bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-Coding RNA in Systemic Sclerosis: A Valuable Tool for Translational and Personalized Medicine
Authors: Rusek Marta , Krasowska Dorota
Published: August 2021

Epigenetic factors are heritable and ultimately play a role in modulating gene expression and, thus, in regulating cell functions. Non-coding RNAs have growing recognition as novel biomarkers and crucial regulators of pathological conditions in humans. Their characteristic feature is being transcribed in a tissue-specific pattern. Now, there is emerging evidence that lncRNAs have been identified to be involved in the differentiation of human skin, wound healing, fibrosis, inflammation, and immunological response. Systemic sclerosis (SSc) is a heterogeneous autoimmune disease characterized by fibrosis, vascular abnormalities, and immune system activation. The pathogenesis remains elusive, but clinical manifestations reveal autoimmunity with the presence of specific autoantibodies, activation of innate and adaptive immunity, vascular changes, and active deposition of extracellular matrix components leading to fibrosis. The use of multi-omics studies, including NGS, RNA-seq, or GWAS, has proposed that the non-coding genome may be a significant player in its pathogenesis. Moreover, it may unravel new therapeutic targets in the future. The aim of this review is to show the pathogenic role of long non-coding RNAs in systemic sclerosis. Investigation of these transcripts’ functions has the potential to elucidate the molecular pathology of SSc and provide new opportunities for drug-targeted therapy for this disorder.
A Draft Genome of the Ginger Species Alpinia nigra and New Insights into the Genetic Basis of Flexistyly
Authors: Ranavat Surabhi , Becher Hannes , Newman Mark F. , Gowda Vinita , Twyford Alex D.
Published: August 2021

Angiosperms possess various strategies to ensure reproductive success, such as stylar polymorphisms that encourage outcrossing. Here, we investigate the genetic basis of one such dimorphism that combines both temporal and spatial separation of sexual function, termed flexistyly. It is a floral strategy characterised by the presence of two morphs that differ in the timing of stylar movement. We performed a de novo assembly of the genome of Alpinia nigra using high-depth genomic sequencing. We then used Pool-seq to identify candidate regions for flexistyly based on allele frequency or coverage differences between pools of anaflexistylous and cataflexistylous morphs. The final genome assembly size was 2 Gb, and showed no evidence of recent polyploidy. The Pool-seq did not reveal large regions with high FST values, suggesting large structural chromosomal polymorphisms are unlikely to underlie differences between morphs. Similarly, no region had a 1:2 mapping depth ratio which would be indicative of hemizygosity. We propose that flexistyly is governed by a small genomic region that might be difficult to detect with Pool-seq, or a complex genomic region that proved difficult to assemble. Our genome will be a valuable resource for future studies of gingers, and provides the first steps towards characterising this complex floral phenotype.
SALL4 and microRNA: The Role of Let-7
Authors: Liu Jun , Sauer Madeline A. , Hussein Shaza G. , Yang Junyu , Tenen Daniel G. , Chai Li
Published: August 2021

SALL4 is a zinc finger transcription factor that belongs to the spalt-like (SALL) gene family. It plays important roles in the maintenance of self-renewal and pluripotency of embryonic stem cells, and its expression is repressed in most adult organs. SALL4 re-expression has been observed in different types of human cancers, and dysregulation of SALL4 contributes to the pathogenesis, metastasis, and even drug resistance of multiple cancer types. Surprisingly, little is known regarding how SALL4 expression is controlled, but recently microRNAs (miRNAs) have emerged as important regulators of SALL4. Due to the ability of regulating targets differentially in specific tissues, and recent advances in systemic and organ specific miRNA delivery mechanisms, miRNAs have emerged as promising therapeutic targets for cancer treatment. In this review, we summarize current knowledge of the interaction between SALL4 and miRNAs in mammalian development and cancer, paying particular attention to the emerging roles of the Let-7/Lin28 axis. In addition, we discuss the therapeutic prospects of targeting SALL4 using miRNA-based strategies, with a focus on the Let-7/LIN28 axis.
Pyrite Morphology and δ34S as Indicators of Deposition Environment in Organic-Rich Shales
Authors: Idrisova Elizaveta , Gabitov Rinat , Karamov Tagir , Voropaev Andrey , Liu Ming-Chang , Bogdanovich Natalia , Spasennykh Mikhail
Published: August 2021

This study is focused on the mineralogical, chemical, and isotopic characterization of pyrites from the rocks of the Bazhenov Formation (Upper Jurassic–Lower Cretaceous organic-rich shales, Western Siberia, Russia). Scanning electron microscopy (SEM) revealed pyrites of different morphologies: small and large framboids, small crystals, and large euhedral crystals; all morphotypes were usually combined into aggregates. Isotope ratio mass spectrometry (IRMS) and secondary ion mass spectrometry (SIMS) showed that small framboids and microcrystalline pyrite are isotopically light, with δ34SCDT varying from −55 to −20‰. Large framboids and euhedral crystals of pyrite are isotopically heavy with δ34SCDT up to +26‰. Both morphology and δ34S were suggested to be controlled by the redox conditions and sedimentation regime. The abundance of small framboids suggests that pyrite sedimentation occurred under anoxic conditions; the presence of the large framboids and euhedral crystals of pyrite suggest the accumulation of sediments occurred at suboxic conditions, possibly in the presence of oxygen.
Pilot Study Using ArcGIS Online to Enhance Students’ Learning Experience in Fieldwork
Authors: Phantuwongraj Sumet , Chenrai Piyaphong , Assawincharoenkij Thitiphan
Published: August 2021

Applying ArcGIS Online application to geological fieldwork provides an alternative way to teach students. This brief report describes an educational innovation for geological fieldwork with the ArcGIS Online application to examine students’ learning experiences. In comparison to traditional classrooms, this teaching method enables students to more easily comprehend how geological structures and features connect through the mapping area. This observation indicates that students can think about the structure and deformation events as spatial continuity during acquisition data gathering in the field. Results from independent t-tests between treated and untreated student groups show that the average post-test scores of the treated students were significantly higher than pre-test scores, at a p = 0.05 level, after using ArcGIS Online in fieldwork designed in this study. Therefore, the ArcGIS Online application plays an important role in changing and developing the geological fieldwork in Thailand at the university scale for students. This teaching method could potentially benefit any science teaching and have applications in other disciplines requiring similar skills as well.
Comparison between Virtual and Traditional Learning Methods for Orthodontic Knowledge and Skills in Dental Students: A Quasi-Experimental Study
Authors: Hakami Zaki
Published: August 2021

A gradual transition from traditional face-to-face learning to online learning has been observed globally following the COVID-19 pandemic. The aim of the study was to compare online and traditional learning methods in relation to orthodontic knowledge and skills acquired in undergraduate courses. A quasi-experimental design was used with two consecutive year classes of 198 dental students at Jazan University, Saudi Arabia. The experimental (virtual) group of 92 students received the content of a clinical orthodontic course virtually using the Blackboard Collaborate™ platform. The control (traditional) group consisted of a previous cohort of 106 students who enrolled in the same course but received traditional classroom education. The students were evaluated through a semester, and both groups obtained the same content and exam questions. The students in the virtual group scored higher in the final theory exam than the traditional group (p-value < 0.05). However, no significant difference in the overall orthodontic knowledge and skills was observed between the groups at the end of the course. Both learning methods showed moderate positive correlation between orthodontic knowledge and skills. In conclusion, virtual learning can serve as an effective alternative to traditional face-to-face learning for teaching orthodontic knowledge and skills to the dental students.
Lipid-Free Parenteral Nutrition Is Associated with an Increased Risk of Hepatic Dysfunction in Surgical Critically Ill Patients: A Retrospective Observational Study
Authors: Wu Shih-Chi , Chen Te-An , Tsai I-Ju , Wang Yu-Chun , Cheng Han-Tsung , Tzeng Chia-Wei , Hsu Chia-Hao , Muo Chih-Hsin
Published: August 2021

To evaluate the effects of lipid-free parenteral nutrition (PN) and various intravenous fat emulsions (IVFEs) on hepatic function in surgical critically ill trauma/acute care surgery patients. We retrospectively reviewed trauma/acute care surgery patients without admission hepatic disorder that received PN. The PN groups include lipid-free, soybean oil/medium-chain triglyceride, olive oil-based, and fish-oil contained PN. We excluded patients with (1) age <18 years, (2) without surgery, (3) preexisting liver injury/diseases, (4) hyperbilirubinemia at admission, (5) received more than one type of PN, and (6) repeated ICU episodes in the same hospitalization. Hepatic dysfunction was considered as serum total–bilirubin >6.0 mg/dL. The demographics, severity score, comorbidities, blood stream infection, and mortality were collected for analyses. The major outcome is hepatic function. We also performed analyses stratified by separated lipid doses (g/kg/day). A total of 249 patients were enrolled. There were no demographic differences among groups. The lipid-free PN group had a higher incidence of hepatic dysfunction and mortality. Compared to the lipid-free group, the other three IVFEs had significantly lower risks of hepatic dysfunction, while the olive oil-based group had a significantly lower risk of 30 and 90-day mortality. After being stratified by separating lipid doses, the soybean oils showed a decreasing trend of hepatic dysfunction and mortality with increased dosage. Fish oil >0.05 g/kg/day was associated with lower hepatic dysfunction incidences. Our findings suggest that, when compared to IVFEs, surgical critically ill patients with trauma/acute care surgery that received lipid-free PN are associated with an increased risk of hepatic dysfunction. In addition, the olive oil-based group had a significantly lower risk of mortality, while fish oil >0.05 g/kg/day was associated with lower incidences of hepatic dysfunction; however, further studies are warranted.
Assessing the Water Quality of Lake Hawassa Ethiopia—Trophic State and Suitability for Anthropogenic Uses—Applying Common Water Quality Indices
Authors: Lencha Semaria Moga , Tränckner Jens , Dananto Mihret
Published: August 2021

The rapid growth of urbanization, industrialization and poor wastewater management practices have led to an intense water quality impediment in Lake Hawassa Watershed. This study has intended to engage the different water quality indices to categorize the suitability of the water quality of Lake Hawassa Watershed for anthropogenic uses and identify the trophic state of Lake Hawassa. Analysis of physicochemical water quality parameters at selected sites and periods was conducted throughout May 2020 to January 2021 to assess the present status of the Lake Watershed. In total, 19 monitoring sites and 21 physicochemical parameters were selected and analyzed in a laboratory. The Canadian council of ministries of the environment (CCME WQI) and weighted arithmetic (WA WQI) water quality indices have been used to cluster the water quality of Lake Hawassa Watershed and the Carlson trophic state index (TSI) has been employed to identify the trophic state of Lake Hawassa. The water quality is generally categorized as unsuitable for drinking, aquatic life and recreational purposes and it is excellent to unsuitable for irrigation depending on the sampling location and the applied indices. Specifically, in WA WQI, rivers were excellent for agricultural uses and Lake Hawassa was good for agricultural uses. However, the CCME WQI findings showed rivers were good for irrigation but lake Hawassa was marginal for agricultural use. Point sources were impaired for all envisioned purposes. The overall category of Lake Hawassa falls under a eutrophic state since the average TSI was 65.4 and the lake is phosphorous-deficient, having TN:TP of 31.1. The monitored point sources indicate that the city of Hawassa and its numerous industrial discharges are key polluters, requiring a fast and consequent set-up of an efficient wastewater infrastructure, accompanied by a rigorous monitoring of large point sources (e.g., industry, hospitals and hotels). In spite of the various efforts, the recovery of Lake Hawassa may take a long time as it is hydrologically closed. Therefore, to ensure safe drinking water supply, a central supply system according to World Health organization (WHO) standards also for the fringe inhabitants still using lake water is imperative. Introducing riparian buffer zones of vegetation and grasses can support the direct pollution alleviation measures and is helpful to reduce the dispersed pollution coming from the population using latrines. Additionally, integrating aeration systems like pumping atmospheric air into the bottom of the lake using solar energy panels or diffusers are effective mitigation measures that will improve the water quality of the lake. In parallel, the implementation and efficiency control of measures requires coordinated environmental monitoring with dedicated development targets.
Prevalence and Correlates of Muscle-Strengthening Activity Participation in Croatia: A Cross-Sectional Study in a National Representative Sample of 4561 Adults
Authors: Radašević Hrvoje , Čvrljak Jelena , Pedišić Željko , Jurakić Danijel
Published: August 2021

The World Health Organization recommends adults to engage in muscle-strengthening activity (MSA) at least two times per week. The aim of this study was to determine the prevalence and correlates of MSA in Croatian adults. We analysed self-reported data collected among 4561 Croatians aged ≥18 years within the European Health Interview Survey (EHIS wave 2). We calculated the weighted prevalence of meeting the MSA guidelines, and odds ratios for different population groups, adjusted for a range of sociodemographic and lifestyle variables in a multivariable logistic regression analysis. The prevalence of meeting the MSA guidelines was 8.0% (95% CI: 7.2, 8.8) in the overall sample, 5.4% (95% CI: 4.5, 6.4) among females, and 10.9% (95% CI: 9.6, 12.3) among males. We found significantly lower odds of meeting the MSA guidelines for females, older age groups, inhabitants of sparsely populated areas, those with a low education level, obese individuals, and those who did not rate their health as “very good” (p < 0.05 for all). The vast majority of Croatian adults do not meet the MSA guidelines. Public health initiatives to promote MSA in Croatia should focus on females, seniors, sparsely populated areas, people with low education, obese individuals, and those with impaired health.
Biomonitoring of Phthalates, Bisphenols and Parabens in Children: Exposure, Predictors and Risk Assessment
Authors: Dualde Pablo , León Nuria , Sanchis Yovana , Corpas-Burgos Francisca , Fernández Sandra F. , Hernández Cristina S. , Saez Guillermo , Pérez-Zafra Erika , Mora-Herranz Antonio , Pardo Olga , Coscollà Clara , López Antonio , Yusà Vicent ,   on behalf of the BIOVAL Task Force
Published: August 2021

Exposure to emerging contaminants, such as phthalates, bisphenols and parabens in children has been associated with possible neurodevelopment and endocrine alterations. In the present study, the biomonitoring of biomarkers in children (5–12 years old) from the Valencia Region (Spain) have been implemented using urines from the BIOVAL program. More than 75% of the children studied (n = 562) were internally exposed (>LOQ) to bisphenols and parabens, and the whole population assessed (n = 557) were exposed to at least one phthalate. The geometric means (GM) of the concentrations of bisphenol A, methyl paraben and propyl paraben were 0.9, 1.4 and 0.39 ng/mL, respectively. Regarding phthalates, monoethyl phthalate GM was 55.0 ng/mL and diethyl hexyl phthalate (as the sum of five metabolites) GM was 60.6 ng/mL. Despite the studied population being widely exposed, the detection frequencies and concentrations were in general lower than in previous studies involving children in Spain and in other countries in recent years. Furthermore, the risk assessment study concluded that the internal exposure to phthalates, bisphenols and parabens is lower than the guidance values established, and, therefore, a health risk derived from the exposure to these compounds in the studied population is not expected.
Parental Control and Adolescent Delinquency Based on Parallel Process Latent Growth Curve Modeling
Authors: Zhu Xiaoqin , Shek Daniel T. L.
Published: August 2021

Although ample evidence demonstrates parental influences on delinquent behavior in adolescent years, few studies have examined how change in adolescent delinquency and change in parental behavior are related to each other, particularly in late adolescence. This study utilized survey data collected over three high school years (N = 3074 Grade 10 students; mean age = 15.57, SD = 0.74 at Time 1) to examine how change trajectory of adolescent-reported delinquency is related to change trajectory of adolescent perceived parental behavioral and psychological control using parallel process growth curve modeling. Results revealed that adolescent delinquency level was negatively associated with both parents’ behavioral control and positively associated with parents’ psychological control at Time 1 (Grade 10). However, adolescent delinquency increased in parallel with decreased parental behavioral control, but not a change in psychological control. Initial paternal behavioral control positively predicted a linear increase slope of adolescent delinquency while initial adolescent delinquency level also positively predicted a linear decrease slope of paternal behavioral control. These results highlight the parallel development of parents’ behavioral control and children’s delinquent behavior and delineate the reciprocal influence between paternal behavioral control and adolescent children’s delinquency.
Overview of Current Practices in the Methamphetamine Testing and Decontamination Industry: An Australian Case Study
Authors: Kuhn Emma J. , Walker G. Stewart , Whiley Harriet , Wright Jackie , Ross Kirstin E.
Published: August 2021

To better protect public health from third-hand exposure to methamphetamine, it is important to understand the techniques and current practices used within the methamphetamine testing and decontamination industry in Australia. A survey was conducted focusing on business owners that advertised testing and/or remediation services online. They were also invited to participate in a follow-up phone interview upon completion. The survey demonstrated that testing and decontamination methods were highly varied, which was expected for an industry with no regulation. Most companies offered methamphetamine testing and remediation which could be a conflict of interest. Participants also shared personal experiences, including the conduct of other industry members, demonstrating both poor practice and/or the competitive nature of the business. Participating business owners were following Australian guidelines to the best of their ability, and many are advocates for regulation to be implemented within the industry. This would address the inconsistencies between companies and establish trust for industry members and the public. It would also provide significant public health protection, which is currently lacking. A more consistent approach to the testing and remediation of methamphetamine contamination, aided by regulation, would address the significant risk to public health caused by third-hand exposure to methamphetamine.
Relationships of Dietary Habits and Physical Activity Status with Non-Alcoholic Fatty Liver Disease Featuring Advanced Fibrosis
Authors: Yabe Yoshito , Kim Taeho , Oh Sechang , Shida Takashi , Oshida Natsumi , Hasegawa Naoyuki , Okada Kosuke , Someya Noriko , Mizokami Yuji , Shoda Junichi
Published: August 2021

(1) Aim: Hepatic fibrosis is a prognostic factor for disease progression in non-alcoholic fatty liver disease (NAFLD). We aimed to determine the relationships between diet, physical activity, and the progression of liver fibrosis. (2) Methods: The 349 participants were categorized by their FibroScan-aspartate aminotransferase score, and they completed a questionnaire regarding their diet and physical activity. (3) Results: There were 233 patients in the negative-on-screening group, 78 in the gray zone group, and 38 in the positive-on-screening group. The frequencies of consumption of soybeans and soybean products and of light-colored vegetables were lower in the positive group; whereas the frequencies of consumption of snack food and fried sweets, jelly and pudding, fried food, and butter, lard, and beef tallow were higher. The odds ratios for the fibrosis progression in patients who consumed fried food ≥4 times/week was 2.21. The positive group also showed lower physical activity level (PAL) and exercise (Ex, metabolic equivalents for tasks (METs)/hour/week). The patients who undertook Ex at >7.5 had an odds ratio of 0.21 for the fibrosis progression. (4) Conclusion: High consumption of fried food and low Ex are risk factors for the fibrosis progression in NAFLD.
Effectiveness of Foodbank Western Australia’s Food Sensations® for Adults Food Literacy Program in Regional Australia
Authors: Dumont Catherine , Butcher Lucy M. , Foulkes-Taylor Frances , Bird Anna , Begley Andrea
Published: August 2021

Background: Food Sensations for Adults, funded by the Western Australian Department of Health, is a four-week nutrition education program focused on food literacy, with demonstrated success amongst Western Australians. In the last two years, 25% of programs have been in regional and remote areas and therefore the aim of this research is to explore the impact of the program in regional areas. Methods: Participants answered validated pre- and post-questionnaires to assess change in food literacy behaviours (2016–2018). Results: Regional participants (n = 451) were more likely to live in low income areas, have lower education levels, and identify as Aboriginal, than metropolitan participants (n = 1398). Regional participants had statistically significantly higher food literacy behaviours in the plan and manage and preparation domains, and lower selection behaviours at baseline than metropolitan participants. Post program, regional participants showed matched improvements with metropolitan participants in the plan and manage, and preparation domains. Food selection behaviour results increased in both groups but were significantly higher in regional participants. Conclusions: The program demonstrates effective behaviour change in all participants; however, the increased disadvantage experienced by people residing outside of major cities highlights the need for additional government support in addressing regional specific barriers, such as higher food costs, to ensure participants gain maximum benefit from future food literacy programs.
Towards Resilient Critical Infrastructures: Understanding the Impact of Coastal Flooding on the Fuel Transportation Network in the San Francisco Bay
Authors: He Yiyi , Lindbergh Sarah , Ju Yang , Gonzalez Marta , Radke John
Published: August 2021

Sea level rise (SLR) and storm surge inundation are major concerns along the coast of the San Francisco Bay (the Bay Area), impacting both coastal communities and critical infrastructure networks. The oil industry comprises a complex and critical infrastructure network located in the Bay Area. There is an urgent need to assess consequences and identify risk-based solutions to increase the resilience of this industrial network in the Bay Area to SLR and storm surge. In this study, a comprehensive multi-modal network model representing the fuel supply system was built. A total of 120 coastal flooding scenarios, including four General Circulation Models, two Representative Concentration Pathways, three percentiles of future SLR estimates, and five planning horizons (20 year intervals from 2000 to 2100) were considered. The impact of coastal flooding on fuel transportation networks was studied at two different scales: regional and local. At the regional scale, basic network properties and network efficiency were analyzed across multiple flooding scenarios. At the local scale, cascading effects of individual node disruptions were simulated. Based on this research, smarter and more holistic risk-based adaptation strategies can be established which could lead to a more resilient fuel transportation network system.
Molecular Dissection of the Gene OsGA2ox8 Conferring Osmotic Stress Tolerance in Rice
Authors: Wang Yinxiao , Du Fengping , Wang Juan , Li Yingbo , Zhang Yue , Zhao Xiuqin , Zheng Tianqing , Li Zhikang , Xu Jianlong , Wang Wensheng , Fu Binying
Published: August 2021

Gibberellin 2-oxidase (GA2ox) plays an important role in the GA catabolic pathway and the molecular function of the OsGA2ox genes in plant abiotic stress tolerance remains largely unknown. In this study, we functionally characterized the rice gibberellin 2-oxidase 8 (OsGA2ox8) gene. The OsGA2ox8 protein was localized in the nucleus, cell membrane, and cytoplasm, and was induced in response to various abiotic stresses and phytohormones. The overexpression of OsGA2ox8 significantly enhanced the osmotic stress tolerance of transgenic rice plants by increasing the number of osmotic regulators and antioxidants. OsGA2ox8 was differentially expressed in the shoots and roots to cope with osmotic stress. The plants overexpressing OsGA2ox8 showed reduced lengths of shoots and roots at the seedling stage, but no difference in plant height at the heading stage was observed, which may be due to the interaction of OsGA2ox8 and OsGA20ox1, implying a complex feedback regulation between GA biosynthesis and metabolism in rice. Importantly, OsGA2ox8 was able to indirectly regulate several genes associated with the anthocyanin and flavonoid biosynthetic pathway and the jasmonic acid (JA) and abscisic acid (ABA) biosynthetic pathway, and overexpression of OsGA2ox8 activated JA signal transduction by inhibiting the expression of jasmonate ZIM domain-containing proteins. These results provide a basis for a future understanding of the networks and respective phenotypic effects associated with OsGA2ox8.
High Risk of Viral Reactivation in Hepatitis B Patients with Systemic Lupus Erythematosus
Authors: Chen Ming-Han , Wu Chien-Sheng , Chen Ming-Huang , Tsai Chang-Youh , Lee Fa-Yauh , Huang Yi-Hsiang
Published: August 2021

HBV reactivation (HBVr) can occur in hepatitis B surface antigen (HBsAg)-positive and negative patients. Here, we determined the incidence of HBVr and its related hepatitis in patients with systemic lupus erythematosus (SLE). From 2000 to 2017, 3307 SLE cases were retrospectively reviewed for episodes of hepatitis. The incidence, long-term outcomes and risk factors associated with HBVr, including HBsAg reverse seroconversion (RS) were analyzed. Among them, 607 had available HBsAg status. Fifty-five (9.1%) patients were positive for HBsAg and 63 (11.4%) were HBsAg-negative/antibody to hepatitis B core antigen (anti-HBc)-positive (resolved hepatitis B infection, RHB). None of them received antiviral prophylaxis before immunosuppressive treatment. During a mean 15.4 years of follow-up, 30 (54.5%) HBsAg-positive patients developed HBVr and seven (23.3%) died of liver failure, whereas only two (3.2%) RHB cases experienced HBsAg reverse seroconversion (RS). Multivariate logistic regression analysis showed that age ≥ 40 years at diagnosis of SLE (HR 5.30, p < 0.001), receiving glucocorticoid-containing immunosuppressive therapy (HR 4.78, p = 0.003), and receiving glucocorticoid ≥ 10 mg prednisolone equivalents (HR 3.68, p = 0.003) were independent risk factors for HBVr in HBsAg-positive patients. Peak level of total bilirubin ≥ 5 mg/dL during HBVr was an independent factor of mortality (p = 0.002). In conclusion, the risk of HBVr was associated with glucocorticoid daily dose. Antiviral prophylaxis is mandatory for SLE patients diagnosed at age of ≥40 years who receive ≥ 10 mg daily dose of oral prednisone or equivalent.
Delivery of Metabolically Neuroactive Probiotics to the Human Gut
Authors: Bron Peter A. , Catalayud Marta , Marzorati Massimo , Pane Marco , Kartal Ece , Dhir Raja , Reid Gregor
Published: August 2021

The human microbiome is a rich factory for metabolite production and emerging data has led to the concept that orally administered microbial strains can synthesize metabolites with neuroactive potential. Recent research from ex vivo and murine models suggests translational potential for microbes to regulate anxiety and depression through the gut-brain axis. However, so far, less emphasis has been placed on the selection of specific microbial strains known to produce the required key metabolites and the formulation in which microbial compositions are delivered to the gut. Here, we describe a double-capsule technology to deliver high numbers of metabolically active cells derived from the 24-strain probiotic product SH-DS01 to the gastrointestinal tract, including the small intestine, where immune responses and adsorption of metabolites into the bloodstream occur. Based on its genome sequence, Limosilactobacillus reuteri SD-LRE2-IT was predicted to have the genetic capacity to de novo produce a specific metabolite of interest to brain health, vitamin B12, which could be confirmed in vitro. Taken together, our data conceptualizes the importance of rationally defined microbial strain characterization based on genomics and metabolomics data, combined with carefully designed capsule technology for delivery of live cells and concomitant functionality in and beyond the gut ecosystem.
Molecular and Pathophysiological Links between Metabolic Disorders and Inflammatory Bowel Diseases
Authors: Hyun Chang-Kee
Published: August 2021

Despite considerable epidemiological evidence indicating comorbidity between metabolic disorders, such as obesity, type 2 diabetes, and non-alcoholic fatty liver disease, and inflammatory bowel diseases (IBD), such as Crohn’s disease and ulcerative colitis, as well as common pathophysiological features shared by these two categories of diseases, the relationship between their pathogenesis at molecular levels are not well described. Intestinal barrier dysfunction is a characteristic pathological feature of IBD, which also plays causal roles in the pathogenesis of chronic inflammatory metabolic disorders. Increased intestinal permeability is associated with a pro-inflammatory response of the intestinal immune system, possibly leading to the development of both diseases. In addition, dysregulated interactions between the gut microbiota and the host immunity have been found to contribute to immune-mediated disorders including the two diseases. In connection with disrupted gut microbial composition, alterations in gut microbiota-derived metabolites have also been shown to be closely related to the pathogeneses of both diseases. Focusing on these prominent pathophysiological features observed in both metabolic disorders and IBD, this review highlights and summarizes the molecular risk factors that may link between the pathogeneses of the two diseases, which is aimed at providing a comprehensive understanding of molecular mechanisms underlying their comorbidity.
Structural and Functional Characterizations of Cancer Targeting Nanoparticles Based on Hepatitis B Virus Capsid
Authors: Heo Yunseok , Jeong Hyeongseop , Yoo Youngki , Yun Ji-Hye , Ryu Bumhan , Cha Young-je , Lee Bo-Ram , Jeon Ye-Eun , Kim Jongmin , Jeong Sojin , Jo Eunji , Woo Jae-Sung , Lee Jeewon , Cho Hyun-Soo , Lee Weontae
Published: August 2021

Cancer targeting nanoparticles have been extensively studied, but stable and applicable agents have yet to be developed. Here, we report stable nanoparticles based on hepatitis B core antigen (HBcAg) for cancer therapy. HBcAg monomers assemble into spherical capsids of 180 or 240 subunits. HBcAg was engineered to present an affibody for binding to human epidermal growth factor receptor 1 (EGFR) and to present histidine and tyrosine tags for binding to gold ions. The HBcAg engineered to present affibody and tags (HAF) bound specifically to EGFR and exterminated the EGFR-overexpressing adenocarcinomas under alternating magnetic field (AMF) after binding with gold ions. Using cryogenic electron microscopy (cryo-EM), we obtained the molecular structures of recombinant HAF and found that the overall structure of HAF was the same as that of HBcAg, except with the affibody on the spike. Therefore, HAF is viable for cancer therapy with the advantage of maintaining a stable capsid form. If the affibody in HAF is replaced with a specific sequence to bind to another targetable disease protein, the nanoparticles can be used for drug development over a wide spectrum.
Laboratory Investigation of Hybrid IgG4 k/λ in MuSK Positive Myasthenia Gravis
Authors: Basile Umberto , Napodano Cecilia , Gulli Francesca , Pocino Krizia , Di Santo Riccardo , Todi Laura , Basile Valerio , Provenzano Carlo , Ciasca Gabriele , Marino Mariapaola
Published: August 2021

Myasthenia gravis with antibodies (Abs) against the muscle-specific tyrosine kinase (MuSK) is a rare autoimmune disorder (AD) of the neuromuscular junction (NMJ) and represents a prototype of AD with proven IgG4-mediated pathogenicity. Thanks to the mechanism of Fab-arm exchange (FAE) occurring in vivo, resulting MuSK IgG4 k/λ Abs increase their interference on NMJ and pathogenicity. The characterization of hybrid MuSK IgG4 as a biomarker for MG management is poorly investigated. Here, we evaluated total IgG4, hybrid IgG4 k/λ, and the hybrid/total ratio in 14 MuSK-MG sera in comparison with 24 from MG with Abs against acetylcholine receptor (AChR) that represents the not IgG4-mediated MG form. In both subtypes of MG, we found that the hybrid/total ratio reflects distribution reported in normal individuals; instead, when we correlated the hybrid/total ratio with specific immune-reactivity we found a positive correlation only with anti-MuSK titer, with a progressive increase of hybrid/total mean values with increasing disease severity, indirectly confirming that most part of hybrid IgG4 molecules are engaged in the anti-MuSK pathogenetic immune-reactivity. Further analysis is necessary to strengthen the significance of this less unknown biomarker, but we retain it is full of a diagnostic-prognostic powerful potential for the management of MuSK-MG.
Involvement of Reactive Oxygen Species in ABA-Induced Increase in Hydraulic Conductivity and Aquaporin Abundance
Authors: Sharipova Guzel , Ivanov Ruslan , Veselov Dmitriy , Akhiyarova Guzel , Shishova Maria , Nuzhnaya Tatyana , Kudoyarova Guzel
Published: August 2021

The role of reactive oxygen species (ROS) in ABA-induced increase in hydraulic conductivity was hypothesized to be dependent on an increase in aquaporin water channel (AQP) abundance. Single ABA application or its combination with ROS manipulators (ROS scavenger ascorbic acid and NADPH oxidase inhibitor diphenyleneiodonium chloride (DPI)) were studied on detached roots of barley plants. We measured the osmotically driven flow rate of xylem sap and calculated root hydraulic conductivity. In parallel, immunolocalization of ABA and HvPIP2;2 AQPs was performed with corresponding specific antibodies. ABA treatment increased the flow rate of xylem, root hydraulic conductivity and immunostaining for ABA and HvPIP2;2, while the addition of antioxidants prevented the effects of this hormone. The obtained results confirmed the involvement of ROS in ABA effect on hydraulic conductivity, in particular, the importance of H2O2 production by ABA-treated plants for the effect of this hormone on AQP abundance.
Mechanisms of Binding Specificity among bHLH Transcription Factors
Authors: de Martin Xabier , Sodaei Reza , Santpere Gabriel
Published: August 2021

The transcriptome of every cell is orchestrated by the complex network of interaction between transcription factors (TFs) and their binding sites on DNA. Disruption of this network can result in many forms of organism malfunction but also can be the substrate of positive natural selection. However, understanding the specific determinants of each of these individual TF-DNA interactions is a challenging task as it requires integrating the multiple possible mechanisms by which a given TF ends up interacting with a specific genomic region. These mechanisms include DNA motif preferences, which can be determined by nucleotide sequence but also by DNA’s shape; post-translational modifications of the TF, such as phosphorylation; and dimerization partners and co-factors, which can mediate multiple forms of direct or indirect cooperative binding. Binding can also be affected by epigenetic modifications of putative target regions, including DNA methylation and nucleosome occupancy. In this review, we describe how all these mechanisms have a role and crosstalk in one specific family of TFs, the basic helix-loop-helix (bHLH), with a very conserved DNA binding domain and a similar DNA preferred motif, the E-box. Here, we compile and discuss a rich catalog of strategies used by bHLH to acquire TF-specific genome-wide landscapes of binding sites.
Establishment of Canine Transitional Cell Carcinoma Cell Lines Harboring BRAF V595E Mutation as a Therapeutic Target
Authors: Jung Hyojik , Bae Kieun , Lee Ja Young , Kim Jung-Hyun , Han Hyun-Jung , Yoon Hun-Young , Yoon Kyong-Ah
Published: August 2021

Transitional cell carcinoma (TCC) is the most common malignant tumor of the canine urinary tract and tends to have a poor prognosis due to its invasive potential. Recent studies have reported that up to 80% of canine urothelial carcinoma has the BRAF V595E mutation, which is homologous to the human V600E mutation. Activating the BRAF mutation is an actionable target for developing effective therapeutic agents inhibiting the BRAF/mitogen-activated protein kinase (MAPK) pathway in canine cancer as well as human cancer. We established novel canine TCC cell lines from two tumor tissues and one metastatic lymph node of canine TCC patients harboring the BRAF V595E mutation. Tumor tissues highly expressed the BRAF mutant and phosphorylated extracellular signal-related kinases (ERK)1/2 proteins. The derived cell lines demonstrated activated MAPK pathways. We also evaluated the cell lines for sensitivity to BRAF inhibitors. Sorafenib, a multiple kinase inhibitor targeting RAF/vascular endothelial growth factor receptor (VEGFR), successfully inhibited the BRAF/MAPK pathway and induced apoptosis. The established canine TCC cell lines responded with greater sensitivity to sorafenib than to vemurafenib, which is known as a specific BRAF inhibitor in human cancer. Our results demonstrated that canine TCC cells showed different responses compared to human cancer with the BRAF V600E mutation. These cell lines would be valuable research materials to develop therapeutic strategies for canine TCC patients.
The Zebrafish Model to Understand Epigenetics in Renal Diseases
Authors: Sopel Nina , Müller-Deile Janina
Published: August 2021

Epigenetic modifications are able to alter gene expression and include DNA methylation, different histone variants, and post-transcriptional modifications (PTMs), such as acetylation or phosphorylation, and through short/long RNAs, respectively. In this review, we focus on current knowledge concerning epigenetic modifications in gene regulation. We describe different forms of epigenetic modifications and explain how epigenetic changes can be detected. The relevance of epigenetics in renal diseases is highlighted with multiple examples and the use of the zebrafish model to study glomerular diseases in general and epigenetics in renal diseases in particular is discussed. We end with an outlook on how to use epigenetic modifications as a therapeutic target for different diseases. Here, the zebrafish model can be employed as a high-throughput screening tool not only to discover epigenetic alterations contributing to disease, but also to test novel substances that change epigenetic signatures in vivo. Therefore, the zebrafish model harbors the opportunity to find novel pathogenic pathways allowing a pre-selection of potential targets and compounds to be tested for renal diseases.
A Missing Data Compensation Method Using LSTM Estimates and Weights in AMI System
Authors: Kwon Hyuk-Rok , Kim Pan-Koo
Published: August 2021

With the expansion of advanced metering infrastructure (AMI) installations, various additional services using AMI data have emerged. However, some data is lost in the communication process of data collection. Hence, to address this challenge, the estimation of the missing data is required. To estimate the missing values in the time-series data generated from smart meters, we investigated four methods, ranging from a conventional method to an estimation method applying long short-term memory (LSTM), which exhibits excellent performance in the time-series field, and provided the performance comparison data. Furthermore, because power usages represent estimates of data that are missing some values in the middle, rather than regular time-series estimation data, the simple estimation may lead to an error where the estimated accumulated power usage in the missing data is larger than the real accumulated power usage appearing in the data after the end of the missing data interval. Therefore, this study proposes a hybrid method that combines the advantages of the linear interpolation method and the LSTM estimation-based compensation method, rather than those of conventional methods adopted in the time-series field. The performance of the proposed method is more stable and better than that of other methods.
New Interventional Therapies beyond Stenting to Treat ST-Segment Elevation Acute Myocardial Infarction
Authors: Vidal-Calés Pablo , Cepas-Guillén Pedro L. , Brugaletta Salvatore , Sabaté Manel
Published: August 2021

Myocardial infarction remains the principal cause of death in Europe. In patients with ST-segment-elevation myocardial infarction (STEMI), a promptly revascularization with primary percutaneous intervention (PCI) has transformed prognosis in the last decades. However, despite increasing successful PCI procedures, mortality has remained unchanged in recent years. Also, due to an unsatisfactory reperfusion, some patients have significant myocardial damage and suffer left ventricular adverse remodeling with reduced function—all that resulting in the onset of heart failure with all its inherent clinical and socioeconomic burden. As a consequence of longer ischemic times, distal thrombotic embolization, ischemia-reperfusion injury and microvascular dysfunction, the resultant myocardial infarct size is the major prognostic determinant in STEMI patients. The improved understanding of all the pathophysiology underlying these events has derived to the development of several novel therapies aiming to reduce infarct size and to improve clinical outcomes in these patients. In this article, based on the mechanisms involved in myocardial infarction prognosis, we review the new interventional strategies beyond stenting that may solve the suboptimal results that STEMI patients still experience.
Sex Differences in the Clinical Features and Outcomes of Patients with Acute Coronary Syndrome Treated with Two Generations (Absorb and Magmaris) of Bioresorbable Vascular Scaffolds
Authors: Włodarczak Adrian , Rola Piotr , Szudrowicz Marek , Łanocha Magdalena , Barycki Mateusz , Kulczycki Jan Jakub , Gosiewska Alicja , Turkiewicz Karol , Lesiak Maciej , Doroszko Adrian
Published: August 2021

Background: Despite the developments in percutaneous coronary interventions (PCI), women are still more likely than men to have unfavorable outcomes after PCI performed in Acute Coronary Syndrome (ACS). The mechanisms of this phenomena are not fully understood. Potential benefits of bioresorbable scaffolds (BRS) may be particularly expressed in the female population. Nevertheless, the data available currently are inconsistent and limited. This study evaluated the gender-related differences in the short-term clinical outcomes in ACS patients treated with implantation of two generations of BRS (first generation, Absorb; second generation, Magmaris). Methods: The study was divided into two arms. To the first one, we qualified 160 patients with ACS treated with PCI who received 210 Absorb scaffolds. The second arm was composed of 193 patients with ACS who underwent PCI with Magmaris implantation. Results: There were no significant sex-related differences in primary endpoints (cardiovascular-death, myocardial infarction, in-stent thrombosis) or principal secondary endpoints (of target-lesion failure, scaffold restenosis, death from any reason, other cardiovascular events) in either generation of BRS in a 1-year follow-up. Conclusions: Both genders tended to have a similar outcome in routine clinical practice following BRS implantation due to ACS. The magnesium bioresorbable scaffold (Magmaris) early outcome seemed to be more favorable in comparison to the Absorb scaffold.
Current Status of Clinical and Genetic Screening of Hereditary Hemorrhagic Telangiectasia Families in Hungary
Authors: Major Tamás , Bereczky Zsuzsanna , Gindele Réka , Balogh Gábor , Rácz Benedek , Bora László , Kézsmárki Zsolt , Brúgós Boglárka , Pfliegler György
Published: August 2021

Hereditary hemorrhagic telangiectasia (HHT) is a rare germline vascular malformation syndrome with a prevalence of 1:5000–1:10,000 [...]
Novel Advances to Post-Stroke Aphasia Pharmacology and Rehabilitation
Authors: Cichon Natalia , Wlodarczyk Lidia , Saluk-Bijak Joanna , Bijak Michal , Redlicka Justyna , Gorniak Leslaw , Miller Elzbieta
Published: August 2021

Aphasia is one of the most common clinical features of functional impairment after a stroke. Approximately 21–40% of stroke patients sustain permanent aphasia, which progressively worsens one’s quality of life and rehabilitation outcomes. Post-stroke aphasia treatment strategies include speech language therapies, cognitive neurorehabilitation, telerehabilitation, computer-based management, experimental pharmacotherapy, and physical medicine. This review focuses on current evidence of the effectiveness of impairment-based aphasia therapies and communication-based therapies (as well as the timing and optimal treatment intensities for these interventions). Moreover, we present specific interventions, such as constraint-induced aphasia therapy (CIAT) and melodic intonation therapy (MIT). Accumulated data suggest that using transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) is safe and can be used to modulate cortical excitability. Therefore, we review clinical studies that present TMS and tDCS as (possible) promising therapies in speech and language recovery, stimulating neuroplasticity. Several drugs have been used in aphasia pharmacotherapy, but evidence from clinical studies suggest that only nootropic agents, donepezil and memantine, may improve the prognosis of aphasia. This article is an overview on the current state of knowledge related to post-stroke aphasia pharmacology, rehabilitation, and future trends.