a fundamental role in the way a shape is perceived and illustrated. To address the curve recognition problem on surfaces, we adopt a generalisation of the Hough Transform (HT) which is able to deal with mathematical curves. In particular, we extend the set of curves so far adopted for curve recognition with the HT and propose a new dictionary of curves to be selected as templates. In addition, we introduce rules of composition and aggregation of curves into patterns, not limiting the recognition to a single curve at a time. Our method recognises various curves and patterns, possibly compound on a 3D surface. It selects the most suitable proﬁle in a family of curves and, deriving from the HT, it is robust to noise and able to deal with data incompleteness. The system we have implemented is open and allows new additions of curves in the dictionary of functions already available.
Fast and Efficient Nearest Neighbor Search for Particle Simulations

Abstract One of the fundamental algorithms in particle simulations is the identiﬁcation and iteration over nearest neighbors of every particle. Well-known examples are SPH or PBD simulations that compute forces and particle-position updates in every simulation step. In order to ﬁnd nearest neighbors for all particles, hash-based, grid-based or tree-based approaches have been developed in the past. The two most prominent and fastest algorithms use virtual and explicitly allocated uniform grids to achieve high performance on Graphics Processing Units (GPUs). However, they have disadvantages with numerous particle simulation domains, either in terms of run time or memory consumption. We present a novel algorithm that can be applied to large simulation domains that signiﬁcantly reduces memory consumption using a shared-memory based neighbor search. Furthermore, we achieve high-performance on our evaluation scenarios that often outperforms existing state-of-the-art methods.