bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of Sand-Control-Installation Failures Provides Insights, Paths Forward
Authors: Feder Judy
Published: November 2020

This article, written by JPT Technology Editor Judy Feder, contains highlights of paper SPE 199251, “Understanding Sand-Control-Installation Failures,” by Raymond Tibbles, SPE, Kesavan Govinathan, SPE, and Ian Mickelburgh, SPE, DuneFront, et al., prepared for the 2020 SPE International Conference and Exhibition on Formation Damage Control, 19-21 February, Lafayette, Louisiana. The paper has not been peer reviewed.

Sand-control-installation failures range from minor issues that can be remedied easily to catastrophic events that put the entire well and investment at risk. The complete paper introduces several case studies of such failures and details the investigative process and techniques used to identify root causes. A commercial software tool incorporating data-analysis techniques and a methodical evaluation work flow were used to understand the cause of the failures and determine how they can be prevented in future operations. Examples include events such as screen and washpipe damage, bridging, hole collapse, and packer-seal failure.

Introduction

Potential modes of failure tradition ally have been investigated with material- balance calculations and surface-pressure measurements. However, this simple approach is unable to diagnose clearly the specific failure mode and often is insufficiently precise to be conclusive, especially for high-value wells. While surface data provide an overview of the operation, the data are influenced by many factors involving the entire system, making it difficult to differentiate multiple events and locate them in the flow path. Mass-balance calculation is also a rudimentary analysis with many inherent assumptions. Often, estimations of perforation or openhole volumes are inaccurate, location of voids cannot be identified in the event of an incomplete pack, and gravel volume and mass measurements do not help in understanding packing mechanisms. Attempts have been made to develop logging techniques to obtain a clearer picture of the outcome of a gravel pack. While this effort has met with some success in cased holes, it has proved to be difficult to apply in open holes. Regardless, identification of the presence of voids in a gravel pack does not provide a clear explanation of why they formed and how they may be prevented in the future.
Predictive value of aberrant right subclavian artery for fetal Chromosome aneuploidy in women of advanced maternal age
Authors: Chen Li-Ping , Zhong Xiao-Hong , You Jian-Hong , Chen Jiang-Hua , Xie Jing-Xian , Chen Xiao-Kang , Chen Xiao-Yan , Lyu Guo-Rong
Published: November 2020

Background: In entire population, aberrant right subclavian artery ( ARSA) was in closely association with chromosomal abnormalities. The risk of fetal chromosomal abnormalities increased with the maternal age exponentially. This situation in advanced maternal age ( AMA )group is uncertain. This study aimed to establish the incidence of ARSA in Chinese AMA and non-AMA women and to determine the frequency of aneuploidy among AMA and non-AMA women with ARSA.Methods: The retrospective study included 13,690 singleton pregnancies which were divided into AMA and non-AMA groups. Integrated obstetric ultrasonic screening, biochemical screening, noninvasive prenatal screening and fetal karyotype analysis were analyzed.Results: 1. The overall incidence of ARSA was 0.69 % with no difference in both age groups. 2. The incidence rate of chromosomal abnormalities in AMA group ( 37 / 2,860 ) was much higher than that in non-AMA group. The risk of chromosomal abnormalities significantly increased with both ARSA detected and additional ultrasound findings. 3. With combined ARSA detected in AMA ones, the lilelihood of the incidence of chromosomal abnormalities increased. 4. Additionally, a case with chimeric ( 45X / 46XX ) was found with isolated ARSA in AMA pregnancy.Conclusion: There is a high prevalence of chromosomal abnormalities in AMA fetuses. ARSA would increase the risk of chromosomal abnormalities in both age groups, especially combined ARSA. Moreover, when combined ARSA is found in AMA ones, it confers a high likelihood of chromosomal abnormalities.
Thyroid Cancer Overdiagnosis and Overtreatment: a cross- sectional study at a thyroid cancer referral center in Ecuador 
Authors: Solis-Pazmino Paola , Salazar-Vega Jorge , Lincango-Naranjo Eddy , Garcia Cristhian , Koupermann Gabriela Jaramillo , Ortiz-Prado Esteban , Ledesma Tannya , Rojas Tatiana , Alvarado-Mafla Benjamin , Carcamo Cesar , Ponce Oscar J. , Brito Juan P.
Published: November 2020

Background: In contrast to the rapid increase in thyroid cancer (TC) incidence, thyroid cancer mortality has remained low and stable over the last decades. In Ecuador, however, TC mortality has increased. The objective of this study is to determine possible drivers of high rates of thyroid cancer mortality, through a cross-sectional analysis of all patients attending a thyroid cancer referral center in Ecuador.Methods: From June 2014 to December 2017, a cross-sectional study was conducted at the Hospital de Especialidades Eugenio Espejo (HEEE), a regional reference public hospital for endocrine neoplasia in adults in Quito, Ecuador. We identified the mechanism of detection, histopathology and treatment modalities from a patient interview and review of clinical records. Results: Among 452 patients, 74.8% were young adults and 94.2% (426) were female. 13.7% had a family history of thyroid cancer, and patients’ median tumor size was 2 cm. The incidental finding was 54.2% whereas 45.8% was non-incidental. Thyroid cancer histology reported that 93.3% had papillary thyroid cancer (PTC), 2.7% follicular, 1.5% Hurtle cells, 1.6% medullary, 0.7% poor differentiated, and 0.2% anaplastic carcinoma. The mean MACIS (metastasis, age, completeness, invasion, and size) score was 4.95 (CI 4.15-5.95) with 76.2% of the thyroid cancer patients having MACIS score less than or equal to 6. The very low and low risk of recurrence was 18.1% (79) and 62% (271) respectively. An analysis of 319 patients with non-metastatic thyroid cancer showed that 10.7% (34) of patients had surgical complications. Moreover, around 62.5% (80 from 128 patients with thyroglobulin laboratory results) of TC patients had a stimulated-thyroglobulin (sTg) value equal or higher than 2 ng/ml. Overall, a poor surgical outcome was present in 35.1% (112) patients. Out of 436 patients with differentiated thyroid carcinoma (DTC), 86% (375) received radioactive iodine (RAI). Conclusion: Thyroid cancer histological characteristics and method of diagnosis are like those described in other reports without any evidence of the high frequency of aggressive thyroid cancer histology. However, we observed evidence of overtreatment and poor surgical outcomes that demand additional studies to understand their association with thyroid cancer mortality in Ecuador.
QMAP-Seq: Quantitative and Multiplexed Analysis of Phenotype by Sequencing
Authors: Brockway Sonia , Wang Geng , Jackson Jasen M. , Amici David R. , Takagishi Seesha R. , Clutter Matthew R. , Bartom Elizabeth T. , Mendillo Marc L.
Published: November 2020

Chemical-genetic interaction profiling in model organisms has proven powerful in providing insights into compound mechanism of action and gene function. However, identifying chemical-genetic interactions in mammalian systems has been limited to low-throughput or computational methods. Here, we develop Quantitative and Multiplexed Analysis of Phenotype by Sequencing (QMAP-Seq), which leverages next-generation sequencing for pooled high-throughput chemical-genetic profiling. We apply QMAP-Seq to investigate how cellular stress response factors affect therapeutic response in cancer. Using minimal automation, we treat pools of 60 cell types—comprising 12 genetic perturbations in five cell lines—with 1,440 compound-dose combinations, generating 86,400 chemical-genetic measurements. QMAP-Seq produces precise and accurate quantitative measures of acute drug response comparable to gold standard assays, but with increased throughput at lower cost. Moreover, QMAP-Seq reveals clinically actionable drug vulnerabilities and functional relationships involving these stress response factors, many of which are activated in cancer. Thus, QMAP-Seq provides a broadly accessible and scalable strategy for chemical-genetic profiling in mammalian cells.
Chemiluminescence imaging of cells (CLIC)
Authors: Fisher Jane , Sørensen Ole E. , Abu-Humaidan Anas H. A.
Published: November 2020

Here we describe a simple, sensitive and robust chemiluminescence-based immunoassay (chemiluminescence imaging of cells; CLIC) for relative quantification of proteins in cells. We first employed this method to quantify complement activation in cultured mammalian cells, and to quantify membrane protein expression, shedding, binding and internalization. Moreover, through specific membrane permeabilization we were able to quantify both cytosolic and nuclear proteins, and their translocation. We validated the CLIC quantification method by performing parallel experiments with other quantification methods like ELISA, qPCR, and immunofluorescence microscopy. The workflow of the immunoassay was found to be advantageous in certain instances when compared to these quantification methods. Since the reagents used for CLIC are common to other immunoassays with no need for specialized equipment, and due to the good linearity, dynamic range and signal stability inherent to chemiluminescence, we suggest that this assay is suitable for both small scale and high throughput relative protein quantification studies in whole cells
Modulation of June Rainfall in India by Winter Salinity Barrier Layer in the Bay of Bengal
Authors: Pang Shanshan , Wang Xidong , Foltz Gregory , Fan Kaigui
Published: November 2020

This study finds that the winter barrier layer (BL) in the Bay of Bengal (BoB) can modulate the subsequent Indian summer monsoon (ISM) onset and associated rainfall variability. In the years when the prior winter BL is anomalously thick, there is anomalous sea surface cooling caused by intensified latent heat flux loss, and this anomalous cooling persists into the following year due to positive cloud–SST feedback. During December–February, it is shown that the vertical entrainment of warmer subsurface water due to anomalously thick BL acts to limit excessive cooling of the sea surface and maintain deep atmospheric convection over the BoB. Then, during March–May, the thinner mixed layer linked to anomalously thick BL allows more shortwave radiation to penetrate below the mixed layer. This tends to reinforce the cold SST anomalies, and advance the onset of ISM and enhance June ISM precipitation through an increase in the tropospheric temperature gradient between land and sea. We also find that most CMIP5 models fail to reproduce the observed relationship between June ISM rainfall and the prior winter BL. This may be attributable to their difficulties in realistically simulating the winter BL in the BoB and ISM precipitation. The present results indicate that it is important to realistically capture the winter BL of the BoB in air–sea coupled models for improving the simulation and prediction of ISM.
Alpha-ketoglutaric acid ameliorates hyperglycemia in diabetes by inhibiting hepatic gluconeogenesis via serpina1e signaling
Authors: Shu Gang , Yuan Yexian , Sun Jia , Zhu Canjun , Feng Jinlong , Ma Zewei , Peng Wentong , Yin Cong , Xu Guli , Xu Pingwen , Jiang Yuwei , Wang Songbo , Zhu Xiaotong , Gao Ping , Wang Lina , Xi Qianyun , Zhang Yongliang , Jiang Qingyan
Published: November 2020

While resistance exercise effectively improves overall health in diabetic patients, the underlying biological mechanism by which resistance exercise improves metabolic function and glucose homeostasis remain mostly unknown. Previously, we identified a myometabolite-mediated metabolic pathway that is essential for the beneficial effects of resistance exercise on metabolic function. We found that resistance exercise-induced α-ketoglutaric acid (AKG) stimulates muscle hypertrophy and fat loss through 2-oxoglutarate receptor 1 (OXGR1)-dependent adrenal activation. Here, we provided evidence for the beneficial effects of AKG on glucose homeostasis in a diet-induced obesity (DIO) mouse model, which are independent of OXGR1. We showed that circulating AKG levels are negatively correlated with the fraction of blood glycated hemoglobin (HbA1c) in both humans and mice and significantly decreased in DIO mice. Consistently, pharmacological elevation of AKG effectively decreased body weight, blood glucose, and hepatic gluconeogenesis without changing insulin sensitivity and glucose tolerance in DIO mice. Notably, OXGR1KO blocked the inhibitory effects of AKG on body weight but failed to affect AKG’s suppression on blood glucose and hepatic gluconeogenesis, indicating distinct mechanisms for AKG’s regulation on energy balance and glucose homeostasis. In supporting this view, we showed that serpina1e, a member of protease inhibitor serpins superfamily, mediates the direct inhibitory effects of AKG on gluconeogenesis in both in vitro hepatocytes and liver slice. By using a liver-specific serpina1e deletion mouse model, we further demonstrated that liver serpina1e is required for the inhibitory effects of AKG on hepatic gluconeogenesis and hyperglycemia in DIO mice. Finally, we provided in vitro evidence to support a model in which AKG decreases hepatic gluconeogenesis by targeting trimethylation of lysine 27 on histone 3 (H3K27me3) in seprina1e promoter region. Our studies established an important role of AKG in glucose homeostasis, and identified the AKG-serpina1e pathway as potential therapeutic targets to attenuate hyperglycemia.
The Relationship Between Frailty and Depression, Quality of Life, Disability, and Hospitalization Among Community-Dwelling Older Adults
Authors: Hayajneh Audai A. , Hammouri Hanan , Al-Satari Eman S. , Wallace Debra C. , Rababa Mohammad
Published: November 2020

Background: Frailty syndrome is characterized by a decline in physiological and psychological reserve that leads to poor health outcomes. Objectives: The current study explored frailty and its impacts on health outcomes among older adults in close-knit Jordanian communities. Methods: A secondary analysis (N=109) of community-dwelling older adults aged 60 years or over was conducted. The Arabic version of the culturally adapted Tilburg Frailty Indicator, the Geriatric Depression Scale, the Montreal Cognitive Assessment, the SF-36 Quality of Life survey, and disability self-reports were used. Results: Despite Jordanian communities being very close-knit, the results indicated a high prevalence of frailty (78%) and depression (38%) and poor outcomes of cognitive dysfunction and low quality of life among the participating older adults. Further, the prevalence of frailty was found to be 4.2 times higher among females than males and 7.2 times higher among single older adults than married older adults. Conclusion: A high prevalence of frailty and its related adverse outcomes was found among older adults in Jordan.
Sarcopenia as A Predictor of Mortality Among the Critically Ill in an Intensive Care Unit: A Systematic Review and Meta-Analysis
Authors: Zhang Xiao-Ming , Chen Denghong , Xie Xiao-Hua , Zhang Jun-E , Zeng Yingchun , Cheng Andy SK
Published: November 2020

Background: The evidence of sarcopenia based on CT-scan as an important prognostic factor for critically ill patients has not seen consistent results. Objective: To determine the impact of sarcopenia on mortality in critically ill patients, we performed a systematic review and meta-analysis to quantify the association between sarcopenia and mortality.Methods: We searched studies from the literature of PubMed, EMBASE, and Cochrane Library from database inception to June 15, 2020. All observational studies exploring the relationship between sarcopenia based on CT-scan and mortality in critically ill patients were included. The search and data analysis were independently conducted by two investigators. A meta-analysis was performed using STATA Version 14.0 software using a fixed effects mode. Results: Fourteen studies with a total of 3,249 participants were included in our meta-analysis. The pooled prevalence of sarcopenia among critically ill patients was 38% (95% CI:36%-39%). Critically ill patients with sarcopenia in intensive care unit have an increased risk of mortality, compared to critically ill patients without sarcopenia (HR=2.22, 95%CI: 1.79-2.75; P<0.001; I2=0.0%). In addition, a subgroup analysis found a significant difference in the association between sarcopenia and mortality when using total psoas muscle area (TPA), skeletal muscle index (SMI), and skeletal muscle area (SMA) to define sarcopenia (HR=2.96,95%CI:1.72-5.11,P<0.001; HR = 2.11,95%CI:1.59-2.80,P<0.01; HR=2.11, 95%CI:1.33-3.33,P=0.001, respectively), whereas the results were not significant when measuring the masseter muscle to define sarcopenia (HR=2.00, 95%CI:0.82-4.90,P=0.129).Conclusion: Sarcopenia increases the risk of mortality in critical illness. Identifying the risk factors of sarcopenia should be routine in clinical assessments, offering corresponding interventions may help medical staff achieve good patient outcomes in ICU departments.
Efficient Crispr-cas9 Mediated Pooled-sgRNAs Assembly Accelerates Targeting Multiple Genes Related to Male Sterility in Cotton 
Authors: Ramadan Mohamed , Alariqi Muna , Ma Yizan , Li Yanlong , Liu Zhenping , Zhang Rui , Jin Shuangxia , Min Ling , Zhang Xianlong
Published: November 2020

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 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

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

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

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

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

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

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

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

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

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

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.
The complexity of genomic mutation dictates the prognosis of acute leukemia with ambiguous lineage
Authors: Huang Jin , Xiao Min , Zhou Jing , Mao Xia , Zhu Li , Liu Songya , Li Qinlu , Wang Jin , Zhou Jianfeng , Cai Haodong , Wang Gaoxiang
Published: November 2020

Background

Acute leukemia with ambiguous lineage (ALAL) is a rare and heterogeneous group of highly aggressive malignancy with poor clinical outcome, limited molecular characterization and lack of general therapeutic recommendations.
Results

In this study, we retrospectively analyzed 1635 acute leukemia cases in our center from January 2012 to June 2018.The diagnose of ALAL was based on either EGIL or 2016 WHO criteria. Totally, 39 patients were included in this study and 30 patients satisfied the WHO criteria. Four patients diagnosed as acute undifferentiated leukemia (AUL) by both classification systems. Genetic analysis showed that mutations detected in bi-phenotypic acute leukemia enriched in genes related to genomic stability and transcriptional regulation; while AUL cases frequently mutated in genes involved in signaling pathway. Survival analysis of all patients included suggested that the prognosis of ALAL was independent of immunophenotype, chromosome karyotype, treatment, but significantly associated with the mutation complexity, also termed numbers of the mutations carried by each patient (Log rank p = 0.009 for progression-free survival [PFS] and Log rank p = 0.047 for overall survival [OS], respectively). Similar results were obtained when the WHO diagnostic system were applied. Among these patients, those excluded by WHO criteria had even worse clinical outcome than the patients included (Log rank p = 0.023 for PFS and Log rank p = 0.031 for OS).
Conclusions

Collectively, the complexity of genomic mutation of ALAL patients seems significantly related to the clinical outcomes. The rationality and clinical applicability of the diagnostic criteria of WHO system need to be evaluated by more large-scale clinical studies.
WITHDRAWN: Re-Investigation of Institutional Quality and Ecological Footprint: A Case Study of Pakistan
Authors: Hussain Muzzammil , Yousaf Hira
Published: November 2020

The discourse on the environment and growth nexus has been an important research agenda. However, the debate on the role of institutional quality (IQ) in environmental degradation is not adequate. Unlike others, this study examines the asymmetric effect of IQ towards ecological footprint (EF) from 1984 to 2014 in Pakistan. The non-linear autoregressive distributive lag model revealed that positive shocks are negatively effecting EF and negative shocks are positively effecting EF. Our findings suggest that a better IQ is substantially reducing EF, whereas energy consumption and economic growth are increasing EF. The study has robust policy implications.
Treatment by Low-Dose Brain Radiation Therapy Improves Memory Performances without Changes of the Amyloid Load in the TgF344-AD Rat Model.
Authors: Ceyzériat Kelly , Zilli Thomas , Fall Aida B. , Millet Philippe , Koutsouvelis Nikolaos , Dipasquale Giovanna , Frisoni Giovanni B. , Tournier Benjamin B. , Garibotto Valentina
Published: November 2020

Background. Alzheimer’s disease (AD) is a neurodegenerative condition affecting memory performance. This pathology is characterized by intracerebral amyloid plaques and tau tangles coupled with neuroinflammation. During the last century, numerous therapeutic trials, targeting amyloid, tau or neuroinflammation, unfortunately failed. Development of new therapeutic approaches for AD is eagerly awaited. In this study, we propose to test the use of low-dose brain radiotherapy (LD-RT). LD-RT showed efficacy to reduce amyloid load in patients with peripheral pathologies and also presents anti-inflammatory effects in patients with systemic inflammatory diseases. Furthermore, previous evidence showed an effect on amyloid load, memory performance and modulation of the immune response in AD mice. Methods. The hemi-brain of 14-15 months old TgF344-AD rats was irradiated with two LD-RT schedules (5 fractions of 2 Gy, delivered weekly or daily). Rats underwent behavioral tests to assess memory and general locomotion, before and/or 4 months post treatment. LD-RT impact on amyloid and neuroinflammation was measured using immunohistology.Results. An improvement of spatial working memory was observed in the daily treated group but not in animals treated weekly. On the other hand, both LD-RT schedules were unable to impact amyloid load. An increase of astrocyte reactivity was observed in TgAD groups compared to wild-type animals but LD-RT did not impact it. The weekly treatment increased CD68+ microglial density in the molecular layer of the hippocampus but no effect was observed with the daily treatment. One major limitation of this study was the already well-established amyloid pathology, which was probably too advanced to observe a potential decrease. Nevertheless, we observed a memory improvement, the main cognitive symptoms of AD, after daily treatment, offering encouraging data to further evaluate the LD-RT therapeutic potential. Conclusions. This study showed a biological effect of LD-RT in an AD rat model on memory performance (after daily treatment) and microglial density (after weekly treatment). The lack of effect of both regimens on amyloid pathology, unexpected, was possibly due to the advanced pathology of our animals. The positive effect on cognition encourages to further evaluate the LD-RT therapeutic potential at an earlier AD stage.
Assessing the sustainability of yellow anaconda (Eunectes notaeus) harvest in northeastern Argentina
Authors: Camera Bruno , Stüssmann Christine , Quintana Itxaso , Waller Tomás , Barros Mariano , Draque Juan , Mucucci Patrício , Miranda Everton
Published: November 2020

Sustainable wildlife management is required to guarantee source species viability; however, it is practiced rarely in the tropics. The yellow anaconda (Eunectes notaeus) has a long history of being harvested for its leather. Since 2002 its harvest has operated under a management program in northeastern Argentina, which relies on adaptive management through limiting the minimum anaconda length, number of hunters and restricting the hunting season. We investigated the effects of the anaconda harvest on its biological parameters based on 2002-2016 data. Here we show that the levels of species exploitation are sustainable. The gradual reduction in the annual hunting effort, due to a decrease in number of hunters and hunting season duration, reduced the total number of anacondas harvested. Conversely, captures per unit effort increased across the study time-period. There was no variation in the mean length of anacondas harvested, or in largest anaconda sizes. Though more females than males were caught, the sex ratio did not vary significantly. We also found that a decrease in mean temperature positively influenced anaconda harvest and the captures of giant individuals. Because sustainable use is a powerful tool for conservation, those discoveries are highly applicable to other species and regions.