bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disturbed temporal dynamics of episodic retrieval activity with preserved spatial activity pattern in amnestic mild cognitive impairment: A simultaneous EEG-fMRI study
Authors: Shu Hao , Gu Lihua , Yang Ping , Lucas Molly V. , Gao Lijuan , Zhang Hongxing , Zhang Haisan , Xu Zhan , Wu Wei , Li Ling , Zhang Zhijun 
Published: September 2020

Abstract
Background
Episodic memory (EM) deficit is the core cognitive dysfunction of amnestic mild cognitive impairment (aMCI). However, the episodic retrieval circuit detected by functional MRI (fMRI) appears preserved in aMCI subjects. To address this discrepancy, this study employed simultaneous electroencephalography (EEG)-fMRI recording to determine whether temporal dynamics of brain episodic retrieval activity were disturbed in patients with aMCI.
Methods
Twenty-six aMCI and 29 healthy control (HC) subjects completed a word-list memory retrieval task during simultaneous EEG-fMRI. The retrieval success activation pattern was detected with fMRI analysis, and the familiarity- and recollection-related components of episodic retrieval activity were identified using event-related potential (ERP) analysis. The fMRI-constrained ERP analysis explored the temporal dynamics of brain activity in the retrieval success pattern, and the ERP-informed fMRI analysis detected fMRI correlates of the ERP components related to familiarity and recollection processes.
Results
The two groups exhibited similar retrieval success patterns in the bilateral posteromedial parietal cortex, the left inferior parietal lobule (IPL), and the left lateral prefrontal cortex (LPFC). The fMRI-constrained ERP analysis showed that the aMCI group did not exhibit old/new effects in the IPL and LPFC that were observed in the HC group. In addition, the aMCI group showed decreased fMRI activity in the precuneus and left hippocampus related to ERP familiarity and recollection components, respectively.
Conclusions
This study identified disturbed temporal dynamics in episodic retrieval activity with a preserved spatial activity pattern in aMCI. Taken together, the simultaneous EEG-fMRI technique demonstrated the potential to identify individuals with a high risk of cognitive deterioration.
Single Cell Analysis of Regions of Interest (SCARI) using a Novel Photoswitchable Tag
Authors: Leun Anne van der , Hoekstra Mirjam , Reinalda Luuk , Scheele Colinda , Toebes Mireille , de Graaff Michel van , Li Hanjie , Bercovich Akhiad , Lubling Yaniv , David Eyal , Thommen Daniela , Tanay Amos , Rheenen Jacco van , Amit Ido , Kasteren Sander van , Schumacher Ton 
Published: September 2020

Abstract
The functional activity and differentiation potential of cells is determined by their interaction with surrounding cells. Approaches that allow the unbiased characterization of cell states while at the same time providing spatial information are of major value to assess this environmental influence. However, most current techniques are hampered by a trade-off between spatial resolution and cell profiling depth. Here, we developed a photoswitch-based technology that allows the isolation and in-depth analysis of live cells from regions of interest in complex ex vivo systems, including human tissues. The use of a highly sensitive 4-nitrophenyl(benzofuran)-cage coupled to nanobodies allowed photoswitching of cells in areas of interest with low-intensity violet light and without detectable phototoxicity. Single cell RNA sequencing of spatially defined CD8+ T cells was used to exemplify the feasibility of identifying location-dependent cell states at the single cell level. Finally, we demonstrate the efficient labeling and photoswitching of cells in live primary human tumor tissue. The technology described here provides a valuable tool for the analysis of spatially defined cells in diverse biological systems, including clinical samples.
Capsid Assembly is Regulated by Amino Acid Residues Asparagine 47 and 48 in The VP2 Protein of Porcine Parvovirus
Authors: Wang Jucai , Liu Yunchao , Chen Yumei , Zhang Teng , Wang Aiping , Wei Qiang , Liu Dongmin , Wang Fangyu , Zhang Gaiping 
Published: September 2020

Abstract
Background: Porcine parvovirus (PPV) is a major cause of reproductive failure in swine, and has caused huge losses throughout the world. Viral protein 2 (VP2) of PPV is a major structural protein that can self-assemble into virus-like particles (VLP) with hemagglutination (HA) activity. In order to identify the essential residues involved in the mechanism of capsid assembly and to further understand the function of HA, we analyzed a series of deletion mutants and site-directed mutations within the N-terminal of VP2 in the Escherichia coli (E. coli) system. Results: Our results showed that deletion of first 47 amino acids from the N-terminal of VP2 protein did not affect capsid assembly, and further truncation to residue 48 Asparagine (Asn, N) caused detrimental effects. Site-directed mutagenesis experiments demonstrated that residue 47Asn reduced the assembly efficiency of PPV VLP, while residue 48Asn destroyed the stability, hemagglutination, and self-assembly characteristics of the PPV VP2 protein. These findings indicated that the residues 47Asn and 48Asn are important amino acid sites to capsid assembly and HA activity. Results from Native PAGE inferred that macromolecular polymers were critical intermediates of the VP2 protein during the capsid assembly process. Site-directed mutation at 48Asn did not affect the association of monomers to form into oligomers, but destroyed the ability of oligomers to assemble into macromolecular particles, influencing both capsid assembly and HA activity. Conclusions: These results demonstrated that PPV capsid assembly is a complex process that is regulated by amino acids 47Asn and 48Asn, which are located at the N-terminal of VP2 and closely related to the association of macromolecular particles. Our findings provide valuable information on the mechanisms of PPV capsid assembly and the possibility of chimeric VLP vaccine development by replacing as much as 47 amino acids at the N-terminal of VP2 protein.
Validation of The Patient-Reported Experience Measure for Care in Chinese Hospitals (PREM-CCH)
Authors: Wang Xuanxuan , Chen Jiaying , Yang Yaling , Burström Bo , Burström Kristina 
Published: September 2020

Abstract
Background: A psychometrically validated instrument to measure patient experience in Chinese public hospitals would be useful and is currently lacking. Our research team developed the Patient-Reported Experience Measure for Care in Chinese Hospitals (PREM-CCH). We aimed to validate this PREM-CCH in the present study.Methods: Data were drawn from a cross-sectional patient survey in 2016. Complete responses from 2,293 outpatients and 1,510 inpatients were included. Separate psychometric evaluation was carried out on outpatient and inpatient PREM-CCHs in terms of exploratory factor analysis, internal consistency, construct validity and criterion validity.Results: The validated outpatient PREM-CCH contained 22 items and five Factors, i.e. Communication and information, Professional competence, Medical costs, Efficiency, and Hospital recommendation. The validated inpatient PREM-CCH contained 19 items and six Factors, i.e. Communication and information, Professional competence, Medical costs, Efficiency, Health outcomes, and Hospital recommendation. The PREM-CCH showed satisfactory internal consistency, construct validity and criterion validity.Conclusions: The PREM-CCH is one of the first validated instruments capturing patient experience of care in the context of Chinese public hospitals. It performed well in the psychometric evaluation. It consists of a basic set of items important to patients that could be applicable to public hospitals in China and actionable to inform quality improvement initiatives.
Automatic Classification of Heterogeneous&nbsp;Slit-Illumination Images Using an Ensemble of Cost-Sensitive Convolutional Neural Networks
Authors: Jiang Jiewei , Wang Liming , Fu Haoran , Long Erping , Sun Yibin , Li Ruiyang , Li Zhongwen , Zhu Mingmin , Liu Zhenzhen , Chen Jingjing , Lin Zhuoling , Wu Xiaohang , Wang Dongni , Liu Xiyang , Lin Haotian 
Published: September 2020

Abstract
Background: Lens opacity seriously affects the visual development of infants. Slit-illumination images play an irreplaceable role in lens opacity detection; however, these images exhibited varied phenotypes with severe heterogeneity and complexity, particularly among pediatric cataracts. Therefore, it is urgently needed to explore an effective computer-aided method to automatically diagnose heterogeneous lens opacity and to provide appropriate treatment recommendations in a timely manner.Methods: We integrated three different deep learning networks and a cost-sensitive method into an ensemble learning architecture, and then proposed an effective model called ECCNN-Ensemble (ensemble of cost-sensitive convolutional neural networks) for automatic lens opacity detection. A total of 470 slit-illumination images of pediatric cataracts were used for training and comparison between the CCNN-Ensemble model and conventional methods. Finally, we used two external datasets (132 independent test images and 79 Internet-based images) to further evaluate the model’s generalizability and effectiveness.Results: Experimental results and comparative analyses demonstrated that the proposed method was superior to conventional approaches and provided clinically meaningful performance in terms of three grading indices of lens opacity: area (specificity and sensitivity; 92.00% and 92.31%), density (93.85% and 91.43%) and opacity location (95.25% and 89.29%). Furthermore, the comparable performance on the independent testing dataset and the internet-based images verified the effectiveness and generalizability of the model. Finally, we developed and implemented a website-based automatic diagnosis software for pediatric cataract grading diagnosis in ophthalmology clinics. Conclusions: The CCNN-Ensemble method demonstrates higher specificity and sensitivity than conventional methods on multi-source datasets. This study therefore provides a practical strategy for heterogeneous lens opacity diagnosis and has the potential to be applied to the analysis of other medical images.
The&nbsp;Germline/Somatic DNA Damage Repair Gene Mutations&nbsp;Modulate the Therapeutic Response&nbsp;in Chinese Patients with Advanced Pancreatic Ductal Adenocarcinoma
Authors: Shui Lin , Li Xiaofen , Peng Yang , Tian Jiangfang , Li Shuangshuang , He Du , Li Ang , Tian Bole , Li Mao , Yi Cheng , Cao Dan 
Published: September 2020

Abstract
Background: PDAC is a fatal disease with molecular heterogeneity, inducing differences in biological behavior and therapeutic strategy. NGS profiles of pathogenic alterations in Chinese PDAC population are limited. We conducted a retrospective study to investigate the predictive role of DNA damage repair (DDR) mutations in precise medicine. Methods: NGS were performed on resected tissues or peripheral blood from 195 Chinese PDAC patients. Baseline clinical or genetic characteristics, and survival status were collected. The Kaplan–Meier survival analyses were performed by the R version 3.6.1.Results: The main driver genes were KRAS, TP53, CDKN2A, and SMAD4. Advanced patients with KRAS mutation showed worse OS than those without (p=0.048). DDR deficiency was identified in 30 (15.38%) of overall patients, mainly involving BRCA2 (n=9, 4.62%), ATM (n=8, 4.10%) and RAD50 genes (n=3, 1.54%). There was no significant improvement of OS between patients with or without DDR mutations (p=0.88). Treatment with platinum-based chemotherapy (p=0.0096) or olaparib (p=0.018) respectively improved the overall survival of patients with DDR mutation. No statistical correlation between tumor mutation burden (TMB) and DDR mutations was identified. Treatment of PD-1 blockades did not bring significiantly improved OS to DDR-mutated patients than intact DDR group (p=0.14). Conclusions: In this multi-center retrospective study, we showed the role of germline and somatic DDR mutation in predicting the efficacy of olaparib and platinum-based chemotherapy. However, DDR alteration has shown limited value in prediction of hypermutational status and the sensitivity to PD-1 blockade.
Clinical Implications of Copy Number Alteration Detection Using Panel-Based Next-Generation Sequencing Data in Myelodysplastic Syndrome
Authors: Kim Yoo-Jin , Jung SeungHyun , Hur Eun-Hye , Choi Eun-Ji , Lee Kyoo-Hyung , Park Hyeon-Chun , Kim Hye-Jung , Kwon Yong-Rim , Park Silvia , Lee Sug Hyung , Chung Yeun-Jun , Lee Je-Hwan 
Published: September 2020

Abstract
Background: Recent advancements in next-generation sequencing (NGS) technologies allow the simultaneous identification of targeted copy number alterations (CNAs) as well as somatic mutations using the same panel-based NGS data. We investigated whether CNAs detected by the targeted NGS data provided additional clinical implications, over somatic mutations, in myelodysplastic syndrome (MDS). Methods: Targeted deep sequencing of 28 well-known MDS-related genes was performed for 266 patients with MDS. Results: Overall, 215 (80.8%) patients were found to have at least one somatic mutation; 67 (25.2%) had at least one CNA; 227 (85.3%) had either a somatic mutation or CNA; 160 had somatic mutations without CNA; and 12 had CNA without somatic mutations. Considering the clinical variables and somatic mutations alone, multivariate analysis demonstrated that sex, revised International Prognostic Scoring System (IPSS-R) and NRAS and TP53 mutations were independent prognostic factors for overall survival. For AML-free survival, these factors were sex, IPSS-R, and mutations in NRAS, DNMT3A, and complex karyotype/TP53 mutations. When we consider clinical variables along with somatic mutations and CNAs, genetic alterations in TET2, LAMB4, U2AF1, and CBL showed additional significant impact on the survivals. Conclusions: Our study suggests that the concurrent detection of somatic mutations and targeted CNAs may provide clinically useful information for the prognosis of MDS patients.
Knockdown of NUSAP1 Inhibits Cell Proliferation and Invasion Through Down-Regulation of TOP2A in Human Glioblastoma
Authors: Hu Yaotian , Xue Zhiyi , Qiu Chen , Feng Zichao , Qi Qichao , Wang Jiwei , Jin Wenxing , Zhong Zhaoyang , Liu Xiaofei , Li Wenjie , Zhang Qing , Huang Bin , Chen Anjing , Wang Jian , Yang Ning , Zhou Wenjing 
Published: September 2020

Abstract
Background: Nucleolar and spindle associated protein 1 (NUSAP1) is an indispensable mitotic regulator, which has been reported to be involved in the development, progression, and metastasis of several types of cancer. Here, we investigated the expression and biological function of NUSAP1 in human glioblastoma multiforme (GBM). Methods: The expression of NUSAP1 on GBM tissues and cells were determined by database analysis, immunohistochemistry and Western blot. EdU assay, transwell assay and flow cytometric analysis were performed to evaluate the effect of NUSAP1 knockdown on GBM cell proliferation, cell invasion and cell apoptosis. RNA sequencing was used to screen for downstream molecules altered in GBM cells after NUSAP1 depletion. An intracranial mice model and bioluminescent imaging were used to assess the effect of NUSAP1 on tumor growth and survival time in vivo. Results: Analysis of the molecular data in CGGA, TCGA and Rembrandt datasets demonstrated that NUSAP1 was significantly up-regulated in GBM relative to low grade gliomas and non-neoplastic brain tissue samples. Kaplan-Meier analysis indicated that patients with tumors showing high NUSAP1 expression exhibited significantly poorer survival in both CGGA (P = 0.002) and Rembrandt cohorts (P = 0.017). Analysis of RNA sequencing data from P3-cells with stable knockdown of NUSAP1 revealed topoisomerase 2A (TOP2A) as a possible molecule down-regulated by the loss of NUSAP1. SiRNA knockdown of either NUSAP1 or TOP2A in U251, T98 and GBM derived patient P3 cells inhibited GBM cell proliferation and invasion, and induced cell apoptosis. Finally, stable knockdown of NUSAP1 with shRNA led to decreased tumor growth in an orthotopic xenograft model of GBM in mice. Conclusions: Taken together, NUSAP1 gene silencing induced apoptosis possibly through the down-regulation of the candidate downstream molecule TOP2A. Interference with the expression of NUSAP1 might therefore inhibit malignant progression in GBM, and NUSAP1 might thus serve as a promising molecular target for GBM treatment.
Lnc-GULP1-2:1 Affects Granulosa Cell Proliferation by Regulating COL3A1 Expression and Localization​
Authors: Yao Guidong , Kong Yue , Yang Guang , Kong Deqi , Xu Yijiang , He Jiahuan , Xu Ziwen , Bai Yucheng , Fan Huiying , He Qina , Sun Yingpu 
Published: September 2020

Abstract
Backgrounds: Long non-coding RNA is a kind of RNA molecule with a transcript length of more than 200 nt and lacking protein coding ability. Recent studies have found that it is widely involved in many pathological and physiological processes. In our previous study, we found that lnc-GULP1-2:1 was significantly down-regulated in the ovarian cortical tissue of patients with primary ovarian insufficiency and predicted that lnc-GULP1-2:1 has a regulatory effect on COL3A1. Results: In this study, we found that lnc-GULP1-2:1 was mainly localized in the cytoplasm of luteinized granulosa cells and was lower expressed in patients with diminished ovarian reserve but highly expressed in patients with polycystic ovary syndrome. Overexpression of lnc-GULP1-2:1 in KGN cells significantly inhibited cell proliferation, which may be related to the regulation of cell cycle related genes CCND2 and p16. To further investigate the regulation of lnc-GULP1-2:1 on COL3A1, RNA analysis revealed a positive correlation between the expression of lnc-GULP1-2:1 and COL3A1 in multiple cell lines, and this was consistent in luteinized granulosa cells from patients with different ovarian functions. We also found that overexpression of lnc-GULP1-2:1 in KGN cells promoted the expression and migration of COL3A1 into the nucleus. Silencing COL3A1 gene in KGN cells also significantly inhibited cell proliferation, which may be related to the regulation of CCND2 gene expression. Conclusions: This study demonstrates that lnc-GULP1-2:1 may participate in the regulation of granulosa cell proliferation by regulating the expression and localization of COL3A1 protein, which will provide a new idea for understanding the regulatory mechanism of follicular development and a new strategy for the diagnosis and treatment of diseases related to follicular development disorders in the future.
Determinants of Self-Reported Correct Knowledge About Tuberculosis Transmission Among Men and Women in Malawi: Evidence from a Nationwide Household Survey.
Authors: Ntenda Peter Austin Morton , Mussa Razak , Gowelo Steve , Sixpence Alick , Bauleni Andy , Simbeye Atusayi , Matengeni Alfred , Banda Godfrey , Stanley Christopher Chikhosi , Banda Susan , Nkoka Onkoka 
Published: September 2020

Abstract
Background: Correct knowledge about transmission of tuberculosis (TB) can influence better health-seeking behaviors, and in turn, it can aid TB prevention in society. Therefore, this study aimed to examine the prevalence and predictors of self-reported correct knowledge about TB transmission among adults in Malawi.Methods: We conducted a secondary analysis of the data obtained from the Malawi Demographic and Health Survey, 2015/16 (MDHS 2015/16). Questions regarding self-reported TB transmission were computed to evaluate the correct knowledge about TB transmission. The factors associated with the correct knowledge about Tb were assessed using univariate and multivariable logistic regression.Results: Overall, the prevalence of correct knowledge about TB transmission in the general population of Malawian adults was 61.5%. Specifically, the prevalence of correct knowledge about TB transmission was 63.6% and 60.8% in men and women, respectively. Those aged 35–44 years, having secondary or high education, belonging to the richest household, being exposed to mass media, being in professional/technical/managerial, having knowledge that “TB can be cured’, and those living in urban areas were significantly associated with correct knowledge about TB transmission.Conclusions: The findings of this study show that if appropriate strategies for TB communication and education to address the rural masses, young individuals, poor individuals, and individuals in the agriculture sector are put it place, can enhance TB prevention in Malawi.
Genetic Polymorphisms of Metabolic Enzyme Genes Associated with Leukocyte Mitochondrial DNA Copy Number in PAHs Exposure Workers
Authors: Li Xinling , Duan Xiaoran , Zhang Hui , Ding Mingcui , Wang Yanbin , Yang Yongli , Yao Wu , Xia Zhaolin , Zhou Xiaoshan , Wang Wei 
Published: September 2020

Abstract
Background: PAHs exposure had been reported to be a risk factor of mtDNAcn in our early study. However, the effect of metabolic enzymes’ genetic polymorphisms on mtDNAcn in PAHs-Exposure workers has not been fully evaluated.Methods: We investigated the effects of metabolic enzymes’ genetic polymorphisms on mtDNAcn among 544 coke oven workers and 238 office staffs. The mtDNAcn of peripheral blood leukocytes was measured using Real-time quantitative polymerase chain reaction method. Polymerase chain reaction and restriction fragment length was used to detect five polymorphisms in GSTT1, GSTM1, GSTP1 rs1695, CYP2E1 rs6413432, and CYP2E1 rs3813867.Results: The mtDNAcn in peripheral blood leukocytes was significantly lower in the exposure group than that in the control group (P < 0.001). The 1-OHPYR had an increasing trend with the genotypes AA→AG→GG of GSTP1 rs1695 in the control group. Generalized linear model indicated that the influencing factors of mtDNAcn were PAHs-exposure [b(95% CI) = -0.420 (-0.469, -0.372), P < 0.001], male [β(95% CI) = -0.058 (-0.103, -0.012), P = 0.013] ,and AA genotype for GSTP1 rs1695 [β(95% CI) = -0.051 (-0.095, -0.008), P = 0.020].Conclusions: The male was susceptibility to PAHs exposure. The AA genotype of GSTP1 rs1695 may influence the toxicity of PAHs and associated with the decreased of mtDNAcn.
Surgical Procedure of Segmentectomy as a Possible Cause of Postoperative Cerebral Embolism: A Case Report
Authors: Chen Peirui , Qing Qiushan , Diao Mingqiang , Sun Xiaokang , Yang Junrong , Lv Jing 
Published: September 2020

Abstract
Background: Cerebral embolism after lobectomy is a life-threatening complication during the early postoperative period. However, it is unclear if cerebral embolism can develop after segmentectomy. Case Presentation: We experienced a case of a 37-year-old man who demonstrated early symptom of acute ischemic stroke in early postoperative period after right upper posterior segmentectomy and performed intra-arterial mechanical thrombectomy (IAMT) successfully.Conclusions: long and irregular pulmonary vein stump (PVS) and endothelial injury caused by surgical procedure may lead to cerebral embolism after segmentectomy. We believe that doing preoperative pulmonary vascular assessment and using appropriate surgical procedure may reduce the rate of cerebral embolism.