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The cartographic landscape analysis of Lake Doshne employs geographic landscape methods, GIS cartographic modeling, and geo-ecological analysis. This study includes hydrochemical analysis of the lake’s water mass, focusing on saline blocks, tropho-saprobiological indicators, and specific toxic action indicators. Three geological sections of anthropogenic and pre-Quaternary complexes, along with a geological–lithological transverse profile of the lake basin, were developed. Additionally, a geographical landscape model of the lake’s natural aquatic complex was presented, distinguishing littoral–sublittoral and profundal aquatic sub-tracts and five types of aquafacies with landscape metric assessments. This approach enables a comprehensive analysis and the creation of cartographic models that can serve as a basis for lake cadastre and optimization of the ecological and landscape conditions in local territories.

Rationale: Colorectal cancer (CRC) is one of the most prevalent oncological diseases with high mortality. Invasive optical (endoscopic) colono- scopy has been recognized as a golden standard for the CRC diagnostics. A promising area is the development of non-invasive tools for CRC diagnosis with circular RNA (circRNA). One of the most sensitive non-invasive tools for detection of cancer RNA markers is considered to be the biosensor methods with the use of nanowire chips with oDNA probes (fragments of DNA oligonucleotides) immobilized on their surface. It has been previously shown that circRNA hsa_circ_0136666_CBC1, hsa_circ_0031263_CBC1, and hsa_circ_0072715_CBC1 are associated with CRC. Aim: To determine the lower limit of concentration sensitivity of detection of CRC-associated circRNA with nanowire chips with immobilized oDNA probes, to demonstrate the usability of these chips for non-invasive detection of circRNA in plasma in the CRC diagnostics, and to establish the potential for the use of nanowire chips for the early CRC diagnosis. Methods: To ensure biospecific binding of the circRNA hsa_circ_0136666_CBC1, hsa_circ_0031263_CBC1, and hsa_circ_0072715_CBC1 (the CRC markers), oDNA probes with the nucleotide sequences complementary to the target circRNA have been immobilized on the nanowire surface. At the study step 1, we detected the lower concentration limit for detection of the target molecules with the use of their analogues, i.e. synthetic model oDNA with the nucleotide sequences complementary to oDNA probes. At the study step 2, we used the nanowire chips with immobilized oDNA probes to detect the circRNA in plasma of the patients with confirmed CRC. Plasma samples from non-cancer patients were used as controls. Results: The lower concentration limit for the detection of DNA analogues of the circRNA hsa_circ_0136666_CBC1, hsa_circ_0031263_CBC1, and hsa_circ_0072715_CBC1 with nanowire chips with oDNA probes was 10-16 М. The analysis of total RNA isolated from plasma of the CRC patients showed a significant increase in the signal from the sensory elements of the nanowire chip. The analysis of plasma samples from the non-cancer patients, the nanowire signal changes were non-significant indicating the absence of detectable concentrations of the circRNA in plasma of the non-cancer patients. Conclusion: We have identified the minimal detectable concentration of the circRNA hsa_circ_0136666_CBC1, hsa_circ_0031263_CBC1, and hsa_circ_0072715_CBC1, associated to the development of CRC, with nanowire chips with immobilized oDNA probes: it was 10-16 М. The experiment showed the usability of such nanowire chips for non-invasive detection of the given circRNA markers in total RNA samples isolated from plasma of CRC patients.

Polymer brushes, as modifying coatings, significantly improve the tribological properties of various contacting surfaces. The friction that arises when an external load is applied and the polymer brushes laterally shift relative to each other is determined by their interaction energy and the depth of interpenetration. If the brushes are immersed in a lowmolecular- weight solvent, the friction force can be controlled by varying the solvent quality through changes in external conditions, such as temperature, chemical composition of the solution, and so on. It should be noted that theoretical studies on the effect of solvent quality on the tribological properties of brushes are practically absent. To determine the influence of solvent quality on the interaction of flat polymer brushes, two complementary approaches were used: analytical and numerical self-consistent field methods. In both cases, a coarse-grained model of polymer brushes was employed. The solvent quality in the model was defined through the Flory-Huggins parameter for polymer-solvent interaction. A quantitative assessment of the overlap zone width, osmotic pressure, and friction force arising when the brushes approach each other was conducted. A theoretical description of the friction force in the low shear rate regime was proposed based on the Brinkman equation for two compressed brushes sliding against each other. It was shown that, with constant total polymerization degree, grafting density, and lateral sliding speed of the brushes relative to each other, the width of the overlap zone decreases following a power law with increasing inter-plane distance, regardless of solvent quality. Under conditions of strong compression of flat polymer brushes, the friction force approaches a certain limiting value, while the friction coefficient tends to zero, independent of solvent quality. In the moderate pressure region, the friction coefficient significantly increases with a decrease in the solubility of the grafted polymers under the same applied external load and the composition of the flat polymer brushes. The analytical method showed high agreement with the data from the numerical simulations. The obtained results allow for predicting the tribological properties of polymer brushes depending on solvent quality and, consequently, predicting the effect of external conditions on the friction force between modified surfaces.

Titanium dioxide (TiO2) was added in different proportions as a filler to the mixture for the production of recycled rubber tiles in order to improve their existing properties. The mechanical properties of novel rubber tiles were analyzed in the context of abrasion resistance, maximum stress (TS), stress at break (TSb), deformation at break (Eb), and hardness. An optimal mixture composition was found comparing the obtained results of mechanical tests; successful improvement of abrasion by 22.1%, Eb by 10.46% and hardness by 17.65% was achieved. Finally, the characterization of the new rubber tile by SEM/EDS and FTIR analysis was carried out, along with the stability and environmental impact assessment based on the leaching test. The accelerated aging test was conducted using a solar simulator, after which the mechanical properties, SEM/EDS, FTIR, and leaching test were re-examined. The results after the accelerated aging test showed that tiles with the addition of TiO2 have better mechanical properties compared to the reference ones; TS improved by 85.71%, Eb by 75.53%, and hardness by 9.43%. Therefore, we concluded that TiO2 as a filler in interaction with rubber and polyurethane composites significantly contributed to the improvement of the existing rubber tile, and the achieved improvements are useful for the original application of these tiles, which is the protection from injuries on playgrounds and sports fields. Also, the improvement achieved extends the service life of this type of tile, which contributes to the quality of this type of material.

The outpatient clinic provides a special institutional service for psychiatric patients who need treatment in an environment similar to a hospital but allows them to return home and integrate into everyday life after therapy. This form of treatment is suitable for patients who do not require hospitalization, but who need a more intensive therapeutic program that includes active treatment. Objective: To examine the differences in mature, immature and neurotic defense mechanisms before and after treatment in the Outpatient Clinic of Psychiatry. Respondents and methods: The research was conducted in 2023. Ninety-two patients treated in the Outpatient Clinic of Psychiatry participated in the research, of which 18 (56.5%) were female and 74 (80.4%) were male, and the mean age of the subjects was M=52.45 (range from 27 to 74; SD=10.34). Demographic Questionnaire and Defense Style Questionnaire (DSQ-40) were used in the research. Results: Overall, looking at defense mechanisms, the results showed that the neurotic defense mechanisms were significantly lower after treatment (t-test; p=0.039). Individually looking at mature defense mechanisms, after treatment the subjects used sublimation significantly less (ttest; p=0.049) while they used humor significantly more (t-test; p=0.008). In the case of neurotic defense mechanisms, after treatment, subjects used pseudo-altruism (t-test; p=0.038) and idealization (t-test; p=0.003) significantly less, while they used reactive formation significantly more t-test; p=0.035); while with immature defense mechanisms after treatment, they used acting out (t-test; p=0.006), denial (t-test; p=0.012) and splitting (t-test; p=0.014) significantly less, while they used passive aggression significantly more (t-test; p=0.002). Conclusion: Despite the relatively short duration of treatment, these findings suggest that even relatively short-term therapeutic procedures can have a significant impact on reducing maladaptive defense mechanisms. These results emphasize the importance of therapeutic interventions in promoting adaptive defense mechanisms and reducing dysfunctional defense strategies. Although further research is needed to understand the long-term effects of therapy on defense mechanisms, these preliminary findings suggest that therapists can successfully intervene in reducing unhealthy defense patterns in their patients even in a relatively short period of time.

The extensive global use of rubber results in significant microplastic pollution from the release of tire wear particles and microplastic leachate, impacting the environment, human health, and ecosystems. Waste tires are normally recycled and used for the production of new products, such as rubber tiles. The presented study aims to show the possibility of further decrease in the negative environmental impact of materials based on recycled rubber. This paper presents the modification of rubber tiles with a titanium dioxide (TiO2) coating, focusing on surface integrity, rubber particle wear release, and the consequent environmental impact of leachate release. Both reference and modified rubber tiles were subjected to artificial accelerated aging in a solar simulator for 4, 6, and 8 weeks, followed by an abrasion test. The carbonyl index was calculated from FTIR characterization after each time frame to indicate the degradation of organic compounds and chemical changes caused by UV exposure. A 24 h leaching test with a liquid-to-sample ratio of 1:20 was performed on both rubber tile samples prior to and after 8 weeks of aging along with the aged wear particles for the purpose of the non-target screening of released organic leachate by LC/MS QTOF. The results of carbonyl indices showed that the TiO2 coating contributes to the stabilization of polymer degradation and, to a certain extent, reduces the leaching of organic compounds, such as phthalates. However, the increased wear and release of rubber particles and the subsequent degradation of organic leachates require further in-depth research.

European mistletoe extract (Iscador Qu) has been studied for decades, but it has not ceased to arouse scientific interest. The purpose was to investigate the impact of Iscador Qu on the antiproliferative potential of 11 standard chemotherapeutic agents on two breast cancer cell lines: MCF-7 low-metastatic and MDA-MB-231 high-metastatic and control cell lines (MCF-10A). MTT-dye reduction assay, FACS analysis, and PI staining were utilized. The most promising combinations acting against the MDA-MB-231 cell line were observed upon the simultaneous application of Iscador Qu (80 µg/mL) and Docetaxel, with 4-fold reduction in IC50. An antagonistic effect was found under treatment with Cisplatin and Iscador Qu (1.5-fold increase in IC50). The response of the low-metastatic breast cancer cell line MCF-7 to the tested combinations was different compared to the high-metastatic one. The most pronounced cytotoxic effect was found for the combination of Oxaliplatin and Iscador Qu (20 µg/mL) (5.2-fold IC50 reduction). An antagonistic effect for MCF-7 line was also observed when combinations with Olaparib and Tamoxifen were applied. This in vitro study offers new combinations between Iscador Qu and standard chemotherapeutic agents that hold great promise in establishing breast cancer therapeutic protocols compared to traditional monotherapies.

Breast cancer survivorship is a recognized risk factor for sexual dysfunction, with various clinical, sociocultural, and psychological factors potentially interacting differently across populations. This study compared sexual dysfunction, anxiety, and depression between females with breast cancer and those without, aiming to identify associated factors. A total of 362 females participated, including 227 with sexual dysfunction and 135 controls. Among them, 195 are breast cancer survivors, while 167 have no personal history of cancer. Key variables were analyzed using Student’s t-test for quantitative data and Fisher’s exact test for categorical data, while logistic regression models were used to assess the association between sexual dysfunction and various factors. Multivariate analysis revealed that, in sexually active females, breast cancer survivorship increased the odds of sexual dysfunction 2.7-fold (95% CI: 1.17–6.49; p = 0.020). Anxiety was significantly associated with sexual dysfunction, regardless of cancer status (AdOR 6.00; 95% CI: 2.50–14.43; p < 0.001). The interaction between cancer survival and anxiety further increased the odds of sexual dysfunction by more than 11-fold (AdOR 11.55; 95% CI: 3.81–35.04; p < 0.001). Additionally, obesity was found to be a protective factor among cancer survivors (AdOR 0.149; 95% CI: 0.027–0.819; p = 0.029). In conclusion, breast cancer has a significant impact on sexual function, with psychological factors like anxiety playing a crucial role. Addressing these issues requires a holistic, patient-centered approach that considers the complex interplay of physical, emotional, and sociocultural factors.

Background: COVID-19 is a caused a pandemic since early January 2020. Sequential Organ Failure Assessment (SOFA) score can assess organ dysfunction in the state of Sepsis MODS. Aim: This study aims to determine the relationship between Blood Sugar Levels, C-Reactive Protein (CRP), and Total Lymphocyte Count (TLC) with SOFA score in COVID-19 patients with Sepsis. Methods: An observational study using the cross-sectional method was carried out in 2020-2021 at Ulin Hospital Banjarmasin with a total sample of 87 participants. Results: Based on the Spearman test, there were a positive correlation between Random Blood Sugar levels and SOFA with the scores r = 0.778 (p = 0.000); significant negative correlation between TLC and SOFA with the score r = -0.409 (p = 0.000); and no significant correlation between CRP and SOFA with the score r = -0.077 (p = 0.507). The multivariate test showed that the correlation value for each Random Blood Sugar with a SOFA score is R=0.664 (p=0.000), and the Total Lymphocyte Count with a SOFA score is R=-0.270 (p=0.001). The statistical analysis model revealed that Blood Sugar Levels and Total Lymphocyte Count could predict SOFA scores of as much as 60.9%. Conclusion: Blood sugar levels can be a marker of poor prognosis in COVID-19 patients with Sepsis. Hyperglycemia can be caused by pancreatic cell damage due to SARS-CoV2 invasion, acute insulin resistance, and inflammation caused by Sepsis and COVID-19. Total Lymphocyte Count is one of the many factors contributing to organ dysfunction caused by Sepsis in COVID-19. Keywords: COVID-19, Sepsis, SOFA Score, Prognosis

Abstract The effects of severe plastic deformation on NiTi alloys’ structure and properties have been extensively studied over the past decades. However, there is a notable lack of systematic data regarding the impact of industrial hot deformation techniques on these alloys. This gap arises from challenges in manufacturing processes related to the unevenness of ingots produced by casting technologies. This study investigates the effects of hot rotary swaging, extrusion, and radial shear rolling on the martensitic transformation, shape memory effect, superelasticity, and damping capacity of NiTi Ni-rich alloys fabricated through powder metallurgy. The properties were investigated under torsional load on wires prepared by spark eroding from deformed rods. Our findings indicate that samples after rolling and extrusion exhibit a superelastic strain of 14 ± 0.5% attributed to a high yield stress of approximately 600–800 MPa and torsional testing providing the material to be fully involved in recovery process. Samples after rolling and swaging demonstrate a high level of reversible strain with a one-way shape memory effect ranging from 5 to 7%. Conversely, extrusion, due to the inhomogeneity of resulting workpieces, induces a complex, multi-stage martensitic transformation that undermines the shape memory effect. Furthermore, all deformation methods except extrusion contribute to increased alloy homogeneity, resulting in a narrower temperature range for martensitic transformations. Rotary swaging notably increases the height of an internal friction peak from 0.015 to 0.045 compared to the undeformed material, whereas rolling gives the lowest value of 0.012 among others. This study provides valuable insights into how hot thermomechanical processing influences the properties of NiTi alloys and shows that powder metallurgy combined with hot deformation can be considered an alternative approach for achieving high functional properties of these alloys.

Abstract Background Cancer-associated fibroblasts (CAFs) are essential components of the tumor microenvironment and play a critical role in cancer progression. Numerous studies have identified significant molecular differences between CAFs and normal tissue-associated fibroblasts (NAFs). In this study, we isolated CAFs and NAFs from liver tumors and conducted a comprehensive analysis of their DNA methylation profiles, integrating our finding with data from studies on other cancer types. Results Our analysis revealed that several CAF samples exhibited aberrant DNA methylation patterns, which corresponded with altered gene expression levels. Notably, DNA methylation at liver CAF-specific CpG sites was linked to survival outcomes in liver cancer datasets. An integrative analysis using publicly available datasets from various cancer types, including lung, prostate, esophageal, and gastric cancers, uncovered common epigenetic abnormalities across these cancers. Among the consistently altered CpGs were cg09809672 (EDARADD), cg07134930 (HDAC4), and cg05935904 (intergenic). These methylation changes were associated with prognosis across multiple cancer types. Conclusion The activation of CAFs by the tumor microenvironment seems to be associated with distinct epigenetic modifications. Remarkably, similar genomic regions tend to undergo hypomethylation in CAFs across different studies and cancer types. Our findings suggest that CAF-associated DNA methylation changes hold potential as prognostic biomarkers. However, further research and validation are necessary to develop and apply such signatures in a clinical setting.

Abstract Aldehydes are ubiquitous in star-forming regions and carbonaceous chondrites, serving as essential intermediates in metabolic pathways and molecular mass growth processes to vital biomolecules necessary for the origins of life. However, their interstellar formation mechanisms have remained largely elusive. Here, we unveil the formation of lactaldehyde (CH3CH(OH)CHO) by barrierless recombination of formyl (HĊO) and 1-hydroxyethyl (CH3ĊHOH) radicals in interstellar ice analogs composed of carbon monoxide (CO) and ethanol (CH3CH2OH). Lactaldehyde and its isomers 3-hydroxypropanal (HOCH2CH2CHO), ethyl formate (CH3CH2OCHO), and 1,3-propenediol (HOCH2CHCHOH) are identified in the gas phase utilizing isomer-selective photoionization reflectron time-of-flight mass spectrometry and isotopic substitution studies. These findings reveal fundamental formation pathways for complex, biologically relevant aldehydes through non-equilibrium reactions in interstellar environments. Once synthesized, lactaldehyde can act as a key precursor to critical biomolecules such as sugars, sugar acids, and amino acids in deep space.

Abstract Community engagement concepts incorporated into service-learning experiences help students in the health professions to connect classroom work with clinical practice and learn strategies and skills to improve community health. Service learning improves team skills, allows students to gain knowledge about communities where they train, and connects them with role models and mentors, which are benefits that may eventually affect their career choices. The California Statewide Area Health Education Centers (AHEC) Program requires students to conduct a community project with a medically underserved population through its AHEC Scholars Program in Community Health, guided by a structured curriculum. The program’s curriculum provides guidelines for the process and reporting of community projects. Between 2018 and 2023, 318 health professions students from 14 disciplines conducted 253 individual or group projects in medically underserved sites. These projects focused on community education, teaching fellow students, patient education, quality improvement in community health centers, and other health-related topics. The outputs from these students’ projects supplied educational information and resources for patients, health centers, community groups, and other students. Several of the projects were interdisciplinary with students from different health disciplines working collaboratively to implement the projects. All participating students reported having positive experiences and engagement with their communities. Two University of California medical schools adopted the AHEC Scholars curriculum as required or elective opportunities in community health. Practice sites and educational institutions benefited from this work as well. This model offers a promising framework for other educational institutions that provide training in underserved communities.

Abstract Background Radiopharmaceutical therapy with 225Ac- and 177Lu-PSMA has shown promising results for the treatment of prostate cancer. However, the distinct physical properties of alpha and beta radiation elicit varying cellular responses, which could be influenced by factors such as tumour morphology. In this study, we use simulations to examine how cell geometry, region of pharmaceutical uptake within the cell to model different internalization fractions, and the presence of tumour hypoxia and necrosis impact nucleus absorbed doses and dose heterogeneity with 225Ac and 177Lu. We also develop nucleus absorbed dose kernels for application to autoradiography images. Methods We used the GATE Monte Carlo software to simulate three geometries of LNCaP prostate cancer cells (spherical, cubic, and ovoid) with activity of 225Ac or 177Lu internalized in the cytoplasm or bound to the extracellular membrane. Nucleus S-values were calculated for each geometry, source region, and isotope. The cell models were used to create nucleus absorbed dose kernels for each source region describing the dose to each nucleus in a cell layer, which were applied to simulated tumours composed of normoxic, hypoxic, or necrotic cancer cells to obtain dose rate maps. Absorbed doses within the tumours and dose heterogeneity were analyzed for each tumour morphology and isotope. Cell geometry made a minimal impact on S-values to the nucleus, however internalization resulted in higher nucleus doses. Applying the kernels to the simulated tumour maps showed that doses to each cell type varied between 225Ac and 177Lu depending on tumour morphology. Dose heterogeneity within tumours was slightly higher with 225Ac, however the tumour morphology made a larger impact on dose heterogeneity compared to the choice of isotope, with hypoxic and necrotic tumours having very heterogeneous dose distributions. Conclusions Cell geometry simplifications may still allow robust results in simulation studies. Furthermore, the morphology of the tumour itself may make a larger impact on treatment response compared to other variables such as ratio of internalization. Finally, nucleus absorbed dose kernels were created that could enable microdosimetric studies with autoradiography.

This study examines elements of the platinum group (PGE), primarily platinum and palladium, as geochemical indicators in the investigation of oil polygenesis. It has been found that, like other trace elements such as nickel, vanadium, and cobalt, platinum group elements and gold can occur in oil fields at both background levels and in elevated or even anomalously high concentrations. The objective of this research is to analyze PGE and trace elements as geochemical markers to identify the geological factors, including endogenous processes, responsible for these unusually high concentrations in oil. A comprehensive review of the literature on this subject was conducted, along with new data on the presence of precious metals in oils from Russia and globally. The study explores the geological mechanisms behind elevated PGE concentrations in oils, utilizing atomic absorption spectroscopy with atomization in the HGA-500 graphite furnace to measure PGE content. Previously, the tellurium co-deposition method (ISO 10478:1994) was used to isolate noble metals from associated elements. Possible geological origins of abnormally high concentrations of platinum metals in oils have been identified. These include endogenous factors such as the spatial proximity of oil fields to ultrabasic rock massifs, the effects of contact-metasomatic processes, and influences from mantle dynamics. Moreover, data concerning mantle elements can serve as indicators of the depth origins of certain hydrocarbon fluids, thus contributing to the study of oil polygenesis.

As digital technologies penetrate all spheres of human life, scientific and technological progress becomes a global development factor. Artificial intelligence (AI) is an advanced and rapidly developing area that has already proved its efficiency in healthcare, finance, and transport. However, AI also poses significant ethical and legal challenges because it can be used to generate and distribute virtual child pornography. The article features methods of generating virtual child pornography through various AI tools, their ethical implications, and the existing legal frameworks that cover these issues. In fact, the existing international and national laws on child abuse fail to take into account AI-generated images. The authors studied cases and legal precedents to highlight the urgent need for robust regulatory legal measures to prevent the misuse of AI technologies, the potential of which should be realized for the benefit of society.

The paper focuses on a hitherto untapped source of a subjective nature, which is on the borderline between private and institutionally requested provenance. Two manuscript memoirs of Emil Kellner, a long-time railway employee, can be found in the State Regional Archive in Prague within the fund of České dráhy, a. s., Prague [Czech Railways, JSC]. They were written in 1954 and 1955 at the instigation of the Railway Archive and the Ministry of Railways. They cover the period from the last third of the 19th century with gaps until 1941. The memoirs provide some interesting facts that were not previously known or, on the contrary, confirm some things already known. The memoirs give an insight into the (everyday), routine life on the railway. The characteristics of the employees and their fates, not excluding the social dimension, are extremely interesting. The memoirs also provide details of dealings with superiors (requests, personal presentations, interventions, patronage, visits to railway management in Vienna or Prague) and transcribed documents (correspondence) depicting railway administration during the monarchy.

Abstract Background Females have a higher age-adjusted incidence of Alzheimer’s Disease (AD) than males, even when accounting for longer lifespan and, therefore, stand to benefit the most from dementia prevention efforts. As exposure to many modifiable risk factors for dementia begins in mid-life, interventions must be implemented from middle-age. Building cognitive reserve, particularly through stimulating avocational activities and occupational attainment presents a crucial, underexplored, dementia prevention approach for mid-life. It is currently unknown, however, whether modifiable lifestyle factors can protect against AD processes, from mid-life, differentially for females and males who carry inherited risk for late-life dementia. To address this gap, this study investigated the impact of biological sex and APOE4 carrier status on the relationship between stimulating activities, occupational attainment, and cognition in mid-life. Methods We leveraged the PREVENT–Dementia program, the world’s largest study investigating the origins and early diagnosis of dementia in mid-life at-risk individuals (N = 700; 40–59 years). Cognitive performance was measured using the Cognito Battery and the Visual Short Term Memory Binding task. Mid-life specific reserve contributors were assessed via the Lifetime of Experiences Questionnaire. Results Females had significantly better episodic and relational memory (p

Abstract Additive manufacturing of metallic parts by Selective Laser Melting (SLM) implies high temperature gradients and small volume of the melt bath. These conditions make the process scales close to those available for state-of-the-art massively parallel atomistic simulations. In the paper, the microscopic mechanisms responsible for the formation of primary microstructure during molten metal solidification are investigated using classical molecular dynamics (CMD). The 316L austenitic stainless steel with face centred cubic lattice, which is widely used in industry including SLM applications was chosen as a material for the CMD simulations. It was shown that solidified material inherits substrate defects and catches new ones, which interact with the solidification front thus producing the primary microstructure. Peculiarities of solidification in different crystallographic directions and solidification front interaction with grain boundaries and newly produced defects (mostly twin boundaries) as well as their formation are under study. Resulting microstructures of virtual samples are compared with those of real samples produced by SLM and analysed by the electron backscatter diffraction (EBSD) method. The comparison shows similarities of EBSD and CMD sample patterns and evidences for the capability of the large-scale atomistic simulations to reproduce main features of the microstructures formed in the metallic SLM additive production.

Abstract Patient-derived xenografts (PDXs) are tumour fragments engrafted into mice for preclinical studies. PDXs offer clear advantages over simpler in vitro cancer models - such as cancer cell lines (CCLs) and organoids - in terms of structural complexity, heterogeneity, and stromal interactions. Here, we characterise 231 colorectal cancer PDXs at the genomic, transcriptomic, and epigenetic levels, along with their response to cetuximab, an EGFR inhibitor used clinically for metastatic colorectal cancer. After evaluating the PDXs’ quality, stability, and molecular concordance with publicly available patient cohorts, we present results from training, interpreting, and validating the integrative ensemble classifier CeSta. This model takes in input the PDXs’ multi-omic characterisation and predicts their sensitivity to cetuximab treatment, achieving an area under the receiver operating characteristics curve > 0.88. Our study demonstrates that large PDX collections can be leveraged to train accurate, interpretable drug sensitivity models that: (1) better capture patient-derived therapeutic biomarkers compared to models trained on CCL data, (2) can be robustly validated across independent PDX cohorts, and (3) could contribute to the development of future therapeutic biomarkers.

Abstract Biaxial nematic liquid crystals are fascinating systems sometimes referred to as the Higgs boson of soft matter because of experimental observation challenges. Here we describe unexpected states of matter that feature biaxial orientational order of colloidal supercritical fluids and gases formed by sparse rodlike particles. Colloidal rods with perpendicular surface boundary conditions exhibit a strong biaxial symmetry breaking when doped into conventional chiral nematic fluids. Minimization of free energy prompts these particles to orient perpendicular to the local molecular director and the helical axis, thereby imparting biaxiality on the hybrid molecular-colloidal system. The ensuing phase diagram features colloidal gas and liquid and supercritical colloidal fluid states with long-range biaxial orientational symmetry, as supported by analytical and numerical modeling at all hierarchical levels of ordering. Unlike for nonchiral hybrid systems, dispersions in chiral nematic hosts display biaxial orientational order at vanishing colloid volume fractions, promising both technological and fundamental research utility.

Abstract Video coding has traditionally been developed to support services such as video streaming, videoconferencing, digital TV, and so on. The main intent was to enable human viewing of the encoded content. However, with the advances in deep neural networks (DNNs), encoded video is increasingly being used for automatic video analytics performed by machines. In applications such as automatic traffic monitoring, analytics such as vehicle detection, tracking and counting, would run continuously, while human viewing could be required occasionally to review potential incidents. To support such applications, a new paradigm for video coding is needed that will facilitate efficient representation and compression of video for both machine and human use in a scalable manner. In this manuscript, we introduce an end-to-end learnable video codec that supports a machine vision task in its base layer, while its enhancement layer, together with the base layer, supports input reconstruction for human viewing. The proposed system is constructed based on the concept of conditional coding to achieve better compression gains. Comprehensive experimental evaluations conducted on four standard video datasets demonstrate that our framework outperforms both state-of-the-art learned and conventional video codecs in its base layer, while maintaining comparable performance on the human vision task in its enhancement layer.

Abstract Background Substantial inequalities in the overall prevalence and patterns of multimorbidity have been widely reported, but the causal mechanisms are complex and not well understood. This study aimed to identify common patterns of multimorbidity in Serbia and assess their relationship with air pollutant concentrations and water quality indicators. Methods This ecological study was conducted on a nationally representative sample of the Serbian population. Data were obtained from the European Health Interview (EHIS) Survey, a periodic study designed to assess population health using widely recognized standardized instruments. The study included 13,069 participants aged 15 and older, randomly selected through a multistage stratified sampling design. Multimorbidity was defined as having two or more self-reported diagnoses of chronic non-communicable diseases. Latent class analysis (LCA) was performed to identify clusters of multimorbidity. Concentrations of particulate matter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3), as well as water quality indicators, were obtained from the Serbian Environmental Protection Agency. Results The overall prevalence of multimorbidity was 33.4% [32.6%—34.2%]. Six latent classes of multimorbidity were identified: Healthy, Multicondition, Cardiovascular, Metabolic syndrome, Respiratory, and Musculoskeletal. Annual increases in PM10 and SO2 concentrations, as well as daily increases in O3 concentrations, significantly raised the odds of having multimorbidity (OR = 1.02, 95% CI 1.02–1.03; OR = 1.01, 95% CI 1.00–1.02 and OR = 1.03, 95% CI 1.02–1.03, respectively). A pattern of increased risk was observed with rising levels of water contamination. Exposure to physico-chemical, microbiological and combined contamination was associated with a 3.92%, 5.17% and 5.54% higher probability, respectively, of having multiple chronic conditions. There was strong evidence that air pollutants, as well as chemical and microbial water contamination, were significantly associated with higher odds of the most common clusters of multimorbidity identified by LCA. Conclusion There is compelling evidence of an association between multimorbidity and environmental pollution, suggesting that exposure to air pollutants and water contaminants may contribute to disease accumulation and help explain geographically and socioeconomically patterned inequalities. These findings underscore the need for extensive studies that simultaneously measure both multimorbidity and pollution to explore their complex interrelationships.

Background: This article explores the relationship that exists between Human-Computer Interaction (HCI) and User Experience (UX), by carrying out an empirical analysis of how HCI elements influence UX in Augmented Reality (AR) interfaces. Objective: The study examines the impact of varied AR interfaces on task performance, error rates, and user satisfaction. Methodology: The research was approached using an interdisciplinary methodology, derived from design-computer science psychology insights. During the research was conducted surveys and experimental studies, as well as case studies to analyze user performance with three levels of AR interfaces: basic AR interface, advanced AR interface, and voice-activated AR interface. Single-dimensional interaction counts were monitored from 800 participants for over 40k interactions. Results: The results indicate that advanced, voice-activated interfaces outperformed basic ones in task completion times and user satisfaction The better the design of an interface was, the more quickly people completed the tasks — to a significant degree (r = -0.82 and p less than 0.01) thus demonstrating that task times are inversely proportional on average to user satisfaction with efficiency during use. In addition, error rates and cognitive load differed significantly between age groups, therefore there is a reason for an adjusted interface according to age. Conclusion: This research offers useful advice for developers of AR, such as incorporating voice commands and affordable options for cross-platform use. The results are important for enhancing AR interface design, especially in fields such as healthcare, education, and industry.

Abstract The zinc finger antiviral protein 1 (ZAP) has broad antiviral activity. ZAP is an interferon (IFN)-stimulated gene, which itself may enhance type I IFN antiviral response. In a previous study, Zika virus was identified as ZAP-resistant and not sensitive to ZAP antiviral activity. Here, we found that ZAP was associated with the inhibition of Zika virus in Vero cells, in the absence of a robust type I IFN system because Vero cells are deficient for IFN-alpha and -beta. Also, quantitative RNA-seq data indicated that endogenous ZAP is associated with altered global gene expression both in the steady state and during Zika virus infection. Further studies are warranted to elucidate this IFN-alpha and -beta independent anti-Zika virus activity and involvement of ZAP.

Abstract The 2024 edition of the One Health symposium explored the intergenerational health impacts of drought and famine in developing countries, with a focus on innovative strategies for resilience-building in healthcare infrastructures. Organized by students of the CIHLMU Center for International Health at Ludwig-Maximilians-Universität Munich, Germany, the event convened experts and participants from diverse backgrounds to address the urgent challenges posed by climate change-induced crises. Through presentations, panel discussions, and collaborative exchanges, the symposium underscored the profound health and socioeconomic implications of climate-related disasters, emphasizing the need for cross-sectoral cooperation and transformative action. Key recommendations emerged, including integrating climate change considerations into health systems, fostering multidisciplinary collaboration, and empowering communities to withstand future challenges. Despite the severity of the current situation, the symposium instilled optimism and determination among participants, inspiring a collective commitment to building a brighter and more resilient future for generations to come.

Abstract Currently, graph-based molecular structure descriptors are frequently used in QSAR (Quantitative Structure-Activity Relationship) and QSPR (Quantitative Structure-Property Relationship) modeling of the properties of chemical compounds. Octane isomers have an important role in the testing of such relationships. In this study, we compute some well-known topological descriptors of the molecular graphs of isomeric octanes and their line graphs, both indices and coindices. Then we analyze the correlation coefficients between the physicochemical properties of the octane isomers and some well-known topological indices and their coindices of the molecular graphs and the line molecular graphs of the octane isomers, to find the particular topological descriptors that have the best predictive values.

Abstract The impact of limited water availability on lettuce growth has been well documented. However, the mechanisms by which lettuce controls seed germination under water stress remain unknown. Germination percentage was evaluated in the cv. Salinas (Lactuca sativa) (L. sativa) × US96UC23 (Lactuca serriola) (L. serriola) recombinant inbred line (RIL) population and USDA germplasm collection using 10% polyethylene glycol (PEG). About 50% of both populations displayed less than 90% germination. The average broad-sense heritability (H 2) for germination percentage was 0.81 across both populations. Two quantitative trait loci (QTL) for germination percentage were identified on chromosomes 4 and 8 in the RIL population. The RNA-Seq and network analyses of wild lettuce, US96UC23, were performed using the control (distilled water, dH2O) and treatment (10% PEG) datasets. The number of differentially expressed genes (DEGs) was 4,095. The top 20 gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were assessed by enrichment analysis. The consensus network analysis captured 44 modules. Gene networks were constructed for the top 20 hub genes in 10 significant modules from each dataset. This study comprehensively explains QTL, GO terms, KEGG pathways, and gene networks associated with lettuce seed germination under osmotic stress.

Abstract The invasive wasp-mimicking Tiger Longicorn Beetle, Xylotrechus chinensis, a potentially lethal pest of mulberry trees (Moraceae: Morus spp.), was first reported in Europe in 2018. In Catalonia its spread has been impressive: one district, four towns, 44 km2 in February 2018; four districts, 12 towns, 378 km2 in July 2020; seven districts, 65 towns, 1134 km2 in December 2023. It is likely the infestation will spread further in the future, in particular along the Mediterranean coast from Spain to Greece. The flight period of this beetle in Mediterranean countries is expanding on both ends (from the end of April to mid-October), probably due to increasing temperatures because of climate change, although this should be further proved. The adult beetle life span is 18–23 days in insectaria, likely somewhat shorter in the wild since they do not feed and spend more energy flying outside. The single treatment with abamectin carried out in a Catalonian town in June 2022 on a sample of 24 trees (12 treated, 12 untreated) has been effective in reducing the infestation of this beetle in relation to untreated trees. But the reduction was not complete since new exit holes appeared during the summer of the following year. Therefore, an additional treatment carried out during the first ten days of October should be tested to achieve a better control of this pest. It would also be worthwhile trying a single treatment of abamectin in mid-July since it should be able to kill larvae hatching before the treatment and still have sufficient residual activity for larvae hatching after the treatment, and thus cover the entire activity period. Also, to get satisfactory mulberry tree protection, it is likely that treatments might have to be repeated for a few consecutive years. Yearly re-infestations from untreated public and/or private mulberry trees are also a concern and make short-term control of this pest difficult, no doubt accounting for the rapid spread of this beetle.

Abstract Manufacturing companies focus on improving productivity, reducing costs, and aligning performance metrics with strategic objectives. In industries like paper manufacturing, minimizing equipment downtime is essential for maintaining high throughput. Leveraging the extensive data generated by these facilities offers opportunities for gaining competitive advantages through data-driven insights, revealing trends, patterns, and predicting future performance indicators like unplanned downtime length, which is essential in optimizing maintenance and minimizing potential losses. This paper explores statistical and machine learning techniques for modeling downtime length probability distributions and correlation with machine vibration measurements. We proposed a novel framework, employing advanced data-driven techniques like artificial neural networks (ANNs) to estimate parameters of probability distributions governing downtime lengths. Our approach specifically focuses on modeling parameters of these distribution, rather than directly modeling probability density function (PDF) values, as is common in other approaches. Experimental results indicate a significant performance boost, with the proposed method achieving up to 30% superior performance in modeling the distribution of downtime lengths compared to alternative methods. Moreover, this method facilitates unsupervised training, making it suitable for big data repositories of unlabelled data. The framework allows for potential expansion by incorporating additional input variables. In this study, machine vibration velocity measurements are selected for further investigation. The study underscores the potential of advanced data-driven techniques to enables companies to make better-informed decisions regarding their current maintenance practices and to direct improvement programs in industrial settings.

Abstract Symbiotic relationships between eukaryotes and prokaryotes played pivotal roles in the evolution of life and drove the emergence of specialized symbiotic structures in animals, plants and fungi. The host-evolved symbiotic structures of microbial eukaryotes – the vast majority of such hosts in nature – remain largely unstudied. Here we describe highly structured symbiosomes within three free-living anaerobic protists (Anaeramoeba spp.). We dissect this symbiosis using complete genome sequencing and transcriptomics of host and symbiont cells coupled with fluorescence in situ hybridization, and 3D reconstruction using focused-ion-beam scanning electron microscopy. The emergence of the symbiosome is underpinned by expansion of gene families encoding regulators of membrane trafficking and phagosomal maturation and extensive bacteria-to-eukaryote lateral transfer. The symbionts reside deep within a symbiosomal membrane network that enables metabolic syntrophy by precisely positioning sulfate-reducing bacteria alongside host hydrogenosomes. Importantly, the symbionts maintain connections to the Anaeramoeba plasma membrane, blurring traditional boundaries between ecto- and endosymbiosis.

Abstract Background Glucose-6-Phosphate Dehydrogenase deficiency (G6PDd) is a common genetic enzymopathy that can induce haemolysis triggered by various factors, including some anti-malarial drugs. Although many Point-of-Care (PoC) tests, such as Standard G6PD™ are available to detect G6PDd, its pooled diagnostic test accuracy (DTA) remains unknown. Methods To estimate the DTA of StandG6PD-BS at various thresholds of G6PDd, a systematic review with a DTA meta-analysis were conducted, searching EMBASE, MEDLINE, and SciELO databases up to April 4, 2024.The included studies were those that measured G6PD activity using StandG6PD-BS (reference test) and spectrophotometry (gold standard) in patients suspected of having G6PDd. The risk of bias (RoB) of the studies was assessed using the QUADAS-2 tool and the certainty of evidence (CoE) with the GRADE approach. For the estimation of within-study DTA, a random-effect bivariate meta-analysis was performed to determine the pooled sensitivity and specificity for 30%, 70%, and 80% enzyme levels’ thresholds, and a graphical analysis of the heterogeneity using crosshair and Confidence Regions on receiver operating characteristic (ROC) space plots. Results After screening 2496 reports, four studies were included with 7864 participants covering all thresholds. Two studies had high RoB in QUADAS-2 domains 2 and 3, and the others had low RoB, with low, moderate, and high heterogeneity at the 30%, 70%, and 80% thresholds, respectively. The pooled sensitivity was 99.1%, 95.7%, and 90% for 30%, 70%, and 80% thresholds, respectively. The pooled specificity was 97.4%; 92.9%; and 89.0% for 30%, 70%, and 80% thresholds, respectively. Conclusion StandG6PD-BS is a PoC test with high sensitivity and specificity to detect G6PDd at different thresholds.

Abstract Human induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NSCs) hold promise for treating neurodegenerative and demyelinating disorders. However, comprehensive studies on their identity and safety remain limited. In this study, we demonstrate that hiPSC-NSCs adopt a radial glia-associated signature, sharing key epigenetic and transcriptional characteristics with human fetal neural stem cells (hfNSCs) while exhibiting divergent profiles from glioblastoma stem cells. Long-term transplantation studies in mice showed robust and stable engraftment of hiPSC-NSCs, with predominant differentiation into glial cells and no evidence of tumor formation. Additionally, we identified the Sterol Regulatory Element Binding Transcription Factor 1 (SREBF1) as a regulator of astroglial differentiation in hiPSC-NSCs. These findings provide valuable transcriptional and epigenetic reference datasets to prospectively define the maturation stage of NSCs derived from different hiPSC sources and demonstrate the long-term safety of hiPSC-NSCs, reinforcing their potential as a viable alternative to hfNSCs for clinical applications.

In this article, the authors consider the noise characteristics of traffic flows in urban conditions. The unevenness of traffic flows in time and space entails a change in noise effects on the environment. The main source of noise pollution is the internal combustion engine, which produces aerodynamic noise and structural noise. Noise level measurements are carried out separately for vehicles in motion and for stationary vehicles. The noise level is directly influenced by the mode of movement of cars, the speed of traffic flow, and the intensity of traffic flow. Deterioration of working and leisure conditions with a high level of traffic noise can lead to a decrease in labor productivity and the occurrence of nervous disorders. Therefore, the protection of the population from the noise generated by transport is not only of social, but also of economic importance. Purpose: to analyze the level of noise impacts of traffic flow in urban conditions. Method and methodology. The methods of observation, statistical analysis, and synthesis were used in the article. Results: noise level measurements were carried out on the selected section of the road network, and calculated data were obtained based on the declared characteristics of the traffic flow. Scope of application of the results: research activities to improve the environmental safety of the traffic flow.

Introduction/purpose: Increased development of hybrid powertrains during the last decade brought high-speed tracked vehicles into the same spotlight as commercial and passenger hybrid vehicles. There are several hybrid powertrain conceptions for high-speed tracked vehicles that are mainly researched, but there is still no clear conclusion which conception is the most efficient. The main obstacle for more intense research is the increased difficulty to produce a battery storage system which provides both high power density and protection and shock resistance. However, there is a certain number of research studies and prototypes developed from simulation models that show satisfactory performance for both asymmetric and symmetric hybrid powertrain conceptions. Methods: The developed and verified hybrid simulation model is improved in terms of command signal unit, so that the powertrain and electric motors in the auxiliary drive can easily be operated in the asymmetric hybrid working regime and the symmetric hybrid working regime. The main goal is to simulate specific working regimes where the asymmetric and symmetric hybrid powertrain performance and energy efficiency can be assessed in order to find the most efficient powertrain conception. Results: The results indicate that the asymmetric hybrid powertrain will have less overall power consumption and a more simple control algorithm, because of controlling just one electric motor. For the same overall power, the asymmetric hybrid powertrain has a smaller turning radius, which is satisfactory. When driven in full power, the symmetric hybrid powertrain will have lower turning radius and better manoeuvrability, but serious increase of power consumption. Conclusion: The asymmetric drive has clearly better power efficiency, but the symmetric drive has an advantage of maximum performance. Performing a pivot turn (around the vertical axis), and making a turn without reducing the vehicle velocity is of great importance, especially considering the most common special purpose of this vehicle and manoeuvring in challenging terrain conditions.

Background. For further development of communication networks, it is planned to use hybrid satellite networks for traffic transmission. However, satellite communication channels have features such as distortion caused by the Doppler effect and increased energy efficiency requirements. Aim of this study is to analyze variants of orthogonal frequency multiplexing methods and modulation methods in order to choose the most stable technology, taking into account destabilizing factors. Method. Comparing different signal processing technologies and studying their resistance to bit errors is the imitation modeling of the communication channel in the Matlab environment. This approach allows creating a model of the communication network, taking into account the main parameters of communication channels, such as the Doppler effect, energy deficiency and destabilizing factors. Results. The distribution of the bit error coefficient for various signal processing technologies, depending on the signal-to-noise ratio, is compared. The method of frequency multiplexing is defined, providing the minimum peak factor and the most resistant to bit error. It is also noted that the effectiveness of all the studied technologies depends on the spacing and modulation constellations, and that it is necessary to adjust the characteristics of the system for each case. Conclusion. The results of this study can be used to improve the quality of communication in difficult interference conditions of hybrid mobile networks of 5 and 6 generations using the satellite segment.

Background: The use of regional anaesthetic techniques for caesarean section and labour analgesia is necessary for quality-driven obstetric anaesthesia as required by European minimum standards for obstetric analgesia and anaesthesia departments, which were issued by the European Society of Anaesthesiology and Intensive Therapy in 2020. The aim of this article is to evaluate the rate of caesarean sections performed using regional anaesthetic techniques and the rates of epidural, remifentanil-PCA, and meperidine analgesia for managing labour pain across the 14 Slovenian obstetric units, respectively. Methods: Data from the Slovenian National Perinatal Information System (NPIS) from 2013 to 2021 were analysed. Results: Spinal anaesthesia was used as a primary anaesthetic method (> 50% of elective caesarean sections) in a half of Slovenian obstetric units. For emergency caesarean sections, regional anaesthetic methods (spinal and epidural) were used in > 50% parturients in 3 obstetric units. Eight obstetric units had an epidural rate of >10%. The use of epidural analgesia has progressively increased in 9 of 14 obstetric units. Remifentanil has been routinely used in 6 obstetric units. Accordingly, the consumption of meperidine has dropped in all but one obstetric unit in Slovenia. Conclusion: In the past decade, considerable progress has been observed in obstetric anaesthesia practice in Slovenia. This is evident from the increased use of regional anaesthesia for caesarean section and labour analgesia. However, there are considerable discrepancies in anaesthetic practices between different obstetric units in Slovenia, a situation the parturients should be informed of well in advance to be able to choose the obstetric unit according to their labour and delivery preferences. In order to avoid the differences in the quality and accessibility of anaesthetic practice between units, it is necessary to increase the number of anaesthesiologists involved in obstetric anaesthesia to ensure 24/7 service of labour analgesia to be able to fulfill minimum European standards for obstetric analgesia and anaesthesia departments.

Abstract Meningiomas are among the most common primary tumors of the central nervous system. In the past several decades, many researchers have emphasized the importance of radiographic findings and their possible role in predicting the various aspects of the meningioma biology. One of the factors most commonly analyzed with respect to the lesions’ clinical behavior is peritumoral brain edema (PTBE), not only one of the most common signs associated with meningiomas, but also a significant clinical problem. Radiographic predictors of PTBE are usually noted as being the size of the tumor, its location, irregular margins, heterogeneity, and the peritumoral arachnoid plane with its pial vascular recruitment. Here, we review the available literature on the topic of these radiographic predictors of PTBE formation, we analyze the methodology of the research conducted, and we highlight the many controversies still present. Indeed, the evidence about PTBE pathogenesis, predictive factors, and clinical significance still seems to be mostly inconclusive, despite intense research in the area. We believe that by highlighting the many inconsistencies in the methodology used, we can showcase how little is actually known about the pathogenesis of PTBE, which in turn has important clinical implications. Additionally, we provide several MR images of intracranial meningiomas from our own practice which, we believe, showcase the unpredictable nature of PTBE, and demonstrate vividly the topics we discuss.

This work is the first part of a large bibliographic review of active queue management algorithms of the Random Early Detection (RED) family, presented in the scientific press from 1993 to 2023. The third part will provide data on algorithms published from 2016 to 2023.

The aim of the present study was to describe the conceptual and operational definitions of the frailty syndrome recommended by the Brazilian Consensus on Frailty in Older People. In 2015, a task force consisting of Brazilian specialists on human aging conducted a bibliographical review on frailty among older people in Brazil and established a consensus on the main findings through periodic meetings. A total of 72 articles were included in the analysis, comprising one systematic review, two conceptual discussions, two methodological descriptions, four longitudinal studies focusing on mortality and worsening of the frailty profile, eight cross-cultural adaptation studies, and 55 cross-sectional or prevalence studies. Forty-five studies (62.5%) used the Cardiovascular Health Study (CHS) frailty scale, of which seven (15.2%) used unadjusted cut-off points for their samples and 17 (36.9%) modified at least one of the five items of the instrument. The prevalence of frailty varied between 6.7 and 74.1%. When the CHS frailty scale was used, the wide range of prevalence — from 8 to 49.3% — depended on the cut-off points used to classify changes in gait speed and handgrip strength, as well as the research setting. The studies were based on four major conceptual models of frailty. Frailty in older people represents a state of physiological vulnerability and should not be confused with disabilities or multi-morbidities. In the Brazilian population, the prevalence of frailty has not yet been adequately estimated, and the cut-off points of the items of the frailty scales should be adapted to the parameters of this population.

Abstract Background Kidney fibrosis is a hallmark of chronic kidney disease (CKD) and compromises the viability of transplanted human bone marrow-derived mesenchymal stromal cells (BM-MSCs). Hence, BM-MSCs were genetically-engineered to express the anti-fibrotic and renoprotective hormone, human relaxin-2 (RLX) and green fluorescent protein (BM-MSCs-eRLX + GFP), which enabled BM-MSCs-eRLX + GFP delivery via a single intravenous injection. Methods BM-MSCs were lentiviral-transduced with human relaxin-2 cDNA and GFP, under a eukaryotic translation elongation factor-1α promoter (BM-MSCs-eRLX + GFP) or GFP alone (BM-MSCs-eGFP). The ability of BM-MSCs-eRLX + GFP to differentiate, proliferate, migrate, produce RLX and cytokines was evaluated in vitro, whilst BM-MSC-eRLX + GFP vs BM-MSCs-eGFP homing to the injured kidney and renoprotective effects were evaluated in preclinical models of ischemia reperfusion injury (IRI) and high salt (HS)-induced hypertensive CKD in vivo. The long-term safety of BM-MSCs-RLX + GFP was also determined 9-months after treatment cessation in vivo. Results When cultured for 3- or 7-days in vitro, 1 × 106 BM-MSCs-eRLX + GFP produced therapeutic RLX levels, and secreted an enhanced but finely-tuned cytokine profile without compromising their proliferation or differentiation capacity compared to naïve BM-MSCs. BM-MSCs-eRLX + GFP were identified in the kidney 2-weeks post-administration and retained the therapeutic effects of RLX in vivo. 1–2 × 106 BM-MSCs-eRLX + GFP attenuated the IRI- or therapeutically abrogated the HS-induced tubular epithelial damage and interstitial fibrosis, and significantly reduced the HS-induced hypertension, glomerulosclerosis and proteinuria. This was to an equivalent extent as RLX and BM-MSCs administered separately but to a broader extent than BM-MSCs-eGFP or the angiotensin-converting enzyme inhibitor, perindopril. Additionally, these renoprotective effects of BM-MSCs-eRLX + GFP were maintained in the presence of perindopril co-treatment, highlighting their suitability as adjunct therapies to ACE inhibition. Importantly, no major long-term adverse effects of BM-MSCs-eRLX + GFP were observed. Conclusions BM-MSCs-eRLX + GFP produced greater renoprotective and therapeutic efficacy over that of BM-MSCs-eGFP or ACE inhibition, and may represent a novel and safe treatment option for acute kidney injury and hypertensive CKD.

Abstract Background Cancer patients are more susceptible to an aggressive course of COVID-19. Developing biomarkers identifying cancer patients at high risk of COVID-19-related death could help determine who needs early clinical intervention. The miRNAs hosted in the genomic regions associated with the risk of aggressive COVID-19 could represent potential biomarkers for clinical outcomes. Patients and methods Plasma samples were collected at The University of Texas MD Anderson Cancer Center from cancer patients (N = 128) affected by COVID-19. Serum samples were collected from vaccinated healthy individuals (n = 23) at the Municipal Clinical Emergency Teaching Hospital in Timisoara, Romania. An in silico positional cloning approach was used to identify the presence of miRNAs at COVID-19 risk-associated genomic regions: CORSAIRs (COvid-19 RiSk AssocIated genomic Regions). The miRNA levels were measured by RT-qPCR. Results We found that miRNAs were enriched in CORSAIR. Low plasma levels of hsa-miR-150-5p and hsa-miR-93-5p were associated with higher COVID-19-related death. The levels of hsa-miR-92b-3p were associated with SARS-CoV-2 test positivity. Peripheral blood mononuclear cells (PBMC) increased secretion of hsa-miR-150-5p, hsa-miR-93-5p, and hsa-miR-92b-3p after in vitro TLR7/8- and T cell receptor (TCR)-mediated activation. Increased levels of these three miRNAs were measured in the serum samples of healthy individuals between one and nine months after the second dose of the Pfizer-BioNTech COVID-19 vaccine. SARS-CoV-2 infection of human airway epithelial cells influenced the miRNA levels inside their secreted extracellular vesicles. Conclusions MiRNAs are enriched at CORSAIR. Plasma miRNA levels can represent a potential blood biomarker for predicting COVID-19-related death in cancer patients.

Abstract Background Regular physical activity (PA) has been proven to help prevent non-communicable diseases and is beneficial for disease management in chronically ill populations. Physical inactivity and recreational screen-based media (SBM) use are related to poor health outcomes and common among youth. This study aimed to (1) investigate PA levels and recreational SBM use of adolescents with JIA over time and (2) compare these behaviours with those of their peers. Methods Data from JIA patients and their peers enrolled in the inception cohort study ICON at 11 German centers were analyzed. Individuals aged 13 and over were followed prospectively with questionnaires concerning PA level, recreational SBM use, and health-related quality of life (HRQoL) at a two-year interval. Group by time interactions were analyzed using linear mixed models. Results Data of 214 patients (mean age at first documentation 14.4 ± 0.9 years, female 63%) and 141 peers could be considered. At first documentation, patients were less physically active compared to their peers (p

Abstract The chicken caecum is colonised by hundreds of different bacterial species. Which of these are targeted by immunoglobulins and how immunoglobulin expression shapes chicken caecal microbiota has been addressed in this study. Using cell sorting followed by sequencing of V3/V4 variable region of 16S rRNA, bacterial species with increased or decreased immunoglobulin coating were determined. Next, we determined also caecal microbiota composition in immunoglobulin knockout chickens. We found that immunoglobulin coating was common and major taxa were coated with immunoglobulins. Similarly, more taxa required immunoglobulin production for caecum colonisation compared to those which became abundant in immunoglobulin-deficient chickens. Taxa with low immunoglobulin coating such as Lactobacillus, Blautia, [Eubacterium] hallii, Megamonas, Fusobacterium and Desulfovibrio all encode S-layer proteins which may reduce interactions with immunoglobulins. Although there were taxa which overgrew in Ig-deficient chickens (e.g. Akkermansia) indicating immunoglobulin production acted to exclude them from the chicken caecum, in most of the cases, immunoglobulin production more likely contributed to fixing the desired microbiota in the chicken caecum.

Abstract Self-adaptive thermoregulation, the mechanism living organisms use to balance their temperature, holds great promise for decarbonizing cooling and heating processes. This functionality can be effectively emulated by engineering the thermal emissivity of materials to adapt to background temperature variations. Yet, solutions that marry large emissivity switching ( $$\varDelta \epsilon$$ Δ ϵ ) with scalability, cost-effectiveness, and design freedom are still lacking. Here, we fill this gap by introducing infrared dipole antennas made of tunable thermochromic materials. We demonstrate that non-spherical antennas (rods, stars and flakes) made of vanadium-dioxide can exhibit a massive (~200-fold) increase in their absorption cross-section as temperature rises. Embedding these antennas in polymer films, or simply spraying them directly, creates free-form thermoregulation composites, featuring an outstanding $$\varDelta \epsilon \sim 0.6$$ Δ ϵ ~ 0.6 in spectral ranges that can be tuned at will. Our research paves the way for versatile self-adaptive heat management solutions (coatings, fibers, membranes, and films) that could find application in radiative-cooling, heat-sensing, thermal-camouflage, and other.

Abstract Endothelial cells are integral components of all vasculature within complex organisms. As they line the blood vessel wall, endothelial cells are constantly exposed to a variety of molecular factors and shear force that can induce cellular damage and stress. However, how endothelial cells are removed or eliminate unwanted cellular contents, remains unclear. The generation of large extracellular vesicles (EVs) has emerged as a key mechanism for the removal of cellular waste from cells that are dying or stressed. Here, we used intravital microscopy of the bone marrow to directly measure the kinetics of EV formation from endothelial cells in vivo under homoeostatic and malignant conditions. These large EVs are mitochondria-rich, expose the ‘eat me’ signal phosphatidylserine, and can interact with immune cell populations as a potential clearance mechanism. Elevated levels of circulating EVs correlates with degradation of the bone marrow vasculature caused by acute myeloid leukaemia. Together, our study provides in vivo spatio-temporal characterization of EV formation in the murine vasculature and suggests that circulating, large endothelial cell-derived EVs can provide a snapshot of vascular damage at distal sites.

Abstract Introduction We aimed to describe the risk profile of RSV infections among children aged ≤ 24 months in Valladolid from January 2010 to August 2022 and to compare them with influenza and COVID-19 controls. Methods We conducted a retrospective cohort study of all laboratory-confirmed RSV, influenza, and COVID-19 infections. We analyzed risk factors for RSV hospitalization and severity (length-of-stay ≥ 8 days, intensive-care-unit admission, in-hospital death or readmission

Abstract Objective Predicting long‐term functional outcomes shortly after a stroke is challenging, even for experienced neurologists. Therefore, we aimed to evaluate multiple machine learning models and the importance of clinical/radiological parameters to develop a model that balances minimal input data with reliable predictions of long‐term functional independency. Methods Our study utilized data from the German Stroke Registry on patients with large anterior vessel occlusion who underwent endovascular treatment. We trained seven machine learning models using 30 parameters from the first day postadmission to predict a modified Ranking Scale of 0–2 at 90 days poststroke. Model performance was assessed using a 20‐fold cross‐validation and one‐sided Wilcoxon rank‐sum tests. Key features were identified through backward feature selection. Results We included 7485 individuals with a median age of 75 years and a median NIHSS score at admission of 14 in our analysis. Our Deep Neural Network model demonstrated the best performance among all models including data from 24 h postadmission. Backward feature selection identified the seven most important features to be NIHSS after 24 h, age, modified Ranking Scale after 24 h, premorbid modified Ranking Scale, intracranial hemorrhage within 24 h, intravenous thrombolysis, and NIHSS at admission. Narrowing the Deep Neural Network model's input data to these features preserved the high performance with an AUC of 0.9 (CI: 0.89–0.91). Interpretation Our Deep Neural Network model, trained on over 7000 patients, predicts 90‐day functional independence using only seven clinical/radiological features from the first day postadmission, demonstrating both high accuracy and practicality for clinical implementation on stroke units.

Introduction The "gold" standard for the treatment of late stages of coxarthrosis is total hip arthroplasty. Direct anterior approach (DAA) refers to minimally invasive surgical interventions in orthopaedics. Extended anesthetic measures in combination with low-traumatic surgical techniques may reduce postoperative pain and accelerate patient's recovery. The purpose of the study was to compare the recovery times of patients after hip arthroplasty using DAA in combination with PENG block, lateral cutaneous femoral nerve (LCFN) block and without extended anesthetic measures. Materials and methods A prospective randomized comparative clinical study was performed, which involved 62 patients divided into two groups: the study one (n = 29) and the control one (n = 33). In both groups, arthroplasty was performed using DAA. Patients of the study group underwent PENG block and LCFN block. The patients in the control group did not receive extended anesthesia. The evaluation criteria were pain assessment using the visual analogue scale (VAS), administration of painkillers, patient’s mobility and the length of hospital stay. Results The VAS score for pain in the study group were lower than in the control group after 6 hours — 3.7 (3.4; 4.1) and 4.3 (4.2; 4.8); 24 hours after surgery — 3.5 (3.3; 3.6) and 4.1 (3.9; 4.5) (p < 0.001). After 48 hours, the indices were comparable: 3.5 (3.1; 4.1) and 3.7 (3.6; 3.9) (p = 0.19). The rate of requests for pain relief in the first 24 hours was lower in the study group than in the control group: 2 (1; 2) and 3 (2; 3) cases (p = 0.003). The results of the manual muscle test after 6 hours and 24 hours were comparable (p > 0.05). The time interval between the end of the operation and the first walking on crutches was shorter in the study group — 3.1 hours (2.9; 3.4) and 3.98 hours (3.8; 4.2) (p < 0.001). The length of hospital stay was shorter in the study group: 1.5 (1.2; 2) and 2.5 (2; 3) days (p < 0.001). Discussion Lower postoperative pain allows faster activation of patients, thus improving the results of the early rehabilitation period. Conclusion The use of PENG block and LCFN block in arthroplasty with the use of DAA has clinical effectiveness in the first 24 hours, and helps to accelerate the postoperative recovery of patients.