bluuebunny/crossref_metadata_2025_split huggingface dataset:
The mutation of Japanese encephalitis virus envelope protein residue 389 attenuates viral neuroinvasiveness
Authors: Huang Rong , He Yajing , Zhang Chenghua , Luo Yue , Chen Chen , Tan Ning , Ren Yang , Xu Kui , Yuan Lei , Yang Jian 
Published: June 2024

AbstractThe envelope (E) protein of the Japanese encephalitis virus (JEV) is a key protein for virus infection and adsorption of host cells, which determines the virulence of the virus and regulates the intensity of inflammatory response. The mutation of multiple aa residues in the E protein plays a critical role in the attenuated strain of JEV. This study demonstrated that the Asp to Gly, Ser, and His mutation of the E389 site, respectively, the replication ability of the viruses in cells was significantly reduced, and the viral neuroinvasiveness was attenuated to different degrees. Among them, the mutation at E389 site enhanced the E protein flexibility contributed to the attenuation of neuroinvasiveness. In contrast, less flexibility of E protein enhanced the neuroinvasiveness of the strain. Our results indicate that the mechanism of attenuation of E389 aa mutation attenuates neuroinvasiveness is related to increased flexibility of the E protein. In addition, the increased flexibility of E protein enhanced the viral sensitivity to heparin inhibition in vitro, which may lead to a decrease in the viral load entering brain. These results suggest that E389 residue is a potential site affecting JEV virulence, and the flexibility of the E protein of aa at this site plays an important role in the determination of neuroinvasiveness.
Increased expression of REG3A promotes tumorigenic behavior in triple negative breast cancer cells
Authors: Jin Xiaoxia , Yang Shuyun , Lu Xiaoyun , Chen Xudong , Dai Wencheng 
Published: June 2024

Abstract
Background
Identifying new targets in triple negative breast cancer (TNBC) remains critical. REG3A (regenerating islet-derived protein 3 A), a calcium-dependent lectin protein, was thoroughly investigated for its expression and functions in breast cancer.

Methods
Bioinformatics and local tissue analyses were employed to identify REG3A expression in breast cancer. Genetic techniques were employed to modify REG3A expression, and the resulting effects on the behaviors of breast cancer cells were examined. Subcutaneous xenograft models were established to investigate the involvement of REG3A in the in vivo growth of breast cancer cells.

Results
Analysis of the TCGA database uncovered increased REG3A levels in human breast cancer tissues. Additionally, REG3A mRNA and protein levels were elevated in TNBC tissues of locally treated patients, contrasting with low expression in adjacent normal tissues. In primary human TNBC cells REG3A shRNA notably hindered cell proliferation, migration, and invasion while triggering caspase-mediated apoptosis. Similarly, employing CRISPR-sgRNA for REG3A knockout showed significant anti-TNBC cell activity. Conversely, REG3A overexpression bolstered cell proliferation and migration. REG3A proved crucial for activating the Akt-mTOR cascade, as evidenced by decreased Akt-S6K1 phosphorylation upon REG3A silencing or knockout, which was reversed by REG3A overexpression. A constitutively active mutant S473D Akt1 (caAkt1) restored Akt-mTOR activation and counteracted the proliferation inhibition and apoptosis induced by REG3A knockdown in breast cancer cells. Crucially, REG3A played a key role in maintaining mTOR complex integrity. Bioinformatics identified zinc finger protein 680 (ZNF680) as a potential REG3A transcription factor. Knocking down or knocking out ZNF680 reduced REG3A expression, while its overexpression increased it in primary breast cancer cells. Additionally, enhanced binding between ZNF680 protein and the REG3A promoter was observed in breast cancer tissues and cells. In vivo, REG3A shRNA significantly inhibited primary TNBC cell xenograft growth. In REG3A-silenced xenograft tissues, reduced REG3A levels, Akt-mTOR inhibition, and activated apoptosis were evident.

Conclusion
ZNF680-caused REG3A overexpression drives tumorigenesis in breast cancer possibly by stimulating Akt-mTOR activation, emerging as a promising and innovative cancer target.
Imprinted DNA methylation of the H19 ICR is established and maintained in vivo in the absence of Kaiso
Authors: Matsuzaki Hitomi , Kimura Minami , Morihashi Mizuki , Tanimoto Keiji 
Published: June 2024

Abstract
Background
Paternal allele-specific DNA methylation of the imprinting control region (H19 ICR) controls genomic imprinting at the Igf2/H19 locus. We previously demonstrated that the mouse H19 ICR transgene acquires imprinted DNA methylation in preimplantation mouse embryos. This activity is also present in the endogenous H19 ICR and protects it from genome-wide reprogramming after fertilization. We also identified a 118-bp sequence within the H19 ICR that is responsible for post-fertilization imprinted methylation. Two mutations, one in the five RCTG motifs and the other a 36-bp deletion both in the 118-bp segment, caused complete and partial loss, respectively, of methylation following paternal transmission in each transgenic mouse. Interestingly, these mutations overlap with the binding site for the transcription factor Kaiso, which is reportedly involved in maintaining paternal methylation at the human H19 ICR (IC1) in cultured cells. In this study, we investigated if Kaiso regulates imprinted DNA methylation of the H19 ICR in vivo.

Results
Neither Kaiso deletion nor mutation of Kaiso binding sites in the 118-bp region affected DNA methylation of the mouse H19 ICR transgene. The endogenous mouse H19 ICR was methylated in a wild-type manner in Kaiso-null mutant mice. Additionally, the human IC1 transgene acquired imprinted DNA methylation after fertilization in the absence of Kaiso.

Conclusions
Our results indicate that Kaiso is not essential for either post-fertilization imprinted DNA methylation of the transgenic H19 ICR in mouse or for methylation imprinting of the endogenous mouse H19 ICR.
Colorectal cancer microbiome programs DNA methylation of host cells by affecting methyl donor metabolism
Authors: Liu Zhi , Zhang Qingqing , Zhang Hong , Yi Zhongyuan , Ma Huihui , Wang Xiaoyi , Wang Jingjing , Liu Yang , Zheng Yi , Fang Weijia , Huang Ping , Liu Xingyin 
Published: June 2024

Abstract
Background
Colorectal cancer (CRC) arises from complex interactions between host and environment, which include the gut and tissue microbiome. It is hypothesized that epigenetic regulation by gut microbiota is a fundamental interface by which commensal microbes dynamically influence intestinal biology. The aim of this study is to explore the interplay between gut and tissue microbiota and host DNA methylation in CRC.

Methods
Metagenomic sequencing of fecal samples was performed on matched CRC patients (n = 18) and healthy controls (n = 18). Additionally, tissue microbiome was profiled with 16S rRNA gene sequencing on tumor (n = 24) and tumor-adjacent normal (n = 24) tissues of CRC patients, while host DNA methylation was assessed through whole-genome bisulfite sequencing (WGBS) in a subset of 13 individuals.

Results
Our analysis revealed substantial alterations in the DNA methylome of CRC tissues compared to adjacent normal tissues. An extensive meta-analysis, incorporating publicly available and in-house data, identified significant shifts in microbial-derived methyl donor-related pathways between tumor and adjacent normal tissues. Of note, we observed a pronounced enrichment of microbial-associated CpGs within the promoter regions of genes in adjacent normal tissues, a phenomenon notably absent in tumor tissues. Furthermore, we established consistent and recurring associations between methylation patterns of tumor-related genes and specific bacterial taxa.

Conclusions
This study emphasizes the pivotal role of the gut microbiota and pathogenic bacteria in dynamically shaping DNA methylation patterns, impacting physiological homeostasis, and contributing to CRC tumorigenesis. These findings provide valuable insights into the intricate host-environment interactions in CRC development and offer potential avenues for therapeutic interventions in this disease.
Pathogenic sequence variant and microdeletion affecting HMGA2 in Silver–Russell syndrome: case reports and literature review
Authors: Yamoto Kaori , Saitsu Hirotomo , Ohkubo Yumiko , Kagami Masayo , Ogata Tsutomu 
Published: June 2024

AbstractSilver–Russell syndrome (SRS) is a representative imprinting disorder characterized by pre- and postnatal growth failure. We encountered two Japanese SRS cases with a de novo pathogenic frameshift variant of HMGA2 (NM_003483.6:c.138_141delinsCT, p.(Lys46Asnfs*16)) and a de novo ~ 3.4 Mb microdeletion at 12q14.2–q15 involving HMGA2, respectively. Furthermore, we compared clinical features in previously reported patients with various genetic conditions leading to compromised IGF2 expression, i.e., HMGA2 aberrations, PLAG1 aberrations, IGF2 aberrations, and H19/IGF2:IG-DMR epimutations (hypomethylations). The results provide further support for HMGA2 being involved in the development of SRS and imply some characteristic features in patients with HMGA2 aberrations.
Intrauterine chilled saline instillation reduces endometrial impairment on MRI after ultrasound-guided percutaneous microwave ablation of uterine adenomyosis
Authors: Zhang Hui-Li , Deng Er-Ya , Zhu Jing-E , Li Jia-Xin , Fu Le , Sun Li-Ping , Peng Cheng-Zhong , Li Xiao-Long , Yu Song-Yuan , Xu Hui-Xiong 
Published: June 2024

Abstract
Objective
To investigate whether intrauterine chilled saline can reduce endometrial impairment during US-guided percutaneous microwave ablation (PMWA) of adenomyosis.

Methods
An open-label, randomized trial was conducted with sixty symptomatic adenomyosis patients who were randomly assigned (1:1) to receive PMWA treatment assisted by intrauterine saline instillation (study group) or traditional PMWA treatment alone (control group). The primary endpoint was endometrial perfusion impairment grade on post-ablation contrast-enhanced MRI. The secondary endpoints were endometrial dehydration grade, ablation rate, and intra-ablation discomfort.

Results
The baseline characteristics of the two groups were similar. The incidence rates of endometrial perfusion impairment on MRI in the study and control groups were 6.7% (2/30) and 46.7% (14/30), respectively (p < 0.001). There were 28 (93.3%), 2 (6.7%), 0, and 0 patients in the study group and 16 (53.3%), 7 (23.3%), 5 (16.7%), and 2 (6.7%) in the control group (p < 0.001) who had grade 0, 1, 2, and 3 perfusion impairment, respectively. Additionally, there were 27 (90%), 3 (10%), and 0 patients in the study group and 19 (63.3%), 10 (33.3%), and 1 (3.3%) in the control group who had grade 0, 1, and 2 endometrial dehydration (p = 0.01). The ablation rates achieved in the study and control groups were 93.3 ± 17% (range: 69.2–139.6%) and 99.7 ± 15.7% (range: 71.5–129.8%), and they were not significantly different (p = 0.14). No significant difference was found in the intra-ablation discomfort.

Conclusion
Intrauterine chilled saline can effectively reduce endometrial impairment after PMWA treatment for adenomyosis.

Critical relevance statement
This trial demonstrated that the instillation of intrauterine chilled saline reduced endometrial impairment on MRI during PMWA of adenomyosis. This approach allows more precise and safe ablation in clinical practice.

Key Points

Endometrial impairment occurs in the PMWA treatment of adenomyosis.

Intrauterine chilled saline can reduce endometrial impairment during PMWA for adenomyosis.

An intrauterine catheter is a practical endometrial protecting method during thermal ablation.

Trial registration:
Chinese Clinical Trial Registry, ChiCTR2100053582. Registered 24 November 2021, www.chictr.org.cn/showproj.html?proj=141090.

Graphical Abstract
Mind the gap: knowledge, attitudes and perceptions on antimicrobial resistance, antimicrobial stewardship and infection prevention and control in long-term care facilities for people with disabilities in the Netherlands
Authors: Hidad S. , de Greeff S. C. , Haenen A. , de Haan F. , Leusink G. L. , Timen A. 
Published: June 2024

Abstract
Background
Antimicrobial resistance (AMR) has become one of the major public health threats worldwide, emphasizing the necessity of preventing the development and transmission of drug resistant microorganisms. This is particularly important for people with vulnerable health conditions, such as people with intellectual disabilities (ID) and long-term care residents. This study aimed to assess the current status of AMR, antimicrobial stewardship (AMS) and infection prevention and control (IPC) in Dutch long-term care facilities for people with intellectual disabilities (ID-LTCFs).

Methods
A web-based cross-sectional survey distributed between July and November 2023, targeting (both nonmedically and medically trained) healthcare professionals working in ID-LTCFs in The Netherlands, to study knowledge, attitudes and perceptions regarding AMR, AMS and IPC.

Results
In total, 109 participants working in 37 long-term care organizations for people with intellectual disabilities throughout the Netherlands completed the questionnaire. The knowledge levels of AMR and IPC among nonmedically trained professionals (e.g., social care professionals) were lower than those among medically trained professionals (p = 0.026). In particular regarding the perceived protective value of glove use, insufficient knowledge levels were found. Furthermore, there was a lack of easy-read resources and useful information regarding IPC and AMR, for both healthcare professionals as well as people with disabilities. The majority of the participants (> 90%) reported that AMR and IPC need more attention within the disability care sector, but paradoxically, only 38.5% mentioned that they would like to receive additional information and training about IPC, and 72.5% would like to receive additional information and training about AMR.

Conclusion
Although the importance of AMR and IPC is acknowledged by professionals working in ID-LTCFs, there is room for improvement in regards to appropriate glove use and setting-specific IPC and hygiene policies. As nonmedically trained professionals comprise most of the workforce within ID-LTCFs, it is also important to evaluate their needs. This can have a substantial impact on developing and implementing AMR, AMS and/or IPC guidelines and policies in ID-LTCFs.
Single-cell and bulk RNA-seq unveils the immune infiltration landscape associated with cuproptosis in cerebral cavernous malformations
Authors: Chen Chengwei , Bao Yuting , Ju Sihan , Jiang Conglin , Zou Xiang , Zhang Xin , Chen Liang 
Published: June 2024

Abstract
Background
Cerebral cavernous malformations (CCMs) are vascular abnormalities associated with deregulated angiogenesis. Their pathogenesis and optimal treatment remain unclear. This study aims to investigate the molecular signatures of cuproptosis, a newly identified type of cell death, associated with CCMs development.

Methods
Bulk RNA sequencing (RNA-seq) from 15 CCM and 6 control samples were performed with consensus clustering and clustered to two subtypes based on expression levels of cuproptosis-related genes (CRGs). Differentially expressed genes and immune infiltration between subtypes were then identified. Machine learning algorithms including the least absolute shrinkage and selection operator and random forest were employed to screen for hub genes for CCMs associated with cuproptosis. Furthermore, Pathway enrichment and correlation analysis were used to explore the functions of hub genes and their association with immune phenotypes in CCMs. An external dataset was then employed for validation. Finally, employing the Cellchat algorithm on a single-cell RNA-seq dataset, we explored potential mechanisms underlying the participation of these hub genes in cell-cell communication in CCMs.

Results
Our study revealed two distinct CCM subtypes with differential pattern of CRG expression and immune infiltration. Three hub genes (BTBD10, PFDN4, and CEMIP) were identified and validated, which may significantly associate with CCM pathogenesis. These genes were found to be significantly upregulated in CCM endothelial cells (ECs) and were validated through immunofluorescence and western blot analysis. Single-cell RNA-seq analysis revealed the cellular co-expression patterns of these hub genes, particularly highlighting the high expression of BTBD10 and PFDN4 in ECs. Additionally, a significant co-localization was also observed between BTBD10 and the pivotal cuproptosis gene FDX1 in Mki67+ tip cells, indicating the crucial role of cuproptosis for angiogenesis in CCMs. The study also explored the cell-cell communication between subcluster of ECs expressing these hub genes and immune cells, particularly M2 macrophages, suggesting a role for these interactions in CCM pathogenesis.

Conclusion
This study identifies molecular signatures linking cuproptosis to CCMs pathogenesis. Three hub genes—PFDN4, CEMIP, and BTBD10—may influence disease progression by modulating immunity. Further research is needed to understand their precise disease mechanisms and evaluate their potential as biomarkers or therapeutic targets for CCMs.
A systematic review on EEG-based neuromarketing: recent trends and analyzing techniques
Authors: Khondakar Md. Fazlul Karim , Sarowar Md. Hasib , Chowdhury Mehdi Hasan , Majumder Sumit , Hossain Md. Azad , Dewan M. Ali Akber , Hossain Quazi Delwar 
Published: June 2024

AbstractNeuromarketing is an emerging research field that aims to understand consumers’ decision-making processes when choosing which product to buy. This information is highly sought after by businesses looking to improve their marketing strategies by understanding what leaves a positive or negative impression on consumers. It has the potential to revolutionize the marketing industry by enabling companies to offer engaging experiences, create more effective advertisements, avoid the wrong marketing strategies, and ultimately save millions of dollars for businesses. Therefore, good documentation is necessary to capture the current research situation in this vital sector. In this article, we present a systematic review of EEG-based Neuromarketing. We aim to shed light on the research trends, technical scopes, and potential opportunities in this field. We reviewed recent publications from valid databases and divided the popular research topics in Neuromarketing into five clusters to present the current research trend in this field. We also discuss the brain regions that are activated when making purchase decisions and their relevance to Neuromarketing applications. The article provides appropriate illustrations of marketing stimuli that can elicit authentic impressions from consumers' minds, the techniques used to process and analyze recorded brain data, and the current strategies employed to interpret the data. Finally, we offer recommendations to upcoming researchers to help them investigate the possibilities in this area more efficiently in the future.
Successful R0 resection after chemotherapy, including nivolumab, for gastric cancer with liver metastases: three case reports
Authors: Kawai Junpei , Yasufuku Itaru , Fukada Masahiro , Asai Ryuichi , Sato Yuta , Tajima Yu Jesse , Saigo Chiemi , Kiyama Shigeru , Makiyama Akitaka , Tanaka Yoshihiro , Okumura Naoki , Murase Katsutoshi , Miyazaki Tatsuhiko , Matsuhashi Nobuhisa 
Published: June 2024

Abstract
Background
Advances in chemotherapy have increased clinical experience with conversion surgery for inoperable advanced gastric cancer. This report describes three patients with unresectable gastric cancer accompanied by multiple liver metastases. In all three patients, nivolumab resolved the liver metastases and subsequent conversion surgery achieved a pathological complete response.

Case presentation
In Case 1, a 68-year-old man with clinical Stage IVB gastric cancer and multiple liver metastases initiated first-line therapy with SOX plus nivolumab. The patient completed 13 cycles; however, only nivolumab was continued for 3 cycles because of adverse events. Distal gastrectomy and partial hepatic resection were performed because of a significant reduction in the size of the liver metastases as observed on magnetic resonance imaging (MRI). In Case 2, a 72-year-old man with clinical Stage IVB gastric cancer and multiple liver metastases initiated first-line therapy with SOX. Because of the subsequent emergence of new liver metastases, the patient transitioned to ramucirumab plus paclitaxel as second-line therapy. Third-line therapy with nivolumab was initiated because of side effects. MRI revealed necrosis within the liver metastasis, and the patient underwent proximal gastrectomy and partial hepatectomy. In Case 3, a 51-year-old woman with clinical Stage IVB gastric cancer accompanied by multiple metastases of the liver and para-aortic lymph nodes began first-line therapy with SOX plus nivolumab. The patient completed 10 cycles; however, only nivolumab was continued for 5 cycles because of adverse events. Computed tomography showed a significant decrease in the size of the para-aortic lymph nodes, while MRI indicated the presence of a singular liver metastasis. Distal gastrectomy and partial hepatic resection were subsequently performed. In all three cases, MRI revealed the presence of liver metastases; however, pathological examination showed no viable tumor cells.

Conclusions
We herein present three cases in which chemotherapy, including nivolumab, elicited a response in patients with multiple unresectable liver metastases, ultimately culminating in R0 resection through conversion surgery. Although MRI showed liver metastases, pathological analysis revealed no cancer, underscoring the beneficial impact of chemotherapy.
Exploring the evolution of facial feminization and masculinization surgery: a bibliometric analysis and visualization study
Authors: Uranbey Omer , Kaygisiz Omer Faruk , Ayrancı Ferhat , Yanik Saim 
Published: June 2024

Abstract
Background
This study aims to conduct a bibliometric analysis of the current literature related to facial feminization surgery (FFS) and facial masculinization surgery (FMS) to understand the patterns, trends, and evolution of research topics. In addition, it aims to objectively identify the important articles that constitute the primary backbone of the FFS/FMS literature and provide a resource for education and new studies in this emerging field.

Results
Using the principles of the Leiden Manifesto, 384 publications from the Web of Science from 1987 to 2023 were analyzed. The analysis included cross-country collaboration, keyword trends, affiliations, co-citation networks, and clustering. The results showed an increasing trend in FFS/FMS publications, with the USA leading in both publications (n = 238) and citations (n = 2420). The most cited journal was the Journal of Plastic and Reconstructive Surgery. The results indicate a high growth rate, with an H-index of 34 and an average citation of 11.41 per article. Co-occurrence analysis revealed evolving keywords such as “forehead” (n = 52) and “quality of life” (n = 44). The timeline view illustrated the terms reflecting current areas of interest such as #patient satisfaction and #gender-affirming care.

Conclusion
The study reveals the influence of countries, institutions, authors, and emerging trends, supporting the anticipation that FFS/FMS will be a critical field of study in the future. The findings contribute to understanding the global landscape of FFS/FMS research, facilitating informed decision-making for researchers, and clinicians in the field of maxillofacial surgery.