bluuebunny/crossref_metadata_2025_split huggingface dataset:
A proteomic repertoire of autoantigens identified from the classic autoantibody clinical test substrate HEp-2 cells
Authors: Wang Julia Y. , Zhang Wei , Rho Jung-hyun , Roehrl Michael W. , Roehrl Michael H. 
Published: September 2020

Abstract
Background
Autoantibodies are a hallmark of autoimmune diseases. Autoantibody screening by indirect immunofluorescence staining of HEp-2 cells with patient sera is a current standard in clinical practice. Differential diagnosis of autoimmune disorders is based on commonly recognizable nuclear and cytoplasmic staining patterns. In this study, we attempted to identify as many autoantigens as possible from HEp-2 cells using a unique proteomic DS-affinity enrichment strategy.

Methods
HEp-2 cells were cultured and lysed. Total proteins were extracted from cell lysate and fractionated with DS-Sepharose resins. Proteins were eluted with salt gradients, and fractions with low to high affinity were collected and sequenced by mass spectrometry. Literature text mining was conducted to verify the autoantigenicity of each protein. Protein interaction network and pathway analyses were performed on all identified proteins.

Results
This study identified 107 proteins from fractions with low to high DS-affinity. Of these, 78 are verified autoantigens with previous reports as targets of autoantibodies, whereas 29 might be potential autoantigens yet to be verified. Among the 107 proteins, 82 can be located to nucleus and 15 to the mitotic cell cycle, which may correspond to the dominance of nuclear and mitotic staining patterns in HEp-2 test. There are 55 vesicle-associated proteins and 12 ribonucleoprotein granule proteins, which may contribute to the diverse speckled patterns in HEp-2 stains. There are also 32 proteins related to the cytoskeleton. Protein network analysis indicates that these proteins have significantly more interactions among themselves than would be expected of a random set, with the top 3 networks being mRNA metabolic process regulation, apoptosis, and DNA conformation change.

Conclusions
This study provides a proteomic repertoire of confirmed and potential autoantigens for future studies, and the findings are consistent with a mechanism for autoantigenicity: how self-molecules may form molecular complexes with DS to elicit autoimmunity. Our data contribute to the molecular etiology of autoimmunity and may deepen our understanding of autoimmune diseases.
Transgenic and knockout analyses of Masculinizer and doublesex illuminated the unique functions of doublesex in germ cell sexual development of the silkworm, Bombyx mori
Authors: Yuzawa Tomohisa , Matsuoka Misato , Sumitani Megumi , Aoki Fugaku , Sezutsu Hideki , Suzuki Masataka G. 
Published: September 2020

Abstract
Background
Masculinizer (Masc) plays a pivotal role in male sex determination in the silkworm, Bombyx mori. Masc is required for male-specific splicing of B. mori doublesex (Bmdsx) transcripts. The male isoform of Bmdsx (BmdsxM) induces male differentiation in somatic cells, while females express the female isoform of Bmdsx (BmdsxF), which promotes female differentiation in somatic cells. Our previous findings suggest that Masc could direct the differentiation of genetically female (ZW) germ cells into sperms. However, it remains unclear whether Masc directly induces spermatogenesis or if it promotes male differentiation in germ cells indirectly by inducing the expression of BmdsxM.

Results
In this study, we performed genetic analyses using the transgenic line that expressed Masc, as well as various Bmdsx knockout lines. We found that Masc-expressing females with a homozygous mutation in BmdsxM showed normal development in ovaries. The formation of testis-like tissues was abolished in these females. On the other hand, Masc-expressing females carrying a homozygous mutation in BmdsxF exhibited almost complete male-specific development in gonads and germ cells. These results suggest that BmdsxM has an ability to induce male development in germ cells as well as internal genital organs, while BmdsxF inhibits BmdsxM activity and represses male differentiation. To investigate whether MASC directly controls male-specific splicing of Bmdsx and identify RNAs that form complexes with MASC in testes, we performed RNA immunoprecipitation (RIP) using an anti-MASC antibody. We found that MASC formed a complex with AS1 lncRNA, which is a testis-specific factor involved in the male-specific splicing of Bmdsx pre-mRNA.

Conclusions
Taken together, our findings suggest that Masc induces male differentiation in germ cells by enhancing the production of BmdsxM. Physical interaction between MASC and AS1 lncRNA may be important for the BmdsxM expression in the testis. Unlike in the Drosophila dsx, BmdsxM was able to induce spermatogenesis in genetically female (ZW) germ cells. To the best of our knowledge, this is the first report that the role of dsx in germ cell sexual development is different between insect species.
Multi-omics profiling highlights lipid metabolism alterations in pigs fed low-dose antibiotics
Authors: Hu Yue , Zhang Yihe , Liu Cong , Qin Rui , Gong Desheng , Wang Ru , Zhang Du , Che Lianqiang , Chen Daiwen , Xin Guizhong , Gao Fei , Hu Qi 
Published: September 2020

AbstractBackgroundIn order to study the relations of hepatocellular functions, weight gain and metabolic imbalance caused by low-dose antibiotics (LDA) via epigenetic regulation of gene transcription, 32 weaned piglets were employed as animal models and randomly allocated into two groups with diets supplemented with 0 or LDA (chlorotetracycline and virginiamycin).ResultsDuring the 4 weeks of the experiment, LDA showed a clear growth-promoting effect, which was exemplified by the significantly elevated body weight and average daily gain. Promoter methylome profiling using liquid hybridization capture-based bisulfite sequencing (LHC-BS) indicated that most of the 745 differential methylation regions (DMRs) were hypermethylated in the LDA group. Several DMRs were significantly enriched in genes related with fatty acids metabolic pathways, such as FABP1 and PCK1. In addition, 71 differentially expressed genes (DEGs) were obtained by strand-specific transcriptome analysis of liver tissues, including ALOX15, CXCL10 and NNMT, which are three key DEGs that function in lipid metabolism and immunity and which had highly elevated expression in the LDA group. In accordance with these molecular changes, the lipidome analyses of serum by LC-MS identified 38 significantly differential lipids, most of which were downregulated in the LDA group.ConclusionsOur results indicate that LDA could induce epigenetic and transcriptional changes of key genes and lead to enhanced efficiency of lipid metabolism in the liver.
Transcriptome analysis of the hypothalamus and pituitary of turkey hens with low and high egg production
Authors: Brady Kristen , Liu Hsiao-Ching , Hicks Julie A. , Long Julie A. , Porter Tom E. 
Published: September 2020

Abstract
Background
High egg producing hens (HEPH) show increased hypothalamic and pituitary gene expression related to hypothalamo-pituitary-gonadal (HPG) axis stimulation as well as increased in vitro responsiveness to gonadotropin releasing hormone (GnRH) stimulation in the pituitary when compared to low egg producing hens (LEPH). Transcriptome analysis was performed on hypothalamus and pituitary samples from LEPH and HEPH to identify novel regulators of HPG axis function.

Results
In the hypothalamus and pituitary, 4644 differentially expressed genes (DEGs) were identified between LEPH and HEPH, with 2021 genes up-regulated in LEPH and 2623 genes up-regulated in HEPH. In LEPH, up-regulated genes showed enrichment of the hypothalamo-pituitary-thyroid (HPT) axis. Beta-estradiol was identified as an upstream regulator regardless of tissue. When LEPH and HEPH samples were compared, beta-estradiol was activated in HEPH in 3 of the 4 comparisons, which correlated to the number of beta-estradiol target genes up-regulated in HEPH. In in vitro pituitary cell cultures from LEPH and HEPH, thyroid hormone pretreatment negatively impacted gonadotropin subunit mRNA levels in cells from both LEPH and HEPH, with the effect being more prominent in HEPH cells. Additionally, the effect of estradiol pretreatment on gonadotropin subunit mRNA levels in HEPH cells was negative, whereas estradiol pretreatment increased gonadotropin subunit mRNA levels in LEPH cells.

Conclusions
Up-regulation of the HPT axis in LEPH and upstream beta-estradiol activation in HEPH may play a role in regulating HPG axis function, and ultimately ovulation rates. Thyroid hormone and estradiol pretreatment impacted gonadotropin mRNA levels following GnRH stimulation, with the inhibitory effects of thyroid hormone more detrimental in HEPH and estradiol stimulatory effects more prominent in LEPH. Responsiveness to thyroid hormone and estradiol may be due to desensitization to thyroid hormone and estradiol in LEPH and HEPH, respectively, due to up-regulation of the HPT axis in LEPH and of the HPG axis in HEPH. Further studies will be necessary to identify possible target gene desensitization mechanisms and elicit the regulatory role of the HPT axis and beta-estradiol on ovulation rates in turkey hens.
COVID19-world: a shiny application to perform comprehensive country-specific data visualization for SARS-CoV-2 epidemic
Authors: Tebé Cristian , Valls Joan , Satorra Pau , Tobías Aurelio 
Published: September 2020

AbstractBackgroundData analysis and visualization is an essential tool for exploring and communicating findings in medical research, especially in epidemiological surveillance.ResultsData on COVID-19 diagnosed cases and mortality, from January 1st, 2020, onwards is collected automatically from the European Centre for Disease Prevention and Control (ECDC). We have developed a Shiny application for data visualization and analysis of several indicators to follow the SARS-CoV-2 epidemic using ECDC data. A country-specific tool for basic epidemiological surveillance, in an interactive and user-friendly manner. The available analyses cover time trends and projections, attack rate, population fatality rate, case fatality rate, and basic reproduction number.ConclusionsThe COVID19-World online web application systematically produces daily updated country-specific data visualization and analysis of the SARS-CoV-2 epidemic worldwide. The application may help for a better understanding of the SARS-CoV-2 epidemic worldwide.
Direct-access to sonographic diagnosis of deep vein thrombosis in general practice: a descriptive cohort study
Authors: Appel Charlotte W. , Balle Annette M. , Krintel Mads M. , Vittrup Axel , Nielsen Agnete H. , Vedsted Peter 
Published: September 2020

Abstract
Background
Suspicion of deep vein thrombosis (DVT) is common and requires urgent and efficient investigation due to hazardous prognosis. The traditional diagnostic pathway can be complex and time-consuming, and innovative solutions may provide easy access to diagnostics and better use of healthcare resources. We aimed to describe use, clinical outcomes and time used when providing general practitioners (GPs) with a direct-access pathway to hospital-based, single whole-leg compression ultrasound (CUS) for patients with suspected DVT. Furthermore we aimed to describe the resources used in the new direct-access pathway and compare it with the previous pathway.

Methods
We conducted a 2-year descriptive cohort study (2016–2017) including 449 consecutively referred patients for diagnosis of DVT in a Danish regional hospital. The previous pathway included pre-test at the medical department, a proximal leg CUS if required based on the pre-test and a re-scan if the first CUS was negative. The new pathway included two strategies: 1) a ‘yes-no strategy’, where GPs referred patients directly to whole-leg CUS and if positive, treated at the medical department and if negative, discharged to the GP, 2) a ‘follow-up strategy’ where GPs could require that patients were seen at the medical department, irrespective of the CUS result. Data included extractions from the Radiology Information and Patient Administrative Systems, and mean salaries of healthcare professionals at Silkeborg Regional Hospital, Denmark. Descriptive statistics were used to describe prevalence, timelines and costs.

Results
GPs referred 318 (71%) patients through the yes-no strategy and 131 (29%) via the follow-up strategy with DVT diagnosed in 48 (15%) and 51 (39%) patients, respectively (p < 0.001). For the 263 patients completed after CUS in the yes-no strategy, median pathway time was 24 min (IQI: 16–36), and for those with DVT (including both strategies) 202 min (IQI: 158–273). Direct-access pathway costs were €49.7 less per patient than the previous pathway.

Conclusion
Direct-access to CUS for suspected DVT was achievable, had short time intervals and required fewer resources. The difference in DVT prevalence indicates that GPs distinguish between patients with low and high risk of DVT.
Effect of trust in primary care physicians on patient satisfaction: a cross-sectional study among patients with hypertension in rural China
Authors: Chen Wenqin , Feng Yingchao , Fang Jiyuan , Wu Jin , Huang Xianhong , Wang Xiaohe , Wu Jian , Zhang Meng 
Published: September 2020

Abstract
Background
In rural areas of China, hypertension is on the rise and it is drawing the Chinese government’s attention. The health outcomes of hypertension management can be positively impacted by patient satisfaction with primary care physicians (PCPs), and the influence of patient trust on satisfaction cannot be ignored. This study aimed to analyze the effect of trust in PCPs on patient satisfaction among patients with hypertension in rural China, and the influence of patients’ socio-demographic characteristics and hypertension-management-related factors.

Methods
A multi-stage stratified random sampling method was adopted to investigate 2665 patients with hypertension in rural China. Patient trust and satisfaction were measured using the Chinese version of the Wake Forest Physician Trust Scale and the European Task Force on Patient Evaluation of General Practice. Multiple linear regression was used to analyze the factors influencing patient satisfaction, and structural equation modeling was conducted to clarify the relationships among patient trust and patient satisfaction with PCPs.

Results
Patients’ trust in their PCPs’ benevolence had a positive main effect on all three satisfaction dimensions (clinical behavior: β = 0.940, p <  0.01; continuity and cooperation: β = 0.910, p <  0.01; and organization of care: β = 0.879, p <  0.01). Patients’ trust in their PCPs’ technical competence had a small negative effect on all three satisfaction dimensions (clinical behavior: β = − 0.077, p <  0.01; continuity and cooperation: β = − 0.136, p <  0.01; and organization of care: β = − 0.064, p <  0.01). Patient satisfaction was also associated with region, gender, insurance status, distance from the nearest medical/health-service institution, and number of visits to PCPs in the past year.

Conclusions
Patients focused more on physicians’ benevolence than on their technical competence. Hence, medical humanities and communication skills education should be emphasized for PCPs. Regarding region-based and health-insurance-based differences, the inequities between eastern, central, and western provinces, as well as between urban and rural areas, must also be addressed.
In search for interplay between stool microRNAs, microbiota and short chain fatty acids in Crohn’s disease - a preliminary study
Authors: Ambrozkiewicz Filip , Karczmarski Jakub , Kulecka Maria , Paziewska Agnieszka , Niemira Magdalena , Zeber-Lubecka Natalia , Zagorowicz Edyta , Kretowski Adam , Ostrowski Jerzy 
Published: September 2020

Abstract
Background
Inflammatory bowel diseases are classic polygenic disorders, with genetic loads that reflect immunopathological processes in response to the intestinal microbiota. Herein we performed the multiomics analysis by combining the large scale surveys of gut bacterial community, stool microRNA (miRNA) and short chain fatty acid (SCFA) signatures to correlate their association with the activity of Crohn’s disease (CD).

Methods
DNA, miRNA, and metabolites were extracted from stool samples of 15 CD patients, eight with active disease and seven in remission, and nine healthy individuals. Microbial, miRNA and SCFA profiles were assessed using datasets from 16S rRNA sequencing, Nanostring miRNA and GC-MS targeted analysis, respectively.

Results
Pairwise comparisons showed that 9 and 23 taxa differed between controls and CD patients with active and inactive disease, respectively. Six taxa were common to both comparisons, whereas four taxa differed in CD patients. α-Diversity was lower in both CD groups than in controls. The levels of 13 miRNAs differed (p-value < 0.05; FC > 1.5) in CD patients and controls before FDR correction and 4 after. Of six SCFAs, the levels of two differed significantly (p-value < 0.05, FC > 1.5) in CD patients and controls, and the levels of four differed in patients with active and inactive CD. PLS-DA revealed models with smallest error rate for controls in bacterial component and inactive disease in metabolites.

Conclusion
A complex interrelationship may exist between gut dysbiosis, miRNA profiling and SCFA level in response to intestinal inflammation.
Effectiveness of a peer-based intervention on loneliness and social isolation of older Chinese immigrants in Canada: a randomized controlled trial
Authors: Lai Daniel W. L. , Li Jia , Ou Xiaoting , Li Celia Y. P. 
Published: September 2020

Abstract
Background
Social isolation is a key concern for immigrant older adults. We examined the effectiveness of a peer-based intervention in reducing loneliness, social isolation, and improving psychosocial well-being with a sample of aging Chinese immigrants.

Methods
Sixty community-dwelling older Chinese immigrants aged 65 and older were randomly assigned to an intervention group and a control group (n = 30 each) in a randomized control parallel trial design. Intervention group participants received an eight-week peer support intervention. Twenty-four volunteers aged 48 to 76 engaged in two-on-one peer support through home visits and telephone calls to provide emotional support, problem-solving support, and community resource sharing. Social workers who are not blinded to the group assignment measured the changes of both the intervention group and the control group participants in a range of psychosocial outcomes including three primary outcomes (loneliness, social support, barriers to social participation) and five secondary outcomes (depressive symptoms, anxiety, life satisfaction, happiness, and purpose in life).

Results
The 30 intervention group participants showed a statistically significant decrease in loneliness and increase in resilience when compared to the 30 control group participants. They reported fewer barriers to social participation, fewer depressive symptoms, increased life satisfaction, and happiness while no such improvements were observed in the control group.

Conclusions
There is a need to further examine the use of peer-based interventions for both program effectiveness and delivery efficiency. In the era of population aging and increasing immigration, diverse aging adults can be trained to fill volunteer support roles via peer-based intervention approaches.

Trial registration
ISRCTN, ISRCTN14572069, Registered 23 December 2019 – Retrospectively registered.
Are we ready for artificial intelligence health monitoring in elder care?
Authors: Ho Anita 
Published: September 2020

Abstract
Background
The world is experiencing a dramatic increase in the aging population, challenging the sustainability of traditional care models that have relied on in-person monitoring. This debate article discusses whether artificial intelligence health monitoring may be suitable enhancement or replacement for elder care.

Main text
Internationally, as life expectancy continues to rise, many countries are facing a severe shortage of direct care workers. The health workforce is aging, and replacement remains a challenge. Artificial intelligence health monitoring technologies may play a novel and significant role in filling the human resource gaps in caring for older adults by complementing current care provision, reducing the burden on family caregivers, and improving the quality of care. Nonetheless, opportunities brought on by these emerging technologies raise ethical questions that must be addressed to ensure that these automated systems can truly enhance care and health outcomes for older adults. This debate article explores some ethical dimensions of using automated health monitoring technologies. It argues that, in order for these health monitoring technologies to fulfill the wishes of older adults to age in place and also to empower them and improve their quality of life, we need deep knowledge of how stakeholders may balance their considerations of relational care, safety, and privacy.

Conclusion
It is only when we design artificial intelligence health monitoring technologies with intersecting clinical and ethical factors in mind that the resulting systems will enhance productive relational care, facilitate independent living, promote older adults’ health outcomes, and minimize waste.
Three-dimensional CT texture analysis of anatomic liver segments can differentiate between low-grade and high-grade fibrosis
Authors: Budai Bettina Katalin , Tóth Ambrus , Borsos Petra , Frank Veronica Grace , Shariati Sonaz , Fejér Bence , Folhoffer Anikó , Szalay Ferenc , Bérczi Viktor , Kaposi Pál Novák 
Published: September 2020

Abstract
Background
CT texture analysis (CTTA) has been successfully used to assess tissue heterogeneity in multiple diseases. The purpose of this work is to demonstrate the value of three-dimensional CTTA in the evaluation of diffuse liver disease. We aimed to develop CTTA based prediction models, which can be used for staging of fibrosis in different anatomic liver segments irrespective of variations in scanning parameters.

Methods
We retrospectively collected CT scans of thirty-two chronic hepatitis patients with liver fibrosis. The CT examinations were performed on either a 16- or a 64-slice scanner. Altogether 354 anatomic liver segments were manually highlighted on portal venous phase images, and 1117 three-dimensional texture parameters were calculated from each segment. The segments were divided between groups of low-grade and high-grade fibrosis using shear-wave elastography. The highly-correlated features (Pearson r > 0.95) were filtered out, and the remaining 453 features were normalized and used in a classification with k-means and hierarchical cluster analysis. The segments were split between the train and test sets in equal proportion (analysis I) or based on the scanner type (analysis II) into 64-slice train 16-slice validation cohorts for machine learning classification, and a subset of highly prognostic features was selected with recursive feature elimination.

Results
A classification with k-means and hierarchical cluster analysis divided segments into four main clusters. The average CT density was significantly higher in cluster-4 (110 HU ± SD = 10.1HU) compared to the other clusters (c1: 96.1 HU ± SD = 11.3HU; p < 0.0001; c2: 90.8 HU ± SD = 16.8HU; p < 0.0001; c3: 93.1 HU ± SD = 17.5HU; p < 0.0001); but there was no difference in liver stiffness or scanner type among the clusters. The optimized random forest classifier was able to distinguish between low-grade and high-grade fibrosis with excellent cross-validated accuracy in both the first and second analysis (AUC = 0.90, CI = 0.85–0.95 vs. AUC = 0.88, CI = 0.84–0.91). The final support vector machine model achieved an excellent prediction rate in the second analysis (AUC = 0.91, CI = 0.88–0.94) and an acceptable prediction rate in the first analysis (AUC = 0.76, CI = 0.67–0.84).

Conclusions
In conclusion, CTTA-based models can be successfully applied to differentiate high-grade from low-grade fibrosis irrespective of the imaging platform. Thus, CTTA may be useful in the non-invasive prognostication of patients with chronic liver disease.