bluuebunny/crossref_metadata_2025 huggingface dataset:
Digital Intermediaries: More than New Actors on a Crowded Media Stage
Authors: González-Tosat Clara , Sádaba-Chalezquer Charo
Published: March 2021

Digitization, digital convergence and digitalization are well-known terms that have caused a huge impact on the media landscape in the last two decades. The embedded consequences of the increase of free information online or the lack of stable profits for media companies are present in the day-to-day practices of news companies. However, there is a lack of understanding of how the emergence of new players has modified the logic and rhythm of the media production chain. In this article, we try to identify a theoretical approach to analyze and classify the different roles and actors considered to be disrupting the media stage. Through a systematic literature review of more than 200 articles published in the last twenty years, we identify and define a term to better understand the nature of these new media players: digital intermediaries. Furthermore, we argue that there is a need for a clear taxonomy regarding digital intermediaries, paying special attention to the shifts in the news companies’ definition and delivery of value.
Generating a Precision Endoxifen Prediction Algorithm to Advance Personalized Tamoxifen Treatment in Patients with Breast Cancer
Authors: Helland Thomas , Alsomairy Sarah , Lin Chenchia , Søiland Håvard , Mellgren Gunnar , Hertz Daniel Louis
Published: March 2021

Tamoxifen is an endocrine treatment for hormone receptor positive breast cancer. The effectiveness of tamoxifen may be compromised in patients with metabolic resistance, who have insufficient metabolic generation of the active metabolites endoxifen and 4-hydroxy-tamoxifen. This has been challenging to validate due to the lack of measured metabolite concentrations in tamoxifen clinical trials. CYP2D6 activity is the primary determinant of endoxifen concentration. Inconclusive results from studies investigating whether CYP2D6 genotype is associated with tamoxifen efficacy may be due to the imprecision in using CYP2D6 genotype as a surrogate of endoxifen concentration without incorporating the influence of other genetic and clinical variables. This review summarizes the evidence that active metabolite concentrations determine tamoxifen efficacy. We then introduce a novel approach to validate this relationship by generating a precision endoxifen prediction algorithm and comprehensively review the factors that must be incorporated into the algorithm, including genetics of CYP2D6 and other pharmacogenes. A precision endoxifen algorithm could be used to validate metabolic resistance in existing tamoxifen clinical trial cohorts and could then be used to select personalized tamoxifen doses to ensure all patients achieve adequate endoxifen concentrations and maximum benefit from tamoxifen treatment.
Genomic Sequencing Results Disclosure in Diverse and Medically Underserved Populations: Themes, Challenges, and Strategies from the CSER Consortium
Authors: Suckiel Sabrina A. , O’Daniel Julianne M. , Donohue Katherine E. , Gallagher Katie M. , Gilmore Marian J. , Hendon Laura G. , Joseph Galen , Lianoglou Billie R. , Mathews Jennifer M. , Norton Mary E. , Odgis Jacqueline A. , Poss Alexis F. , Rego Shannon , Scollon Sarah , Yip Tiffany , Amendola Laura M.
Published: March 2021

Genomic sequencing results need to be effectively communicated across all populations and practice settings. Projects in the Clinical Sequencing Evidence-Generating Research (CSER) consortium enroll diverse racial/ethnic and medically underserved participants across various clinical contexts. This article explores a set of CSER results disclosure cases to expand the evidence base on experiences returning genomic results. Case details were collected using a structured set of questions. We identified common themes in the case set, and assessed challenges and strategies in achieving six relevant results disclosure objectives. CSER-affiliated patient/community stakeholder impressions of the findings were solicited via video conference calls. Seventeen cases across six CSER projects were included. Case themes sorted into four categories: (1) factors influencing participant understanding, (2) participant emotional response, (3) disease burden, and (4) logistical challenges. Challenges meeting results disclosure objectives included a lack of dialogue, health literacy level, unexpected findings, and complex concepts. Strategies were consistent with traditional genetic counseling practice, but also highlighted approaches being evaluated in CSER projects. Patient/community stakeholders supported the identified themes and provided additional suggestions to improve patient understanding and engagement. These experiences add valuable insights into adapting genomic results disclosure practices to best serve all patient populations.
Sagittal Relationship between the Maxillary Central Incisors and the Forehead in Digital Twins of Korean Adult Females
Authors: Cho Seoung-Won , Byun Soo-Hwan , Yi Sangmin , Jang Won-Seok , Kim Jong-Cheol , Park In-Young , Yang Byoung-Eun
Published: March 2021

Objective: Digital twins of adult Korean females were created as a tool to evaluate and compare the sagittal relationship between the maxillary central incisors and the forehead before and after orthodontic treatment. Methods: Digital twins were reconstructed for a total of 50 adult female patients using facial scans and cone-beam computed tomography (CBCT) images. The anteroposterior position of the maxillary central incisor and the forehead inclination were measured. Results: The control group presented a mean of 6.7 mm for the sagittal position and 17.5° for forehead inclination. The study group showed a mean of 9.3 mm for the sagittal position and 13.6° for forehead inclination. Most Korean females seeking orthodontic treatment had their maxillary central incisor anterior to the glabella. In contrast, fewer Korean females who completed their orthodontic treatments had their maxillary central incisor anterior to the glabella. Furthermore, patients who had completed the orthodontic treatment were more likely to have the maxillary central incisor between the forehead facial axis and glabella. Conclusion: The use of digital twins for three-dimensional (3D) analysis of the profile implies a high clinical significance. In addition, as the facial profile of Koreans is different from that of Caucasians, careful consideration should be made when setting treatment goals for the anteroposterior position of the maxillary central incisors.
SLCO1B1 Phenotype and CYP3A5 Polymorphism Significantly Affect Atorvastatin Bioavailability
Authors: Zubiaur Pablo , Benedicto Maria Dolores , Villapalos-García Gonzalo , Navares-Gómez Marcos , Mejía-Abril Gina , Román Manuel , Martín-Vílchez Samuel , Ochoa Dolores , Abad-Santos Francisco
Published: March 2021

Atorvastatin, prescribed for the treatment of hypercholesterolemia, demonstrated overwhelming benefits in reducing cardiovascular morbidity and mortality. However, many patients discontinue therapy due to adverse reactions, especially myopathy. The Dutch Pharmacogenetics Working Group (DPWG) recommends an alternative agent to atorvastatin and simvastatin or a dose adjustment depending on other risk factors for statin-induced myopathy in SLCO1B1 rs4149056 CC or TC carriers. In contrast, the Clinical Pharmacogenetics Implementation Consortium (CPIC) published their guideline on simvastatin, but not on atorvastatin. In this work, we aimed to demonstrate the effect of SLCO1B1 phenotype and other variants (e.g., in CYP3A4/5, UGT enzymes or SLC transporters) on atorvastatin pharmacokinetics. For this purpose, a candidate-gene pharmacogenetic study was proposed. The study population comprised 156 healthy volunteers enrolled in atorvastatin bioequivalence clinical trials. The genotyping strategy comprised a total of 60 variants in 15 genes. Women showed higher exposure to atorvastatin compared to men (p = 0.001), however this difference disappeared after dose/weight (DW) correction. The most relevant pharmacogenetic differences were the following: AUC/DW and Cmax /DW based on (a) SLCO1B1 phenotype (p < 0.001 for both) and (b) CYP3A5*3 (p = 0.004 and 0.018, respectively). As secondary findings: SLC22A1 *2/*2 genotype was related to higher Cmax/DW (ANOVA p = 0.030) and SLC22A1 *1/*5 genotype was associated with higher Vd/F (ANOVA p = 0.032) compared to SLC22A1 *1/*1, respectively. Finally, UGT2B7 rs7439366 *1/*1 genotype was associated with higher tmax as compared with the *1/*3 genotype (ANOVA p = 0.024). Based on our results, we suggest that SLCO1B1 is the best predictor for atorvastatin pharmacokinetic variability and that prescription should be adjusted based on it. We suggest that the CPIC should include atorvastatin in their statin-SLCO1B1 guidelines. Interesting and novel results were observed based on CYP3A5 genotype, which should be confirmed with further studies.
Three-Dimensional Evaluation of Soft Tissue Malar Modifications after Zygomatic Valgization Osteotomy via Geometrical Descriptors
Authors: Olivetti Elena Carlotta , Marcolin Federica , Moos Sandro , Ferrando Alberto , Vezzetti Enrico , Autorino Umberto , Borbon Claudia , Zavattero Emanuele , Gerbino Giovanni , Ramieri Guglielmo
Published: March 2021

Patients with severe facial deformities present serious dysfunctionalities along with an unsatisfactory aesthetic facial appearance. Several methods have been proposed to specifically plan the interventions on the patient’s needs, but none of these seem to achieve a sufficient level of accuracy in predicting the resulting facial appearance. In this context, a deep knowledge of what occurs in the face after bony movements in specific surgeries would give the possibility to develop more reliable systems. This study aims to propose a novel 3D approach for the evaluation of soft tissue zygomatic modifications after zygomatic osteotomy; geometrical descriptors usually involved in face analysis tasks, i.e., face recognition and facial expression recognition, are here applied to soft tissue malar region to detect changes in surface shape. As ground truth for zygomatic changes, a zygomatic openness angular measure is adopted. The results show a high sensibility of geometrical descriptors in detecting shape modification of the facial surface, outperforming the results obtained from the angular evaluation.
Treatment of Cutaneous Melanoma Harboring SMO p.Gln216Arg Mutation with Imiquimod: An Old Drug with New Results
Authors: Troiani Teresa , Napolitano Stefania , Brancaccio Gabriella , Belli Valentina , Nappi Annarita , Miro Caterina , Salvatore Domenico , Dentice Monica , Caraglia Michele , Franco Renato , Giunta Emilio Francesco , De Falco Vincenzo , Ciardiello Davide , Ciardiello Fortunato , Argenziano Giuseppe
Published: March 2021

Melanoma is the most lethal form of skin cancer and its incidence is growing worldwide. In the last ten years, the therapeutic scenario of this disease has been revolutionized by the introduction of targeted therapies and immune-checkpoint inhibitors. However, in patients with many lesions and bulky tumors, in which surgery is no longer feasible, there is a need for new treatment options. Here we report, for the first time to our knowledge, a clinical case where a melanoma patient harboring the SMO p.Gln216Arg mutation has been treated with imiquimod, showing a complete and durable response. To better explain this outstanding response to the treatment, we transfected a melanoma cell line (MeWo) with the SMO p.Gln216Arg mutation in order to evaluate its role in response to the imiquimod treatment. Moreover, to better demonstrate that the antitumor activity of imiquimod was due to its role in suppressing the oncogenic SMO signaling pathway, independently of its immune modulating function, an in vivo experiment has been performed. This clinical case opens up a new scenario for the treatment of melanoma patients identifying a new potentially druggable target.
Associations of Polygenetic Variants at the 11q23 Locus and Their Interactions with Macronutrient Intake for the Risk of 3GO, a Combination of Hypertension, Hyperglycemia, and Dyslipidemia
Authors: Zhou Jun-Yu , Park Sunmin
Published: March 2021

3GO is a condition in which hypertension, hyperglycemia, and dyslipidemia co-occur, and these conditions are related to each other and genetic and environmental factors. We hypothesized that common genetic variants and their interactions with lifestyles influenced 3GO risk. We aimed to explore common genetic variants to affect 3GO risk and their haplotype interaction with lifestyles in a city hospital-based cohort in 58,701 Koreans > 40 years. 3GO was defined as SBP ≥ 140 mmHg and DBP ≥ 90 mmHg for hypertension, fasting blood glucose ≥ 126 mg/dL for hyperglycemia, and LDL ≥ 160 mg/dL or HDL ≤ 40 mg/dL, or triglyceride ≥ 200 mg/dL for dyslipidemia. Haplotypes were generated by genetic variants selected from genome-wide association study ((GWAS) an observational study of the genetic variation of the whole genome in different individuals, used to see if any variation is related to traits) after adjusting for age, sex, area of residence, and body mass index (BMI). Nutrient intakes were assessed using food frequency questionnaires. Interactions between haplotype and lifestyles and 3GO risk were investigated. Parameters related to metabolic syndrome were significantly different in the 0GO, 1–2GO, and 3GO groups, that is, groups of individuals with none, one to two, or all three of the components of 3GO. At the 11q23 locus, KCNQ1_rs2237892, ZPR1_rs2075291, APOA5_rs662799, APOA1_rs5072, and SIK3_rs151139277, influenced 3GO risk, and the minor alleles of their haplotype had a 3GO risk 3.23 times higher than the major alleles. For subjects with a high energy intake, the 3GO risk of the minor alleles was significantly higher than that of the major alleles (OR = 3.230, 95% confidence interval (CI) = 2.062~5.061, p < 0.001). BMI, HbA1c, SBP, and serum concentrations of glucose, HDL, and triglyceride were significantly higher for the minor allele than the major alleles (p < 0.001). The haplotype interacted with the intakes of protein (p = 0.033), digestible carbohydrate (p = 0.012), fat (p = 0.008), and undigestible carbohydrates (p = 0.015) to increase 3GO risk. An interaction was also observed between smoking and the haplotype (p = 0.007). The minor allele effects on 3GO incidence were higher in the high digestible carbohydrate intake and smoking groups. By contrast, the minor allele impacts on 3GO frequencies were much higher in the low intake of undigestible carbohydrates, protein, and fat. In conclusion, people who carry a minor allele of the 11q23 locus haplotype should avoid smoking and replace digestible carbohydrate intake with consuming high-quality protein, healthy fat, and undigestible carbohydrates.
Empowering Financial Education by Banks—Social Media as a Modern Channel
Authors: Kuchciak Iwa , Wiktorowicz Justyna
Published: March 2021

Financial literacy is extremely important, both from the perspective of the financial well-being of individuals and the stability of the financial market and the whole economy. The more financially literate a bank’s customers are, the more frequently and consciously they use financial products and services. Thus, banks are potentially significant stakeholders in the financial education process. Considering that social media have become the leading channel for communication and relationship building, especially regarding young clients, this channel should also be used by banks to increase financial literacy. The aim of this paper is to assess banks’ involvement in financial education activities through social media. We assume that banks use social media as a modern and attractive channel for improving financial education among social media users. The empirical analysis was conducted using several data sources, including non-financial statements and a unique self-collected dataset that describes the specifics of the most popular social media platforms (like Facebook, Twitter, YouTube, Instagram, GoldenLine, and LinkedIn) in the activities of commercial and cooperative banks in Poland between 2010 and 2019. Descriptive statistical methods and cluster analysis were used. The results show that educational activities provided by banks in Poland differ for each social media channel. Additionally, although financial education topics have become more popular among content published by banks, there is a huge disproportion between cooperative and commercial banks. Generally, banks that are more active on social media (mostly commercial banks) also pay more attention to the financial education context.
Forest Area Changes in Cinque Terre National Park in the Last 80 Years. Consequences on Landslides and Forest Fire Risks
Authors: Santoro Antonio , Venturi Martina , Piras Francesco , Fiore Beatrice , Corrieri Federica , Agnoletti Mauro
Published: March 2021

Cinque Terre, one of the most important Italian cultural landscapes, has not been spared from depopulation and agricultural abandonment processes, that involved many rural areas in Europe, as a consequence of socio-economic transformations that occurred after WWII. Depopulation of rural areas, especially in mountains or in terraced areas, caused significant environmental consequences, such as the decrease of biodiversity, the landscape homogenization, the increase of hydrogeological and forest fires risks. Cinque Terre National Park (5TNP) was established in 1999, and, differently from other Italian National Parks, not just for protecting natural habitats, but mainly to preserve, restore and valorize the historical terraced landscape. Moreover, the area is a UNESCO cultural landscape site and it is partly protected by three Sites of Community Importance. The research intended to investigate the transformations that have affected forested areas inside the 5TNP in the period 1936–2018, also highlighting the connections with hydrogeological and forest fires risks, as a support for the Park planning strategies and the conservation of the UNESCO site. Results highlighted that 37% of the current forests are the consequence of dry stones terraces abandonment that occurred in the twentieth century, with negative effects on the stability of steep slopes, hydrogeological risk, forest fires and on the conservation of a unique cultural landscape. This confirms the current national trend showing no deforestation occurring, but rather a continuous increase of forests on abandoned land. While 5TNP policies and actions are effectively aimed at pursuing an equilibrium between cultivated areas and forests, the Sites of Community Importance located inside the Park mainly focuses on the conservation of “natural habitats”, even if the current vegetation is also the result of secondary successions on former cultivated land. The research highlighted the need to valorize “cultural values” in forest planning as well as the importance of forest history for an accurate planning of forest resources in protected areas.
Predicting Shifts in Land Suitability for Maize Cultivation Worldwide Due to Climate Change: A Modeling Approach
Authors: Gao Yuan , Zhang Anyu , Yue Yaojie , Wang Jing’ai , Su Peng
Published: March 2021

Suitable land is an important prerequisite for crop cultivation and, given the prospect of climate change, it is essential to assess such suitability to minimize crop production risks and to ensure food security. Although a variety of methods to assess the suitability are available, a comprehensive, objective, and large-scale screening of environmental variables that influence the results—and therefore their accuracy—of these methods has rarely been explored. An approach to the selection of such variables is proposed and the criteria established for large-scale assessment of land, based on big data, for its suitability to maize (Zea mays L.) cultivation as a case study. The predicted suitability matched the past distribution of maize with an overall accuracy of 79% and a Kappa coefficient of 0.72. The land suitability for maize is likely to decrease markedly at low latitudes and even at mid latitudes. The total area suitable for maize globally and in most major maize-producing countries will decrease, the decrease being particularly steep in those regions optimally suited for maize at present. Compared with earlier research, the method proposed in the present paper is simple yet objective, comprehensive, and reliable for large-scale assessment. The findings of the study highlight the necessity of adopting relevant strategies to cope with the adverse impacts of climate change.
Runoff Volume Reduction Using Green Infrastructure
Authors: Nowogoński Ireneusz
Published: March 2021

Uncontrolled urbanization is a frequent cause behind the local flooding of catchment areas. This also results in a degradation of water quality in receivers, as well as causing a disruption of the natural water cycle in the catchment. Classical solutions, such as retention, do not prove to be sufficient under all conditions. An alternative solution is the application of low impact development (LID), which, in the analysed case, takes the form of rain gardens, infiltration trenches and controlled unsealing of catchment components. The work presents the influence of a few variants of solutions on a selected urbanized catchment located in Gorzów Wielkopolski. The assessment was developed using a simulation model, making use of EPA’s Storm Water Management Model (SWMM) software. The nalysed design variants are compared with the described existing state before the implementation of modernization works. Previous results showing that LID may be ineffective as the only solution in systems overloaded with runoff generated by rainfall of relatively low intensities were confirmed. In the case of existing systems, LID should be applied in combination with classical retention systems or in a treatment train and every opportunity to implement LID whether on a property or urban site must be taken. Such solutions in the analysed cases will allow for a reduction of the maximum outflow intensity from the analysed subcatchment by 9 to 17% depending on the analysed rainfall. The results are similar to those obtained in other implementations. However, the interpretation of the results is not as simple and obvious for overloaded systems. In addition to flow rate reduction, reduction of surcharge in the sewer network and reduction of the volume of local flooding must be considered. LID solutions should also, whenever possible, be looked into as early as the stage of planning the land development of the infrastructure.
Memorial Parking Trees: Resilient Modular Design with Nature-Based Solutions in Vulnerable Urban Areas
Authors: Acosta Fortino , Haroon Stephen
Published: March 2021

Nature-based solutions (NbS) include all the landscape’s ecological components that have a function in the natural or urban ecosystem. Memorial Parking Trees (MPTs) are a new variant of a nature-based solution composed of a bioswale and a street tree allocated in the road, occupying a space that is sub-utilised by parked cars. This infill green practice can maximise the use of street trees in secondary streets and have multiple benefits in our communities. Using GIS mapping and methodology can support implementation in vulnerable neighbourhoods. In this research, we based vulnerability assessments for London, Rio de Janeiro, and Los Angeles on the following three indicators: extreme temperature, air quality, and flood-prone areas. Evidence is emerging that disadvantaged populations may live at higher risks of exposure to environmental hazards. The income and healthcare accessibility of neighbourhoods are the two indicators that will help us target these communities for a better and faster decision-making process. The contrast between the results and the 15-min city concept supports our detecting and prioritising neighbourhoods for MPTS implementation, among other NbS solutions integrated into a more inclusive and sustainable urban design.
Identification of Property Boundaries Using an IFC-Based Cadastral Database
Authors: Barzegar Maryam , Rajabifard Abbas , Kalantari Mohsen , Atazadeh Behnam
Published: March 2021

Property boundaries have a significant importance in cadaster as they define the legal extent of the ownership rights. Among 3D data models, Industry Foundation Class (IFC) provides the potential capabilities for modelling property boundaries in a 3D environment. In some jurisdictions, such as Victoria, Australia, some property boundaries are assigned to the faces of building elements which are modelled as solids in IFC. In order to retrieve these property boundaries, boundary identification analysis should be performed, and faces of building elements should be extracted. However, extracting faces of solids from an IFC file is not possible as faces of solids are not considered as a separate object-type. Therefore, this paper aims to develop a spatial query approach for the identification of property boundaries using 3D spatial operators of a database to address this problem. The viability of the developed approach is tested using an IFC-based 3D cadastral database with two real datasets and one test dataset. The proposed methodology not only supports vertical walls and horizontal roofs but can also be used for detecting boundaries in properties surrounded by complex building structures such as oblique and curved walls and roofs.
Strengthening L3 French Motivation: The Differential Impact of Vision-Enhancing Activities
Authors: Rocher Hahlin Céline , Granfeldt Jonas
Published: March 2021

Even though the European Union has long promoted multilingualism, it has proven difficult to achieve widespread multilingual language competence beyond English through formal education in Europe. In Sweden, high dropout rates have been recorded in second foreign language (SFL) classes, and French is currently the most vulnerable language among the major SFLs with respect to the number of pupils and availability across the country. Therefore, an important question is how to increase the motivation for studying foreign languages other than English (LOTE), especially French. This paper reports on a semester-long quasi-experimental intervention study, with three activities designed to enhance pupils’ ideal L3 self (IL3S) and increase their intended effort (IE) to learn French. Data were collected in two grade 9 intervention classes (n = 45) and in a control class (n = 14) in Sweden using questionnaires and focus group interviews. We measured the effect of the intervention through pre- and post-tests in both groups and additionally after each activity in the intervention classes. The results showed no overall significant effect of the intervention, but a positive effect on IE among the students with the highest level of IL3S prior to the intervention. Moreover, gender differences were found for the initial activity on both IL3S and on IE. The results are discussed in relation to the ease of accessing the self-image and characteristics of IL3S that enhance activities and gender effects. Methodological challenges involved in intervention studies with intact classes are also highlighted.
Complementary Protection in Japan: To What Extent Does Japan Offer Effective International Protection for Those Who Fall Outside the 1951 Refugee Convention?
Authors: Aycock Brian , Hashimoto Naoko
Published: March 2021

This study focuses on what Japan’s Immigration Control and Refugee Recognition Act (ICRRA) calls ‘Special Permission to Stay’ (zairyū tokubetsu kyoka) on humanitarian grounds (SPS), and evaluates the extent to which SPS provides effective international protection for those who are not recognized as refugees in Japan. The evaluation uses the European Union’s Qualification Directive (QD) as a yardstick. This paper explains the legal framework through which Japan offers complementary protection and explores the application of the law in practice. By investigating cases of SPS granted in Japan over a five-year period, the authors infer the prevailing legal interpretations on critical elements of complementary protection policy not clearly defined in the ICRRA. Case law is not widely available in Japan, but the authors have analysed all of the available case summaries provided by the Ministry of Justice only in Japanese. This work represents the first research conducted in English into these summaries. Further, several elite interviews were conducted with key senior immigration officials to gain insight into the inner workings of the Japanese system of SPS. Based upon the empirical evidence collected, the research demonstrates that the ICRRA often lacks clarity and is too discretionary, but that it also provides flexibility that allows a more inclusive application of the law.
Cross-Disorder Analysis of De Novo Variants Increases the Power of Prioritising Candidate Genes
Authors: Li Kuokuo , Ling Zhengbao , Luo Tengfei , Zhao Guihu , Zhou Qiao , Wang Xiaomeng , Xia Kun , Li Jinchen , Li Bin
Published: March 2021

De novo variants (DNVs) are critical to the treatment of neurodevelopmental disorders (NDDs). However, effectively identifying candidate genes in small cohorts is challenging in most NDDs because of high genetic heterogeneity. We hypothesised that integrating DNVs from multiple NDDs with genetic similarity can significantly increase the possibility of prioritising the candidate gene. We catalogued 66,186 coding DNVs in 50,028 individuals with nine types of NDDs in cohorts with sizes spanning from 118 to 31,260 from Gene4Denovo database to validate this hypothesis. Interestingly, we found that integrated DNVs can effectively increase the number of prioritised candidate genes for each disorder. We identified 654 candidate genes including 481 shared candidate genes carrying putative functional variants in at least two disorders. Notably, 13.51% (65/481) of shared candidate genes were prioritised only via integrated analysis including 44.62% (29/65) genes validated in recent large cohort studies. Moreover, we estimated that more novel candidate genes will be prioritised with the increase in cohort size, in particular for some disorders with high putative functional DNVs per individual. In conclusion, integrated DNVs may increase the power of prioritising candidate genes, which is important for NDDs with small cohort size.
A Relationship between NTP and Cell Extract Concentration for Cell-Free Protein Expression
Authors: Takahashi Katsuki , Sato Gaku , Doi Nobuhide , Fujiwara Kei
Published: March 2021

The cell-free protein synthesis (CFPS) that synthesizes mRNA and protein from a template DNA has been featured as an important tool to emulate living systems in vitro. However, an obstacle to emulate living cells by CFPS is the loss of activity in the case of usage of high concentration cell extracts. In this study, we found that a high concentration of NTP which inhibits in the case of lower concentration cell extract restored the loss of CFPS activity using high concentration cell extracts. The NTP restoration was independent of the energy regeneration system used, and NTP derivatives also restored the levels of CFPS using a high concentration cell extract. Experiments using dialysis mode of CFPS showed that continuous exchange of small molecule reduced levels of NTP requirement and improved reaction speed of CFPS using the high concentration of cell extract. These findings contribute to the development of a method to understand the condition of living cells by in vitro emulation, and are expected to lead to the achievement of the reconstitution of living cells from biomolecule mixtures.
Oligodendroglial Energy Metabolism and (re)Myelination
Authors: Tepavčević Vanja
Published: March 2021

Central nervous system (CNS) myelin has a crucial role in accelerating the propagation of action potentials and providing trophic support to the axons. Defective myelination and lack of myelin regeneration following demyelination can both lead to axonal pathology and neurodegeneration. Energy deficit has been evoked as an important contributor to various CNS disorders, including multiple sclerosis (MS). Thus, dysregulation of energy homeostasis in oligodendroglia may be an important contributor to myelin dysfunction and lack of repair observed in the disease. This article will focus on energy metabolism pathways in oligodendroglial cells and highlight differences dependent on the maturation stage of the cell. In addition, it will emphasize that the use of alternative energy sources by oligodendroglia may be required to save glucose for functions that cannot be fulfilled by other metabolites, thus ensuring sufficient energy input for both myelin synthesis and trophic support to the axons. Finally, it will point out that neuropathological findings in a subtype of MS lesions likely reflect defective oligodendroglial energy homeostasis in the disease.
How Effective Is Auditory–Verbal Therapy (AVT) for Building Language Development of Children with Cochlear Implants? A Systematic Review
Authors: Binos Paris , Nirgianaki Elina , Psillas George
Published: March 2021

This systematic review sheds light on the effectiveness of auditory–verbal therapy (AVT) outcomes in children with cochlear implants (CIs). The presented outcome is based on research findings from the last 10 years. The systematic review was designed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and Critical Appraisal of Treatment Evidence (CATE) checklist. Specific keywords were chosen based on the research question and searched on the PubMed database. All searched papers were analysed based on specific exclusion criteria and classified into four evidence levels. The results revealed that children who participated in AV therapy can achieve linguistic skills at the same level as their hearing peers. Voice quality seemed positively affected, placing young children with CIs in the normal range for receptive vocabulary development. In contrast, reading skills seemed less benefited. AV therapy seems to contribute to integration into mainstream society. Despite the recorded speech and language improvements of young children with CIs, the aim of AV therapy is still not fulfilled. AV therapy can be seen as the best clinical practice for young children with CIs till now, but the lack of well-controlled studies is undermining.
Use of Different Types of Biosorbents to Remove Cr (VI) from Aqueous Solution
Authors: Pertile Eva , Dvorský Tomáš , Václavík Vojtěch , Heviánková Silvie
Published: March 2021

This article summarizes the results of a research study that was focused on the possibility of removing Cr (VI) from aqueous solution, using low-cost waste biomaterial in a batch mode. A set of seven biosorbents was used: Fomitopsis pinicola, a mixture of cones, peach stones, apricot stones, Juglans regia shells, orange peels, and Merino sheep wool. Three grain fractions (fr. 1/2, fr. 0.5/1.0, and fr. 0/0.5 mm) of biosorbents were studied. The aim was to find the most suitable biosorbent that can be tested with real samples. The influence of other factors on the course of biosorption was studied as well (chemical activation of the biosorbent, pH value, rotation speed during mixing, temperature, and the influence of biosorbent concentration). The use of chemical activation and adjustment of the pH to 1.1 to 2.0 make it possible to increase their sorption capacity and, for some biosorbents, to shorten the exposure times. Two kinetic models were used for the analysis of the experimental data, to explain the mechanism of adsorption and its possible speed control steps: pseudo-first and pseudo-second-order. The pseudo-second-order kinetic model seems to be the most suitable for the description of the experimental data. The thermodynamic parameters suggest that the biosorption was endothermic and spontaneous. In the biosorption equilibrium study, the adsorption data were described by using Langmuir and Freundlich adsorption isotherms. The Langmuir model was applicable to describe the adsorption data of all biosorbents. Both models are suitable for chemically treated sheep fleece and peach stones.
Molecular and Supramolecular Structure of the Mitochondrial Oxidative Phosphorylation System: Implications for Pathology
Authors: Nesci Salvatore , Trombetti Fabiana , Pagliarani Alessandra , Ventrella Vittoria , Algieri Cristina , Tioli Gaia , Lenaz Giorgio
Published: March 2021

Under aerobic conditions, mitochondrial oxidative phosphorylation (OXPHOS) converts the energy released by nutrient oxidation into ATP, the currency of living organisms. The whole biochemical machinery is hosted by the inner mitochondrial membrane (mtIM) where the protonmotive force built by respiratory complexes, dynamically assembled as super-complexes, allows the F1FO-ATP synthase to make ATP from ADP + Pi. Recently mitochondria emerged not only as cell powerhouses, but also as signaling hubs by way of reactive oxygen species (ROS) production. However, when ROS removal systems and/or OXPHOS constituents are defective, the physiological ROS generation can cause ROS imbalance and oxidative stress, which in turn damages cell components. Moreover, the morphology of mitochondria rules cell fate and the formation of the mitochondrial permeability transition pore in the mtIM, which, most likely with the F1FO-ATP synthase contribution, permeabilizes mitochondria and leads to cell death. As the multiple mitochondrial functions are mutually interconnected, changes in protein composition by mutations or in supercomplex assembly and/or in membrane structures often generate a dysfunctional cascade and lead to life-incompatible diseases or severe syndromes. The known structural/functional changes in mitochondrial proteins and structures, which impact mitochondrial bioenergetics because of an impaired or defective energy transduction system, here reviewed, constitute the main biochemical damage in a variety of genetic and age-related diseases.
Regulation of Inflammation and Oxidative Stress by Formyl Peptide Receptors in Cardiovascular Disease Progression
Authors: Caso Valentina Maria , Manzo Valentina , Pecchillo Cimmino Tiziana , Conti Valeria , Caso Pio , Esposito Gabriella , Russo Vincenzo , Filippelli Amelia , Ammendola Rosario , Cattaneo Fabio
Published: March 2021

G protein-coupled receptors (GPCRs) are the most important regulators of cardiac function and are commonly targeted for medical therapeutics. Formyl-Peptide Receptors (FPRs) are members of the GPCR superfamily and play an emerging role in cardiovascular pathologies. FPRs can modulate oxidative stress through nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent reactive oxygen species (ROS) production whose dysregulation has been observed in different cardiovascular diseases. Therefore, many studies are focused on identifying molecular mechanisms of the regulation of ROS production. FPR1, FPR2 and FPR3 belong to the FPRs family and their stimulation triggers phosphorylation of intracellular signaling molecules and nonsignaling proteins that are required for NADPH oxidase activation. Some FPR agonists trigger inflammatory processes, while other ligands activate proresolving or anti-inflammatory pathways, depending on the nature of the ligands. In general, bacterial and mitochondrial formylated peptides activate a proinflammatory cell response through FPR1, while Annexin A1 and Lipoxin A4 are anti-inflammatory FPR2 ligands. FPR2 can also trigger a proinflammatory pathway and the switch between FPR2-mediated pro- and anti-inflammatory cell responses depends on conformational changes of the receptor upon ligand binding. Here we describe the detrimental or beneficial effects of the main FPR agonists and their potential role as new therapeutic and diagnostic targets in the progression of cardiovascular diseases.
On the Fictitious Grease Lubrication Performance in a Four-Ball Tester
Authors: Joysula Sravan K. , Dube Anshuman , Patro Debdutt , Veeregowda Deepak Halenahally
Published: March 2021

The extreme pressure (EP) behavior of grease is related to its additives that can prevent seizure. However, in this study following ASTM D2596 four-ball test method, the EP behavior of greases was modified without any changes to its additive package. A four-ball tester with position encoders and variable frequency drive system was used to control the speed ramp up time or delay in motor speed to demonstrate higher grease weld load and lower grease friction that were fictitious. A tenth of a second delay in speed ramp up time had showed an increase in the weld load from 7848 N to 9810 N for grease X and 6082 N to 9810 N for grease Y. Further increase in the speed ramp up time to 0.95 s showed that the greases passed the maximum load of 9810 N that was possible in the four-ball tester without seizure. The mechanism can be related to the delay in rise of local temperature to reach the melting point of steel required for full seizure or welding, that was theoretically attributed to an increase in heat loss as the speed ramp-up time was increased. Furthermore, the speed ramp up time increased the corrected load for grease X and Y. This resulted in lower friction for grease X and Y. This fictitious low friction can be attributed to decrease in surface roughness at higher extreme pressure or higher corrected load. This study suggests that speed ramp up time is a critical factor that should be further investigated by ASTM and grease manufacturers, to prevent the use of grease with fictitious EP behavior.
Impact of the Diet on the Formation of Oxidative Stress and Inflammation Induced by Bacterial Biofilm in the Oral Cavity
Authors: Rowińska Ilona , Szyperska-Ślaska Adrianna , Zariczny Piotr , Pasławski Robert , Kramkowski Karol , Kowalczyk Paweł
Published: March 2021

The diet is related to the diversity of bacteria in the oral cavity, and the less diverse microbiota of the oral cavity may favor the growth of pathogenic bacteria of all bacterial complexes. Literature data indicate that disturbances in the balance of the bacterial flora of the oral cavity seem to contribute to both oral diseases, including periodontitis, and systemic diseases. If left untreated, periodontitis can damage the gums and alveolar bones. Improper modern eating habits have an impact on the oral microbiome and the gut microbiome, which increase the risk of several chronic diseases, including inflammatory bowel disease, obesity, type 2 diabetes, cardiovascular disease and cancer. The subject of our consideration is the influence of the traditional diet on the formation of oxidative stress and inflammation caused by bacterial biofilm in the oral cavity. Through dental, biomedical and laboratory studies, we wanted to investigate the effect of individual nutrients contained in specific diets on the induction of oxidative stress inducing inflammation of the soft tissues in the oral cavity in the presence of residual supra- and subgingival biofilm. In our research we used different types of diets marked as W, T, B, F and noninvasively collected biological material in the form of bacterial inoculum from volunteers. The analyzed material was grown on complete and selective media against specific strains of all bacterial complexes. Additionally, the zones of growth inhibition were analyzed based on the disc diffusion method. The research was supplemented with dental and periodontological indicators. The research was supplemented by the application of molecular biology methods related to bacterial DNA isolation, PCR reactions and sequencing. Such selected methods constitute an ideal screening test for the analysis of oral bacterial microbiota. The obtained results suggest that certain types of diet can be an effective prophylaxis in the treatment of civilization diseases such as inflammation of the oral cavity along with periodontal tissues and gingival pockets.
Electrochemical and X-ray Examinations of Erosion Products during Dressing of Superhard Grinding Wheels Using Alternating Current and Ecological Electrolytes of Low Concentration of Chemical Compounds
Authors: Gołąbczak Marcin , Gołąbczak Andrzej , Tomczyk Barbara
Published: March 2021

This article introduces significant cognitive and usable values in the field of abrasive technology especially in the development of new methods of the electrochemical dressing of superhard grinding wheels with metal bonds. Cognitive values mainly concern the elaboration of the theoretical backgrounds of the electrochemical digestion of compounds of grinding wheel metal bond and gumming up products of the cutting surface of grinding wheel (CSGW). Cognitive values also deal with determining the mathematical relationships describing the influence of technological conditions of dressing on shaping of cutting abilities of superhard grinding wheels. On the other hand, the useful values refer to the industry implementation of the elaborated method and equipment for the electrochemical dressing of suparhard grinding wheels using alternating current (ECDGW-AC). The cost of the device for the realization of this process is low and can be applied in the production conditions. The novel achievements presented in the article are: the elaboration of a new method and equipment for electrochemical dressing of superhard grinding wheels (ECDGW-AC), the selection of electrolytes of low concentration of chemical compounds, tests concerning the digestion of grinding wheel metal bond compounds and gumming up products of CSGW using X-ray analysis, as well as the determination of chemical reactions taking place during elaborated new dressing process, the elaboration of mathematical relationships describing influence of technological conditions of this process on dressing speed and shaping of cutting abilities of superhard grinding wheels, and the performance of technological tests of dressing of superhard grinding wheels using ECDGW-AC method. The elaborated method can be used in ambient temperature and does not cause thermal damages of abrasive grains of cutting surface of grinding wheel and is useful not only for dressing super hard grinding wheels but also for correcting their geometrical deviations.
Improvement of the Electronic—Neuronal Interface by Natural Deposition of ECM
Authors: Weigel Tobias , Brennecke Julian , Hansmann Jan
Published: March 2021

The foreign body reaction to neuronal electrode implants limits potential applications as well as the therapeutic period. Developments in the basic electrode design might improve the tissue compatibility and thereby reduce the foreign body reaction. In this work, the approach of embedding 3D carbon nanofiber electrodes in extracellular matrix (ECM) synthesized by human fibroblasts for a compatible connection to neuronal cells was investigated. Porous electrode material was manufactured by solution coelectrospinning of polyacrylonitrile and polyamide as a fibrous porogen. Moreover, NaCl represented an additional particulate porogen. To achieve the required conductivity for an electrical interface, meshes were carbonized. Through the application of two different porogens, the electrodes’ flexibility and porosity was improved. Human dermal fibroblasts were cultured on the electrode surface for ECM generation and removed afterwards. Scanning electron microscopy imaging revealed a nano fibrous ECM network covering the carbon fibers. The collagen amount of the ECM coating was quantified by hydroxyproline-assays. The modification with the natural protein coating on the electrode functionality resulted in a minor increase of the electrical capacity, which slightly improved the already outstanding electrical interface properties. Increased cell numbers of SH-SY5Y cell line on ECM-modified electrodes demonstrated an improved cell adhesion. During cell differentiation, the natural ECM enhanced the formation of neurites regarding length and branching. The conducted experiments indicated the prevention of direct cell-electrode contacts by the modification, which might help to shield temporary the electrode from immunological cells to reduce the foreign body reaction and improve the electrodes’ tissue integration.