bluuebunny/crossref_metadata_2025 huggingface dataset:
Precursory Tidal Triggering of the 2011 Mw 9.0 Tohoku Aftershocks
Authors: Xie Chaodi , Zhu Ye , Ji Yingfeng , Zhu Weiling , Qu Rui
Published: September 2022

Precursory earth tidal triggering is believed to influence earthquake timing preferentially when a region is critically stressed. However, whether and how the recurrence of aftershocks after a giant earthquake is affected by tidal triggering remains perplexing. To provide insight into this study, we utilized the Schuster test to explore the tidally induced stress variation correlated with the 2011 Mw 9.0 Tohoku earthquake aftershock sequence by determining the tidal phase angle at the occurrence time of events and the periodic characteristics of the aftershocks. Our results show that the aftershocks were triggered by short-period tides, including semidiurnal and diurnal tides. The rupture associated with the mainshock likely resulted in a critical stress state in the focal region, which is conducive to tidal triggering. We subdivided the aftershock catalog into several subsets, using a depth of 30 km and a magnitude of 5 as discriminators. The analysis of these subsets reveals that weaker and deeper earthquakes are best correlated with Earth tides, which will be helpful to investigate the mechanisms of tidal correlation.
A Quasi-Static Motion Prediction Model of a Multi-Hull Navigation Vessel in Dynamic Positioning Mode
Authors: Ji Mingyao , Srinivasamurthy Sharath , Nihei Yasunori
Published: September 2022

A Quadmaran vessel is a maritime navigation vessel with four hulls, and is expected to be utilized for high-density water quality observation in aquaculture farms. The performance of the vessel during dynamic positioning (DP) is integral to the accuracy of collected data. However, there are no models available to understand the motion characteristics of the multi-hull vessels in DP mode. Therefore, a computational model was developed to predict the DP motion of the Quadmaran vessel based on quasi-static assumptions. The fluid forces on the hulls, the thrust force of the propellers, and the external wind forces are modelled systematically, assuming the average speed while in DP does not exceed 0.25 m/s. A series of oblique towing tests and static turning tests were conducted on a 1/3 scale model to determine the hydrodynamic coefficients, while the Propeller Open Test was conducted to survey the propeller performance. The wind load was also incorporated into the computational model. Experimental validation tests were conducted in calm water and actual sea areas, and the correlation between experiment and simulation results was good. We concluded that the computational model can predict the DP motion of the Quadmaran vessel with an accuracy of roughly 2 m.
Multi-Level Control and Utilization of Stormwater Runoff
Authors: Zuo Yuhang , Luo Hui , Song Mingzhi , He Baojie , Cai Bingxin , Zhang Wenhao , Yang Mingyu
Published: September 2022

This study proposes the technology of “runoff storage and seepage utilization” for achieving purification of road rainfall–runoff and presents a multi-level series purification system (PBT-GR) comprising porous asphalt pavement (PAP), a bioretention system (BS), a storage tank (T) and a hydroponic green roof (GR). The operation parameters of each component unit were optimized and the contribution of each unit to pollution was analyzed. The results showed that under typical simulated rainfall, the suspended solids (SS), total nitrogen (TN), total phosphorus (TP), Pb, Zn and Cu removal rates by filtration and interception of porous pavement were 62.26 ± 3.19%, 16.29 ± 1.74%, 29.27 ± 1.37%, 37.61 ± 2.58%, 35.57 ± 4.64% and 31.17 ± 3.27%, respectively. The average concentrations of SS, TN, TP, Pb, Zn and Cu in the effluent of the PBT-GR system were 14.70 ± 2.21 mg/L, 1.52 ± 0.24 mg/L, 0.14 ± 0.04 mg/L, 0.09 ± 0.04 mg/L, 0.11 ± 0.03 mg/L and 0.04 ± 0.01mg/L, respectively, which met the water quality standards recommended in the Chinese guidelines and showed a high adaptability to pollution load. The contents of pesticide residues and heavy metals in cultivated vegetables met the national standards. The period required to recoup the investment in the system was approximately 3 years, indicating its good economic feasibility. The present study can provide a valuable reference of the construction of an efficient, low consumption and sustainable urban stormwater treatment system and can contribute to the improvement in the quality of the urban water environment.
Review of Road Dust Resuspension Modelling Approaches and Comparisons Analysis for a UK Case Study
Authors: Galatioto Fabio , Masey Nicola , Murrells Tim , Hamilton Scott , Pommier Matthieu
Published: September 2022

This report provides a review of several measurement studies and campaigns focusing on road dust resuspension (RDS), which is becoming an important source of ambient particulate matter (PM) concentrations. There is a growing requirement from stakeholders, policy makers and scientists for gathering additional data around RDS, since there is a lack of well-established methodologies or those developed for measuring or modelling this source of emissions are not very recent. Moreover, conventional inventory methodologies are not available for this source of emissions, and it is not yet covered in the UK’s National Atmospheric Emissions Inventory (NAEI) neither in the inventory guidebooks at European level. Based on the available literature and models, this paper also seeks to provide some preliminary considerations whether an approach can be tailored for application in air quality models used for modelling ambient PM concentrations in the UK in a consistent manner and demonstrated using a state-of-art air quality modelling tool, namely RapidAir®. The impact of including resuspension emissions on roadside concentrations was modelled in a UK case study with the greatest increases in modelled road PM10 concentrations observed on or near the road surface. The paper concludes with recommendations for longer-term implementation of the proposed improvements such as investigation of the temporal effects of RDS on PM levels; of the influence of different type of tyre materials and mixture (e.g., composition) and designs (e.g., shape, dimensions and tread); and influence of different existing pavements or of new road surface types.
Parameterization of Mean Terminal Velocity of Hydrometeors in Convective Clouds
Authors: Zou Zeyong , Chen Qian , Lu Chunsong , Yang Lei , Zou Qinyao , Sun Boai
Published: September 2022

The relationships between mean terminal velocity and volume mean diameter of different hydrometeors, as well as how they change with different background aerosol concentrations have been investigated with numerical simulations of tropical deep convection from the Weather Forecast and Research Model (WRF), coupled with spectral bin microphysics. The results showed a positive correlation between either the mass-weighted mean terminal velocity (Vm) or the number-weighted mean terminal velocity (Vn) and the volume-mean diameter (Dv), with a correlation coefficient greater than 0.8. The number concentrations of both large and small hydrometeors increase with enhanced aerosol loading, resulting in increased Vm and decreased Vn. The parameterizations of Vm (Vn) were established under different aerosol conditions. The parameterized Vm (Vn) was then compared with default values used in the model when a fixed shape parameter (gamma distribution) was used in the bulk microphysics, which suggests smaller Vm and larger Vn values from the parameterizations. Moreover, the proposed parameterizations were further applied to the Morrison microphysical scheme for the simulation of a convective cloud. Changes in Vm and Vn as mentioned above directly affect the sedimentation of precipitating hydrometeors, such as raindrops, snow, and graupel, which lead to increased (decreased) mass (number) concentration of hydrometeors.
Frost Conditions Due to Climate Change in South-Eastern Europe via a High-Spatiotemporal-Resolution Dataset
Authors: Charalampopoulos Ioannis , Droulia Fotoula
Published: September 2022

Frost incidents comprise significant extreme weather events owing to climate change, possibly endangering the agricultural sector of the already impacted south-eastern European area. Thus, the comprehensive evaluation of the frost conditions under the climate regime for eleven countries was conducted by calculating relevant frost agroclimatic indicators under three time horizons (1985 to 2015, 2005 to 2035 and 2015 to 2045). The Frost Days (FD), Free of Frost Days (FFD), Last Spring Frost (LSF) and First Autumn Frost (FAF) were estimated daily over a grid of 25 × 25 km. We demonstrated that the FD will be reduced according to the balanced A1B emissions scenario over the entire examined area with the mountainous and continental regions being most affected. From 2005 to 2035, a higher LSF reduction is expected over Greece and Albania and the earlier FAF in high altitude areas. All examined regions are projected to face delayed FAF, from 2015 to 2045. In general, all countries will face an increase in the growing season duration owing to the increase of the FFD.
COSMIC-2 Mission Summary at Three Years in Orbit
Authors: Weiss Jan-Peter , Schreiner William S. , Braun John J. , Xia-Serafino Wei , Huang Cheng-Yung
Published: September 2022

We summarize the status of the FORMOSAT-7/COSMIC-2 (COSMIC-2) mission which has completed its first three years in orbit. COSMIC-2 is a joint U.S./Taiwan program consisting of six satellites in low-inclination orbits with the following payloads: Global Navigation Satellite System radio occultation, in-situ ion velocity meter, and tri-band radio frequency beacon. The constellation is in its final orbit configuration and reached mission full operating capability in September 2021. An extensive calibration/validation campaign has to date enabled the release of all baseline neutral atmosphere products and nearly all baseline ionosphere products. The mission is providing usually more than 5000 neutral atmosphere RO profiles per day with a precision better than 2 μrad from 30–60 km altitude. Each day, nearly 12,000 combined total electron content occultations and arcs are generated with absolute accuracy of better than 3 TECU. IVM density precision is at or below the 1% requirement. Neutral atmosphere and ionosphere latency, measured from time of observation to product creation time, is below 30 min median. Data products are delivered in near real-time to operational weather and space weather centers and made available openly to the research community. New ionosphere products specifying the presence and absence of scintillation are under development and planned for future release.
Using Machine Learning Methods to Forecast Air Quality: A Case Study in Macao
Authors: Lei Thomas M. T. , Siu Shirley W. I. , Monjardino Joana , Mendes Luisa , Ferreira Francisco
Published: September 2022

Despite the levels of air pollution in Macao continuing to improve over recent years, there are still days with high-pollution episodes that cause great health concerns to the local community. Therefore, it is very important to accurately forecast air quality in Macao. Machine learning methods such as random forest (RF), gradient boosting (GB), support vector regression (SVR), and multiple linear regression (MLR) were applied to predict the levels of particulate matter (PM10 and PM2.5) concentrations in Macao. The forecast models were built and trained using the meteorological and air quality data from 2013 to 2018, and the air quality data from 2019 to 2021 were used for validation. Our results show that there is no significant difference between the performance of the four methods in predicting the air quality data for 2019 (before the COVID-19 pandemic) and 2021 (the new normal period). However, RF performed significantly better than the other methods for 2020 (amid the pandemic) with a higher coefficient of determination (R2) and lower RMSE, MAE, and BIAS. The reduced performance of the statistical MLR and other ML models was presumably due to the unprecedented low levels of PM10 and PM2.5 concentrations in 2020. Therefore, this study suggests that RF is the most reliable prediction method for pollutant concentrations, especially in the event of drastic air quality changes due to unexpected circumstances, such as a lockdown caused by a widespread infectious disease.
Japanese Knotweed Rhizome Bark Extract Inhibits Live SARS-CoV-2 In Vitro
Authors: Jug Urška , Naumoska Katerina , Malovrh Tadej
Published: September 2022

Coronavirus disease 2019 (COVID-19), a viral infectious respiratory disease, is caused by highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is responsible for the ongoing COVID-19 pandemic. Since very few drugs are known to be effective against SARS-CoV-2, there is a general need for new therapeutics, including plant-based drugs, for the prophylaxis and treatment of infections. In the current study, the activity of a 70% ethanolic(aq) extract of the rhizome bark of Japanese knotweed, an invasive alien plant species, was tested for the first time against the wild-type SARS-CoV-2 virus using a specific and robust virus neutralization test (VNT) on Vero-E6 cells, which best mimics the mechanism of real virus–host interaction. A statistically significant antiviral effect against SARS-CoV-2 (p-value < 0.05) was observed for the 50.8 µg mL−1 extract solution in cell medium. A suitable extract preparation was described to avoid loss of polyphenols throughout filtration of the extract, which was dissolved in cell medium containing fetal bovine serum (FBS). The significance of the differences between the sums of the test and control groups in the incidence of cytopathic effects (CPE) was determined using the one-way ANOVA test. A dose–response relationship was observed, with the cytotoxic effect occurring at higher concentrations of the extract (≥101.6 µg mL−1). The obtained results suggest possible use of this plant material for the production of various products (e.g., packaging, hygiene products, biodisinfectants, etc.) that would be useful against the spread of and for self-protection against COVID-19.
End-to-End Convolutional Neural Network Model to Detect and Localize Myocardial Infarction Using 12-Lead ECG Images without Preprocessing
Authors: Uchiyama Ryunosuke , Okada Yoshifumi , Kakizaki Ryuya , Tomioka Sekito
Published: September 2022

In recent years, many studies have proposed automatic detection and localization techniques for myocardial infarction (MI) using the 12-lead electrocardiogram (ECG). Most of them applied preprocessing to the ECG signals, e.g., noise removal, trend removal, beat segmentation, and feature selection, followed by model construction and classification based on machine-learning algorithms. The selection and implementation of preprocessing methods require specialized knowledge and experience to handle ECG data. In this paper, we propose an end-to-end convolutional neural network model that detects and localizes MI without such complicated multistep preprocessing. The proposed model executes comprehensive learning for the waveform features of unpreprocessed raw ECG images captured from 12-lead ECG signals. We evaluated the classification performance of the proposed model in two experimental settings: ten-fold cross-validation where ECG images were split randomly, and two-fold cross-validation where ECG images were split into one patient and the other patients. The experimental results demonstrate that the proposed model obtained MI detection accuracies of 99.82% and 93.93% and MI localization accuracies of 99.28% and 69.27% in the first and second settings, respectively. The performance of the proposed method is higher than or comparable to that of existing state-of-the-art methods. Thus, the proposed model is expected to be an effective MI diagnosis tool that can be used in intensive care units and as wearable technology.
Bioconversion of Plastic Waste Based on Mass Full Carbon Backbone Polymeric Materials to Value-Added Polyhydroxyalkanoates (PHAs)
Authors: Johnston Brian , Adamus Grazyna , Ekere Anabel Itohowo , Kowalczuk Marek , Tchuenbou-Magaia Fideline , Radecka Iza
Published: September 2022

This review article will discuss the ways in which various polymeric materials, such as polyethylene (PE), polypropylene (PP), polystyrene (PS), and poly(ethylene terephthalate) (PET) can potentially be used to produce bioplastics, such as polyhydroxyalkanoates (PHAs) through microbial cultivation. We will present up-to-date information regarding notable microbial strains that are actively used in the biodegradation of polyolefins. We will also review some of the metabolic pathways involved in the process of plastic depolymerization and discuss challenges relevant to the valorization of plastic waste. The aim of this review is also to showcase the importance of methods, including oxidative degradation and microbial-based processes, that are currently being used in the fields of microbiology and biotechnology to limit the environmental burden of waste plastics. It is our hope that this article will contribute to the concept of bio-upcycling plastic waste to value-added products via microbial routes for a more sustainable future.
Therapeutic Potential of Leaves from Fridericia chica (Bonpl.) L. G. Lohmann: Botanical Aspects, Phytochemical and Biological, Anti-Inflammatory, Antioxidant and Healing Action
Authors: Batalha Adriane Dâmares de Sousa Jorge , Souza Damy Caroline de Melo , Ubiera Rosmery Duran , Chaves Francisco Celio Maia , Monteiro Wuelton Marcelo , da Silva Felipe Moura Araújo , Koolen Hector Henrique Ferreira , Boechat Antônio Luiz , Sartim Marco Aurélio
Published: September 2022

Plants of the species Fridericia chica (Bonpl.) L. G. Lohmann (Bignoniaceae), which are widely distributed in Brazil and named crajiru in the state of Amazonas, are known in folk medicine as a traditional medicine in the form of a tea for the treatment of intestinal colic, diarrhea, and anemia, among other diseases. The chemical analysis of extracts of the leaves has identified phenolic compounds, a class of secondary metabolites that provide defense for plants and benefits to the health of humans. Several studies have shown the therapeutic efficacy of F. chica extracts, with antitumor, antiviral, wound healing, anti-inflammatory, and antioxidant activities being among the therapeutic applications already proven. The healing action of F. chica leaf extract has been demonstrated in several experimental models, and shows the ability to favor the proliferation of fibroblasts, which is essential for tissue repair. The anti-inflammatory activity of F. chica has been clearly demonstrated by several authors, who suggest that it is related to the presence of 3-deoxyanthocyanidins, which is capable of inhibiting pro-inflammatory pathways such as the kappa B (NF-kB) nuclear transcription factor pathway. Another important effect attributed to this species is the antioxidant effect, attributed to phenolic compounds interrupting chain reactions caused by free radicals and donating hydrogen atoms or electrons. In conclusion, the species Fridericia chica has great therapeutic potential, which is detailed in this paper with the objective of encouraging new research and promoting the sum of efforts for the inclusion of herbal medicines in health systems around the world.
Downregulation of Lhx2 Markedly Impairs Wound Healing in Mouse Fetus
Authors: Takaya Kento , Sunohara Ayano , Aramaki-Hattori Noriko , Sakai Shigeki , Okabe Keisuke , Kishi Kazuo
Published: September 2022

Multiple transitions occur in the healing ability of the skin during embryonic development in mice. Embryos up to embryonic day 13 (E13) regenerate completely without a scar after full-thickness wounding. Then, up to E16, dermal structures can be formed, including skin appendages such as hair follicles. However, after E17, wound healing becomes incomplete, and scar formation is triggered. Lhx2 regulates the switch between maintenance and activation of hair follicle stem cells, which are involved in wound healing. Therefore, we investigated the role of Lhx2 in fetal wound healing. Embryos of ICR mice were surgically wounded at E13, E15, and E17, and the expression of Lhx2 along with mitotic (Ki67 and p63) and epidermal differentiation (keratin-10 and loricrin) markers was analyzed. The effect of Lhx2 knockdown on wound healing was observed. Lhx2 expression was not noticed in E13 due to the absence of folliculogenesis but was evident in the epidermal basal layer of E15 and E17 and at the base of E17 wounds, along with Ki67 and p63 expression. Furthermore, Lhx2 knockdown in E15 markedly prolonged wound healing and promoted clear scar formation. Therefore, Lhx2 expression is involved in cell division associated with wound healing and may contribute to scar formation in late embryos.
Common Medications Which Should Be Stopped Prior to Platelet-Rich Plasma Injection
Authors: Gupta Ashim , Jeyaraman Madhan , Maffulli Nicola
Published: September 2022

Osteoarthritis (OA) is an extremely prevalent joint condition in the United States, affecting over 30 million people [...]
Upregulated miR-18a-5p in Colony Forming Unit-Hill’s in Subclinical Cardiovascular Disease and Metformin Therapy; MERIT Study
Authors: Phowira Jason , Ahmed Fahad W. , Bakhashab Sherin , Weaver Jolanta U.
Published: September 2022

Colony forming unit-Hill’s (CFU-Hill’s) colonies are hematopoietic-derived cells that participate in neovasculogenesis and serve as a biomarker for vascular health. In animals, overexpression of miR-18a-5p was shown to be pro-atherogenic. We had shown that well-controlled type 1 diabetes mellitus (T1DM) is characterized by an inflammatory state, endothelial dysfunction, and reduced number of CFU-Hill’s, a model of subclinical cardiovascular disease (CVD). MERIT study explored the role of miR-18a-5p expression in CFU-Hill’s colonies in T1DM, and the cardioprotective effect of metformin in subclinical CVD. In T1DM, miR-18a-5p was significantly upregulated whereas metformin reduced it to HC levels. MiR-18a-5p was inversely correlated with CFU-Hill’s colonies, CD34+, CD34+CD133+ cells, and positively with IL-10, C-reactive protein, vascular endothelial growth factor-D (VEGF-D), and thrombomodulin. The receiver operating characteristic curve demonstrated, miR-18a-5p as a biomarker of T1DM, and upregulated miR-18a-5p defining subclinical CVD at HbA1c of 44.5 mmol/mol (pre-diabetes). Ingenuity pathway analysis documented miR-18a-5p inhibiting mRNA expression of insulin-like growth factor-1, estrogen receptor-1, hypoxia-inducible factor-1α cellular communication network factor-2, and protein inhibitor of activated STAT 3, whilst metformin upregulated these mRNAs via transforming growth factor beta-1 and VEGF. We confirmed the pro-atherogenic effect of miR-18a-5p in subclinical CVD and identified several target genes for future CVD therapies.
MRI Detection of Hepatic N-Acetylcysteine Uptake in Mice
Authors: Chen Johnny , Hwang Dennis W. , Chen Yu-Wen , Chen Tsai-Chen , Yadav Nirbhay N. , Stait-Gardner Timothy , Price William S. , Zheng Gang
Published: September 2022

This proof-of-concept study looked at the feasibility of using a thiol–water proton exchange (i.e., CEST) MRI contrast to detect in vivo hepatic N-acetylcysteine (NAC) uptake. The feasibility of detecting NAC-induced glutathione (GSH) biosynthesis using CEST MRI was also investigated. The detectability of the GSH amide and NAC thiol CEST effect at B0 = 7 T was determined in phantom experiments and simulations. C57BL/6 mice were injected intravenously (IV) with 50 g L−1 NAC in PBS (pH 7) during MRI acquisition. The dynamic magnetisation transfer ratio (MTR) and partial Z-spectral data were generated from the acquisition of measurements of the upfield NAC thiol and downfield GSH amide CEST effects in the liver. The 1H-NMR spectroscopy on aqueous mouse liver extracts, post-NAC-injection, was performed to verify hepatic NAC uptake. The dynamic MTR and partial Z-spectral data revealed a significant attenuation of the mouse liver MR signal when a saturation pulse was applied at −2.7 ppm (i.e., NAC thiol proton resonance) after the IV injection of the NAC solution. The 1H-NMR data revealed the presence of hepatic NAC, which coincided strongly with the increased upfield MTR in the dynamic CEST data, providing strong evidence that hepatic NAC uptake was detected. However, this MTR enhancement was attributed to a combination of NAC thiol CEST and some other upfield MT-generating mechanism(s) to be identified in future studies. The detection of hepatic GSH via its amide CEST MRI contrast was inconclusive based on the current results.
Rebooting Regulatory T Cell and Dendritic Cell Function in Immune-Mediated Inflammatory Diseases: Biomarker and Therapy Discovery under a Multi-Omics Lens
Authors: Kerdidani Dimitra , Papaioannou Nikos E. , Nakou Evangelia , Alissafi Themis
Published: September 2022

Immune-mediated inflammatory diseases (IMIDs) are a group of autoimmune and chronic inflammatory disorders with constantly increasing prevalence in the modern world. The vast majority of IMIDs develop as a consequence of complex mechanisms dependent on genetic, epigenetic, molecular, cellular, and environmental elements, that lead to defects in immune regulatory guardians of tolerance, such as dendritic (DCs) and regulatory T (Tregs) cells. As a result of this dysfunction, immune tolerance collapses and pathogenesis emerges. Deeper understanding of such disease driving mechanisms remains a major challenge for the prevention of inflammatory disorders. The recent renaissance in high throughput technologies has enabled the increase in the amount of data collected through multiple omics layers, while additionally narrowing the resolution down to the single cell level. In light of the aforementioned, this review focuses on DCs and Tregs and discusses how multi-omics approaches can be harnessed to create robust cell-based IMID biomarkers in hope of leading to more efficient and patient-tailored therapeutic interventions.
Spheroidal Model of SKBR3 and U87MG Cancer Cells for Live Imaging of Caspase-3 during Apoptosis Induced by Singlet Oxygen in Photodynamic Therapy
Authors: Pevná Viktória , Máčajová Mariana , Hovan Andrej , Bánó Gregor , Meta Majlinda , Bilčík Boris , Palková Júlia , Huntošová Veronika
Published: September 2022

Aspects related to the response of cells to photodynamic therapy (PDT) have been well studied in cell cultures, which often grow in monolayers. In this work, we propose a spheroidal model of U87MG and SKBR3 cells designed to mimic superficial tumor tissue, small spheroids (<500 µm) suitable for confocal fluorescence microscopy, and larger spheroids (>500 µm) that can be xenografted onto quail chorioallantoic membrane (CAM) to study the effects of PDT in real time. Hypericin was used as a model molecule for a hydrophobic photosensitizer that can produce singlet oxygen (1O2). 1O2 production by hypericin was detected in SKBR3 and U87MG spheroid models using a label-free technique. Vital fluorescence microscopy and flow cytometry revealed the heterogeneity of caspase-3 distribution in the cells of the spheroids. The levels of caspase-3 and apoptosis increased in the cells of spheroids 24 h after PDT. Lactate dehydrogenase activity was evaluated in the spheroids as the most reliable assay to detect differences in phototoxicity. Finally, we demonstrated the applicability of U87MG spheroids on CAM in photodiagnostics. Overall, the variability and applicability of the prepared spheroid models were demonstrated in the PDT study.
Oral Porphyromonas gingivalis and Fusobacterium nucleatum Abundance in Subjects in Primary and Secondary Cardiovascular Prevention, with or without Heterozygous Familial Hypercholesterolemia
Authors: Curia Maria Cristina , Pignatelli Pamela , D’Antonio Domenica Lucia , D’Ardes Damiano , Olmastroni Elena , Scorpiglione Luca , Cipollone Francesco , Catapano Alberico Luigi , Piattelli Adriano , Bucci Marco , Magni Paolo
Published: September 2022

Background: Low-grade chronic inflammation, promoted by dysbiosis of the gut and oral microbiota, has been shown to contribute to individual susceptibility to atherosclerotic cardiovascular disease (ASCVD). High oral Porphyromonas gingivalis (Pg) and lower Fusobacterium nucleatum (Fn) concentrations have been associated with clinical and experimental atherosclerosis. We assessed oral Pg and Fn abundance in very high-risk patients with previously diagnosed ASCVD, with or without heterozygous familial hypercholesterolemia (HeFH), in subjects with HeFH in primary prevention and in healthy subjects. Methods: In this cross-sectional study, 40 patients with previously diagnosed ASCVD (10 with genetically proven HeFH, and 30 without FH), 26 subjects with HeFH in primary prevention, and 31 healthy subjects were selected to quantify oral Pg and Fn abundance by qPCR and assess oral health status. Results: Compared to healthy subjects, patients with previously diagnosed ASCVD showed greater Pg abundance (1101.3 vs. 192.4, p = 0.03), but similar Fn abundance. HeFH patients with ASCVD had an even greater Pg abundance than did non-HeFH patients and healthy subjects (1770.6 vs. 758.4 vs. 192.4, respectively; p = 0.048). No differences were found in the levels of Pg and Fn abundance in HeFH subjects in primary prevention, as compared to healthy subjects. Conclusions: Greater oral Pg abundance is present in very high-risk patients with previously diagnosed ASCVD, with or without FH, suggesting a potential relationship with CV events. Future studies will assess the predictive value of Pg abundance measurement in ASCVD risk stratification.
Evaluating Antibody Pharmacokinetics as Prerequisite for Determining True Efficacy as Shown by Dual Targeting of PD-1 and CD96
Authors: Boch Christina , Reschke Markus , Igney Frederik , Maier Peter , Müller Philipp , Danklmaier Sarah , Das Krishna , Hofer Tamara , Wollmann Guido , Rist Wolfgang
Published: September 2022

One important prerequisite for developing a therapeutic monoclonal antibody is to evaluate its in vivo efficacy. We tested the therapeutic potential of an anti-CD96 antibody alone or in combination with an anti-PD-1 antibody in a mouse colon cancer model. Early anti-PD-1 treatment significantly decreased tumor growth and the combination with anti-CD96 further increased the therapeutic benefit, while anti-CD96 treatment alone had no effect. In late therapeutic settings, the treatment combination resulted in enhanced CD8+ T cell infiltration of tumors and an increased CD8/Treg ratio. Measured anti-PD-1 concentrations were as expected in animals treated with anti-PD-1 alone, but lower at later time points in animals receiving combination treatment. Moreover, anti-CD96 concentrations dropped dramatically after 10 days and were undetectable thereafter in most animals due to the occurrence of anti-drug antibodies that were increasing antibody clearance. Comparison of the anti-PD-1 concentrations with tumor growth showed that higher antibody concentrations in plasma correlated with better therapeutic efficacy. The therapeutic effect of anti-CD96 treatment could not be evaluated, because plasma concentrations were too low. Our findings strongly support the notion of measuring both plasma concentration and anti-drug antibody formation throughout in vivo studies, in order to interpret pharmacodynamic data correctly.
Epithelial-to-Mesenchymal Transition in Metastasis: Focus on Laryngeal Carcinoma
Authors: Goulioumis Anastasios , Gyftopoulos Kostis
Published: September 2022

In epithelial neoplasms, such as laryngeal carcinoma, the survival indexes deteriorate abruptly when the tumor becomes metastatic. A molecular phenomenon that normally appears during embryogenesis, epithelial-to-mesenchymal transition (EMT), is reactivated at the initial stage of metastasis when tumor cells invade the adjacent stroma. The hallmarks of this phenomenon are the abolishment of the epithelial and acquisition of mesenchymal traits by tumor cells which enhance their migratory capacity. EMT signaling is mediated by complex molecular pathways that regulate the expression of crucial molecules contributing to the tumor’s metastatic potential. Effectors of EMT include loss of adhesion, cytoskeleton remodeling, evasion of apoptosis and immune surveillance, upregulation of metalloproteinases, neovascularization, acquisition of stem-cell properties, and the activation of tumor stroma. However, the current approach to EMT involves a holistic model that incorporates the acquisition of potentials beyond mesenchymal transition. As EMT is inevitably associated with a reverse mesenchymal-to-epithelial transition (MET), a model of partial EMT is currently accepted, signifying the cell plasticity associated with invasion and metastasis. In this review, we identify the cumulative evidence which suggests that various aspects of EMT theory apply to laryngeal carcinoma, a tumor of significant morbidity and mortality, introducing novel molecular targets with prognostic and therapeutic potential.
Detection of Preclinical Orthostatic Disorders in Young African and European Adults Using the Head-Up Tilt Test with a Standardized Hydrostatic Column Height: A Pilot Study
Authors: Dorogovtsev Victor N. , Yankevich Dmitry S. , Petrova Marina V. , Torshin Vladimir I. , Severin Aleksander E. , Borisov Ilya V. , Podolskaya Julia A. , Grechko Andrey V.
Published: September 2022

Arterial hypertension (AH) remains the most common disease. One possible way to improve the effectiveness of the primary prevention of AH is to identify and control the preclinical orthostatic disturbances that precede the development of AH. The aim of the study was to determine the feasibility of a new protocol for the head-up tilt test (HUTT) with a standardized hydrostatic column height for the detection of asymptomatic orthostatic circulatory disorders and their racial differences in young African and European adults. Methods. In total, 80 young healthy adults (40 African and 40 European) aged 20–23 years performed the HUTT with a standardized hydrostatic column height of 133 cm. The hemodynamic parameters were recorded using a Task Force Monitor (3040i). The cardio-ankle vascular index (CAVI) was measured using a VaSera VS-2000 volumetric sphygmograph. Results. The baseline and orthostatic hemodynamic changes in both racial groups were within normal limits. Orthostatic circulatory disturbances were not detected in 70% of the European participants and 65% of the African participants; however, preclinical orthostatic hypertension, which precedes AH, was detected using the new HUTT protocol in 32.5% of the African participants and 20% of the European participants. The baseline CAVI was higher in the European group compared to the African group. Conclusion. The results of this study showed the feasibility of the detection of preclinical orthostatic disturbances in young adults and the detection of their racial differences using the HUTT protocol, providing the use of a standard gravity load. Further study on the evolution of preclinical orthostatic disturbances and their relation to increased vascular stiffness is necessary among large samples.
Magnetic Nanotag-Based Colorimetric/SERS Dual-Readout Immunochromatography for Ultrasensitive Detection of Clenbuterol Hydrochloride and Ractopamine in Food Samples
Authors: Wu Ting , Li Jiaxuan , Zheng Shuai , Yu Qing , Qi Kezong , Shao Ying , Wang Chongwen , Tu Jian , Xiao Rui
Published: September 2022

Direct and sensitive detection of multiple illegal additives in complex food samples is still a challenge in on-site detection. In this study, an ultrasensitive immunochromatographic assay (ICA) using magnetic Fe3O4@Au nanotags as a capture/detection difunctional tool was developed for the direct detection of β2-adrenoceptor agonists in real samples. The Fe3O4@Au tag is composed of a large magnetic core (~160 nm), a rough Au nanoshell, dense surface-modified Raman molecules, and antibodies, which cannot only effectively enrich targets from complex solutions to reduce the matrix effects of food samples and improve detection sensitivity, but also provide strong colorimetric/surface-enhanced Raman scattering (SERS) dual signals for ICA testing. The dual readout signals of the proposed ICA can meet the detection requirements in different environments. Specifically, the colorimetric signal allows for rapid visual detection of the analyte, and the SERS signal is used for the sensitive and quantitative detection modes. The proposed dual-signal ICA can achieve the simultaneous determination of two illegal additives, namely, clenbuterol hydrochloride and ractopamine. The detection limits for the two targets via colorimetric and SERS signals were down to ng mL−1 and pg mL−1 levels, respectively. Moreover, the proposed assay has demonstrated high accuracy and stability in real food samples.
A Framework for Biosensors Assisted by Multiphoton Effects and Machine Learning
Authors: Arano-Martinez Jose Alberto , Martínez-González Claudia Lizbeth , Salazar Ma Isabel , Torres-Torres Carlos
Published: September 2022

The ability to interpret information through automatic sensors is one of the most important pillars of modern technology. In particular, the potential of biosensors has been used to evaluate biological information of living organisms, and to detect danger or predict urgent situations in a battlefield, as in the invasion of SARS-CoV-2 in this era. This work is devoted to describing a panoramic overview of optical biosensors that can be improved by the assistance of nonlinear optics and machine learning methods. Optical biosensors have demonstrated their effectiveness in detecting a diverse range of viruses. Specifically, the SARS-CoV-2 virus has generated disturbance all over the world, and biosensors have emerged as a key for providing an analysis based on physical and chemical phenomena. In this perspective, we highlight how multiphoton interactions can be responsible for an enhancement in sensibility exhibited by biosensors. The nonlinear optical effects open up a series of options to expand the applications of optical biosensors. Nonlinearities together with computer tools are suitable for the identification of complex low-dimensional agents. Machine learning methods can approximate functions to reveal patterns in the detection of dynamic objects in the human body and determine viruses, harmful entities, or strange kinetics in cells.
A Local Approach to Better Understand the Spread and Population Growth of the Monk Parakeet as an Invasive Species
Authors: López-Ramírez Sandro , Muñoz Antonio-Román
Published: September 2022

Invasive exotic species are currently a topic of interest for environmental management agencies and the media. This is due to the socio-economic and environmental problems that they are causing or may cause. The Monk Parakeet is a clear example of this, especially in some large cities, where populations are growing quickly, and their distribution continues to expand. In our study, we focused on a population that has been closely monitored during the last 25 years to understand its growth and change on a local scale to determine the maximum sustainable population size in the invaded area and to check when this population began to act as a source of new breeding colonies to adjacent areas. The first breeding of the species occurred in 2002, and from then, the average growth rate (r) of the population was 0.191 until 2016, when it stabilized and declined slightly (r = −0.043). The maximum growth rate occurred during the years 2002 and 2007 and was 0.314. The results obtained give us information about the carrying capacity of the study area, allowing us to explain the dispersal process of the species to neighbouring areas, with populations that have reached maximum size serving as sources of individuals dispersing to suitable areas. In our study area, the species shows a strong preference for building its nests in palm trees and electric utility structures. Our study’s local focus on studying the population dynamics of an invasive species may allow us to understand the increased range of the species on a larger scale, which is necessary in order to be able to design appropriate and effective management strategies.
Elucidating the Neurobiologic Etiology of Comorbid PTSD and Substance Use Disorders
Authors: Hinckley Jesse D. , Danielson Carla Kmett
Published: September 2022

Early childhood maltreatment and other traumatic event experiences (“trauma”) are common among youth, including those with substance use problems including substance use disorders (SUD). Particularly, interpersonal violence is associated with high rates of comorbidity between posttraumatic stress disorder (PTSD) and SUD, and these comorbid disorders exhibit high levels of overlapping symptomatology. Theoretical models proposed to explain the bidirectional relationship between PTSD and SUD include the self-medication hypothesis and susceptibility hypothesis. In this article, we explore neurobiologic changes associated with trauma, PTSD, and SUD that underly dysregulated stress response. Examining lessons learned from recent translational and clinical research, we propose that further elucidating the neurobiologic etiology of comorbid PTSD and SUD will require a collaborative, interdisciplinary approach, including the integration of preclinical and clinical studies, exploration of biologic markers in clinical studies, and accumulation of larger studies and longitudinal studies with the power to study PTSD and SUD. Such research can transform the field and ultimately reduce high rates and costly impairment of co-occurring PTSD and SUD across the lifespan.
Tailored Approach and Multimodal Intraoperative Neuromonitoring in Cerebellopontine Angle Surgery
Authors: Izzo Alessandro , Stifano Vito , Della Pepa Giuseppe Maria , Di Domenico Michele , D'Alessandris Quintino Giorgio , Menna Grazia , D'Ercole Manuela , Lauretti Liverana , Olivi Alessandro , Montano Nicola
Published: September 2022

The cerebellopontine angle (CPA) is a highly complex anatomical compartment consisting of numerous nervous and vascular structures that present mutual and intricate spatial relationships. CPA surgery represents, therefore, a constant challenge for neurosurgeons. Over the years, neurosurgeons have developed and refined several solutions with the aim of maximizing the surgical treatment effects while minimizing the invasiveness and risks for the patient. In this paper, we present our integrated approach to CPA surgery, describing its advantages in treating pathologies in this anatomical district. Our approach incorporates the use of technology, such as neuronavigation, along with advanced and multimodal intraoperative neuromonitoring (IONM) techniques, with the final goal of making this surgery safe and effective.
Clinical Manifestations, Diagnosis, Treatment and Prognosis of Uveitis Induced by Anticancer Drugs: A Review of Literature
Authors: Li Dongchen , Yang Li , Bai Feng , Zeng Shun , Liu Xiaoli
Published: September 2022

There are increasing reports that anticancer drugs, especially immunotherapy and specific targeted therapy, can cause uveitis, but it is not fully understood whether the clinical features of this drug-induced uveitis differ from those of other types of uveitis and whether there are differences between these drugs. We retrospectively reviewed the published cases and case series in PubMed, Embase, Web of Science, and Cochrane from January 2011 to October 2020. We analysed the data, including patients’ basic information, medications used, duration of use, time to onset, clinical manifestations, diagnosis, treatment, and prognosis of uveitis. We focused on the differences in uveitis caused by immunotherapy and specific targeted therapy. Altogether 93 cases (43 men, 48 women, and 2 cases whose gender was not mentioned) reported in 55 articles were included in this study. The average age was 59.6 ± 13.5 years. Eighty percent of the patients had bilateral involvement. Sixty cases were caused by immunotherapy (64.5%), and twenty-six were caused by specific targeted therapy (27.9%). No significant difference was found in the mean time from treatment to onset between the two groups. Anticancer drug-induced uveitis can involve all parts of the uvea from anterior to posterior, manifested as anterior chamber flare, anterior chamber cells, papillitis, macular oedema, subretinal fluid, and choroidal effusion. Anterior uveitis (24 cases, 40.0%) was more common in immunotherapy, and intermediate uveitis (8 cases, 30.8%) was more common in specific targeted therapy. The mean LogMAR visual acuity in specific targeted therapy at presentation was lower than in immunotherapy, but it was not statistically significant. Corticosteroid therapy can effectively control uveitis induced by anticancer drugs. However, the survival prognosis was poor. Among the 19 patients with reported cancer prognosis, seven (36.8%) had no cancer progression, eight (42.1%) had further metastases, and four (21.0%) died of cancer. In conclusion, uveitis caused by anticancer drugs involves both eyes and manifests as various types of uveitis. Patients with specific targeted therapy are more likely to have intermediate uveitis and low vision, and immunotherapy patients are more likely to have anterior uveitis. Corticosteroids are effective against uveitis caused by anticancer drugs.
Sensory Modulation in Children with Developmental Coordination Disorder Compared to Autism Spectrum Disorder and Typically Developing Children
Authors: Ringold Sofronia M , McGuire Riley W , Jayashankar Aditya , Kilroy Emily , Butera Christiana D , Harrison Laura , Cermak Sharon A , Aziz-Zadeh Lisa
Published: September 2022

Developmental Coordination Disorder (DCD) is one of the least studied and understood developmental disorders. One area that has been minimally investigated in DCD is potential issues with sensory modulation. Further, in other neurodevelopmental disorders (e.g., autism spectrum disorder (ASD)) sensory modulation is related to many other challenges (e.g., social issues, repetitive behaviors, anxiety); however, such potential relationships in children with DCD have been largely unexplored. The purpose of this study is to explore sensory modulation differences in DCD and to understand the relationships between sensory modulation and social emotional measures, behavior, and motor skills in DCD in comparison to ASD and typically developing (TD) peers. Participants (aged 8–17) and their caregivers (DCD, N = 26; ASD, N = 57; and TD, N = 53) completed behavioral and clinical measures. The results indicated that 31% of the DCD group showed sensory modulation difficulties, with the DCD group falling between the ASD and TD groups. In the DCD group, sensory modulation was significantly associated with anxiety, empathic concern, repetitive behaviors, and motor skills. Data are compared to patterns seen in ASD and TD groups and implications for interventions are discussed.
Astrocyte-Derived Neuronal Transdifferentiation as a Therapy for Ischemic Stroke: Advances and Challenges
Authors: Gong Siqi , Shao Han , Cai Xiuying , Zhu Juehua
Published: September 2022

After the onset of ischemic stroke, ischemia–hypoxic cascades cause irreversible neuronal death. Neurons are the fundamental structures of the central nervous system, and mature neurons do not renew or multiply after death. Functional and structural recovery from neurological deficits caused by ischemic attack is a huge task. Hence, there remains a need to replace the lost neurons relying on endogenous neurogenesis or exogenous stem cell-based neuronal differentiation. However, the stem cell source difficulty and the risk of immune rejection of the allogeneic stem cells might hinder the wide clinical application of the above therapy. With the advancement of transdifferentiation induction technology, it has been demonstrated that astrocytes can be converted to neurons through ectopic expression or the knockdown of specific components. The progress and problems of astrocyte transdifferentiation will be discussed in this article.