bluuebunny/crossref_metadata_2025_split huggingface dataset:
Large Bi-Ethnic Study of Plasma Proteome Leads to Comprehensive Mapping of cis-pQTL and Models for Proteome-wide Association Studies
Authors: Chatterjee Nilanjan , Zhang Jingning , Dutta Diptavo , Kottgen Anna , Tin Adrienne , Schlosser Pascal , Grams Morgan , Harvey Benjamin , Yu Bing , Boerwinkle Eric , Coresh Josef 
Published: April 2021

Abstract
Improved understanding of the proteome can facilitate the identification of causal mechanisms for complex traits. We conducted a comprehensive analysis of the common variant cis-regulatory genetic architecture of 4,665 plasma proteins from 7,213 European Americans (EA) and 1,871 African Americans (AA) from the Atherosclerosis Risk in Communities (ARIC) cohort study. We identified and fine-mapped 1,992 plasma proteins in EA and 1,605 in AA, which had significant cis- single-nucleotide polymorphism (SNP) associations. Estimates of cis-heritability (cis-h2) for plasma proteins were similar across EA and AA (median cis-h2 = 0.09 for EA and 0.10 for AA). Elastic-net-based models for cis-SNP-based protein prediction produced high accuracy (median R2/cis-h2 = 0.79 for EA and 0.69 for AA). We illustrate the application of these models to conduct proteome-wide association studies (PWAS) for two related complex traits, serum urate and gout, and further conduct conditional analyses to interpret findings in the context of those from transcriptome-wide association studies (TWAS).
A protocol for the detection of genetic markers in saliva by polymerase chain reaction without a nucleic acid purification step: examples of SARS-CoV-2 and GAPDH markers.
Authors: Kannan Surya , Ericsson Johan , Souchelnytskyi Nazariy , Souchelnytskyi Serhiy 
Published: April 2021

Abstract
Background: The objective of this study was to develop a protocol for direct use of saliva in tests for genetic markers, without purification of nucleic acids. Currently, diagnostic tests use purified nucleic acids from clinical samples. This purification step adds time, cost, and affects the quality of testing. Multiple attempts to remove the purification step were reported. Results: We report a protocol for the direct detection of genetic markers in saliva. The protocol is based on collection of saliva in a solution containing a detergent and ethanol, and is compatible with isothermal amplification (LAMP), real-time RT-PCR and RT-PCR. SARS-CoV-2 and GAPDH markers were used as reference markers. We observed that mild detergents allow efficient detection of markers (e.g. GAPDH and SARS-CoV-2), while strong detergent, e.g. sodium dodecyl sulfate, inhibited the PCR reaction. Under these conditions, saliva samples can be stored for 24 h at +40C or -180C with preservation of the markers. Storage at room temperature led to deterioration of marker detection. Snap heating of saliva samples at the time of collection, followed by a storage at the room temperature, provided partial protection.Conclusions: The protocol presented in this report describes collection and storage of saliva for direct detection of genetic markers and is compatible with PCR and LAMP tests.
AGILE: A Seamless Phase I/IIa Platform for the Rapid Evaluation of Candidates for COVID-19 treatment: An update to the structured summary of a study protocol for a randomised platform trial letter
Authors: Griffiths Gareth Owen , FitzGerald Richard , Jaki Thomas , Corkhill Andrea , Reynolds Helen , Ewings Sean , Condie Susannah , Tilt Emma , Johnson Lucy , Radford Mike , Simpson Catherine , Saunders Geoffrey , Yeats Sara , Mozgunov Pavel , Tansley-Hancock Olana , Martin Karen , Downs Nichola , Eberhart Izabela , Martin Jonathan William Brian , Goncalves Cristiana , Song Anna , Fletcher Tom , Byrne Kelly , Lalloo David Griffith , Owen Andrew , Jacobs Michael , Walker Lauren , Lyon Rebecca , Woods Christie , Gibney Jennifer , Chiong Justin , Chandiwana Nomathemba , Jacob Shevin , Lamorde Mohammed , Orrell Catherine , Pirmohamed Munir , Khoo Saye 
Published: April 2021

Abstract
Background:There is an urgent unmet clinical need for the identification of novel therapeutics for the treatment of COVID-19. A number of COVID-19 late phase trial platforms have been developed to investigate (often repurposed) drugs both in the UK and globally (e.g. RECOVERY led by the University of Oxford and SOLIDARITY led by WHO). There is a pressing need to investigate novel candidates within early phase trial platforms, from which promising candidates can feed into established later phase platforms. AGILE grew from a UK-wide collaboration to undertake early stage clinical evaluation of candidates for SARS-CoV-2 infection to accelerate national and global healthcare interventions. Methods/Design:AGILE is a seamless phase I/IIa platform study to establish the optimum dose, determine the activity and safety of each candidate and recommend whether it should be evaluated further. Each candidate is evaluated in its own trial, either as an open label single arm healthy volunteer study or in patients, randomising between candidate and control usually in a 2:1 allocation in favour of the candidate. Each dose is assessed sequentially for safety usually in cohorts of 6 patients. Once a phase II dose has been identified, efficacy is assessed by seamlessly expanding into a larger cohort. AGILE is completely flexible in that the core design in the master protocol can be adapted for each candidate based on prior knowledge of the candidate (i.e. population, primary endpoint and sample size can be amended). This information is detailed in each candidate specific trial protocol of the master protocol.Discussion:Few approved treatments for COVID-19 are available such as dexamethasone, remdesivir and tociluzimab in hospitalised patients. The AGILE platform aims to rapidly identify new efficacious and safe treatments to help end the current global COVID-19 pandemic. We currently have three candidate specific trials within this platform study that are open to recruitment. Trial registrations:EudraCT Number: 2020-001860-27 14th March 2020 ClinicalTrials.gov Identifier: NCT04746183ISRCTN reference: 27106947
Association between serum creatinine level within the normal range and bone mineral density in adolescents
Authors: Pan Kaiyu , Yu Haiyan , Zhu Zhongxin 
Published: April 2021

Abstract
Objective: The circulating level of creatinine is a direct, stable indicator of skeletal muscle mass. However, evidence regarding the correlation between serum creatinine (SCre) and bone health is limited. This study aimed to evaluate the association between SCre level within the normal range and bone mineral density (BMD) in adolescents.Methods: We analyzed data for 3456 adolescents aged 12-19 years from the National Health and Nutrition Examination Survey 2011-2018. Weighted multiple linear regression was conducted to assess the association between SCre and BMD. Weighted generalised additive models and smooth curve fittings were performed to address the nonlinearity of them.Results: After controlling for potential confounding factors, we found that higher SCre levels were associated with higher total BMD in adolescents. This association remained positive in the subgroup analyses stratified by age, gender, or race. Furthermore, this positive association was more prominent in boys than in girls in adolescents aged 12-15 years.Conclusions: These findings indicate that higher SCre levels within the normal range in adolescents aged 12-19 years were associated with higher total BMDs, suggesting that SCre may be a candidate biomarker for bone health in adolescents.
Study on Physical and Chemical Properties of Industrial Silicon Slag
Authors: Qiao Dan , Liang Shuai , Zhao Jian Guo , Peng Xiu Jing , Nie Yong , Li Ye Xin , Cui Yu , Sun Guoxin 
Published: April 2021

Abstract
Silicon slag is a secondary refining byproduct from industrial silicon. The content of industrial silicon in silicon slag is about 20% , which has extremely high economic value. To better achieve the recovery and reuse of industrial silicon slag, the morphology of industrial silicon slag, the occurrence state of elements and especially the interfacial structure between silicon and slag were deeply studied in this paper. The macro and micro morphology and surface composition distribution of the silicon slag were observed by microscope, SEM-EDS and Raman spectroscopy. The phase and composition of the silicon slag were analyzed by XRF and XRD. The results showed that the purity of silicon particles in silicon slag is high up to 99% . The size and shape of silicon in silicon slag were quite different. The interface between silicon and slag is clear and there is no obvious two-phase transition zone, which is conducive to the recycling of silicon. The crushing behavior of silicon slag under different pressure was investigated. These results provide a theoretical basis for further crushing silicon slag and recovering silicon particles. When silicon slag was crushed under certain pressure, the fracture surface of large-size silicon was mostly silicon-silicon interface. Therefore, in order to realize the complete dissociation of slag and silicon, the size of the crushing particle needs to be small enough. In this paper, the physical and chemical properties of industrial silicon slag were studied, which provides a theoretical basis for the efficient separation and recovery of silicon in the slag.
A mechanism of spring Barents Sea ice effect on the extreme summer droughts in northeastern China
Authors: Du YiBo , Zhang Jie , Zhao Siwen , Chen Zhiheng 
Published: April 2021

Abstract
The frequency of extreme drought events in northeastern China (NEC) has increased since the 2000s, and such a decadal anomalous trend may lead to significant stress on agriculture and economic development. The correlation between Arctic sea ice loss in spring and extreme summer droughts over NEC was investigated. The results show that the loss of sea ice over the Barents Sea in spring is associated with extreme droughts and positive height anomalies over NEC in summer. The physical processes include two pathways. First, Arctic ice loss from the Barents Sea to the Kara Sea results in reducing baroclinicity over the ice loss region but increasing baroclinicity over the ice melting region, which is favorable to the wave ridge over northern Europe and negative-phase Summer North Atlantic Oscillation (SNAO). One wave train originates from negative-phase SNAO over North Atlantic–Europe and spreads to central Europe, central Asia, and NEC. Second, another wave motion flux originates from the Barents–Kara Sea propagating eastward, and then disperses southward to NEC. Both wave trains lead to anomalous anticyclonic circulation and westward subtropical high, which favors descending motion and less water vapor flux, thereby contributing to extreme drought.
Extreme windstorms and sting-jets in convection-permitting climate simulations over Europe
Authors: Manning Colin , Kendon Elizabeth J. , Fowler Hayley J. , Roberts Nigel M. , Berthou Ségolène , Suri Dan , Roberts Malcolm J. 
Published: April 2021

Abstract
Extra-tropical windstorms are one of the costliest natural hazards affecting Europe, and windstorms that develop a sting-jet are extremely damaging. A sting-jet is a mesoscale core of very high wind speeds that occurs in Shapiro-Keyser type cyclones, and high-resolution models are required to adequately model sting-jets. Here, we develop a low-cost methodology to automatically detect sting jets, using the characteristic warm seclusion of Shapiro-Keyser cyclones and the slantwise descent of high wind speeds, within pan-European 2.2km convection-permitting climate model (CPM) simulations over Europe. The representation of wind gusts is improved with respect to ERA-Interim reanalysis data compared to observations; this is linked to better representation of cold conveyor belts and sting-jets in the CPM. Our analysis indicates that Shapiro-Keyser cyclones, and those that develop sting-jets, are the most damaging windstorms in present and future climates. The frequency of extreme windstorms is projected to increase by 2100 and a large contribution comes from sting-jet storms. Furthermore, extreme wind speeds and their future changes are underestimated in the GCM compared to the CPM. We conclude that the CPM adds value in the representation of extreme winds and surface wind gusts and can provide improved input for impact models compared to coarser resolution models.
Benefit of combining curcumin, harpagophytum and bromelain to reduce inflammation in osteoarthritic synovial cells
Authors: Brochard Sybille , Pontin Julien , Bernay Benoit , Boumediene Karim , Conrozier Thierry , Baugé Catherine 
Published: April 2021

Abstract
Background: Osteoarthritis is the most common cause of arthritis affecting millions of people worldwide, characterized by joint pain and inflammation. It is a complex disease involving inflammatory factors and affecting the whole joint including synovium. Since drug combination is widely used to treat chronic inflammatory diseases, a similar strategy may be worth of interest to design plant-derived natural products to reduce inflammation in OA joint. Here, we characterized the response of OA synovial cells to lipopolysaccharide (LPS) and investigated the biological action of the combination of curcumin, harpagophytum and bromelain in this original in vitro model of osteoarthritis.Methods: Primary, human synovial cells from OA patients were stimulated with LPS and proteomic analysis was performed. Bioinformatics analysis were performed using Cytoscape App and SkeletalVis databases. Additionally, cells were treated with curcumin, harpagophytum and bromelain alone or the three vegetal compounds together. The expression of genes involved in inflammation, pain or catabolism were determined by RT-PCR. The release of the encoded proteins by these genes and of prostaglandin E2 (PGE2) were also assayed by ELISA. Results: Proteomic analysis demonstrated that LPS induces the expression of numerous proteins involved in OA process in human OA synovial cells. In particular, it stimulates inflammation through the production of pro-inflammatory cytokines (Interleukin-6, IL-6), the catabolism through an increase of metalloproteases (MMP-1, MMP-3, MMP-13), and the production of pain-mediating neurotrophin (Nerve Growth Factor, NGF). These increases were observed at level of mRNA levels and of protein release. LPS also increases the amount of PGE2, another inflammation and pain mediator. At doses tested, vegetal extracts had little effects: only curcumin slightly counteracted the effects of LPS on NGF and MMP13 mRNA, and PGE2, IL-6 and MMP13 release. In contrast the association of curcumin with harpagophytum and bromelain reversed lots of effects of LPS in human OA synovial cells. It significantly reduced the gene expression and/or the release of proteins involved in catabolism (MMP3 and 13), inflammation (IL-6) and pain (PGE2 and NGF).Conclusion: We show that the stimulation of human OA synovial cells with LPS permit to induce protein changes similar to an inflamed OA synovial tissues. In addition, using this model, we demonstrate that the combination of three vegetal compounds, namely curcumin, harpagophytum and bromelain have anti-inflammatory and anti-catabolic action in synovial cells and may thus reduce OA progression and related-pain.
Diagnostic Accuracy of Contrast-enhanced Ultrasonography Liver Imaging Reporting and Data System in Hepatocellular Carcinoma: A Systematic Review
Authors: Li HuiFang , Huang Wei , Zheng Wei , Li Qing , Dai YunZhu , Zheng Lie , Zou RuHai 
Published: April 2021

Abstract
Background: Contrast-enhanced Ultrasonography Liver Imaging Reporting and Data System (CEUS LI-RADS) released by American College of Radiology was a widely used reporting system for patients at risk with hepatocellular carcinoma (HCC). In CEUS LI-RADS, the categories range from definitely benign (LR-1), probably begin (LR-2), intermediate probability of malignancy (LR-3), probably HCC (LR-4) to definitely HCC (LR-5), malignancy (LR-M), or definite tumor in vein (LR-TIV). Methods: We searched MEDLINE, Web of Science, Cochrane, Embase, and Chinese databases to obtain eligible studies reporting on the diagnostic performance of CEUS LI-RADS in patients at risk for HCC. Results: Twelve studies were eligible in the analysis, including 5275 patients, 5739 observations, and 4066 HCCs. The pooled sensitivity and specificity were 70% (95% Confidence Interval [CI] 65%-74%), 94% (95% CI, 91%-96%) of LR-5 category as predictors of HCC, respectively. The pooled sensitivity and specificity of LR-M category as a predictor of non-HCC malignancy were 83% (95% CI, 71%-91%), 94% (95% CI 88%-97%), respectively. The pooled proportions of HCCs were 1% (95% CI 0%-6%) for LR-2, 20% (95% CI, 9%-34%) for LR-3, 78% (95% CI, 67%-88%) for LR-4, 97% (95% CI, 94%-99%) for LR-5, 40% (95% CI, 23%–58%) for LR-M and 100% (95% CI, 93%–100%) for LR-TIV.Conclusion: CEUS LI-RADS is an important tool for the diagnosis of HCC.
RAC1/miR-3613/RAC1 feedback loop contributes to ovarian cancer progression
Authors: Li Changzhong , Leng Ruobing , Meng Yunfang , Li Na , Li Feifei , Zhao Yingzi 
Published: April 2021

Abstract
The RAC1 signal pathway is involved in various tumor cell biological processes. Here, the role of RAC1-miR-3613-RAC1 negative feedback loop in ovarian cancer was explored. Results showed that RAC1 knockdown up-regulated miR-3613, which in turn inhibited RAC1 expression. RAC1 counteracted the inhibitory effect of miR-3613 on the proliferation and invasion of ovarian cancer cells in vitro and on the tumor growth in vivo. In ovarian cancer, miR-3613 expression was negatively correlated with RAC1, and patients with low miR-3613 expression had poor prognosis. These findings indicate the role of RAC1-miR-3613-RAC1 negative feedback loop in the malignant progression of ovarian cancer and its possible therapeutic values.
The Impact of Early Achievement of Therapeutic Levels of Vancomycin in Critically Ill Patients With Confirmed Gram-Positive Infection: A Retrospective Cohort Study
Authors: Sulaiman Khalid Al , Alshaya Abdulrahman , Alsaeed Amjad , Alshehri Nadiyah , Vishwakarma Ramesh , Alzahrani Hamdan , Harbi Shmeylan Al 
Published: April 2021

Abstract
BackgroundVancomycin is a commonly used antibiotic in critically ill patients for various indications. Critical illness imposes pharmacokinetic-pharmacodynamics challenges which makes optimizing vancomycin in this population cumbersome. Data are scarce on the clinical impact of time to therapeutic trough levels of vancomycin in critically ill patients. Objective (s)The aim of this study to evaluate the timing to achieve therapeutic trough level vancomycin on 30-day mortality in critically ill patients.SettingAdult critically ill patients admitted to intensive care units (ICUs) between January 1st, 2017 and December 31st, 2018 at a tertiary teaching hospital.MethodA retrospective cohort study for all adult critically ill patients aged 18 years or older with confirmed gram-positive infection and received vancomycin. We compared early (<48 hours) versus late (≥ 48 hours) attainment of vancomycin therapeutic trough levels. Main outcomesPrimary outcome was the 30-day mortality in critically ill patients. Secondary outcomes were development of resistant organisms, eradicating microorganisms within 4-5 days of vancomycin initiation, vancomycin-induced acute kidney injury (AKI), and ICU LOS. ResultsTwo hundred and nine patients were included. No significant differences between comparative groups in baseline characteristics. Achieving therapeutic levels were associated with better survival at 30 days (OR: 0.48; 95% CI [0.26-0.87]; p<0.01). Additionally, patients who achieved therapeutic levels of vancomycin early were less likely to develop resistant organisms (OR=0.08; 95% CI [0.01-0.59]; p=0.01). Acute kidney injury (AKI) and ICU length of stay (LOS) were not significant between the two groups.ConclusionEarly attainment of vancomycin therapeutic levels was associated with possible survival benefit.
Amplification of Oxidative Stress With Lycorine and Gold-Based Nanocomposites for Synergistic Cascade Cancer Therapy
Authors: Hu Hongzhi , Yang Wenbo , Liang Zihui , Zhou Zezhu , Song Qingcheng , Liu Weijian , Deng Xiangtian , Zhu Jian , Xing Xin , Zhong Binglong , Wang Baichuan , Wang Shangyu , Shao Zengwu , Zhang Yingze 
Published: April 2021

Abstract
BackgroundDespite advances of surgery and neoadjuvant chemotherapy during the past few decades, the therapeutic efficacy of current therapeutic protocol for osteosarcoma (OS) is still seriously compromised by multi-drug resistance and severe side effects. Amplification of intracellular oxidative stress is considered as an effective strategy to induce cancer cell death. The purpose of this study was to develop a novel strategy that can amplify the intracellular oxidative stress for synergistic cascade cancer therapy.Methods and resultsA novel nanocomposite, composed of folic acid (FA) modified mesoporous silica–coated gold nanostars (GNS@MSNs-FA) and traditional Chinese medicine Lycorine (Ly), was rationally designed and developed. Under near-infrared (NIR) irradiation, the obtained GNS@MSNs-FA/Ly could promote a high level of ROS production via inducing mitochondrial dysfunction and potent endoplasmic reticulum (ER) stress. Moreover, glutathione (GSH) depletion during ER stress could reduce ROS scavenging and further enable efficient amplification of intracellular oxidative stress. Both in vitro and in vivo studies demonstrated that GNS@MSNs-FA/Ly coupled with NIR irradiation exhibited excellent antitumor efficacy without noticeable toxicity in MNNG/HOS tumor-bearing mice.Conclusion﻿All these results demonstrated that GNS@MSNs-FA/Ly coupled with NIR irradiation dramatically was able to amplify the intra-tumoral oxidative stress, exhibiting excellent antitumor ability without no obvious systemic toxicity. Taken together, this promising strategy provides a new avenue for the effective cancer synergetic therapy and future clinical translation.
Cordyceps Militaris Carotenoids Protect ARPE-19 Cells From Oxidative Stress Damage Induced By Hydrogen Peroxide
Authors: Lan Lin , Ren YuZhi , Zhou XiangYu , Wang ShengYu , Zhang JinSen , Xie Ling , Qian YeQian , Li YuHang , Li YuFeng , Zhang Liang 
Published: April 2021

Abstract
A retinal disorder known as age-related macular degeneration (AMD) can be very damaging, which may result in vision loss. Cordyceps militaris has antioxidant, anti-inflammatory, anticancer activity and immunomodulatory functions. carotenoids were considered potential therapeutic agents for the treatment of age-related macular degeneration. In this study, we evaluated for the first time the protective effect of purified carotenoids (CMCT) extracted from Cordyceps militaris on hydrogen peroxide (H2O2)-induced damage to human retinal pigment epithelial cells (ARPE-19). The pretreatment of ARPE-19 cells with CMCT (1, 2.5μg/ml) for 12h after exposure to H2O2 (400μM) greatly improved cell viability and injury tolerance. and reduced reactive oxygen species production (ROS) and decreased malondialdehyde (MDA) formation. Furthermore, Bax and Caspase-3 showed increased protein expression and less protein expression of Bcl-2 in cellular oxidative stress by flow cytometry analysis but showed the opposite expression by adding CMCT. Besides, cells were treated with H2O2 and then CMCT restored catalase (CAT), superoxide dismutase (SOD) and glutathione (GSH) enzyme activities to normal levels. Our results suggest that CMCT can protect RPE cells from oxidative stress damage by regulating oxidative activity and anti-apoptotic function. It indicates that CMCT has a potential therapeutic role in oxidative stress-directed protection and prevention of AMD.