bluuebunny/crossref_metadata_2025 huggingface dataset:
Technology for the Recovery of Lithium from Geothermal Brines
Authors: Stringfellow William T. , Dobson Patrick F.
Published: October 2021

Lithium is the principal component of high-energy-density batteries and is a critical material necessary for the economy and security of the United States. Brines from geothermal power production have been identified as a potential domestic source of lithium; however, lithium-rich geothermal brines are characterized by complex chemistry, high salinity, and high temperatures, which pose unique challenges for economic lithium extraction. The purpose of this paper is to examine and analyze direct lithium extraction technology in the context of developing sustainable lithium production from geothermal brines. In this paper, we are focused on the challenges of applying direct lithium extraction technology to geothermal brines; however, applications to other brines (such as coproduced brines from oil wells) are considered. The most technologically advanced approach for direct lithium extraction from geothermal brines is adsorption of lithium using inorganic sorbents. Other separation processes include extraction using solvents, sorption on organic resin and polymer materials, chemical precipitation, and membrane-dependent processes. The Salton Sea geothermal field in California has been identified as the most significant lithium brine resource in the US and past and present efforts to extract lithium and other minerals from Salton Sea brines were evaluated. Extraction of lithium with inorganic molecular sieve ion-exchange sorbents appears to offer the most immediate pathway for the development of economic lithium extraction and recovery from Salton Sea brines. Other promising technologies are still in early development, but may one day offer a second generation of methods for direct, selective lithium extraction. Initial studies have demonstrated that lithium extraction and recovery from geothermal brines are technically feasible, but challenges still remain in developing an economically and environmentally sustainable process at scale.
An Experimental Kinetics Study of Isopropanol Pyrolysis and Oxidation behind Reflected Shock Waves
Authors: Cooper Sean P. , Grégoire Claire M. , Mohr Darryl J. , Mathieu Olivier , Alturaifi Sulaiman A. , Petersen Eric L.
Published: October 2021

Isopropanol has potential as a future bio-derived fuel and is a promising substitute for ethanol in gasoline blends. Even so, little has been done in terms of high-temperature chemical kinetic speciation studies of this molecule. To this end, experiments were conducted in a shock tube using simultaneous CO and H2O laser absorption measurements. Water and CO formation during isopropanol pyrolysis was also examined at temperatures between 1127 and 2162 K at an average pressure of 1.42 atm. Species profiles were collected at temperatures between 1332 and 1728 K and at an average pressure of 1.26 atm for equivalence ratios of 0.5, 1.0, and 2.0 in highly diluted mixtures of 20% helium and 79.5% argon. Species profiles were also compared to four modern C3 alcohol mechanisms, including the impact of recent rate constant measurements. The Li et al. (2019) and Saggese et al. (2021) models both best predict CO and water production under pyrolysis conditions, while the AramcoMech 3.0 and Capriolo and Konnov models better predict the oxidation experimental profiles. Additionally, previous studies have collected ignition delay time (τign) data for isopropanol but are limited to low pressures in highly dilute mixtures. Therefore, real fuel–air experiments were conducted in a heated shock tube with isopropanol for stoichiometric and lean conditions at 10 and 25 atm between 942 and 1428 K. Comparisons to previous experimental results highlight the need for real fuel–air experiments and proper interpretation of shock-tube data. The AramcoMech 3.0 model over predicts τign values, while the Li et al. model severely under predicts τign. The models by Capriolo and Konnov and Saggese et al. show good agreement with experimental τign values. A sensitivity analysis using these two models highlights the underlying chemistry for isopropanol combustion at 25 atm. Additionally, modifying the Li et al. model with a recently measured reaction rate shows improvement in the model’s ability to predict CO and water profiles during dilute oxidation. Finally, a regression analysis was performed to quantify τign results from this study.
Performance of Parallel Connected SiC MOSFETs under Short Circuits Conditions
Authors: Wu Ruizhu , Mendy Simon , Agbo Nereus , Gonzalez Jose , Jahdi Saeed , Alatise Olayiwola
Published: October 2021

This paper investigates the impact of parameter variation between parallel connected SiC MOSFETs on short circuit (SC) performance. SC tests are performed on parallel connected devices with different switching rates, junction temperatures and threshold voltages (VTH). The results show that VTH variation is the most critical factor affecting reduced robustness of parallel devices under SC. The SC current conducted per device is shown to increase under parallel connection compared to single device measurements. VTH shift from bias–temperature–instability (BTI) is known to occur in SiC MOSFETs, hence this paper combines BTI and SC tests. The results show that a positive VGS stress on the gate before the SC measurement reduces the peak SC current by a magnitude that is proportional to VGS stress time. Repeating the measurements at elevated temperatures reduces the time dependency of the VTH shift, thereby indicating thermal acceleration of negative charge trapping. VTH recovery is also observed using SC measurements. Similar measurements are performed on Si IGBTs with no observable impact of VGS stress on SC measurements. In conclusion, a test methodology for investigating the impact of BTI on SC characteristics is presented along with key results showing the electrothermal dynamics of parallel devices under SC conditions.
Ray Effects and False Scattering in Improved Discrete Ordinates Method
Authors: Cheng Yong , Yang Shuihua , Huang Zhifeng
Published: October 2021

The improved discrete ordinates method (IDOM) developed in our previous paper is extended to solve radiative transfer in three-dimensional radiative systems with anisotropic scattering medium. In IDOM, radiative intensities in a large number of new discrete directions are calculated by direct integration of the conventional discrete ordinates method (DOM) results, and radiative heat flux is obtained by integrating radiative intensities in these new discrete directions. Ray effects and false scattering, which tend to compensate each other, are investigated together in IDOM. Results show that IDOM can mitigate both of them effectively with high computation efficiency. Finally, the effect of scattering phase function on radiative transfer is studied. Results of radiative heat flux at boundaries containing media with different scattering phase functions are compared and analyzed. This paper indicates that the IDOM can overcome the shortages of the conventional DOM well while inheriting its advantages such as high computation efficiency and easy implementation.
A New Modeling Framework for Geothermal Operational Optimization with Machine Learning (GOOML)
Authors: Buster Grant , Siratovich Paul , Taverna Nicole , Rossol Michael , Weers Jon , Blair Andrea , Huggins Jay , Siega Christine , Mannington Warren , Urgel Alex , Cen Jonathan , Quinao Jaime , Watt Robbie , Akerley John
Published: October 2021

Geothermal power plants are excellent resources for providing low carbon electricity generation with high reliability. However, many geothermal power plants could realize significant improvements in operational efficiency from the application of improved modeling software. Increased integration of digital twins into geothermal operations will not only enable engineers to better understand the complex interplay of components in larger systems but will also enable enhanced exploration of the operational space with the recent advances in artificial intelligence (AI) and machine learning (ML) tools. Such innovations in geothermal operational analysis have been deterred by several challenges, most notably, the challenge in applying idealized thermodynamic models to imperfect as-built systems with constant degradation of nominal performance. This paper presents GOOML: a new framework for Geothermal Operational Optimization with Machine Learning. By taking a hybrid data-driven thermodynamics approach, GOOML is able to accurately model the real-world performance characteristics of as-built geothermal systems. Further, GOOML can be readily integrated into the larger AI and ML ecosystem for true state-of-the-art optimization. This modeling framework has already been applied to several geothermal power plants and has provided reasonably accurate results in all cases. Therefore, we expect that the GOOML framework can be applied to any geothermal power plant around the world.
The Influence of Temperature on Degradation of Oil and Gas Tubing Made of L80-1 Steel
Authors: Bęben Dariusz
Published: October 2021

Corrosion in the oil and gas industry is very common due to the simultaneous action of a chemically active environment, temperature, and other non-chemical factors, for example, mechanical erosion by friction, and for these reasons corrosion is a very complex process. Corrosion at higher temperatures is an important aspect when extracting natural gas from a field with high temperatures (120 °C in the Lubiatow deposit and 180 °C in the gas well in Kutno). Water in the reservoir is often in the form of steam, with a pressure of about 25 MPa; as a result of its extraction, it cools down, which causes condensation. Condensed water in contact with the acid components of the gas causes corrosion, especially in the presence of aggressive gases, such as CO2 and H2S. Therefore, the aim of the work was to conduct research on the influence of water condensation, as a result of temperature changes in gasses containing CO2 and H2S on the corrosion of L80-1 steel at the junction of extraction pipes with casing pipes. The tests are carried out at temperatures of 65–95 °C, under a pressure of 7.5 MPa, so in quite aggressive conditions. The duration of the studies was 720 h (within a month). The results of the research allowed an answer to be provided for the question of what influence temperature, gas components, and pressure have on the corrosion of the well construction material. Moreover, the results clearly showed the selection of the material for the well, in order to prevent corrosion in aggressive environments.
Evaluating Terrain as a Turbulence Generation Method
Authors: Hawbecker Patrick , Churchfield Matthew
Published: October 2021

When driving microscale large-eddy simulations with mesoscale model solutions, turbulence will take space to develop, known as fetch, on the microscale domain. To reduce fetch, it is common to add perturbations near the boundaries to speed up turbulence development. However, when simulating domains over complex terrain, it is possible that the terrain itself can quickly generate turbulence within the boundary layer. It is shown here that rugged terrain is able to generate turbulence without the assistance of a perturbation strategy; however, the levels of turbulence generated are improved when adding perturbations at the inlet. Flow over smoothed, but not flat, terrain fails to generate adequate turbulence throughout the boundary layer in all tests conducted herein. Sensitivities to the strength of the mean wind speed and boundary layer height are investigated and show that higher wind speeds produce turbulence over terrain features that slower wind speeds do not. Further, by increasing the height of the capping inversion, the effectiveness of topography alone to generate turbulence throughout the depth of the boundary is diminished. In all cases, the inclusion of a perturbation strategy improved simulation performance with respect to turbulence development.
Towards Cross-Standard Compliance Readiness: Security Requirements Model for Smart Grid
Authors: Stojkov Milan , Dalčeković Nikola , Markoski Branko , Milosavljević Branko , Sladić Goran
Published: October 2021

The critical infrastructure is constantly under cyber and physical threats. Applying security controls without guidance or traceability can create a false sense of security. Security standards facilitate security knowledge and control best practices in a more systematic way. However, the number of standards is continually increasing. Product providers that operate in multiple geographical regions often face the obligation to comply with multiple standards simultaneously. This introduces the problem of the convenient interpretation of different standards. Thus, a comprehensive analysis of the requirements from different security standards and guidelines applicable to the smart grid has been performed to detect similarities that can be shaped into entities of the conceptual model for requirement representation. The purpose of the model—presented in a form of a Unified Modeling Language (UML) class diagram—is to give product providers a canonical way to map requirements from arbitrary standards, guidelines, and regulations and accelerate the cross-standard compliance readiness by defining priority for requirement implementation. In addition, the research showed that multiple vectors should impact the priority of the implementation of the security controls defined through the requirements: domain affiliation, the essence of the requirement, associated threats, risks, and social dependencies between actors involved in the implementation. To examine the model correctness, NISTIR 7628—de facto smart grid standard—was used to provide insights into how the model would be used for requirements implementation tracking. The structure of individual requirements was analyzed to detect the building blocks and extract relevant parts that can be mapped to the model components. Further, all requirements were classified into one of the defined domains to provide the basis for referencing similar requirements from different standards. Finally, one arbitrary requirement was used to demonstrate model usage, and depict all available information that can be provided to the users in a custom-made scenario where the need arises to have simultaneous alignment with three standards—NISTIR 7628, NIST 800-53, and IEC 62443-3-3.
Economic Profitability of a Hybrid Approach to Powering Residual Households from Natural Sources in Two Wind Zones of the Lubuskie Voivodeship in Poland
Authors: Kułyk Piotr , Augustowski Łukasz
Published: October 2021

The research was a response to the search for alternative energy sources and the assessment of their profitability and legitimacy of use. The assessment used combined energy sources in the form of wind, solar, and natural gas energy. The research was carried out in various locations with varying degrees of sunlight and in various wind zones, which was motivated by the adopted strategy of increasing the importance of non-conventional energy sources and reducing greenhouse gas emissions. The evaluation was performed using the Homer Grid software. The studies showed the justification for the use of hybrid energy sources, combining renewable and non-renewable sources, at the current stage of development. In the conditions of the Lubuskie Voivodeship, the level of insolation was more important than the more favourable wind zone in such a model. Higher economic efficiency of the hybrid model was obtained in the southern location, with slightly less favourable conditions for wind installations. At the same time, the investments were economically profitable and allowed for their return in the perspective of at least eleven years, even at current prices.
Integrated Modelling of Decentralised Energy Supply in Combination with Electric Vehicle Charging in a Real-Life Case Study
Authors: Göhler Georg , Klingler Anna-Lena , Klausmann Florian , Spath Dieter
Published: October 2021

Intelligent integration of decentralised energy resources, local storage and direct consumption are key factors in achieving the transformation of the energy system. In this study, we present a modular simulation concept that allows the planning of decentralised energy systems for buildings and building blocks. In comparison to related studies, we use a simulation model for energy planning with a high time-resolution from the perspective of the energy system planner. In this study, we address the challenges of the grid connection in combination with an increasing number of electric vehicles (EV) in the future. The here developed model is applied for an innovative building block in Germany with a photovoltaic (PV) system, a combined heat and power (CHP) unit, battery storage and electric vehicles. The results of the simulation are validated with real-life data to illustrate the practical relevance and show that our simulation model is able to support the planning of decentralised energy systems. We demonstrate that without anticipating future electric vehicle charging, the system configurations could be sub-optimal if complete self-sufficiency is the objective: in our case study, the rate of self-sufficiency of the net-zero energy building will be lowered from 100% to 91% if considering electric vehicles. Furthermore, our simulation shows that a peak minimising operation strategy with a battery can prevent grid overloads caused by EV charging in the future. Simulating different battery operation strategies can further help to implement the most useful strategy, without interruption of the current operation.
The Influence of Endurance Training on the Lipid Profile, Body Mass Composition and Cardiovascular Efficiency in Middle-Aged Cross-Country Skiers
Authors: Grzebisz-Zatońska Natalia , Grzywacz Tomasz , Waśkiewicz Zbigniew
Published: October 2021

Monitoring the training of amateur long-distance cross-country skiers (XCS) can help athletes’ achieve a higher exercise capacity and protect their health. The aim of this study was to assess body composition changes and lipid profiles in middle-aged amateur long-distance XCS after four months of training, including specialized roller ski training. The results of the time-to-exhaustion (TTE) test and blood tests and changes in body composition were analyzed with basic descriptive statistics: the paired Wilcoxon test was used to compare the results (initial and final). Spearman’s rank correlation coefficient (R) was used to assess the influence of various variables on maximum oxygen uptake (VO2max). The findings show that training of amateur long-distance XCS improved maximal oxygen uptake (p = 0.008) and had a positive effect on fat reduction, measured in percentages (p = 0.038) and in kilograms (p = 0.023), but did not change blood lipids or other parameters. Further research could focus on other aspects of the annual training cycle: the competition period, and women in a larger group of athletes. Training with roller skis and a cross-country skiing training machine (a specialized machine for strengthening the arms and upper body) can support health and prevent obesity, overweight, and cardiovascular disease.
Pregnancy and Birth Outcomes during the Early Months of the COVID-19 Pandemic: The MOACC-19 Cohort
Authors: Rodríguez-Díaz Marta , Alonso-Molero Jéssica , Cabero-Perez María J. , Llorca Javier , Dierssen-Sotos Trinidad , Gómez-Acebo Inés ,   The MOACC-19 Group
Published: October 2021

The new coronavirus, SARS-CoV-2, is devastating for specific groups of patients, but currently there is not enough information concerning its effects on pregnant women. The purpose of this study is to identify the impact of SARS-CoV-2 infection on pregnancy and the consequences that it could cause. We studied a cohort of pregnant ladies who were tested for SARS-CoV-2 infection by RT-PCR and classified as infected or not infected. The recruitment was carried out in the HUMV hospital, a third-level hospital located in Santander, northern Spain. It started on 23 March 2020 and ended on 14 October 2020. Data from our cohort were compared to another cohort recruited in 2018 at the same hospital. We found that gestational hypertension, placental abruptio, and home exposure to an infected person, among other variables, could be associated with SARS-CoV-2 infection. In conclusion, we consider pregnant women a high-risk group of patients towards a possible SARS-CoV-2 infection, especially those who present with conditions such as gestational hypertension or obesity; moreover, we think that SARS-CoV-2 infection could increase the possibilities of having an abruptio placentae, although this result was found in only a few women, so it requires further confirmation.
Parents’ Perceptions of the Value of Children’s Participation in Pediatric Rehabilitation Services: A Phenomenographic Study
Authors: Kronsell Lisa , Svedberg Petra , Nygren Jens , Larsson Ingrid
Published: October 2021

Ensuring that children have opportunities to be involved in decision-making regarding their own care is associated with quality improvement in pediatric rehabilitation. The aim of the study was to explore parents’ perceptions of the value of children’s participation in pediatric rehabilitation services. Semi-structured interviews were conducted with 17 parents of children with disabilities who visited pediatric rehabilitation services. A phenomenographic analysis method was used. Three categories developed from the analysis describing how participation generated value in terms of empowerment, self-awareness, and independence. The outcome space describes a hierarchical relationship between the categories and their influence on each other. Independence achieved through participation was a core aspect and is at the highest level in the hierarchy since it includes and depends on the outcomes from both empowerment and self-awareness. Parents’ perceptions of the value of children’s participation in pediatric rehabilitation services include the possibility for the child to use their entire capacity through values created in terms of empowerment, self-awareness, and independence, in order to live the best life possible. Children with disabilities are diverse as a group, and further research to identify barriers and facilitators of participation is needed to adjust interventions within pediatric rehabilitation services to ensure that children with disabilities can be increasingly empowered, self-aware, and independent.
Shared Decision-Making Model for Adolescent Smoking Cessation: Pilot Cohort Study
Authors: Chen Kuan-Lun , Hsu Yun-Chen , Li Yi-Hsuan , Guo Fei-Ran , Tsai Jaw-Shiun , Cheng Shao-Yi , Huang Hsien-Liang
Published: October 2021

The control of tobacco use in adolescents is a critical public health issue that has long been studied, yet has received less attention than adult smoking cessation. Shared decision making (SDM) is a method that highlights a patient’s preference-based medical decision. This study aimed to investigate the effects of a novel SDM-integrated cessation model and early intervention on the control of tobacco use in adolescents. The SDM-integrated model provides psychological support and motivational enhancement by involving the participants in making decisions and plans through the three-talk model of the SDM principle. The primary outcome shows positive effects by both increasing the cessation rate (a 25% point abstinence rate at 3 month follow up) and decreasing the number of cigarettes smoked per day (60% of the participants at 3 month follow up) among 20 senior high school participants (mean age, 17.5 years; 95% male). The results also show that the model can achieve the goal of SDM and optimal informed decision making, based on the positive SURE test and the satisfaction survey regarding the cessation model. The SDM cessation model can be further applied to different fields of adolescent substance cessation, yielding beneficial effects regarding reducing potential health hazards. The dissemination of the model may help more adolescent smokers to cease smoking worldwide.
Half-Year Longitudinal Seroprevalence of SARS-CoV-2-Antibodies and Rule Compliance in German Hospital Employees
Authors: Herzberg Jonas , Vollmer Tanja , Fischer Bastian , Becher Heiko , Becker Ann-Kristin , Sahly Hany , Honarpisheh Human , Guraya Salman Yousuf , Strate Tim , Knabbe Cornelius
Published: October 2021

COVID-19, which is caused by SARS-CoV-2, is an occupational health risk, especially for healthcare employees due to their higher exposure and consequently higher risk of symptomatic and asymptomatic infections. This study was designed to determine the longitudinal seroprevalence of specific immunoglobulin-G (IgG) antibodies in employees in a hospital setting. All employees in a secondary care hospital, including healthcare and non-healthcare workers, were invited to participate in this single-center study. After an initial screening, a 6-month follow-up was carried out, which included serological examination for SARS-CoV-2 IgG antibodies and a questionnaire for self-reported symptoms, self-perception, and thoughts about local and national hygiene and pandemic plans. The seroprevalence of SARS-CoV-2 IgG antibodies was 0.74% among 406 hospital employees (0.75% in healthcare workers, 0.72% in non-healthcare workers), initially recruited in April 2020, in their follow-up blood specimens in October 2020. In this study, 30.54% of the participants reported using the official German coronavirus mobile application and the majority were content with the local and national rules in relation to coronavirus-related restrictions. At the 6-month follow-up, the 0.74% seroprevalence was below the reported seroprevalence of 1.35% in the general German population. The prevalence in healthcare workers in direct patient care compared with that in workers without direct patient contact did not differ significantly. Further follow-up to monitor the seroprevalence in the high-risk healthcare sector during the ongoing global pandemic is essential.
Prevalence of Anxiety in Dental Students during the COVID-19 Outbreak: A Meta-Analysis
Authors: Santabarbara Javier , Idoiaga Nahia , Ozamiz-Etxebarria Naiara , Bueno-Notivol Juan
Published: October 2021

Background: Since the onset of the COVID-19 pandemic, the psychological state of university students has been a cause for concern. In particular, odontology students have experienced symptoms of anxiety due to the closure of universities and the suspension of clinical training. Methods: Medline via PubMed was searched for studies on the prevalence of anxiety in dental undergraduates, published from 1 December 2019 to 1 August 2021. Results: A total of fifteen studies were included in this review. Our results show a prevalence of anxiety of 35% reported by dental students, which was independent of gender, response rate or methodological quality. The only significant finding was a lower prevalence of anxiety in studies located in Europe compared to those located in other continents. Conclusions: The results suggest dental students are experiencing significant levels of anxiety during this COVID-19 pandemic and that there seem to be differences between students from different regions of the world. Therefore, it is important to help dental students psychologically as the pandemic situation continues.
Pre-Exposure Prophylaxis (PrEP) Adherence Questionnaire: Psychometric Validation among Sexually Transmitted Infection Patients in China
Authors: Yu Xiaoyue , Xu Chen , Ni Yang , Chang Ruijie , Wang Huwen , Gong Ruijie , Wang Ying , Wang Suping , Cai Yong
Published: October 2021

Background: Ensuring adherence guarantees the efficacy of pre-exposure prophylaxis (PrEP). Methods: We conducted a cross-sectional study among 816 sexually transmitted infection (STI) patients in Shanghai. The questionnaire included self-reported demographic characteristics, self-administered items on adherence to free oral PrEP, and PrEP uptake behavior measurement. We conducted item analysis, reliability analysis, validity analysis and receiver operating characteristic (ROC) curve analysis. Results: Not all items were considered acceptable in the item analysis. The questionnaire had a McDonald’s ω coefficient of 0.847. The scale-level content validity index (CVI) was 0.938 and the item-level CVI of each item ranged from 0.750 to 1. In exploratory factor analysis, we introduced a four-factor model accounting for 79.838% of the aggregate variance, which was validated in confirmatory factor analysis. Adding PrEP adherence questionnaire scores contributed to prediction of PrEP uptake behavior (p < 0.001) in regression analysis. The maximum area under the ROC curve was 0.778 (95% IC: 0.739–0.817). Conclusion: The PrEP adherence questionnaire presented psychometric validation among STI patients.
A Delphi Study Protocol to Identify Recommendations on Physical Activity and Exercise in Patients with Diabetes and Risk of Foot Ulcerations
Authors: Gracia-Sánchez Alba , López-Pineda Adriana , Chicharro-Luna Esther , Gil-Guillén Vicente F.
Published: October 2021

Patients with diabetes mellitus are exposed to important complications, such as diabetic neuropathy or peripheral vascular disease. The evidence on the guidelines that these patients, with a certain risk of suffering foot ulcerations, should follow before, during and after physical exercise is scarce. The objective of this study is to identify the physical exercise guidelines to recommend based on the risk of the foot of the patient with diabetes through a consensus of experts. A three-round Delphi study will be conducted. A scientific committee (multidisciplinary group of four national experts) will review the proposal of experts and the Delphi questionnaire before submitting. A group of experts in the management and approach of the diabetic foot of an international and multidisciplinary nature will form the panel of experts, who must express their degree of (dis)agreement with each of the statements contained in the Delphi questionnaire. The percentage will be calculated in response categories, and a cut-off point of 80% will be set to define the consensus of (dis)agreement of the panelists. The results of the study could provide a series of recommendations on the realization of physical exercise in diabetic patients at risk of suffering foot ulcerations.
Autism Spectrum Disorder and Prenatal or Early Life Exposure to Pesticides: A Short Review
Authors: Miani Alessandro , Imbriani Giovanni , De Filippis Giovanni , De Giorgi Donato , Peccarisi Luigi , Colangelo Manuela , Pulimeno Manuela , Castellone Maria Domenica , Nicolardi Giuseppe , Logroscino Giancarlo , Piscitelli Prisco
Published: October 2021

Background: Autism spectrum disorder (ASD) diagnoses have rapidly increased globally. Both environmental and genetic factors appear to contribute to the development of ASD. Several studies have shown a potential association between prenatal or postnatal pesticide exposure and the risk of developing ASD. Methods: We reviewed the available literature concerning the relationship between early life exposure to pesticides used in agriculture, such as organochlorines, organophosphates and pyrethroids, and ASD onset in childhood. We searched on Medline and Scopus for cohort or case–control studies published in English from 1977 to 2020. Results: A total of seven articles were selected for the review. We found a remarkable association between the maternal exposure to pyrethroid, as well as the exposure to organophosphate during pregnancy or in the first years of childhood, and the risk of ASD onset. This association was found to be less evident with organochlorine pesticides. Pregnancy seems to be the time when pesticide exposure appears to have the greatest impact on the onset of ASD in children. Conclusions: Among the different environmental pollutants, pesticides should be considered as emerging risk factors for ASD. The potential association identified between the exposure to pesticides and ASD needs to be implemented and confirmed by further epidemiological studies based on individual assessment both in outdoor and indoor conditions, including multiple confounding factors, and using statistical models that take into account single and multiple pesticide residues.
Nutrition Supports Deconstructed and Disrupted: An Evaluation of a Multilevel School-Based Intervention during the Time of COVID
Authors: Dombrowski Rachael D. , Bode Bree , Knoff Kathryn A. G. , Mallare James , Moore E. Whitney G. , Kulik Noel
Published: October 2021

The Best Food Forward (BFF) project aims to provide multiple nutrition supports and interventions to improve family food security (FS) and health outcomes associated with FS within two metropolitan school districts. A quasi-experimental time-series design guided a multilevel evaluation for BFF through surveys, biometric screenings, focus groups, and observations among a random sample of caregiver–child dyads. FS, utilization of school meal programs, and nutrition behaviors were observed and analyzed at three time points: preintervention, postintervention pre-COVID-19, and postintervention post-COVID-19. Participants included 122 parents and 162 youth. Families reported (1) an income less than $35,000 annually (48.8%) and (2) a COVID-19-related job loss (36.9%). Parents used Supplemental Nutrition Assistance Programs or Women, Infants, Children benefits prior to (51.1%) and following COVID-19 (50.0%). No significant differences in FS were found. RM-ANOVA indicated an increase in breakfast consumption at home and a decrease in use of the school breakfast program (F(1.78, 74) = 19.64, p < 0.001, partial η2 = 0.21) and school lunch program (F(1.51, 74) = 23.30, p < 0.001, partial η2 = 0.24). Rates of FS and eating behaviors did not change significantly over time. Correlations of program usage and eating behaviors demonstrate the importance of promoting participation in school meal programs. BFF may have prevented significant decreases in FS during COVID-19.
Potential of Melt Electrowritten Scaffolds Seeded with Meniscus Cells and Mesenchymal Stromal Cells
Authors: Korpershoek Jasmijn V. , Ruijter Mylène de , Terhaard Bastiaan F. , Hagmeijer Michella H. , Saris Daniël B.F. , Castilho Miguel , Malda Jos , Vonk Lucienne A.
Published: October 2021

Meniscus injury and meniscectomy are strongly related to osteoarthritis, thus there is a clinical need for meniscus replacement. The purpose of this study is to create a meniscus scaffold with micro-scale circumferential and radial fibres suitable for a one-stage cell-based treatment. Poly-caprolactone-based scaffolds with three different architectures were made using melt electrowriting (MEW) technology and their in vitro performance was compared with scaffolds made using fused-deposition modelling (FDM) and with the clinically used Collagen Meniscus Implants® (CMI®). The scaffolds were seeded with meniscus and mesenchymal stromal cells (MSCs) in fibrin gel and cultured for 28 d. A basal level of proteoglycan production was demonstrated in MEW scaffolds, the CMI®, and fibrin gel control, yet within the FDM scaffolds less proteoglycan production was observed. Compressive properties were assessed under uniaxial confined compression after 1 and 28 d of culture. The MEW scaffolds showed a higher Young’s modulus when compared to the CMI® scaffolds and a higher yield point compared to FDM scaffolds. This study demonstrates the feasibility of creating a wedge-shaped meniscus scaffold with MEW using medical-grade materials and seeding the scaffold with a clinically-feasible cell number and -type for potential translation as a one-stage treatment.
Parathyroid Tumors: Molecular Signatures
Authors: Marini Francesca , Giusti Francesca , Iantomasi Teresa , Brandi Maria Luisa
Published: October 2021

Parathyroid tumors are rare endocrine neoplasms affecting 0.1–0.3% of the general population, including benign parathyroid adenomas (PAs; about 98% of cases), intermediate atypical parathyroid adenomas (aPAs; 1.2–1.3% of cases) and malignant metastatic parathyroid carcinomas (PCs; less than 1% of cases). These tumors are characterized by a variable spectrum of clinical phenotypes and an elevated cellular, histological and molecular heterogeneity that make it difficult to pre-operatively distinguish PAs, aPAs and PCs. Thorough knowledge of genetic, epigenetic, and molecular signatures, which characterize different parathyroid tumor subtypes and drive different tumorigeneses, is a key step to identify potential diagnostic biomarkers able to distinguish among different parathyroid neoplastic types, as well as provide novel therapeutic targets and strategies for these rare neoplasms, which are still a clinical and therapeutic challenge. Here, we review the current knowledge on gene mutations and epigenetic changes that have been associated with the development of different clinical types of parathyroid tumors, both in familial and sporadic forms of these endocrine neoplasms.
Investigating the Molecular Mechanism of H3B-8800: A Splicing Modulator Inducing Preferential Lethality in Spliceosome-Mutant Cancers
Authors: Spinello Angelo , Borišek Jure , Malcovati Luca , Magistrato Alessandra
Published: October 2021

The SF3B1 protein, part of the SF3b complex, recognizes the intron branch point sequence of precursor messenger RNA (pre-mRNA), thus contributing to splicing fidelity. SF3B1 is frequently mutated in cancer and is the target of distinct families of splicing modulators (SMs). Among these, H3B-8800 is of particular interest, as it induces preferential lethality in cancer cells bearing the frequent and highly pathogenic K700E SF3B1 mutation. Despite the potential of H3B-8800 to treat myeloid leukemia and other cancer types hallmarked by SF3B1 mutations, the molecular mechanism underlying its preferential lethality towards spliceosome-mutant cancer cells remains elusive. Here, microsecond-long all-atom simulations addressed the binding/dissociation mechanism of H3B-8800 to wild type and K700E SF3B1-containing SF3b (K700ESB3b) complexes at the atomic level, unlocking that the K700E mutation little affects the thermodynamics and kinetic traits of H3B-8800 binding. This supports the hypothesis that the selectivity of H3B-8800 towards mutant cancer cells is unrelated to its preferential targeting of K700ESB3b. Nevertheless, this set of simulations discloses that the K700E mutation and H3B-8800 binding affect the overall SF3b internal motion, which in turn may influence the way SF3b interacts with other spliceosome components. Finally, we unveil the existence of a putative druggable SF3b pocket in the vicinity of K700E that could be harnessed in future rational drug-discovery efforts to specifically target mutant SF3b.
Cellular Signalling and Photobiomodulation in Chronic Wound Repair
Authors: Leyane Thobekile S. , Jere Sandy W. , Houreld Nicolette N.
Published: October 2021

Photobiomodulation (PBM) imparts therapeutically significant benefits in the healing of chronic wounds. Chronic wounds develop when the stages of wound healing fail to progress in a timely and orderly frame, and without an established functional and structural outcome. Therapeutic benefits associated with PBM include augmenting tissue regeneration and repair, mitigating inflammation, relieving pain, and reducing oxidative stress. PBM stimulates the mitochondria, resulting in an increase in adenosine triphosphate (ATP) production and the downstream release of growth factors. The binding of growth factors to cell surface receptors induces signalling pathways that transmit signals to the nucleus for the transcription of genes for increased cellular proliferation, viability, and migration in numerous cell types, including stem cells and fibroblasts. Over the past few years, significant advances have been made in understanding how PBM regulates numerous signalling pathways implicated in chronic wound repair. This review highlights the significant role of PBM in the activation of several cell signalling pathways involved in wound healing.
Gamma-Aminobutyric Acid (GABA) Promotes Growth in Zebrafish Larvae by Inducing IGF-1 Expression via GABAA and GABAB Receptors
Authors: Athapaththu Athapaththu Mudiyanselage Gihan Kavinda , Molagoda Ilandarage Menu Neelaka , Jayasooriya Rajapaksha Gedara Prasad Tharanga , Choi Yung Hyun , Jeon You-Jin , Park Joung-Hyun , Lee Bae-Jin , Kim Gi-Young
Published: October 2021

Insulin-like growth factor-1 (IGF-1) primarily increases the release of gamma-aminobutyric acid (GABA) in neurons; moreover, it is responsible for the promotion of longitudinal growth in children and adolescents. Therefore, in this study, we investigated whether exogenous GABA supplementation activates IGF-mediated growth performance. Zebrafish larvae treated with GABA at three days post fertilization (dpf) showed a significant increase in the total body length from 6 to 12 dpf through upregulation of growth-stimulating genes, including IGF-1, growth hormone-1 (GH-1), growth hormone receptor-1 (GHR-1), and cholecystokinin A (CCKA). In particular, at 9 dpf, GABA increased total body length from 3.60 ± 0.02 to 3.79 ± 0.03, 3.89 ± 0.02, and 3.92 ± 0.04 mm at concentrations of 6.25, 12.5, and 25 mM, and the effect of GABA at 25 mM was comparable to 4 mM β-glycerophosphate (GP)-treated larvae (3.98 ± 0.02 mm). Additionally, the highest concentration of GABA (50 mM) -induced death in 50% zebrafish larvae at 12 dpf. GABA also enhanced IGF-1 expression and secretion in preosteoblast MC3T3-E1 cells, concomitant with high levels of the IGF-1 receptor gene (IGF-1R). In zebrafish larvae, the GABA-induced growth rate was remarkably decreased in the presence of an IGF-1R inhibitor, picropodophyllin (PPP), which indicates that GABA-induced IGF-1 enhances growth rate via IGF-1R. Furthermore, we investigated the effect of GABA receptors on growth performance along with IGF-1 activation. Inhibitors of GABAA and GABAB receptors, namely bicuculline and CGP 46381, respectively, considerably inhibited GABA-induced growth rate in zebrafish larvae accompanied by a marked decrease in the expression of growth-stimulating genes, including IGF-1, GH-1, GHR-1, and CCKA, but not with an inhibitor of GABAC receptor, TPMPA. Additionally, IGF-1 and IGF-1R expression was impaired in bicuculline and CGP 46381-treated MC3T3-E1 cells, but not in the cells treated with TPMPA. Furthermore, treatment with bicuculline and CGP 46381 significantly downregulated GABA-induced IGF-1 release in MC3T3-E1 cells. These data indicate that GABA stimulates IGF-1 release via GABAA and GABAB receptors and leads to growth promotion performance via IGF-1R.
The Hedgehog-GLI Pathway Regulates MEK5-ERK5 Expression and Activation in Melanoma Cells
Authors: Tusa Ignazia , Gagliardi Sinforosa , Tubita Alessandro , Pandolfi Silvia , Menconi Alessio , Lulli Matteo , Dello Sbarba Persio , Stecca Barbara , Rovida Elisabetta
Published: October 2021

Malignant melanoma is the deadliest skin cancer, with a poor prognosis in advanced stages. We recently showed that the extracellular signal-regulated kinase 5 (ERK5), encoded by the MAPK7 gene, plays a pivotal role in melanoma by regulating cell functions necessary for tumour development, such as proliferation. Hedgehog-GLI signalling is constitutively active in melanoma and is required for proliferation. However, no data are available in literature about a possible interplay between Hedgehog-GLI and ERK5 pathways. Here, we show that hyperactivation of the Hedgehog-GLI pathway by genetic inhibition of the negative regulator Patched 1 increases the amount of ERK5 mRNA and protein. Chromatin immunoprecipitation showed that GLI1, the major downstream effector of Hedgehog-GLI signalling, binds to a functional non-canonical GLI consensus sequence at the MAPK7 promoter. Furthermore, we found that ERK5 is required for Hedgehog-GLI-dependent melanoma cell proliferation, and that the combination of GLI and ERK5 inhibitors is more effective than single treatments in reducing cell viability and colony formation ability in melanoma cells. Together, these findings led to the identification of a novel Hedgehog-GLI-ERK5 axis that regulates melanoma cell growth, and shed light on new functions of ERK5, paving the way for new therapeutic options in melanoma and other neoplasms with active Hedgehog-GLI and ERK5 pathways.
Placental Ischemia Says “NO” to Proper NOS-Mediated Control of Vascular Tone and Blood Pressure in Preeclampsia
Authors: Palei Ana C. , Granger Joey P. , Spradley Frank T.
Published: October 2021

In this review, we first provide a brief overview of the nitric oxide synthase (NOS) isoforms and biochemistry. This is followed by describing what is known about NOS-mediated blood pressure control during normal pregnancy. Circulating nitric oxide (NO) bioavailability has been assessed by measuring its metabolites, nitrite (NO2) and/or nitrate (NO3), and shown to rise throughout normal pregnancy in humans and rats and decline postpartum. In contrast, placental malperfusion/ischemia leads to systemic reductions in NO bioavailability leading to maternal endothelial and vascular dysfunction with subsequent development of hypertension in PE. We end this article by describing emergent risk factors for placental malperfusion and ischemic disease and discussing strategies to target the NOS system therapeutically to increase NO bioavailability in preeclamptic patients. Throughout this discussion, we highlight the critical importance that experimental animal studies have played in our current understanding of NOS biology in normal pregnancy and their use in finding novel ways to preserve this signaling pathway to prevent the development, treat symptoms, or reduce the severity of PE.
Effect of Exogenous Melatonin on the Development of Mice Ovarian Follicles and Follicular Angiogenesis
Authors: Tao Jingli , Zhang Liangliang , Zhang Xuan , Chen Yuanyuan , Chen Qianqian , Shen Ming , Liu Honglin , Deng Shoulong
Published: October 2021

In mammalian, the periodic growth and development of ovarian follicles constitutes the physiological basis of female estrus and ovulation. Concomitantly, follicular angiogenesis exerts a pivotal role in the growth of ovarian follicles. Melatonin (N-acetyl-5-methoxytryptamine, Mel), exists in follicle fluid, was suggested to affect the development of follicles and angiogenesis. This research was conducted to investigate the effects and mechanisms of Mel on the development of ovarian follicles and its angiogenesis. In total, 40 ICR mice at age of 3 weeks were allocated into four groups at liberty: control, Mel, FSH and FSH + Mel for a 12-day trial. Ovaries were collected at 8:00 a.m. on Day 13 for detecting the development of ovarian follicles and angiogenesis. Results indicated that Mel promoted the development of ovarian follicles of 50–250 μm (secondary follicles) and periphery angiogenesis, while FSH remarkably increased the number of antral follicles and periphery angiogenesis. Mechanically, Mel and FSH may regulate the expression of VEGF and antioxidant enzymes in different follicular stages. In conclusion, Mel primarily acted on the secondary follicles, while FSH mainly promoted the development of antral follicles. They both conduced to related periphery angiogenesis by increasing the expression of VEGF. These findings may provide new targets for the regulating of follicular development.