bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adhesion of retinal cells to gold surfaces by biomimetic molecules
Authors: Shpun Gal , Markus Amos , Farah Nairouz , Zalevsky Zeev , Mandel Yossi 
Published: August 2024

BackgroundNeural cell-electrode coupling is crucial for effective neural and retinal prostheses. Enhancing this coupling can be achieved through surface modification and geometrical design to increase neuron-electrode proximity. In the current research, we focused on designing and studying various biomolecules as a method to elicit neural cell-electrode adhesion via cell-specific integrin mechanisms.MethodsWe designed extracellular matrix biomimetic molecules with different head sequences (RGD or YIGSR), structures (linear or cyclic), and spacer lengths (short or long). These molecules, anchored by a thiol (SH) group, were deposited onto gold surfaces at various concentrations. We assessed the modifications using contact angle measurements, fluorescence imaging, and X-ray Photoelectron Spectroscopy (XPS). We then analyzed the adhesion of retinal cells and HEK293 cells to the modified surfaces by measuring cell density, surface area, and focal adhesion spots, and examined changes in adhesion-related gene and integrin expression.ResultsResults showed that YIGSR biomolecules significantly enhanced retinal cell adhesion, regardless of spacer length. For HEK293 cells, RGD biomolecules were more effective, especially with cyclic RGD and long spacers. Both cell types showed increased expression of specific adhesion integrins and proteins like vinculin and PTK2; these results were in agreement with the adhesion studies, confirming the cell-specific interactions with modified surfaces.ConclusionThis study highlights the importance of tailored biomolecules for improving neural cell adhesion to electrodes. By customizing biomolecules to foster specific and effective interactions with adhesion integrins, our study provides valuable insights for enhancing the integration and functionality of retinal prostheses and other neural implants.
Fast power flow calculation for distribution networks based on graph models and hierarchical forward-backward sweep parallel algorithm
Authors: Wang Xinrui , Chen Wengang , Tian Ruimin , Ji Yuze , Zhu Jianfei 
Published: August 2024

IntroductionIn response to the issues of complexity and low efficiency in line loss calculations for actual distribution networks, this paper proposes a fast power flow calculation method for distribution networks based on Neo4j graph models and a hierarchical forward-backward sweep parallel algorithm.MethodsFirstly, Neo4j is used to describe the distribution network structure as a simple graph model composed of nodes and edges. Secondly, a hierarchical forward-backward sweep method is adopted to perform power flow calculations on the graph model network. Finally, during the computation of distribution network subgraphs, the method is combined with the Bulk Synchronous Parallel (BSP) computing model to quickly complete the line loss analysis.Results and DiscussionResults from the IEEE 33-node test system demonstrate that the proposed method can calculate network losses quickly and accurately, with a computation time of only 0.175s, which is lower than the MySQL and Neo4j graph methods that do not consider hierarchical parallel computing.
Developing genomic tools to assist turnip rape [Brassica rapa (L.) subsp.oleifera (DC.) Metzg.] breeding
Authors: Alemu Admas , Sundaramoorthy Jagadeesh , Abreha Kibrom B. , Enyew Muluken , Geleta Mulatu , Carlsson Anders S. 
Published: August 2024

IntroductionTurnip rape is recognized as an oilseed crop contributing to environmentally sustainable agriculture via integration into crop rotation systems. Despite its various advantages, the crop’s cultivation has declined globally due to a relatively low productivity, giving way to other crops. The use of genomic tools could enhance the breeding process and accelerate genetic gains. Therefore, the present research investigated 170 turnip rape accessions representing its global gene pool to identify SNP markers associated nine phenological and agro-morphological traits and estimate the genomic breeding values (GEBVs) of the germplasm through GWAS and genomic prediction analyses, respectively.MethodsField trials were conducted at two sites in northern and southern Sweden to obtain the phenotypic data while genotyping was conducted via the genotyping-by-sequencing (GBS) method. The traits studied include days to flowering (DTF) and maturity (DTM), plant height (PH), seed yield (YLD), thousand seed weight (TSW), silique length (SL), number of siliques (NS), number of seeds per silique (SS), and pod shattering resistance (PSHR).Results and conclusionAnalysis of variance revealed substantial variation among accessions, with significant genotype-by-environment interaction for most traits. A total of 25, 17, 16, 14, 7, 5, 3, and 3 MTAs were identified for TSW, DTF, PH, PSHR, SL, YLD, SS and DTM, respectively. An 80%–20% training-test set genomic prediction analysis was conducted using the ridge regression – BLUP (RR-BLUP) model. The accuracy of genomic prediction for most traits was high, indicating that these tools may assist turnip rape breeders in accelerating genetic gains. The study highlights the potential of genomic tools to significantly advance breeding programs for turnip rape by identifying pivotal SNP markers and effectively estimating genomic breeding values. Future breeding perspectives should focus on leveraging these genomic insights to enhance agronomic traits and productivity, thereby reinstating turnip rape as a competitive and sustainable crop in Sweden and broader global agriculture.
Internalization of therapeutic antibodies into dendritic cells as a risk factor for immunogenicity
Authors: Siegel Michel , Bolender Anna-Lena , Ducret Axel , Fraidling Johannes , Hartman Katharina , Looney Cary M. , Rohr Olivier , Hickling Timothy P. , Kettenberger Hubert , Lechmann Martin , Marban-Doran Céline , Kraft Thomas E. 
Published: August 2024

IntroductionImmunogenicity, the unwanted immune response triggered by therapeutic antibodies, poses significant challenges in biotherapeutic development. This response can lead to the production of anti-drug antibodies, potentially compromising the efficacy and safety of treatments. The internalization of therapeutic antibodies into dendritic cells (DCs) is a critical factor influencing immunogenicity. Using monoclonal antibodies, with differences in non-specific cellular uptake, as tools to explore the impact on the overall risk of immunogenicity, this study explores how internalization influences peptide presentation and subsequently T cell activation.Materials and methodsTo investigate the impact of antibody internalization on immunogenicity, untargeted toolantibodies with engineered positive or negative charge patches were utilized. Immature monocyte-derived DCs (moDCs), known for their physiologically relevant high endocytic activity, were employed for internalization assays, while mature moDCs were used for MHC-II associated peptide proteomics (MAPPs) assays. In addition to the lysosomal accumulation and peptide presentation, subsequent CD4+ T cell activation has been assessed. Consequently, a known CD4+ T cell epitope from ovalbumin was inserted into the tool antibodies to evaluate T cell activation on a single, shared epitope.ResultsAntibodies with positive charge patches exhibited higher rates of lysosomal accumulation and epitope presentation compared to those with negative charge patches or neutral surface charge. Furthermore, a direct correlation between internalization rate and presentation on MHC-II molecules could be established. To explore the link between internalization, peptide presentation and CD4+ T cell activation, tool antibodies containing the same OVA epitope were used. Previous observations were not altered by the insertion of the OVA epitope and ultimately, an enhanced CD4+ T cell response correlated with increased internalization in DCs and peptide presentation.DiscussionThese findings demonstrate that the biophysical properties of therapeutic antibodies, particularly surface charge, play a crucial role in their internalization into DCs. Antibodies internalized faster and processed by DCs, are also more prone to be presented on their surface leading to a higher risk of triggering an immune response. These insights underscore the importance of considering antibody surface charge and other properties that enhance cellular accumulation during the preclinical development of biotherapeutics to mitigate immunogenicity risks.
Identification and verification of disulfidptosis-related genes in sepsis-induced acute lung injury
Authors: Zhang Anqi , Wang Xinyang , Lin Wen , Zhu Haoqi , Pan Jingyi 
Published: August 2024

BackgroundSepsis-induced acute lung injury (ALI) is a common and serious complication of sepsis that eventually progresses to life-threatening hypoxemia. Disulfidptosis is a newly discovered type of cell death associated with the pathogenesis of different diseases. This study investigated the potential association between sepsis-induced acute lung injury and disulfidptosis by bioinformatics analysis.MethodsIn order to identify differentially expressed genes (DEGs) linked to sepsis, we screened appropriate data sets from the GEO database and carried out differential analysis. The key genes shared by DEGs and 39 disulfidptosis–related genes were identified: ACSL4 and MYL6 mRNA levels of key genes were detected in different datasets. We then used a series of bioinformatics analysis techniques, such as immune cell infiltration analysis, protein–protein interaction (PPI) network, genetic regulatory network, and receiver operating characteristic (ROC), to investigate the possible relationship between key genes and sepsis. Then, experimental verification was obtained for changes in key genes in sepsis-induced acute lung injury. Finally, to investigate the relationship between genetic variants of MYL6 or ACSL4 and sepsis, Mendelian randomization (MR) analysis was applied.ResultsTwo key genes were found in this investigation: myosin light chain 6 (MYL6) and Acyl-CoA synthetase long-chain family member 4 (ACSL4). We verified increased mRNA levels of key genes in training datasets. Immune cell infiltration analysis showed that key genes were associated with multiple immune cell levels. Building the PPI network between MYL6 and ACSL4 allowed us to determine that their related genes had distinct biological functions. The co-expression genes of key genes were involved in different genetic regulatory networks. In addition, both the training and validation datasets confirmed the diagnostic capabilities of key genes by using ROC curves. Additionally, both in vivo and in vitro experiments confirmed that the mRNA levels of ACSL4 and MYL6 in sepsis-induced acute lung injury were consistent with the results of bioinformatics analysis. Finally, MR analysis revealed a causal relationship between MYL6 and sepsis.ConclusionWe have discovered and confirmed that the key genes ACSL4 and MYL6, which are linked to disulfidptosis in sepsis-induced acute lung injury, may be useful in the diagnosis and management of septic acute lung injury.
Development and validation of a nomogram to predict the risk of vancomycin-related acute kidney injury in critical care patients
Authors: Bao Peng , Sun Yuzhen , Qiu Peng , Li Xiaohui 
Published: August 2024

BackgroundVancomycin-associated acute kidney injury (AKI) leads to underestimated morbidity in the intensive care unit (ICU). It is significantly important to predict its occurrence in advance. However, risk factors and nomograms to predict this AKI are limited.MethodsThis was a retrospective analysis of two databases. A total of 1,959 patients diagnosed with AKI and treated with vancomycin were enrolled from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. According to the 7:3 ratio, the training set (n = 1,372) and the internal validation set (n = 587) were randomly allocated. The external validation set included 211 patients from the eICU Collaborative Research Database (eICU). Next, to screen potential variables, the least absolute shrinkage and selection operator (LASSO) regression was utilized. Subsequently, the nomogram was developed by the variables of the selected results in the multivariable logistic regression. Finally, discrimination, calibration, and clinical utility were evaluated to validate the nomogram.ResultsThe constructed nomogram showed fine discrimination in the training set (area under the receiver operator characteristic curve [AUC] = 0.791; 95% confidence interval [CI]: 0.758–0.823), internal validation set (AUC = 0.793; 95% CI: 0.742–0.844), and external validation set (AUC = 0.755; 95% CI: 0.663–0.847). Moreover, it also well demonstrated calibration and clinical utility. The significant improvement (P &lt; 0.001) in net reclassification improvement (NRI) and integrated differentiation improvement (IDI) confirmed that the predictive model outperformed others.ConclusionThis established nomogram indicated promising performance in determining individual AKI risk of vancomycin-treated critical care patients, which will be beneficial in making clinical decisions.
Exploring phytochemicals and pharmacological properties of Populus × tomentiglandulosa
Authors: Lee Hak-Dong , Kim Ji Hyun , Choi Jong Hee , Kim Ki Hyun , Ku Jajung , Choi Kyung , Kim Hyun Young , Lee Sanghyun , Cho Ik-Hyun 
Published: August 2024

Populus × tomentiglandulosa (PT), a tree endemic to Korea, shows promising potential as a natural therapeutic agent owing to its potent anti-inflammatory properties. However, the isolation and analysis of phytochemical compounds in PT and related species remains underexplored. Therefore, this study aims to investigate the biochemical profile of PT and evaluate its extracts and fractions for anti-inflammatory activities. Nine compounds were isolated, including two novel flavonoids (luteolin 7-O-β-d-glucuronide butyl ester and chrysoeriol 7-O-β-d-glucuronide butyl ester) from the Salicaceae family for the first time. The ethyl acetate fraction exhibited significant radical scavenging activity against various radicals, including DPPH, ABTS+, •OH, and O2– radicals. PT extracts and the ethyl acetate fraction showed minimal cytotoxicity in Raw 264.7 macrophages at concentrations below 500 and 100 μg/mL, respectively. Furthermore, PT extracts and fractions significantly suppressed the protein expression of proinflammatory mediators (iNOS and IL-6) in LPS-stimulated Raw 264.7 macrophages, highlighting their potent anti-inflammatory effects. These findings suggest that PT holds promise as a valuable natural therapeutic intervention for various oxidative stress and inflammation-related disorders, underscoring the need for further exploration of its clinical applications.
Model informed dose regimen optimizing in development of leritrelvir for the treatment of mild or moderate COVID-19
Authors: Wang Kun , Li Haijun , Li Youyun , Xu Fengyan , Sun Zhongyi , Yang Yuting , Huang Jufang , Chen Xiaoxin 
Published: August 2024

IntroductionLeritrelvir (RAY1216) acts as a main protease inhibitor that hinders the cleavage of viral precursor proteins, thereby inhibiting virus replication of SARS-CoV-2). This antiviral mechanism has shown significant efficacy against the novel coronavirus. Preclinical studies have demonstrated the potent antiviral activity and favorable safety profile of this compound. This study aims to develop a pharmacokinetic model for leritrelvir, with and without ritonavir as a pharmacokinetic enhancer and to evaluate the necessity of co-administration with ritonavir and to investigate different dosage regimens.MethodThe model establishment was based on plasma concentration data from a phase I trial involving 72 subjects in single-ascending dose (SAD), multiple-ascending dose (MAD), and a food effect cohort. Analysis was conducted using a nonlinear mixed-effects model, and clinical trial simulations were carried out.ResultsThe findings of this study demonstrate a favorable safety profile for leritrelvir. With simulation suggests that a 400 mg thrice-daily (TID) regimen may be optimal to maintain the trough concentrations (Ctrough) above levels required for inhibiiting viral replication. While ritonavir was found to enhance exposure, it was deemed unnecessary. Gender and food consumption were identified as significant covariates affecting pharmacokinetic parameters, however, no dose adjustments were deemed necessary.DiscussionThis findings supported by subsequent phase II and phase III trials validated the appropriateness of a 400 mg TID regimen for the administration of leritrelvir.
Body Oxygen Level Test (BOLT) is not associated with exercise performance in highly-trained individuals
Authors: Kowalski Tomasz , Rebis Kinga , Wilk Adrian , Klusiewicz Andrzej , Wiecha Szczepan , Paleczny Bartłomiej 
Published: August 2024

IntroductionThe analysis of chemoreflex and baroreflex sensitivity may contribute to optimizing patient care and athletic performance. Breath-holding tests, such as the Body Oxygen Level Test (BOLT), have gained popularity as a feasible way to evaluate the reflex control over the cardiorespiratory system. According to its proponents, the BOLT score reflects the body’s sensitivity to carbon dioxide and homeostasis disturbances, providing feedback on exercise tolerance. However, it has not yet been scientifically validated or linked with exercise performance in highly-trained individuals. Therefore, we investigated the association of BOLT scores with the results of standard performance tests in elite athletes.MethodsA group of 49 speedskaters performed BOLT, Wingate Anaerobic Test (WAnT), and cardiopulmonary exercise test (CPET) on a cycle ergometer. Peak power, total work, and power drop were measured during WAnT. Time to exhaustion and maximum oxygen uptake were measured during CPET. Spearman’s rank correlation and multiple linear regression were performed to analyze the association of BOLT scores with parameters obtained during the tests, age, somatic indices, and training experience.ResultsNo significant correlations between BOLT scores and parameters obtained during WAnT and CPET were found, r(47) = −0.172–0.013, p = 0.248–0.984. The parameters obtained during the tests, age, somatic indices, and training experience were not significant in multiple linear regression (p = 0.38–0.85). The preliminary regression model showed an R2 of 0.08 and RMSE of 9.78 sec.ConclusionsOur findings did not demonstrate a significant relationship between BOLT scores and exercise performance. Age, somatic indices, and training experience were not significant in our analysis. It is recommended to interpret BOLT concerning exercise performance in highly-trained populations with a great degree of caution.
Benefits of Living Over Deceased Donor Kidney Transplantation in Elderly Recipients. A Propensity Score Matched Analysis of a Large European Registry Cohort
Authors: Toapanta Néstor , Comas Jordi , Revuelta Ignacio , Manonelles Anna , Facundo Carme , Pérez-Saez María José , Vila Anna , Arcos Emma , Tort Jaume , Giral Magali , Naesens Maarten , Kuypers Dirk , Asberg Anders , Moreso Francesc , Bestard Oriol ,   the EKITE consortium
Published: August 2024

Although kidney transplantation from living donors (LD) offers better long-term results than from deceased donors (DD), elderly recipients are less likely to receive LD transplants than younger ones. We analyzed renal transplant outcomes from LD versus DD in elderly recipients with a propensity-matched score. This retrospective, observational study included the first single kidney transplants in recipients aged ≥65 years from two European registry cohorts (2013–2020, n = 4,257). Recipients of LD (n = 408), brain death donors (BDD, n = 3,072), and controlled cardiocirculatory death donors (cDCD, n = 777) were matched for donor and recipient age, sex, dialysis time and recipient diabetes. Major graft and patient outcomes were investigated. Unmatched analyses showed that LD recipients were more likely to be transplanted preemptively and had shorter dialysis times than any DD type. The propensity score matched Cox’s regression analysis between LD and BDD (387-pairs) and LD and cDCD (259-pairs) revealing a higher hazard ratio for graft failure with BDD (2.19 [95% CI: 1.16–4.15], p = 0.016) and cDCD (3.38 [95% CI: 1.79–6.39], p &lt; 0.001). One-year eGFR was higher in LD transplants than in BDD and cDCD recipients. In elderly recipients, LD transplantation offers superior graft survival and renal function compared to BDD or cDCD. This strategy should be further promoted to improve transplant outcomes.
Cosmetonews - orientações sobre produtos cosméticos para pets
Authors: Barbosa Adrielly dos Santos , Prado Ana Beatriz Costa , Lima Antonio Kassio Silva , Feitoza Jéssica Maruyama , Bemfica Larissa Alvarenga , Rodrigues Mayara da Silva , Souza Rebeca Vitória Rodrigues de , Andrade Vívian Lopes de , Pereira Marcela Monteiro , Paes-Pereira Pâmela , Paes Ellen Regina da Costa , Silva Antonio Batista da 
Published: August 2024

No Brasil, mais da metade dos domicílios possuem um animal de estimação. Em 2020, mesmo com a pandemia do novo coronavírus, o mercado pet cresceu em cerca de 13,5%, faturando acima de R$40 bilhões. O país hoje é o terceiro maior mercado pet do mundo, estando atrás apenas dos Estados Unidos e China. A humanização do pet é um dos fatores que auxiliam o crescimento desse mercado. A ausência de critérios e procedimentos para implementação da cosmetovigilância veterinária pela autoridade competente, faz-se necessário investigar junto aos tutores e profissionais da área veterinária a incidência de reações adversas oriundas do uso destes produtos em cães e gatos e avaliar a percepção sobre a segurança dos tutores e profissionais em relação a estes produtos. Da mesma forma que os humanos, os animais também podem apresentar doenças de pele. Uma das doenças de pele mais comuns é a Dermatite atópica (DA), que ocorrem em gatos e cães. O presente projeto orientou e esclareceu a população sobre o uso seguro de cosméticos em animais de estimação.
THEORY OF CONSERVATION OF CULTURAL VALUES: TO THE PROBLEM OF CONTRADICTIONS INTERPRETATION
Authors: Макарова Анастасия Сергеевна 
Published: August 2024

В статье приводится краткий обзор и анализ сформировавшихся представлений о развитии теории реставрации культурных ценностей. Автор статьи отмечает, что традиционно эволюция теории реставрации представляется как движение от поновления к научной реставрации. При этом эти два основополагающих подхода сосуществуют как в исторической перспективе, так и в актуальной практике. Вероятно, отчасти снять это противоречие возможно, рассмотрев теорию реставрации в свете аксиологической концепции культуры, которая позволяет представить культуру как совокупность ценностных ориентиров. Целью реставрационных работ в этом случае можно назвать актуализацию ценностных критериев объекта реставрации, а задачами - поиск методов ее достижения.
The article provides a brief overview and analysis of the theory of restoration of cultural values. The author notes that traditionally evolution of the theory of conservation is presented as a movement from renovation to scientific restoration. Moreover, these two fundamental approaches coexist both in a historical perspective and in actual practice. Probably, it is possible to partially remove this contradiction by viewing the theory of conservation in the light of the axiological theory of culture, which allows us to present culture as a set of value orientations. The goal of conservation in this case can be in actualization of the value criteria of the object, and the tasks in the search for methods of achieving it.