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: November 2019

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. the sequence of Codanin-1 protein does not resemble any known protein.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.
The DNA hypermethylation phenotype of colorectal cancer liver metastases resembles that of the primary colorectal cancers.
Authors: Orjuela Stephany , Menigatti Mirco , Schraml Peter , Kambakamba Patryk , Robinson Mark D. , Marra Giancarlo 
Published: November 2019

Abstract
Background: Identifying molecular differences between primary and metastatic colorectal cancers—now possible with the aid of omics technologies—can improve our understanding of the biological mechanisms of cancer progression and facilitate the discovery of novel treatments for late-stage cancer. We compared the DNA methylomes of primary colorectal cancers (CRCs) and CRC metastases to the liver. Laser microdissection was used to obtain epithelial tissue (10 to 25 x 106 µm2) from sections of fresh-frozen samples of primary CRCs (n=6), CRC liver metastases (n=12), and normal colon mucosa (n=3). DNA extracted from tissues was enriched for methylated sequences with a methylCpG binding domain (MBD) polypeptide-based protocol and subjected to deep sequencing. The performance of this protocol was compared with that of targeted enrichment for bisulfite sequencing used in a previous study of ours.
Results: MBD enrichment captured a total of 322,551 genomic regions (249.5 Mb of the genome) that included over seven million CpG sites. A few of these regions were differentially methylated at an expected false discovery rate (FDR) of 5% in neoplastic tissues (primaries: 0.67%, i.e., 2155 regions containing 279,441 CpG sites; liver metastases: 1%, i.e., 3223 regions containing 312,723 CpG sites) as compared with normal mucosa samples. Most of the differentially methylated regions (DMRs; 94% in primaries; 70% in metastases) were hypermethylated, and almost 80% of these (1882 of 2396) were present in both lesion types. At 5% FDR, no DMRs were detected in liver metastases vs. primary CRC. However, short regions of low-magnitude hypomethylation were frequent in metastases but rare in primaries. Hypermethylated DMRs were far more abundant in sequences classified as intragenic, gene-regulatory, or CpG shelves-shores-island segments, whereas hypomethylated DMRs were equally represented in extragenic (mainly, open-sea) and intragenic (mainly, gene bodies) sequences of the genome. Compared with targeted enrichment, MBD capture provided a better picture of the extension of CRC-associated DNA hypermethylation but was less powerful for identifying hypomethylation.
Conclusions: Our findings demonstrate that the hypermethylation phenotype in CRC liver metastases remains similar to that of the primary tumor, whereas CRC-associated DNA hypomethylation probably undergoes further progression after the cancer cells have migrated to the liver.
Prognostic value of C-reactive protein/albumin ratio in renal cell carcinoma: a systematic review and meta-analysis
Authors: song hualin , xiang Peng , liu Zhifu , hu shuai , Jin Jie 
Published: November 2019

Abstract
Background: There are a mass of studies declared the prognostic significance of C-reactive protein/albumin ratio (CRP/Alb) in renal cell carcinoma (RCC). Nevertheless, these works are controversial. In our study, we investigate the expression of CRP/Alb in RCC and its role in prognosis and clinicopathological features.
Methods: The PubMed, Embase and Cochrane databases were searched systematically for correlative articles published before August 1, 2019. Hazard ratios (HRs) and 95% confidence intervals (CIs) were determined according to eligible studies. And we use fixed and random effects models to calculate on the basis of heterogeneity.
Results: Six relevant studies were identified in this study, 1959 participants included in total. Our results showed that CRP/Alb was related to poor overall survival (HR=1.86, 95% CI: 1.56-2.21). In addition, CRP/Alb was also associated with tumor stage (OR=3.29, 95% CI: 1.66-6.50), lymph node involvement (OR=3.76, 95% CI: 2.57-5.51), metastasis (OR=5.69, 95% CI: 2.40-13.51), Fuhrman nuclear grade (OR=4.21, 95% CI: 3.14-5.64), pTNM (OR=4.34, 95% CI: 1.94-9.70) and tumor size (WMD=2.26, 95% CI: 1.86–2.67). However, CRP/Alb was not associated with necrosis.
Conclusion: Our study illustrates that the higher CRP/Alb expression was correlated with poorer prognosis and more advanced clinicopathological features in RCC patients. High CRP/Alb expression may act as a valuable predictive biomarker for poor prognosis in RCC patients.
Molecular Characterization of Prostate Cancer in Middle Eastern Population Highlights Differences with Western Populations with Prognostic Implication
Authors: Abdelsalam Ramy A. , Khalifeh Ibrahim , Box Alan , Kalantarian Maria , Ghosh Sunita , Abou-Ouf Hatem , Lotfi Tamara , Shahait Mohammed , Palanisamy Nallasivam , Bismar Tarek A. 
Published: November 2019

Abstract
Background To investigate the incidence and prognostication of ERG, PTEN and SPINK1 protein expressions in prostate cancer cohort of Middle Eastern descent in comparison to published data from Western populationMethods Immunohistochemistry for ERG, PTEN and SPINK1 was performed in cohort of localized PCa (n=340). Data correlated to pathological and clinical outcomes and compared to Western populations.Results ERG expression and PTEN loss noted in 123/288 (42.7%) and 91/297 (30.6%) of patients, respectively. SPINK1 expression assessed in subset of cases, noted in 6/150 (4%) of patients. Only ERG expression was associated with grade groups, being more common in lower grade groups (1-3 vs 4-5; p=0.04). In contrast to Western population, PTEN loss foci were more likely to be ERG negative, observed in 81% of tumor foci and patients with PTEN neg/ERG pos were more likely to exhibit biochemical recurrence (OR 2.831; 95% CI: 1.10-726, p=0.03). This association remained significant in multivariate analysis (OR 2.68; 95% CI: 0.98-7.33, p=0.05), after adjusting for GG, path stage and surgical margin.Conclusion This study documents significant differences in key molecular events in PCa in Middle Eastern population compared to Western populations that could explain differences in PCa incidence, progression and prognostication. ERG, PTEN and SPINK1 genomic alteration occur less frequently and the enrichment of ERG for PTEN loss is not observed. Additionally, patients with combined PTEN loss/ERG positive are at highest rate for BCR vs North American Caucasian population where PTEN loss alone seems to be associated with the worst clinical outcome. The data presented here further support differences in clonal evolution between Middle Eastern and Western population in relation to PCa and add further insight to understanding PCa molecular pathways.
Value of digital mammography in predicting lymphovascular invasion of breast cancer
Authors: Liu Zhuangsheng , Li Ruqiong , Liang Keming , Chen Junhao , Chen Xiangmeng , Li Xiaoping , Li Ronggang , Zhang Xin , Yi Lilei , Long Wansheng 
Published: November 2019

Abstract
Background: To use digital mammography, a more popular imaging tool, for predicting lymphovascular invasion(LVI) in breast cancer patients preoperatively.
Methods: 122 cases of invasive ductal carcinoma diagnosed between May 2017 and September 2018 were collected, which were divided into positive group (n=42) and negative group (n=80) according to the presence or absence of LVI.
Results: The differences of these variables(childbearing history, miscarriage history, other breast diseases history, nipple discharge, breast cancer marker CA153, age, ER, PR, HER-2, E-CAD, P53, Ki-67) between LVI positive group and the LVI negative group were not statistically significant, except that of Ki-67 (P=0.012). For the image features of digital mammography, the differences of interstitial edema (P=0.013) and skin thickening (P=0.000) between LVI positive group and negative groups were statistically significant. The differences of other imaging patterns, that is, fibroglandular tissue density, size , solitary/multiple, mass shape, mass margin , subcutaneous fat, axillary adenopathy and so on, between the two groups were not statistically significant. Multiple factor analysis shows that, there are three independent risk factors for predicting LVI occurrence: interstitial edema (OR = 12.610, 95% confidence interval CI: 1.061, 149.922, P=0.045), subcutaneous fat (OR=0.081, 95% confidence interval CI: 0.012, 0.645, P =0.017) and skin thickening (OR=9.041, 95% confidence interval CI: 2.553, 32.022, P=0.001).
Conclusion: Interstitial edema, blurring of subcutaneous fat layer, and skin thickening were independent risk factors for predicting LVI occurrence. When applying these three imaging patterns together, the specificity of LVI prediction was as high as 98.8%.
Sonochemistry in Transition Metal Catalyzed Cross-coupling Reactions: Recent Developments
Authors: Ujwaldev Sankuviruthiyil M. , Rohit K. R. , Radhika Sankaran , Anilkumar Gopinathan 
Published: November 2019

:
Transition metal catalyzed cross-coupling reactions have always been very important
in synthetic organic chemistry due to their versatility in forming all sorts of carbon-carbon
and carbon-hetero atom bonds. Incorporation of ultrasound assistance to these protocols resulted
in milder reaction conditions, faster reaction rates, etc. This review focuses on the contributions
made by ultrasound-assisted protocols towards transition metal catalyzed crosscoupling
reactions.
Hierarchical Extension Based on the Boolean Matrix for LncRNA-Disease Association Prediction
Authors: Tang Lin , Liang Yu , Jin Xin , Liu Lin , Zhou Wei 
Published: November 2019

Background:Accumulating experimental studies demonstrated that long non-coding RNAs (LncRNAs) play crucial roles in the occurrence and development progress of various complex human diseases. Nonetheless, only a small portion of LncRNA–disease associations have been experimentally verified at present. Automatically predicting LncRNA–disease associations based on computational models can save the huge cost of wet-lab experiments.Methods and Result:To develop effective computational models to integrate various heterogeneous biological data for the identification of potential disease-LncRNA, we propose a hierarchical extension based on the Boolean matrix for LncRNA-disease association prediction model (HEBLDA). HEBLDA discovers the intrinsic hierarchical correlation based on the property of the Boolean matrix from various relational sources. Then, HEBLDA integrates these hierarchical associated matrices by fusion weights. Finally, HEBLDA uses the hierarchical associated matrix to reconstruct the LncRNA– disease association matrix by hierarchical extending. HEBLDA is able to work for potential diseases or LncRNA without known association data. In 5-fold cross-validation experiments, HEBLDA obtained an area under the receiver operating characteristic curve (AUC) of 0.8913, improving previous classical methods. Besides, case studies show that HEBLDA can accurately predict candidate disease for several LncRNAs.Conclusion:Based on its ability to discover the more-richer correlated structure of various data sources, we can anticipate that HEBLDA is a potential method that can obtain more comprehensive association prediction in a broad field.
CDK12 Promotes Breast Cancer Progression and Maintains Stemness by Activating c-myc/β -catenin Signaling
Authors: Peng Fang , Yang Chuansheng , Kong Yanan , Huang Xiaojia , Chen Yanyu , Zhou Yangfan , Xie Xinhua , Liu Peng 
Published: November 2019

Background:
CDK12 is a promising therapeutic target in breast cancer with an effective
ability of maintaining cancer cell stemness.

Objective:
We aim to investigate the mechanism of CDK12 in maintaining breast cancer stemness.

Methods:
CDK12 expression level was accessed by using RT-qPCR and IHC. CDK12-altered breast
cancer cell lines MDA-MB-231-shCDK12 and SkBr-3-CDK12 were then established. CCK8, colony
formation assays, and xenograft model were used to value the effect of CDK12 on tumorigenicity.
Transwell assay, mammosphere formation, FACS, and lung metastasis model in vivo were determined.
Western blot further characterized the mechanism of CDK12 in breast cancer stemness
through the c-myc/β-catenin pathway.

Results:
Our results showed a higher level of CDK12 exhibited in breast cancer samples. Tumor
formation, cancer cell mobility, spheroid forming, and the epithelial-mesenchymal transition will be
enhanced in the CDK12high group. In addition, CDK12 was associated with lung metastasis and
maintained breast cancer cell stemness. CDK12high cancer cells presented higher tumorigenicity and
a population of CD44+ subset compared with CDK12low cells. Our study demonstrated c-myc positively
expressed with CDK12. The c-myc/β-catenin signaling was activated by CDK12, which is a
potential mechanism to initiate breast cancer stem cell renewal and may serve as a potential biomarker
of breast cancer prognosis.

Conclusion:
CDK12 overexpression promotes breast cancer tumorigenesis and maintains the
stemness of breast cancer by activating c-myc/β-catenin signaling. Inhibiting CDK12 expression
may become a potential therapy for breast cancer.
Effectiveness of Stem Cell Therapy in the Treatment of Ovarian Disorders and Female Infertility: A Systematic Review
Authors: Ahmadian Shahin , Mahdipour Mahdi , Pazhang Mohammad , Sheshpari Sepideh , Mobarak Halimeh , Bedate Alberto Miranda , Rahbarghazi Reza , Nouri Mohammad 
Published: November 2019

Background:
Infertility is a major problem worldwide. Various strategies are being used to
develop better treatments for infertility and The most trending strategy is the stem cell therapy. In this
study, the literature on stem cell therapy for ovarian disorders is summarized with analysis of current
developments.

Objective:
Different published studies on stem cell-based therapy for the treatment of various types of
ovarian insufficiency and disorders such as Premature Ovarian Insufficiency (POI) in the affected female
population in animal or human clinical studies are systematically reviewed.

Method:
We monitored five databases, including PubMed, Cochrane, Embase, Scopus, and ProQuest.
A comprehensive online search was done using the criteria targeting the application of stem cells in
animal models for menopause. Two independent reviewers carefully evaluated titles and abstracts of
studies. The stem cell type, source, dosage, route of administration were highlighted in various POI
animals models. Non-relevant and review articles were excluded.

Outcomes:
648 published studies were identified during the initial comprehensive search process from
which 41 were selected according to designed criteria. Based on our analysis, stem cells could accelerate
ovarian tissues rejuvenation, regulate systemic sex-related hormones levels and eventually increase
fertility rate.

Conclusion:
The evidence suggests that stem cell-based therapies could be considered as an alternative
modality to deal with women undergoing POI.
A Comparative Analysis of Bark and Leaf Essential Oil and their Chemical Composition, Antioxidant, Anti-inflammatory, Antimicrobial Activities and Genotoxicity of North East Indian Cinnamomum zeylanicum Blume
Authors: Gogoi Roktim , Sarma Neelav , Loying Rikraj , Pandey Sudin Kumar , Begum Twahira , Lal Mohan 
Published: November 2019

Background:
Cinnamomum zeylanicum Blume ( Lauraceae) bark and leaf essential oil
possesses eugenol as the major component. Both the essential oils have the potential antioxidant, anti-
inflammatory, antimicrobial and negligible genotoxicity.

Objective:
A comparative chemical composition and biological evaluation of Cinnamomum zeylanicum
Blume, bark and leaf essential oils, originated from North-East India has been investigated in
the present study.

Methods:
Gas chromatography/mass spectroscopy analysis was used to investigate the chemical
composition of the essential oil samples. DPPH free radical scavenging activity, and reducing power
assay were used for antioxidant activity evaluation. Similarly, egg albumin denaturation assay, protease
inhibitory activities were used for anti-inflammatory activity, while genotoxicity was evaluated
by using Allium cepa assay and antimicrobial activities using disc diffusion and minimum inhibitory
concentration assay.

Results:
The GC/MS results showed that eugenol is the major component of C. zeylanicum bark
(84.48%) and leaf (48.78 %) essential oil. Significant antioxidant activity was observed for both essential
oils in the DPPH free radical scavenging assay (IC50= 103.2 μg/mL, bark; IC50= 234.7
μg/mL, leaf), and reducing power assay (absorbance of 1.802 nm, 0.907 nm in 48 μg/mL for bark
and leaf essential oil respectively). In-vitro anti-inflammatory activity revealed strong potential of
leaf essential oil (protein denaturation assay, IC50= 0.05279 μg/mL; protease inhibitory activity
IC50= 3.607 μg/mL) in comparison to bark essential oil (protein denaturation assay IC50= 0.1491,
protease inhibitory activity IC50= 61.06). Allium cepa root growth test, mitotic index, and chromosomal
aberration test were performed to investigate the genotoxicity of C. zeylanicum bark and leaf
essential oil, which resulted in no toxic nature of both the essential oils. Antimicrobial activity
against eight bacterial and fungal strains revealed good antimicrobial properties with the MIC value
of Staphylococcus aureus at 5 μL/mL (bark), Aspergillus niger at 2.5 μL/mL (bark); Bacillus cereus
at 5 μL/mL (leaf) and Aspergillus niger at 2.5 μL/mL (leaf).

Conclusion:
Collectively, these findings indicated the strong biological potential of both essential
oils, although bark essential possesses better biological activities than the leaf essential oil and could
be used in the food and beverage industries.
A Swinging and Self-Actuating Friction Drive Device Used in Large-Scale Rotary Devices
Authors: Chen Desheng , Xu Qiaoning 
Published: November 2019

Background:
Large-scale rotary devices often employ friction drives in order to be manufactured
easily and usually select a large driving radius to reduce the friction forces needed. In traditional
devices, the driver and driven friction wheels are required to be of higher roundness to avoid slipping
between them. This makes the driven friction wheel difficult to be machined. In addition, generating
adequate contact load between contacting surfaces is essential for friction drives, and the best way to
achieve it is self-actuating loading.

Objective:
The purpose of this paper is to propose and analyze a patent about a new friction drive device,
in which the driver friction wheel can roll along with the driven friction wheel throughout, and the
contact load between the driver and driven friction wheels can be generated on the torque demand.

Methods:
By using two swinging gearboxes, the two driver friction wheels are both swinging, and thus
both can roll along with the driven friction wheel floatingly. Therefore, the driven wheel can have some
deviation in roundness. Besides, this design offers a condition to construct a torque-actuated loading
mechanism. Driven by the input torque, each driver wheel turns and exerts a friction force on the driven
wheel, and then the driven wheel applies a reactive force to each driver wheel. This reactive force tends
to pull the driver wheel to the driven wheel, producing a wedging action. Thus, an appreciable amount
of contact load between the driver and driven wheels will be generated.

Results:
The results show the contact load between the driver and driven friction wheels is directly
proportional to the resistant torque acting on the friction drive device. The results also show that a “frictional
locking” condition for the device to avoid slipping between the driver and driven friction wheels
is needed and it depends on the geometric parameters of the device.

Conclusion:
A swinging and self-actuating friction drive device is developed by using two swinging
gearboxes. Design principles were described and a design example for this friction drive device was
demonstrated. This kind of friction drive device not only offers an alternative way to drive large-scale
rotary devices, but also develops a new method to realize self-actuating loading for friction drives.
A Novel Encryption of Text Messages Using Two Fold Approach
Authors: Sivakumar T. , Veeramani S. , Pandi M. , Gopal G. 
Published: November 2019

Background:
The amount of digital data created and shared via internet has been increasing
every day. The number of security threats has also increased due to the vulnerabilities present in
the network hardware and software. Cryptography is the practice and study of techniques to secure
communication in the presence of third parties. Though there are several cryptosystems to secure the
information, there is a necessity to introduce new methods in order to protect information from the
attackers.

Objective:
To propose a new encryption method using Binary Tree Traversal (BTT) and XOR operation
to protect the text messages.

Methods:
The proposed method uses both transposition and substitution techniques for converting
plaintext into ciphertext. The notion binary tree traversal is adapted as transposition and bitwise
XOR operation is used for substitution.

Results:
The repeating letters appeared in the plaintext are replaced with different cipher letters and
placed on different location in the cipher text. Hence, it is infeasible to identify the plaintext message
easily. The time taken by the proposed method for encryption is very less.

Conclusion:
A simple encryption method using binary tree traversals and XOR operation is developed.
Encrypting data using binary tree traversals is a different way while compared with other traditional
encryption methods. The proposed method is fast, secure and can be used to encrypt short
messages in real time applications.