bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the Impacts of Urban Community Leisure on Subjective Well-Being during COVID-19: A Mixed Methods Case Study
Authors: Wang Jinwei , Zhang Liyan , Sun Yue , Lu Guangjuan , Chen Yanbin , Zhang Saiyin
Published: July 2022

Participating in community leisure activities has become an important way for the public to pursue good health and a high quality of life. However, few studies have focused on the health and welfare effects of participating in urban leisure activities during the COVID-19 pandemic. In response to this gap in the literature, this study drew on the stimulus–organism–response (SOR) theory to examine the effects of community leisure on subjective well-being during the pandemic from the perspective of urban residents. A sample of 1041 urban residents in Beijing, China, was empirically analyzed by applying partial least squares structural equation modeling (PLS-SEM) and fuzzy set qualitative comparative analysis (fsQCA). The PLS-SEM results revealed the net effects of the pandemic influence, leisure satisfaction, leisure environment, and community identity on subjective well-being. The fsQCA provided causal methods for realizing subjective well-being and a necessary condition analysis supplemented the necessary antecedents. The results showed that (1) higher levels of pandemic influence and leisure environment increased leisure satisfaction; (2) pandemic influence, leisure environment, and leisure satisfaction had a positive effect on community identity; (3) pandemic influence, leisure satisfaction, and community identity also combined with leisure environment and leisure time to positively influence subjective well-being; and (4) leisure satisfaction and community identity mediated the impacts of pandemic influence and leisure environment on subjective well-being. This paper contributes not only to empirical evidence but also to theory by constructing and enriching the research models of community leisure and subjective well-being. The practical implications for the public, community managers, and policymakers are also discussed.
Community Wastewater-Based Surveillance Can Be a Cost-Effective Approach to Track COVID-19 Outbreak in Low-Resource Settings: Feasibility Assessment for Ethiopia Context
Authors: Ali Solomon , Gudina Esayas Kebede , Gize Addisu , Aliy Abde , Adankie Birhanemeskel Tegene , Tsegaye Wondwossen , Hundie Gadissa Bedada , Muleta Mahteme Bekele , Chibssa Tesfaye Rufael , Belaineh Rediet , Negessu Demessa , Shegu Dereje , Froeschl Guenter , Wieser Andreas
Published: July 2022

Wastewater surveillance systems have become an important component of COVID-19 outbreak monitoring in high-income settings. However, its use in most low-income settings has not been well-studied. This study assessed the feasibility and utility of wastewater surveillance system to monitor SARS-CoV-2 RNA in Addis Ababa, Ethiopia. The study was conducted at nine Membrane Bio-reactor (MBR) wastewater processing plants. The samples were collected in two separate time series. Wastewater samples and known leftover RT-PCR tested nasopharyngeal swabs were processed using two extraction protocols with different sample conditions. SARS-CoV-2 wastewater RT-PCR testing was conducted using RIDA GENE SARS-CoV-2 RUO protocol for wastewater SARS-CoV-2 RNA testing. Wastewater SARS-CoV-2 RNA RT-PCR protocol adaptation, optimization, and detection were conducted in an Addis Ababa, Ethiopia context. Samples collected during the first time series, when the national COVID-19 case load was low, were all negative. Conversely, samples collected during the second time series were all positive, coinciding with the highest daily reported new cases of COVID-19 in Ethiopia. The wastewater-based SARS-CoV-2 surveillance approach is feasible for Addis Ababa. The COVID-19 wastewater based epidemiological approach can potentially fill the evidence gap in distribution and dynamics of COVID-19 in Ethiopia and other low-income settings.
The Reshaping of the E-Cigarette Retail Environment: Its Evolution and Public Health Concerns
Authors: Berg Carla J. , Melena Albert , Wittman Friedner D. , Robles Tomas , Henriksen Lisa
Published: July 2022

E-cigarette use represents a public health controversy in the US and globally. Despite the potential of e-cigarettes to support cigarette cessation, their use increases health risks and risk for addiction, particularly in young people. Various federal, state, and local laws have impacted tobacco retail in general and e-cigarettes in particular. In the US, 2019–2020 federal laws increased in the minimum legal sales age for tobacco to 21 and banned flavored cartridge-based e-cigarettes. Many states and localities were early adopters of Tobacco 21 and implemented more comprehensive flavor restrictions than the federal ban. Meanwhile, cannabis retail is increasingly being legalized in the US—while cannabis-based product regulation has notable gaps at the federal, state, and local levels. These regulatory complexities have impacted specialized retailers selling e-cigarettes, including “vape shops” that exclusively sell e-cigarettes, “smoke shops” that sell e-cigarettes and other tobacco (and potentially CBD/THC and other un- or under-regulated products), and online retail. This commentary outlines public health concerns related to: (1) youth access; (2) consumer exposure to a broader range of tobacco products and marketing in retail settings where they may seek products to aid in cigarette cessation (i.e., such broad product exposure could hinder cessation attempts); (3) consumer exposure to un-/under-regulated products (e.g., delta-8-THC, kratom); and (4) federal, state, and local regulations being undermined by consumer access to prohibited products online and via the mail. These concerns underscore the need for ongoing surveillance of how retailers and consumers respond to regulations.
A New Health Promotion Program That Includes Wadaiko Rhythm Exercise to Maintain the Health of Persons Excluded from Receiving Specific Health Guidance
Authors: Okuda Suzumi , Tunematsu Miwako , Tabuchi Keiji , Kobayashi Toshio , Kakehashi Masayuki , Nakatani Hisae
Published: July 2022

This study examined the effectiveness of a new health promotion program, which is a collective intervention program aimed at improving lifestyle habits. It was designed as a one-year prospective cohort study. This program targeted non-obese persons at risk of developing lifestyle-related diseases and participants with hypertension, dyslipidemia, or hyperglycemia who were not included in the specific health guidance system in Japan. The Wadaiko rhythm exercise, which is a traditional performing art, is incorporated into this intervention as an enjoyable routine that can help participants continue the program, preventing them from dropping out. After a one-year follow-up, the effectiveness of the health promotion program was evaluated in 18 participants (2 males, 16 females; mean age 65.2 ± 3.4 years) and 92 controls. The results showed that triglyceride in the intervention group significantly decreased (−24.5 mg/dL; p = 0.02; 95% confidence interval [CI], −44.73 to −4.27) and high-density lipoprotein cholesterol significantly increased (+6.1 mg/dL; p < 0.01; 95% CI, 2.46 to 9.65), although levels in the control group did not change. These results suggest that the health promotion program could contribute to lifestyle habit improvements in those who are excluded from receiving specific health guidance.
The Influence of Artificial Light at Night on Asthma and Allergy, Mental Health, and Cancer Outcomes: A Systematic Scoping Review Protocol
Authors: Deprato Andy , Rao Himasha , Durrington Hannah , Maidstone Robert , Adan Ana , Navarro Jose Francisco , Palomar-Cros Anna , Harding Barbara N. , Haldar Prasun , Moitra Saibal , Moitra Tanusree , Melenka Lyle , Kogevinas Manolis , Lacy Paige , Moitra Subhabrata
Published: July 2022

Artificial light at night (ALAN) exposure is associated with the disruption of human circadian processes. Through numerous pathophysiological mechanisms such as melatonin dysregulation, it is hypothesised that ALAN exposure is involved in asthma and allergy, mental illness, and cancer outcomes. There are numerous existing studies considering these relationships; however, a critical appraisal of available evidence on health outcomes has not been completed. Due to the prevalence of ALAN exposure and these outcomes in society, it is critical that current evidence of their association is understood. Therefore, this systematic scoping review will aim to assess the association between ALAN exposure and asthma and allergy, mental health, and cancer outcomes. This systematic scoping review will be conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. We will search bibliographic databases, registries, and references. We will include studies that have described potential sources of ALAN exposure (such as shift work or indoor and outdoor exposure to artificial light); have demonstrated associations with either allergic conditions (including asthma), mental health, or cancer-related outcomes; and are published in English in peer-reviewed journals. We will conduct a comprehensive literature search, title and abstract screening, full-text review, and data collection and analysis for each outcome separately.
The New Age of Organ Donation—What Factors Have an Influence on the Attitude of Older People? An Attitudinal Survey in Southeastern Spain
Authors: Febrero Beatriz , Almela-Baeza Javier , Ros-Madrid Inmaculada , Arias José Alfonso , Ruiz-Manzanera Juan José , Jiménez-Mascuñán María Isabel , Ramírez Pablo
Published: July 2022

Currently, more than half of all donors are aged over 65 years, and previous studies have shown that this group is less willing to support organ donation. Objective: to analyse the attitude of people aged over 65 years toward organ donation and transplantation (ODT) and to determine how their psychosocial profile affects their attitude. Study population: citizens residing in southeastern Spain older than 65 years of age. A representative sample was obtained, which was stratified by gender and geographical location (n = 420). A validated questionnaire about ODT was used. Statistical analysis: a bivariate analysis was performed using the X2 test and a multivariate analysis. The favourable attitude toward the donation of one’s own organs was 53%. The psychosocial variables affecting attitude were mainly: having discussed ODT with one’s family (p < 0.001) or friends (OR 2.223), acceptance of cremation (OR 2.508), and acceptance of an autopsy (OR 2.578). Citizens aged over 65 tend to have an unfavourable attitude toward the donation of their own organs. The lack of dialogue about ODT in social and family settings, and the attitude to the manipulation of one’s own body after death, are aspects of a respondent’s psychosocial profile, which influence this attitude.
Moral Distress and Burnout in Neonatal Intensive Care Unit Healthcare Providers: A Cross-Sectional Study in Italy
Authors: Carletto Sara , Ariotti Maria Chiara , Garelli Giulia , Di Noto Ludovica , Berchialla Paola , Malandrone Francesca , Guardione Roberta , Boarino Floriana , Campagnoli Maria Francesca , Savant Levet Patrizia , Bertino Enrico , Ostacoli Luca , Coscia Alessandra
Published: July 2022

Moral distress (MD) in healthcare providers is widely recognized as a serious issue in critical care contexts. It has the potential to have negative impacts on both personal and professional wellbeing, the quality of care provided and staff turnover. The aim of this study was to investigate the relationship between MD and burnout among neonatal intensive care unit (NICU) healthcare professionals and identify the possible factors associated with its occurrence. Participants were asked to complete an online survey, which covered sociodemographic and professional information and included two self-report questionnaires (Italian Moral Distress Scale-Revised and Maslach Burnout Inventory). The sample comprised 115 healthcare providers (nurses and physiotherapists: 66.1%; physicians: 30.4%; healthcare assistants: 3.5%) working in four NICUs located within the province of Turin, Italy. The results revealed overall low levels of MD, with no significant differences between nurses/physiotherapists and physicians. Nurses/physiotherapists showed a statistically significant higher percentage of personal accomplishment burnout (32.9%) compared with physicians (8.6%; p = 0.012). MD was associated with the emotional exhaustion dimension of burnout. Spirituality and/or religiousness was shown to be a moderating variable. Further research is needed to deepen our understanding of the correlation between MD and burnout and the role of spirituality and/or religiousness as moderators.
A Case Study of Refined Building Climate Zoning under Complicated Terrain Conditions in China
Authors: Zhang Tianyu , Chen Xianyan , Zhang Fen , Yang Zhi , Wang Yong , Li Yonghua , Wei Linxiao
Published: July 2022

In this study, we first found that the few and sparse meteorological stations used in earlier comprehensive studies of building climate zoning in a complicated terrain area like Chongqing, China, may lead to the inapplicability of building energy efficiency standards in some areas. To address this issue, the study used daily data from 1908 extremely dense surface meteorological stations from 2011 to 2020 in Chongqing, China. In order to conduct fine zoning of building climate in Chongqing, China, GB50176-2016 and ASHRAE standard 169-2021 were employed, respectively. The findings indicated that by using the ASHRAE standard, the entire Chongqing region was classified into five climate zones. The Chongqing region was categorized into three different climate zones using China GB50176-2016: cold zone (CZ), hot summer and cold winter zone (HSCWZ), and mild zone (MZ). Not to be overlooked is the MZ (China’s GB50176-2016)/mixed-humid zone (ASHRAE standard), which is primarily situated at higher elevations in the southeast and northeast of Chongqing. In comparison to the HSCWZ/warm-humid zone, these zones have drastically different building energy efficiency regulations and approaches. According to preliminary projections, improved building climate zoning will to some extent increase building energy efficiency and reduce emissions in Chongqing. Finally, this study case can be replicated in different regions with complicated terrain.
General Data Search Algorithms for Earth Simulation Systems with Cyclic Boundaries
Authors: Cao Yu , Chen Yan , Wang Huizan , Zhang Xiaojiang , Zhao Wenjing
Published: July 2022

Grid remapping is one of the most fundamental functions in Earth simulation systems, and is essentially a kind of data interpolation. The key to an efficient interpolation method is how to quickly find the relevant grid points required for interpolation. With the rise of unstructured grid models, the demand for general and efficient interpolation search algorithms is becoming stronger and stronger. KD (K-dimensional) tree has proven to be effective in dealing with unstructured grids. However, it is unable to tackle the cyclic boundary conditions in Earth simulation systems, which restricts the application of KD tree. Taking the nearest neighbor search as an example, this paper introduces two new KD tree-based multi-dimensional data search methods, which break through the limitations of the original method with regards to the cyclic boundary. One method is based on target points duplication, and the other method is based on source points duplication. Their time complexity and space complexity are analyzed and verified by carefully designed experiments. The results show that the method based on target points duplication generally performs better than that based on source points duplication when the data are basically evenly distributed.
Profile of TREM2-Derived circRNA and mRNA Variants in the Entorhinal Cortex of Alzheimer’s Disease Patients
Authors: Urdánoz-Casado Amaya , de Gordoa Javier Sánchez-Ruiz , Robles Maitane , Roldan Miren , Zelaya María Victoria , Blanco-Luquin Idoia , Mendioroz Maite
Published: July 2022

Genetic variants in TREM2, a microglia-related gene, are well-known risk factors for Alzheimer’s disease (AD). Here, we report that TREM2 originates from circular RNAs (circRNAs), a novel class of non-coding RNAs characterized by a covalent and stable closed-loop structure. First, divergent primers were designed to amplify circRNAs by RT-PCR, which were further assessed by Sanger sequencing. Then, additional primer sets were used to confirm back-splicing junctions. In addition, HMC3 cells were used to assess the microglial expression of circTREM2s. Three candidate circTREM2s were identified in control and AD human entorhinal samples. One of the circRNAs, circTREM2_1, was consistently amplified by all divergent primer sets in control and AD entorhinal cortex samples as well as in HMC3 cells. In AD cases, a moderate negative correlation (r = −0.434) was found between the global average area of Aβ deposits in the entorhinal cortex and circTREM2_1 expression level. In addition, by bioinformatics tools, a total of 16 miRNAs were predicted to join with circTREM2s. Finally, TREM2 mRNA corresponding to four isoforms was profiled by RT-qPCR. TREM2 mRNA levels were found elevated in entorhinal samples of AD patients with low or intermediate ABC scores compared to controls. To sum up, a novel circRNA derived from the TREM2 gene, circTREM2_1, has been identified in the human entorhinal cortex and TREM2 mRNA expression has been detected to increase in AD compared to controls. Unraveling the molecular genetics of the TREM2 gene may help to better know the innate immune response in AD.
Structural Bioinformatics and Deep Learning of Metalloproteins: Recent Advances and Applications
Authors: Andreini Claudia , Rosato Antonio
Published: July 2022

All living organisms require metal ions for their energy production and metabolic and biosynthetic processes. Within cells, the metal ions involved in the formation of adducts interact with metabolites and macromolecules (proteins and nucleic acids). The proteins that require binding to one or more metal ions in order to be able to carry out their physiological function are called metalloproteins. About one third of all protein structures in the Protein Data Bank involve metalloproteins. Over the past few years there has been tremendous progress in the number of computational tools and techniques making use of 3D structural information to support the investigation of metalloproteins. This trend has been boosted by the successful applications of neural networks and machine/deep learning approaches in molecular and structural biology at large. In this review, we discuss recent advances in the development and availability of resources dealing with metalloproteins from a structure-based perspective. We start by addressing tools for the prediction of metal-binding sites (MBSs) using structural information on apo-proteins. Then, we provide an overview of the methods for and lessons learned from the structural comparison of MBSs in a fold-independent manner. We then move to describing databases of metalloprotein/MBS structures. Finally, we summarizing recent ML/DL applications enhancing the functional interpretation of metalloprotein structures.
Screening of Genes Related to Sex Determination and Differentiation in Mandarin Fish (Siniperca chuatsi)
Authors: Yang Cheng , Chen Liangming , Huang Rong , Gui Bin , Li Yangyu , Li Yangyang , Li Yongming , Liao Lanjie , Zhu Zuoyan , Wang Yaping
Published: July 2022

Mandarin fish has an XX/XY sex-determination system. The female mandarin fish is typically larger than the male. Sex identification and the discovery of genes related to sex determination in mandarin fish have important theoretical significance in the elucidation of the regulation and evolutionary mechanism of animal reproductive development. In this study, the chromosome-level genome of a female mandarin fish was assembled, and we found that LG24 of the genome was an X chromosome. A total of 61 genes on the X chromosome showed sex-biased expression. Only six gonadal genes (LG24G00426, LG24G003280, LG24G003300, LG24G003730, LG24G004200, and LG24G004770) were expressed in the testes, and the expression of the other gene LG24G003870 isoform 1 in the ovaries was significantly higher than that in the testes (p < 0.01). Five (except LG24G003280 and LG24G003300) of the seven aforementioned genes were expressed at the embryonic development stage, suggesting their involvement in early sex determination. The expression of LG24G004770 (encoding HS6ST 3-B-like) was also significantly higher in female muscles than in male muscles (p < 0.01), indicating other functions related to female growth. ZP3 encoded by LG24G003870 isoform 1 increased the C-terminal transmembrane domain, compared with that encoded by other fish zp3 isoforms, indicating their different functions in sex determination or differentiation. This study provides a foundation for the identification of sex-determining genes in mandarin fish.
Effects of Combined Allogenic Adipose Stem Cells and Hyperbaric Oxygenation Treatment on Pathogenesis of Osteoarthritis in Knee Joint Induced by Monoiodoacetate
Authors: Juskovic Aleksandar , Nikolic Marina , Ljujic Biljana , Matic Aleksandar , Zivkovic Vladimir , Vucicevic Ksenija , Milosavljevic Zoran , Vojinovic Radisa , Jovicic Nemanja , Zivanovic Suzana , Milivojevic Nevena , Jakovljevic Vladimir , Bolevich Sergey , Miletic Kovacevic Marina
Published: July 2022

The beneficial effects of HBO in inflammatory processes make it an attractive type of treatment for chronic arthritis. In addition, the effects of combination therapy based on adipose stem cells and HBO on OA progression have not been fully investigated. The current study explored the efficacy of intra-articular injection of allogeneic adipose-derived mesenchymal stem cells (ADMSCs) combined with hyperbaric oxygenation treatment (HBO) in a rat osteoarthritis (OA) model. The rat OA model was induced by intra-articular injection of monoiodoacetate (MIA) and 7 days after application of MIA rats were divided into five groups: healthy control (CTRL), osteoarthritis (OA), ADMSCs (ADS), the HBO+ADS21day and HBO+ADS28day groups. A single dose of 1 × 106 allogeneic ADMSCs suspended in sterile saline was injected into the knee joint alone or in combination with HBO treatment. Rats were sacrificed at 3 or 4 weeks after MIA injection. Treatment outcomes were evaluated by radiographic, morphological and histological analysis and by specific staining of articular cartilage. We also measured the level of inflammatory and pro/antioxidative markers. We confirmed that combined treatment of ADMSCs and HBO significantly improved the regeneration of cartilage in the knee joint. Rtg score of knee joint damage was significantly decreased in the HBO+ADS21day and HBO+ADS28day groups compared to the OA. However, the positive effect in the HBO+ADS28day group was greater than the HBO+ADS21day group. The articular cartilage was relatively normal in the HBO+ADS28day group, but moderate degeneration was observed in the HBO+ADS21day compared to the OA group. These findings are in line with the histopathological results. A significantly lower level of O2−. was observed in the HBO+ADS28day group but a higher NO level compared to the HBO+ADS21day group. Moreover, in the HBO+ADS28day group significantly higher concentrations of IL-10 were observed but there was no significant difference in proinflammatory cytokine in serum samples. These results indicate that a single intra-articular injection of allogeneic ADMSCs combined with HBO efficiently attenuated OA progression after 28 days with greater therapeutic effect compared to alone ADMSCs or after 3 weeks of combined treatment. Combined treatment might be an effective treatment for OA in humans.
Binding Studies and Lead Generation of Pteridin-7(8H)-one Derivatives Targeting FLT3
Authors: Ghosh Suparna , Cho Seung Joo
Published: July 2022

Ligand modification by substituting chemical groups within the binding pocket is a popular strategy for kinase drug development. In this study, a series of pteridin-7(8H)-one derivatives targeting wild-type FMS-like tyrosine kinase-3 (FLT3) and its D835Y mutant (FL3D835Y) were studied using a combination of molecular modeling techniques, such as docking, molecular dynamics (MD), binding energy calculation, and three-dimensional quantitative structure-activity relationship (3D-QSAR) studies. We determined the protein–ligand binding affinity by employing molecular mechanics Poisson–Boltzmann/generalized Born surface area (MM-PB/GBSA), fast pulling ligand (FPL) simulation, linear interaction energy (LIE), umbrella sampling (US), and free energy perturbation (FEP) scoring functions. The structure–activity relationship (SAR) study was conducted using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA), and the results were emphasized as a SAR scheme. In both the CoMFA and CoMSIA models, satisfactory correlation statistics were obtained between the observed and predicted inhibitory activity. The MD and SAR models were co-utilized to design several new compounds, and their inhibitory activities were anticipated using the CoMSIA model. The designed compounds with higher predicted pIC50 values than the most active compound were carried out for binding free energy evaluation to wild-type and mutant receptors using MM-PB/GBSA, LIE, and FEP methods.
Impact of Polypyridyl Ru Complexes on Angiogenesis—Contribution to Their Antimetastatic Activity
Authors: Gurgul Ilona , Mazuryk Olga , Stachyra Kamila , Olszanecki Rafał , Lekka Małgorzata , Łomzik Michał , Suzenet Franck , Gros Philippe C. , Brindell Małgorzata
Published: July 2022

The use of polypyridyl Ru complexes to inhibit metastasis is a novel approach, and recent studies have shown promising results. We have reported recently that Ru (II) complexes gathering two 4,7-diphenyl-1,10-phenanthroline (dip) ligands and the one being 2,2′-bipyridine (bpy) or its derivative with a 4-[3-(2-nitro-1H-imidazol-1-yl)propyl (bpy-NitroIm) or 5-(4-{4′-methyl-[2,2′-bipyridine]-4-yl}but-1-yn-1-yl)pyridine-2-carbaldehyde semicarbazone (bpy-SC) moieties can alter the metastatic cascade, among others, by modulating cell adhesion properties. In this work, we show further studies of this group of complexes by evaluating their effect on HMEC-1 endothelial cells. While all the tested complexes significantly inhibited the endothelial cell migration, Ru-bpy additionally interrupted the pseudovessels formation. Functional changes in endothelial cells might arise from the impact of the studied compounds on cell elasticity and expression of proteins (vinculin and paxillin) involved in focal adhesions. Furthermore, molecular studies showed that complexes modulate the expression of cell adhesion molecules, which has been suggested to be one of the factors that mediate the activation of angiogenesis. Based on the performed studies, we can conclude that the investigated polypyridyl Ru (II) complexes can deregulate the functionality of endothelial cells which may lead to the inhibition of angiogenesis.
Pharmacological Screening of Venoms from Five Brazilian Micrurus Species on Different Ion Channels
Authors: Kleiz-Ferreira Jessica Matos , Bernaerts Hans , Pinheiro-Junior Ernesto Lopes , Peigneur Steve , Zingali Russolina Benedeta , Tytgat Jan
Published: July 2022

Coral snake venoms from the Micrurus genus are a natural library of components with multiple targets, yet are poorly explored. In Brazil, 34 Micrurus species are currently described, and just a few have been investigated for their venom activities. Micrurus venoms are composed mainly of phospholipases A2 and three-finger toxins, which are responsible for neuromuscular blockade—the main envenomation outcome in humans. Beyond these two major toxin families, minor components are also important for the global venom activity, including Kunitz-peptides, serine proteases, 5′ nucleotidases, among others. In the present study, we used the two-microelectrode voltage clamp technique to explore the crude venom activities of five different Micrurus species from the south and southeast of Brazil: M. altirostris, M. corallinus, M. frontalis, M. carvalhoi and M. decoratus. All five venoms induced full inhibition of the muscle-type α1β1δε nAChR with different levels of reversibility. We found M. altirostris and M. frontalis venoms acting as partial inhibitors of the neuronal-type α7 nAChR with an interesting subsequent potentiation after one washout. We discovered that M. altirostris and M. corallinus venoms modulate the α1β2 GABAAR. Interestingly, the screening on KV1.3 showed that all five Micrurus venoms act as inhibitors, being totally reversible after the washout. Since this activity seems to be conserved among different species, we hypothesized that the Micrurus venoms may rely on potassium channel inhibitory activity as an important feature of their envenomation strategy. Finally, tests on NaV1.2 and NaV1.4 showed that these channels do not seem to be targeted by Micrurus venoms. In summary, the venoms tested are multifunctional, each of them acting on at least two different types of targets.
Ketoconazole Reverses Imatinib Resistance in Human Chronic Myelogenous Leukemia K562 Cells
Authors: Prado-Carrillo Omar , Arenas-Ramírez Abner , Llaguno-Munive Monserrat , Jurado Rafael , Pérez-Rojas Jazmin , Cervera-Ceballos Eduardo , Garcia-Lopez Patricia
Published: July 2022

Chronic myeloid leukemia (CML) is a hematologic disorder characterized by the oncogene BCR-ABL1, which encodes an oncoprotein with tyrosine kinase activity. Imatinib, a BCR-ABL1 tyrosine kinase inhibitor, performs exceptionally well with minimal toxicity in CML chemotherapy. According to clinical trials, however, 20–30% of CML patients develop resistance to imatinib. Although the best studied resistance mechanisms are BCR-ABL1-dependent, P-glycoprotein (P-gp, a drug efflux transporter) may also contribute significantly. This study aimed to establish an imatinib-resistant human CML cell line, evaluate the role of P-gp in drug resistance, and assess the capacity of ketoconazole to reverse resistance by inhibiting P-gp. The following parameters were determined in both cell lines: cell viability (as the IC50) after exposure to imatinib and imatinib + ketoconazole, P-gp expression (by Western blot and immunofluorescence), the intracellular accumulation of a P-gp substrate (doxorubicin) by flow cytometry, and the percentage of apoptosis (by the Annexin method). In the highly resistant CML cell line obtained, P-gp was overexpressed, and the level of intracellular doxorubicin was low, representing high P-gp activity. Imatinib plus a non-toxic concentration of ketoconazole (10 μM) overcame drug resistance, inhibited P-gp overexpression and its efflux function, increased the intracellular accumulation of doxorubicin, and favored greater apoptosis of CML cells. P-gp contributes substantially to imatinib resistance in CML cells. Ketoconazole reversed CML cell resistance to imatinib by targeting P-gp-related pathways. The repurposing of ketoconazole for CML treatment will likely help patients resistant to imatinib.
Therapeutic Potential of Chungsangboha-tang for the Treatment of Asthma: A Review of Preclinical and Clinical Studies
Authors: Kang Sung-Woo , Kim Kwan-Il , Bu Youngmin , Lee Beom-Joon , Jung Hee-Jae
Published: July 2022

In traditional Korean medicine, Chungsangboha-tang (CSBHT) and its modified forms are used to treat various respiratory disorders, including asthma. This study aimed to identify research trends, clarify the effectiveness of CSBHT and related prescriptions, and lay a foundation for future research. We conducted a literature review using PubMed, Embase, Google Scholar, Oriental Medicine Advanced Searching Integrated System, National Digital Science Links, Korean Medical Database, Wanfang Data, and Chinese National Knowledge Infrastructure databases. We analyzed 25 studies, including 5 in vitro studies, 6 animal studies, and 14 human studies. Many studies evaluated the efficacy of CSBHT and its related prescriptions, including experimental studies on its effectiveness in asthma. The main mechanism of action involves the anti-inflammatory effect caused by the regulation of various immune cells, cytokines, and chemokines. In addition, clinical trials on asthma reported the benefits of CSBHT and its related prescriptions. However, there has been no randomized controlled study of clinical trials on the clinical effectiveness of CSBHT in asthma. Therefore, large-scale randomized controlled studies should be conducted in the future.
Similar Levels of Efficacy of Two Different Maintenance Doses of Adalimumab on Clinical Severity and Quality of Life of Patients with Hidradenitis Suppurativa
Authors: Fania Luca , Giovanardi Giulia , Samela Tonia , Caposiena Dante , Chiricozzi Andrea , Antonelli Flaminia , Saraceni Pierluigi , Elia Fulvia , Garcovich Simone , Ciccone Davide , Cannizzaro Maria Vittoria , Miraglia Emanuele , Iacovino Chiara , Giustini Sandra , Skroza Nevena , Mambrin Alessandra , Potenza Concetta , Bianchi Luca , Peris Ketty , Abeni Damiano
Published: July 2022

Adalimumab is the only biologic agent approved for the treatment of moderate-to-severe hidradenitis suppurativa (HS) patients (i.e., with Hurley II or III), which is recommended in two different maintenance doses (i.e., 40 mg weekly or 80 mg every two weeks). We conducted a prospective multicentric study to measure outcomes related to the severity of disease and quality of life (QoL) of patients affected by moderate-to-severe HS, treated with adalimumab at a maintenance dosing of 40 mg or 80 mg. Assessments were performed at baseline (T0) and after 32 weeks of treatment (T32). We enrolled 85 moderate-to-severe HS Italian patients, 43 men (50.6%) and 42 women, aged between 16 and 62 years (median 31 years, interquartile range 24.4–43.8). Statistically significant improvements were observed for clinical status (with a mean reduction of 7.1 points for the International Hidradenitis Suppurativa Severity Score System (IHS4)), pain levels (3.1 mean decrease in VAS), and QoL (3.4 mean improvement in DLQI score). Patients with no comorbidities, and those with higher levels of perceived pain showed significantly greater improvement in QoL than their counterpart from T0 to T32. As for the proportion of patients who at follow-up reached the minimal clinical important difference (MCID) in QoL, significantly higher proportions of success were observed for age (patients in the 29–39 category), pain (patients with higher reported pain), and Hurley stage III. While both treatment regimen groups (i.e., 40 vs. 80 mg) improved significantly, no statistical differences were observed when comparing the two treatment dosages.
Segmentation of Pancreatic Subregions in Computed Tomography Images
Authors: Javed Sehrish , Qureshi Touseef Ahmad , Deng Zengtian , Wachsman Ashley , Raphael Yaniv , Gaddam Srinivas , Xie Yibin , Pandol Stephen Jacob , Li Debiao
Published: July 2022

The accurate segmentation of pancreatic subregions (head, body, and tail) in CT images provides an opportunity to examine the local morphological and textural changes in the pancreas. Quantifying such changes aids in understanding the spatial heterogeneity of the pancreas and assists in the diagnosis and treatment planning of pancreatic cancer. Manual outlining of pancreatic subregions is tedious, time-consuming, and prone to subjective inconsistency. This paper presents a multistage anatomy-guided framework for accurate and automatic 3D segmentation of pancreatic subregions in CT images. Using the delineated pancreas, two soft-label maps were estimated for subregional segmentation—one by training a fully supervised naïve Bayes model that considers the length and volumetric proportions of each subregional structure based on their anatomical arrangement, and the other by using the conventional deep learning U-Net architecture for 3D segmentation. The U-Net model then estimates the joint probability of the two maps and performs optimal segmentation of subregions. Model performance was assessed using three datasets of contrast-enhanced abdominal CT scans: one public NIH dataset of the healthy pancreas, and two datasets D1 and D2 (one for each of pre-cancerous and cancerous pancreas). The model demonstrated excellent performance during the multifold cross-validation using the NIH dataset, and external validation using D1 and D2. To the best of our knowledge, this is the first automated model for the segmentation of pancreatic subregions in CT images. A dataset consisting of reference anatomical labels for subregions in all images of the NIH dataset is also established.
Advances in Digital Holographic Interferometry
Authors: Petrov Viktor , Pogoda Anastsiya , Sementin Vladimir , Sevryugin Alexander , Shalymov Egor , Venediktov Dmitrii , Venediktov Vladimir
Published: July 2022

Holographic interferometry is a well-established field of science and optical engineering. It has a half-century history of successful implementation as the solution to numerous technical tasks and problems. However, fast progress in digital and computer holography has promoted it to a new level of possibilities and has opened brand new fields of its application. In this review paper, we consider some such new techniques and applications.
Climate Change, PTSD, and Cultural Studies. Book Review: Robinson (2020). The Ministry for the Future: A Novel. London: Orbit. ISBN: 978-0316300162
Authors: Bump Jerome F. A.
Published: July 2022

This novel demonstrates how we can face our current crises avoiding both denial and despair. A plausible, positive ending makes this not only a very unusual book in this genre, but probably the most important book you should read on this subject. While there are many interludes and side plots, the focus is on Frank, an American aid worker suffering from heat-wave PTSD, and Mary, the director of the Ministry for the Future, an organization created by the Paris Agreement to advocate for future generations.
Unexpected Formation of 4-[(1-Carbamoyl-3-oxo-1,3-dihydro-2-benzofuran-1-yl)amino]benzoic Acid from 4-[(3-Amino-1-oxo-1H-2-benzopyran-4-yl)amino]benzoic Acid
Authors: Rodríguez Ricaurte , Quiroga-Suavita Felipe , Dotor Robayo Mónica Yadira
Published: July 2022

With the aim of obtaining derivatives belonging to 2′,3′-diphenyl-3H-spiro[[2]benzofuran-1,4′-imidazole]-3,5′(3′H)-dione nucleus, we synthesized 4-[(3-amino-1-oxo-1H-2-benzopyran-4-yl)amino]benzoic acid (a 3,4-diaminoisocoumarine derivative), a known precursor of 4-[(1-carbamoyl-3-oxo-1,3-dihydro-2-benzofuran-1-yl)amino]benzoic acid (a phthalide–carboxamide-bearing system) by a novel methodology that we report here. The reaction conditions were optimized to afford the latter in 62% yield.
Design, Structural Inspection and Bio-Medicinal Applications of Some Novel Imine Metal Complexes Based on Acetylferrocene
Authors: Khalaf Mai M. , Abd El-Lateef Hany M. , Gouda Mohamed , Sayed Fatma N. , Mohamed Gehad G. , Abu-Dief Ahmed M.
Published: July 2022

Some novel imine metal chelates with Cr3+, Mn2+, Fe3+, Co2+, Ni2+, Cu2+, Zn2+, and Cd2+ cations were produced from 2-acetylferrocene and 3-aminophenol. The new acetylferrocene azomethine ligand ((Z)-cyclopenta-1,3-dien-1-yl(2-(1-((3-hydroxyphenyl)imino)ethyl)cyclopenta-2,4-dien-1-yl)iron) and its metal ion chelates were constructed and elucidated using FT-IR, UV/Vis, 1HNMR, DTA/TGA, CHNClM studies, mass spectrometry and SEM analysis. According to the TGA/DTG investigation, the ferrocene moiety spontaneously disintegrates to liberate FeO. The morphology of the free acetylferrocene azomethine via SEM analysis was net-shaped with a size of 64.73 nm, which differed in Cd(II) complex to be a spongy shape with a size of 42.43 nm. The quantum chemical features of the azomethine ligand (HL) were computed, and its electronic and molecular structure was refined theoretically. The investigated acetylferrocene imine ligand behaves as bidinetate ligand towards the cations under study to form octahedral geometries in case of all complexes except in case of Zn2+ is tetrahedral. Various microorganisms were used to investigate the anti-pathogenic effects of the free acetylferrocene azomethine ligand and its metal chelates. Moreover, the prepared ligand and its metal complexes were tested for anticancer activity utilizing four different concentrations against the human breast cancer cell line (MCF7) and the normal melanocyte cell line (HBF4). Furthermore, the binding of 3-aminophenol, 2-acetylferrocene, HL, Mn2+, Cu2+, and Cd2+ metal chelates to the receptor of breast cancer mutant oxidoreductase was discovered using molecular docking (PDB ID: 3HB5).
The Crystalline Structure of Thin Bismuth Layers Grown on Silicon (111) Substrates
Authors: Stanionytė Sandra , Malinauskas Tadas , Niaura Gediminas , Skapas Martynas , Devenson Jan , Krotkus Arūnas
Published: July 2022

Bismuth films with thicknesses between 6 and ∼30 nm were grown on Si (111) substrate by molecular beam epitaxy (MBE). Two main phases of bismuth — α-Bi and β-Bi — were identified from high-resolution X-ray diffraction (XRD) measurements. The crystal structure dependencies on the layer thicknesses of these films were analyzed. β-Bi layers were epitaxial and homogenous in lateral regions that are greater than 200 nm despite the layer thickness. Further, an increase in in-plane 2θ values showed the biaxial compressive strain. For comparison, α-Bi layers are misoriented in six in-plane directions and have β-Bi inserts in thicker layers. That leads to smaller (about 60 nm) lateral crystallites which are compressively strained in all three directions. Raman measurement confirmed the XRD results. The blue-sift of Raman signals compared with bulk Bi crystals occurs due to the phonon confinement effect, which is larger in the thinnest α-Bi layers due to higher compression.
Bond Properties of Magnesium Phosphate Cement-Based Engineered Cementitious Composite with Ordinary Concrete
Authors: Chang Hongtao , Feng Hu , Guo Zeyu , Guo Aofei , Wang Yongkang
Published: July 2022

A magnesium phosphate cement-based engineered cementitious composite (MPC-ECC) was developed using polyvinyl alcohol (PVA) fibers and fly ash. In this study, the bond behavior of MPC-ECC with ordinary concrete was evaluated through single and double shear bond strength tests. The effects of the water to solid mass ratio (W/S), the sand to binder mass ratio (S/B), the molar ratio of MgO to KH2PO4 (M/P), the fly ash content (F), the borax dosage (B), the volume fraction of PVA fibers (Vf), and curing age on the bond behavior of MPC-ECC with ordinary concrete were examined. The results showed that as the W/S increased, the single and double shear bond strengths were gradually reduced. As the S/B increased, the double shear bond strength increased; the single shear bond strength first decreased up to an S/B of 0.1 and then increased. With the increase of M/P, the single and double shear bond strengths increased. With the increase of F, the single shear bond strength first increased up to an F of 30% and then decreased; the double shear bond strength decreased. With the increase of B, the single and double shear bond strengths increased first and then decreased, and their strength reached its maximum at a B of 6%. The increase of Vf improved the single and double shear bond strengths. The research results can provide some technical guidance for repairing concrete structures with MPC-ECC.
Environmental Assessment of Carbon Concrete Based on Life-Cycle Wide Climate, Material, Energy and Water Footprints
Authors: Mostert Clemens , Bock Jannik , Sameer Husam , Bringezu Stefan
Published: July 2022

The construction industry contributes a major share to global warming and resource consumption. Steel-reinforced concrete (SC) is the world’s most important building material, with over 100 million cubic meters used per year in Germany. In order to achieve a resource-efficient and climate-friendly construction sector, innovative technologies and the substitution of materials are required. Carbon concrete (CC) is a composite material made of concrete and a reinforcement of carbon fibers. Due to the non-rusting and high-strength carbon reinforcement, a much longer life-time can be expected than with today’s designs. In addition, the tensile strength of carbon fibers is about six times higher than that of steel, so CC can be designed with a relatively lower concrete content, thus saving cement and aggregates. This research analyzes and compares SC with CC over its entire life-cycle with regard to its climate, material, energy, and water footprints. The assessment is done on material and building level. The results show that the production phase contributes majorly to the environmental impacts. The reinforcements made from rebar steel or carbon fibers make a significant contribution, in particular to the climate, energy, and water footprint. The material footprint is mainly determined by cement and aggregates production. The comparison on the building level, using a pedestrian bridge as an example, shows that the footprints of the CC bridge are lower compared to the SC bridge. The highest saving of 64% is in the material footprint. The water footprint is reduced by 46% and the energy and climate footprint by 26 to 27%. The production of carbon fibers makes a significant contribution of 37% to the climate footprint.
Experimental Validation of Deflections of Temporary Excavation Support Plates with the Use of 3D Modelling
Authors: Kopras Marek , Buczkowski Wiesław , Szymczak-Graczyk Anna , Walczak Zbigniew , Gogolik Sławomir
Published: July 2022

Almost every project is accompanied by earthworks, very often involving various types of excavation, and the work of people in the excavations. One of the most important tasks in earthworks is to ensure that the walls of the excavation are protected against sliding and that people working in and around the excavation are safe. Very often, in addition to criteria relating to safety and stability of the excavation, economic considerations are also an important criterion. This issue arises as early as the design stage and is related to the choice of construction and materials of which the shoring is to be made in such a way as to be able to withstand the pressure of the soil, ground loads resulting from stored excavated material and the operation of working machinery. Ongoing monitoring of the excavations and their reinforcement is also very important. The paper describes the unique results of experimental field tests, the purpose of which was to analyse the values of deflections of steel support plates of temporary excavation carried out on the object in 1:1 scale. The course of the experiment is presented for excavation support plates with a total depth of 6 m. Direct tests of the deflection arrow were carried out using two techniques, traditionally with a patch, and with laser scanning. Field tests were carried out for the designed situation without backfill load as well as for backfill load of 3.84, 15.36, 26.88 and 38.4 kN·m−2, respectively, for two measurement stages. Stage-I of the study consisted in collecting the results for soil in intact condition, whereas Stage-II collected results for loosened soil. The research experiment was supported by numerical calculations performed using the finite difference method in variational approach. The measured maximum deflections ranged from 14.40 to 16 mm, and the calculated values were 14.95 and 14.99 mm. The comparison of calculation results and tests proved to be very consistent. The analysis of the values of deflections showed that backfill load does not have a significant effect on the deflection of the lower plate, but it does affect the deflection of the first plate up to a depth of 1.2 m. Based on the obtained results, it is recommended to assume the limit (maximum) deflection arrow for support plates of temporary excavations at least as wgr = L/130, where L is the span of the plate. The calculation of deflection values was based on deflection values obtained experimentally and numerically for two steel variants: S235JR and S355JR. The wgr indicator of the maximum deflection arrow proposed by the authors is not stipulated by the industry standards, but it can be very helpful for the designing of excavation reinforcement.