bluuebunny/crossref_metadata_2025 huggingface dataset:
Electromyographic Analysis of Exercises on a Gymnastic Horse and a Walking Horse: A Pilot Study
Authors: Pyšková Barbora , Nováková Tereza , Bačáková Radka , Vilímek Miloslav
Published: December 2021

In studies testing the effect of hippotherapy on the human body, no one has yet compared the involvement of the same specific muscles in exercises on a gymnastic (pommel) horse vs. a walking horse. To improve the correct riding seat and to compare the differences in electromyographic activity, we conducted an experimental study to measure the activity of selected muscles on a set of probands of both sexes during three exercises on a gymnastic horse vs. a walking horse. We measured the activity of eight selected muscles, expressed as the percentage value of the maximal voluntary contraction. Maximal voluntary contraction of each muscle was electromyographically measured using Janda’s strength muscle test. These values were used as a standard for values obtained from exercising on a gymnastic horse and a walking horse. The effect of the studied factors was tested by analysis of variance. The muscle activity was statistically significantly affected by the studied factors. It was higher when riding a living horse than a gymnastic horse and in females compared to males. Although the exercises on a gymnastic horse generated lower muscle activity than those on a walking horse, there was a variation among individual muscles that justified further study.
Study on the Influence of Triangular Groove Structure on Steady-State Flow Force Compensation Characteristics
Authors: Li Ruichuan , Ding Xinkai , Lin Jianghai , Chi Feng , Xu Jikang , Cheng Yi , Liu Jilu , Liu Qi
Published: December 2021

In this study, a structurally improved spool was designed. The diameter of one side of the spool stem was reduced, making the spool stem into a rounded table shape. A triangular groove was circumscribed on the step and on the same side. After liquid flow was guided through the triangular groove, the flow direction changed. A flow component in the negative direction was generated, which reversely impacted the liquid flow in the positive direction. The liquid flow angle at the outlet increased; that is, jet angle increased and flow force decreased. The simulation results show that, increasing the depth, H, of the triangular groove has a positive effect on flow-force compensation and was conducive to the stability of the valve core. Properly increasing the groove’s bottom diameter, D1, of the triangular groove was conducive to the stability of the spool, but when D1 was too large, the flow force increased. The experimental results are consistent with the simulation results, which proves that the improved structure can effectively reduce the flow force of the spool.
Pyrophyllite: An Economic Mineral for Different Industrial Applications
Authors: Ali Maaz A. , Ahmed Hussin A. M. , Ahmed Haitham M. , Hefni Mohammed
Published: December 2021

Pyrophyllite (Al2Si4O10(OH)2) is a phyllosilicate often associated with quartz, mica, kaolinite, epidote, and rutile minerals. In its pure state, pyrophyllite exhibits unique properties such as low thermal and electrical conductivity, high refractive behavior, low expansion coefficient, chemical inertness, and high resistance to corrosion by molten metals and gases. These properties make it desirable in different industries such as refractory; ceramic, fiberglass, and cosmetic industries; as filler in the paper, plastic, paint, and pesticide industries; as soil conditioner in the fertilizer industry; and as a dusting agent in the rubber and roofing industries. Pyrophyllite can also serve as an economical alternative in many industrial applications to different minerals as kaolinite, talc, and feldspar. To increase its market value, pyrophyllite must have high alumina (Al2O3) content, remain free of any impurities, and possess as much whiteness as possible. This paper presented a review of pyrophyllite’s industrial applications, its important exploitable properties, and the specifications required for its use in industry. It also presents the most effective and economical techniques for enriching low-grade pyrophyllite ores to make them suitable for various industrial applications.
Comparative Technical-Economical Analysis of Transient Stability Improvements in a Power System
Authors: Tina Giuseppe Marco , Maione Giovanni , Licciardello Sebastiano , Stefanelli Domenico
Published: December 2021

Power systems are rapidly evolving to face the increasing penetration of renewable inverter-based generation units and to improve their reliability and safety. A power system is constantly exposed to sudden changes or disturbances that may affect its stability. In this paper, a comparative analysis of solutions to improve transient stability, both rotor angle and frequency stability, is performed. These solutions are SVC, STATCOM, a fast excitation system, and an additional parallel transmission line. Sensitivity analyses were performed to evaluate the effects of the location of the three-phase fault line and the most effective SVC or STATCOM installation bus. Based on these analyses, the worst-case fault is considered, and the critical fault clearing time is determined as an engineering parameter for comparing the different solutions. For the numerical analysis, the IEEE 9 bus system is considered, and the PowerWorld software tool is used. Rotor angle and frequency stability analyses were performed. Moreover, specifically for SVC and STATCOM, the effects of different values of short-circuit ratios were considered in the context of rotor angle stability analysis. As part of the frequency stability analysis, the use of the remuneration for load shedding service in Italy was considered to perform an economic analysis for SVC and STATCOM.
Development and Evaluation of an Intelligence and Learning System in Jurisprudence Text Mining in the Field of Competition Defense
Authors: Dias Canedo Edna , Aymoré Martins Valério , Coelho Ribeiro Vanessa , dos Reis Vinicius Eloy , Carvalho Chaves Lucas Alexandre , Machado Gravina Rogério , Alberto Moreira Dias Felipe , Lopes de Mendonça Fábio Lúcio , Orozco Ana Lucila Sandoval , Balaniuk Remis , de Sousa Rafael T.
Published: December 2021

A jurisprudence search system is a solution that makes available to its users a set of decisions made by public bodies on the recurring understanding as a way of understanding the law. In the similarity of legal decisions, jurisprudence seeks subsidies that provide stability, uniformity, and some predictability in the analysis of a case decided. This paper presents a proposed solution architecture for the jurisprudence search system of the Brazilian Administrative Council for Economic Defense (CADE), with a view to building and expanding the knowledge generated regarding the economic defense of competition to support the agency’s final procedural business activities. We conducted a literature review and a survey to investigate the characteristics and functionalities of the jurisprudence search systems used by Brazilian public administration agencies. Our findings revealed that the prevailing technologies of Brazilian agencies in developing jurisdictional search systems are Java programming language and Apache Solr as the main indexing engine. Around 87% of the jurisprudence search systems use machine learning classification. On the other hand, the systems do not use too many artificial intelligence and morphological construction techniques. No agency participating in the survey claimed to use ontology to treat structured and unstructured data from different sources and formats.
Computational Modeling of Passive and Active Cooling Methods to Improve PV Panels Efficiency
Authors: Pomares-Hernández Cristhian , Zuluaga-García Edwin Alexander , Escorcia Salas Gene Elizabeth , Robles-Algarín Carlos , Sierra Ortega Jose
Published: December 2021

This paper presents the computational modeling of three cooling systems based on three different methods (passive, active, and hybrid), to improve the efficiency of PV panels when operating beyond the recommended temperature under standard test conditions. All simulations were implemented using the COMSOL Multiphysics software. In the passive method, through-holes were made in the solar panel, to allow the transfer of heat by convection due to the air flow. In the active method, water was used to cool the solar panel, spraying it on the front when the operating temperature reaches a threshold value. The analysis includes both fluid dynamics and heat transfer effects. In addition, a hybrid method that uses both passive and active cooling methods simultaneously was implemented. Finally, a mathematical model for the PV panel is presented, which allowed obtaining the changes in the output power from the reduction in the operating temperature. Results demonstrated improvements in the performance of the solar panel with the implementation of the three cooling systems, showing better performance in the active and hybrid methods compared to the passive method.
Research on Children’s Customized Furniture Design Based on Group Technology
Authors: Xiong Xianqing , Lu Guozhen , Lu Danting
Published: December 2021

Recently, solid wood furniture has become the new direction for the development of Chinese furniture industry. In order to realize solid wood customization, the standardization of solid wood parts is a problem for high priority. In this study, a standardized experimental study on children’s solid wood furniture parts was carried out by using group technology. Twenty pieces of children’s solid wood furniture were selected, including 1084 parts in total with 705 solid wood parts. Then, three key structural features of the parts were analyzed based on the processing similarity principle, including the center line of the long side direction of the parts, the shape of the outside surface of the long side direction and the shape of the outside surface of the short side direction. Moreover, these parts were classified according to the principle of process similarity. Accordingly, a children’s solid wood furniture parts family was established, and the distribution of parts in the family was analyzed. In detail, the parts with the dimensional difference within 2 mm were combined, the dimensional value was mainly based on the value of most parts before the combination and part specifications were optimized on the basis of the original specifications or its 1/2 method. The results show that the category of thickness specification reduced by 20, and the number of parts included in one thickness specification increased by 2.2 times on average. Moreover, the category of width specification reduced by 12, and the number of parts included in one width specification increased by 1.47 times on average. This not only greatly improves the degree of standardization of solid wood parts but also provides theoretical and practical basis for the digital design of mass customized children’s solid wood furniture.
Plant Species Classification and Diversity of the Understory Vegetation in Oak Forests of Swat, Pakistan
Authors: Rahman Ataur , Khan Nasrullah , Ali Kishwar , Ullah Rafi , Khan Muhammad Ezaz Hasan , Jones David Aaron , Rahman Inayat Ur
Published: December 2021

The forest ecosystem has understory vegetation that plays a vital role in sustaining diversity, providing nutrients, and forming a useful association for developing a balanced ecosystem. The current study provides detailed insights into the plant biodiversity and species classification of the understory vegetation of Swat, Pakistan. The floral diversity of the area was comprised of 58 plant species belonging to 32 families. The physiognomy of the studied area was dominated by herbaceous growth form with 47 species. The dominant life-form class was hemicryptophytes with 19 species (33%), followed by nanophanerophytes with 15 species (26%) and therophytes with 13 species (22%). Of the 58 species, 43 plant species were associated with group III clustered by applying Ward’s agglomerative clustering that indicated wide sociability of the species in the studied oak-dominated forests. Group III had higher species richness (10.3), α-diversity (2.74) and β-diversity (9.85), and Margalef index values (3.95). While the group I had maximum Pielous and Simpson index values of 0.97 and 7.13, respectively. Redundancy analysis revealed that seven variables (i.e., latitude, elevation, clay, wilting point, bulk density, saturation, and electric conductivity) were significantly influential concerning the understory vegetation of oak-dominated forests. The understory vegetation of these forests plays an important role in the forest ecosystem of the region. The present study reveals floral divergence and physiognomic scenario of the unexplored study area, which could be an important reference for future ethnobotanical, phytosociological, and conservational endeavors. Moreover, this information is important to the success of efforts intended to prevent the loss of species diversity in these forests by destroying their natural habitats.
Fluorescence Spectroscopy of Enantiomeric Amide Compounds Enforced by Chiral Light
Authors: Belardini Alessandro , Petronijevic Emilija , Ghahri Ramin , Rocco Daniele , Pandolfi Fabiana , Sibilia Concita , Mattiello Leonardo
Published: December 2021

Chirality, the absence of mirror symmetry, governs behavior in most biologically important molecules, thus making the chiral recognition of great importance in the pharmaceutical and agrochemical industries, as well as medicine. Chiral molecules can be characterized by means of optical experiments based on chiro-optical excitation of molecules. Specifically, chiral absorptive materials differently absorb left- and right-circular polarized light, i.e., they possess circular dichroism (CD). Unfortunately, the natural CD of most molecules is very low and lies in the ultraviolet range. Fluorescence-detected CD is a fast and sensitive tool for investigation of chiral molecules which emit light; ultralow CD in absorption can be detected as the difference in emission. In this work, we perform fluorescence-detected CD on novel chiral amide compounds, designed specifically for visible green emission; we synthesize two enantiomeric fluorescent compounds using low-cost starting compounds and easy purification. We investigate different solutions of the enantiomers at different concentrations, and we show that the fluorescence of the intrinsically chiral compounds depends on the polarization state of the penetrating light, which is absorbed at 400 nm and emits across the green wavelength range. We believe that these compounds can be coupled with plasmonic nanostructures, which further shows promise in applications regarding chiral sensing or chiral emission.
Techniques for Calculating Software Product Metrics Threshold Values: A Systematic Mapping Study
Authors: Mishra Alok , Shatnawi Raed , Catal Cagatay , Akbulut Akhan
Published: December 2021

Several aspects of software product quality can be assessed and measured using product metrics. Without software metric threshold values, it is difficult to evaluate different aspects of quality. To this end, the interest in research studies that focus on identifying and deriving threshold values is growing, given the advantage of applying software metric threshold values to evaluate various software projects during their software development life cycle phases. The aim of this paper is to systematically investigate research on software metric threshold calculation techniques. In this study, electronic databases were systematically searched for relevant papers; 45 publications were selected based on inclusion/exclusion criteria, and research questions were answered. The results demonstrate the following important characteristics of studies: (a) both empirical and theoretical studies were conducted, a majority of which depends on empirical analysis; (b) the majority of papers apply statistical techniques to derive object-oriented metrics threshold values; (c) Chidamber and Kemerer (CK) metrics were studied in most of the papers, and are widely used to assess the quality of software systems; and (d) there is a considerable number of studies that have not validated metric threshold values in terms of quality attributes. From both the academic and practitioner points of view, the results of this review present a catalog and body of knowledge on metric threshold calculation techniques. The results set new research directions, such as conducting mixed studies on statistical and quality-related studies, studying an extensive number of metrics and studying interactions among metrics, studying more quality attributes, and considering multivariate threshold derivation.
Organic Ion-Associate Phase Microextraction/Back-Microextraction for Preconcentration: Determination of Nickel in Environmental Water Using 2-Thenoyltrifluoroacetone via GF-AAS
Authors: Kosugi Mitsuhito , Mizuna Kenta , Sazawa Kazuto , Okazaki Takuya , Kuramitz Hideki , Taguchi Shigeru , Hata Noriko
Published: December 2021

An ion-associate phase (IAP) microextraction/ back-microextraction system was applied for the enrichment, separation, and detection of trace amounts of nickel from environmental water samples. Thenoyltrifluoroacetone (HTTA) acted not only as a chelating reagent for nickel, but also as a component of the extraction phase, i.e., IAP. Nickel in a 40 mL sample solution was pH-adjusted with phenolsulfonate (PS−) and tetramethylammonium hydroxide and converted by chelation reaction in the presence of thenoyltrifluoroacetonate (TTA−). When benzyldodecyldimethylammonium ion (C12BzDMA+) was added, a suspension of IAP formed in the solution. The IAP consisted of TTA−, a chelating reagent, the PS−, a component of pH buffer, and C12BzDMA+, which helps extract the chelating complex. When the solution was centrifuged, the IAP separated from the suspension and the nickel-TTA chelate was extracted into the bottom phase of the centrifuge tube. After the aqueous phase was taken away, 100 µL of nitric acid (2 M) solution containing phosphate was used to back-microextract nickel from the IAP. The acid phase was measured via graphite-furnace atomic-absorption spectrometry (GF-AAS). The proposed method facilitated a 400-fold enrichment. The limit of detection was 0.02 µg L−1. The proposed method was applied for the determination of nickel in river water and seawater samples.
Why a New Journal on Bacteria?
Authors: Weimer Bart C.
Published: December 2021

As the inaugural editor-in-chief of the journal Bacteria (ISSN: 2674-1334) [...]
Clinical Features and Predictors for Mortality in Neurolisteriosis: An Administrative Data-Based Study
Authors: Garcia-Carretero Rafael
Published: December 2021

Listeriosis is an uncommon and potentially severe zoonotic bacterial infection that usually occurs in outbreaks instead of isolated cases. In recent years, there has been an increase in the incidence of this disease. One of the most severe of its complications involves the central nervous system (CNS) in a condition known as neurolisteriosis. Here, we describe the demographic and clinical features of patients presenting with neurolisteriosis between 2001 and 2015 using administrative data and attempt to identify potential predictors for mortality. We used the Spanish Minimum Basic Data Set at Hospitalization, a compulsory registry that collects data from clinical discharge reports. Up to 2015, data were coded based on the International Classification of Diseases, 9th Revision, so we used diagnoses and clinical conditions based on these codes. Age, sex, clinical presentation, mortality, and involvement of the CNS were identified. Using algorithms to aggregate data, variables such as immunosuppression and malignant disease were obtained. We analyzed correlations among clinical features and identified risk factors for morbidity and mortality. Between 2001 and 2015 we identified 5180 individuals, with a hospitalization rate of 0.76 per 100,000 population. Most (94%) were adults, and only 5.4% were pregnant women. The average age was 66 years. Neurological involvement was present in 2313 patients (44.7%), mostly meningitis (90.4%). Global mortality was 17%, but mortality in CNS infections was 19.2%. Age, severe sepsis, chronic liver disease, chronic kidney disease, and malignancy were the main risk factors for mortality in patients with CNS infections by Listeria monocytogenes. Although it is uncommon, neurolisteriosis can be a severe condition, associated with a high rate of mortality. Health care providers should be aware of potential sources of infection so that appropriate measures can be taken to prevent it.
SSR-Sequencing Reveals the Inter- and Intraspecific Genetic Variation and Phylogenetic Relationships among an Extensive Collection of Radish (Raphanus) Germplasm Resources
Authors: Li Xiaoman , Wang Jinglei , Qiu Yang , Wang Haiping , Wang Peng , Zhang Xiaohui , Li Caihua , Song Jiangping , Gui Wenting , Shen Di , Yang Wenlong , Cai Bin , Liu Liwang , Li Xixiang
Published: December 2021

Raphanus has undergone a lengthy evolutionary process and has rich diversity. However, the inter- and intraspecific phylogenetic relationships and genetic diversity of this genus are not well understood. Through SSR-sequencing and multi-analysis of 939 wild, semi-wild and cultivated accessions, we discovered that the European wild radish (EWR) population is separated from cultivated radishes and has a higher genetic diversity. Frequent intraspecific genetic exchanges occurred in the whole cultivated radish (WCR) population; there was considerable genetic differentiation within the European cultivated radish (ECR) population, which could drive radish diversity formation. Among the ECR subpopulations, European primitive cultivated radishes (EPCRs) with higher genetic diversity are most closely related to the EWR population and exhibit a gene flow with rat-tail radishes (RTRs) and black radishes (BRs)/oil radishes (ORs). Among Asian cultivated radishes (ACRs), Chinese big radishes (CBRs) with a relatively high diversity are furthest from the EWR population, and most Japanese/Korean big radishes (JKBRs) are close to CBR accessions, except for a few old Japanese landraces that are closer to the EPCR. The CBR and JKBR accessions are independent of RTR accessions; however, phylogenetic analysis indicates that the RTR is sister to the clade of CBR (including JWR), which suggests that the RTR may share the most recent common ancestry with CBRs and JWRs. In addition, Japanese wild radishes (JWRs), (namely, R. sativus forma raphanistroides) are mainly scattered between CBRs and EPCRs in PCoA analysis. Moreover, JWRs have a strong gene exchange with the JKBR, OR and RTR subpopulations. American wild radishes (AWRs) are closely related to European wild and cultivated radishes, and have a gene flow with European small radishes (ESRs), suggesting that the AWR developed from natural hybridization between the EWR and the ESR. Overall, this demonstrates that Europe was the origin center of the radish, and that Europe, South Asia and East Asia appear to have been three independent domestication centers. The EPCR, AWR and JWR, as semi-wild populations, might have played indispensable transitional roles in radish evolution. Our study provides new perspectives into the origin, evolution and genetic diversity of Raphanus and facilitates the conservation and exploitation of radish germplasm resources.
Neural Upscaling from Residue-Level Protein Structure Networks to Atomistic Structures
Authors: Duong Vy T. , Diessner Elizabeth M. , Grazioli Gianmarc , Martin Rachel W. , Butts Carter T.
Published: December 2021

Coarse-graining is a powerful tool for extending the reach of dynamic models of proteins and other biological macromolecules. Topological coarse-graining, in which biomolecules or sets thereof are represented via graph structures, is a particularly useful way of obtaining highly compressed representations of molecular structures, and simulations operating via such representations can achieve substantial computational savings. A drawback of coarse-graining, however, is the loss of atomistic detail—an effect that is especially acute for topological representations such as protein structure networks (PSNs). Here, we introduce an approach based on a combination of machine learning and physically-guided refinement for inferring atomic coordinates from PSNs. This “neural upscaling” procedure exploits the constraints implied by PSNs on possible configurations, as well as differences in the likelihood of observing different configurations with the same PSN. Using a 1 μs atomistic molecular dynamics trajectory of Aβ1–40, we show that neural upscaling is able to effectively recapitulate detailed structural information for intrinsically disordered proteins, being particularly successful in recovering features such as transient secondary structure. These results suggest that scalable network-based models for protein structure and dynamics may be used in settings where atomistic detail is desired, with upscaling employed to impute atomic coordinates from PSNs.
Andrographolide Attenuates Established Pulmonary Hypertension via Rescue of Vascular Remodeling
Authors: Nie Xiaowei , Shen Chenyou , Tan Jianxin , Yang Xusheng , Wang Wei , Dai Youai , Sun Haijian , Wu Zhiyuan , Chen Jingyu
Published: December 2021

Pulmonary hypertension (PH) is characterized by vascular remodeling caused by marked proliferation of pulmonary artery smooth muscle cells (PASMCs). Andrographolide (ANDRO) is a potent anti-inflammatory agent which possesses antioxidant, and has anticarcinogenic activity. The present study examined potential therapeutic effects of ANDRO on PH in both chronic hypoxia and Sugen5416/hypoxia mouse PH models. Effects of ANDRO were also studied in cultured human PASMCs isolated from either healthy donors or PH patients. In vivo, ANDRO decreased distal pulmonary arteries (PAs) remodeling, mean PA pressure and right ventricular hypertrophy in chronic hypoxia- and Sugen/hypoxia-induced PH in mice. ANDRO reduced cell viability, proliferation and migration, but increased cell apoptosis in the PASMCs isolated from PH patients. ANDRO also reversed the dysfunctional bone morphogenetic protein receptor type-2 (BMPR2) signaling, suppressed [Ca2+]i elevation, reactive oxygen species (ROS) generation, and the upregulated expression of IL-6 and IL-8, ET-1 and VEGF in PASMCs from PH patients. Moreover, ANDRO significantly attenuated the activation of TLR4/NF-κB, ERK- and JNK-MAPK signaling pathways and reversed the inhibition of p38-MAPK in PASMCs of PH patients. Further, ANDRO blocked hypoxia-triggered ROS generation by suppressing NADPH oxidase (NOX) activation and augmenting nuclear factor erythroid 2-related factor 2 (Nrf2) expression both in vitro and in vivo. Conventional pulmonary vasodilators have limited efficacy for the treatment of severe PH. We demonstrated that ANDRO may reverse pulmonary vascular remodeling through modulation of NOX/Nrf2-mediated oxidative stress and NF-κB-mediated inflammation. Our findings suggest that ANDRO may have therapeutic value in the treatment of PH.
COVID-19 Prognosis and Mortality Risk Predictions from Symptoms: A Cloud-Based Smartphone Application
Authors: Monjur Ocean , Preo Rahat Bin , Shams Abdullah Bin , Raihan Md. Mohsin Sarker , Fairoz Fariha
Published: December 2021

The coronavirus pandemic overwhelmed many countries and their healthcare systems. Shortage of testing kits and Intensive-Care-Unit (ICU) beds for critical patients have become a norm in most developing countries. This has prompted the need to rapidly identify the COVID-19 patients to stop the spread of the virus and also to find critical patients. The latter is imperative for determining the state of critically ill patients as quickly as possible. This will lower the number of deaths from the infection. In this paper, we propose a cloud-based smartphone application for the early prognosis of COVID-19 infected patients and also predict their mortality risk using their symptoms. Moreover, we heuristically identified the most important symptoms necessary for making such predictions. We have successfully reduced the number of features by almost half for the prognosis and by more than a third for forecasting the mortality risk, compared to the contemporary studies. The application makes the real-time analysis using machine learning models, designed and stored in the cloud. Our machine learning model demonstrates an accuracy, precision, recall, and F1 score of 97.72%, 100%, 95.55%, and 97.70%, respectively, in identifying the COVID-19 infected patients and with an accuracy, precision, recall, and F1 score of 90.83%, 88.47%, 92.94%, and 90.65%, respectively, in forecasting the mortality risk from the infection. The real-time cloud-based approach yields faster responses, which is critical in the time of pandemic for mitigating the infection spread and aiding in the efficient management of the limited ICU resources.
Cadmium-Induced Kidney Injury in Mice Is Counteracted by a Flavonoid-Rich Extract of Bergamot Juice, Alone or in Association with Curcumin and Resveratrol, via the Enhancement of Different Defense Mechanisms
Authors: Cirmi Santa , Maugeri Alessandro , Micali Antonio , Marini Herbert Ryan , Puzzolo Domenico , Santoro Giuseppe , Freni Jose , Squadrito Francesco , Irrera Natasha , Pallio Giovanni , Navarra Michele , Minutoli Letteria
Published: December 2021

Cadmium (Cd) represents a public health risk due to its non-biodegradability and long biological half-life. The main target of Cd is considered the kidney, where it accumulates. No effective treatment for Cd poisoning is available so that several therapeutic approaches were proposed to prevent damages after Cd exposure. We evaluated the effects of a flavonoid-rich extract of bergamot juice (BJe), alone or in association with curcumin (Cur) and resveratrol (Re), in the kidney of mice exposed to cadmium chloride (CdCl2). Male mice were administered with CdCl2 and treated with Cur, Re, or BJe alone or in combination for 14 days. The kidneys were processed for biochemical, structural and morphometric evaluation. Cd treatment significantly increased urea nitrogen and creatinine levels, along with tp53, Bax, Nos2 and Il1b mRNA, while reduced that of Bcl2, as well as glutathione (GSH) content and glutathione peroxidase (GPx) activity. Moreover, Cd caused damages to glomeruli and tubules, and increased Nrf2, Nqo1 and Hmox1 gene expression. Cur, Re and BJe at 40 mg/kg significantly improved all parameters, while BJe at 20 mg/kg showed a lower protective effect. After treatment with the associations of the three nutraceuticals, all parameters were close to normal, thus suggesting a new potential strategy in the protection of renal functions in subjects exposed to environmental toxicants.
Shiga Toxin 2a Induces NETosis via NOX-Dependent Pathway
Authors: Feitz Wouter J. C. , Suntharalingham Samuel , Khan Meraj , Ortiz-Sandoval Carolina G. , Palaniyar Nades , van den Heuvel Lambert P. , van de Kar Nicole C. A. J. , Licht Christoph
Published: December 2021

Shiga toxin (Stx)-producing Escherichia coli (STEC) infection is the most common cause of hemolytic uremic syndrome (HUS), one of the main causes of acute kidney injury in children. Stx plays an important role in endothelium damage and pathogenesis of STEC-HUS. However, the effects of Stx on neutrophils and neutrophil extracellular trap (NET) formation are not well understood. In this study, we investigated how Stx2a affects NET formation and NETotic pathways (NADPH or NOX-dependent and -independent) using neutrophils isolated from healthy donors and patients with STEC-HUS, during the acute and recovery phase of the disease. Stx2a dose-dependently induced NETosis in neutrophils isolated from both healthy controls and STEC-HUS patients. NETosis kinetics and mechanistic data with pathway-specific inhibitors including diphenyleneiodonium (DPI)-, ERK-, and P38-inhibitors showed that Stx2a-induced NETosis via the NOX-dependent pathway. Neutrophils from STEC-HUS patients in the acute phase showed less ROS and NETs formation compared to neutrophils of the recovery phase of the disease and in healthy controls. NETs induced by Stx2a may lead to the activation of endothelial cells, which might contribute to the manifestation of thrombotic microangiopathy in STEC-HUS.
The Bumpy Road towards mTOR Inhibition in Glioblastoma: Quo Vadis?
Authors: Papavassiliou Kostas A. , Papavassiliou Athanasios G.
Published: December 2021

Glioblastoma multiforme (GBM), a grade IV astrocytoma, is a lethal brain tumor with a poor prognosis. Despite recent advances in the molecular biology of GBM, neuro-oncologists have very limited treatment options available to improve the survival of GBM patients. A prominent signaling pathway implicated in GBM pathogenesis is that of the mechanistic target of rapamycin (mTOR). Attempts to target the mTOR pathway with first-generation mTOR inhibitors appeared promising in the preclinical stage; however, results have been disappointing in clinical trials, owing to the heterogeneous nature of GBM, escape mechanisms against treatment, the blood–brain barrier, drug-related toxicities, and the imperfect design of clinical trials, among others. The development of next-generation mTOR inhibitors and their current evaluation in clinical trials have sparked new hope to realize the clinical potential of mTOR inhibitors in GBM. Meanwhile, studies are continuously furthering our understanding of mTOR signaling dysregulation, its downstream effects, and interplay with other signaling pathways in GBM tumors. Therefore, it remains to be seen whether targeting mTOR in GBM will eventually prove to be fruitful or futile.
Morph Composition Matters in the Gouldian Finch (Chloebia gouldiae): Involvement of Red-Headed Birds Increases Vigilance
Authors: Mettke-Hofmann Claudia
Published: December 2021

Animals invest in costly vigilance to detect threats. Joining groups reduces these costs, which can be further reduced in mixed-species assemblages. In colour-polymorphic species, morphs often experience different predation pressure and vary in a variety of traits. However, little is known about differences in vigilance or how group composition affects vigilance. The aim was to investigate whether higher conspicuousness increased vigilance and whether vigilance was reduced in mixed-morph groups like in mixed-species assemblages. I tested vigilance in the colour-polymorphic Gouldian Finch (Chloebia gouldiae). Same sex pairs of different age and of either pure (red-red or black-black) or mixed head colour were exposed to three contexts (familiar, changed and novel environment) and head movements were recorded. All birds reduced the frequency of head movements with increasing novelty, indicating different vigilance strategies (switching from a searching to a tracking strategy) depending on the situation. While vigilance did not differ between morphs, morph composition mattered. Black-headed pairs made fewer head movements than mixed-head colour pairs. Results indicated that conspicuousness did not affect vigilance, possibly due to existing adaptations to reduce predation risk. However, whenever red-headed birds were involved, vigilance increased either because of higher group conspicuousness or prevalence of aggression.
Decreased Intracranial Pressure Elevation and Cerebrospinal Fluid Outflow Resistance: A Potential Mechanism of Hypothermia Cerebroprotection Following Experimental Stroke
Authors: Omileke Daniel , Bothwell Steven W. , Pepperall Debbie , Beard Daniel J. , Coupland Kirsten , Patabendige Adjanie , Spratt Neil J.
Published: December 2021

Background: Elevated intracranial pressure (ICP) occurs 18–24 h after ischaemic stroke and is implicated as a potential cause of early neurological deterioration. Increased resistance to cerebrospinal fluid (CSF) outflow after ischaemic stroke is a proposed mechanism for ICP elevation. Ultra-short duration hypothermia prevents ICP elevation 24 h post-stroke in rats. We aimed to determine whether hypothermia would reduce CSF outflow resistance post-stroke. Methods: Transient middle cerebral artery occlusion was performed, followed by gradual cooling to 33 °C. At 18 h post-stroke, CSF outflow resistance was measured using a steady-state infusion method. Results: Hypothermia to 33 °C prevented ICP elevation 18 h post-stroke (hypothermia ∆ICP = 0.8 ± 3.6 mmHg vs. normothermia ∆ICP = 4.4 ± 2.0 mmHg, p = 0.04) and reduced infarct volume 24 h post-stroke (hypothermia = 78.6 ± 21.3 mm3 vs. normothermia = 108.1 ± 17.8 mm3; p = 0.01). Hypothermia to 33 °C did not result in a significant reduction in CSF outflow resistance compared with normothermia controls (0.32 ± 0.36 mmHg/µL/min vs. 1.07 ± 0.99 mmHg/µL/min, p = 0.06). Conclusions: Hypothermia treatment was protective in terms of ICP rise prevention, infarct volume reduction, and may be implicated in CSF outflow resistance post-stroke. Further investigations are warranted to elucidate the mechanisms of ICP elevation and hypothermia treatment.
Time Course Transcriptome Analysis of Spina Bifida Progression in Fetal Rats
Authors: Murphy Kendall P. , Pathak Bedika , Peiro Jose L. , Oria Marc
Published: December 2021

A better understanding of the transcriptomic modifications that occur in spina bifida may lead to identify mechanisms involved in the progression of spina bifida in utero and the development of new therapeutic strategies that aid in spinal cord regeneration after surgical interventions. In this study, RNA-sequencing was used to identify differentially expressed genes in fetal spinal cords from rats with retinoic acid-induced spina bifida at E15, E17, and E20. Gene ontology, KEGG, and protein–protein interaction analysis were conducted to predict pathways involved in the evolution of the disease. Approximately 3000, 1000 and 300 genes were differentially expressed compared to the control groups at E15, E17 and E20, respectively. Overall, the results suggest common alterations in certain pathways between gestational time points, such as upregulation in p53 and sonic hedgehog signaling at E15 and E17 and downregulation in the myelin sheath at E17 and E20. However, there were other modifications specific to gestational time points, including skeletal muscle development at E15, downregulated glucose metabolism at E17, and upregulated inflammation at E20. In conclusion, this work provides evidence that gestational age during spina bifida repair may be a significant variable to consider during the development of new regenerative therapeutics approaches.
On-Surface Synthesis of Boroxine-Based Molecules
Authors: Turco Elia , Stredansky Matus , Costantini Roberto , Martinez Javier A. , Dell’Angela Martina , Zerbato Elena , Toffoli Daniele , Fronzoni Giovanna , Morgante Alberto , Floreano Luca , Cossaro Albano
Published: December 2021

The on-surface synthesis of boroxine-containing molecules can be a convenient method of introducing specific functionalities. Here, we show the validity of a previously described synthesis protocol on the Au (111) surface by applying it to a different molecular precursor. We study in detail the assembly of the precursor, highlighting possible intermediate stages of the condensation process. We combine scanning tunneling microscopy and X-ray spectroscopies to fully characterize both the morphology and the electronic properties of the system. DFT calculations are presented to assign the main electronic transitions originating the B K-edge absorption spectrum. The study paves the way to a facile strategy for functionalizing a surface with molecules of tailored sizes and compositions.
Effect of Metformin and Simvastatin in Inhibiting Proadipogenic Transcription Factors
Authors: Jakab Jelena , Zjalić Milorad , Mikšić Štefica , Tušek Ivan , Ćosić Vesna , Volarić Nikola , Nakić Dario , Včev Aleksandar , Miškić Blaženka
Published: December 2021

Obesity is a multifactorial chronic disease characterized by the excessive accumulation of fat in adipose tissue driven by hypertrophy and hyperplasia of adipocytes through adipogenesis. Adipogenesis plays a key role in the development of obesity and related metabolic disorders, which makes it potential target for the therapeutic approach to obesity. An increasing number of studies confirm the pleiotropic action of the combined treatment with metformin and statins, suggesting their anti-hypertensive, anti-inflammatory, and anti-adipogenic effect. The aim of this study was to analyze the effect of different doses of metformin (MET) and simvastatin (SIM) on the expression of key transcription factors of adipogenesis. Mouse 3T3-L1 preadipocytes were induced to differentiation in adipogenic medium with sustained MET and SIM treatment to assess the effect on adipogenesis. Nine days after initiating adipogenesis, the cells were prepared for further experiments, including Oil Red O staining, RT-PCR, Western blotting, and immunocytochemistry. Treating the cells with the combination of MET and SIM slightly reduced the intensity of Oil Red O staining compared with the control group, and down-regulated mRNA and protein expression of PPARγ, C/EBPα, and SREBP-1C. In conclusion, the inhibitory effect of MET and SIM on adipocyte differentiation, as indicated by decreased lipid accumulation, appears to be mediated through the down-regulation of adipogenic transcription factors, peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding pro-tein α (C/EBPα), and sterol regulatory element-binding protein 1 (SREBP-1C).
Matrix Metalloproteinases in Human Decidualized Endometrial Stromal Cells
Authors: Hisamatsu Yoji , Murata Hiromi , Tsubokura Hiroaki , Hashimoto Yoshiko , Kitada Masaaki , Tanaka Susumu , Okada Hidetaka
Published: December 2021

Cyclic changes, such as growth, decidualization, shedding, and regeneration, in the human endometrium are regulated by the reciprocal action of female hormones, such as estradiol (E2), and progesterone (P4). Matrix metalloproteases (MMPs) and tissue inhibitors of MMPs (TIMPs) control the invasion of extravillous trophoblast cells after implantation. Several MMPs and TIMPs function in the decidua and endometrial stromal cells (ESCs). Here, we aimed to systematically investigate the changes in MMPs and TIMPs associated with ESC decidualization. We evaluated the expression of 23 MMPs, four TIMPs, and four anti-sense non-coding RNAs from MMP loci. Primary ESC cultures treated with E2 + medroxyprogesterone acetate (MPA), a potent P4 receptor agonist, showed significant down-regulation of MMP3, MMP10, MMP11, MMP12, MMP20, and MMP27 in decidualized ESCs, as assessed by quantitative reverse transcription PCR. Further, MMP15 and MMP19 were significantly upregulated in decidualized ESCs. siRNA-mediated silencing of Heart and Neural Crest Derivatives Expressed 2 (HAND2), a master transcriptional regulator in ESC decidualization, significantly increased MMP15 expression in untreated human ESCs. These results collectively indicate the importance of MMP15 and MMP19 in ESC decidualization and highlight the role of HAND2 in repressing MMP15 transcription, thereby regulating decidualization.
Evaluation of Microbiome Alterations Following Consumption of BIOHM, a Novel Probiotic
Authors: Ghannoum Mahmoud A. , McCormick Thomas S. , Retuerto Mauricio , Bebek Gurkan , Cousineau Susan , Hartman Lynn , Barth Charles , Schrom Kory
Published: December 2021

Gastrointestinal microbiome dysbiosis may result in harmful effects on the host, including those caused by inflammatory bowel diseases (IBD). The novel probiotic BIOHM, consisting of Bifidobacterium breve, Saccharomyces boulardii, Lactobacillus acidophilus, L. rhamnosus, and amylase, was developed to rebalance the bacterial–fungal gut microbiome, with the goal of reducing inflammation and maintaining a healthy gut population. To test the effect of BIOHM on human subjects, we enrolled a cohort of 49 volunteers in collaboration with the Fermentation Festival group (Santa Barbara, CA, USA). The profiles of gut bacterial and fungal communities were assessed via stool samples collected at baseline and following 4 weeks of once-a-day BIOHM consumption. Mycobiome analysis following probiotic consumption revealed an increase in Ascomycota levels in enrolled individuals and a reduction in Zygomycota levels (p value < 0.01). No statistically significant difference in Basidiomycota was detected between pre- and post-BIOHM samples and control abundance profiles (p > 0.05). BIOHM consumption led to a significant reduction in the abundance of Candida genus in tested subjects (p value < 0.013), while the abundance of C. albicans also trended lower than before BIOHM use, albeit not reaching statistical significance. A reduction in the abundance of Firmicutes at the phylum level was observed following BIOHM use, which approached levels reported for control individuals reported in the Human Microbiome Project data. The preliminary results from this clinical study suggest that BIOHM is capable of significantly rebalancing the bacteriome and mycobiome in the gut of healthy individuals, suggesting that further trials examining the utility of the BIOHM probiotic in individuals with gastrointestinal symptoms, where dysbiosis is considered a source driving pathogenesis, are warranted.
Physical Modeling of Snow Gliding: A Case Study in the NW Italian Alps
Authors: Bombelli Giovanni Martino , Confortola Gabriele , Maggioni Margherita , Freppaz Michele , Bocchiola Daniele
Published: December 2021

Snow gliding, a slow movement downhill of snow cover, is complex to forecast and model and yet is extremely important, because it drives snowpack dynamics in the pre-avalanching phase. Despite recent interest in this process and the development of some studies therein, this phenomenon is poorly understood and represents a major point of uncertainty for avalanche forecasting. This study presents a data-driven, physically based, time-dependent 1D model, Poli-Glide, able to predict the slow movement of snowpacks along a flow line at the daily scale. The objective of the work was to create a useful snow gliding model, requiring few, relatively easily available input data, by (i) modeling snowpack evolution from measured precipitation and air temperature, (ii) evaluating the rate and extent of movement of the snowpack in the gliding phase, and (iii) assessing fracture (i.e., avalanching) timing. Such a model could be then used to provide hazard assessment in areas subject to gliding, thereby, and subsequent avalanching. To do so, some simplifying assumptions were introduced, namely that (i) negligible traction stress occurs within soil, (ii) water percolation into snow occurs at a fixed rate, and (iii) the micro topography of soil is schematized according to a sinusoidal function in the absence of soil erosion. The proposed model was then applied to the “Torrent des Marais-Mont de La Saxe” site in Aosta Valley, monitored during the winters of 2010 and 2011, featuring different weather conditions. The results showed an acceptable capacity of the model to reproduce snowpack deformation patterns and the final snowpack’s displacement. Correlation analysis based upon observed glide rates further confirmed dependence against the chosen variables, thus witnessing the goodness of the model. The results could be a valuable starting point for future research aimed at including more complex parameterizations of the different processes that affect gliding.
Clocks in Dreams: Analysis of a Long Dream Series
Authors: Schredl Michael
Published: December 2021

Many dream content analytic studies focus on dream characters, animals, social interactions and so on, but they rarely analyze the frequency of everyday objects in dreams. In the present paper, the frequency and phenomenology of clock dreams in a dream series of 12,476 dreams of a single male dreamer was analyzed. The clock dreams (0.74% of all dreams) show a variety of contexts not only related to the time management of the dreamer within the dream. Interestingly, clocks that belong to the dreamer in waking life occurred very rarely in his dreams. Given that keeping time schedules and appointments in waking life is of importance to almost everyone, the low frequency of clock dreams might be explained by novelty, that is, waking-life experiences that repeat themselves regularly do not show up in dreams that often. Thus, studying everyday objects such as clocks in dreams might help refine the current models describing the continuity between waking and dreaming.