bluuebunny/crossref_metadata_2025 huggingface dataset:
Combination With Glucocoriticoids and/or Immunosuppressants Brings Few Benefits in Patients With Primary Biliary Cholangitis
Authors: Wang Zilong , Jin Rui , Hao Mei , Xie Yandi , Wang Hao , Feng Bo
Published: January 2021

Objective To compare the efficacy of ursodeoxycholic acid (UDCA) monotherapy, and UDCA combined with glucocorticoids and/or immunosuppressants for patients with primary biliary cholangitis (PBC), and to search for relevant factors influencing the efficacy. Methods This retrospective study enrolled 266 patients who were initially diagnosed with PBC were grouped according to different treatment regimes. We analyzed and compared demographic characteristics, immune parameters, biochemistry profiles and other indicators collected at baseline, six months and one year of treatment. The prognosis was evaluated by Paris II standard and GLOBE score. T test, chi-square test and logistic regression were used for statistical analysis. Results According to Paris II standard and GLOBE score, there was no significant difference in one-year response rate and GLOBE score among the three treatment schemes (P > 0.05). GLOBE score > 0.3 indicated a decrease of the long-term survival rate, it was found that the long-term survival rate of the triple therapy group was significantly improved compared with the monotherapy group (p=0.005). Multivariate logistic regression analysis showed that PLT, ALP and ALB levels were risk factors for poor response. For the patients whose IgG levels were elevated but below twice upper limit of normal (ULN), the clinical benefit from combination therapy was not significant compared with monotherapy (p>0.05). Conclusion: Compared with monotherapy, the double therapy did not improve the one-year efficacy and long-term survival rate of PBC patients. However, triple therapy may improve the long-term survival rate of patients, although it does not significantly improve the one-year efficacy.
Using the Geometric Average Hazard Ratio in Sample Size Calculation for Time-to-event Data With Composite Endpoints
Authors: Martínez Jordi Cortés , Geskus Ronald B , Kim KyungMann , Melis Guadalupe Gómez
Published: January 2021

Background: Sample size calculation is a key point in the design of a randomized controlled trial. With time-to-event outcomes, it’s often based on the logrank test. We provide a sample size calculation method for a composite endpoint (CE) based on the geometric average hazard ratio (gAHR) in case the proportional hazards assumption can be assumed to hold for the components, but not for the CE. Methods: The required number of events, sample size and power formulae are based on the non-centrality parameter of the logrank test under the alternative hypothesis which is a function of the gAHR. We use the web platform, CompARE, for the sample size computations. A simulation study evaluates the empirical power of the logrank test for the CE based on the sample size in terms of the gAHR. We consider different values of the component hazard ratios, the probabilities of observing the events in the control group and the degrees of association between the components. We illustrate the sample size computations using two published randomized controlled trials. Their primary CEs are, respectively, progression-free survival (time to progression of disease or death) and the composite of bacteriologically confirmed treatment failure or Staphilococcus aureus related death by 12 weeks. Results: For a target power of 0.80, the simulation study provided mean (± SE) empirical powers equal to 0.799 (±0.004) and 0.798 (±0.004) in the exponential and non-exponential settings, respectively. The power was attained in more than 95% of the simulated scenarios and was always above 0.78, regardless of compliance with the proportional-hazard assumption.Conclusions: The geometric average hazard ratio as an effect measure for a composite endpoint has a meaningful interpretation in the case of non-proportional hazards. Furthermore it is the natural effect measure when using the logrank test to compare the hazard rates of two groups and should be used instead of the standard hazard ratio.
A Bioelectric Model of Carcinogenesis, Including Propagation of Cell Membrane Depolarization and Reversal Therapies
Authors: Carvalho Joao
Published: January 2021

As the main theory of carcinogenesis, the Somatic Mutation Theory, increasingly presents difficulties to explain some experimental observations, different theories are being proposed. A major alternative approach is the Tissue Organization Field Theory, which explains cancer origin as a tissue regulation disease instead of having a mainly cellular origin. This work fits in the latter hypothesis, proposing the bioelectric field, in particular the cell membrane polarization state, and ionic exchange through ion channels and gap junctions, as an important mechanism of cell communication and tissue organization and regulation. Taking into account recent experimental results and proposed bioelectric models, a computational model of cancer initiation was developed, including the propagation of a cell depolarization wave in the tissue under consideration. Cell depolarization leads to a change in its state, with the activation and deactivation of several regulation pathways, increasing cell proliferation and motility, changing its epigenetic state to a more stem cell-like behavior without the requirement of genomic mutation. The intercellular communication via gap junctions leads, in certain circum stances, to a bioelectric state propagation to neighbor cells, in a chain-like reaction, till an electric discontinuity is reached. However, this is a reversible process, and it was shown experimentally that, by implementing a therapy targeted on cell ion exchange channels, it is possible to reverse the state and repolarize cells. This mechanism can be an important alternative way in cancer prevention, diagnosis and therapy, and new experiments are proposed to test the presented hypothesis.
Algebraic Graph-assisted Bidirectional Transformers for Molecular Prediction
Authors: Chen Dong , Gao Kaifu , Nguyen Duc , Chen Xin , Jiang Yi , Wei Guowei , Pan Feng
Published: January 2021

The ability of quantitative molecular prediction is of great significance to drug discovery, human health, and environmental protection. Despite considerable efforts, quantitative prediction of various molecular properties remains a challenge. Although some machine learning models, such as bidirectional encoder from transformer, can incorporate massive unlabeled molecular data into molecular representations via a self-supervised learning strategy, it neglects three-dimensional (3D) stereochemical information. Algebraic graph, specifically, element-specific multiscale weighted colored algebraic graph, embeds complementary 3D molecular information into graph invariants. We propose an algebraic graph-assisted bidirectional transformer (AGBT) model by fusing representations generated by algebraic graph and bidirectional transformer, as well as a variety of machine learning algorithms, including decision trees, multitask learning, and deep neural networks. We validate the proposed AGBT model on five benchmark molecular datasets, involving quantitative toxicity and partition coefficient. Extensive numerical experiments suggest that AGBT outperforms all other existing methods for all these molecular predictions.
Diffusion Model-based Understanding of Unconscious Affective Priming in Continuous Flash Suppression
Authors: Kim Minchul , Kim Jeeyeon , Kim Jaejoong , Jeong Bumseok
Published: January 2021

Affective states influence our decisions even when processed unconsciously. Continuous flash suppression (CFS) is a new variant of binocular rivalry that can be used to render the prime invisible and thus unconscious. Nonetheless, it is unclear how prior information from emotional faces provided by CFS influences subsequent decision making. Here, we employed the CFS priming task to examine the effect of nonconscious information on the evaluation of target words as either positive or negative. The hierarchical diffusion model was used to investigate the underlying mechanisms. Two experiments were performed to investigate the effects of facial identity and facial expression. As a result, a significant affective priming effect on response time was observed only for angry faces but not happy and neutral faces. The results of diffusion model analyses revealed that both the drift rate and nondecisional process are accountable for the ‘positive bias’ - the processing advantage of positive over negative stimuli. Priming effects of facial identity were mapped onto the drift rate and eliminated ‘positive bias’. Meanwhile, positive emotional faces increased the nondecision time with negative target words. The model-based analysis implies that both facial identity and emotion are processed under CFS.
Evaluation of Temporomandibular Disorders Among Dental Students of Saudi Arabia Using Diagnostic Criteria/temporomandibular Disorders (DC/TMD) and Its Association With Biographic, Academic, and Psychosocial Parameters – A Cross-sectional Study
Authors: SRIVAST KUMAR CHANDAN , SHRIVASTAVA DEEPTI , Khan Zafar Ali , Nagarajappa Anil Kumar , Mousa Mohammed Assayed , Hamza May Othman , Al-Johani Khalid , Alam Mohammad Khursheed
Published: January 2021

Background: Temporomandibular disorders (TMD) are a board category of conditions arising from the various components of the temporomandibular joint (TMJ) complex. Bio-psychosocial model is the most accepted theory describing the etiopathogenesis of TMD. Dental students are vulnerable to psychological disorders including anxiety, depression and stress. Hence, the aim of the current study was to evaluate the TMD among dental students of various academic levels and explore the association of TMD with biographic, academic, and psychosocial parameters. Methods: A total of 246 students of a dental school in Saudi Arabia were chosen for the study. After getting consent, all students were examined as per the diagnostic criteria/Temporomandibular disorders (DC/TMD) including components from axis-I and axis-II. Results: The overall cross-sectional prevalence of TMD was found to be 36.99%. Pain arising from the jaw, temple, and peri-auricular area was the most commonly reported symptom and elicited sign during examination. Among the pain-related TMD, myalgia was the commonest diagnosed condition, whereas disc displacement with reduction was found prevalent in intra-articular disorder category. Female (OR=1.94; P=0.004), married (OR=1.74; P=0.04), and students in clinical levels (OR=1.65; P=0.03) were shown to have significantly higher risk to develop TMD. Among the psychosocial parameters, parafunctional habits (OR=2.10; P<0.001) and anxiety (OR=1.55; P=0.04) are shown to increase risk of developing TMD. Students with any TMD reported to have significantly higher pain intensity (OR=1.68; P=0.01) and jaw functional limitations (OR=1.45; P=0.008). Conclusion: Dental students especially in the clinical levels were shown to poses higher risk of developing TMD, hence strategies such as academic counselling and objective evaluation via rubrics should be planned to modify the administration of the curriculum, training methods and evaluation process.
Detection of Unknown Ototoxic Adverse Drug Reactions: An Electronic Healthcare Record-Based Longitudinal Nationwide Cohort Analysis
Authors: Lee Suehyun , Cha Jaehun , Kim Jong-Yeup , Son Gil Myeong , Kim Dong-Kyu
Published: January 2021

Ototoxic medications can lead to significant morbidity. Thus, pre-marketing clinical trials have assessed new drugs that have ototoxic potential. Nevertheless, several ototoxic side effects of drugs may remain undetected. Hence, we sought to retrospectively investigate the potential risk of ototoxic adverse drug reactions among commonly used drugs via a longitudinal cohort study. An electronic health records-based data analysis with a propensity-matched comparator group was carried out. This study was conducted using the MetaNurse algorithm for standard nursing statements on electronic healthcare records and the National Sample Cohort obtained from the South Korea National Health Insurance Service. Five target drugs capable of causing ototoxic adverse drug reactions were identified using MetaNurse; two drugs were excluded after database-based analysis because of the absence of bilateral hearing loss events in patients. Survival analysis, log-rank test, and Cox proportional hazards regression models were used to calculate the incidence, survival rate, and hazard ratio of bilateral hearing loss among patients who were prescribed candidate ototoxic drugs. The adjusted hazard ratio of bilateral hearing loss was 1.31 (1.03–1.68), 2.20 (1.05–4.60), and 2.26 (1.18–4.33) in cimetidine, hydroxyzine, and sucralfate users, respectively. Our results indicated that hydroxyzine and sucralfate may cause ototoxic adverse drug reactions in patients. Thus, clinicians should consider the risk of ototoxicity when prescribing these drugs.
Maternal Pre-pregnancy BMI Associates With Neonate Brain Local Synchrony in the Left Superior Frontal Gyrus: a Pilot Study
Authors: Rajasilta Olli Paul Einari , Häkkinen Suvi , Björnsdotter Malin , Scheinin Noora , Lehtola Satu , Saunavaara Jani , Parkkola Riitta , Lähdesmäki Tuire , Karlsson Linnea , Karlsson Hasse , Tuulari Jetro
Published: January 2021

Introduction: Maternal obesity/overweight during pregnancy has reached epidemic proportions and has been linked with adverse outcomes for the offspring, including cognitive impairment and increased risk for neuropsychiatric disorders. Prior neuroimaging investigations have reported widespread aberrant functional connectivity and white matter tract abnormalities in neonates born to obese mothers. Here we explored whether maternal pre-pregnancy adiposity is associated with alterations in local neuronal synchrony in the neonate brain. Methods: 21 healthy mother-neonate dyads from uncomplicated pregnancies were included in this study (age at scanning 26.14 ± 6.28 days, 12 male). The neonates were scanned with a 6-minute resting-state functional magnetic resonance imaging (rs-fMRI) during natural sleep. Regional homogeneity (ReHo) maps were computed from obtained rs-fMRI data. Multiple regression analysis was performed to assess the association of pre-pregnancy maternal body-mass-index (BMI) and ReHo. Results: Maternal adiposity measured by pre-pregnancy BMI was positively associated with neonate ReHo values within the left superior frontal gyrus (FDR/FWE –corrected p < 0.005). Conclusions: Our results imply that maternal pre-pregnancy BMI associates with local functional synchrony within the neonate left superior frontal gyrus. In line with previous studies, our findings indicate that maternal pre-pregnancy BMI has a programming influence on the developing neonate brain functional networks.
TNK2/ACK1 Strengthen Influenza A Virus Infection by Blocking Viral Matrix 2 Protein(M2) into Lysosome to Degradation
Authors: Zhou Ao , Dong Xia , Tang Bin
Published: January 2021

BackgroundTNK2/ACK1, a non-receptor tyrosine kinase, plays critical roles in signalling transduces and trafficking. Our previous genome-wide CRISPR/CAS9 knockout screen revealed that mutant of TNK2 produced more restrict to influenza virus infection. In this study, we aim to illustrate the role of TNK2 for influenza A virus (IAV) replication in human cells.ResultsCRISPR/Cas9-mediated mutant of TNK2 resulted in a significant reduction in viral proteins expression and viral titres for multiple influenza strains, and furthermore, a decrease of nuclear import of IAV in the infected TNK2 mutant cells was observed in 3h post-infection. Interestingly, TNK2 mutation enhanced the colocalization of LC3 with autophagic receptor p62 and led to the attenuation of influenza virus-caused accumulation of autophagosomes in TNK2 mutant cells. Further, confocal microscopy visualization result showed that influenza viral matrix 2 (M2) was colocalized with Lamp1 in the infected TNK2 mutant cells in early infection, while almost no colocalization between M2 and Lamp1 was observed in IAV-infected wild-type cells. Moreover, TNK2 depletion also affected the trafficking of early endosome and the movement of influenza viral NP and M2.ConclusionsOur results identified TNK2 as a critical host factor for influenza viral M2 protein trafficking, suggesting that TNK2 will be an attractive target for the development of antivirals therapeutics.
Frequent Gain- and Loss-of-Function Mutations of the BjMYB113 Gene Accounted for Leaf Color Variation in Brassica Juncea
Authors: An Guanghui , Chen Jiongjiong
Published: January 2021

Background: Mustard (Brassica juncea) is an important vegetable, and some cultivars have purple leaves and accumulate more anthocyanins than the green. The genetic and evolution of purple trait in mustard has not been well studied. Result: In this study, free-hand sections and metabolomics showed that the purple leaves of mustard accumulated more anthocyanins than green ones. The trait of purple leaves in mustard, Mustard Purple Leaves (MPL), was genetically mapped and a MYB113-like homolog was identified as the candidate gene. We identified three alleles of the MYB113-like gene, BjMYB113a from a purple cultivar, BjMYB113b and BjMYB113c from green cultivars. A total of 45 single nucleotide polymorphisms (SNPs) and 8 InDels were found between the promoter sequences of the purple allele BjMYB113a and the green allele BjMYB113b. On the other hand, the only sequence variation between the purple allele BjMYB113a and the green allele BjMYB113c is an insertion of 1,033-bp fragment in the 3’region of BjMYB113c. Transgenic assay and promoter activity studies showed that the polymorphism in the promoter region was responsible for the up-regulation of the purple allele BjMYB113a and high accumulation of anthocyanin in the purple cultivar. The up-regulation of BjMYB113a increased the expression of genes in the anthocyanin biosynthesis pathway including BjCHS, BjF3H, BjF3’H, BjDFR, BjANS and BjUGFT, and consequently led to high accumulation of anthocyanin. However, the up-regulation of BjMYB113 was compromised by the insertion of 1,033-bp in 3’region of the allele BjMYB113c. Conclusion: Our results contribute to a better understanding of the genetics and evolution of the BjMYB113 gene controlling purple leaves and provide useful information for further breeding programs of mustard.
Genetic Diversity and Emerging Zoonotic Onchocerca Species in Human Populations in Taraba State, Nigeria
Authors: Akafyi Danlami , Ndams Iliya Shehu , Nock Ishaya Haruna , Chechet Gloria , Alfons Renz , Moussa Ibrahim M.
Published: January 2021

Background: A better understanding of parasite population genetic processes in specific biogeography is needed to support onchocerciasis elimination goals. The genetic diversity of Onchocerca microfilariae was explored by amplifying a fragment of the 16S rRNA gene in the endemic area in Taraba State, Nigeria, Methods: Eight (8) communities were selected including six onchocerciasis endemic communities with records of ivermectin treatment having been annually distributed for 10 to 16 years, and two non-onchocerciasis endemic areas. The participants were 211 from endemic and 110 from non-endemic areas as control. Skin snips were taken from consenting participants by convenience sampling methods using a sterile sclera punch, from males and females residing within the communities for ten years and above or since birth, microfilaria and residual skin snips were preserved in RNALater® in a 1.5 ml micro-centrifuge tube. DNA was extracted from microfilariae recovered and from those in residual skin snip specimens. Polymerase Chain Reaction (PCR) amplification using specific primers for 16S genes was done to detect the identity of Onchocerca species. The amplified products were sequenced and analyzed for species identity. Results: Multiple sequence alignment and phylogenetic analysis results showed distinct diversity of two sample sequences (G49_O.v. Gashaka and Y02_O.v. Yorro) from other samples from the study area and other regions, indicating emergence of a new polymorphic strain of O. volvulus. Report of a preliminary case of emerging zoonosis of O. ochengi infection in human (skin snips) sample (O. ochengi G44) in this study. Conclusions: It is clear there is genetic diversity of Onchocerca species and emerging zoonosis in the study site. We suggest further investigation on the extent and potentials of emerging zoonotic onchocerciasis by O. ochengi, in the light of cattle, Simulium vectors, environmental and humans overlap in the study area.
Effect of Temperature on the Dielectric and Magnetic Properties of NiFe2O4@MgFe2O4 and ZnFe2O4@MgFe2O4 Core-shell
Authors: Roumaih Kheled
Published: January 2021

The core-shell of nanoferrites showed quite different properties rather than the nanoferrites counterpart. The nanocomposites of NiFe2O4@MgFe2O4 (NiF@MgF) and ZnFe2O4@MgFe2O4 (ZnF@MgF) are chemically stable and showed very good dielectric and magnetic properties. In this investigation, the temperature-dependent dielectric constant, dielectric loss, and ac-electrical conductivity were measured up to 650 K under different alternating electric field frequencies from 100 Hz to 8 MHz. The obtained data revealed that the mutual effect between the core and the shell samples increases the space charge polarization. Also, the samples showed the semiconducting-metallic behavior which varies between SP, CBH, and QMT models according to the temperatures and the frequencies. Furthermore, the magnetization M(T) was studied of all samples using the Faraday balance method in the temperature range 300-500K. The experimental results of M(T) exhibit good magnetic properties of the core-shell samples, particularly the sample ZnF@MgF. The novelty in this work is an unexpected behavior of ZnF@MgF which possesses magnetization higher than the pure ferrite phase (MgFe2O4), and Curie temperature (TCm) higher than the room temperature. So, the sample ZnF@MgF is a ferrimagnetic substance. Besides, the effective magnetic moment (mEff) and the Curie-Weiss constant (q) for all samples were obtained from the magnetic susceptibility c(T) protocols.
Retroperitoneal Robot-Assisted Laparoscopic Partial Nephrectomy for Horseshoe Kidney: A Case Report
Authors: Zhang Dongxu , Lu Youyi , Sun Fengze , Wang Di , Bao Xingjun , Sun Kai , Wu Jitao , Wang Jipeng
Published: January 2021

Background: Horseshoe kidney (HSK) have always been a challenge for urologists depending on its particular anatomy. We report a case of renal tumor in a patient with HSK, who underwent tumor resection by retroperitoneal robot-assisted laparoscopic partial nephrectomy. Case Presentations: A 47-year-old man presented to our hospital with a solid renal mass. Computed tomography urography (CTU) showed a 4.3 × 4.4 cm mass in the upper pole of the right kidney. Patients received a retroperitoneal robot-assisted laparoscopic partial nephrectomy on basis of three-dimensional (3D) reconstructions.Conclusion: The present case report highlights the feasibility of robot-assisted laparoscopic partial nephrectomy for horseshoe kidney, and the advantages of preoperative 3D reconstructions.
Identification of miR-589-5p as a Potential Prognostic Biomarker of Hepatocellular Carcinoma
Authors: Yao Zhijia , Jiang Chunlin , Weng Huiwen , Fang Shi , Li Heping , Liu Baoxian , Long J
Published: January 2021

Background: MicroRNAs (miRNAs) are small endogenous non-coding RNAs with 22 nucleotides approximately. Numerous studies have reported that microRNAs may hold the potential to serve as biomarkers in diagnosing cancer and predicting prognosis. miR-589-5p is a well-documented oncogenic miRNA implicated in several human cancer types. However, the potential value of miR-589-5p as a biomarker to facilitate early diagnosis and predict prognosis in hepatocellular carcinoma (HCC) patients remains obscure.Methods: miR-589-5p expression was examined by in situ hybridization (ISH) in 10 adjacent normal tissues (ANT), 21 liver fibrosis tissues, 113 HCC tissues, including 22 HCC with grade I, 37 HCC with grade II, 49 HCC with grade III and 5 hepatocholangiocellular carcinoma tissues. Statistical analysis and Kaplan–Meier survival analysis was performed to evaluate the clinical correlation between miR-589-5p expression and clinicopathological features and survival prognosis in HCC patients.Results: miR-589-5p expression was dramatically upregulated in HCC tissues by in situ hybridization (ISH). Overexpression of miR-589-5p was not only positively correlated with poor tumor differentiation degree, increased AFP levels, advanced clinical stage, distant metastatic status and venous invasion, but also predicted poor overall and relapse-free survival in HCC patients. Importantly, the expression levels of miR-589-5p measured by real-time PCR in high-ISH scores tissues were dramatically upregulated compared with those in low-ISH scores tissues, and a strong and positive correlation of miR-589-5p expression levels in real-time PCR with ISH staining index was demonstrated in HCC tissues.Conclusion: our results support the notion that miR-589-5p might hold a promising value as a novel biomarker to facilitate early diagnosis and predict prognosis in HCC patients.
PTEN is a Predictive Biomarker of Trastuzumab Resistance and Prognostic Factor in HER2-overexpressing Gastroesophageal Adenocarcinoma
Authors: Yokoyama Daiju , Hisamori Shigeo , Deguchi Yasunori , Nishigori Tatsuto , Okabe Hiroshi , Kanaya Seiichiro , Manaka Dai , Kadokawa Yoshio , Hata Hiroaki , Minamiguchi Sachiko , Tsunoda Shigeru , Obama Kazutaka , Sakai Yoshiharu
Published: January 2021

IntroductionPoor Trastuzumab (Tmab) response in human epidermal growth factor receptor 2-overexpressing gastric or gastroesophageal junction adenocarcinoma (HER2-GEA) is reported to be associated with loss of phosphatase and tensin homolog (PTEN) expression.MethodsIn a multicenter, retrospective observational study, pathological samples of HER2-GEA patients receiving Tmab-combined chemotherapy were immunohistochemically analyzed for PTEN expression. Primary endpoints were disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). The effect of PI3K pathway inhibitors on HER2-GEA cell lines were evaluated in in-vitro.ResultsAmong 145 HER2-GEA patients, 29 formed the PTEN-loss group and 116 the PTEN-positive group. In patients with target region, DCR was significantly lower in PTEN-loss than in PTEN-positive patients (67% and 87%, respectively, p=0.049). Multivariate analysis demonstrated that PTEN loss was significantly associated with shorter PFS (HR=1.63, p=0.035) and OS (HR=1.83, p=0.022). PTEN knockdown did not affect the cytostatic effect of 5-FU and cisplatin, while Tmab combined with PI3K/mTOR inhibitor NPV-BEZ235 suppressed the proliferation of PTEN knockdown cells which were resistant to Tmab alone.ConclusionIn HER2-GEA patients, PTEN loss is a predictive biomarker of Tmab resistance and prognostic factor. Molecular-targeted therapy with PI3K/mTOR inhibitor would be an effective treatment option for HER2-GEA with PTEN loss.
A Novel CCR7-Related Immune Prognostic Signature for Liver Hepatocellular Carcinoma (LIHC) Based on Immunogenomic Profiling
Authors: Qin Lei , Kuai Jun , Yang Fang , Yang Lu , Sun Peisheng , Zhang Lanfang , Li Guangpeng
Published: January 2021

Object: Explore the specific function of CCR7 in immune mechanism of LIHC, and constructed CCR7-related immune prognostic signature (IPS) for LIHC patients.Methods: The RNA-seq data of LIHC was downloaded from TCGA dataset and the samples were divided into CCR7_H and CCR7_L group. Then, ssGSEA analysis, immune microenvironment analysis, expression level analysis of HLA genes and check point genes were conducted. The differential expression immune genes (DEIGs) were conducted and LASSO Cox was applied to construct CCR7-related IPS. A novel nomogram was constructed to predict survival rate of LIHC patients.Results: The Immune score, Stromal score and ESTAMATE score are higher in CCR_H group, while tumor purity higher in CCR_L group. In CCR7_H group, the HLA genes and immune checkpoint genes have higher expression levels. The CCR7_H group have a favorable prognosis than CCR7_L group. There are 903 DEIGs were identified. The DEIGs mainly enriched in complement activation, adaptive immune response, T cell activation, lymphocyte differentiation and cytokine-cytokine receptor interaction. The IPS consists of 10 genes, including GHV4-59, SCML4, AKR1B10, LINC00426, TRGC1, F2RL2, TRBV10-3, SAMD9L, SLC4A10 and ROR2. Univariate and multivariate Cox analysis showed that the IPS was an independent prognostic factor of LIHC. Conclusions: The CCR7-related IPS and nomogram were constructed and provided for LIHC patients to predict survival rate. This study provided a novel way to analyzed the prognostic effect of CCR7 expression from the perspective of immunology.
Comparison of Coastline Extraction Methods and Block Classification Method to Extract Coastlines based on Remote Sensing
Authors: Li Zongmei , Chen Hongmei , Nie Qin
Published: January 2021

Coastlines change with urbanization, and methods to extract coastlines have been previously reported. However, comparisons of these methods are rare. Based on remote sensing image, methods of coastline extraction, namely, the visual interpretation method, the threshold segmentation method, improved normalized water indexes and edge detection algorithms and were studied in Xiamen City, China. The best method to extract coastlines was then determined. The results show that the visual interpretation method for coastline extraction was inefficient. The threshold segmentation method was suitable for small-scale, but not large-scale, coastline extraction, based on coastline area. Improved normalized water indexes were insensitive to sediment shadows. The Sobel method (edge detection algorithms) was suitable for large-scale coastline extraction but could yield false edges. Finally, the block classification method, which combines the advantages of different extraction methods, specifically the threshold segmentation method and improved normalized water indexes, was studied. The results of this study show that coastline extraction by the block classification method is easier and produces better results than coastline extraction by other methods. Therefore, block classification is recommended for the study of coastlines and coastal ecology in large areas.
The Gut Microbiota is Associated with the Small Intestinal Paracellular Permeability and the Development of the Immune System in Healthy Children During the First Two Years of Life
Authors: Kaczmarczyk Mariusz , Löber Ulrike , Adamek Karolina , Węgrzyn Dagmara , Skonieczna-Żydecka Karolina , Malinowski Damian , Łoniewski Igor , Markó Lajos , Ulas Thomas , Forslund Sofia K. , Łoniewska Beata
Published: January 2021

BackgroundThe intestinal barrier plays an important role in the defense against infections, and nutritional, endocrine, and immune functions. The gut microbiota playing important role in development of the gastrointestinal tract can impact intestinal permeability and immunity during early life, but data concerning this problem are scare.MethodsWe analyzed the microbiota in fecal samples (101 samples in total) collected longitudinally over 24 months from 21 newborns to investigate whether the markers of small intestinal paracellular permeability (zonulin) and immune system development (calprotectin) are linked to the gut microbiota. The results were validated using data from an independent cohort that included the calprotectin and gut microbiota in children during the first year of life. ResultsZonulin levels tended to increase for up to 6 months after childbirth and stabilize thereafter remaining at a high level while calprotectin concentration was high after chilbirth and begun to decline from 6 months of life. The gut microbiota composition and the related metabolic potentials changed during the first two years of life and were correlated with zonulin and calprotectin levels. Feacal calprotectin correlated inversely with alpha diversity (Shannon index, r =-0.30, FDR P (Q)=0.039). It also correlated with seven taxa; i.a. negatively with Ruminococccaceae (r=-0.34, Q=0.046), and Clostridiales (r=-0.34, Q=0.048) and positively with Stapylococcus (r=0.38, Q=0.023) and Staphylococcaceae (r=0.35, Q=0.04), whereas zonulin correlated with 19 taxa; i.a. with Bacillales (r=-0.52, Q=0.0004), Clostridiales (r=0.48, Q=0.001) and the Ruminococcus (torques group) (r=0.40, Q=0.026). When time intevals were considered only changes in abundance of the Ruminococcus (torques group) were associcated with changes in calprotectin (β=2.94, SE=0.8, Q=0.015). The dynamics of stool calprotectin was negatively associated with changes in two MetaCyc pathways: pyruvate fermentation to butanoate (β=-4.54, SE=1.08, Q=0.028) and Clostridium acetobutylicum fermentation (β=-4.48, SE=1.16, Q=0.026). ConclusionsThe small intestinal paracellular permeability, immune system-related markers and gut microbiota change dynamically during the first two years of life. The Ruminococcus (torques group) seems to be especially involved in controlling paracellular permeability. Staphylococcus, Staphylococcaceae, Ruminococcaceae, and Clostridiales, may be potential biomarkers of the immune system. Despite observed correlations their clear causation and health consequences were not proven. Mechanistic studies are required.
Comprehensive Analysis of DNA Methylation Regulator DNA Methyltransferase (DNMT) Family and Ten-Eleven-Translocation (TET) Enzymes Family in Pan-Cancer
Authors: Ouyang Cheng , Li Hao , Sun Liping
Published: January 2021

Background: DNA methyltransferase (DNMT) family and ten-eleven-translocation (TET) family enzymes play pivotal roles in regulating DNA methylation, and are closely related to diverse cancers. This study was designed to clarify the specific roles of DNMT and TET genes in pan-cancers.Methods: The expression, mutation, copy number variations (CNVs), cancer-related pathways, immune cell infiltration correlation, and prognostic potential of DNMT/TET genes were systematically investigated in 33 cancer types using next-generation sequence data from the Cancer Genome Atlas database. Results: DNMT3B was more highly expressed in the majority of tumors analyzed than in normal tissues. Most DNMT/TET genes were frequently mutated in uterine carcinosarcoma, and TET1 and TET2 showed higher mutation frequencies in various cancer types. DNMT3B exhibited inclusive copy number amplification in almost all cancers, such as stomach adenocarcinoma(STAD) and colon adenocarcinoma(COAD)l, while most DNMT/TET genes displayed highly copy number deletion in kidney chromophobe（KICH）. DNMT/TET genes were mainly involved in the following cancer-related pathways: UV response DN, mitotic spindle, cholesterol homeostasis, TGF beat signaling, xenobiotic metabolism, G2/M checkpoint, and E2F targets. DNMT/TET genes were significantly correlated with NK cells, CD4 positive T cells, and Tfh cells. Additionally, Most DNMT/TET genes were significantly associated with lower survival rates of adrenocortical carcinoma (ACC), mesothelioma, and liver hepatocellular carcinoma (LIHC), but played a protective role in thymoma (THYM). Furthermore, overexpression of most DNMT genes, except for DMAP1, was associated worse prognoses in pan-cancer. Conclusion: These results suggest that DNMT/TET genes can serve as potential predictors for prognosis and treatment in pan-cancer, providing new insight for future study.
STING Protects Against Cardiac Dysfunction and Remodelling by Blocking Autophagy
Authors: Xiong Rui , Li Ning , Liu Bohao , He Ruyuan , Jiang Wenyang , Wang Wei , Wang Bo , Geng Qing
Published: January 2021

Background: Heart failure, which is characterized by cardiac remodelling, is one of the most common chronic diseases in the aged. Stimulator of interferon genes (STING) acts as an indispensable molecule modulating immune response and inflammation in many diseases. However, the effects of STING on cardiomyopathy, especially cardiac remodelling are still largely unknown. This study was designed to investigate whether STING could affect cardiac remodelling and to explore the potential mechanisms. Methods: In vivo, aortic binding (AB) surgery was performed to construct the mice model of cardiac remodelling. A DNA microinjection system was used to trigger STING overexpression in mice. The STING mRNA and protein expression levels in mice heart were measured, and the cardiac hypertrophy, fibrosis, inflammation and cardiac function were also evaluated. In vitro, cardiomyocytes stimulated by Ang II and cardiac fibroblasts stimulated by TGF-β to performed to further study effects of STING on cardiac hypertrophy and fibroblast. In terms of mechanisms, the level of autophagy was detected in mice challenged with AB. Rapamycin, a canonical autophagy inducer, intraperitoneal injected into mice to study possible potential pathway.Results: In vivo, the STING mRNA and protein expression levels in mice heart challenged with AB for 6 weeks were significantly increased. STING overexpression significantly mitigated cardiac hypertrophy, fibrosis and inflammation, apart from improving cardiac function. In vitro, experiments further disclosed that STING overexpression in cardiomyocytes induced by Ang II significantly inhibited the level of cardiomyocyte cross-section area and the ANP mRNA. Meanwhile, TGF-β-induced the increase of α-SMA content and collagen synthesis in cardiac fibroblasts could be also blocked by STING overexpression. In terms of mechanisms, mice challenged with AB showed higher level of autophagy compared with the normal mice. However, STING overexpression could reverse the activation of autophagy triggered by AB. Rapamycin, a canonical autophagy inducer, offset the cardioprotective effects of STING in mice challenged with AB. Finally, further experiments unveiled that STING may inhibit autophagy by phosphorylating ULK1 on serine757.Conclusion: STING may prevent cardiac remodelling induced by pressure overload by inhibiting autophagy, which could be a promising therapeutic target in heart failure.
Usefulness of Intraoperative C-Arm Image Intensifier in Reducing Errors of Acetabular Component During Primary Total Hip Arthroplasty: An Application of Widmer’s Method
Authors: Song Joo-Hyoun , Kim Yong-Sik , Kwon Soon-Yong , Lim Young-Wook , Jung Jiyoung , Oh Seungbae
Published: January 2021

Background: Acetabular prosthesis positioning in total hip arthroplasty (THA) is crucial in reducing the risk of dislocation. There has been minimal research on the proper way to put the acetabular components into the safe zone intraoperatively. Assessment of version by intraoperative imaging intensifier is very valuable. The value of Widmer’s method, using the intraoperative C-arm available to determine cup anteversion was assessed.Methods: 101 hips in 91 patients who underwent primary THA were eligible for inclusion. Utilizing intraoperative C-arm images, measurement was performed using the technique described by Widmer. The values obtained using 3D computed tomography postoperatively, which determined the anteversion of the acetabular component, were regarded as the reference standard.Results: The method of Widmer obtained values similar to those obtained using 3D computed tomography and was considered accurate (n.s.). All 101 hips were positioned in the set target zone. Among the 101 hips, the cup position in nine hips (8.9%) was changed. The dislocation rate in our study was 1.0% with all dislocations occurring in hips placed in the target zone. The mean Harris hip score after THA in one year was 94.2 (82-98).Conclusions: The method of Widmer was accurate using intraoperative imaging intensifier for the measurement of the anteversion of the acetabular component during THA, with reference to the anteversion obtained from the 3D computed tomography. Also, utilizing intraoperative C-arm imaging was very useful because it allowed for correction of the position of the acetabular cup.
Breast lesions excised via Vacuum-Assisted System: Could We Get Any Clues for B3 Lesions Before Excision Biopsy?
Authors: Zheng Liang , Zheng Fufu , Xing Zhaomin , Zhang Yunjian , Li Yongxin , Xu Hongbiao , Lai Yuanhui , Li Jie , Wang Wenjian
Published: January 2021

Background: The purpose of this study was to determine the validity of the ultrasound features as well as patient characteristics assigned to B3 (uncertain malignant potential) breast lesions before vacuum-assisted excision biopsy (VAEB).Methods: This study population consisted of 2245 women with breast-nodular abnormalities, which were conducted ultrasound-guided VAEB (US-VAEB). Patient’s clinical and anamnestic data and lesion-related ultrasonic feature variables of B3 were compared with those of benign or malignant cases, using histopathological results as a benchmark. Results: The proportions of benign, B3 and malignant breast lesions were 88.5%, 8.2% and 3.4% respectively. B3 high frequent occurred in BI-RADS-US grade 3 (7.7%), grade 4 (9.3%), grade 4a (11.3%) and grade 4b (9.1%). The overall malignancy underestimation rate of B3 cases was 4.4% (8/183). The more common malignancy underestimation of B3 subtypes were PL/ADH 50% (1/2), ADH 23.1% (3/13), and CSL/RS 16.7% (1/6). And the highly frequent recurrence rates of B3 subtypes were ADH 10% (1/10), PL 4.9% (4/82), and PT 8.6% (6/70). Multivariate binary logistic regression analyses (B3 vs benign) showed that non-menopausal patients (95% CI 1.628-8.616, P = 0.002), single (95% CI 1.370-2.650, P = 0.000) or abundant blood supply (95% CI 1.745-4.150, P = 0.000) nodules via ultrasound examination were significant risk factors for B3 occurrences. Moreover, patients elder than 50 years (95% CI 3.178-19.816, P = 0.000), unclear margin (95% CI 3.571-14.119, P = 0.000) or microcalcification (95% CI 4.010-30.733, P = 0.000) nodules were significantly associated with higher risks of malignant potentials (B3 vs malignant).Conclusion: The results of this study indicate that ultrasound findings and patients’ characteristics could provide valuable information for distinguishing B3 cases from benign or malignant cases before VAEB.
Association Between Violent Video Gaming Exposure and the Attachment Styles Among Lebanese Male Adolescents
Authors: Akel Marwan , Berro Jana , Malaeb Diana , Fahs Iqbal , Haddad Chadia , Hallit Souheil , Obeid Sahar
Published: January 2021

Objectives: to correlate different attachment styles with the exposure of Lebanese male adolescents to violent video games.Methods: This study was carried out between October and December 2019 among 388 Lebanese male adolescents from five Lebanese schools. Results: 190 participants (48.8%, CI: 0.43 – 0.53) were classified as having a high exposure to violent video gaming. Higher age (Beta=-1.64) and higher dismissing attachment style (Beta=-1.38) were significantly associated with less violent video gaming. Higher fearful attachment style (Beta=2.98) was significantly associated with more violent video gaming.Conclusion: This study focuses on the association between different attachment styles and the exposure of Lebanese male adolescents to violent video games. Adolescents with more insecure attachment styles were found to be more exposed to violent video games.
Systematic Expression Analysis of the Diagnostic and Prognostic Value of HEPACAM Family Member 2 in Colon Adenocarcinoma
Authors: Wang Shuai , Ruan Guo-Tian , Gong Yi-Zhen , Liao Cun , Zhang Lei , Gao Feng
Published: January 2021

Background: The diagnostic and prognostic value of HEPACAM family member 2 (HEPACAM2) gene in patients with colon adenocarcinoma (COAD) is rarely reported. Therefore, the purpose of this study is to explore the diagnostic and prognostic value of HEPACAM2 gene in patients with COAD.Methods: Firstly, we analyzed the differential expression levels of HEPACAM2 gene and diagnostic value analysis from different databases. Secondly, univariate and multivariate survival analysis of the prognostic value of HEPACAM2 gene in patients with COAD was performed. Finally, utilizing joint-effects analysis and comprehensive prognosis analysis to investigate the prognostic value of HEPACAM2 and related genes.Results: Differential analyses of multiple databases showed that the HEPACAM2 expression level in COAD tumor tissue was significantly lower than that of adjacent normal tissues. The diagnostic ROC curve results indicated that HEPACAM2 gene had a higher diagnostic value in COAD. The RT-qPCR verification results of COAD tissue in the Guangxi cohort showed that HEPACAM2 expression level in COAD tumor tissue was significantly higher than that of adjacent normal tissues (P<0.001), and the diagnostic value was high in COAD (AUC=0.892). The prognostic value analysis showed that low expression of HEPACAM2 gene had a poorer prognosis of overall survival (OS) in patients with COAD when compared with those patients with high expression of HEPACAM2 gene ((P = 0.038, HR (95% CI) = 0.635(0.414-0.976)). Joint-effects analysis and comprehensive prognosis analysis showed that high expression of HEPACAM2 combined with high expression of CLCA1, high expression of REP15, and high expression of B3GNT6 were associated with a better prognosis of overall COAD OS.Conclusion: The results of this study suggested that the HEPACAM2 may be an independent diagnostic and prognostic biomarker for COAD.
Associations Between Telomere Length and Insulin Resistance in American Adults：A Cross-Sectional Study from the US National Health and Nutrition Examination Survey, 1999–2002
Authors: Gong Rongpeng , Li Zheng , Liu Ya , Luo Gang , Yang Lixin , Wei Xiaoxing
Published: January 2021

BackgroundSome previous studies seemed to confirm a link between telomere length and many chronic diseases, but in recent years, a growing body of evidence has shown a weak link between telomere length and some chronic diseases. In previous studies insulin resistance has been listed as a sign of arterial aging, diabetes, and especially atherosclerosis. However, there is insufficient evidence that telomere length is associated with insulin resistance in US adults. Therefore, we tried to find evidence of telomere length and insulin resistance based on the NHANES1999-2002 database.MethodsWe used multiple logistic regression analysis to test the relationship between telomere length and insulin resistance, and drew a smooth fitting curve between telomere length and insulin resistance without adjustment. At the same time, groups of people were divided according to age, gender, race, etc., and multivariate Logistic analysis was conducted after adjusting covariables to test the association between telomere length and insulin resistance in different groups.ResultsIn this study, after the adjustment of covariables. Telomere length was not associated with insulin resistance in U.S. adults and was not statistically significant.ConclusionsSince there is a significant association between insulin resistance and race, further investigation and study is needed to determine whether telomere length is related to the risk of insulin resistance in other populations. At the same time, more research is needed to explore the link between telomeres and chronic disease in the future.
Unveiling the 46,XY disorder of sex development patients family with a novel mutation in the GATA4 gene
Authors: Li Liwei , Yang Hui , Zhang Junhong , Lv Huijing , Li Qing , Cui Yi , Wu Tongqian , Tian Yuan , Mou Yajun , Chen Xinxin , Wang Shuping , Feng Yanli , Li Shujun , Li Shuping , Hu Pingsheng , Hao Shirui , Dou Xiaowei
Published: January 2021

Background

GATA-binding protein 4 (GATA4) is the critical regulator in gonadal development and its mutation has been reported related with 46,XY disorder of sex development (DSD). Here, we found the two Chinese cases with 46,XY DSD carried the GATA4 mutation. Physical examinations, B-ultrasound and Karyotype analysis were performed and confirmed the two patients with 46,XY DSD.
Results

Sequencing were performed and the heterozygous mutation p.Gly375Arg in GATA4 gene was identified in the 2 cases with 46,XY DSD. Their mother was identified carrying the p.Gly375Arg mutation in GATA4 protein. However, their father and litter sister without 46,XY DSD didn’t be found carrying the p.Gly375Arg mutation in GATA4 gene.
Conclusion

This is the first report that the case with 46,XY DSD carried the mutation Gly375Arg in the GATA4 gene. Our