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This article presents the fundamental principles of robot accuracy. It characterizes a modular robot, describes the measurement setup, and outlines the methodology for evaluating positioning accuracy across different configurations of the modular robot (four, five, and six modules) under varying loads of 6, 10, and 16 kg. An analysis was conducted on the impact of load changes on four- and five-module configurations, as well as the effect of configuration changes on the robot’s performance with 6 and 10 kg loads. The findings indicate that both the number of modules and the load affect positioning accuracy. This article highlights the importance of selecting the optimal configuration based on planned industrial tasks to ensure the highest precision and operational efficiency.

The reconstruction of buildings is a complex process that often requires the consideration of the construction load when selecting correct building materials. Autoclaved aerated concrete (AAC)—which has a lower bulk density (compared to traditional masonry materials)—is very beneficial in such applications. A current trend in AAC development is the utilization of secondary raw materials in high-performance AAC, characterized by higher bulk density and compressive strength than regular AAC. The increase in bulk density is achieved by increasing the content of quartz sand in the mixing water. In this study, part of the siliceous component was replaced by ladle slag, foundry sand, furnace lining, and chamotte block powder. These materials are generated as by-products in metallurgy. The substitution rates were 10% and 30%. The samples were autoclaved in a laboratory autoclave for 8 h of isothermal duration at 190 °C with a saturated water vapor pressure of 1.4 MPa. The physical–mechanical parameters were determined, and the microstructure was described by XRD and SEM analyses. The results were compared with traditional AAC, with silica sand being used as the siliceous component. The measurement results show that sand substitution by the secondary raw material is possible, and it does not have a significant impact on the properties of AAC, and in a proper dosage, it can be beneficial for AAC production.

Abstract Silicate composites have very low conductivity in general. It is possible to achieve an electrical resistivity decrease by adding an electro-conductive filler. The conductive mixture consists of cementitious binder, various types of silica sand, and graphite-based conductive fillers. One of the research focusses is partial substitution of ordinary raw materials by alternative components (waste materials by-products and secondary raw materials) and its influence on composite properties. The alternative components studied were fly ash as a partial binder replacement, waste graphite from two different sources and steel shavings as a substitute for conductive filler. Resistivity of cured conductive silicate-based specimens was analysed in relation to changes in physico-mechanical properties in context of microstructural changes in the hardened cementitious matrix (by optical and scanning electron microscopy with energy disperse analysis). Partial substitution of cement by fly ash was found to reduce the electrical resistivity of the composite. Some of the waste graphite fillers significantly reduce the resistivity of the cement composite and increase the compressive strength. It was proven, that is possible to replace primary conductive fillers by secondary raw materials.

Analysis of the use of reinforced concrete structures confirmed the destruction of reinforced products based on Portland cement due to stray currents, which makes it impossible to achieve the required durability and reliability of structures. The present work shows the results of a study on the diffusion permeability of samples with different degrees of electrical conductivity. The relative value of the electrode potential was measured by the open circuit potential method. The novelty of this work is its analysis of the quantitative and qualitative characteristics of the structure of the mineral matrix with specified electrical properties after long-term exposure to electrochemical corrosion. In this work, an assessment was carried out, for the first time, on the effects of electrochemical corrosion on modified composites with predominantly electrically conductive and electrically insulating properties. An increase in the electrical conductivity of the composite was found to reduce the potential difference. The use of such composites helped protect the reinforcement from electrochemical corrosion.

Neutrophilic inflammation is a hallmark of many monogenic autoinflammatory diseases. Here the authors report a case series of three unrelated boys with perinatal-onset of neutrophilic cutaneous small vessel vasculitis and systemic inflammation, and identify de novo truncating and missense variants in the Src-family tyrosine kinase LYN.

This article discusses creating a methodology for the asymmetric measuring of values and processes of collision forces and pressures of the collaborative robot dependent on time. Furthermore, it verifies the usefulness of this methodology in practice by successfully performing the experimental measurement and verifying the possibility of using these results by analysing and stating the collaboration level for a robot of the given type. According to the suggested methodology, the measurement results are a specific output based on real measured data, which can be easily rated and can quickly determine the collaborative level of any robot. Measurements were aimed at determining the values of pressure and force with which the robot acts at certain speeds related to distance from the base. Due to the controlled symmetrical impact of the robot on the measuring device, the transfer of energy from the robot to the human body was guaranteed. In theoretical terms, this article primarily provides the assembly of the theoretical foundation of the collaborative environment between humans and robots, and a comprehensive overview of the possibilities of using the technical specification ISO/TS 15066:2016 when deploying a robot in collaboration with humans in a collaborative environment. This new information is highly valuable for both manufacturers and users of collaborative robots. The presented article analyses the possibilities of measuring collaboration and safety elements in cooperation with a robot. The most significant practical benefit is the presentation of a methodology for measuring robot collaboration and verifying its functionality by conducting experimental measurements of robot collaboration according to this methodology. The measurement was performed on a robot made by Universal Robots, model UR10. The measurement coordinates were stationed in a way to create a spatial measurement model. Boundary coordinates of the spatial model were as follows: [450; 200], [450; 500], [850; 200], and [850; 500]. Collisions were measured at 8 different speeds for each coordinate (20 mms−1, 50 mms−1, 100 mms−1, 200 mms−1, 250 mms−1, 300 mms−1, 350 mms−1, and 400 mms−1) to enable the observation of changes in accordance with speed. The measured values indicate a significant fact: the closer the collision is to the robot’s base, the higher the collision forces. An important aspect is that the measured values were only for speeds up to 400 mms−1, which is a very low value for industrial use to meet the desired cycle time. It can be stated with absolute certainty that speed has the greatest impact on collision force values. The speed of the collaborative robot arm can therefore be considered a limiting factor for use in industrial applications with a requirement of a short cycle time. Focusing on the results of the measured values, it can be stated that a new finding is the correct design of robotic movements in relation to possible contact with humans is crucial. The result of the measurement according to the proposed methodology is a specific output of realistically measured data, which can be easily evaluated and the level of collaboration of any robot can be quickly determined. The measured data will also serve as a basis for further processing and preparation of new simulation software. It will be possible to use the intended software for detecting and predetermining the safe asymmetric movements of the collaborative robot already at the stage of production preparations, unlike the method of measuring force and pressure on robots which can be used until the time of implementation into production. In the future, this software may also allow users of collaborative robots to easily and quickly evaluate the robots specified.

IntroductionWe analyzed the incidence, risk factors of central nervous system (CNS) relapse, and outcome of CNS involvement in patients with peripheral T-cell lymphomas (PTCL) from the Czech Lymphoma Study Group Registry NiHiL (Clinical Trial gov. NCT03199066).Materials and MethodsOut of 1,040 patients with PTCL, we identified 29 patients (2.79%) with CNS involvement: 2 patients with primary CNS T cell lymphoma, 11 patients with CNS and systemic disease at diagnosis, and 16 patients (1.54%) at CNS relapse. The most common histology with CNS disease was PTCL, not otherwise specified. Progression-free survival (PFS) was defined as the time interval from diagnosis to progression or death. PFS-2 was defined as the interval from the date of a new relapse until the next relapse.ResultsPatients with testicular involvement received intrathecal prophylaxis with methotrexate. High-dose methotrexate-based treatment was administered in 44.8% of patients with CNS disease. Median follow-up was 71.3 months. The difference between the median PFS of 1,027 patients without initial CNS disease (32.6 months) and 11 patients with initial CNS and systemic disease (4.8 months) was significant (p = 0.04). The difference between the median PFS2 in CNS relapses (10.1 months) and 493 relapses outside of CNS (9.1 months) was not significant (p = 0.6). Risk factors for CNS relapses included the following: involvement of more than one extranodal site (p = 0.008), soft tissue involvement (p = 0.003), testicular involvement (p = 0.046), and the presence of B symptoms (p = 0.035). The difference between the median OS of 1,027 patients without initial CNS disease (46.0 months) and 11 patients with initial CNS and systemic disease (18.2 months) was significant (p = 0.02). The median OS2 in CNS relapses was 11.8 months and that in relapses outside of CNS was 21.3 months. CNS involvement was not associated with a significantly worse OS compared to relapsed/refractory patients without CNS involvement (p = 0.1).ConclusionsThe incidence of CNS disease at the time of diagnosis and at relapse in PTCL is low and usually associated with other systemic involvement. The prognosis of PTCL with initial CNS involvement is significantly worse when compared to patients without CNS disease at diagnosis. The outcome of CNS relapse is comparable with relapsed PTCL outside of CNS. The optimal treatment is not defined yet.

Abstract Twenty percent of patients with high‐tumor‐burden (HTB) follicular lymphoma (FL) develop progression/relapse of disease (POD) within 24 months of frontline immunochemotherapy. Unfortunately, about 50% of these patients die within 5 years since POD event. Rituximab maintenance was proven to reduce relapse rate in responding FL, but its role on preventing POD was not defined. We analyzed 1360 HTB‐FL patients from the Czech Lymphoma Study Group registry treated with frontline rituximab‐containing regimen. Of those, 950 cases received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R‐CHOP) and achieved complete or partial remission: 712 patients received rituximab maintenance (MAINT) and 238 were a historical observational cohort (OBS). We have proposed a modified POD24 (mPOD24) endpoint for the chemosensitive patients calculated from the end‐of‐induction (EOI). Survival rates since EOI were as follows: 5‐year overall survival (OS) 86.2% versus 94.5% in the OBS and MAINT groups, respectively (P

This article deals with the design of a methodology for vibration and noise measurement on a six-axis collaborative robotic arm. A vibration and noise measurement methodology is proposed for six robot positions. In each position, measurements were performed under defined equal boundary conditions. The boundary conditions were related to the velocities of the joints and the load on the robotic arm. The second part of the article is an evaluation of the initial experimental results. So far, only the acceleration of the sixth joint of the robotic arm—Wrist 3—has been measured. The aim of the measurements was to verify if the methodology presented can be used for vibration measurements. From the evaluation of the experimental measurements, it was determined that the given methodology can be used for vibration measurements. It was also found that the acceleration is transmitted in the axes other than the axis of motion of the robotic arm. In future experiments, the vibration at the other joints of the robotic arm will be measured and the noise of the robotic arm will be measured to confirm whether the proposed methodology is indeed functional.

Cement composite materials with reduced resistivity are specialized building materials, which are constantly pushing their limits. Research into these composites requires a study of the influences of exposure conditions on resistivity. The mixes selected for the purpose of the research included the reference, pure cement mix, and mixes with proportions of graphite under and above the percolation threshold, with two different types of graphite. It was found that the resistivity of all the tested mixes decreases if moisture grows; the influence of moisture is more significant for mixes with graphite proportions below the percolation threshold. The resistivity of all the tested mixes decreases with increasing temperatures; the influence of a higher temperature (50 °C) is more significant for mixes with graphite proportions above the percolation threshold; however, these mixes are, at the same time, more resistant to permanent changes in resistivity caused by frost (−10 °C). It was found that the action of CO2 causes a reduction in resistivity. Mixes with proportions of graphite above the percolation threshold show higher stability when exposed to CO2. Mixes with proportions of graphite below the percolation threshold are extremely sensitive to horizontally oriented pressure loads. Increases in resistivity caused by vertical pressure loads were by 20–40%. The resistivity of the mixes with proportions of graphite above the percolation threshold was less sensitive to the pressure load.

In this paper, an assembly sequence planning system, based on artificial neural networks, is developed. The problem of artificial neural network itself is largely related to symmetry at every stage of its creation. A new modeling scheme, known as artificial neural networks, takes into account selected DFA (Design for Assembly) rating factors, which allow the evaluation of assembly sequences, what are the input data to the network learning and then estimate the assembly time. The input to the assembly neural network procedure is the sequences for assembling the parts, extended by the assembly’s connection graph that represents the parts and relations between these parts. The operation of a neural network is to predict the assembly time based on the training dataset and indicate it as an output value. The network inputs are data based on selected DFA factors influencing the assembly time. The proposed neural network model outperforms the available assembly sequence planning model in predicting the optimum assembly time for the mechanical parts. In the neural networks, the BFGS (the Broyden–Fletcher–Goldfarb–Shanno algorithm), steepest descent and gradient scaling algorithms are used. The network efficiency was checked from a set of 20,000 test networks with randomly selected parameters: activation functions (linear, logistic, tanh, exponential and sine), the number of hidden neurons, percentage set of training and test dataset. The novelty of the article is therefore the use of parts of the DFA methodology and the neural network to estimate assembly time, under specific production conditions. This approach allows, according to the authors, to estimate which mechanical assembly sequence is the most advantageous, because the simulation results suggest that the neural predictor can be used as a predictor for an assembly sequence planning system.

The objective of the research described in this article is a repeat analysis and comparison of social media communication channels used in Czech, Slovak and Swiss product innovation‑oriented companies, where the Swiss set of companies is used as a benchmark. The research is conducted using the same methodology as previous research described in Chlebovský (2015). The use of the same methodology allows comparison of the both research results and discussion on the development of social media use in marketing communication of production innovation‑oriented companies in selected countries. The primary research was carried out by scanning the social media use of the selected companies. European company database Amadeus, provided by Bureau van Dijk, was used for company selection in all three countries under the same search criteria. The set of companies researched covers the highest turnover product innovation‑oriented companies. Each particular sample set covered 100 companies from each country. The activity of the selected companies on Facebook, YouTube, Twitter, Instagram and LinkedIn were observed and particular metrics were scaled. Microsoft Excel was used for storing, statistical processing and graphic outputs of the research. The hypotheses formulated were statistically tested and the results confirmed. In order to confirm or reject normal data distribution, the Anderson‑Darling Normality Test was performed through all three sample sets. This test rejected normal data distribution for all three data sets. The non‑parametric Mann‑Whitney U test was then used to test the hypothesis. Evaluation of the results in comparison with previous research shows an increase in use of social media in communication of Czech and Slovak companies. Hypothesis tests show that Czech product innovation‑oriented companies are statistically equal in activity and success in communication through social media compared to the Swiss benchmark. Slovak companies are still behind the Swiss benchmark.

Monitoring the condition of building structures based on composite materials in aggressive environments shows that the deterioration of basic properties occurs under the influence of various factors such as temperature and humidity changes, in addition to changes in the chemical composition of air environment. In addition, the composite materials during the operation must retain not only the mechanical properties laid down at the design stage, but also the electro-physical characteristics, regardless of the type of destructive effects. In the current study, the quantitative assessment of the result of the interaction of an aggressive sulphate-containing medium with composites modified with conductive and dielectric additives was carried out. The effect of sulphate attack on the specific electrical conductivity of cement composites was studied. The nature of the interaction was evaluated by changing the properties of the samples of the developed compositions under the influence of a single-normal solution of sodium sulphate. The analysis was carried out by means of potentiometric titration using the exchange interaction method by fixing the degree of absorption of sulphate ions and determining the concentration of calcium ions in the solution. The measurement of the solution potential allowed determination of the quantitative indicators of the rate of calcium hydroxide leaching from the sample structure, which is necessary to assess the intensity of the destruction process and determine the nature of the change in strength properties. Measurements of the electrical resistivity of samples under the constant influence of sulphate aggression were taken during 28 days of observation. A method for quantifying the effect of a sulphate medium on a cement matrix was proposed that enables the material durability to be predicted. The features of changes in the morphology of structural components after exposure to aggressive solution were determined by physical and chemical methods.

Objective of the research described in this article is to analyze and compare the use of social media communication channels in Czech, Slovak and Swiss product innovation oriented companies, where Swiss set of the companies is used as a benchmark. Primary research was made through manual activity scanning of the selected companies within social media. European company database Amadeus provided by Bureau van Dijk was used for the company selection in all three countries under the same search criteria. There were made two research sets of the companies in each country. One set covers top turnover product innovation oriented companies, second set avoided product innovation orientation search criteria and covers top companies by turnover in the respective country. Each particular sample set covered 74 to 100 companies.Activities of the selected companies on Facebook, YouTube, Twitter, Google+ and LinkedIn were manually scanned and particular metrics were scaled. Microsoft Excel was used for storing, statistical processing and graphic outputs of the research. Evaluated results show significant gaps in use of social media communication tools in Czech and Slovak companies comparing to Swiss benchmark. It has been also confirmed that social media communication activity in product innovation oriented companies is equal to other companies. The hypotheses were statistically tested and results confirmed.

Introduction: Cardiovascular disease (CVD) is the leading cause of death in developed countries. An integral part of primary prevention is physical activity. One form of physical activity to be potentially used is yoga, but this activity is associated with lower energy expenditure than that recommended for prevention. The study aimed at assessing the effect of regular yoga sessions on the aerobic capacity of the practitioners and comparing it with the normal population performing physical activity recommended by guidelines. Materials and Methods: Fifty-eight persons (16 males) with a mean age of 50.0 ± 11.06 years comprising the yoga group practiced yoga for at least 1 h a day for over 2 years. They underwent spiroergometry under maximal exercise testing to assess basic performance parameters. Their results were compared with those in 54 age-matched controls (16 males mean age of 48 ± 11.86 years performing a regular aerobic physical activity for at least 7 h a week. Results: The yoga group had statistically significantly higher maximum performance per kilogram (P = 0.007) and maximum oxygen consumption per kilogram per minute (P = 0.028). Conclusions: Despite low energy expenditure, yoga practices are better in some cardiorespiratory fitness parameters than other aerobic activities recommended by current guidelines for CVD prevention.

The original article was already published in issue four of this year. Here, in issue six the same article was erroneously duplicated.

GATA-2 deficiency was recently described as common cause of overlapping syndromes of immunodeficiency, lymphedema, familiar myelodysplastic syndrome or acute myeloid leukemia. The aim of our study was to analyze bone marrow and peripheral blood samples of children with myelodysplastic syndrome or aplastic anemia to define prevalence of the GATA2 mutation and to assess whether mutations in GATA-2 transcription factor exhibit specific immunophenotypic features. The prevalence of a GATA2 mutation in a consecutively diagnosed cohort of children was 14% in advanced forms of myelodysplastic syndrome (refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and myelodysplasia-related acute myeloid leukemia), 17% in refractory cytopenia of childhood, and 0% in aplastic anemia. In GATA-2-deficient cases, we found the most profound B-cell lymphopenia, including its progenitors in blood and bone marrow, which correlated with significantly diminished intronRSS-Kde recombination excision circles in comparison to other myelodysplastic syndrome/aplastic anemia cases. The other typical features of GATA-2 deficiency (monocytopenia and natural killer cell lymphopenia) were less discriminative. In conclusion, we suggest screening for GATA2 mutations in pediatric myelodysplastic syndrome, preferentially in patients with impaired B-cell homeostasis in bone marrow and peripheral blood (low number of progenitors, intronRSS-Kde recombination excision circles and naïve cells).

Objective of the research described in this article is to make an analysis of the usage of marketing communication using both traditional Internet communication channels as well as Social Media Networks by the Czech companies. Primary research was made through on-line questionnaire. Companies across the branches and size categories within the Czech economy were addressed. Companies were selected from the www.firmy.cz portal. Only companies with their own web domain were addressed. The typical respondents were mostly from middle management, especially managers from the marketing or commercial departments. The final number of questionnaire respondents covered in the research is 1009. The main research method was questioning. The questionnaire consisted of three sections with the scale answer questions mainly. Google Refine was used for data processing and Microsoft Excel for statistical processing and graphic outputs of the research. Evaluated results show significant gaps in usage of Internet communication tools in marketing of Czech companies and also deficiency between clear understanding of the respondents how Social Media should be used in marketing communication and real use in the companies. This deficiency was statistically tested and relation between respondents’ perception of the importance of Social Media use for bidirectional communication with stakeholders and non-use of Social Media for bidirectional communication with stakeholders by respondents’ company was confirmed.

Refractory cytopenia of childhood is the most common subtype of myelodysplastic syndrome in children. In this study, we compared the outcome of immunosuppressive therapy using horse antithymocyte globulin (n=46) with that using rabbit antithymocyte globulin (n=49) in 95 patients with refractory cytopenia of childhood and hypocellular bone marrow. The response rate at 6 months was 74% for horse antithymocyte globulin and 53% for rabbit antithymocyte globulin (P=0.04). The inferior response in the rabbit antithymocyte globulin group resulted in lower 4-year transplantation-free (69% versus 46%; P=0.003) and failure-free (58% versus 48%; P=0.04) survival rates in this group compared with those in the horse antithymocyte globulin group. However, because of successful second-line hematopoietic stem cell transplantation, overall survival was comparable between groups (91% versus 85%; P=ns). The cumulative incidence of relapse (15% versus 9%; P=ns) and clonal evolution (12% versus 4%; P=ns) at 4 years was comparable between groups. Our results suggest that the outcome of immunosuppressive therapy with rabbit antithymocyte globulin is inferior to that of horse antithymocyte globulin. Although immunosuppressive therapy is an effective therapy in selected patients with refractory cytopenia of childhood, the long-term risk of relapse or clonal evolution remains. (ClinicalTrial.gov identifiers: NCT00662090)

BackgroundAbsolute lymphocyte count (ALC) and absolute monocyte count (AMC) have been documented as independent predictors of survival in patients with newly diagnosed Diffuse Large B-cell Lymphoma (DLBCL). Analysis of the prognostic impact of ALC and AMC in the context of International Prognostic Index (IPI) and other significant variables in elderly population treated in the R-CHOP regime has not been carried out yet.Methodology/principal findingsIn this retrospective study, a cohort of 443 newly diagnosed DLBCL patients with age ≥ 60 was analyzed. All patients were treated with the R-CHOP therapy. An extensive statistical analysis was performed to identify risk factors of 3-year overall survival (OS). In multivariate analysis, only three predictors proved significant: Eastern Cooperative Oncology Group performance status (ECOG), age and bulky disease presence. These predictors were dichotomized (ECOG ≥ 1, age ≥ 70, bulk ≥ 7.5) to create a novel four-level score. This score predicted 3-year OS of 94.0%, 77.4%, 62.7% and 35.4% in the low-, low-intermediate, high-intermediate and high-risk groups, respectively (PConclusionsThe prognostic role of baseline ALC, AMC or their ratio (LMR) was not confirmed in the multivariate context in elderly population with DLBCL treated with R-CHOP. The newly proposed age-specific index stratifies the elderly population into risk groups more precisely than the conventional IPI and its existing variants.

Integrons are adaptive bacterial devices that rearrange promoter-less gene cassettes into variable ordered arrays under stress conditions, thereby sampling combinatorial phenotypic diversity. Chromosomal integrons often carry hundreds of silent gene cassettes, with integrase-mediated recombination leading to rampant DNA excision and integration, posing a potential threat to genome integrity. How this activity is regulated and controlled, particularly through selective pressures, to maintain such large cassette arrays is unknown. Here, we show a key role of promoter-containing toxin-antitoxin (TA) cassettes as systems that kill the cell when the overall cassette excision rate is too high. These results highlight the importance of TA cassettes regulating the cassette recombination dynamics and provide insight into the evolution and success of integrons in bacterial genomes.

Integrons are genetic elements involved in bacterial adaptation which capture, shuffle and express genes encoding adaptive functions embedded in cassettes. These events are governed by the integron integrase through site-specific recombination between attC and attI integron sites. Using computational and molecular genetic approaches, here we demonstrate that the integrase also catalyses cassette integration into bacterial genomes outside of its known att sites. Once integrated, these cassettes can be expressed if located near bacterial promoters and can be excised at the integration point or outside, inducing chromosomal modifications in the latter case. Analysis of more than 5 × 10 5 independent integration events revealed a very large genomic integration landscape. We identified consensus recombination sequences, named attG sites, which differ greatly in sequence and structure from classical att sites. These results unveil an alternative route for dissemination of adaptive functions in bacteria and expand the role of integrons in bacterial evolution., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Breast radiotherapy can lead to radiation-induced cardiac disease, particularly in left breast cancers. Recent studies have shown that subclinical cardiac lesions, such as myocardial perfusion deficits, may occur early after radiotherapy. The primary method for irradiating breast cancer, known as opposite tangential field radiotherapy, can cause the anterior interventricular coronary artery to receive a high dose of radiation during left breast irradiation. To explore alternative approaches that could reduce the risk of myocardial perfusion defects in patients with left breast cancer, we plan to conduct a prospective single-center study using a combination of deep inspiration breath hold radiotherapy and intensity modulated radiation therapy. The study will use stress and, if necessary, resting myocardial scintigraphy to assess myocardial perfusion. The trial aims to show that reducing the cardiac dose with these techniques can prevent the appearance of early (3-month) and medium-term (6- and 12-month) perfusion disorders.

Improving the tumor reoxygenation to sensitize the tumor to radiation therapy is a cornerstone in radiation oncology. Here, the pre-clinical development of a clinically transferable liposomal formulation encapsulating trans sodium crocetinate (NP TSC) is reported to improve oxygen diffusion through the tumor environment. Early pharmacokinetic analysis of the clinical trial of this molecule performed on 37 patients orient to define the optimal fixed dosage to use in a triple-negative breast cancer model to validate the therapeutic combination of radiation therapy and NP TSC. Notably, it is reported that this formulation is non-toxic in both humans and mice at the defined fixed concentration, provides a normalization of the tumor vasculature within 72 h window after systemic injection, leads to a transient increase (50% improvement) in the tumor oxygenation, and significantly improves the efficacy of both mono-fractionated and fractionated radiation therapy treatment. Together, these findings support the introduction of a first-in-class therapeutic construct capable of tumor-specific reoxygenation without associated toxicities., (© 2022 The Authors. Small published by Wiley-VCH GmbH.)

Integrons confer a rapid adaptation capability to bacteria. Integron integrases are able to capture and shuffle novel functions embedded in cassettes. Here, we investigated cassette recruitment in the Vibrio cholerae chromosomal integron during horizontal transfer. We demonstrated that the endogenous integrase expression is sufficiently triggered, after SOS response induction mediated by the entry of cassettes during conjugation and natural transformation, to mediate significant cassette insertions. These insertions preferentially occur at the attIA site, despite the presence of about 180 attC sites in the integron array. Thanks to the presence of a promoter in the attIA site vicinity, all these newly inserted cassettes are expressed and prone to selection. We also showed that the RecA protein is critical for cassette recruitment in the V. cholerae chromosomal integron but not in mobile integrons. Moreover, unlike the mobile integron integrases, that of V. cholerae is not active in other bacteria. Mobile integrons might have evolved from the chromosomal ones by overcoming host factors, explaining their large dissemination in bacteria and their role in antibioresistance expansion., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Integrons are genetic elements involved in bacterial adaptation to the environment. Sedentary chromosomal integrons (SCIs) can stockpile and rearrange a myriad of different functions encoded in gene cassettes. Through their association with transposable elements and conjugative plasmids, some SCIs have acquired mobility and are now termed Mobile Integrons (MIs). MIs have reached the hospitals and are involved in the rise and spread of antibiotic resistance genes through horizontal gene transfer among numerous bacterial species. Here we aimed at describing methods for the detection of integrons in sequenced bacterial genomes as well as for the experimental characterization of the activity of their different components: the integrase and the recombination sites.

The integron is a bacterial recombination system that allows acquisition, stockpiling and expression of cassettes carrying protein-coding sequences, and is responsible for the emergence and rise of multiresistance in Gram-negative bacteria. The functionality of this system depends on the insertion of promoterless cassettes in correct orientation, allowing their expression from the promoter located upstream of the cassette array. Correct orientation is ensured by strand selectivity of integron integrases for the bottom strand of cassette recombination sites (attC), recombined in form of folded single-stranded hairpins. Here, we investigated the basis of such strand selectivity by comparing recombination of wild-type and mutated attC sites with different lengths, sequences and structures. We show that all three unpaired structural features that distinguish the bottom and top strands contribute to strand selectivity. The localization of Extra-Helical Bases (EHBs) directly favors integrase binding to the bottom strand. The Unpaired Central Spacer (UCS) and the Variable Terminal Structure (VTS) influence strand selectivity indirectly, probably through the stabilization of the bottom strand and the resulting synapse due to the nucleotide skew between the two strands. These results underscore the importance of the single-stranded nature of the attC site that allows such tight control over integron cassette orientation., (© The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.)