bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the generalized law of O-conditionality for interval fuzzy implications
Authors: Zhao Yifan 
Published: May 2022

Interval fuzzy implications play an important role in both theoretical and applied communities of interval-valued fuzzy sets and have been widely studied. Recently, Dimuro et al. analyzed the law of O-conditionality for fuzzy implications in general. However, there is no corresponding researches about the interval extension. To fill the gap, in this paper, we introduce the generalized law of O-conditionality 𝕆 ( X ,   𝕀 ( X ,   Y ) ) ≤ Y (GOC), where 𝕀 is an interval fuzzy implication and 𝕆 is an interval overlap function. Meanwhile, we discuss the advantages one may get using it. Moreover, we consider the conditional antecedent boundary condition (CABC) for interval fuzzy implications derived from interval overlap and grouping functions, including, interval R 𝕆 - ,   ( 𝔾 ,   ℕ ) - ,   ( 𝕆 ,   𝔾 ,   ℕ ) - and ( 𝔾 ,   𝕆 ,   ℕ ) - implications. Finally, we further analyze the generalized law of O-conditionality for these four classes of interval fuzzy implications.
Identifying vocational rehabilitation outreach and service training priorities: A national survey from diverse perspectives
Authors: Bishop Malachy , Lee Deborah , Zhou Kaiqi , Iwanaga Kanako , Chan Fong , Tansey Timothy 
Published: May 2022

BACKGROUND: This article summarizes the results of a needs assessment survey project presented at the 2021 National APSE Virtual Conference. This research was conducted by the Vocational Rehabilitation Technical Assistance Center for Quality Employment (VRTAC-QE), a Technical Assistance Center funded by the Rehabilitation Services Administration, U.S. Department of Education. OBJECTIVE: The purpose of the survey was to determine technical assistance and training needs of state VR counselors in four practice domains: (a) outreach services, (b) pre-employment transition services, (c) vocational rehabilitation services, and (d) employment services. METHODS: A national survey was conducted among 229 state vocational rehabilitation agency (SVRA) professionals, including directors, staff, and VR counselors, and 92 professionals in community-based rehabilitation agencies (CBRA), allowing a comparison of the relative importance ratings of the two groups. RESULTS: The ratings of both SVRA and CBRA professionals were generally aligned, but with some significant differences, as discussed in more detail in Tansey et al. (in press). CONCLUSIONS: The priorities identified through this survey will support the development and implementation of technical assistance activities that are responsive to the needs of SVRA professionals providing vocational rehabilitation to persons with disabilities and increasing the capacity of these agencies to promote quality employment outcomes.
A Computational Pitting Corrosion Model of Magnesium Alloys
Authors: Chang Chia-Jung , Chang Chih-Han , Hung Tin-Kan 
Published: May 2022

Controlling the corrosion rate of implants to maintain mechanical properties during tissue healing is significant in developing magnesium alloy implants. In addition to surface treatment and material properties, the study of geometric alteration and mechanical strength are also vital for implant development. In this study, we developed a three-dimensional model for semi-autonomous computational pitting corrosion. It is based on the Monte Carlo method, modeling magnesium alloy implants toward clinical application. The corrosion probability is based on the number of exposed surfaces to saline and the oxidation characteristics of the elements. The computational results are well compared with the experimental measurement using micro-computed tomography (micro-CT) in 500 h. Subsequently, the computational analysis is extended to 3,000 h of corrosion analysis. The 3D model appears promising to assist the development of biodegradable implants.
Characterization of a Novel LUCAT1/miR-4316/VEGF-A Axis in Metastasis and Glycolysis of Lung Adenocarcinoma
Authors: Wang Lishui , Xie Yan , Wang Jing , Zhang Ying , Liu Shibiao , Zhan Yao , Zhao Yinghui , Li Juan , Li Peilong , Wang Chuanxin 
Published: May 2022

Objective: Accumulating literatures suggested that long non-coding RNAs (lncRNAs) were involved in tumorigenesis and cancer progression in lung adenocarcinoma (LUAD). However, the precise regulatory mechanism of lncRNA Lung cancer-associated transcript 1 (LUCAT1) in LUAD is not well defined. In this study, we aimed to investigate the biological function and mechanism of lncRNA LUCAT1 in regulating tumor migration and glycolysis of LUAD.Methods: High throughput sequencing was performed to identify differentially expressed lncRNAs between LUAD patients and healthy controls. The expression levels of LUCAT1 in LUAD clinical specimens or cell lines were evaluated by In situ hybridization (ISH) and quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Functional experiments, including wound-healing, transwell invasion assays, glucose absorption, lactate metabolism and tumor xenograft experiments were conducted to identify the biological functions of LUCAT1 in LUAD. Silencing of LUCAT1, over-expression of LUCAT1 and miR-4316 were generated in LUAD cell lines to verify the regulatory mode of LUCAT1-mir-4316-VEGFA axis.Results: Our findings revealed that lncRNA LUCAT1 was significantly up-regulated in LUAD serum exosomes, tumor tissues, and LUAD cells in comparison with corresponding controls. Receiver operating characteristic curve (ROC) analysis indicated that the area under the curve (AUC) value of serum exosomal LUCAT1 reached 0.852 in distinguishing LUAD patients from healthy individuals. High expression of LUCAT1 in LUAD patient tissues was associated with enhanced Lymph Node Metastasis (LNM), advanced Tumor Node Metastasis (TNM) stage and poorer clinical outcome in LUAD patients. Knockdown of LUCAT1 inhibited LUAD cell metastasis and glycolysis in vitro as well as tumor metastasis in vivo, while overexpression of LUCAT1 induced a promoted LUAD metastasis and glycolysis. Furthermore, mechanistic investigations revealed that LUCAT1 elevated LUAD cell metastasis and glycolysis by sponging miR-4316, which further led to the upregulation of VEGFA. Finally, the regulatory axis LUCAT1-miR-4316-VEGFA was verified in LUAD.Conclusion: Our present research suggested that LUCAT1 facilitate LUAD cell metastasis and glycolysis via serving as a competing endogenous RNA to regulate miR-4316/VEGFA axis, which provided a novel diagnostic marker and therapeutic target for LUAD patients.
Placental Gene Transcript Proportions are Altered in the Presence of In Utero Arsenic and Cadmium Exposures, Genetic Variants, and Birth Weight Differences
Authors: Deyssenroth Maya A. , Peng Shouneng , Hao Ke , Marsit Carmen J. , Chen Jia 
Published: May 2022

Background:In utero arsenic and cadmium exposures are linked with reduced birth weight as well as alterations in placental molecular features. However, studies thus far have focused on summarizing transcriptional activity at the gene level and do not capture transcript specification, an important resource during fetal development to enable adaptive responses to the rapidly changing in utero physiological conditions. In this study, we conducted a genome-wide analysis of the placental transcriptome to evaluate the role of differential transcript usage (DTU) as a potential marker of in utero arsenic and cadmium exposure and fetal growth restriction.Methods: Transcriptome-wide RNA sequencing was performed in placenta samples from the Rhode Island Child Health Study (RICHS, n = 199). Arsenic and cadmium levels were measured in maternal toenails using ICP-MS. Differential transcript usage (DTU) contrasting small (SGA) and appropriate (AGA) for gestational age infants as well as above vs. below median exposure to arsenic and cadmium were assessed using the DRIMSeq R package. Genetic variants that influence transcript usage were determined using the sQTLseeker R package.Results: We identified 82 genes demonstrating DTU in association with SGA status at an FDR &lt;0.05. Among these, one gene, ORMDL1, also demonstrated DTU in association with arsenic exposure, and fifteen genes (CSNK1E, GBA, LAMTOR4, MORF4L1, PIGO, PSG1, PSG3, PTMA, RBMS1, SLC38A2, SMAD4, SPCS2, TUBA1B, UBE2A, YIPF5) demonstrated DTU in association with cadmium exposure. In addition to cadmium exposure and SGA status, proportions of the LAMTOR4 transcript ENST00000474141.5 also differed by genetic variants (rs10231604, rs12878, and rs3736591), suggesting a pathway by which an in utero exposure and genetic variants converge to impact fetal growth through perturbations of placental processes.Discussion: We report the first genome-wide characterization of placental transcript usage and associations with intrauterine metal exposure and fetal growth restriction. These results highlight the utility of interrogating the transcriptome at finer-scale transcript-level resolution to identify novel placental biomarkers of exposure-induced outcomes.
Structural Features of the Nucleosomal DNA Modulate the Functional Binding of a Transcription Factor and Productive Transcription
Authors: Vinayachandran Vinesh , Bhargava Purnima 
Published: May 2022

A small non-histone protein of budding yeast, Nhp6 has been reported to specifically influence the transcription of a yeast gene, SNR6. The gene is essential, transcribed by the enzyme RNA polymerase III, and codes for the U6snRNA required for mRNA splicing. A translationally positioned nucleosome on the gene body enables the assembly factor TFIIIC binding by juxtaposing its otherwise widely separated binding sites, boxes A and B. We found histone depletion results in the loss of U6 snRNA production. Changing the rotational phase of the boxes and the linear distance between them with deletions in 5 bp steps displayed a helical periodicity in transcription, which gradually reduced with incremental deletions up to 40 bp but increased on further deletions enclosing the pseudoA boxes. Nhp6 influences the transcription in a dose-dependent manner, which is modulated by its previously reported co-operator, an upstream stretch of seven T residues centered between the TATA box and transcription start site. Nhp6 occupancy on the gene in vivo goes up at least 2-fold under the repression conditions. Nhp6 absence, T7 disruption, or shorter A–B box distance all cause the downstream initiation of transcription. The right +1 site is selected with the correct placement of TFIIIC before the transcription initiation factor TFIIIB. Thus, the T7 sequence and Nhp6 help the assembly and placement of the transcription complex at the right position. Apart from the chromatin remodelers, the relative rotational orientation of the promoter elements in nucleosomal DNA, and Nhp6 regulate the transcription of the SNR6 gene with precision.
Identification of Novel Imatinib-Resistant Genes in Gastrointestinal Stromal Tumors
Authors: Cao Lei , Zheng Kunming , Liu Yanhong , Song Peng , Wang Chuntao , Wang Hongzhi , Wang Nan , Zhang Shiwu , Zhao Yongjie 
Published: May 2022

Gastrointestinal stromal tumors (GISTs) are common ICC precursor sarcomas, which are considered to be a potential malignant mesenchymal tumor driven by specific KIT or PDGFRA signals in the gastrointestinal tract. The standard treatment for GIST without metastasis is surgical resection. GIST with metastasis is usually treated with tyrosine kinase inhibitors (TKIs) only but cannot be cured. The TKI imatinib is the main drug of GIST drug therapy. In adjuvant therapy, the duration of imatinib adjuvant therapy is 3 years. It has been proved that imatinib can improve the overall survival time (OS). However, many GIST patients develop drug resistance due to the long-term use of imatinib. We were forced to look for new strategies to treat GIST. The purpose of the current academic work is to study the drug-resistant genes of imatinib and their potential mechanisms. A total of 897 differentially expressed genes (DEGs) were found between imatinib-sensitive cell line GIST882 and imatinib-resistant cell line GIST430 by RNA sequencing (RNA-seq). After analyzing the DEGs, 10 top genes were selected (NDN, FABP4, COL4A1, COLEC11, MEG3, EPHA3, EDN3, LMO3, RGS4, and CRISP2). These genes were analyzed by RT-PCR, and it was confirmed that the expression trend of FABP4, COL4A1, and RGS4 in different imatinib-resistant cell lines was in accord with the GEO database. It is suggested that these genes may play a potential role in the clinical diagnosis and treatment of imatinib resistance in GIST.
Amino Acid Metabolism-Related lncRNA Signature Predicts the Prognosis of Breast Cancer
Authors: Dai Yin-wei , Wen Zhi-kai , Wu Zhi-xuan , Wu Hao-dong , Lv Lin-xi , Yan Cong-zhi , Liu Cong-hui , Wang Zi-qiong , Zheng Chen 
Published: May 2022

Background and Purpose: Breast cancer (BRCA) is the most frequent female malignancy and is potentially life threatening. The amino acid metabolism (AAM) has been shown to be strongly associated with the development and progression of human malignancies. In turn, long noncoding RNAs (lncRNAs) exert an important influence on the regulation of metabolism. Therefore, we attempted to build an AAM-related lncRNA prognostic model for BRCA and illustrate its immune characteristics and molecular mechanism.Experimental Design: The RNA-seq data for BRCA from the TCGA-BRCA datasets were stochastically split into training and validation cohorts at a 3:1 ratio, to construct and validate the model, respectively. The amino acid metabolism-related genes were obtained from the Molecular Signature Database. A univariate Cox analysis, least absolute shrinkage and selection operator (LASSO) regression, and a multivariate Cox analysis were applied to create a predictive risk signature. Subsequently, the immune and molecular characteristics and the benefits of chemotherapeutic drugs in the high-risk and low-risk subgroups were examined.Results: The prognostic model was developed based on the lncRNA group including LIPE-AS1, AC124067.4, LINC01655, AP005131.3, AC015802.3, USP30-AS1, SNHG26, and AL589765.4. Low-risk patients had a more favorable overall survival than did high-risk patients, in accordance with the results obtained for the validation cohort and the complete TCGA cohort. The elaborate results illustrated that a low-risk index was correlated with DNA-repair–associated pathways; a low TP53 and PIK3CA mutation rate; high infiltration of CD4+ T cells, CD8+ T cells, and M1 macrophages; active immunity; and less-aggressive phenotypes. In contrast, a high-risk index was correlated with cancer and metastasis-related pathways; a high PIK3CA and TP53 mutation rate; high infiltration of M0 macrophages, fibroblasts, and M2 macrophages; inhibition of the immune response; and more invasive phenotypes.Conclusion: In conclusion, we attempted to shed light on the importance of AAM-associated lncRNAs in BRCA. The prognostic model built here might be acknowledged as an indispensable reference for predicting the outcome of patients with BRCA and help identify immune and molecular characteristics.
Endoscopic Submucosal Dissection of Deeply Invasive Colorectal Cancers Using the Pocket-Creation Method: Analysis of Vertical Margins
Authors: Morikawa Takaaki , Hayashi Yoshikazu , Fukuda Hisashi , Ishii Hiroaki , Nomura Tatsuma , Ikeda Eriko , Kitamura Masafumi , Kagaya Yuka , Okada Masahiro , Takezawa Takahito , Sunada Keijiro , Lefor Alan Kawarai , Fukushima Noriyoshi , Yamamoto Hironori 
Published: May 2022

Background and aimsThe standard treatment for stage T1b colorectal cancers with 1,000µm or greater submucosal invasion is surgical resection. However, the risk of lymph node metastases is only 1-2% when excluding risk factors for metastases other than depth of submucosal invasion. The number of elderly patients with significant comorbidities is increasing with societal aging in Japan. Therefore, local endoscopic resection of T1b colorectal cancers needs more consideration in the future. We previously showed that the pocket-creation method (PCM) for endoscopic submucosal dissection (ESD) is useful regardless of the morphology, including large sessile tumors with submucosal fibrosis, or location of the colorectal tumor. However, some T1b colorectal cancers have pathologically positive margins even when using the PCM. We retrospectively investigated the causes of failure to achieve negative vertical margins.MethodsWe retrospectively analyzed 953 colorectal tumors in 886 patients resected with the PCM. Finally, 65 pathological T1b colorectal cancers after en bloc resection were included in this study. ESD specimens and recorded procedure videos of T1b cancer resections with pathologically positive vertical margins were reviewed.ResultsThe 65 cancers were divided into positive vertical margin (VM+ group) and negative vertical margin (VM- group) groups with 10 [10/65 (15%)] and 55 [55/65 (85%)] patients in each group, respectively. There was a significant difference in the rate of submucosal fibrosis (P=0.012) and dissection speed (P=0.044). There were no significant differences between the two groups in other regards. When verifying 8/10 available videos in the VM+ group, endoscopic technical factors led to positive vertical margins in five patients, and essential pathological factors of ESD led to positive vertical margins in the other three. Six of these eight patients underwent additional surgical resection. No residual tumor was identified in six T1b cancers. None of these six resected specimens contained lymph node metastases on pathological examination.ConclusionThe PCM resulted in a high rate of negative-vertical-margin resections. The PCM resulted in complete resection of T1b cancers when examining additional surgical specimens. ESD using the PCM is a viable option for the endoscopic treatment of T1b colorectal cancers.
High-Frequency Notable HBV Mutations Identified in Blood Donors With Occult Hepatitis B Infection From Heyuan City of Southern China
Authors: Ye Xianlin , Liu Lihua , Chen Lina , Nie Xianghui , Huang Lu , Ye Denghuang , Zeng Jinfeng , Li Tong , Li Bin , Xu Min , Chen Limin 
Published: May 2022

BackgroundAll Chinese blood centers have implemented mini pool (MP) HBV nucleic acid testing (NAT) together with HBsAg ELISA in routine donor screening since 2015. The prevalence of occult hepatitis B virus infection (OBI) in donors from different regions varies, and the molecular characterization of the HBV DNA and clinical outcomes of these OBIs remain largely unexplored.MethodsBlood donations from Heyuan city in Southern China were screened by HBsAg ELISA and HBV MP8 NAT. Donations with HBsAg-/HBV DNA+ were collected for this study. Molecular characterizations of HBV DNAs were further analyzed by various DNA amplification assays including quantitative PCR (qPCR) and nested PCR, amplifying the basic core and pre-core promoter regions (BCP/PC). The HBsAg (S) region from HBV DNA was isolated by high-volume nucleic acid extraction. Notable mutations were identified by comparison to the HBV reference sequences. The clinical outcomes of the donors with OBIs were further followed for nearly 3 years.ResultsSeventy OBIs from 44,592 donations (0.15%) that we identified and reported previously were enrolled for this current study. HBV sequences were obtained from 44/70 OBIs, and genotyping analysis showed that 42/44 (95.2%) OBIs were genotype B, and 2/44 (4.8%) were genotype C. Interestingly, mutation analysis revealed that various mutations including M133L/T, F134L, P142L, V168A, R169H, S174N, L175S, and V177A of HBV DNA affecting HBsAg detection were observed in genotype B OBIs. Two notable mutations, T47K and L53S, were identified in genotype C OBIs. Follow-up studies showed that 3/31 (9.7%) OBIs converted to HBsAg+ as chronic infections while 1/31 (3.2%) HBV DNA was undetectable (classified as recovery) and 27/31 (87.1%) remained as OBIs.ConclusionVarious notable mutations affecting HBsAg detection were observed in blood donors with OBIs in Heyuan city of Southern China. Follow-up studies showed that most OBIs remained as OBIs with fluctuating or low viral loads. Higher sensitive HBV ID NAT is recommended for donor screening to further reduce the transmission risk of OBIs.
Multi-Scale Spatial Analysis of the Tumor Microenvironment Reveals Features of Cabozantinib and Nivolumab Efficacy in Hepatocellular Carcinoma
Authors: Mi Haoyang , Ho Won Jin , Yarchoan Mark , Popel Aleksander S. 
Published: May 2022

BackgroundConcomitant inhibition of vascular endothelial growth factor (VEGF) and programmed cell death protein 1 (PD-1) or its ligand PD-L1 is a standard of care for patients with advanced hepatocellular carcinoma (HCC), but only a minority of patients respond, and responses are usually transient. Understanding the effects of therapies on the tumor microenvironment (TME) can provide insights into mechanisms of therapeutic resistance.Methods14 patients with HCC were treated with the combination of cabozantinib and nivolumab through the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center. Among them, 12 patients (5 responders + 7 non-responders) underwent successful margin negative resection and are subjects to tissue microarray (TMA) construction containing 37 representative tumor region cores. Using the TMAs, we performed imaging mass cytometry (IMC) with a panel of 27-cell lineage and functional markers. All multiplexed images were then segmented to generate a single-cell dataset that enables (1) tumor-immune compartment analysis and (2) cell community analysis based on graph-embedding methodology. Results from these hierarchies are merged into response-associated biological process patterns.ResultsImage processing on 37 multiplexed-images discriminated 59,453 cells and was then clustered into 17 cell types. Compartment analysis showed that at immune-tumor boundaries from NR, PD-L1 level on tumor cells is significantly higher than remote regions; however, Granzyme B expression shows the opposite pattern. We also identify that the close proximity of CD8+ T cells to arginase 1hi (Arg1hi) macrophages, rather than CD4+ T cells, is a salient feature of the TME in non-responders. Furthermore, cell community analysis extracted 8 types of cell-cell interaction networks termed cellular communities (CCs). We observed that in non-responders, macrophage-enriched CC (MCC) and lymphocyte-enriched CC (LCC) strongly communicate with tumor CC, whereas in responders, such communications were undermined by the engagement between MCC and LCC.ConclusionThese results demonstrate the feasibility of a novel application of multiplexed image analysis that is broadly applicable to quantitative analysis of pathology specimens in immuno-oncology and provides further evidence that CD163-Arg1hi macrophages may be a therapeutic target in HCC. The results also provide critical information for the development of mechanistic quantitative systems pharmacology models aimed at predicting outcomes of clinical trials.