bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Trabecular Meshwork (HTM) Cells Treated with TGF-β2 or Dexamethasone Respond to Compression Stress in Different Manners
Authors: Watanabe Megumi , Sato Tatsuya , Tsugeno Yuri , Umetsu Araya , Suzuki Soma , Furuhashi Masato , Ida Yosuke , Hikage Fumihito , Ohguro Hiroshi
Published: June 2022

To characterize our recently established in vitro glaucomatous human trabecular meshwork (HTM) models using dexamethasone (DEX)- or TGF-β2-treated HTM cells, (1) two-dimensional (2D) cultured HTM cells were characterized by means of the real-time cellular metabolism analysis using a Seahorse analyzer, and (2) the effects of mechanical compression stresses toward the three-dimensional (3D) HTM spheroids were evaluated by analyzing the gene expression of several ECM proteins, inflammatory cytokines, and ER stress-related factors of those 3D HTM spheroid models. The results indicated that (1) the real-time cellular metabolism analysis indicated that TGF-β2 significantly induced an energy shift from mitochondrial oxidative phosphorylation (OXPHOS) into glycolysis, and DEX induced similar but lesser effects. In contrast, ROCK2 inhibition by KD025 caused a substantial reverse energy shift from glycolysis into OXPHOS. (2) Upon direct compression stresses toward the untreated control 3D HTM spheroids, a bimodal fluctuation of the mRNA expressions of ECM proteins was observed for 60 min, that is, initial significant upregulation (0–10 min) and subsequent downregulation (10–30 min) followed by another upregulation (30–60 min); those of inflammatory cytokines and ER stress-related factors were also bimodally changed. However, such compression stresses for 30 min toward TGF-β2- or DEX-treated 3D HTM spheroids induced downregulation of most of those of inflammatory cytokines and ER stress-related factors in addition to upregulation of COL1 and downregulation of FN. The findings presented herein indicate that (1) OXPHOS of the HTM cells was decreased or increased by TGF-β2 or DEX stimulation or ROCK2 inhibition, and (2) mechanical compression stresses toward 3D HTM spheroids may replicate acute, subacute, and chronic HTM models affected by elevated intraocular pressures.
Multiparametric Phenotyping of Circulating Tumor Cells for Analysis of Therapeutic Targets, Oncogenic Signaling Pathways and DNA Repair Markers
Authors: Staudte Stephanie , Klinghammer Konrad , Jurmeister Philipp Sebastian , Jank Paul , Blohmer Jens-Uwe , Liebs Sandra , Rhein Peter , Hauser Anja E. , Tinhofer Ingeborg
Published: June 2022

Detection of circulating tumor cells (CTCs) has been established as an independent prognostic marker in solid cancer. Multiparametric phenotyping of CTCs could expand the area of application for this liquid biomarker. We evaluated the Amnis® brand ImageStream®X MkII (ISX) (Luminex, Austin, TX, USA) imaging flow cytometer for its suitability for protein expression analysis and monitoring of treatment effects in CTCs. This was carried out using blood samples from patients with head and neck squamous cell carcinoma (n = 16) and breast cancer (n = 8). A protocol for negative enrichment and staining of CTCs was established, allowing quantitative analysis of the therapeutic targets PD–L1 and phosphorylated EGFR (phospho–EGFR), and the treatment response marker γH2AX as an indicator of radiation–induced DNA damage. Spiking experiments revealed a sensitivity of 73% and a specificity of 100% at a cut–off value of ≥3 CTCs, and thus confirmed the suitability of the ISX-based protocol to detect phospho–EGFR and γH2AX foci in CTCs. Analysis of PD–L1/–L2 in both spiked and patient blood samples further showed that assessment of heterogeneity in protein expression within the CTC population was possible. Further validation of the diagnostic potential of this ISX protocol for multiparametric CTC analysis in larger clinical cohorts is warranted.
Cancer-Associated Fibroblasts Confer Gemcitabine Resistance to Pancreatic Cancer Cells through PTEN-Targeting miRNAs in Exosomes
Authors: Richards Katherine , Xiao Weikun , Hill Reginald ,   on behalf of the USC Pancreas Research Team
Published: June 2022

Pancreatic ductal adenocarcinoma (PDAC) is currently the third leading cause of cancer-related death in the United States. Even though the poor prognosis of PDAC is often attributed to late diagnosis, patients with an early diagnosis who undergo tumor resection and adjuvant chemotherapy still show tumor recurrence, highlighting a need to develop therapies which can overcome chemoresistance. Chemoresistance has been linked to the high expression of microRNAs (miRs), such as miR-21, within tumor cells. Tumor cells can collect miRs through the uptake of miR-containing lipid extracellular vesicles called exosomes. These exosomes are secreted in high numbers from cancer-associated fibroblasts (CAFs) within the tumor microenvironment during gemcitabine treatment and can contribute to cell proliferation and chemoresistance. Here, we show a novel mechanism in which CAF-derived exosomes may promote proliferation and chemoresistance, in part, through suppression of the tumor suppressor PTEN. We identified five microRNAs: miR-21, miR-181a, miR-221, miR-222, and miR-92a, that significantly increased in number within the CAF exosomes secreted during gemcitabine treatment which target PTEN. Furthermore, we found that CAF exosomes suppressed PTEN expression in vitro and that treatment with the exosome inhibitor GW4869 blocked PTEN suppression in vivo. Collectively, these findings highlight a mechanism through which the PTEN expression loss, often seen in PDAC, may be attained and lend support to investigations into the use of exosome inhibitors as potential therapeutics to improve the effectiveness of chemotherapy.
Novel Pharmacological Treatment Options in Pediatric Glioblastoma—A Systematic Review
Authors: Wyss Johanna , Frank Nicole Alexandra , Soleman Jehuda , Scheinemann Katrin
Published: June 2022

Background: Pediatric glioblastoma (GBM) is an aggressive central nervous system tumor in children that has dismal prognosis. Standard of care is surgery with subsequent irradiation and temozolomide. We aimed to outline currently available data on novel pharmacological treatments for pediatric GBM. Methods: We conducted a systematic literature search in PubMed and Embase, including reports published in English from 2010 to 2021. We included randomized trials, cohort studies and case series. Phase I trials were not analyzed. We followed PRISMA guidelines, assessed the quality of the eligible reports using the Newcastle-Ottawa scale (NOS) and the RoB-2 tool and registered the protocol on PROSPERO. Results: We included 6 out of 1122 screened reports. All six selected reports were prospective, multicenter phase II trials (five single-arm and one randomized controlled trial). None of the investigated novel treatment modalities showed any benefit regarding overall or progression free survival. Conclusions: To date, the role of pharmacological approaches regarding pediatric GBM remains unclear, since no novel treatment approach could provide a significant impact on overall or progression free survival. Further research should aim to combine different treatment strategies in large international multicenter trials with central comprehensive diagnostics regarding subgrouping. These novel treatment approaches should include targeted and immunotherapeutic treatments, potentially leading to a more successful outcome.
Characteristics and Outcomes of Adult Patients in the PETHEMA Registry with Relapsed or Refractory FLT3-ITD Mutation-Positive Acute Myeloid Leukemia
Authors: Martínez-Cuadrón David , Serrano Josefina , Mariz José , Gil Cristina , Tormo Mar , Martínez-Sánchez Pilar , Rodríguez-Arbolí Eduardo , García-Boyero Raimundo , Rodríguez-Medina Carlos , Martínez-Chamorro Carmen , Polo Marta , Bergua Juan , Aguiar Eliana , Amigo María L. , Herrera Pilar , Alonso-Domínguez Juan M. , Bernal Teresa , Espadana Ana , Sayas María J. , Algarra Lorenzo , Vidriales María B. , Vasconcelos Graça , Vives Susana , Pérez-Encinas Manuel M. , López Aurelio , Noriega Víctor , García-Fortes María , Chillón María C. , Rodríguez-Gutiérrez Juan I. , Calasanz María J. , Labrador Jorge , López Juan A. , Boluda Blanca , Rodríguez-Veiga Rebeca , Martínez-López Joaquín , Barragán Eva , Sanz Miguel A. , Montesinos Pau ,   on behalf of the PETHEMA Group
Published: June 2022

This retrospective study investigated outcomes of 404 patients with relapsed/refractory (R/R) FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) acute myeloid leukemia (AML) enrolled in the PETHEMA registry, pre-approval of tyrosine kinase inhibitors. Most patients (63%) had received first-line intensive therapy with 3 + 7. Subsequently, patients received salvage with intensive therapy (n = 261), non-intensive therapy (n = 63) or supportive care only (n = 80). Active salvage therapy (i.e., intensive or non-intensive therapy) resulted in a complete remission (CR) or CR without hematological recovery (CRi) rate of 42%. More patients achieved a CR/CRi with intensive (48%) compared with non-intensive (19%) salvage therapy (p < 0.001). In the overall population, median overall survival (OS) was 5.5 months; 1- and 5-year OS rates were 25% and 7%. OS was significantly (p < 0.001) prolonged with intensive or non-intensive salvage therapy compared with supportive therapy, and in those achieving CR/CRi versus no responders. Of 280 evaluable patients, 61 (22%) had an allogeneic stem-cell transplant after they had achieved CR/CRi. In conclusion, in this large cohort study, salvage treatment approaches for patients with FLT3-ITD mutated R/R AML were heterogeneous. Median OS was poor with both non-intensive and intensive salvage therapy, with best long-term outcomes obtained in patients who achieved CR/CRi and subsequently underwent allogeneic stem-cell transplant.
Healthcare Service Quality from the Point of Healthcare Providers’ Perception at the Time of COVID-19
Authors: Ivanov Olivera , Gojković Zoran , Simeunović Nenad , Gračanin Danijela , Milovančev Aleksandra , Ivanov Dejan , Bojović Marko , Bugarčić Miloš , Stojić Nikola
Published: June 2022

The pandemic of the Coronavirus 19 disease (COVID-19) has had significant impact on healthcare systems worldwide. The present study aims to investigate the service providers’ quality dimensions in public sector hospitals in the Republic of Serbia during the COVID-19 pandemic and to propose a sustainable model for healthcare improvement. The study was conducted from September 2021 to December 2021. A modified SERPERF quality measurement questionnaire was distributed to healthcare workers in nine secondary care public hospitals of the Serbian Autonomous Province of Vojvodina (APV). Six hundred one questionnaires were found to be complete in all aspects and compared to 528 questionnaires from the database of the Provincial Secretariat for Health Care obtained from healthcare workers before the COVID-19 outbreak. The present study suggests that supportive measures during the COVID-19 pandemic are effective and, from the providers’ perception, increase healthcare quality. Continual investment in healthcare would provide sustainable development of healthcare quality in the future, regardless of the pandemic conditions.
Secondary Malignancy in Giant Cell Tumor: A Single-Center Study
Authors: Joo Min Wook , Lee Yong-Suk , Park Hong Sik , Chung Yang-Guk , Yoon Chiyoung
Published: June 2022

Giant cell tumor of bone (GCTB) undergoes a sarcomatous transformation. Secondary malignancy in giant cell tumor (MGCT) is associated with radiotherapy and has a dismal prognosis. We reviewed medical records to investigate the clinicopathological characteristics and prognosis of MGCT patients. The enrollment criterion was high-grade spindle-cell sarcoma, which developed at the site of prior GCTB treatment. Twelve patients were analyzed: six females and six males. The median age was 42.5 years. Benign recurrence occurred in five GCTB patients not treated with radiotherapy. No pulmonary implants were observed. The median latency to the malignant transformation was 63 months. Nine patients were AJCC stage IIB, and three were stage IVA. The median follow-up period after malignant transformation was 62.5 months. Five patients developed local recurrence, and six had distant metastasis. Five-year overall recurrence and metastasis-free survival rates were 61.9%, 66.7%, and 58.3%, respectively. Initial metastasis was a predictive factor for overall survival. Benign local recurrence of GCTB was also a negative factor for metastasis-free survival of MGCT patients. Differences in overall survival according to benign recurrence also showed a tendency toward significance. In our series, secondary MGCT did not occur after radiotherapy. The prognosis was better than previous findings. Benign recurrence of GCTB could reflect the prognosis of MGCT.
Discrete Memristor and Discrete Memristive Systems
Authors: He Shaobo , Zhan Donglin , Wang Huihai , Sun Kehui , Peng Yuexi
Published: June 2022

In this paper, we investigate the mathematical models of discrete memristors based on Caputo fractional difference and G–L fractional difference. Specifically, the integer-order discrete memristor is a special model of those two cases. The “∞”-type hysteresis loop curves are observed when input is the bipolar periodic signal. Meanwhile, numerical analysis results show that the area of hysteresis decreases with the increase of frequency of input signal and the decrease of derivative order. Moreover, the memory effect, characteristics and physical realization of the discrete memristors are discussed, and a discrete memristor with short memory effects is designed. Furthermore, discrete memristive systems are designed by introducing the fractional-order discrete memristor and integer-order discrete memristor to the Sine map. Chaos is found in the systems, and complexity of the systems is controlled by the parameter of the memristor. Finally, FPGA digital circuit implementation is carried out for the integer-order and fractional-order discrete memristor and discrete memristive systems, which shows the potential application value of the discrete memristor in the engineering application field.
Improving ICTs (Mobile Phone and Internet) for Environmental Sustainability in the Western Balkan Countries
Authors: Dedaj But , Ogruk-Maz Gokcen , Carabregu-Vokshi Mjellma , Aliu-Mulaj Luljeta , Kisswani Khalid M.
Published: June 2022

The aim of this paper is to replicate an existing study using the Generalized Method of Moments on the impact of ICT penetration (Mobile Phone and Internet) in Western Balkan countries on environmental sustainability through changing CO2 emissions for the period 2000–2015. A two-step system GMM method is used to handle both endogeneity of the independent and persistency of the dependent variables. Two important findings are derived: First, we find that mobile phones have a positive impact, whereas the Internet has a positive but insignificant impact on CO2 emissions per capita in noninteractive models. The impact of ICTs is insignificant as far as CO2 emission from liquid fuel consumption is concerned in noninteractive specifications. Based on this finding, we suggest policymakers of Western Balkan countries follow interdisciplinary policies and strategies considering ICTs such as Internet penetration to mitigate CO2 emissions. Second, in interactive models, all marginal effects are negative, and in one specification the impact is statistically significant. We argue that increasing Internet penetration has a negative net effect on CO2 emissions from liquid fuel consumption. By calculating the policy threshold for this net effect, we discuss the practical implications for policy making in Kosovo where the average Internet penetration is below this threshold.
Space-Time Conglomerates Analysis of the Forest-Based Power Plants in Brazil (2000–2019)
Authors: Coelho Junior Luiz Moreira , Santos Júnior Edvaldo Pereira
Published: June 2022

Forest based power plants are alternatives in the diversification of domestic energy supply in Brazil, given the growing demand for electricity in recent decades. Evidences of space-time clusters contribute to the understanding of regional development associated with correlated activity. Therefore, this paper analyzed the space-time conglomerates for Brazilian forest-based power plants, from 2000 to 2019. The data used were from the Generation Information System of the National Electric Energy Agency (ANEEL)-SIGA. It detected the existence of clusters by means of scan statistics via space-time permutation, considering the high level of conglomeration. The results show the Center-South region of Brazil with the highest concentration of conglomerates, with black liquor and forest residues being the most used energy resources. The clusters with the highest installed power were in the early 2010s, with the black liquor plants. The regions with the formation of fast-growing forest plantations promoted the existence of conglomerates associated with the pulp and paper and steel industry complexes. It is concluded that there was a conglomeration of forest power plants in the central-south region of Brazil, in which they help in decision-making and guidance of public policies for forestry projects for energy.
Machine Learning for Energy Systems Optimization
Authors: Kim Insu , Kim Beopsoo , Sidorov Denis
Published: June 2022

This editorial overviews the contents of the Special Issue “Machine Learning for Energy Systems 2021” and review the trends in machine learning (ML) techniques for energy system (ES) optimization [...]
Combustion Characterization in a Diffusive Gas Turbine Burner for Hydrogen-Compliant Applications
Authors: Carusotto Salvatore , Goel Prashant , Baratta Mirko , Misul Daniela Anna , Salvadori Simone , Cardile Francesco , Forno Luca , Toppino Marco , Valsania Massimo
Published: June 2022

The target of net-zero emissions set by the 2015 Paris Agreement has strongly commissioned the energy production sector to promote decarbonization, renewable sources exploitation, and systems efficiency. In this framework, the utilization of hydrogen as a long-term energy carrier has great potential. This paper is concerned with the combustion characterization in a non-premixed gas turbine burner, originally designed for natural gas, when it is fed with NG-H2 blends featuring hydrogen content from 0 to 50% in volume. The final aim is to retrofit a 40 MW gas turbine. Starting from the operational data of the engine, a CFD model of the steady-state combustion process has been developed, with reference to the base load NG conditions, by reducing the fuel mass-flow rate by up to 17% to target the baseline turbine inlet temperature. When the fuel is blended with hydrogen, for a given temperature at turbine inlet, an increase in the peak temperature up to 800 K is obtained, if no countermeasures are taken. Furthermore, the flame results are more intense and closer to the injector in the case of hydrogen blending. The results of this work hint at the necessity of carefully analyzing the possible NOx compensation strategies, as well as the increased thermal stresses on the injector.
MW-Assisted Regeneration of 13X Zeolites after N2O Adsorption from Concentrated Streams: A Process Intensification
Authors: Meloni Eugenio , Martino Marco , Pierro Mariaconcetta , Pullumbi Pluton , Brandani Federico , Palma Vincenzo
Published: June 2022

N2O has a global warming potential about 300 times higher than CO2, and even if its contribution to the greenhouse effect is underrated, its abatement in industrial production’s tail gas has become imperative. In this work, we investigate the feasibility of the microwave (MW)-assisted regeneration of a 13X zeolite bed for N2O capture from tail gases. Several consecutive adsorption–desorption cycles were performed to verify the microwave heating effect on the zeolite’s adsorption properties. The results of the experimental tests, performed at N2O concentrations of 10, 20 and 40% vol, highlighted that (i) the steps are perfectly repeatable in terms of both adsorbed and desorbed amount of N2O, meaning that the MWs did not damage the zeolite’s structure, (ii) the presence of both H2O and O2 in the feed stream irreversibly reduces the adsorbent capacity due to nitrites and nitrates formation, and (iii) the presence of H2O alone with N2O still reduces the adsorbent capacity of the zeolites, which can be recovered through MW-assisted regeneration at 350 °C. Moreover, the MW-assisted TSA assured an energy and purge gas saving up to 63% and 82.5%, respectively, compared to a traditional regeneration process, resulting in effective process intensification.
Microgrid Energy Management System Based on Fuzzy Logic and Monitoring Platform for Data Analysis
Authors: Sumarmad Khaizaran Abdulhussein Al , Sulaiman Nasri , Wahab Noor Izzri Abdul , Hizam Hashim
Published: June 2022

Energy management and monitoring systems are significant difficulties in applying microgrids to smart homes. Thus, further research is required to address the modeling and operational parts of the system’s future results for various applications. This paper proposes a new technique for energy management in a microgrid using a robust control approach and the development of a platform for real-time monitoring. The developed controller is based on a fuzzy logic method used in the energy Internet paradigm with connected distributed generators (DGs) in the microgrid. The developed method regulates the power flow of the microgrid, and frequency/voltage regulation improved the load-management performance and monitoring system using the ThingSpeak platform for real-time data analysis. The MATLAB. simulation results show the feasibility and effectiveness of the proposed strategy and the introduced approach in microgrid control under various operating conditions. Additionally, the results show that the proposed monitoring platform facilitates real-time data analysis.
The Use of Cinnamon Essential Oils in Aquaculture: Antibacterial, Anesthetic, Growth-Promoting, and Antioxidant Effects
Authors: Bandeira Junior Guerino , Bianchini Adriane Erbice , de Freitas Souza Carine , Descovi Sharine Nunes , da Silva Fernandes Liana , de Lima Silva Lenise , Cargnelutti Juliana Felipetto , Baldisserotto Bernardo
Published: June 2022

Cinnamon essential oils (EOs) are widely known for their pharmaceutical properties; however, studies investigating the use of these EOs in aquaculture are scarce. The aims of this study were to evaluate the anesthetic effect of bathing silver catfish (Rhamdia quelen) with Cinnamomum cassia EO (CCEO) and its nanoemulsion (NCCEO); the growth-promoting and antioxidant effects of dietary supplementation with CCEO in silver catfish; and the in vitro antibacterial effect of CCEO, NCCEO, and Cinnamomum zeylanicum EO (CZEO) against bacteria isolated from diseased silver catfish. The two cinnamon EOs showed promising antibacterial activity, which was potentiated by the nanoemulsion. CCEO showed satisfactory anesthetic activity in silver catfish, and its nanoemulsion intensified the sedative activity. Supplementation of 1.0 mL CCEO per kg of diet for 60 days increased weight, length, and weight gain when compared to the control group, evidencing the growth-promoting activity of this EO. Dietary supplementation of CCEO for 30 and 60 days also showed an antioxidant effect, as it decreased levels of thiobarbituric acid reactive species and increased the superoxide dismutase activity in the liver of silver catfish. Therefore, cinnamon EOs have a promising use in aquaculture.
Evidence of the Association between Nurse Staffing Levels and Patient and Nurses’ Outcomes in Acute Care Hospitals across Japan: A Scoping Review
Authors: Morioka Noriko , Okubo Suguru , Moriwaki Mutsuko , Hayashida Kenshi
Published: June 2022

We aimed to summarize the evidence of an association between nurse staffing and nursing sensitivity outcomes in Japanese hospitals. A scoping review was conducted and reported following the PRISMA-SR 2020 statement. The ICHUSHI and CiNii databases were searched for published articles written in Japanese and PubMed and CINAHL for those written in English. Out of the 15 included studies, all observational studies, 3 were written in Japanese and the others in English. The nurse staffing level measures were grouped into three categories: patient-to-nurse ratio, nursing hours per patient day, and nurse-to-bed ratio. The outcome measures were grouped into three categories: patient outcome, nursing care quality reported by nurses, and nurse outcome/nursing care quality. Some studies reported that the nursing staff increasingly favored positive patient outcome. Conversely, the findings regarding failure to rescue, in-hospital fracture, and post-operative complications were inconsistent. Although some studies indicated that more nurse staffing was favored toward better patient and nurse outcomes, due to the sparse accumulation of studies and heterogeneity among the findings, it is difficult to draw robust conclusions between nurse staffing level and outcomes in Japanese acute care hospitals.
“We Are Having a Huge Problem with Compliance”: Exploring Preconception Care Utilization in South Africa
Authors: Ukoha Winifred Chinyere , Mtshali Ntombifikile Gloria
Published: June 2022

Background: Preconception care (PCC), a policy directive from the World Health Organisation (WHO), comprises all the health interventions offered to women and couples before conception and is intended to improve their overall health status and the pregnancy outcomes. Although PCC should be an essential part of maternal and child health services in most African countries, its provision and utilization are not widely documented. Hence, this study aimed to explore the factors influencing preconception care utilization among high-risk women in South Africa. Methods: A descriptive qualitative study of 29 purposively selected women and healthcare workers was conducted through individual in-depth interviews using a semi-structured interview guide. The interviews were transcribed verbatim, and the analyses were performed using Nvivo version 12. The Social-Ecological Model (SEM) guided the data analysis. Four levels of factors (the individual, the interpersonal, the community and social, and the policy and institutional) were used to assess what can influence PCC utilization. Findings: The availability of PCC services, the intrahospital referral of women, the referral practices of other healthcare workers, the underutilization of the PCC facility, and resources emerged at the institutional levels, while compliance with PCC appointments, socioeconomic factors, pregnancy planning, assumptions, and knowledge was at the individual levels. Conclusion: The utilization of the preconception care services was inadequate. The primary influencer of preconception care utilization was at the individual, policy, and institutional levels. The availability of preconception care services and the intrahospital referral of women at high risk of adverse pregnancy outcomes positively influenced the women’s PCC utilization, while poor pregnancy planning, and unavailability of PCC policies and guidelines negatively influenced preconception care utilization. Therefore, interventions to improve PCC utilization should focus on the four SEM levels for effectiveness. There is a need to raise PCC awareness and develop policy and guidelines to ensure consistent, standardized practice among healthcare workers.
KNN vs. Bluecat—Machine Learning vs. Classical Statistics
Authors: Rozos Evangelos , Koutsoyiannis Demetris , Montanari Alberto
Published: June 2022

Uncertainty is inherent in the modelling of any physical processes. Regarding hydrological modelling, the uncertainty has multiple sources including the measurement errors of the stresses (the model inputs), the measurement errors of the hydrological process of interest (the observations against which the model is calibrated), the model limitations, etc. The typical techniques to assess this uncertainty (e.g., Monte Carlo simulation) are computationally expensive and require specific preparations for each individual application (e.g., selection of appropriate probability distribution). Recently, data-driven methods have been suggested that attempt to estimate the uncertainty of a model simulation based exclusively on the available data. In this study, two data-driven methods were employed, one based on machine learning techniques, and one based on statistical approaches. These methods were tested in two real-world case studies to obtain conclusions regarding their reliability. Furthermore, the flexibility of the machine learning method allowed assessing more complex sampling schemes for the data-driven estimation of the uncertainty. The anatomisation of the algorithmic background of the two methods revealed similarities between them, with the background of the statistical method being more theoretically robust. Nevertheless, the results from the case studies indicated that both methods perform equivalently well. For this reason, data-driven methods can become a valuable tool for practitioners.
Skin Minerals: Key Roles of Inorganic Elements in Skin Physiological Functions
Authors: Haftek Marek , Abdayem Rawad , Guyonnet-Debersac Pascale
Published: June 2022

As odd as it may seem at first glance, minerals, it is what we are all about…or nearly. Although life on Earth is carbon-based, several other elements present in the planet’s crust are involved in and often indispensable for functioning of living organisms. Many ions are essential, and others show supportive and accessory qualities. They are operative in the skin, supporting specific processes related to the particular situation of this organ at the interface with the environment. Skin bioenergetics, redox balance, epidermal barrier function, and dermal remodeling are amongst crucial activities guided by or taking advantage of mineral elements. Skin regenerative processes and skin ageing can be positively impacted by adequate accessibility, distribution, and balance of inorganic ions.
Influence of Heat Treatment of Electrospun Carbon Nanofibers on Biological Response
Authors: Markowski Jaroslaw , Zambrzycki Marcel , Smolka Wojciech , Panek Agnieszka , Gubernat Maciej , Czaja Paweł , Marzec Mateusz , Fraczek-Szczypta Aneta
Published: June 2022

The main aim of this study is to investigate the effect of fragmentation of electrospun carbon nanofibers (eCNFs) obtained at different temperatures, i.e., at 750 °C, 1000 °C, 1500 °C, 1750 °C and 2000 °C on the cellular response in vitro. In order to assess the influence of nanofibers on biological response, it was necessary to conduct physicochemical, microstructural and structural studies such as SEM, XPS, Raman spectroscopy, HRTEM and surface wettability of the obtained materials. During the in vitro study, all samples made contact with the human chondrocyte CHON-001 cell lines. The key study was to assess the genotoxicity of eCNFs using the comet test after 1 h or 24 h. Special attention was paid to the degree of crystallinity of the nanofibers, the dimensions of the degradation products and the presence of functional groups on their surface. A detailed analysis showed that the key determinant of the genotoxic effect is the surface chemistry. The presence of nitrogen-containing groups as a product of the decomposition of nitrile groups has an influence on the biological response, leading to mutations in the DNA. This effect was observed only for samples carbonized at lower temperatures, i.e., 750 °C and 1000 °C. These results are important with respect to selecting the temperature of thermal treatment of eCNFs dedicated for medical and environmental functions due to the minimization of the genotoxic effect of these materials.
Neurotoxicity of Chronic Co-Exposure of Lead and Ionic Liquid in Common Carp: Synergistic or Antagonistic?
Authors: Ding Weikai , Sultan Yousef , Li Shumei , Wen Wenjun , Zhang Bangjun , Feng Yiyi , Ma Junguo , Li Xiaoyu
Published: June 2022

Previous studies have indicated that the harmful heavy metal lead (Pb) contamination in aquatic systems has caused intelligence development disorders and nervous system function abnormalities in juveniles due to the increased permeability of the blood–brain barrier. Ionic liquids (ILs) are considered “green” organic solvents that can replace traditional organic solvents. Studies have found the presence of ILs in soil and water due to chemical applications or unintentional leakage. Therefore, what would happen if Pb interacted with ILs in a body of water? Could ILs enable Pb to more easily cross the blood–brain barrier? Therefore, we examined the combined exposure of Pb and ILs in common carp at low concentration (18.3 mg L−1 of Pb(CH3COO)2•3 H2O and 11 mg L−1 of the IL 1-methyl-3-octylimidazolium chloride, 5% of their LC50) for 28 days in the present study. The result of a neurobehavioral assay showed that chronic exposure of lead at lower concentrations significantly altered fish movement and neurobehaviors, indicating that lead exposure caused neurotoxicity in the carp. Increases in the neurotransmitter dopamine levels and injuries in the fish brain accounted for neurobehavioral abnormalities induced by lead exposure. Moreover, we also found that lead could easily cross the blood–brain barrier and caused significant bioaccumulation in the brain. Particularly, our study indicated that the ionic liquid could not synergistically promote blood–brain barrier permeability and hence failed to increase the absorption of lead in the fish brain, suggesting that the combined exposure of lead and ILs was not a synergistic effect but antagonism to the neurotoxicity. The results of this study suggested that ILs could recede the Pb induced neurotoxicity in fish.
A Routing and Task-Allocation Algorithm for Robotic Groups in Warehouse Environments
Authors: Chatzisavvas Antonios , Chatzitoulousis Petros , Ziouzios Dimitris , Dasygenis Minas
Published: June 2022

In recent years, the need for robotic fleets in large warehouse environments has constantly increased. The customers require faster services concerning the delivery of their products, making the use of systems such as robots and order-management software more than essential. Numerous researchers have studied the problem of robot routing in a warehouse environment, aiming to suggest an efficient model concerning the robotic fleet’s management. In this research work, a methodology is proposed, providing feasible solutions for optimal pathfinding. A novel algorithm is proposed, which combines Dijkstra’s and Kuhn–Munkers algorithms efficiently. The proposed system considers the factor of energy consumption and chooses the optimal route. Moreover, the algorithm decides when a robot must head to a charging station. Finally, a software tool to visualize the movements of the robotic fleet and the real-time updates of the warehouse environment was developed.
Solution of Steady Incompressible MHD Problems with Quasi-Least Square Method
Authors: Hussain Shahid , Rahman Shams ur , Abbas Suhail , Abbas Munawwar Ali
Published: June 2022

A quasi-least-squares (QLS) mixed finite element method (MFE) based on the L2-inner product is utilized to solve an incompressible magnetohydrodynamic (MHD) model. These models are associated with the three unknown terms, i.e., fluid velocity, fluid pressure, and magnetic field. For the MHD-based models, common theories and algorithms for approximation of the solutions are not always applicable because of the choice of the functional spaces during the utilization of the weak formulation. It is well known that the spaces used for the approximation of the different unknowns, e.g., the spaces for the unknowns, cannot be chosen independently for the variational formulation, and may have to satisfy strict stability conditions such as the inf-sup, or Ladyzhenskaya–Babuska–Brezzi (LBB) condition. The dependency of the selection of the spaces for the unknowns are critical and always not applicable for some pair of unknowns. Because of this, the numerical or theoretical solutions must have to face some stability issue. The proposed scheme (L2-inner product) is introduced to circumvent this deficiency of the conditions (inf-sup or LBB) and obtained a well-posed solution theoretically. The model equations are nonlinear and highly coupled with the combination of Navier–Stokes and Maxwell relations. First, these nonlinear models are made linear around a specific state wherein the modified system represents an algebraic equation in a first-order symmetric form. Secondly, a direct iteration technique is applied to solve the nonlinearities and obtain a theoretical convergent rate for a general initial guess. Theoretical results show that only a single parameter with a single initial guess is sufficient to establish the well-posedness of the solution.
Dose Rate Assessment Exercises with Stylized Phantom of Neon Flying Squid from Northwest Pacific
Authors: Li Jia , Yu Wen , He Jianhua , Zeng Zhi
Published: June 2022

Radiation protection for non-human marine organisms still faces many challenges. To establish a more realistic radiation dosimetry model of cephalopods, this study developed a stylized phantom of neon flying squid (Ommastrephesbartramii) containing ten organs and tissues based on magnetic resonance imaging (MRI) technology. The internal and external dose conversion coefficients for eight radionuclides (134Cs, 137Cs, 131I, 110mAg, 60Co, 54Mn, 65Zn, 95Zr) of each organ/tissue were determined with Monte Carlo simulation using the Geant4 toolkit. Furthermore, with the reported coastal seawater radioactivity levels at the coastal area of Fukushima Daiichi Nuclear Power Plant after the accident in 2011 as the source term, the radiological dose rate for O. bartramii was evaluated with the stylized phantom developed in this study and with the conventional whole-organism ellipsoidal model in the ERICA Assessment Tool. Both results showed that the dose rate for O. bartramii derived from the FDNPP accident releases exceeded the generic no-effects screening benchmark level (10 μGy h−1).
Three Small Cysteine-Free Proteins (CFP1–3) Are Required for Insect-Pathogenic Lifestyle of Metarhizium robertsii
Authors: Mou Ya-Ni , Ren Kang , Xu Si-Yuan , Ying Sheng-Hua , Feng Ming-Guang
Published: June 2022

Unique CFP (cysteine-free protein; 120 aa) has been identified as an extraordinary virulence factor in Beauveria bassiana (Cordycipitaceae), a main source of wide-spectrum fungal insecticides. Its homologs exclusively exist in wide-spectrum insect pathogens of Hypocreales, suggesting their importance for a fungal insect-pathogenic lifestyle. In this study, all three CFP homologs (CFP1–3, 128–145 aa) were proven essential virulence factors in Metarhizium robertsii (Clavicipitaceae). Despite limited effects on asexual cycles in vitro, knockout mutants of cfp1,cfp2 and cfp3 were severely compromised in their capability for normal cuticle infection, in which most tested Galleria mellonella larvae survived. The blocked cuticle infection concurred with reduced secretion of extracellular enzymes, including Pr1 proteases required cuticle penetration. Cuticle-bypassing infection by intrahemocoel injection of ~250 conidia per larva resulted in a greater reduction in virulence in the mutant of cfp1 (82%) than of cfp2 (21%) or cfp3 (25%) versus the parental wild-type. Transcriptomic analysis revealed dysregulation of 604 genes (up/down ratio: 251:353) in the Δcfp1 mutant. Many of them were involved in virulence-related cellular processes and events aside from 154 functionally unknown genes (up/down ratio: 56:98). These results reinforce the essential roles of small CFP homologs in hypocrealean fungal adaptation to insect-pathogenic lifestyle and their exploitability for the genetic improvement of fungal insecticidal activity.
New Species of Large-Spored Alternaria in Section Porri Associated with Compositae Plants in China
Authors: Zhao Lin , Luo Huan , Cheng Hong , Gou Ya-Nan , Yu Zhi-He , Deng Jian-Xin
Published: June 2022

Alternaria is a ubiquitous fungal genus including saprobic, endophytic, and pathogenic species associated with a wide variety of substrates. It has been separated into 29 sections and seven monotypic lineages based on molecular and morphological data. Alternaria sect. Porri is the largest section, containing the majority of large-spored Alternaria species, most of which are important plant pathogens. Since 2015, of the investigations for large-spored Alternaria species in China, 13 species were found associated with Compositae plants based on morphological comparisons and phylogenetic analyses. There were eight known species and five new species (A. anhuiensis sp. nov., A. coreopsidis sp. nov., A. nanningensis sp. nov., A. neimengguensis sp. nov., and A. sulphureus sp. nov.) distributed in the four sections of Helianthiinficientes, Porri, Sonchi, and Teretispora, and one monotypic lineage (A. argyranthemi). The multi-locus sequence analyses encompassing the internal transcribed spacer region of rDNA (ITS), glyceraldehydes-3-phosphate dehydrogenase (GAPDH), Alternaria major allergen gene (Alt a 1), translation elongation factor 1-alpha (TEF1), and RNA polymerase second largest subunit (RPB2), revealed that the new species fell into sect. Porri. Morphologically, the new species were illustrated and compared with other relevant large-spored Alternaria species in the study. Furthermore, A. calendulae, A. leucanthemi, and A. tagetica were firstly detected in Brachyactis ciliate, Carthamus tinctorius, and Calendula officinalis in China, respectively.
Factors Influencing the Coupling of the Development of Rural Urbanization and Rural Finance: Evidence from Rural China
Authors: Zhou Jiali , Fan Xiangbo , Li Chenggang , Shang Guofei
Published: June 2022

This study empirically analyzes factors influencing the coupling and coordinated development of rural urbanization and rural finance. For this purpose, the study employs the coupling degree model and develops a panel quantile model to estimate the coupling degree and coupling coordination degree of rural urbanization and rural finance. Accordingly, the study presents panel data comprising 31 provinces, municipalities, and autonomous regions in China from 2010 to 2019. The empirical results reveal that the coupling degree of rural urbanization and rural finance is relatively low in most study areas. This result suggests that rural urbanization and rural financial development in most provinces in China have not exhibited coordinated development. Further, the results reveal that urban population density negatively affects the coupling and coordination degree of rural urbanization and rural finance. Moreover, the effects of urban population density are more significant in areas with a low coupling coordination degree compared with those with a higher coupling coordination degree. An increase in the quantile gradually decreases the effect of the proportion of educational expenditure to GDP on the degree of rural urbanization and rural financial coupling coordination. However, the effect of financial development efficiency increases accordingly. The per capita GDP, per capita fiscal expenditure, and per capita built-up area significantly affect all the quantiles, indicating a positive correlation. This correlation can promote the coupling and coordinated development of rural urbanization and rural finance. In areas with a low coupling coordination degree, the financial development scale significantly positively affects the coupling coordination degree of rural urbanization and rural finance. In areas with a high coupling coordination degree, the financial development scale significantly negatively correlates with the coupling coordination degree. In addition, a positive correlation exists between the financial development structure and the coupling coordination degree of rural urbanization and rural finance.
Surface and Structural Studies of Age-Related Changes in Dental Enamel: An Animal Model
Authors: Świetlicka Izabela , Tomaszewska Ewa , Muszyński Siemowit , Świetlicki Michał , Skrzypek Tomasz , Grudziński Wojciech , Gruszecki Wiesław I. , Kamiński Daniel , Hułas-Stasiak Monika , Arczewska Marta
Published: June 2022

In the animal kingdom, continuously erupting incisors provided an attractive model for studying the enamel matrix and mineral composition of teeth during development. Enamel, the hardest mineral tissue in the vertebrates, is a tissue sensitive to external conditions, reflecting various disturbances in its structure. The developing dental enamel was monitored in a series of incisor samples extending the first four weeks of postnatal life in the spiny mouse. The age-dependent changes in enamel surface morphology in the micrometre and nanometre-scale and a qualitative assessment of its mechanical features were examined by applying scanning electron microscopy (SEM) and atomic force microscopy (AFM). At the same time, structural studies using XRD and vibrational spectroscopy made it possible to assess crystallinity and carbonate content in enamel mineral composition. Finally, a model for predicting the maturation based on chemical composition and structural factors was constructed using artificial neural networks (ANNs). The research presented here can extend the existing knowledge by proposing a pattern of enamel development that could be used as a comparative material in environmental, nutritional, and pharmaceutical research.
Solution Spaces Associated to Continuous or Numerical Models for Which Integrable Functions Are Bounded
Authors: Villegas-Villalpando Brian , Macías-Díaz Jorge E. , Sheng Qin
Published: June 2022

Boundedness is an essential feature of the solutions for various mathematical and numerical models in the natural sciences, especially those systems in which linear or nonlinear preservation or stability features are fundamental. In those cases, the boundedness of the solutions outside a set of zero measures is not enough to guarantee that the solutions are physically relevant. In this note, we will establish a criterion for the boundedness of integrable solutions of general continuous and numerical systems. More precisely, we establish a characterization of those measures over arbitrary spaces for which real-valued integrable functions are necessarily bounded at every point of the domain. The main result states that the collection of measures for which all integrable functions are everywhere bounded are exactly all of those measures for which the infimum of the measures for nonempty sets is a positive extended real number.
Hepatoprotective Polysaccharides from Geranium wilfordii: Purification, Structural Characterization, and Their Mechanism
Authors: Feng Jia-Yi , Xie Yan-Qing , Zhang Peng , Zhou Qian , Khan Afsar , Zhou Zhi-Hong , Xia Xian-Song , Liu Lu
Published: June 2022

Traditional Chinese Medicine is generally used as a decoction to guard health. Many active ingredients in the decoction are chemical ingredients that are not usually paid attention to in phytochemical research, such as polysaccharides, etc. Based on research interest in Chinese herbal decoction, crude polysaccharides from G. wilfordii (GCP) were purified to obtain two relatively homogeneous polysaccharides, a neutral polysaccharide (GNP), and an acid polysaccharide (GAP) by various chromatographic separation methods, which were initially characterized by GC-MS, NMR, IR, and methylation analysis. Studies on the hepatoprotective activity of GCP in vivo showed that GCP might be a potential agent for the prevention and treatment of acute liver injury by inhibiting the secretion levels of ALT, AST, IL-6, IL-1β, TNF-α, and MDA expression levels, increasing SOD, and the GSH-Px activity value. Further, in vitro assays, GNP and GAP, decrease the inflammatory response by inhibiting the secretion of IL-6 and TNF-α, involved in the STAT1/T-bet signaling pathway.