bluuebunny/crossref_metadata_2025 huggingface dataset:
LTBP1 plays a potential bridge between depressive disorder and glioblastoma
Authors: Fu Xiaojun , Zhang Pei , Song Hongwang , Wu Chenxing , Li Shengzhen , Li Shouwei , Yan Changxiang
Published: April 2020

Background: Glioblastoma multiforme (GBM) is the most malignant tumor in human brain. Diagnosis and treatment of GBM may lead to psychological disorders such as depressive and anxiety disorders. No researches focusing on the correlation between depressive/anxiety disorder and the outcome of GBM. Thus, the aim of this study was to investigate the possibility of depressive/anxiety disorder on the outcome of GBM patients, as well as the overlapped mechanism bridge which could link depressive/anxiety disorders and GBM.Methods: Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder (GAD-7) were used to investigate the psychological condition of GBM patients in our department. To further explore the potential mechanism, bioinformatic methods were used to screen out genes that could be indicators of outcome in GBM, followed by gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and protein-protein interaction (PPI) analysis. Further, cellular experiments were conducted to evaluate the proliferation, migration capacity of primary GBM cells from the patients.Results: It was revealed that patients with higher PHQ-9 and GAD-7 scores had significantly worse prognosis than their lower-scored counterparts. Bioinformatic mining revealed that LTBP1 could be a potential genetic mechanism in both depressive/anxiety disorder and GBM. Primary GBM cells with different expression level of LTBP1 should significantly different proliferation and migration capacity. GO, KEGG analysis confirmed that extracellular matrix (ECM) was the most enriched function of LTBP1. PPI network showed the interaction of proteins altered by LTBP1. Hub genes COL1A2, COL5A1 and COL10A1, as well as mesenchymal marker CD44 and Vimentin were statistically higher expressed in LTBP1 high group; while proneural marker E-cadherin was significantly higher expressed in low LTBP1 group.Conclusion: There is closely correlation between depressive/anxiety disorders and GBM. LTBP1 could be a potential bridge linking the two diseases through the regulation of ECM.
Study on The Change Law of Wave Velocity and Porosity of Triaxial Loaded Coal
Authors: li donghui , liang yanxia , chen shiqiang , zhang kai
Published: April 2020

The mechanical properties of loaded coal time to time, so that the voice wave propagation in coal changes with it. In order to study the relationship between the wave velocity of coal and its mechanical properties.The ultrasonic testing system was used to calculate the wave velocity of loaded coal at different times through laboratory triaxial loading test.The relationship between the wave velocity of loaded coal-body and the confining pressure of different coaxial pressures was analyzed.The results show that the wave velocity is positively correlated with the axial pressure under the same confining pressure. By calculating the variation of wave velocity of different loaded coal bodies. it is concluded that the variation of wave velocity of coal bodies can reflect the mechanical state of coal bodies undergo the compaction stage, the elastic stage and the new stage of crevasse. At the same time, the change of wave velocity in coal is affected by the porosity of the pressure-bearing coal-boby. Porosity was calculated using stress-strain.It was found that porosity and axial pressure presented a good negative correlation under the same confining pressure, and the change in wave velocity is exactly right opposite to the porosity change trend diagram.It can be obtained that the larger the amplitude of wave velocity change is, the smaller the porosity change is, and the smaller the amplitude of wave velocity change is, the larger the porosity change of coal body is, which is consistent with the actual analysis. It verifies the different the pressure-bearing coal-boby change in wave velocity to the feasibility of analyzing the mechanical condition of the loaded coal body. making the analysis more persuasive. It provides basis for coal body bearing and safe mining.
Effectiveness of group counseling with Acceptance and Commitment Therapy (ACT) on sexual Satisfaction of HIV positive women and women with HIV positive husband
Authors: Bokaie mahshid , tahery naieralsadat , Dafeei mariam
Published: April 2020

Background and Aim : AIDS is a progressive, incurable and preventable viral disease that damages the immune system and causes opportunistic infections. The discovery of methods of transmission, prevention and treatment of the disease has prevented researchers from considering the psychological consequences of the disease. The discrimination, adherence to complex treatment regimens, fear of disclosing the disease to the sexual partner exacerbate patients' psychological dissatisfaction and changes their sexual behavior pattern. The present study attempts to investigate the extent of sexual satisfaction of HIV-positive women and their HIV-positive spouses using the Acceptance and Commitment Therapy (ACT). Methods : This double-blind study was performed in 2019 with the aim of investigating the effect of treatment of HIV-positive women and their HIV-positive spouses referred to Behavioral Disease Counseling Center in Yazd and Meybod. 32 eligible women were randomly divided into two groups of 16 and participated in 10 weekly 2-hour sessions. Larsson's demographic and sexual satisfaction questionnaire was used for data collection. Data analysis was done by descriptive statistics and parametric interventions in SPSS software version 16 and significance level 0.05. Findings: There was no significant difference between the two groups in terms of demographic variables. Mean scores of sexual satisfaction before (90.87±13.3) and after intervention (96.31±12.94) and before and one month after the intervention (97.81±12.52) were significantly different in the intervention group. Comparing the mean scores of sexual satisfaction immediately after the intervention and one month later in the intervention group was not significant (P = 0.24). Also, sexual satisfaction was significant between the two groups after the intervention and one month later. Conclusion : The results show that ACT are effective in women with HIV exposure to improve sexual satisfaction. According to the results, it is suggested that this approach be used in order to increase the mental flexibility of patients to accept the disease and the suffering resulting from it, and finally to improve marital relationships and increase sexual satisfaction. In addition, the continuation of sexual health counseling for women is recommended. Trial registration: IRCT20181213041956N1, registered November 2018.
Application of OU processes to modelling temporal dynamics of the human microbiome, and calculating optimal sampling schemes.
Authors: Kenney Toby , Gao Junqiu , Gu Hong
Published: April 2020

Background: The vast majority of Microbiome research so far has focused on the structure of the microbiome at a single time-point. There have been several studies that measure the microbiome from a particular environment over time. However, even in these studies, little has been done to study the temporal dynamics of the microbiome. In this paper, we begin to rectify this situation. We analyse a widely studied microbial data set that contains a time series of the microbiome from four body sites on two healthy individuals. We choose a data set based on healthy individuals because we are interested in the baseline temporal dynamics of the microbiome. Results: For this analysis, we focus on the temporal dynamics of individual genera, ignoring the interactions. We use simple stochastic differential equation models to assess the following three questions. (1) Does the microbiome exhibit temporal continuity? (2) Does the microbiome have a stable state? (3) To better understand the temporal dynamics, how frequently should data be sampled in future studies? We find that a simple Ornstein-Uhlenbeck model which incorporates both temporal continuity and reversion to a stable state fits the data for all genera better than a Brownian motion model that contains only temporal continuity. The Ornstein-Uhlenbeck model also fits the data better than modelling separate time points as independent. Under the Ornstein-Uhlenbeck model, we calculate the variance of the estimated mean reversion rate (the speed with which each genus returns to its stable state). Based on this calculation, we are able to determine the optimal sample schemes for studying temporal dynamics. Conclusions: There is evidence of temporal continuity for at least some genera; there is clear evidence of a stable state; and the optimal sampling frequency for studying temporal dynamics is in the range of one sample every 0.8–3.2 days.
Significance of accurate hilar and intrapulmonary lymph nodes examination in stage IA-IIA non-small cell lung cancer, a retrospective cohort study
Authors: Zhai Wenyu , Duan Fangfang , Zheng Yuzhen , Yan Qihang , Dai Shuqin , Chen Tao , Chen Jianlong , Wang Junye
Published: April 2020

Background The examination of lymph node plays an important part in the nodal staging of non-small cell lung cancer (NSCLC). Till present, on the role of hilar and intrapulmonary (N1) station lymph node (LN) examined is not fully appreciated. In this study, we aimed to confirm the significance of N1 lymph node examined in the long-term survival for stage IA-IIA NSCLC patients and find the minimum number of lymph nodes.Methods The data of patients who underwent radical lobectomy and confirmed as lymph node non-metastatsized from January 2008 to March 2018 were retrospectively screened. Pathology records were reviewed for the number of lymph nodes examined. Kaplan-Meier method and Cox regression model were used to identify survival and prognostic factors.Results The median number of resected N1 LNs was 8. The number of patients with 0-2 N1 LNs, 3-5 N1 LNs, 6-8 N1 LNs, 9-11 N1 LNs and more than 11 N1 LNs examined was 181, 425, 477, 414 and 531, respectively. Gender (P=0.004), age (P<0.001), tumor size (P=0.004), differentiation degree (P=0.001) and the number of N1 LNs examined (P=0.008) were the independent prognostic factors of overall survival. Gender (P=0.006), age (P=0.031), tumor size (P=0.001), differentiation degree (P=0.001), vascular invasion (P=0.034) and the number of N1 LNs examined (P=0.007) were the independent prognostic factors of disease-free survival. Conclusion Increasing the number of N1 LNs examination could improve the long-term survival of T1-2N0 NSCLC patients. At least six LNs should be examined in surgical and pathological management.
Characteristics of high carbon ash as a raw material for spontaneous combustion inhibitor and its field demonstration
Authors: Park Seok Un , Kim Jae Kwan , Shin Dong Ik
Published: April 2020

In this study, we examined the physical chemistry, fuel characteristics and combustion reactivity of high carbon ash as a raw material for spontaneous combustion inhibitor in order to solve the problem of spontaneous combustion which has been often occurring in coal yard of coal-fired power plants in Korea. The high carbon ash has higher activation energy and lower frequency factor than bituminous coal, so combustion began at a relatively higher temperature than bituminous coal. In case of fly ash, the heat transfer characteristics were better than those of bottom ash and pond ash, and in case of coarse particles of fly ash, they were found to be highly applicable as a raw material for spontaneous combustion inhibitor due to their relatively high unburned carbon content. As a result of manufacturing spontaneous combustion inhibitors along with asphalt and PFAD (palm fatty acid distillate), the contact angle to water was more than 90° regardless of the mixing ratio, showing hydrophobic surface characteristics, and it was found that the hardness and viscosity of spontaneous combustion inhibitors increased as the mixing ratio of high carbon ash increased. In addition, when spontaneous combustion inhibitors manufactured were applied to coal stockpiles in coal yard at coal-fired power plants, there was little change in the internal temperature of coal stockpiles and the highest value of instantaneous increasing rate per minute was found to be lowered from 1.60°C/min to 0.061°C/min, indicating that spontaneous combustion inhibitors using high carbon coal ash had a great effect of preventing spontaneous combustion.
Hyperphosphorylation Renders Tau Prone to Aggregate and to Cause Cell Death
Authors: Liu Mengyu , Sui Dexin , Dexheimer Thomas , Hovde Stacy , Deng Xiexiong , Wang Kuang-Wei , Lin Hsin Lian , Chien Hsiao-Tien , Kweon Hye Kyong , Kuo Nora Sheen , Ayoub Christopher A. , Jimenez-Harrison Daniela , Andrews Philip C. , Kwok Roland , Bochar Daniel A , Kuret Jeff , Fortin Jessica , Tsay Yeou-Guang , Kuo Min-Hao
Published: April 2020

BackgroundAlzheimer’s disease (AD) is an irreversible neurodegenerative disease without a cure or prevention to date. The defining features of AD include neurofibrillary tangles (NFTs) of hyperphosphorylated tau fibrils, and the senile plaques of β amyloid (Aβ) aggregates. In addition to AD, aggregation of hyperphosphorylated tau underlies approximately 20 neurodegenerative disorders collectively known as tauopathies, suggesting a pathogenic role of tau fibrils. The majority of AD disease-modifying drug trials targeted Aβ control, which have yet to produce satisfactory outcomes. The interest of developing anti-NFT drugs has been increasing. However, an effective method that produces hyperphosphorylated tau with disease relevant characters to support drug discovery is lacking.MethodsWe previously reported the PIMAX system for the production of recombinant proteins bearing a desired post-translational modification. Here we use PIMAX to express hyperphosphorylated tau (p-tau) in E. coli, and subjected this p-tau to mass spectrometry mapping of phosphorylation, to biochemical and biophysical assays of fibrillogenesis, and to cell culture treatment for the effects of hyperphosphorylation on tau molecular characters.ResultsMass spectrometry mapped p-tau phosphorylation to phosphoepitopes linked to AD pathological progression. In stark contrast to the unmodified tau that required an inducer for efficient aggregation, and which had only mild effects on cell functions, p-tau formed fibrils in an inducer-free and redox-independent manner. Immediately after the purification, a disease-specific conformation recognized by the MC-1 monoclonal antibody was readily detectable, which continued to increase during the fibrillization reaction. When applied to cultured cells, p-tau triggered a spike of mitochondrial superoxide, induced apoptosis, and caused cell death at sub-micromolar concentrations. In both aggregation and cytotoxicity assays, p-tau exhibited seeding activities that converted the unmodified tau into a cytotoxic species with increased propensity for fibrillization, consistent with the emerging view that hyperphosphorylated tau spreads in a prion-like fashion.ConclusionsHyperphosphorylation potentiates tau fibrillization and cytotoxicity. These characters are consistent with the model that abnormally phosphorylated tau plays a direct role in neurodegeneration in tauopathies. We suggest that p-tau produced by PIMAX affords a feasible tool for drug discovery and disease mechanistic studies for Alzheimer's disease and other tauopathies.
Estrogen inhibits the apoptosis of spiral ganglion cells in C57BL/6J mice with presbycusis by downregulating AQP4.
Authors: Chen Long , Yang Yu-qi , Li Xue-rui , Feng Zi-yi , Han Zi-wei , Ma Ke-tao , Li Li , Si Jun-qiang
Published: April 2020

BackgroundEstrogen has a protective effect on age-related hearing loss (ARHL), but the mechanism has not been elucidated. Cochlear spiral ganglion neurons (SGN) are an important link between the cochlear hair cells and the auditory center. This study used C57BL/6J mice as models of elderly individuals to observe the protective effect of estrogen against cochlear spiral ganglion cell apoptosis.MethodsFifty mice were divided into the following five groups (10 mice/group): the young group at 3 months of age (3 m), the elderly group at 12 months of age (12 m), the ovariectomized group at 12 months of age (12 m ovx), the ovariectomized group at 12 months of age + estrogen treatment for 1 month (E2 1 m), and the ovariectomized group at 12 months of age + estrogen treatment for 2 months (E2 2 m). The auditory brain stem response (ABR) was analyzed to detect changes in the hearing threshold, enzyme-linked immunosorbent assays (ELISAs) were used to determine the serum estrogen levels,Hematoxylin eosin (HE) staining and transmission electron microscopy (TEM) were used to observe the morphological changes in the cochlea spiral ganglion neurons (SGN), and TUNEL staining was used to observe the apoptosis of SGN. The expression of AQP4 was observed by immunofluorescence, and the mRNA expression levels of AQP4, Caspase-3, Bax and Bcl-2 in the cochlea spiral ganglion were determined by qRT-PCR. Cell experiments: Primary cultures of spiral ganglion cells were divided into a control group (SGC), DMSO group, D-gal group, D-gal + E2 group, D-gal + TGN020 group and D-gal + E2 + TGN020 group. Immunofluorescence was used to observe the AQP4 expression, qRT-PCR was used to observe the AQP4, Caspase-3, Bax and Bcl-2 mRNA expression levels, and flow cytometry was used to observe the apoptosis rate.ResultsAn increased hearing threshold was observed in the elderly mice (P < 0.001). After removal of the ovaries, the hearing threshold of the mice in the 12 m ovx group was higher than it was in the 12 m control group (P < 0.05), and this increased threshold was accompanied by an increased loss of spiral ganglion cells, increased apoptosis (P < 0.01), and increased AQP4 expression (P < 0.001). Treatment with exogenous estrogen reversed all these changes. Cell experiments: D-gal increased the apoptosis rate (P < 0.001) and AQP4 expression (P < 0.001). Estrogen and the AQP4 inhibitor TGN020 both reduced the apoptosis rate and AQP4 expression.Conclusion﻿Estrogen inhibited apoptosis of cochlear spiral ganglion cells in aged C57BL/6J mice by downregulating AQP4, thus achieving a protective effect on ARHL.
Boundarylessness and sleep quality among virtual team members – a cross-sectional study from Germany
Authors: Rohwer Elisabeth , Kordsmeyer Ann-Christin , Harth Volker , Mache Stefanie
Published: April 2020

Background
In the course of globalisation and digitalisation, new ways of work become increasingly prevalent. To remain competitive as an organisation, cooperation across time, place, and organisational boundaries becomes necessary. Virtual teamwork offers these advantages, but can also be both, an opportunity and a burden, for employees. The aim of this study is to gain first insights into job demands and resources in virtual teamwork to create a basis for deducing appropriate health promotion and prevention measures.
Methods
In this cross-sectional study, an online questionnaire was used to examine the relationship between boundarylessness as a job demand, psychological detachment as a personal resource, as well as perceived stress and sleep quality as health outcomes among 46 employees in virtual teamwork in Germany. Data collection lasted from October 2019 to January 2020. Validated scales were used for the questionnaire, except for virtuality. Due to insufficient operationalisation to date, a virtuality scale was developed based on the current state of research. The data were analysed with multiple regression analyses.
Results
The results show that virtuality and perceived stress impaired sleep quality of virtual team members in this sample. In contrast, successful psychological detachment from work was positively related to sleep quality. There were no significant results for boundarylessness. Virtual team members with managerial responsibility showed higher levels of psychological detachment.
Conclusion
The study provides first insights in the relationship between virtual teamwork and employee health in the German context. Further research, particularly on job demands in virtual teamwork, is needed to derive concrete health promotion and prevention measures.
Differentially expressed genes SNRPC and PRPF38A are potential biomarkers candidates for osteosarcoma
Authors: Chang Sheng , Cao Yang
Published: April 2020

Background: Osteosarcoma (osteogenic sarcoma, OS) is a primary cause of morbidity and mortality and is associated with poor prognosis in the field of orthopedic. Globally, rates of OS are highest among 15 to 25-year-old adolescent. However, the mechanism of gene regulation and signaling pathway is unknown. Material and Methods: GSE9508, including 34 OS samples and 5 non-malignant bone samples, was gained from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were picked out by GEO2R online R soft tool. Furthermore, the protein-protein interaction (PPI) network between the DEGs was molded utilizing STRING online software. Afterward, PPI network of DEGs was constructed. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs were carried out on DAVID online tool and visualized via cytoscape software. Subsequently, module analysis of PPI was performed by using MCODE app. What’s more, prognosis-related genes were screened by using online databases including GEPIA, UALCAN and cBioPortal databases. Results: Totally, 671 DEGs were picked out, including 501 up-regulated genes and 170 down-regulated genes. Moreover, 22 hub genes were identified to be significantly expressed in PPI network (16 up-regulated and 6 down-regulated). We found that spliceosome signaling pathway may provide a potential target in OS. Furthermore, on the basis of common crucial pathway, PRPF38A and SNRPC were closely associated with spliceosome. Conclusion: This study showed that SNRPC and PRPF38A are potential biomarkers candidates for osteosarcoma.
Establishment of an integrated model for predicting survival and guiding treatment in local recurrence nasopharyngeal carcinoma
Authors: Xie Hao-Jun , Sun Xue-Song , Jia Guo-Dong , Sun Rui , Luo Dong-Hua , Liu Li-Ting , Guo Shan-Shan , Liu Sai-Lan , Tang Lin-Quan , Chen Qiu-Yan , Mai Hai-Qiang
Published: April 2020

Objective:In this study, we aimed to establish an integrated prognostic model for local recurrence nasopharyngeal carcinoma (lrNPC) patients, and evaluate the benefit of re-radiotherapy (RT) in patients with different risk levels.Materials and methods:In total, 271 patients with lrNPC were retrospectively reviewed in this study. Overall survival (OS) was the primary endpoint. Multivariate analysis was performed to select the significant prognostic factors (P<0.05). A prognostic model for OS was derived by recursive partitioning analysis (RPA) combining independent predictors using the algorithm of optimized binary partition.Results:Three independent prognostic factors (age, relapsed T [rT] stage, and Epstein-Barr virus [EBV] DNA) were identified from multivariable analysis. Five prognostic groups were derived from an RPA model that combined rT stage and EBV DNA. After further pair-wise comparisons of survival outcome in each group, three risk groups were generated. We investigated the role of re-RT in different risk groups, and found that re-RT could benefit patients in the low (P<0.001) and intermediate-risk subgroups (P=0.017), while no association between re-RT and survival benefit was found in the high-risk subgroup (P=0.328).Conclusion:Age, rT stage and EBV DNA were identified as independent predictors for lrNPC. We established an integrated RPA-based prognostic model for OS incorporating rT stage and EBV DNA, which could guide individual treatment for lrNPC.
Peripheral cytokine levels as predictive biomarkers of benefit from immune checkpoint inhibitors in cancer therapy
Authors: Ji Shoujian , Chen Huan , Yang Keyan , Zhang Guanxiong , Mao Beibei , Hu Ying , Zhang Henghui , Xu Jianming
Published: April 2020

Background：Currently, only a small subset of cancer patients can benefit from anti-PD-1/PD-L1 monotherapy, indicating that further predictive biomarkers are needed. Methods：In the retrospective study, plasma samples were collected before anti-PD-L1/PD-L1 treatment in two subset of patients. A total of 59 immunological factors, including cytokines, chemokines, and soluble immune checkpoints, were measured by using a multiplex immunoassay kit. Moreover, multiplex immunohistochemistry (mIHC) was performed in a subgroup of patients.Results：In the discovery cohort, multiplex immunoassay profiling data revealed that both soluble PD-L1 and C-C motif chemokine 5 (CCL5/RANTES) showed rising trends across the three subgroups PD, SD and CR/PR. Further investigation demonstrated the predictive and prognostic value of the pre-treatment levels of PD-L1, CCL5/RANTES, and their combinatorial signature the “2-cytokine signature”. As expected, the signature-high patients displayed a remarkably increased disease control rate (DCR) and prolonged survival versus that of the lower subgroup. More importantly, the relevance between the three signatures and the efficiency of immunotherapy was confirmed in the pan-cancer validation cohort. Notably, the significant association between the “2-cytokine signature” and longer survival was validated. Further quantitative analyses of the tumor microenvironment composition suggested a link between the “2-cytokine signature” and NK cell infiltration.Conclusions：A combined peripheral signature comprising CCL5/RANTES and soluble PD-L1 appears to be an effective biomarker to predict benefit from anti-PD-1/PD-L1 monotherapy. Our study underscores that peripheral immunological features may play an essential role in guiding patient selection and are worthy of future prospective investigations.
Clinical efficacy and safety in patients treated with teicoplanin with a target trough concentration of 20 μg/mL using a regimen of 12 mg/kg for five doses within the initial 3 days
Authors: Ueda Takashi , Takesue Yoshio , Nakajima Kazuhiko , Ichiki Kaoru , Ishikawa Kaori , Takai Yoshiko , Yamada Kumiko , Tsuchida Toshie , Otani Naruhito , Takahashi Yoshiko , Ishihara Mika , Takubo Shingo , Ikeuchi Hiroki , Uchino Motoi , Kimura Takeshi
Published: April 2020

Background: A trough concentration (Cmin) ≥20 μg/mL of teicoplanin is recommended for the treatment of serious methicillin-resistant Staphylococcus aureus (MRSA) infections. However available data are limited because it is difficult to attain this target Cmin.Methods: Pharmacokinetics and adverse events were evaluated in all eligible patients. For clinical efficacy, patients who had bacteremia/complicated MRSA infections were analyzed. The primary endpoint for clinical efficacy was an early clinical response at 72–96 h after the start of therapy. Five dosed of 12 mg/kg or 10 mg/kg was administered as an enhanced or conventional high loading dose regimen, respectively. The Cmin was obtained at 72 h after the first dose.Results: Overall, 512 patients were eligible, and 76 patients were analyzed for treatment efficacy. The proportion of patients achieving the target Cmin range (20–40 μg/mL) by the enhanced regimen was significantly higher than for the conventional regimen (75.2% versus 41.0%, p < 0.001). In multivariate analysis, Cmin ≥20 μg/mL was an independent factor for an early clinical response (odds ratio 3.95, 95% confidence interval 1.25–12.53). There was no significant difference in the occurrence of adverse events between patients who did or did not achieve a Cmin ≥20 μg/mL.Conclusion: A target Cmin ≥20 μg/mL might improve early clinical responses during the treatment of difficult MRSA infections using 12 mg/kg teicoplanin for five doses within the initial 3 days.
Characterization of 1q Duplication by Array Comparative Genomic Hybridization in Acute Myeloid Leukemia Patients with t(8;16)(p11.2;p13.3)
Authors: Liu Meng , Ren Yuan , Wang Xianfu , Lu Xianglan , Li Ming , Kim Young Mi , Li Shibo , Zhang Lijun
Published: April 2020

Background: Acute myeloid leukemia (AML) is a complex hematological disease characterized by genetic and clinical heterogeneity. The identification and understanding of chromosomal abnormalities are important for the diagnosis and management of AML patients. Compared to recurrent chromosomal translocations in AML, t(8;16)(p11.2;p13.3) can be found in any age group, but is very rare and typically associated with poor prognosis. Methods: Cytogenetic studies were performed among 1,824 AML patients from our oncology database in the last 20 years by karyotype analysis. Fluorescence in situ hybridization (FISH) was used to further confirm the chromosomal translocation fusion. Array comparative genome hybridization (aCGH) was carried out to characterize the additional chromosomal segments in patients with t(8;16)(p11.2;p13.3). Results: Three patients with t(8;16)(p11.2;p13.3) were identified. One patient was pure t(8;16)(p11.2;p13.3), and the other two had an additional chromosomal anomaly of 1q duplication. Interestingly, the molecular size and position of this 1q duplication were similar in both patients, showing as 46.7 Mb and 49.9 Mb, respectively. Conclusion: 1q duplication is a recurrent event in AML patients with t(8;16)(p11.2;p13.3), indicating it could also play a role of an unfavorable prognostic factor.
Utility of 18F-FDG PET/CT for Predicting Pathologic Complete Response in Luminal HER2-Negative Breast Cancer Patients Receiving Neoadjuvant Chemotherapy
Authors: Lee In Hee , Lee Soo Jung , Lee Jeeyeon , Jung Jinhyang , Park Hoyong , Jeong Shin Young , Lee Sang-woo , Chae Yee Soo
Published: April 2020

Purpose: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) is a predictor of improved outcomes in breast cancer. In patients with luminal-type breast cancer, the response to NAC is variable and mostly limited. This study was an investigation of the predictive relevance of parameters of 18 F-FDG PET/CT for the pCR to NAC in patients with luminal HER2–negative breast cancer. Methods: A total of 109 consecutive hormone receptor-positive and HER2-negative breast cancer patients who were treated with NAC were enrolled in this prospective cohort study. The relationships between pretreatment 18 F-FDG PET/CT and clinical outcomes including pathologic response to NAC were evaluated. Results: All patients finished their planned NAC cycles and eight patients (7.3%) achieved pCR. In the receiver operating characteristic (ROC) curve analysis, pSUVmax exhibited high sensitivity and specificity for predicting pCR. Furthermore, multivariate logistic regression analysis revealed pSUVmax as a predictive factor for pCR (hazard ratio = 17.452; 95% CI = 1.847 – 164.892; p = 0.013). Conclusion: The results of this study suggest that 18 F-FDG PET/CT pSUVmax is a predictive factor for pCR of luminal HER2-negative breast cancer to NAC.
Artificial Neural Networks Improve LDCT Lung Cancer Screening: A Comparative Validation Study
Authors: Hsu Yin-Chen , Tsai Yuan-Hsiung , Weng Hsu-Huei , Hsu Li-Sheng , Tsai Ying-Huang , Lin Yu-Ching , Hung Ming-Szu , Fang Yu-Hung , Chen Chien-Wei
Published: April 2020

Background: This study proposes a prediction model for the automatic assessment of lung cancer risk based on an artificial neural network (ANN) with a data-driven approach to the low-dose computed tomography (LDCT) standardized structure report. Methods: This comparative validation study analysed a prospective cohort from Chiayi Chang Gung Memorial Hospital, Taiwan. In total, 836 asymptomatic patients who had undergone LDCT scans between February 2017 and August 2018 were included, comprising 27 lung cancer cases and 809 controls. A derivation cohort of 602 participants (19 lung cancer cases and 583 controls) was collected to construct the ANN prediction model. A comparative validation of the ANN and Lung-RADS was conducted with a prospective cohort of 234 participants (8 lung cancer cases and 226 controls). The areas under the curves (AUCs) of the receiver operating characteristic (ROC) curves were used to compare the prediction models. Results: At the cut-off of category 3, the Lung-RADS had a sensitivity of 12.5%, specificity of 96.0%, positive predictive value of 10.0%, and negative predictive value of 96.9%. At its optimal cut-off value, the ANN had a sensitivity of 75.0%, specificity of 85.0%, positive predictive value of 15.0%, and negative predictive value of 99.0%. The area under the ROC curve was 0.764 for the Lung-RADS and 0.873 for the ANN (P=0.01). The heatmap plot demonstrates the leading items, i.e., solid nodules, partially solid nodules, and ground-glass nodules, as the significant predictors of malignant outcomes.Conclusions: Compared to the Lung-RADS, the ANN provided better sensitivity for the detection of lung cancer in an Asian population. In addition, the ANN provided a more refined discriminative ability than the Lung-RADS for lung cancer risk stratification with population-specific demographic characteristics. When lung nodules are detected and documented in a standardized structured report, ANNs may better provide important insights for lung cancer prediction than conventional rule-based criteria.Trial registration: Not applicable.
Efficacy of transfusion pre-medications on attenuating transfusion reaction in adults: A systematic review and meta-analysis
Authors: Yu Shiyuan , Liu Yawei , Gao Yanxia , Lu Xin , Zhao Lina , Ge Zengzheng , Zhu Huadong , Yi Li
Published: April 2020

Background – Transfusion pre-medications are generally administered in patients prior to blood transfusion. However, the use of transfusion pre-medications is largely experience-based instead of evidence-based. Our meta-analysis aimed to combine the most updated evidence and demonstrate the efficacy of transfusion pre-medications on attenuating transfusion reaction among patients. Material and Method – Pubmed, EMBASE, Cochrane Library, Wanfang database, CNKI, CMB was searched for related articles. Data from transfusion pre-medications treated group and transfusion pre-medications free group was collected. Baseline characteristics between groups were compared using SPSS 19.0. RevMan 5.3 was used to pool the collected data for meta-analysis between groups. OR and SMD were used to demonstrate the outcomes. Results - Eight eligible articles (6 case control studies and 2 RCT) were identified, including 22060 cases. Administered transfusion pre-medications included dexamethasone, chlorpheniramine or promethazine. Baseline characteristics showed no significant difference between groups regarding age and gender. There was no significant difference between transfusion pre-medications treated group and transfusion pre-medications free group concerning the rate of fever, itchy, rash, airway spasm and overall transfusion reaction. Conclusion – Dexamethasone, chlorpheniramine or promethazine is probably not a candidate for prevention of transfusion reaction. Avoiding experienced use of such transfusion pre-medications before blood transfusion may reduce the number of adverse drug reaction and clinical trial is still needed in the future to figure out the treatment for alleviating transfusion reaction.
Non-monotonous growth and motion of the South Atlantic Anomaly
Authors: Amit Hagay , Terra-Nova Filipe , Lézin Maxime , Trindade Ricardo
Published: April 2020

The South Atlantic Anomaly (SAA) is a region at Earth’s surface where the intensity of the magnetic field is particularly low. Accurate characterization of the SAA is important for both fundamental understanding of core dynamics and the geodynamo as well as societal issues such as the erosion of instruments at surface observatories and onboard spacecrafts. Previous studies applied crude measures of the SAA. Here we propose new measures to better characterize the SAA area and center, accounting for global dipole changes and shape anisotropy. Applying our characterization to a geomagnetic field model covering the historical era, we find that the mean SAA area increase and westward drift rates are twice slower than previously reported. Our results reveal that the SAA area and center are much more time-dependent, including episodes of area decrease, eastward drift and rapid southward drift. We interpret these special events in terms of the secular variation of relevant large-scale geomagnetic flux patches on the core-mantle boundary. Our characterization may be used as a constraint on Earth-like numerical dynamo models.
Efficacy of Orbital Radiotherapy in Moderate-to-Severe Active Graves’ Orbitopathy Including Long-lasting Disease
Authors: Choi Jin Hwa , Lee Jeong Kyu
Published: April 2020

Background: We aimed to explore the efficacy of orbital radiotherapy (RT) in patients with moderate-to-severe active Graves’ orbitopathy (GO), including long-lasting disease, and to determine the predictive factors associated with treatment response. Methods: This was a retrospective study of 62 moderate-to-severe active GO patients treated with RT. Demographic data and ophthalmic findings prior to RT and at 3 and 6 months afterward were analyzed. Computed tomography was performed before and after RT to compare orbital volume change. We used logistic regression to determine the predictive factors for treatment response. Subjects were divided into early- and late-active phase groups based on GO duration of 24 months and treatment outcomes were compared with each other to observe the effects of RT timing on treatment response. Results: Forty (64.5%) and forty-six (74.1%) patients experienced improvements in GO at 3 and 6 months after radiotherapy, respectively. Ocular parameters such as clinical activity score (CAS), proptosis, extraocular muscle (EOM) limitation, and compressive optic neuropathy (CON) were improved by RT. Volumes of EOM significantly decreased after RT. The enlargement of EOMs and EOM limitation were predictive factors for a good response to RT. At 6 months after RT, 22 (68.8%) patients of late-active phase group exhibited improvement in GO, which is comparable to the number of 24 (80.0%) patients of early-active phase group. In the late-active phase group, CAS, diplopia, and visual acuity were improved significantly, but there was no change in EOM limitation. Conclusions: In moderate-to-severe active GO patients, orbital RT may help improve high CAS, proptosis, EOM limitation, and CON. The orbital RT in long-lasting active GO patients may be considered as treatments for the relief of symptoms including high CAS and poor visual acuity.
Combining texture features of whole slide images improves prognostic prediction of recurrence-free survival for cutaneous melanoma patients
Authors: Peng Yanbin , Chu Yunfeng , Chen Zhong , Zhou Wen , Wan Shengxiang , Xiao Yingfeng , Zhang Youlong , Li Jialu
Published: April 2020

Background: Accurate prediction of recurrence-free survival (RFS) is important for the prognosis of cutaneous melanoma patients. The image-based pathological examination remains as the gold standard for diagnosis. It is of clinical interest to account for computer-aided processing of pathology image when performing prognostic analysis.Methods: We enrolled in this study a total of 152 patients from TCGA-SKCM with complete information in recurrence-related survival time, baseline variables (clinicopathologic variables, mutation status of BRAF and NRAS genes), gene expression data and whole slide image (WSI) features. We preprocessed WSI to segment global or nucleus areas, and extracted 3 types of texture features from each region. We performed cross validation and used multiple evaluation metrics including C-index and time-dependent AUC to determine the best model of predicting recurrence events. We further performed differential gene expression analysis between the higher and lower-risk groups within AJCC pathologic tumor stage III patients to explore the underlying molecular mechanisms driving risk stratification. Results: The model combining baseline variables and WSI features had the best performance among models with any other types of data integration. The prognostic risk score generated by this model could provide a higher-resolution risk stratification within pathologically-defined subgroups. We found the selected image features captured important immune-related variations, such as the aberration of expression in T cell activation and proliferation gene sets, and therefore contributed to the improved prediction. Conclusions: Our study provided a prognostic model based on the combination of baseline variables and computer-processed WSI features. This model provided more accurate prediction than models based on other types of data combination in recurrence-free survival analysis. Trail registration: This study was based on public open data from TCGA and hence the study objects were retrospectively registered.
Fabrication and electrical characteristics of flash-sintered SiO2-doped ZnO-Bi2O3-MnO2 varistors
Authors: Peng Pai , Niu Jingpeng , Shi Liyi , Mei Yunzhu , Du Sanming , Liu Juan , XU Dong
Published: April 2020

The dense ZnO-Bi 2 O 3 -MnO 2 - x SiO 2 (ZBMS) varistors were fabricated by flash sintering method under the low temperature of 850 o C within 2 minutes. The phase structure, density, microstructure, and electrical characteristics of the flash-sintered ZBMS varistors with different SiO 2 doping content were investigated. According to the XRD analysis, many secondary phases were detected due to the doping of SiO 2 . Meanwhile, the average grain size decrease with increasing SiO 2 doping content. In addition, the electrical properties of all samples were analyzed. The improved nonlinear characteristics were obtained in SiO 2 doped samples, which can be attributed to the ion migration and oxygen absorption induced by the doping of SiO 2 . The flash-sintered ZBMS varistor ceramics exhibited excellent comprehensive electrical properties, with the nonlinear coefficient of 24.5, the threshold voltage and leakage current of 385 V/mm and 11.8 µA, respectively.
Bixin Attenuates Experimental Autoimmune Encephalomyelitis by Suppressing TXNIP/NLRP3 inflammasome Activity and Activating Nrf2 Signaling
Authors: Yu Ye , Wu Dong-ming , Li Jing , Deng Shi-hua , Liu Teng , Zhang Ting , He Miao , Zhao Yang-yang , Xu Ying
Published: April 2020

Background Multiple sclerosis (MS), an autoimmune and degenerative disease, is characterized by demyelination and chronic neuroinflammation.Bixin is a carotenoid isolated from the seeds of Bixa orellana that exhibits various potent pharmacological activities, including antioxidant, anti-inflammation, and anti-tumor. However, the effects of bixin on MS remain elusive.Methods To evaluate the effects and underlying molecular mechanisms of bixin on MS, experimental autoimmune encephalomyelitis (EAE) was established in C57BL/6 mice, which were treated with intragastric administration of bixin solutions. To evaluate the molecular mechanisms of bixin, quantitative reverse-transcription PCR, western blot, immunohistochemistry, and enzyme-linked immunosorbent assay analyses were performed.Results We found that bixin significantly improved the symptoms in EAE mice, and suppressed microglia aggregation and TXNIP/NLRP3 inflammasome activity by scavenging excessive reactive oxygen species (ROS). Furthermore, bixin activated nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream genes in EAE mice, and these effects were suppressed upon inhibiting Nrf2 expression with the Nrf2 inhibitor ML385.Conclusions Bixin prevented neuroinflammation and demyelination in EAE mice mainly by scavenging ROS through activation of the Nrf2 signaling pathway. Taken together, our results indicate that bixin is a promising therapeutic candidate to treat MS.
Guidelines and best practice recommendations on contraception and safe abortion care service provision amid COVID-19 pandemic: Scoping review.
Authors: Tolu Lemi Belay , Feyissa Garumma Tolu
Published: April 2020

Introduction: During pandemics there is uncertainty and information overload. Policy makers and health professionals prefer to use summarized evidence of practice recommendations. The aim of this scoping review is therefore to identify available best guidelines, consensus statements, standard of practice and practice recommendations on contraception and safe abortion care service provision during the COVID-19 pandemics.Methods: We searched guideline databases and websites of professional associations and international organizations working on sexual and reproductive health to locate guidelines, protocols, consensus statements and practice recommendations on sexual reproductive health services (SRH) during COVID-19 pandemics. Additionally, we searched: MEDLINE, EMBASE and Google Scholar. We included English records labelled guideline, or recommendation, or consensus, or practice parameter, or position papers on contraception and safe abortion care service practice during the COVID-19 pandemics. Data extraction was done by two independent reviewers using a customized tool that was developed to record the key information of the source that’s relevant to the review question. The difference between the two authors on data extraction was resolved by discussion.Results: Eleven records on safe abortion care and nine records on contraception service were identified. Identified recommendations were categorized into thematic areas. The records addressed approaches to the safe medication and surgical abortion, self-serving family planning and long term and reversible contraception. We haven’t employed any of the quality assessment tools as the pandemic is new clinical entity and evidences are based on expert opinion and limited clinical evidence.Conclusions: Consensus statements and recommendations consistently stated that there should be access to contraception service and safe abortion care during the COVID-19 pandemics with the concerted effort of service re-organization. The practice recommendations focus on innovative ways of service provision to minimize patient and staff exposure to COVID-19 as well as alleviate the burden on the health care system. These include utilizing telemedicine or digital health and community/home-based care or self-care.
Network theoretic analysis of JAK/STAT pathway and extrapolation to drugs and viruses including COVID-19
Authors: Banerjee Arindam , Goswami Rudra Prosad , Chatterjee Moumita
Published: April 2020

Whenever some phenomenon can be represented as a graph or a network it seems pertinent to explore how much the mathematical properties of that network impact the phenomenon. In this study we explore the same philosophy in the context of immunology. Our objective was to assess the correlation of “size” (number of edges and minimum vertex cover) of the JAK/STAT network with treatment effect in rheumatoid arthritis (RA), phenotype of viral infection and effect of immunosuppressive agents on a system infected with the coronavirus. We extracted the JAK/STAT pathway from Kyoto Encyclopedia of Genes and Genomes (KEGG, hsa04630). The effects of the following drugs, and their combinations, commonly used in RA were tested: methotrexate, prednisolone, rituximab, tocilizumab, tofacitinib and baricitinib. Following viral systems were also tested for their ability to evade the JAK/STAT pathway: Measles, Influenza A, West Nile virus, Japanese B virus, Yellow Fever virus, respiratory syncytial virus, Kaposi’s sarcoma virus, Hepatitis B and C virus, cytomegalovirus, Hendra and Nipah virus and Coronavirus. Good correlation of edges and minimum vertex cover with clinical efficacy were observed (for edge, rho= -0.815, R2= 0.676, p=0.007, for vertex cover rho= -0.793, R2= 0.635, p=0.011). In the viral systems both edges and vertex cover were associated with acuteness of viral infections. In the JAK/STAT system already infected with coronavirus, maximum reduction in size was achieved with baricitinib. To conclude, algebraic and combinatorial invariant of a network may explain its biological behaviour. At least theoretically, baricitinib may be an attractive target for treatment of coronavirus infection.