bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the interactions between Codanin-1 and C15Orf41, two proteins implicated in Congenital dyserythropoietic anemia type I disease
Authors: Swickley Grace , Bloch Yehoshua , Malka Lidor , Meiri Adi , Noy-Lotan Sharon , Yanai Amiel , Tamary Hannah , Motro Benny 
Published: February 2020

Abstract
Background Congenital dyserythropoietic anemia type I (CDA I), is an autosomal recessive disease with macrocytic anemia in which erythroid precursors in the bone marrow exhibit pathognomonic abnormalities including spongy heterochromatin and chromatin bridges. We have shown previously that the gene mutated in CDA I encodes Codanin-1, a ubiquitously expressed and evolutionarily conserved large protein. Recently, an additional etiologic factor for CDA I was reported, C15Orf41, a predicted nuclease. Mutations in both CDAN1 and C15Orf41 genes results in very similar erythroid phenotype. However, the possible relationships between these two etiologic factors is not clear. Results We demonstrate here that Codanin-1 and C15Orf41 bind to each other, and that Codanin-1 stabilizes C15Orf41. C15Orf41 protein is mainly nuclear and Codanin-1 overexpression shifts it to the cytoplasm. Phylogenetic analyses demonstrated that even though Codanin-1 is an essential protein in mammals, it was lost from several diverse and unrelated animal taxa. Interestingly, C15Orf41 was eliminated in the exact same animal taxa. This is an extreme case of the Phylogenetic Profiling phenomenon, which strongly suggests common pathways for these two proteins. Lastly, as the 3D structure is more conserved through evolution than the protein sequence, we have used the Phyre2 alignment program to find structurally homologous proteins. We found that Codanin-1 is highly similar to CNOT1, a conserved protein which serves as a scaffold for proteins involved in mRNA stability and transcriptional control. Conclusions The physical interaction and the stabilization of C15Orf41 by Codanin-1, combined with the phylogenetic co-existence and co-loss of these two proteins during evolution, suggest that the major function of the presumptive scaffold protein, Codanin-1, is to regulate C15Orf41 activities. The similarity between Codanin-1 and CNOT1 suggest that Codanin-1 is involved in RNA metabolism and activity, and opens up a new avenue for the study of the molecular pathways affected in CDAI.
Identification of the regulatory networks and hub genes controlling alfalfa floral pigmentation variation using RNA-sequencing analysis
Authors: Duan Hui-Rong , Wang Li-Rong , Cui Guang-Xin , Zhou Xue-Hui , Duan Xiao-Rong , Yang Hongshan 
Published: February 2020

Abstract
Background: To understand the gene expression networks controlling flower color formation in alfalfa, flowers anthocyanins were identified using two materials with contrasting flower colors, namely Defu and Zhongtian No. 3, and transcriptome analyses of PacBio full-length sequencing combined with RNA sequencing were performed, across four flower developmental stages. Results: Malvidin and petunidin glycoside derivatives were the major anthocyanins in the flowers of Defu, which were lacking in the flowers of Zhongtian No. 3. The two transcriptomic datasets provided a comprehensive and systems-level view on the dynamic gene expression networks underpinning alfalfa flower color formation. By weighted gene coexpression network analyses, we identified candidate genes and hub genes from the modules closely related to floral developmental stages. PAL, 4CL, CHS, CHR, F3’H, DFR, and UFGT were enriched in the important modules. Additionally, PAL6, PAL9, 4CL18, CHS2, 4 and 8 were identified as hub genes. Thus, a hypothesis explaining the lack of purple color in the flower of Zhongtian No. 3 was proposed. Conclusions: These analyses identified a large number of potential key regulators controlling flower color pigmentation, thereby providing new insights into the molecular networks underlying alfalfa flower development.
Clinically useful prediction of hospital admissions in an older population
Authors: Marcusson Jan , Nord Magnus , Dong Huan-Ji , Lyth Johan 
Published: February 2020

Abstract
Background: The healthcare for older adults is insufficient in many countries, not designed to meet their needs and is often described as disorganized and reactive. Prediction of older persons at risk of admission to hospital may be one important way for the future healthcare system to act proactively when meeting increasing needs for care. Therefore, we wanted to develop and test a clinically useful model for predicting hospital admissions of older persons based on routine healthcare data.

Methods : We used the healthcare data on 40,728 persons, 75-109 years of age to predict hospital in-ward care in a prospective cohort. Multivariable logistic regression was used to identify significant factors predictive of unplanned hospital admission. Model fitting was accomplished using forward selection. The accuracy of the prediction model was expressed as area under the receiver operating characteristic (ROC) curve, AUC.

Results: The prediction model consisting of 38 variables exhibited a good discriminative accuracy for unplanned hospital admissions over the following 12 months (AUC 0·69 [95% confidence interval, CI 0·68–0·70]) and was validated on external datasets. Clinically relevant proportions of predicted cases of 40 or 45% resulted in sensitivities of 62 and 66%, respectively. The corresponding positive predicted values (PPV) was 31% and 29%, respectively.

Conclusion : A prediction model based on routine administrative healthcare data from older persons can be used to find patients at risk of admission to hospital. Identifying the risk population can enable proactive intervention for older patients with as-yet unknown needs for healthcare.
KLF4 alleviates cerebral vascular injury by ameliorating vascular endothelial inflammation and regulating tight junction protein expression following ischemic stroke
Authors: Zhang Xinyu , Wang Lu , Han Zhenxiang , Dong Jing , Pang Defang , Fu Yuan , Li Longxuan 
Published: February 2020

Abstract
Background
Although inflammatory cell adhesion molecules (CAMs) and anti-inflammation factor- kruppel-like transcription factor (KLF) 4 have all been reported to be induced after cerebral ischemic stroke (CIS), the close temporal and spatial relationship between expressions of CAMs and KLF4 following CIS, and whether and how CAMs and KLF-4 contribute to development of CIS-induced vascular injury are still unclear.

Methods
Here, we first examined the correlation between serum levels of CAMs/KLF4 and infarct volume in acute CIS patients. Then, we determined relationship between CAMs and KLF4 in mice after focal cerebral ischemia. Finally, we investigated the mechanism of KLF4 in protecting against oxygen-glucose deprivation-induced brain endothelial cell injury.

Results
Our results demonstrated that patients with moderate to severe CIS had higher serum levels of three CAMs including E-selectin, inter-cellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) but lower levels of KLF4 at 48 hours after acute event as compared to patients with minor CIS. The expression levels of three CAMs as well as KLF4 all correlated well with the infarct volume in all the CIS subjects at that time. Although the expressions of three CAMs and KLF4 were all induced in the ischemic hemisphere following focal cerebral ischemia, but the peak timing and distribution patterns of their expression were different: the induction of KLF4 lagged behind that of the CAMs in the ischemic penumbra, furthermore, the dual immunofluorescent studies displayed that high expression of KLF4 was always associated with relatively less cerebral vascular endothelial inflammation response in the ischemic hemisphere, and vice versa. Mechanistic analyses revealed that KLF4 alleviated CIS-induced cerebral vascular injury by regulating endothelial expressions of CAMs, nuclear factor-kB and tight junction proteins.

Conclusions
These data indicate that KLF4 confers vascular protection against cerebral ischemic injury, suggesting that circulating CAMs and KLF4 might be used as potential biomarkers for predicting the prognosis of acute ischemic stroke, and also providing a new proof of concept and potential targets for future prevention and treatment of CIS.
Reversed paired-gRNA plasmid cloning strategy for efficient genome editing in Escherichia coli
Authors: Ding Tingting , Huang Chaoyong , Liang Zeyu , Ma Xiaoyan , Wang Ning , Huo Yi-Xin 
Published: February 2020

Abstract
Background: Co-expression of two distinct guide RNAs (gRNAs) has been used to facilitate the application of CRISPR/Cas9 system in fields such as large genomic deletion. The paired gRNAs are often placed adjacently in the same direction and expressed individually by two identical promoters, constituting direct repeats (DRs) which are susceptible to self-homologous recombination. As a result, the paired-gRNA plasmids cannot remain stable, which greatly prevents scalable application of the CRISPR/Cas9 system. Results: To address this limitation, different DRs-involved paired-gRNA plasmids were designed and the events of recombination were characterized. Deletion between DRs occurred with high frequencies during plasmid construction and subsequent plasmid propagation. This recombination event was RecA-independent, which agreed with the replication slippage model. To increase plasmid stability, a reversed paired-gRNA plasmids (RPGPs) cloning strategy was developed by converting DRs to the more stable invert repeats (IRs), which completely eliminated DRs-induced recombination. Using RPGPs, rapid deletion of chromosome fragments up to 100 kb with an efficiency of 83.33% was achieved in Escherichia coli.Conclusions: The RPGPs cloning strategy serves as a general solution to avoid plasmid RecA-independent recombination. It can be adapted to applications that rely on paired gRNAs or repeated genetic parts.
The expression and Clinical Significance of miRNA-135a and Bach1 in colorectal cancer
Authors: Wang Jian , Zhang Yuchen , Jiang Zhiyang , Tao Guoqing , Zhu fei yan 
Published: February 2020

Abstract
AIM
To explore the correlation between the expression of miRNA-135a and Bach1 in colorectal cancer tissue and the patient's clinical information.
Methods
60 patients with colorectal carcinoma were treated as a control group. Real-time quantitative PCR assays and immunohistochemistry method were performed to detect the expression of miRNA-135a and Bach1 in 60 colorectal carcinoma and adjacent normal tissues, and the clinical and pathological classifications had also been investigated. The SPSS 19.00 software was used. All data represent mean±SD of three independent experiments. P<0.05 was considered statistically significant. Results
miRNA-135a expression levels increased significantly in the colon cancer tissues compared with the non-tumor control tissues(P<0.01). miRNA-135a expression levels were higher in stage III/IV than in stage I/II colon cancer patients. The expression level of Bach1 in colorectal cancer was significantly lower(P<0.01). Bach1 and miRNA-135a were negatively correlated.
Conclusions: The levels of miRNA-135a and Bach1 were opposite , the over-expression of miRNA-135a might decrease Bach1, which may be involved in the pathogenesis of colorectal cancer.
Assessment of the results and the haematologic side effects of the 3D conformal and the IMRT/ARC therapies delivered during the craniospinal irradiation of childhood tumors, in a follow-up period of 5 years
Authors: Lőcsei Zoltán , Farkas Róbert , Farkas Kornélia Borbásné , Sebestyén Klára , Sebestyén Zsolt , Musch Zoltán , Vojcek Ágnes , Benedek Noémi , Mangel László , Ottóffy Gábor 
Published: February 2020

Abstract
Objectives The craniospinal irradiation (CSI) of childhood tumors with Rapidarc technique is a new way of treatment. Our objective was to compare the acute haematologic toxicity pattern during 3D conformal radiotherapy with the application of the novel techniques. Materials and methods Data from patients treated between 2007 and 2014 has been collected and seven patients were identified in each of both treatment groups. The acute blood toxicity results were obtained, after establishing a general linear model, by using the SPSS software. Furthermore, the dose exposure of the organs-at-risk has been compared. Patients have been followed-up for a minimum of five years, then progression-free survival and overall survival data were assessed. Results After the assessment of the laboratory parameters of the two groups, it may be concluded that no significant differences were detected in terms of the mean dose exposures of the normal tissues or the acute hematological side-effects during the IMRT/ARC and the 3D conformal treatment. Laboratory parameters significantly decreased compared to the baseline values during the treatment weeks. Nevertheless, no significant differences were detected between the two groups. No remarkable differences were confirmed between the two groups regarding the five-year progression-free survival and overall survival, and no signs of serious irradiation organ toxicity were observed during the follow-up period in either of the groups. Conclusion Rapidarc technique can be used safely even for the treatment of childhood tumors, as the extent of normal tissue dose exposures and that of acute hematological side effects is not higher.
Molecular characterization of Leishmania tropica and Leishmania major from stray dogs and patients in Saudi Arabia
Authors: Alanazi Abdullah D , Alouffi Abdulazi S Alouffi S , Alyousif Mohamed S Alyousif S , Rahi Abdulsadah A , Ali Magada A , Brayner Fabio A , Mendoza-Roldan Jairo Alfonso , Otranto Domenico 
Published: February 2020

Abstract
Background: Leishmania major and Leishmania tropica cause cutaneous leishmaniasis in humans and dogs in several parts of the world, with a large number of cases recorded in the Middle East. However, when occurring in sympatry in the same area, the role of each species in the epidemiology of cutaneous leishmaniasis is not clear.Methods: To determine the prevalence and to identify the species of Leishmania that infect humans and stray dogs in Riyadh and Al-Qaseem (Saudi Arabia), blood samples were collected from stray dogs (n = 311) and human patients (n = 27). A conventional PCR coupled with a nested PCR (n PCR) were applied in this study.Results: A conventional PCR coupled with a nested PCR (n PCR) showed that seven patients (25.9%) from Riyadh city and Al-Qaseem province were infected by L. major and L. tropica and five dogs (1.6%) by L. tropica.Conclusions: This is one of the first molecular studies of leishmaniasis from Saudi Arabia. The relationship between the sand fly vectors and the reservoirs of both Leishmania spp. is still scarcely known in this region, and further epidemiological investigations of domestic and wild canine infected with L. major and L. tropica are needed towards a control and prevention of the infection in canine and human populations.
Open versus endoscopic carpal tunnel release: A systematic review and meta-analysis of randomized controlled trials
Authors: Li Yueying , Luo Wenqi , Wu Guangzhi , Cui Shusen , Gu Xiaossong , Zhang Zhan 
Published: February 2020

Abstract
Background Endoscopic carpal tunnel release (ECTR) and open carpal tunnel release (OCTR) both have advantages and disadvantages for the treatment of carpal tunnel syndrome (CTS). We compared the effectiveness and safety of ECTR and OCTR based on evidence from a high-level randomized controlled trial. MethodsWe comprehensively searched PubMed, EMBASE, Cochrane Library, Web of Science, and Medline to identify relevant articles published until August 2019. Data regarding operative time, grip strength, Boston Carpal Tunnel Questionnaire scores, digital sensation, patient satisfaction, key pinch strength, return to work time, and complications were extracted and compared. All mean differences (MD) and odds ratios (OR) were expressed as ECTR relative to OCTR. Results Twenty-eight studies were included in our meta-analysis. ECTR was associated with significantly higher satisfaction rates (MD, 3.13; 95% confidence interval [CI], 1.43 to 4.82; P = 0.0003), greater key pinch strengths (MD, 0.79 kg; 95% CI, 0.27 to 1.32; P = 0.003), earlier return to work times (MD, -7.25 days; 95% CI, -14.31 to -0.19; P = 0.04), higher transient nerve injury rates (OR, 4.87; 95% CI, 1.37 to 17.25; P = 0.01), and a lower incidence of scar-related complications (OR, 0.20; 95% CI, 0.07 to 0.59; P = 0.004). There were no significant differences between the two methods in terms of permanent nerve injury (OR, 1.93; 95% CI, 0.58 to 6.40; P = 0.28). Conclusions Overall, evidence from randomized controlled trials indicates that ECTR results in better recovery of daily life functions than OCTR, as revealed by higher satisfaction rates, greater key pinch strengths, earlier return to work times, and fewer scar-related complications. Our findings suggest that patients with CTS can be effectively managed with ECTR.
The Effect of Posterior Capsule Repair in Total Hip Arthroplasty: A Systematic Review and Meta-Analysis
Authors: Sun Xiaobo , Zhu Xingyang , Zeng Yuqing , Zhang Haitao , Zeng Jianchun , Feng Wenjun , Li Jie , Zeng Yirong 
Published: February 2020

Abstract
Background: Prior studies have compared the posterior capsule repair group in primary total hip arthroplasty by posterior approach with the control group without posterior capsule repair, suggesting that the posterior capsule repair group had better clinical outcomes. However, it is still a controversy which treatment is more helpful for hip diseases.The purpose of our article is to obtain the postoperative outcomes between the 2 procedures. Methods: We performed a systematic search by browsing the MEDLINE, EMBASE, Cochrane Library. There is no restriction on the date of publication. Before we submit our manuscript, we have re-searched the literatures again, including the articles which directly compared the postoperative outcomes of the 2 procedures. Results: A total of 8 comparative studies were included in our meta-analysis. The posterior capsule repair group showed less dislocation rate, higher HHS, and even less postoperative Bleeding volume, however, there is no significant difference in ROM between the 2 groups. Conclusion: In conclusion, according to the current evidence, repairing posterior capsule during primary THA may have better functional outcomes, less dislocation incidence, and less loss of blood.
Diagnostic acuuracy of cerebrospinal fluid and serum-isolated exosomes for glioblastoma: a systematic review and meta-analysis
Authors: Jafari Davod , Tiyuri Amir , Rezaei Elmnaz , Moradi Yousef , Jafari Rasool , Shoorijeh Farzaneh Jokar , Barati Mahmood 
Published: February 2020

Abstract
Glioblastoma (GBM) is the most malignant glioma cancer with a high morbidity and mortality worldwide. Unfortunately, a routine method is not available for screening or preoperative early detection of GBM. However, early detection in a none-invasive or minimally invasive method could be beneficial and increase the survival rate. In this systematic review and meta-analysis, we aimed to examine the diagnostic accuracy of exosomal RNAs that were extracted from patients’ CSF or serum for GBM diagnosis. We searched Web of Science, Scopus, PubMed (including Medline), Embase and ProQuest (as databases for grey literature) up to December 2019; we also performed backward and forward reference checking of included and relevant studies. Finally, included studies were assessed with QUADAS-2 checklist and their data extracted. We carried out a meta-analysis of included study, regarding to the diagnostic meta-analysis guidelines for obtaining pooled accuracy estimates. In addition, sensitivity analysis and meta-regression were also conducted. We retrived 1730 records from databases, nine of them included in systematic review and qualitative synthesis. Six studies were considered to statistical analysis and performed diagnostic meta-analysis. Our results suggested that the pooled sensitivity and specificity of exosomal biomarkers for GBM were 0.76 and 0.80, respectively. In addition, the pooled positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were 3.7, 0.30 and 12, respectively. The overall area under the curve (AUC) of exosomal biomarkers for GBM diagnosis was found to be 0.85. According to our results, the value of 0.85 for AUC, suggesting that exosomal biomarkers might serve as a high potential and non-invasive diagnostic tool for GBM.
Decreased expression of ubiquitin-specific protease 10 correlates unfavorable prognosis in colorectal cancer
Authors: Kim Kyungeun , Huh Tom , Park Yoonho , Koo Dong-Hoe , Kim Hungdai , Hwang Ilseon , Choi Chel Hun , Yi Joo Mi , Chung Joon-Yong 
Published: February 2020

Abstract
Background: Ubiquitin-specific proteases (USPs) play an important role in fundamental cellular processes. Among these, USP10 is known for its association with tumor development and progression of multiple cancers. Here, we found a potential link between USP10 and p14ARF in colorectal cancer.

Methods: USP10 and p14ARF protein expression was assessed via immunohistochemistry (IHC) on a tissue microarray from 280 colorectal cancer cases. IHC scores were evaluated by digital image analysis and compared with patients’ outcomes. In addition, we examined DNA hypermethylation in colorectal cancer cell lines and tissues, which were matched with adjacent normal colon samples.

Results: USP10 expression (USP10 loss ) was lost in 18.6% of samples (52/280 cases), which was linked to lymphovascular invasion ( p =0.019) and distant metastases ( p <0.001). Similarly, loss of p14ARF expression (p14ARF loss ) was associated with more advanced tumors. USP10 expression correlated positively with p14ARF expression ( r =0.617, p <0.001). USP10 loss , p14ARF loss , and loss of both USP10 and p14ARF (USP10 loss /p14ARF loss ) were significantly associated with shorter disease-free survival and overall survival in comparison to USP10 intact , p14ARF intact , and USP10 intact /p14ARF intact , respectively. Multivariate analysis revealed that USP10 loss (Hazard ratio=2.07, p =0.046) and USP10 loss /p14ARF loss (Hazard ratio=1.41, p =0.010) are independent prognostic factors for disease-free survival in colorectal cancer patients. Furthermore, aberrant hypermethylation of the USP10 promoter region was found in colorectal cancer cell lines and tissues.

Conclusions: The present results suggest that USP10 loss is a potential prognostic marker for colorectal cancer.