bluuebunny/crossref_metadata_2025 huggingface dataset:
An Overview of Coacervates: The Special Disperse State of Amphiphilic and Polymeric Materials in Solution
Authors: Moulik Satya Priya , Rakshit Animesh Kumar , Pan Animesh , Naskar Bappaditya
Published: September 2022

Individual amphiphiles, polymers, and colloidal dispersions influenced by temperature, pH, and environmental conditions or interactions between their oppositely charged pairs in solvent medium often produce solvent-rich and solvent-poor phases in the system. The solvent-poor denser phase found either on the top or the bottom of the system is called coacervate. Coacervates have immense applications in various technological fields. This review comprises a concise introduction, focusing on the types of coacervates, and the influence of different factors in their formation, structures, and stability. In addition, their physicochemical properties, thermodynamics of formation, and uses and multifarious applications are also concisely presented and discussed.
An Evaluation of Nutritional and Therapeutic Factors Affecting Pre-Weaned Calf Health and Welfare, and Direct-Fed Microbials as a Potential Alternative for Promoting Performance—A Review
Authors: Davies Sarah J. , Esposito Giulia , Villot Clothilde , Chevaux Eric , Raffrenato Emiliano
Published: September 2022

The priority for calf rearing has been to maintain good health and welfare in order to promote and sustain future production. However, there have been numerous reports of undesirable levels of morbidity and mortality amongst pre-weaned calves. This may be mitigated or exacerbated by nutritional management practices. Some areas of concern include colostrum feeding, utilization of waste milk, and restrictive milk feeding regimes. Antibiotics may be prescribed at lethal or sub-inhibitory doses to treat or prevent disease. However, extensive antibiotic use may disrupt the gastrointestinal microbiota and aid in expanding the antibiotic resistant gene pool. In an attempt to reduce the use of antibiotics, there is a demand to find alternative performance enhancers. Direct-fed microbials, also known as probiotics, may comply with this role. A DFM consists of live microorganisms that are biologically active and able to confer health benefits onto the host. Lactic acid bacteria have been the most frequently investigated; however, this field of research has expanded to include spore-forming bacteria and live yeast preparations. This review aims to provide a comprehensive evaluation of the nutritional management strategies that may increase a calf’s susceptibility to morbidity and mortality, the efficacy and sustainability of antibiotics as a tool for managing calf health and welfare, and the potential for DFMs as a supportive strategy for promoting calf wellbeing.
Diabetic Ketoacidosis Was Associated with High Morbidity and Mortality in Hospitalized Patients with COVID-19 in the NYC Public Health System
Authors: Parthasarathy Sahana , Chamorro-Pareja Natalia , Kharawala Amrin , Hupart Kenneth H , Curcio Joan , Coyle Christina , Buchnea Daniel , Karamanis Dimitris , Faillace Robert , Palaiodimos Leonidas , Kishore Preeti
Published: September 2022

Background: COVID-19 has been associated with a higher risk of death in patients with diabetes mellitus (DM). However, there is a dearth of data regarding the effects of diabetic ketoacidosis (DKA) in these patients. We explored the in-hospital outcomes of patients who presented with COVID-19 and DKA. Methods: A propensity score-matched observational retrospective cohort study was conducted in hospitalized patients with COVID-19 in the public healthcare system of New York City from 1 March 2020 to 31 October 2020. Patients were matched, and a subgroup analysis of patients with DKA and COVID-19 and patients without COVID-19 was conducted. Results: 13,333 (16.0%) patients with COVID-19 and 70,005 (84.0%) without COVID-19 were included in the analysis. The in-hospital mortality rate was seven-fold in patients with DKA and COVID-19 compared to patients with COVID-19 and without DKA (80 (36.5%) vs. 11 (5.4%), p < 0.001). Patients with COVID-19 and DKA had a two-fold higher likelihood for in-hospital death (OR: 1.95; 95% CI: 1.41–2.70; p < 0.001) after adjusting for multiple variables. Conclusions: DKA was associated with significantly higher in-hospital mortality in hospitalized patients with COVID-19.
A High-Precision and Low-Cost Broadband LEO 3-Satellite Alternate Switching Ranging/INS Integrated Navigation and Positioning Algorithm
Authors: Ye Lvyang , Gao Ning , Yang Yikang , Li Xue
Published: September 2022

To solve the problem of location services in harsh environments, we propose an integrated navigation algorithm based on broadband low-earth-orbit (LEO) satellite communication and navigation integration with 3-satellite alternate switch ranging. First, we describe the algorithm principle and processing flow in detail; next, we analyze and model the ranging error source and propose a combined multipath and non-line-of-sight (NLOS) error analysis model, which avoids discussing the complex multipath number of paths and its modeling process; in addition, we also propose a multimodal Gaussian noise-based interference model and analyze and model the LEO satellite orbital disturbance. The final simulation results show that our proposed algorithm can not only effectively overcome inertial navigation system (INS) divergence, but also achieve high positioning accuracy, especially when continuous ranging values are used. It can still ensure good anti-interference performance and robustness in terms of path and noise interference and by alternately switching ranging, there are other potential advantages. Compared to some of the existing representative advanced algorithms, it has higher accuracy, stronger stability and lower cost. Furthermore, it can be used as a location reference solution for real-time location services and life search and rescue in harsh environments with incomplete visual satellites and can also be used as a technical reference design solution for the future integration of communication and navigation (ICN).
Medium-Scale UAVs: A Practical Control System Considering Aerodynamics Analysis
Authors: Ale Isaac Mohammad Sadeq , Luna Marco Andrés , Ragab Ahmed Refaat , Ale Eshagh Khoeini Mohammad Mehdi , Kalra Rupal , Campoy Pascual , Flores Peña Pablo , Molina Martin
Published: September 2022

Unmanned aerial vehicles (UAVs) have drawn significant attention from researchers over the last decade due to their wide range of possible uses. Carrying massive payloads concurrent with light UAVs has broadened the aeronautics context, which is feasible using powerful engines; however, it faces several practical control dilemmas. This paper introduces a medium-scale hexacopter, called the Fan Hopper, alimenting Electric Ducted Fan (EDF) engines to investigate the optimum control possibilities for a fully autonomous mission carrying a heavy payload, even of liquid materials, considering calculations of higher orders. Conducting proper aerodynamic simulations, the model is designed, developed, and tested through robotic Gazebo simulation software to ensure proper functionality. Correspondingly, an Ardupilot open source autopilot is employed and enhanced by a model reference adaptive controller (MRAC) for the attitude loop to stabilize the system in case of an EDF failure and adapt the system coefficients when the fluid payload is released. Obtained results reveal less than a 5% error in comparison to desired values. This research reveals that tuned EDFs function dramatically for large payloads; meanwhile, thermal engines could be substituted to maintain much more flight endurance.
Sociodemographic and Digital Education Factors Are Associated to General Health, Coping Strategies, and Academic Outcomes of Undergraduate Students during the Post-Pandemic Period
Authors: Tinella Luigi , Tinterri Andrea , Dipace Anna , Ladogana Manuela , Loiodice Isabella , Bosco Andrea
Published: September 2022

The COVID-19 pandemic suddenly and forever changed the lives of many undergraduate students around the globe, forcing them to switch to online learning while undergoing social confinement within their homes. It is now well-established that this prolonged period of uncertainty impacted students’ well-being, health, and academic achievement. However, how student-related factors, such as coping strategies as well as sociodemographic, contextual, and technological variables, are linked to digital education factors is currently less understood. Using multiple regression analysis, this study investigates the results of an online questionnaire administered to students from two universities in southern Italy, differing in positioning and size, as well as policies and attitude towards digital learning. The results of this study show the positive effects of expertise with digital devices and university digital learning policies on students’ perceived general health. Conversely, isolation and lack of relational connectedness negatively impacted students’ health. Furthermore, this study highlights the role of different coping strategies, demonstrating that active forms of coping have a positive effect on students’ health, whereas avoidance strategies have the opposite effect. Taken together, this study provides crucial links between the many factors influencing students’ experience with online learning and health, and provides useful indications to promote the uptake of and adaptation to online learning.
Hydrothermal Carbonization Process of Digestate from Sewage Sludge: Chemical and Physical Properties of Hydrochar in Terms of Energy Application
Authors: Wilk Małgorzata , Gajek Marcin , Śliz Maciej , Czerwińska Klaudia , Lombardi Lidia
Published: September 2022

Hydrochars (HTCD) derived from digestates, namely D1 and D2 (from two plants) of sewage sludge, were examined with respect to their fuel properties. The hydrothermal carbonization (HTC) tests were performed at temperatures of 200 and 220 °C, for 2 and 4 h of residence times, and with 1:10 and 1:8 digestate to water ratios (D/W), causing an increase of ash content (max. 55.8%), and a decrease c.a. 20% of the higher heating value except for a slight increase to 15 kJ/kg at 200 °C and 4 h in hydrochars. Conversely, the combustion profiles of hydrochars moved towards higher temperatures (225–257 °C) and finished earlier at lower temperatures (423–438 °C). The HTCD from D1 and D2 showed very similar properties under the same conditions (200 °C, 4 h, 1:8 D/W) for combustion characteristic temperatures, indices and profiles. The best efficiency was found for HTCD2. In addition, the polluted post-processing liquid phase was treated by a distillation process providing 30% higher pH, 50% lower BOD values, up to 15 times lower COD values, and c.a. three times lower conductivity.
Research on Interruption Performance of Environmentally Friendly C4F7N Mixed-Gas-Insulated Switchgear
Authors: Bian Chenxi , He Baina , Lin Xin , Liu Yujia , Lou Hui , Kong Lingzhe , Dai Xueting , Wu Shuo , Meng Fantao , Liu Yang
Published: September 2022

SF6, which is currently widely used in gas-insulated power transmission equipment, is a greenhouse gas with a very strong greenhouse effect. Therefore, developing environmentally friendly gas insulation equipment to gradually reduce the use of SF6 has become a hot research topic. As the most potential alternative gas, C4F7N is of great significance to study the electrical characteristics of the medium-voltage switching field to promote the green development of the power industry. Based on multi-physical field coupling to construct the 40.5 kV circuit breaker mode, this paper uses C4F7N/CO2 mixed gas to compare and study the dynamic characteristics of a C4F7N/CO2 mixed gas circuit breaker when breaking the short-circuit current and the dielectric recovery strength with no-load breaking, as well as to evaluate the electrical performance of C4F7N mixed gas in a 40.5 kV breaker with the gas breakdown criterion. The results show that mixing O2 in a high current can improve the breaking performance of an environmental protection circuit breaker and increasing the C4F7N mass fraction can enhance the dielectric recovery strength of the environmentally friendly circuit breaker. Considering the overall performance of the gas, the 5%C4F7N/90% CO2/5%O2 mixed gas has some alternative potential.
The Thermal Comfort Problem in Public Space during the Climate Change Era Based on the Case Study of Selected Area in Lublin City in Poland
Authors: Przesmycka Natalia , Kwiatkowski Bartłomiej , Kozak Małgorzata
Published: September 2022

Noticeable climate change in recent years is reducing the comfort of public spaces in the urban environment, and is becoming an element of urban policies. The adaptation to climate change requires the development of new design guidelines for the development of public spaces. The appropriate definition of development density, choice of building materials, technologies, planting species, and the used directions is a challenge that depends on local conditions. A representative public space located in the area of a multi-family housing estate built in the second half of the 20th century in Lublin (Poland) was selected for the study. The space has undergone redevelopment twice in the last 10 years. The aim of the study was to determine to what extent the executed and designed changes actually improve the thermal comfort of users. Quantitative and qualitative indicators of the successive phases of the investment were analyzed in the context of projected climate change. The simulation was developed using the ENVI-met version 5.0 software. As a result of the changes made, there has been an improvement in usability and comfort. Five simulations were carried out for the warmest day of the year for one of the public spaces in the city of Lublin. The sensation of PET thermal comfort was investigated for people aged 35 and 75, as a particularly sensitive group. The obtained result proved that the elderly feel higher temperature rates than younger people. In one of the simulations, new plantings were proposed to improve the local microclimate. The material temperatures of paved surfaces were also investigated. The article shows how the local microclimate and people’s desire to stay in a given space can be improved with new tree planting.
An Asynchronous AAA Blockchain-Based Protocol for Configuring Information Systems
Authors: Bajor Michał , Niemiec Marcin
Published: September 2022

The increasing number of security breaches in centralized systems provides the necessity to introduce decentralization in more fields. The Blockchain is a widely utilized decentralization technology that is implemented in various industries. Therefore, this technology can be used to protect sensitive services, such as those associated with the configuration changing of information systems. This article proposes a new protocol operating as a decentralization layer over any configuration scheme. It uses smart contracts—programs existing on the Blockchain—to keep track of configuration proposals and authorize new configurations. The configuration change can be proposed at any time. However, only once it is authorized by appropriate parties can it be introduced to the system. The new protocol provides an additional security layer, ensuring that every action is accounted for and authenticated. Furthermore, it enforces that administrators authorize every change. The protocol was designed to be flexible and easily adaptable to scenarios that did not use distributed ledger technology before. It uses the HTTP protocol with the JSON standard for protocol messages to allow easier adoption and transparency. The features of the proposed protocol were analyzed from a security point of view as well as from the financial perspective related to costs of using Blockchain technology. Security analysis shows that the protocol is resilient to the most common security risks that haunt state-of-the-art IT systems. Additionally, the authors proved that this solution could be implemented in both private and public Blockchains. A reference implementation was shared in a public repository. The proposed protocol was also compared with the most similar state-of-the-art work in the academic research highlighting the key differences and improvements.
Polycomb Directed Cell Fate Decisions in Development and Cancer
Authors: German Beatriz , Ellis Leigh
Published: September 2022

The polycomb group (PcG) proteins are a subset of transcription regulators highly conserved throughout evolution. Their principal role is to epigenetically modify chromatin landscapes and control the expression of master transcriptional programs to determine cellular identity. The two mayor PcG protein complexes that have been identified in mammals to date are Polycomb Repressive Complex 1 (PRC1) and 2 (PRC2). These protein complexes selectively repress gene expression via the induction of covalent post-translational histone modifications, promoting chromatin structure stabilization. PRC2 catalyzes the histone H3 methylation at lysine 27 (H3K27me1/2/3), inducing heterochromatin structures. This activity is controlled by the formation of a multi-subunit complex, which includes enhancer of zeste (EZH2), embryonic ectoderm development protein (EED), and suppressor of zeste 12 (SUZ12). This review will summarize the latest insights into how PRC2 in mammalian cells regulates transcription to orchestrate the temporal and tissue-specific expression of genes to determine cell identity and cell-fate decisions. We will specifically describe how PRC2 dysregulation in different cell types can promote phenotypic plasticity and/or non-mutational epigenetic reprogramming, inducing the development of highly aggressive epithelial neuroendocrine carcinomas, including prostate, small cell lung, and Merkel cell cancer. With this, EZH2 has emerged as an important actionable therapeutic target in such cancers.
Informal Caregivers’ Health Literacy in Lisbon, Portugal: A Profile for Health Promotion Prioritization
Authors: Costa Andreia , Loura David de Sousa , Nogueira Paulo , Melo Graça , Gomes Idalina , Ferraz Isabel , Viegas Laura , Henriques Maria Adriana
Published: September 2022

Health literacy (HL) allows people to access, understand and evaluate health information. Informal caregivers’ levels of HL may impact long-term care outcomes. ‘Informal caregivers’ profile in Lisbon county: a health community approach’ is a nurse-led research project aiming to assess informal caregivers’ health literacy and associated factors in Lisbon county, as well as to foster the development of a local-specific health literacy strategy. A survey to identify a health/social caregiver profile, including questions about HL (HLS-EU-PT), was submitted to a representative sample of carers. Descriptive and bivariate inferential analysis was developed. Informal caregivers’ level of HL was mostly sufficient (n = 99, 38%). More than 60% of caregivers have limited HL regarding health promotion. ‘Access’, ‘Appraisal’ and ‘Use’ are the information processing stages with lower mean scores of HL. Carers with low HL levels appear to be older and to have less education, low knowledge of community resources and decreased wellbeing (p < 0.05). A strategy focused on health promotion-related HL through primary care resources can potentially improve caregivers’ knowledge, competencies and motivation, as well as health system sustainability. Reported HLS-EU-PT scores deserve special attention. Future work should emphasize the role of HL-associated factors and health outcomes for caregivers and cared-for persons.
Use of Patient-Reported Data within the Acute Healthcare Context: A Scoping Review
Authors: Kynoch Kathryn , Ameen Mary , Ramis Mary-Anne , Khalil Hanan
Published: September 2022

Patient-reported outcome measures (PROMs), patient-reported experience measures (PREMs) and patient satisfaction surveys provide important information on how care can be improved. However, data collection does not always translate to changes in practice or service delivery. This scoping review aimed to collect, map and report on the use of collected patient-reported data used within acute healthcare contexts for improvement to care or processes. Using JBI methods, an extensive search was undertaken of multiple health databases and trial registries for published and unpublished studies. The concepts of interest included the types and characteristics of published patient experience and PROMs research, with a specific focus on the ways in which data have been applied to clinical practice. Barriers and facilitators to the use of collected data were also explored. From 4057 records, 86 papers were included. Most research was undertaken in North America, Canada or the UK. The Hospital Consumer Assessment of Healthcare Providers and Systems tool (HCAHPS) was used most frequently for measuring patient satisfaction. Where reported, data were applied to improve patient-centred care and utilization of health resources. Gaps in the use of patient data within hospital services are noticeable. Engaging management and improving staff capability are needed to overcome barriers to implementation.
The Effectiveness of Pharmacist Interventions in the Management of Patient with Renal Failure: A Systematic Review and Meta-Analysis
Authors: Jasińska-Stroschein Magdalena
Published: September 2022

The existing trials have focused on a variety of interventions to improve outcomes in renal failure; however, quantitative evidence comparing the effect of performing multidimensional interventions is scarce. The present paper reviews data from previous randomized controlled trials (RCTs), examining interventions performed for patients with chronic kidney disease (CKD) and transplants by multidisciplinary teams, including pharmacists. Methods: A systematic search with quality assessment was performed using the revised Cochrane Collaboration’s ‘Risk of Bias’ tool. Results and Conclusion: Thirty-three RCTs were included in the review, and the data from nineteen protocols were included in further quantitative analyses. A wide range of outcomes was considered, including those associated with progression of CKD, cardiovascular risk factors, patient adherence, quality of life, prescription of relevant medications, drug-related problems (DRPs), rate of hospitalizations, and death. The heterogeneity between studies was high. Despite low-to-moderate quality of evidence and relatively short follow-up, the findings suggest that multidimensional interventions, taken by pharmacists within multidisciplinary teams, are important for improving some clinical outcomes, such as blood pressure, risk of cardiovascular diseases and renal progression, and they improve non-adherence to medication among individuals with renal failure.
Does Trauma Exacerbate Criminal Behavior? An Exploratory Study of Child Maltreatment and Chronic Offending in a Sample of Chinese Juvenile Offenders
Authors: Yao Xuening , Zhang Hongwei , Zhao Ruohui
Published: September 2022

(1) Background: Maltreated children are at increased risk for juvenile delinquency. Extant research has explored the effect of child maltreatment on either the initial risk of juvenile delinquency or general juvenile recidivism. However, little is known regarding the effect of child maltreatment on chronic offending. (2) Methods: Using a sample of 695 male juvenile offenders incarcerated in a centralized juvenile reformatory of the province X located in Southwest China, this study investigates both the prevalence of child maltreatment and the effect of child maltreatment on chronic offending among the juvenile offenders. Descriptive statistical analyses and multinomial logistic regression were utilized to conduct the analyses. (3) Results: A vast majority of the juvenile offenders experienced at least one type of child maltreatment. Moreover, maltreatment was generally found to be more prevalent in chronic offenders than in one-time offenders and recidivists. Results from a series of logistic regression analyses revealed that among five specific maltreatment types, only physical abuse exerted a statistically significant and positive impact on chronic offending. (4) Conclusions: The findings highlight the importance of providing early prevention and intervention programs to juvenile offenders who were physically abused in order to reduce general chronic offending as well as chronic violent offending.
Correction: Lim et al. Patient-Reported Questionnaires to Identify Adverse Drug Reactions: A Systematic Review. Int. J. Environ. Res. Public Health 2021, 18, 11877
Authors: Lim Renly , Ellett Lisa Kalisch , Roughead Elizabeth E. , Cheah Phaik Yeong , Masnoon Nashwa
Published: September 2022

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Anti-Inflammatory Effect of Sparstolonin B through Inhibiting Expression of NF-κB and STAT-1
Authors: Kim Nayeon , Kim Chaeyeong , Ryu Soo Ho , Kim Go Oun , Bae Jong-Sup
Published: September 2022

Sparstolonin B (SsnB), which is found in Sparganium stoloniferum, prevents the synthesis of inflammatory mediators and is related to functional pathways of survival. In this study, we assessed the possible protective functions of SsnB on lipopolysaccharide (LPS)-induced inflammatory responses. We determined the functions of SsnB on controlling heme oxygenase (HO)-1, cyclooxygenase (COX-)2, and inducible nitric oxide synthase (iNOS) in LPS-activated human umbilical vein endothelial cells (HUVECs). Furthermore, the distinct function of SsnB on the expression of iNOS and well-known pro-inflammatory mediators, such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β, were assessed in the pulmonary histological status of LPS-injected mice. SsnB upregulated the HO-1 production, inhibited luciferase-NF-κB interaction, and lowered COX-2/PGE2 and iNOS/NO, which lead to the reduction of STAT-1 phosphorylation. Moreover, SsnB enhanced the nuclear translocation of Nrf2, elevated the binding activity between Nrf2 and antioxidant response elements (AREs), and weakened IL-1β expression on LPS-treated HUVECs. SsnB-suppressed iNOS/NO synthesis was restored by the process of the RNAi inhibition of HO-1. In experiment with an LPS-injected animal model, SsnB remarkably decreased the iNOS expression in the pulmonary biostructure and TNF-α level in the bronchoalveolar lavage fluid (BALF). Therefore, these results demonstrate that SsnB is responsible for inflammation ameliorative activity by controlling iNOS through inhibition of both NF-κB expression and p-STAT-1. Therefore, SsnB could be a candidate for promoting novel clinical substances to remedy pathologic inflammation.
Nutritional Component Analyses in Different Varieties of Actinidia eriantha Kiwifruit by Transcriptomic and Metabolomic Approaches
Authors: Jia Huimin , Tao Junjie , Zhong Wenqi , Jiao Xudong , Chen Shuangshuang , Wu Mengting , Gao Zhongshan , Huang Chunhui
Published: September 2022

Actinidia eriantha is a unique germplasm resource for kiwifruit breeding. Genetic diversity and nutrient content need to be evaluated prior to breeding. In this study, we looked at the metabolites of three elite A. eriantha varieties (MM-11, MM-13 and MM-16) selected from natural individuals by using a UPLC-MS/MS-based metabolomics approach and transcriptome, with a total of 417 metabolites identified. The biosynthesis and metabolism of phenolic acid, flavonoids, sugars, organic acid and AsA in A. eriantha fruit were further analyzed. The phenolic compounds accounted for 32.37% of the total metabolites, including 48 phenolic acids, 60 flavonoids, 7 tannins and 20 lignans and coumarins. Correlation analysis of metabolites and transcripts showed PAL (DTZ79_15g06470), 4CL (DTZ79_26g05660 and DTZ79_29g0271), CAD (DTZ79_06g11810), COMT (DTZ79_14g02670) and FLS (DTZ79_23g14660) correlated with polyphenols. There are twenty-three metabolites belonging to sugars, the majority being sucrose, glucose arabinose and melibiose. The starch biosynthesis-related genes (AeglgC, AeglgA and AeGEB1) were expressed at lower levels compared with metabolism-related genes (AeamyA and AeamyB) in three mature fruits of three varieties, indicating that starch was converted to soluble sugar during fruit maturation, and the expression level of SUS (DTZ79_23g00730) and TPS (DTZ79_18g05470) was correlated with trehalose 6-phosphate. The main organic acids in A. eriantha fruit are citric acid, quinic acid, succinic acid and D-xylonic acid. Correlation analysis of metabolites and transcripts showed ACO (DTZ79_17g07470) was highly correlated with citric acid, CS (DTZ79_17g00890) with oxaloacetic acid, and MDH1 (DTZ79_23g14440) with malic acid. Based on the gene expression, the metabolism of AsA acid was primarily through the L-galactose pathway, and the expression level of GMP (DTZ79_24g08440) and MDHAR (DTZ79_27g01630) highly correlated with L-Ascorbic acid. Our study provides additional evidence for the correlation between the genes and metabolites involved in phenolic acid, flavonoids, sugars, organic acid and AsA synthesis and will help to accelerate the kiwifruit molecular breeding approaches.
Single-Step Genome Editing of Small Ruminant Embryos by Electroporation
Authors: Mahdi Ahmed K. , Medrano Juan F. , Ross Pablo J.
Published: September 2022

We investigated the possibility of single-step genome editing in small ruminants by CRISPR-Cas9 zygote electroporation. We targeted SOCS2 and PDX1 in sheep embryos and OTX2 in goat embryos, utilizing a dual sgRNA approach. Gene editing efficiency was compared between microinjection and three different electroporation settings performed at four different times of embryo development. Electroporation of sheep zygotes 6 h after fertilization with settings that included short high-voltage (poring) and long low-voltage (transfer) pulses was efficient at producing SOCS2 knock-out blastocysts. The mutation rate after CRISPR/Cas9 electroporation was 95.6% ± 8%, including 95.4% ± 9% biallelic mutations; which compared favorably to 82.3% ± 8% and 25% ± 10%, respectively, when using microinjection. We also successfully disrupted the PDX1 gene in sheep and the OTX2 gene in goat embryos. The biallelic mutation rate was 81 ± 5% for PDX1 and 85% ± 6% for OTX2. In conclusion, using single-step CRISPR-Cas9 zygote electroporation, we successfully introduced biallelic deletions in the genome of small ruminant embryos.
ZBP1: A Powerful Innate Immune Sensor and Double-Edged Sword in Host Immunity
Authors: Hao Yu , Yang Bo , Yang Jinke , Shi Xijuan , Yang Xing , Zhang Dajun , Zhao Dengshuai , Yan Wenqian , Chen Lingling , Zheng Haixue , Zhang Keshan , Liu Xiangtao
Published: September 2022

Z-conformation nucleic acid binding protein 1 (ZBP1), a powerful innate immune sensor, has been identified as the important signaling initiation factor in innate immune response and the multiple inflammatory cell death known as PANoptosis. The initiation of ZBP1 signaling requires recognition of left-handed double-helix Z-nucleic acid (includes Z-DNA and Z-RNA) and subsequent signaling transduction depends on the interaction between ZBP1 and its adapter proteins, such as TANK-binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), receptor-interacting serine/threonine-protein kinase 1 (RIPK1), and RIPK3. ZBP1 activated innate immunity, including type-I interferon (IFN-I) response and NF-κB signaling, constitutes an important line of defense against pathogenic infection. In addition, ZBP1-mediated PANoptosis is a double-edged sword in anti-infection, auto-inflammatory diseases, and tumor immunity. ZBP1-mediated PANoptosis is beneficial for eliminating infected cells and tumor cells, but abnormal or excessive PANoptosis can lead to a strong inflammatory response that is harmful to the host. Thus, pathogens and host have each developed multiplex tactics targeting ZBP1 signaling to maintain strong virulence or immune homeostasis. In this paper, we reviewed the mechanisms of ZBP1 signaling, the effects of ZBP1 signaling on host immunity and pathogen infection, and various antagonistic strategies of host and pathogen against ZBP1. We also discuss existent gaps regarding ZBP1 signaling and forecast potential directions for future research.
Impact of G-Quadruplex Structures on Methylation of Model Substrates by DNA Methyltransferase Dnmt3a
Authors: Loiko Andrei G. , Sergeev Alexander V. , Genatullina Adelya I. , Monakhova Mayya V. , Kubareva Elena A. , Dolinnaya Nina G. , Gromova Elizaveta S.
Published: September 2022

In mammals, de novo methylation of cytosines in DNA CpG sites is performed by DNA methyltransferase Dnmt3a. Changes in the methylation status of CpG islands are critical for gene regulation and for the progression of some cancers. Recently, the potential involvement of DNA G-quadruplexes (G4s) in methylation control has been found. Here, we provide evidence for a link between G4 formation and the function of murine DNA methyltransferase Dnmt3a and its individual domains. As DNA models, we used (i) an isolated G4 formed by oligonucleotide capable of folding into parallel quadruplex and (ii) the same G4 inserted into a double-stranded DNA bearing several CpG sites. Using electrophoretic mobility shift and fluorescence polarization assays, we showed that the Dnmt3a catalytic domain (Dnmt3a-CD), in contrast to regulatory PWWP domain, effectively binds the G4 structure formed in both DNA models. The G4-forming oligonucleotide displaced the DNA substrate from its complex with Dnmt3a-CD, resulting in a dramatic suppression of the enzyme activity. In addition, a direct impact of G4 inserted into the DNA duplex on the methylation of a specific CpG site was revealed. Possible mechanisms of G4-mediated epigenetic regulation may include Dnmt3a sequestration at G4 and/or disruption of Dnmt3a oligomerization on the DNA surface.
An Innovative Approach to Tissue Processing and Cell Sorting of Fixed Cells for Subsequent Single-Cell RNA Sequencing
Authors: Mutisheva Ivanina , Robatel Steve , Bäriswyl Lukas , Schenk Mirjam
Published: September 2022

Although single-cell RNA sequencing (scRNA-seq) is currently the gold standard for the analysis of cell-specific expression profiles, the options for processing, staining, and preserving fresh cells remain very limited. Immediate and correct tissue processing is a critical determinant of scRNA-seq success. One major limitation is the restricted compatibility of fixation approaches, which must not destabilize or alter antibody labeling or RNA content or interfere with cell integrity. An additional limitation is the availability of expensive, high-demand cell-sorting equipment to exclude debris and dead or unwanted cells before proceeding with sample sequencing. The goal of this study was to develop a method that allows cells to be fixed and stored prior to FACS sorting for scRNA-seq without compromising the quality of the results. Finally, the challenge of preserving as many living cells as possible during tissue processing is another crucial issue addressed in this study. Our study focused on pancreatic ductal adenocarcinoma samples, where the number of live cells is rather limited, as in many other tumor tissues. Harsh tissue dissociation methods and sample preparation for analysis can negatively affect cell viability. Using the murine pancreatic cancer model Pan02, we evaluated the semi-automated mechanical/enzymatic digestion of solid tumors by gentleMACS Dissociator and compared it with mechanical dissociation of the same tissue. Moreover, we investigated a type of cell fixation that is successful in preserving cell RNA integrity yet compatible with FACS and subsequent scRNA-sequencing. Our protocol allows tissue to be dissociated and stained in one day and proceeds to cell sorting and scRNA-seq later, which is a great advantage for processing clinical patient material.
Physiological and Molecular Characteristics of Southern Leaf Blight Resistance in Sweet Corn Inbred Lines
Authors: Xiong Caiyun , Mo Haiwei , Fan Jingsheng , Ren Wenchuang , Pei Hu , Zhang Yahui , Ma Ziwei , Wang Wenyi , Huang Jun
Published: September 2022

Southern corn leaf blight is one of the most widespread foliar diseases in maize-producing areas worldwide and can seriously reduce the yield and quality of sweet corn. However, the molecular mechanisms underlying the disease in sweet corn have not been widely reported. In this study, two sweet corn inbred lines, resistant K13 (RK13) and susceptible K39 (SK39), were used to explore the disease resistance mechanism of southern leaf blight. We observed morphological characteristics and assessed the changes in protective enzymatic activity in sweet corn leaves after inoculation of C. heterostrophus. RNA-seq was performed to elucidate the transcriptional dynamics and reveal the key pathways involved in southern leaf blight resistance without pathogens (Mock) and at 1 and 3 days post inoculation (1 and 3 dpi). Differentially expressed genes (DEGs) were identified in the SK39 group (including three pairwise combinations: SK39−0d_vs_SK39−1d, SK39−1d_vs_SK39−3d and SK39−1d_vs_SK39−3d), the RK13 group (including three pairwise combinations: RK13−0d_vs_RK13−1d, RK13−1d_vs_RK13−3d and RK13−1d_vs_RK13−3d), and the SK39_vs_RK13 group (including three pairwise combinations: SK39−0d_vs_RK13−0d, SK39−1d_vs_RK13−1d, and SK39−3d_vs_RK13−3d). In our study, 9455 DEGs from the RK13 group, 9626 from the SK39 group, and 9051 DEGs from the SK39_vs_RK13 group were obtained. Furthermore, 2775, 163, and 185 DEGs were co-expressed at SK39_vs_RK13, RK13, and SK39, respectively. A functional analysis of the DEGs revealed that five pathways—i.e., photosynthesis, plant hormone signal transduction, MAPK signaling pathway, phenylpropanoid biosynthesis, and biosynthesis of secondary metabolites—and transcription factor families play crucial roles in disease resistance. The results from the present study enabled the identification of the JA and SA signaling pathways, which are potentially involved in the response to southern leaf blight in maize. Our findings also highlight the significance of ZIM transcription factors and pathogenesis-related (PR) genes during pathogen infection. This study preliminarily explored the molecular mechanisms of the interaction between sweet corn and C. heterostrophus and provides a reference for identifying southern leaf blight resistance genes in the future.
Open Questions in Cold Atmospheric Plasma Treatment in Head and Neck Cancer: A Systematic Review
Authors: Perrotti Vittoria , Caponio Vito Carlo Alberto , Muzio Lorenzo Lo , Choi Eun Ha , Marcantonio Maria Carmela Di , Mazzone Mariangela , Kaushik Nagendra Kumar , Mincione Gabriella
Published: September 2022

Over the past decade, we witnessed a promising application of cold atmospheric plasma (CAP) in cancer therapy. The aim of this systematic review was to provide an exhaustive state of the art of CAP employed for the treatment of head and neck cancer (HNC), a tumor whose late diagnosis, local recurrence, distant metastases, and treatment failure are the main causes of patients’ death. Specifically, the characteristics and settings of the CAP devices and the in vitro and in vivo treatment protocols were summarized to meet the urgent need for standardization. Its molecular mechanisms of action, as well as the successes and pitfalls of current CAP applications in HNC, were discussed. Finally, the interesting emerging preclinical hypotheses that warrant further clinical investigation have risen. A total of 24 studies were included. Most studies used a plasma jet device (54.2%). Argon resulted as the mostly employed working gas (33.32%). Direct and indirect plasma application was reported in 87.5% and 20.8% of studies, respectively. In vitro investigations were 79.17%, most of them concerned with direct treatment (78.94%). Only eight (33.32%) in vivo studies were found; three were conducted in mice, and five on human beings. CAP showed pro-apoptotic effects more efficiently in tumor cells than in normal cells by altering redox balance in a way that oxidative distress leads to cell death. In preclinical studies, it exhibited efficacy and tolerability. Results from this systematic review pointed out the current limitations of translational application of CAP in the urge of standardization of the current protocols while highlighting promising effects as supporting treatment in HNC.
Leukotriene A4 Hydrolase and Hepatocyte Growth Factor Are Risk Factors of Sudden Cardiac Death Due to First-Ever Myocardial Infarction
Authors: Landfors Fredrik , Vikström Simon , Wennberg Patrik , Jansson Jan-Håkan , Andersson Jonas , Chorell Elin
Published: September 2022

Patients at a high risk for sudden cardiac death (SCD) without previous history of cardiovascular disease remain a challenge to identify. Atherosclerosis and prothrombotic states involve inflammation and non-cardiac tissue damage that may play active roles in SCD development. Therefore, we hypothesized that circulating proteins implicated in inflammation and tissue damage are linked to the future risk of SCD. We conducted a prospective nested case–control study of SCD cases with verified myocardial infarction (N = 224) and matched controls without myocardial infarction (N = 224), aged 60 ± 10 years time and median time to event was 8 years. Protein concentrations (N = 122) were measured using a proximity extension immunoassay. The analyses revealed 14 proteins significantly associated with an increased risk of SCD, from which two remained significant after adjusting for smoking status, systolic blood pressure, BMI, cholesterol, and glucose levels. We identified leukotriene A4 hydrolase (LTA4H, odds ratio 1.80, corrected confidence interval (CIcorr) 1.02–3.17) and hepatocyte growth factor (HGF; odds ratio 1.81, CIcorr 1.06–3.11) as independent risk markers of SCD. Elevated LTA4H may reflect increased systemic and pulmonary neutrophilic inflammatory processes that can contribute to atherosclerotic plaque instability. Increased HGF levels are linked to obesity-related metabolic disturbances that are more prevalent in SCD cases than the controls.
Stepped-Frequency Continuous-Wave Signal Processing Method for Human Detection Using Radars for Sensing Rooms through the Wall
Authors: Kozlov Roman , Gavrilov Konstantin , Shevgunov Timofey , Kirdyashkin Vladimir
Published: September 2022

The problem of detecting moving and stationary people in a room with a specialized radar system sensing through the wall is considered in the paper. The high-range resolution of the system is achieved by effective processing of reflected ultra-wideband stepped-frequency continuous-wave signals (SFCW). The paper presents a new method which is based on normalization of complex-valued samples of the received SFCW signals and extends traditional processing steps including quadrature-phase demodulation, sampling and inverse discrete Fourier transform. The proposed method is aimed at improving the performance of the interperiodic difference and variance of sample algorithms which are briefly described in relation to the SFCW radar system. The computer modeling showed that the introduced normalization mitigates the background noise and merely decreases the artifacts commonly appearing in radar images due to the non-uniform amplitude-frequency characteristics of the radar circuits. The described algorithms were implemented in a software part of the real-time working prototype of the radar system designed and assembled at the University research center. The results of field experiments confirmed the advantage of the proposed method in typical scenarios and showed the increase of the signal-to-noise ratio to 5 dB compared to traditional radar algorithm-processing SFCW signals.
Effects of COVID-19 on Arrhythmia
Authors: Zhan Yujia , Yue Honghua , Liang Weitao , Wu Zhong
Published: September 2022

The World Health Organization announced that COVID-19, with SARS-CoV-2 as its pathogen, had become a pandemic on 11 March 2020. Today, the global epidemic situation is still serious. With the development of research, cardiovascular injury in patients with COVID-19, such as arrhythmia, myocardial injury, and heart failure, is the second major symptom in addition to respiratory symptoms, and cardiovascular injury is related to the prognosis and mortality of patients. The incidence of arrhythmia in COVID-19 patients ranges from 10% to 20%. The potential mechanisms include viral infection-induced angiotensin-converting enzyme 2 expression change, myocarditis, cytokine storm, cardiac injury, electrophysiological effects, hypoxemia, myocardial strain, electrolyte abnormalities, intravascular volume imbalance, drug toxicities and interactions, and stress response caused by virus infection. COVID-19 complicated with arrhythmia needs to be accounted for and integrated in management. This article reviews the incidence, potential mechanisms, and related management measures of arrhythmia in COVID-19 patients.
Conundrum of Classifying Subtypes of Pulmonary Hypertension—Introducing a Novel Approach to Classify “Borderline” Patients in a Population with Severe Aortic Stenosis Undergoing TAVI
Authors: Boxhammer Elke , Gharibeh Sarah X. , Wernly Bernhard , Kelm Malte , Franz Marcus , Kretzschmar Daniel , Hoppe Uta C. , Lauten Alexander , Lichtenauer Michael
Published: September 2022

Background: Transcatheter aortic valve implantation (TAVI) is an established therapeutic option in patients with severe aortic valve stenosis (AS) and a high surgical risk profile. Pulmonary hypertension (PH)—often co-existing with severe AS—is associated with a limited factor for prognosis and survival. The purpose of this study was to evaluate the prevalence of PH in patients undergoing TAVI, classify these patients based on right heart catheter (RHC) measurements in different PH subtypes, and analyze prognostic values on survival after TAVI. Methods: 284 patients with severe AS underwent an RHC examination for hemodynamic assessment prior to TAVI and were categorized into subtypes of PH according to the 2015 European Society of Cardiology (ESC) guidelines. TAVI patients were followed-up with for one year with regard to 30-days and 1-year mortality as primary endpoints. Results: 74 of 284 participants showed a diastolic pressure gradient (DPG) < 7 mmHg and a pulmonary vascular resistance (PVR) > 3 Wood units (WU) and could not be formally allocated to either isolated post-capillary PH (ipc-PH) or combined pre- and post-capillary PH (cpc-PH). Therefore, a new subgroup called “borderline post-capillary PH” (borderlinepc-PH) was introduced. Compared with TAVI patients with pre-capillary PH (prec-PH), ipc-PH patients suffering from borderlinepc-PH (HR 7.114; 95% CI 2.015–25.119; p = 0.002) or cpc-PH (HR 56.459; 95% CI 7.738–411.924; p < 0.001) showed a significantly increased 1-year mortality. Conclusions: Postcapillary PH was expanded to include the so-called “borderlinepc-PH” variant in addition to the ipc-PH and cpc-PH subtypes. The one-year survival after TAVI was significantly different between the subgroups, with the worst prognosis for borderlinepc-PH and cpc-PH.