bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of methylation-driven genes prognosis signature and immune microenvironment in uterus corpus endometrial cancer
Authors: Liu JinHui , Ji ChengJian , Wang Yichun , Zhang Cheng , Zhu HongJun 
Published: July 2021

Abstract
Background
Uterus corpus endometrial cancer (UCEC) is the main malignant tumor in gynecology, with a high degree of heterogeneity, especially in terms of prognosis and immunotherapy efficacy. DNA methylation is one of the most important epigenetic modifications. Studying DNA methylation can help predict the prognosis of cancer patients and provide help for clinical treatment. Our research aims to discover whether abnormal DNA methylation can predict the prognosis of UCEC and reflect the patient's tumor immune microenvironment.

Patients and methods
The clinical data, DNA methylation data, gene expression data and somatic mutation data of UCEC patients were all downloaded from the TCGA database. The MethylMix algorithm was used to integrate DNA methylation data and mRNA expression data. Univariate Cox regression analysis, Multivariate Cox regression analysis, and Lasso Cox regression analysis were used to determine prognostic DNA methylation-driven genes and to construct an independent prognostic index (MDS). ROC curve analysis and Kaplan–Meier survival curve analysis were used to evaluate the predictive ability of MDS. GSEA analysis was used to explore possible mechanisms that contribute to the heterogeneity of the prognosis of UCEC patients.

Results
3 differential methylation-driven genes (DMDGs) (PARVG, SYNE4 and CDO1) were considered as predictors of poor prognosis in UCEC. An independent prognostic index was finally established based on 3 DMDGs. From the results of ROC curve analysis and survival curve analysis, MDS showed excellent prognostic ability in TCGA-UCEC. A new nomogram based on MDS and other prognostic clinical indicators has also been successfully established. The C-index of the nomogram for OS prediction was 0.764 (95% CI = 0.702–0.826). GSEA analysis suggests that there were differences in immune-related pathways among patients with different prognosis. The abundance of M2 macrophages and M0 macrophages were significantly enhanced in the high-risk group while T cells CD8, Eosinophils and Neutrophils were markedly elevated in the low-risk group. Meanwhile, patients in the low-risk group had higher levels of immunosuppressant expression, higher tumor mutational burden and immunophenoscore (IPS) scores. Joint survival analysis revealed that 7 methylation-driven genes could be independent prognostic factors for overall survival for UCEC.

Conclusion
We have successfully established a risk model based on 3 DMDGs, which could accurately predict the prognosis of patients with UCEC and reflect the tumor immune microenvironment.
Markov chain Monte Carlo Gibbs sampler approach for estimating haplotype frequencies among multiple malaria infected human blood samples
Authors: Ken-Dror Gie , Sharma Pankaj 
Published: July 2021

AbstractBackgroundMalaria patients can have two or more haplotypes in their blood sample making it challenging to identify which haplotypes they carry. In addition, there are challenges in measuring the type and frequency of resistant haplotypes in populations. This study presents a novel statistical method Gibbs sampler algorithm to investigate this issue.ResultsThe performance of the algorithm is evaluated on simulated datasets consisting of patient blood samples characterized by their multiplicity of infection (MOI) and malaria genotype. The simulation used different resistance allele frequencies (RAF) at each Single Nucleotide Polymorphisms (SNPs) and different limit of detection (LoD) of the SNPs and the MOI. The Gibbs sampler algorithm presents higher accuracy among high LoD of the SNPs or the MOI, validated, and deals with missing MOI compared to previous related statistical approaches.ConclusionsThe Gibbs sampler algorithm provided robust results when faced with genotyping errors caused by LoDs and functioned well even in the absence of MOI data on individual patients.
Residual malaria in Jazan region, southwestern Saudi Arabia: the situation, challenges and climatic drivers of autochthonous malaria
Authors: Al-Mekhlafi Hesham M. , Madkhali Aymen M. , Ghailan Khalid Y. , Abdulhaq Ahmed A. , Ghzwani Ahmad Hassn , Zain Khalid Ammash , Atroosh Wahib M. , Alshabi Alkhansa , Khadashi Hussein A. , Darraj Majid A. , Eisa Zaki M. 
Published: July 2021

Abstract
Background
Saudi Arabia and Yemen are the only two countries in the Arabian Peninsula that are yet to achieve malaria elimination. Over the past two decades, the malaria control programme in Saudi Arabia has successfully reduced the annual number of malaria cases, with the lowest incidence rate across the country reported in 2014. This study aims to investigate the distribution of residual malaria in Jazan region and to identify potential climatic drivers of autochthonous malaria cases in the region.

Methods
A cross-sectional study was carried out from 1 April 2018 to 31 January 2019 in Jazan region, southwestern Saudi Arabia, which targeted febrile individuals attending hospitals and primary healthcare centres. Participants’ demographic data were collected, including age, gender, nationality, and residence. Moreover, association of climatic variables with the monthly autochthonous malaria cases reported during the period of 2010–2017 was retrospectively analysed.

Results
A total of 1124 febrile subjects were found to be positive for malaria during the study period. Among them, 94.3 and 5.7% were infected with Plasmodium falciparum and Plasmodium vivax, respectively. In general, subjects aged 18–30 years and those aged over 50 years had the highest (42.7%) and lowest (5.9%) percentages of malaria cases. Similarly, the percentage of malaria-positive cases was higher among males than females (86.2 vs 13.8%), among non-Saudi compared to Saudi subjects (70.6 vs 29.4%), and among patients residing in rural rather than in urban areas (89.8 vs 10.2%). A total of 407 autochthonous malaria cases were reported in Jazan region between 2010 and 2017. Results of zero-inflated negative binomial regression analysis showed that monthly average temperature and relative humidity were the significant climatic determinants of autochthonous malaria in the region.

Conclusion
Malaria remains a public health problem in most governorates of Jazan region. The identification and monitoring of malaria transmission hotspots and predictors would enable control efforts to be intensified and focused on specific areas and therefore expedite the elimination of residual malaria from the whole region.
Association between egg consumption and arterial stiffness: a longitudinal study
Authors: Ji Naiwen , Huang Zhe , Zhang Xinyuan , Sun Yuanyuan , Ye Shumao , Chen Shuohua , Tucker Katherine L. , Wu Shouling , Gao Xiang 
Published: July 2021

Abstract
Background
Inconsistent associations between egg consumption and cardiovascular disease (CVD) risk have been observed in previous studies. This study aims to longitudinally investigate the association between egg consumption and altered risk of arterial stiffness, a major pre-clinical pathogenic change of CVD, which was assessed by brachial-ankle pulse wave velocity (baPWV).

Methods
A total of 7315 Chinese participants from the Kailuan Study, free of CVD and cancer were included in this study. Egg consumption was assessed by a semi-quantitative validated food frequency questionnaire in 2014. baPWV was repeatedly measured at baseline and during follow-up (mean follow-up: 3.41 years). General linear regression was used to calculate means of baPWV change rate across different egg consumption groups, adjusting for age, sex, baseline baPWV, healthy eating index, total energy, social-economic status, blood pressure, obesity, smoking, lipid profiles, and fasting glucose concentrations.

Results
Compared to the annual baPWV change rate in participants with 0–1.9 eggs/wk. (adjusted mean: 35.9 ± 11.2 cm/s/y), those consuming 3–3.9 eggs/wk. (adjusted mean: 0.2 ± 11.4 cm/s/y) had the lowest increase in baPWV during follow-up (P-difference = 0.002). Individuals with low (0–1.9 eggs/wk) vs. high (5+ eggs /wk) egg intake showed similar changes in baPWV.

Conclusions
In this large-scale longitudinal analysis, we did not find a significant difference in arterial stiffness, as assessed by baPWV level, between low and high egg consumption groups. However, moderate egg consumption (3–3.9 eggs/wk) appeared to have beneficial effects on arterial stiffness.
LDL mediated delivery of Paclitaxel and MRI imaging probes for personalized medicine applications
Authors: Rakhshan Sahar , Alberti Diego , Stefania Rachele , Bitonto Valeria , Geninatti Crich Simonetta 
Published: July 2021

Abstract
Background
The combination of imaging and therapeutic agents in the same smart nanoparticle is a promising option to perform a minimally invasive imaging guided therapy. In this study, Low density lipoproteins (LDL), one of the most attractive biodegradable and biocompatible nanoparticles, were used for the simultaneous delivery of Paclitaxel (PTX), a hydrophobic antitumour drug and an amphiphilic contrast agent, Gd-AAZTA-C17, in B16-F10 melanoma cell line. These cells overexpress LDL receptors, as assessed by flow cytometry analysis.

Results
PTX and Gd-AAZTA-C17 loaded LDLs (LDL-PTX-Gd) have been prepared, characterized and their stability was assessed under 72 h incubation at 37 °C and compared to LDL loaded with Gd-AAZTA-C17 (LDL-Gd) and LDL-PTX. The cytotoxic effect of LDL-PTX-Gd was evaluated by MTT assay. The anti-tumour drug loaded into LDLs showed a significantly higher toxicity on B16-F10 cells with respect to the commercially available formulation Paclitaxel kabi (PTX Kabi) used in clinical applications. Tumour cells uptake was initially assessed by ICP-MS and MRI on B16-F10 cell line. By the analysis of the image signal intensity, it was possible to extrapolate the amount of internalized PTX indirectly by the decrease of relaxation times caused by Gd, proportional to its concentration. Finally, the treatment with PTX loaded LDL on B16-F10 tumour bearing mice resulted in a marked reduction of tumour growth compared to the administration of PTX Kabi alone.

Conclusions
LDLs are selectively taken-up by tumour cells and can be successfully exploited for the selective delivery of Paclitaxel and imaging agents. For the first time the anon invasive “in vivo” determination of the amount of PTX accumulated in the tumour was possible, thanks to the use of theranostic agents of natural origin.

Graphic abstract
Bone mesenchymal stem cells stimulation by magnetic nanoparticles and a static magnetic field: release of exosomal miR-1260a improves osteogenesis and angiogenesis
Authors: Wu Di , Chang Xiao , Tian Jingjing , Kang Lin , Wu Yuanhao , Liu Jieying , Wu Xiangdong , Huang Yue , Gao Bo , Wang Hai , Qiu Guixing , Wu Zhihong 
Published: July 2021

Abstract
Background
The therapeutic potential of exosomes derived from stem cells has attracted increasing interest recently, because they can exert similar paracrine functions of stem cells and overcome the limitations of stem cells transplantation. Exosomes derived from bone mesenchymal stem cells (BMSC-Exos) have been confirmed to promote osteogenesis and angiogenesis. The magnetic nanoparticles (eg. Fe3O4, γ-Fe2O3) combined with a static magnetic field (SMF) has been commonly used to increase wound healing and bone regeneration. Hence, this study aims to evaluate whether exosomes derived from BMSCs preconditioned with a low dose of Fe3O4 nanoparticles with or without the SMF, exert superior pro-osteogenic and pro-angiogenic activities in bone regeneration and the underlying mechanisms involved.

Methods
Two novel types of exosomes derived from preconditioned BMSCs that fabricated by regulating the contents with the stimulation of magnetic nanoparticles and/or a SMF. Then, the new exosomes were isolated by ultracentrifugation and characterized. Afterwards, we conducted in vitro experiments in which we measured osteogenic differentiation, cell proliferation, cell migration, and tube formation, then established an in vivo critical-sized calvarial defect rat model. The miRNA expression profiles were compared among the exosomes to detect the potential mechanism of improving osteogenesis and angiogenesis. At last, the function of exosomal miRNA during bone regeneration was confirmed by utilizing a series of gain- and loss-of-function experiments in vitro.

Results
50 µg/mL Fe3O4 nanoparticles and a 100 mT SMF were chosen as the optimum magnetic conditions to fabricate two new exosomes, named BMSC-Fe3O4-Exos and BMSC-Fe3O4-SMF-Exos. They were both confirmed to enhance osteogenesis and angiogenesis in vitro and in vivo compared with BMSC-Exos, and BMSC-Fe3O4-SMF-Exos had the most marked effect. The promotion effect was found to be related to the highly riched miR-1260a in BMSC-Fe3O4-SMF-Exos. Furthermore, miR-1260a was verified to enhance osteogenesis and angiogenesis through inhibition of HDAC7 and COL4A2, respectively.

Conclusion
These results suggest that low doses of Fe3O4 nanoparticles combined with a SMF trigger exosomes to exert enhanced osteogenesis and angiogenesis and that targeting of HDAC7 and COL4A2 by exosomal miR-1260a plays a crucial role in this process. This work could provide a new protocol to promote bone regeneration for tissue engineering in the future.

Graphical abstract
The MCM3AP-AS1/miR-126/VEGF axis regulates cancer cell invasion and migration in endometrioid carcinoma
Authors: Yu Jie , Fan Qiqi , Li Lingling 
Published: July 2021

Abstract
Background
Long non-coding RNA (lncRNA) MCM3AP-AS1 plays an oncogenic role in several malignancies, but its role in endometrioid carcinoma (EC) is unclear. This study was carried out to explore the role of MCM3AP-AS1 in EC.

Methods
A total of 60 EC patients were enrolled in this study. Expression levels of MCM3AP Antisense RNA 1 (MCM3AP-AS1), microRNA-126 (miR-126), and vascular endothelial growth factor (VEGF) in tissues and transfetced cells were measured by RT-qPCR. Cell transfections were performed to explore the interaction among MCM3AP-AS1, miR-126 and VEGF. Transwell assays were perfromed to evaluate the invasion and migration abilities of HEC-1 cells after transfection.

Results
MCM3AP-AS1 was upregulated in EC and predicted poor survival. MCM3AP-AS1 directly interacted with miR-126. In EC cells, overexpression of MCM3AP-AS1 and miR-126 did not significantly affect the expression of each other. In addition, overexpression of MCM3AP-AS1 increased the expression levels of VEGF, a target of miR-126. Moreover, overexpression of MCM3AP-AS1 and VEGF increased the migration and invasion rates of EC cells, while overexpression of miR-126 suppressed these cell behaviors. Overexpression of MCM3AP-AS1 attenuated the role of miR-126 in cell invasion and migration.

Conclusions
Therefore, MCM3AP-AS1 may serve as a competing endogenous RNA (ceRNA) of miR-126 to upregulate VEGF, thereby regulating cancer cell behaviors in EC.
MiR-191-5p is upregulated in culture media of implanted human embryo on day fifth of development
Authors: Acuña-González Ricardo Josué , Olvera-Valencia Mercedes , López-Canales Jorge Skiold , Lozano-Cuenca Jair , Osorio-Caballero Mauricio , Flores-Herrera Héctor 
Published: July 2021

AbstractBackgroundMorphological features are the most common criteria used to select human embryos for transfer to a receptive uterine cavity. However, such characteristics are not valid for embryos in cellular arrest. Even aneuploid embryos can have normal morphology, and some euploid embryos have aberrant morphology. The aim of this study was to quantify the expression profile of hsa-miR-21-3p, -24-1-5p, -191-5p, and -372-5pin culture media on day 5 ofin vitroembryo development, and compare the profiles of two groups of media classified by outcome: successful (n = 25) or unsuccessful (n = 25) implantation pregnancy.MethodsFifty patients were accepted in the Department of Reproductive Biology of a Hospital in México City, based on the Institutional inclusion criteria forin vitrofertilization. Embryos were transferred to the women on day 5 of cultivation, and the culture media were collected. RNA was isolated from each culture medium with TRIzol reagent, and microRNA (miRNA) expression was detected through RT-PCR with specific primers. Expression bands were quantified by reading optical density.ResultsThere was a 5.2-fold greater expression of hsa-miR-191-5pin the pregnancy-related culture media (p ≤ 0.001) and a 1.6-fold greater level of hsa-miR-24-1-5p(p = 0.043) in the media corresponding to non-pregnant women. No significant difference existed between the two groups hsa-miR-21-3p(p = 0.38) or hsa-miR-372-5p(p = 0.41).ConclusionsRegarding adequatein vitroembryo development, hsa-miR-191-5pcould possibly represent a positive biomarker, while has-miR-24-1-5pmay indicate poor prognosis. This former miRNA modulates IGF2BP-1 and IGF2R, associated with the implantation window. On the other hand, hsa-miR-24-1-5pmay be related to a poor prognosis of human embryo development.
Determinant factors for adherence to antiretroviral therapy among adult HIV patients at Dessie Referral Hospital, South Wollo, Northeast Ethiopia: a case–control study
Authors: Abdu Mehd , Walelgn Betelhem 
Published: July 2021

Abstract
Introduction
World health organization defined adherence as the extent to which a person’s behavior – taking medications, following a diet, or executing lifestyle changes correspond with agreed recommendations from the health care provider. There is a contradiction among studies and previous studies conducted in the study area used a cross-sectional study design. This study aimed to identify determinant factors for adherence to antiretroviral treatment among people living with HIV at Dessie Referral Hospital by using an unmatched case–control study design.

Methods and materials
an institution-based unmatched case–control study design was used on a total sample of 582 (146 controls and 436 cases). Each respondent was selected by consecutive random sampling. The collected data were entered and analyzed by using Statistical Package for Social Science version 25.0. Multivariable binary logistic regression analysis was used to identify variables that were statistically significant determinants.

Result
The mean age of the respondents was 41.64 years. About 61.5% of the participants were females. Patients with baseline HIV stage I was more likely to be adherent to the prescribed HIV medicine (AOR: 2.194 95% CI: 1.116, 4.314) as compared with those with baseline WHO stage IV. Patients who did not take anti-tuberculosis medication collaterally with the prescribed HIV medicine were more likely to be adherent (AOR: 2.271 95% CI: 1.257, 4.102). Patients who took antiretroviral therapy for more than 24 months were more likely to be adherent (AOR: 3.665 95% CI: 1.321, 10.170).

Conclusion
Initiation of antiretroviral therapy at the later stage of the disease and taking anti-tuberculosis concomitantly were negatively associated with adherence. Being on antiretroviral therapy for a longer duration has a positive association. Health facilities and professionals should strictly apply strategies for the prevention of tuberculosis among HIV patients to avoid concomitant use of anti-tuberculosis medications.
Fluorescence of ocular surface in a Covid -19 patient after Favipiravir treatment: a case report
Authors: Doran Mehmet Ali , Aytogan Hasan , Ayıntap Emre 
Published: July 2021

Abstract
Background
Favipiravir is used in treatment of Covid-19 patients. We aimed to share of ocular surface fluorescence in a patient after Favipiravir treatment in this case report.

Case presentation
A 20-year-old male patient declared no known systemic disease prior to Covid-19. He applied to us with blurry vision and blue light reflection after Covid-19 treatment with Favipiravir. We observed bilateral fluorescence on his eyes and fluorescence of his nails. Biomicroscopic examination was insignificant.

Conclusion
We investigated the fluorescence of favipiravir tablets under ultraviolet light. Drug demonstrated fluorescence. We recorded the favipiravir fluorescence in-vitro. This appears to be a strong evidence in terms of the linkage between the fluorescence of the ocular surface and favipiravir.
Novel TNC-PDGFD fusion in fibrosarcomatous dermatofibrosarcoma protuberans: a case report
Authors: Chen Yuan , Shi Ying-zhou , Feng Xiao-he , Wang Xiao-tong , He Xiang-lei , Zhao Ming 
Published: July 2021

Abstract
Background
Dermatofibrosarcoma protuberans (DFSP) is a superficial fibroblastic tumor characterized by high rate of local recurrence and low metastatic potential. Fibrosarcomatous transformation can rarely arise in DFSP either de novo or as recurrent, which represents a form of tumor progression and carries an increased risk of metastasis over classic DFSP. Cytogenetically, DFSP is characterized by a recurrent unbalanced chromosome translocation t (17;22)(q22;q13), leading to the formation of COL1A1-PDGFB fusion transcript that is present in more than 90% of cases. Alternative fusions involving the PDGFD with partners of COL6A3 or EMILIN2 have recently been documented in less than 2% of cases. Herein, we report a DFSP with fibrosarcomtous morphology harboring a novel TNC-PDGFD fusion.

Case presentation
A 54-year-old female presented with a slowly growing mass in the right thigh. Excision demonstrated a 2-cm ovoid, well-circumscribed, gray-white, mass. Microscopic examination revealed a partially encapsulated subcutaneous nodule without dermal connection. The neoplasm was composed of cellular and fairly uniform spindle cells with brisk mitoses, arranged in elongated fascicles and herringbone patterns, with focal collagenized stroma. The neoplastic cells were positive for CD34 and smooth muscle actin. Fluorescence in-situ hybridization analyses showed negative for COL1A1-PDGFB fusion as well as NTRK1/2/3 rearrangements. A subsequent RNA sequencing detected an in-frame fusion between exon 15 of TNC and exon 6 of PDGFD. This fusion was further confirmed by nested reverse transcription polymerase chain reaction amplification followed by Sanger sequencing. A diagnosis of fibrosarcomatous DFSP was rendered and the patient was in good status at a follow-up of 12 months after the operation.

Conclusions
We report a fibrosarcomatous DFSP with novel TNC-PDGFD fusion, which adds to the pathologic and genetic spectrum of PDGFD-rearranged DFSP.