bluuebunny/crossref_metadata_2025 huggingface dataset:
Drug Repurposing: The Mechanisms and Signaling Pathways of Anti-Cancer Effects of Anesthetics
Authors: Wu King-Chuen , Liao Kai-Sheng , Yeh Li-Ren , Wang Yang-Kao
Published: July 2022

Cancer is one of the leading causes of death worldwide. There are only limited treatment strategies that can be applied to treat cancer, including surgical resection, chemotherapy, and radiotherapy, but these have only limited effectiveness. Developing a new drug for cancer therapy is protracted, costly, and inefficient. Recently, drug repurposing has become a rising research field to provide new meaning for an old drug. By searching a drug repurposing database ReDO_DB, a brief list of anesthetic/sedative drugs, such as haloperidol, ketamine, lidocaine, midazolam, propofol, and valproic acid, are shown to possess anti-cancer properties. Therefore, in the current review, we will provide a general overview of the anti-cancer mechanisms of these anesthetic/sedative drugs and explore the potential underlying signaling pathways and clinical application of these drugs applied individually or in combination with other anti-cancer agents.
A Biosensor Platform for Point-of-Care SARS-CoV-2 Screening
Authors: Georgas Antonios , Agiannis Konstantinos , Papakosta Vasiliki , Priftis Panagiotis , Angelopoulos Spyridon , Ferraro Angelo , Hristoforou Evangelos
Published: July 2022

The COVID-19 pandemic remains a constant threat to human health, the economy, and social relations. Scientists around the world are constantly looking for new technological tools to deal with the pandemic. Such tools are the rapid virus detection tests, which are constantly evolving and optimizing. This paper presents a biosensor platform for the rapid detection of spike protein both in laboratory conditions and in swab samples from hospitalized patients. It is a continuation and improvement of our previous work and consists of a microcontroller-based readout circuit, which measures the capacitance change generated in an interdigitated electrode transducer by the presence either of sole spike protein or the presence of SARS-CoV-2 particles in swab samples. The circuit efficiency is calibrated by its correlation with the capacitance measurement of an LCR (inductance (L), capacitance (C), and resistance (R)) meter. The test result is made available in less than 2 min through the microcontroller’s LCD (liquid-crystal display) screen, whereas at the same time, the collected data are sent wirelessly to a mobile application interface. The novelty of this research lies in the potential it offers for continuous and effective screening of SARS-CoV-2 patients, which is facilitated and enhanced, providing big data statistics of COVID-19 in terms of space and time. This device can be used by individuals for SARS-CoV-2 testing at home, by health professionals for patient monitoring, and by public health agencies for monitoring the spatio-temporal spread of the virus.
A Rotatable Paper Device Integrating Reverse Transcription Loop-Mediated Isothermal Amplification and a Food Dye for Colorimetric Detection of Infectious Pathogens
Authors: Nguyen Hanh An , Choi Heewon , Lee Nae Yoon
Published: July 2022

In this study, we developed a rotatable paper device integrating loop-mediated isothermal amplification (RT-LAMP) and a novel naked-eye readout of the RT-LAMP results using a food additive, carmoisine, for infectious pathogen detection. Hydroxyl radicals created from the reaction between CuSO4 and H2O2 were used to decolor carmoisine, which is originally red. The decolorization of carmoisine can be interrupted in the presence of DNA amplicons produced by the RT-LAMP reaction due to how DNA competitively reacts with the hydroxyl radicals to maintain the red color of the solution. In the absence of the target DNA, carmoisine is decolored, owing to its reaction with hydroxyl radicals; thus, positive and negative samples can be easily differentiated based on the color change of the solution. A rotatable paper device was fabricated to integrate the RT-LAMP reaction with carmoisine-based colorimetric detection. The rotatable paper device was successfully used to detect SARS-CoV-2 and SARS-CoV within 70 min using the naked eye. Enterococcus faecium spiked in milk was detected using the rotatable paper device. The detection limits for the SARS-CoV-2 and SARS-CoV targets were both 103 copies/µL. The rotatable paper device provides a portable and low-cost tool for detecting infectious pathogens in a resource-limited environment.
Extracellular Vesicles from BMSCs Prevent Glucocorticoid-Induced BMECs Injury by Regulating Autophagy via the PI3K/Akt/mTOR Pathway
Authors: Ma Jinhui , Shen Mengran , Yue Debo , Wang Weiguo , Gao Fuqiang , Wang Bailiang
Published: July 2022

Osteonecrosis of the femoral head (ONFH) is a common clinical disease with a high disability rate. Injury of bone microvascular endothelial cells (BMECs) caused by glucocorticoid administration is one of the important causes of ONFH, and there is currently a lack of effective clinical treatments. Extracellular vesicles derived from bone stem cells (BMSC-EVs) can prevent ONFH by promoting angiogenesis and can inhibit cell apoptosis by regulating autophagy via the PI3K/Akt/mTOR signaling pathway. The present study aimed to investigate the effect of extracellular vesicles derived from bone marrow stem cells (BMSC) on a glucocorticoid-induced injury of BMECs and possible mechanisms. We found that BMSC-EVs attenuated glucocorticoid-induced viability, angiogenesis capacity injury, and the apoptosis of BMECs. BMSC-EVs increased the LC3 level, but decreased p62 (an autophagy protein receptor) expression, suggesting that BMSC-Exos activated autophagy in glucocorticoid-treated BMECs. The protective effects of BMSC-EVs on the glucocorticoid-induced injury of BMECs was mimicked by a known stimulator of autophagy (rapamycin) and could be enhanced by co-treatment with an autophagy inhibitor (LY294002). BMSC-EVs also suppressed the PI3K/Akt/mTOR signaling pathway, which regulates cell autophagy, in glucocorticoid-treated BMECs. In conclusion, the results indicate that BMSC-EVs prevent the glucocorticoid-induced injury of BMECs by regulating autophagy via the PI3K/Akt/mTOR pathway.
Pt/Au Nanoparticles@Co3O4 Cataluminescence Sensor for Rapid Analysis of Methyl Sec-Butyl Ether Impurity in Methyl Tert-Butyl Ether Gasoline Additive
Authors: Shi Zhaoxia , Xia Ling , Li Gongke , Hu Yufei
Published: July 2022

High purity methyl tert-butyl ether (MTBE) can be used to adjust gasoline octane values. However, an isomer, methyl sec-butyl ether (MSBE), is the main by-product of its industrial production, and this affects the purity of MTBE. Pt/Au NPs@Co3O4 composites with a hollow dodecahedron three-dimensional structure were synthesized using ZIF-67 as a template, with Pt and Au nanoparticles (NPs) evenly distributed on the shell of the hollow structure. A CTL sensor was established for the determination of MSBE based on the specificity of Pt/Au NPs@Co3O4. The experimental results showed that Pt/Au NPs@Co3O4 had a strong specific cataluminescence (CTL) response to MSBE, with no interference from MTBE. The linear range was 0.10–90 mg/L, the limit of detection was 0.031 mg/L (S/N = 3), the RSD was 2.5% (n = 9), and a complete sample test could be completed in five minutes. The sensor was used to detect MSBE in MTBE of different purity grades, with recoveries ranging from 92.0% to 109.2%, and the analytical results were consistent with those determined by gas chromatography. These results indicate that the established method was accurate and reliable, and could be used for rapid analysis of MTBE gasoline additive.
A Comparison of Emergency Department Revisit Rates of Pediatric Patients between Pre-COVID-19 and COVID-19 Periods
Authors: Namgung Myeong , Lee Dong Hoon , Bae Sung Jin , Chung Ho Sub , Park Ji Young , Kim Keon , Lee Choung Ah , Kim Duk Ho , Kim Eui Chung , Lim Jee Yong , Han Sang Soo , Choi Yoon Hee
Published: July 2022

Unscheduled revisits to emergency departments (EDs) are important because they indicate the quality of emergency care. However, the characteristics of pediatric patients visiting EDs changed during the coronavirus disease (COVID-19) pandemic, and these changes may have affected their revisit patterns. Therefore, we aimed to compare the ED revisit patterns of pediatric patients between the pre-COVID-19 and COVID-19 periods. This retrospective multicenter study included patients aged below 18 years who visited the ED in the pre-COVID-19 and COVID-19 periods. ED revisit rates were analyzed using five age groups and three visit-revisit intervals. In the pre-COVID-19 period, the revisit rates decreased with increasing age. In the COVID-19 period, the revisit rates were the lowest for the group aged 4–6 years, and the rates increased for those aged ≥7 years. In conclusion, there were changes in the patterns of revisit rates of pediatric patients according to age between the pre-COVID-19 and COVID-19 periods. Therefore, it is necessary to identify the reasons for revisits according to age and establish strategies to reduce the revisit rates of pediatric patients.
Balanced Circular Packing Problems with Distance Constraints
Authors: Romanova Tetyana , Pankratov Olexandr , Litvinchev Igor , Stetsyuk Petro , Lykhovyd Oleksii , Marmolejo-Saucedo Jose Antonio , Vasant Pandian
Published: July 2022

The packing of different circles in a circular container under balancing and distance conditions is considered. Two problems are studied: the first minimizes the container’s radius, while the second maximizes the minimal distance between circles, as well as between circles and the boundary of the container. Mathematical models and solution strategies are provided and illustrated with computational results.
Are We Identifying Malnutrition in Hospitalized Patients with Hematologic Malignancies? Results from a Quality Clinical Audit
Authors: Kanioura Eftychia , Tzanninis Ioannis-Georgios , Poulia Kalliopi-Anna , Stamou Aliki , Liaskas Athanasios , Politis Dimitrios , Kaoura Athina , Garefalakis Georgios , Viniou Nora Athina , Diamantopoulos Panagiotis
Published: July 2022

Disease-related malnutrition (DRM) is highly prevalent among patients with hematologic malignancies. The aim of the present study was to evaluate the prevalence of DRM in hospitalized patients with hematologic malignancies and investigate the level of awareness of DRM among the medical team treating this group of patients. A cross sectional quality clinical audit took place in two hematology units of a tertiary university hospital. Inpatients were screened within 48 h of their admission using the Malnutrition Universal Screening Tool (MUST) to identify their nutritional risk, and they were reassessed to identify the implemented interventions during their hospitalization. One hundred eighty-five patients were included in the audit analysis. On admission, 37.3% of the audited population was identified as being at high risk of malnutrition according to the MUST score. Forty-nine (26.5%) patients reported reduced food intake during the past 5 days, while four (2.2%) reported no food intake. During the hospitalization, only five patients (2.7%) received nutritional support, as indicated. Low levels of awareness of the early detection and treatment of DMS were found. Moreover, the prevalence of DRM and low nutritional intake was reported to be low. Measures to increase awareness of DMR in the medical team and better coordination of the nutrition support teams is vital to ensure better management and early nutrition intervention in hematological patients.
An Educational Evaluation of Thiel Cadavers as a Model for Teaching Suturing Skills to Dental Students during the COVID-19 Pandemic
Authors: Macluskey Michaelina , Anderson Angela S. , Gribben Mark , Shepherd Simon D.
Published: July 2022

Suturing is an essential skill in dentistry and not one easily acquired. The COVID-19 pandemic prompted a change to the use of Thiel cadavers and online resources with the aim of improving skill acquisition using the best model available. This study investigated the utility of the Thiel cadaver for teaching suturing skills and the potential impact of the lockdown. Fifty-seven year 4 students attended a teaching session. Student views on this teaching were explored via a questionnaire survey and qualitative data collected from a focus group. Data were analysed using an inductive approach. The response rate was 53% (30 students) for the questionnaire with 9 students participating in the focus group. Independent feedback was provided by two members of the teaching staff. Online video resources were very well received by the students with 97% agreeing that it was useful preparation. Ninety percent (90%) thought that the cadaveric model was suitable for this teaching and realistic. Positive emergent themes from the focus group centred on the use of the cadaveric model and the positive and relaxed teaching and learning environment. Staff perceived this model as superior to previously used models. There were no reported negative pandemic impacts and the cadaver model was well received.
Rolling Bearing Fault Diagnosis Based on WOA-VMD-MPE and MPSO-LSSVM
Authors: Jin Zhihao , Chen Guangdong , Yang Zhengxin
Published: July 2022

In order to further improve the accuracy of fault identification of rolling bearings, a fault diagnosis method based on the modified particle swarm optimization (MPSO) algorithm optimized least square support vector machine (LSSVM), combining parameter optimization variational mode decomposition (VMD) and multi-scale permutation entropy (MPE), was proposed. Firstly, to solve the problem of insufficient decomposition and mode mixing caused by the improper selection of mode component K and penalty factor α in VMD algorithm, the whale optimization algorithm (WOA) was used to optimize the penalty factor and mode component number in the VMD algorithm, and the optimal parameter combination (K, α) was obtained. Secondly, the optimal parameter combination (K, α) was used for the VMD of the rolling bearing vibration signal to obtain several intrinsic mode functions (IMFs). According to the Pearson correlation coefficient (PCC) criterion, the optimal IMF component was selected, and its optimal multi-scale permutation entropy was calculated to form the feature set. Finally, K-fold cross-validation was used to train the MPSO-LSSVM model, and the test set was input into the trained model for identification. The experimental results show that compared with PSO-SVM, LSSVM, and PSO-LSSVM, the MPSO-LSSVM fault diagnosis model has higher recognition accuracy. At the same time, compared with VMD-SE, VMD-MPE, and PSO-VMD-MPE, WOA-VMD-MPE can extract more accurate features.
Measuring and Promoting Self-Regulation for Equity and Quality of Online Learning: New Evidence from a Multi-Institutional Survey during COVID-19
Authors: Guo Jiao , King Ronnel B. , Ding Qinnan , Fan Miaomiao
Published: July 2022

Self-regulation is a core concept to understand the metacognitive, motivational, and emotional aspects of learning. The outbreak of COVID-19 resulted in large numbers of courses being shifted online, thus providing a large-scale setting to collect new empirical evidence to shed light on the specific challenges that different learner subgroups struggle with in the authentic online learning environment and then to provide practical implications to improve the learning outcomes by promoting learners’ online self-regulation. Based on a survey of 64,949 participants enrolled at 39 universities in a metropolitan city of China during the pandemic, we developed the Undergraduate Online Self-regulated Learning Questionnaire (UOSL), tested the reliability and construct validity of the UOSL items, and then built regression models to estimate the associations between online self-regulation and mastery of eight skills across different subgroups in a diverse student body. Disadvantaged subgroups such as rural, first-generation college students reported significantly lower UOSL scores as well as lower skill mastery in online learning. After controlling self-regulation in the regression model, these gaps related to student demographics have shrunk substantially and some become statistically insignificant (e.g., the gender gap in online skill mastery). The findings highlight the critical role of the targeted interventions of self-regulation to promote equity and enhance quality in the online teaching design and learning support.
Classification of Left and Right Coronary Arteries in Coronary Angiographies Using Deep Learning
Authors: Eschen Christian Kim , Banasik Karina , Christensen Alex Hørby , Chmura Piotr Jaroslaw , Pedersen Frants , Køber Lars , Engstrøm Thomas , Dahl Anders Bjorholm , Brunak Søren , Bundgaard Henning
Published: July 2022

Multi-frame X-ray images (videos) of the coronary arteries obtained using coronary angiography (CAG) provide detailed information about the anatomy and blood flow in the coronary arteries and play a pivotal role in diagnosing and treating ischemic heart disease. Deep learning has the potential to quickly and accurately quantify narrowings and blockages of the arteries from CAG videos. A CAG consists of videos acquired separately for the left coronary artery and the right coronary artery (LCA and RCA, respectively). The pathology for LCA and RCA is typically only reported for the entire CAG, and not for the individual videos. However, training of stenosis quantification models is difficult when the RCA and LCA information of the videos are unknown. Here, we present a deep learning-based approach for classifying LCA and RCA in CAG videos. Our approach enables linkage of videos with the reported pathological findings. We manually labeled 3545 and 520 videos (approximately seven videos per CAG) to enable training and testing of the models, respectively. We obtained F1 scores of 0.99 on the test set for LCA and RCA classification LCA and RCA classification on the test set. The classification performance was further investigated with extensive experiments across different model architectures (R(2+1)D, X3D, and MVIT), model input sizes, data augmentations, and the number of videos used for training. Our results showed that CAG videos could be accurately curated using deep learning, which is an essential preprocessing step for a downstream application in diagnostics of coronary artery disease.
Effects of Coating on the Electrochemical Performance of a Nickel-Rich Cathode Active Material
Authors: Hassan Eman , Amiriyan Mahdi , Frisone Dominic , Dunham Joshua , Farahati Rashid , Farhad Siamak
Published: July 2022

Due to their safety and high power density, one of the most promising types of all-solid-state lithium batteries is the one made with the argyrodite solid electrolyte (ASE). Although substantial efforts have been made toward the commercialization of this battery, it is still challenged by some technical issues. One of these issues is to prevent the side reactions at the interface of the ASE and the cathode active material (CAM). A solution to address this issue is to coat the CAM particles with a material that is compatible with both ASE and CAM. Prior studies show that the lithium niobate, LiNbO3, (LNO) is a promising material for coating CAM particles to reduce the interfacial side reactions. However, no systematic study is available in the literature to show the effect of coating LNO on CAM performance. This paper aims to quantify the effect of LNO coating on the electrochemical performance of a nickel-rich CAM. The electrochemical performance parameters that are studied are the capacity, cycling performance, and rate performance of the coated-CAM; and the effectiveness of the coating to prevent the side reactions at the ASE and CAM interface is out of the scope of this study. To eliminate the effect of side reactions at the ASE and CAM interface, we conduct all tests in the organic liquid electrolyte (OLE) cells to solely present the effect of coating on the CAM performance. For this purpose, 0.5 wt.% and 1 wt.% LNO are used to coat the LiNi0.6Mn0.2Co0.2O2 (NMC-60) CAM through two synthesizing methods. Consequently, the effects of the synthesizing method and the coating weight percentage on the NMC-60 performance are presented.
Deflection of Hydraulic Fractures and Shear Stress Disturbance Considering Thermal Effects: A Numerical Case Study
Authors: Liu Nana , Wang Yongliang
Published: July 2022

Quantitative characterization of propagation behaviors and morphology of hydraulic fractures is crucial for controlling and optimizing hydrofracturing effects. To study the disturbance deflection behaviors of multiple hydraulic fractures, a three-dimensional field-scale numerical model for multistage fracturing is established to study the shear stress disturbance and unstable propagation behavior of hydraulic fractures under different perforation cluster spacing. In the model, the thermal diffusion, fluid flow and deformation in reservoirs are considered to describe the thermal-hydro-mechanical coupling. In the numerical case study, the derived results show that the thermal effect between fracturing fluid and rock matrix is an important factor affecting fracture propagation, and thermal effects may increase the extent of fracture propagation. The size of stress shadow areas and the deflection of hydraulic fractures will increase with a decrease in multiple perforation cluster spacing in horizontal wells. The shear stress disturbance caused by fracture propagation is superimposed in multiple fractures, resulting in the stress shadow effect and deflection of fractures.
Is Stress Taking the Pleasure Out of Food?—A Characterization of the Food Pleasure Profiles, Appetite, and Eating Behaviors of People with Chronic Stress
Authors: Hyldelund Nikoline Bach , Frederiksen Chanette , Byrne Derek Victor , Andersen Barbara Vad
Published: July 2022

Psychological stressors frequently occur in modern society, and are associated with general anhedonic traits (inability to experience pleasure) and altered eating behavior. As eating behavior is largely motivated by a desire for pleasure, the Food Pleasure Scale (FPS) was introduced as a new research tool for investigating aspects of pleasure from food-related experiences. Thereby, insights on whether some aspects of pleasure are more affected by stress than others can be investigated, and can help explain why changes in eating behavior are seen when under the influence of stress. A consumer survey including n = 190 Danish consumers all with moderate or high levels of perceived stress was conducted to explore the perception of pleasure from food, general appetite, meal patterns, as well as specific food preferences. The study showed that the majority found pleasure in the sensory modalities of food, as well as in the ‘comforting’ aspects of food pleasure. Furthermore, the moderately stressed respondents had fewer main meals and more post-dinner snacks and night meals, as compared to before falling ill, whereas the highly stressed group showed signs of anhedonic traits and losing appetite altogether. The present study contributes to our understanding of how a common condition, such as chronic stress, can affect individual, as well as public, health.
Investigation of Biomedical Students’ Knowledge on Glaucoma Reveals a Need for Education: A Cross-Sectional Study
Authors: Vucinovic Ana , Bukic Josipa , Rusic Doris , Leskur Dario , Perisin Ana Seselja , Cohadzic Tin , Luksic Marko , Modun Darko
Published: July 2022

Background: Glaucoma has been recognized as one of the leading global causes of irreversible blindness. Patients with primary open-angle glaucoma rarely present with visual symptoms, at least early in the course of the disease. It is important to recognize and treat the disease before there are irreversible changes. Methods: This cross-sectional study was conducted at the University of Split School of Medicine from October to November 2021. Participants were biomedical students who completed a questionnaire. Results: In total, 312 students participated in this study. Interestingly, only 12.2% of students identified that primary open-angle glaucoma was asymptomatic. Only 42.6% of all students recognized glaucoma as being the main cause of irreversible blindness. Pharmacy students less frequently recognized high blood pressure and diabetes mellitus as risk factors for glaucoma. Students who completed an ophthalmology course more frequently recognized that successful glaucoma treatment prevents blindness, compared to students who did not complete the course, 79.1% vs. 48.7%, p < 0.001. Conclusion: The results showed that students’ knowledge on the subject is low, even after they passed their ophthalmology course. However, knowledge of glaucoma is crucial for early disease identification and the prevention of blindness. Therefore, it is important that all future health care professionals acquire adequate education.
Reported Injuries from Sharp Objects among Healthcare Workers in Central Greece
Authors: Patsopoulou Anna , Anyfantis Ioannis , Papathanasiou Ioanna V. , Fradelos Evangelos C. , Malliarou Maria , Tsaras Konstantinos , Malli Foteini , Papagiannis Dimitrios
Published: July 2022

Sharp injuries (SIs) are incidents or accidents caused by a needle, blades (such as scalpels) or other medical instruments which penetrate the skin. They are among the major work-related injuries in healthcare professionals. The purpose of this study is to estimate SIs in healthcare workers (HCWs) in Central Greece. Method: A cross-sectional descriptive study through an online survey in healthcare facilities in Central Greece was conducted. Snowball sampling contributed to further dissemination of the survey among the target population. The modified version of the EPINet questionnaire was used with self-reported answers of the participants via electronic Google form. Results: Analysis of collected data indicated that 74.1% of the participants had at least one injury, with the highest number of injuries occurring in nursing staff at 65.1% and 62.3% of injuries recorded in the morning shift. With respect to the site of the injury, participants reported 33.1% of the injuries in the patient’s room, 11.8% in the nurse’s station, 9.6% in the Emergency Department (ED), 9.2% in the Intensive Care Unit (ICU), 8.4% in blood sampling, 8.4% in surgery, and only 7.8% in laboratories or other places. Additionally, hands were the most frequently affected body part (96%), while 69.6% of the workers did not report the injury and 53% of them did not apply the procedures and guidelines defined by the healthcare organization (employer). Relative factors to the injury are age, level of education, shifts, and possibly sex. Conclusions: SIs are the “Achilles heel” of health workers. The high incidence and low reporting rate of SIs highlights the need for specialized training and education. Age, work experience, and shift appear to significantly affect the incidence of injury.
Body Language Analysis in Healthcare: An Overview
Authors: Abdulghafor Rawad , Turaev Sherzod , Ali Mohammed A. H.
Published: July 2022

Given the current COVID-19 pandemic, medical research today focuses on epidemic diseases. Innovative technology is incorporated in most medical applications, emphasizing the automatic recognition of physical and emotional states. Most research is concerned with the automatic identification of symptoms displayed by patients through analyzing their body language. The development of technologies for recognizing and interpreting arm and leg gestures, facial features, and body postures is still in its early stage. More extensive research is needed using artificial intelligence (AI) techniques in disease detection. This paper presents a comprehensive survey of the research performed on body language processing. Upon defining and explaining the different types of body language, we justify the use of automatic recognition and its application in healthcare. We briefly describe the automatic recognition framework using AI to recognize various body language elements and discuss automatic gesture recognition approaches that help better identify the external symptoms of epidemic and pandemic diseases. From this study, we found that since there are studies that have proven that the body has a language called body language, it has proven that language can be analyzed and understood by machine learning (ML). Since diseases also show clear and different symptoms in the body, the body language here will be affected and have special features related to a particular disease. From this examination, we discovered that it is possible to specialize the features and language changes of each disease in the body. Hence, ML can understand and detect diseases such as pandemic and epidemic diseases and others.
Dependence Structure between Bitcoin and Economic Policy Uncertainty: Evidence from Time–Frequency Quantile-Dependence Methods
Authors: Nasreen Samia , Tiwari Aviral Kumar , Jiang Zhuhua , Yoon Seong-Min
Published: July 2022

In this study, the dependence between Bitcoin (BTC) and economic policy uncertainty (EPU) of USA and China is estimated by applying the latest methodology of quantile cross-spectral dependence. Daily data comprising a total of 1947 observations and covering the period of 1 October 2013 to 31 January 2019 are used in this study. The findings indicate that a positive return interdependence between BTC and EPU is high in the short term, and this dependence decreases as investment horizons increase from weekly to yearly. The information on the time-varying and time–frequency structure of interdependence is also extracted by applying wavelet coherence analysis. The estimated results of wavelet coherence suggest that the correlation between BTC and EPU is positive during a short-term investment horizon. Finally, the frequency domain Breitung and Candelon causality test is applied, and results show the evidence of insignificant causality between Bitcoin and EPU. Overall, the findings highlight the diversification benefits of Bitcoin during the period of uncertainty.
Novel MLR-RF-Based Geospatial Techniques: A Comparison with OK
Authors: Ahmed Waqas , Muhammad Khan , Glass Hylke Jan , Chatterjee Snehamoy , Khan Asif , Hussain Abid
Published: July 2022

Geostatistical estimation methods rely on experimental variograms that are mostly erratic, leading to subjective model fitting and assuming normal distribution during conditional simulations. In contrast, Machine Learning Algorithms (MLA) are (1) free of such limitations, (2) can incorporate information from multiple sources and therefore emerge with increasing interest in real-time resource estimation and automation. However, MLAs need to be explored for robust learning of phenomena, better accuracy, and computational efficiency. This paper compares MLAs, i.e., Multiple Linear Regression (MLR) and Random Forest (RF), with Ordinary Kriging (OK). The techniques were applied to the publicly available Walkerlake dataset, while the exhaustive Walker Lake dataset was validated. The results of MLR were significant (p < 10 × 10−5), with correlation coefficients of 0.81 (R-square = 0.65) compared to 0.79 (R-square = 0.62) from the RF and OK methods. Additionally, MLR was automated (free from an intermediary step of variogram modelling as in OK), produced unbiased estimates, identified key samples representing different zones, and had higher computational efficiency.
Immunomodulatory Properties of PI3K/AKT/mTOR and MAPK/MEK/ERK Inhibition Augment Response to Immune Checkpoint Blockade in Melanoma and Triple-Negative Breast Cancer
Authors: Zhang Zhizhu , Richmond Ann , Yan Chi
Published: July 2022

Hyperactivation of PI3K/AKT/mTOR and MAPK/MEK/ERK signaling pathways is commonly observed in many cancers, including triple-negative breast cancer (TNBC) and melanoma. Moreover, the compensatory upregulation of the MAPK/MEK/ERK pathway has been associated with therapeutic resistance to targeted inhibition of the PI3K/AKT/mTOR pathway, and vice versa. The immune-modulatory effects of both PI3K and MAPK inhibition suggest that inhibition of these pathways might enhance response to immune checkpoint inhibitors (ICIs). ICIs have become the standard-of-care for metastatic melanoma and are recently an option for TNBC when combined with chemotherapy, but alternative options are needed when resistance develops. In this review, we present the current mechanistic understandings, along with preclinical and clinical evidence, that outline the efficacy and safety profile of combinatorial or sequential treatments with PI3K inhibitors, MAPK inhibitors, and ICIs for treatment of malignant melanoma and metastatic TNBC. This approach may present a potential strategy to overcome resistance in patients who are a candidate for ICI therapy with tumors harboring either or both of these pathway-associated mutations.
RNA-Seq Provides Insights into VEGF-Induced Signaling in Human Retinal Microvascular Endothelial Cells: Implications in Retinopathy of Prematurity
Authors: Ramshekar Aniket , Bretz Colin A. , Hartnett M. Elizabeth
Published: July 2022

The pathophysiology of retinopathy of prematurity (ROP) is postulated to first involve delayed intraretinal vascularization, followed by intravitreal neovascularization (IVNV). Although intravitreal agents that reduce the bioactivity of vascular endothelial growth factor (VEGF) are used to treat IVNV, concerns exist regarding their effects on intraretinal vascularization. In an experimental ROP model, VEGF receptor 2 (VEGFR2) knockdown in retinal endothelial cells reduced IVNV and promoted intraretinal vascularization, whereas knockdown of a downstream effector, signal transducer and activator of transcription 3 (STAT3) in retinal endothelial cells only reduced IVNV. In this study, we tested the hypothesis that the different pathways involved in VEGF-triggered VEGFR2 signaling and VEGF-triggered STAT3 signaling in retinal endothelial cells would allow us to delineate signaling pathways involved in IVNV from those involved in intraretinal vascularization in ROP. To address our hypothesis, we used RNA-sequencing and pathway enrichment analysis to determine changes in the transcriptome of cultured human retinal microvascular endothelial cells (HRMECs). Of the enriched pathways, inactivation of oncostatin M signaling was predicted by either KDR or STAT3 knockdown in the presence of VEGF. Activation of kinetochore metaphase signaling was predicted by KDR knockdown, whereas inactivation was predicted by STAT3 knockdown in the presence of VEGF. Inactivation of signaling by the Rho family of GTPases was predicted by KDR knockdown, but activation was predicted by STAT3 knockdown in the presence of VEGF. Taken together, our data identified unique signaling pathway differences between VEGF-triggered VEGFR2 and VEGF-triggered STAT3 in HRMECs that might have implications in ROP.
Genomic and Immunological Characterization of Hypermucoviscous Carbapenem-Resistant Klebsiella pneumoniae ST25 Isolates from Northwest Argentina
Authors: Albarracin Leonardo , Ortiz Moyano Ramiro , Vargas Juan Martin , Andrade Bruno G. N. , Cortez Zamar Juan , Dentice Maidana Stefania , Fukuyama Kohtaro , Kurata Shoichiro , Jure María Ángela , Kitazawa Haruki , Villena Julio
Published: July 2022

In recent years, an increase in the prevalence hypermucoviscous carbapenem-resistant Klebsiella pneumoniae with sequence type 25 (ST25) was detected in hospitals of Tucuman (Northwest Argentina). In this work, the virulence and the innate immune response to two K. pneumoniae ST25 strains (LABACER 01 and LABACER 27) were evaluated in a murine model after a respiratory challenge. In addition, comparative genomics was performed with K. pneumoniae LABACER01 and LABACER27 to analyze genes associated with virulence. Both LABACER01 and LABACER27 were detected in the lungs of infected mice two days after the nasal challenge, with LABACER01 counts significantly higher than those of LABACER27. Only LABACER01 was detected in hemocultures. Lactate dehydrogenase (LDH) and albumin levels in bronchoalveolar lavage (BAL) samples were significantly higher in mice challenged with LABACER01 than in LABACER27-infected animals, indicating greater lung tissue damage. Both strains increased the levels of neutrophils, macrophages, TNF-α, IL-1β, IL-6, KC, MCP-1, IFN-γ, and IL-17 in the respiratory tract and blood, with the effect of LABACER01 more marked than that of LABACER27. In contrast, LABACER27 induced higher levels of IL-10 in the respiratory tract than LABACER01. Genomic analysis revealed that K. pneumoniae LABACER01 and LABACER27 possess virulence factors found in other strains that have been shown to be hypervirulent, including genes required for enterobactin (entABCDEF) and salmochelin (iroDE) biosynthesis. In both strains, the genes of toxin–antitoxin systems, as well as regulators of the expression of virulence factors and adhesion genes were also detected. Studies on the genetic potential of multiresistant K. pneumoniae strains as well as their cellular and molecular interactions with the host are of fundamental importance to assess the association of certain virulence factors with the intensity of the inflammatory response. In this sense, this work explored the virulence profile based on genomic and in vivo studies of hypermucoviscous carbapenem-resistant K. pneumoniae ST25 strains, expanding the knowledge of the biology of the emerging ST25 clone in Argentina.
Accelerated Wound Border Closure Using a Microemulsion Containing Non-Inhibitory Recombinant α1-Antitrypsin
Authors: Gimmon Alon , Sherker Lior , Kojukarov Lena , Zaknoun Melodie , Lior Yotam , Fadel Tova , Schuster Ronen , Lewis Eli C. , Silberstein Eldad
Published: July 2022

Wound healing requires a non-compromising combination of inflammatory and anti-inflammatory processes. Human α1-antitrypsin (hAAT), a circulating glycoprotein that rises during acute-phase responses and during healthy pregnancies, is tissue-protective and tolerance-inducing; although anti-inflammatory, hAAT enhances revascularization. hAAT blocks tissue-degrading enzymes, including neutrophil elastase; it is, therefore, unclear how wound healing might improve under hAAT-rich conditions. Here, wound healing was examined in the presence of recombinant hAAT (hAATWT) and protease-inhibition-lacking hAAT (hAATCP). The impact of both hAAT forms was determined by an epithelial cell gap closure assay, and by excisional skin injuries via a microemulsion optimized for open wounds. Neutrophilic infiltration was examined after 8 h. According to results, both hAAT forms accelerated epithelial gap closure and excisional wound closure, particularly at early time points. Unlike dexamethasone-treated wounds, both resulted in closed borders at the 8-h time point. In untreated and hAATCP-treated wounds, leukocytic infiltrates were widespread, in hAATWT-treated wounds compartmentalized and in dexamethasone-treated wounds, scarce. Both hAAT forms decreased interleukin-1β and increased VEGF gene expression. In conclusion hAAT improves epithelial cell migration and outcomes of in vivo wounds irrespective of protease inhibition. While both forms of hAAT allow neutrophils to infiltrate, only native hAAT created discrete neutrophilic tissue clusters.
The Influence of Glow and Afterglow Cold Plasma Treatment on Biochemistry, Morphology, and Physiology of Wheat Seeds
Authors: Starič Pia , Mravlje Jure , Mozetič Miran , Zaplotnik Rok , Šetina Batič Barbara , Junkar Ita , Vogel Mikuš Katarina
Published: July 2022

Cold plasma (CP) technology is a technique used to change chemical and morphological characteristics of the surface of various materials. It is a newly emerging technology in agriculture used for seed treatment with the potential of improving seed germination and yield of crops. Wheat seeds were treated with glow (direct) or afterglow (indirect) low-pressure radio-frequency oxygen plasma. Chemical characteristics of the seed surface were evaluated by XPS and FTIR analysis, changes in the morphology of the seed pericarp were analysed by SEM and AFM, and physiological characteristics of the seedlings were determined by germination tests, growth studies, and the evaluation of α-amylase activity. Changes in seed wettability were also studied, mainly in correlation with functionalization of the seed surface and oxidation of lipid molecules. Only prolonged direct CP treatment resulted in altered morphology of the seed pericarp and increased its roughness. The degree of functionalization is more evident in direct compared to indirect CP treatment. CP treatment slowed the germination of seedlings, decreased the activity of α-amylase in seeds after imbibition, and affected the root system of seedlings.
Comparative Transcriptome Analysis Reveals the Gene Expression and Regulatory Characteristics of Broad-Spectrum Immunity to Leaf Rust in a Wheat–Agropyron cristatum 2P Addition Line
Authors: Ji Xiajie , Liu Taiguo , Xu Shirui , Wang Zongyao , Han Haiming , Zhou Shenghui , Guo Baojin , Zhang Jinpeng , Yang Xinming , Li Xiuquan , Li Lihui , Liu Weihua
Published: July 2022

Wheat leaf rust (caused by Puccinia triticina Erikss.) is among the major diseases of common wheat. The lack of resistance genes to leaf rust has limited the development of wheat cultivars. Wheat–Agropyron cristatum (A. cristatum) 2P addition line II-9-3 has been shown to provide broad-spectrum immunity to leaf rust. To identify the specific A. cristatum resistance genes and related regulatory pathways in II-9-3, we conducted a comparative transcriptome analysis of inoculated and uninoculated leaves of the resistant addition line II-9-3 and the susceptible cultivar Fukuhokomugi (Fukuho). The results showed that there were 66 A. cristatum differentially expressed genes (DEGs) and 1389 wheat DEGs in II-9-3 during P. triticina infection. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and gene set enrichment analysis (GSEA) revealed that the DEGs of II-9-3 were associated with plant–pathogen interaction, MAPK signaling pathway–plant, plant hormone signal transduction, glutathione metabolism, and phenylpropanoid biosynthesis. Furthermore, many defense-related A. cristatum genes, such as two NLR genes, seven receptor kinase-encoding genes, and four transcription factor-encoding genes, were identified. Our results indicated that the key step of resistance to leaf rust involves, firstly, the gene expression of chromosome 2P upstream of the immune pathway and, secondly, the effect of chromosome 2P on the co-expression of wheat genes in II-9-3. The disease resistance regulatory pathways and related genes in the addition line II-9-3 thus could play a critical role in the effective utilization of innovative resources for leaf rust resistance in wheat breeding.
Ca2+ Signalling and Hypoxia/Acidic Tumour Microenvironment Interplay in Tumour Progression
Authors: Audero Madelaine Magalì , Prevarskaya Natalia , Fiorio Pla Alessandra
Published: July 2022

Solid tumours are characterised by an altered microenvironment (TME) from the physicochemical point of view, displaying a highly hypoxic and acidic interstitial fluid. Hypoxia results from uncontrolled proliferation, aberrant vascularization and altered cancer cell metabolism. Tumour cellular apparatus adapts to hypoxia by altering its metabolism and behaviour, increasing its migratory and metastatic abilities by the acquisition of a mesenchymal phenotype and selection of aggressive tumour cell clones. Extracellular acidosis is considered a cancer hallmark, acting as a driver of cancer aggressiveness by promoting tumour metastasis and chemoresistance via the selection of more aggressive cell phenotypes, although the underlying mechanism is still not clear. In this context, Ca2+ channels represent good target candidates due to their ability to integrate signals from the TME. Ca2+ channels are pH and hypoxia sensors and alterations in Ca2+ homeostasis in cancer progression and vascularization have been extensively reported. In the present review, we present an up-to-date and critical view on Ca2+ permeable ion channels, with a major focus on TRPs, SOCs and PIEZO channels, which are modulated by tumour hypoxia and acidosis, as well as the consequent role of the altered Ca2+ signals on cancer progression hallmarks. We believe that a deeper comprehension of the Ca2+ signalling and acidic pH/hypoxia interplay will break new ground for the discovery of alternative and attractive therapeutic targets.
The Multivalent Polyampholyte Domain of Nst1, a P-Body-Associated Saccharomyces cerevisiae Protein, Provides a Platform for Interacting with P-Body Components
Authors: Choi Yoon-Jeong , Lee Yujin , Lin Yuxi , Heo Yunseok , Lee Young-Ho , Song Kiwon
Published: July 2022

The condensation of nuclear promyelocytic leukemia bodies, cytoplasmic P-granules, P-bodies (PBs), and stress granules is reversible and dynamic via liquid–liquid phase separation. Although each condensate comprises hundreds of proteins with promiscuous interactions, a few key scaffold proteins are required. Essential scaffold domain sequence elements, such as poly-Q, low-complexity regions, oligomerizing domains, and RNA-binding domains, have been evaluated to understand their roles in biomolecular condensation processes. However, the underlying mechanisms remain unclear. We analyzed Nst1, a PB-associated protein that can intrinsically induce PB component condensations when overexpressed. Various Nst1 domain deletion mutants with unique sequence distributions, including intrinsically disordered regions (IDRs) and aggregation-prone regions, were constructed based on structural predictions. The overexpression of Nst1 deletion mutants lacking the aggregation-prone domain (APD) significantly inhibited self-condensation, implicating APD as an oligomerizing domain promoting self-condensation. Remarkably, cells overexpressing the Nst1 deletion mutant of the polyampholyte domain (PD) in the IDR region (Nst1∆PD) rarely accumulate endogenous enhanced green fluorescent protein (EGFP)-tagged Dcp2. However, Nst1∆PD formed self-condensates, suggesting that Nst1 requires PD to interact with Dcp2, regardless of its self-condensation. In Nst1∆PD-overexpressing cells treated with cycloheximide (CHX), Dcp2, Xrn1, Dhh1, and Edc3 had significantly diminished condensation compared to those in CHX-treated Nst1-overexpressing cells. These observations suggest that the PD of the IDR in Nst1 functions as a hub domain interacting with other PB components.
CDK1 Promotes Epithelial–Mesenchymal Transition and Migration of Head and Neck Squamous Carcinoma Cells by Repressing ∆Np63α-Mediated Transcriptional Regulation
Authors: Chen Huimin , Hu Ke , Xie Ying , Qi Yucheng , Li Wenjuan , He Yaohui , Fan Shijie , Liu Wen , Li Chenghua
Published: July 2022

∆Np63α is a key transcription factor overexpressed in types of squamous cell carcinomas (SCCs), which represses epithelial–mesenchymal transition (EMT) and cell migration. In this study, we found that CDK1 phosphorylates ∆Np63α at the T123 site, impairing its affinity to the target promoters of its downstream genes and its regulation of them in turn. Database analysis revealed that CDK1 is overexpressed in head and neck squamous cell carcinomas (HNSCCs), especially the metastatic HNSCCs, and is negatively correlated with overall survival. We further found that CDK1 promotes the EMT and migration of HNSCC cells by inhibiting ∆Np63α. Altogether, our study identified CDK1 as a novel regulator of ΔNp63α, which can modulate EMT and cell migration in HNSCCs. Our findings will help to elucidate the migration mechanism of HNSCC cells.