bluuebunny/crossref_metadata_2025 huggingface dataset:
Musical Enjoyment and Reward: From Hedonic Pleasure to Eudaimonic Listening
Authors: Reybrouck Mark , Eerola Tuomas
Published: May 2022

This article is a hypothesis and theory paper. It elaborates on the possible relation between music as a stimulus and its possible effects, with a focus on the question of why listeners are experiencing pleasure and reward. Though it is tempting to seek for a causal relationship, this has proven to be elusive given the many intermediary variables that intervene between the actual impingement on the senses and the reactions/responses by the listener. A distinction can be made, however, between three elements: (i) an objective description of the acoustic features of the music and their possible role as elicitors; (ii) a description of the possible modulating factors—both external/exogenous and internal/endogenous ones; and (iii) a continuous and real-time description of the responses by the listener, both in terms of their psychological reactions and their physiological correlates. Music listening, in this broadened view, can be considered as a multivariate phenomenon of biological, psychological, and cultural factors that, together, shape the overall, full-fledged experience. In addition to an overview of the current and extant research on musical enjoyment and reward, we draw attention to some key methodological problems that still complicate a full description of the musical experience. We further elaborate on how listening may entail both adaptive and maladaptive ways of coping with the sounds, with the former allowing a gentle transition from mere hedonic pleasure to eudaimonic enjoyment.
Zero-Carbon Communities: Research Hotspots, Evolution, and Prospects
Authors: Zhu Yunxi , Koutra Sesil , Zhang Jiazhen
Published: May 2022

Global warming is a worldwide concern, with buildings generating more than 40% of the annual global CO2 emissions. A commonly accepted system of global standards for zero-carbon buildings and communities has not yet been established. In this research, the development history, hotspots, and trends at the urban scale with theoretical and data support are summarized based on the Web of Science (WoS) Core Collection. The review contains works from 1997 to 2022. A total of 19,014 papers were collected, with an overall increasing trend in the number of articles with specific keywords. The scope of the research is broad, covering the environment, sciences, ecology, chemistry, material science, physics, meteorology, atmospheric sciences, and so on. The hotspots in the low-carbon community (LCC) and zero-carbon community (ZCC) involve a wide range of disciplines, and collaborative research between related disciplines should be strengthened to propose practical solutions for the development of zero-carbon cities. The establishment of the ZCC mainly focuses on a zero-carbon-emission construction and zero-carbon operations. This research found approaches such as the choices of building construction and material, a waste recycling system, a regenerating energy system, transportation, and an examination of the community composition to realize the ZCC. In the literature it is presented that the difficulties in the construction of the ZCC are due to the lack of research in practice, operation, and subsequent maintenance. Moreover, other scholars can deepen the research on the hotspots of ZCC.
Review of Culture in Maintenance Management of Public Buildings in Developing Countries
Authors: Ogunbayo Babatunde Fatai , Aigbavboa Clinton Ohis , Thwala Wellington , Akinradewo Opeoluwa , Ikuabe Matthew , Adekunle Samuel Adeniyi
Published: May 2022

Studies have shown that culture is one of the significant elements that influence the behavior of doing things the right way, without which there is a hindrance to the attainment of set goals. It has also been stated that culture is essential to maintaining public buildings, which is significant to national development. However, the level of abandonment and deterioration of public buildings is high due to a lack of culture among stakeholders in the maintenance process. Therefore, through a literature review from over 100 recent publications, this study measured culture as a variable that influences effective maintenance management of buildings. This was carried out to enlighten maintenance managers and policymakers within the developing countries regarding the significance of maintenance culture and possible measures for improving the attitude of stakeholders on the maintenance process. It was also carried out to develop a new maintenance focus (behavioral change) for maintenance managers and policymakers, especially in developing countries, to manage the available public buildings and other proposed ones effectively.
Analyzing Electricity Consumption Factors of Buildings in Seoul, Korea Using Multiscale Geographically Weighted Regression
Authors: Jo Hanghun , Kim Heungsoon
Published: May 2022

The recent increase in energy consumption worldwide has accelerated global warming. Thus, developed countries are aiming to reduce energy consumption in cities and promote eco-friendly policies. Buildings account for most of the energy used in a city. Therefore, it is necessary to identify the factors that affect electrical energy consumption in urban buildings. In this study, we use multiscale geographically weighted regression (MGWR) to analyze these urban characteristic factors at the global and local scales in Seoul, Korea. It is found that population and household characteristics, outdoor temperature, green and water areas, building area according to building usage, and construction age significantly affect the electrical energy consumption of buildings. In addition, the influences of these variables change with the region. Variables with different coefficients by region are winter temperature, green and water area, and households with three or more persons. The results confirm that even within a city, the influence of the aforementioned factors varies in terms of spatial distribution and patterns. This study is significant as it carried out basic research for energy consumption reduction in buildings by deriving related influencing factors.
Microclimate of Air Cavities in Ventilated Roof and Façade Systems in Nordic Climates
Authors: Ingebretsen Sara Bredal , Andenæs Erlend , Kvande Tore
Published: May 2022

Accurate values for the climatic conditions in an air cavity, hereby called the microclimate, are crucial when calculating and simulating the performance of a ventilated roof and façade system. The climatic stress of its components and their mould and rot potential influence the long-term durability of the roof or façade. A scoping study is conducted to gain an overview on research and the scientific literature on the microclimate of air cavities in ventilated roofing and claddings in Nordic climates. From the body of the research literature, 21 scientific works were of particular interest, and their findings are summarized. The review shows that only a limited number of studies discuss the microclimate of air cavities. Roofs are discussed to a greater and more varied degree compared to façades and air cavities behind solar panels. However, the results cannot be compared and validated against each other to generally describe the microclimate of air cavities, as the surveyed papers approach the subject differently. This knowledge gap indicates that calculations and simulations can be performed without knowing whether the results represent reality. If the structure of ventilated roof and façade systems are only designed based on experience, it can be difficult to be proactive and adapt to future climate changes. Further studies are needed to determine the relation between the exterior climate and the air cavity microclimate, so that future climate predictions can be used to simulate the long-term performance of ventilated roof and façade systems.
Eight Years of Real-Life Experience with Smoothened Inhibitors in a Swiss Tertiary Skin Referral Center
Authors: Grossmann Lara E. , Ramelyte Egle , Nägeli Mirjam C. , Dummer Reinhard
Published: May 2022

Background: The hedgehog inhibitors vismodegib and sonidegib are approved for the treatment of advanced basal cell carcinoma. This study reports the experiences with these therapies in a tertiary skin referral center in daily practice. Methods: A retrospective, observational, single-center study analyzing medical records of patients with aBCC treated with a smoothened (SMO) inhibitor outside a clinical trial for at least one month between 2013 and 2021. Results: In total, 33 patients were included: 21 (64%) patients were treated with vismodegib, 3 (9%) patients with sonidegib and 9 (27%) patients with both treatments subsequently. With vismodegib, the best overall response was complete response (CR) in 33% cases, and partial response (PR) in 33% cases. Under sonidegib, 42% patients achieved CR and 17% PR. Mean duration to next treatment was 33 and 14 months for vismodegib and sonidegib, respectively. Adverse events varied in frequency between continuous and intermittent dosing and they were the most common reason for therapy discontinuation. Conclusions: Our real-world data illustrate the pitfalls and benefits of HhIs as well as the impact of different dosing regimens on adverse events, patient adherence and response. Treatment duration remains limited by adverse events and resistance. Additional treatment options, including immunotherapy and drug combinations, are needed.
Clinical Management of Neuroendocrine Neoplasms in Clinical Practice: A Formal Consensus Exercise
Authors: Bartolomei Mirco , Berruti Alfredo , Falconi Massimo , Fazio Nicola , Ferone Diego , Lastoria Secondo , Pappagallo Giovanni , Seregni Ettore , Versari Annibale
Published: May 2022

Many treatment approaches are now available for neuroendocrine neoplasms (NENs). While several societies have issued guidelines for diagnosis and treatment of NENs, there are still areas of controversy for which there is limited guidance. Expert opinion can thus be of support where firm recommendations are lacking. A group of experts met to formulate 14 statements relative to diagnosis and treatment of NENs and presented herein. The nominal group and estimate-talk-estimate techniques were used. The statements covered a broad range of topics from tools for diagnosis to follow-up, evaluation of response, treatment efficacy, therapeutic sequence, and watchful waiting. Initial prognostic characterization should be based on clinical information as well as histopathological analysis and morphological and functional imaging. It is also crucial to optimize RLT for patients with a NEN starting from accurate characterization of the patient and disease. Follow-up should be patient/tumor tailored with a shared plan about timing and type of imaging procedures to use to avoid safety issues. It is also stressed that patient-reported outcomes should receive greater attention, and that a multidisciplinary approach should be mandatory. Due to the clinical heterogeneity and relative lack of definitive evidence for NENs, personalization of diagnostic–therapeutic work-up is crucial.
Whole-Exome Sequencing Reveals Clinical Potential of Circulating Tumor DNA from Peritoneal Fluid and Plasma in Endometrial Cancer
Authors: Ju Hye-Yeon , Ho Jung Yoon , Kang Jun , Hur Soo Young , Kim Sejin , Choi Youn Jin , Han Mi-Ryung
Published: May 2022

Endometrial cancer (EC) is the most common type of gynecological cancer. Studies comparing tumor gDNA and ctDNA isolated from the plasma and peritoneal fluid of EC patients are limited. Whole-exome sequencing and P53 immunohistochemistry of 24 paired tissue, plasma, and peritoneal fluid samples from 10 EC patients were performed to analyze somatic mutations, copy number alterations, microsatellite instability, and mutational signatures. Mutations in cancer-related genes (KMT2C, NOTCH2, PRKAR1A, SDHA, and USP6) and genes related to EC (ARID1A, CTNNB1, PIK3CA, and PTEN) were identified with high frequencies among the three samples. TP53 and POLE mutations, which are highly related to the molecular classification of EC, were identified based on several key observations. The ctDNA of two patients with negative peritoneal fluid presented TP53 mutations concordant with those in tissues. ctDNA from the plasma and peritoneal fluid of a patient with positive cytology harbored both TP53 and POLE mutations, although none were detected in tissues. Additionally, the patient presented with wild type P53 immunohistochemistry, with a focal “high” expression in a “low” wild type background. The tissues and peritoneal fluid of 75% EC patients showed concordant microsatellite instability. Furthermore, we observed strong mutational concordance between the peritoneal fluid and tumors. Our data suggest that the ctDNA from peritoneal fluid might be a suitable biomarker for identifying the mutational landscape of EC and could complement tumor heterogeneity.
Single-Cell Analyses of a Novel Mouse Urothelial Carcinoma Model Reveal a Role of Tumor-Associated Macrophages in Response to Anti-PD-1 Therapy
Authors: Xu Dongbo , Wang Li , Wieczorek Kyle , Zhang Yali , Wang Zinian , Wang Jianmin , Xu Bo , Singh Prashant K. , Wang Yanqing , Zhang Xiaojing , Wu Yue , Smith Gary J. , Attwood Kristopher , Zhang Yuesheng , Goodrich David W. , Li Qiang
Published: May 2022

Approximately 80% of patients with advanced bladder cancer do not respond to immune checkpoint inhibitor (ICI) immunotherapy. Therefore, there is an urgent unmet need to develop clinically relevant preclinical models so that factors governing immunotherapy responses can be studied in immunocompetent mice. We developed a line of mouse triple knockout (TKO: Trp53, Pten, Rb1) urothelial carcinoma organoids transplanted into immunocompetent mice. These bladder tumors recapitulate the molecular phenotypes and heterogeneous immunotherapy responses observed in human bladder cancers. The TKO organoids were characterized in vivo and in vitro and compared to the widely used MB49 murine bladder cancer model. RNAseq analysis of the TKO tumors demonstrated a basal subtype. The TKO xenografts demonstrated the expression of urothelial markers (CK5, CK7, GATA3, and p63), whereas MB49 subcutaneous xenografts did not express urothelial markers. Anti-PD-1 immunotherapy resulted in a mixed pattern of treatment responses for individual tumors. Eight immune cell types were identified (basophils, B cells, dendritic cells, macrophages, monocytes, neutrophils, NK cells, and T cells) in ICI-treated xenografts. Responder xenografts displayed significantly increased immune cell infiltration (15.3%, 742 immune cells/4861 total cells) compared to the non-responder tumors (10.1%, 452 immune cells/4459 total cells, Fisher Exact Test p < 0.0001). Specifically, there were more T cells (1.0% vs. 0.4%, p = 0.002) and macrophages (8.6% vs. 6.4%, p = 0.0002) in responder xenografts than in non-responder xenografts. In conclusion, we have developed a novel preclinical model that exhibits a mixed pattern of response to anti-PD-1 immunotherapy. The higher percentage of macrophage tumor infiltration in responders suggests a potential role for the innate immune microenvironment in regulating ICI treatment responses.
Exercise Counteracts the Deleterious Effects of Cancer Cachexia
Authors: Tsitkanou Stavroula , Murach Kevin A. , Washington Tyrone A. , Greene Nicholas P.
Published: May 2022

Cancer cachexia (CC) is a multifactorial syndrome characterised by unintentional loss of body weight and muscle mass in patients with cancer. The major hallmarks associated with CC development and progression include imbalanced protein turnover, inflammatory signalling, mitochondrial dysfunction and satellite cell dysregulation. So far, there is no effective treatment to counteract muscle wasting in patients with CC. Exercise training has been proposed as a potential therapeutic approach for CC. This review provides an overview of the effects of exercise training in CC-related mechanisms as well as how factors such as cancer comorbidities, exercise modality and biological sex can influence exercise effectiveness in CC. Evidence in mice and humans suggests exercise training combats all of the hallmarks of CC. Several exercise modalities induce beneficial adaptations in patients/animals with CC, but concurrent resistance and endurance training is considered the optimal type of exercise. In the case of cancer patients presenting comorbidities, exercise training should be performed only under specific guidelines and precautions to avoid adverse effects. Observational comparison of studies in CC using different biological sex shows exercise-induced adaptations are similar between male and female patients/animals with cancer, but further studies are needed to confirm this.
Role of yUbp8 in Mitochondria and Hypoxia Entangles the Finding of Human Ortholog Usp22 in the Glioblastoma Pseudo-Palisade Microlayer
Authors: De Luca Veronica , Leo Manuela , Cretella Elisabetta , Montanari Arianna , Saliola Michele , Ciaffi Gabriele , Vecchione Andrea , Stoppacciaro Antonella , Filetici Patrizia
Published: May 2022

KAT Gcn5 and DUB Ubp8 are required for respiration and mitochondria functions in budding yeast, and in this study we show that loss of respiratory activity is acquired over time. Interestingly, we show that absence of Ubp8 allows cells to grow in hypoxic conditions with altered mitophagy. Comparatively, the aggressive glioblastoma (GBM) multiforme tumor shows survival mechanisms able to overcome hypoxia in the brain. Starting from yeast and our findings on the role of Ubp8 in hypoxia, we extended our analysis to the human ortholog and signature cancer gene Usp22 in glioblastoma tumor specimens. Here we demonstrate that Usp22 is localized and overexpressed in the pseudo-palisade tissue around the necrotic area of the tumor. In addition, Usp22 colocalizes with the mitophagy marker Parkin, indicating a link with mitochondria function in GBM. Collectively, this evidence suggests that altered expression of Usp22 might provide a way for tumor cells to survive in hypoxic conditions, allowing the escape of cells from the necrotic area toward vascularized tissues. Collectively, our experimental data suggest a model for a possible mechanism of uncontrolled proliferation and invasion in glioblastoma.
Keratinocytes: An Enigmatic Factor in Atopic Dermatitis
Authors: Das Pamelika , Mounika Pappula , Yellurkar Manoj Limbraj , Prasanna Vani Sai , Sarkar Sulogna , Velayutham Ravichandiran , Arumugam Somasundaram
Published: May 2022

Atopic dermatitis (AD), characterized by rashes, itching, and pruritus, is a chronic inflammatory condition of the skin with a marked infiltration of inflammatory cells into the lesion. It usually commences in early childhood and coexists with other atopic diseases such as allergic rhinitis, bronchial asthma, allergic conjunctivitis, etc. With a prevalence rate of 1–20% in adults and children worldwide, AD is gradually becoming a major health concern. Immunological aspects have been frequently focused on in the pathogenesis of AD, including the role of the epidermal barrier and the consequent abnormal cytokine expressions. Disrupted epidermal barriers, as well as allergic triggers (food allergy), contact allergens, irritants, microbes, aggravating factors, and ultraviolet light directly initiate the inflammatory response by inducing epidermal keratinocytes, resulting in the abnormal release of various pro-inflammatory mediators, inflammatory cytokines, and chemokines from keratinocytes. In addition, abnormal proteinases, gene mutations, or single nucleotide polymorphisms (SNP) affecting the function of the epidermal barrier can also contribute towards disease pathophysiology. Apart from this, imbalances in cholinergic or adrenergic responses in the epidermis or the role played by immune cells in the epidermis such as Langerhans cells or antigen-presenting cells can also aggravate pathophysiology. The dearth of specific biomarkers for proper diagnosis and the lack of a permanent cure for AD necessitate investigation in this area. In this context, the widespread role played by keratinocytes in the pathogenesis of AD will be reviewed in this article to facilitate the opening up of new avenues of treatment for AD.
Regulation of Dynamic Cell Adhesion by Integrin-Integrin Crosstalk
Authors: Gahmberg Carl G. , Grönholm Mikaela , Madhavan Sudarrshan
Published: May 2022

Most cells express several integrins. The integrins are able to respond to various cellular functions and needs by modifying their own activation state, but in addition by their ability to regulate each other by activation or inhibition. This crosstalk or transdominant regulation is strictly controlled. The mechanisms resulting in integrin crosstalk are incompletely understood, but they often involve intracellular signalling routes also used by other cell surface receptors. Several studies show that the integrin cytoplasmic tails bind to a number of cytoskeletal and adaptor molecules in a regulated manner. Recent work has shown that phosphorylations of integrins and key intracellular molecules are of pivotal importance in integrin-cytoplasmic interactions, and these in turn affect integrin activity and crosstalk. The integrin β-chains play a central role in regulating crosstalk. In addition to Integrin-integrin crosstalk, crosstalk may also occur between integrins and related receptors, including other adhesion receptors, growth factor and SARS-CoV-2 receptors.
Proteostasis Response to Protein Misfolding in Controlled Hypertension
Authors: Teixeira Manuel , Trindade Dário , Gouveia Marisol , Eller-Borges Roberta , Magalhães Sandra , Duarte Ana , Ferreira Miriam , Simões Maria I. , Conceição Maria , Nunes Alexandra , Henriques Ana Gabriela , Ribeiro Fernando , Vieira Sandra I.
Published: May 2022

Hypertension is the most determinant risk factor for cardiovascular diseases. Early intervention and future therapies targeting hypertension mechanisms may improve the quality of life and clinical outcomes. Hypertension has a complex multifactorial aetiology and was recently associated with protein homeostasis (proteostasis). This work aimed to characterize proteostasis in easy-to-access plasma samples from 40 individuals, 20 with controlled hypertension and 20 age- and gender-matched normotensive individuals. Proteostasis was evaluated by quantifying the levels of protein aggregates through different techniques, including fluorescent probes, slot blot immunoassays and Fourier-transform infrared spectroscopy (FTIR). No significant between-group differences were observed in the absolute levels of various protein aggregates (Proteostat or Thioflavin T-stained aggregates; prefibrillar oligomers and fibrils) or total levels of proteostasis-related proteins (Ubiquitin and Clusterin). However, significant positive associations between Endothelin 1 and protein aggregation or proteostasis biomarkers (such as fibrils and ubiquitin) were only observed in the hypertension group. The same is true for the association between the proteins involved in quality control and protein aggregates. These results suggest that proteostasis mechanisms are actively engaged in hypertension as a coping mechanism to counteract its pathological effects in proteome stability, even when individuals are chronically medicated and presenting controlled blood pressure levels.
The Regulatory-T-Cell Memory Phenotype: What We Know
Authors: Khantakova Julia N. , Bulygin Aleksey S. , Sennikov Sergey V.
Published: May 2022

In immunology, the discovery of regulatory T (Treg) cells was a major breakthrough. Treg cells play a key role in pregnancy maintenance, in the prevention of autoimmune responses, and in the control of all immune responses, including responses to self cells, cancer, infection, and a transplant. It is currently unclear whether Treg cells are capable of long-term memory of an encounter with an antigen. Although the term “immunological memory” usually means an enhanced ability to protect the body from reinfection, the memory of the suppressive activity of Treg cells helps to avoid the state of generalized immunosuppression that may result from the second activation of the immune system. In this review, we would like to discuss the concept of regulatory memory and in which tissues memory Treg cells can perform their functions.
Dopamine Reduces SARS-CoV-2 Replication In Vitro through Downregulation of D2 Receptors and Upregulation of Type-I Interferons
Authors: Limanaqi Fiona , Zecchini Silvia , Dino Borana , Strizzi Sergio , Cappelletti Gioia , Utyro Olga , Vanetti Claudia , Garziano Micaela , Saulle Irma , Clerici Mario , Biasin Mara
Published: May 2022

Recent evidence suggests that SARS-CoV-2 hinders immune responses via dopamine (DA)-related mechanisms. Nonetheless, studies addressing the specific role of DA in the frame of SARS-CoV-2 infection are still missing. In the present study, we investigate the role of DA in SARS-CoV-2 replication along with potential links with innate immune pathways in CaLu-3 human epithelial lung cells. We document here for the first time that, besides DA synthetic pathways, SARS-CoV-2 alters the expression of D1 and D2 DA receptors (D1DR, D2DR), while DA administration reduces viral replication. Such an effect occurs at non-toxic, micromolar-range DA doses, which are known to induce receptor desensitization and downregulation. Indeed, the antiviral effects of DA were associated with a robust downregulation of D2DRs both at mRNA and protein levels, while the amount of D1DRs was not significantly affected. While halting SARS-CoV-2 replication, DA, similar to the D2DR agonist quinpirole, upregulates the expression of ISGs and Type-I IFNs, which goes along with the downregulation of various pro-inflammatory mediators. In turn, administration of Type-I IFNs, while dramatically reducing SARS-CoV-2 replication, converges in downregulating D2DRs expression. Besides configuring the CaLu-3 cell line as a suitable model to study SARS-CoV-2-induced alterations at the level of the DA system in the periphery, our findings disclose a previously unappreciated correlation between DA pathways and Type-I IFN response, which may be disrupted by SARS-CoV-2 for host cell invasion and replication.
Hypoxia Induces Autophagy in Human Dendritic Cells: Involvement of Class III PI3K/Vps34
Authors: Monaci Sara , Coppola Federica , Rossi Daniela , Giuntini Gaia , Filippi Irene , Marotta Giuseppe , Sozzani Silvano , Carraro Fabio , Naldini Antonella
Published: May 2022

Hypoxia is a component of both physiological and pathological conditions, including inflammation, solid tumors, and lymphoid tissues, where O2 demand is not balanced by O2 supply. During their lifespan, dendritic cells (DCs) are exposed to different pO2 and activate different adaptive responses, including autophagy, to preserve their viability and functions. Autophagy plays multiple roles in DC physiology. Very recently, we demonstrated that hypoxia shapes autophagy in DCs upon their differentiation state. Here, we proposed a role for PI3Ks, and especially class III PI3K/Vps34, that could be relevant in hypoxia-induced autophagy, in either immature or mature DCs. Hypoxia inhibited mTOR phosphorylation and activated a pro-autophagic program. By using different pharmacological inhibitors, we demonstrated that hypoxia-induced autophagy was mediated by PI3Ks, especially by Vps34. Furthermore, Vps34 expression was enhanced by LPS, a TLR4 ligand, along with the promotion of autophagy under hypoxia. The Vps34 inhibitor, SAR405, abolished hypoxia-induced autophagy, inhibited pro-survival signaling and viability, and increased the expression of proinflammatory cytokines. Our results underlined the impact of autophagy in the maintenance of DC homeostasis at both cell survival and inflammatory response levels, therefore, contributing to a better understanding of the significance of autophagy in DC physiology and pathology.
The Search for Cancer Biomarkers: Assessing the Distribution of INDEL Markers in Different Genetic Ancestries
Authors: Andrade Roberta B. , Cavalcante Giovanna C. , Amador Marcos A. T. , Moreira Fabiano Cordeiro , Khayat André S. , Assumpção Paulo P. , Ribeiro-dos-Santos Ândrea , Santos Ney P. C. , Santos Sidney
Published: May 2022

Cancer is a multifactorial group of diseases, being highly incident and one of the leading causes of death worldwide. In Brazil, there is a great variation in cancer incidence and impact among the different geographic regions, partly due to the genetic heterogeneity of the population in this country, composed mainly by European (EUR), Native American (NAM), African (AFR), and Asian (ASN) ancestries. Among different populations, genetic markers commonly present diverse allelic frequencies, but in admixed populations, such as the Brazilian population, data is still limited, which is an issue that might influence cancer incidence. Therefore, we analyzed the allelic and genotypic distribution of 12 INDEL polymorphisms of interest in populations from the five Brazilian geographic regions and in populations representing EUR, NAM, AFR, and ASN, as well as tissue expression in silico. Genotypes were obtained by multiplex PCR and the statistical analyses were done using R, while data of tissue expression for each marker was extracted from GTEx portal. We highlight that all analyzed markers presented statistical differences in at least one of the population comparisons, and that we found 39 tissues to be differentially expressed depending on the genotype. Here, we point out the differences in genotype distribution and gene expression of potential biomarkers for risk of cancer development and we reinforce the importance of this type of study in populations with different genetic backgrounds.
DeepMHADTA: Prediction of Drug-Target Binding Affinity Using Multi-Head Self-Attention and Convolutional Neural Network
Authors: Deng Lei , Zeng Yunyun , Liu Hui , Liu Zixuan , Liu Xuejun
Published: May 2022

Drug-target interactions provide insight into the drug-side effects and drug repositioning. However, wet-lab biochemical experiments are time-consuming and labor-intensive, and are insufficient to meet the pressing demand for drug research and development. With the rapid advancement of deep learning, computational methods are increasingly applied to screen drug-target interactions. Many methods consider this problem as a binary classification task (binding or not), but ignore the quantitative binding affinity. In this paper, we propose a new end-to-end deep learning method called DeepMHADTA, which uses the multi-head self-attention mechanism in a deep residual network to predict drug-target binding affinity. On two benchmark datasets, our method outperformed several current state-of-the-art methods in terms of multiple performance measures, including mean square error (MSE), consistency index (CI), rm2, and PR curve area (AUPR). The results demonstrated that our method achieved better performance in predicting the drug–target binding affinity.
In Vitro Assessment of Bio-Functional Properties from Lactiplantibacillus plantarum Strains
Authors: Letizia Francesco , Albanese Gianluca , Testa Bruno , Vergalito Franca , Bagnoli Diletta , Di Martino Catello , Carillo Petronia , Verrillo Lucia , Succi Mariantonietta , Sorrentino Elena , Coppola Raffaele , Tremonte Patrizio , Lombardi Silvia Jane , Di Marco Roberto , Iorizzo Massimo
Published: May 2022

In recent years, alongside the conventional screening procedures for the evaluation of probiotics for human usage, the pharmaceutical and food industries have encouraged scientific research towards the selection of new probiotic bacterial strains with particular functional features. Therefore, this study intended to explore novel functional properties of five Lactiplantibacillus plantarum strains isolated from bee bread. Specifically, antioxidant, antimicrobial and β-glucosidase activities, exopolysaccharides (EPS) production and the ability to synthesize γ-aminobutyric acid (GABA) were evaluated. The results demonstrated that the investigated L. plantarum strains were effective in inhibiting the growth of some human opportunistic pathogens in vitro (Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Enterococcus faecalis and Staphylococcus aureus). Moreover, the evaluation of antioxidant and β-glucosidase activity and of EPS and GABA production, revealed a different behavior among the strains, testifying how these properties are strongly strain-dependent. This suggests that a careful selection within a given species is important in order to identify appropriate strains for specific biotechnological applications. The results highlighted that the five strains of L. plantarum are promising candidates for application as dietary supplements in the human diet and as microbial cultures in specific food productions.
Sandwich Structure to Enhance the Mechanical and Electrochemical Performance of TaN/(Ta/Ti)/TiN Multilayer Films Prepared by Multi-Arc Ion Plating
Authors: Tu Rong , Yang Mai , Yuan Yang , Min Rui , Li Qizhong , Yang Meijun , Ji Baifeng , Zhang Song
Published: May 2022

TaN/(Ta/Ti)/TiN multilayer films at various target to substrate distances (dts), composed of hexagonal TaN, (t-Ta/fcc-Ti) and fcc-TiN with a sandwich structure, were prepared via multi-arc ion plating. With increasing dts, the deposition rate of the films first increased and then decreased, and the average grain size increased from 11.9 to 13.9 nm and then decreased to 10.4 nm. The TaN/(Ta/Ti)/TiN multilayer films have a high ratio of hardness to elastic modulus (H/E*) and H3/E*2 ratios, displaying an outstanding level of both hardness and toughness compared with Ta-related films. The nano-multilayer TaTi interlayers inhibited the columnar structure and prolonged the corrosion diffusion path by increasing stable interfaces. The TaN/(Ta/Ti)/TiN multilayer film at dts = 220 mm exhibited comprehensive properties, including a high hardness of 25 GPa, strong adhesion strength of 68 N, low coefficient of friction of 0.41, low wear rate of 2.7 × 10−6 mm3(mN)−1 and great corrosion resistance in 3.5 wt% NaCl solution, showing promising application as a protective coating.
Intumescent Coatings for Fire Resistance of Steel Structures: Current Approaches for Qualification and Design
Authors: de Silva Donatella , Nuzzo Iolanda , Nigro Emidio , Occhiuzzi Antonio
Published: May 2022

Intumescent coatings (ICs) are often used for protecting steel buildings during a fire when the structural, aesthetic, and architectural features of the structural members should be preserved. Indeed, ICs form a thin protective layer on the steel surface, that if exposed to fire or elevated temperatures, expands in volume with a consequent reduction in density. Hence, the protective layer captivates heat and protects the structural member from damage or elevated deformation. This reactive fire protection is designed using prescriptive tables, in which the IC thickness is chosen according to the required fire resistance, critical temperature, and section factor of the steel element. These tables are elaborated on the basis of the tests results according to the UNI EN 13381-8 standard, which is the reference for characterizing reactive systems such as ICs. For its reactive nature, this fire protection has to be applied to the structure in a controlled manner, and it is good practice to verify its correct application by measuring thickness and adhesion in situ through regulated methods. The qualification process of IC systems in Italy can be realized through a voluntary certification within the scope of a European technical assessment or by means of a national technical assessment certificate that is mandatory. All these aspects related to qualification, assessment, and design of ICs are often ignored by both designers and manufacturers, especially in Italy. Therefore, this paper describes all the approaches, introducing the main technical differences, in order to provide a sort of guideline on the use of these reactive fire protections.
Gas Sensors Based on Titanium Oxides (Review)
Authors: Ramanavicius Simonas , Jagminas Arunas , Ramanavicius Arunas
Published: May 2022

Nanostructured titanium compounds have recently been applied in the design of gas sensors. Among titanium compounds, titanium oxides (TiO2) are the most frequently used in gas sensing devices. Therefore, in this review, we are paying significant attention to the variety of allotropic modifications of titanium oxides, which include anatase, rutile, brukite. Very recently, the applicability of non-stoichiometric titanium oxide (TiO2−x)-based layers for the design of gas sensors was demonstrated. For this reason, in this review, we are addressing some research related to the formation of non-stoichiometric titanium oxide (TiO2−x) and Magnéli phase (TinO2n−1)-based layers suitable for sensor design. The most promising titanium compounds and hetero- and nano-structures based on these compounds are discussed. It is also outlined that during the past decade, many new strategies for the synthesis of TiO2 and conducting polymer-based composite materials were developed, which have found some specific application areas. Therefore, in this review, we are highlighting how specific formation methods, which can be used for the formation of TiO2 and conducting polymer composites, can be applied to tune composite characteristics that are leading towards advanced applications in these specific technological fields. The possibility to tune the sensitivity and selectivity of titanium compound-based sensing layers is addressed. In this review, some other recent reviews related to the development of sensors based on titanium oxides are overviewed. Some designs of titanium-based nanomaterials used for the development of sensors are outlined.
Computed Tomographic Epidurography in Patients with Low Back Pain and Leg Pain: A Single-Center Observational Study
Authors: Yokosuka Kimiaki , Sato Kimiaki , Yamada Kei , Yoshida Tatsuhiro , Shimazaki Takahiro , Morito Shinji , Nishida Kouta , Matsuo Atsushi , Fudo Takuma , Shiba Naoto
Published: May 2022

This study was conducted to analyze the findings and benefits of computed tomography (CT) epidurography in patients with low back and leg pain and compare these findings with those of magnetic resonance imaging (MRI) images. In total, 495 intervertebral discs from 99 patients with low back and leg pain who underwent percutaneous epidural adhesiolysis (epidural neuroplasty or percutaneous adhesiolysis) were examined. The axial views of CT epidurography were classified into six types to examine each intervertebral disc: round type, ellipse type, spike type, Benz mark, incomplete block, complete block, and non-contrast. MRI images were graded from A to D using the Schizas classification. Notably, 176 images were round-type and ellipse-type axial views, and 138 were spike-type and Benz-mark views; Schizas classification Grades A and B were observed in 272 and 47 MRI images, respectively. The incomplete block and complete block axial images did not significantly differ in CT epidurography and Schizas classification Grades C and D. The images showing Benz marks existed only at the L4/5 and L5/S intervertebral levels and only in 14.7% of patients. The ratio of normal shadows differed between MRI images and CT epidurography. Therefore, CT epidurography may enable a detailed evaluation of the epidural space.
Unusual Clinical Manifestations in a Mexican Patient with Sanfilippo B Syndrome
Authors: Fernández-Hernández Liliana , Reyna-Fabián Miriam Erandi , Alcántara-Ortigoza Miguel Angel , Aláez-Verson Carmen , Flores-Lagunes Luis L. , Carrillo-Sánchez Karol , González-del Angel Ariadna
Published: May 2022

We present an unusual Mexican patient affected with mucopolysaccharidosis type IIIB (MPS IIIB; also called Sanfilippo B syndrome, MIM #252920) bearing clinical features that have not previously been described for MPS IIIB (growth arrest, hypogonadotropic hypogonadism, and congenital heart disease). Chromosomal microarray analysis was useful in identifying runs of homozygosity at 17q11.1–q21.33 and supporting the diagnosis of an underlying autosomal recessive condition. Sanger sequencing of NAGLU (17q21.2, MIM*609701) allowed us to identify a pathogenic homozygous p.(Arg234Cys) genotype. This NAGLU allele could be related to that previously described in an Iberian MPS IIIB founder haplotype; results from the polymorphic marker D17S800 and rs2071046 led us to hypothesize that it may have been introduced to Mexico through the Spanish settlement. The analysis of a clinical exome sequencing ruled out other monogenic etiologies for the previously undescribed clinical MPS IIIB manifestations. Our findings contribute to further delineating the MPS IIIB phenotype and suggest possible phenotype–genotype correlations.
Hepatocellular Carcinoma with Gastrointestinal Involvement: A Systematic Review
Authors: Urhut Cristiana Marinela , Sandulescu Larisa Daniela , Streba Liliana , Iovanescu Vlad Florin , Sandulescu Sarmis Marian , Danoiu Suzana
Published: May 2022

In this paper, we aimed to evaluate clinical and imagistic features, and also to provide a diagnostic algorithm for patients presenting with gastrointestinal involvement from hepatocellular carcinoma (HCC). We conducted a systematic search on the PubMed, Scopus and Web of Science databases to identify and collect papers oncases of HCC with gastrointestinal involvement. This search was last updated on 29 April 2022. One hundred and twenty-three articles were included, corresponding to 197 patients. The majority of the patients were male (87.30%), with a mean age of 61.21 years old. The analysis showed large HCCs located mainly in the right hepatic lobe, and highly elevated alfa-fetoprotein (mean = 15,366.18 ng/mL). The most frequent etiological factor was hepatitis B virus (38.57%). Portal vein thrombosis was present in 27.91% of cases. HCC was previously treated in most cases by transarterial chemoembolization (32.99%) and surgical resection (28.93%). Gastrointestinal lesions, developed mainly through direct invasion and hematogenous routes, were predominantly detected in the stomach and duodenum in equal measure—27.91%. Gastrointestinal bleeding was the most common presentation (49.74%). The main diagnostic tools were esophagogastroduodenoscopy (EGD) and computed tomography. The mean survival time was 7.30 months. Gastrointestinal involvement in HCC should be included in the differential diagnosis of patients with underlying HCC and gastrointestinal manifestations or pathological findings in EGD.
Data Legacies, Epistemic Anxieties, and Digital Imaginaries in Archaeology
Authors: Huggett Jeremy
Published: May 2022

Archaeology operates in an increasingly data-mediated world in which data drive knowledge and actions about people and things. Famously, data has been characterized as “the new oil”, underpinning modern economies and at the root of many technological transformations in society at large, even assuming a near-religious power over thought and action. As the call for this Special Issue recognizes, archaeological research is socially and historically situated and consequently influenced by these same broader developments. In archaeology, as in the wider world, data is the foundation for knowledge, but its capacity is rarely reflected upon. This paper offers just such a reflection: a meditation on the nature of archaeological digital data and the challenges for its (re)use. It asks what we understand by data: its etymology and comprehension, its exceptionality and mutability, its constructs and infrastructures, and its origins and consequences. The concept of the archaeological data imaginary is introduced to better understand approaches to the collection and use of archaeological data, and a case study examines how knowledge is mediated and remediated through the data embedded in grey literature. Appreciating the volatility and unpredictability of digital data is key in understanding its potential for use and reuse in the creation of archaeological knowledge.
Metaverse Framework: A Case Study on E-Learning Environment (ELEM)
Authors: Dahan Neama A. , Al-Razgan Muna , Al-Laith Ali , Alsoufi Muaadh A. , Al-Asaly Mahfoudh S. , Alfakih Taha
Published: May 2022

Metaverse is a vast term that can contain every digital thing in the future. Therefore, life domains, such as learning and education, should have their systems redirected to adopt this topic to keep their availability and longevity. Many papers have discussed the metaverse, the applications to run on, and the historical progress to have the metaverse the way it is today. However, the framework of the metaverse itself is still unclear, and its components cannot be exactly specified. Although E-Learning systems are a need that has developed over the years along with technology, the structures of the available E-Learning systems based on the metaverse are either not well described or are adopted, in their best case, as just a 3D environment. In this paper, we examine some previous works to find out the special technologies that should be provided by the metaverse framework, then we discuss the framework of the metaverse if applied as an E-Learning environment framework. This will make it easy to develop future metaverse-based applications, as the proposed framework will make the virtual learning environments work smoothly on the metaverse. In addition, E-Learning will be a more interactive and pleasant process.
Oxidation of Antipsychotics
Authors: Shnayder Natalia A. , Abdyrakhmanova Aiperi K. , Nasyrova Regina F.
Published: May 2022

Antipsychotics (APs) are psychotropic drugs that generally have a psycholeptic effect, capable of reducing psychotic symptoms and psychomotor agitation. This class of drugs is widely used in psychiatric practice, especially for the treatment of psychosis in schizophrenia and other psychotic disorders. Most APs pass through a biotransformation process, or metabolism, after they enter the body before being eliminated. There are three phases of AP metabolism. Cytochrome P450 (CYP) monooxygenase (mixed-function oxidase) plays a central role in most AP biotransformation. CYP’s functional activity depends on gene–drug and drug–drug interaction and influences on the occurrence of adverse drug reactions (ADRs). So, it is extremely important for a practicing psychiatrist to know the oxidation pathway of APs, since most of them are metabolized in the liver. This is important both to prevent ADRs and to avoid unwanted drug–drug interactions, which will undoubtedly increase the effectiveness and safety of AP therapy.
Heterogeneous Responses of Alpine Treelines to Climate Warming across the Tibetan Plateau
Authors: Wang Yafeng , Li Daihan , Ren Ping , Ram Sigdel Shalik , Camarero Jesús Julio
Published: May 2022

The Tibetan Plateau hosts a continuous distribution of alpine treelines from the Qilian Mountains to the Hengduan Mountains and the Himalaya Mountains. However, not much is known about the broadscale alpine treeline dynamics and their responses to climate warming across the Tibetan Plateau. Herein, we collected a total of 59 treeline sites across different forest regions of the Tibetan Plateau and the related field data (i.e., upward advance magnitude, tree recruitment and height growth), expansion potential (i.e., elevational difference between the current treeline and the tree species line (EP)) and vegetation TI (an index of species interactions) from the published references. Site characteristics (e.g., elevation, slope and aspect) and the related environmental factors were used to analyze the relationships between treeline shifts and environmental variables. Despite increases in the recruitment and growth of trees at most treeline sites, alpine treeline positions showed heterogeneous responses to climate warming. Most treelines advanced over the last century, while some treelines showed long-term stability. EP was significantly and positively linked to the summer warming rate and treeline shifts, suggesting that the position of current tree species line is of crucial importance in evaluating treeline dynamics under climate change. In addition, warming-induced treeline advances were modulated by plant–plant interactions. Overall, this study highlighted the heterogeneous responses of regional-scale alpine treelines to climate warming on the Tibetan Plateau.