bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral Exposure to House Dust Mite Activates Intestinal Innate Immunity
Authors: Benedé Sara , Pérez-Rodríguez Leticia , Martínez-Blanco Mónica , Molina Elena , López-Fandiño Rosina
Published: March 2021

Scope: House dust mite (HDM) induces Th2 responses in lungs and skin, but its effects in the intestine are poorly known. We aimed to study the involvement of HDM in the initial events that would promote sensitization through the oral route and eventually lead to allergy development. Methods and results: BALB/c mice were exposed intragastrically to proteolytically active and inactive HDM, as such, or in combination with egg white (EW), and inflammatory and type 2 responses were evaluated. Oral administration of HDM, by virtue of its proteolytic activity, promoted the expression, in the small intestine, of genes encoding tight junction proteins, proinflammatory and Th2-biasing cytokines, and it caused expansion of group 2 innate immune cells, upregulation of Th2 cytokines, and dendritic cell migration and activation. In lymphoid tissues, its proteolytically inactivated counterpart also exerted an influence on the expression of surface DC molecules involved in interactions with T cells and in Th2 cell differentiation, which was confirmed in in vitro experiments. However, in our experimental setting we did not find evidence for the promotion of sensitization to coadministered EW. Conclusion: Orally administered HDM upregulates tissue damage factors and also acts as an activator of innate immune cells behaving similarly to potent oral Th2 adjuvants.
In Vitro Screening of Chicken-Derived Lactobacillus Strains that Effectively Inhibit Salmonella Colonization and Adhesion
Authors: Hai Dan , Lu Zhaoxin , Huang Xianqing , Lv Fengxia , Bie Xiaomei
Published: March 2021

Inhibition of Salmonella by Lactobacillus has been a popular research topic for decades; however, the inhibition potential of chicken-derived Salmonella by chicken-derived Lactobacillus has not yet been studied. In this study, 89 strains of Lactobacillus from chicken intestines were isolated by national standard method, Gram staining, physiological, and biochemical experiments and molecular sequencing; The inhibition characteristics of 89 strains of chicken derived Lactobacillus against 10 strains Salmonella (S. Enteritidis SE05, SC31, SC21, SC72 SC74, SC79, SC83, SC87; S. bongori SE47; S. Typhimurium, SC85) were detected by agar inhibition zone, The results showed that the inhibition zone of 24 strains of chicken derived Lactobacillus was more than 10 mm, which indicated that the isolated chicken derived Lactobacillus could effectively inhibit the growth of Salmonella; The drug resistance and bile salt tolerance of these 24 strains were analyzed, The results showed that the standard strains LG and L76 were not resistant, and the other 22 Lactobacillus strains showed different degrees of resistance. The strains LAB24, LAB26, LAB53, LAB69, and L76 showed good tolerance at the concentration of 3 g/L bile salt; Caco-2 cell experiment and flow cytometry were used to analyze the inhibitory effect of chicken derived Lactobacillus on the adhesion of Salmonella to Caco-2 cells, The results showed that 16 probiotics could effectively inhibit the adhesion of Salmonella to Caco-2 cells. Twelve probiotics were identified by molecular biology. The results showed that L76 was Enterococcus faecalis, and the other 11 strains were Lactobacillus.
Influence of Inhibitory Compounds on Biofuel Production from Oxalate-Rich Rhubarb Leaf Hydrolysates Using Thermoanaerobacter thermohydrosulfuricus Strain AK91
Authors: Orlygsson Johann , Scully Sean Michael
Published: March 2021

The present investigation is on bioethanol and biohydrogen production from oxalate-rich rhubarb leaves which are an underutilized residue of rhubarb cultivation. Rhubarb leaves can be the feedstock for bioethanol and biohydrogen production using thermophilic, anaerobic bacteria. The fermentation of second-generation biomass to biofuels by Thermoanaerobacter has already been reported as well as their high ethanol and hydrogen yields although rhubarb biomass has not been examined for this purpose. Thermoanaerobacter thermohydrosulfuricus strain AK91 was characterized (temperature and pH optima, substrate utilization spectrum) which demonstrates that the strain can utilize most carbohydrates found in lignocellulosic biomass. Additionally, the influence of specific culture conditions, namely the partial pressure of hydrogen and initial glucose concentration, were investigated in batch culture and reveals that the strain is inhibited. Additionally, batch experiments containing common inhibitory compounds, namely carboxylic acids and aldehydes, some of which are present in high concentrations in rhubarb. Strain AK91 is not affected by alkanoic carboxylic acids and oxalate up to at least 100 mM although the strain was inhibited by 40 mM of malate. Interestingly, strain AK91 demonstrated the ability to reduce alkanoic carboxylic acids to their primary alcohols; more detailed studies with propionate as a model compound demonstrated that AK91’s growth is not severally impacted by high propionate loadings although 1-propanol titers did not exceed 8.5 mM. Additionally, ethanol and hydrogen production from grass and rhubarb leaf hydrolysates was investigated in batch culture for which AK91 produced 7.0 and 6.3 mM g−1, respectively.
Maternal Vitamin and Mineral Supplementation and Rate of Maternal Weight Gain Affects Placental Expression of Energy Metabolism and Transport-Related Genes
Authors: Diniz Wellison J. S. , Reynolds Lawrence P. , Borowicz Pawel P. , Ward Alison K. , Sedivec Kevin K. , McCarthy Kacie L. , Kassetas Cierrah J. , Baumgaertner Friederike , Kirsch James D. , Dorsam Sheri T. , Neville Tammi L. , Forcherio J. Chris , Scott Ronald R. , Caton Joel S. , Dahlen Carl R.
Published: March 2021

Maternal nutrients are essential for proper fetal and placental development and function. However, the effects of vitamin and mineral supplementation under two rates of maternal weight gain on placental genome-wide gene expression have not been investigated so far. Furthermore, biological processes and pathways in the placenta that act in response to early maternal nutrition are yet to be elucidated. Herein, we examined the impact of maternal vitamin and mineral supplementation (from pre-breeding to day 83 post-breeding) and two rates of gain during the first 83 days of pregnancy on the gene expression of placental caruncles (CAR; maternal placenta) and cotyledons (COT; fetal placenta) of crossbred Angus beef heifers. We identified 267 unique differentially expressed genes (DEG). Among the DEGs from CAR, we identified ACAT2, SREBF2, and HMGCCS1 that underlie the cholesterol biosynthesis pathway. Furthermore, the transcription factors PAX2 and PAX8 were over-represented in biological processes related to kidney organogenesis. The DEGs from COT included SLC2A1, SLC2A3, SLC27A4, and INSIG1. Our over-representation analysis retrieved biological processes related to nutrient transport and ion homeostasis, whereas the pathways included insulin secretion, PPAR signaling, and biosynthesis of amino acids. Vitamin and mineral supplementation and rate of gain were associated with changes in gene expression, biological processes, and KEGG pathways in beef cattle placental tissues.
Filling the Gaps in the Cyanobacterial Tree of Life—Metagenome Analysis of Stigonema ocellatum DSM 106950, Chlorogloea purpurea SAG 13.99 and Gomphosphaeria aponina DSM 107014
Authors: Marter Pia , Huang Sixing , Brinkmann Henner , Pradella Silke , Jarek Michael , Rohde Manfred , Bunk Boyke , Petersen Jörn
Published: March 2021

Cyanobacteria represent one of the most important and diverse lineages of prokaryotes with an unparalleled morphological diversity ranging from unicellular cocci and characteristic colony-formers to multicellular filamentous strains with different cell types. Sequencing of more than 1200 available reference genomes was mainly driven by their ecological relevance (Prochlorococcus, Synechococcus), toxicity (Microcystis) and the availability of axenic strains. In the current study three slowly growing non-axenic cyanobacteria with a distant phylogenetic positioning were selected for metagenome sequencing in order to (i) investigate their genomes and to (ii) uncover the diversity of associated heterotrophs. High-throughput Illumina sequencing, metagenomic assembly and binning allowed us to establish nearly complete high-quality draft genomes of all three cyanobacteria and to determine their phylogenetic position. The cyanosphere of the limnic isolates comprises up to 40 heterotrophic bacteria that likely coexisted for several decades, and it is dominated by Alphaproteobacteria and Bacteriodetes. The diagnostic marker protein RpoB ensured in combination with our novel taxonomic assessment via BLASTN-dependent text-mining a reliable classification of the metagenome assembled genomes (MAGs). The detection of one new family and more than a dozen genera of uncultivated heterotrophic bacteria illustrates that non-axenic cyanobacteria are treasure troves of hidden microbial diversity.
Differences in Hospital Costs among Octogenarians and Nonagenarians Following Primary Total Joint Arthroplasty
Authors: Fang Christopher , Hagar Andrew , Gordon Matthew , Talmo Carl T. , Mattingly David A. , Smith Eric L.
Published: March 2021

The proportion of patients over the age of 90 years continues to grow, and the anticipated demand for total joint arthroplasty (TJA) in this population is expected to rise concomitantly. As the country shifts to alternative reimbursement models, data regarding hospital expenses is needed for accurate risk-adjusted stratification. The aim of this study was to compare total in-hospital costs following primary TJA in octogenarians and nonagenarians, and to determine the primary drivers of cost. This was a retrospective analysis from a single institution in the U.S. We used time-drive activity-based costing (TDABC) to capture granular total hospital costs for each patient. 889 TJA’s were included in the study, with 841 octogenarians and 48 nonagenarians. Nonagenarians were more likely to undergo total hip arthroplasty (THA) (70.8% vs. 42.4%; p < 0.0001), had higher ASA classification (2.6 vs. 2.4; p = 0.049), and were more often privately insured (35.4% vs. 27.8%; p = 0.0001) as compared to octogenarians. Nonagenarians were more often discharged to skilled nursing facilities (56.2% vs. 37.5%; p = 0.0011), experienced longer operating room (OR) time (142 vs. 133; p = 0.0201) and length of stay (3.7 vs. 3.1; p = 0.0003), and had higher implant and total in-hospital costs (p < 0.0001 and 0.0001). Multivariate linear regression showed implant cost (0.700; p < 0.0001), length of stay (0.546; p < 0.0001), and OR time (0.288; p < 0.0001) to be the strongest associations with overall costs. Primary TJA for nonagenarians was more expensive than octogenarians. Targeting implant costs, length of stay, and OR time can reduce costs for nonagenarians in order to provide cost-effective value-based care.
Components and Related Factors of Nursing Interventions for Improving Resilience in Cancer Patients Undergoing Chemotherapy
Authors: Shimada Shiena , Aoyanagi Michiko , Sumi Naomi
Published: March 2021

Resilience is considered an effective concept for cancer patients, but nursing interventions for improving resilience have not been studied adequately yet. We aimed to explore the components and related factors of nursing interventions for promoting resilience among cancer patients receiving chemotherapy (NIPRPC). This cross-sectional study included 68 facilities from 396 cancer hospitals in Japan. Participants were 377 nurses who worked at the outpatient chemotherapy center or cancer ward. They completed self-administered questionnaires including the NIPRPC items and Resilience Scale for Nurses, etc. We conducted factor, correlational, and regression analysis. Based on the exploratory factor analysis, six-dimensional factor components: “Support for patients during the present situation and increasing their self-affirmation”, “Support for self-help”, “Support for utilizing the cancer medical team”, “Support for obtaining family cooperation”, “Support for maintaining regular lifestyle during chemotherapy”, and “Support for interacting with cancer patients and utilizing necessary information”. The strong related factors for all six factors were the resilience of the nurses and the number of collaborations with multiple occupations. Our findings will help nurses improve the psychosocial quality of life of cancer patients and address their needs related to cancer chemotherapy treatment.
Qualitative Study of General Public Views towards Adverse Drug Reactions in Lithuania
Authors: Valinciute-Jankauskiene Agne , Kubiliene Loreta
Published: March 2021

Direct patient reporting of adverse drug reactions (ADRs) is available in many countries, as patients are often knowledgeable about their health conditions and medicines. This study aimed to assess whether patients can recognize ADRs and whether they know how to proceed with ADR reporting. The study also assesses ADR information sources and the main barriers to reporting. Through the purposive and snowball sampling techniques, 42 consumers participated in focus group discussions. All discussions were audio recorded, transcribed verbatim, and analyzed for thematic content analysis. The thematic content analysis yielded four major themes: knowledge about medication safety, ADRs, and pharmacovigilance; information sources about medicines and ADRs; knowledge about ADR reporting; attitudes towards ADR reporting; benefits of ADR reporting; barriers to ADR reporting. Participants were able to identify ADRs and used different information sources about medicines and ADRs to confirm their beliefs. However, the poor communication between consumers, pharmacists, and physicians is the main barrier to ADR reporting. This study identified the challenges in relation to pharmacovigilance in Lithuania from patients’ perspectives. Our study indicated a lack of clearly set standards and communication guidelines between patients, physicians, and pharmacists. Active pharmacovigilance might help develop consumer habits regarding the reporting of ADRs in the presence of spontaneous pharmacovigilance.
Predictors of Burnout in Healthcare Workers during the COVID-19 Pandemic
Authors: Cotel Adriana , Golu Florinda , Pantea Stoian Anca , Dimitriu Mihai , Socea Bogdan , Cirstoveanu Catalin , Davitoiu Ana Maria , Jacota Alexe Florentina , Oprea Bogdan
Published: March 2021

The purpose of this study was to identify the predictors of burnout in healthcare workers during the COVID-19 pandemic. Data were collected from March to June in 2020, during the COVID-19 pandemic, from employees of two Romanian hospitals. Five hundred and twenty-three healthcare workers completed a series of questionnaires that measured burnout, job demands, job resources, and personal resources. Among the respondents, 14.5% had a clinical level of exhaustion (the central component of burnout). Three job demands (work–family conflict, lack of preparedness/scope of practice, emotional demands), three job resources (training, professional development, and continuing education; supervision, recognition, and feedback; autonomy and control), and one personal resource (self-efficacy) were significant predictors of burnout, explaining together 37% of the variance in healthcare workers’ burnout. Based on our results, psychological interventions during the COVID-19 pandemic for healthcare employees should focus primarily on these demands and resources.
Lead Emissions and Population Vulnerability in the Detroit Metropolitan Area, 2006–2013: Impact of Pollution, Housing Age and Neighborhood Racial Isolation and Poverty on Blood Lead in Children
Authors: Moody Heather A. , Grady Sue C.
Published: March 2021

This research investigates the relationships between airborne and depositional industrial lead emission concentrations modeled using Environmental Protection Agency’s (EPA’s) American Meteorological Society/Environmental Protection Agency Regulatory Model (AERMOD) and childhood blood lead levels (BLL) in the Detroit Metropolitan Area (DMA) 2006–2013. Linear and mediation interaction regression models estimated the effects of older housing and airborne and depositional lead emission concentrations on black and white childhood BLLs, controlling for neighborhood levels of racial isolation and poverty—important social structures in the DMA. The results showed a direct relationship between airborne and depositional lead emissions and higher childhood BLL, after controlling for median housing age. Lead emissions also exacerbated the effect of older housing on black and white children’s BLLs (indirect relationship), after controlling for social structures. Findings from this research indicate that black and white children exposed to lead-based paint/pipes in older housing are further impacted by industrial lead pollution that may lead to permanent neurological damage.
Perspectives on the Health Effects of Hurricanes: A Review and Challenges
Authors: Waddell Samantha L. , Jayaweera Dushyantha T. , Mirsaeidi Mehdi , Beier John C. , Kumar Naresh
Published: March 2021

Hurricanes are devastating natural disasters which dramatically modify the physical landscape and alter the socio-physical and biochemical characteristics of the environment, thus exposing the affected communities to new environmental stressors, which persist for weeks to months after the hurricane. This paper has three aims. First, it conceptualizes potential direct and indirect health effects of hurricanes and provides an overview of factors that exacerbate the health effects of hurricanes. Second, it summarizes the literature on the health impact of hurricanes. Finally, it examines the time lag between the hurricane (landfall) and the occurrence of diseases. Two major findings emerge from this paper. Hurricanes are shown to cause and exacerbate multiple diseases, and most adverse health impacts peak within six months following hurricanes. However, chronic diseases, including cardiovascular disease and mental disorders, continue to occur for years following the hurricane impact.
Time for ‘Green’ during COVID-19? Inequities in Green and Blue Space Access, Visitation and Felt Benefits
Authors: Astell-Burt Thomas , Feng Xiaoqi
Published: March 2021

We hypothesized that visits to green and blue spaces may have enabled respite, connection and exercise during the COVID-19 pandemic, but such benefits might have been inequitably distributed due to differences in financial difficulties, opportunities to work from home, and localized restrictions in spatial mobility generated by ‘lockdowns’. A nationally representative online and telephone survey conducted in 12–26 October on the Social Research Centre’s Life in AustraliaTM panel (aged ≥ 18 y, 78.8% response, N = 3043) asked about access, visitation, and felt benefits from green and/or blue spaces. Increasing financial difficulty was associated with less time in and fewer visits to green and/or blue spaces, as well as fewer different types visited. Financial difficulty was also associated with feelings that visits to green and/or blue space had less benefit for maintaining social connection. Working from home was associated with more frequent and longer visitation to green and/or blue spaces, as well as discovery of ones previously unvisited. Working from home was also associated with increased levels of exercise and respite resulting from visits to green and/or blue spaces. Residents of Melbourne, a city of 4.9 million who were in ‘lockdown’ at the time of the survey, appeared more likely to benefit from visits to green and/or blue spaces than residents of Sydney, Australia’s largest city at 5.2 million, who were not in lockdown. Residents of Melbourne compared with Sydney reported consistently increased visitation of, discovery of, and greater levels of various felt benefits derived from green and/or blue spaces, including more respite, connection, and exercise. Comparatively shorter distances to preferred green and/or blue spaces and closure of alternative settings at the time of the survey completion in Melbourne compared with Sydney may provide partial explanation, though more acute responses to experiencing green and/or blue spaces within highly cognitively demanding antecedent conditions posed by lockdown are also plausible and warrant further investigation with other health indicators. These results were robust to adjustment for a range of covariates including preferences for natural settings, which were consistently associated with greater levels of green and/or blue space visitation and felt benefits. Collectively, these results indicate that parallel efforts to generate (or renew) felt connection to natural settings, to increase working from home opportunities, and to mitigate financial difficulties may be important to help maximize the population health benefits of urban planning strategies intended to improve the availability of, and to reduce inequities in access to, green and blue spaces. Benefits felt more commonly by people living through lockdown underlines the role previous investments in green and blue space have played in enabling coping during the COVID-19 pandemic.
The Carbon Footprint of Marathon Runners: Training and Racing
Authors: Castaignède Laurent , Veny Frederic , Edwards Johnathan , Billat Véronique
Published: March 2021

Marathon running leaves a significant carbon footprint regarding CO2 emissions; for example, 37 percent of New York Marathon participants travel internationally to New York. The aim of this study is to estimate the CO2 footprint of a person training and competing in a marathon; we will also propose methods to minimize the CO2 footprint because of transportation. In addition, we also examine the influence of food practices and hygiene on training and racing a marathon. Methods: We estimated the annual carbon footprint of one person taking part in a marathon. We considered all training, racing, and travelling (local and international) for one person (we are going to give him the first name of “Henri”), and then compared his CO2 footprint with his colleagues playing tennis and soccer. The excess CO2 footprint whilst running and for shoes, clothing, books, magazines, insurance, travel, hygiene, laundry, and resources for electronics and additional food consumed were calculated. For competitions, we estimated and compared the CO2 emission from transportation to national vs. international marathon (New York). Results: We estimated that our runner emitted 4.3 tons of CO2 equivalent (CO2e), including all greenhouse gases. A transatlantic flight to New York corresponded to 3.5 tons CO2, which is 83% of the annual carbon footprint of an average French citizen which is about 11 tons CO2e/year. This leads to a sudden 40% increase in Henri’s annual carbon footprint. Conclusions: By focusing on the additional carbon footprint from one year of marathon training and racing, and traveling locally versus internationally, this sport still has a potentially significant carbon footprint that runners and race organizers ought to consider. We wanted to answer a growing question of marathon runners who are wondering about the carbon footprint of their sports practice in following with a new environmentalist trend that considers not traveling anymore to participate in marathons and to stay local. However, the representativeness in the selection of calculation objectives is very low. There is no need for statistics since this study is a theoretical simulation of traditional training and competition practices of marathon runners.
Interest in Sexually Transmitted Infections: Analysis of Web Search Data Terms in Eleven Large German Cities from 2015 to 2019
Authors: Pilz Anna Caroline , Tizek Linda , Rüth Melvin , Seiringer Peter , Biedermann Tilo , Zink Alexander
Published: March 2021

Incidence of sexually transmitted infections (STIs) such as chlamydia, gonorrhea, and syphilis has increased in recent years in the US and in European countries. In order to implement effective educational programs, the interests of target populations have to be identified. Since the internet is an important source of information-gathering on health issues, this study investigates web search data in large German cities related to STIs. Google Ads Keyword Planner was used to identify STI-related terms and their search volume in eleven German cities from June 2015 to May 2019. The data obtained were analyzed descriptively with regard to total search volumes, search volumes of specific thematic areas, and search volumes per 100,000 inhabitants. Overall, 741 terms with a total search volume of 5,142,560 queries were identified, with more than 70% of all search queries including a specific disease and “chlamydia” being the overall most often searched term (n = 1,196,160). Time courses of search behavior displayed a continuous interest in STIs with synchronal and national rather than regional peaks. Volumes of search queries lacked periodic patterns. Based on the findings of this study, a more open public discussion about STIs with linkage to increased media coverage and clarification of responsibilities among all STI-treating disciplines concerning management of STIs seem advisable.
Repatriations of Ill and Injured Travelers and Emigrants to Switzerland: A Retrospective Analysis at a Tertiary Emergency Department from 2013–2018
Authors: Brockhus Lara , Eich Anne-Sophie , Exadaktylos Aristomenis , Jachmann Anne , Klukowska-Rötzler Jolanta
Published: March 2021

Background: As more and more people are travelling abroad, there are also increasing numbers who fall ill or have accidents in foreign countries. Some patients must be repatriated. While it has been reported that the number of repatriations is rising steadily, little is known about patients’ characteristics, calling for in depth investigations of this patient group. Methods: We have conducted a retrospective study including 447 patients repatriated to the Emergency Department at the University Hospital (Inselspital) in Bern, Switzerland from 2013–2018. Results: Between 2013 and 2018, the number of repatriated patients increased by 42.6%, from 54 to 77 cases. In total, 59% of these patients were male and the median age was 60 years. Overall, 79% of patients were repatriated from European countries, with the top five countries being Italy, France, Spain, Germany and Austria. About half the cases (51.9%) were caused by illness, the other half by accidents. In total, 127 patients had to undergo surgical intervention abroad; another 194 patients underwent surgery after repatriation. The hospitalization rate was 81.4%, with a median length of in-hospital stay of 9 days (IQR 5–14) at the Inselspital. The mortality rate of at the Inselspital hospitalized patients was 4.4%, with 16 patients dying within the first 30 days after repatriation. The median cost per case was 12,005.79 CHF (IQR 4717.66–24,462.79). A multiple regression analysis showed a significant association of total costs with hospitalization (p = 0.001), surgical intervention (p = 0.001), as well as treatment in the intensive care unit (p = 0.001). Conclusions: The number of repatriations has been continuously increasing in recent years and reached a mean value of more than one case per week at the Inselspital (77 cases per year in 2018). The 30 day-mortality rate of 4.4% and the median cost per case are relatively high, demonstrating a neglected Public Health concern. These findings may provide impetus—not only for further research into repatriations but also for Public Health Promotion strategies.
Addition of Grape Skin and Stems Extracts in Wines during the Storage to Reduce the Sulfur Dioxide: Impact on Red Wine Quality
Authors: Casquete Rocío , Benito María José , Pérez-Nevado Francisco , Martínez Ana , Martín Alberto , de Guía Córdoba María
Published: March 2021

This study aimed to evaluate the usefulness of bioactive extracts obtained from red wine by-products, such as grape skins and stems, for reducing or eliminating the use of SO2 in red wine production. Special attention was focused on guaranteeing the microbiological stability of the red wines and protecting them against oxidation. Therefore, the antioxidant and antimicrobial activities of the extracts and red wines were studied. Red grape stems and skins, by-products of the wine industry, from six types of monovarietal wines, were used. Extracts obtained from stems displayed higher concentrations of total phenolic compounds and higher in vitro antioxidant activity. Both stem and skin extracts demonstrated higher antimicrobial activity against pathogenic bacteria and lower activity against yeasts. In the wines produced, higher antimicrobial and antioxidant activities were observed, mainly in the skin extract batches. This study highlights that bioactive extracts obtained from by-products of wine making could be used to reduce or eliminate the use of SO2 in wine production. In this way, healthier red wines could be obtained while guaranteeing their microbiological stability and protecting them from oxidation. Furthermore, the use of these by-products is strongly associated with the circular economy, as they could help to reduce the environmental impact of the wine industry.
Determinants of Financial Performance in China’s Intelligent Manufacturing Industry: Innovation and Liquidity
Authors: Zhang Guanghong , Lee Yune
Published: March 2021

This study focuses on the mediation channels through which the financial performance of intelligent manufacturing industries closely related to the Fourth Industrial Revolution has been affected. Along with compiling a massive volume of datasets publicized by the Chinese government and other authoritative institutions, a survey of the 317 listed enterprises of the intelligent manufacturing industries in China has been established for statistical analysis. Using Structural Equation Modeling (SEM), this research tests six hypotheses and confirms the inter-factor impact relationship between exogenous and endogenous factors. We find that innovation efforts mainly led by increasing investment in Research & Development (R&D), along with high liquidity, surely lead to good financial performance, whereas innovation efforts alone do not. Government support policy has been found to be closely related not only to higher liquidity, but to good financial performance through the common channel of R&D investment. Regional innovation capability has been revealed to be related to R&D investments, and, furthermore, to liquidity, which shows that the regional innovation system in China has been functioning relatively well to induce enterprises to increase investments and secure higher liquidity, and finally contribute to achieving better business performance. However, regional economic development shows no relationship with R&D investments, and consequently neither with liquidity nor with performance.
Different miRNA Profiles in Plasma Derived Small and Large Extracellular Vesicles from Patients with Neurodegenerative Diseases
Authors: Sproviero Daisy , Gagliardi Stella , Zucca Susanna , Arigoni Maddalena , Giannini Marta , Garofalo Maria , Olivero Martina , Dell’Orco Michela , Pansarasa Orietta , Bernuzzi Stefano , Avenali Micol , Cotta Ramusino Matteo , Diamanti Luca , Minafra Brigida , Perini Giulia , Zangaglia Roberta , Costa Alfredo , Ceroni Mauro , Perrone-Bizzozero Nora I. , Calogero Raffaele A. , Cereda Cristina
Published: March 2021

Identifying biomarkers is essential for early diagnosis of neurodegenerative diseases (NDs). Large (LEVs) and small extracellular vesicles (SEVs) are extracellular vesicles (EVs) of different sizes and biological functions transported in blood and they may be valid biomarkers for NDs. The aim of our study was to investigate common and different miRNA signatures in plasma derived LEVs and SEVs of Alzheimer’s disease (AD), Parkinson’s disease (PD), Amyotrophic Lateral Sclerosis (ALS) and Fronto-Temporal Dementia (FTD) patients. LEVs and SEVs were isolated from plasma of patients and healthy volunteers (CTR) by filtration and differential centrifugation and RNA was extracted. Small RNAs libraries were carried out by Next Generation Sequencing (NGS). MiRNAs discriminate all NDs diseases from CTRs and they can provide a signature for each NDs. Common enriched pathways for SEVs were instead linked to ubiquitin mediated proteolysis and Toll-like receptor signaling pathways and for LEVs to neurotrophin signaling and Glycosphingolipid biosynthesis pathway. LEVs and SEVs are involved in different pathways and this might give a specificity to their role in the spreading of the disease. The study of common and different miRNAs transported by LEVs and SEVs can be of great interest for biomarker discovery and for pathogenesis studies in neurodegeneration.
Molecular Regulation of Skeletal Muscle Growth and Organelle Biosynthesis: Practical Recommendations for Exercise Training
Authors: Solsona Robert , Pavlin Laura , Bernardi Henri , Sanchez Anthony MJ
Published: March 2021

The regulation of skeletal muscle mass and organelle homeostasis is dependent on the capacity of cells to produce proteins and to recycle cytosolic portions. In this investigation, the mechanisms involved in skeletal muscle mass regulation—especially those associated with proteosynthesis and with the production of new organelles—are presented. Thus, the critical roles of mammalian/mechanistic target of rapamycin complex 1 (mTORC1) pathway and its regulators are reviewed. In addition, the importance of ribosome biogenesis, satellite cells involvement, myonuclear accretion, and some major epigenetic modifications related to protein synthesis are discussed. Furthermore, several studies conducted on the topic of exercise training have recognized the central role of both endurance and resistance exercise to reorganize sarcomeric proteins and to improve the capacity of cells to build efficient organelles. The molecular mechanisms underlying these adaptations to exercise training are presented throughout this review and practical recommendations for exercise prescription are provided. A better understanding of the aforementioned cellular pathways is essential for both healthy and sick people to avoid inefficient prescriptions and to improve muscle function with emergent strategies (e.g., hypoxic training). Finally, current limitations in the literature and further perspectives, notably on epigenetic mechanisms, are provided to encourage additional investigations on this topic.
Epigenetic Changes Governing Scn5a Expression in Denervated Skeletal Muscle
Authors: Carreras David , Martinez-Moreno Rebecca , Pinsach-Abuin Mel·lina , Santafe Manel M. , Gomà Pol , Brugada Ramon , Scornik Fabiana S. , Pérez Guillermo J. , Pagans Sara
Published: March 2021

The SCN5A gene encodes the α-subunit of the voltage-gated cardiac sodium channel (NaV1.5), a key player in cardiac action potential depolarization. Genetic variants in protein-coding regions of the human SCN5A have been largely associated with inherited cardiac arrhythmias. Increasing evidence also suggests that aberrant expression of the SCN5A gene could increase susceptibility to arrhythmogenic diseases, but the mechanisms governing SCN5A expression are not yet well understood. To gain insights into the molecular basis of SCN5A gene regulation, we used rat gastrocnemius muscle four days following denervation, a process well known to stimulate Scn5a expression. Our results show that denervation of rat skeletal muscle induces the expression of the adult cardiac Scn5a isoform. RNA-seq experiments reveal that denervation leads to significant changes in the transcriptome, with Scn5a amongst the fifty top upregulated genes. Consistent with this increase in expression, ChIP-qPCR assays show enrichment of H3K27ac and H3K4me3 and binding of the transcription factor Gata4 near the Scn5a promoter region. Also, Gata4 mRNA levels are significantly induced upon denervation. Genome-wide analysis of H3K27ac by ChIP-seq suggest that a super enhancer recently described to regulate Scn5a in cardiac tissue is activated in response to denervation. Altogether, our experiments reveal that similar mechanisms regulate the expression of Scn5a in denervated muscle and cardiac tissue, suggesting a conserved pathway for SCN5A expression among striated muscles.
Omics Approaches in Adipose Tissue and Skeletal Muscle Addressing the Role of Extracellular Matrix in Obesity and Metabolic Dysfunction
Authors: Anguita-Ruiz Augusto , Bustos-Aibar Mireia , Plaza-Díaz Julio , Mendez-Gutierrez Andrea , Alcalá-Fdez Jesús , Aguilera Concepción María , Ruiz-Ojeda Francisco Javier
Published: March 2021

Extracellular matrix (ECM) remodeling plays important roles in both white adipose tissue (WAT) and the skeletal muscle (SM) metabolism. Excessive adipocyte hypertrophy causes fibrosis, inflammation, and metabolic dysfunction in adipose tissue, as well as impaired adipogenesis. Similarly, disturbed ECM remodeling in SM has metabolic consequences such as decreased insulin sensitivity. Most of described ECM molecular alterations have been associated with DNA sequence variation, alterations in gene expression patterns, and epigenetic modifications. Among others, the most important epigenetic mechanism by which cells are able to modulate their gene expression is DNA methylation. Epigenome-Wide Association Studies (EWAS) have become a powerful approach to identify DNA methylation variation associated with biological traits in humans. Likewise, Genome-Wide Association Studies (GWAS) and gene expression microarrays have allowed the study of whole-genome genetics and transcriptomics patterns in obesity and metabolic diseases. The aim of this review is to explore the molecular basis of ECM in WAT and SM remodeling in obesity and the consequences of metabolic complications. For that purpose, we reviewed scientific literature including all omics approaches reporting genetic, epigenetic, and transcriptomic (GWAS, EWAS, and RNA-seq or cDNA arrays) ECM-related alterations in WAT and SM as associated with metabolic dysfunction and obesity.
Dysbiosis in the Development of Type I Diabetes and Associated Complications: From Mechanisms to Targeted Gut Microbes Manipulation Therapies
Authors: Gradisteanu Pircalabioru Gratiela , Corcionivoschi Nicolae , Gundogdu Ozan , Chifiriuc Mariana-Carmen , Marutescu Luminita Gabriela , Ispas Bogdan , Savu Octavian
Published: March 2021

Globally, we are facing a worrying increase in type 1 diabetes mellitus (T1DM) incidence, with onset at younger age shedding light on the need to better understand the mechanisms of disease and step-up prevention. Given its implication in immune system development and regulation of metabolism, there is no surprise that the gut microbiota is a possible culprit behind T1DM pathogenesis. Additionally, microbiota manipulation by probiotics, prebiotics, dietary factors and microbiota transplantation can all modulate early host–microbiota interactions by enabling beneficial microbes with protective potential for individuals with T1DM or at high risk of developing T1DM. In this review, we discuss the challenges and perspectives of translating microbiome data into clinical practice. Nevertheless, this progress will only be possible if we focus our interest on developing numerous longitudinal, multicenter, interventional and double-blind randomized clinical trials to confirm their efficacy and safety of these therapeutic approaches.
Comparative Analysis of CREB3 and CREB3L2 Protein Expression in HEK293 Cells
Authors: Oh-hashi Kentaro , Yamamoto Ayumi , Murase Ryoichi , Hirata Yoko
Published: March 2021

We performed a comparative analysis of two ER-resident CREB3 family proteins, CREB3 and CREB3L2, in HEK293 cells using pharmacological and genome editing approaches and identified several differences between the two. Treatment with brefeldin A (BFA) and monensin induced the cleavage of full-length CREB3 and CREB3L2; however, the level of the full-length CREB3 protein, but not CREB3L2 protein, was not noticeably reduced by the monensin treatment. On the other hand, treatment with tunicamycin (Tm) shifted the molecular weight of the full-length CREB3L2 protein downward but abolished CREB3 protein expression. Thapsigargin (Tg) significantly increased the expression of only full-length CREB3L2 protein concomitant with a slight increase in the level of its cleaved form. Treatment with cycloheximide and MG132 revealed that both endogenous CREB3 and CREB3L2 are proteasome substrates. In addition, kifunensine, an α-mannosidase inhibitor, significantly increased the levels of both full-length forms. Consistent with these findings, cells lacking SEL1L, a crucial ER-associated protein degradation (ERAD) component, showed increased expression of both full-length CREB3 and CREB3L2; however, cycloheximide treatment downregulated full-length CREB3L2 protein expression more rapidly in SEL1L-deficient cells than the full-length CREB3 protein. Finally, we investigated the induction of the expression of several CREB3 and CREB3L2 target genes by Tg and BFA treatments and SEL1L deficiency. In conclusion, this study suggests that both endogenous full-length CREB3 and CREB3L2 are substrates for ER-associated protein degradation but are partially regulated by distinct mechanisms, each of which contributes to unique cellular responses that are distinct from canonical ER signals.
A Review of the Pharmacological Activities and Recent Synthetic Advances of γ-Butyrolactones
Authors: Hur Joonseong , Jang Jaebong , Sim Jaehoon
Published: March 2021

γ-Butyrolactone, a five-membered lactone moiety, is one of the privileged structures of diverse natural products and biologically active small molecules. Because of their broad spectrum of biological and pharmacological activities, synthetic methods for γ-butyrolactones have received significant attention from synthetic and medicinal chemists for decades. Recently, new developments and improvements in traditional methods have been reported by considering synthetic efficiency, feasibility, and green chemistry. In this review, the pharmacological activities of natural and synthetic γ-butyrolactones are described, including their structures and bioassay methods. Mainly, we summarize recent advances, occurring during the past decade, in the construction of γ-butyrolactone classified based on the bond formation in γ-butyrolactone between (i) C5-O1 bond, (ii) C4-C5 and C2-O1 bonds, (iii) C3-C4 and C2-O1 bonds, (iv) C3-C4 and C5-O1 bonds, (v) C2-C3 and C2-O1 bonds, (vi) C3-C4 bond, and (vii) C2-O1 bond. In addition, the application to the total synthesis of natural products bearing γ-butyrolactone scaffolds is described.
Deletion of Irf4 in T Cells Suppressed Autoimmune Uveitis and Dysregulated Transcriptional Programs Linked to CD4+ T Cell Differentiation and Metabolism
Authors: Kang Minkyung , Lee Hyun-Su , Choi Jin Kyeong , Yu Cheng-Rong , Egwuagu Charles E.
Published: March 2021

Interferon regulatory factor-4 (IRF4) and IRF8 regulate differentiation, growth and functions of lymphoid and myeloid cells. Targeted deletion of irf8 in T cells (CD4-IRF8KO) has been shown to exacerbate colitis and experimental autoimmune uveitis (EAU), a mouse model of human uveitis. We therefore generated mice lacking irf4 in T cells (CD4-IRF4KO) and investigated whether expression of IRF4 by T cells is also required for regulating T cells that suppress autoimmune diseases. Surprisingly, we found that CD4-IRF4KO mice are resistant to EAU. Suppression of EAU derived in part from inhibiting pathogenic responses of Th17 cells while inducing expansion of regulatory lymphocytes that secrete IL-10 and/or IL-35 in the eye and peripheral lymphoid tissues. Furthermore, CD4-IRF4KO T cells exhibit alterations in cell metabolism and are defective in the expression of two Ikaros zinc-finger (IKZF) transcription factors (Ikaros, Aiolos) that are required for lymphocyte differentiation, metabolism and cell-fate decisions. Thus, synergistic effects of IRF4 and IkZFs might induce metabolic reprogramming of differentiating lymphocytes and thereby dynamically regulate relative abundance of T and B lymphocyte subsets that mediate immunopathogenic mechanisms during uveitis. Moreover, the diametrically opposite effects of IRF4 and IRF8 during EAU suggests that intrinsic function of IRF4 in T cells might be activating proinflammatory responses while IRF8 promotes expansion of immune-suppressive mechanisms.
Interactions of Lipid Droplets with the Intracellular Transport Machinery
Authors: Dejgaard Selma Yilmaz , Presley John F.
Published: March 2021

Historically, studies of intracellular membrane trafficking have focused on the secretory and endocytic pathways and their major organelles. However, these pathways are also directly implicated in the biogenesis and function of other important intracellular organelles, the best studied of which are peroxisomes and lipid droplets. There is a large recent body of work on these organelles, which have resulted in the introduction of new paradigms regarding the roles of membrane trafficking organelles. In this review, we discuss the roles of membrane trafficking in the life cycle of lipid droplets. This includes the complementary roles of lipid phase separation and proteins in the biogenesis of lipid droplets from endoplasmic reticulum (ER) membranes, and the attachment of mature lipid droplets to membranes by lipidic bridges and by more conventional protein tethers. We also discuss the catabolism of neutral lipids, which in part results from the interaction of lipid droplets with cytosolic molecules, but with important roles for both macroautophagy and microautophagy. Finally, we address their eventual demise, which involves interactions with the autophagocytotic machinery. We pay particular attention to the roles of small GTPases, particularly Rab18, in these processes.
Modeling of Information Processes in Social Networks
Authors: Yablochnikov Sergey , Kuptsov Mikhail , Mahiboroda Maksim
Published: March 2021

In order to model information dissemination in social networks, a special methodology of sampling statistical data formation has been implemented. The probability distribution laws of various characteristics of personal and group accounts in four social networks are investigated. Stochastic aspects of interrelations between these indicators were analyzed. The classification of groups of social network users is proposed, and their characteristic features and main empirical regularities of mutual transitions are marked. Regression models of forecasting changes in the number of users of the selected groups have been obtained.
A Quaternion Gated Recurrent Unit Neural Network for Sensor Fusion
Authors: Onyekpe Uche , Palade Vasile , Kanarachos Stratis , Christopoulos Stavros-Richard
Published: March 2021

Recurrent Neural Networks (RNNs) are known for their ability to learn relationships within temporal sequences. Gated Recurrent Unit (GRU) networks have found use in challenging time-dependent applications such as Natural Language Processing (NLP), financial analysis and sensor fusion due to their capability to cope with the vanishing gradient problem. GRUs are also known to be more computationally efficient than their variant, the Long Short-Term Memory neural network (LSTM), due to their less complex structure and as such, are more suitable for applications requiring more efficient management of computational resources. Many of such applications require a stronger mapping of their features to further enhance the prediction accuracy. A novel Quaternion Gated Recurrent Unit (QGRU) is proposed in this paper, which leverages the internal and external dependencies within the quaternion algebra to map correlations within and across multidimensional features. The QGRU can be used to efficiently capture the inter- and intra-dependencies within multidimensional features unlike the GRU, which only captures the dependencies within the sequence. Furthermore, the performance of the proposed method is evaluated on a sensor fusion problem involving navigation in Global Navigation Satellite System (GNSS) deprived environments as well as a human activity recognition problem. The results obtained show that the QGRU produces competitive results with almost 3.7 times fewer parameters compared to the GRU.