BDNF, sHLA-G, and sTREM-1 are useful blood biomarkers for identifying grade IV glioma patients.

Inflammation and immunity belong to the main factors influencing tumor growth. In this study, we attempted to identify a profile of biomarkers associated with gliomas. We found decreased serum levels of sTREM-1 (soluble triggering receptor expressed on myelocytes) and increased levels of IL-10 in all grades of glioma patients in comparison with healthy controls (sTREM-1: grade II: p=0.0051, grade III: p=0.02, grade IV: p=0.01; IL-10: grade II: p=0.0017, grade III: p=0.03, grade IV: p=0.007). However, we did not find any combination of tested markers with good sensitivity and specificity in grades II and III of glioma patients to discriminate them from healthy controls. In grade IV glioma patients, two sets of markers showed promising results in distinguishing patients from healthy people. For the first set consisting of four selected markers, sTREM-1, sHLA-G, BDNF, and IL-13, the ROC curves indicate a good discriminatory capability for glioblastoma patients (AUC=0.9510). The best discriminatory capability for glioblastoma patients (AUC=0.9534) was found for the second set consisting of three selected markers sTREM-1, sHLA-G, and BDNF with 79.2% sensitivity and 94.1% specificity.

Processing Real-Life Recordings of Facial Expressions of Polish Sign Language Using Action Units.

Automatic translation between the national language and sign language is a complex process similar to translation between two different foreign languages. A very important aspect is the precision of not only manual gestures but also facial expressions, which are extremely important in the overall context of a sentence. In this article, we present the problem of including facial expressions in the automation of Polish-to-Polish Sign Language (PJM) translation-this is part of an ongoing project related to a comprehensive solution allowing for the animation of manual gestures, body movements and facial expressions. Our approach explores the possibility of using action unit (AU) recognition in the automatic annotation of recordings, which in the subsequent steps will be used to train machine learning models. This paper aims to evaluate entropy in real-life translation recordings and analyze the data associated with the detected action units. Our approach has been subjected to evaluation by experts related to Polish Sign Language, and the results obtained allow for the development of further work related to automatic translation into Polish Sign Language.

HLA-G 5'URR regulatory polymorphisms are associated with the risk of developing gliomas.

BACKGROUND: Human leukocyte antigen G (HLA-G) belongs to non-classical MHC class I molecules that is involved in the suppression of immune response. As HLA-G plays important role in the maintenance of fetal tolerance, its overexpression has been associated with tumor progression. For the regulation of HLA-G levels, genetic variants within the 5' upstream regulatory region (5'URR) are of crucial importance. Our study aimed to analyze the association between 16 HLA-G 5'URR variants, sHLA-G level and clinical variables in glioma patients. METHODS: We investigated 59 patients with gliomas (mean age 54.70 ± 15.10 years) and 131 healthy controls (mean age 41.45 ± 9.75 years). Patient's blood was obtained on the day of surgical treatment. The HLA-G 5'URR polymorphisms were typed by direct sequencing and the plasma level of sHLA-G assessed by ELISA. RESULTS: Haploblock within HLA-G 5'URR consisting of -762T, -716G, -689G, -666T, -633A, followed by -486C and -201A alleles were significantly more frequent in patients with gliomas than in the controls (p < 0.05). No correlation of HLA-G 5'URR variants with sHLA-G plasma level was found. Analysis of HLA-G 5'URR variants with main clinical variables in patients with grade IV gliomas revealed that haploblock carriers of -762CT, -716TG, -689AG, -666GT, -633GA, -486AC, -477GC, -201GA followed by -369AC carriers tend to have lower age at onset as compared to other genotype carriers (p = 0.04). CONCLUSION: Our results suggest genetic association of HLA-G 5'URR variants with risk of developing gliomas and possible contribution of HLA-G to disease pathology.

Cauda equina neuroendocrine tumors show biological features distinct from other paragangliomas and visceral neuroendocrine tumors.

Cauda equina neuroendocrine tumors (CENETs) are neoplasms of uncertain histogenesis with overlapping features between those of paragangliomas (PGs) and visceral neuroendocrine tumors (NETs). We have explored their biological relationship to both subsets of neuroendocrine neoplasms. The clinical and radiological features of a cohort of 23 CENETs were analyzed. A total of 21 cases were included in tissue microarrays, along with a control group of 38 PGs and 83 NETs. An extensive panel of antibodies was used to assess epithelial phenotype (cytokeratins, E-cadherin, EpCAM, Claudin-4, EMA, CD138), neuronal and neuroendocrine features (synaptophysin, chromogranin A, INSM1, neurofilaments, NeuN, internexin-α, calretinin), chromaffin differentiation (GATA3, Phox2b, tyrosine hydroxylase), and possible histogenesis (Sox2, T-brachyury, Oct3/4, Sox10). The cohort included 5 women (22%) and 18 men (78%). The average age at the time of surgery was 48.3 years (range from 21 to 80 years). The average diameter of the tumors was 39.27 mm, and invasion of surrounding structures was observed in 6/21 (29%) tumors. Follow-up was available in 16 patients (median 46.5 months). One tumor recurred after 19 months. No metastatic behavior and no endocrine activity were observed. Compared to control groups, CENETs lacked expression of epithelial adhesion molecules (EpCAM, CD138, E-cadherin, Claudin-4), and at the same time, they lacked features of chromaffin differentiation (GATA3, Phox2b, tyrosine hydroxylase). We observed no loss of SDHB. Cytokeratin expression was present in all CENETs. All the CENETs showed variable cytoplasmic expression of T-brachyury and limited nuclear expression of Sox2. These findings support the unique nature of the neoplasm with respect to NETs and PGs.

Rivaroxaban lyospheres prepared by a dimethyl sulfoxide-based spray-freeze-drying process.

Spray-freeze-drying (SFD) processes are usually using aqueous solvent systems, which however, exclude the use of SFD for poorly water-soluble drugs/excipients. Here, we evaluated dimethyl sulfoxide for its suitability in formulating SFD particles (lyospheres®). Rivaroxaban was spray-freeze-dried from DMSO solutions containing polyvinyl pyrrolidone (PVP; Kollidon® 25), vinylpyrrolidone-vinyl acetate copolymer (PVP-VA; Kollidon® VA64) or polyvinyl alcohol 4-88 (PVA) forming porous lyospheres® (median particle size 250 to 350 µm). Rivaroxaban was amorphous with all three polymers, which in combination with the high porosity resulted in rapid dissolution in vitro within 10 min. Consequently, this translated in lower Tmax (0.5-1.0 h) after oral administration of lyospheres® to rats (compared with Tmax of 4 h with coarse rivaroxaban). Lyosphere formulations achieved a distinct bioavailability increase (AUC(0-inf) = 1487 ± 657 ng*h/ml with PVP; 4426 ± 1553 ng*h/ml with PVP-VA; 9569 ± 3868 ng*h/ml with PVA lyospheres®; whereas 385 ± 145 ng*h/ml with coarse rivaroxaban). These in vitro and in vivo results underlined the benefit of using DMSO in SFD that can broaden the applicability of the SFD process to a much larger repertoire of poorly water-soluble drugs/excipients.

HLA-G 14bp Ins/Del Polymorphism, Plasma Level of Soluble HLA-G, and Association with IL-6/IL-10 Ratio and Survival of Glioma Patients.

HLA-G is an immune checkpoint molecule with immunosuppressive and anti-inflammatory activities, and its expression and level of its soluble form (sHLA-G) may play an important role in tumor prognosis. The HLA-G 14bp ins/del polymorphism and the plasma level of soluble HLA-G (sHLA-G) were investigated by a polymerase chain reaction and ELISA, respectively, in 59 glioma patients. A significantly higher proportion of glioma patients had the 14 nt insert in both homozygous and heterozygous states compared to the control group. Glioma patients also had higher plasma levels of sHLA-G. Patients with methylated MGMT promoters had lower levels of sHLA-G than those with unmethylated MGMT promoters. The level of sHLA-G negatively correlated with the overall survival of patients. Glioblastoma patients who survived more than one year after diagnosis had lower levels of sHLA-G than those surviving less than one year. Patients with sHLA-G levels below the cut-off value of 40 U/mL survived significantly longer than patients with sHLA-G levels above 40 U/mL. The levels of sHLA-G were also negatively correlated with the level of IL-6 (p = 0.0004) and positively with IL-10/IL-6 (p = 0.046). Conclusion: The presence of the 14 nt insert in both homozygous and heterozygous states of the HLA-G 14bp ins/del polymorphism is more frequent in glioma patients and the elevated plasma levels of sHLA-G are negatively associated with their survival.

Preference-Driven Classification Measure.

Classification is one of the main problems of machine learning, and assessing the quality of classification is one of the most topical tasks, all the more difficult as it depends on many factors. Many different measures have been proposed to assess the quality of the classification, often depending on the application of a specific classifier. However, in most cases, these measures are focused on binary classification, and for the problem of many decision classes, they are significantly simplified. Due to the increasing scope of classification applications, there is a growing need to select a classifier appropriate to the situation, including more complex data sets with multiple decision classes. This paper aims to propose a new measure of classifier quality assessment (called the preference-driven measure, abbreviated p-d), regardless of the number of classes, with the possibility of establishing the relative importance of each class. Furthermore, we propose a solution in which the classifier's assessment can be adapted to the analyzed problem using a vector of preferences. To visualize the operation of the proposed measure, we present it first on an example involving two decision classes and then test its operation on real, multi-class data sets. Additionally, in this case, we demonstrate how to adjust the assessment to the user's preferences. The results obtained allow us to confirm that the use of a preference-driven measure indicates that other classifiers are better to use according to preferences, particularly as opposed to the classical measures of classification quality assessment.

Designing highly porous amorphous celecoxib particles by spray freeze drying leads to accelerated drug absorption in-vivo.

Poorly water-soluble drugs are still a major challenge to overcome in order to achieve sufficiently high oral bioavailability. Spray freeze drying (SFD) is proposed here as an alternative for the preparation of amorphous, free-flowing porous celecoxib spheres for enhanced drug dissolution. Tertiary butyl alcohol solutions of celecoxib + excipient (povidone, hydroxypropyl methylcellulose acetate succinate (HPMC-AS) and Soluplus®) at variable ratios were sprayed into a cooled spray tower, followed by vacuum freeze drying. Final porous particles were free-flowing, highly spherical (circularity ≥ 0.96) and mean diameters ranging from 210 to 800 µm, depending on excipient and drug content. XRPD measurements showed that Celecoxib was amorphous in all formulations and remained stable during 6 months storage. Kollidon 25 and HPMC-AS combinations resulted in the highest dissolution rates as well as dissolved drug amounts (30.4 ± 1.5 µg/ml and 41.8 ± 1.7 µg/ml) which in turn was 2-fold and 1.3-fold increase compared to film casted amorphous reference formulations, respectively. This phenomenon also translated into a faster onset of the drug absorption in-vivo, with significantly lower tmax values, while AUC values were non-significantly lowered compared to amorphous references. The high porosity of SFDs led to the advantageous accelerated dissolution which also translated into faster onset of absorption in-vivo.

Real-World Data Difficulty Estimation with the Use of Entropy.

In the era of the Internet of Things and big data, we are faced with the management of a flood of information. The complexity and amount of data presented to the decision-maker are enormous, and existing methods often fail to derive nonredundant information quickly. Thus, the selection of the most satisfactory set of solutions is often a struggle. This article investigates the possibilities of using the entropy measure as an indicator of data difficulty. To do so, we focus on real-world data covering various fields related to markets (the real estate market and financial markets), sports data, fake news data, and more. The problem is twofold: First, since we deal with unprocessed, inconsistent data, it is necessary to perform additional preprocessing. Therefore, the second step of our research is using the entropy-based measure to capture the nonredundant, noncorrelated core information from the data. Research is conducted using well-known algorithms from the classification domain to investigate the quality of solutions derived based on initial preprocessing and the information indicated by the entropy measure. Eventually, the best 25% (in the sense of entropy measure) attributes are selected to perform the whole classification procedure once again, and the results are compared.

Minimum Query Set for Decision Tree Construction.

A new two-stage method for the construction of a decision tree is developed. The first stage is based on the definition of a minimum query set, which is the smallest set of attribute-value pairs for which any two objects can be distinguished. To obtain this set, an appropriate linear programming model is proposed. The queries from this set are building blocks of the second stage in which we try to find an optimal decision tree using a genetic algorithm. In a series of experiments, we show that for some databases, our approach should be considered as an alternative method to classical ones (CART, C4.5) and other heuristic approaches in terms of classification quality.

Spray Freeze Dried Lyospheres® for Nasal Administration of Insulin.

Pharmacologically active macromolecules, such as peptides, are still a major challenge in terms of designing a delivery system for their transport across absorption barriers and at the same time provide sufficiently high long-term stability. Spray freeze dried (SFD) lyospheres® are proposed here as an alternative for the preparation of fast dissolving porous particles for nasal administration of insulin. Insulin solutions containing mannitol and polyvinylpyrrolidone complemented with permeation enhancing excipients (sodium taurocholate or cyclodextrins) were sprayed into a cooled spray tower, followed by vacuum freeze drying. Final porous particles were highly spherical and mean diameters ranged from 190 to 250 µm, depending on the excipient composition. Based on the low density, lyospheres resulted in a nasal deposition rates of 90% or higher. When tested in vivo for their glycemic potential in rats, an insulin-taurocholate combination revealed a nasal bioavailability of insulin of 7.0 ± 2.8%. A complementary study with fluorescently labeled-dextrans of various molecular weights confirmed these observations, leading to nasal absorption ranging from 0.7 ± 0.3% (70 kDa) to 10.0 ± 3.1% (4 kDa). The low density facilitated nasal administration in general, while the high porosity ensured immediate dissolution of the particles. Additionally, due to their stability, lyospheres provide an extremely promising platform for nasal peptide delivery.

Hemorrhagic Epidermoid Cyst in Cerebellar Vermis: Case Report and Review of the Literature.

Intracranial epidermoid cysts are slow growing congenital avascular neoplasms that spread across the basal surface of the brain. They most commonly occur in the paramedial region in the cerebellopontine angle and the parasellar region. Despite its generally benign nature, sporadically they can be accompanied with hemorrhage or very rarely undergo malignant transformation. The authors present a case report of a patient with a hemorrhagic vermian epidermoid cyst and a review of all published similar cases.

Muscle Tissue as a Surrogate for In Vitro Drug Release Testing of Parenteral Depot Microspheres.

Despite the importance of drug release testing of parenteral depot formulations, the current in vitro methods still require ameliorations in biorelevance. We have investigated here the use of muscle tissue components to better mimic the intramuscular administration. For convenient handling, muscle tissue was used in form of a freeze-dried powder, and a reproducible process of incorporation of tested microspheres to an assembly of muscle tissue of standardized dimensions was successfully developed. Microspheres were prepared from various grades of poly(lactic-co-glycolic acid) (PLGA) or ethyl cellulose, entrapping flurbiprofen, lidocaine, or risperidone. The deposition of microspheres in the muscle tissue or addition of only isolated lipids into the medium accelerated the release rate of all model drugs from microspheres prepared from ester-terminated PLGA grades and ethyl cellulose, however, not from the acid-terminated PLGA grades. The addition of lipids into the release medium increased the solubility of all model drugs; nonetheless, also interactions of the lipids with the polymer matrix (ad- and absorption) might be responsible for the faster drug release. As the in vivo drug release from implants is also often faster than in simple buffers in vitro, these findings suggest that interactions with the tissue lipids may play an important role in these still unexplained observations.

In-vitro drug release testing of parenteral formulations via an agarose gel envelope to closer mimic tissue firmness.

Current in vitro drug-release testing of the sustained-release parenterals represents the in vivo situation insufficiently. In this work, a thin agarose hydrogel layer surrounding the tested dosage form was proposed to mimic the tissue. The method was applied on implantable formulations of different geometries (films, microspheres, and cylindrical implants); prepared from various polymers (several Resomer® grades or ethyl cellulose) and loaded with different model drugs: flurbiprofen, lidocaine or risperidone. The hydrogel layer did not possess any retarding effect on the released drug and acted as a physical restriction to swelling and/or plastic deformation of the tested dosage forms. This led to a different surface area available for drug-release compared with testing in release medium alone and correspondingly to significantly different release profiles of the majority of the formulations obtained between the two methods (e.g. t50% = 18 days in pure release medium vs. t50% = 26 days in gel-setup for risperidone loaded Resomer® 503 H films or t50% = 7 days vs. t50% = 19 days for risperidone loaded Resomer® 503 H microspheres). The limited space for swelling and the rigidity of the agarose gel might mimic the tight encapsulation of the dosage form in the tissue better than the conventional liquid medium.

Substance use in Roma population in contact with social workers in the Czech Republic: A cross-sectional questionnaire survey.

An increasing number of studies have focused on the topic of Roma communities and social exclusion in the Czech Republic, however, substance use has been surveyed only marginally. This paper brings new data on the patterns of substance use among Roma population in contact with social workers (546 respondents). Substance use, including daily smoking and regular excessive alcohol drinking, has been 2-6 times higher among Roma compared to the general population. Current illicit substance use was reported by 1/3 of the respondents (46.7% of males, 17.8% of females) with cannabis (27.1%) and methamphetamine (11.9%) being the most reported substances.

Permutation Entropy as a Measure of Information Gain/Loss in the Different Symbolic Descriptions of Financial Data.

Financial markets give a large number of trading opportunities. However, over-complicated systems make it very difficult to be effectively used by decision-makers. Volatility and noise present in the markets evoke a need to simplify the market picture derived for the decision-makers. Symbolic representation fits in this concept and greatly reduces data complexity. However, at the same time, some information from the market is lost. Our motivation is to answer the question: What is the impact of introducing different data representation on the overall amount of information derived for the decision-maker? We concentrate on the possibility of using entropy as a measure of the information gain/loss for the financial data, and as a basic form, we assume permutation entropy with later modifications. We investigate different symbolic representations and compare them with classical data representation in terms of entropy. The real-world data covering the time span of 10 years are used in the experiments. The results and the statistical verification show that extending the symbolic description of the time series does not affect the permutation entropy values.

Geocoding of worldwide patent data.

The dataset provides geographic coordinates for inventor and applicant locations in 18.8 million patent documents spanning over more than 30 years. The geocoded data are further allocated to the corresponding countries, regions and cities. When the address information was missing in the original patent document, we imputed it by using information from subsequent filings in the patent family. The resulting database can be used to study patenting activity at a fine-grained geographic level without creating bias towards the traditional, established patent offices.

Silk Fibroin as a Novel Alcohol-Resistant Excipient for Sustained-Release Tablet Formulation.

Concomitant intake of alcoholic beverages with sustained-release oral formulations may potentially lead to dose dumping. Alcohol-resistance testing is currently a requirement for the manufacturers by regulatory authorities. Silk fibroin produced by silkworm Bombyx mori is suggested in this work as a potential alternative to a narrow spectrum of alcohol-resistant excipients. Oxycodone HCl, tramadol HCl, and flurbiprofen were selected as model drugs and formulated with regenerated silk fibroin either in the form of an amorphous solid dispersion or as a physical mixture and compressed into tablets. Preliminary compactability and tampering-resistance studies were performed. The ethanol-resistance was tested in media containing 5%, 10%, 20%, or 40% (v/v) ethanol concentration. Drug release profiles were compared using f2 similarity factor. Good mechanical tampering-resistance (tensile strength of 14.6 MPa at 400 MPa compression pressure) was obtained for tablets compressed from physical mixture. Tablets compressed from amorphous solid dispersion had lower tensile strength (2.2 MPa) but showed chemical tampering-resistance to extraction by pure ethanol (7.1% of oxycodone HCl after 24 h). Drug release is controlled predominantly by swelling and diffusion. With an increasing ethanol concentration in release medium, the tablets swelled less, resulting in a slower release. This trend was similar for all tested drugs and for both physical states formulations. No dose dumping occurred in the presence of ethanol; therefore, silk fibroin could be considered as an alternative alcohol-resistant excipient for sustained release application.