bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Newly Built rAAV-SaCas9 Genome Editing System Enables Muscle-Directed Gene Editing to Improve Muscular Atrophy
Authors: Weng Shaoting , Li Xingyu , Zhao Yitian , Gao Feng , Shi Mengmeng , Yang Haoxiang , Han Liqiang , Wang Jiang , Yang Guoyu 
Published: May 2020

Abstract
Background

At present, genome editing at specific sites in vivo is affected by many factors, including the choice of vector, the efficiency of editing proteins and the influence of the internal environment. These factors make gene editing ineffective and even have adverse effects.
Methods

Here, we report a single rAAV containing SaCas9 and guide RNAs under the control of subtle EF1a and tRNA promoters. The capacity of rAAV was compressed, and we inserted the sequence of the green fluorescent protein eGFP into rAAV. The efficiency of rAAV gene editing in vivo and in vitro was analyzed by time point and virus titer. In addition, we used the rAAV9-SaCas9 system to knock out the myostatin gene in the thigh muscles of muscle-atrophic mice.
Results

We demonstrated that the gene editing elements regulated by the rAAV-SaCas9 system can be expressed. By increasing the amount of rAAV and the reaction time, the editing efficiency of myostatin and the expression level of eGFP protein can be improved in vitro and vivo. Furthermore, We demonstrated that muscle cells were improved by knockout partial myostatin gene in a mouse model of muscular dystrophy.
Conclusions

The rAAV-SaCas9 system can be expressed in a stable and long-term manner. The system has substantial therapeutic potential in treating muscular atrophy.
Half graben inversion tectonics revealed by gravity modeling in the Mikawa Bay Region, Central Japan
Authors: Miyakawa Ayumu , Abe Tomoya , Sumita Tatsuya , Otsubo Makoto 
Published: May 2020

Abstract
The Mikawa Bay Region, central Japan, is characterized by many active faults recording Quaternary activity. It is, however, difficult to understand the overall tectonic character of the region due to the thick sediments in this region. We estimated the depth and the structure of the basement top in the Mikawa Bay Region through the analysis of gravity data, compiling publicly available gravity data and our own gravity measurements in the central part of the region. The gravity basement map shows the deepening of the basement top from the Nishi-Mikawa Plain to the Chita Peninsula. Two-dimensional modeling constrains the orientation of the Utsumi and Takahama faults. The fact that the basement top structure related to the Kou Fault is insignificant in the gravity data indicates that the geometry of the Kou Fault is small relative to that of the Utsumi Fault. The basement top structure from the Nishi-Mikawa Plain to the Chita Peninsula reveals a half graben structure bounded by the Utsumi Fault. The inverse motion of the Utsumi Fault, which underwent normal faulting during the Miocene followed by recent reverse faulting, is interpreted to reflect the inversion tectonics of the half graben. The timing of the inversion tectonics, i.e. the reverse faulting of the Miocene normal fault, can be compared to an episode of basin inversion observed at the eastern margin of the Japan Sea, northeastern Japan. The Takahama Fault in the center of the Nishi-Mikawa Plain is considered to have formed as a result of the backthrust of the Utsumi Fault under inversion tectonics. If the Takahama Fault is indeed the backthrust fault of the Utsumi Fault, the root of the Takahama Fault may be deep such that the Takahama Fault is seismogenic and linked to the 1945 Mikawa earthquake.
Circulating tumor DNA as a prognostic marker in high-risk endometrial cancer
Authors: Feng Weiwei , Jia Nan , Jiao Hai-ning , Chen Jun , Chen Yan , Zhang Yueru , Zhu Menghan , Zhu Chongying , Shen Lifei , Long Wenqing 
Published: May 2020

Abstract
Background Currently, there is no reliable blood-based marker to track tumor recurrence in endometrial cancer (EC) patients. Liquid biopsies, specifically, circulating tumor DNA (ctDNA) analysis emerged as a way to monitor tumor metastasis. The objective of this study was to examine the feasibility of ctDNA in recurrence surveillance and prognostic evaluation of high-risk EC.Methods Tumor tissues from nine high-risk EC patients were collected during primary surgery and tumor DNA was subjected to next generation sequencing to obtain the initial mutation spectrum using a 78 cancer-associated gene panel. Baseline and serial post-operative plasma samples were collected and droplet digital PCR (ddPCR) assays for patient-specific mutations were developed to track the mutations in the ctDNA in serial plasma samples. Log-rank test was used to assess the association between detection of ctDNA before or after surgery and disease-free survival.Results Somatic mutations were identified in all of the cases. The most frequent mutated genes were PTEN, FAT4, ARID1A, TP53, ZFHX3, ATM, and FBXW7. For each patient, personalized ddPCR assays were designed for one-to-three high-frequent mutations. DdPCR analysis and tumor panel sequencing had a high level of agreement in the assessment of the mutant allele fractions in baseline tumor tissue DNA. CtDNA was detected in 67% (6 of 9) of baseline plasma samples, which was not predictive of disease-free survival (DFS). CtDNA was detected in serial post-operative plasma samples (ctDNA tracking) of 44% (4 of 9) of the patients, which predicted tumor relapse. The DFS was a median of 9 months (ctDNA detected) versus median DFS undefined (ctDNA not detected), with a hazard ratio of 17.43 (95% CI, 1.616–188.3). The sensitivity of post-operative ctDNA detection in estimating tumor relapse was 100% and specificity was 83.3%, which was superior to CA125 or HE4.Conclusions Personalized ctDNA detection was effective and stable for high-risk EC. CtDNA tracking in post-operative plasma is valuable for predicting tumor recurrence.
Mechanical Model of Directional Continuous Bamboo Fiber Opening
Authors: Zhang Wei , Yao Wenbin , Yu Weipeng 
Published: May 2020

Abstract
Based on the principle of directional continuous fiber opening of bamboo, the calculation model of the continuous beams in opening bamboo fiber is proposed.The continuous beam method is used to derive the moment equation of bamboo continuous fiber opening process. The mechanical model of bamboo directional continuous fiber opening is established, with the quantitative relationship found between the fiber opening parameters, e.g. the external load, the roll distance, the strength of the bamboo. The fiber opening test further verifies that the bamboo fiber opening model is correct .The research in this paper provides a theoretical basis for the precise control of directional continuous fiber opening of bamboo.
Highly sensitive droplet digital PCR method for detection of de novo EGFR T790M mutation in patients with Non-small cell lung cancer
Authors: Wang Xun , Li Xiao , Guo Haifa , Zhu Lingxiang , Peng Zhiyong , Wang Jun , Yang Fan , Guo Yong 
Published: May 2020

Abstract
Background

This study was aimed to investigate the allelic relation between de novo T790M and concomitant sensitizing EGFR mutations in EGFR-TKIs naïve NSCLCs and to explore whether the formalin-fixed and paraffin-embedded (FFPE) materials affect the detection of de novo T790M mutation.

Methods

300 consecutive EGFR-TKI naïve NSCLCs who received surgical resection between January 2016 and June 2018 was retrospectively investigated. All the snap-frozen tumor tissues from 300 NSCLCs were screened by droplet digital PCR (ddPCR) for the detection of de novo T790M mutation. The allelic relation between de novo T790M mutation and concomitant sensitizing EGFR mutations was also investigated. Furthermore, we assessed de novo T790M mutation in paired FFPE specimens of 50 patients which included tumor tissues and paired normal lung tissues of the pretreatment NSCLCs to investigate whether FFPE materials affect the detection of de novo T790M mutation.

Results

The de novo T790M mutation was observed in four patients which included one patient of single de novo T790M mutation and three patients of de novo T790M mutation coexisting with L858R mutation. The incidence of de novo T790M in pretreatment NSCLCs who harboring EGFR mutations was 2.9% (4/139). All the de novo T790M mutations were detected in cis with the concomitant L858R mutations for the three NSCLCs. Our ddPCR method demonstrated that the frequency of de novo T790M mutation were ranging from 0.1% to 0.5% among 90% (45/50) of the FFPE tumor samples and 92% (46/50) of the paired FFPE adjacent normal lung samples. The frequency of de novo T790M mutation in the paired snap-frozen samples were all below 0.1%.

Conclusion

Our study demonstrated that most de novo T790M mutation were detected in cis with concomitant sensitizing mutations for pretreatment NSCLCs. Analytical cut-off of ddPCR assay for FFPE specimens should be validated carefully considering the possibility of FFPE-derived artificial gene mutations.
LC-ESI-MS/GC-MS Based Metabolite Profiling of Chlorophytum comosum (Thunb.) Jaques and evaluation of its antioxidant and antiproliferative effects on lung and breast cancer cell lines
Authors: ADHAMI SHEHLA , Farooqi Humaira , ABDIN MALIK ZAINUL , PRASAD RAM , MALIK ASRAR AHMAD 
Published: May 2020

Abstract
Background Chlorophytum comosum popularly known as Spider Ivy is an important medicinal plant in traditional Chinese medicine utilized in the treatment of many ailments, however its detailed chemical composition and biological activity is not much explored. The present study aims to identify different chemical constituents present in roots and leaves of Chlorophytum comosum and investigates its antioxidant, antiproliferative and haemolytic effects on breast (MCF-7) and lung cancer cell lines (A549, H1299) as compared to normal lung (L-132) cell lines. Methods Chemical constituents from aqueous roots and leaves extracts were identified using LC-ESI-MS/GC-MS. The identified compounds were annotated based on match of mass spectral database with the literature using NIST 14 and METLIN databases. Antioxidant activity was checked using DPPH, FRAP and TPC assays. The antiproliferative effects of ethanolic roots and leaf extracts of Chlorophytum comosum were measured by MTT assay on breast (MCF-7), lung cancer (A549 & H1299) and normal lung (L-132) cell lines. The toxicity studies of the extracts were carried out using Haemolytic assay. Results GC-MS analysis identified 34 new metabolites in roots and 17 from leaves, while as 17 compounds from roots and 7 from leaves were detected by LC-ESI-MS. Significant antiproliferative effects were observed on MCF-7 & A549 cell lines with IC50 values ranging from 31.94 µg/ml to 77.84 µg/ml while no marked response was observed against normal cell line. Haemolysis studies revealed no significant toxicity of the extracts towards the biological system. Conclusion Our study is the first preliminary report on the detailed chemical composition and antiproliferative potential of Chlorophytum comosum, indicating significant specific antiproliferative activities against lung (A549) and breast (MCF-7) cancer cell lines. However, further studies are required to understand the mechanism involved in cytotoxic properties of Chlorophytum comosum.
Improving precision of field inventory estimation of above ground biomass through an alternative view on plot biomass
Authors: Kleinn Christoph , Magnussen Steen , Noelke Nils , Magdon Paul , Álvarez-González Juan Gabriel , Fehrmann Lutz , Pérez-Cruzado César 
Published: May 2020

Abstract
We contrast a new continuous approach (CA) to estimation of plot level above-ground biomass (AGB) in forest inventories with the current approach of deriving the AGB estimate exclusively from the tree-level AGB predicted for each tree in a plot; henceforth called DA (discrete approach). In CA the AGB in a forest is modelled as a continuous surface and the AGB estimate for a fixed area plot is computed as the integral of the AGB surface taken over the plot. Hence with CA, the portions of biomass in plot-trees that extend across a plot perimeter is ignored while the biomass from trees outside the plot reaching inside the plot is added. We use a sampling simulation with data from a fully mapped 2 ha area to illustrate, that important differences in plot-level AGB estimates can emerge, and that one should expect CA-based estimates of AGB to be less variable than with the DA, which translates to a higher precision of estimates from field plots: in our case study, for a target precision of estimation of 5%, the required sample size was 27% lower for small plots of 100m2 when using the CA and 10% lower for larger plots of 1700m2. We discuss practical issues to implementing CA in field inventories and discuss the expected potential for applications that model biomass from remote sensing data.
Socio-economic Determinants of Maternal Healthcare Utilization in Addis Ababa
Authors: Mossie Muluneh Yigzaw , Sandy Peter 
Published: May 2020

Abstract
Background

Despite progresses over the last two decades, Ethiopia is one of the countries in the world with significant number of maternal deaths and service use for antenatal, labour and childbirth is low. This study intended to identify the underlying causes of low coverage of maternal health services in Addis Ababa.
Methods

We conducted a comparative cross-sectional study in Addis Ababa in July 2017. A three stage sampling technique was applied to select the study population. The first step was to select study Ketenas using simple random sampling. The villages within the Ketenas were then identified, which led to the second stage of the sampling process. In the third stage, a fixed number of 20 households per village were selected with an equal probability random selection from the newly created household listing. All women aged 18–49 years who gave birth one year preceding the date of data collection were then invited to a face-to-face interview. Both multiple linear regression and logistic regression were applied to estimate crude and adjusted associations.
Results

Less than 45.0% of women from the poorest households received all the recommended ANC contacts at the right time, while 71.4% of women from richest households received all the recommended contacts at the right time. The majority of women from poorest households gave birth at health centres (66.2%), followed by public hospitals (30.9%). The largest proportion of women from richest households gave birth at private hospitals (46.1%), followed by public hospitals (16.1%). Meanwhile, only 52.5% of women with primary education had all the recommended ANC contacts, while 78.5% of women who completed tertiary education had all the recommended ANC contacts (p < 0.001). Women from richest households were less likely to face multiple barriers to use maternal health services as compared to women from poorest households (OR = 0.57, p = 0.032).
Conclusion

There is a huge inequality in maternal healthcare coverage in Addis Ababa. To achieve universal maternal health coverage, affordability of the service is not adequate although it is one of the requirements. Other underlining social determinants deserve the attention of policy makers and program designers.
The changing patterns of Non-communicable diseases and injuries in Nepal from 1990-2017: A review of evidence from Global Burden of Disease Study 2017
Authors: Mishra Shiva Raj , Shrestha Nipun , Gyawali Bishal , Vaidya Abhinav , Schwarz Dan , Neupane Dinesh , Aryal Krishna , Shrestha Abha , Karmacharya Biraj , Koirala Bhagawan , Shrestha Archana 
Published: May 2020

Abstract
Background Nepal has made significant strides towards its commitment to achieve universal health coverage in the past few decades. However, the paucity of evidence on morbidity, mortality and trends in non-communicable diseases (NCDs) has posed a significant hindrance in targeting resources for prevention, screening and treatment services. Thus, we conducted a systematic review of the existing evidence on the distribution of NCDs and their trends in Nepal from 1990 to 2017.Methods We analysed data on disability adjusted life years (DALYs), years lived with disability, years of life lost due to NCDs in Nepal and its comparator countries (Afghanistan, Bangladesh, Bhutan, India, Maldives, Pakistan and Sri Lanka) from 1990 to 2017 using all available data sources from Global Burden of Disease 2017. We also conducted supplemental analysis using data from the 2016 Nepal Demographic Health Survey (NDHS) to further elucidate the provincial level prevalence of key NCD risk factors.Results The result showed that between 1990 and 2017, life expectancy at birth increased by 14 years, from 58 years to 71 years on an average in Nepal. The three leading causes of DALYs in 2017 were cardiovascular diseases (CVDs), maternal and neonatal disorders and chronic respiratory diseases. High systolic blood pressure, smoking and high fasting plasma glucose were leading contributors to the NCD DALYs burden in 2017. At any ages ≥ 40 years, NCDs and injuries were responsible for 75–82% of total DALYs. Injuries, self-harm and violence, mental, neurological and musculoskeletal disorders superseded CVDs to become the leading causes of DALYs in young population aged 15–35 years.Conclusions CVDs were the leading causes of death in 2017 followed by chronic respiratory diseases and cancers. Data such as these are an important tool for framing a coherent policy response towards achieving the sustainable development goals, and the targets set by Nepal’s first Multi-sectoral Action plan on NCDs (2014–2020).
A Chinese Family with Noonan Syndrome Associated with a Heterozygous LZTR1 Mutation
Authors: Zhao Xiu , Wang Li , Lan Zhangzhang , Lin Feifei , Zhang Wenyong , Zhe Su 
Published: May 2020

Abstract
Background

Noonan syndrome (NS) is a multisystem disorder resulting from pathogenic mutations in more than 15 genes, among which LZTR1 is newly discovered. However, its role in NS pathogenesis remains unclear, including its inheritance pattern.
Methods

We herein report a family with LZTR-related NS. We collected clinical data of the proband and her families. Four of them completed the whole exon sequencing.
Results

Two children with NS inherited the same heterozygous LZTR1 variant, c.1149 + 1G > T, from their affected mother. Moreover, the proband was diagnosed as NS accompanied by growth hormone deficiency (GHD) without other associated gene mutations.
Conclusion

The variant c.1149 + 1G > T of LZTR1 was previously reported in autosomal recessive NS, but this is the first report of an autosomal dominant form. Our reported cases provided evidence for a more complex inheritance pattern resulting from LZTR1 c.1149 + 1G > T mutation. Occasionally, NS patients can have GHD.
Bioinformatic Analysis Reveals Novel Hub Genes pathways associated with IgA nephropathy
Authors: Jiang xue , Xu Zhijie , Du Yuanyuan , Chen Hongyu 
Published: May 2020

Abstract
Background Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulopathy worldwide. However, the molecular events underlying IgAN remain to be fully elucidated. The aim of the study is to identify novel biomarkers of IgAN through bioinformatics analysis and elucidate the possible molecular mechanism. Methods Based on the microarray data GSE93798 and GSE37460 were downloaded from the Gene Expression Omnibus database, the diﬀerentially expressed genes (DEGs) between IgAN samples and normal controls were identified. With DEGs, we further performed a series of functional enrichment analyses. Protein-protein interaction (PPI) networks of the DEGs were built with the STRING online search tool and visualized by using Cytoscape, then further identified the hub gene and most important module in DEGs, Biological Networks Gene Oncology tool (BiNGO) were then performed to elucidate the molecular mechanism of IgAN. Results A total of 148 DEGs were recognized, consisting of 53 upregulated genes and 95 downregulated genes. GO analysis indicates that DEGs for IgAN were mainly enriched in extracellular exosome, region and space, fibroblast growth factor stimulus, inflammatory response, and innate immunity. The modules analysis showed that genes in the top 1 significant modules of PPI network were mainly associated with innate immune response, integrin-mediated signaling pathway and inflammatory response respectively. The top 10 hub genes were constructed in PPI network, which could well distinguish the IgAN and control group in monocytes sample and tissue sample. We finally identified ITGB2 and FCER1G gene may have important roles in the development of IgAN. Conclusions We identified a series of key genes along with the pathways that were most closely related with IgAN initiation and progression. Our results provide a more detailed molecular mechanism for the development of IgAN and novel candidate genes targets of IgAN.
ABTB2 regulatory variant as predictor of epirubicin-based neoadjuvant chemotherapy in luminal A breast cancer
Authors: Gong Yajie , Hu Nanlin , Ma Li , Li Wentong , Cheng Xiang , Zhang Yi , Zhu Ying , Yang Yang , Peng Xiating , Zou Danyi , Tian Jianbo , Yang Lan , Mei Shufang , Wang Xiaoyang , Lo Chun-han , Chang Jiang , Hou Tieying , Zhang Hong , Xu Binghe , Zhong Rong , Yuan Peng 
Published: May 2020

Abstract
Background: Epirubicin combined with docetaxel is the cornerstone of neoadjuvant chemotherapy(NAC) for breast cancer. The efficacy of NAC for luminal A breast cancer patients is very limited, and single nucleotide polymorphism is one of the most important factor that influence the efficacy. Our study aimed to explore genetic markers for the efficacy of epirubicin combined with docetaxel for NAC in patients with luminal A breast cancer.Methods: A total of 421 patients with two stages of luminal A breast cancer were enrolled in this study from 2 centers. Among them 231 patients included in discovery cohort and 190 patients are in replication cohort. All patients received epirubicin 75mg/m2 and docetaxel 75mg/m2 on day 1, 21 days. a cycle for 2 to 6 cycles. Before treatment, 2ml of peripheral blood was collected from each patient to isolate genomic DNA. Fourteen functional variants potentially regulating epirubicin/docetaxel response genes were prioritized by CellMiner and bioinformatics approaches. Moreover, biological assays were performed to determine the effect of genetic variations on response to chemotherapy.Results: The patients carrying rs6484711 variant A allele suffered a poor response to epirubicin and docetaxel for NAC (OR=0.63, 95% CI: 0.44-0.89, P=0.010) in combined stage. Moreover, expression quantitative trait loci (eQTL) analyses and luciferase reporter assays revealed that rs6484711 A allele significantly increased the expression of ABTB2. Subsequent biological assays illustrated that upregulation of ABTB2 significantly reduced the apoptosis rate of breast cancer cells and enhanced the chemo-resistance to epirubicin. Conclusions: Our study demonstrated rs6484711 polymorphism regulating ABTB2 expression might predict efficacy to epirubicin based NAC in luminal A breast cancer patients. These results provided valuable information about potential role of genetic variations in individualized chemotherapy.