bluuebunny/crossref_metadata_2025 huggingface dataset:
MAPK Signaling Pathway was Dysregulated in Acute Myeloid Leukemia with RUNX1 Mutations
Authors: he Mingmin , Cai Xiongwei , Zeng Yuanyuan
Published: May 2021

The purpose of this study was to investigate the relationship between RUNX1 mutations and MAPK signaling pathway in acute myeloid leukemia (AML). In this study, we analyzed miRNA expression with 5 mutant RUNX1 and 9 wild-type RUNX1 cases from TCGA database of AML. Six miRNAs were differently expressed with significance, and three of them were related to overall survival. Predicted target genes of these 3 miRNAs were highly enriched in MAPK signaling pathway by functional enrichment with miRWalk3.0. Besides, genes among RUNX1 associated genes directly regulated by RUNX1 were involved in MAPK signaling pathway, too. Taken together, we demonstrate three DEmiRNAs and three genes correlated to RUNX1 were correlated with prognosis in AML, and RUNX1 modulated MAPK signaling pathway in AML.
Surface Charge-Dependent Mitochondrial Response to Similar Intracellular Nanoparticle Contents at Sublethal Dosages
Authors: Jin Xiaoting , Yu Haiyi , Zhang Ze , Cui Tenglong , Wu Qi , Liu Xiaolei , Gao Jie , Zhao Xingchen , Shi Jianbo , Qu Guangbo , Jiang Guibin
Published: May 2021

Background: Considering the inevitability for humans to be frequently exposed to nanoparticles (NPs), understanding the biosafety of NPs is important for rational usage. As an important part of the innate immune system, macrophages are widely distributed in vital tissues and are also a dominant cell type that engulfs particles. Mitochondria are one of the most sensitive organelles when macrophages are exposed to NPs. However, previous studies have mainly reported the mitochondrial response upon high-dose NP treatment. Herein, with gold nanoparticles (AuNPs) as a model, we investigated the mitochondrial alterations induced by NPs at a sublethal concentration.Results: At a similar internal exposure dose, different AuNPs showed distinct degrees of effects on mitochondrial alterations, including reduced tubular mitochondria, damaged mitochondria, increased reactive oxygen species (ROS), and decreased adenosine triphosphate (ATP). Cluster analysis, two-way ANOVA, and multiple linear regression suggested that the surface properties of AuNPs were the dominant determinants of the mitochondrial response. Based on the correlation analysis, the mitochondrial response was increased with the change in zeta potential from negative to positive. The alterations in mitochondrial respiratory chain proteins indicated that complex V was an indicator of the mitochondrial response to low-dose NPs.Conclusion: Our current study suggests potential hazards of modified AuNPs on mitochondria even under sublethal dose, indicates the possibility of surface modification in biocompatibility improvement, and provides a new way to better evaluation of nanomaterials biosafety.
Environmental Enrichment Protects Offspring of Preeclamptic-Like Rat Model From Cognitive Decline
Authors: Lu Huiqing , Gong Lili , Xu Huangfang , Zhou Qiongjie , Zhao Huanqiang , Wu Suwen , Hu Rong , Li Xiaotian
Published: May 2021

Background: Preeclampsia affects 5-8% of all pregnancies and contributes to adverse pregnancy and birth outcome. In addition to short-term effects of preeclampsia, it can exert long-term adverse effects on offspring. Numerous studies has demonstrated that offspring of preeclamptic women exhibited cognitive deficit from childhood to old age. However, effective ways to improving their cognitive ability remains to be investigated. The aim of this study was to explore whether Environmental Enrichment in early life could restore cognitive ability of offspring of preeclampsia rat model, as well as cellular and molecular mechanism by which EE improve cognitive ability.Methods: L-NAME was used to establish preeclampsia rat model. The spatial learning and memory ability of 56-day-old offspring was evaluated by Morris Water Maze. Immunofluorescence was performed to evaluate cell proliferation and apoptosis in the DG region of hippocampus. qRT-PCR was performed to examine the expression level of neurogenesis-associated genes and inflammatory cytokines. Enzyme-linked immune absorbent assay was performed to evaluate the concentration of Vascular endothelial growth factor (VEGF) and inflammatory cytokines in the hippocampus.Results: The administration of L-NAME led to increased systolic blood pressure and urine protein level of pregnant rat. Offspring in L-NAME group exhibited impaired spatial learning ability and memory. The hippocampus neurogenesis and synaptic plasticity was impaired in offspring of L-NAME group. Furthermore, the cell apoptosis in hippocampus was increased in L-NAME group. The hippocampus was skewed to a pro-inflammatory profile, reflected by increased inflammatory cytokines level. While EE improved cognitive ability of offspring in L-NAME group and resulted in increased hippocampal neurogenesis and synaptic proteins expression level, decreased apoptosis level and inflammatory cytokines.Conclusions: Environment Enrichment resolves cognitive impairment in offspring of preeclampsia rat model by improving hippocampal neurogenesis and synaptic plasticity, normalizing the apoptosis level and the inflammation balance.
Metagenomics Revealing Molecular Profiling of Microbial Community Structure and Metabolic Capacity In Bamucuo, Tibet
Authors: Wei Cai , Sun Dan , Yuan Wenliang , Li Lei , Dai Chaoxu , Chen Zuozhou , Zeng Xiaomin , Wang Shihang , Tang Yifan , Jiang Shouwen , Wu Zhichao , Peng Xiaoning , Jiang Linhua , peng Sihua
Published: May 2021

Background: The Qinghai-Tibet Plateau (QTP) is the highest plateau in the world, and the microorganisms there play vital ecological roles in the global biogeochemical cycle; however, detailed information on the microbial communities in QTP is still lacking. Results: Here, we performed a landscape survey of the microorganisms in Bamucuo, Tibet, resulting in 160,212 (soil) and 135,994 (water) contigs by shotgun metagenomic methods, and generated 75 nearly complete metagenome-assembled genomes (MAGs). Proteobacteria, Actinobacteria and Firmicutes were found to be the three most dominant bacterial phyla, while Euryarchaeota was the most dominant archaeal phylum. Surprisingly, Pandoravirus salinus was found in the soil microbial community. The KEGG annotations showed that the genes related to metabolism accounted for 62.9% (soil) and 58.4% (water), respectively. Of the 75 MAGs, 63 were found to contain the genes related to all the six carbon fixation pathways, and the heavy metal resistance genes, the pressure response subsystem, and the secondary metabolite biosynthesis gene clusters (BGCs) were discovered to be abundant. Conclusions: We concluded that the microorganisms in Bamucuo fix carbon mainly through the 3-hydroxypropionic bi-cycle pathway; this study, for the first time, characterized the microbial community composition and metabolic capacity in QTP high-altitude areas (with an altitude of 4,555 meters), confirmed that QTP is a huge and valuable resource bank in which more new non-resistant antibiotics and many other bioactive substances could be developed, and provided the expanded information for further microbial community studies in QTP.
Improved Catalytic Performance of Carrier-Free Immobilized Lipase by Advanced Cross-Linked Enzyme Aggregates Technology
Authors: Jiaojiao Xia , Yan Yan , Zou Bin , Onyinye Adesanya Idowu
Published: May 2021

The cross-linked enzyme aggregates (CLEAs) are one of the technologies that quickly immobilize the enzyme without a carrier. This carrier-free immobilization method has the advantages of simple operation, high reusability and low cost. In this study, ionic liquid with amino group (1-aminopropyl-3-methylimidazole bromide，IL) was used as the novel functional surface molecule to modify industrialized lipase (Candida rugosa lipase, CRL). The enzymatic properties of the prepared CRL-FIL-CLEAs were investigated. The activity of CRL-FIL-CLEAs (5.51 U/mg protein) was 1.9 times higher than that of CRL-CLEAs without surface modification (2.86 U/mg protein). After incubation at 60℃ for 50 min, CRL-FIL-CLEAs still maintained 61% of its initial activity, while the value for CRL-CLEAs was only 22%. After repeated use for five times, compared with the 22% residual activity of CRL-CLEAs, the value of CRL-FIL-CLEAs was 51%. Further kinetic analysis indicated that the Km values for CRL-FIL-CLEAs and CRL-CLEAs were 4.80 mM and 8.06 mM, respectively, which was inferred that the affinity to substrate was increased after modification. Based on the above results, it was indicated that this method provided a new idea for the effective synthesis of immobilized enzyme.
Comparing Infant and Toddler Sleep Patterns Prior to and During the First Wave of Home Confinement Due to COVID-19 in Spain
Authors: Cassanello Pia , Irene Ruiz-Botia , Pere Sala-Castellvi , Carlos Martin Juan , Martínez-Sanchez Jose , Albert Balaguer
Published: May 2021

IntroductionRecent literature has shown that sleep patterns are shaped during the first years of life, playing a relevant role in children’s functioning. We focused on comparing sleep patterns in infants and toddlers in Spain before and during COVID-19 home confinement to assess the immediate impact on sleep patterns. Methodse compared data from two cross-sectional surveys from parents of 1,658 children three to 36 months of age from Spain. One conducted before COVID-19 (2017-2018, n=1,380) and another during COVID-19 pandemic (March-May of 2020, n=254). We used an internet self-administrated questionnaire using the Brief Infant Sleep Questionnaire (BISQ) criteria in both surveys.ResultsDuring confinement infants and toddlers went to sleep later (median bedtime 21.5 before confinement vs. 21.6 during confinement p=0.004). We found a statistically significant increase in infants’ and toddlers’ sleep latency by >30 minutes during confinement (p<0.001). Based on the recommended BISQ criteria for classifying inadequate sleep patterns, we observed a statistically significant increase in poor sleepers meeting at least one criterion during confinement (p<0.001). ConclusionsParents during COVID-19 home confinement reported several factors affecting the quality of their children’s sleep. Follow-up studies can help understand the potential long-term effects of the COVID-19 pandemic on sleep patterns.
Spatial Modeling of Relationship Between Soil Erosion Factors and Land-use Changes at Sub-Watershed Scale for the Talar Watershed, Iran
Authors: Mircholli Fahimeh , Khanghah Maziar Mohammadi , Sadeghi Seyed Hamidreza
Published: May 2021

Soil erosion is one of the most common types of land degradation. To provide useful information for proper management, quantitative soil erosion evaluation and identification of effective factors are needed. However, rare studies have been reported on spatial modeling of soil erosion in connection with affective factors to prioritize the locality and the type of erosion control measures Hence, the aim of this study was to (1) assess erosion-prone areas in the Talar Watershed, Iran, using the Revised Universal Soil Loss Equation (RUSLE) model, and (2) investigate the relationship between soil erosion variability and land-use changes. Toward that, the ordinary least squares (OLS), geographically weighted regression (GWR) models, and Principal Component Analysis (PCA) were used to analyze spatial relationships between soil erosion, and land-use, and the RUSLE factors. The results of the OLS and GWR models indicated these relationships are spatially non-stationary and GWR models had a good predictive performance rather than OLS with lower Akaike's Information Criterion (from 254.31 to 276.81 in OLS, and from 247.87 to 269.42 in GWR) and higher adjusted R2 values (from 0.12 to 0.54 in OLS, and from 0.36 to 0.66 in GWR). Among the aforementioned variables, LS factor, P factor, forest, and irrigated land were the most effective variables in GWR models. The results of PCA showed PC1 and PC2 explained 66.2 % of the variation in soil erosion concerning land-use and the RUSLE factors. These results provided appropriate references for managers and experts in the proper planning of the study watershed.
Microscopic Nuclei Classification, Segmentation, and Detection with improved Deep Convolutional Neural Networks (DCNN)
Authors: Alom Md Zahangir , Asari Vijayan K. , Parwani Anil , Taha Tarek M.
Published: May 2021

BackgroundNuclei classification, segmentation, and detection from pathological images are challenging tasks due to cellular heterogeneity in the Whole Slide Images (WSI).MethodsIn this work, we propose advanced DCNN models for nuclei classification, segmentation, and detection tasks. The Densely Connected Neural Network (DCNN) and Densely Connected Recurrent Convolutional Network(DCRN) models are applied for the nuclei classification tasks. The Recurrent Residual U-Net (R2U-Net) and the R2UNet-based regression model named as the University of Dayton Net (UD-Net) are applied for nuclei segmentation and detection tasks respectively.The experiments are conducted on publicly available datasets including Routine Colon Cancer (RCC) classification and detection and the Nuclei Segmentation Challenge 2018 datasets for segmentation task. The performance of the proposed methods is compared against the existing approaches in terms of precision, recall, Dice Coefficient (DC), Mean Squared Error (MSE), F1-score, and overall testing accuracy by performing pixels and cell-level analysis.ResultsThe experimental results demonstrate around 2.2% and 4.5% higher performance in terms of F1-score for nuclei classification and detection tasks when compared to the recently published DCNN based method. Also, for nuclei segmentation, the R2U-Net shows around 91.63% testing accuracy in terms of DC which is around 0.76% higher compared to the U-Net model.ConclusionThe proposed methods demonstrate robustness with better quantitative and qualitative results in three different tasks for analyzing the WSI.
The Effect of Preserving Pregnancy in Cervical Cancer Diagnosed During Pregnancy: A Retrospective Study
Authors: He Zuoxi , Xie Chuan , Qi Xiaorong , Hu Zhengjun , He Yuedong
Published: May 2021

ObjectiveCervical cancer diagnosed during pregnancy is a rare event, and data regarding efficacy of cancer treatment during pregnancy is limited. This study aimed to assess the safety of continuation of the pregnancy for mother and fetus when concomitantly diagnosed with cervical cancer.MethodsThis study retrospectively analyzed all cervical cancer patients diagnosed while pregnant or immediately postpartum, inclusive from Jan 2010 to June 2019 at our institute. Patient clinical details and follow-up were obtained from hospital records. ResultsThe study comprised 40 patients with clinical cancer stages of ⅠA1 (1/40, 2.5%); ⅠB1 (15/40, 37.5%); IB2 (10/40, 25%); ⅡA (12/40, 30%); and ⅡB (2/40, 5%). There were 38 patients diagnosed during pregnancy, and 2 diagnosed in the postpartum period. Of the 38 patients, 17 were diagnosed in the first trimester, 13 in the second trimester, and 8 in the third trimester. Ten of 38 patients (26.3%) continued their pregnancy after learning of their diagnosis; 7 (70%) in the third trimester and 3 (30%) in the second trimester. The mean time from diagnosis to surgery in the patients who continued their pregnancy was 52.7 days, which was statistically significantly greater than the termination of pregnancy group (52.7 vs 16.3 days, P < 0.01). Notably, there was no survival difference between the 2 groups (100% vs 90.91%, P =0.54), and none of the pregnant women who ultimately died had delayed treatment due to pregnancy. Similarly, the surgical estimated blood loss and operative duration comparing the 2 groups were not significantly different. ConclusionsIn the present study, the gestational age of pregnancy at the time of initial diagnosis of cervical cancer was an important determinant in the disease management. Continuation of the pregnancy when diagnosed with cervical cancer did not affect the oncologic outcome of the mother nor increase either surgical or obstetric complications. Additionally, the use of neoadjuvant chemotherapy did not threaten the health of the fetus. These results may be useful in counseling patients facing the diagnosis of cervical cancer during pregnancy.
MMP-14-targeted Nanoprobe for in vivo Fluorescence Imaging of Rupture-prone Carotid Plaques
Authors: Han Mengtao , Liu Kaining , Xiao Hongqiu , Sun Tao , Wang Fei , He Yiming , Wang Donghai
Published: May 2021

Background: The identification of rupture-prone carotid plaques for preventing stroke remains a clinical challenge. Macrophage matrix metalloproteinase (MMP)-14, which contributes to plaque progression and destabilisation, could be a promising biomarker for plaque imaging. This study aimed to design and synthesise an MMP-14-targeted nanoprobe to noninvasively visualise the behaviour of M1 macrophages in atherosclerotic plaques.Methods: A fluorescence molecular imaging probe (AuNPs@PEG-Peptide-Cy5.5) was constructed by covalently attaching the fluorescent dye cyanine (Cy) 5.5, an MMP-14 substrate, and polyethylene glycol (PEG) 5000-wrapped gold nanoparticles (AuNPs), and then administered via tail vein injection to carotid atherosclerosis models for in vivo fluorescence imaging. Additionally, carotid tissues and cultured macrophages were analysed for nanoprobe binding, and MMP-14 and inflammation-related marker expression was evaluated by polymerase chain reaction, western blotting, and immunohistochemistry.Results: MMP-14 expression significantly increased with plaque progression, along with the upregulation of MMP-2 and inflammatory M1 markers, CD68 and F4/80, and significant downregulation of the M2 marker CD206. All of cell, tissue and in vivo fluorescence imaging exhibited a favourable targeting efficacy of AuNPs@PEG-Peptide-Cy5.5 for MMP-14.Conclusions: MMP-14, a cell membrane-anchoring enzyme, can serve as a biomarker of vulnerable plaques, and MMP-14 substrate-based AuNPs@PEG-Peptide-Cy5.5, with an intense fluorescence signal after activation and good biocompatibility, can be applied to screen for and monitor plaque progression in vivo.
Artificial Intelligence to Predict Mortality in Critically ill COVID-19 Patients Using Data from the First 24h: A Case Study from Lombardy Outbreak
Authors: Greco Massimiliano , Angelotti Giovanni , Caruso Pier Francesco , Zanella Alberto , Stomeo Niccolò , Costantini Elena , Protti Alessandro , Pesenti Antonio , Grasselli Giacomo , Cecconi Maurizio
Published: May 2021

Introduction: SARS-CoV-2 infection was first identified at the end of 2019 in China, and subsequently spread globally. COVID-19 disease frequently affects the lungs leading to bilateral viral pneumonia, progressing in some cases to severe respiratory failure requiring ICU admission and mechanical ventilation. Risk stratification at ICU admission is fundamental for resource allocation and decision making, considering that baseline comorbidities, age, and patient conditions at admission have been associated to poorer outcomes. Supervised machine learning techniques are increasingly diffuse in clinical medicine and can predict mortality and test associations reaching high predictive performance. We assessed performances of a machine learning approach to predict mortality in COVID-19 patients admitted to ICU using data from the Lombardy ICU Network.Methods: this is a secondary analysis of prospectively collected data from Lombardy ICU network. To predict survival at 7-,14- and 28 days we built two different models; model A included patient demographics, medications before admission and comorbidities, while model B also included the data of the first day since ICU admission. 10-fold cross validation was repeated 2500 times, to ensure optimal hyperparameter choice. The only constrain imposed to model optimization was the choice of logistic regression as final layer to increase clinical interpretability. Different imputation and over-sampling techniques were employed in model training.Results 1503 patients were included, with 766 deaths (51%). Exploratory analysis and Kaplan-Meier curves demonstrated mortality association with age and gender. Model A and B reached the greatest predictive performance at 28 days (AUC 0.77 and 0.79), with lower performance at 14 days (AUC 0.72 and 0.74) and 7 days (AUC 0.68 and 0.71). Male gender, age and number of comorbidities were strongly associated with mortality in both models. Among comorbidities, chronic kidney disease and chronic obstructive pulmonary disease demonstrated association. Mode of ventilatory assistance at ICU admission and Fraction of Inspired oxygen were associated with mortality in model B.Conclusions Supervised machine learning models demonstrated good performance in prediction of 28-day mortality. 7-days and 14-days predictions demonstrated lower performance. Machine learning techniques may be useful in emergency phases to reach higher predictive performance with reduced human supervision using complex data.
Clinical Outcomes of Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma of the Extremities: Analysis of Recurrence Factors
Authors: Zeniya Toshiki , Emori Makoto , Tsuchie Hiroyuki , Nagasawa Hiroyuki , Iba Kousuke , Mizushima Emi , Keira Yoshiko , Shimizu Junya , Murahashi Yasutaka , Teramoto Atsushi , Miyakoshi Naohisa , Sugita Shintaro , Hasegawa Tadashi , Shimada Yoichi , Yamashita Toshihiko
Published: May 2021

Background: Atypical lipomatous tumors/well-differentiated liposarcomas (ALT/WDLPS) are low-grade, slow-growing, and locally aggressive tumors. We investigated clinical outcomes and recurrence factors for ALT/WDLPS of the extremities.Patients and Methods: The variables were evaluated as potential recurrence factor using Fisher’s exact test. The 5-year recurrence-free survival (RFS) rate was calculated using the Kaplan-Meier method, and differences in survival were assessed using a log-rank test in univariate analyses. Results: Sixty-two patients were identified, including 29 men and 33 women. The median age was 63.7 years (range, 34–82 years). The average maximum tumor diameter was 15.9 cm (range, 5–28 cm). The maximum tumor diameter (≥20 cm) was significantly associated with local recurrence (p=0.049). Ten patients (16.1%) developed local recurrence, and the mean time to recurrence was 48.4 months (range, 5–161 months).Conclusions: Tumor diameter ≥20 cm was identified as a risk factor for recurrence.
Effects of Systemic Diseases on Graft Preparation in Descemet Membrane Endothelial Keratoplasty
Authors: Özkan Burak , Koçluk Yusuf , Kasım Burcu
Published: May 2021

Purpose: To evaluate the effects of the systemic diseases and drugs of the donor on Descemet’s membrane (DM) graft preparation.Methods: 78 corneas of 58 donors, of whom the DM grafts were used in Descemet’s membrane endothelial keratoplasty (DMEK) surgery, between January 2018 – January 2020, were enrolled in this retrospective study. The hospital records of the donors were analyzed. Age, gender, blood type, systemic diseases, and drugs; complete blood count, biochemistry panel for liver and kidney functions in the last 48 hours, and the drugs used in the hospital, if any, in the last 24 hours were recorded. The grafts with tears that occurred while preparation, were included in group 1, and the successful grafts with no tears were included in group 2.Results: There were no statistically significant differences in the characteristics of the donors between groups. However, the breast cancer and the use of sevelamer were found to be significantly higher in group 1 (p=0.010, p=0.033, respectively)Conclusion: Although diabetic donors have been reported to be inappropriate candidates for the preparation of DM grafts for DMEK, most of the donors with several systemic diseases including diabetes can be used in DMEK surgery, with the right technique in DM graft preparation.
Numerical Investigation of Tunnel Face Sability using Forepoling or Fiberglass Nails
Authors: GEORGIOU DIMITRIOS , KAVVADAS MICHAEL , KALOS ALEXANDROS
Published: May 2021

Pre-support of tunnel excavation faces using fiberglass nails or forepoling umbrellas aims to improve face stability in cases where an unsupported excavation face will develop uncontrollably large face extrusion, leading to face instability. The paper presents the results of a large set of parametric 3D numerical analyses of tunnel face excavation by the Finite Element Code Simulia Abaqus, using various degrees of reinforcement by fiberglass nails or forepoling umbrellas. The analyses use the average face extrusion as a measure of face stability, considering that face instability is associated with large face extrusions while the safety factor against face instability can be correlated with lower face extrusions in case of pre-supported tunnel faces. The results of the analyses are normalized and a set of semi-empirical formulae and design graphs are produced to calculate the safety factor of supported tunnel faces against instability and other useful quantities in tunnel design (average face extrusion, volume loss and deconfinement coefficient) as a function of ground strength, overburden depth and amount of face reinforcement. The analyses show that tunnel face reinforcement with FG nails is much more effective and less costly in securing face stability than the use of forepoling umbrellas. It is shown that even a coarse grid of FG nails can achieve better results than very heavy forepoling, and the difference in effectiveness is more pronounced in weaker ground and or deeper tunnels.
Pitchfork and Hopf Bifurcations of Geared Systems in Permanent Contact Regime
Authors: Azimi Mohsen
Published: May 2021

Gears are known as important mechanical parts with various industrial applications. Many researchers investigated the complex nonlinear behavior of the geared systems by studying the effect of the clearance between the gears in mesh. This is while some studied the effect of both nonlinear suspension and clearance on nonlinear characteristics of such systems. Most of these studies are under assumption that the system operates under lightly loaded operational condition, where the separation of the teeth in mesh occurs. Alternatively, in this work, it is assumed that the transmitting load is big enough that gears in mesh do not separate and consequently the clearance between the teeth do not participates in the dynamic response of the system. Then analytical and numerical techniques are used to investigate the effect of nonlinear suspension on the dynamic behavior of the system. The results show that nonlinearity of the suspension has a great in uence on the creation of the nontrivial equilibria or limit cycle within the unstable regions, which for the right range of the parameters, can affect the rate of the amplitude detonation and stabilization of the system.
Statistical Feature–Based Steganalysis for Pixel-Value Differencing Steganography
Authors: Lin Wen-Bin , Lai Tai-Hung , Chang Ko-Chin
Published: May 2021

The security and embedding capacity of pixel-value differencing (PVD) steganography is superior to that of least significant bit replacement steganography. Several studies have proposed extended PVD steganography methods that use the original concept of PVD steganography. The majority of the studies have verified their security against regular-singular detection analysis or pixel difference histogram attacks. Weighted stego image steganalysis is the state-of-the-art technology for PVD steganography. This study proposed a suitable parameter for the estimator based on different relative embedding ratios and the size of normal embedding blocks. The experimental results revealed that the proposed technology does not require advance knowledge of the original image. In addition, the proposed method is accurate and precise at any embedding ratio. In the future, this method may be utilized to analyze the security of extended PVD steganography.
Microplastic Exposure Across Trophic Levels: Effects on the Host Microbiota of Freshwater Organisms
Authors: Varg Javier Edo , Outomuro David , Kunce Warren , Kuehrer Lukas , Svanbäck Richard , Johansson Frank
Published: May 2021

BackgroundMicroplastics are a pervasive pollutant widespread in sea- and freshwater from anthropogenic sources, and together with the presence of pesticides, they can have physical and chemical effects on aquatic organisms and on their microbiota. Few studies have explored the combined effects of microplastics and pesticides on the host microbiome, and more importantly, the effects across multiple trophic levels. In this work, we studied the effects of exposure to microplastics and the pesticide deltamethrin on the diversity and abundance of the host microbiome across a three-level food chain: daphnids-damselfly-dragonflies. Daphnids were the only organism exposed to 1µm microplastic beads, and they were fed to damselfly larvae. Those damselfly larvae were exposed to delthametrin, and then fed to the dragonfly larvae. The microbiotas of the daphnids, damselflies and dragonflies were analyzed. ResultsOur results suggest that the exposure to microplastics and deltamethrin had negative carry-over effects on the diversity and abundance of the microbiome across the three trophic levels. Moreover, the exposure to deltamethrin on the damselflies negatively affected their survival rate in the presence of the dragonfly predator, but no such effects were found on damselflies exposed to only microplastics. Conclusions﻿Our study highlights the importance of evaluating ecotoxicological effects at the community level. Importantly, the indirect exposure to microplastics and pesticides through diet can potentially have bottom-up effects in the trophic webs.
Clinical outcome of Laparoscopic and Robot-assisted Radical Cystectomy for Bladder Cancer in a Retrospective Study
Authors: Bai YuChen , Wang Shuai , Zheng Wei , Quan Jing , Wei Fei , Zhang Qi , Qi XiaoLong , Zhang DaHong
Published: May 2021

Background: With the rapid development of surgical technics and instruments, more and more bladder cancer patients are being treated by laparoscopic radical cystectomy (LRC) and robot-assisted radical cystectomy (RARC) .The aim of this retrospective study was to compare the perioperative and long-term outcomes of patients who underwent cystectomy by these two surgical approaches. Methods: We performed a retrospective review of the prospectively collected database of our hospital to identify patients with clinical stage Ta/T1/Tis to T3 who underwent RARC and LRC. Perioperative outcomes, recurrence, and overall survival (OS) were analyzed. Results: From March 2010 to December 2019, there were total of 218 patients, which including 82(38%) patients with LRC and 136(62%) patients with RARC. No perioperative death was observed in both groups. Tumor recurrence, death from any causes, and cancer-specific death occurred in 77, 55, and 39 patients respectively. The 5-year DFS, OS, and CSS rates for all included patients were 55.4%, 62.4%, and 66.4%, respectively. There were no significantly statistically differences between the RARC group and the LRC group for number of lymph nodes harvested, positive lymph node rate, positive margin rate and postoperative pathological stage (all P>0.05). Patients undergoing RARC had lower median estimated blood loss (180mL vs. 250 mL; P 0.015) and 90-days postoperative complications (30.8% vs. 46.3%; P 0.013) than LRC.Conclusions: For selected patients with RARC and LRC, both were safe and effective with a low complication rate and similar long-term outcome compared two groups. Moreover, the robotic approach resulted in lower median estimated blood loss and better outcome in postoperative complications.
A Phase II Study of Sequential Treatment With Anthracycline and Taxane Followed By Eribulin in Patients With HER2-Negative, Locally Advanced Breast Cancer (JBCRG-17)
Authors: Fukada Ippei , Ito Yoshinori , Kondo Naoto , Ohtani Shoichiro , Hattori Masaya , Tokunaga Eriko , Matusnami Nobuki , Mashino Kohjiro , Kosaka Taijiro , Tanabe Masahiko , Yotusmoto Daisuke , Yamanouchi Kosho , Sawaki Masataka , Kashiwaba Masahiro , Kawabata Hidetaka , Kuroi Katsumasa , Morita Satoshi , Ohno Shinji , Toi Masakazu , Masuda Norikazu
Published: May 2021

PurposeThe sequence of taxanes (T) followed by anthracyclines (A) as neoadjuvant chemotherapy (NAC) has been the standard of care for almost 20 years for locally advanced breast cancer (LABC). Sequential administration of eribulin (E) following A/T could provide a greater response rate for women with LABC.MethodsIn this single-arm, multicenter, Phase II prospective study, the patients received 4 cycles of the FEC regimen and 4 cycles of taxane. After the A/T-regimen, 4 cycles of E were administered followed by surgical resection. The primary endpoint was the clinical response rate. Eligible patients were women aged 20 years or older, with histologically confirmed invasive breast cancer, clinical Stage IIIA (T2-3 and N2 only), Stage IIIB, and Stage IIIC, HER2-negative.ResultsA preplanned interim analysis aimed to validate the trial assumptions was conducted after treatment of 20 patients and demonstrated that clinical progressive disease (cPD) rates in the E phase were significantly higher (30%) than assumed. Therefore, the Independent Data Monitoring Committee recommended stopping the study. Finally, 53 patients were enrolled, and 26 patients received the A/T/E-regimen. The overall observed clinical response rate (RR) was 73% (19/26); RRs were 77% (20/26) in the AT phase and 23% (6/26) in the E phase. Thirty percent (8/26) of patients had PD in the E phase, 6 of whom had achieved cCR/PR in the AT phase. Reported grade >3 AEs related to E were neutropenia (42%), white blood cell count decrease (27%), febrile neutropenia (7.6%), weight gain (3.8%), and weight loss (3.8%)ConclusionSequential administration of eribulin after the A/T-regimen provided no additional effect for LABC patients. Future research should continue to focus on identifying specific molecular biomarkers that can improve response rates.
Detection of SFTS Virus RNA and Total Antibodies in Wild Animals, Jiangsu, China, 2014-2019
Authors: Liang Shuyi , Li Zhifeng , Zhang Nan , Wang Xiaochen , Hu Jianli
Published: May 2021

Background Severe fever with thrombocytopenia syndrome (SFTS) is a novel infectious disease caused by severe fever with thrombocytopenia syndrome virus (SFTSV). Currently, SFTS is endemic to some areas in China, and wild animals are considered to play important roles in the circulation of SFTSV in the environment. Wild animals monitoring for SFTSV has been fulfilled since 2014 in Jiangsu Province. We studied the results of the detection to provide basic data for better diagnosis of wild animals. Methods This research was conducted in Jiangsu Province from 2014 to 2019. Sera of wild animals (Rodents, pheasants and hedgehogs) were collected to detect SFTSV both RNA and total antibodies by qRT-PCR and enzyme-linked immunosorbent assay. Statistical analysis was performed by using SPSS 25.0 (Chicago, IL, USA).Results A total of 95.8% (1298/1355) of the specimens had the same SFTSV RNA and total antibodies detection results. However, there was a significant difference between the detection rates of SFTSV RNA and total antibodies, and the detection consistency was very poor. The detection rate of SFTSV total antibodies was highest in hedgehogs(19.54%).Conclusions SFTSV total antibodies testing was preferred method during wild animals surveillance. Also, hedgehog could be a competent reservoir for SFTSV.
A Novel Signature Based on Pyroptosis-Related Genes for Predicting Breast Cancer
Authors: Shen Shuang , Chen Xin , Qu Rui , Guo Youming , Su Yingying , Jiang Hang , Luo Libo
Published: May 2021

Background: Breast cancer (BC) surpassed lung cancer as the most frequent malignant tumour in women. In recent years, pyroptosis has revealed itself as an inflammatory form of programmed cell death. However, it is unclear as to the expression of genes associated with pyroptosis in BC and its relationship to prognosis. Results: In this study, we identified 31 pyroptosis regulators that are differentially expressed between BC and normal breast. The differently expressed genes (DEG) allow BC patients to be divided into three subtypes. Through single-factor and multi-factor COX regression and the application of least absolute contraction and selection operator (LASSO) Cox regression method, the survival prognostic value of each gene related to pyroptosis in The Cancer Genome Atlas (TCGA) cohort was evaluated, and a 4-gene signature was constructed. BC patients of the TCGA cohort are divided into low-risk or high-risk groups by risk score. The survival of the low-risk group was significantly higher than the high-risk group (P <0.001). Using the median risk score from the TCGA cohort, BC patients from the Gene Expression Omnibus (GEO) cohort were divided into two risk sub-groups and similar conclusions were drawn. In combination with clinicopathological characteristics, the risk score is an independent predictive factor of OS in BC patients. Gene ontology (GO) and Kyoto Encylopedia of Genes and Genomes (KEGG) indicated that the high-risk group's immune genes were enriched and immune status was reduced. Conclusions: In conclusion, pyroptosis-related genes are important for tumour immunity and can be used to predict the prognosis of BC.
Routing Algorithms as Tools for Integrating Social Distancing with Emergency Evacuation
Authors: Tsai Yi-Lin , Rastogi Chetanya , Kitanidis Peter K. , Field Christopher B.
Published: May 2021

We explore the implications of integrating social distancing with emergency evacuation, as would be expected when a hurricane approaches a city during the COVID-19 pandemic. Specifically, we compare DNN (Deep Neural Network)-based and non-DNN methods for generating evacuation strategies that minimize evacuation time while allowing for social distancing in emergency vehicles. A central question is whether a DNN-based method provides sufficient extra routing efficiency to accommodate increased social distancing in a time-constrained evacuation operation. We describe the problem as a Capacitated Vehicle Routing Problem and solve it using a non-DNN solution (Sweep Algorithm) and a DNN-based solution (Deep Reinforcement Learning). The DNN-based solution can provide decision-makers with more efficient routing than the typical non-DNN routing solution. However, it does not come close to compensating for the extra time required for social distancing, and its advantage disappears as the emergency vehicle capacity approaches the number of people per household.
Fat-Burning or Fat-Shaming? Theme and Community Overlap Between Online, Weight-Stigmatizing and Exercise-Promoting Networks.
Authors: Rojas-Sánchez Ahuitz , Harris Jenine K. , Sarrazin Philippe , Chalabaev Aïna
Published: May 2021

Purpose: This study aimed to determine if networks of users consistently posting about exercise and fat exist and overlap on social media sites.Method: We collected 3,772,507 posts from Twitter that included the words “fat” and “exercise”. Using network structure methods, we identified communities of interconnected users and overlaps between those tweeting “fat” and those tweeting “exercise”. Results: Common word pairings were identified using Natural Language Processing (NLP). Networks of users consistently talking about exercise (n=3,573) and fat (n=2,007) were found on Twitter. An increased mean total-degree and reduced average path length indicate that the fitness-talk network serves as a connecting bridge between highly scattered communities of the weight-talk network. Conclusion: We identified groups on Twitter dedicated to consistently producing weight stigmatizing content and promoting exercise with weight-loss messages. These groups partially overlap with pro-health groups which could lead to users looking for exercise advice in Twitter to find themselves immersed in a stigmatizing network.
Assessment of Bidirectional Relationships Between 98 Genera of the Human Gut Microbiota and Amyotrophic Lateral Sclerosis: A 2-Sample Mendelian Randomization Study
Authors: Zhang Linjing , Zhuang Zhenhuang , Zhang Gan , Huang Tao , Fan Dongsheng
Published: May 2021

BackgroundGrowing evidence suggests a mutual interaction between gut microbiome alterations and ALS pathogenesis. However, previous studies were susceptible to potential confounding factors and reverse causation bias, likely leading to inconsistent and biased results. Therefore, to decipher the potentially mutual relationship between gut microbiota and ALS, we used a bidirectional two-sample MR approach to examine the associations between the gut microbiome and ALS. Effects of potential metabolites on ALS were also estimated in MR design.ResultsUsing the inverse variance-weighted method, OTU10032 unclassified Enterobacteriaceae species-level OTU and unclassified Acidaminococcaceae were associated with a higher risk of ALS (per relative abundance: OR, 1.04; 95% CI, 1.01–1.07; P = 0.011 and OR, 1.02; 95% CI, 1.01–1.04; P = 0.009, respectively). Importantly, Gamma-Glu-Phe was showed potential deleterious effects on the risk of ALS (genetically predicted per a 1-standard deviation increase in the level of Gamma-Glu-Phe: OR, 1.96; 95% CI, 1.50–2.55; P = 0.012). Sensitivity analysis of the two candidate genera and metabolites using the MR-Egger and weighted-median methods produced similar estimates, and no horizontal pleiotropy or outliers were observed. Intriguingly, genetically predicted ALS was associated with an increase in the relative abundance of OTU4607_Sutterella (per 1-unit higher log odds: β, 2.23; 95% CI, 1.27–3.18; P = 0.020) and Lactobacillales_ORDER (per 1-unit higher log odds: β, 0.51; 95% CI, 0.09–0.94; P = 0.019).ConclusionsOur findings provide novel evidence supporting the bidirectional relationship between the gut microbiota and ALS and highlight that a transsynaptic, glutaminergic, excitotoxic mechanism could provide a pathogenic basis for ALS. These results may contribute to designing microbiome- and microbiome-dependent metabolite interventions in future ALS clinical trials.
Imidacloprid Induces Oxidative Stress and Genotoxicity in Nile Tilapia: The Role of Ascorbic Acid Combined Exposure
Authors: El-Garawani Islam M. , Khallaf Elsayed A. , Alne-na-ei Alaa A. , Elgendy Rehab G. , Mersal Gaber A.M. , El-Seedi Hesham R.
Published: May 2021

Imidacloprid (Imid), a systemic neonicotinoid insecticide, is broadly used worldwide. It is reported to contaminate aquatic systems. This study was proposed to evaluate oxidative stress and genotoxicity of Imid on Nile tilapia (Oreochromis niloticus) and the protective effect of ascorbic acid (Asc). O. niloticus juveniles (30.4 ± 9.3 g, 11.9 ± 1.3 cm) were divided into six groups (n=10/replicate). For 21 days, two groups were exposed to sub-lethal concentrations of Imid (8.75 ppm, 1/20 of 72h-LC50 & 17.5 ppm, 1/10 of 72h-LC50); other two groups were exposed to Asc (50 ppm) in combination with Imid (8.75 & 17.5 ppm); one group was exposed to Asc (50 ppm) in addition to a group of unexposed fish which served as controls. Oxidative stress was assessed in the liver where the level of enzymatic activities including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) in addition to mRNA transcripts and, Lipid peroxidation (LPO) were evaluated. Moreover, mitotic index (MI) and comet assay were performed, in addition to the erythrocytic micronucleus (MN), and nuclear abnormalities (NA) were observed to assess genotoxicity in fish. Imid exposure induced significant (p˂ 0.05) changes in the antioxidant profile of the juveniles' liver by increasing the activities and gene expression of SOD, CAT and GPX as well as elevating the levels of LPO. DNA strand breaks in gill cells, erythrocytes and hepatocytes along with erythrocytic MN and NA were also significantly elevated in Imid-exposed groups. MI showed a significant (p˂ 0.05) decrease associated with Imid exposure. Asc administration induced a significant amelioration towards the Imid toxicity (8.75 & 17.5 ppm). A significant protective potency against the genotoxic effects of Imid was evidenced in Asc co-treated groups. Collectively, results highlight the importance of Asc as a protective agent against Imid-induced oxidative stress and genotoxicity in O. niloticus juveniles.
Aged Pu-Erh Tea Reduced Oxidative Stress-Mediated Inflammation in DSS-Induced Colitis Mice by Regulating Intestinal Microbes
Authors: Hu Shanshan , Li Shi , Liu Yan , Sun Kang , Luo Liyong , Zeng Liang
Published: May 2021

Background: Colitis is associated with gut microbiological disorders and oxidative stress-mediated intestinal inflammation. Pu-erh tea has been used as a beverage for bioactive potential in antioxidation and anti-inflammation. With increase of storage, the change of its bioactive components creates the difference of health care function. However, there is no evidence to show whether the storage period of Pu-erh tea affects its anti-inflammatory and anti-oxidant capacity in the colitis, or even intestinal protection. Results: In this study, 3.5% DSS-induced colitis mice were treated with 10 mg/kg bw/day extracts, aged 14 years (P2006) and unaged (P2020) Pu-erh tea respectively, for 1 week. It was found that Pu-erh tea, especially P2006, inhibited the intestinal oxidative stress-mediated inflammation signaling pathway (TLR4/MyD88/ROS/p38 MAPK/NF-κB p65), up-regulated the expression of intestinal tight junction proteins (Mucin-2, zonula occludens 1, occluding), promoted M2 polarization of macrophages, and in turn, improved the intestinal immune barrier, which stemmed from the reshaping of intestinal microbiota (e.g., increased Lachnospiraceae_NK4A136_group and Akkermansia levels). Conclusions: These results indicate that the changes of intestinal microflora caused by aged Pu-erh are the key to alleviate DSS-induced colitis, and speculate that drinking aged Pu-erh tea (10 mg/kg bw/day in mice, a human equivalent dose of 7 g/60 kg bw /day) has a practical effect on alleviating and preventing the development of intestinal inflammation.
Predictive Role of CC-Chemokine Ligand 2 in Digestive System Cancers: A Meta-Analysis
Authors: Liao Guixiang , Zhao Zhihong , Fu Yuxiang
Published: May 2021

Background: CC-chemokine ligand 2 (CCL2) expression as a prognostic factor in digestive system cancers (DSCs) is inconclusive. Methods:Thus, our aim was to summarize the prognostic role of CCL2 in DSCs. Electronic database was carefully searched. Studies focusing on CCL2 expression as a prognostic marker in DSCs were included for analysis. Pooled data for survival outcomes and clinical features were recorded in terms of the hazard ratio (HR) or odds ratio (OR) and the 95% confidence interval (CI).Results: In all,1,458 patients with DSCs from 11 studies were included for analysis.The pooled data revealed that high CCL2 expression group was more easy to occur the presence of distal metastases (OR = 3.83, 95% CI: 1.98–7.38, P < 0.001), severer tumor invasion (OR = 2.38, 95% CI: 1.31–4.34, P = 0.005), and advanced Tumor Nodal Metastasis stages (OR = 2.47, 95% CI: 1.12–5.45, P = 0.02). Moreover, poorer overall survival (HR = 2.09, P < 0.001) were observed in the group with high CCL2 expression. High levels of CCL2 also indicated dismay disease-free survival (HR = 1.87, P = 0.005) .Conclusions: Our findings indicate that CCL2 can serve as a prognostic indicator in DSCs.