bluuebunny/crossref_metadata_2025 huggingface dataset:
A Framework for Understanding the Nature of Questions Asked by Audience Participants at Science Cafés
Authors: Nesseth Nina M. , Henson Amy M. , Barriault Chantal L.
Published: October 2021

Science Cafés are events designed as public engagement tools that create the opportunity for open dialogue between members of the general public and experts on the issue being discussed at the event. This study explores the nature of questions being asked by audience participants during discussion sessions of Science Café events. It was conducted by coding audio recordings of audience participant engagements at 41 Science Café events held between 2010 and 2019. The result of this analysis produced a novel taxonomic framework to describe audience participant behaviors in terms of their learning goals. This framework was evaluated by applying it to samples of Science Café question data selected by Science Café topic theme. Comparisons between question-asking behaviors for specific Science Café topics and overall trends in question-asking behaviors for all Science Cafés revealed significant changes in audience participant learning goals when asking questions at Science Cafés centered on different topic types. Implications for understanding Science Café audiences and potential developments for Science Café events as public science engagement tools are discussed.
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

Background

The 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 Findings

The 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.

Conclusions

Although 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.
Endotoxins and Non-Alcoholic Fatty Liver Disease
Authors: Kessoku Takaomi , Kobayashi Takashi , Imajo Kento , Tanaka Kosuke , Yamamoto Atsushi , Takahashi Kota , Kasai Yuki , Ozaki Anna , Iwaki Michihiro , Nogami Asako , Honda Yasushi , Ogawa Yuji , Kato Shingo , Higurashi Takuma , Hosono Kunihiro , Yoneda Masato , Okamoto Takayuki , Usuda Haruki , Wada Koichiro , Kobayashi Noritoshi , Saito Satoru , Nakajima Atsushi
Published: October 2021

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. It occurs with a prevalence of up to 25%, of which 10–20% cases progress to nonalcoholic steatohepatitis (NASH), cirrhosis, and liver cancer. The histopathology of NASH is characterized by neutrophilic infiltration, and endotoxins from gram-negative rods have been postulated as a contributing factor. Elevations in endotoxin levels in the blood can be classified as intestinal and hepatic factors. In recent years, leaky gut syndrome, which is characterized by impaired intestinal barrier function, has become a significant issue. A leaky gut may prompt intestinal bacteria dysbiosis and increase the amount of endotoxin that enters the liver from the portal vein. These contribute to persistent chronic inflammation and progressive liver damage. In addition, hepatic factors suggest that liver damage can be induced by low-dose endotoxins, which does not occur in healthy individuals. In particular, increased expression of CD14, an endotoxin co-receptor in the liver, may result in leptin-induced endotoxin hyper-responsiveness in obese individuals. Thus, elevated blood endotoxin levels contribute to the progression of NASH. The current therapeutic targets for NASH treat steatosis and liver inflammation and fibrosis. While many clinical trials are underway, no studies have been performed on therapeutic agents that target the intestinal barrier. Recently, a randomized placebo-controlled trial examined the role of the intestinal barrier in patients with NAFLD. To our knowledge, this study was the first of its kind and study suggested that the intestinal barrier may be a novel target in the future treatment of NAFLD.
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

Objective

To characterize the incidence, type, and risk factors of severe infections (SI) in patients with autoimmune kidney diseases treated with rituximab (RTX).

Methods

We 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.

Results

A 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.

Conclusions

After 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.
Maximizing the Utility of Transcriptomics Data in Inflammatory Skin Diseases
Authors: Wu Jingni , Fang Zhixiao , Liu Teng , Hu Wei , Wu Yangjun , Li Shengli
Published: October 2021

Inflammatory skin diseases are induced by disorders of the host defense system of the skin, which is composed of a barrier, innate and acquired immunity, as well as the cutaneous microbiome. These disorders are characterized by recurrent cutaneous lesions and intense itch, which seriously affecting life quality of people across all ages and ethnicities. To elucidate molecular factors for typical inflammatory skin diseases (such as psoriasis and atopic dermatitis), transcriptomic profiling assays have been largely performed. Additionally, single-cell RNA sequencing (scRNA-seq) as well as spatial transcriptomic profiling have revealed multiple potential translational targets and offered guides to improve diagnosis and treatment strategies for inflammatory skin diseases. High-throughput transcriptomics data has shown unprecedented power to disclose the complex pathophysiology of inflammatory skin diseases. Here, we will summarize discoveries from transcriptomics data and discuss how to maximize the transcriptomics data to propel the development of diagnostic biomarkers and therapeutic targets in inflammatory skin diseases.
Sea-Surface Slicks and Their Effect on the Concentration of Plastics and Zooplankton in the Coastal Waters of Rapa Nui (Easter Island)
Authors: Gallardo Camila , Ory Nicolas C. , Gallardo María de los Ángeles , Ramos Marcel , Bravo Luis , Thiel Martin
Published: October 2021

The abundance and distribution of plastic debris at the sea surface shows considerable variability over different spatial scales. Some of the oceanographic processes at small (<1 km) and submeso (1–10 km) scales manifest themselves as slicks at the sea surface, which might have the potential to concentrate organisms and particles (such as positively buoyant plastics), putting species that feed in these areas at risk of ingesting plastics. Slicks can be filaments, lines, meanders, or patches, which are lighter in color and smoother in surface roughness compared to the surrounding area. Here we tested the hypothesis that passive particles (including plastics) and organisms are aggregated in the surface waters within these slicks. According to their main features (orientation to coast and/or wind), the studied slicks were most likely generated by oceanographic processes such as topographically controlled fronts, other types of fronts and internal waves. Neuston samples were collected from the sea surface inside and outside of slicks (n= 11 sites with slicks) in the coastal waters of Rapa Nui (Easter Island) during two campaigns in austral summer (January 2018) and autumn (April 2019). In general, passive particles, including plastics, exuviae, eggs and foraminiferans, were found more frequently inside than outside the slicks. In some cases, motile zooplankton organisms such as chaetognaths, vertically migrating crustaceans and early developmental stages (EDS) of fish were also more common within the slicks. In addition, a positive relationship was found between plastics and planktonic organisms such as foraminiferans, snails and jellyfish (e.g.,Velella velella), although a strong correlation was also found with fish EDS and chaetognaths. These results suggest that surface slicks are areas of aggregation for both passive particles and active organisms, thus playing an important ecological role in food retention and particle concentration where the risk of plastic ingestion by fish and seabirds is enhanced.
Gene Sets and Mechanisms of Sulfate-Reducing Bacteria Biofilm Formation and Quorum Sensing With Impact on Corrosion
Authors: Tripathi Abhilash Kumar , Thakur Payal , Saxena Priya , Rauniyar Shailabh , Gopalakrishnan Vinoj , Singh Ram Nageena , Gadhamshetty Venkataramana , Gnimpieba Etienne Z. , Jasthi Bharat K. , Sani Rajesh Kumar
Published: October 2021

Sulfate-reducing bacteria (SRB) have a unique ability to respire under anaerobic conditions using sulfate as a terminal electron acceptor, reducing it to hydrogen sulfide. SRB thrives in many natural environments (freshwater sediments and salty marshes), deep subsurface environments (oil wells and hydrothermal vents), and processing facilities in an industrial setting. Owing to their ability to alter the physicochemical properties of underlying metals, SRB can induce fouling, corrosion, and pipeline clogging challenges. Indigenous SRB causes oil souring and associated product loss and, subsequently, the abandonment of impacted oil wells. The sessile cells in biofilms are 1,000 times more resistant to biocides and induce 100-fold greater corrosion than their planktonic counterparts. To effectively combat the challenges posed by SRB, it is essential to understand their molecular mechanisms of biofilm formation and corrosion. Here, we examine the critical genes involved in biofilm formation and microbiologically influenced corrosion and categorize them into various functional categories. The current effort also discusses chemical and biological methods for controlling the SRB biofilms. Finally, we highlight the importance of surface engineering approaches for controlling biofilm formation on underlying metal surfaces.
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.
Cortical Thickness Differences Are Associated With Chemical Synaptic Transmission Upregulated Genes in Degeneration of Mild Cognitive Impairment
Authors: Cai Suping , Huang Kexin , Yang Fan , Wang Xuwen , Wu Sijia , Wang Yubo , Huang Liyu
Published: October 2021

Mild cognitive impairment (MCI) is a transition between normal cognition (NC) and Alzheimer’s disease (AD). Differences in cortical thickness (ΔCT) have been reported in cases that degenerate from MCI to AD. The aspects of genetic and transcriptional variation related to ΔCT are vague. In this study, using an 8-year longitudinal follow-up outcome, we investigated the genetic correlates of ΔCT in MCI subjects with degeneration from MCI to AD (MCI_AD). We employed partial least squares regression (PLSR) on brain T1-weighted magnetic resonance imaging (MRI) images of 180 participants [143 stable MCI (MCI_S) participants and 37 MCI_AD participants] and brain gene expression data from the Allen Institute for Brain Science (AIBS) database to investigate genes associated with ΔCT. We found that upregulated PLS component 1 ΔCT-related genes were enriched in chemical synaptic transmission. To verify the robustness and specificity of the results, we conducted PLSR analysis invalidation and specificity datasets and performed weighted gene co-expression network analysis instead of PLSR for the above three datasets. We also used gene expression data in the brain prefrontal cortex from the Gene Expression Omnibus (GEO) database to indirectly validate the robustness and specificity of our results. We conclude that transcriptionally upregulated genes involved in chemical synaptic transmission are strongly related to global ΔCT in MCI patients who experience degeneration from MCI to AD.
Measuring Anxiety-Like Behaviors in Rodent Models of Traumatic Brain Injury
Authors: Tucker Laura B. , McCabe Joseph T.
Published: October 2021

Anxiety is a common complaint following acquired traumatic brain injury (TBI). However, the measurement of dysfunctional anxiety behavioral states following experimental TBI in rodents is complex. Some studies report increased anxiety after TBI, whereas others find a decreased anxiety-like state, often described as increased risk-taking behavior or impulsivity. These inconsistencies may reflect a lack of standardization of experimental injury models or of behavioral testing techniques. Here, we review the most commonly employed unconditioned tests of anxiety and discuss them in a context of experimental TBI. Special attention is given to the effects of repeated testing, and consideration of potential sensory and motor confounds in injured rodents. The use of multiple tests and alternative data analysis methods are discussed, as well as the potential for the application of common data elements (CDEs) as a means of providing a format for documentation of experimental details and procedures of each published research report. CDEs may improve the rigor, reproducibility, as well as endpoint for better relating findings with clinical TBI phenotypes and the final goal of translation. While this may not resolve all incongruities in findings across laboratories, it is seen as a way forward for standardized and universal data collection for improvement of data quality and sharing, and advance therapies for neuropsychiatric symptoms that often present for decades following TBI.
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 < 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.
Neural Circuits for Social Interactions: From Microcircuits to Input-Output Circuits
Authors: Xu Sen , Jiang Ming , Liu Xia , Sun Yahan , Yang Liang , Yang Qinghu , Bai Zhantao
Published: October 2021

Social behaviors entail responses to social information and requires the perception and integration of social cues through a complex cognition process that involves attention, memory, motivation, and emotion. Neurobiological and molecular mechanisms underlying social behavior are highly conserved across species, and inter- and intra-specific variability observed in social behavior can be explained to large extent by differential activity of a conserved neural network. However, neural microcircuits and precise networks involved in social behavior remain mysterious. In this review, we summarize the microcircuits and input-output circuits on the molecular, cellular, and network levels of different social interactions, such as social exploration, social hierarchy, social memory, and social preference. This review provides a broad view of how multiple microcircuits and input-output circuits converge on the medial prefrontal cortex, hippocampus, and amygdala to regulate complex social behaviors, as well as a potential novel view for better control over pathological development.
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 <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.
Tracking-Based Interactive Assessment of Saccades, Pursuits, Visual Field, and Contrast Sensitivity in Children With Brain Injury
Authors: Mooney Scott W. J. , Alam Nazia M. , Prusky Glen T.
Published: October 2021

Visual deficits in children that result from brain injury, including cerebral/cortical visual impairment (CVI), are difficult to assess through conventional methods due to their frequent co-occurrence with cognitive and communicative disabilities. Such impairments hence often go undiagnosed or are only determined through subjective evaluations of gaze-based reactions to different forms, colors, and movements, which limits any potential for remediation. Here, we describe a novel approach to grading visual health based on eye movements and evidence from gaze-based tracking behaviors. Our approach—the “Visual Ladder”—reduces reliance on the user’s ability to attend and communicate. The Visual Ladder produces metrics that quantify spontaneous saccades and pursuits, assess visual field responsiveness, and grade spatial visual function from tracking responses to moving stimuli. We used the Ladder to assess fourteen hospitalized children aged 3 to 18 years with a diverse range of visual impairments and causes of brain injury. Four children were excluded from analysis due to incompatibility with the eye tracker (e.g., due to severe strabismus). The remaining ten children—including five non-verbal children—were tested multiple times over periods ranging from 2 weeks to 9 months, and all produced interpretable outcomes on at least three of the five visual tasks. The results suggest that our assessment tasks are viable in non-communicative children, provided their eyes can be tracked, and hence are promising tools for use in a larger clinical study. We highlight and discuss informative outcomes exhibited by each child, including directional biases in eye movements, pathological nystagmus, visual field asymmetries, and contrast sensitivity deficits. Our findings indicate that these methodologies will enable the rapid, objective classification and grading of visual impairments in children with CVI, including non-verbal children who are currently precluded from most vision assessments. This would provide a much-needed differential diagnostic and prognostic tool for CVI and other impairments of the visual system, both ocular and cerebral.
Comparative Efficacy and Safety of Dopamine Agonists in Advanced Parkinson's Disease With Motor Fluctuations: A Systematic Review and Network Meta-Analysis of Double-Blind Randomized Controlled Trials
Authors: Ruan Xinglin , Lin Fabin , Wu Dihang , Chen Lina , Weng Huidan , Yu Jiao , Wang Yingqing , Chen Ying , Chen Xiaochun , Ye Qinyong , Meng Fangang , Cai Guoen
Published: October 2021

Background: Movement fluctuations are the main complication of Parkinson's disease (PD) patients receiving long-term levodopa (L-dopa) treatment. We compared and ranked the efficacy and safety of dopamine agonists (DAs) with regard to motor fluctuations by using a Bayesian network meta-analysis (NMA) to quantify information from randomized controlled trials (RCTs).

Methods and Findings: We carried out a systematic review and meta-analysis, and only RCTs comparing DAs for advanced PD were included. Electronic databases (PubMed, Embase, and Cochrane Library) were systematically searched for relevant studies published until January 2021. Two reviewers independently extracted individual study data and evaluated studies for risk of bias using the Cochrane Risk of Bias tool. Network meta-analyses using a Bayesian framework were used to calculate the related parameters. The pre-specified primary and secondary outcomes were efficacy (“ON” time without troublesome dyskinesia, “OFF” time, “ON” time, “UPDRS-III,” and “UPDRS-II”) and safety [treatment-emergent adverse events (TEAE) and other adverse events] of DAs. The results are presented as the surface under the cumulative ranking (SUCRA) curve. A total of 20 RCTs assessing 6,560 patients were included. The general DA effects were ranked from high to low with respect to the amount of “ON” time without troublesome dyskinesia as follows: apomorphine (SUCRA = 97.08%), pramipexole_IR (probability = 79.00%), and ropinirole_PR (SUCRA = 63.92%). The general safety of DAs was ranked from high to low with respect to TEAE as follows: placebo (SUCRA = 74.49%), pramipexole_ER (SUCRA = 63.6%), sumanirole (SUCRA = 54.07%), and rotigotine (SUCRA = 53.84%).

Conclusions: This network meta-analysis shows that apomorphine increased “ON” time without troublesome dyskinesia and decreased “OF” time for advanced PD patients. The addition of pramipexole, ropinirole, or rotigotine to levodopa treatment in advanced PD patients with motor fluctuations increased “ON” time without troublesome dyskinesia, improved the UPDRS III scores, and ultimately ameliorated the UPDRS II scores, thereby maximizing its benefit. This NMA of pramipexole, ropinirole, and rotigotine represents an effective treatment option and has an acceptable safety profile in patients with advanced PD.
Changes in the Gut Microbiome and Predicted Functional Metabolic Effects in an Australian Parkinson’s Disease Cohort
Authors: Kenna Jade E. , Chua Eng Guan , Bakeberg Megan , Tay Alfred , McGregor Sarah , Gorecki Anastazja , Horne Malcolm , Marshall Barry , Mastaglia Frank L. , Anderton Ryan S.
Published: October 2021

Background: There has been increasing recognition of the importance of the gut microbiome in Parkinson’s disease (PD), but the influence of geographic location has received little attention. The present study characterized the gut microbiota and associated changes in host metabolic pathways in an Australian cohort of people with PD (PwP).

Methods: The study involved recruitment and assessment of 87 PwP from multiple Movement Disorders Clinics in Australia and 47 healthy controls. Illumina sequencing of the V3 and V4 regions of the 16S rRNA gene was used to distinguish inter-cohort differences in gut microbiota; KEGG analysis was subsequently performed to predict functional changes in host metabolic pathways.

Results: The current findings identified significant differences in relative abundance and diversity of microbial operational taxonomic units (OTUs), and specific bacterial taxa between PwP and control groups. Alpha diversity was significantly reduced in PwP when compared to controls. Differences were found in two phyla (Synergistetes and Proteobacteria; both increased in PwP), and five genera (Colidextribacter, Intestinibacter, Kineothrix, Agathobaculum, and Roseburia; all decreased in PwP). Within the PD cohort, there was no association identified between microbial composition and gender, constipation or use of gastrointestinal medication. Furthermore, KEGG analysis identified 15 upregulated and 11 downregulated metabolic pathways which were predicted to be significantly altered in PwP.

Conclusion: This study provides the first comprehensive characterization of the gut microbiome and predicted functional metabolic effects in a southern hemisphere PD population, further exploring the possible mechanisms whereby the gut microbiota may exert their influence on this disease, and providing evidence for the incorporation of such data in future individualized therapeutic strategies.
Pre-diagnosis Dairy Product Intake and Ovarian Cancer Mortality: Results From the Ovarian Cancer Follow-Up Study (OOPS)
Authors: Jiang Luo , Gong Ting-Ting , Gao Song , Li Xiu-Qin , Liu Fang-Hua , Wen Zhao-Yan , Wei Yi-Fan , Yan Shi , Hou Rui , Wu Qi-Jun
Published: October 2021

Background: Dairy product consumption is associated with ovarian cancer (OC) incidence. However, limited evidence is available on its influence on OC mortality.

Methods: The association between pre-diagnostic dairy product intake and OC mortality was investigated in the OC follow-up study, which included a hospital-based cohort (n = 853) of women diagnosed with epithelial OC between 2015 and 2020. Pre-diagnosis diet information was collected using a validated food frequency questionnaire. Deaths were ascertained up to March 31, 2021 via death registry linkage. Cox proportional hazards model was used to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI) for the aforementioned association.

Results: A total of 130 women died during the median follow-up of 37.2 months (interquartile: 24.7–50.2 months). Comparisons of highest to lowest tertile intake showed that pre-diagnosis dairy product use was associated with total OC mortality (HR = 2.03, 95% CI = 1.21–3.40, p trend = 0.06). In addition, short survival was separately associated with protein (HR = 2.09, 95% CI = 1.25–3.49, p trend < 0.05), fat (HR = 2.16, 95% CI = 1.30–3.61, p trend < 0.05), and calcium (HR = 2.03, 95% CI = 1.21–3.4, p trend = 0.06) from dairy intake. Similar positive magnitudes were observed for menopausal status, residual lesions, histological type, and body mass index, although not all of these factors showed statistical significance.

Conclusion: Pre-diagnosis dairy product consumption, including protein, fat, and calcium from dairy intake, was associated with higher mortality among OC survivors.
Development and Application of Patient-Derived Cancer Organoidsin Clinical Management of Gastrointestinal Cancer: A State-of-the-Art Review
Authors: Zhang Ruobing , Guo Tiantian , Ji Lulin , Yin Yirui , Feng Shuitu , Lu Weihong , Zhang Fei , Zhu Maoshu , Liu Shugang , Jiang Jinhua , Zeng Fanwei
Published: October 2021

Human gastrointestinal cancer (e.g., gastric cancer and colorectal cancer) has been a leading cause of cancer-related deaths worldwide and has imposed a great threat to the public health. Although early-stage gastrointestinal cancer can be effectively treated by surgery, followed by postoperative chemotherapy, patients with advanced gastrointestinal cancer often exhibit poor prognosis and cancer relapse due to the absence of effective personalized treatment strategies. Patient-derived cancer organoid technology has been rapidly developed in recent years, and its emergence has opened up an unprecedented approach to model human cancers in vitro. Patient-derived cancer organoids involve the ex vivo culture of fragments of freshly resected human tumors that retain the histological features of original tumors. This review thoroughly discussed the evolutionary process of human gastrointestinal organoids cultured since 2009, and highlighted the potentials of patient-derived cancer organoids in clinical management of gastrointestinal cancer in terms of advances achieved in cancer modelling compared with conventional modelling methods, high-throughput drug screening, and development of personalized treatment selection. Additionally, the current limitations of patient-derived cancer organoids and the potential solutions to overcome these problems were summarized.
TERT Alterations Predict Tumor Progression in De Novo High-Grade Meningiomas Following Adjuvant Radiotherapy
Authors: Deng Jiaojiao , Sun Shuchen , Chen Jiawei , Wang Daijun , Cheng Haixia , Chen Hong , Xie Qing , Hua Lingyang , Gong Ye
Published: October 2021

Background

Adjuvant radiotherapy (RT) is one of the most commonly used treatments for de novo high-grade meningiomas (HGMs) after surgery, but genetic determinants of clinical benefit are poorly characterized.

Objective

We describe efforts to integrate clinical genomics to discover predictive biomarkers that would inform adjuvant treatment decisions in de novo HGMs.

Methods

We undertook a retrospective analysis of 37 patients with de novo HGMs following RT. Clinical hybrid capture-based sequencing assay covering 184 genes was performed in all cases. Associations between tumor clinical/genomic characteristics and RT response were assessed. Overall survival (OS) and progression-free survival (PFS) curves were plotted using the Kaplan–Meier method.

Results

Among the 172 HGMs from a single institution, 42 cases (37 WHO grade 2 meningiomas and five WHO grade 3 meningiomas) were identified as de novo HGMs following RT. Only TERT mutations [62.5% C228T; 25% C250T; 12.5% copy number amplification (CN amp.)] were significantly associated with tumor progression after postoperative RT (adjusted p = 0.003). Potential different somatic interactions between TERT and other tested genes were not identified. Furthermore, TERT alterations (TERT-alt) were the predictor of tumor progression (Fisher’s exact tests, p = 0.003) and were associated with decreased PFS (log-rank test, p = 0.0114) in de novo HGMs after RT.

Conclusion

Our findings suggest that TERT-alt is associated with tumor progression and poor outcome of newly diagnosed HGM patients after postoperative RT.