bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptomic Analysis Identified ARHGAP Family as a Novel Biomarker Associated With Tumor-Promoting Immune Infiltration and Nanomechanical Characteristics in Bladder Cancer
Authors: Yang Chen , Wu Siqi , Mou Zezhong , Zhou Quan , Zhang Zheyu , Chen Yiling , Ou Yuxi , Chen Xinan , Dai Xiyu , Xu Chenyang , Liu Na , Jiang Haowen
Published: July 2021

Bladder cancer (BCa) is a common lethal urinary malignancy worldwide. The role of ARHGAP family genes in BCa and its association with immuno-microenvironment remain largely unknown. ARHGAP family expression and immune infiltration in BCa were analyzed by bioinformatics analysis. Then, we investigated cell proliferation, invasion, and migration in vivo and in vitro of the ARHGAP family. Furthermore, atomic force microscopy (AFM) was employed in measuring cellular mechanical properties of BCa cells. The results demonstrated that ARHGAP family genes correlate with a tumor-promoting microenvironment with a lower Th1/Th2 cell ratio, higher DC cell infiltration, higher Treg cell infiltration, and T-cell exhaustion phenotype. Silencing ARHGAP5, ARHGAP17, and ARHGAP24 suppressed BCa cell proliferation, migration, and metastasis. Knocking down of ARHGAPs in T24 cells caused a relatively higher Young’s modulus and lower adhesive force and cell height. Taken together, ARHGAP family genes promote BCa progressing through establishing a tumor-promoting microenvironment and promoting cancer progression.
Development and Validation of a Ferroptosis-Related Gene Signature for Overall Survival Prediction in Lung Adenocarcinoma
Authors: Tian Qi , Zhou Yan , Zhu Lizhe , Gao Huan , Yang Jin
Published: July 2021

Background: Ferroptosis is an iron-dependent programmed cell death process. Recent studies have found that ferroptosis inducers hold promising potential in the treatment of lung adenocarcinoma (LUAD). However, the comprehensive analysis about the prognostic value of ferroptosis-related genes in LUAD remains to be elucidated.

Methods: The RNA sequencing data and corresponding clinical information were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A total of 259 ferroptosis-related genes were extracted from FerrDb website. The ferroptosis-related prognostic signature was developed by least absolute shrinkage and selection operator (LASSO) Cox regression analysis in TCGA LUAD cohort, and then validated by 5 independent GEO cohorts. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were performed to identify the difference in biological processes and functions between different risk groups. The expression levels of core prognostic genes were then verified in LUAD samples by immunohistochemistry (IHC) and erastin-treated LUAD cell lines by real-time polymerase chain reaction (PCR). The potential roles of GPX2 and DDIT4 as ferroptosis drivers in LUAD cell line were further confirmed by in vitro experiments.

Results: A total of 20 intersecting genes between 70 ferroptosis-related DEGs and 45 potential prognostic genes were obtained for LASSO Cox regression analysis. The ferroptosis-related prognostic signature was developed by 7 core prognostic DEGs, and stratified LUAD patients into two risk groups. Kaplan-Meier analysis showed that the overall survival (OS) of LUAD patients in the high-risk group was significantly worse than that of the low-risk group. External validation of 5 independent GEO cohorts further confirmed that the ferroptosis-related prognostic signature was an ideal biomarker for predicting the survival of LUAD patients. Significant enrichment of fatty acid metabolism and cell cycle-related pathways were found in different risk groups. The expression patterns of 7 core prognostic genes in LUAD and adjacent normal lung tissues were validated by IHC, which was almost consistent with the results from public database. Furthermore, the changes related to cell cycle and ferroptosis after erastin treatment were also validated in LUAD cell lines. In addition, silencing GPX2 or DDIT4 could partially reverse the erastin-induced ferroptosis.

Conclusion: In summary, the ferroptosis-related prognostic signature based on 7 core prognostic DEGs indicated superior predictive performance of LUAD patients. Targeting ferroptosis holds potential to be a therapeutic alternative for LUAD.
RNA Methylation in Systemic Lupus Erythematosus
Authors: Lv Xinyi , Liu Xiaomin , Zhao Ming , Wu Haijing , Zhang Wuiguang , Lu Qianjin , Chen Xiangmei
Published: July 2021

Systemic lupus erythematosus (SLE) is an autoimmune disease with complicated clinical manifestations. Although our understanding of the pathogenesis of SLE has greatly improved, the understanding of the pathogenic mechanisms of SLE is still limited by disease heterogeneity, and targeted therapy is still unavailable. Substantial evidence shows that RNA methylation plays a vital role in the mechanisms of the immune response, prompting speculation that it might also be related to the occurrence and development of SLE. RNA methylation has been a hot topic in the field of epigenetics in recent years. In addition to revealing the modification process, relevant studies have tried to explore the relationship between RNA methylation and the occurrence and development of various diseases. At present, some studies have provided evidence of a relationship between RNA methylation and SLE pathogenesis, but in-depth research and analysis are lacking. This review will start by describing the specific mechanism of RNA methylation and its relationship with the immune response to propose an association between RNA methylation and SLE pathogenesis based on existing studies and then discuss the future direction of this field.
Binary Surfactant–Mediated Tunable Nanotip Growth on Gold Nanoparticles and Applications in Photothermal Catalysis
Authors: Mi Xiaohu , Zhang Tingting , Zhang Baobao , Ji Min , Kang Bowen , Kang Chao , Fu Zhengkun , Zhang Zhenglong , Zheng Hairong
Published: July 2021

Plasmonic nanostructures with sharp tips are widely used for optical signal enhancement because of their strong light-confining abilities. These structures have a wide range of potential applications, for example, in sensing, bioimaging, and surface-enhanced Raman scattering. Au nanoparticles, which are important plasmonic materials with high photothermal conversion efficiencies in the visible to near-infrared region, have contributed greatly to the development of photothermal catalysis. However, the existing methods for synthesizing nanostructures with tips need the assistance of poly(vinylpyrrolidone), thiols, or biomolecules. This greatly hinders signal detection because of stubborn residues. Here, we propose an efficient binary surfactant–mediated method for controlling nanotip growth on Au nanoparticle surfaces. This avoids the effects of surfactants and can be used with other Au nanostructures. The Au architecture tip growth process can be controlled well by adjusting the ratio of hexadecyltrimethylammonium bromide to hexadecyltrimethylammonium chloride. This is due to the different levels of attraction between Br−/Cl− and Au3+ ions. The surface-enhanced Raman scattering and catalytic abilities of the synthesized nanoparticles with tips were evaluated by electromagnetic simulation and photothermal catalysis experiments (with 4-nitrothiophenol). The results show good potential for use in surface-enhanced Raman scattering applications. This method provides a new strategy for designing plasmonic photothermal nanostructures for chemical and biological applications.
Interferon-lambda 3 and 4 Polymorphisms Increase Sustained Virological Responses and Regulate Innate Immunity in Antiviral Therapy With Pegylated Interferon-Alpha
Authors: Silva Andréa Marques Vieira da , Alvarado-Arnez Lucia Elena , Azamor Tamiris , Batista-Silva Leonardo Ribeiro , Leal-Calvo Thyago , Bezerra Ohanna Cavalcanti de Lima , Ribeiro-Alves Marcelo , Kehdy Fernanda de Souza Gomes , Neves Patrícia Cristina da Costa , Bayma Camilla , Silva Jane da , Souza Alessandro Fonseca de , Muller Marcelo , Andrade Elisabete Ferreira de , Andrade Ana Carolina Magalhães , Santos Eliane Matos dos , Xavier Janaína Reis , Maia Maria De Lourdes De Sousa , Meireles Rolando Páez , Cuni Hugo Nodarse , Sander Guilherme Becker , Picon Paulo Dornelles , Matos Denise C S , Moraes Milton Ozório
Published: July 2021

Sustained virologic response (SVR) in chronic hepatitis C (CHC) treatment denotes that the host genetics controls the immune response and unequivocally contribute to viral clearance or disease severity. In this context, single nucleotide polymorphisms (SNPs) in the locus of interferon lambda 3 and 4 genes (IFNL3/4) have been important genetic markers of responsiveness to CHC as prognostic markers for the pegylated-Interferon-alpha/ribavirin (Peg-IFN-α/RBV). Here, we analyzed 12 SNPs at the IFNL3/4 region in 740 treatment-naïve patients with CHC infected with hepatitis C virus (HCV) genotypes 1, 2, or 3 treated with Peg-IFN-α/RBV. Individually, rs12979860-CC, rs8109886-CC, or rs8099917-TT were predictive markers of SVR, while rs12979860-CC demonstrated the stronger effect. Besides, the genotypic combination of these three predictors’ genotypes, CC/CC/TT, increased the rate of SVR. Serum levels of cytokines and gene expression analysis on the genes IFNL3, IFNL4, IFNA1, and some of the IFN-stimulated genes (ISGs) were measured in a subgroup of 24 treated patients and 24 healthy volunteers. An antagonist effect was highlighted between the expression of IFNL3/4 and IFNA1 mRNA among patients. Besides, a prominent production of the pro-inflammatory chemokines CCL4 and CXCL10 was observed at a 12-week treatment follow-up. Lower serum levels of these chemokines were detected in patients with an rs12979860-CC genotype associated with the better treatment outcome. Also, lower expression levels of the IFI6, IFI16, IRF9 genes were observed among rs12979860-CC individuals. In conclusion, a combination of the genotypes at the IFNL3/4 locus can act as a better marker for the prognosis for virological responses in an admixed Brazilian population presenting the modulating effect over innate immunity and inflammation that are controlling the outcome of the viral infection, but also other infectious diseases. This study is registered on the ClinicalTrials.gov platform (accession number NCT01889849 and NCT01623336).
Prognostic Value of Natriuretic Peptides for All-Cause Mortality, Right Ventricular Failure, Major Adverse Events, and Myocardial Recovery in Advanced Heart Failure Patients Receiving a Left Ventricular Assist Device: A Systematic Review
Authors: Janssen Eva , Jukema J. Wouter , Beeres Saskia L. M. A. , Schalij Martin J. , Tops Laurens F.
Published: July 2021

Aims: Major adverse event (MAE) rates during left ventricular assist device (LVAD) therapy in advanced heart failure (HF) patients are high, and impair quality of life and survival. Prediction and risk stratification of MAEs in order to improve patient selection and thereby outcome during LVAD therapy is therefore warranted. Circulating natriuretic peptides (NPs) are strong predictors of MAEs and mortality in chronic HF patients. However, whether NPs can identify patients who are at risk of MAEs and mortality or tend toward myocardial recovery after LVAD implantation is unclear. The aim of this systematic review is to analyze the prognostic value of circulating NP levels before LVAD implantation for all-cause mortality, MAEs and myocardial recovery after LVAD implantation.

Methods and Results: Electronic databases were searched for studies analyzing circulating NP in adults with advanced HF before LVAD implantation in relation to mortality, MAEs, or myocardial recovery after LVAD implantation. Twenty-four studies published between 2008 and 2021 were included. Follow-up duration ranged from 48 hours to 5 years. Study sample size ranged from 14 to 15,138 patients. Natriuretic peptide levels were not predictive of all-cause mortality. However, NPs were predictive of right ventricular failure (RVF) and MAEs such as ventricular arrhythmias, moderate or severe aortic regurgitation, and all-cause rehospitalization. No relation between NPs and myocardial recovery was found.

Conclusion: This systematic review found that NP levels before LVAD implantation are not predictive of all-cause mortality after LVAD implantation. Thus, NP levels may be of limited value in patient selection for LVAD therapy. However, NPs help in risk stratification of MAEs and may be used to identify patients who are at risk for RVF, ventricular arrhythmias, moderate or severe aortic regurgitation, and all-cause rehospitalization after LVAD implantation.
Research on Deep Convolutional Neural Network Time-Frequency Domain Seismic Signal Denoising Combined With Residual Dense Blocks
Authors: Gao Zhitao , Zhang Song , Cai Jianxian , Hong Li , Zheng Jiangshan
Published: July 2021

Deep Convolutional Neural Networks (DCNN) have the ability to learn complex features and are thus widely used in the field of seismic signal denoising with low signal-to-noise ratio (SNR). However, the current convolutional deep network used for seismic signal noise reduction does not make full use of the feature information extracted from all convolution layers in the network, and thus cannot fit the seismic signal with high SNR. To deal with this problem, this paper proposes the DnRDB model, a convolutional deep network time-frequency domain seismic signal denoising model combined with residual dense blocks (RDB). The model is mainly composed of several RDB in series. The input of each convolution layer in each RDB module is formed by the output of all the previous convolution layers. Meanwhile, even if the number of layers is increased, the fusion of the seismic signal features learned by the RDB modules can still achieve full extraction of seismic signals. Furthermore, deepening the model structure by concatenating multiple RDB modules enables further useful feature information to be extracted, which improves the SNR of seismic signals. The DnRDB model was trained and tested using the Stanford Global Seismic Dataset. The experimental results show that the DnRDB model can effectively recover seismic signals and remove various forms of noise. Even in the case of high noise, the denoised signal still has a high SNR. When the DnRDB model is compared with other denoising approaches such as wavelet threshold, empirical mode decomposition, and different deep learning methods, the results indicate that it performs best overall in denoising the same segment of the noisy seismic signal; the denoised signal also has less waveform distortion. Use of the DnRDB model in subsequent seismic signal processing work indicates that it can help the phase recognition algorithm improve the accuracy of seismic recognition through noise reduction.
Assessing the Social Validity of the SAFMEDS Strategy From the Perspective of Teachers and Children
Authors: Owen Kaydee , Watkins Richard C. , Beverley Michael , Hughes J. Carl
Published: July 2021

The Say-All-Fast-Minute-Every-Day-Shuffled (SAFMEDS) strategy promotes fluency across several skills and contexts. However, few studies have reported the social validity key stakeholders associate with using the strategy in schools. Assessing social validity may provide us with some insight into factors that may affect engagement, implementation fidelity, and persistent use of the intervention after the termination of a research study. Study 1 details the findings from a survey completed by teachers who have used the strategy in their schools (N = 55). Using thematic analysis, we identified three themes: 1) factors that promote and limit progress, 2) confidence, and 3) inherent advantages of the SAFMEDS strategy. These themes encapsulate teachers experiences of implementing the strategy under the real-word conditions of the classroom and the accompanying advantages and potential challenges they face. Within study 2, we discuss themes arising from interviews with children (N = 26) about their views and experiences of using the SAFMEDS strategy. These children had used the strategy with their teacher for one academic year to promote fast and accurate recall of arithmetic facts. Analysis of these transcripts revealed five further themes relating to children’s engagement with the strategy: 1) enjoyment, 2) data, 3) sense of achievement, 4) skills, and 5) home use. Collectively these themes have potential impact with regards to future training and support models for the SAFMEDS strategy.
Omics Multi-Layers Networks Provide Novel Mechanistic and Functional Insights Into Fat Storage and Lipid Metabolism in Poultry
Authors: Ghafouri Farzad , Bahrami Abolfazl , Sadeghi Mostafa , Miraei-Ashtiani Seyed Reza , Bakherad Maryam , Barkema Herman W. , Larose Samantha
Published: July 2021

Fatty acid metabolism in poultry has a major impact on production and disease resistance traits. According to the high rate of interactions between lipid metabolism and its regulating properties, a holistic approach is necessary. To study omics multilayers of adipose tissue and identification of genes and miRNAs involved in fat metabolism, storage and endocrine signaling pathways in two groups of broiler chickens with high and low abdominal fat, as well as high-throughput techniques, were used. The gene–miRNA interacting bipartite and metabolic-signaling networks were reconstructed using their interactions. In the analysis of microarray and RNA-Seq data, 1,835 genes were detected by comparing the identified genes with significant expression differences (p.adjust < 0.01, fold change ≥ 2 and ≤ −2). Then, by comparing between different data sets, 34 genes and 19 miRNAs were detected as common and main nodes. A literature mining approach was used, and seven genes were identified and added to the common gene set. Module finding revealed three important and functional modules, which were involved in the peroxisome proliferator-activated receptor (PPAR) signaling pathway, biosynthesis of unsaturated fatty acids, Alzheimer’s disease metabolic pathway, adipocytokine, insulin, PI3K–Akt, mTOR, and AMPK signaling pathway. This approach revealed a new insight to better understand the biological processes associated with adipose tissue.
Defining Cost-Effective Solutions in Designing Marine Protected Areas, Using Systematic Conservation Planning
Authors: Galparsoro Ibon , Borja Ángel
Published: July 2021

Environmental conservation is currently one of the main objectives of marine management. It is agreed that effective management requires evaluating the tradeoffs between protection and economic costs for negatively impacted maritime activities. For these reasons, integrated approaches combining ecological and socio-economic aspects are needed to achieve nature conservation and sustainability targets. Here, we present an approach to identify cost-effective priority marine areas for protection through a Systematic Conservation Planning method, adopting the Basque Country as case study (SE Bay of Biscay). Eight protection scenarios were defined, targeting a combination of protection features: benthic habitats, biological value of cetaceans, birds, macroalgae, and macroinvertebrates, potential provision of ecosystem services, and habitat sensitivity to human activities. In turn, the total fishing pressure produced by artisanal fisheries was adopted as a measure of the socio-economic costs of protection (assuming, for this research, that fishing would be banned in the protected areas). The results indicated that existing marine protected areas (MPAs) were very close to achieving prescribed protection targets, while these targets could be achieved by increasing the size of the existing MPAs. Higher costs were associated with the declaration of areas that were targeting a larger number of protection features. Nevertheless, cost/effectiveness was higher in these cases, with the environmental benefits outweighing a comparatively smaller increase in cost. However, the most cost-effective scenarios were those that included the extension of already existing MPAs. The method implemented can assist managers and decision makers in identifying conservation gaps and ecosystem components that require special attention. In addition, the approach can be used to develop management strategies that may be adopted under different protection scenarios. Thus, the approach proposed here could be used to inform ecosystem-based marine spatial planning.
Theoretical Study of Abnormal Thermal Expansion of CuSCN and Effect on Electronic Structure
Authors: Sun Pengju , Gao Qilong , Liu Junzhe , Liang Erjun , Sun Qiang
Published: July 2021

CuSCN, as a new type of inorganic hole-transporting semiconductor with a wide bandgap (>3.4 eV), is attracting much attention in the fabrication of perovskite solar cells. In this article, by using first-principles density functional theory (DFT) and the quasi-harmonic approximation (QHA) approach, we have studied lattice dynamics and abnormal thermal expansion of the system, including α- and β-CuSCN phases. The influence of the abnormal thermal expansion of the lattice on the electronic structure, especially on the bandgap of the system, was explored and discussed. We found that due to the shearing modes and the three acoustic modes along the direction of the c-axis, the α- and β-CuSCN show a negative thermal expansion (NTE) in the direction of the c-axis. The torsion modes of the Cu–N–C–S atomic chains in the α-CuSCN may lead to an NTE in the directions of the a, b-axes of the α-phase. As a result, our theoretical results demonstrated that the α-CuSCN exhibits an anisotropic bulk NTE. While the β-CuSCN displays a strong uniaxial negative thermal expansion in the direction of the c-axis, in the directions of the a, b-axes, it exhibits positive thermal expansion. Our DFT calculations also predicted that the α-CuSCN has a direct bandgap, which increases slightly with increasing temperature. However, the β-CuSCN has an indirect bandgap at low temperature, which converts to a direct bandgap near the temperature of 375 K due to the strong positive expansion in the ab plane of the phase. Our work revealed the mechanisms of the abnormal thermal expansion of the two phases and a strong coupling between the anisotropic thermal expansion and the electronic structures of the system.
Elevation of Serum Cytokine Profiles and Liver Metabolomic Normalization in Early Convalescence of COVID-19 Patients
Authors: Lou Yan , He Xiaoying , Deng Mingxia , Hu Xingjiang , Yang Xi , Liu Lin , Hu Yunzhen , He Lingjuan , Wang Jiali , Zhang Li , Zhao Qingwei , Lu Xiaoyang , Qiu Yunqing
Published: July 2021

Coronavirus disease 2019 (COVID-19) has become a global public health concern. We aimed to study the cytokine profile during the convalescent phase and its association with liver functions. We performed a retrospective study to investigate the longitudinal dynamic serum cytokine, liver function, and metabolomic profiles, as well as their potential correlations, from the viral replication phase to early convalescence. Our results demonstrated that liver injury was common. Liver injury was significantly associated with higher levels of interleukin (IL)-6 and IL-10 (p < 0.05). However, alanine aminotransferase levels decreased during the first week after hospital discharge (p < 0.01). In parallel, T-cell and B-cell immune response-stimulating cytokine IL-4, but not IL-2, was significantly elevated (p < 0.05). Furthermore, interferon-γ (IFN-γ) and tumor necrosis factor-α (TFN-α) levels increased, in contrast to the decrease in IL-6 and IL-10 levels; liver function returned to normal. The metabolomic analysis supported active recovery during early convalescence of COVID-19 patients that had distinct metabolic profiles associated with the hepatic tricarboxylic acid cycle, amino acid metabolism, and lipid metabolism. In addition, we identified a metabolomic association of IL-4 with liver repair. Our findings suggest that discharged patients continue to recover from the physiological effects of COVID-19, and the association of IL-4, IL-6, and IL-10 levels with metabolic changes and liver function repair may have important implications for clinical manifestations and treatment of COVID-19.
Microbial Profiles of Retail Pacific Oysters (Crassostrea gigas) From Guangdong Province, China
Authors: Yu Mingjia , Wang Xiaobo , Yan Aixian
Published: July 2021

Oysters are one of the main aquatic products sold in coastal areas worldwide and are popular among consumers because of their delicious taste and nutritional value. However, the microorganisms present in oysters may pose health risks to consumers. In this study, the microbial communities of Pacific oysters (Crassostrea gigas) collected from aquatic product markets in three cities (Guangzhou, Zhuhai, and Jiangmen) of Guangdong Province, China, where raw oysters are popular, were investigated. The plate counts of viable bacteria in oysters collected in the three cities were all approximately 2 log colony-forming units/g. High-throughput sequencing analysis of the V3–V4 region of the 16Sribosomal DNA gene showed a high level of microbial diversity in oysters, as evidenced by both alpha and beta diversity analysis. Proteobacteria, Bacteroidetes, and Firmicutes were the dominant phyla of the microorganisms present in these samples. A variety of pathogenic bacteria, including the fatal foodborne pathogen Vibrio vulnificus, were found, and Vibrio was the dominant genus. Additionally, the relationship between other microbial species and pathogenic microorganisms may be mostly symbiotic in oysters. These data provide insights into the microbial communities of retail oysters in the Guangdong region and indicate a considerable risk related to the consumption of raw oysters.
Epigenetic Mechanisms in DNA Double Strand Break Repair: A Clinical Review
Authors: Fernandez Alejandra , O’Leary Connor , O’Byrne Kenneth J , Burgess Joshua , Richard Derek J , Suraweera Amila
Published: July 2021

Upon the induction of DNA damage, the chromatin structure unwinds to allow access to enzymes to catalyse the repair. The regulation of the winding and unwinding of chromatin occurs via epigenetic modifications, which can alter gene expression without changing the DNA sequence. Epigenetic mechanisms such as histone acetylation and DNA methylation are known to be reversible and have been indicated to play different roles in the repair of DNA. More importantly, the inhibition of such mechanisms has been reported to play a role in the repair of double strand breaks, the most detrimental type of DNA damage. This occurs by manipulating the chromatin structure and the expression of essential proteins that are critical for homologous recombination and non-homologous end joining repair pathways. Inhibitors of histone deacetylases and DNA methyltransferases have demonstrated efficacy in the clinic and represent a promising approach for cancer therapy. The aims of this review are to summarise the role of histone deacetylase and DNA methyltransferase inhibitors involved in DNA double strand break repair and explore their current and future independent use in combination with other DNA repair inhibitors or pre-existing therapies in the clinic.
Single Image Defogging Method Based on Image Patch Decomposition and Multi-Exposure Image Fusion
Authors: Liu Qiuzhuo , Luo Yaqin , Li Ke , Li Wenfeng , Chai Yi , Ding Hao , Jiang Xinghong
Published: July 2021

Bad weather conditions (such as fog, haze) seriously affect the visual quality of images. According to the scene depth information, physical model-based methods are used to improve image visibility for further image restoration. However, the unstable acquisition of the scene depth information seriously affects the defogging performance of physical model-based methods. Additionally, most of image enhancement-based methods focus on the global adjustment of image contrast and saturation, and lack the local details for image restoration. So, this paper proposes a single image defogging method based on image patch decomposition and multi-exposure fusion. First, a single foggy image is processed by gamma correction to obtain a set of underexposed images. Then the saturation of the obtained underexposed and original images is enhanced. Next, each image in the multi-exposure image set (including the set of underexposed images and the original image) is decomposed into the base and detail layers by a guided filter. The base layers are first decomposed into image patches, and then the fusion weight maps of the image patches are constructed. For detail layers, the exposure features are first extracted from the luminance components of images, and then the extracted exposure features are evaluated by constructing gaussian functions. Finally, both base and detail layers are combined to obtain the defogged image. The proposed method is compared with the state-of-the-art methods. The comparative experimental results confirm the effectiveness of the proposed method and its superiority over the state-of-the-art methods.
MANF Is Neuroprotective in Early Stages of EAE, and Elevated in Spinal White Matter by Treatment With Dexamethasone
Authors: Nam Jinhan , Koppinen Tapani K. , Voutilainen Merja H.
Published: July 2021

Multiple sclerosis (MS) is a progressive autoimmune disease characterized by T-cell mediated demyelination in central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) is a widely used in vivo disease model of MS. Glucocorticoids such as dexamethasone (dex) function as immunosuppressants and are commonly used to treat acute exacerbations of MS. Dex is also often used as a positive control in EAE studies, as it has been shown to promote motor behavior, inhibit immune cell infiltration into the CNS and regulate the activation of glial cell in EAE. This study further validated the effects of intravenously administrated dex by time-dependent fashion in EAE. Dex postponed clinical signs and motor defects in early stages of EAE. Histological analysis revealed that the degeneration of myelin and axons, as well as the infiltration of peripheral immune cells into the white matter of spinal cord was inhibited by dex in early stages of EAE. Additionally, dex-treatment delayed the neuroinflammatory activation of microglia and astrocytes. Furthermore, this study analyzed the expression of the neurotrophic factor mesencephalic astrocyte-derived neurotrophic factor (MANF) in EAE, and the effect of treatment with dex on MANF-expression. We show that in dex-treated EAE mice expression MANF increased within myelinated areas of spinal cord white matter. We also show that intravenous administration with hMANF in EAE mice improved clinical signs and motor behavior in the early stage of EAE. Our report gives insight to the progression of EAE by providing a time-dependent analysis. Moreover, this study investigates the link between MANF and the EAE model, and shows that MANF is a potential drug candidate for MS.
What Do We Mean by Behavioral Disinhibition in Frontotemporal Dementia?
Authors: Magrath Guimet Nahuel , Miller Bruce L. , Allegri Ricardo F. , Rankin Katherine P.
Published: July 2021

Behavioral variant frontotemporal dementia, unlike other forms of dementia, is primarily characterized by changes in behavior, personality, and language, with disinhibition being one of its core symptoms. However, because there is no single definition that captures the totality of behavioral symptoms observed in these patients, disinhibition is an umbrella term used to encompass socially disruptive or morally unacceptable behaviors that may arise from distinct neural etiologies. This paper aims to review the current knowledge about behavioral disinhibition in this syndrome, considering the cultural factors related to our perception of behavior, the importance of phenomenological interpretation, neuroanatomy, the brain networks involved and, finally, a new neuroscientific theory that offers a conceptual framework for understanding the diverse components of behavioral disinhibition in this neurodegenerative disorder.
The Importance of Reporting Energy Values of Human Milk as Metabolizable Energy
Authors: Fenton Tanis R. , Elmrayed Seham
Published: July 2021

Nutrition science has a convention to report metabolizable energy instead of gross energy. Metabolizable energy at 4 kilocalories per gram for protein and carbohydrate, 9 kcal per gram for fat (kilojoules: 17 and 37, respectively) represents the food energy available for metabolism. However, this convention to use metabolizable energy has not been uniformly applied to human milk. Human milk is often reported as gross energy, which is about 5–10% higher than metabolizable energy. To obtain accurate human milk energy estimates, milk samples need to contain the same proportion of high fat hind milk that an infant obtains.
Efficacy and Safety of Transarterial Chemoembolization in Elderly Patients of Advanced Hepatocellular Carcinoma With Portal Vein Tumor Thrombus: A Retrospective Study
Authors: Tang Qinghe , Huang Wei , Liang Jun , Xue Junli
Published: July 2021

Objective

The aim of the current study was to evaluate the safety and efficacy of transcatheter arterial chemoembolization (TACE) in elderly patients diagnosed as advanced hepatocellular carcinoma (HCC) accompanied with different types of portal vein tumor thrombosis (PVTT).

Methods

Elderly HCC patients aged 70-year-old and above from January 2015 to December 2019 were included in this retrospective study. Efficacy data including OS, PFS, DCR, and ORR and safety data were collected in the indicated groups. Outcomes of HCC patients in the TACE group were compared with those patients in the best supportive care (BSC) group. Subgroup analyses were also conducted in the patients with different types of PVTT.

Results

Among 245 elderly HCC patients, 124 were enrolled in this study. Out of these, 50.0% (n=62) underwent BSC treatment while 50.0% (n=62) underwent TACE. There were no major differences in the baseline characteristics of the two treatment groups. TACE treatment was associated with better median OS compared with BSC alone (11.30 m vs. 7.80 m; P<0.001). Subgroup analyses showed that patients with type I and type II PVTT could benefit from TACE compared with BSC, based on that OS was 14.30 m vs. 7.80 m (P=0.007) and 13.00 m vs. 8.00 m (P=0.002), respectively. The DCR in the TACE group was 62.90%, and 17.74% in the BSC group (p<0.001). The proportion of ORR in TACE group was 35.48%, while 0.00% in the BSC group (p<0.001). Multivariable analyses showed that patients undergoing TACE treatment had 52% lower odds of mortality compared with patients undergoing BSC treatment (HR: 0.48; 95%CI: 0.32-0.72). Similarly, the media PFS was improved following TACE treatment (7.50 m vs. 4.00 m; P<0.001). TACE could significantly prolong the PFS in both type I and type II PVTT subgroups, without greatly significant improvement in type III PVTT patients (4.50 m vs. 2.70 m; P=0.103). Type III PVTT patients in the TACE group had more AEs than type I and type II PVTT patients. According to multivariable analyses, PVTT types (type III vs. type I-II) (HR: 2.18; 95%CI: 1.29-3.70; P=0.004), tumor diameter (>5 cm vs. ≤5 cm) (HR: 1.94; 95%CI: 1.28-2.93; P=0.002), and treatment (TACE vs. BSC) (HR: 0.48; 95%CI: 0.32-0.72; P<0.001) were independent indicators of overall survival.

Conclusions

In elderly advanced HCC patients with PVTT, palliative TACE treatment can be an accessible effective measure to improve the OS and PFS for both type I and type II PVTT patients.
Lamprey Immune Protein Mediates Apoptosis of Lung Cancer Cells Via the Endoplasmic Reticulum Stress Signaling Pathway
Authors: Song Xiaoping , Xu Xiangting , Lu Jiali , Chi Xiaoyuan , Pang Yue , Li Qingwei
Published: July 2021

Lamprey immune protein (LIP), a novel protein derived from the Lampetra japonica, has been shown to exert efficient tumoricidal actions without concomitant damage to healthy cells. Our study aimed to ascertain the mechanisms by which LIP inhibits lung cancer cells, thus delineating potential innovative therapeutic strategies. LIP expression in lung cancer cells was evaluated by western blotting and immunohistochemistry. Functional assays, such as high-content imaging, 3D-structured illumination microscopy (3D-SIM) imaging, flow cytometry, and confocal laser scanning microscopy, were performed to examine the proliferation and lung cancer cell apoptosis. Tumor xenograft assays were performed using an in vivo imaging system. We observed that LIP induces the decomposition of certain lung cancer cell membranes by destroying organelles such as the microtubules, mitochondria, and endoplasmic reticulum (ER), in addition to causing leakage of cytoplasm, making the maintenance of homeostasis difficult. We also demonstrated that LIP activates the ER stress pathway, which mediates lung cancer cell apoptosis by producing reactive oxygen species (ROS). In addition, injection of LIP significantly retarded the tumor growth rate in nude mice. Taken together, these data revealed a role of LIP in the regulation of lung cancer cell apoptosis via control of the ER stress signaling pathway, thus revealing its possible application in lung cancer treatment.
Clinical Implications of Nonbiological Factors With Colorectal Cancer Patients Younger Than 45 Years
Authors: Liu Qi , Zhang Ruoxin , Li Qingguo , Li Xinxiang
Published: July 2021

Background

To evaluate the clinical implications of non-biological factors (NBFs) with colorectal cancer (CRC) patients younger than 45 years.

Methods

In the present study, we have conducted Cox proportional hazard regression analyses to evaluate the prognosis of different prognostic factors, the hazard ratios (HRs) were shown with 95% confidence intervals (CIs). Kaplan–Meier method was utilized to compare the prognostic value of different factors with the log-rank test. NBF score was established according to the result of multivariate Cox analyses.

Results

In total, 15129 patients before 45 years with known NBFs were identified from the SEER database. Only county-level median household income, marital status and insurance status were NBFs that significantly corelated with the cause specifical survival in CRC patients aged less than 45 years old (P < 0.05). Stage NBF 1 showed 50.5% increased risk of CRC-specific mortality (HR = 1.505, 95% CI = 1.411-1.606, P < 0.001). Stage NBF 0 patients were associated with significantly increased CRC-specific survival (CCSS) when compared with the stage NBF 1 patients in different AJCC TNM stages.

Conclusions

NBF stage (defined by county-level median household income, marital status and insurance status) was strongly related to the prognosis of CRC patients. NBFs should arouse enough attention of us in clinical practice of patients younger than 45 years.
Identification of Predictive Biomarkers for Lymph Node Involvement in Obese Women With Endometrial Cancer
Authors: López-Ozuna Vanessa M. , Kogan Liron , Hachim Mahmood Y. , Matanes Emad , Hachim Ibrahim Y. , Mitric Cristina , Kiow Lauren Liu Chen , Lau Susie , Salvador Shannon , Yasmeen Amber , Gotlieb Walter H.
Published: July 2021

Obesity, an established risk factor for endometrial cancer (EC), is also associated to increased risks of intraoperative and postoperative complications. A reliable tool to identify patients at low risk for lymph node (LN) metastasis may allow minimizing the surgical staging and omit lymphadenectomy in obese patients. To identify molecular biomarkers that could predict LN involvement in obese patients with EC we performed gene expression analysis in 549 EC patients using publicly available transcriptomic datasets. Patients were filtrated according to cancer subtype, weight (>30 kg/m2) and LN status. While in the LN+ group, NEB, ANK1, AMIGO2, LZTS1, FKBP5, CHGA, USP32P1, CLIC6, CEMIP, HMCN1 and TNFRSF10C genes were highly expressed; in the LN- group CXCL14, FCN1, EPHX3, DDX11L2, TMEM254, RNF207, LTK, RPL36A, HGAL, B4GALNT4, KLRG1 genes were up-regulated. As a second step, we investigated these genes in our patient cohort of 35 patients (15 LN+ and 20 LN-) and found the same correlation with the in-silico analysis. In addition, immunohistochemical expression was confirmed in the tumor tissue. Altogether, our findings propose a novel panel of genes able to predict LN involvement in obese patients with endometrial cancer.
Hypertension in Children and Adolescents: A Position Statement From a Panel of Multidisciplinary Experts Coordinated by the French Society of Hypertension
Authors: Bouhanick Béatrice , Sosner Philippe , Brochard Karine , Mounier-Véhier Claire , Plu-Bureau Geneviève , Hascoet Sébastien , Ranchin Bruno , Pietrement Christine , Martinerie Laetitia , Boivin Jean Marc , Fauvel Jean Pierre , Bacchetta Justine
Published: July 2021

Hypertension is much less common in children than in adults. The group of experts decided to perform a review of the literature to draw up a position statement that could be used in everyday practice. The group rated recommendations using the GRADE approach. All children over the age of 3 years should have their blood pressure measured annually. Due to the lack of data on cardiovascular morbidity and mortality associated with blood pressure values, the definition of hypertension in children is a statistical value based on the normal distribution of blood pressure in the paediatric population, and children and adolescents are considered as having hypertension when their blood pressure is greater than or equal to the 95th percentile. Nevertheless, it is recommended to use normative blood pressure tables developed according to age, height and gender, to define hypertension. Measuring blood pressure in children can be technically challenging and several measurement methods are listed here. Regardless of the age of the child, it is recommended to carefully check for a secondary cause of hypertension as in 2/3 of cases it has a renal or cardiac origin. The care pathway and principles of the therapeutic strategy are described here.
Sequential Treatment of Biliary Atresia With Kasai Hepatoportoenterostomy and Liver Transplantation: Benefits, Risks, and Outcome in 393 Children
Authors: Tambucci Roberto , de Magnée Catherine , Szabo Margot , Channaoui Aniss , Pire Aurore , de Meester de Betzenbroeck Vanessa , Scheers Isabelle , Stephenne Xavier , Smets Françoise , Sokal Etienne M. , Reding Raymond
Published: July 2021

Introduction: Surgical treatment of biliary atresia (BA) is still based on sequential strategy with Kasai hepatoportoenterostomy (KP) followed by liver transplantation (LT), in case of complicated secondary biliary cirrhosis. Concerns have been expressed regarding the risks of LT related to previous KP, suggesting primary LT as an exclusive treatment of BA.

Methods: Single-center retrospective analysis including 393 pediatric patients who underwent LT for BA from 1993 to 2018, categorized into two groups: with (KP) or without (NoKP) previous KP. Pre-LT clinical condition was estimated considering age at LT, time on waiting list, pediatric end-stage liver disease score (PELD), and presence of portal vein hypoplasia. Post-LT outcome was evaluated considering patient and graft survival rates, and need for early reoperation due to abdominal or graft-related complications (<45 days after LT).

Results: Two-hundred ninety-six patients (75.3%) were categorized in the KP group, and 97 (24.7%) in the NoKP group. Median age at LT was 1.14 years in the KP group and 0.85 years in the NoKP group (p < 0.0001). PELD score was significantly less severe in KP patients (p < 0.05). One-year patient survival rates were 96.9 and 96.8% in the KP and NoKP groups, respectively (p = 0.43), and the corresponding graft survival was 92.5 and 94.8% (p = 0.97). The need for early reoperation was more frequent in the KP group (29.8%) vs. NoKP group (12.4%, p = 0.01). The rate of bowel perforation was non-significantly higher in the KP group (8.1%) vs. NoKP group (3.1%, p = 0.11).

Conclusions: The sequential strategy including KP and LT allowed performing LT in patients with significant older age and better clinical conditions, when compared to those transplanted without previous KP. Patient and graft survivals were not impacted by previous KP. Although previous KP was associated with an increased rate of post-LT surgical complications, bowel perforation and bleeding did not occur significantly more frequently. Such results support the current strategy based on sequential treatment.
An Ethnobotanical Study of Medicinal Plants in Mersin (Turkey)
Authors: Emre Gizem , Dogan Ahmet , Haznedaroglu Mehmet Zeki , Senkardes Ismail , Ulger Mahmut , Satiroglu Aysen , Can Emmez Berivan , Tugay Osman
Published: July 2021

This comprehensive ethnobotanical study carried out in Mersin province, which is located in the southern part of Anatolia, east of the Mediterranean Sea, compiles details on plants used in folk medicine and ethnopharmacological information obtained through face-to-face interviews. The aim was to collect and identify plants used for therapeutic purposes by local people and to record information on traditional herbal medicine. Plant specimens were collected in numerous excursions. Additionally, informant consensus factor and use value (UV) were calculated for information gathered. This study identifies 93 plant taxa belonging to 43 families and records their usage in folk medicine; 83 taxa are wild and the remaining 10 are cultivated. The most commonly used plants belong to Lamiaceae, representing 15.0% of the total, while the Rosaceae, Malvaceae, Hypericaceae, Asteraceae and Cupressaceae families each represented another 5.4%. As a result of this investigation, we determine 189 medicinal usages of 93 taxa. The UV values indicate that the most important medicine plants are Hypericum perforatum (0.80), Cedrus libani (0.78), Quercus coccifera (0.77), Arum dioscoridis (0.76) and Juniperus drupaceae (0.74). We observed that most of the drugs are prepared using the infusion method (27.6%). As a conclusion, the study finds that traditional folk medicine usage is still common, especially among the rural population of Mersin.
Antitumor Effects of Carvacrol and Thymol: A Systematic Review
Authors: Sampaio Laeza Alves , Pina Lícia Tairiny Santos , Serafini Mairim Russo , Tavares Débora dos Santos , Guimarães Adriana Gibara
Published: July 2021

Background: It is estimated that one in five people worldwide faces a diagnosis of a malignant neoplasm during their lifetime. Carvacrol and its isomer, thymol, are natural compounds that act against several diseases, including cancer. Thus, this systematic review aimed to examine and synthesize the knowledge on the antitumor effects of carvacrol and thymol.

Methods: A systematic literature search was carried out in the PubMed, Web of Science, Scopus and Lilacs databases in April 2020 (updated in March 2021) based on the PRISMA 2020 guidelines. The following combination of health descriptors, MeSH terms and their synonyms were used: carvacrol, thymol, antitumor, antineoplastic, anticancer, cytotoxicity, apoptosis, cell proliferation, in vitro and in vivo. To assess the risk of bias in in vivo studies, the SYRCLE Risk of Bias tool was used, and for in vitro studies, a modified version was used.

Results: A total of 1,170 records were identified, with 77 meeting the established criteria. The studies were published between 2003 and 2021, with 69 being in vitro and 10 in vivo. Forty-three used carvacrol, 19 thymol, and 15 studies tested both monoterpenes. It was attested that carvacrol and thymol induced apoptosis, cytotoxicity, cell cycle arrest, antimetastatic activity, and also displayed different antiproliferative effects and inhibition of signaling pathways (MAPKs and PI3K/AKT/mTOR).

Conclusions: Carvacrol and thymol exhibited antitumor and antiproliferative activity through several signaling pathways. In vitro, carvacrol appears to be more potent than thymol. However, further in vivo studies with robust methodology are required to define a standard and safe dose, determine their toxic or side effects, and clarify its exact mechanisms of action.

This systematic review was registered in the PROSPERO database (CRD42020176736) and the protocol is available at https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=176736.