bluuebunny/crossref_metadata_2025_split huggingface dataset:
New Species of Macroalgae from Tamengo Formation, Ediacaran, Brazil
Authors: Diniz Cleber Q. C. , Leme Juliana de Moraes , Boggiani Paulo C. 
Published: October 2021

The Tamengo Formation (Corumbá Group) is an important Ediacaran stratigraphic unit in South America due to the presence of metazoan fossils and geochemistry data of carbonate rocks, with excellent geochronological delimitation (between 555–541 Ma) obtained by U–Pb dating on volcanic zircons. The present work shows three new species of macroalgae found as carbonaceous compressions and studied for their morphology and taxonomy. All new taxa are characterized as centric macroalgae; Tamengophyton espinosa sp. nov. is a fan-shaped alga with striated thalli, dichotomous branches, trichomes with perpendicular growth, and a connecting membrane. Ladariella hidria sp. nov. is formed by a set of striated and branched thalli in a cylindrical form with almond-shaped structures in the top. Ladariophyton veinosa sp. nov. is characterized by the main growth thallus and an enlarged longitudinal structure at the center. These new occurrences of macroalgae add to the largest life assemblages in the Neoproterozoic of South America, which contributes to documentation of the evolutionary history of macroalgae and the paleoecological settings of the Late Ediacaran.
Bayesian Age-Period-Cohort Prediction of Mortality of Type 2 Diabetic Kidney Disease in China: A Modeling Study
Authors: Wu Xiaoming , Du Jianqiang , Li Linchang , Cao Wangnan , Sun Shengzhi 
Published: October 2021

BackgroundThe burden of type 2 diabetic kidney disease (DKD) continues to rise in China. We analyzed time trends in DKD mortality and associations with age, period, and birth cohort from 1990 to 2019, made projections up to 2030, and examined the drivers of deaths from DKD.Methods and FindingsThe number of DKD deaths in China from 1990 to 2019 was obtained from the GBD 2019. We used age-period-cohort modeling to estimate age, period, and cohort effects in DKD mortality between 1990 and 2019. We calculated net drift (overall annual percentage change), local drift (annual percentage change in each age group), longitudinal age curves (expected longitudinal age-specific rates), period, and cohort relative risks. We used Bayesian age-period-cohort analysis with integrated nested Laplace approximations to project future age-specific DKD death cases from 2020 to 2030. We used a validated decomposition algorithm to attribute changes in DKD deaths to population growth, population aging, and epidemiologic changes from 1990 to 2030. From 1990 to 2019, the age-standardized mortality rate of DKD in China was relatively stable, but the absolute number of DKD deaths showed a noticeable increasing trend. The overall annual percentage change (net drift) was -0.75% (95% confidence interval, CI: -0.93 to -0.57) for males and -1.90% (95% CI, -2.19 to -1.62) for females. The age-specific annual percentage changes (local drifts) were below zero in all age groups from 1990 to 2019 except for males aged above 65 to 69 years, and for females aged above 70 to 74 years. The risk of DKD deaths increased exponentially with age for both sexes after controlling for period deviations. The Bayesian age-period-cohort analysis projects that there would be 88,803 deaths from DKD in 2030, increased by 224.2% from 1990. Despite a decrease in age-specific DKD death rates, the reduction would be entirely offset by population aging.ConclusionsAlthough China has made progress in reducing DKD deaths, demographic changes have entirely offset the progress. The burden of DKD deaths is likely to continue increasing. Our findings suggest that large-scale screening is imperative for DKD control and prevention, particularly for high-risk groups.
A Novel Model Based on Genomic Instability-Associated Long Non-Coding RNAs for Predicting Prognosis and Response to Immunotherapy in Patients With Lung Adenocarcinoma
Authors: Tu Guangxu , Peng Weilin , Cai Qidong , Zhao Zhenyu , Peng Xiong , He Boxue , Zhang Pengfei , Shi Shuai , Wang Xiang 
Published: October 2021

Background: Emerging scientific evidence has shown that long non-coding RNAs (lncRNAs) exert critical roles in genomic instability (GI), which is considered a hallmark of cancer. To date, the prognostic value of GI-associated lncRNAs (GI-lncRNAs) remains largely unexplored in lung adenocarcinoma (LUAC). The aims of this study were to identify GI-lncRNAs associated with the survival of LUAC patients, and to develop a novel GI-lncRNA-based prognostic model (GI-lncRNA model) for LUAC.Methods: Clinicopathological data of LUAC patients, and their expression profiles of lncRNAs and somatic mutations were obtained from The Cancer Genome Atlas database. Pearson correlation analysis was conducted to identify the co-expressed mRNAs of GI-lncRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted to determine the main biological function and molecular pathways of the differentially expressed GI-lncRNAs. Univariate and multivariate Cox proportional hazard regression analyses were performed to identify GI-lncRNAs significantly related to overall survival (OS) for construction of the GI-lncRNA model. Kaplan–Meier survival analysis and receiver operating characteristic curve analysis were performed to evaluate the predictive accuracy. The performance of the newly developed GI-lncRNA model was compared with the recently published lncRNA-based prognostic index models.Results: A total of 19 GI-lncRNAs were found to be significantly associated with OS, of which 9 were identified by multivariate analysis to construct the GI-lncRNA model. Notably, the GI-lncRNA model showed a prognostic value independent of key clinical characteristics. Further performance evaluation indicated that the area under the curve (AUC) of the GI-lncRNA model was 0.771, which was greater than that of the TP53 mutation status and three existing lncRNA-based models in predicting the prognosis of patients with LUAC. In addition, the GI-lncRNA model was highly correlated with programed death ligand 1 (PD-L1) expression and tumor mutational burden in immunotherapy for LUAC.Conclusion: The GI-lncRNA model was established and its performance was found to be superior to existing lncRNA-based models. As such, the GI-lncRNA model holds promise as a more accurate prognostic tool for the prediction of prognosis and response to immunotherapy in patients with LUAC.
Construction of Prognostic Risk Model of 5-Methylcytosine-Related Long Non-Coding RNAs and Evaluation of the Characteristics of Tumor-Infiltrating Immune Cells in Breast Cancer
Authors: Huang Zhidong , Li Junjing , Chen Jialin , Chen Debo 
Published: October 2021

Purpose: The role of 5-methylcytosine-related long non-coding RNAs (m5C-lncRNAs) in breast cancer (BC) remains unclear. Here, we aimed to investigate the prognostic value, gene expression characteristics, and correlation between m5C-lncRNA risk model and tumor immune cell infiltration in BC.Methods: The expression matrix of m5C-lncRNAs in BC was obtained from The Cancer Genome Atlas database, and the lncRNAs were analyzed using differential expression analysis as well as univariate and multivariate Cox regression analysis to eventually obtain BC-specific m5C-lncRNAs. A risk model was developed based on three lncRNAs using multivariate Cox regression and the prognostic value, accuracy, as well as reliability were verified. Gene set enrichment analysis (GSEA) was used to analyze the Kyoto Encyclopedia of Genes and Genomes signaling pathway enrichment of the risk model. CIBERSORT algorithm and correlation analysis were used to explore the characteristics of the BC tumor-infiltrating immune cells. Finally, reverse transcription-quantitative polymerase chain reaction was performed to detect the expression level of three lncRNA in clinical samples.Results: A total of 334 differential m5C-lncRNAs were identified, and three BC-specific m5C-lncRNAs were selected, namely AP005131.2, AL121832.2, and LINC01152. Based on these three lncRNAs, a highly reliable and specific risk model was constructed, which was proven to be closely related to the prognosis of patients with BC. Therefore, a nomogram based on the risk score was built to assist clinical decisions. GSEA revealed that the risk model was significantly enriched in metabolism-related pathways and was associated with tumor immune cell infiltration based on the analysis with the CIBERSORT algorithm.Conclusion: The efficient risk model based on m5C-lncRNAs associated with cancer metabolism and tumor immune cell infiltration could predict the survival prognosis of patients, and AP005131.2, AL121832.2, and LINC01152 could be novel biomarkers and therapeutic targets for BC.
Case Report: Contiguous Xq22.3 Deletion Associated with ATS-ID Syndrome: From Genotype to Further Delineation of the Phenotype
Authors: Smetana Jan , Vallova Vladimira , Wayhelova Marketa , Hladilkova Eva , Filkova Hana , Horinova Vera , Broz Petr , Mikulasova Aneta , Gaillyova Renata , Kuglík Petr 
Published: October 2021

Alport syndrome with intellectual disability (ATS-ID, AMME complex; OMIM #300194) is an X-linked contiguous gene deletion syndrome associated with an Xq22.3 locus mainly characterized by hematuria, renal failure, hearing loss/deafness, neurodevelopmental disorder (NDD), midface retrusion, and elliptocytosis. It is thought that ATS-ID is caused by the loss of function of COL4A5 (ATS) and FACL4 (ACSL4) genes through the interstitial (micro)deletion of chromosomal band Xq22.3. We report detailed phenotypic description and results from genome-wide screening of a Czech family with diagnosis ATS-ID (proband, maternal uncle, and two female carriers). Female carriers showed mild clinical features of microscopic hematuria only, while affected males displayed several novel clinical features associated with ATS-ID. Utilization of whole-exome sequencing discovered the presence of approximately 3 Mb of deletion in the Xq23 area, which affected 19 genes from TSC22D3 to CHRDL1. We compared the clinical phenotype with previously reported three ATS-ID families worldwide and correlated their clinical manifestations with the incidence of genes in both telomeric and centromeric regions of the deleted chromosomal area. In addition to previously described phenotypes associated with aberrations in AMMECR1 and FACL4, we identified two genes, members of tripartite motif family MID2 and subunit of the proteasome PA700/19S complex (PSMD10), respectively, as prime candidate genes responsible for additional clinical features observed in our patients with ATS-ID. Overall, our findings further improve the knowledge about the clinical impact of Xq23 deletions and bring novel information about phenotype/genotype association of this chromosomal aberration.
Bioinformatics Analysis Explores Potential Hub Genes in Nonalcoholic Fatty Liver Disease
Authors: Wu Chutian , Zhou Yun , Wang Min , Dai Guolin , Liu Xiongxiu , Lai Leizhen , Tang Shaohui 
Published: October 2021

Background: Nonalcoholic fatty liver disease (NAFLD) is now recognized as the most prevalent chronic liver disease worldwide. However, the dysregulated gene expression for NAFLD is still poorly understood.Material and methods: We analyzed two public datasets (GSE48452 and GSE89632) to identify differentially expressed genes (DEGs) in NAFLD. Then, we performed a series of bioinformatics analyses to explore potential hub genes in NAFLD.Results: This study included 26 simple steatosis (SS), 34 nonalcoholic steatohepatitis (NASH), and 13 healthy controls (HC). We observed 6 up- and 19 down-regulated genes in SS, and 13 up- and 19 down-regulated genes in NASH compared with HC. Meanwhile, the overlapping pathways between SS and NASH were PI3K-Akt signaling pathway and pathways in cancer. Then, we screened out 10 hub genes by weighted Gene Co-Expression Network Analysis (WGCNA) and protein-protein interaction (PPI) networks. Eventually, we found that CYP7A1/GINS2/PDLIM3 were associated with the prognosis of hepatocellular carcinoma (HCC) in the TCGA database.Conclusion: Although further validation is still needed, we provide useful and novel information to explore the potential candidate genes for NAFLD prognosis and therapeutic options.
The Risk of Severe Infections Following Rituximab Administration in Patients With Autoimmune Kidney Diseases: Austrian ABCDE Registry Analysis
Authors: Odler Balazs , Windpessl Martin , Krall Marcell , Steiner Maria , Riedl Regina , Hebesberger Carina , Ursli Martin , Zitt Emanuel , Lhotta Karl , Antlanger Marlies , Cejka Daniel , Gauckler Philipp , Wiesholzer Martin , Saemann Marcus , Rosenkranz Alexander R. , Eller Kathrin , Kronbichler Andreas 
Published: October 2021

ObjectiveTo characterize the incidence, type, and risk factors of severe infections (SI) in patients with autoimmune kidney diseases treated with rituximab (RTX).MethodsWe conducted a multicenter retrospective cohort study of adult patients with immune-related kidney diseases treated with at least one course of RTX between 2015 and 2019. As a part of the ABCDE Registry, detailed data on RTX application and SI were collected. SI were defined by Common Terminology Criteria for Adverse Events v5.0 as infectious complications grade 3 and above. Patients were dichotomized between “nephrotic” and “nephritic” indications. The primary outcome was the incidence of SI within 12 months after the first RTX application.ResultsA total of 144 patients were included. Twenty-five patients (17.4%) presented with SI, mostly within the first 3 months after RTX administration. Most patients in the nephritic group had ANCA-associated vasculitis, while membranous nephropathy was the leading entity in the nephrotic group. Respiratory infections were the leading SI (n= 10, 40%), followed by urinary tract (n=3, 12%) and gastrointestinal infections (n=2, 8%). On multivariable analysis, body mass index (BMI, 24.6 kg/m2versus 26.9 kg/m2, HR: 0.88; 95%CI: 0.79-0.99; p=0.039) and baseline creatinine (HR: 1.25; 95%CI: 1.04-1.49; p=0.017) were significantly associated with SI. All patients in the nephritic group (n=19; 100%) who experienced a SI received oral glucocorticoid (GC) treatment at the time of infection. Hypogammaglobulinemia was frequent (58.5%) but not associated with SI.ConclusionsAfter RTX administration, impaired kidney function and lower BMI are independent risk factors for SI. Patients with nephritic glomerular diseases having concomitant GC treatment might be at higher risk of developing SI.
The Hepatoprotective Effect of Piperine Against Thioacetamide-Induced Liver Fibrosis in Mice: The Involvement of miR-17 and TGF-β/Smads Pathways
Authors: Abdelhamid Amr M. , Selim Ayman , Zaafan Mai A. 
Published: October 2021

Liver fibrosis is characterized by a series of events including activation of quiescent hepatic stellate cells (HSCs) into proinflammatory, contractile, and fibrogenic myofibroblasts, which is the primary trigger for the fibrogenesis process. HSC activation involves many signaling pathways such as the TGF-β/smads pathway. Specific microRNAs have been identified to play a crucial role in the activation of HSCs via various signaling pathways. Piperine has recently been studied as a promising anti-fibrotic agent against pancreatic fibrosis through altering the TGF-β1/Smad pathway. Hence, the current study evaluated the beneficial effects of piperine in thioacetamide-induced liver fibrosis in mice through the modulation of miRNA-17 and TGF-β/smads pathways. Mice were allocated into three groups randomly. Thioacetamide was used to induce liver fibrosis for 6 weeks. Starting from the fourth week of the experiment, mice were treated with piperine daily for 21 days. Piperine treatment resulted in a significant downregulation of miRNA-17 expression, leading to the restoration of smad-7 accompanied with marked inhibition of TGF-β/smads signaling with further suppression of the activated HSCs and collagen deposition in the hepatocytes. In conclusion, piperine has the potential to be a promising therapeutic drug for the treatment of liver fibrosis through inhibiting the TGF-β/smads pathway.
Changes of Structural and Functional Attention Control Networks in Subclinical Hypothyroidism
Authors: Yin Jingjing , Xie Lei , Luo DongXue , Huang Jinzhuang , Guo Ruiwei , Zheng Yanmin , Xu Wencan , Duan Shouxing , Lin Zhirong , Ma Shuhua 
Published: October 2021

Objective: This study aimed to explore the structural changes in patients with subclinical hypothyroidism (SCH) using voxel-based morphometry (VBM) and to investigate the altered attentional control networks using functional MRI (fMRI) during the performance of a modified Stroop task with Chinese characters.Methods: High-resolution three-dimensional (3D) T1-weighted images and an fMRI scan were taken from 18 patients with SCH and 18 matched control subjects. The Montreal Cognitive Assessment Chinese-revised (MoCA-CR) and the Stroop task were used to evaluate the cognitive and attention control of the participants.Results: Compared to controls, the VBM results showed decreased gray matter volumes (GMVs) in bilateral prefrontal cortices (PFCs, including middle, medial, and inferior frontal gyri), cingulate gyrus, precuneus, left middle temporal gyrus, and insula in patients with SCH. The fMRI results showed a distributed network of brain regions in both groups, consisting of PFCs (including superior and middle and inferior frontal cortices), anterior cingulate cortex (ACC), posterior cingulate cortex, and precuneus, as well as the insula and caudate nucleus. Compared to controls, the SCH group had lower activation of the above brain areas, especially during the color-naming task. In addition, the normalized GMV (nGMV) was negatively correlated with thyroid-stimulating hormone (TSH) level (r = −0.722, p &lt; 0.001).Conclusion: Results indicate that patients with SCH exhibit reduced GMVs, altered BOLD signals, and activation in regions associated with attention control, which further suggest that patients with SCH may have attentional control deficiency, and the weakened PFC–ACC–precuneus brain network might be one of the neural mechanisms. Negative correlations between nGMV and TSH suggest that TSH elevation may induce abnormalities in the cortex.
Treatment of Multiple Sclerosis With Teriflunomide. Multicenter Study of Real Clinical Practice in the Valencian Community-Spain
Authors: Landete Lamberto , Pérez-Miralles Francisco , García Sara , Belenguer Antonio , Gascón Francisco , Domínguez Jose Andres , Carcelén-Gadea María , Quintanilla-Bordás Carlos , Navarro Laura , Gabaldón Laura , Casanova Bonaventura 
Published: October 2021

Introduction:We have different treatment alternatives for relapsing-remitting multiple sclerosis–RRMS–within the so-called platform drugs. It would be desirable to know the ideal drug for each patient. Real clinical practice studies provide us with data on drug efficacy in the medium and long term, safety beyond clinical trials, and can help us to know the patient profile appropriate for each therapy.Material and Methods:An observational multicenter study of real clinical practice in patients with RRMS who were treated with teriflunomide in the Valencian Community, since teriflunomide was authorized in Spain. The database created for this study collects retrospectively patients followed prospectively in the MS clinics.Objectives:To analyze the efficacy and safety of teriflunomide treatment in patients with RRMS under the conditions of real clinical practice, and to identify a patient profile responding to the treatment.Results:We obtained data from 340 patients who received at least one dose of 14 mg teriflunomide. The patients were 69.4% female to 30.6% male, had a mean age of 46.4 years, and a mean time of progression of MS of 11.5 years. The mean pre-teriflunomide relapse rate was 0.4 years, the mean EDSS scorewas 1.98, IgG Oligoclonal bands were present in the CSF of 66.2% of the patients, IgM Oligoclonal bands were present in 46.9%, and the mean number of gadolinium-enhancing lesions was 1.07 lesions per patient at the beginning of treatment. The average number of treatments previously received was 1.04, and 28.53% were naïve. After a follow-up of up to 4 years, a reduction in the annualized and cumulative annualized relapse rate was observed in the first year, in the second year, and in the third year, compared to the pre-treatment year. The EDSS scores were stabilized throughout the follow-up. Likewise, there was a reduction in gadolinium-enhancing lesions in the 1st and 2nd years compared to the pre-treatment period. Applying different generalized multiple linear regression models, we identified a profile of a responding patient to teriflunomide as a male without IgM oligoclonal bands in the CSF, a previous EDSS score of &lt;3, and more than 5 years duration of MS.
A Simple Gain-Based Evaluation of the Video Head Impulse Test Reliably Detects Normal Vestibulo-Ocular Reflex Indicative of Stroke in Patients With Acute Vestibular Syndrome
Authors: Machner Björn , Erber Kira , Choi Jin Hee , Sprenger Andreas , Helmchen Christoph , Trillenberg Peter 
Published: October 2021

Objective: The head impulse test (HIT) assesses the vestibulo-ocular reflex (VOR) and is used to differentiate vestibular neuritis (abnormal VOR) from stroke (normal VOR) in patients presenting with an acute vestibular syndrome (AVS). The video-oculography-based HIT (vHIT) quantifies VOR function and provides information imperceptible for the clinician during clinical bedside HIT. However, the vHIT—like an electrocardiogram—requires experienced interpretation, which is especially difficult in the emergency setting. This calls for a simple, reliable and rater-independent way of analysis.Methods: We retrospectively collected 171 vHITs performed in patients presenting with AVS to our emergency department. Three neuro-otological experts comprehensively assessed the vHITs including interpretability (artifacts), VOR gain (eye/head velocity ratio), velocity profile (abrupt decline) and corrective saccades (overt/covert). Their consensus rating (abnormal/peripheral vs. normal/central) was compared to a simple algorithm that automatically classified the vHITs based on a single VOR gain cutoff (0.7).Results: Inter-rater agreement between experts was high (Fleiss' kappa = 0.74). Five (2.9 %) vHITs were “uninterpretable” according to experts' consensus, 80 (46.8 %) were rated “normal” and 86 (50.3 %) “abnormal”. The algorithm had substantial agreement with the experts' consensus (Cohen's kappa = 0.75). Importantly, it correctly classified all of the normal/central vHITs denoted by the experts (100% specificity) and at the same time it had sufficient sensitivity (75.6%) in detecting abnormal/peripheral vHITs.Conclusion: A simple, automated, gain-based evaluation of the vHIT reliably detects normal/central VOR and may be a feasible and effective tool to screen AVS patients for potentially underlying stroke in the emergency setting.