bluuebunny/crossref_metadata_2025_split huggingface dataset:
CCL2/CCR2 signaling in cancer pathogenesis
Authors: Hao Qiongyu , Vadgama Jaydutt V. , Wang Piwen 
Published: May 2020

AbstractChemokines are a family of small cytokines, which guide a variety of immune/inflammatory cells to the site of tumor in tumorigenesis. A dysregulated expression of chemokines is implicated in different types of cancer including prostate cancer. The progression and metastasis of prostate cancer involve a complex network of chemokines that regulate the recruitment and trafficking of immune cells. The chemokine CCL2 and its main receptor CCR2 have been receiving particular interest on their roles in cancer pathogenesis. The up-regulation of CCL2/CCR2 and varied immune conditions in prostate cancer, are associated with cancer advancement, metastasis, and relapse. Here we reviewed recent findings, which link CCL2/CCR2 to the inflammation and cancer pathogenesis, and discussed the therapeutic potential of CCL2/CCR2 axis in cancer treatment based on results from our group and other investigators, with a major focus on prostate cancer.
Whole blood transcriptomic investigation identifies long non-coding RNAs as regulators in sepsis
Authors: Cheng Lixin , Nan Chuanchuan , Kang Lin , Zhang Ning , Liu Sheng , Chen Huaisheng , Hong Chengying , Chen Youlian , Liang Zhen , Liu Xueyan 
Published: May 2020

Abstract
Background
Sepsis is a fatal disease referring to the presence of a known or strongly suspected infection coupled with systemic and uncontrolled immune activation causing multiple organ failure. However, current knowledge of the role of lncRNAs in sepsis is still extremely limited.

Methods
We performed an in silico investigation of the gene coexpression pattern for the patients response to all-cause sepsis in consecutive intensive care unit (ICU) admissions. Sepsis coexpression gene modules were identified using WGCNA and enrichment analysis. lncRNAs were determined as sepsis biomarkers based on the interactions among lncRNAs and the identified modules.

Results
Twenty-three sepsis modules, including both differentially expressed modules and prognostic modules, were identified from the whole blood RNA expression profiling of sepsis patients. Five lncRNAs, FENDRR, MALAT1, TUG1, CRNDE, and ANCR, were detected as sepsis regulators based on the interactions among lncRNAs and the identified coexpression modules. Furthermore, we found that CRNDE and MALAT1 may act as miRNA sponges of sepsis related miRNAs to regulate the expression of sepsis modules. Ultimately, FENDRR, MALAT1, TUG1, and CRNDE were reannotated using three independent lncRNA expression datasets and validated as differentially expressed lncRNAs.

Conclusion
The procedure facilitates the identification of prognostic biomarkers and novel therapeutic strategies of sepsis. Our findings highlight the importance of transcriptome modularity and regulatory lncRNAs in the progress of sepsis.
TDAG8 deficiency reduces satellite glial number and pro-inflammatory macrophage number to relieve rheumatoid arthritis disease severity and chronic pain
Authors: Dai Shih-Ping , Hsieh Wei-Shan , Chen Chien-Hua , Lu Yueh-Hao , Huang Hsu-Shan , Chang Der-Ming , Huang Shir-Ly , Sun Wei-Hsin 
Published: May 2020

Abstract
Background
The autoimmune disease rheumatoid arthritis (RA) affects approximately 1% of the global population. RA is characterized with chronic joint inflammation and often associated with chronic pain. The imbalance of pro-inflammatory and anti-inflammatory macrophages is a feature of RA progression. Glial cells affecting neuronal sensitivity at both peripheral and central levels may also be important for RA progression and associated pain. Genetic variants in the T cell death-associated gene 8 (TDAG8) locus are found to associate with spondyloarthritis. TDAG8 was also found involved in RA disease progression and associated hyperalgesia in the RA mouse model. However, its modulation in RA remains unclear.

Methods
To address this question, we intra-articularly injected complete Freund’s adjuvant (CFA) into TDAG8+/+, TDAG8−/− or wild-type mice, followed by pain behavioral tests. Joints and dorsal root ganglia were taken, sectioned, and stained with antibodies to observe the number of immune cells, macrophages, and satellite glial cells (SGCs). For compound treatments, compounds were intraperitoneally or orally administered weekly for 9 consecutive weeks after CFA injection.

Results
We demonstrated that TDAG8 deletion slightly reduced RA pain in the early phase but dramatically attenuated RA progression and pain in the chronic phase (> 7 weeks). TDAG8 deletion inhibited an increase in SGC number and inhibition of SGC function attenuated chronic phase of RA pain, so TDAG8 could regulate SGC number to control chronic pain. TDAG8 deletion also reduced M1 pro-inflammatory macrophage number at 12 weeks, contributing to the attenuation of chronic RA pain. Such results were further confirmed by using salicylanilide derivatives, CCL-2d or LCC-09, to suppress TDAG8 expression and function.

Conclusions
This study demonstrates that TDAG8 deletion reduced SGC and M1 macrophage number to relieve RA disease severity and associated chronic pain. M1 macrophages are critical for the development and maintenance of RA disease and pain, but glial activation is also required for the chronic phase of RA pain.
Automated quantitative analysis of Ki-67 staining and HE images recognition and registration based on whole tissue sections in breast carcinoma
Authors: Feng Min , Deng Yang , Yang Libo , Jing Qiuyang , Zhang Zhang , Xu Lian , Wei Xiaoxia , Zhou Yanyan , Wu Diwei , Xiang Fei , Wang Yizhe , Bao Ji , Bu Hong 
Published: May 2020

Abstract
Background
The scoring of Ki-67 is highly relevant for the diagnosis, classification, prognosis, and treatment in breast invasive ductal carcinoma (IDC). Traditional scoring method of Ki-67 staining followed by manual counting, is time-consumption and inter−/intra observer variability, which may limit its clinical value. Although more and more algorithms and individual platforms have been developed for the assessment of Ki-67 stained images to improve its accuracy level, most of them lack of accurate registration of immunohistochemical (IHC) images and their matched hematoxylin-eosin (HE) images, or did not accurately labelled each positive and negative cell with Ki-67 staining based on whole tissue sections (WTS). In view of this, we introduce an accurate image registration method and an automatic identification and counting software of Ki-67 based on WTS by deep learning.

Methods
We marked 1017 breast IDC whole slide imaging (WSI), established a research workflow based on the (i) identification of IDC area, (ii) registration of HE and IHC slides from the same anatomical region, and (iii) counting of positive Ki-67 staining.

Results
The accuracy, sensitivity, and specificity levels of identifying breast IDC regions were 89.44, 85.05, and 95.23%, respectively, and the contiguous HE and Ki-67 stained slides perfectly registered. We counted and labelled each cell of 10 Ki-67 slides as standard for testing on WTS, the accuracy by automatic calculation of Ki-67 positive rate in attained IDC was 90.2%. In the human-machine competition of Ki-67 scoring, the average time of 1 slide was 2.3 min with 1 GPU by using this software, and the accuracy was 99.4%, which was over 90% of the results provided by participating doctors.

Conclusions
Our study demonstrates the enormous potential of automated quantitative analysis of Ki-67 staining and HE images recognition and registration based on WTS, and the automated scoring of Ki67 can thus successfully address issues of consistency, reproducibility and accuracy. We will provide those labelled images as an open-free platform for researchers to assess the performance of computer algorithms for automated Ki-67 scoring on IHC stained slides.
Novel role of PAF1 in attenuating radiosensitivity in cervical cancer by inhibiting IER5 transcription
Authors: Zheng Jing-Jie , He Yue , Liu Yang , Li Feng-Shuang , Cui Zhen , Du Xiao-Meng , Wang Chun-Peng , Wu Yu-Mei 
Published: May 2020

Abstract
Background
Radiosensitivity is limited in cervical cancer (CC) patients due to acquired radiation resistance. In our previous studies, we found that immediate-early response 5 (IER5) is upregulated in CC cells upon radiation exposure and decreases cell survival by promoting apoptosis. The details on the transcriptional regulation of radiation-induced IER5 expression are unknown. Studies in recent years have suggested that Pol II-associated factor 1 (PAF1) is a pivotal transcription factor for certain genes “induced” during tumor progression. In this study, we investigated the role of PAF1 in regulating IER5 expression during CC radiotherapy.

Methods
PAF1 expression in CC cells was measured by western blotting, immunohistochemistry, and qRT-PCR, and the localization of PAF1 and IER5 was determined by immunofluorescence. The effect of PAF1 and IER5 knockdown by siRNA in Siha and Hela cells was studied by western blotting, qRT-PCR, CCK-8 assay, and flow cytometry. The physical interaction of PAF1 with the IER5 promoter and enhancers was confirmed using chromatin immunoprecipitation and qPCR with or without enhancers knockout by CRISPR/Cas9.

Results
We confirmed that PAF1 was highly expressed in CC cells and that relatively low expression of IER5 was observed in cells with highly expressed PAF1 in the nucleus. PAF1 knockdown in Siha and Hela cells was associated with increased expression of IER5, reduced cell viability and higher apoptosis rate in response to radiation exposure, while simultaneous PAF1 and IER5 knockdown had little effect on the proportion of apoptotic cells. We also found that PAF1 hindered the transcription of IER5 by promoting Pol II pausing at the promoter-proximal region, which was primarily due to the binding of PAF1 at the enhancers.

Conclusions
PAF1 reduces CC radiosensitivity by inhibiting IER5 transcription, at least in part by regulating its enhancers. PAF1 might be a potential therapeutic target for overcoming radiation resistance in CC patients.
Single approach to double-channel core decompression and bone grafting with structural bone support for treating osteonecrosis of the femoral head in different stages
Authors: Yue Ju’an , Guo Xiaozhong , Wang Randong , Li Bing , Sun Qiang , Liu Wangyan , Chen Jiao , Li Yingnan 
Published: May 2020

Abstract
Background
We created a novel method—single approach to double-channel core decompression and bone grafting with structural bone support (SDBS)—to treat early-stage osteonecrosis of the femoral head (ONFH) by improving the Phemister technique. This study aimed to evaluate the results of SDBS for early-stage ONFH.

Methods
Altogether, 53 patients (73 hips) were treated using SDBS during 2016–2018. Bilateral (20 patients) and unilateral (33 patients = 18 left hips, 15 right hips) ONFH was diagnosed. According to the Association Research Circulation Osseous classification stages, the femoral heads were staged as IIB (n = 15), IIC (n = 19), IIIA (n = 34), IIIB (n = 4), and IIIC (n = 1). The Harris hip score was used to evaluate the hips’ clinical function, computed tomography to evaluate subchondral fractures, and plain radiography to assess the extent of femoral head collapse.

Results
The average follow-up was 20.71 ± 6.65 months (6–36 months). At the patients’ last follow-up, 4 hips were found to require arthroplasty. Thus, the overall femoral head survival rate was 94.52% (69/73). Also, the overall Harris score (84.44 ± 14.57) was significantly higher than that preoperatively (77.67 ± 14.37) (P = 0.000). The combined excellent and good rate (76.71%) was significantly higher than that preoperatively (38.36%) (P = 0.000). Imaging showed that 16 femoral heads had some ONFH progression. The average length of stay was 6.15 ± 0.86 days. The average incision measured 2.69 ± 0.30 cm. Intraoperative blood loss was 61.20 ± 4.81 ml. There were no complications during or after the operation.

Conclusion
SDBS is an effective method for treating early-stage ONFH. It is a hip-preserving surgical approach to slow/prevent ONFH progression.
Mitochondria dysfunction in the pathogenesis of Alzheimer’s disease: recent advances
Authors: Wang Wenzhang , Zhao Fanpeng , Ma Xiaopin , Perry George , Zhu Xiongwei 
Published: May 2020

AbstractAlzheimer’s disease (AD) is one of the most prevalent neurodegenerative diseases, characterized by impaired cognitive function due to progressive loss of neurons in the brain. Under the microscope, neuronal accumulation of abnormal tau proteins and amyloid plaques are two pathological hallmarks in affected brain regions. Although the detailed mechanism of the pathogenesis of AD is still elusive, a large body of evidence suggests that damaged mitochondria likely play fundamental roles in the pathogenesis of AD. It is believed that a healthy pool of mitochondria not only supports neuronal activity by providing enough energy supply and other related mitochondrial functions to neurons, but also guards neurons by minimizing mitochondrial related oxidative damage. In this regard, exploration of the multitude of mitochondrial mechanisms altered in the pathogenesis of AD constitutes novel promising therapeutic targets for the disease. In this review, we will summarize recent progress that underscores the essential role of mitochondria dysfunction in the pathogenesis of AD and discuss mechanisms underlying mitochondrial dysfunction with a focus on the loss of mitochondrial structural and functional integrity in AD including mitochondrial biogenesis and dynamics, axonal transport, ER-mitochondria interaction, mitophagy and mitochondrial proteostasis.
The link between varicella and immune system: which children will develop acute cerebellitis?
Authors: Bozzola Elena , Carsetti Rita , Piano Mortari Eva , Masci Marco , Spina Giulia , Villani Alberto 
Published: May 2020

Abstract
Introduction
Varicella may complicate with cerebellitis in previously healthy children, requiring hospitalization. Aim of our study was to define whether children who experienced varicella cerebellitis have a normal immune system.

Methods
Patients over 3 years of age admitted at Bambino Gesù Children from January 2006 till June 2016 for cerebellitis in varicella were asked to participate to the follow-up study. The immune status was evaluated clinically and by laboratory investigations.

Results
Twenty-five patients were included in the study. At follow up, at least one immunological alteration was detected in 80% of patients. To avoid bias due to possible effects of the recent disease, we separately analyzed patients who had the follow-up control at least 1 year (Group 1) or between 1 month and 1 year (Group 2) after the hospitalization for acute varicella cerebellitis. The results were similar in both groups with immunological alterations detected in 84,6 and 75% of the patients, respectively.

Conclusions
Our preliminary results indicate that sub-clinical immunological defects may correlate to cerebellitis in varicella.
Patient-reported outcome measures for monitoring primary care patients with depression (PROMDEP): study protocol for a randomised controlled trial
Authors: Kendrick Tony , Moore Michael , Leydon Geraldine , Stuart Beth , Geraghty Adam W. A. , Yao Guiqing , Lewis Glyn , Griffiths Gareth , May Carl , Dewar-Haggart Rachel , Williams Samantha , Zhu Shihua , Dowrick Christopher 
Published: May 2020

Abstract
Background
Benefits to patients from reduced depression have been shown from monitoring progress with patient-reported outcome measures (PROMs) in psychological therapy and mental health settings. This approach has not yet been researched in the United Kingdom for primary care, which is where most people with depression are treated in the United Kingdom.

Methods
This is a parallel-group cluster randomised trial with 1:1 allocation to intervention and control. Patients who are age 18+ years, with a new episode of depressive disorder/symptoms, meet the inclusion criteria. Patients with current depression treatment, comorbid dementia/psychosis/substance misuse/suicidal ideas are excluded. The intervention includes the Administration of Patient Health Questionnaire (PHQ-9) as a PROM within 2 weeks of diagnosis and at follow-up 4 weeks later. General practitioners are trained in interpreting scores and asked to take them into account in their treatment decisions. Patients are given written feedback on scores and suggested treatments. The primary outcome measure is Depression on the Beck Depression Inventory BDI-II at 12 weeks. Secondary outcomes include BDI-II at 26 weeks, changes in drug treatments and referrals, social functioning (Work & Social Adjustment Scale) and quality of life (EQ-5D) at 12 and 26 weeks, service use over 26 weeks (modified Client Services Receipt Inventory) to calculate NHS costs, and patient satisfaction at 26 weeks (Medical Informant Satisfaction Scale). The sample includes 676 total participants from 113 practices across three centres. Randomisation is achieved by computerised sequence generation. Blinding is impossible given the nature of the intervention (self-report outcome measures prevent rating bias). Differences at 12 and 26 weeks between intervention and controls in depression, social functioning and quality of life are analysed using linear mixed models, adjusted for socio-demographics, baseline depression, anxiety, and clustering, while including practice as a random effect. Patient satisfaction, quality of life (QALYs) and costs over 26 weeks will be compared between arms. Qualitative process analysis includes interviews with 15–20 GP/NPs and 15–20 patients per arm to reflect trial results and implementation issues, using Normalization Process Theory as a theoretical framework.

Discussion
If PROMs are helpful in improving patient outcomes for depression even to a small extent, then they are likely to be good value for money, given their low cost. The benefits could be considerable, given that depression is common, disabling, and costly.

Trial registration
ISRCTN no: 17299295. Registered 1st October 2018.
Evaluation of an intervention to support decisions on disclosure in the employment setting (DECIDES): study protocol of a longitudinal cluster-randomized controlled trial
Authors: Janssens K. M. E. , van Weeghel J. , Henderson C. , Joosen M. C. W. , Brouwers E. P. M. 
Published: May 2020

Abstract
Background
Unemployment rates are higher among people with mental health issues/illness (MHI) than in the general working population, and many of them face the dilemma of whether or not to disclose their MHI when searching for employment. Disclosure can lead to rejection and discrimination, but alternatively can also have important advantages that may be necessary to retain employment. Whether disclosure decisions lead to sustainable employment depends on many factors, of which unemployed people themselves can only influence their decision to disclose or not and the way in which they communicate. This study evaluates the cost-effectiveness of an intervention to support unemployed people with MHI in their disclosure decision and communication.

Methods
This is a two-armed, clustered, randomized controlled trial with longitudinal design and randomization at organization level. An intervention will be examined, which consists of a disclosure decision aid tool (CORAL.NL) for unemployed people and workplace stigma-awareness training especially designed for employment specialists, which focusses on how to support unemployed people in their disclosure decisions. Participants in the intervention group are unemployed people who receive support from trained employment specialists from organizations allocated to the intervention group, and receive the CORAL.NL decision aid after baseline. The control group consists of unemployed people who receive support as usual from employment specialists from different organizations allocated to the control group. Primary outcomes are: cost-effectiveness of the intervention, e.g. healthcare costs, having employment, days until start of employment, independency of social security, having other forms of employment and decision making about disclosing MHI. Secondary outcomes are mental health and wellbeing, stigma and discrimination and work-related factors. Financial income data are collected via the registration systems of Dutch municipalities and Statistics Netherlands, and by questionnaires at baseline, and at 3, 6 and 12 months.

Discussion
If using a decision aid to decide about disclosure of MHI leads to people finding and retaining employment more often, this study will contribute to lowering healthcare and societal costs.

Trial registration
Netherlands Trial Register: NL7798. Registered on 4 June 2019.
High-flow nasal cannula versus standard oxygen therapy assisting sedation during endoscopic retrograde cholangiopancreatography in high risk cases (OTHER): study protocol of a randomised multicentric trial
Authors: Thiruvenkatarajan Venkatesan , Dharmalingam Ashok , Arenas Gilberto , Wahba Medhat , Steiner Reinhard , Kadam Vasanth Rao , Tran Andre , Currie John , Van Wijk Roelof , Quail Anthony , Ludbrook Guy 
Published: May 2020

Abstract
Background
Endoscopic retrograde cholangiopancreatography (ERCP) is an increasingly common intervention in the treatment of pancreaticobiliary disorders. Patients are often elderly with complex co-morbidities. While monitored anaesthesia care with sedation is commonly used for most cases, few would require general anaesthesia with an endotracheal tube. Both low-flow and high-flow nasal cannulas (HFNC) are established ways of delivering supplemental oxygen, but it is unclear whether one technique is better than the other. HFNC seems a promising tool for advanced procedures but evidence to support its application in high-risk ERCP cases is limited. The rate of oxygen desaturation during endoscopy has been reported to be as high as 11%–50% and the method of oxygen delivery for ERCP merits further study.

Methods/design
This is a prospective, randomised, multicentre trial comparing the efficacy of oxygen supplementation through HFNC versus low-flow nasal cannula during ERCP, in a cohort of patients at risk of adverse respiratory events. A total of 132 patients will be recruited across three sites and randomly assigned to either the low-flow or the HFNC group. The primary outcome is the proportion of patients experiencing hypoxia, defined by any event of SpO2 < 90%. The secondary outcomes include parameters centred on oxygenation, requirement of airway manoeuvres, successful completion of procedure, perioperative complications, patient satisfaction and cost analysis of the consumables. An intention-to-treat principle will be applied while analysing.

Discussion
The demand for ERCPs is likely to increase in the future with the aging population. Our study results may lead to improved outcomes and reduce airway-related complications in patients undergoing ERCPs. The results will be presented at national and international meetings and published in peer-reviewed journals.

Trial registration
www.ANZCTR.org.au, CTRN12619000397112. Registered on 12 March 2019.