bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Microstructure, Weld Heat Input, and Mechanical Properties of Mg–Al–Zn Alloy GTA Weldments
Authors: Babu Nagumothu Kishore , Talari Mahesh Kumar , Srirangam Prakash , AlFaify Abdullah Yahia , Rehman Ateekh Ur
Published: April 2022

The present study investigated the influence of welding speed on the microstructure, hardness, and tensile properties of the AZ31 Mg alloy gas tungsten arc (GTA) welds that were prepared using alternating current (AC). A microstructural examination of the weld metal and base metal was performed using stereo, optical, and scanning electron microscopy (HR-SEM and EDS) techniques. The microstructure of all fusion zones consists of two parts: a columnar zone, adjacent to the fusion boundary, and equiaxed grains, in the centre of the weld fusion zone. It is shown that the average width of the equiaxed zone present at the centre of the fusion zone increases with increasing welding speed. Metallographic examination shows that the highest welding speed (5 mm/s) results in the smallest average grain size. The welds prepared with high welding speed exhibit an increase in strength, hardness, and ductility compared with other welding speeds, which is attributed to low heat input.
Experimental Study on Settlement Behavior of Ballasted Tracks with Polymer Compound-Coated Gravel
Authors: Choi Jung-Youl
Published: April 2022

The ballast used in ballasted railway tracks transmits load from the rails and ties to the subgrade during train travel, and directly affects the overall track support performance and elastic behavior of the ballasted track. Due to the material limitations of the ballast, it is difficult to quantitatively manage its performance, status, and shape maintenance, and the use of the ballast requires continuous maintenance and management work. In this study on a proposed ballast material, ballast box tests and numerical analyses were performed to examine the performance of the ballast that has a gravel coating layer and can be used semi-permanently while maintaining the shape of the ballast against impacts, abrasion, and friction. The results show that the coated ballast’s performance ensured constant stiffness in comparison to that of a normal ballast.
An End-of-Line Test System for Pneumatic ABS Controllers in Commercial Vehicles
Authors: Xu Jun , Xiang Qian , Li Gangyan
Published: April 2022

To remedy the defects of conventional pneumatic ABS (anti-lock Braking system) controller testing equipment for commercial vehicles, such as low efficiency and difficult testing condition configurations, a workflow was proposed based on the unit integration test mode. The relationship among the operation logic of the ABS valves, test conditions, and wheel speed was derived through the simulation of a multi-condition configuration. Then, a wheel speed simulation model was set up by taking the test conditions as inputs, and it was implanted into an embedded control unit. Next, the hardware module and the underlying drivers as well as an application algorithm for the application layer were designed. A prototype of the EOL (end-of-line) test system was built. The test results show that the prototype can not only achieve a rapid test condition configuration and accurate fault location but that it can also meet the requirements for test efficiency.
Special Issue on Recent Developments in Orthodontics on Craniofacial Orthopedics
Authors: Maspero Cinzia , Abate Andrea , Lanteri Valentina
Published: April 2022

This Special Issue was proposed with the aim of highlighting the recent developments in orthodontics on craniofacial orthopedics [...]
Special Issue on Current Techniques and Materials in Dentistry
Authors: Motoyoshi Mitsuru
Published: April 2022

In the field of dentistry, the use of regenerative therapy, as well as biocompatible and biomimetic materials, is well-established [...]
Malcertificate: Research and Implementation of a Malicious Certificate Detection Algorithm Based on GCN
Authors: Liu Jingru , Luktarhan Nurbol , Chang Yuyuan , Yu Wenjie
Published: April 2022

Encryption is widely used to ensure the security and confidentiality of information. Because people trust in encryption technology, a series of attack methods based on certificates have been derived. Malicious certificates protect many malicious behaviors and threaten data security. To counter this threat, machine learning algorithms are widely used in malicious certificate detection. However, the detection efficiency of such algorithms largely depends on whether the extracted features can effectively represent the data. In contrast, graph convolutional networks (GCNs) can automatically extract useful features. GCNs are powerful at fitting graph data, which can improve the effectiveness of learning systems by efficiently embedding prior knowledge in an end-to-end manner. In this paper, we propose an algorithm for detecting malicious digital certificates with GCNs. Firstly, we transform the digital certificate dataset with pem document structure into a corpus of graph structure based on attribute co-occurrence and document attribute relations. Then, we put the graph structure certificate dataset into a GCN for training. The results of the experiment show that GCN is very effective in certificate classification and outperforms traditional machine learning algorithms and extant neural network algorithms. The accuracy of our algorithm to detect malicious certificates is 97.41%. This shows that our algorithm is very effective.
Analysis of the Effect of Economic Development on Air Quality in Jiangsu Province Using Satellite Remote Sensing and Statistical Modeling
Authors: Jia Jia , You Yan , Yang Shanlin , Shang Qingmei
Published: April 2022

In recent decades, the economy of China has developed rapidly, but this has brought widespread damage to the environment, which forces us to explore a sustainable, green, economic development model. Therefore, it is particularly necessary to clarify the relationship between economic development and environmental pollution. In this paper, we used satellite remote sensing tropospheric NO2 vertical column density (VCD) as an air quality indicator; the total exports, total imports, and industrial electricity consumption as the economic indicators; and the wind speed, temperature, and planetary boundary layer height as the meteorological factors to perform a Generalized Additive Modeling (GAM) analysis. By deducing the influence of meteorological factors, the relationship between economic indicators and the air quality indicator can be determined. When total exports increased by one billion USD (United States Dollar), the tropospheric NO2 VCDs of Nanjing and Suzhou increased by about 15% and 6%, respectively. The tropospheric NO2 VCDs of Suzhou increased by about 5% when the total imports increased by one billion USD. In addition, when the industrial electricity consumption increased by one billion kWh, the tropospheric NO2 VCDs of Nanjing, Suzhou and Xuzhou increased by about 25%, 12%, and 59%, respectively. This study provides a method to quantify the contribution of economic growth to air pollution, which is helpful for better understanding of the relationship between economic development and air quality.
TP53 Pathogenic Variants in Early-Onset Breast Cancer Patients Fulfilling Hereditary Breast and Ovary Cancer and Li-Fraumeni-like Syndromes
Authors: da Silva Paula Francinete Faustino , Goveia Rebeca Mota , Teixeira Thaís Bomfim , Gamba Bruno Faulin , de Lima Aliny Pereira , Rogatto Sílvia Regina , Silveira-Lacerda Elisângela de Paula
Published: April 2022

TP53 gene mutation is the most common genetic alteration in human malignant tumors and is mainly responsible for Li-Fraumeni syndrome. Among the several cancers related to this syndrome, breast cancer (BC) is the most common. The TP53 p.R337H germline pathogenic variant is highly prevalent in Brazil’s South and Southeast regions, accounting for 0.3% of the general population. We investigated the prevalence of TP53 germline pathogenic variants in a cohort of 83 BC patients from the Midwest Brazilian region. All patients met the clinical criteria for hereditary breast and ovarian cancer syndrome (HBOC) and were negative for BRCA1 and BRCA2 mutations. Moreover, 40 index patients fulfilled HBOC and the Li-Fraumeni-like (LFL) syndromes criteria. The samples were tested using next generation sequencing for TP53. Three patients harbored TP53 missense pathogenic variants (p.Arg248Gln, p.Arg337His, and p.Arg337Cys), confirmed by Sanger sequencing. One (1.2%) patient showed a large TP53 deletion (exons 2–11), which was also confirmed. The p.R337H variant was detected in only one patient. In conclusion, four (4.8%) early-onset breast cancer patients fulfilling the HBOC and LFL syndromes presented TP53 pathogenic variants, confirming the relevance of genetic tests in this group of patients. In contrast to other Brazilian regions, TP53 p.R337H variant appeared with low prevalence.
Hepatocellular Carcinoma: The Role of MicroRNAs
Authors: Khare Sharad , Khare Tripti , Ramanathan Raghu , Ibdah Jamal A.
Published: April 2022

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. HCC is diagnosed in its advanced stage when limited treatment options are available. Substantial morphologic, genetic and epigenetic heterogeneity has been reported in HCC, which poses a challenge for the development of a targeted therapy. In this review, we discuss the role and involvement of several microRNAs (miRs) in the heterogeneity and metastasis of hepatocellular carcinoma with a special emphasis on their possible role as a diagnostic and prognostic tool in the risk prediction, early detection, and treatment of hepatocellular carcinoma.
Carbohydrate Metabolism Parameters of Adult Glial Neoplasms According to Immunohistochemical Profile
Authors: Obukhova Larisa , Nikiforova Olga , Kontorshchikova Claudia , Medyanik Igor , Orlinskaya Natalya , Grishin Artem , Kontorshchikov Michael , Shchelchkova Natalya
Published: April 2022

This research aimed to investigate the interrelationship of carbohydrate metabolism parameters and immunohistochemical characteristics of glial tumors. Tumor tissue, peritumoral area, and adjacent noncancerous tissue fragments of 20 patients with gliomas of varying degrees of anaplasia were analyzed. The greatest differences in the carbohydrate metabolism compared to adjacent noncancerous tissues were identified in the tumor tissue: reduction in the levels of lactate and glycogen synthase kinase-3β. Significant differences with adjacent noncancerous tissues for the peritumoral zone were not found. The activity of the carbohydrate metabolism enzymes was different depending on the immunohistochemical glioma profile, especially from Ki 67 level. Bioinformatic analysis of the interactions of immunohistochemical markers of gliomas and carbohydrate metabolism enzymes using the databases of STRING, BioGrid, and Signor revealed the presence of biologically significant interactions with glycogen synthase kinase 3β, hexokinase, glucose-6-phosphate dehydrogenase, and transketolase. The established interconnection of glycolysis with methylation of the promoter of O-6-methylguanine-DNA-methyltransferase (MGMT) of gliomas can be used to increase chemotherapy efficiency.
Common Shared Pathogenic Aspects of Small Vessels in Heart and Brain Disease
Authors: Moretti Rita , Janjusevic Milijana , Fluca Alessandra Lucia , Saro Riccardo , Gagno Giulia , Pierri Alessandro , Padoan Laura , Restivo Luca , Derin Agnese , Beltrami Antonio Paolo , Caruso Paola , Sinagra Gianfranco , Aleksova Aneta
Published: April 2022

Small-vessel disease (SVD), also known as microvascular endothelial dysfunction, is a disorder with negative consequences for various organs such as the heart and brain. Impaired dilatation and constriction of small vessels in the heart lead to reduced blood flow and ischemia independently of coronary artery disease (CAD) and are associated with major cardiac events. SVD is usually a silent form of subcortical vascular burden in the brain with various clinical manifestations, such as silent-lacunar-ischemic events and confluent white-matter hyperintensities. Imaging techniques are the main help for clinicians to diagnose cardiac and brain SVD correctly. Markers of inflammation, such as C-reactive protein, tumor-necrosis-factor α, and interleukin 6, provide insight into the disease and markers that negatively influence nitric-oxide bioavailability and promote oxidative stress. Unfortunately, the therapeutic approach against SVD is still not well-defined. In the last decades, various antioxidants, oxidative stress inhibitors, and superoxide scavengers have been the target of extensive investigations due to their potential therapeutic effect, but with unsatisfactory results. In clinical practice, traditional anti-ischemic and risk-reduction therapies for CAD are currently in use for SVD treatment.
Signal-On Fluorescence Biosensor for Highly Sensitive Detection of miRNA-21 Based on DNAzyme Assisted Double-Hairpin Molecular Beacon
Authors: Fang Chenxin , Yang Yuxing , Zou Shuhao , Ouyang Ping , Qing Yang , Han Jialun , Li Haiyu , Wang Zhencui , Du Jie
Published: April 2022

Although miRNAs exist in small quantities in the human body, they are closely related to the abnormal expression of genes in diseases such as tumors. Therefore, sensitive detection of miRNAs is very important for the prevention and treatment of various tumors and major diseases. The purpose of this study is to develop a label-free sensing strategy based on the co-action of double-hairpin molecular beacons and deoxyribozymes (DNAzymes) for highly sensitive detection of miRNA-21. The target miRNA-21 promotes the assembly of DNAzyme with a complete catalytic core region. At the presence of Mg2+, DNAzyme cuts a substrate into short chains, which open the double hairpin molecular beacon, and then form G-quadruplexs at both ends, specifically binding more ThT to generate a amplified fluorescent signal. The cut substrate will be replaced by the uncut ones in the next stage, increasing the concentration of reactants, and thus further improving the fluorescence intensity. This DNAzyme assisted double hairpin molecular beacon has a certain degree of discrimination for substances with single base mismatches, and the detection limit of miRNA-21 is 0.13 pM, lower than that of the many other analysis. Further, this detection has good selectivity and sensitivity in serum. Therefore, this strategy provides a simple, fast and low-cost platform for the sensitive detection of miRNA-21, having potential applications in early cancer diagnosis.
Potential Factors That Contribute to Post-COVID-19 Fatigue in Women
Authors: Rudroff Thorsten , Workman Craig D. , Bryant Andrew D.
Published: April 2022

Mortality of acute coronavirus disease (COVID-19) is higher in men than in women. On the contrary, women experience more long-term consequences of the disease, such as fatigue. In this perspective article, we proposed a model of the potential factors that might contribute to the higher incidence of post-COVID-19 fatigue in women. Specifically, psycho-physiological factors are features that might increase central factors (e.g., inflammation) and result in greater perceptions of fatigue. Furthermore, pre-existing conditions likely play a prominent role. This model offers a framework for researchers and clinicians, and future research is required to validate our proposed model and elucidate all mechanisms of the increased incidence and prevalence of post-COVID-19 fatigue in women.
Effect of Despotic Leadership on Employee Turnover Intention: Mediating Toxic Workplace Environment and Cognitive Distraction in Academic Institutions
Authors: Iqbal Javed , Asghar Ali , Asghar Muhammad Zaheer
Published: April 2022

Despotic leadership builds adverse emotions and turnover intentions in the employees of an educational organization. This study investigated the relationships among despotic leadership, toxic workplace environment, cognitive distraction, and employee turnover intention. This study is based on social exchange theory (SET), social psychology theories of behavioral intention formation (such as the theory of reasoned action and the theory of planned behavior), and of the despotic leadership style. A survey questionnaire containing 28 items was completed by 240 faculty members from four Chinese universities. The responses were documented on a seven-point Likert scale. We applied PLS–SEM (partial least squares structural equation modeling) to measure the effects. The outcomes showed that despotic leadership influenced employee turnover intention in academic institutions. Toxic workplace environment correlates with employee turnover intention. Cognitive distraction also correlates with employee turnover intention. Toxic workplace environment mediates the relationship between despotic leadership and employee turnover intention. Similarly, cognitive distraction mediates the relationship between despotic leadership and employee turnover intention. The study concluded that despotic leadership, toxic workplace environment, and cognitive distraction might increase employee turnover intention. This study adds to the literature in the field of despotic leadership, toxic workplace environment, cognitive distraction, and employee turnover intention in academic institutions. Furthermore, it offers valuable and practical implications along with recommendations for future research.
Artificial Intelligence Decision-Making Transparency and Employees’ Trust: The Parallel Multiple Mediating Effect of Effectiveness and Discomfort
Authors: Yu Liangru , Li Yi
Published: April 2022

The purpose of this paper is to investigate how Artificial Intelligence (AI) decision-making transparency affects humans’ trust in AI. Previous studies have shown inconsistent conclusions about the relationship between AI transparency and humans’ trust in AI (i.e., a positive correlation, non-correlation, or an inverted U-shaped relationship). Based on the stimulus-organism-response (SOR) model, algorithmic reductionism, and social identity theory, this paper explores the impact of AI decision-making transparency on humans’ trust in AI from cognitive and emotional perspectives. A total of 235 participants with previous work experience were recruited online to complete the experimental vignette. The results showed that employees’ perceived transparency, employees’ perceived effectiveness of AI, and employees’ discomfort with AI played mediating roles in the relationship between AI decision-making transparency and employees’ trust in AI. Specifically, AI decision-making transparency (vs. non-transparency) led to higher perceived transparency, which in turn increased both effectiveness (which promoted trust) and discomfort (which inhibited trust). This parallel multiple mediating effect can partly explain the inconsistent findings in previous studies on the relationship between AI transparency and humans’ trust in AI. This research has practical significance because it puts forward suggestions for enterprises to improve employees’ trust in AI, so that employees can better collaborate with AI.
Study on Parameters’ Influence and Optimal Design of Tuned Inerter Dampers for Seismic Response Mitigation
Authors: Zhang Ruoyu , Huang Jizhong , Cao Meigen , Luo Qingyang , Guo Xiuwei
Published: April 2022

In this paper, parameter analyses of a tuned inerter damper (TID) are carried out based on the displacement mitigation ratio. The optimal design of TID based on the closed-form solution method is carried out and compared with the fixed-point method. Meanwhile, applicable conditions of two methods are discussed in wider range of values of objective function under different inherent damping ratios. Finally, seismic responses of SDOF system with TID are carried out, which verifies the feasibility of the closed-form solution optimization method. Compared with the fixed-point method, the inherent damping ratio of the original structure is considered in the closed-form solution method, and the optimal damping ratio of a TID is smaller than that of the fixed-point method under same displacement mitigation ratio. The parameters’ combination of a TID designed by the fixed-point method obtains a vibration mitigation effect with a larger damping ratio by cooperating with the deformation enhancement effect of the inerter, which may make the vibration mitigation effect of the TID lower than that of the VD in structures with large inherent damping ratios. However, the deformation enhancement effect on the damping element of the inerter can be fully used by using the closed-form solution method. Better applicability and robustness are shown in closed-form solution method. Under the same displacement mitigation ratio, the damping ratio of a TID obtained by using the closed-form solution method is about one tenth of that obtained by using the fixed-point method, which can realize the lightweight design of the TID.
Investigations of the Mechanical Properties and Durability of Reactive Powder Concrete Containing Waste Fly Ash
Authors: Du Yubing , Wang Shiyu , Hao Wenru , Shi Feiting , Wang Hui , Xu Feng , Du Tao
Published: April 2022

Waste fly ash (WFA) with pozzolanic activities may be advantageous to the mechanical properties of reactive powder concrete (RPC) when WFA partially replaces cement in RPC. In this study, RPC specimens with 0–25% WFA were prepared under the curing temperatures of 0, 20, and 40 °C for 3 to 120 days. The flowability of fresh RPC, the mechanical strengths, and the NaCl freeze–thaw damage were investigated. Additionally, the following carbonation depths after different NaCl freeze–thaw cycles and the leaching amount of toxic metal elements were also determined experimentally. The results indicated that the incorporation of WFA could decrease the slump flow of fresh RPC due to the relatively smaller particle size of WFA. With an increase in the WFA content, the early-age flexural and compressive strengths first exhibited an increasing and then decreasing trend. However, WFA will always deteriorate the long-term mechanical properties, and both flexural and compressive strengths can be reduced by up to 25% when cured for 120 days. A higher temperature (i.e., 40 °C) was found to benefit the mechanical properties, especially when cured for 3 days. The RPC with 10% WFA exhibited the optimum salt-freezing resistance with an approximately 30% reduction in the mass loss rate when the NaCl freeze–thaw cycles reached 300. The improvement in durability can be attributed to a more compact microstructure of RPC with WFA through microscopic observations. The relationships between the mass and mechanical strength loss rates can be expressed through positive correlation quadratic functions. The carbonation depth decreased following a quadratic function with increasing mass ratios of WFA and NaCl freeze–thaw cycles. The leaching amounts of Cr and Zn increased with increasing WFA content over time, and the cumulative values reached equilibrium at 5 months.
Response of Functionally Graded Preplaced Aggregate Fibrous Concrete with Superior Impact Strength
Authors: Murali Gunasekaran , Prasad Nandhu , Abid Sallal R. , Vatin Nikolai Ivanovich
Published: April 2022

This research examines the modified drop-mass impact performance on functionally graded preplaced aggregate fibrous concrete (FPAFC) against repeated low-velocity impacts. Three-layered FPAFCs were prepared with the outer layers reinforced with steel and polypropylene fibers to evaluate the impact resistance. For comparison, both one- and two-layered concretes were cast simultaneously. The modified version of the impact test was suggested to the ACI 544 drop-mass impact test to decrease the scattered test data. The modification was a replacement of the steel ball with a steel bar to apply a line impact instead of the single-point impact. This modification distributes the impact energy over a broader area and reduces the scattering of results. The study parameters for the tests were impact numbers, which cause first cracking and failure; ductility index; and mode of failure. In addition, three methods of the two-parameter Weibull distribution were used to examine the dispersed test results, which were presented in terms of reliability. Results revealed that the specimens comprising 3.6% steel fibers at the top layer and no fiber at the middle layer exhibited the highest percentage improvements of 633% and 2732% recorded for the cracking and failure impact number, respectively. The percentage difference in impact strength results between these two methods ranged from −14% to 75% for cracking impact number and from 6.8% to 57.2% for failure impact number. The coefficient of variation value calculated from the modified impact test was reduced and ranged from 20.3% to 56.1% for cracking impact number and from 15.2% to 65.3% for failure impact number, compared with the same mixtures from the ACI 544 test method. This phenomenon indicates that the modified impact test delivered a lower scattering of results by introducing a line of impact using a steel bar rather than a single-point impact.
Characterization of the Peri-Membrane Fluorescence Phenomenon Allowing the Detection of Urothelial Tumor Cells in Urine
Authors: Gutierrez Charly , Pinson Xavier , Jarnouen Kathleen , Charpentier Marine , Pineau Raphael , Lallement Laëtitia , Pedeux Rémy
Published: April 2022

Urine cytology is non-invasive, easy to collect, with medium sensitivity and a high specificity. It is an effective way to detect high-grade bladder cancer (BC), but it is less effective on low-grade BC because the rate of equivocal results is much higher. Recently, the fluorescent properties of plasma membranes of urothelial tumor cells (UTC) found in urine cytology have been shown to be useful in improving the early detection of BC. This phenomenon is called peri-membrane fluorescence (PMF). Based on previous studies that have identified the PMF on UTCs, the main objective was to characterize this phenomenon. For this study, a software was specially created to quantify the PMF of all tested cells and different treatments performed. PMF was not found to be a morphological and discriminating feature of UTCs, all cells in shape and not from urine show PMF. We were able to highlight the crucial role of plasma membrane integrity in the maintenance of PMF. Finally, it was found that the induction of a strong cellular stress induced a decrease in PMF, mimicking what was observed in non-tumor cells collected from urine. These results suggest that PMF is found in cells able to resist this stress, such as tumor cells.
Secondary Oral Cancer after Systemic Treatment of Hematological Malignancies and Oral GVHD: A Systematic Review
Authors: Janowiak-Majeranowska Aleksandra , Osowski Jakub , Mikaszewski Bogusław , Majeranowski Alan
Published: April 2022

(1) Purpose: In this article, the authors decided to systematically review the available literature to identify potential correlations regarding secondary oral carcinoma occurring after hematological systemic treatment and oral chronic graft-versus-host disease. (2) Methods: Medline (PubMed) and Scopus (Elsevier) databases were searched, including articles from the years 2002–2022. The 33 unique results were assessed by a PRISMA flowchart, and we rejected 24 papers and included 9 articles in the review. (3) Results: The majority of patients suffered from the oral form of chronic graft-versus-host disease before the diagnosis of oral malignancy. Two common cancer sites were the tongue and buccal mucosa. The exact percentage of secondary oral carcinoma after hematopoietic stem cell transplantation could not be estimated due to a lack of data. (4) Conclusions: Every physician taking part in the follow-up of patients after hematological treatment should be aware of the possibility of secondary neoplastic disease in the oral cavity, especially in patients with oral graft-versus-host disease. Proper follow-up protocols and monitoring are needed in this patient group as the cause of these cancers appears to be multifactorial.
Putative Clinical Potential of ERBB2 Amplification Assessment by ddPCR in FFPE-DNA and cfDNA of Gastroesophageal Adenocarcinoma Patients
Authors: Boldrin Elisa , Mazza Marcodomenico , Piano Maria Assunta , Alfieri Rita , Montagner Isabella Monia , Magni Giovanna , Scaini Maria Chiara , Vassallo Loretta , Rosato Antonio , Pilati Pierluigi , Scapinello Antonio , Curtarello Matteo
Published: April 2022

Anti-HER2 monoclonal antibody trastuzumab improves the survival of those patients with advanced gastroesophageal adenocarcinoma (GEA) exhibiting HER2/ERBB2 overexpression/amplification. The current gold standard methods used to diagnose the HER2 status in GEA are immunohistochemistry (IHC) and silver or fluorescence in situ hybridization (SISH or FISH). However, they do not permit spatial and temporal tumor monitoring, nor do they overcome intra-cancer heterogeneity. Droplet digital PCR (ddPCR) was used to implement the assessment of HER2 status in formalin-fixed paraffin-embedded (FFPE) tumor DNA from a retrospective cohort (86 patients) and in cell-free DNA (cfDNA) samples from a prospective cohort (28 patients). In comparison to IHC/SISH, ddPCR assay revealed ERBB2 amplification in a larger patient fraction, including HER2 2+ and 0–1+ of the retrospective cohort (45.3% vs. 15.1%). In addition, a considerable number of HER2 2+ and 0–1+ prospective patients who were negative in FFPE by both IHC/SISH and ddPCR, showed ERBB2 amplification in the cfDNA collected just before surgery. cfDNA analysis in a few longitudinal cases revealed an increasing ERBB2 trend at progression. In conclusion, ddPCR in liquid biopsy may improve the detection rate of HER2 positive patients, preventing those patients who could benefit from targeted therapy from being incorrectly excluded.
Target Therapy for Extramedullary Relapse of FLT3-ITD Acute Myeloid Leukemia: Emerging Data from the Field
Authors: Duminuco Andrea , Maugeri Cinzia , Parisi Marina , Mauro Elisa , Fiumara Paolo Fabio , Randazzo Valentina , Salemi Domenico , Agueli Cecilia , Palumbo Giuseppe Alberto , Santoro Alessandra , Di Raimondo Francesco , Vetro Calogero
Published: April 2022

FMS-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase family member. Mutations in FLT3, as well known, represent the most common genomic alteration in acute myeloid leukemia (AML), identified in approximately one-third of newly diagnosed adult patients. In recent years, this has represented an important therapeutic target. Drugs such as midostaurin, gilteritinib, and sorafenib, either alone in association with conventional chemotherapy, play a pivotal role in AML therapy with the mutated FLT3 gene. A current challenge lies in treating forms of AML with extramedullary localization. Here, we describe the general features of myeloid sarcoma and the ability of a targeted drug, i.e., gilteritinib, approved for relapsed or refractory disease, to induce remission of these extramedullary leukemic localizations in AML patients with FLT3 mutation, analyzing how in the literature, there is an important development of cases describing this promising potential for care.
Expression Profiles of GILZ and Annexin A1 in Human Oral Candidiasis and Lichen Planus
Authors: Mozaffari Mahmood S. , Abdelsayed Rafik
Published: April 2022

Adrenal glands are the major source of glucocorticoids, but recent studies indicate tissue-specific production of cortisol, including that in the oral mucosa. Both endogenous and exogenous glucocorticoids regulate the production of several proteins, including the glucocorticoid-induced leucine zipper (GILZ) and Annexin A1, which play important roles in the regulation of immune and inflammatory responses. Common inflammation-associated oral conditions include lichen planus and candidiasis, but the status of GILZ and Annexin A1 in these human conditions remains to be established. Accordingly, archived paraffin-embedded biopsy samples were subjected to immunohistochemistry to establish tissue localization and profile of GILZ and Annexin A1 coupled with the use of hematoxylin–eosin stain for histopathological assessment; for comparison, fibroma specimens served as controls. Histopathological examination confirmed the presence of spores and pseudohyphae for oral candidiasis (OC) specimens and marked inflammatory cell infiltrates for both OC and oral lichen planus (OLP) specimens compared to control specimens. All specimens displayed consistent and prominent nuclear staining for GILZ throughout the full thickness of the epithelium and, to varying extent, for inflammatory infiltrates and stromal cells. On the other hand, a heterogeneous pattern of nuclear, cytoplasmic, and cell membrane staining was observed for Annexin A1 for all specimens in the suprabasal layers of epithelium and, to varying extent, for inflammatory and stromal cells. Semi-quantitative analyses indicated generally similar fractional areas of staining for both GILZ and Annexin A1 among the groups, but normalized staining for GILZ, but not Annexin A1, was reduced for OC and OLP compared to the control specimens. Thus, while the cellular expression pattern of GILZ and Annexin A1 does not differentiate among these conditions, differential cellular profiles for GILZ vs. Annexin A1 are suggestive of their distinct physiological functions in the oral mucosa.
Regulation of Cardiac Fibroblast GLS1 Expression by Scleraxis
Authors: Chattopadhyaya Sikta , Nagalingam Raghu S. , Ledingham D. Allison , Moffatt Teri L. , Al-Hattab Danah S. , Narhan Pavit , Stecy Matthew T. , O’Hara Kimberley A. , Czubryt Michael P.
Published: April 2022

Fibrosis is an energy-intensive process requiring the activation of fibroblasts to myofibroblasts, resulting in the increased synthesis of extracellular matrix proteins. Little is known about the transcriptional control of energy metabolism in cardiac fibroblast activation, but glutaminolysis has been implicated in liver and lung fibrosis. Here we explored how pro-fibrotic TGFβ and its effector scleraxis, which drive cardiac fibroblast activation, regulate genes involved in glutaminolysis, particularly the rate-limiting enzyme glutaminase (GLS1). The GLS1 inhibitor CB-839 attenuated TGFβ-induced fibroblast activation. Cardiac fibroblast activation to myofibroblasts by scleraxis overexpression increased glutaminolysis gene expression, including GLS1, while cardiac fibroblasts from scleraxis-null mice showed reduced expression. TGFβ induced GLS1 expression and increased intracellular glutamine and glutamate levels, indicative of increased glutaminolysis, but in scleraxis knockout cells, these measures were attenuated, and the response to TGFβ was lost. The knockdown of scleraxis in activated cardiac fibroblasts reduced GLS1 expression by 75%. Scleraxis transactivated the human GLS1 promoter in luciferase reporter assays, and this effect was dependent on a key scleraxis-binding E-box motif. These results implicate scleraxis-mediated GLS1 expression as a key regulator of glutaminolysis in cardiac fibroblast activation, and blocking scleraxis in this process may provide a means of starving fibroblasts of the energy required for fibrosis.
Progesterone Receptor Signaling in the Uterus Is Essential for Pregnancy Success
Authors: Cope Dominique , Monsivais Diana
Published: April 2022

The uterus plays an essential role in the reproductive health of women and controls critical processes such as embryo implantation, placental development, parturition, and menstruation. Progesterone receptor (PR) regulates key aspects of the reproductive function of several mammalian species by directing the transcriptional program in response to progesterone (P4). P4/PR signaling controls endometrial receptivity and decidualization during early pregnancy and is critical for the establishment and outcome of a successful pregnancy. PR is also essential throughout gestation and during labor, and it exerts critical roles in the myometrium, mainly by the specialized function of its two isoforms, progesterone receptor A (PR-A) and progesterone receptor B (PR-B), which display distinct and separate roles as regulators of transcription. This review summarizes recent studies related to the roles of PR function in the decidua and myometrial tissues. We discuss how PR acquired key features in placental mammals that resulted in a highly specialized and dynamic role in the decidua. We also summarize recent literature that evaluates the myometrial PR-A/PR-B ratio at parturition and discuss the efficacy of current treatment options for preterm birth.
The Puf-A Protein Is Required for Primordial Germ Cell Development
Authors: Ko Chi-Fong , Chang Yi-Chieh , Cho Huan-Chieh , Yu John
Published: April 2022

Puf-A, a nucleolar Puf domain protein, is required for ribosome biogenesis. A study of Puf-A in zebrafish has shown that Puf-A is highly expressed in primordial germ cells (PGCs) and participates in PGC development. However, it remains unclear how Puf-A governs PGC development in mammals. Here, we generated transgenic mice carrying inducible Puf-A shRNA and obtained double heterozygous mice with Puf-A shRNA and Oct4-EGFP to examine the behavior of PGCs. It was found that the knockdown of Puf-A led to the loss of a considerable number of PGCs and a slowdown of the movement of the remaining PGCs. Puf-A and NPM1 colocalized in clusters in the nuclei of the PGCs. The silencing of Puf-A resulted in the translocation of NPM1 from nucleolus to nucleoplasm and the hyperactivation of p53 in the PGCs. The PGCs in Puf-A knockdown embryos showed a significant increase in subpopulations of PGCs at G1 arrest and apoptosis. Moreover, the expression of essential genes associated with PGC maintenance was decreased in the Puf-A knockdown PGCs. Our study showed that Puf-A governed PGC development by regulating the growth, survival, and maintenance of PGCs. We also observed the alterations of NPM1 and p53 upon Puf-A knockdown to be consistent with the previous study in cancer cells, which might explain the molecular mechanism for the role of Puf-A in PGC development.
Novel Therapeutic Effects in Rat Spinal Cord Injuries: Recovery of the Definitive and Early Spinal Cord Injury by the Administration of Pentadecapeptide BPC 157 Therapy
Authors: Perovic Darko , Milavic Marija , Dokuzovic Stjepan , Krezic Ivan , Gojkovic Slaven , Vranes Hrvoje , Bebek Igor , Bilic Vide , Somun Nenad , Brizic Ivan , Skorak Ivan , Hriberski Klaudija , Sikiric Suncana , Lovric Eva , Strbe Sanja , Kubat Milovan , Boban Blagaic Alenka , Skrtic Anita , Seiwerth Sven , Sikiric Predrag
Published: April 2022

Recently, marked therapeutic effects pertaining to the recovery of injured rat spinal cords (1 min compression injury of the sacrocaudal spinal cord (S2-Co1) resulting in tail paralysis) appeared after a single intraperitoneal administration of the stable gastric pentadecapeptide BPC 157 at 10 min post-injury. Besides the demonstrated rapid and sustained recovery (1 year), we showed the particular points of the immediate effect of the BPC 157 therapy that began rapidly after its administration, (i) soon after injury (10 min), or (ii) later (4 days), in the rats with a definitive spinal cord injury. Specifically, in counteracting spinal cord hematoma and swelling, (i) in rats that had undergone acute spinal cord injury, followed by intraperitoneal BPC 157 application at 10 min, we focused on the first 10–30 min post-injury period (assessment of gross, microscopic, and gene expression changes). Taking day 4 post-injury as the definitive injury, (ii) we focused on the immediate effects after the BPC 157 intragastric application over 20 min of the post-therapy period. Comparable long-time recovery was noted in treated rats which had definitive tail paralysis: (iii) the therapy was continuously given per orally in drinking water, beginning at day 4 after injury and lasting one month after injury. BPC 157 rats presented only discrete edema and minimal hemorrhage and increased Nos1, Nos2, and Nos3 values (30 min post-injury, (i)) or only mild hemorrhage, and only discrete vacuolation of tissue (day 4, (ii)). In the day 4–30 post-injury study (iii), BPC 157 rats rapidly presented tail function recovery, and no demyelination process (Luxol fast blue staining).
Evening Primrose Extracts Inhibit PDGF-BB-Induced Vascular Smooth Muscle Cell Proliferation and Migration by Regulating Cell-Cycle-Related Proteins
Authors: Lee Jin-Ho , Kim Min Jeong , Woo Keun-Jung , Hong Joonpyo , Kim Sun-Hong , Kim Tack-Joong
Published: April 2022

The proliferation and migration of vascular smooth muscle cells (VSMCs) are important factors in the occurrence of cardiovascular diseases, such as blood flow abnormalities, stroke and atherosclerosis. Evening primrose, known as Oenothera biennis, is a plant native to Korea that exerts physiological activities, such as antioxidant effects, the inhibition of lipid accumulation and the prevention of muscle atrophy. However, the function of evening primrose stem (EVP) in the regulation of VSMC proliferation and migration and the underlying mechanisms have not been identified. In this study, the effect of EVP on the platelet-derived growth factor (PDGF)-induced proliferation and migration of VSMCs was investigated. The results show that PDGF-BB-induced proliferation of VSMCs was inhibited by EVP at concentrations of 25, 50 or 100 μg/mL in a concentration-dependent manner, and a migration assay showed that EVP inhibited cell migration. Cell cycle analysis was performed to confirm the mechanism by which cell proliferation and migration was inhibited. The results indicate that proteins involved in the cell cycle, such as cyclin, CDK and phosphorylated Rb, were downregulated by EVP at concentrations of 100 μg/mL, thereby increasing the proportion of cells in the G0/G1 phase and inhibiting cell cycle progression. In the PDGF receptor (PDGFR) signaling pathway, phosphorylation of the PDGFR was inhibited by EVP at concentrations of 100 μg/mL, and PLCγ phosphorylation was also decreased. The PDGF-BB-induced effect of EVP on the proliferation of VSMCs involved the inhibition of Akt phosphorylation and the reduction in the phosphorylation of MAPK proteins such as ERK, P38 and JNK. In conclusion, the results demonstrate that EVP inhibited PDGF-BB-induced VSMC proliferation and migration by regulating cell-cycle-related proteins.
The Effect of Bond Coat Roughness on the CMAS Hot Corrosion Resistance of EB-PVD Thermal Barrier Coatings
Authors: Xie Zhihang , Liu Qing , Lee Kuan-I. , Zhu Wang , Wu Liberty T. , Wu Rudder T.
Published: April 2022

In a high-temperature, high-flame-velocity, and high-pressure gas corrosion environment, the intercolumnar pores and gaps of electron beam–physical vapor deposition (EB-PVD) thermal barrier coatings (TBCs) may serve as infiltration channels for molten calcium–magnesium–alumino–silicate (CMAS), leading to the severe degradation of TBCs. In order to clarify the relationship between the roughness of the bond coat and the CMAS corrosion resistance of the EB-PVD TBCs, 7 wt.% yttria-stabilized zirconia (7YSZ) TBCs were prepared on the surfaces of four different roughness-treated bond coats. The effect of the bond coat roughness on the columnar microstructure of the EB-PVD YSZ was investigated. The effect of the change of the bond coat’s microstructure on the CMAS corrosion resistance of the EB-PVD YSZ was studied in detail. The results showed that the reduction in the roughness of the bond coat contributes to the improved formation of the EB-PVD YSZ columns. The small and dense columns are similar to a lotus leaf-like structure, which could reduce the wettability of CMAS and minimize the spread area between the coating and the CMAS melt. Thus, the CMAS corrosion resistance of the coating can be greatly improved. This preparation process also provides a reference for the preparation of other TBC materials, improving the resistance to CMAS hot corrosion.
As-Sintered Manganese-Stabilized Zirconia Ceramics with Excellent Electrical Conductivity
Authors: Gao Ling , Guan Ruidong , Zhang Shengnan , Zhi Hao , Jin Changqing , Jin Lihua , Wei Yongxing , Wang Jianping
Published: April 2022

As promising electrolyte materials in intermediate-temperature solid oxide fuel cells (IT-SOFCs), Sc-stabilized ZrO2 (ScSZ) and Y-stabilized ZrO2 (YSZ) electrolytes continue to be plagued by high cost and low intermediate conductivity. To mitigate these problems, Mn has been chosen as a new stabilization element for the synthesis of Mn-stabilized ZrO2 ceramics (MnSZ) through solid state sintering. Microstructures and electrical properties of micron-crystalline Zr1−xMnxO2−δ (x = 0.15, 0.20 and 0.25) ceramics electrolytes for IT-SOFCs have been systematically evaluated. Within the applied doping content, Mn2+ ions can enter the ZrO2 crystal lattice, leading to the formation of single cubic phase samples. Electrical conductivity measurements in the temperature range between 400 °C and 1000 °C show a sharp increase in conductivity due to Mn doping. The highest conductivity is obtained from the Zr0.75Mn0.25O2−δ samples, being 0.0144 S/cm at 600 °C and 0.182 S/cm at 1000 °C. The electrical conductivity at 600 °C is twice higher than that of the YSZ and two orders of magnitude higher than that of the ScSZ. These properties can fulfill the conductivity requirement (∼1 × 10−2 S/cm) for the electrolyte. Therefore, based on this study, we propose that Mn stabilized ZrO2 is a promising candidate as a solid electrolyte for IT-SOFCs.
Enhancement of the Stability of Encapsulated Pomegranate (Punica granatum L.) Peel Extract by Double Emulsion with Carboxymethyl Cellulose
Authors: Hady Essam , Youssef Mahmoud , Aljahani Amani H. , Aljumayi Huda , Ismail Khadiga Ahmed , El-Damaty El-Sayed , Sami Rokkaya , El-Sharnouby Gamal
Published: April 2022

Pomegranate peel enriched with high value of bioactive phenolics with valuable health benefits. However, after extraction of the phenolic compounds, diverse factors can affect their stability. Therefore, we, herein, aimed to prepare W1/O/W2 double nanoemulsions loaded with phenolic-rich extract from pomegranate peel in the W1 phase. Double emulsions were fabricate during a two-step emulsification technique. Furthermore, the influence of sodium carboxymethyl cellulose (CMC) in the outer aqueous phase was also investigated. We found that W1/O/W2 emulsions containing phenolic-rich extract showed good physical stability, especially in the particle size, polydispersity index, zeta potential, and creaming index. Intriguingly, high encapsulation rates of pomegranate polyphenols >95% were achieved; however, emulsion with CMC had the best encapsulation stability during storage. Thus, our study provides helpful information about the double nanoemulsions delivery system for polyphenols generated from pomegranate peel, which may lead to the development of innovative polyphenol-enriched functional foods.
Impact of Anode Thickness on Breakdown Mechanisms in Vertical GaN PiN Diodes with Planar Edge Termination
Authors: Ebrish Mona , Porter Matthew , Jacobs Alan , Gallagher James , Kaplar Robert , Gunning Brendan , Hobart Karl , Anderson Travis
Published: April 2022

GaN vertical PiN diodes with different anode thicknesses were fabricated on three native GaN wafers with the same p-layer doping concentrations, and planar hybrid edge termination. The breakdown behavior in terms of the breakdown voltage and the electroluminescence were studied as functions of the anode thickness. A repeatable avalanche breakdown and highest breakdown voltage were measured with the thinnest anode of 300 nm and with the thinnest edge termination region. This indicates the efficacy of the nitrogen-implanted hybrid edge termination design that comprises of junction termination and guard rings hybrid design. As the anode thickness increases, the edge termination thickness increases, and the devices exhibit lower breakdown voltages and less robust breakdown characteristics, often destructive. From this study, we also conclude that a very high p-layer doping of 2 × 1019 cm−3 is not s practical doping level, because it is too sensitive to the edge termination thickness.