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INTRODUCTION. In some areas of international sports regulation, it is lex sportiva (for example, the establishment of rules for sports competitions) or the law created by the State / States (for example, the fight against crime in sports) that plays a dominant role. In a number of areas, international sports law and lex sportiva exercise regulatory impact simultaneously. The purpose of the article is to examine how these two sets of regulations contribute to the observance of human rights in sport. The author's three goals were to analyze the process of interference of regulatory efforts based on examples of prohibiting discrimination, using lex mitior, and countering doping in sports.MATERIALS AND METHODS. In each case, the author listed the applicable international legal acts and acts of lex sportivа, studied the domestic and foreign doctrine, used the jurisprudence of the European Court of Human Rights (ECtHR) and the Court of Arbitration for Sport (CAS).The author utilised such general scientific methods as the substratum (content), structural and system approaches. The comparative and hermeneutical approaches should be named as specific scientific methods that were used.RESEARCH RESULTS. Th author characterised the content of the international legal and corporate standards that have been formed in the spheres of prohibiting discrimination, using lex mitior, and countering doping. As a result of their comparison, she comes to the following conclusions: international law and lex sportiva are unanimous in their intent to eliminate discrimination in sports; lex sportiva seeks to apply the legal standard of lex mitior; in the field of anti-doping, a number of inconsistencies have been identified between international legal and corporate standards recognized by lex sportiva.DISCUSSION AND CONCLUSIONS. The prohibition of discrimination is an example of harmonization, as a result of which the requirements of international sports law and lex sportiva complement and strengthen each other. The second case is an example of the successful reception by lex sportiva of the legal concept of lex mitior, which is well-known to national and international law. When countering doping at the present stage, it is lex sportiva that dominates, and the failure to fully comply with the requirements of "due process" and, in particular, with the presumption of innocence in respect of professional athletes is a cause of concern to the academic community and the ECtHR.

Precise, targeted genome editing by CRISPR/Cas9 is key for basic research and translational approaches in model and non-model systems. While active in all species tested so far, editing efficiencies still leave room for improvement. The bacterial Cas9 needs to be efficiently shuttled into the nucleus as attempted by fusion with nuclear localization signals (NLSs). Additional peptide tags such as FLAG- or myc-tags are usually added for immediate detection or straightforward purification. Immediate activity is usually granted by administration of preassembled protein/RNA complexes. We present the ‘hei-tag (high efficiency-tag)’ which boosts the activity of CRISPR/Cas genome editing tools already when supplied as mRNA. The addition of the hei-tag, a myc-tag coupled to an optimized NLS via a flexible linker, to Cas9 or a C-to-T (cytosine-to-thymine) base editor dramatically enhances the respective targeting efficiency. This results in an increase in bi-allelic editing, yet reduction of allele variance, indicating an immediate activity even at early developmental stages. The hei-tag boost is active in model systems ranging from fish to mammals, including tissue culture applications. The simple addition of the hei-tag allows to instantly upgrade existing and potentially highly adapted systems as well as to establish novel highly efficient tools immediately applicable at the mRNA level.

Introduction: Computer assisted surgery in total knee arthroplasty (TKA) should improve accuracy of both femoral and tibial components placement. This study evaluated the functional outcomes of computer navigated total knee arthroplasty through the Knee Society Score (KSS) and Tegner Lysholm Knee Scoring Scale (TLKSS).Materials and Methods: Between September 2007 and February 2013, 180 patients (200 knees; 109 females and 71 males; mean age: 64 years) undergoing computer-assisted TKA were recruited. Plain radiographs and CT scans were performed post-operatively to evaluate alignment. The clinical outcomes were measured using the KSS and TLKSS pre-operatively and after 6, 12 and 36 months.Results: The mean follow-up duration was 2.5 years. The mean tourniquet time was 72 ± 13.4 min, and patients received an average of 0.6 ± 0.82 units of blood after surgery. The average preoperative KSS functional score of 44.6 ± 13.7 improved to 80.4 ± 16.4 after 2 years. The average preoperative TLKSS improved to 71.4 ± 13.5 after 2 years. The mechanical axis was within ±3° in all patients. No axial malalignments were observed on TC Scan. Three patients (1.6% of cases) required revision.Conclusion: Computer assisted TKA allows reproducible alignment and kinematics, reducing outliers, provides ligament balancing and ensures good short term outcomes in terms of KSS functional score and TLKSS. [ABSTRACT FROM AUTHOR]

Modern biotechnology is progressed to sequence-specific, site-directed, precise, and safe strategies for genetic manipulation. The genome-editing strategy is being proposed as one of the most promising tools for genomic study and crop improvement. The basic mechanism involved in genetic manipulations through programmable nucleases is recognition of target genomic loci and binding of effector DNA-binding domain (DBD), double-strand breaks (DSBs) in target DNA by the restriction endonucleases (FokI and Cas) and the repair of DSBs through homology-directed recombination (HDR) or non-homologous end joining (NHEJ). The less efficient and more precise HDR results in the replacement of nucleotides, whereas the more efficient and error-prone NHEJ results in the insertion or deletion of nucleotides. The genome-editing strategies like ZFN, TALEN, and CRISPR/Cas involved in genome editing are being employed to add the desirable trait(s) and remove the undesirable. The impact of gene editing application in crop improvement has proven it the next-generation tool to enhance agricultural productivity. The modifications in crop plants include biotic and abiotic stresses, nutritional improvements, alteration in phenotype, and other characters such as crafting male sterility, haploid production, and increase in yield. The repurposing of CRISPR applications by catalytically inactive Cas9 marks CRISPR as an indispensable tool for genome editing and beyond in biological research. However, the genome-edited plants may have unintended alteration(s) that create biosafety risks. The tools are eventually progressing for more accuracy and efficiency to ensure the safety of consumers and the environment. This article is an attempt to review these genome-editing strategies, the biochemistry attributed to application in crop improvement, and the associated challenges. [ABSTRACT FROM AUTHOR]

Multimedia Broadcast Multicast Service (MBMS)-dedicated cell is a Long Term Evolution (LTE) based broadcast transmission mode with both high transmission efficiency and good compatibility with LTE unicast systems. However, since the physical design of Cell Acquisition Subframe (CAS), which is the control part of an MBMS-dedicated cell transmission period, does not take into account the long delay spread channels in Medium Tower Medium Power (MTMP) and High Tower High Power (HTHP) cells, receivers would probably suffer from multipath aliasing errors in practical transmission. This paper analyzes the impact of aliasing errors on channel estimation (CHE) accuracy and proposes an Aliasing-Elimination CHE algorithm for CAS reception. In the proposed algorithm, the pre-decoded Physical Broadcast Channel (PBCH) is reconstructed and utilized to generate a complete multipath distribution within the entire OFDM symbol length. By using this full-symbol length multipath distribution, the proposed algorithm eliminates aliasing errors effectively. Simulation results and complexity analysis show that the proposed CHE algorithm achieves a significant performance improvement compared to conventional CHE algorithms in long delay spread channels, with acceptable increment in complexity. [ABSTRACT FROM AUTHOR]

Diabetes is considered to be one of the important factors affecting the prognosis of patients undergoing carotid endarterectomy (CEA), but its effect on carotid stenting (CAS) has not been determined. We performed this analysis to evaluate the impact of diabetes mellitus (DM) on carotid stenting. Studies were searched in the MEDLINE, EMBASE, and Cochrane Library databases for all available studies comparing the outcomes of diabetic and nondiabetic patients who underwent CAS. A meta-analysis was performed using the Mantel-Haenszel model to calculate odds ratios (ORs) with RevMan 5.3 software. Five studies with high quality were ultimately included. A total of 3364 patients underwent CAS, including 1042 diabetic patients and 2322 nondiabetic patients. Meta-analysis showed that there was no statistically significant difference in the risk of perioperative stroke(OR,1.20;95%CI,0.74–1.97;P = 0.46;I2 = 24%), transient ischemic attack(TIA)(OR,1.46;95%CI,0.80–2.66;P=0.22;I2=37%), myocardial infarction(MI)(OR,1.12;95%CI,0.47–2.67;P=0.80;I2=0%), mortality (OR,1.77;95%CI,0.91–3.42;P = 0.09;I2=0%), and composite of stroke or death (OR,1.26;95%CI,0.87–1.81;P = 0.22;I2=35%) between diabetic and nondiabetic patients receiving CAS. Sensitivity analysis showed that the meta-analysis results of all outcome events were stable. Compared with nondiabetic patients, diabetes did not increase the risk of the following: perioperative stroke, TIA, MI, mortality, and composite of stroke or death in patients receiving CAS. This study may be used to guide carotid artery stenosis patients with diabetes to choose the optimal treatment option. However, due to the limited number of studies and the different technical levels of institutions, the results should be interpreted caution. [ABSTRACT FROM AUTHOR]

It's an evolution of its own kind that a technology changed the interface of biology in such a short expanse of time. Merely a decade ago, scientists reported that the CRISPR-Cas (clustered regularly interspaced short Palindromic repeats-CRISPR associated) system is the part of bacteria and archea's adaptive immune system which helps in withstanding the attack against invading viruses by acquiring genetic records of invaders to facilitate robust interference upon reinfection. In this Review, we discuss the evolution of CRISPR along the time and recent advances in understanding the vivid mechanism by which Cas proteins respond to foreign nucleic acids and how these systems have been harnessed for precise genome manipulation in plants. With the advancement in this technology, it will become easier to genetically modify the plants for crop improvement. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus is a worsening worldwide health problem. It constitutes a major global health concern. Sitagliptin selectively inhibits dipeptidyl peptidase-4 (DPP-4) to manage type 2 diabetes mellitus (T2DM). It regulates the blood glucose level without risk of hypoglycemia or increase in body weight. In our study we investigated the effects of Sitagliptin on DNA and chromosomes in cultured human lymphocytes. Aim: To assess the genotoxic and cytotoxic effects of different concentrations of Sitagliptin on cultured human lymphocytes. Material and Methods: Cultures were divided into 6 groups: control, positive control (Cisplatin) at concentration of 10 μg/mL and 4 different concentrations of Sitagliptin (125,250,500,1000 μg/mL). Sitagliptin genotoxicity and cytotoxicity were determined by using chromosomal aberrations (CAs), mitotic index (MI), comet assay and nucleic acids electrophoresis. Results: There was high significant increase in total chromosomal aberrations (TCAs) at 500, 1000 μg/mL of Sitagliptin compared to control. Other studied concentrations of Sitagliptin exhibited an increase in TCAs without significant relation. Compared to control, there was a significant increase in mitotic index at 125 μg/mL of Sitagliptin but non-significant increase at 250 μg/mL of Sitagliptin. However, at 500, 1000 μg/mL of Sitagliptin, there was a significant decrease in MI. Regarding comet assay, there was significant and high significant increase in total DNA damage at 500,1000 μg/mL of Sitagliptin respectively. Nucleic acids electrophoresis not digested with RNase showed that optical density value of RNA was maximum at 125 μg/mL then gradually decreased till reach the minimum level at 1000 μg/mL of Sitagliptin indicating its toxicity. Genomic DNA fragmentation results indicated that Sitagliptin caused a slight damage of DNA in the form of necrosis in a concentration dependent manner. Conclusion: Sitagliptin induces significant genotoxic and cytotoxic effects on the cultured human lymphocytes at concentrations of (500, 1000 μg/mL). [ABSTRACT FROM AUTHOR]

Objectives: This retrospective study compared two mandibular reconstruction procedures—conventional reconstruction plates (CR) and patient-specific implants (PSI)—and evaluated their accuracy of reconstruction and clinical outcome. Methods: Overall, 94 patients had undergone mandibular reconstruction with CR (n = 48) and PSI (n = 46). Six detectable and replicable anatomical reference points, identified via computer tomography, were used for defining the mandibular dimensions. The accuracy of reconstruction was assessed using pre- and postoperative differences. Results: In the CR group, the largest difference was at the lateral point of the condyle mandibulae (D2) -1.56 mm (SD = 3.8). In the PSI group, the largest difference between preoperative and postoperative measurement was shown at the processus coronoid (D5) with +1.86 mm (SD = 6.0). Significant differences within the groups in pre- and postoperative measurements were identified at the gonion (D6) [ t (56) = -2.217; p =.031 <.05]. In the CR group, the difference was 1.5 (SD = 3.9) and in the PSI group -1.04 (SD = 4.9). CR did not demonstrate a higher risk of plate fractures and post-operative complications compared to PSI. Conclusion: For reconstructing mandibular defects, CR and PSI are eligible. In each case, the advantages and disadvantages of these approaches must be assessed. The functional and esthetic outcome of mandibular reconstruction significantly improves with the experience of the surgeon in conducting microvascular grafts and familiarity with computer-assisted surgery. Interoperator variability can be reduced, and training of younger surgeons involved in planning can be reaching better outcomes in the future. [ABSTRACT FROM AUTHOR]

Cutibacterium acnes is an important member of the human skin microbiome and plays a critical role in skin health and disease. C. acnes encompasses different phylotypes that have been found to be associated with different skin phenotypes, suggesting a genetic basis for their impact on skin health. Here, we present a comprehensive comparative analysis of 255 C. acnes genomes to provide insights into the species genetic diversity and identify unique features that define various phylotypes. Results revealed a relatively small and open pan genome (6,240 genes) with a large core genome (1,194 genes), and three distinct phylogenetic clades, with multiple robust sub-clades. Furthermore, we identified several unique gene families driving differences between distinct C. acnes clades. Carbohydrate transporters, stress response mechanisms and potential virulence factors, potentially involved in competitive growth and host colonization, were detected in type I strains, which are presumably responsible for acne. Diverse type I-E CRISPR-Cas systems and prophage sequences were detected in select clades, providing insights into strain divergence and adaptive differentiation. Collectively, these results enable to elucidate the fundamental differences among C. acnes phylotypes, characterize genetic elements that potentially contribute to type I-associated dominance and disease, and other key factors that drive the differentiation among clades and sub-clades. These results enable the use of comparative genomics analyses as a robust method to differentiate among the C. acnes genotypes present in the skin microbiome, opening new avenues for the development of biotherapeutics to manipulate the skin microbiota. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown better pain reduction utilizing femoral nerve block (FNB) in patients who underwent hip fracture surgery. However, few studies have focused on the recovery of physical function after FNB, and most studies excluded patients with dementia. We investigated the association between FNB performed in the operating room and the recovery of physical function after hip fracture surgery, including patients with dementia.Methods: A total of 103 patients with a mean age of 87.4 years who underwent hip fracture surgery under spinal anesthesia between July 2015 and December 2017 (46 patients receiving a single injection of FNB and 57 standard care) were enrolled. Patients with FNB versus standard care were matched by a propensity score to adjust for patient characteristics. An anesthesiologist performed FNB with 20ml of 0.2% ropivacaine, and the standard care group received intravenous 1000 mg acetaminophen or 50mg flurbiprofen once after surgery. After matching, 78 patients were analyzed. Our primary outcome was 3-day cumulated ambulation score (CAS, 0-18 points) and secondary outcomes were 1-day CAS on postoperative day 1-3 and length of hospital stay. We also stratified patient groups based on the presence of dementia and fracture type.Results: Patients undergoing FNB had significantly better 3-day CAS compared to standard care (mean [SD], 8.72 [3.42] vs 7.33 [2.62]; mean difference, 1.38 [95%CI; 0.03 - 2.74]; p = 0.048) and 1-day CAS on postoperative day two (mean [SD], 3.10 [1.39] vs 2.56 [0.94]; mean difference, 0.54 [0.01 - 1.07]; p = 0.049). Length of hospital stay did not significantly differ among the two groups (p = 0.65). Larger positive effect was likely to be seen for patients with a femoral neck fractures and for those without dementia.Conclusions: Patients who underwent surgery with spinal anesthesia plus FNB had better ambulatory status early after hip fracture surgery compared to patients not offered FNB. The beneficial association between FNB and ambulatory status was likely to be observed especially in patients with femoral neck fracture and without dementia. [ABSTRACT FROM AUTHOR]

This paper provides theoretical and practical implications for the application of agent-based models (ABMs) to address the issue of coevolutionary business-IS alignment. The implications stem from the following arguments: (a) the alignment issue can be modelled by an ABM to describe the features of complex adaptive systems (CAS); (b) the coevolutionary principles of business and IS alignment stipulate individual behaviours and guide organisational order; (c) ABM development and experimentation offer guidance to better explain how organisations control the alignment trajectory with coevolutionary principles. To extend the extant coevolutionary research on alignment, this paper develops an ABM for a hierarchical organisational structure and validates three coevolutionary principles. [ABSTRACT FROM AUTHOR]

This article discusses a series of theoretical and practical issues regarding the taxation of individual part-time contracts. From 1 January 2020, the over-taxation of this type of contracts is eliminated and the gross revenue received will be used as a basis for the calculation of social security and health insurance contributions, instead of the gross minimum domestic salary. The pronouncement introducing these provisions is Law 263/2019 on amending Law 227/2015 regarding the Tax Code, which is intended to eliminate the increased CAS and CASS payments for part-time employees or employees with performancerelated pay. This article analyses issues in relation with individual part-time contracts, the rights of part-time employees, employers’ obligations, salary calculations, and filing and payment obligations.

Abstract Background The traditional method of bacterial identification based on 16S rRNA is a widely used and very effective detection method, but this method still has some deficiencies, especially in the identification of closely related strains. A high homology with little differences is mostly observed in the 16S sequence of closely related bacteria, which results in difficulty to distinguish them by 16S rRNA-based detection method. In order to develop a rapid and accurate method of bacterial identification, we studied the possibility of identifying bacteria with other characteristic fragments without the use of 16S rRNA as detection targets. Results We analyzed the potential of using cas (CRISPR-associated proteins) gene as a target for bacteria detection. We found that certain fragment located in the casx gene was species-specific and could be used as a specific target gene. Based on these fragments, we established a TaqMan MGB Real-time PCR method for detecting bacteria. We found that the method used in this study had the advantages of high sensitivity and good specificity. Conclusions The casx gene-based method of bacterial identification could be used as a supplement to the conventional 16 s rRNA-based detection method. This method has an advantage over the 16 s rRNA-based detection method in distinguishing the genetic relationship between closely-related bacteria, such as subgroup bacteria, and can be used as a supplement to the 16 s rRNA-based detection method.

Razprava analizira pojem mimesis

Cutibacterium acnes is an important member of the human skin microbiome and plays a critical role in skin health and disease. C. acnes encompasses different phylotypes that have been found to be associated with different skin phenotypes, suggesting a genetic basis for their impact on skin health. Here, we present a comprehensive comparative analysis of 255 C. acnes genomes to provide insights into the species genetic diversity and identify unique features that define various phylotypes. Results revealed a relatively small and open pan genome (6,240 genes) with a large core genome (1,194 genes), and three distinct phylogenetic clades, with multiple robust sub-clades. Furthermore, we identified several unique gene families driving differences between distinct C. acnes clades. Carbohydrate transporters, stress response mechanisms and potential virulence factors, potentially involved in competitive growth and host colonization, were detected in type I strains, which are presumably responsible for acne. Diverse type I-E CRISPR-Cas systems and prophage sequences were detected in select clades, providing insights into strain divergence and adaptive differentiation. Collectively, these results enable to elucidate the fundamental differences among C. acnes phylotypes, characterize genetic elements that potentially contribute to type I-associated dominance and disease, and other key factors that drive the differentiation among clades and sub-clades. These results enable the use of comparative genomics analyses as a robust method to differentiate among the C. acnes genotypes present in the skin microbiome, opening new avenues for the development of biotherapeutics to manipulate the skin microbiota.

ObjectivesThis retrospective study compared two mandibular reconstruction procedures—conventional reconstruction plates (CR) and patient-specific implants (PSI)—and evaluated their accuracy of reconstruction and clinical outcome.MethodsOverall, 94 patients had undergone mandibular reconstruction with CR (n = 48) and PSI (n = 46). Six detectable and replicable anatomical reference points, identified via computer tomography, were used for defining the mandibular dimensions. The accuracy of reconstruction was assessed using pre- and postoperative differences.ResultsIn the CR group, the largest difference was at the lateral point of the condyle mandibulae (D2) -1.56 mm (SD = 3.8). In the PSI group, the largest difference between preoperative and postoperative measurement was shown at the processus coronoid (D5) with +1.86 mm (SD = 6.0). Significant differences within the groups in pre- and postoperative measurements were identified at the gonion (D6) [t(56) = -2.217; p = .031

Стаття присвячена сутності та особливостям стандартів бухгалтерської фінансової звітності, затверджених у Сполучених Штатах Америки, Китайській Народній Республіці та Європейському Союзі. Проаналізовано подібності та відмінності відносно Міжнародних стандартів фінансової звітності. Досліджено алгоритми прийняття змін у відповідних національних стандартах, спричинені оновленням міжнародних. З’ясовано історичні аспекти формування Китайських національних стандартів бухгалтерського обліку та ступінь впливу Загальноприйнятих принципів бухгалтерського обліку на функціонування ринку капіталу в США. Виокремлено основне джерело розбіжностей у фінансовій звітності країн-учасниць ЄС. Виявлено наслідки використання різних методів оцінки вартості активів, затверджених у кожній з досліджуваних територіальних одиниць, на фінансовий результат діяльності підприємств.

CRISPR-Cas allows us to introduce desired genome editing, including mutations, epitopes, and deletions, with unprecedented efficiency. The development of CRISPR-Cas has progressed to such an extent that it is now applicable in various fields, with the help of model organisms. C. elegans is one of the pioneering animals in which numerous CRISPR-Cas strategies have been rapidly established over the past decade. Ironically, the emergence of numerous methods makes the choice of the correct method difficult. Choosing an appropriate selection or screening approach is the first step in planning a genome modification. This report summarizes the key features and applications of CRISPR-Cas methods using C. elegans, illustrating key strategies. Our overview of significant advances in CRISPR-Cas will help readers understand the current advances in genome editing and navigate various methods of CRISPR-Cas genome editing.

Small extracellular vesicles (sEVs) are naturally occurring vesicles that have the potential to be manipulated to become promising drug delivery vehicles for on-demand in vitro and in vivo gene editing. Here, we developed the modular safeEXO platform, a prototype sEV delivery vehicle that is mostly devoid of endogenous RNA and can efficaciously deliver RNA and ribonucleoprotein (RNP) complexes to their intended intracellular targets manifested by downstream biologic activity. We also successfully engineered producer cells to produce safeEXO vehicles that contain endogenous Cas9 (safeEXO-CAS) to effectively deliver efficient ribonucleoprotein (RNP)-mediated CRISPR genome editing machinery to organs or diseased cells in vitro and in vivo . We confirmed that safeEXO-CAS sEVs could co-deliver ssDNA, sgRNA and siRNA, and efficaciously mediate gene insertion in a dose-dependent manner. We demonstrated the potential to target safeEXO-CAS sEVs by engineering sEVs to express a tissue-specific moiety, integrin alpha-6 (safeEXO-CAS-ITGA6), which increased their uptake to lung epithelial cells in vitro and in vivo . We tested the ability of safeEXO-CAS-ITGA6 loaded with EMX1 sgRNAs to induce lung-targeted editing in mice, which demonstrated significant gene editing in the lungs with no signs of morbidity or detectable changes in immune cell populations. Our results demonstrate that our modular safeEXO platform represents a targetable, safe, and efficacious vehicle to deliver nucleic acid-based therapeutics that successfully reach their intracellular targets. Furthermore, safeEXO producer cells can be genetically manipulated to produce safeEXO vehicles containing CRISPR machinery for more efficient RNP-mediated genome editing. This platform has the potential to improve current therapies and increase the landscape of treatment for various human diseases using RNAi and CRISPR approaches., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Immunoglobulin superfamily (IgSF) members are known for their role as glycoproteins expressed on the surface of immune cells, enabling protein-protein interactions to sense external signals during immune responses. However, the functions of immunoglobulins localized within subcellular compartments have been less explored. In this study, we identified an endoplasmic reticulum (ER)-localized immunoglobulin, IgSF member 6 (IgSF6), that regulates ER stress and the inflammatory response in intestinal macrophages. Igsf6 expression is sustained by microbiota and significantly upregulated upon bacterial infection. Mice lacking Igsf6 displayed resistance to Salmonella typhimurium challenge but increased susceptibility to dextran sulfate sodium-induced colitis. Mechanistically, deficiency of Igsf6 enhanced inositol-requiring enzyme 1α/-X-box binding protein 1 pathway, inflammatory response, and reactive oxygen species production leading to increased bactericidal activity of intestinal macrophages. Inhibition of reactive oxygen species or inositol-requiring enzyme 1α-X-box binding protein 1 pathway reduced the advantage of Igsf6 deficiency in bactericidal capacity. Together, our findings provide insight into the role of IgSF6 in intestinal macrophages that modulate the ER stress response and maintain intestinal homeostasis., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The goal of this research is to develop the "Cognitive Intervention Program with PASS Theory-Based Games" and to test it on the cognitive processing areas and academic performance of students with special learning disabilities. A pre-test/post-test control group experimental model was used in the study. This study was carried out on a total of 20 students who were diagnosed with a special learning disability, 10 of whom were in the experimental group and 10 were in the control group. The program was applied to the experimental group 1 hour per week for a total of 24 hours. Individually applied Cognitive Assessment System (CAS) and "Weighted Year-End Grade Point Averages (WGPA)" were used as data collection tools in the study. The children in the control group, on the other hand, continued their academic support activities within the scope of their current curriculum. In the analysis of the data, Unrelated (Independent) Group t-Test and Related (Dependent) Group t-Test were applied. As a result of the research, it was found that the cognitive processing areas and WGPA post-test scores of the experimental group were significantly higher than the pre-test scores, and the post-test scores of the experimental group were also significantly higher than the post-test scores of the control group. This finding shows that the program is effective in cognitive processing areas and academic performance of students with a diagnosis of special learning disability. [ABSTRACT FROM AUTHOR]

Background: Oro‐facial dysfunctions (OFDs; oro‐facial myofunctional disorders) in children and childhood apraxia of speech (CAS) often cause severe problems in articulation, chewing, swallowing and oral posture. Objectives: Pathognomonic symptoms could yet not be identified, but central problems in planning, programming, timing and automating oro‐facial, as well as other fine motor skills, are assumed to be affected. Methods: To investigate the nature of motor and coordinative deficits in OFD and CAS, digitomotography was applied. The testing focused on recording frequency, force, rhythm and regularity of the index finger including speeded and metronome tapping tasks. 25 children with OFD (7 girls and 18 boys, age 7.9 ± 2.3) and 5 children with CAS (0 girls and 5 boys, age 7.6 ± 2.3), and 31 healthy controls (12 girls and 19 boys, age 9.3 ± 2.2) were tested. Statistical significance was accepted at α = 0.05. ANOVA test, non‐parametric Mann‐Whitney U test, Kruskal‐Wallis test and Spearman's rank correlation coefficient were used. Results: Cross‐sectional data revealed consistent significant differences between children with OFD and healthy controls concerning frequency, force, rhythm and regularity of index finger tapping. Individuals with CAS showed particularly low results. Tapping results correlated with disease burden. Conclusion: These findings support that underlying superordinated sensorimotor deficits exist. This may help phenotyping and influence diagnostical and therapeutical approaches. [ABSTRACT FROM AUTHOR]

This article revolves around the recent pronunciation of the Swiss Federal Tribunal regarding an arbitrator bias during the proceeding before the Court of Arbitration for Sport, which has resulted in the annulment of the eight years ineligibility sanction for the Chinese swimmer Sun Yang. [ABSTRACT FROM AUTHOR]

Global navigation satellite systems (GNSSs) provide accurate positioning and timing services in a large gamut of sectors, including financial institutions, Industry 4.0, and Internet of things (IoT). Any industrial system involving multiple devices interacting and/or coordinating their functionalities needs accurate, dependable, and trustworthy time synchronization, which can be obtained by using authenticated GNSS signals. However, GNSS vulnerabilities to time-spoofing attacks may cause security issues for their applications. Galileo is currently developing new services aimed at providing increased security and robustness against attacks, such as the open service navigation message authentication (OS-NMA) and commercial authentication service (CAS). In this paper, we propose a robust and secure timing protocol that is independent of external time sources, and solely relies on assisted commercial authentication service (ACAS) and OS-NMA features. We analyze the performance of the proposed timing protocol and discuss its security level in relation to malicious attacks. Lastly, experimental tests were conducted to validate the proposed protocol.

The coronavirus disease 2019 (COVID-19) outbreak has caused not only significant physical health problems but also mental health disorders. Anxiety and fear appear to be the main psychological symptoms associated with COVID-19. The aim of this study was to investigate whether anxiety and fear related to COVID-19 are influenced by sociodemographics and whether specific conditions, such as positivity for COVID-19 or death among relatives and friends, can further enhance these symptoms. In this cross-sectional study, 697 Italians responded to an online survey assessing sociodemographic information, the presence/absence of positive cases, or deaths due to COVID-19 among relatives or acquaintances. The Coronavirus Anxiety Scale (CAS) and Fear of COVID-19 Scale (FCS-19S) were administered in order to assess the levels of anxiety and fear associated with COVID-19. The data were collected in November 2020. Anxiety and fear scores were positively correlated. Both male and female subjects with higher CAS scores also displayed higher FCS-19S scores. The CAS and FCS-19S scores tended to increase with age, with older subjects exhibiting higher scores than younger subjects. Additionally, respondents with lower educational levels demonstrated higher scores on both the CAS and FCS-19S. Similarly, respondents living with older people and/or experiencing the death of one or more relatives due to COVID-19 exhibited corresponding outcomes. This study demonstrates how the levels of anxiety and fear, measured by CAS and FCS-19S associated with COVID-19, are influenced by gender, age, cohabitation status, educational levels, and the presence of positive cases or deaths due to COVID-19.

Type IV CRISPR systems encode CRISPR associated (Cas)-like proteins that combine with small RNAs to form multi-subunit ribonucleoprotein complexes. However, the lack of Cas nucleases, integrases, and other genetic features commonly observed in most CRISPR systems has made it difficult to predict type IV mechanisms of action and biological function. Here we summarize recent bioinformatic and experimental advancements that collectively provide the first glimpses into the function of specific type IV subtypes. We also provide a bioinformatic and structural analysis of type IV-specific proteins within the context of multi-subunit (class 1) CRISPR systems, informing future studies aimed at elucidating the function of these cryptic systems.

The coronavirus disease 2019 (COVID-19) outbreak has caused not only significant physical health problems but also mental health disorders. Anxiety and fear appear to be the main psychological symptoms associated with COVID-19. The aim of this study was to investigate whether anxiety and fear related to COVID-19 are influenced by sociodemographics and whether specific conditions, such as positivity for COVID-19 or death among relatives and friends, can further enhance these symptoms. In this cross-sectional study, 697 Italians responded to an online survey assessing sociodemographic information, the presence/absence of positive cases, or deaths due to COVID-19 among relatives or acquaintances. The Coronavirus Anxiety Scale (CAS) and Fear of COVID-19 Scale (FCS-19S) were administered in order to assess the levels of anxiety and fear associated with COVID-19. The data were collected in November 2020. Anxiety and fear scores were positively correlated. Both male and female subjects with higher CAS scores also displayed higher FCS-19S scores. The CAS and FCS-19S scores tended to increase with age, with older subjects exhibiting higher scores than younger subjects. Additionally, respondents with lower educational levels demonstrated higher scores on both the CAS and FCS-19S. Similarly, respondents living with older people and/or experiencing the death of one or more relatives due to COVID-19 exhibited corresponding outcomes. This study demonstrates how the levels of anxiety and fear, measured by CAS and FCS-19S associated with COVID-19, are influenced by gender, age, cohabitation status, educational levels, and the presence of positive cases or deaths due to COVID-19. [ABSTRACT FROM AUTHOR]

Taking as its point of departure, situations arising in classrooms exposed to a heavy use of CAS, exemplified by the Danish upper secondary school mathematics program, the paper discusses the use of "old" cognitive frameworks of mathematics education as an alternative to more recent theoretical developments in the field. The paper draws on three rich examples of CAS use in relation to the following: mathematical concept formation; mathematical proofs and proving; and classroom teaching. Each of these examples illustrates aspects of CAS use that appear better captured and addressed through "old" frameworks. This includes the mathematics specific learning difficulties that a heavy CAS use gives rise to; the inexpedient use of CAS in proofs in textbooks; and the tacit norms and contracts surrounding CAS use in the classroom. The paper thus serves as a call to continuously consulting our research back catalogue, also when addressing problems and challenges which at first sight appear "new", such as the constantly evolving digital technologies for learning and teaching mathematics. [ABSTRACT FROM AUTHOR]

The integration of surgical knowledge into virtual planning systems plays a key role in computer-assisted surgery. The knowledge is often implicitly contained in the implemented algorithms. However, a strict separation would be desirable for reasons of maintainability, reusability and readability. Along with the Department of Oral and Maxillofacial Surgery at Heidelberg University Hospital, we are working on the development of a virtual planning system for mandibular reconstruction. In this work we describe a process for the structured acquisition and representation of surgical knowledge for mandibular reconstruction. Based on the acquired knowledge, an RDF(S) ontology was created. The ontology is connected to the virtual planning system via a SPARQL interface. The described process of knowledge acquisition can be transferred to other surgical use cases. Furthermore, the developed ontology is characterised by a reusable and easily expandable data model. [ABSTRACT FROM AUTHOR]

In the last decade, collaborative assembly systems (CAS) are becoming increasingly common due to their ability to merge the flexibility of a manual assembly system with the performance of traditional robotics. Technical constraints, e.g., dedicated tools or resources, or performance requirements, e.g., throughput, could encourage the use of a CAS built around a multi-robot and multi-operator layout, i.e., with a number of resources greater than 2. Starting from the development of a prototype multi-robot multi-operator collaborative workcell, a simulation environment was developed to evaluate the makespan and the degree of collaboration in multi-robot multi-operator CAS. From the simulation environment, a mathematical model was conceptualized. The presented model allows estimating, with a certain degree of accuracy, the performances of the system. The results have investigated how several process characteristics, i.e. the number and type of resources, the resources layout, the task allocation method, and the number of feeding devices, influence the degree of collaboration between the resources. Lastly, the authors propose a compact analytic formulation, based on an exponential function, and define the methods and the influence factors to determine its parameters. [ABSTRACT FROM AUTHOR]

The discovery of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) system, and its development into a set of powerful tools for manipulating the genome, has revolutionized genome editing. Precise, targeted CRISPR/Cas-based genome editing has become the most widely used platform in organisms ranging from plants to animals. The CRISPR/Cas system has been extensively modified to increase its efficiency and fidelity. In addition, the fusion of various protein motifs to Cas effector proteins has facilitated diverse set of genetic manipulations, such as base editing, transposition, recombination, and epigenetic regulation. The CRISPR/Cas system is undergoing continuous development to overcome current limitations, including off-target effects, narrow targeting scope, and issues associated with the delivery of CRISPR components for genome engineering and therapeutic approaches. Here, we review recent progress in a diverse array of CRISPR/Cas-based tools. We also describe limitations and concerns related to the use of CRISPR/Cas technologies. [ABSTRACT FROM AUTHOR]

Type IV CRISPR systems encode CRISPR associated (Cas)-like proteins that combine with small RNAs to form multi-subunit ribonucleoprotein complexes. However, the lack of Cas nucleases, integrases, and other genetic features commonly observed in most CRISPR systems has made it difficult to predict type IV mechanisms of action and biological function. Here we summarize recent bioinformatic and experimental advancements that collectively provide the first glimpses into the function of specific type IV subtypes. We also provide a bioinformatic and structural analysis of type IV-specific proteins within the context of multi-subunit (class 1) CRISPR systems, informing future studies aimed at elucidating the function of these cryptic systems. [ABSTRACT FROM AUTHOR]

Background: Rituximab (RTX), a chimeric human-murine anti-CD20 monoclonal antibody, has been used for treatment of active moderate-severe Graves' orbitopathy (GO) since 2004 as second-line therapy in patients unresponsive to intravenous steroids. We conducted an open-label prospective study (EUDRACT 2012-001980-53) in which patients were treated with a single infusion of only 100 mg RTX to analyze the efficacy and safety of this low dose. Methods: Seventeen patients, of whom nine had disease that was unresponsive to intravenous methylprednisolone and eight with newly diagnosed GO, were enrolled. Disease activity was assessed with the clinical activity score (CAS) and severity with a composite ophthalmic score. Long-term surgical treatment and quality of life were also assessed, as well as treatment-related adverse events. Results: Mean baseline CAS was 4.56 ± 0.96 and decreased to 1.25 ± 1.14 at 24 weeks (p = 0.001). Disease inactivation occurred within 24 weeks in >90% of patients and was unrelated to disease duration. Severity improved in about 60% of patients, with no relapses. All patients showed peripheral depletion of CD20+ and CD19+ cells at the end of RTX infusion (60 minutes). Two patients required surgical orbital decompression because of optic neuropathy (ON). Among adverse events observed, there was one patient who developed a cytokine release syndrome. Conclusions: A dose of 100 mg RTX is effective in patients with active moderate-severe GO. Low doses are better tolerated, expose patients to immune suppression for a shorter period of time, and are extremely cost effective, compared with higher doses. This dose, consistently with all other immunosuppressants, does not prevent the progression of GO to dysthyroid ON. [ABSTRACT FROM AUTHOR]

Purpose: Endovascular robotics is an emerging technology within the developing field of medical robotics. This was a prospective evaluation to assess safety and feasibility of robotic-assisted carotid artery stenting. Materials and Methods: Consecutive cases of carotid artery stenting cases performed over period of 24 months, from May 2015 to October 2016, using the Magellan Robotic System (Hansen, Mountain View, CA) were included. All cases utilised the robotic system to navigate the arch, obtain a stable position in the common carotid artery, followed by manual manipulation of Embolic Protection Devices and self-expandable stents through the robotic catheter. Patients demographics, clinical indications, anatomical features, technical and clinical success, complication rate and hospital stay were prospectively recorded. Results: Thirteen patients, 10 males (78.5%), with an average age of 68.7 years were treated. Mean follow up time was 30 months. Ten patients (91%) were symptomatic at presentation. Anatomical indications for endovascular stent insertion were previous open surgery to the neck ± radiotherapy (87.5%) and hostile anatomy for open surgery (12.5%). Technical success was 100% and the robotic system demonstrates enhanced stability during arch and lesion crossing. There were no neurological complications post-operatively. Average hospital stay was 3 days (range 2–6 days) and a change in serum creatinine of −7.8 μmol/L. There was no documented case of in stent restenosis, new or worsening neurology during follow-up. Conclusion: These results illustrate safety and feasibility of robotic endovascular revascularisation for carotid disease and demonstrates potential to enhance peri-procedural safety through improved control and stability. [ABSTRACT FROM AUTHOR]

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The sulfur (S) isotope composition of carbonate associated sulfate (CAS) in carbonate rocks has been used to assess variations in paleo-oceanographic redox conditions and its relationship to biotic changes in Earth's history, including the Smithian – Spathian transition. However, previous CAS studies of the Olenekian are mostly based on nearshore continental shelf sections and report highly variable δ34S values mostly offset from those of contemporaneous evaporites, casting doubt on the utility of the CAS proxy during this interval. The current study presents new CAS isotopic data from three well-dated carbonate successions which were deposited in continental shelf (Qiakong) and offshore marine (Wadi Musjah and Jebel Aweri) environments during the Olenekian (Smithian – Spathian). The aim of the study was to constrain the temporal and spatial variations in sulfur cycling and its relation to marine redox and faunal changes across the Smithian – Spathian transition (ca. 250.5–248.8 Ma). The CAS dataset is complemented by rare earth element (REE) concentration data and thin section petrography. Using a suite of optical and geochemical techniques, the preservation of near-primary CAS isotopic information in the studied samples is evaluated. Results indicate that of the three sections investigated, the offshore sections mostly preserve near-primary marine sulfate S-isotope compositions while the continental shelf Qiakong section suffers from post-depositional alteration of CAS. Comparisons of our new, as well as previously published CAS δ34S data, with the evaporite δ34S record suggests that although Olenekian CAS δ34S values may have been modified by diagenetic processes, a global and primary seawater δ34S trend can be delineated as follows: seawater δ34S values increased across the middle Smithian and Smithian – Spathian boundary (SSB). Based on our new CAS data, this increase was in the order of 9 ‰ over ca. 1.14 million years. Other short-term variability in the CAS δ34S record most likely reflects diagenetic processes. The middle Smithian to SSB δ34S increase is attributed to a global increase in microbial sulfate reduction and pyrite burial associated with decreasing ocean dissolved oxygen during this time. Calculations of the rate of sulfur cycling and box modeling constraints indicate that Olenekian marine sulfur cycle perturbations occurred while the seawater sulfate reservoir only had between 10 and 25% of the modern marine sulfate inventory. Furthermore, results from the current study suggest that variations in ocean dissolved oxygen levels, inferred from the δ34S and REE data, are not consistently correlated with nektonic faunal changes during the Olenekian in the studied sections. As such, faunal turnover during the Olenekian is unlikely to be explained exclusively by abiotic factors such as ocean-atmosphere oxygenation levels. • Global CAS records preserve primary long-term marine δ34S trends in the Olenekian. • Global δ34S records support increased MSR and pyrite burial across the SSB. • Olenekian δ34S trends support decreasing ocean dissolved oxygen across the SSB. • Olenekian seawater sulfate concentration was 10–25% of modern seawater inventory. • No consistent link between ocean dissolved oxygen levels and conodont diversity. [ABSTRACT FROM AUTHOR]

• A mathematical model on rotating tapered anisotropic thin-walled biconvex beam is formulated for CAS layup. • The effect of bending-torsion coupling on the first few natural frequencies under rotation is presented. • Transverse shear, primary and secondary warping is considered in the model. • Stability of the modes are studied under high rotation speeds using modal assurance criteria. • Effects of centrifugal acceleration, warping and inertial warping on the dynamic behaviour are studied. Accurate modelling and prediction of dynamic characteristics for rotating thin-walled blades have drawn attention as it is an essential part of structural health monitoring for various engineering and civil applications such as wind turbine, helicopter and aeroplane blades. With the advent of structural tailoring techniques, various non-classical effects and couplings implicitly affecting the behaviour of such structures are yet not fully explored. In this regard, the present work proposes a numerical model for finding the free vibration characteristics of anisotropic tapered biconvex closed cross-section beam under rotating conditions. The model is derived based on energy method following the Ritz approximation. Circumferentially asymmetric stiffness (CAS) ply configuration is considered in order to study the impact of flexural torsional coupling on the vibration characteristics. Transverse shear effects, primary and secondary warping were also included in the current model. Mode switching phenomenon is dissected elaborately for the first few frequencies under rotating and nonrotating conditions. The impact of rotational effects like centrifugal acceleration, centrifugal warping, inertial warping on the first few frequencies is also demonstrated. An iterative technique is adapted to solve the equations having these rotational effects. Modal Assurance Criterion (MAC) is done in order to judge the consistency of the modes at different rotating speeds. [ABSTRACT FROM AUTHOR]