bluuebunny/crossref_metadata_2025_split huggingface dataset:
A universal TLR7-nanoparticle adjuvant promotes broad immune responses against heterologous strains of Influenza and SARS-CoV-2
Authors: Yin Qian , Luo Wei , Mallajosyula Venkata Vamsee Aditya , Bo Yang , Guo Jing , Xie Jinghang , Sun Meng , Verma Rohit , Constantz Christian , Wagar Lisa , Li Jing , Sola Elsa , Gupta Neha , Kask Oliver , Rao Jianghong , Chien Yueh-hsiu , Cheng Jianjun , Pulendran Bali , Davis Mark 
Published: October 2021

Abstract
Fully effective vaccines for viruses such as Influenza and SARS-CoV-2 must elicit a diverse repertoire of antibodies against multiple drifted virus strains. However, how to achieve a diverse response has no general solution except to combine multiple strains, which risks diluting the response for all strains included. Here, we describe the synthesis of a universal, toll-like receptor 7 agonist (TLR7)-nanoparticle adjuvant, TLR7-NP, constructed from TLR7 agonist-initiated ring-opening polymerization of lactide and self-assembly with poly(ethylene glycol)-b-poly(lactic-co-glycolic acid). When mixed with Alum-adsorbed antigens, this TLR7-NP adjuvant elicited cross-reactive antibodies for both dominant and subdominant epitopes, as well as antigen-specific CD8+ T cell responses. TLR7-NPs adjuvanted influenza subunit vaccine successfully protected mice from heterologous viral challenge. TLR7-NPs also enhanced the antibody response to a SARS-CoV-2 subunit vaccine against multiple variants and revealed the mobilization of a virus-like response. We further demonstrate enhanced antigen-specific responses in human tonsil organoids with this novel adjuvant.
Bioinformatics Analysis of a Regulatory lncRNA–miRNA–mRNA Network and Signaling Pathways in Patients With Cardiomyopathy
Authors: Chen Tao , Liu Yu-Yao , Li Shu-Jun , Che Hong , Ge Sheng-Lin 
Published: October 2021

Abstract
Background:Cardiomyopathy is a disease with a very low cure rate and a very complex pathogenesis.Although genes are known to play an important role in various types of cardiomyopathy, the specific mechanism has not been well studied.Methods:We screened the GSE29819 dataset from the Gene Expression Omnibus database (GEO) for long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) with significant differences using R software. microRNAs (miRNAs) regulated by the lncRNAs were retrieved from the miRcode database. The downstream target genes of the miRNAs were predicted by miRDB, miRTarBase, and TargetScan, and genes consistent with the original dataset were selected to construct a lncRNA–miRNA–mRNA network. Finally, the biological effects of these genes were studied by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis.Results: 223 differentially expressed genes and 13 differentially expressed lncRNAs has been screened in the cardiomyopathy tissues.After database screening and matching, the final lncRNA–miRNA–mRNA network included three lncRNAs, eight miRNAs, and nine mRNAs. These nine genes are mainly involved in the prolactin signaling pathway, EGFR tyrosine kinase inhibitor resistance, toxoplasmosis, the chemokine signaling pathway, and the PI3K–Akt signaling pathway. In the PI3K–Akt signaling pathway, the expression levels of these genes are significantly upregulated compared with the control group, and the main genes involved in regulation are JAK2/DDIT4/FOXO3. JAK2 and FOXO3 play an important regulatory role in the PI3K–Akt signaling pathway.Conclusion:The AC017002–miRNA-590-5p–FOXO3 network may be involved in the pathogenesis of cardiomyopathy, which will enable the determination of new markers to predict cardiomyopathy, and thus reduce the risk of developing the disease.
Effect of Serum Bisphenol A and Low T3 on Short-Term Prognosis of Young Patients with Intracerebral Hemorrhage
Authors: wang guoping , Chen Jinhua , Qiao Zhongdong , Zhao Lili , Guo Dongxing , Guo Ping , Wang Aiven , Sun Wanli , Zhang Lifang , Feng Cueiping , Lyu Jiyuan 
Published: October 2021

Abstract
BackgroundBisphenol A (BPA) is an environmental chemical substance, and the widespread use of plastic products, its hazards can be said to be ubiquitous. We aimed to evaluate the relationship between serum bisphenol A (BPA), biomarkers and recent mortality in pats with young interacerebral hemorrhage (YICH) and different thyroid functions,and the cumulative consumption of plastic products.MethodsUsing a multi-center longitudinal prospective study, the research team recruited 600 YICH patients and divided them into two subgroups according to their thyroid function, of which 320 (53.3%) were in the low T3.Sub-clinical hypothyroidism(SCH) was 280 (46.6%) and control group (n = 600).All patients received serum BPA, and biomarker blood draws.ResultsEach log unit of BPA increased by 0.204 standard deviation unit (P<0.003).BPA(0.91±0.14)vs(0.765±0.13)vs(0.535±0.11)pg/ml,thrombin(1.35±0.18) vs (0.66±0.15) vs (0.66 ±0.15) ng/ml, MMP-9 (104±10 vs (53±8.1)vs(53±8.1) pg/ml,both P＜0.01. Serum BPA is positively correlated with biomarker, 24hDBPCV, and was negatively correlated LT3 and niR-451. Multiple linear regression showed that BPA was an independent risk factor affecting the percentage increase of nDBP (β = 0.286), P <0.01.Mortality rate showed 2 ,15 and 30 days of patients in the LT3 and the SCH of 4.7%vs 2.5%,6.25% vs 3.75%,4.68%vs 2.5%,P<0.01.ConclusionThus, Long-term exposure to BPA levels may be related to the occurrence of YICH, High BPA exposure strongly predicts the risk of ICH in young patients. Activation of NF-κB signaling pathway, secondary thyroid function and ABP changes, together to construct an inflammatory response program, is related to the risk of short-term death. There is a significant difference in recent mortality compared to LT3 vs SCH. Trial registrationThe trial is registered at clinical .gov (www.medresman.Chi CTR1900023626)
Dynamic Analysis of QTLs on Plant Height with Single Segment Substitution Lines in Rice
Authors: Fu Yu , Zhao Hongyuan , Huang Jiongkai , Zhu Haitao , Luan Xin , Bu Suhong , Liu Zupei , Meng Lijun , Liu Guifu , Zhang Guiquan , Wang Shaokui 
Published: October 2021

Abstract
Dynamic regulation of QTLs remains mysterious. Single segment substitution lines (SSSLs) and conditional QTL mapping and functional QTL mappings are ideal materials and methods to explore dynamics of QTLs for complex traits. This paper analyzed the dynamics of QTLs on plant height with SSSLs in rice. Five SSSLs were verified with plant height QTLs first. All five QTLs had significant positive effects at one or more developmental stages except QTL1. They interacted each other, with negative effects before 72 d after transplanting and positive effects since then. The five QTLs selectively expressed in specific periods, mainly in the periods from 35 to 42 d and from 49 to 56 d after transplanting. Expressions of epistasis were dispersedly in various periods, negative effects appearing mainly before 35 d. The five QTLs brought the inflexion point ahead of schedule, accelerated growth and degradation, and changed the peak plant height, while their interactions had the opposite effects. The information will be helpful to understand the genetic mechanism for developmental traits.
ZNF384 Gene Rearrangement in Acute Lymphocytic Leukemia with Kidney Involvement as the First Manifestation is Associated with Poor Prognosis: A Case Report
Authors: Ma Jinlong , Guan Jiaheng , Chen Baoan 
Published: October 2021

Abstract
Background: Novel fusion genes such as ZNF384 have been identified in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in recent years. Patients harboring ZNF384 rearrangement have a distinctive immunophenotype with weak CD10 and aberrant CD13 and/or CD33 expression, which makes ZNF384-rearranged ALL a unique subtype of BCP-ALL. However, research on the prognostic significance of ZNF384 rearrangement has been limited to date.Case presentation: We described a 17-year-old young woman who was diagnosed with ALL and had kidney involvement as the first manifestation, which was very rare in the existing studies. FISH analysis indicated a rearrangement of ZNF384 according to its probe. The patient had a typical characteristic immunophenotype of ZNF384 rearrangement with CD10 being negative but CD13 and CD33 being positive. She had an unfavorable prognosis since she responded poorly to chemotherapy and developed a relapse shortly after reaching CR.Conclusion: The importance of the ZNF384 gene rearrangement in terms of prognosis remains unclear. We reported a young woman harboring ZNF384 rearrangement in ALL with kidney involvement. She experienced different treatments, but her prognosis remained poor. Since ZNF384 rearrangement may act as a negative prognostic predictor, early detection based on its characteristic immunophenotype is of great necessity.
Identification of Potentially Functional Circular RNAs hsa_circ_0070934 and hsa_circ_0004315 as Prognostic Factor of Hepatocellular Carcinoma by Integrated Bioinformatics Analysis
Authors: Morovat Pejman , Morovat Saman , Ashrafi Arash M. , Teimourian Shahram 
Published: October 2021

Abstract
Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide, which has a high mortality rate and poor treatment outcomes with yet unknown molecular basis. It seems that gene expression plays a pivotal role in the pathogenesis of the disease. Circular RNAs (circRNAs) can interact with microRNAs (miRNAs) to regulate gene expression in various malignancies by acting as competitive endogenous RNAs (ceRNAs). However, the potential pathogenesis roles of the ceRNA network among circRNA/miRNA/mRNA in HCC are unclear. In this study, first, the HCC circRNA expression data were obtained from three Gene Expression Omnibus microarray datasets (GSE164803, GSE94508, GSE97332), and the differentially expressed circRNAs (DECs) were identified using R limma package. Also, the liver hepatocellular carcinoma (LIHC) miRNA and mRNA sequence data were retrieved from TCGA, and differentially expressed miRNAs (DEMIs) and mRNAs (DEGs) were determined using the R DESeq2 package. Second, CSCD website was used to uncover the binding sites of miRNAs on DECs. The DECs' potential target miRNAs were revealed by conducting an intersection between predicted miRNAs from CSCD and downregulated DEMIs. Third, some related genes were uncovered by intersecting targeted genes predicted by miRWalk and targetscan online tools with upregulated DEGs. The ceRNA network was then built using the Cytoscape software. The functional enrichment and the overall survival time of these potential targeted genes were analyzed, and a PPI network was constructed in the STRING database. Network visualization was performed by Cytoscape, and ten hub genes were detected using the CytoHubba plugin tool. Four DECs (hsa_circ_0000520, hsa_circ_0008616, hsa_circ_0070934, hsa_circ_0004315) were obtained and six miRNAs (hsa-miR-542-5p, hsa-miR-326, hsa-miR-511-5p, hsa-miR-195-5p, hsa-miR-214-3p, and hsa-miR-424-5p) which are regulated by the above DECs were identified. Then 543 overlapped genes regulated by six miRNAs mentioned above were predicted. Functional enrichment analysis showed that these genes are mostly associated with cancer regulation functions. Ten hub genes (TTK،AURKB, KIF20A، KIF23، CEP55، CDC6، DTL، NCAPG، CENPF، PLK4) have been screened from the PPI network of the 204 survival-related genes. KIF20A, NCAPG, TTK, PLK4, and CDC6 were selected for the highest significant p-values. In the end, a circRNA-miRNA-mRNA regulatory axis was established for five final selected hub genes. This study implies the potential pathogenesis of the obtained network and proposes that the two DECs (has_circ_0070934 and has_circ_0004315) may be important prognostic factor for HCC.
Epidermal Microbiomes of Triakis Semifasciata Are Consistent Across Captive and Wild Environments
Authors: Goodman Asha , Papudeshi Bhavya , Doane Michael P. , Johnson Colton , Mora Maria , Kerr Emma , Torres Melissa , Nero Jennifer , Lima Laís , Nosel Andrew P. , Dinsdale Elizabeth A. 
Published: October 2021

Abstract
Background: Characterizations of sharks-microbe systems in wild environments have outlined patterns of species-specific microbiomes; however, whether captivity affects these trends has yet to be determined. We used high-throughput shotgun sequencing to assess the epidermal microbiome belonging to leopard sharks (Triakis semifasciata) in captive (Birch Aquarium, La Jolla California), semi-captive (<1 year in captivity; Scripps Institute of Oceanography, California) and wild environments (Moss Landing and La Jolla, California). Results: Here we report captive environments do not drive microbiome composition of T. semifasciata to significantly diverge from wild counterparts as life-long captive sharks maintain a species-specific epidermal microbiome resembling those associated with semi-captive and wild populations. Major taxonomic composition shifts observed were inverse changes of top taxonomic contributors across captive duration, specifically an increase of Pseudoalteromonadaceae and consequent decrease of Pseudomonadaceae relative abundance as T. semifasciata increased duration in captive conditions. Moreover, we show captivity did not lead to significant losses in microbial α-diversity of shark epidermal communities. Finally, we present a novel association between T. semifasciata and the Muricauda genus as MAGs revealed a consistent relationship across captive, semi-captive, and wild populations. Conclusions: Our report illustrates the importance of conservation programs for coastal fishes as epidermally-associated microbes of near-shore shark species do not suffer detrimental impacts from long or short-term captivity. Our findings also expand on current understanding of shark epidermal microbiomes, explore the effects of ecologically different scenarios on benthic shark microbe associations, and highlight novel microbial associations that are consistent across captive gradients.
Real-Time Monitoring and Alarm System in Underground Coal Mines Using Smart Helmets (A Case Study: Tabas Coal Mine)
Authors: Ghadyani Daniyal , Badraddini Amirhossein , Kazemi Mohammad Mirzehi Kalateh , Sarfarazi Vahab , Mostofi Sohrab Naser , Khodabandeloo Vahid 
Published: October 2021

Abstract
Regarding the hazard-prone working conditions in underground mines, synchronous monitoring and alarm system is vital to increase the safety. By analyzing the accidents in underground mines in Iran, it can be deduced that most fatalities are related to harmful gas leakage, objects drop off on the head, and not using helmets by the staff. Therefore, a smart helmet with the capability of measuring harmful gasses (regarding the type of the mine), detection of the existence of the helmet on the head, temperature and humidity measurement, and detection of blow on the head is designed and fabricated to eliminate the present dangers and problems. This system displays the evaluated data on a developed software through wireless data transmission hardware. The data transmission hardware is the primary link between the intelligent safety helmet and the software. To follow the idea, practical experiments have been performed in Parvadeh four and East Parvadeh of Tabas coal mine to confirm the validity of data transmission that culminated in successful results. The results were altered by the complexity of the design of the underground spaces so that in a straight direction, data transmission was held until 430 meters. However, further progress was not possible due to tunnel limitations. Data transmission was reduced to 190 meters in access horizons with curvatures or tilts. According to present standards, some thresholds are defined for each of the mentioned cases such that alarm protocol is activated by exceeding these thresholds in critical circumstances. Then the helmet user and the software’s operator will be informed of the occurred danger and will settle the problem.
Gene Expression Profiles in Sporadic ALS Fibroblasts Define Disease Subtypes and The Metabolic Effects of the Investigational Drug EH301
Authors: Fels Jasmine A. , Casalena Gabriella , Konrad Csaba , Holmes Holly , Dellinger Ryan W. , Manfredi Giovanni 
Published: October 2021

Abstract
Background: Majority of ALS cases are sporadic (sALS), as they lack defined genetic causes. Metabolic alterations shared between the nervous system and skin fibroblasts have emerged in ALS. Recently, we found that a subgroup of sALS fibroblasts (sALS1) is characterized by metabolic profiles (metabotype) distinct from other sALS cases (sALS2) and controls, suggesting that metabolic therapies could be effective in sALS. The metabolic modulators nicotinamide riboside and pterostilbene (EH301) are under clinical development for the treatment of ALS. Here, we studied the metabolome and transcriptome of sALS cells to understand the molecular bases of sALS metabotypes and the impact of EH301.Methods: Six fibroblast cell lines (3 male and 3 female subjects of similar ages) were used for each group (sALS1, sALS2, and controls). Metabolomics and transcriptomics were investigated at baseline and after EH301 treatment. Differential gene expression (DEGs) and metabolite abundance were assessed by a Wald Test and ANOVA, respectively, with FDR correction, and pathway analyses were performed. EH301 protection against metabolic stress was tested by thiol depletion. Weighted gene co-expression network analysis (WGCNA) was used to investigate the association of metabolic and clinical features and was also performed on the Answer ALS dataset from induced motor neurons (iMN). A machine learning model based on DEGs was tested as a sALS disease progression predictor. Results: We found that the sALS1 transcriptome is distinct from sALS2 and that EH301 modifies gene expression differently in sALS1, sALS2, and controls. Furthermore, EH301 had strong protective effects against metabolic stress, which is linked to anti-inflammatory and antioxidant pathways. WGCNA revealed that ALS functional rating scale and metabotypes are associated with gene modules enriched for cell cycle, immunity, autophagy, and metabolism terms, which are modified by EH301. Meta-analysis of publicly available transcriptomics data from iMNs confirmed functional associations of genes correlated with disease traits. A small subset of genes differentially expressed in sALS fibroblasts could be used in a machine learning model to predict disease progression.Conclusions: Multi-omics analyses of patient-derived fibroblasts highlighted differential metabolic and transcriptomic profiles in sALS metabotypes, which translate into differential responses to the investigational drug EH301.
Predicting Retinal Sensitivity Using Optical Coherence Tomography Parameters in Central Serous Chorioretinopathy
Authors: Kanda Satoru , Zhou Han Peng , Inoue Tatsuya , Fujino Ryosuke , Sugiura Aya , Aoyama Yurika , Kadonosono Kazuaki , Maruyama-Inoue Maiko , Obata Ryo , Asaoka Ryo 
Published: October 2021

Abstract
Purpose
To predict the change of retinal sensitivity using optical coherence tomography (OCT) parameters in eyes with central serous chorioretinopathy (CSC).
Methods
Twenty-three eyes of 23 patients with CSC were enrolled. Retinal sensitivity was measured twice with a microperimetry in all examined eyes. OCT measurement was simultaneously conducted. The relationship between retinal sensitivities and the thicknesses of i) retinal nerve fiver layer + ganglion cell layer (RNFL+GCL), ii) inner nuclear layer (INL) iii) outer nuclear layer (ONL) and iV) serous retinal detachment height (SRDH) were investigated in a point-wise manner. We also investigated the association between the change of retinal sensitivity and OCT parameters at baseline.
Results
The mean age of participants was 49.8 ± 10.7 years. The mean SRDH was significantly lower (p<0.001) and the mean retinal sensitivity (p<0.001) was significantly higher in the 2nd examination compared to the 1st measurements, however LogMAR visual acuity (VA) was not significantly different between the two measurements (p=0.063). LogMAR VA was associated with retinal sensitivity both in the 1st and 2nd measurements (p<0.001). The retinal sensitivity in the 2nd examination was significantly correlated with retinal sensitivity, RNFL+GCL, INL, ONL, SRDH in the 1st examination and the improvement of SRDH.
Conclusions
Retinal sensitivity was associated with retinal structure in eyes with CSC; these parameters were useful to predict the change of visual function before the treatment.
Being A Safe Place: A Qualitative Study Exploring Perceptions As To How A Rural Community Hospice Could Respond To Enactment of Voluntary Assisted Dying Legislation
Authors: Auret Kirsten , Pikora Terri , Gersbach Kate 
Published: October 2021

Abstract
Background: There is a lack of research to guide the implementation of voluntary assisted dying legislation within a hospice setting. Furthermore, there is limited published information related to the expectations of the community and staff to assist decision making regarding voluntary assisted dying in a community hospice. The aim of this study was to explore the expectations of staff, volunteers and members of the community as how a rural community hospice could respond in relation to enactment of Voluntary Assisted Dying legislation. Methods: A total of 63 Hospice staff and volunteers and community members participated in 11 workshops. This qualitative study used a grounded theory approach to analyse the workshop transcripts. Results: While there was not a consensus view on community expectation, there was agreement among the participants for respect for a patient’s individuality and choices. Furthermore, care offered in hospice needs to remain non-judgemental and patient focused regardless of whether voluntary assisted dying policy was implemented or not. Both opportunities and risks associated with implementation were identified by the participants. Conclusion: There was common ground around the respect for the dying person and the ideal of a “safe place” despite opposing views on what this may mean in practice. There is a need for clarity in organisational responses around policy, risk management, education, and staff support.
Multiple Context Learning Networks for Visual Question Answering
Authors: Zhang Pufen , Lan Hong 
Published: October 2021

Abstract
In recently years, some visual question answering (VQA) methods that emphasize the simultaneous understanding of both the context of image and question have been proposed. Despite the effectiveness of these methods, they fail to explore a more comprehensive and generalized context learning tactics. To address this issue, we propose a novel Multiple Context Learning Networks (MCLN) to model the multiple contexts for VQA. Three kinds of contexts are investigated, namely visual context, textual context and a special visual-textual context that ignored by previous methods. Moreover, three corresponding context learning modules are proposed. These modules endow image and text representations with context-aware information based on a uniform context learning strategy. And they work together to form a multiple context learning layer (MCL). Such MCL can be stacked in depth and which describe high-level context information by associating intra-modal contexts with inter-modal context. On the VQA v2.0 datasets, the proposed model achieves 71.05% and 71.48% on test-dev set and test-std set respectively, and gains better performance than the previous state-of-the-art methods. In addition, extensive ablation studies have been carried out to examine the effectiveness of the proposed method.