bluuebunny/crossref_metadata_2025_split huggingface dataset:
D-arginine Enhances the Effect of Alpha-Amylase on Disassembling Actinomyces viscosus Biofilm
Authors: Li Baosheng , Cai Qing , Wang Zixuan , Qiao Shuwei , Ou Yanzhen , Ma Rui , Luo Chuanfu , Meng Weiyan 
Published: March 2022

Peri-implantitis is the leading cause of dental implant failure, initially raised by biofilm accumulation on the implant surface. During the development of biofilm,Actinomyces viscosus(A. viscosus) plays a pivotal role in initial attachment as well as the bacterial coaggregation of multispecies pathogens. Hence, eliminating theA. viscosus-associated biofilm is fundamental for the regeneration of the lost bone around implants. Whereas clinical evidence indicated that antimicrobials and debridement did not show significant effects on the decontamination of biofilm on the implant surface. In this study, alpha-amylase was investigated for its effects on disassemblingA. viscosusbiofilm. Then, in order to substantially disperse biofilm under biosafety concentration, D-arginine was employed to appraise its enhancing effects on alpha-amylase. In addition, molecular dynamics simulations and molecular docking were conducted to elucidate the mechanism of D-arginine enhancing alpha-amylase. 0.1–0.5% alpha-amylase showed significant effects on disassemblingA. viscosusbiofilm, with definite cytotoxicity toward MC3T3-E1 cells meanwhile. Intriguingly, 8 mM D-arginine drastically enhanced the eradication ofA. viscosusbiofilm biomass by 0.01% alpha-amylase with biosafety in 30 min. The exopolysaccharides of biofilm were also thoroughly hydrolyzed by 0.01% alpha-amylase with 8 mM D-arginine. The biofilm thickness and integrity were disrupted, and the exopolysaccharides among the extracellular matrix were elusive. Molecular dynamics simulations showed that with the hydrogen bonding of D-arginine to the catalytic triad and calcium-binding regions of alpha-amylase, the atom fluctuation of the structure was attenuated. The distances between catalytic triad were shortened, and the calcium-binding regions became more stable. Molecular docking scores revealed that D-arginine facilitated the maltotetraose binding process of alpha-amylase. In conclusion, these results demonstrate that D-arginine enhances the disassembly effects of alpha-amylase onA. viscosusbiofilm through potentiating the catalytic triad and stabilizing the calcium-binding regions, thus providing a novel strategy for the decontamination of biofilm contaminated implant surface.
Identification and Development of Inflammatory Response–Related Genes Signature Associated With Prognosis Evaluation and Immune Status of Bladder Cancer
Authors: Zheng Haoxiang , Luo Weihan , Li Yuqing , Peng Guoyu , Zhou Dewang , Tang Dongdong , Cheng Jiwen , Wu Song 
Published: March 2022

Background: Bladder urothelial carcinoma (BLCA) is one of the most common malignant tumors with high morbidity and recurrence rate. The study aims to establish a prediction model to elaborate the relation between inflammatory response and prognosis of BLCA and thus to evaluate the potential prognostic value of inflammatory response–related genes (IRGs) in therapeutic choices.Methods: The study utilized the gene expression profiles from the The Cancer Genome Atlas and Gene Expression Omnibus (GSE32894) datasets. Differentially expressed IRGs between normal and tumor tissues were identified, and 10 of them were correlated with overall survival (OS) (p &lt; 0.05). Then, the LASSO–Cox regression analysis was applied to optimize the signature. RNA sequencing data of patients with BLCA from GSE32894 were applied as a validation set. Cox regression analyses of the seven-gene signature were performed to examine the efficiency of signature in predicting prognosis. Receiver operating characteristic curve analysis was applied to measure the predictive performance of the risk score for OS. Analysis of independent prognostic factors, downstream functional enrichment, drug sensitivity, and immune features were included in this study.Results: The IRG signature (LDLR, ROS1, MMP14, TNFAIP6, MYC, PTGER4, and RIPK2) was used to divide patients into high- and low-risk groups. Cox regression analyses revealed that the risk score was an independent predictive factor. Functional enrichment analysis revealed that genes were enriched in prognosis-related molecular functions and immune-related biological processes. Drug sensitivity and tumor microenvironment correlation analysis indicated that the signature was related to immunotherapy effect.Conclusion: The study defined a new prognostic signature consisting of seven IRGs, which could effectively predict the prognosis of patients with BLCA and reveal relationship of immune features in BLCA with different risk scores. The study also provided a possible indicator for targeted therapy.
Substantial Intestinal Microbiota Differences Between Patients With Ulcerative Colitis From Ghana and Denmark
Authors: Mirsepasi-Lauridsen Hengameh Chloé , Vranckx Katleen , Nielsen Henrik Vedel , Andersen Lee O’Brien , Archampong Timothy , Krogfelt Karen Angeliki , Petersen Andreas Munk 
Published: March 2022

BackgroundUlcerative colitis (UC) is a relapsing nontransmural inflammatory disease that is restricted to the colon and is characterized by flare-ups of bloody diarrhea. In this study, we aimed to investigate intestinal bacterial diversity in healthy controls and patients with UC with and without active disease, from Ghana and Denmark.MethodsThe study included 18 UC patients (9 with active and 9 with inactive disease) and 18 healthy controls from Ghana. In addition 16 UC patients from Denmark (8 UC with active and 8 UC with inactive disease) and 19 healthy controls from Denmark. Microbiota diversity analysis relied on sequencing of ribosomal small subunit genes. Purified genomic DNA was submitted to PCR using a primer set targeting prokaryotes and eukaryotes. The purified DNA was sequenced on the Illumina MiSeq system in a 2 × 250 bp set up (Illumina, San Diego, CA, USA). Blinded analysis of the taxonomy table was performed using BioNumerics-7.5 (Applied Maths NV, Sint-Martens-Latem, Belgium).ResultsWhen analyzing the taxonomy data for prokaryotes, cluster and principal component analysis shows Danish healthy controls clustered together, but separate from healthy controls from Ghana, which also clustered together. The Shannon diversity index (SDI) for prokaryotes shows significant differences between Danish healthy controls and patients in comparison with the corresponding groups from Ghana (p = 0.0056). Significant increased abundance of Escherichia coli was detected in healthy controls from Ghana in comparison with healthy controls from Denmark. The SDI of the prokaryotes ranges between 0 and 3.1 in the Ghana study groups, while in the Danish study groups it ranges between 1.4 and 3.2, the difference is however not significant (p = 0.138). Our data show a significant increased abundance of eukaryotes species in the healthy control group from Ghana and Denmark in comparison with patient groups from Ghana and Denmark.ConclusionOverall, healthy controls and patients with UC from Denmark have increased diversity of prokaryotes. Healthy controls from Denmark and Ghana have increased abundance of eukaryotes in comparison with UC patient groups from Denmark and Ghana.
Role of Contrast-Enhanced Ultrasound in the Evaluation of Patients With Suspected Renal Arterial Stenosis
Authors: Wang Yang , Li Yan , Wang Siyu , Ma Na , Ren Junhong 
Published: March 2022

ObjectivesTo explore the role of Contrast-enhanced ultrasound (CEUS) in the evaluation of patients with suspected renal artery stenosis and analyze the causes of the misdiagnosis and missed diagnosis.MethodsThe data of 40 patients (80 renal arteries) diagnosed with RAS by CEUS in Beijing Hospital from September 2018 to October 2020 were compared with their digital subtraction angiography (DSA) results to analyze the causes underlying missed diagnosis and misdiagnosis of RAS by CEUS.Results1. Compared with the gold standard DSA results, the AUC of the ROC curve of CEUS in detecting normal renal artery and renal artery stenosis was 0.961, the sensitivity was 96.4%, the specificity was 95.8%, and the Kappa value of the consistency analysis was 0.912 (P &lt; 0.01); 2. Compared with the gold standard DSA results, the ROC curve of CEUS in distinguishing renal artery stenosis ≥70% from &lt;70% stenosis has an AUC of 0.916, a sensitivity of 90.9%, a specificity of 92.3%, and the Kappa value of the consistency analysis is 0.77 (P &lt; 0.01); 3. CEUS missed two cases (one for mild stenosis and one for moderate stenosis), and the detection rate of renal artery stenosis was 97.5% (78/80); A total of 65 renal arteries diagnosed by CEUS were consistent with DSA, and the diagnostic accuracy of CEUS for the degree of stenosis was 81.25% (65/80); Among the 13 misdiagnosed renal arteries, 4 of them can be corrected to the same degree as DSA by the reference to hemodynamic index, and the diagnosis rate of the degree of renal artery stenosis by ultrasonography (combined with CEUS and hemodynamic indicators) can be improved to 86.25%.Conclusions1. CEUS can clearly show the renal arteries, and is consistent with DSA in distinguishing normal renal artery stenosis from renal artery stenosis, as well as renal artery stenosis ≥70% and &lt;70% stenosis; 2. CEUS showed good performance in detecting normal renal artery and renal artery stenosis, and the missed diagnosis is concentrated on mild and moderate stenosis; 3. CEUS combined with hemodynamic indicators (Doppler ultrasound) can improve the accurate diagnosis rate of renal artery stenosis by ultrasonography; 4. The most important factor for the accurate diagnosis of renal artery stenosis by CEUS is the operator's standardized examination, which is not only related to the duration of the operator has been engaged in this inspection, but also related to whether the operator has received professional training in relevant aspects. These all indicate the necessity and importance of the standardized operation of renal artery contrast-enhanced ultrasound examination, and professional training should be given to operators.
Influence of Different Segmentations on the Diagnostic Performance of Pericoronary Adipose Tissue
Authors: Wen Didi , An Rui , Lin Shushen , Yang Wangwei , Jia Yuyang , Zheng Minwen 
Published: March 2022

ObjectiveTo investigate the influence of different segmentations on the diagnostic performance of pericoronary adipose tissue (PCAT) CT attenuation and radiomics features for the prediction of ischemic coronary artery stenosis.MethodsFrom June 2016 to December 2018, 108 patients with 135 vessels were retrospectively analyzed in the present study. Vessel-based PCAT was segmented along the 40 mm-long proximal segments of three major epicardial coronary arteries, while lesion-based PCAT was defined around coronary lesions. CT attenuation and radiomics features derived from two segmentations were calculated and extracted. The diagnostic performance of PCAT CT attenuation or radiomics models in predicting ischemic coronary stenosis were also compared between vessel-based and lesion-based segmentations.ResultsThe mean PCAT CT attenuation was −75.7 ± 9.1 HU and −76.1 ± 8.1 HU (p = 0.395) for lesion-based and vessel-based segmentations, respectively. A strong correlation was found between vessel-based and lesion-based PCAT CT attenuation for all cohort and subgroup analyses (all p &lt; 0.01). A good agreement for all cohort and subgroup analyses was also detected between two segmentations. The diagnostic performance was comparable between vessel-based and lesion based PCAT CT attenuation in predicting ischemic stenosis. The radiomics features of PCAT based on vessel or lesion segmentation can both adequately identify the ischemic stenosis. However, no significant difference was detected between the two segmentations.ConclusionsThe quantitative evaluation of PCAT can be reliably measured both from vessel-based and lesion-based segmentation. Furthermore, the radiomics analysis of PCAT may potentially help predict hemodynamically significant coronary artery stenosis.
Neuropsychological Outcomes in Individuals With Type 1 and Type 2 Diabetes
Authors: Putnam Nathaniel M. , Reynolds Evan L. , Banerjee Mousumi , Mizokami-Stout Kara , Albright Dana , Lee Joyce , Pop-Busui Rodica , Feldman Eva L. , Callaghan Brian C. 
Published: March 2022

ObjectiveTo determine the prevalence of neuropsychological outcomes in individuals with type 1 diabetes compared to individuals with type 2 diabetes or without diabetes, and to evaluate the association of diabetes status and microvascular/macrovascular complications with neuropsychological outcomes.Patients and MethodsWe used a nationally representative healthcare claims database of privately insured individuals (1/1/2001-12/31/2018) to identify individuals with type 1 diabetes. Propensity score matching was used as a quasi-randomization technique to match type 1 diabetes individuals to type 2 diabetes individuals and controls. Diabetes status, microvascular/macrovascular complications (retinopathy, neuropathy, nephropathy, stroke, myocardial infarction, peripheral vascular disease, amputations), and neuropsychological outcomes (mental health, cognitive, chronic pain, addiction, sleep disorders) were defined using ICD-9/10 codes. Logistic regression determined associations between diabetes status, microvascular/macrovascular complications, and neuropsychological outcomes.ResultsWe identified 184,765 type 1 diabetes individuals matched to 524,602 type 2 diabetes individuals and 522,768 controls. With the exception of cognitive disorders, type 2 diabetes individuals had the highest prevalence of neuropsychological outcomes, followed by type 1 diabetes, and controls. After adjusting for the presence of microvascular/macrovascular complications, type 1 diabetes was not significantly associated with a higher risk of neuropsychological outcomes; however, type 2 diabetes remained associated with mental health, cognitive, and sleep disorders. The presence of microvascular/macrovascular complications was independently associated with each neuropsychological outcome regardless of diabetes status.ConclusionMicrovascular/macrovascular complications are associated with a high risk of neuropsychological outcomes regardless of diabetes status. Therefore, preventing microvascular and macrovascular complications will likely help reduce the likelihood of neuropsychological outcomes either as the result of similar pathophysiologic processes or by preventing the direct and indirect consequences of these complications. For individuals with type 2 diabetes, risk factors beyond complications (such as obesity) likely contribute to neuropsychological outcomes.
Drivers of Soil Total Nitrogen and Phosphorus Storage in Alpine Wetland Across the Three Rivers Source Region on the Qinghai-Tibetan Plateau
Authors: Nie Xiuqing , Wang Dong , Zhou Guoying , Xiong Feng , Ren Lining , Chen Yongzhe , Ma Kali , Zhong Zebing , Du Yangong 
Published: March 2022

Although soil total nitrogen (STN) and soil total phosphorus (STP) play significant roles in terrestrial ecosystem function, their storage and driving factors in the alpine wetlands of the Qinghai-Tibetan Plateau remain unclear. In this study, we estimated STN and STP storage and their controlling factors, including vegetation, soil, and climate characteristics, using data collected from 50 sites across the wetlands in the Three Rivers Source Region. STN and STP storage in the top 30 cm of soil were 62.12 ± 37.55 Tg N and 9.24 ± 2.90 Tg P, respectively. Although STN density did not differ significantly for different vegetation types (i.e., alpine meadow and alpine wetland), belowground biomass showed a positive relationship with STN density. Mean annual precipitation (MAP) showed a significant positive relationship with STN density, whereas the effects of mean annual temperature on STN density were minor. Compared with the effects of vegetation and climatic factors, soil characteristics were found to not only exert a significant effect on STN density, but also influence the effects of climate and vegetation on STN density. For STP density, soil characteristics were found to be a significant controlling factor, whereas the effects of biomass and climatic factors were minor. The studied climate, soil, and vegetation characteristics jointly explained ∼54% of STN variance, whereas soil characteristics explained only 20% of STP variation. MAP indirectly affected STN density via effects on vegetation and soil, and its direct effect on STN density was minor. This indicated a strong relationship between biotic and abiotic effects and STN density. Identification of the factors influencing STN and STP variance in alpine wetlands contributes to our understanding of the biogeochemical cycle in high-altitude regions.
MAP3K1 Variant Causes Hyperactivation of Wnt4/β-Catenin/FOXL2 Signaling Contributing to 46,XY Disorders/Differences of Sex Development
Authors: Chen Hong , Chen Qingqing , Zhu Yilin , Yuan Ke , Li Huizhu , Zhang Bingtao , Jia Zexiao , Zhou Hui , Fan Mingjie , Qiu Yue , Zhuang Qianqian , Lei Zhaoying , Li Mengyao , Huang Wendong , Liang Li , Yan Qingfeng , Wang Chunlin 
Published: March 2022

Background: 46,XY disorders/differences of sex development (46,XY DSD) are congenital conditions that result from abnormal gonadal development (gonadal dysgenesis) or abnormalities in androgen synthesis or action. During early embryonic development, several genes are involved in regulating the initiation and maintenance of testicular or ovarian-specific pathways. Recent reports have shown that MAP3K1 genes mediate the development of the 46,XY DSD, which present as complete or partial gonadal dysgenesis. Previous functional studies have demonstrated that some MAP3K1 variants result in the gain of protein function. However, data on possible mechanisms of MAP3K1 genes in modulating protein functions remain scant.Methods: This study identified a Han Chinese family with the 46,XY DSD. To assess the history and clinical manifestations for the 46,XY DSD patients, the physical, operational, ultra-sonographical, pathological, and other examinations were performed for family members. Variant analysis was conducted using both trio whole-exome sequencing (trio WES) and Sanger sequencing. On the other hand, we generated transiently transfected testicular teratoma cells (NT2/D1) and ovary-derived granular cells (KGN), with mutant or wild-type MAP3K1 gene. We then performed functional assays such as determination of steady-state levels of gender related factors, protein interaction and luciferase assay system.Results: Two affected siblings were diagnosed with 46,XY DSD. Our analysis showed a missense c.556A &gt; G/p.R186G variant in the MAP3K1 gene. Functional assays demonstrated that the MAP3K1R186G variant was associated with significantly decreased affinity to ubiquitin (Ub; 43–49%) and increased affinity to RhoA, which was 3.19 ± 0.18 fold, compared to MAP3K1. The MAP3K1R186G led to hyperphosphorylation of p38 and GSK3β, and promoted hyperactivation of the Wnt4/β-catenin signaling. In addition, there was increased recruitment of β-catenin into the nucleus, which enhanced the expression of pro-ovarian transcription factor FOXL2 gene, thus contributing to the 46,XY DSD.Conclusion: Our study identified a missense MAP3K1 variant associated with 46,XY DSD. We demonstrated that MAP3K1R186G variant enhances binding to the RhoA and improves its own stability, resulting in the activation of the Wnt4/β-catenin/FOXL2 pathway. Taken together, these findings provide novel insights into the molecular mechanisms of 46,XY DSD and promotes better clinical evaluation.
Comparative Transcriptomic Analysis Reveals the Regulated Expression Profiles in Oreochromis niloticus in Response to Coinfection of Streptococcus agalactiae and Streptococcus iniae
Authors: Cui Miao , Wang Zibin , Yang Yongchun , Liu Ru , Wu Min , Li Yujie , Zhang Qizhong , Xu Delin 
Published: March 2022

Tilapia (Oreochromis sp.) is one of the important economical fishes in the world. Streptococcosis is commonly found in tilapia, causing severe and devastating effects in tilapia cultures. Streptococcus agalactiae and Streptococcus iniae are the predominant pathogens causing tilapia streptococcosis. To understand the molecular mechanisms underlying differential streptococcal infection patterns, Nile tilapias (Oreochromis niloticus) were infected by 1 × 107 CFU/mL S. agalactiae, 1 × 107 CFU/mL S. iniae, and 1 × 107 CFU/mL S. agalactiae and S. iniae (1:1), respectively, and transcriptome analysis was conducted to the intestine samples of Nile tilapia (Oreochromis niloticus) at 6, 12, 24 h, and 7 days post-infection. A total of 6,185 genes that differentially expressed among groups were identified. Eight differentially expressed genes (DEGs) including E3 ubiquitin-protein ligase TRIM39-like, C-X-C motif chemokine 10-like(CXCL 10), C-C motif chemokine 19-like, interleukin-1 beta-like, IgM heavy chain VH region, partial, IgG Fc-binding protein, proteasome subunit beta type-8 (PSMB8), and ATP synthase F(0) complex subunit B1, mitochondrial that involved in the immune system were selected, and their expression levels in the coinfection group were significantly higher than those in either of the single infection groups. These genes were associated with four different KEGG pathways. Additionally, the differential expression of eight DEGs was validated by using the RT-qPCR approach, and their immunological importance was discussed. The results provided insights into the responses of tilapia against S. agalactiae and S. iniae at the transcriptome level, promoting our better understanding of immune responses for aquatic animal against Streptococcus.
Screening of Long Non-coding RNAs Biomarkers for the Diagnosis of Tuberculosis and Preliminary Construction of a Clinical Diagnosis Model
Authors: Chen Juli , Wu Lijuan , Lv Yanghua , Liu Tangyuheng , Guo Weihua , Song Jiajia , Hu Xuejiao , Li Jing 
Published: March 2022

BackgroundPathogenic testing for tuberculosis (TB) is not yet sufficient for early and differential clinical diagnosis; thus, we investigated the potential of screening long non-coding RNAs (lncRNAs) from human hosts and using machine learning (ML) algorithms combined with electronic health record (EHR) metrics to construct a diagnostic model.MethodsA total of 2,759 subjects were included in this study, including 12 in the primary screening cohort [7 TB patients and 5 healthy controls (HCs)] and 2,747 in the selection cohort (798 TB patients, 299 patients with non-TB lung disease, and 1,650 HCs). An Affymetrix HTA2.0 array and qRT-PCR were applied to screen new specific lncRNA markers for TB in individual nucleated cells from host peripheral blood. A ML algorithm was established to combine the patients’ EHR information and lncRNA data via logistic regression models and nomogram visualization to differentiate PTB from suspected patients of the selection cohort.ResultsTwo differentially expressed lncRNAs (TCONS_00001838 and n406498) were identified (p &lt; 0.001) in the selection cohort. The optimal model was the “LncRNA + EHR” model, which included the above two lncRNAs and eight EHR parameters (age, hemoglobin, lymphocyte count, gamma interferon release test, weight loss, night sweats, polymorphic changes, and calcified foci on imaging). The best model was visualized by a nomogram and validated, and the accuracy of the “LncRNA + EHR” model was 0.79 (0.75–0.82), with a sensitivity of 0.81 (0.78–0.86), a specificity of 0.73 (0.64–0.79), and an area under the ROC curve (AUC) of 0.86. Furthermore, the nomogram showed good compliance in predicting the risk of TB and a higher net benefit than the “EHR” model for threshold probabilities of 0.2–1.ConclusionLncRNAs TCONS_00001838 and n406498 have the potential to become new molecular markers for PTB, and the nomogram of “LncRNA + EHR” model is expected to be effective for the early clinical diagnosis of TB.