bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficient Crispr-cas9 Mediated Pooled-sgRNAs&nbsp;Assembly Accelerates Targeting Multiple Genes Related to Male Sterility in Cotton&nbsp;
Authors: Ramadan Mohamed , Alariqi Muna , Ma Yizan , Li Yanlong , Liu Zhenping , Zhang Rui , Jin Shuangxia , Min Ling , Zhang Xianlong 
Published: November 2020

Abstract
Background: Upland cotton (Gossypium hirsutum), harboring a complex allotetraploid genome consists of A and D subgenomes. The genes in have multiple copies with high sequence similarity that makes genetic, genomic and functional analysis extremely challenging. The recent accessibility of CRISPR/Cas9 tool offers the ability to modify targeted locus efficiently in various complicated plant genomes. However, current cotton transformation method targeting one gene requires a complicated, long and laborious regeneration process. Hence, optimizing strategy to target multiple genes is of great value in cotton functional genomics and practical applications of genetic engineering.Results: To target multiple genes in a single experiment, 112 plant development-related genes were knocked out via optimized CRISPR-Cas9 system. We optimized the key steps of pooled sgRNAs assembly method by which 116 sgRNAs pooled together into 4 groups (each group consisted of 29 sgRNAs). Each group of sgRNAs was compiled in one PCR reaction which subsequently went through one round of vector construction, transformation, sgRNAs identification and also one round of genetic transformation. Through the genetic transformation mediated Agrobacterium, we successfully generated more than 800 plants. For mutants identification, Next Generation Sequencing technology has been used and results showed that all generated plants were positive and all targeted genes were covered. Interestingly, among all the transgenic plants, 85% harbored a single sgRNA insertion, 9% two insertions, 3% three different sgRNAs insertions, 2.5% mutated sgRNAs. These plants with different targeted sgRNAs exhibited numerous combinations of phenotypes in plant flowering tissues. Conclusion: All targeted genes were successfully edited with high specificity which makes our pooled sgRNAs assembly a simple, fast and efficient method/strategy to target multiple genes in one time and surely accelerated the study of genes function in cotton.
Vpr R36w and R77Q&nbsp;Mutations Alter HIV-1 Replication and Cytotoxicity in T Lymphocytes
Authors: Solis-Leal Antonio , Karlinsey Dalton C. , Lopez J. Brandon , Planelles Vicente , Poole Brian D. , Berges Bradford 
Published: November 2020

Abstract
Background: Acquired immunodeficiency syndrome (AIDS) is caused when HIV depletes CD4+ helper T cell levels in infected patients. Distinct AIDS development rates have shown that there are Rapid Progressor (RP) and Long-Term Non-Progressor (LTNP) patients, but the circumstances governing these differences in the kinetics of helper T cell depletion are poorly understood. Mutations in the Viral Protein R (Vpr) gene have been suggested to have a direct impact on helper T cell depletion. Interactions of Vpr with both host and viral factors affect cellular activities such as cell cycle progression and apoptosis. The Vpr mutants R36W and R77Q have been associated with RP and LTNP phenotypes, respectively; however, these findings are still controversial. This study examines the effects that Vpr mutations have in the context of HIV-1 infection of the HUT78 T cell line, using replication-competent CXCR4-tropic virus strains. Results: Our results show a replication enhancement of the R36W mutant accompanied by increased cytotoxicity. Interestingly, the R77Q mutant showed a unique enhancement of apoptosis (measured by Annexin V and TUNEL staining) and G2 cell cycle arrest; these effects were not seen with WT, R36W or Vpr null viruses. Thus, point mutations in Vpr can exhibit profound differences in mechanisms and rates of cell killing. Conclusions: The vpr gene is thought to be an important virulence factor in Human Immunodeficiency Virus type 1 (HIV-1). Vpr polymorphisms have been associated with different rates of AIDS progression. However, there is controversy about the cytopathic and virulence phenotypes of Vpr mutants, with contradictory conclusions about the same mutants. Here, we examine the replication capacity, apoptotic induction, and G2 cell cycle arrest phenotypes of three vpr mutants compared to wild-type HIV-1. One mutant associated with rapid AIDS progression replicated more efficiently and killed cells more rapidly than wild-type HIV-1. Another mutant associated with slow AIDS progression triggered apoptosis more efficiently than wild-type HIV-1 and showed significant levels of G2 cell cycle arrest. These results shed additional light on the role of vpr polymorphisms in T cell killing by HIV-1 and may help to explain the role of Vpr in different rates of AIDS progression.
Moderate Innovator trap – Does Convergence of Innovation Performance Occur in the World Economy?
Authors: Kowalski Arkadiusz , Rybacki Jakub 
Published: November 2020

Abstract

Based on β and σ convergence analysis, we find high persistence of innovation gap for international innovation indices reported by the European Commission. Our research confirms the diverging scientific potential across the analyzed economies. On the other hand, estimation provides the evidence of convergence in case of R&D expenses and relative position on global technological frontier. We propose a simple fixed effect panel regression measuring relative innovativeness potential. Our model suggests that current ranking leaders i.e. Nordic countries (Sweden, Denmark and Finland) and Germany are likely to further outpace the United States. Central and Eastern Europe countries are achieving greatest relative gains, but are unlikely to exceed 70% of US potential. Peripheral Europe countries, South Africa, Turkey and Russia are projected to further lose innovativeness position, despite weaker initial position.
Clinical Outcomes Observation in Stage IIB–III Cervical Cancer Treated by Adjuvant Surgery Following Concurrent Chemoradiotherapy
Authors: Li Yong , Chen Zhiying , Wang Xiang , Li Xiumei , Zhou Jie , Zhang Yongchun 
Published: November 2020

Abstract
Objective: To explore the feasibility of adjuvant surgery following concurrent chemoradiation therapy (CCRT) in stage ⅡB–Ⅲ cervical cancer. And analyze risk factors of recurrence after surgery. Methods: Forty-nine patients diagnosed with stage ⅡB–Ⅲ cervical cancer were reviewed retrospectively. Investigated the risk factors of recurrence after surgery using Chi-squared Test and further analyzed multiple factors affecting postoperative recurrence using the multi-factor logistic regression. Furthermore, the correlation of surgery outcomes (including operation time, bleeding, and hospitalization date and surgery complications) with the time which carried out between CCRT and completion surgery was analyzed. Results: Tumor histology and residual tumor in the cervix were significantly associated with postoperative recurrence (P = 0.014 and P = 0.040, respectively). Logistic regression analysis demonstrated that the independent risk factors of postoperative recurrence were age and residual tumor in the cervix (P = 0.017 and P = 0.030, respectively). Compared with completion surgery was carried out ≤ 6 weeks after CCRT, the operation time, bleeding, hospitalization date and surgery complications were more than > 6 weeks group. Moreover, bleeding and surgery complications were statistically significant (P = 0.019 and P = 0.044, respectively). Conclusion: CCRT combined surgery for stage ⅡB–Ⅲ cervical cancer was feasible, reduced the rate of postoperative recurrence and surgery complications were tolerated. CCRT combined surgery might improve the local control of lesion.
Establishment of a Prognostic Stemness Signature for Cervical Squamous Cell Carcinoma
Authors: Sun Xiwen , Wang Fang , Zhao Jiayao , Zhou Jianwei 
Published: November 2020

Abstract
Background: The aim of this study was to construct a robust stemness-related gene signature for predicting prognosis of cervical squamous cell carcinoma (CSCC).Methods: Expression data for the PCBC database-derived pluripotent stem cell (PSC) samples were collected using the one-class logistic regression (OCLR) method to calculate stemness indexes (mRNAsi) of samples derived from the TCGA dataset. Functions of possible mRNAsi-related stemness genes extracted through WGCNA were then examined by enrichment analysis. Most representative stemness genes for prognosis prediction were screened to construct a stemness-related gene signature by shrinkage estimate and univariate analysis. Next, the TCGA dataset and the GSE44001 external dataset were incorporated into that model and classified to evaluate the model efficiency and stability in patient prognosis prediction and classification according to the Riskscore. The associations between the Riskscore and clinical characteristics as well as relevant signaling pathways were also explored. Moreover, the prognosis predicting efficiency of the stemness-related gene signature was compared with those of CSCC prognostic signatures reported in other studies.Results: According to the findings, mRNAsi showed significant correlation with key oncogene mutation degrees (including DMD, KMT2C, EP300 and MUC4), infiltrating stroma cells and the CIMP classification for CSCC cases. The 8-stemness gene signature in this study achieved high stability and accuracy in prognosis prediction for CSCC cases. In the meanwhile, the model provided diverse therapeutic targets to precisely treat CSCC in clinical practice based on various subtype-specific stemness genes.Conclusion: Our present study suggested that the 8 stemness gene signature can help to screen out novel stem-related diagnostic indicators, therapeutic targets and prognostic predictors in CSCC.
Bioinformatics Analysis and Identification of the Expression and Mechanism of Immune-related Gene MAPT in Hepatocellular Carcinoma
Authors: Jiang Yan , Chen Duan-kai , Liu Fa-hui , Gong Qi-ming , Zhuo Chen-yi , Qun-qingXv  , Qian-liTang  
Published: November 2020

Abstract
MAPT (Microtubule Associated Protein Tau) is a Protein Coding gene. Aberrant expression of MAPT has been reported to be associated with several types of tumors, such as gastric, breast, and colorectal cancer, and so on. However, the role of MAPT in HCC (Hepatic carcinoma) is still poorly understood. In our research, MAPT-related data mining and analyzing were used publicly-available data from TCGA, GEO, Oncomine, and HPA databases. The survival curve was shown and analyzed by using Kaplan Meier Plotter. Gene Set Enrichment Analysis (GSEA), TIMER, STRING, and R package were used to explore the function and potential mechanism of MAPT in HCC. The results show that MAPT is overexpressed in HCC samples and is correlated with worse prognosis of patients with HCC. Bioinformatics analysis showed that MAPT contributed to the development of tumors through a variety of mechanisms. In conclusion, the Up-regulation of MAPT was significantly linked to poor prognosis in HCC patients, and it could be a new therapeutic target for HCC therapy.
Effect of Omalizumab for Autoimmune Progesterone Dermatitis Refractory to Bilateral Oophorectomy: a case report
Authors: Varghese Akshay , Paul Terri , Kim Harold , Uum Stan Van , Vadas Peter , Azzola Alescia 
Published: November 2020

Abstract
Background Autoimmune progesterone dermatitis (APD) is a rare skin condition caused by sensitivity to high levels of progesterone secreted during the luteal phase of the menstrual cycle. This may be due to various pathophysiological mechanisms including a Type I and Type IV hypersensitivity reaction. Here we present the case of a patient with APD whose episodic flares were controlled by the addition of omalizumab, after a bilateral oophorectomy failed to resolve her symptoms. Case Presentation A 34-year-old female presented to our Endocrine Clinic with marked Cushingoid features secondary to high-dose oral prednisone prescribed for APD diagnosed 6 years earlier. She first developed a pruritic maculopapular rash on her arms and legs just after the birth of her second child in 2009. The rash was also associated with headaches and diffuse angioedema. It presented in a cyclical fashion, beginning one to two weeks before the start of her menstrual cycle, and ending shortly after it was complete. The severity of symptoms increased as time went on, and flare-ups began to also include dyspnea, nausea, vomiting and abdominal pain. Her symptoms improved with administration of oral prednisone, but she continued to experience breakthrough symptoms. After multiple failed treatment modalities, she elected bilateral oophorectomy in 2018. However, her symptoms of APD persisted and she still required high-dose oral prednisone. Her condition was further complicated by vasomotor menopausal symptoms and progressive iatrogenic Cushing’s syndrome. She eventually was started on Omalizumab, which suppressed further recurrences of APD symptoms and allowed her to wean off prednisone. Vasomotor menopausal symptoms responded well to the addition of conjugated estrogens with bazedoxifene. However, her symptoms of diffuse bony pain and arthralgias which started whilst on prednisone have persisted in spite of discontinuing prednisone. Conclusions To our knowledge, this is only the third case of APD which was successfully treated with Omalizumab and the first case where a bilateral oophorectomy failed to resolve symptoms of APD in the literature. This case also demonstrates the complications of vasomotor menopausal symptoms secondary to a bilateral oophorectomy, as well as the adverse effects of long-term glucocorticoid therapy.
Coagulation indicators and their association with apoptosis ,flammatory indicators and Sharp scores of rheumatoid arthritis
Authors: Wang Xin , Liu Jian 
Published: November 2020

Abstract
Background

Recent studies have shown that coagulations indicators hava a strong correlation with apoptosis ,flammatory indexes.In the present study, we measured coagulation indicators such PAF,PGI2 and TXB2 in patients with RA and investigated their association with apoptosis,flammatory indicators and Sharp scores of rheumatoid arthritis (RA).
Methods

A total of 90 patients diagnosed with rheumatoid arthritis were enrolled for comparisons. The clinical and laboratory data of patients were retrospectively reviewed. The X-ray findings of both hands were scored according to Sharp's criteria. In addition, the statistics of patients with apoptosis indicator,coagulation indicator and flammatory indicator. Explored the relationship between coagulation indiccators and the above indicators.
Results

In this study,there was a strong correlation between the abnormal increase of apoptosis parameters,immune inflammation indicators,Sharp Score and the increase of coagulation indicator in patients with rheumatoid arthritis, and the increase of Sharp Scores,Caspase-3,FasL indexes or the decrease of C-reactive protein (CRP)could be risk factors for the development of RA. The higher the coagulation indicator, the higher the Sharp score,and the high parameters of hypercoagulable state RA.
Conclusions

Higher coagulation indicators are associated with RA disease activity, as well as apoptosis ,flammatory indicators and decreased physical activity. Moreover, coagulation indicator are associated with Sharp scores.Coagulation indicator are important for the diagnosis of rheumatoid arthritis and are potential markers of activity and hypercoagulable state in RA patients.
Targeting area and comparing the effect of different land use/land cover (LULC) scenarios on greenhouse gases (GHGs) emission reduction (Case study: Hyrcanian forests in Iran)
Authors: Kamyab Hamidreza , Asadolahi Zahra 
Published: November 2020

Abstract
Background

Because the greenhouse gases (GHGs) emissions are known to be strongly influenced by land use/land cover (LULC) change, reducing emissions from deforestation and degradation (REDD) mechanism has attracted much attention as a strategy for understanding how different LULC scenarios effect on the GHGs emissions. Transition to other LULC types is one of the major challenges of Iran's Hyrcanian forests in Golestan province. To consider how LULC change scenarios affect GHGs, REDD project was executed in a period of 30 years (2018–2048) at intervals of 5 years. In this regard, study area was divided into the project area and leakage belt based on the Multi Criteria Evaluation (MCE) derived forest suitability map. In the baseline scenario, it was assumed that the trend of past LULC changes will continue.
Results

By implementation of the project scenario, some degradation activities were controlled. Project scenario was executed with different project success rates (PSR) of 90, 80, 70, 60 and 50% to examine its efficiency rate in reducing GHGs emissions. According to the results, 38206.8 hectares of forests within the project area will be destroyed by 2047 under the baseline. The destroyed area will be reach 39784.4 hectares in the leakage belt. The highest rate of forest destruction in the project area will occur in the last 5 years (1352 hectares per year), so the highest CO2 and non-CO2 emissions equal to 662655.3 tons/year and 278.94 tCO2e/year will happen in the last 5 years (2042–2047). Based on the results, reducing the PSR affected the efficiency of the project scenario. The highest and lowest rates of emissions reduction were observed respectively with PSR of 90 and 50%.
Conclusions

That's very important for developing countries especially Iran that are facing many challenging forest conservation decisions. This study innovated in methodology by integrating the MCE into the REDD steps. The MCE as a spatial targeting method could be applied to increase the efficiency of the REDD project, as we illustrated for the case of Hyrcanian forests.
The utility of sputum supernatant as an alternative liquid biopsy specimen for next-generation sequencing-based genomic profiling
Authors: Qin Ling , Guo Ting , Yang Huaping , Deng Pengbo , Gu Qihua , Liu Chi , Wu Mengping , Lizaso Analyn , Li Bing , Zhang Sa , Chen Zhiqiu , Hu Chengping 
Published: November 2020

Abstract
Background

Comprehensive mutation profiling has become a standard clinical practice in the management of advanced lung cancer. In addition to tissue and plasma, other body fluids are also being actively explored as alternative sources of tumor DNA. In this study, we investigated the potential of induced sputum obtained from patients with non-small cell lung cancer (NSCLC) for mutation profiling.
Methods

Capture-based targeted sequencing was performed on matched tumor, plasma, and induced sputum samples of 41 treatment-naïve patients with NSCLC using 168 gene panel.
Results

Comparative analysis on the mutation detection using matched tumor sample as reference revealed detection rates of 76.9% for plasma, 72.4% for sputum-supernatant, and 65.7% for sputum-sediment samples. Plasma, sputum-supernatant, and sputum-sediment achieved positive predictive values of 73.3%, 80.4%, and 55.6% and sensitivities of 50.0%, 36.9%, 31.3%, respectively, relative to tumor samples for 168 genes. Sputum-supernatants had significantly higher concordance rates relative to matched tumor samples (69.2% vs 37.8%; P = 0.031) and maximum allelic fraction (P < 0.001) than its matched sputum-sediments. Sputum-supernatants had comparable detection rates (71.4% vs. 67.9%; P = 1) but with significantly higher maximum allelic fraction than their matched plasma samples (P = 0.003). Furthermore, sputum-supernatant from smokers had a significantly higher maximum allelic fraction than sputum-supernatant from non-smokers (P = 0.021).
Conclusions

Our study demonstrated that supernatant fraction from induced sputum is a better sampling source than its sediment and has comparable performance as plasma samples. Induced sputum from NSCLC patients could serve as an alternative media for next-generation sequencing-based mutation profiling.
Integrated Multi-Omics Analyses Reveal the Molecular Basis of Tryptophol Over-Accumulation in Saccharomyces Cerevisiae
Authors: Gong Xiaowei , Luo Huajun , Hong Liu , Wu Jun , Song Chunxia , Zhao Wei , Wu Wenyu , Han Yi , Dao Ya , Zhang Xia , Zhu Donglai , Luo Yiyong 
Published: November 2020

Abstract
BackgroundTryptophol (TOL) is a metabolic derivative of tryptophan (Trp) and shows pleiotropic effects in humans, plants and microbes. The mechanisms of TOL biosynthesis were first explored several decades ago. Nonetheless, a systematic interpretation of TOL over-accumulation is still lacking.ResultsBased on TOL yield, a suitable transformation medium (TM1) was used to culture Saccharomyces cerevisiae strain KMLY1-2. The dynamics of TOL production, cell growth, and gene transcription revealed that TOL production was dependent on cell density and the expression of key genes. Additionally, the effects of Trp and phenylalanine (Phe) on TOL production were tested, and the results showed that Trp can significantly facilitate TOL accumulation, but output plateaued (231.02−266.31 mg/L) at Trp concentrations ≥0.6 g/L. In contrast, Phe reduced the stimulatory effect of Trp, which strongly depended on the Phe concentration. To elucidate the molecular basis and regulatory mechanism of TOL overproduction, an integrated analysis of metabolomics, genomics, and transcriptomics was performed. The results revealed that 1) both the Ehrlich pathway and tryptamine-dependent pathway were involved in S. cerevisiae TOL biosynthesis; 2) Trp increased TOL production by enhancing the Ehrlich pathway, in which the steps of transamination (including aminotransferase genes aro9, aat1, bat2 and his5) and decarboxylation (including decarboxylase genes aro10 and pdc5) played important roles. Of course, this process was assisted by amino acid permease genes agp1 and tat2, dihydrolipoyl dehydrogenase gene lpd1, and transcriptional activator gene aro80, etc.; 3) Phe restricted TOL biosynthesis by repressing the transcript levels of genes such as aat1, his5, aro10, pdc5 and aro80, thus interfering with the transamination and decarboxylation reactions; and 4) under sufficient Trp conditions, the de novo Trp biosynthetic pathway and central carbon metabolism (glycolysis, pentose phosphate pathway, and citrate cycle) of S. cerevisiae were weakened, while the content of some amino acids increased, which may be related to the promotion of yeast cell growth by Trp.ConclusionsIn this study, TOL production of S. cerevisiae was significantly improved, and our integrated multi-omics analyses have provided insights into the understanding of TOL over-accumulation, which will be useful for future production of TOL using metabolic engineering strategies.