bluuebunny/crossref_metadata_2025 huggingface dataset:
Case-Control Study on the Routes of Transmission of SARS-CoV-2 after the Third Pandemic Wave in Tuscany, Central Italy
Authors: Levi Miriam , Cereda Giulia , Cipriani Francesco , Voller Fabio , Baccini Michela
Published: January 2023

The emergence of hyper-transmissible SARS-CoV-2 variants that rapidly became prevalent throughout the world in 2022 made it clear that extensive vaccination campaigns cannot represent the sole measure to stop COVID-19. However, the effectiveness of control and mitigation strategies, such as the closure of non-essential businesses and services, is debated. To assess the individual behaviours mostly associated with SARS-CoV-2 infection, a questionnaire-based case-control study was carried out in Tuscany, Central Italy, from May to October 2021. At the testing sites, individuals were invited to answer an online questionnaire after being notified regarding the test result. The questionnaire collected information about test result, general characteristics of the respondents, and behaviours and places attended in the week prior to the test/symptoms onset. We analysed 440 questionnaires. Behavioural differences between positive and negative subjects were assessed through logistic regression models, adjusting for a fixed set of confounders. A ridge regression model was also specified. Attending nightclubs, open-air bars or restaurants and crowded clubs, outdoor sporting events, crowded public transportation, and working in healthcare were associated with an increased infection risk. A negative association with infection, besides face mask use, was observed for attending open-air shows and sporting events in indoor spaces, visiting and hosting friends, attending courses in indoor spaces, performing sport activities (both indoor and outdoor), attending private parties, religious ceremonies, libraries, and indoor restaurants. These results might suggest that during the study period people maintained a particularly responsible and prudent approach when engaging in everyday activities to avoid spreading the virus.
Distribution Characteristics and Influencing Factors of Organochlorine Pesticides in Agricultural Soil from Xiamen City
Authors: Gao Ziqiang , Chen Yixian , Qin Qijin , Wang Rui , Dai Zhineng
Published: January 2023

The concentration and distribution of 15 organochlorine pesticides in the soil of Xiamen City were determined. Overall, among the 15 selected target pesticides, 14 organochlorine pesticides (OCPs) were detected (hexachlorobenzene was not). The range of detected pesticides was undetected−10.04 ng/g, the total detection rate was 35.2%, and the three pollutants with the highest detection rate in all samples were Heptachlor (66.7%), δ-Hexachlorocyclohexane (60.0%), and p, p′-Dichlorodiphenyldichloroethane (58.3%). The degree of pollution in descending order was Tong’an > Xiang’an > Jimei > Haicang. Linear regression analysis of soil properties and OCP concentration distribution revealed that OCPs were positively correlated with water content, dissolved organic carbon, and pH and negatively correlated with cation exchange capacity. The origin of OCPs was evaluated using the relationship between the parent compound and its metabolites, with possible new hexachlorocyclohexane and isomer (HCHs) input. By comparing the risk screening values of ΣHCHs and ΣDDTs in “Soil Environmental Quality Standards”, the concentrations in all soil samples were lower than the standard values, which indicated that the OCP residues in Xiamen were very low.
Cost Consequence Analysis of Belimumab versus Standard of Care for the Management of Systemic Lupus Erythematosus in Saudi Arabia: A Retrospective Cohort Study
Authors: Alsuwayegh Aseel , Almaghlouth Ibrahim A. , Almasaoud Majed Ali , Alzaid Abdullah Sulaiman , Alsuhaibani Adel Abdulaziz , Almana Lyan Hassan , Alabdulkareem Sara Mohammed , Abudahesh Joud Abdullah , AlRuthia Yazed
Published: January 2023

Background: Belimumab use for the management of systemic lupus erythematosus (SLE) has been limited, in part due to its high acquisition cost relative to the standard of care (SoC) and the uncertainties about its cost-effectiveness. Therefore, the aim of this study was to compare the cost and effectiveness of belimumab versus the SoC alone for the management of SLE using real-world data from the perspective of public healthcare payers in Saudi Arabia. Methods: Data were retrieved from a national prospective cohort of SLE, Saudi Arabia. Adult SLE patients (≥18 yrs.) treated with belimumab plus the SoC or the SoC alone for at least six months were recruited. The effectiveness was measured using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). Unit costs for health services and prescription drugs were retrieved from the Saudi ministry of health. Nonparametric bootstrapping with inverse probability weighting was conducted to generate the 95% confidence limits for the cost and effectiveness. Results: A total of 15 patients on belimumab plus the SoC and 41 patients on the SoC alone met the inclusion criteria and were included in the analysis. The majority of patients were females (91.07%) with a mean age of 38 years. The mean difference in cost and SLEDAI-2K score reduction between belimumab versus the SoC were USD 5303.16 [95% CI: USD 2735.61–USD 7802.52] and 3.378 [95% CI: 1.769–6.831], respectively. Belimumab demonstrated better effectiveness but higher cost in 96% of the bootstrap cost-effectiveness distributions. Conclusion: Future studies should use more robust research designs and a larger sample size to confirm the findings of this study.
Improvement of Sexual Function and Sleep Quality in Patients with Atopic Dermatitis Treated with Dupilumab: A Single-Centre Prospective Observational Study
Authors: Ureña-Paniego Clara , Montero-Vílchez Trinidad , Sanabria-de-la-Torre Raquel , Soto-Moreno Alberto , Molina-Leyva Alejandro , Arias-Santiago Salvador
Published: January 2023

Atopic dermatitis (AD) is a chronic inflammatory skin disease presenting as xerosis, eczema and intense pruritus. These symptoms negatively impact patients’ quality of life. However, the effect of AD on sexual function and sleep quality and how treatment with dupilumab could modify them have not been explored in depth. The aim of this study is to assess the effects of dupilumab on sexual and sleep quality in patients with AD. For that purpose, an observational prospective study was designed. Patients were evaluated at baseline and after 16 weeks of dupilumab treatment. Disease severity was assessed by Eczema Area and Severity (EASI) and SCORing Atopic Dermatitis index (SCORAD). Sexual function was evaluated using validated questionnaires, for men via the International Index of Erectile Dysfunction 5 (IIEF-5) and for women via the Female Sexual Function Index (FSFI). Sleep impairment was recorded through Pittsburgh Sleep Quality Index (PSQI). Thirty-two patients, with a mean age of 30.53 ± 14.48 years old, were included. Regarding sex, 59.8% (20) were female. Most patients had a severe disease reflected in a mean basal EASI of 23.24 ± 6.74 and a SCORAD of 54.07 ± 13.89. Clinical scores improved after dupilumab treatment. At baseline, 47.37% women presented sexual dysfunction and 66.67% men had erectile dysfunction. FSFI improved from 23.51 to 27.93 points (p = 0.008) after dupilumab. Desire, arousal, satisfaction and pain were the components with great improvement. Women with a great improvement in FSFI showed greater clinical results and increased quality of life. At first, 96.9% (31/32) of participants presented with poor sleep quality. After treatment with dupilumab, sleep quality was enhanced and PSQI scores decreased from 12.8 points at baseline to 7.73 points (p < 0.001). In conclusion, dupilumab is associated with reduced sexual dysfunction, mainly in women, and sleep quality.
Rich Intercultural Music Engagement Enhances Cultural Understanding: The Impact of Learning a Musical Instrument Outside of One’s Lived Experience
Authors: Li Marjorie , Olsen Kirk , Davidson Jane , Thompson William
Published: January 2023

Rich intercultural music engagement (RIME) is an embodied form of engagement whereby individuals immerse themselves in foreign musical practice, for example, by learning a traditional instrument from that culture. The present investigation evaluated whether RIME with Chinese or Middle Eastern music can nurture intercultural understanding. White Australian participants were randomly assigned to one of two plucked-string groups: Chinese pipa (n = 29) or Middle Eastern oud (n = 29). Before and after the RIME intervention, participants completed measures of ethnocultural empathy, tolerance, social connectedness, explicit and implicit attitudes towards ethnocultural groups, and open-ended questions about their experience. Following RIME, White Australian participants reported a significant increase in ethnocultural empathy, tolerance, feelings of social connection, and improved explicit and implicit attitudes towards Chinese and Middle Eastern people. However, these benefits differed between groups. Participants who learned Chinese pipa reported reduced bias and increased social connectedness towards Chinese people, but not towards Middle Eastern people. Conversely, participants who learned Middle Eastern oud reported a significant increase in social connectedness towards Middle Eastern people, but not towards Chinese people. This is the first experimental evidence that participatory RIME is an effective tool for understanding a culture other than one’s own, with the added potential to reduce cultural bias.
Heat Hazard Control in High-Temperature Tunnels: Experimental Study of Coupled Cooling with Ventilation and Partial Insulation for Synergistic Geothermal Extraction
Authors: Wang Junjian , Li Zijun , Li Gang , Xu Yu
Published: January 2023

The problem of heat hazard in tunnel engineering has seriously affected the normal work of personnel and machinery. After combining the heat hazard control method of controlling the energy source and blocking the energy transfer, a technical scheme of precise thermal insulation at the working face in concert with geothermal energy extraction is proposed, forming a coupled cooling method of ventilation and partial thermal insulation. By building a scaled model test platform, the temperature field of the working area was analyzed, and the effect of factors, such as with or without a thermal insulation layer, ventilation velocity, and surrounding rock temperature on the cooling limit, was discussed. The feasibility of extracting energy and enhancing cooling through the heat exchange layer was judged. The results show that the partial thermal insulation can effectively weaken the heat dissipation of the surrounding rock and enhance the ventilation and cooling effect, which can reduce the average ventilation limit temperature of the working area by 1.6 °C. The addition of the heat exchange layer can further improve the tunnel environment on the basis of partial insulation, making the cooling limit temperature drop by another 3.1 °C, and the heat exchange layer can work for one year to extract geothermal energy 4.5 × 108 J. The coupled cooling scheme of ventilation and partial thermal insulation is practical and useful, which can provide technical ideas for improving the thermal environment of the tunnel.
The Relationship between the Transmission of Different SARS-CoV-2 Strains and Air Quality: A Case Study in China
Authors: Ma Ruiqing , Zhang Yeyue , Zhang Yini , Li Xi , Ji Zheng
Published: January 2023

Coronavirus Disease 2019 (COVID-19) has been a global public health concern for almost three years, and the transmission characteristics vary among different virus variants. Previous studies have investigated the relationship between air pollutants and COVID-19 infection caused by the original strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, it is unclear whether individuals might be more susceptible to COVID-19 due to exposure to air pollutants, with the SARS-CoV-2 mutating faster and faster. This study aimed to explore the relationship between air pollutants and COVID-19 infection caused by three major SARS-CoV-2 strains (the original strain, Delta variant, and Omicron variant) in China. A generalized additive model was applied to investigate the associations of COVID-19 infection with six air pollutants (PM2.5, PM10, SO2, CO, NO2, and O3). A positive correlation might be indicated between air pollutants (PM2.5, PM10, and NO2) and confirmed cases of COVID-19 caused by different SARS-CoV-2 strains. It also suggested that the mutant variants appear to be more closely associated with air pollutants than the original strain. This study could provide valuable insight into control strategies that limit the concentration of air pollutants at lower levels and would better control the spread of COVID-19 even as the virus continues to mutate.
The Family and Community Nurses Cultural Model in the Times of the COVID Outbreak: A Focused Ethnographic Study
Authors: Barisone Michela , Busca Erica , Bassi Erika , De Luca Enrico , Profenna Emanuele , Suardi Barbara , Dal Molin Alberto
Published: January 2023

The ageing population, increasingly frail and chronically ill, and COVID-19 pandemic challenges have highlighted national health systems’ vulnerability and, more strongly/to a greater extent, the pivotal role of the family and community nurse (FCN). However, the recent introduction of FCNs in primary care settings has yet to be explored in Italy. This study aimed to identify the FCNs’ cultural model and its implementation during the COVID-19 outbreak. A focused ethnographic study was performed in a primary care community service in northern Italy. Participants were FCNs (N = 5), patients and caregivers (N = 12). Qualitative data were collected through semi-structured interviews, field notes, observation of FCNs’ activities and access to documents. Qualitative analysis identified themes concerned with crucial aspects of FCNs’ activities, role implementation, and their relationship with patients and families. This study illuminated how the FCN strategically takes care of and identifies patients’ and community needs. Although the COVID-19 outbreak hindered effective FCN project implementation, this study highlighted that the pandemic provided a chance to better identify cultural, organisational and educational weaknesses that need to be addressed to support the full accomplishment of FCNs’ scope of practice.
Thromboprophylaxis in Pregnant Women with COVID-19: An Unsolved Issue
Authors: Varlas Valentin Nicolae , Borș Roxana Georgiana , Plotogea Mihaela , Iordache Madalina , Mehedințu Claudia , Cîrstoiu Monica Mihaela
Published: January 2023

SARS-CoV-2 infection in pregnant women is of growing interest due to controversy over the use of antiplatelet and/or anticoagulant drugs during pregnancy and postpartum. Pregnant women are susceptible to develop severe forms of viral infections due to pregnancy-related immune alterations, changes in lung functions, and hypercoagulability. The association of pregnancy with SARS-CoV-2 infection can cause an increased incidence of thrombotic complications, especially in the case of patients with some genetic variants that favor inflammation and thrombosis. Compared to the general population, pregnant women may be at increased risk of thrombotic complications related to COVID-19. The lack of extensive clinical trials on thromboprophylaxis and extrapolating data from non-pregnant patients lead to major discrepancies in treating pregnant women with COVID-19. Currently, a multidisciplinary team should determine the dose and duration of prophylactic anticoagulant therapy for these patients, depending on the disease severity, the course of pregnancy, and the estimated due date. This narrative review aims to evaluate the protective effect of thromboprophylaxis in pregnant women with COVID-19. It is unknown at this time whether antiplatelet or anticoagulant therapy initiated at the beginning of pregnancy for various diseases (preeclampsia, intrauterine growth restriction, thrombophilia) offers a degree of protection. The optimal scheme for thromboprophylaxis in pregnant women with COVID-19 must be carefully established through an individualized decision concerning gestational age and the severity of the infection.
How Different Predominant SARS-CoV-2 Variants of Concern Affected Clinical Patterns and Performances of Infected Professional Players during Two Soccer Seasons: An Observational Study from Split, Croatia
Authors: Nincevic Jasna , Jurcev-Savicevic Anamarija , Versic Sime , Modric Toni , Turic Ante , Bandalovic Ante , Becir Boris , Mijakovic Marijana , Bocina Ivana , Sekulic Damir
Published: January 2023

There are limited data describing clinical patterns and match running performance (MRP) among players with COVID-19 infection before and after infection, particularly related to different predominant SARS-CoV-2 variants, as well as in comparison to uninfected players. This observational study was conducted during two consecutive soccer seasons in one professional club in Split, Croatia. There were four clusters of mild, self-limited, or asymptomatic infection characterised by low adherence to preventive measures. Infected players had significantly more symptoms (t-test = 3.24; p = 0.002), a longer period of physical inactivity (χ2 = 10.000; p = 0.006) and a longer period of self-assessment for achieving full fitness (χ2 = 6.744; p = 0.034) in the 2020–2021 season (Wuhan wild strain and Alpha variant) than in the 2021–2022 season (Omicron variant). It was also found that, despite the milder clinical presentation of the infection in the 2021–2022 season, the players had significantly more abnormal laboratory findings (χ2 = 9.069240; p = 0.002), although without clinical significance at the time of the study. As for the MRP, player performance in the 2021–2022 season was not negatively affected by the Omicron variant, while there was an improvement in MRP in scores for a sample of all players. The RTP protocol was correctly applied because it helped the athletes to recover their pre-infection physical capacities relatively quickly. This study advances the understanding that an optimally and individually planned RTP protocol is crucial for the MRP of infected players. Future research needs to replicate the findings of abnormal laboratory results and extend the study focusing on their potential long-term clinical significance.
Wound Pain as a Determinant of Function in Patients Hospitalised for Burns
Authors: Budzyńska Anna , Talarska Dorota , Bączyk Grażyna
Published: January 2023

Burn wounds most often occur on visible parts of the body. They therefore cause fear of disfigurement and rejection by those around them. In addition, they cause pain. The main aim of this study was to analyse factors affecting the functioning of patients hospitalised for burns. The study included 57 patients hospitalised for burns. Each person was surveyed twice: on day seven after admission and on the day of discharge from the hospital. The following research tools were used: a personal questionnaire to collect clinical data and the scales of the Katz Activities of Daily Living (ADL), the short-form McGill Pain Questionnaire (SF-MPQ), the Beck Depression Inventory (BDI) and the Satisfaction with Appearance Scale (SWAP). On the discharge day, compared to day 7, there was an improvement in the patient’s level of functioning in all areas analysed. Pain intensity (p < 0.0001), depression (p < 0.0001) and dissatisfaction with appearance (p = 0.0239) decreased significantly. Improvements in daily functioning were also obtained (p < 0.0001). Multiple regression was performed to estimate the effect of selected variables on patients’ level of functioning. Burn area (p = 0.0126), pain level (questionnaire part B: p = 0.0004 and questionnaire part C: p = 0.0208) and gender (p = 0.0413) had a significant impact on the level of daily functioning. Pain complaints are the most crucial predictor affecting the functional status and depression levels in burn wound patients. Increased levels of depression promote dissatisfaction with one’s appearance.
Knowledge of Self-Isolation Rules in the UK for Those Who Have Symptoms of COVID-19: A Repeated Cross-Sectional Survey Study
Authors: Smith Louise E. , West Robert , Potts Henry W. W. , Amlȏt Richard , Fear Nicola T. , Rubin G. James , Michie Susan
Published: January 2023

Objectives: To investigate knowledge of self-isolation rules and factors associated with knowledge. Methods: Repeated cross-sectional online surveys (n ≈ 2000 UK adults) between 9 November 2020 and 16 February 2022 (78,573 responses from 51,881 participants). We computed a composite measure of knowledge of self-isolation rules and investigated associations between knowledge and survey wave, socio-demographic characteristics (age, gender, UK nation, index of multiple deprivation), trust in government, and participants’ belief that they had received enough information about self-isolation. Results: In total, 87.9% (95% CI 87.7% to 88.1%, n = 67,288/76,562) of participants knew that if they had symptoms of COVID-19 they should ‘self-isolate’. However, only 62.8% (n = 48,058/76,562, 95% CI 62.4% to 63.1%) knew the main rules regarding what that meant. Younger people had less knowledge than older people, and men had less knowledge than women. Knowledge was lower in people living in England versus in Scotland, Wales, and Northern Ireland. The pattern of association between knowledge and trust in government was unclear. Knowledge was lower in people living in a more deprived area and those who did not believe they had enough information about self-isolation. Knowledge was lower in December 2020 to January 2021, compared with before and after this period. Conclusions: Approximately 63% of UK adults between November 2020 and February 2022 appeared to know the main rules regarding self-isolation if symptomatic with COVID-19. Knowledge was lower in younger than older people, men than women, those living in England compared with Scotland, Wales or Northern Ireland, and those living in more deprived areas.
Linking the Urban Environment and Health: An Innovative Methodology for Measuring Individual-Level Environmental Exposures
Authors: Krenz Kimon , Dhanani Ashley , McEachan Rosemary R. C. , Sohal Kuldeep , Wright John , Vaughan Laura
Published: January 2023

Environmental exposures (EE) are increasingly recognised as important determinants of health and well-being. Understanding the influences of EE on health is critical for effective policymaking, but better-quality spatial data is needed. This article outlines the theoretical and technical foundations used for the construction of individual-level environmental exposure measurements for the population of a northern English city, Bradford. The work supports ‘Connected Bradford’, an entire population database linking health, education, social care, environmental and other local government data over a period of forty years. We argue that our current understanding of environmental effects on health outcomes is limited both by methodological shortcomings in the quantification of the environment and by a lack of consistency in the measurement of built environment features. To address these shortcomings, we measure the environmental exposure for a series of different domains including air quality, greenspace and greenness, public transport, walkability, traffic, buildings and the built form, street centrality, land-use intensity, and food environments as well as indoor dwelling qualities. We utilise general practitioners’ historical patient information to identify the precise geolocation and duration of a person’s residence. We model a person’s local neighbourhood, and the probable routes to key urban functions aggregated across the city. We outline the specific geospatial procedure used to quantify the environmental exposure for each domain and use the example of exposure to fast-food outlets to illustrate the methodological challenges in the creation of city and nationwide environmental exposure databases. The proposed EE measures will enable critical research into the relationship and causal links between the built environment and health, informing planning and policy-making.
The Interactive Effects between Drought and Air Pollutants on Children’s Upper Respiratory Tract Infection: A Time-Series Analysis in Gansu, China
Authors: Li Yanlin , Sun Jianyun , Lei Ruoyi , Zheng Jie , Tian Xiaoyu , Xue Baode , Luo Bin
Published: January 2023

As a destructive and economic disaster in the world, drought shows an increasing trend under the continuous global climate change and adverse health effects have been reported. The interactive effects between drought and air pollutants, which may also be harmful to respiratory systems, remain to be discussed. We built the generalized additive model (GAM) and distributed lag nonlinear model (DLNM) to estimate the effects of drought and air pollutants on daily upper respiratory infections (URTI) outpatient visits among children under 6 in three cities of Gansu province. The Standardized Precipitation Index (SPI) based on monthly precipitation (SPI-1) was used as an indicator of drought. A non-stratified model was established to explore the interaction effect of SPI-1 and air pollutants. We illustrated the number of daily pediatric URTI outpatient visits increased with the decrease in SPI-1. The interactive effects between air pollutants and the number of daily pediatric URTIs were significant. According to the non-stratified model, we revealed highly polluted and drought environments had the most significant impact on URTI in children. The occurrence of drought and air pollutants increased URTI in children and exhibited a significant interactive effect.
Modulation of Unfolded Protein Response Restores Survival and Function of β-Cells Exposed to the Endocrine Disruptor Bisphenol A
Authors: Daian Laura Maria , Tanko Gabriela , Vacaru Andrei Mircea , Ghila Luiza , Chera Simona , Vacaru Ana-Maria
Published: January 2023

Diabetes is a metabolic disease that currently affects nearly half a billion people worldwide. β-cells dysfunction is one of the main causes of diabetes. Exposure to endocrine-disrupting chemicals is correlated with increased diabetes incidence. We hypothesized that treatment with bisphenol A (BPA) induces endoplasmic reticulum (ER) stress that activates the unfolded protein response (UPR), leading to impaired function of the β-cells, which over time, can cause diabetes. In this study, we aimed to evaluate UPR pathways activation under BPA treatment in β-cells and possible recovery of ER homeostasis. MIN6 cells (mouse insulinoma cell line) and isolated pancreatic islets from NOR (non-obese diabetes resistant) mice were treated with BPA. We analyzed the impact of BPA on β-cell viability, the architecture of the early secretory pathway, the synthesis and processing of insulin and the activation of UPR sensors and effectors. We found that the addition of the chemical chaperone TUDCA rescues the deleterious effects of BPA, resulting in improved viability, morphology and function of the β-cells. In conclusion, we propose that modulators of UPR can be used as therapeutic interventions targeted towards regaining β-cells homeostasis.
Insights into the Molecular Mechanisms Regulating Cell Behavior in Response to Magnetic Materials and Magnetic Stimulation in Stem Cell (Neurogenic) Differentiation
Authors: Mocanu-Dobranici Alexandra-Elena , Costache Marieta , Dinescu Sorina
Published: January 2023

Magnetic materials and magnetic stimulation have gained increasing attention in tissue engineering (TE), particularly for bone and nervous tissue reconstruction. Magnetism is utilized to modulate the cell response to environmental factors and lineage specifications, which involve complex mechanisms of action. Magnetic fields and nanoparticles (MNPs) may trigger focal adhesion changes, which are further translated into the reorganization of the cytoskeleton architecture and have an impact on nuclear morphology and positioning through the activation of mechanotransduction pathways. Mechanical stress induced by magnetic stimuli translates into an elongation of cytoskeleton fibers, the activation of linker in the nucleoskeleton and cytoskeleton (LINC) complex, and nuclear envelope deformation, and finally leads to the mechanical regulation of chromatin conformational changes. As such, the internalization of MNPs with further magnetic stimulation promotes the evolution of stem cells and neurogenic differentiation, triggering significant changes in global gene expression that are mediated by histone deacetylases (e.g., HDAC 5/11), and the upregulation of noncoding RNAs (e.g., miR-106b~25). Additionally, exposure to a magnetic environment had a positive influence on neurodifferentiation through the modulation of calcium channels’ activity and cyclic AMP response element-binding protein (CREB) phosphorylation. This review presents an updated and integrated perspective on the molecular mechanisms that govern the cellular response to magnetic cues, with a special focus on neurogenic differentiation and the possible utility of nervous TE, as well as the limitations of using magnetism for these applications.
Identification of Long Noncoding RNAs That Exert Transcriptional Regulation by Forming RNA–DNA Triplexes in Prostate Cancer
Authors: Liang Yugang , Lu Yali , Chen Qin , Cheng Yihang , Ma Yunsheng , Huang Yan , Qiu Minyan , Li Yao
Published: January 2023

Long noncoding RNAs (lncRNAs) are involved in transcriptional regulation, and their deregulation is associated with the development of various human cancers, including prostate cancer (PCa). However, their underlying mechanisms remain unclear. In this study, lncRNAs that interact with DNA and regulate mRNA transcription in PCa were screened and identified to promote PCa development. First, 4195 protein-coding genes (PCGs, mRNAs) were obtained from the The Cancer Genome Atlas (TCGA) database, in which 1148 lncRNAs were differentially expressed in PCa. Then, 44,270 pairs of co-expression relationships were calculated between 612 lncRNAs and 2742 mRNAs, of which 42,596 (96%) were positively correlated. Among the 612 lncRNAs, 392 had the potential to interact with the promoter region to form DNA:DNA:RNA triplexes, from which lncRNA AD000684.2(AC002128.1) was selected for further validation. AC002128.1 was highly expressed in PCa. Furthermore, AD000684.2 positively regulated the expression of the correlated genes. In addition, AD000684.2 formed RNA–DNA triplexes with the promoter region of the regulated genes. Functional assays also demonstrated that lncRNA AD000684.2 promotes cell proliferation and motility, as well as inhibits apoptosis, in PCa cell lines. The results suggest that AD000684.2 could positively regulate the transcription of target genes via triplex structures and serve as a candidate prognostic biomarker and target for new therapies in human PCa.
GBA1 Gene Mutations in α-Synucleinopathies—Molecular Mechanisms Underlying Pathology and Their Clinical Significance
Authors: Granek Zuzanna , Barczuk Julia , Siwecka Natalia , Rozpędek-Kamińska Wioletta , Kucharska Ewa , Majsterek Ireneusz
Published: January 2023

α-Synucleinopathies comprise a group of neurodegenerative diseases characterized by altered accumulation of a protein called α-synuclein inside neurons and glial cells. This aggregation leads to the formation of intraneuronal inclusions, Lewy bodies, that constitute the hallmark of α-synuclein pathology. The most prevalent α-synucleinopathies are Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). To date, only symptomatic treatment is available for these disorders, hence new approaches to their therapy are needed. It has been observed that GBA1 mutations are one of the most impactful risk factors for developing α-synucleinopathies such as PD and DLB. Mutations in the GBA1 gene, which encodes a lysosomal hydrolase β-glucocerebrosidase (GCase), cause a reduction in GCase activity and impaired α-synuclein metabolism. The most abundant GBA1 gene mutations are N370S or N409S, L444P/L483P and E326K/E365K. The mechanisms by which GCase impacts α-synuclein aggregation are poorly understood and need to be further investigated. Here, we discuss some of the potential interactions between α-synuclein and GCase and show how GBA1 mutations may impact the course of the most prevalent α-synucleinopathies.
Comprehensive Analysis of KCNJ14 Potassium Channel as a Biomarker for Cancer Progression and Development
Authors: Alasiri Glowi
Published: January 2023

Cancer is a global epidemic that has affected millions of lives. Discovering novel cancer targets is widely viewed as a key step in developing more effective therapies for cancer and other fatal illnesses. More recently, potassium (K+) channels have been studied as a potential biological target for the creation of cancer treatments. Potassium Inwardly Rectifying Channel Subfamily J Member 14 (KCNJ14) is one of the cancer genome’s least investigated genes. This study conducted a comprehensive examination of the relationships between KCNJ14 gene expression analysis, survival, RNA modification, immunotherapy participation, and cancer stemness using several databases. KCNJ14 was shown to be dysregulated in a variety of cancers, including lung, intestinal, head and neck, oesophageal, and stomach. Additionally, KCNJ14 was shown to be linked to RNA and DNA stemness in 18 and 15 different tumour types, respectively. Moreover, KCNJ14 was discovered to be positively linked with immunological checkpoints and suppressor cells and to have a negative immunophenoscore (IPS). KCNJ14 was linked to tumour mutation burden (TMB), microsatellite instability (MSI), neoantigen (NEO), and programmed death ligand 1 (PD-L1); all four are potential targets for immunotherapies. In addition, a favourable relationship between genomic-instability markers such as heterozygosity (LOH), homologous recombination deficiency (HRD), and mutant-allele tumour heterogeneity (MATH) was demonstrated with KCNJ14. Based on these novel findings, KCNJ14 may be a useful independent prognostic biomarker for a range of cancers.
Oleracone F Alleviates Cognitive Impairment and Neuropathology in APPswe/PSEN1dE9 Mice by Reducing the Expression of Vascular Cell Adhesion Molecule and Leukocyte Adhesion to Brain Vascular Endothelial Cells
Authors: Kwon Young-Sun , Ko Jin-Sung , Oh Se-Young , Han Young Taek , Jo Sangmee Ahn
Published: January 2023

Alzheimer’s disease (AD) is the most common neurodegenerative disease and the blood–brain barrier dysfunction has been suggested as a key pathological feature of the disease. Our research group successfully established a synthetic protocol for oleracones, a novel series of flavonoids isolated from the plant extract of Portulaca oleracea L. (PO). PO extract was reported to have anti-inflammatory and antioxidant effects, enhancing cognitive function. Thus, we investigated the effects and mechanism of oleracones on cognition using AD model transgenic mice (Tg; APPswe/PSEN1dE9). Oleracone F treatment significantly improved memory dysfunction in Tg mice. Oleracone F decreased the number, burden, and immunoreactivity of amyloid plaques and amyloid precursor protein (APP) protein levels in the brains of Tg mice compared to wild-type mice. Oleracone F also alleviated inflammation observed in Tg mice brains. In vitro studies in human microvascular endothelial cells (HBMVECs) demonstrated that oleracones D, E, and F blocked the elevations in VCAM-1 protein induced by tumor necrosis factor-α (TNF-α), hindering leukocyte adhesion to HBMVECs. Taken together, our results suggest that oleracones ameliorated cognitive impairment by blocking TNF-α-induced increases in VCAM-1, thereby reducing leukocyte infiltration to the brain and modulating brain inflammation.
Assessment of the Molecular Responses of an Ancient Angiosperm against Atypical Insect Oviposition: The Case of Hass Avocados and the Tephritid Fly Anastrepha ludens
Authors: Aluja Martín , Vázquez-Rosas-Landa Mirna , Cerqueda-García Daniel , Monribot-Villanueva Juan L. , Altúzar-Molina Alma , Ramírez-Vázquez Mónica , Velázquez-López Olinda , Rosas-Saito Greta , Alonso-Sánchez Alexandro G. , Ortega-Casas Rafael , Enríquez-Valencia Adrián José , Guerrero-Analco José A. , Ibarra-Laclette Enrique
Published: January 2023

Anastrepha spp. (Diptera: Tephritidae) infestations cause significant economic losses in commercial fruit production worldwide. However, some plants quickly counteract the insertion of eggs by females by generating neoplasia and hindering eclosion, as is the case for Persea americana Mill., cv. Hass (Hass avocados). We followed a combined transcriptomics/metabolomics approach to identify the molecular mechanisms triggered by Hass avocados to detect and react to the oviposition of the pestiferous Anastrepha ludens (Loew). We evaluated two conditions: fruit damaged using a sterile pin (pin) and fruit oviposited by A. ludens females (ovi). We evaluated both of the conditions in a time course experiment covering five sampling points: without treatment (day 0), 20 min after the treatment (day 1), and days 3, 6, and 9 after the treatment. We identified 288 differentially expressed genes related to the treatments. Oviposition (and possibly bacteria on the eggs’ surface) induces a plant hypersensitive response (HR), triggering a chitin receptor, producing an oxidative burst, and synthesizing phytoalexins. We also observed a process of cell wall modification and polyphenols biosynthesis, which could lead to polymerization in the neoplastic tissue surrounding the eggs.
Lycorine Carbamate Derivatives for Reversing P-glycoprotein-Mediated Multidrug Resistance in Human Colon Adenocarcinoma Cells
Authors: Sancha Shirley A. R. , Szemerédi Nikoletta , Spengler Gabriella , Ferreira Maria-José U.
Published: January 2023

Multidrug resistance (MDR) is a major challenge in cancer chemotherapy. Aiming at generating a small library of anticancer compounds for overcoming MDR, lycorine (1), a major Amaryllidaceae alkaloid isolated from Pancratium maritimum, was derivatized. Thirty-one new compounds (2–32) were obtained by chemical transformation of the hydroxyl groups of lycorine into mono- and di-carbamates. Compounds 1–32 were evaluated as MDR reversers, through the rhodamine-123 accumulation assay by flow cytometry and chemosensitivity assays, in resistant human colon adenocarcinoma cancer cells (Colo 320), overexpressing P-glycoprotein (P-gp, ABCB1). Significant inhibition of P-gp efflux activity was observed for the di-carbamate derivatives, mainly those containing aromatic substituents, at non-cytotoxic concentrations. Compound 5, bearing a benzyl substituent, and compounds 9 and 25, with phenethyl moieties, were among the most active, exhibiting strong inhibition at 2 µM, being more active than verapamil at 10-fold higher concentration. In drug combination assays, most compounds were able to synergize doxorubicin. Moreover, some derivatives showed a selective antiproliferative effect toward resistant cells, having a collateral sensitivity effect. In the ATPase assay, selected compounds (2, 5, 9, 19, 25, and 26) were shown to behave as inhibitors.
An Overview of Inter-Tissue and Inter-Kingdom Communication Mediated by Extracellular Vesicles in the Regulation of Mammalian Metabolism
Authors: Castaño Carlos , Novials Anna , Párrizas Marcelina
Published: January 2023

Obesity and type 2 diabetes are associated with defects of insulin action in different tissues or alterations in β-cell secretory capacity that may be triggered by environmental challenges, inadequate lifestyle choices, or an underlying genetic predisposition. In addition, recent data shows that obesity may also be caused by perturbations of the gut microbiota, which then affect metabolic function and energy homeostasis in the host. Maintenance of metabolic homeostasis in complex organisms such as mammals requires organismal-level communication, including between the different organs and the gut microbiota. Extracellular vesicles (EVs) have been identified in all domains of life and have emerged as crucial players in inter-organ and inter-kingdom crosstalk. Interestingly, EVs found in edible vegetables or in milk have been shown to influence gut microbiota or tissue function in mammals. Moreover, there is a multidirectional crosstalk mediated by EVs derived from gut microbiota and body organs that has implications for host health. Untangling this complex signaling network may help implement novel therapies for the treatment of metabolic disease.
Associations between Endothelial Lipase, High-Density Lipoprotein, and Endothelial Function Differ in Healthy Volunteers and Metabolic Syndrome Patients
Authors: Klobučar Iva , Stadler Julia T. , Klobučar Lucija , Lechleitner Margarete , Trbušić Matias , Pregartner Gudrun , Berghold Andrea , Habisch Hansjörg , Madl Tobias , Marsche Gunther , Frank Saša , Degoricija Vesna
Published: January 2023

Metabolic syndrome (MS) is characterized by endothelial- and high-density lipoprotein (HDL) dysfunction and increased endothelial lipase (EL) serum levels. We examined the associations between EL serum levels, HDL (serum levels, lipid content, and function), and endothelial function in healthy volunteers (HV) and MS patients. Flow-mediated dilation (FMD), nitroglycerin-mediated dilation (NMD), serum levels of HDL subclasses (measured by nuclear magnetic resonance (NMR) spectroscopy), and EL serum levels differed significantly between HV and MS patients. The serum levels of triglycerides in large HDL particles were significantly positively correlated with FMD and NMD in HV, but not in MS patients. Cholesterol (C) and phospholipid (PL) contents of large HDL particles, calculated as HDL1-C/HDL1-apoA-I and HDL1-PL/HDL1-apoA-I, respectively, were significantly negatively correlated with FMD in HV, but not in MS patients. Cholesterol efflux capacity and arylesterase activity of HDL, as well as EL, were correlated with neither FMD nor NMD. EL was significantly negatively correlated with HDL-PL/HDL-apoA-I in HV, but not in MS patients, and with serum levels of small dense HDL containing apolipoprotein A-II in MS patients, but not in HV. We conclude that MS modulates the association between HDL and endothelial function, as well as between EL and HDL. HDL cholesterol efflux capacity and arylesterase activity, as well as EL serum levels, are not associated with endothelial function in HV or MS patients.
Hybrid Molecules Consisting of Lysine Dendrons with Several Hydrophobic Tails: A SCF Study of Self-Assembling
Authors: Shavykin Oleg V. , Mikhtaniuk Sofia E. , Fatullaev Emil I. , Neelov Igor M. , Leermakers Frans A. M. , Brito Mariano E. , Holm Christian , Borisov Oleg V. , Darinskii Anatoly A.
Published: January 2023

In this article, we used the numerical self-consistent field method of Scheutjens–Fleer to study the micellization of hybrid molecules consisting of one polylysine dendron with charged end groups and several linear hydrophobic tails attached to its root. The main attention was paid to spherical micelles and the determination of the range of parameters at which they can appear. A relationship has been established between the size and internal structure of the resulting spherical micelles and the length and number of hydrophobic tails, as well as the number of dendron generations. It is shown that the splitting of the same number of hydrophobic monomers from one long tail into several short tails leads to a decrease in the aggregation number and, accordingly, the number of terminal charges in micelles. At the same time, it was shown that the surface area per dendron does not depend on the number of hydrophobic monomers or tails in the hybrid molecule. The relationship between the structure of hybrid molecules and the electrostatic properties of the resulting micelles has also been studied. It is found that the charge distribution in the corona depends on the number of dendron generations G in the hybrid molecule. For a small number of generations (up to G=3), a standard double electric layer is observed. For a larger number of generations (G=4), the charges of dendrons in the corona are divided into two populations: in the first population, the charges are in the spherical layer near the boundary between the micelle core and shell, and in the second population, the charges are near the periphery of the spherical shell. As a result, a part of the counterions is localized in the wide region between them. These results are of potential interest for the use of spherical dendromicelles as nanocontainers for drug delivery.
Estimating Total Quantitative Protein Content in Escherichia coli, Saccharomyces cerevisiae, and HeLa Cells
Authors: Dolgalev Georgii V. , Safonov Taras A. , Arzumanian Viktoriia A. , Kiseleva Olga I. , Poverennaya Ekaterina V.
Published: January 2023

The continuous improvement of proteomic techniques, most notably mass spectrometry, has generated quantified proteomes of many organisms with unprecedented depth and accuracy. However, there is still a significant discrepancy in the reported numbers of total protein molecules per specific cell type. In this article, we explore the results of proteomic studies of Escherichia coli, Saccharomyces cerevisiae, and HeLa cells in terms of total protein copy numbers per cell. We observe up to a ten-fold difference between reported values. Investigating possible reasons for this discrepancy, we conclude that neither an unmeasured fraction of the proteome nor biases in the quantification of individual proteins can explain the observed discrepancy. We normalize protein copy numbers in each study using a total protein amount per cell as reported in the literature and create integrated proteome maps of the selected model organisms. Our results indicate that cells contain from one to three million protein molecules per µm3 and that protein copy density decreases with increasing organism complexity.
Analysis of Non-Amyloidogenic Mutations in APP Supports Loss of Function Hypothesis of Alzheimer’s Disease
Authors: Kim Meewhi , Bezprozvanny Ilya
Published: January 2023

Proteolytic processing of amyloid precursor protein (APP) plays a critical role in pathogenesis of Azheimer’s disease (AD). Sequential cleavage of APP by β- and γ-secretases leads to generation of Aβ40 (non-amyloidogenic) and Aβ42 (amyloidogenic) peptides. Presenilin-1 (PS1) or presenilin-2 (PS2) act as catalytic subunits of γ-secretase. Multiple familial AD (FAD) mutations in APP, PS1, or PS2 affect APP proteolysis by γ-secretase and influence levels of generated Aβ40 and Aβ42 peptides. The predominant idea in the field is the “amyloid hypothesis” that states that the resulting increase in Aβ42:Aβ40 ratio leads to “toxic gain of function” due to the accumulation of toxic Aβ42 plaques and oligomers. An alternative hypothesis based on analysis of PS1 conditional knockout mice is that “loss of function” of γ-secretase plays an important role in AD pathogenesis. In the present paper, we propose a mechanistic hypothesis that may potentially reconcile these divergent ideas and observations. We propose that the presence of soluble Aβ peptides in endosomal lumen (and secreted to the extracellular space) is essential for synaptic and neuronal function. Based on structural modeling of Aβ peptides, we concluded that Aβ42 peptides and Aβ40 peptides containing non-amyloidogenic FAD mutations in APP have increased the energy of association with the membranes, resulting in reduced levels of soluble Aβ in endosomal compartments. Analysis of PS1-FAD mutations also revealed that all of these mutations lead to significant reduction in both total levels of Aβ produced and in the Aβ40/Aβ42 ratio, suggesting that the concentration of soluble Aβ in the endosomal compartments is reduced as a result of these mutations. We further reasoned that similar changes in Aβ production may also occur as a result of age-related accumulation of cholesterol and lipid oxidation products in postsynaptic spines. Our analysis more easily reconciled with the “loss of γ-secretase function” hypothesis than with the “toxic gain of Aβ42 function” idea. These results may also explain why inhibitors of β- and γ- secretase failed in clinical trials, as these compounds are also expected to significantly reduce soluble Aβ levels in the endosomal compartments.