bluuebunny/crossref_metadata_2025 huggingface dataset:
Reverse chemistry of iron under high pressure and the distribution of elements in the deep Earth
Authors: Wang Xiaoli , Feng Xiaolei , Li Jianfu , Khodagholian Dalar , Lin Jiani , Jackson Matthew , Spera Frank , Redfern Simon , Miao Maosheng
Published: December 2020

We demonstrate a remarkable change of chemical trend of iron under high pressure that is of great importance for understanding the distribution of elements in the Earth’s mantle and core. Using a massive-scale first principles study, we show that while reacting with p-block elements under increasing pressure from ambient to that of Erath’s core, iron tends to reverse its chemical nature, changing from an electron donor (reductant) to an electron acceptor, and oxidizes p-block elements. Such reverse chemistry significantly impacts the stoichiometries, bond types and strengths, structures and properties of iron compounds under deep planetary conditions, making many p-block elements that are conventionally labeled lithophile or chalcophile to highly siderophile. The chemical binding strengths with iron show an inverse correlation with the depletion of p-block elements in silicate Earth. Furthermore, silicon shows a distinct anomaly in its bonding to iron, which suggests silicon may readily be incorporated into Earth’s core.
Large Metallicity Variations in the Galactic Interstellar Medium
Authors: De Cia Annalisa , Jenkins Edward , Ledoux Cedric , Fox Andrew , Ramburth-Hurt Tanita , Konstantopoulou Christina , Petitjean Patrick
Published: December 2020

Metals in the neutral Interstellar Medium (ISM) of galaxies are crucial for the formation and evolution of galaxies, stars, cosmic dust, molecules, and planets. However, understanding the metal abundances in the neutral ISM is complicated by the presence of cosmic dust. Large quantities of metals are missing from the observable gas-phase because they are incorporated into dust grains. This phenomenon is called dust depletion. Until recently, the metallicity of the neutral ISM in the vicinity of the Sun was assumed to be Solar. In this paper we directly measure the metallicity of the neutral ISM, by quantifying dust depletion without making as- sumptions on the gas metallicity, using Hubble Space Telescope (HST) and Very Large Telescope (VLT) spectra of 25 hot bright stars. We find that the dust-corrected metal- licity in the neutral ISM in our Galaxy is not always Solar, but shows large variations spreading over a factor of 10 and including many regions of low metallicity, down to ∼ 17% Solar and possibly below. Pristine gas infalling towards the Galactic disk in the form of intermediate and high-velocity clouds could cause the observed chemical inhomogeneities on scales of tens of pc. This has a profound impact for the chemical evolution of galaxies.
Nuclear Factor-kappaB Regulates the Transcription of NADPH Oxidase 1 in Human Alveolar Epithelial Cells
Authors: Wu Weijing , Li Li , Su Xiaoshan , ZHU ZHIXING , Lin Xiaoping , Zhang Jiamin , Zhuang Zesen , Cai Hongyi , Huang Wenjie
Published: December 2020

Objective Acute lung injury (ALI) is characterized by inflammation and oxidative stress. Nuclear factor-kappaB (NF-κB) mediates the expression of various inflammation-related genes, including the NADPH oxidase family. This study aimed to identify the potential regulatory role of NF-𝜅B on NADPH oxidases in TNF-α-induced oxidative stress in human alveolar epithelial cells. Methods Type II alveolar epithelial cell-derived A549 cells were treated with TNF-α for 24 hours to establish ALI cell models. RT-PCR, western blot, DCFH-DA ROS assay, Alibaba 2.1 online analysis, electrophoretic mobility shift assays and luciferase reporter analysis were employed to identify the potential regulatory role of NF-𝜅B on NADPH oxidases in TNF-α-induced oxidative stress in human alveolar epithelial cells. Results The expression of NF-κB/p65 was notably upregulated in TNF-α-stimulated A549 cells. NF-κB knockdown by siRNA significantly inhibited the TNF-α-induced ROS generation. Moreover, NF-𝜅B/p65 siRNA could inhibite the activation of NOX1, NOX2 and NOX4 mRNA and protein expression in TNF-α-stimulated A549 cells. The next study demonstrated that NF-𝜅B activated the transcription of NOX1 by binding to the -261 to -252 bp (NOX1/κB2, TAAAAATCCC) region of NOX1 promoter in TNF-α-stimulated A549 cells. Conclusion Our data demonstrated that NF-κB can aggravate TNF-α-induced ALI by regulating the activation of ROS generation and the expression of NOX1, NOX2 and NOX4. Moreover, NF-𝜅B could promote the NOX1 transcriptional activity via binding its promoter in TNF-α-stimulated A549 cells.
Simulated and Experimental Study of Sediments Sampling Parameters Based on the VOF Method
Authors: He Shudong , Peng YouDuo , Jin Yongping , Yan Jian , Wan Buyan
Published: December 2020

Sediments in the seabed hold vital clues to the study of marine geology, microbial communities and history of ocean life, and the remote operated vehicle (ROV) mounted tubular sampling is an important way to obtain sediments. However, sampling in the seabed is a particularly difficult and complicated task due to the difficulty accessing deep water layers. The sampling is affected by the sampler’s structural parameters, operation parameters and the interaction between the sampling tube and sediments, which usually results in low volume and coring rate of sediments obtained. This paper simulated the soft viscous seabed sediments as non-Newtonian Herschel-Bulkley viscoplastic fluids and established a numerical model for the tubular sampling based on the volume of fluid (VOF) method. The influence rules of the sampling tube diameter, drainage area rate, penetration velocity, and sediments dynamic viscosity on coring rate and volume were studied. The results showed that coring volume was negatively correlated with all the parameters except the sampling tube diameter. Furthermore, coring rate decreased with increases in penetration velocity, drainage area rate, and sediments dynamic viscosity. The coring rate first increased and then decreased with increasing of the sampling tube diameter, and the peak value was also influenced by penetration velocity. Then, based on the numerical simulation results, an experimental sampling platform was set up and real-world sampling experiments were conducted. The simulation results tallied with the experimental results, with a maximum absolute error of only 4.6%, which verified that the numerical simulation model accurately reflected real-world sampling. The findings in this paper can provide a theoretical basis for facilitating the optimal design of the geometric structure of the seabed sediments samplers and the parameters in the sampling process.
A Raman Algorithm to Estimate Human Age From Protein Structural Variations in Autopsy Skin Samples: the Proteins’ Biological Clock
Authors: Miyamori Daisuke , Uemura Takeshi , Zhu Wenliang , Fujikawa Kei , Teramukai Satoshi , Pezzotti Giuseppe , Ikegaya Hiroshi
Published: December 2020

The recent increase of the number of unidentified cadavers has become a serious problem in the world. As a simple and objective method for age estimation, we attempted to utilize Raman spectrometry for forensic identification. Raman spectroscopy is an optical-based vibrational spectroscopic technique that provides detailed information about molecular composition and structure. Building upon our previous proof-of-concept study, Raman spectra of abdominal skin sample were measured in 132 autopsy cases and protein-folding intensity ratio (RPF) was calculated. There was a strong negative correlation between age and RPF with a Pearson correlation coefficient r = 0.878. The results of cross validation suggested that Model 2 (the square of RPF) is the best model with lowest mean squared error (127.9) and highest coefficient of determination (0.743) among the four models. Our results indicate that the there is a high correlation between the age and RPF. The Raman biological clock of protein folding can be used as a simple and objective forensic age estimation method of unidentified cadavers.
Risk Factors for Orbital Implant Extrusion After Evisceration
Authors: Kim Ju Mi , Sung Jae Yun , Lim Hyung Bin , Choi Eunjung , Lee Sung Bok
Published: December 2020

Purpose: This study analyzed risk factors for extrusion of orbital implants after evisceration by comparing patients with and without implant extrusion.Design: Retrospective study.Methods: We retrospectively reviewed the medical records of patients who underwent evisceration with primary implant placement by a single surgeon from January 2005 to December 2019 at Chungnam National University Hospital. Age, sex, underlying systemic diseases, axial length of the fellow eye, the cause of evisceration, endophthalmitis type, implant type and size, and preoperative computed tomography findings were evaluated. Logistic regression analysis was used to identify the risk factors for implant extrusion.Results: Of the 140 eyes of 140 patients, extrusion occurred in 5 eyes (3.6%). Endophthalmitis (odds ratio (OR), 15.49; 95% confidence interval (CI), 1.70 to 2038.56; p = 0.010), endogenous endophthalmitis (OR, 18.73; 95% CI, 3.22 to 125.21, p = 0.002), orbital cellulitis (OR, 320.54; 95% CI, 29.67 to 44801.64; p < 0.001), implant size (OR, 0.50; 95% CI, 0.30 to 0.79; p = 0.004), and hydroxyapatite for the implant (OR, 0.07; 95% CI, 0.00 to 0.66; p = 0.016) were risk factors for implant extrusion in univariate logistic regression analysis. Multiple logistic regression analysis identified orbital cellulitis as the only risk factor for extrusion (OR, 52.98; 95% CI, 2.18 to 15367.34; p = 0.009).Conclusions: Evisceration with primary orbital implantation is a feasible option in endophthalmitis, but the risk of extrusion should be taken into consideration. When performing evisceration in a patient with orbital cellulitis, secondary implantation should be carried out only after any infection is controlled.
Skin-Integrated Electromechanical Systems for Characterization of Deep Tissue Biomechanics
Authors: Rogers John , Song Enming , Xie Zhaoqian , Bai Wubin , Luan Haiwen , Ji Bowen , Ning Xin , Xia Yu , Baek Janice Mihyun , Lee Yujin , Avila Raudel , Chen Huang-Yu , Kim Jae-Hwan , Madhvapathi Surabhi , Yao Kuanming , Won Sang , Zhang Xinyuan , Myers Daniel , Mei Yongfeng , Guo Xu , Xu Shuai , Yu Xinge , Huang Yonggang
Published: December 2020

Compact electronic systems that perform rapid, precise mechanical characterization of living biological tissues have important potential uses in monitoring and diagnosing various types of human-health disorders. Active devices that perform high-precision, real-time evaluations of deep tissue structures (millimeter-scale) in a precise, digital and non-invasive fashion could complement capabilities of recently-reported approaches for sensing tissue biomechanics at superficial depths (typically micrometer-scale). This paper introduces a miniature electromagnetic platform that combines a vibratory actuator with a soft strain-sensing sheet for determining the Young’s modulus of soft biological tissues, with specific focus on skin. Experimental and computational studies establish the operational principles and performance attributes through evaluations of synthetic and biological materials, including human skin at various body locations across healthy subject volunteers. The results demonstrate dynamic monitoring of elastic modulus at characteristic depths between ~1 and ~8 mm, depending on the sensor designs. Arrays of such devices support capabilities in both depth profiling and spatial mapping. Clinical studies on patients with skin disorders highlight potential for accurate targeting of lesions associated with psoriasis, as examples of practical medical utility.
Cytotoxic and Anti-excitotoxic Effects of Selected Plant and Algal Extracts Using Comet and Cell Viability Assays
Authors: Al-Dbass Abeer , Amina Musarat , Musayeib Nawal Al , Bhat Ramesa Shafi , Al-Rashed Sara , Marraiki Najat , Fahmy Rania , El-Ansary Afaf
Published: December 2020

Excess glutamate in the central nervous system may be a major cause of neurodegenerative diseases with gradual loss and dysfunction of neurons. Primary or secondary metabolites from medicinal plants and algae show potential for treatment of glutamate-induced excitotoxicity. Three plant extracts were evaluated for impact on glutamate excitotoxicity-induced in primary cultures of retinal ganglion cells. These cells were treated separately in seven groups: control; Plicosepalus. curviflorus treated; Saussurea lappa treated; Cladophora glomerate treated. Cells were treated independently with 5, 10, 50, or 100 µg/ml of extracts of plant or alga material, respectively, for 2 h. Glutamate-treated cells (48 h with 5, 10, 50, or 100 µM glutamate); and P. curviflorus/glutamate; S. lappa/glutamate; C. glomerata/glutamate [pretreatment with extract for 2 h (50 and 100 µg/ml) before glutamate treatment with 100 µM for 48 h]. Comet and MTT assays were used to assess cell damage and cell viability. The number of viable cells fell significantly after glutamate exposure. Exposure to plant extracts caused no notable effect of viability. All tested plants extracts showed a protective effect against glutamate excitotoxicity-induced RGC death. Use of these extracts for neurological conditions related to excitotoxicity and oxidative stress might prove beneficial.
The Utilization of Warfarin Dosing Algorithms in China: An Electronic Survey Study
Authors: Liu Yaxin , Wu Tian , Kuang Yun , Ning Xiaoyi , Xie Jinlian , Guo Chengxian , Xiang Yuxia , Jiang Weihong , Yang Guoping
Published: December 2020

Background: Warfarin, a key anticoagulant medication, has a narrow therapeutic window and individual difference. Many warfarin dosing algorithms have been developed and been proved to have clinical benefits. However, the utilization of algorithms by medical professionals in China was unknown. We conducted an online survey to investigate the use and requirements of warfarin dosing algorithms among Chinese medical professionals. Method: A questionnaire survey was conducted via WeChat to investigate the utilization of warfarin dosing algorithms by medical professionals in seven regions of China. The content of questionnaire was included general characteristics of participants, condition of anticoagulant therapy, utilization of warfarin dosing algorithms and demand for function of an assistant warfarin dosing system we proposed.Results: A total of 399 participants completed the survey. Although most medical professionals use warfarin for anticoagulant therapy, some of them (15.04%) were not familiar with warfarin’s individual difference. As high as 32.97% of clinicians ruled out genotypes when using warfarin. The vast majority of anticoagulant medical professionals believed warfarin dosing algorithms can have clinical benefits, but only 20.80% of them usually use algorithms for anticoagulant therapy. Conclusion: Warfarin dosing algorithms have high evaluation while not good utilization among Chinese anticoagulant medical professionals. If warfarin dosing algorithms and assistant tools aimed to Chinese population were developed, to some extent can improve anticoagulant therapy in China.
Historical Tree Species Height Growth Pattern Associated With Climate Change in Western North America
Authors: Messaoud Yassine , Reid Anya , Tchebakova Nadezhda M. , Hofgaard Annika , Messsaoud Faouzi
Published: December 2020

BackgroundThe climate variables effect on tree growth in boreal and temperate forests has received increased interest in the global context of climate change. However, most studies are geographically limited and involved few tree species. Here, sixteen tree species across western North America were used to investigate tree response to climate change at the species range scale. MethodsForest inventory data from 36,944 stands established between 1600 and 1968 throughout western Canada and USA were summarized. Height growth (total height at breast-height age of 50 years) of healthy dominant and co-dominant trees were related to annual and summer temperatures, annual and summer Palmer Drought Severity Index (PDSI, and tree establishment date (ED). Climate-induced height growth patterns were then tested to determine links to spatial environment (soil conditions and geographic locations), species range (coastal, interior, and both ranges) and species traits (shade tolerance and leaf form), using linear mixed model for the global height growth and general linear model to test the height growth patterns for each species. ResultsIncrease of temperatures and PDSI had a positive effect on height growth for most of the study species, whereas Alaska yellow-cedar (Chamaecyparis nootkatensis, (D. Don) Spach) height growth declined with ED. All explaining variables and the interactions explained 59% of the total height growth variance. Although tree height growth response was species-specific, increased height growth during the 20th century was more pronounced for coastal ranged species, high shade tolerant species, and broadleaf species. Furthermore, height growth increase occurred mostly on rich soil, at the northernmost species range, and, unexpectedly, at lower elevations. A decline in height growth for some species further north and especially higher in elevation possibly related to increased cloudiness and precipitation. However, drought conditions remain in interior areas despite moving northward and upward that decrease height growth. ConclusionThese results highlight the general trend (species characteristics and range) and the species-specific height patterns, indicating the spatio-temporal complexity of the growth response to recent global climate change.
A novel nomogram for predicting survival in patients with severe acute pancreatitis: an analysis based on the large MIMIC-III clinical database
Authors: Han Di di , Xu Shuo Feng , Li Zhuo Cheng , Zhang Ming Lu , Yang Rui , Zheng Shuai , Wang Chen Zi , Lyu Jun
Published: December 2020

Background Severe acute pancreatitis (SAP) can cause various complications. Septic shock is a relatively common and serious complication that causes uncontrolled systemic inflammatory response syndrome, which is one of the main causes of death. This study aimed to develop a nomogram for predicting the overall survival of SAP patients during the initial 24 hours following admission. Materials and Methods All data utilized in this study were obtained from the MIMIC-III (Medical Information Mart for Intensive Care III) database. The data were analyzed using multivariate Cox regression, and the performance of the proposed nomogram was evaluated based on Harrell’s concordance index (C-index) and the area under the receiver operating characteristic curve(AUC). The clinical value of the prediction model was tested using decision-curve analysis (DCA). The primary outcomes were 28-day,60-day, and 90-day mortality rates. Results The 850 patients included in the analysis comprised 595 in the training cohort and 255 in the validation cohort. The training cohort consisted of 353 (59.3%) males and 242 (40.7%) females with SAP. Multivariate Cox regression showed that weight, sex, insurance status, explicit sepsis, SAPSII score, Elixhauser score, bilirubin, anion gap, creatinine, hematocrit, hemoglobin, RDW, SpO 2 , and respiratory rate were independent prognostic factors for the survival of SAP patients admitted to an intensive care unit. The predicted values were compared using C-indexes, calibration plots, integrated discrimination improvement, net reclassification improvement, and DCA. Conclusions We have identified some important demographic and laboratory parameters related to the prognosis of patients with SAP, and have used them to establish a more accurate and convenient nomogram for evaluating their 28-day, 60-day, and 90-day all-cause mortality rates. The prognostic value of the novel nomogram is superior to that of the traditional SAPSII scoring system alone.
A More Efficient Observation Way With Electric Dipole Sources
Authors: wang xianxiang , Chang yongbang , Deng Juzhi
Published: December 2020

The Ex and Hz amplitude are monotonic functions of the resistivity, and numerical algorithm can be utilized to obtain the high-precision apparent resistivity for all frequencies. On this basis, we focus on the comparative analysis of the resolution for Ex field, Hz field, and Cagniard apparent resistivity to conductive and resistance targets, which proves that the Ex field may have a better resolution for the resistance bodies, and the Hz field can better identify the conductive target. Besides, the electromagnetic data is often distorted by the static effect, which seriously affects the application effect of the electromagnetic method. The influence of the static effect on the Ex field, Hz field, is also analyzed. The apparent resistivity based on the Ex field and Cagniard apparent resistivity are severely affected by the static effect which can cover deep anomalous bodies, but the apparent resistivity based on the Hz field is almost unaffected by the static effect. At last, a more efficient observation way is provided for the resistance and conductive targets, respectively.
Identification of Biomarkers and Study of Mechanisms Related to Metastatic of Osteosarcoma Based on Integrated Bioinformatics Analyses
Authors: Wu Guangzhi , Zhang Minglei
Published: December 2020

BackgroundOsteosarcoma (OS) is a serious threat to public health. Because of high morbidity and fairly complicated pathogenesis. The study aim to identify candidate biomarkers and research the molecular mechanisms correlated of patients with metastatic OS. MethodsThe GSE21257 was downloaded from Gene Expression Omnibus(GEO) database, and the differentially expressed RNAs (DERs) were identified and functional enriched analysis by statistical soft-ware in R. Subsequently, the co-expression modules and its clinical characteristics of OS were identified by weighted gene co-expression network analysis (WGCNA) Following, the KEGG pathways directly related to metastatic OS was to researched by the Comparative Toxicogenomics Database 2019 update (CTD). Finally, the “survival” package in R was used to survival analysis and the DERs were verified using another independent profiling GSE14827. ResultsA total of 1,464 DERs were classified including 702 up-regulated and 762 down-regulated. In addition, a total of 1248 DERs were obtained by WGCNA analysis, the blue modules is the highest negative correlation (P=0) and the turquoise modules is highest positive correlation (P=3E-196) among all correlations with OS metastatic. The lncRNA-mRNA co-expression network including 4 lncRNAs and 507 mRNAs, and the cytokine-cytokine receptor interaction and JAK-STAT signaling pathway were found significantly correlation with metastatic. Finally, the increased expression levels of IFNGR1, lower DLEU1 and DLEU2 related to better prognosis. Which were significantly consistent in the another independent profiling GSE14827. ConclusionsA bioinformatics analysis related to the IFNGR1, DLEU1 and DLEU2 may as candidate biomarkers for metastatic OS.
The Construct and Predictive Validity Testing of Indonesian Entrepreneurial Competence Inventory-Situational Judgment Test Model (Long Version)
Authors: Riyanti Benedicta Prihatin Dwi , Suryani Angela Oktavia , Sandroto Christine Winstinindah , Soeharso Silverius Y.
Published: December 2020

This research aimed to test the internal and external validity of the Indonesian Entrepreneurial Competence Inventory that was constructed based on situational judgment test (SJT) model. Spencer’s entrepreneurial competence theory and interviews with entrepreneurs were employed to build the items. The internal construct validity was tested by applying confirmatory factor analysis (CFA), while the external construct validity was tested by implementing correlations with other tests that were theoretically correlate with entrepreneurial competency, namely the previous entrepreneurial competence (Likert-scale model) and risk behaviour. The predictive validity was analysed by using correlation testing with an instrument assessing balance scorecard measurement of entrepreneurial achievement. A sample of 149 entrepreneurs from industrial cities in Indonesia was recruited via convenience sampling. The CFA analyses showed that nine dimensions of the Indonesian Entrepreneurial Competences Inventory were valid. In the correlation testing with risk taking behaviour and business success, all of the dimensions were significantly valid, except the see and act on opportunity dimension. However, in the correlation with the previous entrepreneurial competence scale, the significant correlation was found only with commitment to work. In further analysis, the correlation between dimensions of the current inventory and dimensions of the previous scale showed that the significant correlations were found between competence of seeing opportunity and commitment to work, assertiveness, and persuasion. The impact to the future research and practice application were discussed.
Factors Associated With Risky Sexual Behaviour Amongst Students at a Training College in Limpopo Province, South Africa
Authors: Murudi-Manganye Nthuseni Sharon , Mashau Ntsieni , Ramathuba Dorah
Published: December 2020

Background: Globally students who attend colleges indulge in risky sexual practices which in turn expose them to sexually transmitted infections. Risky sexual practices such as multiple sexual partners, unprotected sex, and transactional sex continue to pose risks of sexual transmitted infections, unwanted pregnancy as well as increased termination of pregnancy amongst young people. Engaging in risky sexual behaviour is associated with various factors. Therefore, the reported study was aimed at describing the factors associated with risky sexual behaviour amongst students at a training college in South Africa. Methods: The study adopted a quantitative, cross-sectional descriptive design to describe factors associated with risky sexual behaviour amongst students. Data was collected through a self-administered questionnaire among 307 students who were random sampled. The Statistical Package for Social Sciences version 23.0 was used to analyse data. Results: Among the respondents, 70,7% were females and 29.3% were males. Majority of the respondents 51.2% were staying at a rental place and about 49% were depending on the National Financial Aids Scheme (NSFAS). Staying at alone at a rental place and depending on the NSFAS is associated to engaging in risky sexual behaviours. Conclusions: Environmental factors and socio-economic factors contribute to risky sexual behaviours among students at a training college in Limpopo. Intervention to address the contributing factors should be implemented to curb the burden of engaging in risky sexual behaviours.
Exogenous Surfactant Versus Placebo in the Treatment of Moderate and Severe ARDS in COVID-19: The Pilot Study of a Clinical Trial
Authors: Ghahremani Mehdi , Fathi Mohammad , Massoudi Nilofar , Tavana Sasan , Fani Kamal , Nooraee Navid , Alamdari Nasser Malekpour , Besharat Sara , Abrandabadi Arash Najafi , Pirsalehi Ali , Khatiri Mohammad Ali Khabiri , Pouya Maryam Amini , Rajaei Samira , Dabbagh Ali
Published: December 2020

The authors have requested that this preprint be removed from Research Square.
Conditional Intravesical Recurrence-free Survival Rate after Radical Nephroureterectomy with Bladder Cuff Excision for Upper Urothelial Carcinoma
Authors: Chung Jae Hoon , Song Wan , Kang Minyong , Jeon Hwang Gyun , Jeong Byong Chang , Seo Seong IL , Jeon Seong Soo , Lee Hyun Moo , Sung Hyun Hwan
Published: December 2020

To evaluate the incidence and risk factors of (intravesical recurrence) IVR by analyzing a relatively large number of patients who underwent radical nephroureterectomy with bladder cuff excision (RNUx) for upper urothelial carcinoma (UTUC). Additionally, conditional IVR-free survival in patients with UTUC who had no history of bladder cancer and no concomitant bladder cancer was evaluated. We retrospectively analyzed the data of 1,095 patients with UTUC who underwent RNUx. The baseline characteristics, bladder tumor history, and UTUC characteristics were analyzed to evaluate oncological outcomes. To determine the factors affecting IVR, surgical modality, use of preoperative ureteroscopic examination (URS), TNM stage, and pathological outcomes were evaluated. Multivariable Cox regression analyses were performed to evaluate factors affecting IVR, and conditional IVR-free survival rate was analyzed using Kaplan–Meier curves. Among the 1,095 patients, 462 patients developed IVR and mean time of IVR was 13.08 ± 0.84 months after RNUx. A total of 30.74% of the IVR group and 15.32% of the without IVR group had a past history of bladder cancer (p < 0.001). In the multivariable analysis, a previous history of bladder cancer, multifocal tumors, the use of preoperative URS, the extravesical bladder cuffing method, lymph node involvement, positive surgical margins, and the use of adjuvant chemotherapy were determined to affect the IVR. The conditional IVRF rate at 12 months after RNUx was 74.0%, for those who IVRF for 12 months, the IVRF rate was 87.1% for the next 12 months (24 months after RNUx), and for the patients who IVRF for 24 months, the IVRF rate was 93.6% for the next 12 months (36 months after RNUx) and the IVRF rate was 97.3% for the next 12 months in IVRF of 60 months patients. The mean IVRF survival period of all patients was 136.84 months, 156.24 months in the patients with 6 months IVRF, 175.38 months for the patients with 12 months IVRF, 189.14 months for the patients with 36 months IVRF, and mean IVRF survival period was 178.21 months in 60 months IVRF patients. In 24 months IVRF patients after RNUx, only URS was evaluated to independently affect IVR (HR 1.945, p = 0.040). In patients with 36 months or more IVRF, there was no significant factor affecting IVR. Active IVR assessment is required until 36 months after RNUx. In addition, patient education and regular screening test such as urine analysis and cytology are required for patients who had IVRF for 36 months or longer.
Retrospective Non-target Analysis to Support Regulatory Water Monitoring: From Masses of Interest to Recommendations via in silico workflows
Authors: Lai Adelene , Singh Randolph R. , Kovalova Lubomira , Jaeggi Oliver , Kondic Todor , Schymanski Emma L.
Published: December 2020

BackgroundApplying non-target analysis (NTA) in regulatory environmental monitoring remains challenging - instead of having exploratory questions, regulators usually already have specific questions related to environmental protection aims. Additionally, data analysis can seem overwhelming because of the large data volumes and many steps required. This work aimed to identify environmental chemical unknowns via retrospective NTA within the scope of a pre-existing Swiss environmental monitoring campaign focusing on industrial chemicals. The research question addressed immediate regulatory priorities: identify pollutants with industrial point sources occurring at the highest intensities over two time points. Samples from 22 wastewater treatment plants obtained in 2018 and measured using liquid chromatography-high resolution mass spectrometry were retrospectively analysed by i) performing peak-picking to identify masses of interest, ii) prescreening and quality-controlling spectra, and iii) tentatively identifying priority “known unknown” pollutants by leveraging environmentally-relevant chemical information provided by Swiss, Swedish, EU-wide, and American regulators. This regulator-supplied information was incorporated into MetFrag, an in silico identification tool replete with “post-relaunch” features used here. This study’s unique regulatory context posed challenges in data quality and volume that were directly addressed with the prescreening, quality control, and identification workflow developed. ResultsOne confirmed and twenty-one tentative identifications were achieved, suggesting the presence of compounds as diverse as manufacturing reagents, adhesives, pesticides, and pharmaceuticals in the samples. More importantly, an in-depth interpretation of the results in the context of environmental regulation and actionable next steps are discussed. The prescreening and quality control workflow is openly accessible within the R package Shinyscreen, and adaptable to any (retrospective) analysis requiring automated quality control of mass spectra and non-target identification, with potential applications in environmental and metabolomics analyses. ConclusionsNTA in regulatory monitoring is critical for environmental protection, but bottlenecks in data analysis and results interpretation remain. The prescreening and quality control workflow, and interpretation work performed here are crucial steps towards scaling up NTA for environmental monitoring.
TaGST1 Gene and Its Regulatory Factor WRKY74 Mediate Copper Tolerance by Effecting Glutathione Accumulation in Wheat
Authors: Li Ge-Zi , Zheng Yong-Xing , Chen Shi-Juan , Liu Jin , Wang Peng-Fei , Wang Yong-Hua , Guo Tian-Cai , Kang Guo-Zhang
Published: December 2020

Background: Copper (Cu) is an important plant micronutrient; however, excessive Cu can disturb the protein structure, affect plant growth and development, and pose as a potential human health risk. Glutathione S-transferase (GST) is the key enzyme in glutathione (GSH) synthesis; it plays crucial role in Cu detoxification. Nonetheless, its regulatory mechanisms remain largely unclear.Results: A Cu-induced TaGST1 gene had been identified in this study. And the regulatory factor TaWRKY74 had been screen out by Yeast one-hybrid (Y1H) method. Their binding were checked by using another Y1H and luciferase (LUC) assays, indicated that TaWRKY74 bound to the TaGST1 promoter via W-box sequence. Moreover, TaWRKY74 or TaGST1 expression, GST activity, and GSH content were significantly inhibited in transiently TaWRKY74-silenced wheat plants under Cu stress. However, the contents of hydrogen peroxide (H2O2), malondialdehyde (MDA), and Cu were significantly increased. Further investigation found that transiently ectopic overexpression of TaWRKY74 increased GSH content, whereas decreased MDA content during Cu stress. Notably, exogenous application of GSH could reversed the adverse effects of transiently TaWRKY74-silenced wheat plants during Cu stress. Conclusions: These results indicated that TaWRKY74 regulated TaGST1 expression and affected GSH synthesis under Cu stress, and could be useful to ameliorate Cu toxicity for crop food safety.
Bracken Growth, Toxin Production and Transfer From Plant to Soil - A Two-year Monitoring Study
Authors: Garcia-Jorgensen Daniel B. , Diamantopoulos Efstathios , Kisielius Vaidotas , Rosenfjeld Mette , Rasmussen Lars H. , Strobel Bjarne W. , Hansen Hans Chr. B.
Published: December 2020

Background: Bracken fern (Pteridium aquilinum) is known to produce several toxic glycosides, of which ptaquiloside (PTA) is the most well documented. PTA may release from bracken to soil and leach to surface and groundwater. This study presents the first comprehensive long-term (2018-2019) monitoring study of bracken biomass, PTA content in the biomass, release by precipitation and soil solution concentrations at 50 cm depth. Moreover, lab experiments were carried to estimate the degradation of PTA, for different soil horizons and moisture contents. Results: The PTA content in bracken was highest at the beginning of the season, following a decreasing trend towards negligible values at the end of the season. The maximum seasonal PTA mass in the canopy was observed early in the summer, with values up to 1600 mg m-2. PTA is washed in high amounts by precipitation, with releases of up to 13.1 mg PTA m-2 during a single rain event. Concentrations of PTA in soil pore water were positively correlated with the mass of PTA in the canopy during the growing season. Peak concentrations of PTA in the soil solution were observed in July, with an average concentration of 1050 ng L-1.Conclusions: The production of PTA in bracken was found to be proportional to biomass production, while the mass of PTA being released is a function of volume and intensity of precipitation, as well as the bracken canopy development stage. Leaching of PTA takes place in the form of pulses linked to precipitation events, with soil pore water concentrations exceeding levels which are known to pose a risk to human health.
Association Between Dietary Phytochemical Index and Breast Cancer: a Case-control Study
Authors: Ghoreishy Seyed Mojtaba , Aminianfar Azadeh , Benisi-Kohansal Sanaz , Azadbakht Leila , Esmaillzadeh Ahmad
Published: December 2020

Background: Dietary intake of isoflavones has been positively associated with risk of breast cancer (BC) in some earlier studies. In addition, most studies on diet-disease associations came from western countries and limited data are available in the Middle-East. Methods: This case-control study was performed on 350 women with breast cancer aged over 30 years old who were recruited from hospitals or private clinics in Isfahan, Iran. All patients were diagnosed with BC during the maximum of the last 6 months using physical examination and mammography findings. Using cluster method sampling, 700 apparently healthy age- and socioeconomic status-matched controls were randomly selected from healthy women who had no relationship with BC patients and had no familial history of BC. Data on dietary intakes were collected using a validated food frequency questionnaire. The DPI was calculated based on dietary energy derived from foods rich in phytochemicals (kcal) divided by total daily energy intake (kcal) of each participant. Results: Mean ± SD age and BMI in the study participants were 62.4±10.8 y and 24.3±5.2 kg/m2, respectively. In the crude model, participants in the highest quartile of DPI had 63% lower odds of breast cancer compared to those in the lowest quartile (95% CI: 0.26, 0.54; P-trend <0.001). After adjustment for potential confounders, this inverse association became strengthened (95% CI: 0.22, 0.49; P-trend <0.001). Further adjustment for BMI did not change the association (OR for the highest quartile vs. the lowest quartile = 0.40, 95% CI: 0.26, 0.60; P-trend <0.001). Conclusion: In conclusion, a protective association was observed between DPI and BC in this case-control study. Therefore, high consumption of foods rich in phytochemicals such as fruits, vegetables and whole grains might help reducing the odds of BC among women.
Primary Hepatic Epithelioid Hemangioendothelioma: A Case Report and Literature Review
Authors: Wang Jing Rui , Lu Bei , Cai Yang
Published: December 2020

Background: Epithelioid hemangioendothelioma(EHE) is a low-grade malignant tumor of vascular origin. The rarity of HEHE make the diagnosis and treatment of this entity very challenging. Case presentation: We report a case of a 69-year-old female patient suffering from HEHE who complained of "Abdominal distension pain with dizziness, appetite loss more than half a month". Enhanced computed tomography (CT) of the upper abdomen indicated multiple space-occupying lesions in the liver. The pathological results of color ultrasound puncture suggested HEHE. We performe transcatheter arterial chemoembolization (TACE) and relevant examinations according to the patient's condition and the patient choice. Follow-up examinations 18 months after discharge did not demonstrate tumor recurrence.Conclusions:HEHE is a relatively rare hepatic malignant tumor derived from vascular endothelial cells, with low incidence, atypical clinical manifestations, difficult diagnosis, and the diagnosis can only be confirmed with pathological results. Currently, appropriate treatment methods should be selected according to the specific conditions of patients.
Combining Cell Therapy with Autologous Schwann Cell and Bone Marrow-derived Mesenchymal Stem Cell in Patients with Subacute Complete Spinal Cord Injury: Safety Considerations and Possible Outcomes
Authors: Yazdani Saeed Oraee , Akhlaghpasand Mohammadhosein , Golmohammadi Maryam , Hafizi Maryam , Zomorrod Mina Soufi , Kabir Nima Mohseni , Oraee-Yazdani Maryam , Zali Alireza , Soleimani Masoud
Published: December 2020

Background Cellular transplantations have promising effects on treating spinal cord injury (SCI) patients. Safety alongside the complementary characteristics of Mesenchymal stem cells (MSC) and Schwann cells (SC) are suggested to be the two of the best candidates in SCI treatment. In this study, we assessed the safety and efficacy of intrathecal co-transplantation of autologous bone marrow MSC and SC in the patients with subacute traumatic complete SCI.Methods Eleven patients with complete SCI (American Spinal Injury Association Impairment Scale (AIS); grade A) were enrolled in this study during the subacute period of injury. The patients received intrathecal autologous combination of MSC and SC and were followed-up for 12 months. We assessed neurological changes by American Spinal Injury Association’s (ASIA) sensory-motor scale, functional recovery by spinal cord independence measure (SCIM-III), and subjective changes along with adverse events (AE) with our checklist. Furthermore, electromyography (EMG), nerve conduction velocity (NCV), magnetic resonance imaging (MRI), and urodynamic study (UDS) were conducted for all the patients at the baseline, 6 months, and one year after the intervention.Results Light touch ASIA score alterations were approximately the same as the pinprick changes (11.6 ± 13.1 and 12 ± 13, respectively) in 50% of the cervical and 63% of the lumbar-thoracic patients and both were more than the motor score alterations (9.5 ± 3.3 in 75% of the cervical and 14% of the lumbar-thoracic patients). SCIM III total scores (21.2 ± 13.3) and all its sub-scores (“respiration and sphincter management” (15 ± 9.9), “mobility” (9.5 ± 13.3), and “self-care” (6 ± 1.4)) had significant changes after cell injection. Our findings support that the most remarkable positive, subjective improvements were in trunk movement, equilibrium in standing/sitting position, sensation of the bladder and rectal filling, and ability of voluntary voiding. Our safety evaluation revealed no systemic complications and radiological images showed no neoplastic overgrowth, syringomyelia, or pseudo-meningocele.Conclusion The present study showed that autologous SC and bone marrow-derived MSC transplantation at the subacute stage of SCI could reveal significant improvement in sensory and neurological functions among the patients. It appears that using this combination of cells is safe and effective for clinical application to the spinal cord regeneration during the subacute period.
Identification of Differentially Expressed Genes Triggered by Aberrant Methylation in Idiopathic Pulmonary Fibrosis Using Integrated Bioinformatic Analysis
Authors: Chen Shuaijun , Zhang Jun , Ma Wanli , Ye Hong
Published: December 2020

BackgroundIdiopathic pulmonary fibrosis (IPF) is a relentlessly progressive and fatal fibrotic lung disease all over the world, and specific pathogenesis is still not well understood. DNA methylation is an essential epigenetic mechanism, which likely contributes to the progress of IPF. The purpose of this study is to identify aberrantly methylated differentially expressed genes (DEGs) in IPF and to explore the underlying mechanisms of IPF by using integrated bioinformatics analysis.MethodGene expression profiles and gene methylation profile were downloaded and analyzed to identify the aberrantly methylated‐differentially expressed genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Search Tool for the Retrieval of Interacting Genes Database (STRING) and Gene set enrichment analysis (GSEA) were used to evaluate function of DEGs. RT-PCR was used to verify the mRNA levels of DEGs in mice with pulmonary fibrosis.ResultsBy analyzing the differentially expressed genes of the three IPF expression profiles, and taking the intersection, we got 143 co-upregulated genes and 104 co-downregulated genes; GO and KEGG pathway analysis of the DEGs suggested these genes involved in the extracellular matrix organization, multicellular organismal homeostasis. Combining the sequencing data of two IPF methylation chips, we have identified genes that may be regulated by methylation in IPF. Finally, we obtained the mRNA expression of DEGs using a mouse model of pulmonary fibrosis.ConclusionThrough integrated analysis and experimental verification, we found a series of biomarkers which were regulated by methylation should be potential therapeutic targets for IPF.
Conceptual Framework for Task Shifting and Task Sharing: An International Delphi Study
Authors: Orkin Aaron , Rao Sampreeth , Venugopal Jeyasakthi , Kithulegoda Natasha , Wegier Pete , Ritchie Stephen D. , VanderBurgh David , Martiniuk Alexandra , Salamanca-Buentello Fabio , Upshur Ross
Published: December 2020

BackgroundTask shifting and sharing (TS/S) involves the redistribution of health tasks within workforces and communities. Conceptual frameworks lay out the key factors, constructs, and variables involved in a given phenomenon, as well as the relationships between those factors. Though TS/S is a leading strategy to address health worker shortages and improve access to services worldwide, a conceptual framework for this approach is lacking.MethodsWe used an online Delphi process to engage an international panel of scholars with experience in knowledge synthesis concerning TS/S and develop a conceptual framework for TS/S. We invited 55 prospective panellists to participate in a series of questionnaires exploring the purpose of TS/S and the characteristics of contexts amenable to TS/S programmes. Panellist responses were analysed and integrated through an iterative process to achieve consensus on the elements included in the conceptual framework. ResultsThe panel achieved consensus concerning the included concepts after three Delphi rounds among 15 panelists.The COATS Framework (Concepts and Opportunities to Advance Task Shifting and Task Sharing) offers a refined definition of TS/S and a general-purpose statement to guide TS/S programmes. COATS describes that opportunities for health system improvement arising from TS/S programmes depending on the implementation context, and enumerates eight essential conditions and important considerations for launching TS/S interventions.ConclusionThe COATS Framework offers an essential theoretical and conceptual model for TS/S programmes. The COATS Framework is comprehensive and adaptable, and can guide refinements in policy, programme development, evaluation, and research to improve TS/S globally.