bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protective mechanism of rhubarb anthraquinone glycosides in rats with cerebral ischaemia–reperfusion injury: interactions between medicine and intestinal flora
Authors: Li Qiuying , Guo Ying , Yu Xiahui , Liu Wenhong , Zhou Liping 
Published: June 2020

Abstract
Background
Anthraquinone glycosides extracted from rhubarb have been proven to have significant therapeutic effects on ischaemic stroke. It is well known that anthraquinone glycosides are not easily absorb. Thus, how can rhubarb anthraquinone glycosides (RAGs) exert protective effects on the brain? Is this protective effect related to interactions between RAGs and intestinal flora?

Methods
The model used in this study was established by middle cerebral artery occlusion (MCAO) and reperfusion. Twenty-seven adult male Sprague–Dawley (SD) rats were randomly divided into 3 groups: the normal group (A) (non-MCAO + 0.5% sodium carboxymethyl cellulose (CMC-Na)), model group (B) (MCAO + 0.5% CMC-Na) and medicine group (C) (MCAO + RAGs (15 mg/(kg day)). The rats were fed by gavage once a day for 7 days. Fresh faeces were collected from the normal group to prepare the intestinal flora incubation liquid. Add RAGs, detect the RAGs and the corresponding anthraquinone aglycones by HPLC–UV at different time points. On the 8th day, the rats were euthanized, and the colonic contents were collected and analysed by high-throughput sequencing. In addition, 12 adult male SD rats were randomly divided into 2 groups: the normal group (D) (non-MCAO + RAGs (15 mg/(kg day)) and model group (E) (MCAO + RAGs (15 mg/(kg day)). The rats were fed by gavage immediately after reperfusion. Blood was collected from the orbital venous plexus, and the RAGs and anthraquinone aglycones were detected by HPLC–UV.

Results
The abundance and diversity of the intestinal flora in rats decreased after cerebral ischaemia–reperfusion injury (CIRI). RAGs could effectively improve the abundance of the intestinal flora. In addition, in vitro metabolism studies showed that RAGs were converted into anthraquinone aglycones by intestinal flora. In the in vivo metabolism studies, RAGs could not be detected in the plasma; in contrast, the corresponding anthraquinone aglycones could be detected. Absorption of RAGs may be inhibited in rats with CIRI.

Conclusions
CIRI may lead to intestinal flora disorder in rats, and after the administration of RAGs, the abundance of intestinal flora can be improved. RAGs can be metabolized into their corresponding anthraquinone aglycones by intestinal flora so that they can be absorbed into the blood.
Medical expenditure for patients with hemophilia in urban China: data from medical insurance information system from 2013 to 2015
Authors: Gong Guang-wen , Chen Ying-chun , Fang Peng-qian , Min Rui 
Published: June 2020

Abstract
Background
Hemophilia, a high-cost disease, is the only rare disease covered by basic medical insurance in all province of China. However, very few studies have estimated the medical expenditure of patients with this rare disease Therefore, this study is aimed at evaluating the medical expenditure of patients with hemophilia and identifying its determinants.

Methods
The study population included 450 patients with hemophilia who were extracted from the national insurance database between 2014 and 2016. An independent-sample Kolmogorov–Smirnov test was performed to compare the medical expenditure of patients with hemophilia covered under urban employee basic medical insurance (UEBMI) and urban residence basic medical insurance (URBMI). Quantile regression analysis was conducted to explore the factors that affect the medical expenditure of patients with hemophilia.

Results
The total annual medical expenditure of patients with hemophilia in 2013, 2014, and 2015 had median of ¥7167 (US$ 1156), ¥3522 (US$ 577), and ¥4197 (US$ 677), respectively. The median medical expenditures of patients with hemophilia covered by UEBMI were ¥10,991 (US$ 1773), ¥2301 (US$ 377) and ¥8074 (US$ 1302), those of patients covered by URBMI were ¥4000 (US$ 645), ¥5717 (US$ 937) and ¥3141 (US$ 507) from 2013 to 2015. The differences in the medical expenditure of patients with hemophilia between UEBMI and URBMI from 2013 to 2015 were statistically significant. The number of admissions and the number of hospital days were statistically significant and positive for all quantiles. The types of medical service were statistically significant and negative for 50th quantile, and the reimbursement ratio was statistically significant and positive for 50th and 75th quantiles. (p < 0.05).

Conclusion
The medical expenditure of patients with hemophilia was lower than that of patients with other common rare diseases that were not included in the scope of basic medical insurance reimbursement. It was also observed that the medical expenditure was mainly influenced by the severity of disease, and partly affected by the reimbursement rate.
Prospective cardiovascular magnetic resonance imaging in adults with Alström syndrome: silent progression of diffuse interstitial fibrosis
Authors: Baig Shanat , Dowd Rory , Edwards Nicola C. , Hodson James , Fabritz Larissa , Vijapurapu Ravi , Liu Boyang , Geberhiwot Tarekegn , Steeds Richard P. 
Published: June 2020

Abstract
Background
Alström syndrome (ALMS) is a rare ciliopathy characterised by early onset insulin resistance, obesity, and dyslipidaemia and is a model for diseases that have huge social, health and economic impact. Cardiomyopathy develops in the majority, with high rates of morbidity and mortality, the definitive features of which are coarse replacement fibrosis and diffuse myocardial fibrosis (DIF). The pathogenesis of heart failure is thought to involve fibroblast accumulation and expansion of the extracellular matrix with excess protein deposition, leading to distorted organ architecture and impaired contractile function. Consecutive adults with genetically proven ALMS attending the National Centre for Rare Disease in Birmingham, England were studied. All patients underwent serial CMR, echocardiography and venous blood sampling, with computed tomography coronary angiography (CTCA) performed to assess severity of CAD. The aims of this study were: 1) to evaluate changes over time in DIF by cardiovascular magnetic resonance tissue characterization in ALMS; 2) to examine whether changes in DIF are associated with alteration in systolic or diastolic function; and 3) to evaluate the frequency and severity of coronary artery disease as a confounder for progression of ischaemic versus non-ischaemic fibrosis.

Results
In total, 30/32 adults (63% male; 67% White British) participated. The median age at first scan was 21.3 years (interquartile range: 19.0–32.6) and participants were followed for a maximum of 67 months. Only 4 patients had significant coronary artery stenosis on post-mortem, invasive coronary angiography or CTCA. Mid short axis myocardial T1 times, myocardial extracellular volume, and left ventricular mass increased significantly over time, by an average of 21.8 ms (95% CI 17.4–26.1; p < 0.001), 1.1 percentage points (0.6–1.6, p < 0.001), and 2.8 g/m2 (1.9–3.7; p < 0.001) per year, respectively. These changes were not associated with significant deterioration in myocardial structure or function.

Conclusions
This is the first comprehensive prospective study demonstrating progression of DIF in ALMS over time, although no structural or functional consequences were noted within a median three and a half years’ follow up. Further study is warranted to define whether DIF is a by-stander or the driver to impaired contractile function, heart failure and death.
Non-coding RNAs shuttled via exosomes reshape the hypoxic tumor microenvironment
Authors: Wang Wenyu , Han Youngjin , Jo Hyun A , Lee Juwon , Song Yong Sang 
Published: June 2020

AbstractExosomes are small extracellular vesicles secreted by almost all the cells. Molecular cargos of exosomes can partially reflect the characteristics of originating cells. Exosome-mediated cell-to-cell interactions in the microenvironment are critical in cancer progression. Hypoxia, a key pro-cancerous feature of the tumor microenvironment, alters the releasing and contents of exosomes. A growing body of evidence shows that hypoxia induces more aggressive phenotypes in cancer. Of note, non-coding RNAs shuttled in hypoxic tumor-derived exosomes have been demonstrated as fundamental molecules in regulating cancer biology and remodeling tumor microenvironment. Furthermore, these hypoxic tumor-derived exosomal non-coding RNAs can be detected in the body fluids, serving as promising diagnostic and prognostic biomarkers. The current review discusses changes in cancer behaviors regulated by exosomes-secreted non-coding RNAs under hypoxic conditions.
Th17 cells inhibit CD8+ T cell migration by systematically downregulating CXCR3 expression via IL-17A/STAT3 in advanced-stage colorectal cancer patients
Authors: Wang Dan , Yu Weina , Lian Jingyao , Wu Qian , Liu Shasha , Yang Li , Li Feng , Huang Lan , Chen Xinfeng , Zhang Zhen , Li Aitian , Liu Jinbo , Sun Zhenqiang , Wang Junxia , Yuan Weitang , Zhang Yi 
Published: June 2020

AbstractBackgroundCD8+T cell trafficking to the tumor site is essential for effective colorectal cancer (CRC) immunotherapy. However, the mechanism underlying CD8+T cell infiltration in colorectal tumor tissues is not fully understood. In the present study, we investigated CD8+T cell infiltration in CRC tissues and the role of chemokine–chemokine receptor signaling in regulation of T cell recruitment.MethodsWe screened chemokines and cytokines in healthy donor and CRC tissues from early- and advanced-stage patients using multiplex assays and PCR screening. We also utilized transcription factor activation profiling arrays and established a xenograft mouse model.ResultsCompared with tumor tissues of early-stage CRC patients, CD8+T cell density was lower in advanced-stage tumor tissues. PCR screening showed that CXCL10 levels were significantly increased in advanced-stage tumor tissues. CXCR3 (the receptor of CXCL10) expression on CD8+T cells was lower in the peripheral blood of advanced-stage patients. The migratory ability of CD8+T cells to CXCL10 depended on CXCR3 expression. Multiplex arrays showed that IL-17A was increased in advanced-stage patient sera, which markedly downregulated CXCR3 expression via activating STAT3 signaling and reduced CD8+T cell migration. Similar results were found after CD8+T cells were treated with Th17 cell supernatant. Adding anti-IL-17A or the STAT3 inhibitor, Stattic, rescued these effects in vitro and in vivo. Moreover, survival analysis showed that patients with low CD8 and CXCR3 expression and high IL-17A levels had significantly worse prognosis.ConclusionsCD8+T cell infiltration in advanced-stage tumor was systematically inhibited by Th17 cells via IL-17A/STAT3/CXCR3 axis. Our findings indicate that the T cell infiltration in the tumor microenvironment may be improved by inhibiting STAT3 signaling.
IMpower, CASPIAN, and more: exploring the optimal first-line immunotherapy for extensive-stage small cell lung cancer
Authors: Huang Chengliang , Gan Gregory N. , Zhang Jun 
Published: June 2020

AbstractThe life expectancy of extensive-stage small cell lung (ES-SCLC) cancer patients has not improved in the last 2–3 decades until two recent trials (CASPIAN and IMpower133) showing the addition of anti-programmed death ligand (PD-L1) therapy to chemotherapy has survival benefit over chemotherapy alone. However, such benefit is relatively small and was not even observed in some other trials using immunotherapy, raising the question of optimal chemoimmunotherapy combination in the 1st-line setting for ES-SCLC. Here, we discussed several thought-provoking questions with the focus on IMpower133 and CASPIAN trials.
Evolving therapy of adult acute lymphoblastic leukemia: state-of-the-art treatment and future directions
Authors: Samra Bachar , Jabbour Elias , Ravandi Farhad , Kantarjian Hagop , Short Nicholas J. 
Published: June 2020

AbstractRecent years have witnessed major advances that have improved outcome of adults with acute lymphoblastic leukemia (ALL). The emergence of the concept of measurable residual disease has fine-tuned our prognostic models and guided our treatment decisions. The treatment paradigms of ALL have been revolutionized with the advent of tyrosine kinase inhibitors targeting BCR-ABL1, monoclonal antibodies targeting CD20 (rituximab), antibody-drug conjugates targeting CD22 (inotuzumab ozogamicin), bispecific antibodies (blinatumomab), and CD19 chimeric antigen receptor T cell therapy (tisagenlecleucel). These highly effective new agents are allowing for novel approaches that reduce reliance on intensive cytotoxic chemotherapy and hematopoietic stem cell transplantation in first remission. This comprehensive review will focus on the recent advances and future directions in novel therapeutic strategies in adult ALL.
Circular RNA hsa_circ_0078607 suppresses ovarian cancer progression by regulating miR-518a-5p/Fas signaling pathway
Authors: Zhang Nan , Jin Yue , Hu Qiubo , Cheng Shanshan , Wang Chao , Yang Zhiyou , Wang Yu 
Published: June 2020

Abstract
Background
Increasing researches have demonstrated the critical functions of circular RNAs (circRNAs) in the progression of malignant tumors, including ovarian cancer. In this study, we aim to investigate abnormally expression of hsa_circ_0078607 and the role of hsa_circ_0078607 during ovarian cancer pathogenesis.

Methods
RT-PCR were used to detect the expression of circ_0078607 in ovarian cancer tissues. To determine the functional roles of circ_0078607 in ovarian cancer, cell proliferation and cell invasion assays were performed. Bioinformatics and luciferase reporter analysis were used to predict the target of circ_0078607.

Results
In the present study, we first found that circ_0078607 was downregulated in ovarian cancer. Forced circ_0078607 expression significantly suppressed proliferation and promoted apoptosis of ovarian cancer cells. Mechanically, bioinformatics and luciferase reporter analysis identified miR-518a-5p as a direct target of circ_0078607, while Fas as a direct target of miR-518a-5p. MiR-518a-5p negatively regulated Fas in ovarian cancer cells, while overexpression of circ_0078607 could increase the expression of Fas inhibited by miR-518a-5p. Furthermore, overexpression of circ_0078607 could inhibit the proliferation and invasion of ovarian cancer cells caused by miR-518a-5p mimic.

Conclusion
The results of the present study revealed that circ_0078607 suppressed ovarian cancer progression by sponging oncogenic miR-518a-5p to induce Fas expression, which may provide new therapeutic approach for ovarian cancer.
Admission decisions to intensive care units in the context of the major COVID-19 outbreak: local guidance from the COVID-19 Paris-region area
Authors: Azoulay Élie , Beloucif Sadek , Guidet Bertrand , Pateron Dominique , Vivien Benoît , Le Dorze Matthieu 
Published: June 2020

AbstractSARS-CoV-2 has caused a global pandemic unprecedented in size, spread, severity, and mortality. The influx of patients with severe or life-threatening disease means that in some cases, the available medical resources are not sufficient to meet the needs of all patients. Hence, healthcare providers may be forced to make difficult choices about which patients should be referred to the ICU. This document is intended to provide conceptual support to all healthcare teams currently engaged in the frontline management of the COVID-19 pandemic. It aims to assist physicians in the decision-making process for ICU admission and to help them provide uninterrupted and high-quality care.
Optimisation of the ActWELL lifestyle intervention programme for women attending routine NHS breast screening clinics
Authors: Anderson Annie S. , Craigie Angela M. , Gallant Stephanie , McAdam Chloe , Macaskill E. Jane , McKell Jennifer , Mutrie Nanette , O’Carroll Ronan E. , Sattar Naveed , Stead Martine , Treweek Shaun 
Published: June 2020

Abstract
Background
Around 30% of post-menopausal breast cancer is related to excess body fat, alcohol intake and low levels of physical activity. Current estimates suggest that there is a 12% increased risk in post-menopausal breast cancer for every 5 kg/m2 increase in body mass index (BMI). Despite this evidence there are few lifestyle programmes directed towards breast cancer risk reduction. This paper describes the process of optimising of the ActWELL programme which aims to support weight management in women invited to attend routine National Health Service (NHS) breast screening clinics.

Methods
A feasibility study of a prototype programme aiming to change lifestyle behaviours was successfully undertaken. The programme used educational approaches and behaviour change techniques delivered by lifestyle coaches using individual face to face meetings and telephone sessions. To optimise the intervention for a definitive randomised controlled trial of weight management, data from the feasibility trial, focus group discussions conducted with the target population, feedback from the trial public advisory group and comments from peer reviewers were obtained. Concepts from implementation research provided further guidance to assist in the refinement of the intervention, which was then discussed and agreed by all investigators and the Trial Steering Group.

Results
The results from the feasibility trial were considered appropriate for moving on to a full trial with 70% of participants finding the programme acceptable. The primary outcomes (weight loss and physical activity) provided an important focus for design input from the target group. The contributions highlighted the need to review programme duration, coach contact time, content and use of behaviour change techniques and communications generally (e.g. science and evidence, non-judgemental approaches and avoiding guilt). In addition, the need for emphasis on support rather than education became apparent. The recommendations from peer reviewers focussed on the magnitude of effort required to achieve the intended weight loss and weight loss maintenance. Implementation science supported the use of the capability/opportunity/motivation (COM-B)model in overall design.

Conclusions
The optimisation process has facilitated the development and evaluation of a programme that enables the delivery of a promising intervention to achieve weight management in post-menopausal women.

Trial registration
ISRCTN: ISRCTN11057518. Registered on 21 July 2017. Retrospectively registered.
Toxigenic and non-toxigenic patterns I, II and III and biofilm-forming ability in Bacteroides fragilis strains isolated from patients diagnosed with colorectal cancer
Authors: Jasemi Seyedesomaye , Emaneini Mohammad , Fazeli Mohammad Sadegh , Ahmadinejad Zahra , Nomanpour Bizhan , Sadeghpour Heravi Fatemah , Sechi Leonardo A. , Feizabadi Mohammad Mehdi 
Published: June 2020

Abstract
Background
Enterotoxigenic Bacteroides fragilis (ETBF) associated with the initiation and progression of colorectal cancer (CRC) has been alarmingly reported all over the world. In this study, simultaneous investigation of toxigenic and non-toxigenic patterns I, II and III and biofilm formation ability of Bacteroides fragilis isolated from patients with colorectal cancer was performed.

Methods
Thirty-one patients diagnosed with CRC and thirty-one control subjects were recruited in this study. Specimens were cultured on BBE and BBA culture media. Classical phenotypic identification tests and PCR was performed to verify Bacteroides fragilis presence. Also, biofilm-forming ability and expression of bft gene were assessed under biofilm and planktonic forms.

Results
A total of 68 B.fragilis was isolated from all colorectal tissue, of which 13 isolates (19.1%) (11 isolates from CRC and 2 from normal tissue) were positive for bft gene. The abundance patterns of I, II and III were as follow in descending order; pattern I > pattern III > pattern II in CRC subjects and pattern II > pattern III > pattern I in normal tissues. Also, pattern I showed higher biofilm formation ability compared to other patterns. Toxin expression was significantly reduced in biofilm form comparing with planktonic form.

Conclusions
Based on our findings, there was a difference between the abundance of patterns I, II, and III and biofilm formation in isolates obtained from CRC and normal tissues. Biofilm formation ability and toxin encoding gene (bft) are two main virulence factors in B. fragilis pathogenicity which require more investigation to treat B. fragilis infections effectively.
Transcriptional consequences of MBD5 disruption in mouse brain and CRISPR-derived neurons
Authors: Seabra Catarina M. , Aneichyk Tatsiana , Erdin Serkan , Tai Derek J. C. , De Esch Celine E. F. , Razaz Parisa , An Yu , Manavalan Poornima , Ragavendran Ashok , Stortchevoi Alexei , Abad Clemer , Young Juan I. , Maciel Patricia , Talkowski Michael E. , Gusella James F. 
Published: June 2020

Abstract
Background
MBD5, encoding the methyl-CpG-binding domain 5 protein, has been proposed as a necessary and sufficient driver of the 2q23.1 microdeletion syndrome. De novo missense and protein-truncating variants from exome sequencing studies have directly implicated MBD5 in the etiology of autism spectrum disorder (ASD) and related neurodevelopmental disorders (NDDs). However, little is known concerning the specific function(s) of MBD5.

Methods
To gain insight into the complex interactions associated with alteration of MBD5 in individuals with ASD and related NDDs, we explored the transcriptional landscape of MBD5 haploinsufficiency across multiple mouse brain regions of a heterozygous hypomorphic Mbd5+/GT mouse model, and compared these results to CRISPR-mediated mutations of MBD5 in human iPSC-derived neuronal models.

Results
Gene expression analyses across three brain regions from Mbd5+/GT mice showed subtle transcriptional changes, with cortex displaying the most widespread changes following Mbd5 reduction, indicating context-dependent effects. Comparison with MBD5 reduction in human neuronal cells reinforced the context-dependence of gene expression changes due to MBD5 deficiency. Gene co-expression network analyses revealed gene clusters that were associated with reduced MBD5 expression and enriched for terms related to ciliary function.

Limitations
These analyses included a limited number of mouse brain regions and neuronal models, and the effects of the gene knockdown are subtle. As such, these results will not reflect the full extent of MBD5 disruption across human brain regions during early neurodevelopment in ASD, or capture the diverse spectrum of cell-type-specific changes associated with MBD5 alterations.

Conclusions
Our study points to modest and context-dependent transcriptional consequences of Mbd5 disruption in the brain. It also suggests a possible link between MBD5 and perturbations in ciliary function, which is an established pathogenic mechanism in developmental disorders and syndromes.