bluuebunny/crossref_metadata_2025_split huggingface dataset:
A machine learning framework for genotyping the structural variations with copy number variant
Authors: Zheng Tian , Zhu Xiaoyan , Zhang Xuanping , Zhao Zhongmeng , Yi Xin , Wang Jiayin , Li Hongle 
Published: August 2020

Abstract
Background
Genotyping of structural variation is an important computational problem in next generation sequence data analysis. However, in cancer genomes, the copy number variant(CNV) often coexists with other types of structural variations which significantly reduces the accuracy of the existing genotype methods. The bias on sequencing coverage and variant allelic frequency can be observed on a CNV region, which leads to the genotyping approaches that misinterpret the heterozygote as a homozygote. Furthermore, other data signals such as split mapped read, abnormal read will also be misjudged because of the CNV. Therefore, genotyping the structural variations with CNV is a complicated computational problem which should consider multiple features and their interactions.

Methods
Here we proposed a computational method for genotyping indels in the CNV region, which introduced a machine learning framework to comprehensively incorporate a set of data features and their interactions. We extracted fifteen kinds of classification features as input and different from the traditional genotyping problem, here the structure of variant may fall into types of normal homozygote, homozygous variant, heterozygous variant without CNV, heterozygous variant with a CNV on the mutated haplotype, and heterozygous variant with a CNV on the wild haplotype. The Multiclass Relevance Vector Machine (M-RVM) was used as a machine learning framework combined with the distribution characteristics of the features.

Results
We applied the proposed method to both simulated and real data, and compared it with the existing popular softwares include Gindel, Facets, GATK, and also compared with other machine learning cores: Support Vector Machine, Lanrange-SVM with OVO multiple classification, Naïve Bayes and BP Neural Network. The results demonstrated that the proposed method outperforms others on accuracy, stability and efficiency.

Conclusion
This work shows that the genotyping of structural variations on the CNV region cannot be solved as a traditional genotyping problem. More features should be used to efficiently complete the five-category task. According to the result, the proposed method can be a practical algorithm to correct genotype structural variations with CNV on the next generation sequence data. The source codes have been uploaded at https://github.com/TrinaZ/Mixgenotypefor academic usage only.
MicroRNA-214-3p inhibits the stem-like properties of lung squamous cell cancer by targeting YAP1
Authors: Lu Tingting , Yang Ying , Li Ziming , Lu Shun 
Published: August 2020

Abstract
Background
Emerging evidence reveals that microRNAs (miRNAs) play a crucial role in tumor progression, but the underlying mechanism of microRNAs in lung squamous cell cancer (LSCC) remains unclear.

Method
Western-blotting and quantitative real-time PCR (q-PCR) were carried out to detect mRNA and protein expression. Cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8), colony-forming assay or sphere-forming assay, respectively.

Results
MiR-214-3p was markedly de-regulated in LSCC tissues and was inversely related to the level of Yes-associated protein1 (YAP1), which is the core transcription regulator of the Hippo signaling pathway. Kaplan–Meier survival curves illustrated that patients with high miR-214-3p expression demonstrated more favorable clinical outcomes. MiR-214-3p overexpression (OE) repressed proliferation and cancer stem-like cells (CSCs) properties in vitro and in vivo xenograft mouse model. Mechanistically, luciferase activity assay revealed that miR-214-3p directly targets YAP1 by specifically binding on the 3′ UTR of YAP1.

Conclusion
MiR-214-3p plays a pivotal role in CSCs properties by targeting YAP1, which provides a potential treatment strategy for LSCC patients.
Efficacy of artemether-lumefantrine for treating uncomplicated Plasmodium falciparum cases and molecular surveillance of drug resistance genes in Western Myanmar
Authors: Wu Yanrui , Soe Myat Thut , Aung Pyae Linn , Zhao Luyi , Zeng Weilin , Menezes Lynette , Yang Zhaoqing , Kyaw Myat Phone , Cui Liwang 
Published: August 2020

Abstract
Background
Currently, artemisinin-based combination therapy (ACT) is the first-line anti-malarial treatment in malaria-endemic areas. However, resistance in Plasmodium falciparum to artemisinin-based combinations emerging in the Greater Mekong Sub-region is a major problem hindering malaria elimination. To continuously monitor the potential spread of ACT-resistant parasites, this study assessed the efficacy of artemether-lumefantrine (AL) for falciparum malaria in western Myanmar.

Methods
Ninety-five patients with malaria symptoms from Paletwa Township, Chin State, Myanmar were screened for P. falciparum infections in 2015. After excluding six patients with a parasite density below 100 or over 150,000/µL, 41 P. falciparum patients were treated with AL and followed for 28 days. Molecular markers associated with resistance to 4-amino-quinoline drugs (pfcrt and pfmdr1), antifolate drugs (pfdhps and pfdhfr) and artemisinin (pfk13) were genotyped to determine the prevalence of mutations associated with anti-malarial drug resistance.

Results
For the 41 P. falciparum patients (27 children and 14 adults), the 28-day AL therapeutic efficacy was 100%, but five cases (12.2%) were parasite positive on day 3 by microscopy. For the pfk13 gene, the frequency of NN insert after the position 136 was 100% in the day-3 parasite-positive group as compared to 50.0% in the day-3 parasite-negative group, albeit the difference was not statistically significant (P = 0.113). The pfk13 K189T mutation (10.0%) was found in Myanmar for the first time. The pfcrt K76T and A220S mutations were all fixed in the parasite population. In pfmdr1, the Y184F mutation was present in 23.3% of the parasite population, and found in both day-3 parasite-positive and -negative parasites. The G968A mutation of pfmdr1 gene was first reported in Myanmar. Prevalence of all the mutations in pfdhfr and pfdhps genes assessed was over 70%, with the exception of the pfdhps A581G mutation, which was 3.3%.

Conclusions
AL remained highly efficacious in western Myanmar. Pfk13 mutations associated with artemisinin resistance were not found. The high prevalence of mutations in pfcrt, pfdhfr and pfdhps suggests high-degree resistance to chloroquine and antifolate drugs. The pfmdr1 N86/184F/D1246 haplotype associated with selection by AL in Africa reached > 20% in this study. The detection of > 10% patients who were day-3 parasite-positive after AL treatment emphasizes the necessity of continuously monitoring ACT efficacy in western Myanmar.
The value of local consolidative therapy in Osimertinib-treated non-small cell lung cancer with oligo-residual disease
Authors: Zeng Ya , Ni Jianjiao , Yu Fan , Zhou Yue , Zhao Yang , Li Shuyan , Guo Tiantian , Chu Li , Yang Xi , Chu Xiao , Cai Xuwei , Zhu Zhengfei 
Published: August 2020

AbstractBackgroundThere was no study investigating real-world utilization and outcome of LCT in Osimertinib-treated NSCLC with oligo-residual disease. This study was to analyze the clinical value of local consolidative therapy (LCT) in Osimertinib-treated non-small cell lung cancer (NSCLC) patients with oligo-residual disease.MethodsPatients receiving standard Osimertinib treatment and developing oligo-residual disease (five or fewer residual metastatic lesions) were retrospectively reviewed. Local therapies performed to the oligo-residual tumor lesions or primary lung site before Osimertinib treatment failure were considered as LCT.ResultsOf 108 patients recruited, first-line and second-line Osimertinib were administered in 25 and 83 patients, respectively, while LCT was performed in 14 patients. With a median follow-up of 43.6 months, 69 patients developed progressive disease. LCT significantly improved progression-free survival (PFS) (NR vs 12.8 months,p = 0.01) and was independently associated with prolonged PFS (HR = 0.29, 95%CI 0.12 to 0.68,p = 0.004). Patients receiving LCT had a numerically longer overall survival (OS) (85.8 vs 77.1 months,p = 0.58) and after adjusting for potentially confounding factors, LCT was associated with a non-significantly prolonged OS (HR = 0.37, 95%CI 0.12–1.16,p = 0.089). Pattern of failure analyses indicated that progressive disease developed at the originally existed oligo-residual lesions in 76.2% of the 63 patients who didn’t receive LCT and had Osimertinib treatment failure. Of note, 7 (70%) of the 10 patients who had oligo-residual cranial disease but didn’t receive LCT, developed more than five progressive lesions in the brain, which were no longer suitable for stereotactic radiosurgery.ConclusionAmong Osimertinib-treated NSCLC patients having oligo-residual lesions, LCT could improve local control and significantly increase PFS, which need to be verified by further investigations.
The relationship between ACL reconstruction and meniscal repair: quality of life, sports return, and meniscal failure rate—2- to 12-year follow-up
Authors: Rodríguez-Roiz Juan M. , Sastre-Solsona Sergi , Popescu Dragos , Montañana-Burillo Jordi , Combalia-Aleu Andres 
Published: August 2020

Abstract
Background
Few studies have approached in a long-term follow-up of meniscal repair at an amateur level, specially studying variables as a quality of life and failure rate. The purpose of this review is to study medium to long-term clinical results in patients at amateur sports patients, that have required meniscal sutures at our center, with or without ACL reconstruction. We evaluate the objective function of the knee, as well as patients’ return to sports activities, quality of life, and the rate of failed repair and study of the possible reasons.

Methods
This was an observational retrospective study. Ninety-two patients who regularly perform amateur sports activities (Tegner 4 to 7) were assessed, with a minimum follow-up period of 2 years, divided into 2 groups: group 1, isolated meniscal suture (43 cases) and group 2, associated to ACL reconstruction (49 cases). Each patient made this test in 2019: Lysholm and Tegner (validated for Spanish) before a knee injury and after surgery, motivation to return to sports activity (Likert scale with 3 items: low, regular, or high), and quality of life through SD-12 test.

Results
High return to amateur sports rate (92%) was even higher in the isolated meniscal repair group in comparison to the group with associated ACL. We have not found statistically significant differences between sports return and age, gender, injured meniscus, chondral injuries, preoperative Tegner score, or motivation. No significant differences in physical or mental health fields between both groups. Meniscal repair failed in 12 patients (13%). Higher rate of failure in isolated bucket-handle tear injuries (p < 0.0062). No statistically significant association was found between the other variables studied.

Conclusions
Good results with 92% of sports return, low rate of complications, and low retear rate, even lower when is associated with ACL reconstruction and in external meniscus repair, and high values at SF-12 between 2 groups.
The lateral habenula is critically involved in histamine-induced itch sensation
Authors: Ko Hyoung-Gon 
Published: August 2020

AbstractLateral habenula (LHb) is a brain region acting as a hub mediating aversive response against noxious, stressful stimuli. Growing evidences indicated that LHb modulates aminergic activities to induce avoidance behavior against nociceptive stimuli. Given overlapped neural circuitry transmitting pain and itch information, it is likely that LHb have a role in processing itch information. Here, we examined whether LHb is involved in itchy response induced by histamine. We found that histamine injection enhances Fos (+) cells in posterior portion within parvocellular and central subnuclei of the medial division (LHbM) of the LHb. Moreover, chemogenetic suppression of LHbM reduced scratching behavior induced by histamine injection. These results suggest that LHb is required for processing itch information to induce histaminergic itchy response.
miRNA expression profile changes in the peripheral blood of monozygotic discordant twins for epithelial ovarian carcinoma: potential new biomarkers for early diagnosis and prognosis of ovarian carcinoma
Authors: Tuncer Seref Bugra , Erdogan Ozge Sukruoglu , Erciyas Seda Kilic , Saral Mukaddes Avsar , Celik Betul , Odemis Demet Akdeniz , Turkcan Gozde Kuru , Yazici Hulya 
Published: August 2020

AbstractBackgroundOvarian cancer is the second most common gynecologic cancer with high mortality rate and generally diagnosed in advanced stages. The 5-year disease-free survival is below 40%. MicroRNAs, subset of the non-coding RNA molecules, regulate the translation in post transcriptional level by binding to specific mRNAs to promote or degrade the target oncogenes or tumor suppressor genes. Abnormal expression of miRNAs were found in numerous human cancer, including ovarian cancer. Investigating the miRNAs derived from the peripheral blood samples can be used as a marker in the diagnose, treatment and prognosis of ovarian cancer. We aimed to find biological markers for early diagnosis of ovarian cancer by investigating BRCA1 gene mutation carrier monozygotic discordant twins and their high risk healthy family individual’s miRNAs.MethodsThe study was conducted on monozygotic twins discordant for ovarian cancer, and the liquid biopsy exploration of miRNAs was performed on mononuclear cells that were isolated from the peripheral blood samples. The miRNA expression profile changes in the study were found by using microarray analysis. miRNA isolation procedure performed from the lymphocyte in accordance with the kit protocol. The presence and quality of the isolated miRNAs screened by electrophoresis. Raw data logarithmic analysis was studied by identifying the threshold, normalization, correlation, mean and median values. Target proteins were detected for each miRNA by using different algorithms.ResultsAfter the comparison of monozygotic discordant twins for epithelial ovarian carcinoma upregulation of the 4 miRNAs, miR-6131, miR-1305, miR-197-3p, miR-3651 and downregulation of 4 miRNAs, miR-3135b, miR-4430, miR-664b-5p, miR-766-3p were found statically significant.ConclusionsThe detected 99 miRNAs out of 2549 miRNAs might be used in the clinic as new biological indicators in the diagnosis and follow up of epithelial ovarian cancer with complementary studies. ThemiRNA expressionprofiles were identified to be statistically significant in the evaluation of ovarian cancer etiology, BRCA1 mutation status, and ovarian cancer risk in accordance with the obtained data.There is a need for validation of the miRNAs which were particularly detected between monozygotic twins and its association with ovarian cancer was emphasized in our study in wider cohorts including ovarian cancer patients, and healthy individuals.
The receptor binding domain of SARS-CoV-2 spike protein is the result of an ancestral recombination between the bat-CoV RaTG13 and the pangolin-CoV MP789
Authors: Flores-Alanis Alejandro , Sandner-Miranda Luisa , Delgado Gabriela , Cravioto Alejandro , Morales-Espinosa Rosario 
Published: August 2020

Abstract
Objective
In December 2019 a novel coronavirus (SARS-CoV-2) that is causing the current COVID-19 pandemic was identified in Wuhan, China. Many questions have been raised about its origin and adaptation to humans. In the present work we performed a genetic analysis of the Spike glycoprotein (S) of SARS-CoV-2 and other related coronaviruses (CoVs) isolated from different hosts in order to trace the evolutionary history of this protein and the adaptation of SARS-CoV-2 to humans.

Results
Based on the sequence analysis of the S gene, we suggest that the origin of SARS-CoV-2 is the result of recombination events between bat and pangolin CoVs. The hybrid SARS-CoV-2 ancestor jumped to humans and has been maintained by natural selection. Although the S protein of RaTG13 bat CoV has a high nucleotide identity with the S protein of SARS-CoV-2, the phylogenetic tree and the haplotype network suggest a non-direct parental relationship between these CoVs. Moreover, it is likely that the basic function of the receptor-binding domain (RBD) of S protein was acquired by the SARS-CoV-2 from the MP789 pangolin CoV by recombination and it has been highly conserved.
Aspirin mediates histone methylation that inhibits inflammation-related stemness gene expression to diminish cancer stemness via COX-independent manner
Authors: Zhang Xiaoyuan , Du Renle , Luo Na , Xiang Rong , Shen Wenzhi 
Published: August 2020

Abstract
Background
The widely recognized anti-cancer potential of aspirin has created a broad interest to explore the clinical benefits of aspirin in cancer therapy. However, the current understanding of the molecular mechanisms involved in the anti-cancer potential of aspirin remains limited.

Methods
Cancer stemness assays which contained ALDH, side population, chemo-resistance, sphere formation, and tumorigenesis were performed to validate aspirin function in vitro and in vivo. Histone modification assay was performed to check the effect of aspirin on histone methylation as well as the activity of HDAC and KDM6A/B. Inhibitor in vivo assay was performed to evaluate therapeutic effects of various inhibitor combination manners.

Results
In regards to in vitro studies, aspirin diminishes cancer cell stemness properties which include reducing the ALDH+ subpopulation, side population, chemo-resistance, and sphere formation in three cancer types. In regards to in vivo studies, aspirin decreases tumor growth and metastasis and prolongs survival. In addition, our results showed that aspirin inhibits inflammation-related stemness gene expression (especially ICAM3) identified by a high-throughput siRNA platform. In regards to the underlying molecular mechanism of action, aspirin reduces histone demethylase (KDM6A/B) expression that mediates histone methylation and suppresses gene expression via a COX-independent manner. In regards to therapeutic strategies, aspirin combined HDM inhibitors, ICAM3 downstream signaling Src/PI3K inhibitors, or ICAM3 inhibitor Lifitigrast prevents cancer progression in vivo.

Conclusions
The aforementioned findings suggest a molecular model that explains how aspirin diminishes cancer cell stemness properties. These findings may provide novel targets for therapeutic strategies involving aspirin in the prevention of cancer progression.
Extracellular vesicles derived from mesenchymal stromal cells mitigate intestinal toxicity in a mouse model of acute radiation syndrome
Authors: Accarie Alison , l’Homme Bruno , Benadjaoud Mohamed Amine , Lim Sai Kiang , Guha Chandan , Benderitter Marc , Tamarat Radia , Sémont Alexandra 
Published: August 2020

Abstract
Background
Human exposure to high doses of radiation resulting in acute radiation syndrome and death can rapidly escalate to a mass casualty catastrophe in the event of nuclear accidents or terrorism. The primary reason is that there is presently no effective treatment option, especially for radiation-induced gastrointestinal syndrome. This syndrome results from disruption of mucosal barrier integrity leading to severe dehydration, blood loss, and sepsis. In this study, we tested whether extracellular vesicles derived from mesenchymal stromal cells (MSC) could reduce radiation-related mucosal barrier damage and reduce radiation-induced animal mortality.

Methods
Human MSC-derived extracellular vesicles were intravenously administered to NUDE mice, 3, 24, and 48 h after lethal whole-body irradiation (10 Gy). Integrity of the small intestine epithelial barrier was assessed by morphologic analysis, immunostaining for tight junction protein (claudin-3), and in vivo permeability to 4 kDa FITC-labeled dextran. Renewal of the small intestinal epithelium was determined by quantifying epithelial cell apoptosis (TUNEL staining) and proliferation (Ki67 immunostaining). Statistical analyses were performed using one-way ANOVA followed by a Tukey test. Statistical analyses of mouse survival were performed using Kaplan-Meier and Cox methods.

Results
We demonstrated that MSC-derived extracellular vesicle treatment reduced by 85% the instantaneous mortality risk in mice subjected to 10 Gy whole-body irradiation and so increased their survival time. This effect could be attributed to the efficacy of MSC-derived extracellular vesicles in reducing mucosal barrier disruption. We showed that the MSC-derived extracellular vesicles improved the renewal of the small intestinal epithelium by stimulating proliferation and inhibiting apoptosis of the epithelial crypt cells. The MSC-derived extracellular vesicles also reduced radiation-induced mucosal permeability as evidenced by the preservation of claudin-3 immunostaining at the tight junctions of the epithelium.

Conclusions
MSC-derived extracellular vesicles promote epithelial repair and regeneration and preserve structural integrity of the intestinal epithelium in mice exposed to radiation-induced gastrointestinal toxicity. Our results suggest that the administration of MSC-derived extracellular vesicles could be an effective therapy for limiting acute radiation syndrome.
Triple nostrils in a calf
Authors: Tsuka Takeshi , Saito Ai , Okamoto Yoshiharu , Sunden Yuji , Morita Takehito , Nishimura Ryo , Murahata Yusuke , Azuma Kazuo , Yamashita Masamichi , Osaki Tomohiro , Ito Norihiko , Imagawa Tomohiro 
Published: August 2020

Abstract
Background
Nasal abnormalities are rare in bovines. In humans, nasal deformities are mainly classified as proboscis lateralis or supernumerary nostrils. This report discusses the etiology of triple nostrils in a calf, based on computed tomography, magnetic resonance imaging, and endoscopy.

Case presentation
A female Holstein calf presented with triple nostrils. The following abnormalities were observed: (1) formation of a small and flat blind-ended middle nostril between the right and left nostrils; (2) presence of a hair-bearing surface on the muzzle; (3) abnormal curvature of the nasal septum, resulting in a narrower right nasal cavity due to transformation of the nasal bones; and (4) formation of a bone-like structure within the nasal septum. These findings were similar to those of supernumerary nostrils in humans.

Conclusions
To the best of our knowledge, this represents the first description of a calf with triple nostrils. The use of imaging modalities is necessary for investigating the etiology of triple nostrils.