Search

The present study explores the process of agile transformation and the implementation of agile work practices in industrial companies, outlining an appropriate theoretical conceptual framework for the agile transformation of organizations. The purpose of this research is to discuss theoretical approaches explaining agile transformation and agile work practices in industrial companies, to present a conceptual framework, and to assess the effectiveness of the framework on the example of selected German industrial companies. For the research, a descriptive research design was chosen to substantiate the structural perspective of agile transformation and agile work practices in industrial companies and to reveal the interaction between these dimensions, while seeking to present the conceptual framework. A qualitative research strategy with semi-structured interviews was applied. This article proposes a concept of agile transformation of industrial companies, encompassing new insights. Agile transformation is referred to as the ability of companies to remain stable by employing agile work practices, preparing for and adapting to changes in the new environment while stressing the importance of the selected leadership style within the context of the organizational culture, and finally, using the experience gained to strengthen the agile transformation competencies and emphasizing the leadership of the managers as they perform a decisive role in implementing agile transformation in the company, managing the agile work practices and uncertainty. At the end of the article, a conceptual framework is presented that reflects the key structural parts. The conceptual framework was validated on the example of selected five strongest German industrial companies. Expert assessments revealed the choice of the leader as trainer (as the most suitable leadership type) and its effect on the implementation of agile transformation in the company, seeking to navigate to an agile way of working (when the manager helps identify the areas of improvement in agile work methods and processes). The experts also highlighted the effectiveness of agile work practice implementation (allowing to suggest expansion opportunities for industrial companies, enabling the effectiveness and sustainable competitiveness in the sector) and noted the interaction between the two dimensions.

The article is devoted to the concept of "committing" a prohibited act (crime) constituting the central concepts of the Penal Code . The choice of this topic is due to the fact that the word "commit" has not been adequately explained, apart from earlier studies, which is a sufficient reason to deepen this topic from the research perspective. It is not difficult to notice that defining the limits of the word "commit" will have a fundamental impact on the interpretation of the provisions of the Penal Code and the grounds for holding another person criminally responsible. Therefore, the study aims to determine what this "committing" is within the meaning of the Penal Code. The analysis is carried out from the linguistic interpretation of the word "commit", which does not give an unambiguous result, transferring the considerations to the ground of a legal interpretation consisting in supplementing it with the notions of "prohibited act" and "crime", which, taken together, only give it a statutory understanding. The article also points out that the legislator uses the word "to commit" in the Penal Code in various forms of time, which is of fundamental interpretation importance, because the words "commits", "committed" or "will" or "may commit" should be interpreted differently. which linguistically describe behaviors with different time points, which translates into the scope of application of the provisions that apply to them from the perspective of the time of committing a prohibited act within the meaning of Art. 6 1 of the Penal Code. The article highlights the difference between "committing a prohibited act" and "committing a crime". The author points out that the legislator inconsistently uses these terms, using the narrower concept of "committing a crime" in regulations that will also apply to "committed prohibited act", which may (but does not have to) be a crime. It is an undesirable procedure from the perspective of the so-called the terminological consequence of labeling the same behaviors with the same terms. It is also important from the perspective of the so-called presumption of innocence, as defined in art. 5 1 of the Code of Criminal Procedure, according to which the crime is only a legally judged act. The final part of the article is devoted to identifying specific behaviors that constitute "committing" a prohibited act (crime). Author includes both gradual and phenomenal forms of a prohibited act, which is not obvious at first glance, since the legislator in Art. 13 1 of the Penal Code and art. 16 1 of the Penal Code it relates the subjective side of the punishable preparation and attempts to "commit" a prohibited act, despite the fact that these behaviors in fact aim at the final, completed form of the crime.

Abstract. Introduction:. Pregabalin, which acts on the α2δ-1 subunit of voltage-gated calcium channels, relieves ≥50% of pain in a third of individuals with fibromyalgia. Thus far, preclinical studies of pregabalin have predominantly used male animals. Objectives:. The purpose of our study was to investigate potential sex differences in the analgesic efficacy of pregabalin that may contribute to disparities in human outcomes. Methods:. We used a mouse model of chronic widespread muscle pain (CWP) to test the effects of pregabalin on muscle hyperalgesia, nonreflexive pain, and motor behaviors. The CWP pain model combines 2 pH 4.0 saline injections, spaced 5 days apart, into the gastrocnemius muscle and produces bilateral muscle hyperalgesia. Furthermore, we explored sex differences in the mRNA and protein expression of the α2δ-1 subunit of voltage-gated calcium channels in the dorsal horn of the spinal cord and dorsal root ganglia after development of CWP. Results:. Pregabalin fully attenuated muscle hyperalgesia bilaterally in male but not female mice with equal motor deficits produced in both sexes. In addition, using the conditioned place preference test, mice of both sexes with CWP spent significantly more time in the pregabalin-paired chamber compared with baseline, but not significantly greater than pain-free controls. Chronic widespread muscle pain produced no changes in α2δ-1 subunit mRNA or protein expression in the dorsal horn of the spinal cord or dorsal root ganglia in either sex. Conclusion:. Overall, these findings indicate pregabalin may be more effective in treating CWP in males, but the factors leading to these differences are not fully understood.

Background: Chronic liver disease diagnoses depend on liver biopsy histopathological assessment. However, due to the limitations associated with biopsy, there is growing interest in the use of quantitative digital pathology to support pathologists. We evaluated the performance of computational algorithms in the assessment of hepatic inflammation in an autoimmune hepatitis in which inflammation is a major component. Methods: Whole-slide digital image analysis was used to quantitatively characterize the area of tissue covered by inflammation [Inflammation Density (ID)] and number of inflammatory foci per unit area [Focal Density (FD)] on tissue obtained from 50 patients with autoimmune hepatitis undergoing routine liver biopsy. Correlations between digital pathology outputs and traditional categorical histology scores, biochemical, and imaging markers were assessed. The ability of ID and FD to stratify between low-moderate (both portal and lobular inflammation ≤1) and moderate-severe disease activity was estimated using the area under the receiver operating characteristic curve (AUC). Results: ID and FD scores increased significantly and linearly with both portal and lobular inflammation grading. Both ID and FD correlated moderately-to-strongly and significantly with histology (portal and lobular inflammation; 0.36≤R≤0.69) and biochemical markers (ALT, AST, GGT, IgG, and gamma globulins; 0.43≤R≤0.57). ID (AUC: 0.85) and FD (AUC: 0.79) had good performance for stratifying between low-moderate and moderate-severe inflammation. Conclusion: Quantitative assessment of liver biopsy using quantitative digital pathology metrics correlates well with traditional pathology scores and key biochemical markers. Whole-slide quantification of disease can support stratification and identification of patients with more advanced inflammatory disease activity.

The paper introduces an original method for effective spatial data processing, particularly important for land administration and real estate governance. This approach integrates Unmanned Aerial Vehicle (UAV) data acquisition and processing with Artificial Intelligence (AI) and Geometric Transformation algorithms. The results reveal that: (1) while the separate applications of YOLO and Hough Transform algorithms achieve building detection rates up to 77% and 83%, respectively, (2) a novel methodology is proposed to combine spatial data and assess their quality of the detected buildings by comparing the generated building polygons with existing cadastral maps. The evaluation uses a polygon-based comparison approach, which computes metrics such as Precision, Recall, F1-Score, and Accuracy based on the spatial relationships between predicted and reference building contours, (3) the weighted model showed about 7 % improvement in accuracy compared to cadastral data. This innovative approach substantially improves spatial data processing, aiding in implementing principles for real estate good governance and offering a valuable asset for various land administration applications.

Asia is the center of Tilia (Malvaceae) species diversity. However, the ectomycorrhizal (ECM) relations of Asian Tilia are scarcely studied. This study provides the first description of ECM communities of Tilia kiusiana, a rare tree endemic to southwestern Japan. Across the natural distribution of T. kiusiana, ECM fungal communities hosted by the species were investigated in three study sites: Hyōgo (H) and Yamaguchi (Y) on Honshu Island, and Ōita (O) on Kyushu Island. Using molecular methods, T. kiusiana was revealed to host a high diversity of fungi belonging to 25 ECM lineages (16, 17, and 14 lineages on sites H, Y, and O, respectively). The ECM communities of T. kiusiana and the previously studied endemic T. japonica were compared to the available data on other ECM tree genera in Japan, revealing that three Ascomycota ECM lineages (/genea-humaria, marcelleina-peziza gerardii, /tuber-helvella) show a preference towards Tilia hosts. While the total lineage richness did not differ among the compared host tree genera, Tilia communities exhibited higher effective lineage richness at higher (less sensitive to rare taxa) diversity orders. Despite their relative rarity, Tilia trees might play an important role in mixed forests: maintaining the diversity of ECM Ascomycota and potentially buffering the ECM fungal biodiversity loss in cases of ECM tree host diversity decline.

The issue of similarity in the real estate market is a widely recognized aspect of analysis, yet it remains underexplored in scientific research. This study aims to address this gap by introducing the concept of a Property Cognitive Information System (PCIS), which offers an innovative approach to analyzing similarity in the real estate market. The PCIS introduces non-classical and alternative solutions, departing from the conventional data analysis practices commonly employed in the real estate market. Moreover, the study delves into the integration of artificial intelligence (AI) in the PCIS. The paper highlights the value added by the PCIS, specifically discussing the validity of using automatic ML-based solutions to objectify the results of synergistic data processing in the real estate market. Furthermore, the article establishes a set of essential assumptions and recommendations that contribute to a well-defined and interpretable notion of similarity in the context of human-machine analyses. By exploring the intricacies of similarity in the real estate market through the innovative PCIS and AI-based solutions, this research seeks to broaden the understanding and applicability of data analysis techniques in this domain.

Abstract The very shallow marine basin of Puck Lagoon in the southern Baltic Sea, on the Northern coast of Poland, hosts valuable benthic habitats and cultural heritage sites. These include, among others, protected Zostera marina meadows, one of the Baltic’s major medieval harbours, a ship graveyard, and likely other submerged features that are yet to be discovered. Prior to this project, no comprehensive high-resolution remote sensing data were available for this area. This article describes the first Digital Elevation Models (DEMs) derived from a combination of airborne bathymetric LiDAR, multibeam echosounder, airborne photogrammetry and satellite imagery. These datasets also include multibeam echosounder backscatter and LiDAR intensity, allowing determination of the character and properties of the seafloor. Combined, these datasets are a vital resource for assessing and understanding seafloor morphology, benthic habitats, cultural heritage, and submerged landscapes. Given the significance of Puck Lagoon’s hydrographical, ecological, geological, and archaeological environs, the high-resolution bathymetry, acquired by our project, can provide the foundation for sustainable management and informed decision-making for this area of interest.

Objectives: The purpose of this study is to evaluate the association between lymphopenia and survival in women with locally advanced cervical cancer (LACC) treated with definitive chemoradiation (CRT). Methods: We retrospectively reviewed patients with LACC treated at a single institution from 2004 to 2021. Patient and treatment characteristics were recorded along with baseline absolute lymphocyte counts (ALC). Overall survival (OS), progression free survival (PFS), and local control (LC) were calculated from start of treatment to date of last follow-up. Cox regression and competing risks regression model were performed to evaluate whether baseline ALC was associated with OS, PFS, or LC. Results: 246 patients met study inclusion criteria with stage IB – IV disease with a median follow up of 2.8 years (range 0.2–13.4 years). 5-year OS, PFS, and LC were 68.4 % (95 % CI 61.7–75.9), 57.2 % (95 % CI 50.4–64.8), and 79.0 % (95 % CI 73.0–84.4), respectively. Baseline lymphopenia (ALC

Purpose/objective(s)To evaluate rates of clinical complete response (cCR), surgery-free survival, permanent ostomy-free survival, and factors associated with these outcomes in patients treated with total neoadjuvant therapy (TNT) with intent for non-operative management of rectal adenocarcinoma.MethodsA retrospective review was conducted of patients treated with TNT for stage II-IV rectal adenocarcinoma (n=45) at our institution between 2013 – 2022 with curative intent. All patients received radiation with concurrent capecitabine and additional chemotherapy, either prior to or following chemoradiation (CRT), with intent for non-operative management. Response rates were determined based on post-treatment MRI and endoscopy. Kaplan-Meier method was utilized to estimate the 1- and 2-year surgery- and permanent ostomy-free survivals. Cox regression was used to evaluate associations between surgery- and permanent ostomy-free survivals and various factors of interest, including patient and tumor characteristics and clinical response. Chi-squared analysis compared rates of cCR and surgery by sequence of TNT modality and cell count ratios.ResultsOf the 45 patients treated with TNT, most patients had low-lying rectal tumors with a median distance of 4.1 cm from the anal verge (range, 0.0 – 12.0). Overall, 64.4% (n=29) achieved cCR after TNT. 13 patients (28.9%) underwent surgical resection following TNT, 12 of whom had incomplete response and one who elected to undergo surgery after reaching cCR. At median follow up of 32.0 months (range, 7.1 – 86.1), 22.2% (n=10) of patients had a permanent colostomy, with only 2 of these completed for tumor regrowth after cCR. At one and two years, respectively, surgery-free survival was 77.3% and 66.2%, and permanent ostomy-free survival was 90.9% and 78.2%. Rates of cCR were higher in patients who received CRT first compared to those who received chemotherapy first (72.2% vs. 33.3%, p=0.029) and rates of surgery were also lower in patients who received CRT first compared to those who received chemotherapy first (19.4% vs. 66.7%, p=0.005). On Cox regression model, cCR on 6 month post-CRT endoscopy was associated with surgery-free survival (p=0.006) and permanent ostomy-free survival (p=0.033). Clinical response at earlier follow up points did not predict surgery- nor permanent ostomy-free survival.ConclusionThese results support evidence that TNT may be a non-surgical option for select patients with rectal adenocarcinoma who desire organ preservation. In this investigation at a single institution, the treatment response on 6-month post-CRT endoscopy was the best predictor of surgery- and permanent ostomy-free survival, which are outcomes that are important to patient quality of life. CRT followed by consolidation chemotherapy was associated with higher rates of cCR and lower rates of surgery compared to those treated with induction chemotherapy.

In this paper we derive mathematical description of TCP (Transmission Control Protocol) retransmission probability based on Jacobson’s smoothing algorithm that belongs to EWMA (Exponentially Weighted Moving Average) category. This description is parametrized on the probability density function (pdf) of RTT (Round Trip Time) samples and α, β – two primary parameters of Jacobson’s algorithm. Although it is not a close form expression, it is formulated as an effective algorithm that let us to explicitly calculate the values of RTO (Retransmission Time Out) probability as a function of α, β and the pdf of RTT samples. We achieve the effectiveness of this approach by applying smart discretization of the state space and replacement of continuous functions with discrete approximate equivalents. In this way, we mitigate the cardinality of discrete distributions we deal with that results in linear (n+m) instead of multiplicative (n⋅m) growth of computational complexity. We provide the evaluation of RTO probability for a wide set of α, β parameter values and differently shaped Normal and Laplace pdfs the RTT samples are taken from. The obtained numerical results let us to draw some conclusions regarding the choice of optimal values of α, β parameters as well as the impact of pdf the RTT samples are taken from.

Abstract The central nervous system (CNS) is home to neuronal and glial cells. Traditionally, glia was disregarded as just the structural support across the brain and spinal cord, in striking contrast to neurons, always considered critical players in CNS functioning. In modern times this outdated dogma is continuously repelled by new evidence unravelling the importance of glia in neuronal maintenance and function. Therefore, glia replacement has been considered a potentially powerful therapeutic strategy. Glial progenitors are at the center of this hope, as they are the source of new glial cells. Indeed, sophisticated experimental therapies and exciting clinical trials shed light on the utility of exogenous glia in disease treatment. Therefore, this review article will elaborate on glial-restricted progenitor cells (GRPs), their origin and characteristics, available sources, and adaptation to current therapeutic approaches aimed at various CNS diseases, with particular attention paid to myelin-related disorders with a focus on recent progress and emerging concepts. The landscape of GRP clinical applications is also comprehensively presented, and future perspectives on promising, GRP-based therapeutic strategies for brain and spinal cord diseases are described in detail.

Abstract Background Evidence-based parenting programmes have strong evidence in preventing and mitigating violence, but in-person programmes are challenging to deliver at scale. ParentApp is an open-source, offline-first app-based adaptation of the Parenting for Lifelong Health for Parents and Teens programme to promote playful and positive parenting, reduce risks for sexual violence victimisation, and prevent violence against adolescents. This study aims to evaluate the effectiveness and cost-effectiveness of ParentApp compared to an attention-control group. Methods This study is a two-arm pragmatic cluster-randomised controlled trial to test whether ParentApp reduces adolescent physical abuse, emotional abuse, and sexual violence risks and victimisation at 1 month and 12 months post-intervention. Caregivers of adolescents aged 10–17 years and their adolescent children (N = 2400 caregiver-adolescent dyads) will be recruited in urban and peri-urban communities in the Mwanza region of Tanzania. A total of 80 study clusters will be stratified and randomised (1:1) to the intervention group, who will receive ParentApp with support through a WhatsApp group, or to an attention-control group, who will receive a water, sanitation, and hygiene app. Quantitative data will be collected through outcomes questionnaires with caregivers and adolescents, administered at baseline, 4 months post-baseline, and 16 months post-baseline, as well as through routine implementation data and ParentApp engagement data. Qualitative data will be collected through individual interviews and focus groups with caregivers, adolescents, and implementing partner staff. Discussion App-based interventions have the potential to expand access to evidence-based parenting support, but currently lack rigorous evidence in low- and middle-income countries. This is the first known randomised control trial of a hybrid digital parenting programme to prevent the abuse of adolescents in low- and middle-income settings. Trial registration The trial was registered on the Open Science Framework on 14 March 2023, registration: OSF.IO/T9FXZ .

Optical frequency comb (OFC) emission in quantum cascade lasers (QCLs) is highly attractive for applications in metrology and sensing. Recently, coherent OFC mode-locking with large intermodal spacing was demonstrated in QCLs. These self-starting harmonic frequency combs (HFCs) show highly phase-stable operation and promise interesting perspectives towards optical or even quantum communication. Here, we present a detailed multi-domain modeling approach for the numerical study of QCLs. Our theoretical characterization is divided into stationary carrier transport simulations, based on the ensemble Monte Carlo method, and dynamical simulations of the light-matter interaction, based on multi-level Maxwell-density matrix equations. We investigate the influence of the chosen eigenstate basis on the gain spectrum and present self-consistent simulation results of stable HFC operation in a double metal terahertz QCL. In our simulations, the studied QCL gain medium shows self-starting harmonic mode-locking for different bias and waveguide configurations, resulting in a mode spacing of up to twelve times the cavity round trip frequency. Furthermore, we characterize the spectral time evolution of the coherent HFC formation process, yielding the spontaneous build-up of a dense multimode state which is gradually transferred into a broad and clear harmonic OFC state.

Background: Multiparametric MRI markers of liver health corrected T1 (cT1) and proton density fat fraction (PDFF) have shown utility in the management of various chronic liver diseases. We assessed the normal population reference range of both cT1 and PDFF in healthy child and adult volunteers without any known liver disease. Methods: A retrospective multi-centre pooled analysis of 102 child and young adult (9.1 years (6–18)) volunteers from three centres: Children’s Memorial Health Institute (N = 21), University Hospital Southampton (N = 28) and Hospital Infantil de Mexico (N = 53). Sex and ethnic differences were investigated for both cT1 and PDFF. Age effects were investigated with comparison to a pooled adult cohort from the UK Biobank (N = 500) and CoverScan (N = 71), covering an age range of 21 to 81 years. Results: cT1 values were normally distributed with a median of 748 ms (IQR: 725–768 ms; 2.5–97.5 percentiles: 683–820 ms). PDFF values followed a normal distribution with a median of 1.7% (IQR: 1.3–1.9%; 2.5–97.5 percentiles: 1–4.4%). There were no significant age and sex differences in cT1 and PDFF between children and young adults. No differences in cT1 and PDFF were found between ethnicities. Age comparisons showed statistically significant, but clinically negligible, cT1 (748 ms vs. 732 ms) and PDFF (2.4% vs. 1.9%) differences between paediatric and adult groups, respectively. Conclusions: Median healthy cT1 and PDFF reference ranges in children and young adults fall within the reported limits for normal of 800 ms and 5%, respectively.

Mutations in the human PURA gene cause the neurodevelopmental PURA syndrome. In contrast to several other monogenetic disorders, almost all reported mutations in this nucleic acid-binding protein result in the full disease penetrance. In this study, we observed that patient mutations across PURA impair its previously reported co-localization with processing bodies. These mutations either destroyed the folding integrity, RNA binding, or dimerization of PURA. We also solved the crystal structures of the N- and C-terminal PUR domains of human PURA and combined them with molecular dynamics simulations and nuclear magnetic resonance measurements. The observed unusually high dynamics and structural promiscuity of PURA indicated that this protein is particularly susceptible to mutations impairing its structural integrity. It offers an explanation why even conservative mutations across PURA result in the full penetrance of symptoms in patients with PURA syndrome.

Modern video streaming services require quality assurance of the presented audiovisual material. Quality assurance mechanisms allow streaming platforms to provide quality levels that are considered sufficient to yield user satisfaction, with the least possible amount of data transferred. A variety of measures and approaches have been developed to control video quality, e.g., by adapting it to network conditions. These include objective matrices of the quality and thresholds identified by means of subjective perceptual judgments. The former group of matrices has recently gained the attention of (multi) media researchers. They call this area of study “Quality of Experience” (QoE). In this paper, we present a theoretical model based on review of previous QoE’s models. We argue that most of them represent the bottom-up approach to modeling. Such models focus on describing as many variables as possible, but with a limited ability to investigate the causal relationship between them; therefore, the applicability of the findings in practice is limited. To advance the field, we therefore propose a structural, top-down model of video QoE that describes causal relationships among variables. This novel top-down model serves as a practical guide for structuring QoE experiments, ensuring the incorporation of influential factors in a confirmatory manner.

The digital representation of seafloor, a challenge in UNESCO’s Ocean Decade initiative, is essential for sustainable development support and marine environment protection, aligning with the United Nations’ 2030 program goals. Accuracy in seafloor representation can be achieved through remote sensing measurements, including acoustic and laser sources. Ground truth information integration facilitates comprehensive seafloor assessment. The current seafloor mapping paradigm benefits from the object-based image analysis (OBIA) approach, managing high-resolution remote sensing measurements effectively. A critical OBIA step is the segmentation process, with various algorithms available. Recent artificial intelligence advancements have led to AI-powered segmentation algorithms development, like the Segment Anything Model (SAM) by META AI. This paper presents the SAM approach’s first evaluation for seafloor mapping. The benchmark remote sensing dataset refers to Puck Lagoon, Poland and includes measurements from various sources, primarily multibeam echosounders, bathymetric lidar, airborne photogrammetry, and satellite imagery. The SAM algorithm’s performance was evaluated on an affordable workstation equipped with an NVIDIA GPU, enabling CUDA architecture utilization. The growing popularity and demand for AI-based services predict their widespread application in future underwater remote sensing studies, regardless of the measurement technology used (acoustic, laser, or imagery). Applying SAM in Puck Lagoon seafloor mapping may benefit other seafloor mapping studies intending to employ AI technology.

The concept of homogeneity in the real estate market is a well-known analysis aspect, yet it remains a significant challenge in practical implementation. This study aims to fill this research gap by introducing the HELIOS concept (Homogeneity Estate Linguistic Intelligence Omniscient Support), presenting a new approach to real estate market analyses. In a world increasingly mindful of environmental, social, and economic concerns, HELIOS is a novel concept grounded in linguistic intelligence and machine learning to reshape how we perceive and analyze real estate data. By exploring the synergies between human expertise and technological capabilities, HELIOS aims not only to enhance the efficiency of real estate analyses but also to contribute to the broader goal of sustainable and responsible data practices in the dynamic landscape of property markets. Additionally, the article formulates a set of assumptions and suggestions to improve the effectiveness and efficiency of homogeneity analysis in mass valuation, emphasizing the synergy between human knowledge and the potential of machine technology.

This paper proposes a mathematical model for the shading profiles of a PV module with thin, long linear elements. The model includes the brightness distribution over the entire shading region (umbra, penumbra, and antumbra). A corresponding calculation code in the form of m-files has been prepared for the MATLAB environment. The input data for the calculations are the coordinates of the Sun’s position in the sky, the dimensions and spatial orientation of the shading element, and the spatial orientation of the shaded PV module. The correctness of the model was verified by a measurement experiment carried out under actual outdoor weather conditions. Statistical analysis of the comparison between the measurement data from the experiment and the model showed its high accuracy. As part of this research work, it was also checked how shading with thin linear elements affects the current–voltage characteristics of the module. It turned out that even a small linear shading could reduce the power output of the module by more than 6%, with the distribution of this shading across the individual cells of the module being extremely important.

We previously have shown that mRNA-based engineering may enhance mesenchymal stem cell (MSC) trafficking. However, optimal conditions for in vitro mRNA engineering of MSCs are unknown. Here, we investigated several independent variables: (1) transfection factor (Lipofectamine 2000 vs. TransIT), (2) mRNA purification method (spin column vs. high-performance liquid chromatography [HPLC] column), and (3) mRNA capping (ARCA vs. β-S-ARCA D1 and β-S-ARCA D2). Dependent variables included protein production based on mRNA template (measured by the bioluminescence of reporter gene luciferase over hours), MSC metabolic activity corresponding with their wellbeing measured by CCK-8 over days, and endogenous expression of genes by RT-qPCR related to innate intracellular immune response and decapping at two time points: days 2 and 5. We have found that Lipofectamine 2000 outperforms TransIT, and used it throughout the study. Then, we showed that mRNA must be purified by HPLC to be relatively neutral to MSCs in terms of metabolic activity and endogenous protein production. Ultimately, we demonstrated that β-S-ARCA D1 enables higher protein production but at the cost of lower MSC metabolic activity, with no impact on RT-qPCR results. Thus Lipofectamine 2000-based in vitro transfection of HPLC-purified and ARCA- or β-S-ARCA D1-capped mRNA is optimal for MSC engineering.

Abstract The blood–brain barrier (BBB) is a sophisticated structure whose full functionality is required for maintaining the executive functions of the central nervous system (CNS). Tight control of transport across the barrier means that most drugs, particularly large size, which includes powerful biologicals, cannot reach their targets in the brain. Notwithstanding the remarkable advances in characterizing the cellular nature of the BBB and consequences of BBB dysfunction in pathology (brain metastasis, neurological diseases), it remains challenging to deliver drugs to the CNS. Herein, we outline the basic architecture and key molecular constituents of the BBB. In addition, we review the current status of approaches that are being explored to temporarily open the BBB in order to allow accumulation of therapeutics in the CNS. Undoubtedly, the major concern in field is whether it is possible to open the BBB in a meaningful way without causing negative consequences. In this context, we have also listed few other important key considerations that can improve our understanding about the dynamics of the BBB.

This paper presents ‘Daily Video’, an innovative application designed to facilitate longitudinal studies in the realm of quality of experience (QoE). The application simulates real-life video service consumption and collects daily subjective quality assessments from users, promoting an in-depth understanding of user engagement and habits over time. Key features include scheduling, customised queries, user feedback, device orientation tracking and instant access to results, all of which enhance the application’s adaptability and usability for a variety of experimental conditions. The application, available as open-source code, supports state-of-the-art QoE research.