bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of a Novel Tombusviridae Species Isolated From Paris polyphylla var. yunnanensis
Authors: Zhao Mingfu , Chen Lu , Anane Rex Frimpong , Wang Zhe , Chen Zeli , Gao Like , Wen Guosong 
Published: May 2021

Abstract
A novel virus, Paris virus 2 (ParV2), was isolated from diseased Paris polyphylla var. yunnanensis, and its complete genome sequence was determined and analyzed. ParV2 is a positive-sense single-stranded RNA (+ssRNA) virus with a genome size of 4118 nucleotides. The ParV2 genome contains six putative open reading frames (ORFs) that encode proteins with predicted molecular weights of 40.14, 100.26, 7.31, 7.85, 26.09, and 8.77 kDa. The first ORF (ORF1) of ParV2 encodes a putative protein of 40.14 kDa (p40, nt: 20-1096), whiles the second ORF (ORF2, 888 aa) containing the GDD motif encodes the highly conserved RNA-dependent RNA polymerase protein (RdRP, nt:20-2683, p100, 100.26 kDa) of viruses in the family Tombusviridae. Multiple sequence alignments analysis showed that the complete genome sequence of ParV2 shares 31.7-55.5% nucleotide sequence identities with viruses in the family Tombusviridae. Ginger chlorotic fleck-associated tombusvirus (GCFaV-1,Accession No.QKE30557) had the highest sequence identity (55.5%) with ParV2, and also shares 59.2% RdRp and 34.9% CP amino acid sequence identity with GCFaV-1.Sequence comparisons and phylogenetic analysis of RdRp suggested that ParV2 is a novel member of the family Tombusviridae, and its closest known relative is GCFaV-1.
Evolutionary Analysis of Transcriptional Regulation Mediated by Cdx2 in Rodents
Authors: Liang Weizheng , Li Guipeng , Cui Huanhuan , Wang Yukai , Wei Wencheng , Sun Siyue , Gan Diwen , Chen Rui , Yi Hongyang , Schaefke Bernhard , Hu Yuhui , Zhou Qi , Li Wei , Chen Wei 
Published: May 2021

Abstract
Background: Differences in gene expression, which arises from divergence in cis-regulatory elements or alterations in transcription factors (TFs) binding specificity, are one of the most important causes of phenotypic diversity during evolution. On one hand, changes in the cis-elements located in the vicinity of target genes affect TF binding and/or local chromatin environment, thereby modulating gene expression in one-to-one manner. On the other hand, alterations in trans-factors influence the expression of their target genes in a more pleiotropic fashion. Although evolution of amino acid sequences is much slower than that of non-coding regulatory elements, particularly for the TF DNA binding domains (DBD)， it is still possible that changes in TF-DBD might have the potential to drive large phenotypic changes if the resulting effects have a net positive effect on the organism’s fitness. If so, species-specific changes in TF-DBD might be positively selected. So far, however, this possibility has been largely unexplored.Results: By protein sequence analysis, we observed high sequence conservation in the DNA binding domain (DBD) of the transcription factor Cdx2 across many vertebrates, whereas three amino acid changes were exclusively found in mouse Cdx2 (mCdx2), suggesting potential positive selection in the mouse lineage. Multi-omics analyses were then carried out to investigate the effects of these changes. Surprisingly, there were no significant functional differences between mCdx2 and its rat homologue (rCdx2), and none of the three amino acid changes had any impact on its function. Finally, we used rat-mouse allodiploid embryonic stem cells (RMES) to study the cis effects of Cdx2-mediated gene regulation between the two rodents. Interestingly, whereas Cdx2 binding is largely divergent between mouse and rat, the transcriptional effect induced by Cdx2 is conserved to a much larger extent.Conclusions: There were no significant functional differences between mCdx2 and its rat homologue (rCdx2), and none of the three amino acid changes had any impact on its function. Moreover, Cdx2 binding is largely divergent between mouse and rat, the transcriptional effect induced by Cdx2 is conserved to a much larger extent.
Neutrophil–Lymphocyte Ratio Predicts Overall Survival in Elderly Patients With Unresectable or Recurrent Gastric Cancer
Authors: Yamauchi Yoshiya , Sofuni Atsushi , Suzuki Yuka , Kurosawa Takashi , Iwasaki Kenichi , Tsuchida Akihiko , Itoi Takao 
Published: May 2021

Abstract
BackgroundThe relationship between various systemic inflammatory biomarkers and outcomes in patients with a variety of solid cancers has been reported. However, the relevance of these markers is unclear in elderly patients with unresectable or recurrent gastric cancer (GC). This retrospective study was conducted to identify specific factors associated with the survival of elderly patients with GC.Methods Patients with GC undergoing chemotherapy at our institution from April 2014 to April 2020 were included in the study. The patients were categorized into either the young group (Y group; aged <70 years) or the elderly group (E group; aged ≥70 years). The association between overall survival (OS) and pre-treatment values of systemic biomarkers, including the neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio, and Glasgow prognostic score, was evaluated using the Kaplan–Meier method and log-rank test in each group. Univariate and multivariate analyses using Cox proportional hazards regression were used to investigate the prognostic factors associated with OS in each group.ResultsA total of 112 patients were eligible for inclusion in the analysis. The patients were categorized into the Y and E groups based on their age, and each group consisted of 56 patients. In both groups, high NLR and high Glasgow prognostic score were associated with poor OS (Y: p = 0.002 and p = 0.009; E: p < 0.001 and p = 0.045, respectively), whereas the platelet–lymphocyte ratio was not (Y: p = 0.296; E: p = 0.346). Univariate and multivariate Cox regression analyses revealed that poor performance status was correlated with poor OS in the Y group (hazard ratio: 2.56; 95% confidence interval: 1.02–6.43; p = 0.045). However, in the E group, NLR was the only independent prognostic factor of OS (hazard ratio: 4.22; 95% confidence interval: 1.69–10.56; p = 0.002). ConclusionsPoor performance status was an independent marker of poor prognosis in the Y group, whereas a high NLR was an independent marker in the E group. Thus, NLR may be a specific biomarker for predicting the OS of elderly patients with unresectable GC.
The Association Between Non-Suicidal Self-Injury of Adolescents and the COVID-19: The Lesson We Should Notice
Authors: Du Na , Ouyang Yingjie , Xiao Yu , Li Yunge 
Published: May 2021

Abstract
Background: Non-suicidal self-injury (NSSI) in psychiatric hospitalized adolescents keeps growing after the outbreak of COVID-19. This study aims to explore the relationship between the pandemic and the NSSI among adolescents, focusing on the underlying reasons. Methods: Through the retrospective analysis of medical record data retrieved from the electronic medical record system from January 2016 to March 2021, 609 medical records of adolescents were obtained. The main potential influencing factors were determined by the method of inductive content analysis. Results: Among the 609 adolescents, 420 subjects had NSSI, while 189 did not. We found the percentage of NSSI adolescents in 2016 was only 29.2% (7/24), reaching 34.5% (29/55) in 2017, 45.7% (42/92) in 2018, 61.3% (76/124) in 2019, 92.5% (196/212) in 2020, and 95.9% (70/73) in 2021. In the Binary logistic regression model, gender (OR=0.075), age (OR=1.215), single parent (OR=7.751) , experienced trauma (OR=2.214), social isolation (OR=8.313), body bully (OR=3.116), mobile phone overused (OR=4.199), committed suicide (OR=9.276), and before/after pandemic (OR=5.421) were significantly associated with NSSI. When comparing the differences in influencing factors between the pre-pandemic and the post-pandemic group, the results showed that experiencing trauma and suffering body bullying played less role in the appearance of NSSI, while the family constitution, relationship with parents, mobile phone use, and stressful learning have become the important factors. Conclusions: The pandemic has increased the risk of NSSI among adolescents and changed the influencing factors of this behavior. Tailored intervention gearing toward the changed risk factors should be formulated.
Revalorization of Sunflower Stalk Pitch As Feedstock for the Coproduction of Pectin and Glucose Using a Two-Step Dilute Acid Pretreatment Process
Authors: Zhang Qibo , Ma Xutong , Zhou Xin , Xu Yong 
Published: May 2021

Abstract
Background: Sunflower stalk pith, residue from the processing of sunflower, is rich in pectin and cellulose, thereby acting as an economic raw material for the acquisition of these compounds. In order to increase the commercial value of sunflower processing industry, a two-step sequential dilute sulfuric acid treatment combined with subsequent enzymatic hydrolysis was conducted on spent sunflower stalk pith to obtain the value-added products, pectin and glucose. Results: In this study, pectin was firstly extracted with a mild condition to avoid pectin degradation, which conducted at 95℃ with a pH of 2.0 for 2 h, and approximately 0.12 g/g of pectin could be recovered. Then the remaining solids followed by extracted pectin were subjected to the reinforced treatment process with 0.75% H2SO4 at 150 oC for 30 min to further improving enzymatic hydrolysis efficiency. Moreover, a fed-batch enzymatic hydrolysis was successfully performed with a solid 16% content, the glucose titer reached 103.1 g/L with a yield of 83.6 %.Conclusion: Finally, approximately 140 g pectin and 260 g glucose were produced from 1 kg of raw sunflower stalk pith using the integrated biorefinery process. This work put forward a two-step dilute acid pretreatment combined with enzymatic hydrolysis method to produce pectin and glucose from sunflower spent waste.
The Relationship of the Efficiency of Energy Conversion Into Growth as an Indicator for the Determination of the Optimal Dosage for Mutation Breeding With the Appearance of Chromosomal Bridges, Ring Chromosomes, Micronuclei and Incomplete Mitosis After Gamma Irradiation of Kernels of Triticum Turgidum Ssp. Durum L. Cultivar Orania
Authors: VON WELL EBEN , FOSSEY ANNABEL , BOOYSE MARDÉ 
Published: May 2021

Abstract
BackgroundA 50% growth reduction of seedling height (GR50) after acute gamma irradiation of dormant kernels is widely used as a measure of irradiation damage to obtain the ideal irradiation dosage for mutation breeding. It became clear in recent years that the GR50 is not sensitive enough to predict the ideal gamma irradiation dosage for mutation breeding and it predicts a value that is higher than ideal. The study aim was to determine whether root, shoot and seedling growth on the one side and the efficiency of energy conversion into growth on the other are measuring different growth retardation effects of gamma irradiation that are the result of DNA damage (bridges, ring chromosomes, micronuclei, incomplete mitosis) in Triticum turgidum ssp. durum. If the efficiency of energy conversion into growth is measuring different effects, the usefulness of efficiency of energy conversion into growth to predict the optimal dosage for mutation breeding will be investigated. ResultsThe kernels were gamma irradiated from 50 - 350 Gy using a 60Cobalt source. The kernels were left to germinate and grow for a period of 132 hours for the shoot and root growth and the efficiency of energy conversion into growth determination and for a period of 47.5 hours for the determination of the number of bridges, ring chromosomes, micronuclei and incomplete mitosis. The control differed highly significantly from 50 Gy and higher dosages and from 250 Gy and higher dosages for root and shoot growth respectively and from 250 Gy for the efficiency of energy conversion into growth. There was a highly significant increase in the number of bridges and micronuclei between 50 Gy and 150 Gy together with the higher irradiation dosages and only from 250 Gy for the ring chromosomes and interphase cells with incomplete mitosis. Root and seedling growth on the one hand and the efficiency of energy conversion into growth on the other were found to be measuring different effects of gamma irradiation on plant growth. ConclusionThe optimal dosage for mutation breeding was determined by making use of the efficiency of energy conversion into growth.
Multi-omic Analysis of Familial Adenomatous Polyposis Reveals Molecular Pathways and Polyclonal Spreading Associated with Early Tumorigenesis
Authors: Snyder Michael , Horning Aaron , Esplin Edward , Wu Si , Hanson Casey , Bararpour Nasim , Nevins Stephanie , Jiang Lihua , Contrepoi Kevin , Lee Hayan , Guha Tuhin , Hu Zheng , Laquindanum Rozelle , Mills Meredith , Chaib Hassan , Chiu Roxanne , Jian Ruiqi , Chan Joanne , Ellenberger Mathew , Khan Aziz , Michael Basil , Bahmani Bahareh , Esplin Glen , Shen Jeanne , Lancaster Samuel , Ladabaum Uri , Kundaje Anshul , Longacre Teri , Greenleaf William , Curtis Christina , Ford James , Becker Winston 
Published: May 2021

Abstract
Familial adenomatous polyposis (FAP) is a genetic disease causing hundreds of premalignant polyps in affected patients, leading to colorectal cancer (CRC), and is an ideal model to study early transition to CRC. We performed deep multi-omic profiling of 135 normal mucosal, benign and dysplastic polyps and adenocarcinoma samples from 6 FAP patients who consented to broad data sharing. Whole genome sequencing indicates that spatially separated polyps from the same donor harbor numerous mutations in common, but evolve independently, consistent with a model of polyclonal origin and spreading. Transcriptomic, proteomic, metabolomic and lipidomic analyses revealed a dynamic choreography of thousands of molecular and cellular events that occur during early hyperplasia, dysplasia and cancer formation. These involve processes such as cell proliferation, immune response, alterations in metabolism (including amino acids, lipids), hormones, and extracellular matrix proteins. Interestingly, activation of the arachidonic acid pathway was found to occur early in hyperplasia; this pathway is targeted by aspirin/NSAIDs, a common preventative treatment of FAP patients. Overall, our results reveal key genomic, cellular and molecular events during the earliest steps in cancer formation and potential mechanisms of pharmaceutical prophylaxis.
Efficacy and Safety of Intra-Articular Hyaluronic Acid Injection (NRD101 / SUVENYL®) in Patients With Knee Osteoarthritis: a Multicenter, Randomized, Double-blind, Parallel, Active Control, Non-Inferiority Clinical Study
Authors: Wang Haoyang , Wang Wei , Xu Yongsheng , Li Jianan , Liu Kang , Kobayashi Ryota , Matsuda Yuya , Zhou Zongke , Weng Xisheng 
Published: May 2021

Abstract
BackgroundIntra-articular injection of hyaluronic acid (HA) has favorable effects on pain relief and knee function along with the low incidence of serious adverse reactions. Although various HA products are available for the treatment of knee osteoarthritis, it is still controversial whether differences in HA products have any clinically significant difference in efficacy and safety. In light of the above, the efficacy and safety of intra-articular injection of biological fermentation–derived high-molecular-weight HA (NRD101) was investigated in a double-blind comparative manner in Chinese patients with knee osteoarthritis.MethodA multicenter, prospective, randomized, double-blind, parallel, active control, non-inferiority study was conducted in Chinese patients with knee osteoarthritis. Patients were randomized to receive five consecutive weekly injections of either NRD101 or Artz (a non-crosslinked low-molecular-weight HA derived from combs of roosters) followed by 4 weeks follow-up. The primary efficacy endpoint was the change from baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) NRS pain subscale score at Week 5. Secondary efficacy endpoints included WOMAC stiffness and physical function subscale score, local pain, range of joint motion, and overall improvement.ResultsAmong 267 randomized patients, 259 patients completed the study. The change from baseline in WOMAC NRS pain subscale score at Week 5 was −2.98 ± 0.193 in the NRD101 group and −2.66 ± 0.194 in the Artz group, and the trial met the non-inferiority criteria. Efficacy in the NRD101 group tended to be consistently higher than in the Artz group for most items of WOMAC. Several subgroup analyses also showed differences between the two groups, tending to favor NRD101. Adverse events were seen in 26.0% (34/131) of patients in the NRD101 group and 38.3% (51/133) in the Artz group.ConclusionsNRD101 improved knee pain in Chinese patients with osteoarthritis after five consecutive weekly injections. NRD101 tended to be somewhat more effective than Artz. No new safety concerns were identified.Trial registration: JapicCTI, JapicCTI-173531. Registered 10 March 2017, https://www.clinicaltrials.jp/cti-user/trial/Search.jsp
Analysis of Co-Expression Module of Liver Metastasis Genes in Colorectal Cancer and Mining of Potential High-Expression Biomarkers
Authors: Wang Xuehu , Li Nie , Wang Yun , Yin Xiaoping , Zheng Yongchang 
Published: May 2021

Abstract
AimsThe Hub genes highly related to the disease were found from the gene co-expression module, and the potential high expression genes were analyzed to predict the liver metastasis of colorectal cancer, so as to provide reference for subsequent targeted therapy.MethodsIn this study, we used the public data set of GEO database (GSE50760) to analyze the gene co-expression of liver metastasis of colon cancer, primary colon cancer and normal colon tissue (54 cases) and 50 cases of clinical cases. The functional annotations based on GO database are enriched, and the functional annotations of five gene modules are obtained through the enrichment of biological processes. Then the data mining is carried out to find the sub-networks with high adjacency in the gene co-expression network. At the same time, these sub-networks are annotated to find oncogenes related to liver metastasis of colorectal cancer.ResultsThis experiment found that KRAS, APC, FBXW7, PIK3CA, TP53 were highly correlated with liver metastasis of colorectal cancer. Finally, two protein genes STAT1 and MAPK1 were found by MCODE, which may be highly correlated with liver metastasis of colorectal cancer. Two new genes with high expression proteins found in this experiment have potential cancer, which has not been reflected in previous studies.Conclusion﻿According to clinical data, KRAS, APC, FBXW7, PIK3CA, TP53 are related to colorectal cancer liver metastasis, and the analysis of the data set shows that STAT1 and MAPK1 are not only related to colorectal cancer liver metastasis oncogene but also related to clinically obtained genes.
A radical polymer for highly efficient solar evaporation and gas separation
Authors: Liu Wei , Yang Ming , Liu Jing , Yang Meijia , Li Jing , Lu Yanqiu , Japip Susilo , Chen Zhongxin , Wu Ji , Li Feng , Zhang Sui 
Published: May 2021

Abstract
The unique magnetic, electronic and optical features derived from their unpaired electrons have made radical polymers an attractive material platform for various applications. Here, we report solution-processable radical polymer membranes with multi-level porosities and study the impact of free radicals on important membrane separation processes including solar vapor generation, hydrogen separation and CO2 capture. The radical polymer is a supreme light absorber over the full solar irradiation range with sufficient water transport channels, leading to a highly efficient solar evaporation membrane. In addition, the radical polymer with micropores and adjustable functional groups are broad-spectrum gas separation membranes for both hydrogen separation and CO2 capture. First principle calculations indicate that the conjugated polymeric network bearing radicals is more chemically reactive with CO2, compared with H2, N2 and CH4. This is evidenced by a high CO2 permeability in gas separation membranes made of the conjugated radical polymer.
Larotinib in Patients with Advanced and Previously Treated Esophageal Squamous Cell Carcinoma with Epidermal Growth Factor Receptor Overexpression or Amplification: An Open-Label, Multicenter Phase 1b Study
Authors: Xu Jianming , Liu Lianke , Liu Rongrui , Bai Yuxian , Zheng Yulong , Zhang Shu , Li Ning , Yang Jianwei , Fan Qingxia , Wang Xiuwen , Zeng Shan , Zhang Yingjun , Zhang Weihong , Zhuang Yulei , Kang Ning , Zhou Qinghong , Jiang Yingzhi , Huang Yue , Sun Hongmei 
Published: May 2021

Abstract
PurposeLarotinib is a new first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. This open-label, phase 1b study is aimed to evaluate the efficacy, safety of larotinib in patients with advanced esophageal squamous cell carcinoma (ESCC) with EGFR overexpression or amplification pretreated with one or more system regimens, and to recommend appropriate dose for its further study.MethodsPatients received larotinib orally at 3 doses (250, 300, 350 mg), once daily. Clinical response was evaluated every 8-weeks according to RECIST v1.1 criteria by both investigators and independent radiology review (IRC).Results81 patients were enrolled. The investigator-assessed overall response rate (ORR) was 13.7% (10/73), all responses were observed in the 350 mg group of which ORR up to 20.0% (10/50), with 10 of them having EGFR overexpression and 4 having EGFR amplification. Per IRC assessment, ORR for all patients and 350 mg group were 13.9% (10/72) and 16.3% (8/50). In the 350 mg group, median overall survival (OS) and progression-free survival (PFS) were 8.0 (95% CI, 4.9–10.2) months and 3.4 (95%CI, 2.4–3.7) months, respectively. The most common treatment-related adverse events (TRAEs) were diarrhea, rash and palmar-plantar erythrodysesthesia syndrome, elevated AST/ALT, vomiting, similarly with other EGFR TKIs.ConclusionLarotinib demonstrated promising antitumor activity and manageable safety profiles in patients with pre-treated advanced ESCC with EGFR overexpression or amplification, especially at the dose of 350 mg, which showed better efficacy and acceptable safety. A phase 3 study is underway on 350 mg larotinib in ESCC patients with EGFR overexpression.Trial registrationNCT03888092, registered on March 25, 2019, retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT03888092