Introduction: SETD2, a histone H3-K36 trimethyltransferase, is necessary for regulation of proper intron splicing. SETD2 is frequently inactivated in kidney cancer. We hypothesized that SETD2 deficiency would cause aberrant translation of retained introns (ATaRI) that could serve as potential immunotherapeutic targets in SETD2-mutant states. Methods and Results: We detected increased presence of retained introns in SETD2-mutant vs WT tumors in two publicly available renal cell carcinoma RNA-seq data sets. We hypothesized that if intronic sequences translated into proteins, accumulation of misfolded proteins would activate the Unfolded Protein Response (UPR). The UPR pathway was strongly transcriptionally enriched as measured by GSEA, as were several immunotherapy-relevant pathways, suggesting that tumors are inflamed, possibly related to the antigenic nature of translated introns. To investigate this further, we generated Setd2-isogenic mouse renal cancer cells using CRISPR in the RENCA cell line. RNAseq followed by GSEA confirmed upregulation of UPR pathway transcriptional signature in the Setd2-null condition, supporting our observation in human tumors. Indicators of UPR activation such as cleavage of ATF6 and increase in ATF4 and Xbp1 levels in Setd2 deficient vs. unedited RENCA cells, as well as nuclear translocation of ATF6 in SETD2-mutant human kidney cancer samples validates these findings. We then measured the presence of ATaRI-derived peptides in Setd2-mutant RENCA cells using mass spectrometry, detecting 47 such peptides. Using publicly available proteomics data from one human data set, we preliminarily identified peptides translated from 151 introns that are retained in SETD2-mutant cases. Applying netMHCpan to both the human and murine data, we found that detectable ATaRI peptides were predicted to generate multiple 10-amino acid-long peptides which strongly bind to the 8 murine MHC or to the 20 most common human HLA receptors. We propose that these presentable peptides might activate an immune response to SETD2-mutant renal cell carcinoma. Conclusions: We identified intron retention which may cause activation of the UPR as a feature of SETD2-mutant kidney cancer. ATaRI peptides are detectable and should be presented to the adaptive immune system. These features may represent a new therapeutic vulnerability for exploitation as a rationale for personalized medicine. Citation Format: Marya T. Kozinova, Alexander Metz, Robert Uzzo, Janusz Franco-Barraza, Michael Slifker, Jessica Peskin, Angel Fernández Sanromán, Samra Turajlic, Edna Cukierman, Phillip Phillip Abbosh. SETD2 loss in renal cell carcinoma generates peptides from aberrantly translated retained introns. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6794.

A cosmetologia tornou-se uma ciência multidisciplinar que vem ocupando cada vez mais espaço, estimulando a realização de pesquisas voltadas ao bem-estar dos consumidores. O presente estudo objetivou realizar uma revisão da literatura sobre os aspectos relacionados ao controle de qualidade microbiológico de produtos cosméticos industrializados. Trata-se de uma revisão integrativa com seleção dos estudos nas bases de dados Portal de Periódicos da CAPES, PubMed, Scientific Eletronic Library Online (Scielo), Biblioteca Virtual em Saúde (BVS) e Google Acadêmico, por meio dos Descritores em Ciências da Saúde nos idiomas português e inglês, de 2015 a 2022. A Farmacopeia brasileira foi incorporada como base de informações. Identificou-se que as análises das amostras investigadas (batons, máscaras de cílios, bases faciais, manteiga de cacau, dentre outros) em cada estudo apontaram a presença de microrganismos, sejam bactérias e/ou fungos. Apesar das diretrizes apresentadas na legislação brasileira que dispõem sobre os procedimentos e requisitos para a regularização de produtos de higiene pessoal, cosméticos e perfumes, as pesquisas revelaram, antes ou após o uso de cosméticos, a presença de microrganismos para além dos limites estabelecidos pela ANVISA. Recomenda-se maior rigor no controle de qualidade das indústrias cosméticas e cumprimento das Boas Práticas de Manipulação para a prevenção de riscos à saúde dos usuários de cosméticos industrializados.

Metals and topological insulators have in common that they cannot be described by exponentially localized wave-functions. Here we establish a relationship between these two seemingly unrelated observations. The connection is explicit in the low-lying states of the spectral localizer of trivial metals, an operator that measures the obstruction to finding localized eigenstates. The low-lying spectrum of the spectral localizer of metals is determined by the zero-mode solutions of Dirac fermions with a varying mass parameter. We use this observation, valid in any dimension, to determine the difference between the localizer spectrum of trivial and topological metals, and conjecture the spectrum of the localizer for fractional quantum Hall edges. Because the localizer is a local real-space operator, it may be used as a tool to differentiate between non-crystalline topological and trivial metals, and to characterize strongly correlated systems, for which local topological markers are scarce.

Analysis and modeling of wireless communication systems are dependent on the validity of the wide-sense stationarity uncorrelated scattering (WSSUS) assumption. However, in high-mobility scenarios, the WSSUS assumption is approximately fulfilled just over a short time period. This paper focuses on the stationarity evaluation of high-mobility multi-band channels. We evaluate the stationarity time, the time over which WSSUS is fulfilled approximately. The investigation is performed over real, measured high-mobility channels for two frequency bands, 2.55 and 25.5 GHz. Furthermore, we demonstrate the influence of the user velocity on the stationarity time. We show that the stationarity time decreases with increased relative velocity between the transmitter and the receiver. Furthermore, we show the similarity of the stationarity regions between sub-6 GHz and mmWave channels. Finally, we demonstrate that the sub-6 GHz channels are characterized by longer stationarity time.

Quality of Experience (QoE) multidimensional concept is the key for successful delivery of multimedia services. Higher user requirements for new experiences such as augmented reality, virtual reality, and future 6G services set higher requirements for QoE. A more complex QoE space requires the use of data mining methods in order to process the data for better QoE prediction. The increased dimensionality of the QoE space becomes a limiting factor for achieving the desired QoE prediction accuracy. Existing studies considering the QoE multidimensional concept with approaches that overcome the challenge of increased QoE space dimensionality are of great importance for future research. Accordingly, this article aims to review the applications of Feature Selection (FS) methods in video QoE modeling. It provides a comprehensive overview of the existing studies with the categorization and review of applied FS methods with reference to the data collection and data modeling steps. The analysis included 71 studies which provides overview of the FS methods applications in video QoE modeling depending on the input Influence Factor (IF) dimension sizes, type of IFs, QoE prediction methods used and QoE evaluation type. Our review revealed the advantages of using FS methods in video QoE modeling, frequency of application of FS methods with potential of applying more FS methods in a series or a parallel, gives an overview of the achieved dimensionality reduction degree for different methods, and provides insights in opportunities for researchers for applying FS methods on complex multidimensional QoE space.

The focus of this study is on the significance of location in establishing distribution centers. The key question when selecting a location is regarding which location would contribute the most to the growth of a company’s business through the establishment of distribution centers. To answer this question, we conducted research in the Brčko District of BiH in order to determine the best location for a distribution center using expert decision-making based on linguistic values. In order to use these values when selecting locations, a fuzzy set was formed using the IMF SWARA (Improved Fuzzy Stepwise Weight Assessment Ratio Analysis) and fuzzy CRADIS (Compromise Ranking of Alternatives from Distance to the Ideal Solution) methods. The IMF SWARA method was utilized to determine the weights of the criteria, and the fuzzy CRADIS method was employed to rank the locations based on expert ratings. The location for the construction of distribution centers at Bodarište was rated the worst, while the McGowern Base location was rated the best. Based on these findings, the research question was answered, and it was demonstrated that fuzzy methods could be utilized in the selection of distribution center locations. Hence, we recommend that future research be performed on the application of fuzzy methods in the expert selection of potential sites for distribution centers.

Mass spectrometry analysis can be performed by introducing samples directly to mass spectrometry, allowing the increase of the analysis throughput; however, some disadvantages of direct-to-mass spectrometry analysis include susceptibility to matrix effects and risk of instrument contamination from inadequate sample preparation. Solid-phase microextraction is one of the most suitable sample preparation methods for direct-to-mass spectrometry analysis, as it offers matrix-compatible coatings which ensure analyte enrichment with minimal or no interference from matrix. One of the ways solid-phase microextraction can be coupled directly to mass spectrometry is via a microfluidic open interface. This manuscript reports improvements made to the initial microfluidic open interface design, where the system components have been simplified to mostly commercially available materials. In addition, the analysis of samples has been automated by implementing software that fully controls the analysis workflow, where the washing procedure is optimized to completely reduce the carryover. Herein, the extraction and desorption time profiles from thin and thick SPME devices was studied where the overall workflow consisted of high-throughput sample preparation of 1.3 min per 96 samples and <1 min per sample instrumental analysis.

We consider the problem of adaptive stabilization for discrete-time, multi-dimensional linear systems with bounded control input constraints and unbounded stochastic disturbances, where the parameters of the system are unknown. To address this challenge, we propose a certainty-equivalent control scheme combining online parameter estimation with saturated linear control. We establish the existence of a high probability stability bound on the closed-loop system, under additional assumptions on the system and noise processes. Numerical examples are presented to illustrate our results.

The marine environment has a significant impact on life on Earth. Organisms residing in it are vital for the ecosystem but also serve as an inexhaustible source of biologically active compounds. Herein, the biodiversity of two brown seaweeds, Dictyota dichotoma and Dictyota fasciola from the Adriatic Sea, was evaluated. The aim of the study was the determination of differences in compound composition while comparing their activities, including antioxidant, antimicrobial, and enzyme inhibition, in connection to human digestion, dermatology, and neurological disorders. Chemical analysis revealed several terpenoids and steroids as dominant molecules, while fucoxanthin was the main identified pigment in both algae. D. dichotoma had higher protein, carbohydrate, and pigment content. Omega-6 and omega-3 fatty acids were identified, with the highest amount of dihomo-γ-linolenic acid and α-linolenic acid in D. dichotoma. Antimicrobial testing revealed a dose-dependent inhibitory activity of methanolic fraction against Escherichia coli and Staphylococcus aureus. Moderate antioxidant activity was observed for both algae fractions, while the dietary potential was high, especially for the D. fasciola dichloromethane fraction, with inhibition percentages of around 92% for α-amylase and 57% for pancreatic lipase at 0.25 mg/mL. These results suggest that Dictyota species might be a potent source of naturally derived agents for obesity and diabetes.

Background: The transfemoral (TF) arterial approach is still the most commonly used approach for performing diagnostic coronary angiography in most centers in the world as well as in Bosnia and Herzegovina. Recently, the transradial (TR) arterial approach has gained more and more supporters among interventional cardiologists. Objective: The aim of the study was to compare the duration of the procedure, the amount of delivered ionizing radiation, the amount of applied contrast agent, the frequency of procedural complications and patient comfort during coronary angiography performed via TR and TF arterial approach. Methods: The total sample of 240 respondents was divided into two groups in such a way that the first group consisted of 121 respondents who underwent coronary angiography using TR arterial approach, and the second group consisted of 119 respondents who underwent coronary angiography using TF arterial approach. The Mann-Whitney U test was used to verify the research objective. Results: The obtained research results showed that the duration of coronary angiography and the amount of radiation was greater when using TR arterial approach compared to TF approach. There is no statistically significant difference in relation to the amount of applied contrast medium and the frequency of complications between the two approaches. Periprocedural and postprocedural comfort was better in patents who underwent TR approach. Conclusion: The findings of this study show that diagnostic coronary angiography performed via the TR arterial approach is as safe for the patient as diagnostic coronary angiography performed via the TF arterial approach. With both approaches, there is no significant difference in the amount of contrast agent used nor in the frequency of complications. Procedure duration and radiation exposure are shorter when TF arterial approach i used, while patient comfort is better when the TR arterial approach is used.

Introduction: Aorto-pulmonary

The aim of this study was to determine whether single-base extension (SBE) chemistry can be applied to forensic practice of testing the target single nucleotide polymorphisms (SNPs) of the mitochondrial DNA (mtDNA) Hypervariable Region 1 (HV1). Despite itsweak discrimination power, high copy number of mtDNA per cell and its stability against degradation guarantee mtDNA testing a place in modern forensic genetics. In this research, buccal swab samples were obtained from 294 individuals from Bosnia and Herzegovina. Following DNA isolation using QIAamp® DNA Mini Kit, full sequencing of HV1 was completed using chain-termination Sanger sequencing method. SBE reactions were then performed by targeting 13 SNPs that were identified to be the most frequent in the study population. Uniplex SBE reactions for each individual SNP, as well as two multiplex reactions were prepared for both pure and mixed samples. The results showed complete agreement of the Sanger sequencing results with SBE reactions for both uniplex and multiplex reactions. The results obtained with SBE were encouraging in regard to multiplexing and processing of the mixed samples, since the allele of the minor contributor to the sample was observed in SBE electropherogram in all prepared mixtures. SBE method is limited by the fact that only target SNPs of interest will be analyzed, meaning that they must be carefully selected and curated for each population. However, typing with SBE protocol is accurate, as compared to the golden standard of Sanger sequencing, but was more time- and labor-efficient and simpler to analyze, therefore offering a suitable alternative when Sanger sequencing is not available, given that polymorphic SNPs are known for the population of interest.

Solution synthesis afforded five novel neutral heteroleptic octahedral paramagnetic mononuclear oxidovanadium(IV) complexes of general composition [VO(bpy)L], where L is a dianionic tridentate ONO-donor hydrazone ligand derived from 2-furoic acid hydrazide and salicylaldehyde and its 5-substituted derivatives. Characterization was carried out by elemental analysis, mass spectrometry, infrared, electron, NMR, and EPR spectroscopy, cyclic voltammetry and conductometry. The molecular and crystal structure of the complex with 5-chloro-salicylaldehyde 2-furoic acid hydrazone (2) was determined. The quantum chemical properties of the vanadium complexes were studied at B3LYP and M062X levels with the lanl2dz basis set using Gaussian. Additionally, Swiss-ADME analysis was performed and complex (4), featuring a 5-nitro substituent on the hydrazone ligand, was selected for further investigation. The effects of the in vivo application of the complex on selected biochemical parameters in healthy and diabetic Wistar rats were investigated. Strong antidiabetic effect associated with moderate hypoalbuminemia was observed. Furthermore, the interaction of complexes with BSA was studied by spectrofluorimetry. A significant conformational change of BSA in the presence of vanadium complexes was found. Synchronous fluorescence spectra revealed significant changes in the tyrosine microenvironment of BSA. The FRET analysis was also used and the non-radiative process of energy transfer is elucidated. Thermodynamic data suggest van der Waals forces and hydrogen bonding as predominant binding modes of complexes to BSA.