bluuebunny/crossref_metadata_2025_split huggingface dataset:
Untargeted metabolomics and transcriptomics identified glutathione metabolism disturbance and PCS and TMAO as potential biomarkers for ER stress in lung
Authors: Wang Zijing , Ma Peng , Wang Yisa , Hou Biyu , Zhou Can , Tian He , Li Bowen , Shui Guanghou , Yang Xiuying , Qiang Guifen , Yin Chengqian , Du Guanhua 
Published: July 2021

AbstractEndoplasmic reticulum (ER) stress is a cellular state that results from the overload of unfolded/misfolded protein in the ER that, if not resolved properly, can lead to cell death. Both acute lung infections and chronic lung diseases have been found related to ER stress. Yet no study has been presented integrating metabolomic and transcriptomic data from total lung in interpreting the pathogenic state of ER stress. Total mouse lungs were used to perform LC–MS and RNA sequencing in relevance to ER stress. Untargeted metabolomics revealed 16 metabolites of aberrant levels with statistical significance while transcriptomics revealed 1593 genes abnormally expressed. Enrichment results demonstrated the injury ER stress inflicted upon lung through the alteration of multiple critical pathways involving energy expenditure, signal transduction, and redox homeostasis. Ultimately, we have presented p-cresol sulfate (PCS) and trimethylamine N-oxide (TMAO) as two potential ER stress biomarkers. Glutathione metabolism stood out in both omics as a notably altered pathway that believed to take important roles in maintaining the redox homeostasis in the cells critical for the development and relief of ER stress, in consistence with the existing reports.
Development and validation in 500 female samples of a TP-PCR assay to identify AFF2 GCC expansions
Authors: Silva Cecília , Maia Nuno , Santos Flávia , Rodrigues Bárbara , Marques Isabel , Santos Rosário , Jorge Paula 
Published: July 2021

AbstractOver 100 X-linked intellectual disability genes have been identified, with triplet repeat expansions at the FMR1 (FRAXA) and AFF2 (FRAXE) genes being the causative agent in two of them. The absence of FRAXE pathognomonic features hampers early recognition, delaying testing and molecular confirmation. Hence, our laboratory uses a multiplex PCR-based strategy to genotype both FRAXA and FRAXE. However, AFF2 expansions are missed giving rise to an uninformative result in around 20% of female samples. To rule out undetected expansions and confirm homozygosity Southern blot analysis is performed being labour- and resource-intensive. The aim of this study is to develop a timely and economic triplet-primed amplification (TP-PCR) screening strategy to size the AFF2 GCC repeat and accurately assess homozygosity as well as pinpoint multiplex-PCR false negatives in female samples. In order to achieve this, validation was performed in a cohort of 500 females with a previous uninformative FRAXE PCR result. Interestingly, the presence of a T > C SNP (rs868949662), contiguous to the GCC repetitive tract, allows triplet primer binding in two additional repeats, increasing the discrimination power of the TP-PCR assay in heterozygous and homozygous samples. Twelve alleles outside the normal range were recognized: eight intermediate and four premutated, which seems relevant considering the rarity of the AFF2 expansions. All genotypes are concordant with that obtained by Southern blotting, confirming this as a strict, reproducible and low-cost homozygosity screening strategy that enables the identification of small expanded alleles missed by the routine multiplex-PCR due to allele dropout. Overall, this assay is capable of spotting multiplex-PCR false negatives besides identifying alleles up to > 80 GCC repeats. Furthermore, the occurrence of intermediate repeat sizes with unexpected frequency, introduces new areas of clinical research in this cohort in understanding these less explored AFF2 repeat sizes and newly associated phenotypes.
Neuroanatomical correlates of the perception of body axis orientation during body tilt: a voxel-based morphometry study
Authors: Tani Keisuke , Tanaka Satoshi 
Published: July 2021

AbstractAccurate perception of the orientations of the body axis and gravity is essential for actions. The ability to perceive these orientations during head and body tilt varies across individuals, and its underlying neural basis is unknown. To address this, we investigated the association between inter-individual differences in local gray matter (GM) volume and inter-individual differences in the ability to estimate the directions of body longitudinal axis or gravity during whole-body tilt using voxel-based morphometry (VBM) analysis in 50 healthy adults (20–46 years, 25 men and 25 women). Although no anatomical regions were identified relating to performance requiring estimates of gravitational direction, we found a significant correlation between the GM volume in the right middle occipital gyrus and the ability to estimate the body axis orientation. This finding provides the first evidence on neuroanatomical substrates of the perception of body axis orientation during body tilt.
An integrated machine learning framework for a discriminative analysis of schizophrenia using multi-biological data
Authors: Ke Peng-fei , Xiong Dong-sheng , Li Jia-hui , Pan Zhi-lin , Zhou Jing , Li Shi-jia , Song Jie , Chen Xiao-yi , Li Gui-xiang , Chen Jun , Li Xiao-bo , Ning Yu-ping , Wu Feng-chun , Wu Kai 
Published: July 2021

AbstractFinding effective and objective biomarkers to inform the diagnosis of schizophrenia is of great importance yet remains challenging. Relatively little work has been conducted on multi-biological data for the diagnosis of schizophrenia. In this cross-sectional study, we extracted multiple features from three types of biological data, including gut microbiota data, blood data, and electroencephalogram data. Then, an integrated framework of machine learning consisting of five classifiers, three feature selection algorithms, and four cross validation methods was used to discriminate patients with schizophrenia from healthy controls. Our results show that the support vector machine classifier without feature selection using the input features of multi-biological data achieved the best performance, with an accuracy of 91.7% and an AUC of 96.5% (p < 0.05). These results indicate that multi-biological data showed better discriminative capacity for patients with schizophrenia than single biological data. The top 5% discriminative features selected from the optimal model include the gut microbiota features (Lactobacillus, Haemophilus, and Prevotella), the blood features (superoxide dismutase level, monocyte-lymphocyte ratio, and neutrophil count), and the electroencephalogram features (nodal local efficiency, nodal efficiency, and nodal shortest path length in the temporal and frontal-parietal brain areas). The proposed integrated framework may be helpful for understanding the pathophysiology of schizophrenia and developing biomarkers for schizophrenia using multi-biological data.
Implication of FDG-PET/CT without synchronous colonic lesion in patients with stenotic left-sided colorectal cancer
Authors: Lee Jong Il , Cho Sang Sik , Shin Ui Sup , Jeon Byong Ho , Moon Sun Mi , Kim Younjoo , Yang Ki Young , Kim Byung Il 
Published: July 2021

AbstractAlthough 18-fluoro-2-deoxy-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) is useful for detecting synchronous colorectal cancer (CRC) in stenotic CRC, long-term outcomes of patients without synchronous FDG-avid lesions are not well reported. We investigated postoperative colonoscopy results in patients with left-sided stenosing CRC without synchronous FDG-avid lesions. In this retrospective review, 754 patients with left-sided CRC without synchronous FDG-avid lesions on preoperative 18F-FDG PET/CT were divided into two groups based on the completeness of preoperative colonoscopy. Propensity score matching was performed to balance baseline characteristics. Results of postoperative colonoscopy were compared in both the unmatched and matched cohorts. At 1 and 5 years after surgery, the cumulative risk of advanced adenoma (AA) or carcinoma (CA) in all patients, risk of CA, and additional surgical risk were 1.8% and 10.1%, 0.1% and 0.4%, and 0% and 0.5%, respectively. In both cohorts, the AA risk was significantly higher in the incomplete colonoscopy group. However, the risk of CA showed no between-group difference in the matched cohort. Additional surgical risk did not differ between the two groups. Thus, the finding of negative FDG-avid lesions in the proximal colon in addition to the target CRC ensures the absence of additional lesions warranting surgical plan changes.
The role of FOSL1 in stem-like cell reprogramming processes
Authors: Pecce Valeria , Verrienti Antonella , Fiscon Giulia , Sponziello Marialuisa , Conte Federica , Abballe Luana , Durante Cosimo , Farina Lorenzo , Filetti Sebastiano , Paci Paola 
Published: July 2021

AbstractCancer stem-like cells (CSCs) have self-renewal abilities responsible for cancer progression, therapy resistance, and metastatic growth. The glioblastoma stem-like cells are the most studied among CSC populations. A recent study identified four transcription factors (SOX2, SALL2, OLIG2, and POU3F2) as the minimal core sufficient to reprogram differentiated glioblastoma (GBM) cells into stem-like cells. Transcriptomic data of GBM tissues and cell lines from two different datasets were then analyzed by the SWItch Miner (SWIM), a network-based software, and FOSL1 was identified as a putative regulator of the previously identified minimal core. Herein, we selected NTERA-2 and HEK293T cells to perform an in vitro study to investigate the role of FOSL1 in the reprogramming mechanisms. We transfected the two cell lines with a constitutive FOSL1 cDNA plasmid. We demonstrated that FOSL1 directly regulates the four transcription factors binding their promoter regions, is involved in the deregulation of several stemness markers, and reduces the cells’ ability to generate aggregates increasing the extracellular matrix component FN1. Although further experiments are necessary, our data suggest that FOSL1 reprograms the stemness by regulating the core of the four transcription factors.
Age period cohort analysis of chewing ability in Korea from 2007 to 2018
Authors: Kim Nam-Hee , Kawachi Ichiro 
Published: July 2021

AbstractThere have been marked improvements in oral health in Korea during the past 10 years, including chewing ability. We sought to disentangle age, period, and cohort effects in chewing ability between 2007 and 2018. We analyzed data from the Korea National Health and Nutrition Examination Survey. The main variable was chewing difficulty, which was assessed among participants aged 20 years and older. APC analysis revealed three trends in chewing difficulty: (1) there was an increase in chewing difficulty starting at around 60 years of age (age effect), (2) there was a steady decrease in chewing difficulty during the observation period (period effect), and (3) chewing ability improved with each successive generation born after 1951 (cohort effect). Regarding recent improvements in chewing ability, cohort effects were somewhat more important than period effects.
Circulating miRNA is a useful diagnostic biomarker for nonalcoholic steatohepatitis in nonalcoholic fatty liver disease
Authors: Kim Tae Hyung , Lee Yoonseok , Lee Young-Sun , Gim Jeong-An , Ko Eunjung , Yim Sun Young , Jung Young Kul , Kang SeongHee , Kim Moon Young , Kim Hayeon , Kim Baek-hui , Kim Ji Hoon , Seo Yeon Seok , Yim Hyung Joon , Yeon Jong Eun , Um Soon Ho , Byun Kwan Soo 
Published: July 2021

AbstractNonalcoholic steatohepatitis (NASH) is considered as a progressive form of nonalcoholic fatty liver disease (NAFLD). To distinguish NASH from nonalcoholic fatty liver (NAFL), we evaluated the diagnostic value of circulating miRNAs. Small RNA sequencing was performed on 12 NAFL patients and 12 NASH patients, and the miRNA expression was compared. After selecting miRNAs for the diagnosis of NASH, we analyzed the diagnostic accuracy of each miRNA and the combination of miRNAs. External validation was performed using quantitative reverse transcription PCR. Among the 2,588 miRNAs, 26 miRNAs significantly increased in the NASH group than in the NAFL group. Among the 26 elevated miRNAs in the NASH group, 8 miRNAs were selected, and in silico analysis was performed. Only four miRNAs (miR-21-5p, miR-151a-3p, miR-192-5p, and miR-4449) showed significant area under the receiver operating characteristic curve (AUC) values for NASH diagnosis. The combination of the four miRNAs showed satisfactory diagnostic accuracy for NASH (AUC 0.875; 95% CI 0.676–0.973). External validation revealed similar diagnostic accuracy for NASH (AUC 0.874; 95% CI 0.724–0.960). NASH represents significantly distinct miRNA expression profile compared with NAFL. The combination of serum circulating miRNAs can be used as a novel biomarker for the NASH diagnosis in NAFLD.
Genetic characterization and implications for conservation of the last autochthonous Mouflon population in Europe
Authors: Satta Valentina , Mereu Paolo , Barbato Mario , Pirastru Monica , Bassu Giovanni , Manca Laura , Naitana Salvatore , Leoni Giovanni Giuseppe 
Published: July 2021

AbstractPopulation genetic studies provide accurate information on population structure, connectivity, and hybridization. These are key elements to identify units for conservation and define wildlife management strategies aimed to maintain and restore biodiversity. The Mediterranean island of Sardinia hosts one of the last autochthonous mouflon populations, descending from the wild Neolithic ancestor. The first mouflon arrived in Sardinia ~ 7000 years ago and thrived across the island until the twentieth century, when anthropogenic factors led to population fragmentation. We analysed the three main allopatric Sardinian mouflon sub-populations, namely: the native sub-populations of Montes Forest and Mount Tonneri, and the reintroduced sub-population of Mount Lerno. We investigated the spatial genetic structure of the Sardinian mouflon based on the parallel analysis of 14 highly polymorphic microsatellite loci and mitochondrial D-loop sequences. The Montes Forest sub-population was found to harbour the ancestral haplotype in the phylogeny of European mouflon. We detected high levels of relatedness in all the sub-populations and a mitochondrial signature of hybridization between the Mount Lerno sub-population and domestic sheep. Our findings provide useful insights to protect such an invaluable genetic heritage from the risk of genetic depletion by promoting controlled inter-population exchange and drawing informed repopulation plans sourcing from genetically pure mouflon stocks.
Elevated S-adenosylhomocysteine induces adipocyte dysfunction to promote alcohol-associated liver steatosis
Authors: Arumugam Madan Kumar , Chava Srinivas , Rasineni Karuna , Paal Matthew C. , Donohue Terrence M. , Osna Natalia A. , Kharbanda Kusum K. 
Published: July 2021

AbstractIt has been previously shown that chronic ethanol administration-induced increase in adipose tissue lipolysis and reduction in the secretion of protective adipokines collectively contribute to alcohol-associated liver disease (ALD) pathogenesis. Further studies have revealed that increased adipose S-adenosylhomocysteine (SAH) levels generate methylation defects that promote lipolysis. Here, we hypothesized that increased intracellular SAH alone causes additional related pathological changes in adipose tissue as seen with alcohol administration. To test this, we used 3-deazaadenosine (DZA), which selectively elevates intracellular SAH levels by blocking its hydrolysis. Fully differentiated 3T3-L1 adipocytes were treated in vitro for 48 h with DZA and analysed for lipolysis, adipokine release and differentiation status. DZA treatment enhanced adipocyte lipolysis, as judged by lower levels of intracellular triglycerides, reduced lipid droplet sizes and higher levels of glycerol and free fatty acids released into the culture medium. These findings coincided with activation of both adipose triglyceride lipase and hormone sensitive lipase. DZA treatment also significantly reduced adipocyte differentiation factors, impaired adiponectin and leptin secretion but increased release of pro-inflammatory cytokines, IL-6, TNF and MCP-1. Together, our results demonstrate that elevation of intracellular SAH alone by DZA treatment of 3T3-L1 adipocytes induces lipolysis and dysregulates adipokine secretion. Selective elevation of intracellular SAH by DZA treatment mimics ethanol’s effects and induces adipose dysfunction. We conclude that alcohol-induced elevations in adipose SAH levels contribute to the pathogenesis and progression of ALD.
Blood glutamate scavengers increase pro-apoptotic signaling and reduce metastatic melanoma growth in-vivo
Authors: Goldshmit Yona , Perelroizen Rita , Yakovchuk Alex , Banyas Evgeni , Mayo Lior , David Sari , Benbenishty Amit , Blinder Pablo , Shalom Moshe , Ruban Angela 
Published: July 2021

AbstractInhibition of extracellular glutamate (Glu) release decreases proliferation and invasion, induces apoptosis, and inhibits melanoma metastatic abilities. Previous studies have shown that Blood-glutamate scavenging (BGS), a novel treatment approach, has been found to be beneficial in attenuating glioblastoma progression by reducing brain Glu levels. Therefore, in this study we evaluated the ability of BGS treatment to inhibit brain metastatic melanoma progression in-vivo. RET melanoma cells were implanted in C56BL/6J mice to induce brain melanoma tumors followed by treatment with BGS or vehicle administered for fourteen days. Bioluminescent imaging was conducted to evaluate tumor growth, and plasma/CSF Glu levels were monitored throughout. Immunofluorescence staining of Ki67 and 53BP1 was used to analyze tumor cell proliferation and DNA double-strand breaks. In addition, we analyzed CD8, CD68, CD206, p-STAT1 and iNOS expression to evaluate alterations in tumor micro-environment and anti-tumor immune response due to treatment. Our results show that BGS treatment reduces CSF Glu concentration and consequently melanoma growth in-vivo by decreasing tumor cell proliferation and increasing pro-apoptotic signaling in C56BL/6J mice. Furthermore, BGS treatment supported CD8+ cell recruitment and CD68+ macrophage invasion. These findings suggest that BGS can be of potential therapeutic relevance in the treatment of metastatic melanoma.
Mechanical properties of CAD/CAM-fabricated in comparison to conventionally fabricated functional regulator 3 appliances
Authors: Roser Christoph , Hodecker Lutz D. , Koebel Chris , Lux Christopher J. , Ruckes Dorothee , Rues Stefan , Zenthöfer Andreas 
Published: July 2021

AbstractManufacturing of Fränkel's functional regulator 3 (FR3) is complicated and requires extensive knowledge from the dental technician. To determine whether FR3s produced by CAD/CAM techniques (CAD-FR3) meet similar mechanical properties like conventional FR3s (Con-FR3), for each of 10 patient cases, three CAD-FR3 designs (palatal connector cross-section 3 × 3 mm, 4 × 1 mm or 5 × 2 mm) and one Con-FR3 were subjected to cyclic loading and subsequent fracture testing in a universal testing device. Transversal load capacity (Fmax(FR3)) and stiffness were compared among the different CAD-FR3 designs and Con-FR3s using Friedman and Wilcoxon tests with a significance level of α = 0.05. All CAD-FR3 designs had significantly higher mean Fmax(FR3) (p ≤ 0.007) and stiffness (p ≤ 0.005) than the Con-FR3s. The CAD-FR33×3 had the highest mean Fmax(FR3) (98.2 ± 26.2 N) and stiffness (37.1 ± 15.5 N/mm), closely followed by the CAD-FR35×2 (Fmax(FR3): 90.3 ± 24.7 N; stiffness: 30.0 ± 12.3 N/mm). Among the CAD appliances, CAD-FR34×1 had the lowest values (p ≤ 0.007 for all pairwise tests) with Fmax(FR3) of 45.8 ± 17.9 N and stiffness of 12.5 ± 7.3 N/mm. CAD-FR3s have superior mechanical properties in comparison to Con-FR3s if certain design parameters are followed. Further clinical investigations have to examine if they can serve as an alternative in practice.
Inhibitory control mediates the interaction between serotonin transporter gene (5-HTTLPR) and peer victimization on adolescent depressive symptoms
Authors: Lin Xiaonan , Cao Yanmiao , Ji Linqin , Zhang Wenxin 
Published: July 2021

AbstractMany efforts have been devoted to investigating the effect of the interaction between the serotonin transporter gene (5-HTTLPR) and environment (G × E) on depression, but they yield mixed results. The inconsistency has suggested that G × E effects may be more complex than originally conceptualized, and further study is warranted. This study explored the association among5-HTTLPR, peer victimization and depressive symptoms and the underlying mediating role of inhibitory control in this association. A total of 871 Chinese Han adolescents (Mage = 15.32 years, 50.3% girls) participated and provided saliva samples from which the5-HTTLPRwas genotyped. This study found that5-HTTLPRinteracted with peer victimization in predicting depressive symptoms. Adolescents carrying L allele reported more depressive symptoms than SS carriers when exposed to higher level of peer victimization. Furthermore, adolescents’ inhibitory control deficits mediated the association between5-HTTLPR × peer victimization and depressive symptoms. These findings suggested that one pathway in which G × E may confer vulnerability to depressive symptoms is through disruptions to adolescents’ inhibitory control system.
Extracellular detection of neuronal coupling
Authors: Guzman Elmer , Cheng Zhuowei , Hansma Paul K. , Tovar Kenneth R. , Petzold Linda R. , Kosik Kenneth S. 
Published: July 2021

AbstractWe developed a method to non-invasively detect synaptic relationships among neurons from in vitro networks. Our method uses microelectrode arrays on which neurons are cultured and from which propagation of extracellular action potentials (eAPs) in single axons are recorded at multiple electrodes. Detecting eAP propagation bypasses ambiguity introduced by spike sorting. Our methods identify short latency spiking relationships between neurons with properties expected of synaptically coupled neurons, namely they were recapitulated by direct stimulation and were sensitive to changing the number of active synaptic sites. Our methods enabled us to assemble a functional subset of neuronal connectivity in our cultures.
Zinc systematics quantify crustal thickness control on fractionating assemblages of arc magmas
Authors: Chiaradia M. 
Published: July 2021

AbstractUnderstanding the processes leading to the broad chemical variability of arc magmas is an essential, yet not fully elucidated, issue in Earth Sciences. Here, I show that Zn–MgO–SiO2 systematics of magmatic arc rocks correlate significantly with arc thickness. Because Zn–MgO–SiO2 systematics are mostly controlled by fractionation of different mineral phases, this suggests a systematic change in the proportions of fractionating mineral assemblages depending on arc thickness. Using a mass balance model with a Monte Carlo approach, I show that Zn–MgO–SiO2 systematics can be quantitatively explained by a continuous transition from plagioclase-dominated fractionating assemblages in thin arcs to amphibole-garnet-magnetite-dominated assemblages in increasingly thicker arcs. Most likely, such a systematic change results from the increase of average depth of magma differentiation that is ultimately controlled by arc thickness. Results presented have implications on the causes of different geochemical trends in arcs, the role of arcs as H2O filters, and their association with porphyry deposits.