bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effective production of kojic acid in engineered Aspergillus niger
Authors: Wu Liu , Zhang Licheng , Li Xiaojie , Lv Ruitong , Cao Wei , Gao Weixia , Liu Jiao , Xie Zhoujie , Liu Hao 
Published: February 2023

Abstract
Background
Kojic acid (KA) is a widely used compound in the cosmetic, medical, and food industries, and is typically produced by Aspergillus oryzae. To meet increasing market demand, it is important to optimize KA production through seeking alternatives that are more economic than current A. oryzae-based methods.

Results
In this study, we achieved the first successful heterologous production of KA in Aspergillus niger, an industrially important fungus that does not naturally produce KA, through the expression of the kojA gene from A. oryzae. Using the resulting KA-producing A. niger strain as a platform, we identified four genes (nrkA, nrkB, nrkC, and nrkD) that negatively regulate KA production. Knocking down nrkA or deleting any of the other three genes resulted in a significant increase in KA production in shaking flask cultivation. The highest KA titer (25.71 g/L) was achieved in a pH controlled batch bioreactor using the kojA overexpression strain with a deletion of nrkC, which showed a 26.7% improvement compared to the KA titer (20.29 g/L) that was achieved in shaking flask cultivation.

Conclusion
Our study demonstrates the potential of using A. niger as a platform for studying KA biosynthesis and regulation, and for the cost-effective production of KA in industrial strain development.
Sensor-based assessment of social isolation in community-dwelling older adults: a scoping review
Authors: Khan Shehroz S. , Gu Tiancheng , Spinelli Lauren , Wang Rosalie H. 
Published: February 2023

AbstractSocial isolation (SI) is a state of low social interaction with peers associated with various adverse health consequences in older adults living in the community. SI is most often assessed through retrospective self-reports, which can be prone to recall or self-report biases and influenced by stigma. Ambient and wearable sensors have been explored to objectively assess SI based on interactions of a person within the environment and physiological data. However, because this field is in its infancy, there is a lack of clarity regarding the application of sensors and their data in assessing SI and the methods to develop these assessments. To understand the current state of research in sensor-based assessment of SI in older adults living in the community and to make recommendations for the field moving forward, we conducted a scoping review. The aims of the scoping review were to (i) map the types of sensors (and their associated data) that have been used for objective SI assessment, and (ii) identify the methodological approaches used to develop the SI assessment. Using an established scoping review methodology, we identified eight relevant articles. Data from motion sensors and actigraph were commonly applied and compared and correlated with self-report measures in developing objective SI assessments. Variability exists in defining SI, feature extraction and the use of sensors and self-report assessments. Inconsistent definitions and use of various self-report scales for measuring SI create barriers to studying the concept and extracting features to build predictive models. Recommendations include establishing a consistent definition of SI for sensor-based assessment research and development and consider capturing its complexity through innovative domain-specific features.
“They talked to me rudely”. Women perspectives on quality of post-abortion care in public health facilities in Kenya
Authors: Ouedraogo Ramatou , Kimemia Grace , Igonya Emmy Kageha , Athero Sherine , Wanjiru Shelmith , Bangha Martin , Juma Kenneth 
Published: February 2023

Abstract
Background
Access to safe abortion is legally restricted in Kenya. Therefore, majority women seeking abortion services in such restrictive contexts resort to unsafe methods and procedures that result in complications that often require treatment in health facilities. Most women with abortion-related complications end up in public health facilities. Nevertheless, evidence is limited on the quality of care provided to patients with abortion complications in public health facilities in Kenya.

Methods
Data for this paper are drawn from a qualitative study that included interviews with 66 women who received post-abortion care in a sample of primary, secondary and tertiary public health facilities in Kenya between November 2018 and February 2019. The interviews focused on mechanisms of decision-making while seeking post-abortion care services, care pathways within facilities, and perceptions of patients on quality of care received including respect, privacy, confidentiality, communication and stigma.

Findings
The participants’ perceptions of the quality of care were characterized as either “bad care” or “good care”, with the good care focusing on interpersonal aspects such as friendliness, respect, empathy, short waiting time before receiving services, as well as the physical or functional aspects of care such as resolution of morbidity and absence of death. Majority of participants initially reported that they received “good care” because they left the facility with their medical problem resolved. However, when probed, about half of them reported delays in receiving care despite their condition being an emergency (i.e., severe bleeding and pain). Participants also reported instances of abuse (verbal and sexual) or absence of privacy during care and inadequate involvement in decisions around the nature and type of care they received. Our findings also suggest that healthcare providers treated patients differently based on their attributes (spontaneous versus induced abortion, single versus married, young versus older). For instance, women who experienced miscarriages reported supportive care whereas women suspected to have induced their abortions felt stigmatized.

Conclusion
These findings have far reaching implications on efforts to improve uptake of post-abortion care, care seeking behaviors and on how to assess quality of abortion care. There should be emphasis on interventions meant to enhance processes and structural indicators of post-abortion care services meant to improve patients’ experiences throughout the care process. Moreover, more efforts are needed to advance the tools and approaches for assessing women experiences during post-abortion care beyond just the overriding clinical outcomes of care.
VLPs containing stalk domain and ectodomain of matrix protein 2 of influenza induce protection in mice
Authors: Shi Lili , Long Ying , Zhu Yanyan , Dong Jingjian , Chen Yan , Feng Hao , Sun Xianliang 
Published: February 2023

Abstract
Background
As a result of antigenic drift, current influenza vaccines provide limited protection against circulating influenza viruses, and vaccines with broad cross protection are urgently needed. Hemagglutinin stalk domain and ectodomain of matrix protein 2 are highly conserved among influenza viruses and have great potential for use as a universal vaccine.

Methods
In this study, we co-expressed the stalk domain and M2e on the surface of cell membranes and generated chimeric and standard virus-like particles of influenza to improve antigen immunogenicity. We subsequently immunized BALB/c mice through intranasal and intramuscular routes.

Results
Data obtained demonstrated that vaccination with VLPs elicited high levels of serum-specific IgG (approximately 30-fold higher than that obtained with soluble protein), induced increased ADCC activity to the influenza virus, and enhanced T cell as well as mucosal immune responses. Furthermore, mice immunized by VLP had elevated level of mucosal HA and 4M2e specific IgA titers and cytokine production as compared to mice immunized with soluble protein. Additionally, the VLP-immunized group exhibited long-lasting humoral antibody responses and effectively reduced lung viral titers after the challenge. Compared to the 4M2e-VLP and mHA-VLP groups, the chimeric VLP group experienced cross-protection against the lethal challenge with homologous and heterologous viruses. The stalk domain specific antibody conferred better protection than the 4M2e specific antibody.

Conclusion
Our findings demonstrated that the chimeric VLPs anchored with the stalk domain and M2e showed efficacy in reducing viral loads after the influenza virus challenge in the mice model. This antibody can be used in humans to broadly protect against a variety of influenza virus subtypes. The chimeric VLPs represent a novel approach to increase antigen immunogenicity and are promising candidates for a universal influenza vaccine.
DEPDC1 and KIF4A synergistically inhibit the malignant biological behavior of osteosarcoma cells through Hippo signaling pathway
Authors: Yang Mingming , Zhang Hang , Gao Shichang , Huang Wei 
Published: February 2023

AbstractThe treatment of osteosarcoma (OS) is still mainly surgery combined with systematic chemotherapy, and gene therapy is expected to improve the survival rate of patients. This study aimed to explore the effect of DEP domain 1 protein (DEPDC1) and kinesin super-family protein 4A (KIF4A) in OS and understand its mechanism. Th expression of DEPDC1 and KIF4A in OS cells was detected by RT-PCR and western blot. The viability, proliferation, invasion and migration of OS cells and tube formation of human umbilical vein endothelial cells (HUVECs) after indicated treatment were in turn detected by CCK-8 assay, EdU staining, wound healing assay, transwell assay and tube formation assay. The interaction between DEPDC1 and KIF4A was predicted by STRING and confirmed by co-immunoprecipitation. The expression of epithelial-mesenchymal transition (EMT)-related proteins, tube formation-related proteins and Hippo signaling pathway proteins was detected by western blot. As a result, the expression of DEPDC1 and KIF4A was all increased in U2OS cells. Down-regulation of DEPDC1 suppressed the viability, proliferation, invasion and migration of U2OS cells and tube formation of HUVECs, accompanied by the increased expression of E-cadherin and decreased expression of N-cadherin, Vimentin and VEGF. DEPDC1 was confirmed to be interacted with KIF4A. Upregulation of KIF4A partially reversed the effect of DEPDC1 interference on the above biological behaviors of U2OS cells. Down-regulation of DEPDC1 promoted the expression of p-LATS1 and p-YAP in Hippo signaling pathway, which was reversed by upregulation of KIF4A. In conclusion, down-regulation of DEPDC1 inhibited the malignant biological behavior of OS cells through the activation of Hippo signaling pathway, which could be reversed by upregulation of KIF4A.
Broadly applicable TCR-based therapy for multiple myeloma targeting the immunoglobulin J chain
Authors: Meeuwsen Miranda H. , Wouters Anne K. , Wachsmann Tassilo L. A. , Hagedoorn Renate S. , Kester Michel G. D. , Remst Dennis F. G. , van der Steen Dirk M. , de Ru Arnoud H. , van Hees Els P. , Kremer Martijn , Griffioen Marieke , van Veelen Peter A. , Falkenburg J. H. Frederik , Heemskerk Mirjam H. M. 
Published: February 2023

Abstract
Background
The immunoglobulin J chain (Jchain) is highly expressed in the majority of multiple myeloma (MM), and Jchain-derived peptides presented in HLA molecules may be suitable antigens for T-cell therapy of MM.

Methods
Using immunopeptidomics, we identified Jchain-derived epitopes presented by MM cells, and pHLA tetramer technology was used to isolate Jchain-specific T-cell clones.

Results
We identified T cells specific for Jchain peptides presented in HLA-A1, -A24, -A3, and -A11 that recognized and lysed JCHAIN-positive MM cells. TCRs of the most promising T-cell clones were sequenced, cloned into retroviral vectors, and transferred to CD8 T cells. Jchain TCR T cells recognized target cells when JCHAIN and the appropriate HLA restriction alleles were expressed, while JCHAIN or HLA-negative cells, including healthy subsets, were not recognized. Patient-derived JCHAIN-positive MM samples were also lysed by Jchain TCR T cells. In a preclinical in vivo model for established MM, Jchain-A1, -A24, -A3, and -A11 TCR T cells strongly eradicated MM cells, which resulted in 100-fold lower tumor burden in Jchain TCR versus control-treated mice.

Conclusions
We identified TCRs targeting Jchain-derived peptides presented in four common HLA alleles. All four TCRs demonstrated potent preclinical anti-myeloma activity, encouraging further preclinical testing and ultimately clinical development.
Targeting STAT3-VISTA axis to suppress tumor aggression and burden in acute myeloid leukemia
Authors: Mo Jianshan , Deng Lin , Peng Keren , Ouyang Shumin , Ding Wen , Lou Linlin , Lin Ziyou , Zhu Jianzheng , Li Jingwei , Zhang Qiyi , Wang Pengyan , Wen Yuanzhen , Chen Xiaobing , Yue Peibin , Lu Jin-Jian , Zhu Kai , Zheng Yongjiang , Wang Yuanxiang , Zhang Xiaolei 
Published: February 2023

AbstractThe acute myeloid leukemia (AML) patients obtain limited benefits from current immune checkpoint blockades (ICBs), although immunotherapy have achieved encouraging success in numerous cancers. Here, we found that V-domain Ig suppressor of T cell activation (VISTA), a novel immune checkpoint, is highly expressed in primary AML cells and associated with poor prognosis of AML patients. Targeting VISTA by anti-VISTA mAb boosts T cell-mediated cytotoxicity to AML cells. Interestingly, high expression of VISTA is positively associated with hyperactive STAT3 in AML. Further evidence showed that STAT3 functions as a transcriptional regulator to modulate VISTA expression by directly binding to DNA response element of VISTA gene. We further develop a potent and selective STAT3 inhibitor W1046, which significantly suppresses AML proliferation and survival. W1046 remarkably enhances the efficacy of VISTA mAb by activating T cells via inhibition of STAT3 signaling and down-regulation of VISTA. Moreover, combination of W1046 and VISTA mAb achieves a significant anti-AML effect in vitro and in vivo. Overall, our findings confirm that VISTA is a potential target for AML therapy which transcriptionally regulated by STAT3 and provide a promising therapeutic strategy for immunotherapy of AML.
Radiographic damage in early rheumatoid arthritis is associated with increased disability but not with pain—a 5-year follow-up study
Authors: Eberhard Anna , Rydell Emil , Forslind Kristina , Bergman Stefan , Mandl Thomas , Olofsson Tor , Jacobsson Lennart T. H. , Turesson Carl 
Published: February 2023

Abstract
Objectives
To evaluate how radiographic damage, overall and measured as joint space narrowing score (JSNS) and erosion score (ES), as well as other clinical and laboratory measures, relate to disability and pain in early rheumatoid arthritis (RA).

Methods
An inception cohort of 233 patients with early RA, recruited in 1995–2005, was followed for 5 years. Disability was assessed with the Health Assessment Questionnaire (HAQ), and pain with a visual analogue scale (VAS; 0–100 mm). Radiographs of hands and feet were evaluated using the Sharp-van der Heijde score (SHS), including JSNS and ES. The relation for radiographic scores and other clinical parameters with pain and HAQ were evaluated cross-sectionally by multivariate linear regression analysis and over time using generalized estimating equations.

Results
ES was significantly associated with HAQ cross-sectionally at inclusion, after 2 and after 5 years, and over time. Associations for HAQ with SHS and JSNS were weaker and less consistent compared with those for ES. There was no association between radiographic scores and pain at any visit. Both HAQ and pain were associated with parameters of disease activity. The strongest cross-sectional associations were found for the number of tender joints (adjusted p<0.001 at all visits).

Conclusion
Joint damage was associated with disability already in early RA. Erosions of hands and feet appear to have a greater influence on disability compared with joint space narrowing early in the disease. Pain was associated with other factors than joint destruction in early RA, in particular joint tenderness—suggesting an impact of pain sensitization.
DU-Net-Cloud: a smart cloud-edge application with an attention mechanism and U-Net for remote sensing images and processing
Authors: Kong Jiayuan , Zhang Yanjun 
Published: February 2023

AbstractIn recent ages, the use of deep learning approaches to extract ground object information from remote sensing high-resolution images has attracted extensive attention in many fields. Nevertheless, due to the high similarity of features between roads, prevailing deep learning semantic segmentation networks commonly demonstrate reduced continuity in road segmentation. Besides this, the role of advanced computing technologies including cloud and edge infrastructures has also become very important due to large number of images and their storage requirements. In order to better study the road details in images related to remote sensing, this paper suggests a road extraction technique which is basically founded on Dimensional U-Net (DU-Net) network. At the deepening level of the U-Net network, a parallel attention mechanism, known as ProCBAM, is added and implemented to the feature transmission step of the classical U-Net network. Moreover, we use and implement the edge-cloud architecture to develop and construct a unique remote sensing image service system that integrates several datacenters and their related edge infrastructure. In the proposed system, the edge network is primarily used for caching and distributing the processed remote sensing images, while the remote datacenter serves as the cloud platform and is responsible for the storage and processing of original remote sensing images. The results show that the proposed cloud enabled DU-Net model has achieved good performance in road segmentation. We observed that it can achieve improved road segmentation and resolve the issue of reduced continuity of road segmentation when compared with other state-of-the-art learning networks. Moreover, our empirical evaluations suggest that the proposed system not only distributes the workload of processing tasks across the edges but also achieves data efficiency among them, which enhances image processing efficiency and reduces data transmission costs.
Analysis of the differential expression and prognostic relationship of DEGs in AML based on TCGA database
Authors: Gao Yue , Jia Yinnong , Yu Zhengmin , Ji Xinyu , Liu Xiaowen , Han Lei , Zhang Hengdong , Zhu Baoli , Xu Ming 
Published: February 2023

Abstract
Background
Acute myeloid leukemia (AML) is a common and lethal hematological malignant hyperplastic disease originating from hematopoietic stem cells. The purpose of this study is to obtain the key differentially expressed gene (DEG) related to the survival of AML by The Cancer Genome Atlas (TCGA) database and to verify these genes by a clinical follow-up investigation, in order to identify valuable predictive and prognostic biomarkers for early diagnosis of AML and predict the survival rates.

Methods
The RNA sequencing (RNA-Seq) data and clinical information of TCGA-LAML were downloaded from the TCGA database. After that we (1) screened the survival-related DEGs by Cox regression analysis, (2) selected the cytogenetics risk-related DEGs by DESeq2 R package, and (3) filtrated the genes in the top10 pathways of up-regulated and down-regulated of Normalization Enrichment Score (NES) by Gene Set Enrichment Analysis (GSEA). Finally, we focused the intersectional genes of above three parts as the key gene of the present study. The following Multivariate.
Longitudinal study of the short- and long-term effects of hospitalisation and oral trimethoprim-sulfadiazine administration on the equine faecal microbiome and resistome
Authors: Theelen Mathijs J. P. , Luiken Roosmarijn E. C. , Wagenaar Jaap A. , Sloet van Oldruitenborgh-Oosterbaan Marianne M. , Rossen John W. A. , Schaafstra Femke J. W. C. , van Doorn David A. , Zomer Aldert L. 
Published: February 2023

AbstractBackgroundHospitalisation and antimicrobial treatment are common in horses and significantly impact the intestinal microbiota. Antimicrobial treatment might also increase levels of resistant bacteria in faeces, which could spread to other ecological compartments, such as the environment, other animals and humans. In this study, we aimed to characterise the short- and long-term effects of transportation, hospitalisation and trimethoprim-sulfadiazine (TMS) administration on the faecal microbiota and resistome of healthy equids.MethodsIn a longitudinal experimental study design, in which the ponies served as their own control, faecal samples were collected from six healthy Welsh ponies at the farm (D0–D13-1), immediately following transportation to the hospital (D13-2), during 7 days of hospitalisation without treatment (D14–D21), during 5 days of oral TMS treatment (D22–D26) and after discharge from the hospital up to 6 months later (D27–D211). After DNA extraction, 16S rRNA gene sequencing was performed on all samples. For resistome analysis, shotgun metagenomic sequencing was performed on selected samples.ResultsHospitalisation without antimicrobial treatment did not significantly affect microbiota composition. Oral TMS treatment reduced alpha-diversity significantly. Kiritimatiellaeota, Fibrobacteres and Verrucomicrobia significantly decreased in relative abundance, whereas Firmicutes increased. The faecal microbiota composition gradually recovered after discontinuation of TMS treatment and discharge from the hospital and, after 2 weeks, was more similar to pre-treatment composition than to composition during TMS treatment. Six months later, however, microbiota composition still differed significantly from that at the start of the study and Spirochaetes and Verrucomicrobia were less abundant. TMS administration led to a significant (up to 32-fold) and rapid increase in the relative abundance of resistance genessul2,tetQ,ant6-1a, andaph(3”)-lb.lnuCsignificantly decreased directly after treatment. Resistance genes sul2(15-fold) andtetQ(six-fold) remained significantly increased 6 months later.ConclusionsOral treatment with TMS has a rapid and long-lasting effect on faecal microbiota composition and resistome, making the equine hindgut a reservoir and potential source of resistant bacteria posing a risk to animal and human health through transmission. These findings support the judicious use of antimicrobials to minimise long-term faecal presence, excretion and the spread of antimicrobial resistance in the environment.
YULINK regulates vascular formation in zebrafish and HUVECs
Authors: Lin Hsin-Hung , Kuo Ming-Wei , Fan Tan-Chi , Yu Alice L. , Yu John 
Published: February 2023

AbstractBackgroundThe distinct arterial and venous cell fates are dictated by a combination of various genetic factors which form diverse types of blood vessels such as arteries, veins, and capillaries. We report here that YULINK protein is involved in vasculogenesis, especially venous formation.MethodsIn this manuscript, we employed gene knockdown, yeast two-hybrid, FLIM-FRET, immunoprecipitation, and various imaging technologies to investigate the role of YULINK gene in zebrafish and human umbilical vein endothelial cells (HUVECs).ResultsKnockdown ofYULINKduring the arterial-venous developmental stage of zebrafish embryos led to the defective venous formation and abnormal vascular plexus formation. Knockdown ofYULINKin HUVECs impaired their ability to undergo cell migration and differentiation into a capillary-like tube formation. In addition, the phosphorylated EPHB4 was decreased inYULINKknockdown HUVECs. Yeast two-hybrid, FLIM-FRET, immunoprecipitation, as well as imaging technologies showed that YULINK colocalized with endosome related proteins (EPS15, RAB33B or TICAM2) and markers (Clathrin and RHOB). VEGF-induced VEGFR2 internalization was also compromised inYULINKknockdown HUVECs, demonstrating to the involvement of YULINK.ConclusionThis study suggests that YULINK regulates vasculogenesis, possibly through endocytosis in zebrafish and HUVECs.