bluuebunny/crossref_metadata_2025 huggingface dataset:
Calibration of Spalart-Allmaras model for simulation of corner flow separation in linear compressor cascade
Authors: Matsui Kotaro , Perez Ethan , Kelly Ryan , Tani Naoki , Jemcov Aleksandar
Published: May 2021

This study focuses on the calibration of Spalart--Allmaras turbulence model parameters using the Bayesian inference approach to reproduce experimental measurements of corner flow separation in linear compressor cascade. The quantity of interest selected for the calibration process is the pitchwise distribution of Mach number in the wake of the linear compressor cascade. The model parameters are assumed to be random variables obeying uniform prior probability distributions. Sensitivity analysis is used to rank the importance and select the most influential turbulence model parameters for the calibration process. The sensitivity ranking indicates that two model parameters cb1 and kappa are the most influential random variables resulting in a two--parameter Bayesian calibration process. The likelihood distribution is specified in the form of the Gauss distribution to include the experimental uncertainty. The likelihood distribution is used together with prior distribution
to compute posterior probabilities of selected model parameters. The polynomial chaos expansion is employed as a surrogate model to reduce the cost of posterior calculation. Numerical simulations with calibrated turbulence parameters show a significant increase in the accuracy of Mach number profile prediction for separated flows in linear compressor cascade. Numerical simulations also demonstrate that the calibrated set of model coefficients produce accurate predictions of the total pressure and Mach number profiles for the range of incidence angles that were not part of the calibration process.
STEM education for Industry 4.0 in technical and vocational high schools: Investigation of teacher professional development
Authors:   Science, Technology, Engineering, and Mathematics Education Research Center, Istanbul Aydin University, Istanbul, Turkey, Akgunduz Devrim , Mesutoglu Canan ,   Science, Technology, Engineering, and Mathematics Education Research Center, Istanbul Aydin University, Istanbul, Turkey
Published: June 2021

The goals of this study were to investigate technical and vocational education (TVET) teachers’ progress in their knowledge, perceptions, and competencies related to Industry 4.0 components and Science, Technology, Engineering, and Mathematics (STEM) within the context of a professional development program. A case study design was followed to reveal in-depth information on teacher improvement. Data sources included the Teacher Knowledge Survey, Teacher Perceptions Survey, and Industry 4.0 and STEM Competencies Survey. Results indicated significant improvement in teachers’ Industry 4.0 competencies and their content knowledge of Industry 4.0 components and STEM. Teachers reported a culture of collaboration in their school, increased teacher and student motivation, and positive attitudes toward TVET with implementation of the STEM PD program. The results point to the need to help teachers in designing certain aspects of STEM lesson plans including the integration of mobile programming, robotic programming and virtual reality meaningfully into the lesson content. Further implications for research and practice are presented in light of the findings.
Editorial
Authors:   College of Education, Univerity of Otago, Sexton Steven S.
Published: June 2021

Editorial Volume 32, issue 2
Faktor Risiko Konsumsi Soft Drink dengan Kejadian Kegemukan pada Remaja di SMK Kristen Bala Keselamatan Palu
Authors: Faisal Elvyrah , Anayanti Ridha
Published: May 2021

Adolescents are an age group that is prone to nutritional problems including obesity. Adolescent lifestyles that can trigger obesity include the consumption of soft drinks. The highest sweetener content in food and beverages is found in soft drinks, and it accounts for 12% of the total carbohydrate requirement which can trigger obesity. The purpose of this study was to determine the risk factors for soft drink consumption on the incidence of obesity in adolescents at the Vocational High School for Safety in Palu in 2018. This type of research used a case-control study. The sample in this study amounted to 64 people who were divided into 32 cases and 32 controls. A sampling of cases was carried out by the total population. Data collection techniques use digital scales and microtome to determine nutritional status, and the Semi-Quantitative Food Frequency Questionnaire form to determine the frequency and level of consumption of soft drinks. The analysis showed that the p-value for the frequency of soft drink consumption was 0.802 and the level for consumption of soft drinks was 0.297, with the OR value for the frequency of consumption of soft drinks = 1.485  and the OR value for the level of consumption = 1.98. The conclusion is that there is no relationship between the frequency of consumption of soft drinks, the level of consumption of soft drinks with the incidence of obesity in adolescents at the Vocational School of Salvation Army Palu. but have a risk respectively 1.485 times and 1.98 times the incidence of obesity. It is recommended that schools pay more attention to the types of drinks that are marketed in the school environment and teenagers are expected to be wiser in choosing snacks.
Efektifitas Kombinasi Teknik Counter Pressure dan Pelvic Rocking Terhadap Penurunan Nyeri Kala I Fase Aktif Persalinan Normal di Puskesmas Kayamanya
Authors: Noya Fransisca , Nilda Yulita Siregar
Published: May 2021

Penelitian ini bertujuan untuk menganalisis efektifitas  kombinasi teknik counter pressure dan pelvic rocking terhadap penurunan nyeri kala I fase aktif persalinan di Puskesmas Kayamanya. Rancangan penelitian yang pakai yaitu  studi Quasi Eksperimental, dengan rancangan  pretest-posttest control group design. Pengambilan sampel pada penelitian ini adalah non probability sampling berupa teknik consecutive sampling. Data diolah dan dianalisis dengan menggunakan distribusi frekuensi dengan ukuran persentase dan uji t – dependent. Hasil penelitian menunjukkan pada kelompok intervensi, sebelum diberikan perlakuan kombinasi teknik counter pressure dan pelvic rocking  rerata sebesar 6,3 dan setelah  intervensi  1,73. Kombinasi tehnik Counter-pressure dan pelvic rocking memberikan hasil selisih rerata 4,6 yang artinya lebih besar dibandingkan dengan nilai rerata  teknik counter pressure yaitu 2,3. Hasil uji statistik menggunakan uji  t-dependent  menunjukkan terdapat perbedaan bermakna sebelum dan setelah perlakuan pada kelompok intervensi dan kelompok kontrol dengan nilai p < 0,05. Kombinasi teknik counter pressure dan pelvic rocking lebih baik dalam penurunan nyeri kala I fase aktif persalinan normal dibandingkan teknik counter pressure
Imunostimulator Ekstrak Etanol Anredera Cordifolia Terhadap Titer Widal Salmonella typhi O Pada Rattus Norvergicus Galur Wistar
Authors: Pancawari Ariami  , Addien Faqih Pajenengan  , Maruni Wiwin Diarti Wiwin
Published: May 2021

Tujuan penelitian yaitu menganalisis ekstrak etanol daun Anreder acordifolia sebagai imunostimulator terhadap titer widal S. typhi O pada hewan coba tikus putih jantan galur wistar. Jenis penelitian yaitu quasi-eksperiment dengan design non equivalent control group. Penelitian ini menggunakan hewan coba tikus putih jantan galur wistar. Konsentrasi ekstrak etanol daun binahong yang diberikan sebesar 75%. Hewan coba diinduksikan antigen S.typhi O dua kali dengan volume  0,2 mL secara intra peritonial, diinkubasi selama 7 hari. Pemeriksaan Titer Widal S.typhi O dengan cara kualitatif dan semi kuantitatif. Hasil penelitian menunjukkan bahwa titer tertinggi yang dapat terdeteksi pada seluruh kelompok kontrol yaitu 1/640 dan seluruh kelompok perlakuan yaitu 1/1.280 yang membuktikan adanya peningkatan titer setelah pemberian ekstrak etanol daun Anredera cordifolia. Hasil uji mann-whitney menunjukkan nilai p = 0,025, p < 0,05 yang membuktikan adanya perbedaan yang signifikan antara kelompok kontrol dan kelompok perlakuan yang diberikan. Kesimpulan ekstrak etanol daun Anredera cordifolia berpotensi sebagai imunostimulator terhadap titer widal S.typhi O pada hewan coba tikus putih jantan galur wistar.
Effectiveness of Family Empowerment towards Diet Compliance and Family Independence in Caring for Family Members with Diabetes Mellitus: A Systematic Review
Authors: Nizar Angga Miftakhul Nizar , Kusnanto  , Lilik Herawati
Published: May 2021

Diabetes mellitus has now become a major problem in non-communicable diseases whose prevalence continues to increase. Lack of family independence and client non-compliance with the diet program greatly affects blood sugar levels. This study needs to evaluate the effectiveness of family empowerment towards diet compliance and family independence in caring for family members with diabetes mellitus. A systematic review searched five electronic databases (Scopus, sciencedirect, pubmed, research gate, and google scholar) with the last ten years (2011-2021). The quality of the articles used in this study was assessed using the Joanna Briggs Institute Guideline. The prism protocol is also used to review each journal. We found 15 studies out of a total of 5,865 studies that discussed family empowerment in increasing family independence and dietary adherence in family members suffering from diabetes mellitus. Family empowerment is one method that is quite effective in increasing family independence and adherence to diet programs. There are six articles (40%) that state that planned behavior theory is effective in increasing family independence and dietary adherence to family members suffering from diabetes mellitus. From all the articles analyzed, there are several effective theories to empower families to change the behavior of family independence and individual diet compliance, namely the theory of planned behavior. However, this study is not strong enough to provide an assessment that family empowerment based on the theory of planned behavior and empowerment is the best way to increase independence, therefore further research is needed.
The Effectiveness of Spiritual Psychotherapy on Patients with Mental Disorders: A Systematic Review
Authors: Wahyudi Ahmad Wahyudi , Ah Yusuf  , Mundakir
Published: May 2021

Recently, the research analyzes the relationship between religion and spirituality has grown rapidly.Many mental health clinics have implemented interventions on religious and spirituality-based mental disorders. This article aimed to examine the effectiveness of handling mental-based mental disorders from various studies that have been conducted. Methods: The articles used in this systematic review were searched in the SCOPUS, PROQUEST, SPRINGERLINK, SAGE and SCIENCEDIRECT databases which is published between 2016-2020. The keyword used were "mental disorders" or "mental illness" and “spiritual” or “religious”, with the use of the phrase Boolean Operators. The articles selected according to the inclusion criteria include articles stating the effectiveness of spiritual healing for mental disorders, articles that analyzed mental illness patients in RCT, case-control studies and experiment. The articles obtained then were analyzed with the DSVIA conclusion table (design, sampling, variables, intervention and analysis). Results: There were 15 articles that meet the criteria as a systematic review.Thestudy result showed that there was a relationship between religious/spiritual involvement and mental disorders (positive). The findings from previous research indicated that religion play an important role in many situations because religious beliefs and rules affect people's lives. Conclusions:The majority of the previous literature stated a significant relationship between religious beliefs and practices and mental health.
Rab GTPases: Central Coordinators of Membrane Trafficking in Cancer
Authors: Jin Hongyuan , Tang Yuanxin , Yang Liang , Peng Xueqiang , Li Bowen , Fan Qin , Wei Shibo , Yang Shuo , Li Xinyu , Wu Bo , Huang Mingyao , Tang Shilei , Liu Jingang , Li Hangyu
Published: June 2021

Tumor progression involves invasion, migration, metabolism, autophagy, exosome secretion, and drug resistance. Cargos transported by membrane vesicle trafficking underlie all of these processes. Rab GTPases, which, through coordinated and dynamic intracellular membrane trafficking alongside cytoskeletal pathways, determine the maintenance of homeostasis and a series of cellular functions. The mechanism of vesicle movement regulated by Rab GTPases plays essential roles in cancers. Therefore, targeting Rab GTPases to adjust membrane trafficking has the potential to become a novel way to adjust cancer treatment. In this review, we describe the characteristics of Rab GTPases; in particular, we discuss the role of their activation in the regulation of membrane transport and provide examples of Rab GTPases regulating membrane transport in tumor progression. Finally, we discuss the clinical implications and the potential as a cancer therapeutic target of Rab GTPases.
Transition From PCR-Ribotyping to Whole Genome Sequencing Based Typing of Clostridioides difficile
Authors: Seth-Smith Helena M. B. , Biggel Michael , Roloff Tim , Hinic Vladimira , Bodmer Thomas , Risch Martin , Casanova Carlo , Widmer Andreas , Sommerstein Rami , Marschall Jonas , Tschudin-Sutter Sarah , Egli Adrian
Published: June 2021

Clostridioides difficile causes nosocomial outbreaks which can lead to severe and even life-threatening colitis. Rapid molecular diagnostic tests allow the identification of toxin-producing, potentially hypervirulent strains, which is critical for patient management and infection control. PCR-ribotyping has been used for decades as the reference standard to investigate transmission in suspected outbreaks. However, the introduction of whole genome sequencing (WGS) for molecular epidemiology provides a realistic alternative to PCR-ribotyping. In this transition phase it is crucial to understand the strengths and weaknesses of the two technologies, and to assess their correlation. We aimed to investigate ribotype prediction from WGS data, and options for analysis at different levels of analytical granularity. Ribotypes cannot be directly determined from short read Illumina sequence data as the rRNA operons including the ribotype-defining ISR fragments collapse in genome assemblies, and comparison with traditional PCR-ribotyping results becomes impossible. Ribotype extraction from long read Oxford nanopore data also requires optimization. We have compared WGS-based typing with PCR-ribotyping in nearly 300 clinical and environmental isolates from Switzerland, and in addition from the Enterobase database (n=1778). Our results show that while multi-locus sequence type (MLST) often correlates with a specific ribotype, the agreement is not complete, and for some ribotypes the resolution is insufficient. Using core genome MLST (cgMLST) analysis, there is an improved resolution and ribotypes can often be predicted within clusters, using cutoffs of 30-50 allele differences. The exceptions are ribotypes within known ribotype complexes such as RT078/RT106, where the genome differences in cgMLST do not reflect the ribotype segregation. We show that different ribotype clusters display different degrees of diversity, which could be important for the definition of ribotype cluster specific cutoffs. WGS-based analysis offers the ultimate resolution to the SNP level, enabling exploration of patient-to-patient transmission. PCR-ribotyping does not sufficiently discriminate to prove nosocomial transmission with certainty. We discuss the associated challenges and opportunities in a switch to WGS from conventional ribotyping for C. difficile.
Hemodynamic Abnormalities in the Aorta of Turner Syndrome Girls
Authors: Johnston Lauren , Allen Ruth , Hall Barrientos Pauline , Mason Avril , Kazakidi Asimina
Published: June 2021

Congenital abnormalities in girls and women with Turner syndrome (TS), alongside an underlying predisposition to obesity and hypertension, contribute to an increased risk of cardiovascular disease and ultimately reduced life expectancy. We observe that children with TS present a greater variance in aortic arch morphology than their healthy counterparts, and hypothesize that their hemodynamics is also different. In this study, computational fluid dynamic (CFD) simulations were performed for four TS girls, and three age-matched healthy girls, using patient-specific inlet boundary conditions, obtained from phase-contrast MRI data. The visualization of multidirectional blood flow revealed an increase in vortical flow in the arch, supra-aortic vessels, and descending aorta, and a correlation between the presence of aortic abnormalities and disturbed flow. Compared to the relatively homogeneous pattern of time-averaged wall shear stress (TAWSS) on the healthy aortae, a highly heterogeneous distribution with elevated TAWSS values was observed in the TS geometries. Visualization of further shear stress parameters, such as oscillatory shear index (OSI), normalized relative residence time (RRTn), and transverse WSS (transWSS), revealed dissimilar heterogeneity in the oscillatory and multidirectional nature of the aortic flow. Taking into account the young age of our TS cohort (average age 13 ± 2 years) and their obesity level (75% were obese or overweight), which is believed to accelerate the initiation and progression of endothelial dysfunction, these findings may be an indication of atherosclerotic disease manifesting earlier in life in TS patients. Age, obesity and aortic morphology may, therefore, play a key role in assessing cardiovascular risk in TS children.
Temperature Impact on Magnesium Isotope Fractionation in Cultured Foraminifera
Authors: Dämmer Linda K. , van Dijk Inge , de Nooijer Lennart , van der Wagt Bas , Wilckens Frederike K. , Zoetemelk Bridget , Reichart Gert-Jan
Published: June 2021

Element incorporation in shell calcite precipitated by foraminifera reflects the chemical and physical properties of the seawater the foraminifera lived in and can therefore be used to reconstruct paleo environmental conditions. One of the most prominent proxies for past seawater temperature is Mg/Ca of foraminiferal calcite. Still, in addition to seawater temperature, also biomineralization processes impact foraminiferal Mg/Ca values. As the impact of biomineralization plays a major role and is not necessarily constant, it is imperative to identify the mechanism by which Mg is incorporated and thereby understand how temperature influences Mg incorporation. Biomineralization is discriminating against Mg to different degrees and hence investigating the fractionation of Mg isotopes at different temperatures and for species with contrasting calcification pathways can be used to better understand the pathway of Mg during biomineralization. Overall, we observe that foraminifera with higher Mg content have δ26Mg values closer to those of seawater. Moreover, controlled temperature culture experiments show that parallel to an increase in Mg/Ca, δ26Mg in the tests of large benthic foraminifer Amphistegina lessonii decreases when sea water temperatures increase. This negative correlation between shell Mg/Ca and δ26Mg suggests a two-step control on the incorporation of Mg during biomineralization. Using a simple model, we can explain both trends as a result of a stable Mg pool, which is only little fractionated with respect to sea water and a temperature dependent Mg pool which shows a higher fractionation with respect to sea water during biomineralization. The stable, not much fractionated pool is relatively large in high Mg foraminifera, whereas for the low Mg foraminifera the transport of Mg over a cell membrane probably results in the observed inverse correlation. Here we present a model using the Mg isotope fractionation we established for A. lessonii to explain the general trends for both high- and low-Mg/Ca foraminifera. A process-based understanding remains crucial a robust interpretation of foraminiferal Mg-isotopes.
Continuous Spatio-Temporal High-Resolution Estimates of SWE Across the Swiss Alps – A Statistical Two-Step Approach for High-Mountain Topography
Authors: Guidicelli Matteo , Gugerli Rebecca , Gabella Marco , Marty Christoph , Salzmann Nadine
Published: June 2021

Snow and precipitation estimates in high-mountain regions typically suffer from low temporal and spatial resolution and large uncertainties. Here, we present a two-step statistically based model to derive spatio-temporal highly resolved estimates of snow water equivalent (SWE) across the Swiss Alps. A multiple linear regression model (Step-1 MLR) was first used to combine the CombiPrecip radar-gauge product with the precipitation and wind speed (10 m from the ground) of the numerical weather prediction model COSMO-1 in order to adjust the precipitation estimates. Step-1 MLR was trained with SWE data from a cosmic ray sensor (CRS) installed on the Plaine Morte glacier and tested with SWE data from a CRS on the Findel glacier. Step-1 MLR was then applied to the entire area of eight Swiss glaciers and evaluated with scattered end-of-season in-situ manual SWE measurements. The cumulative estimates of Step-1 MLR were found to agree well with the end-of-season measurements. The observed differences can partially be explained by considering the radar visibility, melting processes and preferential snow deposition, which are dictated by the local topography and local weather conditions. To address these limitations of Step-1 MLR, several high-resolution topographical parameters and a solar radiation parameter were included in the subsequent MLR version (Step-2 MLR). Step-2 MLR was evaluated by means of cross-validation, and it showed an overall correlation of 0.78 and a mean bias error of 4 mm with respect to end-of-season in-situ measurements. Step-2 MLR was also evaluated for non-glacierized regions by evaluating it against twice-monthly manual SWE measurements at 44 sites in the Swiss Alps. In such a setting, the Step-2 model showed an overall weaker correlation (0.53) and a higher mean bias error (31 mm). On the other hand, negative variations of the measured SWE were removed because of the lower altitude of the sites, thereby leading to more pronounced melting periods, which again increased the correlation values to 0.63 and reduced the mean bias error to 12 mm. Such results confirm the high potential of the model for applications to other mountainous regions.
Quantitative Analysis of the Effects of an Earthquake on Rainfall Thresholds for Triggering Debris-Flow Events
Authors: Liu Shuang , Hu Kaiheng , Zhang Qun , Zhang Shaojie , Hu Xudong , Tang Desheng
Published: June 2021

The impacts of destructive earthquakes on rainfall thresholds for triggering the debris flows have not yet been well investigated, due to lacks of data. In this study, we have collected the debris-flow records from the Wenchuan, Lushan, and Jiuzhaigou earthquake-affected areas in Sichuan Province, China. By using a meteorological dataset with 3 h and 0.1° resolutions, the dimensionless effective rainfall and rainfall intensity-duration relationships were calculated as the possible thresholds for triggering the debris flows. The pre- and post-seismic thresholds were compared to evaluate the impacts of the various intensities of earthquakes. Our results indicate that the post-quake thresholds are much smaller than the pre-seismic ones. The dimensionless effective rainfall shows the impacts of the Wenchuan, Lushan, and Jiuzhaigou earthquakes to be ca. 26, 27, and 16%, respectively. The Wenchuan earthquake has the most significant effect on lowering the rainfall intensity-duration curve. Rainfall threshold changes related to the moment magnitude and focal depth are discussed as well. Generally, this work may lead to an improved post-quake debris-flow warning strategy especially in sparsely instrumented regions.
Genome-Wide Variants Associated With Longitudinal Survival Outcomes Among Individuals With Coronary Artery Disease
Authors: Dungan Jennifer R. , Qin Xue , Hurdle Melissa , Haynes Carol S. , Hauser Elizabeth R. , Kraus William E.
Published: June 2021

Objective

Coronary artery disease (CAD) is an age-associated condition that greatly increases the risk of mortality. The purpose of this study was to identify gene variants associated with all-cause mortality among individuals with clinically phenotyped CAD using a genome-wide screening approach.

Approach and Results

We performed discovery (n = 684), replication (n = 1,088), and meta-analyses (N = 1,503) for association of genomic variants with survival outcome using secondary data from White participants with CAD from two GWAS sub-studies of the Duke Catheterization Genetics Biorepository. We modeled time from catheterization to death or last follow-up (median 7.1 years, max 12 years) using Cox multivariable regression analysis. Target statistical screening thresholds were p × 10–8 for the discovery phase and Bonferroni-calculated p-values for the replication (p < 5.3 × 10–4) and meta-analysis (p < 1.6 × 10–3) phases. Genome-wide analysis of 785,945 autosomal SNPs revealed two SNPs (rs13007553 and rs587936) that had the same direction of effect across all three phases of the analysis, with suggestive p-value association in discovery and replication and significant meta-analysis association in models adjusted for clinical covariates. The rs13007553 SNP variant, LINC01250, which resides between MYTIL and EIPR1, conferred increased risk for all-cause mortality even after controlling for clinical covariates [HR 1.47, 95% CI 1.17–1.86, p(adj) = 1.07 × 10–3 (discovery), p(adj) = 0.03 (replication), p(adj) = 9.53 × 10–5 (meta-analysis)]. MYT1L is involved in neuronal differentiation. TSSC1 is involved in endosomal recycling and is implicated in breast cancer. The rs587936 variant annotated to DAB2IP was associated with increased survival time [HR 0.65, 95% CI 0.51–0.83, p(adj) = 4.79 × 10–4 (discovery), p(adj) = 0.02 (replication), p(adj) = 2.25 × 10–5 (meta-analysis)]. DAB2IP is a ras/GAP tumor suppressor gene which is highly expressed in vascular tissue. DAB2IP has multiple lines of evidence for protection against atherosclerosis.

Conclusion

Replicated findings identified two candidate genes for further study regarding association with survival in high-risk CAD patients: novel loci LINC01250 (rs13007553) and biologically relevant candidate DAB2IP (rs587936). These candidates did not overlap with validated longevity candidate genes. Future research could further define the role of common variants in survival outcomes for people with CAD and, ultimately, improve longitudinal outcomes for these patients.
A Compendium of Age-Related PheWAS and GWAS Traits for Human Genetic Association Studies, Their Networks and Genetic Correlations
Authors: Kim Seung-Soo , Hudgins Adam D. , Gonzalez Brenda , Milman Sofiya , Barzilai Nir , Vijg Jan , Tu Zhidong , Suh Yousin
Published: June 2021

The rich data from the genome-wide association studies (GWAS) and phenome-wide association studies (PheWAS) offer an unprecedented opportunity to identify the biological underpinnings of age-related disease (ARD) risk and multimorbidity. Surprisingly, however, a comprehensive list of ARDs remains unavailable due to the lack of a clear definition and selection criteria. We developed a method to identify ARDs and to provide a compendium of ARDs for genetic association studies. Querying 1,358 electronic medical record-derived traits, we first defined ARDs and age-related traits (ARTs) based on their prevalence profiles, requiring a unimodal distribution that shows an increasing prevalence after the age of 40 years, and which reaches a maximum peak at 60 years of age or later. As a result, we identified a list of 463 ARDs and ARTs in the GWAS and PheWAS catalogs. We next translated the ARDs and ARTs to their respective 276 Medical Subject Headings diseases and 45 anatomy terms. The most abundant disease categories are neoplasms (48 terms), cardiovascular diseases (44 terms), and nervous system diseases (27 terms). Employing data from a human symptoms-disease network, we found 6 symptom-shared disease groups, representing cancers, heart diseases, brain diseases, joint diseases, eye diseases, and mixed diseases. Lastly, by overlaying our ARD and ART list with genetic correlation data from the UK Biobank, we found 54 phenotypes in 2 clusters with high genetic correlations. Our compendium of ARD and ART is a highly useful resource, with broad applicability for studies of the genetics of aging, ARD, and multimorbidity.
In Vivo Inhibition of MicroRNA-326 in a NOD.H-2h4 Mouse Model of Autoimmune Thyroiditis
Authors: Zhao Na , Wang Zhenzhen , Cui Xuejiao , Wang Shuo , Fan Chenling , Li Yushu , Shan Zhongyan , Teng Weiping
Published: June 2021

Background

Previous studies reported that various miRNAs participate in autoimmune diseases, but the potential regulatory mechanism of miRNAs in autoimmune thyroiditis (AIT) needs further exploration.

Objective

This study aimed to further verify that miR-326 contributes to AIT by regulating Th17/Treg balance through Ets-1 using lentiviral gene delivery through tail vein and thyroid injection in NOD.H-2h4 mice.

Materials and Methods

Five-week-old NOD.H-2h4 mice were divided randomly into tail vein and thyroid injection groups, and each received either mmu-miR-326 sponge (LV-sponge) or lentiviral vector control. Mice were divided for tail vein injection: the therapeutic LV-ctrl, therapeutic LV-sponge, prophylactic LV-ctrl, and prophylactic LV-sponge groups. The control group was fed high-iodine water without vein injection. The thyroid infiltration of lymphocytes and serum TgAb value were investigated by thyroid hematoxylin and eosin (HE) staining and ELISA, respectively. Ets-1 and lymphocyte counts were measured by RT-PCR, western blotting, and flow cytometry. The thyroid CD4+IL-17a+ cells and CD4+Ets-1+ cells were detected by immunofluorescence, and the serum cytokines were tested by ELISA.

Results

In the tail vein injection groups, the thyroid inflammatory score and serum TgAb titer were significantly lower in the LV-sponge groups than in the control and LV-ctrl groups while Ets-1 protein expression in mouse spleens was increased in the LV-sponge groups. Moreover, Th17/Treg ratio declined in the LV-sponge group and decreased significantly in the prophylactic LV-sponge group (P = 0.036) tested by flow cytometry. Immunofluorescence showed that, in LV-sponge groups, CD4+IL-17a+ cells were decreased significantly (P = 0.001), while CD4+Ets-1+ cells were increased significantly in the LV-sponge group (P = 0.029). The serum IL-17/IL-10 was decreased significantly in the LV-sponge group (P < 0.05). In the thyroid injection groups, the thyroid inflammatory score and serum TgAb titer in the LV-sponge group decreased significantly compared with those in the LV-ctrl group (P < 0.05). In addition, in LV-sponge groups, CD4+IL-17a+ cells were decreased, while CD4+Ets-1+ cells were increased significantly in the inhibition group evaluated by immunofluorescence. Moreover, tail vein injection of LV-sponge resulted in much lower TgAb levels in thyroiditis compared with thyroid injection.

Conclusion

MiR-326 targeted therapy may be a promising approach for AIT. In addition, tail vein injection may achieve a better intervention effect than thyroid injection.
Citrullination and PAD Enzyme Biology in Type 1 Diabetes – Regulators of Inflammation, Autoimmunity, and Pathology
Authors: Yang Mei-Ling , Sodré Fernanda M. C. , Mamula Mark J. , Overbergh Lut
Published: June 2021

The generation of post-translational modifications (PTMs) in human proteins is a physiological process leading to structural and immunologic variety in proteins, with potentially altered biological functions. PTMs often arise through normal responses to cellular stress, including general oxidative changes in the tissue microenvironment and intracellular stress to the endoplasmic reticulum or immune-mediated inflammatory stresses. Many studies have now illustrated the presence of ‘neoepitopes’ consisting of PTM self-proteins that induce robust autoimmune responses. These pathways of inflammatory neoepitope generation are commonly observed in many autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, and type 1 diabetes (T1D), among others. This review will focus on one specific PTM to self-proteins known as citrullination. Citrullination is mediated by calcium-dependent peptidylarginine deiminase (PAD) enzymes, which catalyze deimination, the conversion of arginine into the non-classical amino acid citrulline. PADs and citrullinated peptides have been associated with different autoimmune diseases, notably with a prominent role in the diagnosis and pathology of rheumatoid arthritis. More recently, an important role for PADs and citrullinated self-proteins has emerged in T1D. In this review we will provide a comprehensive overview on the pathogenic role for PADs and citrullination in inflammation and autoimmunity, with specific focus on evidence for their role in T1D. The general role of PADs in epigenetic and transcriptional processes, as well as their crucial role in histone citrullination, neutrophil biology and neutrophil extracellular trap (NET) formation will be discussed. The latter is important in view of increasing evidence for a role of neutrophils and NETosis in the pathogenesis of T1D. Further, we will discuss the underlying processes leading to citrullination, the genetic susceptibility factors for increased recognition of citrullinated epitopes by T1D HLA-susceptibility types and provide an overview of reported autoreactive responses against citrullinated epitopes, both of T cells and autoantibodies in T1D patients. Finally, we will discuss recent observations obtained in NOD mice, pointing to prevention of diabetes development through PAD inhibition, and the potential role of PAD inhibitors as novel therapeutic strategy in autoimmunity and in T1D in particular.
B7-H7 Is Inducible on T Cells to Regulate Their Immune Response and Serves as a Marker for Exhaustion
Authors: Luu Khang , Schwarz Herbert , Lundqvist Andreas
Published: June 2021

The discovery of immune checkpoints highlights the complexity of T cell signalling during an immune response. Upon activation, T cells express several molecules to regulate their function and to prevent overactivation. B7 homolog 7 (B7-H7) is expressed in tumours and associated with a worse prognosis. However, conflicting data regarding its function suggest that it can be both stimulatory and inhibitory. In this study we report that B7-H7 is also expressed on T cells upon cross-linking of CD3 and CD28 and that additional stimulationviaCD137 further enhances the expression of B7-H7. B7-H7 is preferentially expressed on exhausted Th1 and Tc1 cells with an impaired secretion of TNF-α and IFN-γ. Blockade of B7-H7 with its natural receptor, recombinant CD28H, enhances T cell proliferation and activation. Thus, B7-H7 represents another target for immunotherapy and a biomarker to select for active effector T cells with relevance for adoptive cell transfer therapy.
Key Macrophage Responses to Infection With Mycobacterium tuberculosis Are Co-Regulated by microRNAs and DNA Methylation
Authors: Looney Monika , Lorenc Rachel , Halushka Marc K. , Karakousis Petros C.
Published: June 2021

Tuberculosis (TB) is the leading cause of death from infection with a single bacterial pathogen. Host macrophages are the primary cell type infected with Mycobacterium tuberculosis (Mtb), the organism that causes TB. Macrophage response pathways are regulated by various factors, including microRNAs (miRNAs) and epigenetic changes that can shape the outcome of infection. Although dysregulation of both miRNAs and DNA methylation have been studied in the context of Mtb infection, studies have not yet investigated how these two processes may jointly co-regulate critical anti-TB pathways in primary human macrophages. In the current study, we integrated genome-wide analyses of miRNA abundance and DNA methylation status with mRNA transcriptomics in Mtb-infected primary human macrophages to decipher which macrophage functions may be subject to control by these two types of regulation. Using in vitro macrophage infection models and next generation sequencing, we found that miRNAs and methylation changes co-regulate important macrophage response processes, including immune cell activation, macrophage metabolism, and AMPK pathway signaling.
Experimental Study on Influence of Temperature to Control Performance for Viscoelastic Materials Pounding Tuned Mass Damper
Authors: Ye Dehui , Tan Jie , Liang Yabin , Feng Qian
Published: May 2021

The pounding tuned mass damper (PTMD) is a novel passive damper that absorbs and dissipates energy by an auxiliary tuned spring-mass system. Viscoelastic materials are attached to the interface of the limitation collar in the PTMD so that the energy dissipation capacity can be enhanced. Previous studies have successfully demonstrated the effectiveness of PTMD at room temperature. However, in practice, the PTMD may face a broad temperature range, which can affect the mechanical properties of the viscoelastic materials. Thus, the study of vibration control effectiveness of PTMD at different temperatures is of great significance for its practical engineering application. In this paper, a series of experiments were conducted to investigate the performance of a PTMD in a temperature-controlled environment. A PTMD device was designed to suppress the vibration of a portal frame structure and tested across environmental temperatures ranging from –20°C to 45°C. The displacement reduction ratios demonstrated the temperature robustness of the PTMD. Additionally, the numerical results validated the accuracy of the pounding force model and the performance of PTMD.
Metabolic Evaluation in Patients With Hepatitis C Treated With Direct Antiviral Agents
Authors: Estefan Sergio , Brandão-Melo Carlos Eduardo , dos Santos Silva Cintia Marques , Gomes Danilo Cosme Klein , Cardoso Paula , Costa Marcia Helena S.
Published: May 2021

Epidemiological data clearly indicate a link between hepatitis C virus (HCV) and altered glucose homeostasis.

Objective: To evaluate the response of treatment with direct antiviral agents (DAAs) on metabolic variables of patients with hepatitis C.

Methods: Observational, cross-sectional study in a sample of patients with hepatitis C starting therapy with DAAs followed on the hepatology division of Federal University of Rio de Janeiro State. Data were collected in two stages: before the start of therapy and between 12 and 52 weeks after obtaining the sustained virological response.

Results: In the baseline assessment of the 97 patients selected, 19.3% were obese, 38.6% were overweight, 50% were hypertensive, 43.8% were pre-diabetic, 12.5% were diabetic, 31.2% were dyslipidemic, and 21.8% had metabolic syndrome. There was an increase in total cholesterol and LDL levels (p < 0.001), and a non-significant reduction in blood glucose, glycated hemoglobin, insulin, and HOMA-IR levels after treatment. In the post-treatment, there was a reduction in fibrosis (p = 0.016), with a reduction in the levels of GGT, AST, and ALT (all with p < 0.001), as well as in the FIB4 and APRI scores (both with p < 0.001) and in the degree of fibrosis evaluated by elastography represented in kPa (p = 0.006). The blood glucose level was higher in patients with steatosis (p = 0.039) after treatment. There was a positive pre-treatment correlation between the degree of fibrosis (kPa) and FIB4 (r = 0.319, p = 0.004), APRI (r = 0.287, p = 0.010), and the NAFLD score (r = 0.275, p = 0.016).

Conclusion: Patients with hepatitis C had a high prevalence of metabolic disturbance in the pre-treatment phase, but the therapy did not show beneficial effects, especially on glucose metabolism.
Development of a Potent Antimicrobial Peptide With Photodynamic Activity
Authors: Zhang Di , Chen Jingyi , Jing Qian , Chen Zheng , Ullah Azeem , Jiang Longguang , Zheng Ke , Yuan Cai , Huang Mingdong
Published: June 2021

The emergence of antibiotic-resistant bacteria poses a serious challenge to medical practice worldwide. A small peptide with sequence RWRWRW was previously identified as a core antimicrobial peptide with limited antimicrobial spectrum to bacteria, especially Gram-positive bacteria. By conjugating this peptide and its analogs with lipophilic phthalocyanine (Pc), we identified a new antibiotic peptide [PcG3K5(RW)3]. The peptide demonstrates increased antimicrobial effect to both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. In addition, Pc also provides added and potent antimicrobial effect upon red light illumination. The inhibitory efficacy of PcG3K5(RW)3 was increased by ~140-fold to nanomolar range upon illumination. Moreover, PcG3K5(RW)3 was safe for mammalian cell and promoted wound healing in the mouse infection model. Our work provides a new direction to optimize antimicrobial peptides to enhance antimicrobial efficacy.
Effect of Sunlight on the Efficacy of Commercial Antibiotics Used in Agriculture
Authors: Khan Sebastian J. , Osborn Amanda M. , Eswara Prahathees J.
Published: June 2021

Antibiotic stewardship is of paramount importance to limit the emergence of antibiotic-resistant bacteria in not only hospital settings, but also in animal husbandry, aquaculture, and agricultural sectors. Currently, large quantities of antibiotics are applied to treat agricultural diseases like citrus greening disease (CGD). The two commonly used antibiotics approved for this purpose are streptomycin and oxytetracycline. Although investigations are ongoing to understand how efficient this process is to control the spread of CGD, to our knowledge, there have been no studies that evaluate the effect of environmental factors such as sunlight on the efficacy of the above-mentioned antibiotics. We conducted a simple disc-diffusion assay to study the efficacy of streptomycin and oxytetracycline after exposure to sunlight for 7- or 14-day periods usingEscherichia coliandBacillus subtilisas the representative strains of Gram-negative and Gram-positive organisms, respectively. Freshly prepared discs and discs stored in the dark for 7 or 14 days served as our controls. We show that the antibiotic potential of oxytetracycline exposed to sunlight dramatically decreases over the course of 14 days against bothE. coliandB. subtilis. However, the effectiveness of streptomycin was only moderately impacted by sunlight. It is important to note that antibiotics that last longer in the environment may play a deleterious role in the rise and spread of antibiotic-resistant bacteria. Further studies are needed to substantively analyze the safety and efficacy of antibiotics used for broader environmental applications.
Diverse Trajectories Drive the Expression of a Giant Virus in the Oomycete Plant Pathogen Phytophthora parasitica
Authors: Hannat Sihem , Pontarotti Pierre , Colson Philippe , Kuhn Marie-Line , Galiana Eric , La Scola Bernard , Aherfi Sarah , Panabières Franck
Published: June 2021

Giant viruses of amoebas, recently classified in the class Megaviricetes, are a group of viruses that can infect major eukaryotic lineages. We previously identified a set of giant virus sequences in the genome of Phytophthora parasitica, an oomycete and a devastating major plant pathogen. How viral insertions shape the structure and evolution of the invaded genomes is unclear, but it is known that the unprecedented functional potential of giant viruses is the result of an intense genetic interplay with their hosts. We previously identified a set of giant virus sequences in the genome of P. parasitica, an oomycete and a devastating major plant pathogen. Here, we show that viral pieces are found in a 550-kb locus and are organized in three main clusters. Viral sequences, namely RNA polymerases I and II and a major capsid protein, were identified, along with orphan sequences, as a hallmark of giant viruses insertions. Mining of public databases and phylogenetic reconstructions suggest an ancient association of oomycetes and giant viruses of amoeba, including faustoviruses, African swine fever virus (ASFV) and pandoraviruses, and that a single viral insertion occurred early in the evolutionary history of oomycetes prior to the Phytophthora–Pythium radiation, estimated at ∼80 million years ago. Functional annotation reveals that the viral insertions are located in a gene sparse region of the Phytophthora genome, characterized by a plethora of transposable elements (TEs), effectors and other genes potentially involved in virulence. Transcription of viral genes was investigated through analysis of RNA-Seq data and qPCR experiments. We show that most viral genes are not expressed, and that a variety of mechanisms, including deletions, TEs insertions and RNA interference may contribute to transcriptional repression. However, a gene coding a truncated copy of RNA polymerase II along a set of neighboring sequences have been shown to be expressed in a wide range of physiological conditions, including responses to stress. These results, which describe for the first time the endogenization of a giant virus in an oomycete, contribute to challenge our view of Phytophthora evolution.
Iron Sulfide Enhanced the Dechlorination of Trichloroethene by Dehalococcoides mccartyi Strain 195
Authors: Li Yaru , Zhao He-Ping , Zhu Lizhong
Published: June 2021

Iron sulfide (FeS) nanoparticles have great potential in environmental remediation. Using the representative species Dehalococcoides mccartyi strain 195 (Dhc 195), the effect of FeS on trichloroethene (TCE) dechlorination was studied with hydrogen and acetate as the electron donor and carbon source, respectively. With the addition of 0.2 mM Fe2+ and S2–, the dechlorination rate of TCE was enhanced from 25.46 ± 1.15 to 37.84 ± 1.89 μmol⋅L–1⋅day–1 by the in situ formed FeS nanoparticles, as revealed through X-ray diffraction. Comparing the tceA gene copy numbers between with FeS and without FeS, real-time polymerase chain reaction (PCR) indicated that the abundance of the tceA gene increased from (2.83 ± 0.13) × 107 to (4.27 ± 0.21) × 108 copies/ml on day 12. The transcriptional activity of key genes involved in the electron transport chain was upregulated after the addition of FeS, including those responsible for the iron–sulfur cluster assembly protein gene (DET1632) and transmembrane transport of iron (DET1503, DET0685), cobalamin (DET0685, DET1139), and molybdenum (DET1161) genes. Meanwhile, the reverse transcription of tceA was increased approximately five times on the 12th day. These upregulations together suggested that the electron transport of D. mccartyi strain 195 was enhanced by FeS for apparent TCE dechlorination. Overall, the present study provided an eco-friendly and effective method to achieve high remediation efficiency for organohalide-polluted groundwater and soil.