bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti-interleukin 4 receptor α antibody for the treatment of Chinese bullous pemphigoid patients with diverse comorbidities and a 1-year follow-up: a monocentric real-world study
Authors: Wang Si-Hang , Shan Ying , Li Si-Zhe , Zuo Ya-Gang
Published: July 2023

Background

Bullous pemphigoid (BP) is a common subepidermal bullous disorder that lacks adequate treatment alternatives. Dupilumab, an anti-interleukin (IL) 4 receptor α antibody blocking Th2 molecules IL-4 and 13, has been used off-label and shown to be effective in refractory BP cases.

Methods

BP patients with various disease severities and comorbidities were included in this case series. All patients received dupilumab alone or in combination with immunosuppressants in a real-world setting. Complete remission (CR) was defined as the absence of pruritus symptoms and previous BP eruptions, with only hyperpigmentation patches and without newly occurring lesions for at least 4 weeks. Disease relapse was classified as the appearance of three or more new lesions within 1 month or at least one large urticarial or eczematous lesion that did not resolve within a week.

Findings

Ten individuals were enrolled in this case series. Pruritus symptoms and BP eruptions improved significantly in nine patients (90%). Seven patients (70%) attained CR, including all mild-to-moderate (100%) cases and three of six (50%) severe BP cases. At the dupilumab monotherapy stage, eosinophilia was observed in two severe cases. One patient out of seven (14.3%) relapsed after 1 year of follow-up after CR.

Conclusion

Treatment of BP with diverse comorbidities with anti-IL-4 receptor α antibody provides further credentials to a prospective randomized study. More impressive efficacy and safety profiles were observed in patients with mild-to-moderate disease after 1 year of follow-up. Eosinophilia may occur in patients receiving dupilumab monotherapy.
Intranasal immunization with a Bucl8-based vaccine ameliorates bacterial burden and pathological inflammation, and promotes an IgG2a/b dominant response in an outbred mouse model of Burkholderia infection
Authors: Grund Megan , Choi Soo Jeon , Powell Lillie , Lukomski Slawomir
Published: July 2023

Burkholderia pseudomallei is a gram-negative bacterium that is the etiological agent of the tropical disease melioidosis. Currently, there is no licensed vaccine for melioidosis, but numerous candidates are being tested for protective efficacy and characterization of the elicited immune response. Our lab has previously reported the immunogenicity of a Bucl8-protein-based peptide antigen, designated L1-CRM197 (Cross-reacting material 197). When given subcutaneously, this vaccine formulation promoted a strong Th2 (IgG1) antibody response, however immunization did not protect from death. In this study, we hypothesized that an intranasally administered L1-CRM197 vaccine would induce protective mucosal immunity. To evaluate vaccine efficacy, we developed a surrogate Burkholderia infection model that employs outbred CD-1 mice which imitates the immunogenetic diversity of humans. Mice were immunized with either L1-CRM197 adjuvanted with fluorinated cyclic diguanosine monophosphate (FCDG) or with FCDG-only control. These mice were then challenged intranasally with an infectious dose of a luminescent strain of B. thailandensis E264 two weeks post-immunization, and correlates of protection were assessed in euthanized mice on days 1, 2, 3, and 7 post-infection. Overall, intranasal vaccination, compared to subcutaneous administration, induced a stronger Th1 (IgG2a/2b) to Th2 (IgG1) antibody response and promoted anti-L1 nasal, pulmonary, and systemic IgA. Additionally, sera IgG from L1-CRM197-vaccinated mice recognized whole-cell B. thailandensis and B. pseudomallei, a select agent exempt strain Bp82. Vaccination ameliorated disease indicators, including luminescent signal and bacterial cell counts, weight and temperature loss, and organ weight, which negatively correlated with IgG2a antibody levels and mucosa-stimulating cytokines IL-13 and IL-9. L1-CRM197-vaccinated mice also had earlier resolution of inflammatory and tissue-damaging cytokines compared to the FCDG-only controls. These results suggest a balanced humoral and cell-mediated response, along with mucosa-based immunity are beneficial for protection. Future efforts should further assess mucosal cellular and humoral mechanisms of protection and test such protection, using aerosolized B. pseudomallei select agent strain(s).
Application of spatial transcriptomics analysis using the Visium system for the mouse nasal cavity after intranasal vaccination
Authors: Toyama Sakiko , Honda Tomoko , Iwabuchi Sadahiro , Hashimoto Shinichi , Yamaji Kenzaburo , Tokunaga Yuko , Matsumoto Yusuke , Kawaji Hideya , Miyazaki Takashi , Kikkawa Yoshiaki , Kohara Michinori
Published: July 2023

Intranasal vaccines that elicit mucosal immunity are deemed effective against respiratory tract infections such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but their ability to induce humoral immunity characterized by immunoglobulin A (IgA) and IgG production is low. It has been reported that vaccination with a mixture of a viscous base carboxyvinyl polymer (CVP) and viral antigens induced robust systemic and mucosal immune responses. In this study, we analyzed the behavior of immunocompetent cells in the nasal cavity over time by spatial transcriptome profiling induced immediately after antigen vaccination using CVP. We established a method for performing spatial transcriptomics using the Visium system in the mouse nasal cavity and analyzed gene expression profiles within the nasal cavity after intranasal vaccination. Glycoprotein 2 (Gp2)-, SRY-box transcription factor 8 (Sox8)-, or Spi-B transcription factor (Spib)-expressing cells were increased in the nasal passage (NP) region at 3–6 hr after SARS-CoV-2 spike protein and CVP (S-CVP) vaccination. The results suggested that microfold (M) cells are activated within a short period of time (3–6 hr). Subsequent cluster analysis of cells in the nasal cavity showed an increase in Cluster 9 at 3–6 hr after intranasal vaccination with the S-CVP. We found that Il6 in Cluster 9 had the highest log2 fold values within the NP at 3–6 hr. A search for gene expression patterns similar to that of Il6 revealed that the log2 fold values of Edn2, Ccl20, and Hk2 also increased in the nasal cavity after 3–6 hr. The results showed that the early response of immune cells occurred immediately after intranasal vaccination. In this study, we identified changes in gene expression that contribute to the activation of M cells and immunocompetent cells after intranasal vaccination of mice with antigen-CVP using a time-series analysis of spatial transcriptomics data. The results facilitated the identification of the cell types that are activated during the initial induction of nasal mucosal immunity.
Immediate response of paddy soil microbial community and structure to moisture changes and nitrogen fertilizer application
Authors: Han Linrong , Qin Hongling , Wang Jingyuan , Yao Dongliang , Zhang Leyan , Guo Jiahua , Zhu Baoli
Published: July 2023

Water and fertilizer managements are the most common practices to maximize crop yields, and their long-term impact on soil microbial communities has been extensively studied. However, the initial response of microbes to fertilization and soil moisture changes remains unclear. In this study, the immediate effects of nitrogen (N)-fertilizer application and moisture levels on microbial community of paddy soils were investigated through controlled incubation experiments. Amplicon sequencing results revealed that moisture had a stronger influence on the abundance and community composition of total soil bacteria, as well as ammonia oxidizing-archaea (AOA) and -bacteria (AOB). Conversely, fertilizer application noticeably reduced the connectivity and complexity of the total bacteria network, and increasing moisture slightly exacerbated these effects. NH4+-N content emerged as a significant driving force for changes in the structure of the total bacteria and AOB communities, while NO3−-N content played more important role in driving shifts in AOA composition. These findings indicate that the initial responses of microbial communities, including abundance and composition, and network differ under water and fertilizer managements. By providing a snapshot of microbial community structure following short-term N-fertilizer and water treatments, this study contributes to a better understanding of how soil microbes respond to long-term agriculture managements.
Being a morning man has causal effects on the cerebral cortex: a Mendelian randomization study
Authors: Yang Fan , Liu Ru , He Sheng , Ruan Sijie , He Binghua , Li Junda , Pan Linghui
Published: July 2023

Introduction

Numerous studies have suggested a connection between circadian rhythm and neurological disorders with cognitive and consciousness impairments in humans, yet little evidence stands for a causal relationship between circadian rhythm and the brain cortex.

Methods

The top 10,000 morningness-related single-nucleotide polymorphisms of the Genome-wide association study (GWAS) summary statistics were used to filter the instrumental variables. GWAS summary statistics from the ENIGMA Consortium were used to assess the causal relationship between morningness and variates like cortical thickness (TH) or surficial area (SA) on the brain cortex. The inverse-variance weighted (IVW) and weighted median (WM) were used as the major estimates whereas MR-Egger, MR Pleiotropy RESidual Sum and Outlier, leave-one-out analysis, and funnel-plot were used for heterogeneity and pleiotropy detecting.

Results

Regionally, morningness decreased SA of the rostral middle frontal gyrus with genomic control (IVW: β = −24.916 mm, 95% CI: −47.342 mm to −2.490 mm, p = 0.029. WM: β = −33.208 mm, 95% CI: −61.933 mm to −4.483 mm, p = 0.023. MR Egger: β < 0) and without genomic control (IVW: β = −24.581 mm, 95% CI: −47.552 mm to −1.609 mm, p = 0.036. WM: β = −32.310 mm, 95% CI: −60.717 mm to −3.902 mm, p = 0.026. MR Egger: β < 0) on a nominal significance, with no heterogeneity or no outliers.

Conclusions and implications

Circadian rhythm causally affects the rostral middle frontal gyrus; this sheds new light on the potential use of MRI in disease diagnosis, revealing the significance of circadian rhythm on the progression of disease, and might also suggest a fresh therapeutic approach for disorders related to the rostral middle frontal gyrus-related.
Radiopharmaceutical extravasations: a twenty year mini-review
Authors: Osborne Dustin R.
Published: July 2023

Interest and research into radiopharmaceutical extravasation concepts has risen with the increase in use of radiopharmaceutical therapies, growing access to novel molecular imaging agents, and recent regulatory controversies. This mini-review will examine the literature of the last twenty years to summarize the history of radiopharmaceutical extravasations, determine key trends in imaging and therapies, and highlight critical gaps in research that currently exist. The intent of this work is to provide a summary of this complex topic that helps build awareness and promotes new innovations in this interesting aspect of theranostic radiopharmaceuticals.
Significance of 4D US parameters for the clinical treatment of female patients with stress urinary incontinence
Authors: Jiang Changqin , Zhang Song , Chen Jing , Zhang Yangyang , Cai Keke , Chen Wei , Wu Yuanyuan , Liang Chaozhao
Published: July 2023

Background

Stress urinary incontinence (SUI) that has been associated with abnormal pelvic floor muscle function or morphology is a common condition. This research aimed to study the impact of the four-dimensional (4D) pelvic floor ultrasound on the treatment of female patients with clinical diagnosis of SUI and to evaluate its clinical significance on SUI.

Methods

We enrolled 51 women with SUI. Before transobturator suburethral tape procedures, the patients underwent 4D pelvic floor ultrasonography. The measurements include residual urine volume, bladder detrusor thickness in resting state, the vertical distance from the bladder neck to the posterior inferior edge of pubic symphysis at rest and Valsalva movement, posterior angle of bladder urethra, and urethral rotation angle. The degree of movement of the bladder neck (the difference between the vertical distance from the bladder neck to the posterior inferior edge of the pubic symphysis under the resting state and the maximum Valsalva movement) and the formation of a funnel at the internal orifice of the urethra were calculated.

Results

The mean bladder detrusor thickness was 2.6 ± 0.9 mm, the vertical distance from the bladder neck to the posterior inferior edge of pubic symphysis was 27.7 ± 4.5 mm, the posterior angle of the bladder was 122.7 ± 18.9°, the vertical distance from the rectal ampulla to the posterior inferior edge of pubic symphysis was 18.5 ± 4.6 mm, and the mean area of hiatus of the levator ani muscle was 22.1 ± 6.0 cm2. The mean posterior angle of the bladder on Valsalva was 159.3 ± 23.1°, and the mean urethral rotation angle was 67.2 ± 21.4°.

Conclusions

The 4D pelvic floor ultrasound is a reliable method in evaluating preoperational morphological characteristics of patients with SUI. With the help of the 4D pelvic floor ultrasound, the individualized treatment regimen can be developed and, more importantly, the inappropriate surgical decision can be avoided.
European Society for Organ Transplantation (ESOT) Consensus Statement on the Role of Pancreas Machine Perfusion to Increase the Donor Pool for Beta Cell Replacement Therapy
Authors: Ferrer-Fàbrega Joana , Mesnard Benoît , Messner Franka , Doppenberg Jason B. , Drachenberg Cinthia , Engelse Marten A. , Johnson Paul R. V. , Leuvenink Henri G. D. , Oniscu Gabriel C. , Papalois Vassilios , Ploeg Rutger J. , Reichman Trevor W. , Scott William E , Vistoli Fabio , Berney Thierry , Jacobs-Tulleneers-Thevissen Daniel , Kessaris Nicos , Weissenbacher Annemarie , Ogbemudia Ann Etohan , White Steve , Branchereau Julien
Published: July 2023

The advent of Machine Perfusion (MP) as a superior form of preservation and assessment for cold storage of both high-risk kidney’s and the liver presents opportunities in the field of beta-cell replacement. It is yet unknown whether such techniques, when applied to the pancreas, can increase the pool of suitable donor organs as well as ameliorating the effects of ischemia incurred during the retrieval process. Recent experimental models of pancreatic MP appear promising. Applications of MP to the pancreas, needs refinement regarding perfusion protocols and organ viability assessment criteria. To address the “Role of pancreas machine perfusion to increase the donor pool for beta cell replacement,” the European Society for Organ Transplantation (ESOT) assembled a dedicated working group comprising of experts to review literature pertaining to the role of MP as a method of improving donor pancreas quality as well as quantity available for transplant, and to develop guidelines founded on evidence-based reviews in experimental and clinical settings. These were subsequently refined during the Consensus Conference when this took place in Prague.
Hierarchical Control and Economic Optimization of Microgrids Considering the Randomness of Power Generation and Load Demand
Authors: Shan Yinghao , Ma Liqian , Yu Xiangkai
Published: July 2023

Hierarchical control has emerged as the main method for controlling hybrid microgrids. This paper presents a model of a hybrid microgrid that comprises both AC and DC subgrids, followed by the design of a three-layered control method. An economic objective function is then constructed to account for the uncertainty of power generation and load demand, and the optimal power guidance value is determined using the particle swarm optimization algorithm. The optimized power output is subsequently used to guide the tertiary control in the microgrid, mitigating potential safety and stability issues. Finally, the performance of each control layer is compared under dynamic changes in AC and DC loads, as well as stochastic variations in power generation and load consumption. Simulation results demonstrate that the hybrid microgrid can function stably, ensuring reliable and cost-effective AC and DC bus voltage supply despite the randomness of power generation and load demand.
Energy Flexibility and towards Resilience in New and Old Residential Houses in Cold Climates: A Techno-Economic Analysis
Authors: Rehman Hassam ur , Hasan Ala
Published: July 2023

One of the main sectors that contribute to climate change is the buildings sector. While nearly zero-energy buildings are becoming a new norm in many countries in the world, research is advancing towards energy flexibility and resilience to reach energy efficiency and sustainability goals. Combining the energy flexibility and energy resilience concept is rare. In this article, we aim to investigate the effect of energy efficiency in a new single-family building on the energy flexibility potential and resilience characteristics and compare these with those for an old building in the cold climate of Finland. These two objectives are dependent on the buildings’ respective thermal mass. The heat demands of the two buildings are compared. Their technical and economic performance are calculated to compare their flexibility and resilience characteristics. Dynamic simulation software is used to model the buildings. The results show that the old building has better flexibility and higher energy cost savings when including the energy conservation activation strategy. In the old building, savings can be around EUR 400 and flexibility factor can be around 24–52% depending on the activation duration and strategy. The new building, due to higher efficiency, may not provide higher energy cost savings, and the energy conservation activation strategy is better. In the new building, savings can be around EUR 70 and the flexibility factor reaches around 7–14% depending on the activation duration and strategy. The shifting efficiency of the new house is better compared to that of the old house due to its higher storage capacity. For energy resilience, the new building is shown to be better during power outages. The new building can be habitable for 17 h, while the old building can provide the same conditions for 3 h only. Therefore, it is essential to consider both energy flexibility and resilience as this can impact performance during the energy crisis.
The Use of Dolomite to Produce a Magnesium Potassium Phosphate Matrix for Radioactive Waste Conditioning
Authors: Kulikova Svetlana A. , Belova Kseniya Y. , Frolova Anna V. , Vinokurov Sergey E.
Published: July 2023

Magnesium potassium phosphate (MPP) matrix MgKPO4 × 6H2O is a known material for radioactive waste (RW) conditioning; magnesium oxide MgO is used in the classical method of matrix synthesis. The aim of the work was to investigate the possibility of using the widely available natural mineral raw material dolomite, incorporating mixed magnesium and calcium carbonate, for the production of this matrix. To control the quality of the samples obtained, their phase and elemental compositions, microstructure, density, volumetric and apparent porosity, compressive strength, and hydrolytic stability were studied. As a result, it was found that using dolomite powder pre-calcined at 720 °C for 1.5 h, samples of matrix whose properties meet the regulatory requirements for solidified RW were obtained. Thus, a new, cost-effective method of synthesis of the MPP matrix has been demonstrated to solve the RW solidification problem.
Backstepping Control of NPC Multilevel Converter Interfacing AC and DC Microgrids
Authors: Barros J. Dionísio , Rocha Luis , Silva J. Fernando
Published: July 2023

This work introduces modified backstepping methods to design controllers for neutral point clamped (NPC) converters interfacing a DC/AC microgrid. The modified backstepping controllers are derived from a proper converter model, represented in dq coordinates, and are designed to regulate the DC voltage and to balance the two NPC converter DC capacitor voltages through a DC offset in the sinusoidal pulse width modulation (SPWM) carriers. The averaged and separated dynamics backstepping controllers also enforce nearly sinusoidal AC currents at a given power factor. The two proposed NPC converter controllers are evaluated through MATLAB/Simulink simulations and experimental implementation using a laboratory prototype. Simulations and experimental results show that the two modified backstepping controllers regulate the microgrid DC voltage in steady state and in transient operation, even with load disturbances or DC voltage reference changes, while enforcing nearly AC sinusoidal currents at a given power factor or injected reactive power. The modified backstepping-controlled NPC converter is bidirectional, converting energy from DC renewable energy sources or storage systems to AC or charging storage systems from AC. The results also highlight the effective balancing of the NPC DC capacitor voltages.
Assessment of a NOx Measurement Procedure for Periodic Technical Inspection (PTI) of Light-Duty Diesel Vehicles
Authors: Franzetti Jacopo , Selleri Tommaso , Ferrarese Christian , Melas Anastasios , Manara Dario , Giechaskiel Barouch , Suarez-Bertoa Ricardo
Published: July 2023

A Periodic Technical Inspection (PTI) of vehicles promotes road safety and environmental protection. Indeed, a PTI is also used to verify the proper functioning of the vehicle’s aftertreatment system (ATS) over its lifetime. While the current Directive 2014/45/EU, which covers the PTI, does not require a NOx emissions measurement, the ongoing revision of the roadworthiness package aims at including new methods for measuring exhaust NOx and particle number (PN) emissions. PTI tests are required to be simple, quick, inexpensive and effective. In this study, a new methodology for a NOx measurement during the PTIs of Diesel vehicles equipped with a selective catalytic reduction (SCR) unit is assed. Seven Euro 6 light-duty Diesel vehicles fulfilling post-Real Driving Emissions (RDE) regulations were tested. The NOx-PTI methodology consists of measuring NOx emissions from the vehicle tailpipe at engine low idle speed after properly conditioning the vehicle ATS. In such conditions, a well-functioning SCR unit reduced NOx emissions and the methodology proved to be suitable to discriminate between functioning and malfunctioning SCR systems.
Silver Ions Inhibit Bacterial Movement and Stall Flagellar Motor
Authors: Russell Benjamin , Rogers Ariel , Yoder Ryan , Kurilich Matthew , Krishnamurthi Venkata Rao , Chen Jingyi , Wang Yong
Published: July 2023

Silver (Ag) in different forms has been gaining broad attention due to its antimicrobial activities and the increasing resistance of bacteria to commonly prescribed antibiotics. However, various aspects of the antimicrobial mechanism of Ag have not been understood, including how Ag affects bacterial motility, a factor intimately related to bacterial virulence. Here, we report our study on how Ag+ ions affect the motility of E. coli bacteria using swimming, tethering, and rotation assays. We observed that the bacteria slowed down dramatically by >70% when subjected to Ag+ ions, providing direct evidence that Ag+ ions inhibit the motility of bacteria. In addition, through tethering and rotation assays, we monitored the rotation of flagellar motors and observed that the tumbling/pausing frequency of bacteria increased significantly by 77% in the presence of Ag+ ions. Furthermore, we analyzed the results from the tethering assay using the hidden Markov model (HMM) and found that Ag+ ions decreased bacterial tumbling/pausing-to-running transition rate significantly by 75%. The results suggest that the rotation of bacterial flagellar motors was stalled by Ag+ ions. This work provided a new quantitative understanding of the mechanism of Ag-based antimicrobial agents in bacterial motility.
Clopidogrel Administration Impairs Post-Stroke Learning and Memory Recovery in Mice
Authors: Paul Marina , Paul Jonathan W. , Hinwood Madeleine , Hood Rebecca J. , Martin Kristy , Abdolhoseini Mahmoud , Johnson Sarah J. , Pollack Michael , Nilsson Michael , Walker Frederick R.
Published: July 2023

Clopidogrel, which is one of the most prescribed antiplatelet medications in the world, is given to stroke survivors for the prevention of secondary cardiovascular events. Clopidogrel exerts its antiplatelet activity via antagonism of the P2Y12 receptor (P2RY12). Although not widely known or considered during the initial clinical trials for clopidogrel, P2RY12 is also expressed on microglia, which are the brain’s immune cells, where the receptor facilitates chemotactic migration toward sites of cellular damage. If microglial P2RY12 is blocked, microglia lose the ability to migrate to damaged sites and carry out essential repair processes. We aimed to investigate whether administering clopidogrel to mice post-stroke was associated with (i) impaired motor skills and cognitive recovery; (ii) physiological changes, such as survival rate and body weight; (iii) changes in the neurovascular unit, including blood vessels, microglia, and neurons; and (iv) changes in immune cells. Photothrombotic stroke (or sham surgery) was induced in adult male mice. From 24 h post-stroke, mice were treated daily for 14 days with either clopidogrel or a control. Cognitive performance (memory and learning) was assessed using a mouse touchscreen platform (paired associated learning task), while motor impairment was assessed using the cylinder task for paw asymmetry. On day 15, the mice were euthanized and their brains were collected for immunohistochemistry analysis. Clopidogrel administration significantly impaired learning and memory recovery, reduced mouse survival rates, and reduced body weight post-stroke. Furthermore, clopidogrel significantly increased vascular leakage, significantly increased the number and appearance of microglia, and significantly reduced the number of T cells within the peri-infarct region post-stroke. These data suggest that clopidogrel hampers cognitive performance post-stroke. This effect is potentially mediated by an increase in vascular permeability post-stroke, providing a pathway for clopidogrel to access the central nervous system, and thus, interfere in repair and recovery processes.
Current Review of Increasing Animal Health Threat of Per- and Polyfluoroalkyl Substances (PFAS): Harms, Limitations, and Alternatives to Manage Their Toxicity
Authors: Peritore Alessio Filippo , Gugliandolo Enrico , Cuzzocrea Salvatore , Crupi Rosalia , Britti Domenico
Published: July 2023

Perfluorinated and polyfluorinated alkyl substances (PFAS), more than 4700 in number, are a group of widely used man-made chemicals that accumulate in living things and the environment over time. They are known as “forever chemicals” because they are extremely persistent in our environment and body. Because PFAS have been widely used for many decades, their presence is evident globally, and their persistence and potential toxicity create concern for animals, humans and environmental health. They can have multiple adverse health effects, such as liver damage, thyroid disease, obesity, fertility problems, and cancer. The most significant source of living exposure to PFAS is dietary intake (food and water), but given massive industrial and domestic use, these substances are now punctually present not only domestically but also in the outdoor environment. For example, livestock and wildlife can be exposed to PFAS through contaminated water, soil, substrate, air, or food. In this review, we have analyzed and exposed the characteristics of PFAS and their various uses and reported data on their presence in the environment, from industrialized to less populated areas. In several areas of the planet, even in areas far from large population centers, the presence of PFAS was confirmed, both in marine and terrestrial animals (organisms). Among the most common PFAS identified are undoubtedly perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA), two of the most widely used and, to date, among the most studied in terms of toxicokinetics and toxicodynamics. The objective of this review is to provide insights into the toxic potential of PFAS, their exposure, and related mechanisms.
Peripheral Inflammatory Markers in Autism Spectrum Disorder and Attention Deficit/Hyperactivity Disorder at Adolescent Age
Authors: Ferencova Nikola , Visnovcova Zuzana , Ondrejka Igor , Hrtanek Igor , Bujnakova Iveta , Kovacova Veronika , Macejova Andrea , Tonhajzerova Ingrid
Published: July 2023

Autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) are associated with immune dysregulation. We aimed to estimate the pro- and anti-inflammatory activity/balance in ASD and ADHD patients at a little-studied adolescent age with respect to sex. We evaluated 20 ASD patients (5 girls, average age: 12.4 ± 1.9 y), 20 ADHD patients (5 girls, average age: 13.4 ± 1.8 y), and 20 age- and gender-matched controls (average age: 13.2 ± 1.9 y). The evaluated parameters included (1) white blood cells (WBCs), neutrophils, monocytes, lymphocytes, platelets, platelet distribution width (PDW), mean platelet volume, and derived ratios, as well as (2) cytokines—interferon-gamma, interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, and IL-10, tumor necrosis factor-alpha (TNF-α), and derived profiles and ratios. ASD adolescents showed higher levels of WBC, monocytes, IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, and IL-10, macrophages (M)1 profile, and anti-inflammatory profile than the controls, with ASD males showing higher monocytes, IL-6 and IL-10, anti-inflammatory profile, and a lower T-helper (Th)1/Th2+T-regulatory cell ratio than control males. The ADHD adolescents showed higher levels of PDW, IL-1β and IL-6, TNF-α, M1 profile, proinflammatory profile, and pro-/anti-inflammatory ratio than the controls, with ADHD females showing a higher TNF-α and pro-/anti-inflammatory ratio than the control females and ADHD males showing higher levels of IL-1β and IL-6, TNF-α, and M1 profile than the control males. Immune dysregulation appeared to be different for both neurodevelopmental disorders in adolescence.
CRK12: A Key Player in Regulating the Phaseolus vulgaris-Rhizobium tropici Symbiotic Interaction
Authors: Lecona Antonino M. , Nanjareddy Kalpana , Blanco Lourdes , Piazza Valeria , Vera-Núñez José Antonio , Lara Miguel , Arthikala Manoj-Kumar
Published: July 2023

Cysteine-rich receptor-like kinases (CRKs) are a type of receptor-like kinases (RLKs) that are important for pathogen resistance, extracellular reactive oxygen species (ROS) signaling, and programmed cell death in plants. In a previous study, we identified 46 CRK family members in the Phaseolus vulgaris genome and found that CRK12 was highly upregulated under root nodule symbiotic conditions. To better understand the role of CRK12 in the Phaseolus–Rhizobia symbiotic interaction, we functionally characterized this gene by overexpressing (CRK12-OE) and silencing (CRK12-RNAi) it in a P. vulgaris hairy root system. We found that the constitutive expression of CRK12 led to an increase in root hair length and the expression of root hair regulatory genes, while silencing the gene had the opposite effect. During symbiosis, CRK12-RNAi resulted in a significant reduction in nodule numbers, while CRK12-OE roots showed a dramatic increase in rhizobial infection threads and the number of nodules. Nodule cross sections revealed that silenced nodules had very few infected cells, while CRK12-OE nodules had enlarged infected cells, whose numbers had increased compared to controls. As expected, CRK12-RNAi negatively affected nitrogen fixation, while CRK12-OE nodules fixed 1.5 times more nitrogen than controls. Expression levels of genes involved in symbiosis and ROS signaling, as well as nitrogen export genes, supported the nodule phenotypes. Moreover, nodule senescence was prolonged in CRK12-overexpressing roots. Subcellular localization assays showed that the PvCRK12 protein localized to the plasma membrane, and the spatiotemporal expression patterns of the CRK12-promoter::GUS-GFP analysis revealed a symbiosis-specific expression of CRK12 during the early stages of rhizobial infection and in the development of nodules. Our findings suggest that CRK12, a membrane RLK, is a novel regulator of Phaseolus vulgaris-Rhizobium tropici symbiosis.
Bifidobacterium infantis-Mediated Herpes Simplex Virus-TK/Ganciclovir Treatment Inhibits Cancer Metastasis in Mouse Model
Authors: Wang Changdong , Shen Yanxi , Ma Yongping
Published: July 2023

Previous studies have found that Bifidobacterium infantis-mediated herpes simplex virus-TK/ganciclovir (BF-TK/GCV) reduces the expression of VEGF and CD146, implying tumor metastasis inhibition. However, the mechanism by which BF-TK/GCV inhibits tumor metastasis is not fully studied. Here, we comprehensively identified and quantified protein expression profiling for the first time in gastric cancer (GC) cells MKN−45 upon BF-TK/GCV treatment using quantitative proteomics. A total of 159 and 72 differential expression proteins (DEPs) were significantly changed in the BF-TK/GCV/BF-TK and BF-TK/GCV/BF/GCV comparative analysis. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis enriched some metastasis-related pathways such as gap junction and cell adhesion molecules pathways. Moreover, the transwell assay proved that BF-TK/GCV inhibited the invasion and migration of tumor cells. Furthermore, immunohistochemistry (IHC) demonstrated that BF-TK/GCV reduced the expression of HIF−1α, mTOR, NF-κB1-p105, VCAM1, MMP13, CXCL12, ATG16, and CEBPB, which were associated with tumor metastasis. In summary, BF-TK/GCV inhibited tumor metastasis, which deepened and expanded the understanding of the antitumor mechanism of BF-TK/GCV.
Comparative Study of FSW, MIG, and TIG Welding of AA5083-H111 Based on the Evaluation of Welded Joints and Economic Aspect
Authors: Habba Mohamed I. A. , Alsaleh Naser A. , Badran Takwa E. , El-Sayed Seleman Mohamed M. , Ataya Sabbah , El-Nikhaily Ahmed E. , Abdul-Latif Akrum , Ahmed Mohamed M. Z.
Published: July 2023

Selecting an economically suitable welding technique and optimizing welding parameters to obtain high joint quality is considered a challenge for expanding the 5xxx aluminum alloy series in various industrial applications. This work aims to investigate the effect of applying different welding techniques, tungsten inert gas (TIG) and metal inert gas (MIG), as fusion welding processes compared to friction stir welding (FSW), a solid-state joining process, on the joint performance of the produced 5 mm thick similar AA5083-H111 butt weldments at different welding conditions. Different methods were used to evaluate the quality of the produced joints, including visual inspection, radiographic testing (RT), and macrostructure evaluation, in addition to hardness and tensile tests. The fracture surface of the tensile-failed specimens was also investigated using a scanning electron microscope (SEM). Furthermore, the current study ended with an economic analysis of the welding techniques used. The results showed that, for the friction stir-welded joints, the radiographic films revealed defect-free joints at the two applied travel speeds of 100 mm/min and 400 mm/min and a constant tool rotating speed of 400 rpm. In addition, only one joint was welded by MIG at a welding current of 130 Amp, with a 19 L/min flow rate of pure argon. In contrast, the radiographic films showed internal defects such as lack of fusion (LOF), lack of penetration (LOP), and porosity (P) for the two joints welded by TIG and one joint welded by MIG. The hardness of the welded joints was enhanced over the AA5083-H111 base material (BM) by 24–29, 31–35, and 46–50% for the MIG, TIG, and FSW joints, respectively. The maximum ultimate tensile strength was obtained for the FSW joint welded at a 400 mm/min travel speed. Adopting FSW in shipbuilding applications can further produce the AA5083-H11 joints with higher quality and efficiency than fusion welding techniques such as MIG and TIG processes. In addition, time and cost comparisons between TIG, MIG, and FSW were performed for five-millimeter-thick and one-meter-long AA5083-H111.
Effect of Cold Pressing Deformation on Microstructure and Residual Stress of 7050 Aluminum Alloy Die Forgings
Authors: Li Huiqu , Wang Liang , He Weiwei , Cheng Liqiang , Chen Junzhou , Yi Linna
Published: July 2023

Large-scale, high-strength aluminum alloy forgings are essential components in the aerospace industry, with benefits including increasing strength and decreasing weight. Accurate shape-property control is the secret to forging quality. This study uses the alloy 7050 to experimentally evaluate the parametric influence of cold compression on residual stress and mechanical characteristics. The evolutions of mechanical properties, microstructure and residual stress are theoretically studied using various cold compression strains from 1% to 5% on an equivalent part, of which the results are further applied on a complicated rib-structured die forging. It is demonstrated that increasing the compression strain reduces the tensile strength of the material, but has little impact on conductivity and fracture toughness. According to the TEM results, compression also encourages the precipitation and growth of precipitated phases, particularly in positions with high dislocation densities after aging. Cold compression significantly reduces residual stress; nevertheless, as compression strain increases, residual stress first decreases and then increases. With the use of rib-structured forging, it is observed that the compression strain for 7050 aluminum alloy ranges from 2% to 4%, and the combined pressing method of the rib and web improves the uniformity of residual stress.
Event-Triggered Robust State Estimation for Nonlinear Networked Systems with Measurement Delays against DoS Attacks
Authors: Wang Min , Liu Huabo
Published: July 2023

In this paper, we focus on the event-triggered robust state estimation problems for nonlinear networked systems with constant measurement delays against denial-of-service (DoS) attacks. The computation of the extended Kalman filter (EKF) generates errors of linearization approximations, which can result in increased state estimation errors, and subsequently amplifies the linearization errors. DoS attacks interfere with the transmission of measurements sent to the remote robust state estimator by overloading the communication networks, while the communication rate of the communication channel is constrained. Therefore, an event-triggered robust state estimation algorithm based on sensitivity penalization with an explicit packet arrival parameter is derived to defend against DoS attacks and linearization errors. Meanwhile, the presence of measurement delays precludes the direct use of conventional state estimation algorithms, prompting us to devise an innovative state augmentation method. The results of the numerical simulations show that the proposed robust state estimator can appreciably improve the accuracy of state estimation.
Adoption and Use of the NHS App in England: a mixed-methods evaluation
Authors: KC Sukriti , Reidy Claire , Laverty Anthony A , Papoutsi Chrysanthi , Powell John , Tewolde Salina , Costelloe Céire , Gudgin Bernard , Greaves Felix
Published: July 2023

Background

The NHS App was launched as a ‘front door’ to digitally enabled health services, offering a range of services including appointment booking and ordering prescriptions. The extent of App use and its impacts on digital inclusion is under-explored.

Aim

To evaluate patterns of App uptake and adoption among different population groups.

Method

Interrupted time series analyses explored aggregate monthly App usage from January 2019 - May 2021. Regression model assessed differences in App registration by markers of GP level socio-demographic variables. Qualitative interviews and focus groups involving 83 participants were conducted and analysed thematically.

Results

There were 8,524,882 App downloads and 4,449,869 registrations. Negative binomial models found 25% less registrations in the most deprived practices (P<0.001) and 44% more registrations in the largest practices (P<0.001). Registration was 36% more in practices with the highest percentage of White patients (P<0.001) and 23% more in practices with highest percentage of 15–34-year-olds (P<0.001). In contrast, App registration was 13% less in practices with highest percentage of males (P<0.001) and 2% less in those with highest percentage of people with long-term care needs (P<0.001). Qualitative evaluation found that the App was not perceived as relevant or accessible for all and there are important cultural considerations (for example, language barriers and some restrictions in symptom checking for non-White skin). However, it can enable patients to hold services accountable.

Conclusion

There is high uptake of the NHS App but there are differences in adoption rates among different population groups and issues of relevance and accessibility, that warrant further work.
Transición energética y litio nuevos “comunes” y otros extractivismos
Authors: Montalván Zambrano Digno Jose , Wences Isabel
Published: July 2023

Este trabajo presenta las nuevas formas de extractivismo asociadas al discurso de la transición energética formulado por el Norte Global. En específico, estudia como la creciente demanda de litio está generando sobre América Latina diversos “impactos locales” y “efectos derrame”, especialmente, sobre pueblos indígenas. En sintonía con lo anterior, problematizamos el uso de narrativas que pretenden consagrar a los elementos necesarios para la producción, distribución y almacenamiento de la energía renovable como bienes comunes globales o materias primas críticas. Postulamos, en línea con diversos estudios en la materia, que detrás de estos términos aparentemente contra hegemónicos, pueden esconderse intereses corporativos, propios del capitalismo verde, dirigidos a desterritorializar los conflictos y a garantizar el suministro de lo que, desde el Norte Global, se denominan materias primas fundamentales para la industria de las tecnologías renovables.
EXPRESS METHOD FOR DETERMINATION OF BIODIESEL FUEL IN MIXED FUEL BY THIN LAYER CHROMATOGRAPHY
Authors:   Tambov State University named after G.R. Derzhavin, Romantsova Svetlana , Gladysheva Irina ,   Tambov State University named after G.R. Derzhavin, Vervekina Natalia ,   Tambov State University named after G.R. Derzhavin, Nagornov Stanislav ,   All-Russian Research Institute for the Use of Machinery and Petroleum Products in Agriculture, Lixutina Anna ,   All-Russian Research Institute for Use of Machinery and Petroleum Products in Agriculture
Published: July 2023

Biodiesel fuel (BF) can be an additive to diesel fuel used in agricultural production to increase the cetane number and lubricating properties. Such an additive can be biodiesel fuel. Regulations allow the addition of 7% BF to petroleum fuels. An express method that allows the consumer to quickly determine its presence was developed. The possibility of determining BF in a mixture with petroleum by thin-layer chromatography (TLC) has been studied for the first time. Samples of BF obtained by transesterification of rapeseed, sunflower, linseed, corn, radish and camelina oils were synthesized for this investigation. The solubility of BF in a number of organic solvents was studied for the first time to select the suitable eluent. It has been established that biodiesel fuel is highly soluble not only in non-polar hydrocarbons (benzene, toluene, octane, petroleum ether), but also in chloroform and monohydric alcohols of normal and branched structure (propyl, butyl, isobutyl, and isoamyl alcohols). Biodiesel is insoluble in solvents with a higher dielectric constant (such as acetone or glycerol). The same solvents were investigated as eluents for the separation of fuel oil and biodiesel by thin layer chromatography. It has been shown that alcohols, chloroform and acetone are not suitable as eluents; but it is possible to use toluene. The value of the retardation factor Rf for the main spot of petroleum fuel is 0.86, and for biodiesel fuel is 0.6 (eluent is toluene). It has been established that it is possible to determine the presence of biodiesel fuel synthesized from various types of oils using TLC (eluent is toluene). Also, petroleum ether can be recommended as an eluent for analysis in the field. The TLC method can be used to detect the presence of biodiesel at concentrations from 2% and above.
RESISTANCE TO ROLLING OF WHEELS OF A HARVEST TROLLEY DEPENDING ON THEIR SIZE AND AGROPHONE
Authors:   Bryansk State Agrarian University, Ozherelev Viktor , Somin Valery ,   Bryansk State Agrarian University
Published: July 2023

The use of a special garden cart to move the picker during manual harvesting of strawberries significantly increases labor productivity. At the same time, the choice of the size of its wheels, as a rule, is not associated with the bearing capacity of the soil between rows and rolling resistance. The aim of the study was to identify the relationship between the parameters of the agrophone, the size of the wheels and the resistance to rolling of the trolley. Wheels with a diameter of 300, 400, 500 and 700 mm have been tested. The area of the contact patch on a hard surface at a tire pressure of 160 kPa was taken as a complex characteristic of the wheel. The tests were carried out on four types of agrophone typical for strawberry plantations. The cart was rolled over tinned aisles, aisles covered with straw, over black steam three weeks after processing and compacted with the collectors' feet at the end of the harvesting season. The criterion for assessing the bearing capacity of the soil in the aisles was its hardness at a depth of 20 mm. During the tests, the cart was loaded with ballast weighing 72 kg, simulating the weight of the collector. The force was recorded with an electronic dynamometer DEXP BM-10 (China), with a measurement limit of 500N and a measurement error of 0.5N. The test results were processed in Excel and STATISTICA 10. The regression equations connecting the main process parameters were obtained. It was found that the effect of soil hardness on the final result is 2.7 times higher than the effect of the wheel parameters. At the same time, mulching the row spacing with straw increases the rolling resistance of the wheels by 4.3 - 11.8%, depending on their diameter. Moreover, the difference increases with the growth of the specified parameter.