bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intricate crosstalk between MYB and noncoding RNAs in cancer
Authors: Hu Dingyu , Shao Wenjun , Liu Li , Wang Yanyan , Yuan Shunling , Liu Zhaoping , Liu Jing , Zhang Ji 
Published: December 2021

AbstractMYB is often overexpressed in malignant tumors and plays a carcinogenic role in the initiation and development of cancer. Deletion of the MYB regulatory C-terminal domain may be a driving mutation leading to tumorigenesis, therefore, different tumor mechanisms produce similar MYB proteins. As MYB is a transcription factor, priority has been given to identifying the genes that it regulates. All previous attention has been focused on protein-coding genes. However, an increasing number of studies have suggested that MYB can affect the complexity of cancer progression by regulating tumor-associated noncoding RNAs (ncRNAs), such as microRNAs, long-non-coding RNAs and circular RNAs. ncRNAs can regulate the expression of numerous downstream genes at the transcription, RNA processing and translation levels, thereby having various biological functions. Additionally, ncRNAs play important roles in regulating MYB expression. This review focuses on the intricate crosstalk between oncogenic MYB and ncRNAs, which play a pivotal role in tumorigenesis, including proliferation, apoptosis, angiogenesis, metastasis, senescence and drug resistance. In addition, we discuss therapeutic strategies for crosstalk between MYB and ncRNAs to prevent the occurrence and development of cancer.
Attenuated expression of SNF5 facilitates progression of bladder cancer via STAT3 activation
Authors: Ding Hua , Huang Yaqin , Shi Jiazhong , Wang Liwei , Liu Sha , Zhao Baixiong , Liu Yuting , Yang Jin , Chen Zhiwen 
Published: December 2021

Abstract
Background
SWI/SNF, a well-known ATP-dependent chromatin-remodeling complex, plays an essential role in several biological processes. SNF5, the core subunit of the SWI/SNF remodeling complex, inactivated in 95% of malignant rhabdoid tumors (MRT), highlighting its significance in tumorigenesis. However, the role of SNF5 in bladder cancer (BC) remains unknown. In this study, we aimed to investigate the function and potential clinical applicability of SNF5 in BC.

Methods
Data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and Cancer Cell Line Encyclopedia (CCLE) databases were used to evaluate the clinical significance of SNF5 in BC. We performed Gene Set Enrichment Analysis (GSEA) and functional assays to investigate the role of SNF5 in BC. Genomics of Drug Sensitivity in Cancer (GDSC) and drug-susceptibility tests were performed to identify the potential value of SNF5 in the treatment of BC.

Results
Low SNF5 expression conferred a poor prognosis and was significantly associated with the N-stage in BC. ROC curves indicated that SNF5 could distinguish BC from the normal tissues. In vitro and in vivo functional assays demonstrated that attenuated SNF5 expression could promote cell proliferation and enhance migration by STAT3 activation. We imputed that low SNF5 expression could confer greater resistance against conventional first-line drugs, including cisplatin and gemcitabine in BC. GDSC and drug-resistance assays suggested that low SNF5 expression renders T24 and 5637 cells high sensitivity to EGFR inhibitor gefitinib, and combination of EZH2 inhibitor GSK126 and cisplatin.

Conclusions
To the best of our knowledge, the present study, for the first time, showed that low SNF5 expression could promote cell proliferation and migration by activating STAT3 and confer poor prognosis in BC. Importantly, SNF5 expression may be a promising candidate for identifying BC patients who could benefit from EGFR-targeted chemotherapy or cisplatin in combination with EZH2 inhibitor treatment regimens.
Salvianolic acid B targets mortalin and inhibits the migration and invasion of hepatocellular carcinoma via the RECK/STAT3 pathway
Authors: Teng Mengying , Hu Chunyan , Yang Bingmo , Xiao Wei , Zhou Qian , Li Yuan , Li Zhong 
Published: December 2021

Abstract
Background
Tumor migration and invasion is a complex and diverse process that involves the epithelial–mesenchymal transition (EMT) of tumor cells and degradation of the extracellular matrix by matrix metalloproteases (MMPs). Mortalin is an important oncogene. It has been reported to play an important role in tumor migration and invasion through various signaling pathways, but the underlying mechanism is not fully understood.

Methods
Here, we investigated the role of mortalin in the migration of the hepatocellular carcinoma (HCC) cell lines HepG2 and HCCLM3.

Results
The overexpression of mortalin in HepG2 cells decreased the protein level of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) and activated the phosphorylation and acetylation of STAT3, thereby up-regulating matrix metalloproteinase 9 (MMP9) and promoting cell migration and invasion. In contrast, in HCCLM3 cells, mortalin knockdown increased the expression of RECK, inhibited the STAT3 pathway and the activity of MMP9, and inhibited cell migration and invasion. Furthermore, we found that salvianolic acid B, a caffeic acid phenethyl ester analog, specifically bound to mortalin and increased the degradation of mortalin proteasomes through ubiquitination, thereby up-regulating RECK, inhibiting STAT3, and finally inhibiting the migration and invasion of HCC cells.

Conclusion
Our work suggested that mortalin is a potential therapeutic target for hepatocellular carcinoma.
The molecular mechanisms of fluoroquinolone resistance found in rectal swab isolates of Enterobacterales from men undergoing a transrectal prostate biopsy: the rationale for targeted prophylaxis
Authors: Piekarska Katarzyna , Zacharczuk Katarzyna , Wołkowicz Tomasz , Mokrzyś Mateusz , Wolaniuk Natalia , Nowakowska Magdalena , Szempliński Stanisław , Dobruch Jakub , Gierczyński Rafał 
Published: December 2021

Abstract
Background
Transrectal ultrasound-guided prostate biopsy (TRUS-Bx) is considered an essential urological procedure for the histological diagnosis of prostate cancer. It is, however, considered a “contaminated” procedure which may lead to infectious complications. Recent studies suggest a significant share of fluoroquinolone-resistant rectal flora in post-biopsy infections.

Methods
The molecular mechanisms of fluoroquinolone resistance, including PMQR (plasmid-mediated quinolone resistance) as well as mutation in the QRDRs (quinolone-resistance determining regions) of gyrA, gyrB, parC and parE, among Enterobacterales isolated from 32 of 48 men undergoing a prostate biopsy between November 2015 and April 2016 were investigated. Before the TRUS-Bx procedure, all the patients received an oral antibiotic containing fluoroquinolones.

Results
In total, 41 Enterobacterales isolates were obtained from rectal swabs. The MIC of ciprofloxacin and the presence of common PMQR determinants were investigated in all the isolates. Nine (21.9%) isolates carried PMQR with qnrS as the only PMQR agent detected. DNA sequencing of the QRDRs in 18 Enterobacterales (E. coli n = 17 and E. cloacae n = 1) isolates with ciprofloxacin MIC ≥ 0.25 mg/l were performed. Substitutions in the following codons were found: GyrA—83 [Ser → Leu, Phe] and 87 [Asp → Asn]; GyrB codon—605 [Met → Leu], ParC codons—80 [Ser → Ile, Arg] and 84 [Glu → Gly, Met, Val, Lys], ParE codons—458 [Ser → Ala], 461 [Glu → Ala] and 512 [Ala → Thr]. Six isolates with ciprofloxacin MIC ≥ 2 mg/l had at least one mutation in GyrA together with qnrS.

Conclusions
This study provides information on the common presence of PMQRs among Enterobacterales isolates with ciprofloxacin MIC ≥ 0.25 mg/l, obtained from men undergoing TRUS-Bx. This fact may partially explain why some men develop post-TRUS-Bx infections despite ciprofloxacin prophylaxis.
Optimization of metabolism to improve efficacy during CAR-T cell manufacturing
Authors: Zhang Meng , Jin Xin , Sun Rui , Xiong Xia , Wang Jiaxi , Xie Danni , Zhao MingFeng 
Published: December 2021

AbstractChimeric antigen receptor T cell (CAR-T cell) therapy is a relatively new, effective, and rapidly evolving therapeutic for adoptive immunotherapies. Although it has achieved remarkable effect in hematological malignancies, there are some problems that remain to be resolved. For example, there are high recurrence rates and poor efficacy in solid tumors. In this review, we first briefly describe the metabolic re-editing of T cells and the changes in metabolism during the preparation of CAR-T cells. Furthermore, we summarize the latest developments and newest strategies to improve the metabolic adaptability and antitumor activity of CAR-T cells in vitro and in vivo.
Multi-omics approach to COVID-19: a domain-based literature review
Authors: Montaldo Chiara , Messina Francesco , Abbate Isabella , Antonioli Manuela , Bordoni Veronica , Aiello Alessandra , Ciccosanti Fabiola , Colavita Francesca , Farroni Chiara , Najafi Fard Saeid , Giombini Emanuela , Goletti Delia , Matusali Giulia , Rozera Gabriella , Rueca Martina , Sacchi Alessandra , Piacentini Mauro , Agrati Chiara , Fimia Gian Maria , Capobianchi Maria Rosaria , Lauria Francesco Nicola , Ippolito Giuseppe 
Published: December 2021

Abstract
Background
Omics data, driven by rapid advances in laboratory techniques, have been generated very quickly during the COVID-19 pandemic. Our aim is to use omics data to highlight the involvement of specific pathways, as well as that of cell types and organs, in the pathophysiology of COVID-19, and to highlight their links with clinical phenotypes of SARS-CoV-2 infection.

Methods
The analysis was based on the domain model, where for domain it is intended a conceptual repository, useful to summarize multiple biological pathways involved at different levels. The relevant domains considered in the analysis were: virus, pathways and phenotypes. An interdisciplinary expert working group was defined for each domain, to carry out an independent literature scoping review.

Results
The analysis revealed that dysregulated pathways of innate immune responses, (i.e., complement activation, inflammatory responses, neutrophil activation and degranulation, platelet degranulation) can affect COVID-19 progression and outcomes. These results are consistent with several clinical studies.

Conclusions
Multi-omics approach may help to further investigate unknown aspects of the disease. However, the disease mechanisms are too complex to be explained by a single molecular signature and it is necessary to consider an integrated approach to identify hallmarks of severity.
Nationwide epidemiological characteristics of chronic fatigue syndrome in South Korea
Authors: Lim Eun-Jin , Lee Jin-Seok , Lee Eun-Jung , Jeong Seok-Ju , Park Ho-Young , Ahn Yo-Chan , Son Chang-Gue 
Published: December 2021

Abstract
Background
Chronic fatigue syndrome (CFS) is a long-term disabling illness accompanied by medically unexplained fatigue. This study aimed to explore the epidemiological characteristics of CFS in South Korea.

Methods
Using the nationwide medical records provided by the Korean Health Insurance Review & Assessment Service (HIRA), we analyzed the entire dataset for CFS patients diagnosed by physicians in South Korea from January 2010 to December 2020.

Results
The annual mean incidence of CFS was estimated to be 44.71 ± 6.10 cases per 100,000 individuals [95% CI: 40.57, 48.76], and the prevalence rate was 57.70 ± 12.20 cases per 100,000 individuals [95% CI: 49.40, 65.79]. These two rates increased by 1.53- and 1.94-fold from 2010 to 2020, respectively, and showed an increasing trend with aging and an approximately 1.5-fold female predominance.

Conclusions
This study is the first to report the nationwide epidemiological features of CFS, which reflects the clinical reality of CFS diagnosis and care in South Korea. This study will be a valuable reference for studies of CFS in the future.
Neurogenesis-dependent antidepressant-like activity of Hericium erinaceus in an animal model of depression
Authors: Chong Pit Shan , Poon Chi Him , Roy Jaydeep , Tsui Ka Chun , Lew Sze Yuen , Phang Michael Weng Lok , Tan Rachael Julia Yuenyinn , Cheng Poh Guat , Fung Man-Lung , Wong Kah Hui , Lim Lee Wei 
Published: December 2021

AbstractBackgroundDepression is a severe neuropsychiatric disorder that affects more than 264 million people worldwide. The efficacy of conventional antidepressants are barely adequate and many have side effects.Hericium erinaceus(HE) is a medicinal mushroom that has been reported to have therapeutic potential for treating depression.MethodsAnimals subjected to chronic restraint stress were given 4 weeks HE treatment. Animals were then screened for anxiety and depressive-like behaviours. Gene and protein assays, as well as histological analysis were performed to probe the role of neurogenesis in mediating the therapeutic effect of HE. Temozolomide was administered to validate the neurogenesis-dependent mechanism of HE.ResultsThe results showed that 4 weeks of HE treatment ameliorated depressive-like behaviours in mice subjected to 14 days of restraint stress. Further molecular assays demonstrated the 4-week HE treatment elevated the expression of several neurogenesis-related genes and proteins, including doublecortin, nestin, synaptophysin, brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), phosphorylated extracellular signal-regulated kinase, and phosphorylated cAMP response element-binding protein (pCREB). Increased bromodeoxyuridine-positive cells were also observed in the dentate gyrus of the hippocampus, indicating enhanced neurogenesis. Neurogenesis blocker temozolomide completely abolished the antidepressant-like effects of HE, confirming a neurogenesis-dependent mechanism. Moreover, HE induced anti-neuroinflammatory effects through reducing astrocyte activation in the hippocampus, which was also abolished with temozolomide administration.ConclusionHE exerts antidepressant effects by promoting neurogenesis and reducing neuroinflammation through enhancing the BDNF-TrkB-CREB signalling pathway.
Traditional chinese medicine syndromes classification associates with tumor cell and microenvironment heterogeneity in colorectal cancer: a single cell RNA sequencing analysis
Authors: Lu Yiyu , Zhou Chungen , Zhu Meidong , Fu Zhiliang , Shi Yong , Li Min , Wang Wenhai , Zhu Shibo , Jiang Bin , Luo Yunquan , Su Shibing 
Published: December 2021

Abstract
Background
Colorectal cancer (CRC) is one of the common gastrointestinal malignancies, tumor heterogeneity is the main cause of refractory CRC. Syndrome differentiation is the premise of individualized treatment of traditional Chinese medicine (TCM), but TCM syndrome lacks objective identification in CRC. This study is to investigate the correlation and significance of tumor heterogeneity and TCM syndromes classification in CRC.

Methods
In this study, we using scRNA-seq technology, investigate the significance of tumor heterogeneity in TCM syndromes classification on CRC.

Results
The results showed that 662 cells isolated from 11 primary CRC tumors are divided into 14 different cell clusters, and each cell subtype and its genes have different functions and signal transduction pathways, indicating significant heterogeneity. CRC tumor cell clusters have different proportions in Excess, Deficiency and Deficiency-Excess syndromes, and have their own characteristic genes, gene co-expression networks, gene functional interpretations as well as monocle functional evolution. Moreover, there were significant differences between the high expressions of MUC2, REG4, COL1A2, POSTN, SDPR, GPX1, ELF3, KRT8, KRT18, KRT19, FN1, SERPINE1, TCF4 and ZEB1 genes in Excess and Deficiency syndrome classification in CRC (P < 0.01).

Conclusions
The Excess and Deficiency syndromes classification may be related to tumor heterogeneity and its microenvironment in CRC.
Abolished ketamine effects on the spontaneous excitatory postsynaptic current of medial prefrontal cortex neurons in GluN2D knockout mice
Authors: Han Dae Hee , Hong Ilgang , Choi Ja Eun , Park Pojeong , Baek Jun-Yeong , Park HyoJin , Ide Soichiro , Mishina Masayoshi , Ikeda Kazutaka , Kaang Bong-Kiun 
Published: December 2021

AbstractKetamine, a non-competitive antagonist of the N-methyl-d-aspartate receptor (NMDAR), generates a rapidly-acting antidepressant effect. It exerts psychomimetic effects, yet demands a further investigation of its mechanism. Previous research showed that ketamine did no longer promote hyperlocomotion in GluN2D knockout (KO) mice, which is a subunit of NMDAR. In the present study, we tested whether GluN2D-containing NMDARs participate in the physiological changes in the medial prefrontal cortex (mPFC) triggered by ketamine. Sub-anesthetic dose of ketamine (25 mg/kg) elevated the frequency of spontaneous excitatory postsynaptic currents (sEPSC) in wild-type (WT) mice, but not in GluN2D KO mice, 1 h after the injection. The amplitude of sEPSC and paired-pulse ratio (PPR) were unaltered by ketamine in both WT and GluN2D KO mice. These findings suggest that GluN2D-containing NMDARs might play a role in the ketamine-mediated changes in glutamatergic neurons in mPFC and, presumably, in ketamine-induced hyperlocomotion.
Footwear comfort: a systematic search and narrative synthesis of the literature
Authors: Menz Hylton B. , Bonanno Daniel R. 
Published: December 2021

AbstractObjectiveTo provide a narrative synthesis of the research literature pertaining to footwear comfort, including definitions, measurement scales, footwear design features, and physiological and psychological factors.MethodsA systematic search was conducted which yielded 101 manuscripts. The most relevant manuscripts were selected based on the predetermined subheadings of the review (definitions, measurement scales, footwear design features, and physiological and psychological factors). A narrative synthesis of the findings of the included studies was undertaken.ResultsThe available evidence is highly fragmented and incorporates a wide range of study designs, participants, and assessment approaches, making it challenging to draw strong conclusions or implications for clinical practice. However, it can be broadly concluded that (i) simple visual analog scales may provide a reliable overall assessment of comfort, (ii) well‐fitted, lightweight shoes with soft midsoles and curved rocker‐soles are generally perceived to be most comfortable, and (iii) the influence of sole flexibility, shoe microclimate and insoles is less clear and likely to be more specific to the population, setting and task being performed.ConclusionFootwear comfort is a complex and multifaceted concept that is influenced not only by structural and functional aspects of shoe design, but also task requirements and anatomical and physiological differences between individuals. Further research is required to delineate the contribution of specific shoe features more clearly, and to better understand the interaction between footwear features and individual physiological attributes.
Helicopter emergency medical service for time critical interfacility transfers of patients with cardiovascular emergencies
Authors: Meuli Lorenz , Zimmermann Alexander , Menges Anna-Leonie , Tissi Mario , Becker Stefan , Albrecht Roland , Pietsch Urs 
Published: December 2021

Abstract
Background
The goal of improving quality through centralisation of specialised medical services must be balanced against potential harm caused by delayed access to emergency treatments in rural areas. This study aims to assess the duration of transfers of critically ill patients with cardiovascular emergencies from smaller hospitals to major medical centres by a helicopter emergency medical service (HEMS) in Switzerland.

Methods
This retrospective observational cohort study includes all consecutive emergency interfacility transfers (IFTs) conducted by Switzerland’s largest HEMS provider between July 3rd, 2019, and March 31st, 2021. All patients with acute myocardial infarction, non-traumatic strokes, ruptured aortic aneurysms, and other acute vascular emergencies were included. The duration and distance of each HEMS IFT were compared to calculated distances and duration of travel for the same missions using ground-based transportation (GEMS). The ground-based mission distance beyond which the total mission duration of HEMS is expected to be faster than GEMS was calculated.

Findings
A total of 645 patients were transferred for stroke (n = 364), myocardial infarction (n = 252) and other acute vascular emergencies (n = 29). The median total mission duration from emergency call to landing at the destination was 59.9 (IQR 51.5 to 70.5) minutes. The median road distance for the same missions was 60 (IQR 43 to 72) km. Regression analysis revealed that HEMS is expected to be faster if the road distance is more than 51.3 km.

Interpretation
Centralisation of specialised medical services should be accompanied by a comprehensive and specialised rescue chain. HEMS in Switzerland ensures time-sensitive IFT in medical emergencies, even in topographically challenging terrain.

Graphical Abstract
Dispatch accuracy of physician-staffed emergency medical services in trauma care in south-east Norway: a retrospective observational study
Authors: Samdal Martin , Thorsen Kjetil , Græsli Ola , Sandberg Mårten , Rehn Marius 
Published: December 2021

Abstract
Background
Selection of incidents and accurate identification of patients that require assistance from physician-staffed emergency medical services (P-EMS) remain essential. We aimed to evaluate P-EMS availability, the underlying criteria for dispatch, and the corresponding dispatch accuracy of trauma care in south-east Norway in 2015, to identify areas for improvement.

Methods
Pre-hospital data from emergency medical coordination centres and P-EMS medical databases were linked with data from the Norwegian Trauma Registry (NTR). Based on a set of conditions (injury severity, interventions performed, level of consciousness, incident category), trauma incidents were defined as complex, warranting P-EMS assistance, or non-complex. Incident complexity and P-EMS involvement were the main determinants when assessing the triage accuracy. Undertriage was adjusted for P-EMS availability and response and transport times.

Results
Among 19,028 trauma incidents, P-EMS were involved in 2506 (13.2%). The range of overtriage was 74–80% and the range of undertriage was 20–32%. P-EMS readiness in the event of complex incidents ranged from 58 to 70%. The most frequent dispatch criterion was “Police/fire brigade request immediate response” recorded in 4321 (22.7%) of the incidents. Criteria from the groups “Accidents” and “Road traffic accidents” were recorded in 10,875 (57.2%) incidents, and criteria from the groups “Transport reservations” and “Unidentified problem” in 6025 (31,7%) incidents. Among 4916 patient pathways in the NTR, 681 (13.9%) could not be matched with pre-hospital data records.

Conclusions
Both P-EMS availability and dispatch accuracy remain suboptimal in trauma care in south-east Norway. Dispatch criteria are too vague to facilitate accurate P-EMS dispatch, and pre-hospital data is inconsistent and insufficient to provide basic data for scientific research. Future dispatch criteria should focus on the care aspect of P-EMS. Better tools for both dispatch and incident handling for the emergency medical coordination centres are essential. In general, coordination, standardisation, and integration of existing data systems should enhance the quality of trauma care and increase patient safety.