bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can statistical adjustment guided by causal inference improve the accuracy of effect estimation? A simulation and empirical research based on meta-analyses of case–control studies
Authors: Yan Ruohua , Liu Tianyi , Peng Yaguang , Peng Xiaoxia 
Published: December 2020

Abstract
Background
Statistical adjustment is often considered to control confounding bias in observational studies, especially case–control studies. However, different adjustment strategies may affect the estimation of odds ratios (ORs), and in turn affect the results of their pooled analyses. Our study is aimed to investigate how to deal with the statistical adjustment in case–control studies to improve the validity of meta-analyses.

Methods
Three types of adjustment strategies were evaluated including insufficient adjustment (not all preset confounders were adjusted), full adjustment (all confounders were adjusted under the guidance of causal inference), and improper adjustment (covariates other than confounders were adjusted). We carried out a series of Monte Carlo simulation experiments based on predesigned scenarios, and assessed the accuracy of effect estimations from meta-analyses of case–control studies by combining ORs calculated according to different adjustment strategies. Then we used the data from an empirical review to illustrate the replicability of the simulation results.

Results
For all scenarios with different strength of causal relations, combining ORs that were comprehensively adjusted for confounders would get the most precise effect estimation. By contrast, combining ORs that were not sufficiently adjusted for confounders or improperly adjusted for mediators or colliders would easily introduce bias in causal interpretation, especially when the true effect of exposure on outcome was weak or none. The findings of the simulation experiments were further verified by the empirical research.

Conclusions
Statistical adjustment guided by causal inference are recommended for effect estimation. Therefore, when conducting meta-analyses of case–control studies, the causal relationship formulated by exposure, outcome, and covariates should be firstly understood through a directed acyclic graph, and then reasonable original ORs could be extracted and combined by suitable methods.
Dental visits in Medicaid-enrolled youth with mental illness: an analysis of administrative claims data
Authors: Stockbridge Erica L. , Dhakal Eleena , Griner Stacey B. , Loethen Abiah D. , West Joseph F. , Vera Joseph W. , Nandy Karabi 
Published: December 2020

Abstract
Background
State Medicaid plans across the United States provide dental insurance coverage to millions of young persons with mental illness (MI), including those with attention deficit hyperactivity disorder (ADHD), depression, anxiety, bipolar disorder, and schizophrenia. There are significant oral health challenges associated with MI, and providing dental care to persons with MI while they are young provides a foundation for future oral health. However, little is known about the factors associated with the receipt of dental care in young Medicaid enrollees with MI. We aimed to identify mental and physical health and sociodemographic characteristics associated with dental visits among this population.

Methods
We retrospectively analyzed administrative claims data from a Medicaid specialty health plan (September 2014 to December 2015). All enrollees in the plan had MI and were ≥ 7 years of age; data for enrollees aged 7 to 20 years were analyzed. We used two-level, mixed effects regression models to explore the relationships between enrollee characteristics and dental visits during 2015.

Results
Of 6564 Medicaid-enrolled youth with MI, 29.0% (95% CI, 27.9, 30.1%) had one or more visits with a dentist or dental hygienist. Within youth with MI, neither anxiety (Adjusted odds ratio [AOR] = 1.15, p = 0.111), post-traumatic stress disorder (AOR = 1.31, p = 0.075), depression (AOR = 1.02, p = 0.831), bipolar disorder (AOR = 0.97, p = 0.759), nor schizophrenia (AOR = 0.83, p = 0.199) was associated with dental visits in adjusted analyses, although having ADHD was significantly associated with higher odds of dental visits relative to not having this condition (AOR = 1.34, p < 0.001). Age, sex, race/ethnicity, language, and education were also significantly associated with visits (p < 0.05 for all).

Conclusions
Dental utilization as measured by annual dental visits was lower in Medicaid-enrolled youth with MI relative to the general population of Medicaid-enrolled youth. However, utilization varied within the population of Medicaid-enrolled youth with MI, and we identified a number of characteristics significantly associated with the receipt of dental services. By identifying these variations in dental service use this study facilitates the development of targeted strategies to increase the use of dental care in – and consequently improve the current and long-term wellbeing of – the vulnerable population of Medicaid-enrolled youth with MI.
Effectiveness of training interventions to improve quality of medical certification of cause of death: systematic review and meta-analysis
Authors: Gamage U. S. H. , Mahesh Pasyodun Koralage Buddhika , Schnall Jesse , Mikkelsen Lene , Hart John D. , Chowdhury Hafiz , Li Hang , McLaughlin Deirdre , Lopez Alan D. 
Published: December 2020

Abstract
Background
Valid cause of death data are essential for health policy formation. The quality of medical certification of cause of death (MCCOD) by physicians directly affects the utility of cause of death data for public policy and hospital management. Whilst training in correct certification has been provided for physicians and medical students, the impact of training is often unknown. This study was conducted to systematically review and meta-analyse the effectiveness of training interventions to improve the quality of MCCOD.

Methods
This review was registered in the International Prospective Register of Systematic Reviews (PROSPERO; Registration ID: CRD42020172547) and followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. CENTRAL, Ovid MEDLINE and Ovid EMBASE databases were searched using pre-defined search strategies covering the eligibility criteria. Studies were selected using four screening questions using the Distiller-SR software. Risk of bias assessments were conducted with GRADE recommendations and ROBINS-I criteria for randomised and non-randomised interventions, respectively. Study selection, data extraction and bias assessments were performed independently by two reviewers with a third reviewer to resolve conflicts. Clinical, methodological and statistical heterogeneity assessments were conducted. Meta-analyses were performed with Review Manager 5.4 software using the ‘generic inverse variance method’ with risk difference as the pooled estimate. A ‘summary of findings’ table was prepared using the ‘GRADEproGDT’ online tool. Sensitivity analyses and narrative synthesis of the findings were also performed.

Results
After de-duplication, 616 articles were identified and 21 subsequently selected for synthesis of findings; four underwent meta-analysis. The meta-analyses indicated that selected training interventions significantly reduced error rates among participants, with pooled risk differences of 15–33%. Robustness was identified with the sensitivity analyses. The findings of the narrative synthesis were similarly suggestive of favourable outcomes for both physicians and medical trainees.

Conclusions
Training physicians in correct certification improves the accuracy and policy utility of cause of death data. Investment in MCCOD training activities should be considered as a key component of strategies to improve vital registration systems given the potential of such training to substantially improve the quality of cause of death data.
Updated adolescent diagnostic criteria for polycystic ovary syndrome: impact on prevalence and longitudinal body mass index trajectories from birth to adulthood
Authors: Tay Chau Thien , Hart Roger J. , Hickey Martha , Moran Lisa J. , Earnest Arul , Doherty Dorota A. , Teede Helena J. , Joham Anju E. 
Published: December 2020

Abstract
Background
Polycystic ovary syndrome (PCOS) is challenging to diagnose. While the 2003 Rotterdam criteria are widely used for adults, the 2018 international PCOS guideline recommended updated Rotterdam criteria with both hyperandrogenism and oligo-anovulation for adolescents based on evidence-informed expert consensus. This study compared the prevalence of PCOS using updated and original Rotterdam criteria in community-based adolescents and explored long-term body mass index (BMI) trajectories across different diagnostic phenotypes.

Methods
Overall, 227 postmenarchal adolescent females from the prospective cohort Raine Study undertook comprehensive PCOS assessment at age 14–16 years. Detailed anthropometric measurements were collected from birth until age 22 years. Cross-sectional and longitudinal BMI were analyzed using t tests and generalized estimating equations.

Results
PCOS was diagnosed in 66 (29.1%) participants using original criteria versus 37 (16.3%) participants using updated Rotterdam criteria. Using updated criteria, participants with PCOS had higher BMI than participants without PCOS from prepubertal. Only the phenotype meeting the updated criteria was significantly associated with higher long-term BMI gain whereas other PCOS phenotypes had similar BMI trajectories to participants without PCOS (p < 0.001).

Conclusions
The use of the 2018 updated Rotterdam criteria reduces over-diagnosis of PCOS in adolescents and identifies those at the greatest risk of long-term weight gain, a key contributor to disease severity and long-term health implications. The BMI trajectories of females with PCOS on updated criteria diverge prepubertally compared to those without PCOS. This work supports targeting adolescents diagnosed with PCOS on the 2018 updated criteria for early lifestyle interventions to prevent long-term health complications.
Changes in oxidation-antioxidation function on the thymus of chickens infected with reticuloendotheliosis virus
Authors: Yang Dahan , Zhao Chenhui , Zhang Meixi , Zhang Shujun , Zhai Jie , Gao XueLi , Liu Chaonan , Lv Xiaoping , Zheng Shimin 
Published: December 2020

Abstract
Background
Reticuloendotheliosis virus (REV) is a retrovirus that causes severe immunosuppression in poultry. Animals grow slowly under conditions of oxidative stress. In addition, long-term oxidative stress can impair immune function, as well as accelerate aging and death. This study aimed to elucidate the pathogenesis of REV from the perspective of changes in oxidative-antioxidative function following REV infection.

Methods
A total of 80 one-day-old specific pathogen free (SPF) chickens were randomly divided into a control group (Group C) and an REV-infected group (Group I). The chickens in Group I received intraperitoneal injections of REV with 104.62/0.1 mL TCID50. Thymus was collected on day 1, 3, 7, 14, 21, 28, 35, and 49 for histopathology and assessed the status of oxidative stress.

Results
In chickens infected with REV, the levels of H2O2 and MDA in the thymus increased, the levels of TAC, SOD, CAT, and GPx1 decreased, and there was a reduction in CAT and Gpx1 mRNA expression compared with the control group. The thymus index was also significantly reduced. Morphological analysis showed that REV infection caused an increase in the thymic reticular endothelial cells, inflammatory cell infiltration, mitochondrial swelling, and nuclear damage.

Conclusions
These results indicate that an increase in oxidative stress enhanced lipid peroxidation, markedly decreased antioxidant function, caused thymus atrophy, and immunosuppression in REV-infected chickens.
Identification of LINC02310 as an enhancer in lung adenocarcinoma and investigation of its regulatory network via comprehensive analyses
Authors: Zhao Wenyuan , Wang Jun , Luo Qingxi , Peng Wei , Li Bin , Wang Lei , Zhang Chunfang , Duan Chaojun 
Published: December 2020

Abstract
Background
Lung adenocarcinoma (LADC) is a major subtype of non-small cell lung cancer and has one of the highest mortality rates. An increasing number of long non-coding RNAs (LncRNAs) were reported to be associated with the occurrence and progression of LADC. Thus, it is necessary and reasonable to find new prognostic biomarkers for LADC among LncRNAs.

Methods
Differential expression analysis, survival analysis, PCR experiments and clinical feature analysis were performed to screen out the LncRNA which was significantly related to LADC. Its role in LADC was verified by CCK-8 assay and colony. Furthermore, competing endogenous RNA (ceRNA) regulatory network construction, enrichment analysis and protein–protein interaction (PPI) network construction were performed to investigate the downstream regulatory network of the selected LncRNA.

Results
A total of 2431 differentially expressed LncRNAs (DELncRNAs) and 2227 differentially expressed mRNAs (DEmRNAs) were from The Cancer Genome Atlas database. Survival analysis results indicated that lnc-YARS2-5, lnc-NPR3-2 and LINC02310 were significantly related to overall survival. Their overexpression indicated poor prognostic. PCR experiments and clinical feature analysis suggested that LINC02310 was significantly correlated with TNM-stage and T-stage. CCK-8 assay and colony formation assay demonstrated that LINC02310 acted as an enhancer in LADC. In addition, 3 targeted miRNAs of LINC02310 and 414 downstream DEmRNAs were predicted. The downstream DEmRNAs were then enriched in 405 Gene Ontology terms and 11 Kyoto Encyclopedia of Genes and Genomes pathways, which revealed their potential functions and mechanisms. The PPI network showed the interactions among the downstream DEmRNAs.

Conclusions
This study verified LINC02310 as an enhancer in LADC and performed comprehensive analyses on its downstream regulatory network, which might benefit LADC prognoses and therapies.
Genetic and clinical phenotypic analysis of familial stapes sclerosis caused by an NOG mutation
Authors: Yu Rong , Jiang Hongqun , Liao Huihuang , Luo Wugen 
Published: December 2020

AbstractBackgroundThe noggin protein encoded by the NOG gene can interfere with the binding of bone morphogenetic protein to its receptor, thus affecting bone and joint development. The symptoms include abnormal skeletal development and conductive deafness.MethodsIn a retrospective study, clinical data of the proband and her family members, including 8 people and 50 healthy normal controls, were collected. Second-generation sequencing was performed on peripheral blood samples from them.ResultsThe sequencing analysis indicated that in the proband, theNOGgene had a c.532T > C, p.C178R (cytosine deletion, NM_005450.6:c.532T > C), leading to an amino acid change. The proband's father, grandmother, second sister, and third sister also had this mutation, whereas family members with normal phenotypes did not have the mutation.ConclusionAnalysis of this family showed that the novel presentation of the c.532T > C, p.C178R mutation in theNOGgene resulted in syndrome-type autosomal dominant inheritance reflected in a mild clinical phenotype, which is of great importance for further studies of the clinical phenotype and pathogenesis of stapes sclerosis.
Designing next generation recombinant protein expression platforms by modulating the cellular stress response in Escherichia coli
Authors: Guleria Richa , Jain Priyanka , Verma Madhulika , Mukherjee Krishna J. 
Published: December 2020

Abstract
Background
A cellular stress response (CSR) is triggered upon recombinant protein synthesis which acts as a global feedback regulator of protein expression. To remove this key regulatory bottleneck, we had previously proposed that genes that are up-regulated post induction could be part of the signaling pathways which activate the CSR. Knocking out some of these genes which were non-essential and belonged to the bottom of the E. coli regulatory network had provided higher expression of GFP and L-asparaginase.

Results
We chose the best performing double knockout E. coli BW25113ΔelaAΔcysW and demonstrated its ability to enhance the expression of the toxic Rubella E1 glycoprotein by 2.5-fold by tagging it with sfGFP at the C-terminal end to better quantify expression levels. Transcriptomic analysis of this hyper-expressing mutant showed that a significantly lower proportion of genes got down-regulated post induction, which included genes for transcription, translation, protein folding and sorting, ribosome biogenesis, carbon metabolism, amino acid and ATP synthesis. This down-regulation which is a typical feature of the CSR was clearly blocked in the double knockout strain leading to its enhanced expression capability. Finally, we supplemented the expression of substrate uptake genes glpK and glpD whose down-regulation was not prevented in the double knockout, thus ameliorating almost all the negative effects of the CSR and obtained a further doubling in recombinant protein yields.

Conclusion
The study validated the hypothesis that these up-regulated genes act as signaling messengers which activate the CSR and thus, despite having no casual connection with recombinant protein synthesis, can improve cellular health and protein expression capabilities. Combining gene knockouts with supplementing the expression of key down-regulated genes can counter the harmful effects of CSR and help in the design of a truly superior host platform for recombinant protein expression.
The Gαi protein subclass selectivity to the dopamine D2 receptor is also decided by their location at the cell membrane
Authors: Polit Agnieszka , Rysiewicz Beata , Mystek Paweł , Błasiak Ewa , Dziedzicka-Wasylewska Marta 
Published: December 2020

Abstract
Background
G protein-coupled receptor (GPCR) signaling via heterotrimeric G proteins plays an important role in the cellular regulation of responses to external stimuli. Despite intensive structural research, the mechanism underlying the receptor–G protein coupling of closely related subtypes of Gαi remains unclear. In addition to the structural changes of interacting proteins, the interactions between lipids and proteins seem to be crucial in GPCR-dependent cell signaling due to their functional organization in specific membrane domains. In previous works, we found that Gαs and Gαi3 subunits prefer distinct types of membrane-anchor lipid domains that also modulate the G protein trimer localization. In the present study, we investigated the functional selectivity of dopamine D2 long receptor isoform (D2R) toward the Gαi1, Gαi2, and Gαi3 subunits, and analyzed whether the organization of Gαi heterotrimers at the plasma membrane affects the signal transduction.

Methods
We characterized the lateral diffusion and the receptor–G protein spatial distribution in living cells using two assays: fluorescence recovery after photobleaching microscopy and fluorescence resonance energy transfer detected by fluorescence-lifetime imaging microscopy. Depending on distribution of data differences between Gα subunits were investigated using parametric approach–unpaired T-test or nonparametric–Mann–Whitney U test.

Results
Despite the similarities between the examined subunits, the experiments conducted in the study revealed a significantly faster lateral diffusion of the Gαi2 subunit and the singular distribution of the Gαi1 subunit in the plasma membrane. The cell membrane partitioning of distinct Gαi heterotrimers with dopamine receptor correlated very well with the efficiency of D2R-mediated inhibition the formation of cAMP.

Conclusions
This study showed that even closely related subunits of Gαi differ in their membrane-trafficking properties that impact on their signaling. The interactions between lipids and proteins seem to be crucial in GPCR-dependent cell signaling due to their functional organization in specific membrane domains, and should therefore be taken into account as one of the selectivity determinants of G protein coupling.
Circular RNA expression profiles and features in NAFLD mice: a study using RNA-seq data
Authors: Yuan Xinlu , Diao Jianjun , Du Anqing , Wen Song , Zhou Ligang , Pan Yangbin 
Published: December 2020

Abstract
Background
Nonalcoholic fatty liver disease (NAFLD) is primarily characterized by the hepatic cholesterol accumulation. Circular RNA (circRNA), one of noncoding RNA, involves in many liver diseases progression. However, no recent studies on circRNA expression profiles in NAFLD have been reported previously.

Methods
A NAFLD mouse model was constructed by providing high-fat diet (HFD) for 32 weeks. The circRNAs expression profile in normal mice and NAFLD mice were determined using high-output RNA sequencing method and bioinformatics methods, while the differentially expressed circRNAs were confirmed using Sanger sequencing and qRT-PCR. The circRNA-miRNA network was also predicted. The biological functions of circRNAs were annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG).

Results
The results demonstrated the successful construction of NAFLD mice model by immunohistology and serology assay. In total, 93 dysregulated circRNAs were observed, including 57 upregulated circRNAs and 36 downregulated circRNAs, in the NAFLD group. The circRNA-miRNA network revealed the complex interaction between circRNAs and its potential miRNA targets in NAFLD. The characteristic of tissue-specific expression in circRNA was demonstrated. The differentially expressed circRNAs with important biological function were also annotated using GO and KEGG. Both DDAH1 and VAV3 genes were found to be associated with the NAFLD development.

Conclusions
Taken together, this study demonstrated the circRNAs expression profile and features in NAFLD, which may provide potential biological markers for the pathogenesis of NAFLD.
A systematic literature review and meta-analysis of characterization of canine parvoviruses 2 prevalent in mainland China
Authors: Dong Bo , Zhang Gaoqiang , Zhang Jiajia , Bai Junyu , Lin Weiming 
Published: December 2020

Abstract
Background
Canine parvovirus 2 (CPV-2) is a pathogenic virus that infects dogs, causing a highly infectious disease. Monitoring CPV-2 spread is an important part of prevention; however, the prevalence and epidemiological characteristics of CPV-2 have not been systematically evaluated and analyzed in mainland China. Therefore, a systematic review and meta-analysis were performed to assess prevalence and epidemiological characteristics of CPV-2 in domestic dogs in mainland China.

Methods
In this study, Chinese and English literature on CPV-2 epidemiology published between January 2006 and December 2019 was evaluated. Regarding meta-analysis, the random-effect model was employed by forest plot with 95% of confidence interval. The number of CPV-2 infections was identified and the pooled prevalence of infection, as well as the epidemiological characteristics, was calculated using meta-analysis.

Results
A total of 39 studies (data from 137,844 dogs) met the evaluation criteria and were used in our study. The pooled prevalence of CPV-2 infection in mainland China was 36%. CPV-2 infection were associated with age, breed, sampling season and immunization status, but not with gender, publication time and diagnostic methods.

Conclusions
Our results indicated that CPV-2 is prevalent among dogs in China. It is therefore necessary to carry out continuous surveillance and epidemiological studies of CPV-2. In addition, accordingly, effective measures should be taken to prevent the transmission and spread of CPV-2 among the Chinese dog population.