bluuebunny/crossref_metadata_2025 huggingface dataset:
Microplastics in Sea Turtles, Marine Mammals and Humans: A One Environmental Health Perspective
Authors: Meaza Idoia , Toyoda Jennifer H , Wise Sr John Pierce
Published: February 2021

Microplastics are ubiquitous pollutants in the marine environment and a health concern. They are generated directly for commercial purposes or indirectly from the breakdown of larger plastics. Examining a toxicological profile for microplastics is a challenge due to their large variety of physico-chemical properties and toxicological behavior. In addition to their concentration, other parameters such as polymer type, size, shape and color are important to consider in their potential toxicity. Microplastics can adsorb pollutants such as polycyclic aromatic hydrocarbons (PAHs) or metals on their surface and are likely to contain plastic additives that add to their toxicity. The observations of microplastics in seafood increased concern for potential human exposure. Since literature considering microplastics in humans is scarce, using a One Environmental Health approach can help better inform about potential human exposures. Marine mammals and sea turtles are long-lived sentinel species regularly used for biomonitoring the health status of the ocean and share trophic chain and habitat with humans. This review considers the available research regarding microplastic and plastic fiber exposures in humans, marine mammals and turtles. Overall, across the literature, the concentration of microplastics, size, color, shape and polymer types found in GI tract and feces from sea turtles, marine mammals and humans are similar, showing that they might be exposed to the same microplastics profile. Additionally, even if ingestion is a major route of exposure due to contaminated food and water, dermal and inhalation studies in humans have provided data showing that these exposures are also health concerns and more effort on these routes of exposures is needed. In vitro studies looked at a variety of endpoints showing that microplastics can induce immune response, oxidative stress, cytotoxicity, alter membrane integrity and cause differential expression of genes. However, these studies only considered three polymer types and short-term exposures, whereas, due to physiological relevance, prolonged exposures might be more informative.
Soil Bacterial Communities and Diversity in Alpine Grasslands on the Tibetan Plateau Based on 16S rRNA Gene Sequencing
Authors: Jiang Hongmao , Chen Youchao , Hu Yang , Wang Ziwei , Lu Xuyang
Published: February 2021

The Tibetan Plateau, widely known as the world’s “Third Pole,” has gained extensive attention due to its susceptibility to climate change. Alpine grasslands are the dominant ecosystem on the Tibetan Plateau, albeit little is known about the microbial community and diversity among different alpine grassland types. Here, soil bacterial composition and diversity in the upper soils of five alpine grassland ecosystems, alpine meadow (AM), alpine steppe (AS), alpine meadow steppe (AMS), alpine desert (AD), and alpine desert steppe (ADS), were investigated based on the 16S rRNA gene sequencing technology. Actinobacteria (46.12%) and Proteobacteria (29.67%) were the two dominant soil bacteria at the phylum level in alpine grasslands. There were significant differences in the relative abundance at the genus level among the five different grassland types, especially for the Rubrobacter, Solirubrobacter, Pseudonocardia, Gaiella, Haliangium, and Geodermatophilus. Six alpha diversity indices were calculated based on the operational taxonomic units (OTUs), including Good’s coverage index, phylogenetic diversity (PD) whole tree index, Chao1 index, observed species index, Shannon index, and Simpson index. The Good’s coverage index value was around 0.97 for all the grassland types in the study area, meaning the soil bacteria samplings sequenced sufficiently. No statistically significant difference was shown in other diversity indices’ value, indicating the similar richness and evenness of soil bacteria in these alpine grasslands. The beta diversity, represented by Bray–Curtis dissimilarity and the non-metric multidimensional scaling (NMDS), showed that OTUs were clustered within alpine grasslands, indicating a clear separation of soil bacterial communities. In addition, soil organic matter (SOM), total nitrogen (TN), total phosphorus (TP), pH, and soil water content (SWC) were closely related to the variations in soil bacterial compositions. These results indicated that soil bacterial taxonomic compositions were similar, while soil bacterial community structures were different among the five alpine grassland types. The environmental conditions, including SOM, TN, TP, pH, and SWC, might influence the soil bacterial communities on the Tibetan Plateau.
Identification of Potential Driver Genes Based on Multi-Genomic Data in Cervical Cancer
Authors: Xu Yuexun , Luo Hui , Hu Qunchao , Zhu Haiyan
Published: February 2021

Background: Cervical cancer became the third most common cancer among women, and genome characterization of cervical cancer patients has revealed the extensive complexity of molecular alterations. However, identifying driver mutation and depicting molecular classification in cervical cancer remain a challenge.

Methods: We performed an integrative multi-platform analysis of a cervical cancer cohort from The Cancer Genome Atlas (TCGA) based on 284 clinical cases and identified the driver genes and possible molecular classification of cervical cancer.

Results: Multi-platform integration showed that cervical cancer exhibited a wide range of mutation. The top 10 mutated genes were TTN, PIK3CA, MUC4, KMT2C, MUC16, KMT2D, SYNE1, FLG, DST, and EP300, with a mutation rate from 12 to 33%. Applying GISTIC to detect copy number variation (CNV), the most frequent chromosome arm-level CNVs included losses in 4p, 11p, and 11q and gains in 20q, 3q, and 1q. Then, we performed unsupervised consensus clustering of tumor CNV profiles and methylation profiles and detected four statistically significant expression subtypes. Finally, by combining the multidimensional datasets, we identified 10 potential driver genes, including GPR107, CHRNA5, ZBTB20, Rb1, NCAPH2, SCA1, SLC25A5, RBPMS, DDX3X, and H2BFM.

Conclusions: This comprehensive analysis described the genetic characteristic of cervical cancer and identified novel driver genes in cervical cancer. These results provide insight into developing precision treatment in cervical cancer.
Case Report: Exome Sequencing Identified a Novel Compound Heterozygous Variation in PLOD2 Causing Bruck Syndrome Type 2
Authors: Zhang Jing , Hu Huaying , Mu Weihong , Yu Mei , Chen Wenqi , Mi Dongqing , Yang Kai , Guo Qing
Published: February 2021

Bruck Syndrome (BRKS) is a rare type of recessive osteogenesis imperfecta (OI) and consists of two subtypes, BRKS1 and BRKS2, which are caused by variations in FKBP10 and PLOD2 genes, respectively. In this study, a family that had experienced multiple miscarriages and recurrent fetal skeletal dysplasia was recruited for the purpose of a multiplatform laboratory investigation. Prenatal genetic testing with whole-exome sequencing (WES) identified a compound heterozygous variation in the PLOD2 gene with two variants, namely c.2038C>T (p.R680*) and c.191_201+3 delATACTGTGAAGGTA (p.Y64Cfs*12). The amino acids affected by the two variants maintained conserved across species. And the result of immunohistochemistry (IHC) indicated that the expression of PLOD2 protein in the proband's osteochondral tissue was significantly decreased. These findings in our study expanded the variation spectrum of PLOD2 gene, provided solid evidence for the family's counseling in regard to future pregnancies, strongly supported the application of WES in prenatal diagnosis, and might give insight into the understanding of PLOD2 function.
Correlations Between Tumor Mutation Burden and Immunocyte Infiltration and Their Prognostic Value in Colon Cancer
Authors: Zhou Zhangjian , Xie Xin , Wang Xuan , Zhang Xin , Li Wenxin , Sun Tuanhe , Cai Yifan , Wu Jianhua , Dang Chengxue , Zhang Hao
Published: February 2021

Background

Colon cancer has a huge incidence and mortality worldwide every year. Immunotherapy could be a new therapeutic option for patients with advanced colon cancer. Tumor mutation burden (TMB) and immune infiltration are considered critical in immunotherapy but their characteristics in colon cancer are still controversial.

Methods

The somatic mutation, transcriptome, and clinical data of patients with colon cancer were obtained from the TCGA database. Patients were divided into low or high TMB groups using the median TMB value. Somatic mutation landscape, differentially expressed genes, and immune-related hub genes, Gene Ontology and KEGG, gene set enrichment, and immune infiltration analyses were investigated between the two TMB groups. Univariate and multivariate Cox analyses were utilized to construct a prognostic gene signature. The differences in immune infiltration, and the expression of HLA-related genes and checkpoint genes were investigated between the two immunity groups based on single sample gene set enrichment analysis. Finally, a nomogram of the prognostic prediction model integrating TMB, immune infiltration, and clinical parameters was established. Calibration plots and receiver operating characteristic curves (ROC) were drawn, and the C-index was calculated to assess the predictive ability.

Results

Missense mutations and single nucleotide polymorphisms were the major variant characteristics in colon cancer. The TMB level showed significant differences in N stage, M stage, pathological stage, and immune infiltration. CD8+ T cells, activated memory CD4+ T cells, activated NK cells, and M1 macrophages infiltrated more in the high-TMB group. The antigen processing and presentation signaling pathway was enriched in the high-TMB group. Two immune related genes (CHGB and SCT) were identified to be correlated with colon cancer survival (HR = 1.39, P = 0.01; HR = 1.26, P = 0.02, respectively). Notably, the expression of SCT was identified as a risk factor in the immune risk model, in which high risk patients showed poorer survival (P = 0.04). High immunity status exhibited significant correlations with immune response pathways, HLA-related genes, and immune checkpoint genes. Finally, including nine factors, our nomogram prediction model showed better calibration (C-index = 0.764) and had an AUC of 0.737.

Conclusion

In this study, we investigated the patterns and prognostic roles of TMB and immune infiltration in colon cancer, which provided new insights into the tumor microenvironment and immunotherapies and the development of a novel nomogram prognostic prediction model for patients with colon cancer.
Anti-Pentraxin Antibodies in Autoimmune Diseases: Bystanders or Pathophysiological Actors?
Authors: Brilland Benoit , Vinatier Emeline , Subra Jean-François , Jeannin Pascale , Augusto Jean-François , Delneste Yves
Published: February 2021

Pentraxins are soluble innate immunity receptors involved in sensing danger molecules. They are classified as short (CRP, SAP) and long pentraxin subfamilies, including the prototypic long pentraxin PTX3. Pentraxins act mainly as bridging molecules favoring the clearance of microbes and dead cells. They are also involved in many other biological processes, such as regulation of complement activation, inflammation and tissue homeostasis. Autoantibodies directed against pentraxins have been reported in various autoimmune diseases, especially in systemic lupus erythematosus and ANCA-associated vasculitis. In this review, we review the main biological characteristics and functions of pentraxins and summarize data concerning autoantibodies directed against pentraxins in the context of autoimmune diseases and discuss their potential pathological role.
Therapeutic Effects of (5R)-5-Hydroxytriptolide on Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via lncRNA WAKMAR2/miR-4478/E2F1/p53 Axis
Authors: Zhou Xinpeng , Xie Duoli , Huang Jie , Lu Aiping , Wang Rongsheng , Jin Yehua , Zhang Runrun , Chang Cen , Xu Lingxia , Xu Linshuai , Fan Junyu , Liang Chao , He Dongyi
Published: February 2021

Rheumatoid arthritis (RA) is an autoimmune disease. Fibroblast-like synoviocytes (FLS) serve a major role in synovial hyperplasia and inflammation in RA. (5R)-5-hydroxytriptolide (LLDT-8), a novel triptolide derivative, shows promising therapeutic effects for RA and is now in phase II clinical trials in China. However, the underlying mechanism of LLDT-8 is still not fully understood. Here, we found that LLDT-8 inhibited proliferation and invasion of RA FLS, as well as the production of cytokines. Microarray data demonstrated that LLDT-8 upregulated the expression of long non-coding RNA (lncRNA) WAKMAR2, which was negatively associated with proliferation and invasion of RA FLS, as well as the production of pro-inflammatory cytokines. Knockdown of WAKMAR2 abolished the inhibitory effects of LLDT-8 on RA FLS. Mechanistically, WAKMAR2 sponged miR-4478, which targeted E2F1 and downstreamed p53 signaling. Rescue experiments indicated that the inhibitory effects of LLDT-8 on RA FLS were dependent on WAKMAR2/miR-4478/E2F1/p53 axis.
Use of the JAK Inhibitor Ruxolitinib in the Treatment of Hemophagocytic Lymphohistiocytosis
Authors: Keenan Camille , Nichols Kim E. , Albeituni Sabrin
Published: February 2021

Hemophagocytic lymphohistiocytosis (HLH) is a rare hyperinflammatory syndrome driven by overactive T cells and macrophages that abundantly secrete numerous pro-inflammatory cytokines, including interferon (IFN)-gamma, interleukin (IL)-1-beta, IL-2, IL-6, IL-10, IL-18, and tumor necrosis factor (TNF). The release of these and other cytokines underlies many of the clinical and pathologic manifestations of HLH, which if left untreated, can lead to multi-organ failure and death. The advent of etoposide-based regimens, such as the Histiocyte Society HLH-94 and HLH-2004 protocols, has substantially decreased the mortality associated with HLH. Nevertheless, the 5-year survival remains low at ~60%. To improve upon these results, studies have focused on the use of novel cytokine-directed therapies to dampen inflammation in HLH. Among the agents being tested is ruxolitinib, a potent inhibitor of the Janus Kinase (JAK) and Signal Transducer and Activation of Transcription (STAT) pathway, which functions downstream of many HLH-associated cytokines. Here, we review the basic biology of HLH, including the role of cytokines in disease pathogenesis, and discuss the use of ruxolitinib in the treatment of HLH.
PDIA5 is Correlated With Immune Infiltration and Predicts Poor Prognosis in Gliomas
Authors: Zhang Hao , He Jialin , Dai Ziyu , Wang Zeyu , Liang Xisong , He Fengqiong , Xia Zhiwei , Feng Songshan , Cao Hui , Zhang Liyang , Cheng Quan
Published: February 2021

Gliomas are the most common and lethal primary malignant tumor of the brain. Routine treatment including surgical resection, chemotherapy, and radiotherapy produced limited therapeutic effect, while immunotherapy targeting the glioma microenvironment has offered a novel therapeutic option. PDIA5 protein is the member of PDI family, which is highly expressed in glioma and participates in glioma progression. Based on large-scale bioinformatics analysis, we discovered that PDIA5 expression level is upregulated in aggressive gliomas, with high PDIA5 expression predicting poor clinical outcomes. We also observed positive correlation between PDIA5 and immune infiltrating cells, immune related pathways, inflammatory activities, and other immune checkpoint members. Patients with high PDIA5 high-expression benefited from immunotherapies. Additionally, immunohistochemistry revealed that PDIA5 and macrophage biomarker CD68 were upregulated in high-grade gliomas, and patients with low PDIA5 level experienced favorable outcomes among 33 glioma patients. Single cell RNA sequencing exhibited that PDIA5 was in high level presenting in neoplastic cells and macrophages. Cell transfection and co-culture of glioma cells and macrophages revealed that PDIA5 in tumor cells mediated macrophages exhausting. Altogether, our findings indicate that PDIA5 overexpression is associated with immune infiltration in gliomas, and may be a promising therapeutic target for glioma immunotherapy.
Whale-Watching Management: Assessment of Sustainable Governance in Uramba Bahía Málaga National Natural Park, Valle del Cauca
Authors: Soto-Cortés Laura V. , Luna-Acosta Andrea , Maya Diana Lucía
Published: February 2021

As the growth of the whale-watching activity increases rapidly around the world, the challenge of responsible management and sustainability also rises. Without suitable management, operators may try to maximize their own profits by breaking the rules, which may negatively affect cetaceans. In this paper, the applicability of conditions for sustainability governance in humpback whale-watching was evaluated. To achieve this purpose, semi-structured interviews were conducted in Uramba Bahía Málaga National Natural Park, Colombia. Results of this study showed that humpback whale-watching is characterized by unevenness in connections with markets, income inequality and the distribution of operators across several villages and cities. The combination of which restricts cooperation between operators. Nevertheless, there are informal agreements among the operators, and some operators are motivated to form associations. Besides, environmental entities have been responsible of regulation in lack of community-based management. However, this still does not achieve effective enforcement of the rules. Stakeholders (communities and government authorities) must mediate trust and reciprocity among operators to improve the situation. It is important to involve all operators to fill gaps in the limited government monitoring capacity and absence of sanctions. This is relevant to continue monitoring the evolution of the whale-watching in this and other Marine Protected Areas, so that the sustainability of the activity is not affected in the future.
Progress of Studies on Circulation Dynamics in the East China Sea: The Kuroshio Exchanges With the Shelf Currents
Authors: Liu Zhiqiang , Gan Jianping , Hu Jianyu , Wu Hui , Cai Zhongya , Deng Yongfei
Published: February 2021

This paper reviews recent advances in the circulation dynamics of the Kuroshio and its interaction with shelf currents in the East China Sea (ECS). The annually averaged Kuroshio volume transport varies between 19 and 24 Sv, based on different observations, but there is no consensus on which season its volume transport peaks. The Kuroshio is intensified over the central slope of the ECS from that off the northeast of Taiwan. The total Kuroshio intrusion into the ECS shelf is estimated to be 1.3–1.4 Sv, deduced from the observed volume transport of exchange flow in the Taiwan and Tsushima Straits, based on the assumption of volume conversation over the shelf. However, the uncertainty regarding this estimation remains due to the absence of sufficient observations and understanding of the Kuroshio dynamics. The Kuroshio intrusions over the shelf off the northeast of Taiwan and southwest of Kyushu are stimulated by planetary or topographic β -effect associated with the alongshore variations in the ECS slope topography and altered by variations in the Kuroshio intensity, shear stress, and baroclinicity. Multilayered exchanges between the Kuroshio and shelf currents were found between 100- and 200-m isobaths along the central ECS slope. The spatial variations in these exchanges are governed by cross-isobath transport by geostrophy, whereas bottom Ekman transport may play a predominant role in altering the integrated exchange flow along the slope. Although the intrusion is greatly modulated along the path of the Kuroshio in the ECS by variable slope topography, there are few observations on the spatial variations of these exchange flows. The characteristics and variations in the circulation and hydrographic properties of waters between 100- and 200-m isobaths significantly determine the general ECS circulation, about which consensus has still not been attained.
Effects of Brazing Technology on Hermeticity of Alumina Ceramic-Metal Joint Used in Nuclear Power Plants
Authors: Deng Nengmei , Zhao Jun , Yang Lilin , Zheng Zhiqin
Published: February 2021

Taking the brazing mechanism of alumina ceramics and kovar alloys as the main research object, based on the molybdenum–manganese metallization method, the influence of the direct and indirect brazing processes on the morphology of the final connected layer is explored. Combined with SEM, EDS, the microscopic morphology, and hermeticity affecting the final ceramic–metal composite component is discussed. Finally, through the indirect brazing process, various ceramic–metal composite joints with good airtightness satisfying the requirements were prepared.
Serum IRAP, a Novel Direct Biomarker of Prediabetes and Type 2 Diabetes?
Authors: Trocmé Candice , Gonnet Nicolas , Di Tommaso Margaux , Samouda Hanen , Cracowski Jean-Luc , Cracowski Claire , Lambert-Porcheron Stéphanie , Laville Martine , Nobécourt Estelle , Gaddhab Chiraz , Le Lay Allan , Bohn Torsten , Poitou Christine , Clément Karine , Al-Mulla Fahd , Bitar Milad S. , Bottari Serge P.
Published: February 2021

Insulin resistance (IR), currently called prediabetes (PD), affects more than half of the adult population worldwide. Type 2 diabetes (T2D), which often follows in the absence of treatment, affects more than 475 million people and represents 10–20% of the health budget in industrialized countries. A preventive public health policy is urgently needed in order to stop this constantly progressing epidemic. Indeed, early management of prediabetes does not only strongly reduce its evolution toward T2D but also strongly reduces the appearance of cardiovascular comorbidity as well as that of associated cancers. There is however currently no simple and reliable test available for the diagnosis or screening of prediabetes and it is generally estimated that 20–60% of diabetics are not diagnosed. We therefore developed an ELISA for the quantitative determination of serum Insulin-Regulated AminoPeptidase (IRAP). IRAP is associated with and translocated in a stoechiometric fashion to the plasma membrane together with GLUT4 in response to insulin in skeletal muscle and adipose tissue which are the two major glucose storage sites. Its extracellular domain (IRAPs) is subsequently cleaved and secreted in the blood stream. In T2D, IRAP translocation in response to insulin is strongly decreased. Our patented sandwich ELISA is highly sensitive (≥10.000-fold “normal” fasting concentrations) and specific, robust and very cost-effective. Dispersion of fasting plasma concentration values in a healthy population is very low (101.4 ± 15.9 μg/ml) as compared to those of insulin (21–181 pmol/l) and C-peptide (0.4–1.7 nmol/l). Results of pilot studies indicate a clear correlation between IRAPs levels and insulin sensitivity. We therefore think that plasma IRAPs may be a direct marker of insulin sensitivity and that the quantitative determination of its plasma levels should allow large-scale screening of populations at risk for PD and T2D, thereby allow the enforcement of a preventive health policy aiming at efficiently reducing this epidemic.
Zic Family Member 2 (ZIC2): a Potential Diagnostic and Prognostic Biomarker for Pan-Cancer
Authors: Lv Zhengtong , Qi Lin , Hu Xiheng , Mo Miao , Jiang Huichuan , Fan Benyi , Li Yuan
Published: February 2021

Background: As a transcription factor, Zinc finger protein ZIC2 can interact with various DNAs and proteins. Current studies have shown that ZIC2 plays an oncogene role in various cancers. In this study, we systematically characterize the prevalence and predictive value of ZIC2 expression across multiple cancer types.

Methods: We mined several public databases, including Oncomine, the Cancer Genome Atlas (TCGA), cBioPortal, Kaplan-Meier Plotter and PrognoScan to evaluated the differentially expressed ZIC2 between tumor samples and normal control samples in pan-cancner, and then explored the association between ZIC2 expression and patient survival, prognosis and clinicopathologic stage. We also analyzed the relationship between tumor mutation burden (TMB), microsatellite instability (MSI), tumor microenvironment, tumor- and immune-related genes and ZIC2 expression. Finally, we explored the potential signaling pathway mechanism through gene set enrichment analysis (GSEA).

Results: ZIC2 expression was higher in most cancer tissues compared with adjacent normal tissues. High ZIC2 expression was associated with worse prognosis and a higher clinicopathologic stage. ZIC2 expression was strongly associated with the TMB, MSI, tumor microenvironment and tumor- and immune-related genes. The GSEA revealed that multiple tumor- and immune-related pathways were differentially enriched in ZIC2 high or low expression phenotype.

Conclusion: ZIC2 expression may be a potential prognostic molecular biomarker of poor survival in pan-cancer and may act as an oncogene with a strong effect in the processes of tumorigenesis and progression.
Brain Inspired Sequences Production by Spiking Neural Networks With Reward-Modulated STDP
Authors: Fang Hongjian , Zeng Yi , Zhao Feifei
Published: February 2021

Understanding and producing embedded sequences according to supra-regular grammars in language has always been considered a high-level cognitive function of human beings, named “syntax barrier” between humans and animals. However, some neurologists recently showed that macaques could be trained to produce embedded sequences involving supra-regular grammars through a well-designed experiment paradigm. Via comparing macaques and preschool children's experimental results, they claimed that human uniqueness might only lie in the speed and learning strategy resulting from the chunking mechanism. Inspired by their research, we proposed a Brain-inspired Sequence Production Spiking Neural Network (SP-SNN) to model the same production process, followed by memory and learning mechanisms of the multi-brain region cooperation. After experimental verification, we demonstrated that SP-SNN could also handle embedded sequence production tasks, striding over the “syntax barrier.” SP-SNN used Population-Coding and STDP mechanism to realize working memory, Reward-Modulated STDP mechanism for acquiring supra-regular grammars. Therefore, SP-SNN needs to simultaneously coordinate short-term plasticity (STP) and long-term plasticity (LTP) mechanisms. Besides, we found that the chunking mechanism indeed makes a difference in improving our model's robustness. As far as we know, our work is the first one toward the “syntax barrier” in the SNN field, providing the computational foundation for further study of related underlying animals' neural mechanisms in the future.
SDL Index Predicts Stroke-Associated Pneumonia in Patients After Endovascular Therapy
Authors: Zhang Bowei , Zhao Wenbo , Wu Chuanjie , Wu Longfei , Hou Chengbei , Klomparens Kara , Ding Yuchuan , Li Chuanhui , Chen Jian , Duan Jiangang , Zhang Yunzhou , Chang Hong , Ji Xunming
Published: February 2021

Objective: This study aimed to develop and validate a novel index to predict SAP for AIS patients who underwent endovascular treatment.

Methods: A study was conducted in an advanced comprehensive stroke center from January 2013 to December 2019 aiming to develop and validate a novel index to predict SAP for AIS patients who underwent endovascular treatment. This cohort consisted of a total of 407 consecutively registered AIS patients who underwent endovascular therapy, which was divided into derivation and validation cohorts. Multiple blood parameters as well as demographic features, vascular risk factors, and clinical features were carefully evaluated in the derivation cohort. The independent predictors were obtained using multivariable logistic regression. The scoring system was generated based on the β-coefficients of each independent risk factor.

Results: Ultimately, a novel predictive model: the SDL index (stroke history, dysphagia, lymphocyte count < 1.00 × 103/μL) was developed. The SDL index showed good discrimination both in the derivation cohort (AUROC: 0.739, 95% confidence interval, 0.678–0.801) and the validation cohort (AUROC: 0.783, 95% confidence interval, 0.707–0.859). The SDL index was well-calibrated (Hosmer–Lemeshow test) in the derivation cohort (P = 0.389) and the validation cohort (P = 0.692). We therefore divided our population into low (SDL index = 0), medium (SDL index = 1), and high (SDL index ≥ 2) risk groups for SAP. The SDL index showed good discrimination when compared with two existing SAP prediction models.

Conclusions: The SDL index is a novel feasible tool to predict SAP risk in acute ischemic stroke patients post endovascular treatment.
Altered Frequency-Dependent Brain Activation and White Matter Integrity Associated With Cognition in Characterizing Preclinical Alzheimer’s Disease Stages
Authors: Wang Siyu , Rao Jiang , Yue Yingying , Xue Chen , Hu Guanjie , Qi Wenzhang , Ma Wenying , Ge Honglin , Zhang Fuquan , Zhang Xiangrong , Chen Jiu
Published: February 2021

Background

Subjective cognitive decline (SCD), non-amnestic mild cognitive impairment (naMCI), and amnestic mild cognitive impairment (aMCI) are regarded to be at high risk of converting to Alzheimer’s disease (AD). Amplitude of low-frequency fluctuations (ALFF) can reflect functional deterioration while diffusion tensor imaging (DTI) is capable of detecting white matter integrity. Our study aimed to investigate the structural and functional alterations to further reveal convergence and divergence among SCD, naMCI, and aMCI and how these contribute to cognitive deterioration.

Methods

We analyzed ALFF under slow-4 (0.027–0.073 Hz) and slow-5 (0.01–0.027 Hz) bands and white matter fiber integrity among normal controls (CN), SCD, naMCI, and aMCI groups. Correlation analyses were further utilized among paired DTI alteration, ALFF deterioration, and cognitive decline.

Results

For ALFF calculation, ascended ALFF values were detected in the lingual gyrus (LING) and superior frontal gyrus (SFG) within SCD and naMCI patients, respectively. Descended ALFF values were presented mainly in the LING, SFG, middle frontal gyrus, and precuneus in aMCI patients compared to CN, SCD, and naMCI groups. For DTI analyses, white matter alterations were detected within the uncinate fasciculus (UF) in aMCI patients and within the superior longitudinal fasciculus (SLF) in naMCI patients. SCD patients presented alterations in both fasciculi. Correlation analyses revealed that the majority of these structural and functional alterations were associated with complicated cognitive decline. Besides, UF alterations were correlated with ALFF deterioration in the SFG within aMCI patients.

Conclusions

SCD shares structurally and functionally deteriorative characteristics with aMCI and naMCI, and tends to convert to either of them. Furthermore, abnormalities in white matter fibers may be the structural basis of abnormal brain activation in preclinical AD stages. Combined together, it suggests that structural and functional integration may characterize the preclinical AD progression.
Overexpression of EZH2/NSD2 Histone Methyltransferase Axis Predicts Poor Prognosis and Accelerates Tumor Progression in Triple-Negative Breast Cancer
Authors: Gao Bo , Liu Xiumin , Li Zhengjin , Zhao Lixian , Pan Yun
Published: February 2021

Two histone methyltransferases, enhancer of zeste homolog 2 (EZH2) and nuclear SET domain-containing 2 (NSD2), are aberrantly expressed in several types of human cancers. However, the regulatory relationship between EZH2 and NSD2 and their prognostic values in breast cancer (BC) have not been fully elucidated. In this study, we demonstrated that EZH2 and NSD2 were overexpressed in BC compared with benign lesions and normal tissues using tissue microarray, immunohistochemistry, and bioinformatic databases. Both EZH2 and NSD2 expression were associated with pathological grade of tumor and lymph node metastasis. A comprehensive survival analysis using Kaplan-Meier Plotter database indicated that EZH2 expression was negatively correlated with relapse-free survival (RFS), overall survival (OS), distant metastasis-free survival (DMFS), and postprogression survival (PPS) in 3951 BC patients, and NSD2 expression was negatively correlated with RFS and DMFS. Notably, EZH2 and NSD2 expression were coordinately higher in triple-negative breast cancer (TNBC) than that in other subtypes. Stable knockdown of EZH2 using lentiviral shRNA vector significantly reduced the proliferation, migration and invasion abilities of TNBC cell line MDA-MB-231 and MDA-MB-468, and downregulated NSD2 expression as well as the levels of H3K27me3 and H3K36me2, two histone methylation markers catalyzed by EZH2 and NSD2, respectively. By contrast, overexpression of EZH2 using adenovirus vector displayed an inverse phenotype. Furthermore, knockdown of NSD2 in EZH2-overexpressing cells could dramatically attenuate EZH2-mediated oncogenic effects. Bioinformatic analysis further revealed the function and pathway enrichments of co-expressed genes and interactive genes of EZH2/NSD2 axis, suggesting that EZH2/NSD2 axis was associated with cell division, mitotic nuclear division and transition of mitotic cell cycle in TNBC. Taken together, EZH2/NSD2 axis may act as a predictive marker for poor prognosis and accelerate the progression of TNBC.
Obesity Connected Metabolic Changes in Type 2 Diabetic Patients Treated With Metformin
Authors: Aleidi Shereen M. , Dahabiyeh Lina A. , Gu Xinyun , Al Dubayee Mohammed , Alshahrani Awad , Benabdelkamel Hicham , Mujammami Muhammad , Li Liang , Aljada Ahmad , Abdel Rahman Anas M.
Published: February 2021

Metformin is widely used in the treatment of Type 2 Diabetes Mellitus (T2DM). However, it is known to have beneficial effects in many other conditions, including obesity and cancer. In this study, we aimed to investigate the metabolic effect of metformin in T2DM and its impact on obesity. A mass spectrometry (MS)-based metabolomics approach was used to analyze samples from two cohorts, including healthy lean and obese control, and lean as well as obese T2DM patients on metformin regimen in the last 6 months. The results show a clear group separation and sample clustering between the study groups due to both T2DM and metformin administration. Seventy-one metabolites were dysregulated in diabetic obese patients (30 up-regulated and 41 down-regulated), and their levels were unchanged with metformin administration. However, 30 metabolites were dysregulated (21 were up-regulated and 9 were down-regulated) and then restored to obese control levels by metformin administration in obese diabetic patients. Furthermore, in obese diabetic patients, the level of 10 metabolites was dysregulated only after metformin administration. Most of these dysregulated metabolites were dipeptides, aliphatic amino acids, nucleic acid derivatives, and urea cycle components. The metabolic pattern of 62 metabolites was persistent, and their levels were affected by neither T2DM nor metformin in obesity. Interestingly, 9 metabolites were significantly dysregulated between lean and obese cohorts due to T2DM and metformin regardless of the obesity status. These include arginine, citrulline, guanidoacetic acid, proline, alanine, taurine, 5-hydroxyindoleacetic acid, and 5-hydroxymethyluracil. Understanding the metabolic alterations taking place upon metformin treatment would shed light on possible molecular targets of metformin, especially in conditions like T2DM and obesity.
Role of PI3-Kinase in Angiotensin II-Induced Cardiac Hypertrophy: Class I Versus Class III
Authors: Zhong Tiecheng , Wang Zonggui , Niloy Sayeman Islam , Shen Yue , O’Rourke Stephen T. , Sun Chengwen
Published: February 2021

Cardiac hypertrophy is an adaptive response to cardiac overload initially but turns into a decompensated condition chronically, leading to heart failure and sudden cardiac death. The molecular mechanisms involved in cardiac hypertrophy and the signaling pathways that contribute to the switch from compensation to decompensation are not fully clear. The aim of the current study was to examine the role of PI3-kinases Class I (PI3KC1) and Class III (PI3KC3) in angiotensin (Ang) II-induced cardiac hypertrophy. The results demonstrate that treatment of cardiomyocytes with Ang II caused dose-dependent increases in autophagy, with an increasing phase followed by a decreasing phase. Ang II-induced autophagic increases were potentiated by inhibition of PI3KC1 with LY294002, but were impaired by inhibition of PI3KC3 with 3-methyladenine (3-MA). In addition, blockade of PI3KC1 significantly attenuated Ang II-induced ROS production and cardiomyocyte hypertrophy. In contrast, blockade of PI3KC3 potentiated Ang II-induced ROS production and cardiac hypertrophy. Moreover, blockade of PI3KC1 by overexpression of dominant negative p85 subunit of PI3KC1 significantly attenuated Ang II-induced cardiac hypertrophy in normotensive rats. Taken together, these results demonstrate that both PI3KC1 and PI3KC3 are involved in Ang II-induced cardiac hypertrophy by different mechanisms. Activation of PI3KC1 impairs autophagy activity, leading to accumulation of mitochondrial ROS, and, hence, cardiac hypertrophy. In contrast, activation of PI3KC3 improves autophagy activity, thereby reducing mitochondrial ROS and leads to a protective effect on Ang II-induced cardiac hypertrophy.
Pathogenesis of Acute Kidney Injury in Coronavirus Disease 2019
Authors: Qian Jing-Yi , Wang Bin , Lv Lin-Li , Liu Bi-Cheng
Published: February 2021

Since the outbreak of Coronavirus Disease 2019 (COVID-19) in Wuhan, China, in December of 2019, it has rapidly become a global pandemic. Although acute respiratory disorder is the main manifestation of COVID-19, acute kidney injury (AKI) is another important extrapulmonary complication, which has a critical impact on the prognosis and mortality of patients. Current understanding about the exact pathogenesis of AKI in COVID-19 is unclear. Several studies have suggested that intrarenal, pre-renal and post-renal factors mediated collaboratively by direct virus attack, overloaded immune responses, drugs, sepsis, coagulation dysfunction, and underlying diseases may all be involved in the pathogenesis of AKI. This article reviews the current understanding of the pathogenesis of AKI in COVID-19.
Impact of Time-Restricted Feeding to Late Night on Adaptation to a 6 h Phase Advance of the Light-Dark Cycle in Mice
Authors: Ren Baoyin , Ma Changxiao , Chen Lihong , FitzGerald Garret A. , Yang Guangrui
Published: February 2021

In modern society, more and more people suffer from circadian disruption, which in turn affects health. But until now, there are no widely accepted therapies for circadian disorders. Rhythmic feeding behavior is one of the most potent non-photic zeitgebers, thus it has been suggested that it was important to eat during specific periods of time (time-restricted feeding, TRF) so that feeding is aligned with environmental cues under normal light/dark conditions. Here, we challenged mice with a 6 h advanced shift, combined with various approaches to TRF, and found that food restricted to the second half of the nights after the shift facilitated adaptation. This coincided with improved resilience to sepsis. These results raise the possibility of reducing the adverse responses to jet lag by subsequent timing of food intake.
Carvacrol, a Plant Metabolite Targeting Viral Protease (Mpro) and ACE2 in Host Cells Can Be a Possible Candidate for COVID-19
Authors: Javed Hayate , Meeran Mohamed Fizur Nagoor , Jha Niraj Kumar , Ojha Shreesh
Published: February 2021

The recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started in December 2019, resulting in the coronavirus disease-19 (COVID-19) pandemic. Coronaviruses are solely accountable for rising mortality and socioeconomic saddles. Presently, there are few repurposed drugs such as remdesivir or favipiravir approved for the treatment of COVID-19, although vaccines and plasma therapy is also subject to emergency approval. However, some potential natural treatments and cures have also been proposed. Molecules of natural origin showed therapeutic importance such as antiviral, anti-inflammatory, and antioxidant activity, and could be useful drug candidates for treating COVID-19. In recent years, essential oils have shown promising therapeutic effects against many viral diseases. Carvacrol is one of the monoterpene phenol with abundant presence in essential oils of many aromatic plants, including thyme and oregano. It is being used as food flavoring, additive, and preservatives. Carvacrol is also used as a fragrance in cosmetic products. A number of research studies have shown biological actions of carvacrol with its therapeutic potential is of clinical significance. The in vitro and in vivo studies have shown multiple pharmacological properties such as anticancer, anti-fungal, anti-bacterial, anti-oxidant, anti-inflammatory, vasorelaxant, hepatoprotective, and spasmolytic. This review highlights the various biological and pharmacological properties of carvacrol within the scope of COVID-19.
How and Why Does the Attitude-Behavior Gap Differ Between Product Categories of Sustainable Food? Analysis of Organic Food Purchases Based on Household Panel Data
Authors: Schäufele Isabel , Janssen Meike
Published: February 2021

Organic agriculture promotes the transformation toward sustainability because of positive effects for the environment. The organic label on food products enables consumers to make more sustainable purchasing decisions. Although the global market for organic food has grown rapidly in recent years, only a part of the organic product range benefits from this positive trend. To develop the organic market further, it is important to understand the food-related values and attitudes that drive the purchase of organic food. Previous research on this topic has suffered from two main weaknesses. Firstly, most studies have been based on surveys and rely on stated behavior instead of actual purchase behavior. Secondly, the focus of most extant studies is predominantly on organic food in general or on food products with a relatively high organic market share, such as milk and eggs. To address this knowledge gap, the present study analyzes the value-attitude-behavior relationship by means of structural equation modeling using household purchase panel data from GfK. The paper provides evidence for the existence of an attitude-behavior gap in the organic market, with this gap found to be much stronger in the case of meat, frozen food, cheese, and sweets than for organic purchases in total. Analysis in different product categories reveals that while purchase behavior is driven by the same food-related values, their relative importance differs.
Knowledge and Will: An Explorative Study on the Implementation of School-Wide Positive Behavior Support in Sweden
Authors: Nylén Kata , Karlberg Martin , Klang Nina , Ogden Terje
Published: February 2021

School-wide positive behavior support (SWPBIS) is a well-evaluated school approach to promoting a positive school climate and decreasing problem behaviors. Initial implementation is one of the most critical stages of program implementation. In this qualitative study, the initial implementation of SWPBIS in Swedish schools was studied using an implementation model of behavior change as guidance for interviews and analyses. The study makes significant contributions to previous research as little is known of the implementation of SWPBIS in Swedish context. Focus-group interviews were conducted with 59 professionals on implementation teams from nine schools. Themes were extracted according to implementation team members' perceptions and descriptions of how the initial implementation was carried out. The results of this study revealed relevant themes within the three domains of Capability, Opportunity, and Motivation. Core features were found under the themes of knowledge and experience of similar evidence-based programs, process or result orientation, time, manual content, organizational prerequisites, team functioning, implementation leadership, program as a unifying factor, program aligning with staff beliefs, plausible expectations, and emotional reinforcement. Results are discussed in terms of how they can be used in continuing to develop the Swedish model of SWPBIS. Implications regarding implementation in Swedish schools are discussed, as is the applicability of the model of behavior change for studying implementation in schools.
Changes in Relationship Commitment Across the Transition to Parenthood: Pre-pregnancy Happiness as a Protective Resource
Authors: Ter Kuile Hagar , Finkenauer Catrin , van der Lippe Tanja , Kluwer Esther S.
Published: February 2021

The transition to parenthood is both a joyous and a challenging event in a relationship. Studies to date have found mostly negative effects of the birth of the first child on the parental relationship. We propose that partners' pre-pregnancy individual happiness may serve as a buffer against these negative effects. We predicted that parents who are happy prior to pregnancy fare better in terms of relationship commitment after childbirth than unhappy parents. To test our prediction, we used data of a 5-wave longitudinal study among 109 Dutch newlywed couples who had their first child during the study and a comparison group of 55 couples who remained childless. We found that the relationship commitment of fathers with higher pre-pregnancy happiness and fathers with a partner with higher pre-pregnancy happiness increased slightly in the years after childbirth, whereas the relationship commitment of fathers with lower pre-pregnancy happiness and fathers with a partner with lower pre-pregnancy happiness decreased. In addition, the relationship commitment of mothers with a happier partner prior to pregnancy decreased only slightly across the transition to parenthood but showed a steeper decline for mothers with a partner with average or lower pre-pregnancy happiness. In line with the idea that happiness acts as a resource when partners have to deal with relationship challenges, individual happiness predicted changes in relationship commitment for parents, but not for partners who remained childless.
Superior Performance in Skilled Golfers Characterized by Dynamic Neuromotor Processes Related to Attentional Focus
Authors: Wang Kuo-Pin , Frank Cornelia , Tsai Yen-yu , Lin Kao-Hung , Chen Tai-Ting , Cheng Ming-Yang , Huang Chung-Ju , Hung Tsung-Min , Schack Thomas
Published: February 2021

The meshed control theory assumes that cognitive control and automatic processes work together in the natural attention of experts for superior performance. However, the methods adopted by previous studies limit their capacity to provide in-depth information on the neuromotor processes. This experiment tested the theory with an alternative approach. Twelve skilled golfers were recruited to perform a putting task under three conditions: (1) normal condition, with no focus instruction (NC), (2) external focus of attention condition (EC), and (3) internal focus of attention condition (IC). Four blocks of 10 putts each were performed under each condition. The putting success rate and accuracy were measured and electroencephalographies (EEGs) were recorded. The behavioral results showed that the NC produced a higher putting success rate and accuracy than the EC and IC. The EEG data showed that the skilled golfers’ attentional processes in the NC initially resembled those in the EC and then moved toward those in the IC just before putting. This indicates a switch from more automatic processes to cognitive control processes while preparing to putt. The findings offer support for the meshed control theory and indicate the dynamic nature of neuromotor processes for the superior performance of athletes in challenging situations.