bluuebunny/crossref_metadata_2025 huggingface dataset:
CRISPR-Cas9 Gene Editing for Fruit and Vegetable Crops: Strategies and Prospects
Authors: Wan Lili , Wang Zhuanrong , Tang Mi , Hong Dengfeng , Sun Yuhong , Ren Jian , Zhang Na , Zeng Hongxia
Published: July 2021

Fruit and vegetable crops are rich in dietary fibre, vitamins and minerals, which are vital to human health. However, many biotic stressors (such as pests and diseases) and abiotic stressors threaten crop growth, quality, and yield. Traditional breeding strategies for improving crop traits include a series of backcrosses and selection to introduce beneficial traits into fine germplasm, this process is slow and resource-intensive. The new breeding technique known as clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein-9 (Cas9) has the potential to improve many traits rapidly and accurately, such as yield, quality, disease resistance, abiotic stress tolerance, and nutritional aspects in crops. Because of its simple operation and high mutation efficiency, this system has been applied to obtain new germplasm resources via gene-directed mutation. With the availability of whole-genome sequencing data, and information about gene function for important traits, CRISPR-Cas9 editing to precisely mutate key genes can rapidly generate new germplasm resources for the improvement of important agronomic traits. In this review, we explore this technology and its application in fruit and vegetable crops. We address the challenges, existing variants and the associated regulatory framework, and consider future applications.
Impact of the Childcare Physical Activity (PLAY) Policy on Young Children’s Physical Activity and Sedentary Time: A Pilot Clustered Randomized Controlled Trial
Authors: Szpunar Monika , Driediger Molly , Johnson Andrew M. , Vanderloo Leigh M. , Burke Shauna M. , Irwin Jennifer D. , Shelley Jacob , Timmons Brian W. , Tucker Patricia
Published: July 2021

Background: The importance of daily physical activity is crucial for healthy development during the early years. Currently, a formal written physical activity policy is lacking in Canadian childcare centers, but holds promise for offering consistent physical activity opportunities. With eight recommendations, the Childcare PLAY policy is an evidence-informed, institutional-level document, targeting children’s physical activity, outdoor play, and sedentary time. The purpose of this study was to examine the impact of the Childcare Physical Activity (PLAY) policy on the physical activity and sedentary time of young children (18 months–4 years) in childcare. Methods: Nine childcare centers in London, Ontario participated in the cluster, randomized controlled trial. The centers in the control condition (n = 4) continued their typical daily routines, while the centers in the intervention condition (n = 5) implemented the PLAY policy for eight weeks. To assess physical activity levels, toddlers and preschoolers wore ActiGraph wGT3X-BT accelerometers for five consecutive days during childcare hours, at baseline, mid- and post-intervention, and at the six-month follow-up. Raw accelerometry data were converted to 15 s epochs, and age- and device-specific cut-points were applied. The participants with two or more days of at least 5 h/day of wear-time at baseline, and at one additional time point, were included in the linear mixed-effects models. An adjusted alpha (p < 0.017) was used to account for multiple comparison bias. Results: A total of 148 children (31.92 ± 7.41 months) had valid accelerometry data. The intervention resulted in a significant increase in light physical activity among the participants in the experimental group at the six-month follow-up (+1.07 min/h, an 11.16% increase; p = 0.0017). The intervention did not have a statistically significant effect on the total physical activity, moderate-to-vigorous physical activity, or sedentary time. Conclusions: The findings indicate that the Childcare PLAY policy was effective at increasing the toddlers’ and preschoolers’ light physical activity. This pilot intervention appears promising for supporting some improved movement behaviors among children in childcare settings; however, additional investigations are needed to explore the feasibility and effectiveness with larger and more-diverse samples.
Changes in Core Competencies among Korean University Students Due to Remote Learning during the COVID-19 Pandemic
Authors: Jang Sunjoo , Lee Haeyoung
Published: July 2021

This study aimed to determine the academic performance and learning skills of students who studied through remote teaching methods during the coronavirus disease 2019 (COVID-19) pandemic. It was conducted in February 2021 with 398 university students in South Korea. Data were collected through online surveys. Generalized estimating equations (GEEs) with an autoregressive correlation structure were employed to distinguish differences in core competencies, academic performance, satisfaction, and usefulness of teaching methods before 2019 and after the COVID-19 pandemic. The findings revealed that the overall core competencies of participants were significantly lower in 2020 than before the COVID-19 pandemic. Furthermore, knowledge construction, responsibility practice, and socialization were significantly low during the COVID-19 pandemic, whereas information management and identity value did not show a significant difference. However, problem-solving was higher during the COVID-19 pandemic. Enhancing the core competencies of university students is integral in the new learning environment of the post-COVID-19 era. It is necessary to devise approaches that improve the effectiveness of remote teaching methods and simultaneously augment student satisfaction.
Investigating and Managing the Impact of Using Untreated Wastewater for Irrigation on the Groundwater Quality in Arid and Semi-Arid Regions
Authors: Abd-Elhamid Hany F. , Abd-Elmoneem Shaimaa M. , Abdelaal Gamal M. , Zeleňáková Martina , Vranayova Zuzana , Abd-Elaty Ismail
Published: July 2021

This study aims to investigate the impact of using untreated wastewater in irrigation. Different scenarios of management were applied by mixing it with treated wastewater or freshwater on groundwater quality. A hypothetical case study is presented. The numerical model of MODFLOW is used in the simulation by applying four stages (21 scenarios) including: different values of pumping rates, changing wastewater recharge rates, and a combination of the previous scenarios. Additionally, protection scenario for groundwater was applied by using different values of mixing of freshwater with wastewater. The simulation was carried out for the contamination of Chemical Oxygen Demand COD and the concentration reached 48.6 ppm at a depth of 25 m and 19.41 ppm at a depth of 50 m in the base case. The results showed a negative impact on groundwater quality had occurred due to increasing the pumping rates, wastewater recharge rates, and combination between two scenarios, which led to an increase of the contaminants in the aquifers. However, positive protection effects occurred due to mixing the wastewater with treated wastewater. The results of COD concentration in groundwater using treated wastewater reached 81.82, 77.88, 74.03, 70.12, and 66.15 ppm at a depth of 25 m and 53.53, 50.95, 48.43, 45.87, and 43.28 ppm at a depth of 50 m, at concentrations of 93, 88.52, 84.14, 79.7, and 75.19 ppm with constant pumping and recharge rates of 4320 m3/d and 547.5 mm/year, respectively. The using of treated wastewater could improve the groundwater quality to be used in the irrigation process and help to minimize groundwater contamination. Moreover, the abstraction of the groundwater should be optimized, and the qualities of wastewater should be constrained in agriculture to protect the groundwater quality.
Reopening International Borders without Quarantine: Contact Tracing Integrated Policy against COVID-19
Authors: Yu Zidong , Zhu Xiaolin , Liu Xintao , Wei Tao , Yuan Hsiang-Yu , Xu Yang , Zhu Rui , He Huan , Wang Hui , Wong Man Sing , Jia Peng , Guo Song , Shi Wenzhong , Chen Wu
Published: July 2021

With the COVID-19 vaccination widely implemented in most countries, propelled by the need to revive the tourism economy, there is a growing prospect for relieving the social distancing regulation and reopening borders in tourism-oriented countries and regions. This need incentivizes stakeholders to develop border control strategies that fully evaluate health risks if mandatory quarantines are lifted. In this study, we have employed a computational approach to investigate the contact tracing integrated policy in different border-reopening scenarios in Hong Kong, China. Explicitly, by reconstructing the COVID-19 transmission from historical data, specific scenarios with joint effects of digital contact tracing and other concurrent measures (i.e., controlling arrival population and community nonpharmacological interventions) are applied to forecast the future development of the pandemic. Built on a modified SEIR epidemic model with a 30% vaccination coverage, the results suggest that scenarios with digital contact tracing and quick isolation intervention can reduce the infectious population by 92.11% compared to those without contact tracing. By further restricting the inbound population with a 10,000 daily quota and applying moderate-to-strong community nonpharmacological interventions (NPIs), the average daily confirmed cases in the forecast period of 60 days can be well controlled at around 9 per day (95% CI: 7–12). Two main policy recommendations are drawn from the study. First, digital contact tracing would be an effective countermeasure for reducing local virus spread, especially when it is applied along with a moderate level of vaccination coverage. Second, implementing a daily quota on inbound travelers and restrictive community NPIs would further keep the local infection under control. This study offers scientific evidence and prospective guidance for developing and instituting plans to lift mandatory border control policies in preparing for the global economic recovery.
Self-Esteem and Binge Eating among Adolescent Boys and Girls: The Role of Body Disinvestment
Authors: Cella Stefania , Cipriano Annarosa , Aprea Cristina , Cotrufo Paolo
Published: July 2021

Although low self-esteem and body disinvestment have been recognized as potential risk factors for disordered eating, no studies have explored how these factors may work together to predict binge eating in adolescents. Therefore, we hypothesized a path model for girls and boys separately to investigate whether the body’s investment dimensions (feelings towards the body, physical touch, body care, body protection) mediate the relationship between self-esteem and binge eating, and age moderate such relationships. Participants were 1046 Italian students aged between 11 and 19 years (472 girls, Mage = 14.17; 574 boys, Mage = 14.60) screened through self-report measures. Both models showed an acceptable fit (males: χ2(22) = 30.441; RMSEA = 0.026; CFI = 0.99; TLI = 0.97; SRMR = 0.023; females: χ2(22) = 34.723; RMSEA = 0.35; CFI = 0.98; TLI = 0.95; SRMR = 0.029). Negative body feelings and reduced body protection fully mediated the relationship between self-esteem and binge eating, regardless of gender. Our findings highlight the importance of interventions promoting body emotional investment to reduce adolescents’ vulnerability to binge eating.
Compliance with the 24-Hour Movement Behavior Guidelines and Associations with Adiposity in European Preschoolers: Results from the ToyBox-Study
Authors: Decraene Marga , Verbestel Vera , Cardon Greet , Iotova Violeta , Koletzko Berthold , Moreno Luis A. , Miguel-Berges María L. , Gurzkowska Beata , Androutsos Odysseas , Manios Yannis , De Craemer Marieke
Published: July 2021

In 2019, the World Health Organization (WHO) published 24 h movement behavior guidelines for preschoolers with recommendations for physical activity (PA), screen time (ST), and sleep. The present study investigated the proportion of preschoolers complying with these guidelines (on a total week, weekdays and weekend days), and the associations with adiposity. This cross-sectional study included 2468 preschoolers (mean age: 4.75 years; 41.9% boys) from six European countries. The associations were investigated in the total sample and in girls and boys separately. PA was objectively assessed by step counts/day. Parent-reported questionnaires provided ST and sleep duration data. Generalized estimating equations were used to analyze the association between guideline compliance and adiposity indicators, i.e., body mass index (BMI) z-score and waist to height ratio (WHR). Only 10.1% of the preschoolers complied with the 24 h movement behavior guidelines, 69.2% with the sleep duration guideline, 39.8% with the ST guideline and 32.7% with the PA guideline. No association was found between guideline compliance with all three movement behaviors and adiposity. However, associations were found for isolated weekday screen time (BMI z-scores and WHR: p = 0.04) and weekend day sleep duration (BMI z-scores and WHR: p = 0.03) guideline compliance with both lower adiposity indicators. The latter association for sleep duration was also found in girls separately (BMI z-scores: p = 0.02; WHR: p = 0.03), but not in boys. Longitudinal studies, including intervention studies, are needed to increase preschoolers’ guideline compliance and to gain more insight into the manifestation of adiposity in children and its association with 24 h movement behaviors from a young age onwards.
What Do Public Health Graduates Do and Where Do They Go? An Analysis of Job Destinations and Mismatch in Australian Public Health Graduates
Authors: Watts Rory David , Bowles Devin C. , Fisher Colleen , Li Ian W.
Published: July 2021

Background: It is not well understood what occupations public health graduates have after graduation, nor is it well known whether their education provides them with the relevant knowledge and skills to feel well matched to their occupations. Furthermore, it is commonly presumed that public health graduates work in government, and investments in education would bolster this workforce. Methods: We aimed to describe the common occupations of Australian public health graduates, describe the heterogeneity of graduate destinations, describe the level of mismatch that graduates report, and compare these results with other fields of study. We used eight years of Australian graduate survey data (2008–2015) from the Graduate Destinations Survey, examining outcomes data from 8900 public health graduates from four levels of education. We compared occupation and industry heterogeneity, and level of occupational mismatch between public health graduates, and graduates from other fields of education. Results: Public health graduates report having a broad set of occupations in a broad set of industries after graduation, and this breadth is dissimilar to most health degrees. Furthermore, public health graduates tend to have average or lower-than-average rates of mismatch. Conclusions: Despite going into a broad set of occupations and industries, graduates from public health tend to report being well prepared given their education. Given that both occupation and industry outcomes are heterogeneous for graduates, an investment in public health education does not guarantee an increase in the governmental public health workforce.
The Use of Physical Restraints on Geriatric Patients: Culture and Attitudes among Healthcare Professionals at Intermediate Care Hospitals in Majorca. A Qualitative Study Protocol
Authors: Carrero-Planells Alba , Urrutia-Beaskoa Ana , Moreno-Mulet Cristina
Published: July 2021

The use of physical restraints is a common practice in the care of hospitalised and institutionalised elderly people. This use is determined by factors related to the patients, their families, the healthcare professionals, the institution, and prevailing social values. Today, however, this practice is often questioned because of its physical, psychological, moral, ethical, and legal repercussions. The present study explores attitudes among healthcare professionals towards the physical restraint of geriatric patients in intermediate care hospitals in Majorca. This study is based on a qualitative design, combining an ethnomethodological approach with critical discourse analysis. The theoretical framework is drawn from Foucault’s work in this field and from Haslam’s theory of mechanisation. Individual interviews will be conducted with physicians, nurses, and nursing assistants at intermediate care hospitals in Majorca. The analysis will focus on these professionals’ knowledge, attitudes, and practices regarding the use of such measures, seeking to identify the factors, especially institutional factors, that determine the use of restraints. It is essential to determine the prevailing culture among healthcare professionals regarding the use of physical restraints on geriatric patients in order to design and propose a more dignified health care model in which such restraints are eliminated.
Big Data-Enabled Solutions Framework to Overcoming the Barriers to Circular Economy Initiatives in Healthcare Sector
Authors: Kazançoğlu Yiğit , Sağnak Muhittin , Lafcı Çisem , Luthra Sunil , Kumar Anil , Taçoğlu Caner
Published: July 2021

Ever-changing conditions and emerging new challenges affect the ability of the healthcare sector to survive with the current system, and to maintain its processes effectively. In the healthcare sector, the conservation of the natural resources is being obstructed by insufficient infrastructure for managing residual waste resulting from single-use medical materials, increased energy use, and its environmental burden. In this context, circularity and sustainability concepts have become essential in healthcare to meliorate the sector’s negative impacts on the environment. The main aim of this study is to identify the barriers related to circular economy (CE) in the healthcare sector, apply big data analytics in healthcare, and provide solutions to these barriers. The contribution of this research is the detailed examination of the current healthcare literature about CE adaptation, and a proposal for a big data-enabled solutions framework to barriers to circularity, using fuzzy best-worst Method (BWM) and fuzzy VIKOR. Based on the findings, managerial, policy, and theoretical implementations are recommended to support sustainable development initiatives in the healthcare sector.
Sialic Acid—Modified Nanoparticles—New Approaches in the Glioma Management—Perspective Review
Authors: Wielgat Przemyslaw , Niemirowicz-Laskowska Katarzyna , Wilczewska Agnieszka Z. , Car Halina
Published: July 2021

The cell surface is covered by a dense and complex network of glycans attached to the membrane proteins and lipids. In gliomas, the aberrant sialylation, as the final stage of glycosylation, is an important regulatory mechanism of malignant cell behavior and correlates with worse prognosis. Better understanding of the role of sialylation in cellular and molecular processes opens a new way in the development of therapeutic tools for human brain tumors. According to the recent clinical observation, the cellular heterogeneity, activity of brain cancer stem cells (BCSCs), immune evasion, and function of the blood–brain barrier (BBB) are attractive targets for new therapeutic strategies. In this review, we summarize the importance of sialic acid-modified nanoparticles in brain tumor progression.
Treat Me Well or Will Resist: Uptake of Mobile Genetic Elements Determine the Resistome of Corynebacterium striatum
Authors: Leyton Benjamin , Ramos Juliana Nunes , Baio Paulo Victor Pereira , Veras João Flávio Carneiro , Souza Cassius , Burkovski Andreas , Mattos-Guaraldi Ana Luíza , Vieira Verônica Viana , Abanto Marin Michel
Published: July 2021

Corynebacterium striatum, a bacterium that is part of the normal skin microbiota, is also an opportunistic pathogen. In recent years, reports of infections and in-hospital and nosocomial outbreaks caused by antimicrobial multidrug-resistant C. striatum strains have been increasing worldwide. However, there are no studies about the genomic determinants related to antimicrobial resistance in C. striatum. This review updates global information related to antimicrobial resistance found in C. striatum and highlights the essential genomic aspects in its persistence and dissemination. The resistome of C. striatum comprises chromosomal and acquired elements. Resistance to fluoroquinolones and daptomycin are due to mutations in chromosomal genes. Conversely, resistance to macrolides, tetracyclines, phenicols, beta-lactams, and aminoglycosides are associated with mobile genomic elements such as plasmids and transposons. The presence and diversity of insertion sequences suggest an essential role in the expression of antimicrobial resistance genes (ARGs) in genomic rearrangements and their potential to transfer these elements to other pathogens. The present study underlines that the resistome of C. striatum is dynamic; it is in evident expansion and could be acting as a reservoir for ARGs.
The Potential of OMICs Technologies for the Treatment of Immune-Mediated Inflammatory Diseases
Authors: Anchang Charles Gwellem , Xu Cong , Raimondo Maria Gabriella , Atreya Raja , Maier Andreas , Schett Georg , Zaburdaev Vasily , Rauber Simon , Ramming Andreas
Published: July 2021

Immune-mediated inflammatory diseases (IMIDs), such as inflammatory bowel diseases and inflammatory arthritis (e.g., rheumatoid arthritis, psoriatic arthritis), are marked by increasing worldwide incidence rates. Apart from irreversible damage of the affected tissue, the systemic nature of these diseases heightens the incidence of cardiovascular insults and colitis-associated neoplasia. Only 40–60% of patients respond to currently used standard-of-care immunotherapies. In addition to this limited long-term effectiveness, all current therapies have to be given on a lifelong basis as they are unable to specifically reprogram the inflammatory process and thus achieve a true cure of the disease. On the other hand, the development of various OMICs technologies is considered as “the great hope” for improving the treatment of IMIDs. This review sheds light on the progressive development and the numerous approaches from basic science that gradually lead to the transfer from “bench to bedside” and the implementation into general patient care procedures.
4-Acetyl-Antroquinonol B Improves the Sensitization of Cetuximab on Both Kras Mutant and Wild Type Colorectal Cancer by Modulating the Expression of Ras/Raf/miR-193a-3p Signaling Axis
Authors: Chu Yi Cheng , Tsai Tung-Yao , Yadav Vijesh Kumar , Deng Li , Huang Chun-Chih , Tzeng Yew-Min , Yeh Chi-Tai , Chen Ming-Yao
Published: July 2021

The KRAS mutation is one of the leading driver mutations in colorectal cancer (CRC), and it is usually associated with poor prognosis and drug resistance. Therapies targeting the epidermal growth factor receptor (EFGR) are widely used for end-stage CRC. However, patients with KRAS mutant genes cannot benefit from this therapy because of Ras signaling activation by KRAS mutant genes. Our previous study revealed the anti-proliferative effect of 4-acetyl-antroquinonol B (4-AAQB) on CRC cells, but whether the drug is effective in KRAS-mutant CRC remains unknown. We screened CRC cell lines harboring the KRAS mutation, namely G12A, G12C, G12V and G13D, with one wild type cell line as the control; SW1463 and Caco-2 cell lines were used for further experiments. Sulforhodamine B assays, together with the clonogenicity and invasion assay, revealed that KRAS-mutant SW1463 cells were resistant to cetuximab; however, 4-AAQB treatment effectively resensitized CRC cells to cetuximab through the reduction of colony formation, invasion, and tumorsphere generation and of oncogenic KRAS signaling cascade of CRC cells. Thus, inducing cells with 4-AAQB before cetuximab therapy could resensitize KRAS-mutant, but not wild-type, cells to cetuximab. Therefore, we hypothesized that 4-AAQB can inhibit KRAS. In silico analysis of the publicly available GEO (GSE66548) dataset of KRAS-mutated versus KRAS wild-type CRC patients confirmed that miR-193a-3p was significantly downregulated in the former compared with the latter patient population. Overexpression of miR-193a-3p considerably reduced the oncogenicity of both CRC cells. Furthermore, KRAS is a key target of miR-193a-3p. In vivo treatment with the combination of 4-AAQB and cetuximab significantly reduced the tumor burden of a xenograft mice model through the reduction of the expression of oncogenic markers (EGFR) and p-MEK, p-ERK, and c-RAF/p-c-RAF signaling, with the simultaneous induction of miR-193a-3p expression in the plasma. In summary, our findings provide strong evidence regarding the therapeutic effect of 4-AAQB on KRAS-mutant CRC cells. Furthermore, 4-AAQB effectively inhibits Ras singling in CRC cells, through which KRAS-mutant CRC can be resensitized to cetuximab.
The Efficacy of Anti-PD-L1 Treatment in Melanoma Is Associated with the Expression of the ECM Molecule EMILIN2
Authors: Fejza Albina , Polano Maurizio , Camicia Lucrezia , Poletto Evelina , Carobolante Greta , Toffoli Giuseppe , Mongiat Maurizio , Andreuzzi Eva
Published: July 2021

The use of immune checkpoint inhibitors has revolutionized the treatment of melanoma patients, leading to remarkable improvements in the cure. However, to ensure a safe and effective treatment, there is the need to develop markers to identify the patients that would most likely respond to the therapies. The microenvironment is gaining attention in this context, since it can regulate both the immunotherapy efficacyand angiogenesis, which is known to be affected by treatment. Here, we investigated the putative role of the ECM molecule EMILIN-2, a tumor suppressive and pro-angiogenic molecule. We verified that the EMILIN2 expression is variable among melanoma patients and is associated with the response to PD-L1 inhibitors. Consistently, in preclinical settings,the absence of EMILIN-2 is associated with higher PD-L1 expression and increased immunotherapy efficacy. We verified that EMILIN-2 modulates PD-L1 expression in melanoma cells through indirect immune-dependent mechanisms. Notably, upon PD-L1 blockage, Emilin2−/− mice displayed improved intra-tumoral vessel normalization and decreased tumor hypoxia. Finally, we provide evidence indicating that the inclusion of EMILIN2 in a number of gene expression signatures improves their predictive potential, a further indication that the analysis of this molecule may be key for the development of new markers to predict immunotherapy efficacy.
Cell Sources for Cultivated Meat: Applications and Considerations throughout the Production Workflow
Authors: Reiss Jacob , Robertson Samantha , Suzuki Masatoshi
Published: July 2021

Cellular agriculture is an emerging scientific discipline that leverages the existing principles behind stem cell biology, tissue engineering, and animal sciences to create agricultural products from cells in vitro. Cultivated meat, also known as clean meat or cultured meat, is a prominent subfield of cellular agriculture that possesses promising potential to alleviate the negative externalities associated with conventional meat production by producing meat in vitro instead of from slaughter. A core consideration when producing cultivated meat is cell sourcing. Specifically, developing livestock cell sources that possess the necessary proliferative capacity and differentiation potential for cultivated meat production is a key technical component that must be optimized to enable scale-up for commercial production of cultivated meat. There are several possible approaches to develop cell sources for cultivated meat production, each possessing certain advantages and disadvantages. This review will discuss the current cell sources used for cultivated meat production and remaining challenges that need to be overcome to achieve scale-up of cultivated meat for commercial production. We will also discuss cell-focused considerations in other components of the cultivated meat production workflow, namely, culture medium composition, bioreactor expansion, and biomaterial tissue scaffolding.
Diagnostic Tools and Biomarkers for Severe Drug Eruptions
Authors: Yoshioka Manabu , Sawada Yu , Nakamura Motonobu
Published: July 2021

In accordance with the development of human technology, various medications have been speedily developed in the current decade. While they have beneficial impact on various diseases, these medications accidentally cause adverse reactions, especially drug eruption. This delayed hypersensitivity reaction in the skin sometimes causes a life-threatening adverse reaction, namely Stevens-Johnson syndrome and toxic epidermal necrolysis. Therefore, how to identify these clinical courses in early time points is a critical issue. To improve this problem, various biomarkers have been found for these severe cutaneous adverse reactions through recent research. Granulysin, Fas ligands, perforin, and granzyme B are recognized as useful biomarkers to evaluate the early onset of Stevens-Johnson syndrome and toxic epidermal necrolysis, and other biomarkers, such as miRNAs, high mobility group box 1 protein (HMGB1), and S100A2, which are also helpful to identify the severe cutaneous adverse reactions. Because these tools have been currently well developed, updates of the knowledge in this field are necessary for clinicians. In this review, we focused on the detailed biomarkers and diagnostic tools for drug eruption and we also discussed the actual usefulness of these biomarkers in the clinical aspects based on the pathogenesis of drug eruption.
PAR2-Induced Tissue Factor Synthesis by Primary Cultures of Human Kidney Tubular Epithelial Cells Is Modified by Glucose Availability
Authors: Humphries Tyrone L. R. , Shen Kunyu , Iyer Abishek , Johnson David W. , Gobe Glenda C. , Nikolic-Paterson David , Fairlie David P. , Vesey David A.
Published: July 2021

Coagulopathies common to patients with diabetes and chronic kidney disease (CKD) are not fully understood. Fibrin deposits in the kidney suggest the local presence of clotting factors including tissue factor (TF). In this study, we investigated the effect of glucose availability on the synthesis of TF by cultured human kidney tubular epithelial cells (HTECs) in response to activation of protease-activated receptor 2 (PAR2). PAR2 activation by peptide 2f-LIGRLO-NH2 (2F, 2 µM) enhanced the synthesis and secretion of active TF (~45 kDa) which was blocked by a PAR2 antagonist (I-191). Treatment with 2F also significantly increased the consumption of glucose from the cell medium and lactate secretion. Culturing HTECs in 25 mM glucose enhanced TF synthesis and secretion over 5 mM glucose, while addition of 5 mM 2-deoxyglucose (2DOG) significantly decreased TF synthesis and reduced its molecular weight (~40 kDa). Blocking glycosylation with tunicamycin also reduced 2F-induced TF synthesis while reducing its molecular weight (~36 kDa). In conclusion, PAR2-induced TF synthesis in HTECs is enhanced by culture in high concentrations of glucose and suppressed by inhibiting either PAR2 activation (I-191), glycolysis (2DOG) or glycosylation (tunicamycin). These results may help explain how elevated concentrations of glucose promote clotting abnormities in diabetic kidney disease. The application of PAR2 antagonists to treat CKD should be investigated further.
Hydrophilic and Hydrophobic Effects on the Structure and Themodynamic Properties of Confined Water: Water in Solutions
Authors: Mallamace Francesco , Mallamace Domenico , Chen Sow-Hsin , Lanzafame Paola , Papanikolaou Georgia
Published: July 2021

NMR spectroscopy is used in the temperature range 180–350 K to study the local order and transport properties of pure liquid water (bulk and confined) and its solutions with glycerol and methanol at different molar fractions. We focused our interest on the hydrophobic effects (HE), i.e., the competition between hydrophilic and hydrophobic interactions. Nowadays, compared to hydrophilicity, little is known about hydrophobicity. Therefore, the main purpose of this study is to gain new information about hydrophobicity. As the liquid water properties are dominated by polymorphism (two coexisting liquid phases of high and low density) due to hydrogen bond interactions (HB), creating (especially in the supercooled regime) the tetrahedral networking, we focused our interest to the HE of these structures. We measured the relaxation times (T1 and T2) and the self-diffusion (DS). From these times, we took advantage of the NMR property to follow the behaviors of each molecular component (the hydrophilic and hydrophobic groups) separately. In contrast, DS is studied in terms of the Adam–Gibbs model by obtaining the configurational entropy (Sconf) and the specific heat contributions (CP,conf). We find that, for the HE, all of the studied quantities behave differently. For water–glycerol, the HB interaction is dominant for all conditions; water–methanol, two different T-regions above and below 265 K are observable, dominated by hydrophobicity and hydrophilicity, respectively. Below this temperature, where the LDL phase and the HB network develops and grows, with the times and CP,conf change behaviors leading to maxima and minima. Above it, the HB becomes weak and less stable, the HDL dominates, and hydrophobicity determines the solution.
Perinatal High-Fat Diet Influences Ozone-Induced Responses on Pulmonary Oxidant Status and the Molecular Control of Mitophagy in Female Rat Offspring
Authors: Rouschop Sven H. , Snow Samantha J. , Kodavanti Urmila P. , Drittij Marie-José , Maas Lou M. , Opperhuizen Antoon , van Schooten Frederik J. , Remels Alexander H. , Godschalk Roger W.
Published: July 2021

Previous research has shown that a perinatal obesogenic, high-fat diet (HFD) is able to exacerbate ozone-induced adverse effects on lung function, injury, and inflammation in offspring, and it has been suggested that mitochondrial dysfunction is implicated herein. The aim of this study was to investigate whether a perinatal obesogenic HFD affects ozone-induced changes in offspring pulmonary oxidant status and the molecular control of mitochondrial function. For this purpose, female Long-Evans rats were fed a control diet or HFD before and during gestation, and during lactation, after which the offspring were acutely exposed to filtered air or ozone at a young-adult age (forty days). Directly following this exposure, the offspring lungs were examined for markers related to oxidative stress; oxidative phosphorylation; and mitochondrial fusion, fission, biogenesis, and mitophagy. Acute ozone exposure significantly increased pulmonary oxidant status and upregulated the molecular machinery that controls receptor-mediated mitophagy. In female offspring, a perinatal HFD exacerbated these responses, whereas in male offspring, responses were similar for both diet groups. The expression of the genes and proteins involved in oxidative phosphorylation and mitochondrial biogenesis, fusion, and fission was not affected by ozone exposure or perinatal HFD. These findings suggest that a perinatal HFD influences ozone-induced responses on pulmonary oxidant status and the molecular control of mitophagy in female rat offspring.
Cardiovascular and Cerebrovascular Implications of Growth Restriction: Mechanisms and Potential Treatments
Authors: Rock Charmaine R. , White Tegan A. , Piscopo Beth R. , Sutherland Amy E. , Miller Suzanne L. , Camm Emily J. , Allison Beth J.
Published: July 2021

Fetal growth restriction (FGR) is a common complication of pregnancy, resulting in a fetus that fails to reach its genetically determined growth potential. Whilst the fetal cardiovascular response to acute hypoxia is well established, the fetal defence to chronic hypoxia is not well understood due to experiment constraints. Growth restriction results primarily from reduced oxygen and nutrient supply to the developing fetus, resulting in chronic hypoxia. The fetus adapts to chronic hypoxia by redistributing cardiac output via brain sparing in an attempt to preserve function in the developing brain. This review highlights the impact of brain sparing on the developing fetal cardiovascular and cerebrovascular systems, as well as emerging long-term effects in offspring that were growth restricted at birth. Here, we explore the pathogenesis associated with brain sparing within the cerebrovascular system. An increased understanding of the mechanistic pathways will be critical to preventing neuropathological outcomes, including motor dysfunction such as cerebral palsy, or behaviour dysfunctions including autism and attention-deficit/hyperactivity disorder (ADHD).
Polyphasic Approach Utilized for the Identification of Two New Toxigenic Members of Penicillium Section Exilicaulis, P. krskae and P. silybi spp. nov.
Authors: Labuda Roman , Bacher Markus , Rosenau Thomas , Gasparotto Erika , Gratzl Hannes , Doppler Maria , Sulyok Michael , Kubátová Alena , Berger Harald , Cank Kristof , Raja Huzefa A. , Oberlies Nicholas H. , Schüller Christoph , Strauss Joseph
Published: July 2021

Two new species, Penicillium krskae (isolated from the air as a lab contaminant in Tulln (Austria, EU)) and Penicillium silybi (isolated as an endophyte from asymptomatic milk thistle (Silybum marianum) stems from Josephine County (Oregon, USA)) are described. The new taxa are well supported by phenotypic (especially conidial ornamentation under SEM, production of red exudate and red pigments), physiological (growth at 37 °C, response to cycloheximide and CREA), chemotaxonomic (production of specific extrolites), and multilocus phylogenetic analysis using RNA-polymerase II second largest subunit (RPB2), partial tubulin (benA), and calmodulin (CaM). Both new taxa are resolved within the section Exilicaulis in series Restricta and show phylogenetic affiliation to P. restrictum sensu stricto. They produce a large spectrum of toxic anthraquinoid pigments, namely, monomeric anthraquinones related to emodic and chloremodic acids and other interesting bioactive extrolites (i.e., endocrocin, paxilline, pestalotin, and 7-hydroxypestalotin). Of note, two bianthraquinones (i.e., skyrin and oxyskyrin) were detected in a culture extract of P. silybi. Two new chloroemodic acid derivatives (2-chloro-isorhodoptilometrin and 2-chloro-desmethyldermoquinone) isolated from the exudate of P. krskae ex-type culture were analyzed by nuclear magnetic resonance (NMR) and liquid chromatography–mass spectrometry (LC–MS).
Risk Implications for the Role of Budgets in Implementing Post-Acquisition Systems Integration Strategies
Authors: Razi Nazila , More Elizabeth , Shen Gensheng
Published: July 2021

This paper studies the role of budgets in implementing the systems integration strategies in an Australian post-acquisition case of two organisations and reducing its associated often-regarded high risks. It attempts a fresh narrative approach to examine the evolution of accounting and its effects on the challenges of post-acquisition integration processes by using the performative approach such as the sociotechnical networks of Actor Network Theory in a broader analytical framework as a possible solution to reducing the risks inherent in systems integration. The methodology of the case study is based on Callon’s model of Four-Moment translation where integration strategy and budgets are regarded as social practice and defined relationally as bundles of activities and take form in and through practice and interaction between diverse actors and actants. A qualitative approach is adopted in the examination of the systems integration networks in an Australian post-acquisition case. Data was collected and analysed using semi-structured interviews. It was found, through the examination of the routine practices of systems integration strategy making and how people enact and draw on a certain financial report on a daily basis to perform systems integration network strategies, that material forms of accounting act as a powerful structuring and inscription tool in integration activities, thus shaping integration strategic options and post-acquisition economic conditions of the organisation. The result shows how the risk could be reduced in the post-acquisition system integration. The research contributes to the risk, change, and accounting literatures by providing insights into the mundane and ordinary practices of different aspects of integration strategy making, and the way employees enact and draw on accounting numbers on a day-to-day basis to perform systems integration network strategies. This case study facilities this research to be further developed and broadened in terms of other cases, industries, and countries.
Flow Mechanism Characterization of Porous Oil-Containing Material Base on Micro-Scale Pore Modeling
Authors: Yan Ke , Yin Tingting , Sun Jiannan , Hong Jun , Zhu Yongsheng
Published: July 2021

The self-lubricating effect of the porous oil-containing cage is realized by storing and releasing lubricants through its internal micro-scale pore structure. The internal flow and heat transfer process in the micron-submicron pore structure is crucial to the self-lubricating mechanism of the porous oil-containing cage. To this end, a new modeling method of porous cage was proposed based on random seeds theory, and the local two-dimensional models of porous cage with different micro-scale pore structure were established. The multiphysics coupling simulation analysis of lubricating oil inside the porous cage with the effect of centrifugal force and thermal expansion was carried out based on the COMSOL Multiphysics platform. In order to characterize the micro-scale pore structure, new structural parameter indicators, such as relative surface perimeter, effective porosity, tortuosity and fluid properties related to the internal flow process, were all extracted from the above models. Combing with the Hagen–Poiseuille equation, a flow resistance model of oil flow inside the porous oil-containing cage was obtained. Finally, comparison of simulation results and analytical solutions of the micro-scale resistance model was carried out to verify the correctness of the micro-scale resistance model. The work provides a new direction for the study of the lubrication mechanism of the porous oil-containing cage.
Human Olfactory Mucosa Stem Cells Delivery Using a Collagen Hydrogel: As a Potential Candidate for Bone Tissue Engineering
Authors: Simorgh Sara , Milan Peiman Brouki , Saadatmand Maryam , Bagher Zohreh , Gholipourmalekabadi Mazaher , Alizadeh Rafieh , Hivechi Ahmad , Arabpour Zohreh , Hamidi Masoud , Delattre Cédric
Published: July 2021

For bone tissue engineering, stem cell-based therapy has become a promising option. Recently, cell transplantation supported by polymeric carriers has been increasingly evaluated. Herein, we encapsulated human olfactory ectomesenchymal stem cells (OE-MSC) in the collagen hydrogel system, and their osteogenic potential was assessed in vitro and in vivo conditions. Collagen type I was composed of four different concentrations of (4 mg/mL, 5 mg/mL, 6 mg/mL, 7 mg/mL). SDS-Page, FTIR, rheologic test, resazurin assay, live/dead assay, and SEM were used to characterize collagen hydrogels. OE-MSCs encapsulated in the optimum concentration of collagen hydrogel and transplanted in rat calvarial defects. The tissue samples were harvested after 4- and 8-weeks post-transplantation and assessed by optical imaging, micro CT, and H&E staining methods. The highest porosity and biocompatibility were confirmed in all scaffolds. The collagen hydrogel with 7 mg/mL concentration was presented as optimal mechanical properties close to the naïve bone. Furthermore, the same concentration illustrated high osteogenic differentiation confirmed by real-time PCR and alizarin red S methods. Bone healing has significantly occurred in defects treated with OE-MSCs encapsulated hydrogels in vivo. As a result, OE-MSCs with suitable carriers could be used as an appropriate cell source to address clinical bone complications.
Change of Oxidation Mechanisms by Laser Chemical Machined Rim Zone Modifications of 42CrMo4 Steel
Authors: Schupp Alexander , Pütz René Daniel , Beyss Oliver , Beste Lucas-Hermann , Radel Tim , Zander Daniela
Published: July 2021

The oxidation mechanism of metals depends, among other factors, on the surface integrity. The surface and rim zone properties are often determined by the manufacturing process that was used to machine the material. Laser chemical machining (LCM) is a manufacturing process that uses laser radiation as a localized and selective heat source to activate a chemical reaction between an electrolyte and a metallic surface. The objective of this work is first to investigate how different LCM processes affect the rim zone properties of 42CrMo4. For this purpose, the surface chemistry is analyzed by EDS and XPS, phases and residual stresses are determined by XRD, and the morphology is investigated by SEM. Second, the influence of these modified rim zones on the oxidation properties of the steel at 500 °C in air is to be demonstrated in oxidation tests by in situ XRD and subsequent SEM/EDS investigations. A decisive influence of the oxides formed on the surface of 42CrMo4 during LCM in different electrolytes (NaNO3 solution and H3PO4) at two different laser powers on the high-temperature oxidation properties was demonstrated. These oxides were supposed to act as nucleation sites for oxide layer formation at 500 °C and led to an overall increase in oxide layer thickness after high-temperature oxidation compared to non-LCM-processed surfaces.
Effect of Calcination Temperature and Chemical Composition of PAN-Derived Carbon Microfibers on N2, CO2, and CH4 Adsorption
Authors: Ojeda-López Reyna , Ramos-Sánchez Guadalupe , García-Mendoza Cinthia , C. S. Azevedo Diana , Guzmán-Vargas Ariel , Felipe Carlos
Published: July 2021

This work investigates the interplay of carbonization temperature and the chemical composition of carbon microfibers (CMFs), and their impact on the equilibration time and adsorption of three molecules (N2, CO2, and CH4). PAN derived CMFs were synthesized by electrospinning and calcined at three distinct temperatures (600, 700 and 800 °C), which led to samples with different textural and chemical properties assessed by FTIR, TGA/DTA, XRD, Raman, TEM, XPS, and N2 adsorption. We examine why samples calcined at low/moderate temperatures (600 and 700 °C) show an open hysteresis loop in nitrogen adsorption/desorption isotherms at −196.15 °C. The equilibrium time in adsorption measurements is nearly the same for these samples, despite their distinct chemical compositions. Increasing the equilibrium time did not allow for the closure of the hysteresis loop, but by rising the analysis temperature this was achieved. By means of the isosteric enthalpy of adsorption measurements and ab initio calculations, adsorbent/adsorbate interactions for CO2, CH4 and N2 were found to be inversely proportional to the temperature of carbonization of the samples (CMF-600 > CMF-700 > CMF-800). The enhancement of adsorbent/adsorbate interaction at lower carbonization temperatures is directly related to the presence of nitrogen and oxygen functional groups on the surface of CMFs. Nonetheless, a higher concentration of heteroatoms also causes: (i) a reduction in the adsorption capacity of CO2 and CH4 and (ii) open hysteresis loops in N2 adsorption at cryogenic temperatures. Therefore, the calcination of PAN derived microfibers at temperatures above 800 °C is recommended, which results in materials with suitable micropore volume and a low content of surface heteroatoms, leading to high CO2 uptake while keeping acceptable selectivity with regards to CH4 and moderate adsorption enthalpies.