bluuebunny/crossref_metadata_2025_split huggingface dataset:
ASC proneural factors are necessary for chromatin remodeling during neuroectodermal to neuroblast fate transition to ensure the timely initiation of the neural stem cell program
Authors: Theodorou Vasiliki , Stefanaki Aikaterini , Drakos Minas , Triantafyllou Dafne , Delidakis Christos 
Published: May 2022

AbstractBackgroundIn both Drosophila and mammals, the achaete-scute (ASC/ASCL) proneural bHLH transcription factors are expressed in the developing central and peripheral nervous systems, where they function during specification and maintenance of the neural stem cells in opposition to Notch signaling. In addition to their role in nervous system development, ASC transcription factors are oncogenic and exhibit chromatin reprogramming activity; however, the impact of ASC on chromatin dynamics during neural stem cell generation remains elusive. Here, we investigate the chromatin changes accompanying neural commitment using an integrative genetics and genomics methodology.ResultsWe found that ASC factors bind equally strongly to two distinct classes of cis-regulatory elements: open regions remodeled earlier during maternal to zygotic transition by Zelda and less accessible, Zelda-independent regions. Both classes of cis-elements exhibit enhanced chromatin accessibility during neural specification and correlate with transcriptional regulation of genes involved in a variety of biological processes necessary for neuroblast function/homeostasis. We identified an ASC-Notch regulated TF network that includes likely prime regulators of neuroblast function. Using a cohort of ASC target genes, we report that ASC null neuroblasts are defectively specified, remaining initially stalled, unable to divide, and lacking expression of many proneural targets. When mutant neuroblasts eventually start proliferating, they produce compromised progeny. Reporter lines driven by proneural-bound enhancers display ASC dependency, suggesting that the partial neuroblast identity seen in the absence of ASC genes is likely driven by other, proneural-independent, cis-elements. Neuroblast impairment and the late differentiation defects of ASC mutants are corrected by ectodermal induction of individual ASC genes but not by individual members of the TF network downstream of ASC. However, in wild-type embryos, the induction of individual members of this network induces CNS hyperplasia, suggesting that they synergize with the activating function of ASC to consolidate the chromatin dynamics that promote neural specification.ConclusionsWe demonstrate that ASC proneural transcription factors are indispensable for the timely initiation of the neural stem cell program at the chromatin level by regulating a large number of enhancers in the vicinity of neural genes. This early chromatin remodeling is crucial for both neuroblast homeostasis as well as future progeny fidelity.
Genome of a giant isopod, Bathynomus jamesi, provides insights into body size evolution and adaptation to deep-sea environment
Authors: Yuan Jianbo , Zhang Xiaojun , Kou Qi , Sun Yamin , Liu Chengzhang , Li Shihao , Yu Yang , Zhang Chengsong , Jin Songjun , Xiang Jianhai , Li Xinzheng , Li Fuhua 
Published: May 2022

Abstract
Background
The deep-sea may be regarded as a hostile living environment, due to low temperature, high hydrostatic pressure, and limited food and light. Isopods, a species-rich group of crustaceans, are widely distributed across different environments including the deep sea and as such are a useful model for studying adaptation, migration, and speciation. Similar to other deep-sea organisms, giant isopods have larger body size than their shallow water relatives and have large stomachs and fat bodies presumably to store organic reserves. In order to shed light on the genetic basis of these large crustaceans adapting to the oligotrophic environment of deep-sea, the high-quality genome of a deep-sea giant isopod Bathynomus jamesi was sequenced and assembled.

Results
B. jamesi has a large genome of 5.89 Gb, representing the largest sequenced crustacean genome to date. Its large genome size is mainly attributable to the remarkable proliferation of transposable elements (84%), which may enable high genome plasticity for adaptive evolution. Unlike its relatives with small body size, B. jamesi has expanded gene families related to pathways of thyroid and insulin hormone signaling that potentially contribute to its large body size. Transcriptomic analysis showed that some expanded gene families related to glycolysis and vesicular transport were specifically expressed in its digestive organs. In addition, comparative genomics and gene expression analyses in six tissues suggested that B. jamesi has inefficient lipid degradation, low basal metabolic rate, and bulk food storage, suggesting giant isopods adopt a more efficient mechanism of nutrient absorption, storage, and utilization to provide sustained energy supply for their large body size.

Conclusions
Taken together, the giant isopod genome may provide a valuable resource for understanding body size evolution and adaptation mechanisms of macrobenthic organisms to deep-sea environments.
The interaction between long non-coding RNA LINC01564 and POU2F1 promotes the proliferation and metastasis of gastric cancer
Authors: Wang Jixu , Hou Futao , Tang Lusheng , Xiao Ke , Yang Tengfei , Wang Zhiqiang , Liu Gu 
Published: May 2022

Abstract
Background
An increasing number of studies have demonstrated that long non-coding RNAs (lncRNAs) serve as key regulators in tumor development and progression. However, only a few lncRNAs have been functionally characterized in gastric cancer (GC).

Methods
Bioinformatics analysis was conducted to find lncRNAs that are associated with GC metastasis. RNA FISH, RIP, and RNA pull down assays were used to study the complementary binding of LINC01564 complementary to the 3′UTR of transcription factor POU2F1. The transcription activation of LINC01564 by POU2F1 as a transcription factor was examined by ChIP assay. In vitro assays such as MTT, cell invasion assay, and clonogenic assay were conducted to examined the impacts of LINC01564 and POU2F1 on GC cell proliferation and invasion. Experiments in vivo were performed to access the impacts of LINC01564 and POU2F1 on GC metastasis.

Results
The results showed that LINC01564 complementary bound to the 3′UTR of POU2F1 to form an RNA duplex, whereby stabilizing POU2F1 mRNA and increasing the enrichment in cells. The level of LINC01564 was also increased by POU2F1 through transcription activation. In vitro assays showed that LINC01564 promoted the proliferation, invasion and migration of GC cells through increasing POU2F1. In vivo experiments indicate the promotion of GC proliferation and metastasis by the interaction between LINC01564 and POU2F1.

Conclusion
Taken together, our results indicate that the interaction between LINC01564 and POU2F1 promotes the proliferation, migration and invasion of GC cells.
St13 protects against disordered acinar cell arachidonic acid pathway in chronic pancreatitis
Authors: Cao Rong-chang , Yang Wan-jun , Xiao Wang , Zhou Lei , Tan Jie-hui , Wang Meng , Zhou Zhi-tao , Chen Huo-ji , Xu Jia , Chen Xue-mei , Jin Yang-chen , Lin Jia-yu , Zeng Jun-ling , Li Shu-ji , Luo Min , Hu Guo-dong , Jin Jin , Yang Xiao-bing , Huo Da , Zhou Jie , Zhang Guo-wei 
Published: May 2022

Abstract
Background
Early diagnosis and treatment of chronic pancreatitis (CP) are limited. In this study, St13, a co-chaperone protein, was investigated whether it constituted a novel regulatory target in CP. Meanwhile, we evaluated the value of micro-PET/CT in the early diagnosis of CP.

Methods
Data from healthy control individuals and patients with alcoholic CP (ACP) or non-ACP (nACP) were analysed. PRSS1 transgenic mice (PRSS1Tg) were treated with ethanol or caerulein to mimic the development of ACP or nACP, respectively. Pancreatic lipid metabolite profiling was performed in human and PRSS1Tg model mice. The potential functions of St13 were investigated by crossing PRSS1Tg mice with St13−/− mice via immunoprecipitation and lipid metabolomics. Micro-PET/CT was performed to evaluate pancreatic morphology and fibrosis in CP model.

Results
The arachidonic acid (AA) pathway ranked the most commonly dysregulated lipid pathway in ACP and nACP in human and mice. Knockout of St13 exacerbated fatty replacement and fibrosis in CP model. Sdf2l1 was identified as a binding partner of St13 as it stabilizes the IRE1α-XBP1s signalling pathway, which regulates COX-2, an important component in AA metabolism. Micro-PET/CT with 68Ga-FAPI-04 was useful for evaluating pancreatic morphology and fibrosis in CP model mice 2 weeks after modelling.

Conclusion
St13 is functionally activated in acinar cells and protects against the cellular characteristics of CP by binding Sdf2l1, regulating AA pathway. 68Ga-FAPI-04 PET/CT may be a very valuable approach for the early diagnosis of CP. These findings thus provide novel insights into both diagnosis and treatment of CP.
VCP interaction with HMGB1 promotes hepatocellular carcinoma progression by activating the PI3K/AKT/mTOR pathway
Authors: Pu Zhangya , Duda Dan G. , Zhu Yuanyuan , Pei Siya , Wang Xiaofang , Huang Yan , Yi Panpan , Huang Zebing , Peng Fang , Hu Xingwang , Fan Xuegong 
Published: May 2022

Abstract
Background
Hepatocellular carcinoma (HCC) is the most common pathological type of liver cancer. Valosin-containing protein (VCP) is a member of the AAA-ATPase family associated with multiple molecular functions and involved in tumor metastasis and prognosis. However, the role of VCP in HCC progression is still unclear.

Methods
We examined the expression of VCP in HCC using the RNA sequencing and microarray data from public databases and measured it in clinical samples and cell lines by western blot, and immunohistochemistry (IHC). We also evaluated the correlation between VCP and clinical features. The VCP-interacting proteins were identified by co-immunoprecipitation combined with mass spectrometry (CoIP/MS). The underlying molecular mechanisms were investigated using in vitro and in vivo models of HCC.

Results
We found that VCP expression is significantly increased in tumor tissues and is associated with advanced TNM stages and poorer prognosis in HCC patients. In vitro analyses revealed that VCP overexpression promoted HCC cell proliferation, migration, and invasion via PI3K/AKT/mTOR pathway activation. Conversely, VCP knockdown resulted in the reverse phenotypes. In vivo studies indicated that up-regulated VCP expression accelerated tumor growth in a subcutaneous HCC model. The D1 domain of VCP and A box of HMGB1 were identified as the critical regions for their interaction, and D1 area was required for the tumor-promoting effects induced by VCP expression. VCP enhanced the protein stability of HMGB1 by decreasing its degradation via ubiquitin–proteasome process. Inhibition of HMGB1 markedly attenuated VCP-mediated HCC progression and downstream activation of PI3K/AKT/mTOR signals.

Conclusion
Collectively, these findings demonstrate that VCP is a potential prognostic biomarker in HCC and exhibits oncogenic roles via PI3K/AKT/mTOR pathway activation. HMGB1 played an essential role in VCP-mediated HCC progression, indicating that VCP and HMGB1 are potential therapeutic targets in human HCC.
5-fluorouracil treatment of patient-derived scaffolds from colorectal cancer reveal clinically critical information
Authors: Salerno Simona , Ståhlberg Anders , Holdfeldt André , Bexe Lindskog Elinor , Landberg Göran 
Published: May 2022

Abstract
Background
Colorectal cancer is a commonly diagnosed cancer worldwide. Unfortunately, many patients do not respond to standard chemotherapy treatments and develop disease relapse and metastases. Besides cancer cell specific genetic changes, heterogeneity in the tumor microenvironment contribute to the clinical presentation of the disease and can potentially also influence drug resistance. By using a recently developed patient-derived scaffold method monitoring how a standardized reporter cancer cell line adapts to various microenvironments treated with chemotherapy, we wanted to clarify how individual patient specific microenvironments influence the chemotherapy response in colorectal cancer.

Methods
Surgically resected colorectal cancer specimens from 89 patients were decellularized to produce patient-derived scaffold, which were seeded with HT29 cells, cultured for 3 weeks, and treated with 5-fluorouracil. Gene expression changes of adapted and treated HT29 cells were monitored by qPCR and compared with clinical parameters including disease-free survival.

Results
The effects of 5-fluorouracil treatment varied between different patient-derived scaffold, but generally induced a reduced expression of proliferation genes and increased expression of pluripotency and epithelial-to-mesenchymal transition genes. Interestingly, patient-derived scaffold cultures obtained from patients with disease recurrences showed a significantly less pronounced anti-proliferative effect of 5-fluorouracil and more pronounced increase of pluripotency, with MKI67 and POU5F1 being among the most significant genes linked to disease relapse in colorectal cancer.

Conclusions
Colorectal patient-derived scaffold can decode clinically relevant tumor microenvironmental influence of 5-fluorouracil treatment effects opening up for optimized precision medicine in colorectal cancer treatment.
Single-cell landscape of immunocytes in patients with extrahepatic cholangiocarcinoma
Authors: Xu Lei , Lu Yun , Deng Zhengdong , Li Xiangyu , Shi Yuanxin , Zhao Kai , Yao Wei , Wang Jianming 
Published: May 2022

Abstract
Background
The intricate landscape of immunocytes in the tumor microenvironment (TME) is fundamental to immunotherapy but notably under-researched in extrahepatic cholangiocarcinoma (ECCA).

Methods
Single-cell RNA sequencing technology was conducted to make an in-depth analysis of immunocytes from matched tumor tissues, paratumor tissues and peripheral blood from ECCA patients. The potential cellular interactions between two cell populations were analyzed with software CellPhoneDB (v2.1.7).

Results
We obtained 13526 cells and characterized the transcriptomes and heterogeneity of different clusters and subclusters of immunocytes from ECCA, including CD4+ T cells, CD8+ T cells, B cells and myeloid immunocytes. We observed the rarely described immunocyte subclusters "intermediate" exhausted CD8+ T (CD8+ Tex) cells and “nonclassic” plasmacytes (CD27+ CD138+ CD38−). In addition, we identified potential immunotherapy targets, for example, ACP5, MAGEH1, TNFRSF9 and CCR8 for Tregs and MT1 for CD8+ Tex cells. We also found strong cellular interactions among Treg cells, M2 macrophages and CD8+ Tex cells through ligand–receptor analysis, implying that potential cellular cross-linkage promoted the immunosuppressive nature of the TME.

Conclusions
In a word, our study illuminated the components of the TME and revealed potential cellular interactions at the individual cellular level in ECCA, we aimed to provide a new perspective for further immunological studies and immunotherapy of ECCA.
Observation of curative effect on meridian theory-based extracorporeal shock wave therapy for non-specific low back pain: study protocol for a randomized controlled trial
Authors: Fan Yongfu , Liu Feilai , Li Mengna , Ruan Xiaodi , Wu Mingli , Su Kaiqi , Gao Jing , Feng Xiaodong 
Published: May 2022

Abstract
Background
Non-specific low back pain (NLBP) is a major global socioeconomic burden, and the prevalence of NLBP is still on the rise. At present, there is no ideal drug to cure this disease. This may be the reason why patients often use complementary therapies. Among them, extracorporeal shock wave therapy (ESWT) has gradually received more attention and has become the main treatment method for NLBP. The purpose of this study is to provide scientific evidence for the effect and safety of meridian theory-based ESWT on NLBP.

Objective
This study aims to evaluate the effect and safety of meridian theory-based ESWT on NLBP. This study will also provide more high-quality experimental evidence for the clinical application of meridian theory-based ESWT for the treatment of NLBP in future.

Methods
The study design is a single-blind, multi-center, randomized controlled trial. 66 patients with NLBP, aged 18 to 60 years, will be randomly divided into two groups: the experimental group (N = 33), which will receive meridian theory-based ESWT application, and the control group (N = 33) which will receive conventional ESWT treatment. These two applications will be carried out twice a week for two weeks. The primary outcome will be the Visual Analog Scale (VAS), and the secondary outcomes will be Oswestry Disability Index (ODI), Surface Electromyography (sEMG), and Patient Health Questionnaire-15 (PHQ-15). All outcomes will be evaluated at baseline and after the intervention (7 days, 14 days).

Discussion
Results of this trial will contribute to providing rigorous clinical evidence for the efficacy and security of meridian theory-based ESWT for NLBP.
Trial registration: Chinese Clinical Trial Registry, ChiCTR2100051049. Registered on 10 September 2021, http://www.chictr.org.cn/showproj.aspx?proj=46316.
Effect of human follicle-stimulating hormone on immunomodulatory function of decidual mesenchymal stem cells by reducing interleukin-6 levels
Authors: He Yi-bo , Zhang Li , Zhou Lin-li , Chen Yi-min , Lu Jia-hong , Chen Jie , Liu Yong-lin 
Published: May 2022

Abstract
Objective
Women with an elevated basal FSH indicate diminished ovarian reserve and reduced oocyte and embryo numbers. DMSCs are likely to be involved in immune tolerance of pregnancy maintenance. We investigate the effect of follicle-stimulating hormones on the immunomodulatory functions of DMSCs.

Methods
DMSCs were primary cultured from decidual tissue. Pretreated DMSCs with mitomycin C, combined with CD4+ T lymphocytes, DMSCs + CD4+T co-culture system was established. Different physiological dose FSH (3 ng/ml,10 ng/ml,30 ng/ml,100 ng/ml) were used to co-culture system. Cytokines (IFN-γ, IL-2, IL-4, IL-6, IL-10, TNF-α) and other proteins (FSHR, MyD88) were measured.

Results
Compared with the control group (FSH (0 ng/mL) + CD4+T + DMSCs), the FSH concentration was 10, 30, and 100 ng/ml, IL-6 levels were significantly reduced (P < 0.05). IL-6, MyD88 protein expression was remarkably decreased (P < 0.05).

Conclusion
FSH/FSHR could negatively regulate the immunosuppressive function of DMSCs by reducing secretion of IL-6 levels through MyD88 pathways, but upstream and downstream signalling pathways require further validation.
A nationwide survey on the implementation of infection prevention and control components in 1442 hospitals in the Republic of Korea: comparison to the WHO Infection Prevention and Control Assessment Framework (IPCAF)
Authors: Jeong Yoolwon , Joo Hyeyoung , Bahk Hyunjung , Koo Hyunsuk , Lee Hyungmin , Kim Kinam 
Published: May 2022

Abstract
Background
The current SARS-CoV-2 pandemic continues to underscore the inadequacy of infection prevention and control (IPC) and the importance of its sound establishment in healthcare facilities. The Infection Prevention and Control Assessment Framework (IPCAF) by the World Health Organization allows systematic assessment of IPC capacity in healthcare facilities and has been applied in many national-level surveys. This study aims to assess the IPC capacity of Korean hospitals as well as their strengths and pitfalls by analyzing the results of the first government-led nationwide IPC survey in comparison to the IPCAF frame.

Methods
The Korean National Infection Prevention and Control Survey (KNIPCS) was conducted from February to March 2018. The survey questionnaire for KNIPCS was developed through a series of expert consultations and a round of pre-testing in two randomly selected hospitals. The survey questionnaire was distributed to a total of 2108 hospitals. Although the survey preceded the release of IPCAF, its contents complied with IPCAF to a large extent, allowing exploration of its results with regards to IPCAF.

Results
All tertiary hospitals and 96.5% of general hospitals had implemented IPC teams, whereas the percentage was lower for long-term care hospitals (6.3%). A similar trend was observed for IPC surveillance and monitoring activities across hospital types. The percentage of interactive IPC training was lower than 30% in all hospital groups. Disinfection was frequently monitored in all hospital types (e.g. 97.3% in general hospitals and 85.3% in long-term care hospitals). However, activities regarding antimicrobial resistance, such as multi-drug resistant pathogen screening, were weak in hospitals (25%) and long-term care hospitals (25%), compared to tertiary hospitals (83.3%) and general hospitals (57.7%).

Conclusions
In general, essential IPC structures, such as IPC teams and programs, were well in place in most tertiary and general hospitals in Korea. These hospital groups also actively conducted various IPC activities. As most previous legislative and multimodal policy measures have targeted these hospital groups, we speculate that future policy efforts should encompass long-term care hospitals and smaller-sized hospitals to strengthen the IPC capacity of these hospital groups. Efforts should also be put forth to promote IPC training and antimicrobial activities.
Immunogenicity and safety of heterologous versus homologous prime-boost schedules with an adenoviral vectored and mRNA COVID-19 vaccine: a systematic review
Authors: Lv Jingjing , Wu Hui , Xu Junjie , Liu Jiaye 
Published: May 2022

Abstract
Background
Heterologous prime-boost with ChAdOx1 nCoV-19 vector vaccine (ChAd) and a messenger RNA vaccine (BNT or mRNA-1273) has been widely facilitating mass coronavirus disease 2019 (COVID-19) immunisation. This review aimed to synthesize immunogenicity and reactogenicity of heterologous immunisations with ChAd and BNT (mRNA-1273) vaccine compared with homologous ChAd or BNT (mRNA-1273) immunisation.

Methods
PubMed, Web of Science, and Embase databases were searched from inception to March 7, 2022. Immunogenicity involving serum antibodies against different SAS-CoV-2 fragments, neutralizing antibody, or spike-specific T cells response were compared. Any, local and systemic reactions were pooled by meta-analysis for comparison.

Results
Of 14,571 records identified, 13 studies (3024 participants) were included for analysis. Compared with homologous BNT/BNT vaccination, heterologous ChAd/BNT schedule probably induced noninferior anti-spike protein while higher neutralizing antibody and better T cells response. Heterologous ChAd/BNT (mRNA-1273) immunisation induced superior anti-spike protein and higher neutralizing antibody and better T cells response compared with homologous ChAd/ChAd vaccination. Heterologous ChAd/BNT (mRNA-1273) had similar risk of any reaction (RR = 1.30, 95% CI: 0.86−1.96) while higher risk of local reactions (RR = 1.65, 95% CI: 1.27−2.15) and systemic reactions (RR = 1.49, 95% CI: 1.17−1.90) compared with homologous ChAd/ChAd vaccination. There was a higher risk of local reactions (RR = 1.16, 95% CI: 1.03−1.31) in heterologous ChAd/BNT (mRNA-1273) vaccination compare with homologous BNT/BNT but a similar risk of any reaction (RR = 1.03, 95% CI: 0.79−1.34) and systemic reactions (RR = 0.89, 95% CI: 0.60−1.30).

Conclusions
Heterologous ChAd/BNT schedule induced at least comparable immunogenicity compared with homologous BNT/BNT and better immunogenicity compared with homologous ChAd/ChAd vaccination. The synthetical evidence supported the general application of heterologous prime-boost vaccination using ChAd and BNT COVID-19 vaccines.

Graphical Abstract