bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circular RNA CRIM1 functions as a ceRNA to promote nasopharyngeal carcinoma metastasis and docetaxel chemoresistance through upregulating FOXQ1
Authors: Hong Xiaohong , Liu Na , Liang Yelin , He Qingmei , Yang Xiaojing , Lei Yuan , Zhang Panpan , Zhao Yin , He Shiwei , Wang Yaqin , Li Junyan , Li Qian , Ma Jun , Li Yingqin 
Published: February 2020

Abstract
Background
Circular RNAs (circRNAs), a new type of noncoding RNA (ncRNA), have been identified as significant gene expression regulators and are involved in cancer progression. However, the roles of circRNAs in nasopharyngeal carcinoma (NPC) remain largely unknown.

Methods
Here, the expression profile of circRNAs in a pair of NPC cell lines with different metastatic abilities (S18 and S26 cells) was analyzed by RNA-sequencing. Quantitative reverse transcription PCR was used to detect the expression level of circCRIM1 in NPC cells and tissues. Then, function experiments in vitro and in vivo were performed to evaluate the effects of circCRIM1 on NPC metastasis and EMT. Mechanistically, RNA immunoprecipitation, luciferase reporter assay, pull-down assay with biotinylated miRNA, fluorescent in situ hybridization were performed to confirm the interaction between circCRIM1 and miR-422a in NPC. The clinical value of circCRIM1 was evaluated in NPC metastasis and chemosensitivity.

Results
We identified that circCRIM1 was upregulated in highly metastatic NPC cells. CircCRIM1 was also overexpressed in NPC tissues with distant metastasis, and its overexpression promoted NPC cell metastasis and EMT. Mechanistically, circCRIM1 competitively bound to miR-422a and prevented the suppressive effects of miR-422a on its target gene FOXQ1, which finally led to NPC metastasis, EMT and docetaxel chemoresistance. Furthermore, high circCRIM1 expression was associated with unfavorable survival in NPC patients. We established a prognostic model based on circCRIM1 expression and N stage that effectively predicted the risk of distant metastasis and treatment response to docetaxel-containing induction chemotherapy in NPC patients.

Conclusions
Our findings reveal the critical role of circCRIM1 specifically in promoting NPC metastasis and chemoresistance via a ceRNA mechanism and provide an exploitable biomarker and therapeutic target for prognosis and treatment resistance in NPC patients.
Current advances and outlooks in immunotherapy for pancreatic ductal adenocarcinoma
Authors: Fan Jia-qiao , Wang Meng-Fei , Chen Hai-Long , Shang Dong , Das Jugal K. , Song Jianxun 
Published: February 2020

AbstractPancreatic ductal adenocarcinoma (PDAC) is an incurable cancer resistant to traditional treatments, although a limited number of early-stage patients can undergo radical resection. Immunotherapies for the treatment of haematological malignancies as well as solid tumours have been substantially improved over the past decades, and impressive results have been obtained in recent preclinical and clinical trials. However, PDAC is likely the exception because of its unique tumour microenvironment (TME). In this review, we summarize the characteristics of the PDAC TME and focus on the network of various tumour-infiltrating immune cells, outlining the current advances in PDAC immunotherapy and addressing the effect of the PDAC TME on immunotherapy. This review further explores the combinations of different therapies used to enhance antitumour efficacy or reverse immunodeficiencies and describes optimizable immunotherapeutic strategies for PDAC. The concordant combination of various treatments, such as targeting cancer cells and the stroma, reversing suppressive immune reactions and enhancing antitumour reactivity, may be the most promising approach for the treatment of PDAC. Traditional treatments, especially chemotherapy, may also be optimized for individual patients to remodel the immunosuppressive microenvironment for enhanced therapy.
Translation and functional roles of circular RNAs in human cancer
Authors: Lei Ming , Zheng Guantao , Ning Qianqian , Zheng Junnian , Dong Dong 
Published: February 2020

AbstractCircular RNAs (circRNAs) are a new class of non-coding RNAs formed by covalently closed loops through backsplicing. Recent methodologies have enabled in-depth characterization of circRNAs for identification and potential functions. CircRNAs play important roles in various biological functions as microRNA sponges, transcriptional regulators and combining with RNA binding proteins. Recent studies indicated that some cytoplasmic circRNAs can be effectively translated into detectable peptides, which enlightened us on the importance of circRNAs in cellular physiology function. Internal Ribosome Entry site (IRES)- and N6-methyladenosines (m6A)-mediated cap-independent translation initiation have been suggested to be potential mechanism for circRNA translation. To date, several translated circRNAs have been uncovered to play pivotal roles in human cancers. In this review, we introduced the properties and functions of circRNAs, and characterized the possible mechanism of translation initiation and complexity of the translation ability of circRNAs. We summarized the emerging functions of circRNA-encoded proteins in human cancer. The works on circRNA translation will open a hidden human proteome, and enhance us to understand the importance of circRNAs in human cancer, which has been poorly explored so far.
microRNAs Orchestrate Pathophysiology of Breast Cancer Brain Metastasis: Advances in Therapy
Authors: Kanchan Ranjana K. , Siddiqui Jawed A. , Mahapatra Sidharth , Batra Surinder K. , Nasser Mohd W. 
Published: February 2020

AbstractBrain metastasis (BM) predominantly occurs in triple-negative (TN) and epidermal growth factor 2 (HER2)-positive breast cancer (BC) patients, and currently, there is an unmet need for the treatment of these patients. BM is a complex process that is regulated by the formation of a metastatic niche. A better understanding of the brain metastatic processes and the crosstalk between cancer cells and brain microenvironment is essential for designing a novel therapeutic approach. In this context, the aberrant expression of miRNA has been shown to be associated with BM. These non-coding RNAs/miRNAs regulate metastasis through modulating the formation of a metastatic niche and metabolic reprogramming via regulation of their target genes. However, the role of miRNA in breast cancer brain metastasis (BCBM) is poorly explored. Thus, identification and understanding of miRNAs in the pathobiology of BCBM may identify a novel candidate miRNA for the early diagnosis and prevention of this devastating process. In this review, we focus on understanding the role of candidate miRNAs in the regulation of BC brain metastatic processes as well as designing novel miRNA-based therapeutic strategies for BCBM.
Global peak left atrial longitudinal strain assessed by transthoracic echocardiography is a good predictor of left atrial appendage thrombus in patients in sinus rhythm with heart failure and very low ejection fraction – an observational study
Authors: Kurzawski Jacek , Janion-Sadowska Agnieszka , Zandecki Lukasz , Piatek Lukasz , Koziel Dorota , Sadowski Marcin 
Published: February 2020

Abstract
Background
Peak left atrial longitudinal strain (PALS) can help identify left atrial appendage thrombus (LAAT) in patients with atrial fibrillation. Nevertheless, few studies have been performed in patients in sinus rhythm without established indications for anticoagulation but with increased risk of LAAT, such as heart failure (HF) with severe left ventricular systolic dysfunction patients. The primary aim of this study was to identify clinical and transthoracic echocardiography predictors of LAAT in HF patients with very low left ventricular ejection fraction and sinus rhythm. The secondary objective was to analyze frequencies and predictors of a composite clinical endpoint of death or hospitalization for ischemic stroke.

Methods
We included 63 patients with HF, left ventricular ejection fraction < 25%, sinus rhythm at presentation, no history of atrial fibrillation, and without any established indications for anticoagulation. We determined whether clinical and transthoracic echocardiography parameters, including left atrial strain analysis, predicted LAAT. Transesophageal echocardiography was performed in all patients. When LAAT was detected, anticoagulation was recommended. The participants were followed for a median of 28.6 months (range 4–40) to determine the composite endpoint.

Results
LAAT was found in 20 (31.7%) patients. Global PALS was the best independent predictor of LAAT in univariate and multivariate logistic regression analyses (Gini coefficient 0.65, area under the receiver-operating characteristic curve 0.83). A global PALS value below 8% was a good discriminator of LAAT presence (odds ratio 30.4, 95% CI 7.2–128, p <  0.001). During follow-up, 18 subjects (28.6%) reached the composite clinical endpoint. CHA2DS2-VASc score, use of angiotensin-converting-enzyme inhibitors or angiotensin receptor blockers, and body surface area were significant predictors for the composite endpoint of death or hospitalization for ischemic stroke in the multivariate regression model.

Conclusions
LAAT was relatively common in our group of HF patients and PALS has shown prognostic potential in LAAT identification. Further research is needed to determine whether initiation of anticoagulation or additional screening supported by PALS measurements will improve clinical outcomes in these patients.
Clemastine improves hypomyelination in rats with hypoxic–ischemic brain injury by reducing microglia-derived IL-1β via P38 signaling pathway
Authors: Xie Di , Ge Xiaoli , Ma Yanli , Tang Jialong , Wang Yang , Zhu Yajie , Gao Chengjin , Pan Shuming 
Published: February 2020

Abstract
Background
Microglia activation is associated with the development of hypoxic–ischemic brain injury (HIBI). Neuroinflammation suppression might be a suitable therapeutic target in hypoxic oligodendrocyte injury. This study aims to determine whether clemastine can improve hypomyelination by suppressing the activated microglia and promoting the maturation of oligodendrocyte progenitor cells (OPCs) in HIBI.

Methods
A bilateral common carotid artery occlusion (BCCAO) rat model that received continuous intraperitoneal injection (1 mg/kg) for 14 days was employed to elaborate the neuroprotection effects of clemastine. Interleukin-1β (IL-1β), nod-like receptor protein 3 (NLRP3), histamine H1 receptor, and OPC differentiation levels in the corpus callosum were measured. Primary cultured OPCs and co-culture of microglia and OPCs were used to explore the link between microglia activation and hypomyelination. Data were evaluated by one-way ANOVA with Fisher’s protected least significant difference test.

Results
Clemastine treatment could reverse hypomyelination and restrain the upregulation of IL-1β and NLRP3 in the corpus callosum of BCCAO rats. Primary cultured OPCs treated with IL-1β showed failed maturation. However, clemastine could also reverse the OPC maturation arrest by activating the extracellular signal-regulated kinase (ERK) signaling pathway. Co-culture of microglia and OPCs with oxygen glucose deprivation treatment exhibited IL-1β and NLRP3 upregulation. Clemastine could downregulate NLRP3 and IL-1β and reverse hypomyelination by inhibiting the p38 signaling pathway.

Conclusions
Clemastine could restrain microglia activation, improve axonal hypomyelination in BCCAO rats, and thus might be a viable strategy to inhibit hypomyelination in the corpus callosum of patients with HIBI.
Effects of inflammation on the kynurenine pathway in schizophrenia — a systematic review
Authors: Pedraz-Petrozzi Bruno , Elyamany Osama , Rummel Christoph , Mulert Christoph 
Published: February 2020

AbstractBackgroundIn the last decade, there has been growing evidence that an interaction exists between inflammation and the kynurenine pathway in schizophrenia. Additionally, many authors found microglial activation in cases of schizophrenia due to inflammatory mechanisms related mostly to an increase of pro-inflammatory cytokines. In order to gain new insights into the pathophysiology of schizophrenia, it is important to incorporate the latest published evidence concerning inflammatory mechanisms and kynurenine metabolism. This systematic review aims to collect reliable recent findings within the last decade supporting such a theory.MethodsA structured search of electronic databases was conducted for publications between 2008 and 2018 to identify eligible studies investigating patients with schizophrenia/psychosis and the relationship between inflammation and kynurenine pathway. Applicable studies were systematically scored using the NIH Quality Assessment Tools. Two researchers independently extracted data on diagnosis (psychosis/schizophrenia), inflammation, and kynurenine/tryptophan metabolites.ResultsTen eligible articles were identified where seven studies assessed blood samples and three assessed cerebrospinal fluid in schizophrenic patients.Of these articles:Four investigated the relationship between immunoglobulins and the kynurenine pathway and found correlations between IgA-mediated responses and levels of tryptophan metabolites (i.e., kynurenine pathway).Five examined the correlation between cytokines and kynurenine metabolites where three showed a relationship between elevated IL-6, TNF-α concentrations, and the kynurenine pathway.Only one study discovered correlations between IL-8 and the kynurenine pathway.Two studies showed correlations with lower concentrations of IL-4 and the kynurenine pathway.Moreover, this systematic review did not find a significant correlation between CRP (n = 1 study), IFN-γ (n = 3 studies), and the kynurenine pathway in schizophrenia.InterpretationThese results emphasize how different inflammatory markers can unbalance the tryptophan/kynurenine pathway in schizophrenia. Several tryptophan/kynurenine pathway metabolites are produced which can, in turn, underlie different psychotic and cognitive symptoms via neurotransmission modulation. However, due to heterogeneity and the shortage of eligible articles, they do not robustly converge to the same findings. Hence, we recommend further studies with larger sample sizes to elucidate the possible interactions between the various markers, their blood vs. CSF ratios, and their correlation with schizophrenia symptoms.
Factors affecting cytological results of endoscopic ultrasound guided-fine needle aspiration during learning
Authors: Lai Jian-Han , Lin Hsiang-Hung , Lin Ching-Chung 
Published: February 2020

Abstract
Background
Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is a standard procedure used to obtain tissue samples for diagnosis of solid retroperitoneal tumours. However, this procedure demands high technical expertise and requires a strong learning curve. Our aim was to identify factors associated with false-negative EUS-FNA results during the learning for endoscopists.

Methods
Our retrospective analysis was based on the EUS-FNA specimens collected by two novice endoscopists in 200 patients with retroperitoneal lesions who had confirmed image- or tissue-based diagnoses of malignancy or benign lesions.

Results
In the first 40 performances endoscopists, the false-negative diagnostic rate of EUS-FNA was higher among patients with chronic pancreatitis than in patients without chronic pancreatitis. Patients who underwent FNA through the trans-duodenal puncture route also had lower success cytological diagnosis rate than through the trans-gastric puncture route. The rate of successful cytological diagnoses with EUS-FNA improved after 40 procedures and was not influenced by chronic pancreatitis presentation or difference puncture route.

Conclusion
Regarding the learning curve, more than 40 procedures were required to achieve a stable success rate of EUS-FNA. Chronic pancreatitis and trans-duodenal puncture route are the predictive factors for a false-negative FNA cytological result during learning.

Trial registration
This was a retrospective study.
Hybrid dysgenesis in Drosophila virilis results in clusters of mitotic recombination and loss-of-heterozygosity but leaves meiotic recombination unaltered
Authors: Hemmer Lucas W. , Dias Guilherme B. , Smith Brittny , Van Vaerenberghe Kelley , Howard Ashley , Bergman Casey M. , Blumenstiel Justin P. 
Published: February 2020

AbstractBackgroundTransposable elements (TEs) are endogenous mutagens and their harmful effects are especially evident in syndromes of hybrid dysgenesis. InDrosophila virilis, hybrid dysgenesis is a syndrome of incomplete gonadal atrophy that occurs when males with multiple active TE families fertilize females that lack active copies of the same families. This has been demonstrated to cause the transposition of paternally inherited TE families, with gonadal atrophy driven by the death of germline stem cells. Because there are abundant, active TEs in the male inducer genome, that are not present in the female reactive genome, theD. virilissyndrome serves as an excellent model for understanding the effects of hybridization between individuals with asymmetric TE profiles.ResultsUsing theD. virilissyndrome of hybrid dysgenesis as a model, we sought to determine how the landscape of germline recombination is affected by parental TE asymmetry. Using a genotyping-by-sequencing approach, we generated a high-resolution genetic map ofD. virilisand show that recombination rate and TE density are negatively correlated in this species. We then contrast recombination events in the germline of dysgenic versus non-dysgenic F1 females to show that the landscape of meiotic recombination is hardly perturbed during hybrid dysgenesis. In contrast, hybrid dysgenesis in the female germline increases transmission of chromosomes with mitotic recombination. Using a de novo PacBio assembly of theD. virilisinducer genome we show that clusters of mitotic recombination events in dysgenic females are associated with genomic regions with transposons implicated in hybrid dysgenesis.ConclusionsOverall, we conclude that increased mitotic recombination is likely the result of early TE activation in dysgenic progeny, but a stable landscape of meiotic recombination indicates that either transposition is ameliorated in the adult female germline or that regulation of meiotic recombination is robust to ongoing transposition. These results indicate that the effects of parental TE asymmetry on recombination are likely sensitive to the timing of transposition.
A pilot study using environmental screening to determine the prevalence of Mycobacterium avium subspecies paratuberculosis (MAP) and antimicrobial resistance (AMR) in Irish cattle herds
Authors: Ramovic Elvira , Madigan Gillian , McDonnell Shannon , Griffin Denise , Bracken Elaine , NiGhallchoir Eadaoin , Quinless Emma , Galligan Aoife , Egan John , Prendergast Deirdre M. 
Published: February 2020

Abstract
Background
Dairy and beef cattle can be reservoirs of many pathogens, including Salmonella and Mycobacterium avium subsp. paratuberculosis (MAP), the causative agent of Johne’s disease (JD). Farm environments may provide potential entry points for the transmission of infectious agents into the food chain. Antibiotics are used to treat a wide variety of infections on farms, and administration of antimicrobial agents to cattle is considered to be a driving factor for antimicrobial resistance (AMR). Control of JD and AMR are priority for animal health initiatives in Ireland. A national JD pilot programme was introduced by Animal Health Ireland in 2014, while the national action plan launched by Department of Health and Department of Agriculture, Food and Marine introduced in 2017 aims to improve the surveillance of AMR. The current investigation was undertaken as a pilot study to determine the proportion of herds positive for MAP, Salmonella species (Salmonella spp), commensal Escherichia coli (E. coli), Extended-spectrum beta-lactamase (ESBL) AmpC β-lactamase and carbapenemase-producing E. coli from 157 environmental faecal samples in Irish farms.

Results
MAP was detected in 10.2% of samples collected; on culture in 4 (4.9%) of the dairy herds and from 1 (1.3%) of the beef/suckler herds, and by PCR in 10 (12.3%) and 6 (7.9%) of these herds respectively. All culture positive herds were also positive by PCR. An additional 11 herds were positive by PCR only. Salmonella was not detected, while commensal E. coli were isolated from 70.7% of the samples (111/157) with 101 of these isolates shown to be fully susceptible to all antimicrobials tested. Of the 27 presumptive ESBL AmpC β-lactamase producing E. coli detected, one isolate was resistant to ten antimicrobials, nine isolates were resistant to nine antimicrobials, and four isolates were resistant to eight antimicrobials. Carbapenemase-producing E. coli were not isolated.

Conclusions
The results highlight the importance of monitoring farm environments for Johne’s disease. This disease is a growing concern for dairy and beef producers in Ireland, and sampling the farm environment may offer a useful means to rapidly screen for the presence of MAP. Non-pathogenic common enteric commensal and multiple-drug-resistant E. coli may contribute to AMR acting as a reservoir and transferring resistance to other species/pathogens in the environment.
Metabolic dependencies govern microbial syntrophies during methanogenesis in an anaerobic digestion ecosystem
Authors: Zhu Xinyu , Campanaro Stefano , Treu Laura , Seshadri Rekha , Ivanova Natalia , Kougias Panagiotis G. , Kyrpides Nikos , Angelidaki Irini 
Published: February 2020

AbstractMethanogenesis, a biological process mediated by complex microbial communities, has attracted great attention due to its contribution to global warming and potential in biotechnological applications. The current study unveiled the core microbial methanogenic metabolisms in anaerobic vessel ecosystems by applying combined genome-centric metagenomics and metatranscriptomics. Here, we demonstrate that an enriched natural system, fueled only with acetate, could support a bacteria-dominated microbiota employing a multi-trophic methanogenic process. Moreover, significant changes, in terms of microbial structure and function, were recorded after the system was supplemented with additional H2. Methanosarcina thermophila, the predominant methanogen prior to H2 addition, simultaneously performed acetoclastic, hydrogenotrophic, and methylotrophic methanogenesis. The methanogenic pattern changed after the addition of H2, which immediately stimulated Methanomicrobia-activity and was followed by a slow enrichment of Methanobacteria members. Interestingly, the essential genes involved in the Wood-Ljungdahl pathway were not expressed in bacterial members. The high expression of a glycine cleavage system indicated the activation of alternative metabolic pathways for acetate metabolism, which were reconstructed in the most abundant bacterial genomes. Moreover, as evidenced by predicted auxotrophies, we propose that specific microbes of the community were forming symbiotic relationships, thus reducing the biosynthetic burden of individual members. These results provide new information that will facilitate future microbial ecology studies of interspecies competition and symbiosis in methanogenic niches.