bluuebunny/crossref_metadata_2025_split huggingface dataset:
GSDME and its role in cancer: From behind the scenes to the front of the stage
Authors: De Schutter Elke , Croes Lieselot , Ibrahim Joe , Pauwels Patrick , Op de Beeck Ken , Vandenabeele Peter , Van Camp Guy 
Published: November 2020

AbstractGasdermin E (GSDME), a gene originally involved in hereditary hearing loss, has been associated with several types of cancer in the last two decades. Recently, GSDME was identified as a pore‐forming molecule, which is activated following caspase‐3‐mediated cleavage resulting in so‐called secondary necrosis following apoptotic cell death, or in primary necrotic cell death without an apoptotic phase, so‐called pyroptosis‐like. This implication in cell death execution suggests its potential role as a tumor suppressor. GSDME also exhibited a cancer type‐specific differential methylation pattern between tumor tissues and normal cells, implying GSDME gene methylation as both a pan‐cancer and cancer type‐specific detection biomarker. A bit paradoxically, GSDME protein expression is considered to be less suited as biomarker, and although its ablation does not protect the cell against eventual cell death, its protein expression might still operate in tumor immunogenicity due to its capacity to induce (secondary) necrotic cell death, which has enhanced immunogenic properties. Additionally, GSDME gene expression has been shown to be associated with favorable prognosis following chemotherapy, and it could therefore be a potential predictive biomarker. We provide an overview of the different associations between GSDME gene methylation, gene expression and tumorigenesis, and explore their potential use in the clinic. Our review only focuses on GSDME and summarizes the current knowledge and most recent advances on GSDME's role in cancer formation, its potential as a biomarker in cancer and on its promising role in immunotherapies and antitumor immune response.
Multi‐omics integration identifies a selective vulnerability of colorectal cancer subtypes to YM155
Authors: Zhan Tianzuo , Faehling Verena , Rauscher Benedikt , Betge Johannes , Ebert Matthias P. , Boutros Michael 
Published: November 2020

AbstractTumor heterogeneity is a major challenge to the treatment of colorectal cancer (CRC). Recently, a transcriptome‐based classification was developed, segregating CRC into four consensus molecular subtypes (CMS) with distinct biological and clinical characteristics. Here, we applied the CMS classification on CRC cell lines to identify novel subtype‐specific drug vulnerabilities. We combined publicly available transcriptome data from multiple resources to assign 157 CRC cell lines to CMS. By integrating results from large‐scale drug screens, we discovered that the CMS1 subtype is highly vulnerable to the BIRC5 suppressor YM155. We confirmed our results using an independent panel of CRC cell lines and demonstrated a 100‐fold higher sensitivity of CMS1. This vulnerability was specific to YM155 and not observed for commonly used chemotherapeutic agents. In CMS1 CRC, low concentrations of YM155 induced apoptosis and expression signatures associated with ER stress‐mediated apoptosis signaling. Using a genome‐wide CRISPR/Cas9 screen, we further discovered a novel role of genes involved in LDL‐receptor trafficking as modulators of YM155 sensitivity in the CRC cell line HCT116. Our work shows that combining drug response data with CMS classification in cell lines can reveal selective vulnerabilities and proposes YM155 as a novel subtype‐specific drug.
Associations between hematological parameters and disease severity in patients with SARS‐CoV‐2 infection
Authors: Lin Sha , Mao Weilin , Zou Qianda , Lu Siming , Zheng Shufa 
Published: November 2020

AbstractBackgroundThe emergence and rapid spread of the deadly novel coronavirus disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a swiftly evolving public health crisis worldwide. SARS‐CoV‐2 infection is characterized by the development and progression of inflammatory responses. Hematological parameters, such as white blood cells (WBCs) and their subpopulations, red cell distribution width, platelet count, mean platelet volume, plateletcrit, and derived markers such as neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), and lymphocyte‐to‐monocyte ratio, are established biomarkers of inflammatory responses. We aimed to investigate associations between hematological parameters and disease severity in patients with SARS‐CoV‐2 infection.MethodsWe retrospectively analyzed data from 68 patients with confirmed SARS‐CoV‐2 infection. Twenty‐two patients had mild illness, and 46 had moderate or severe illness at the time of admission. Univariate and multivariate regression analyses were used to identify correlates of disease severity. The areas under receiver operating characteristic curves were calculated to estimate and compare the predictive values of different diagnostic markers.ResultsMean lymphocyte and monocyte counts were lower while WBC counts, neutrophil counts, NLR, and PLR were higher in patients with severe disease compared with those with mild disease (all P < .01). Univariate analysis revealed that older age, high WBC counts, high neutrophil counts, high NLR, high PLR, low monocyte counts, and low lymphocyte counts were independent correlates of severe illness. Multivariate analysis identified high NLR as the only independent correlate of severe illness. Receiver operating characteristic curve analysis showed that NLR had the highest area under curve of all hematological parameters.ConclusionAmong hematological parameters, the NLR showed superior prediction of disease severity in patients with SARS‐CoV‐2 infection. Thus, the NLR could be a valuable parameter to complement conventional measures for identification of patients at high risk for severe disease.
Drug biotransformation process favored by fungal biofilms formed on a proposed fixed bed‐airlift hybrid reactor
Authors: Bianchini Luiz F , da Silva Ramos Romeu CP , de Oliveira Nicoly S , de Paula Rafaela C , Rosa Rosimeire T , Glassey Jarka , Rosa Edvaldo AR 
Published: November 2020

AbstractBACKGROUNDFungi have the great ability to biotransform drugs, making it possible to direct their application to obtaining new molecules. Our group developed a hybrid fixed bed‐airlift reactor (FB‐ALR) model that allows the formation of Cunninghamella elegans (or other fungi) biofilm and biotransformation of diclofenac (DCF).RESULTSHydrodynamic and rheological parameters [(mixing time (tM), linear gas velocity (UG), liquid linear velocity (UL), gas hold‐up (εG), viscosity (v)], mass transfer (kLa) and biomass formation were superior than those obtained in conventional airlift reactor (ALR) and bubble column reactor. The higher performance of FB‐ALR is a result of the improvement in the oxygenation process, in addition to the reticulate baffle used by the fungus as a support for adhesion and proliferation as biofilm. The formation of fungal biofilms, in addition to reducing the viscosity of the system, favored the retention of DCF, thus facilitating the processes of biotransformation. High‐performance liquid chromatography analyses confirmed such theory.CONCLUSIONFungal biofilms present considerable biotransforming activity, making FB‐ALR the highest yielding biotransformation system amongst those tested herein. © 2020 Society of Chemical Industry (SCI)
Water and alcohol extracts from Diaphragma juglandis on anti‐fatigue and antioxidative effects in vitro and vivo
Authors: Hu Gaoshuang , Gao Shan , Mou Dehua 
Published: November 2020

AbstractBACKGROUNDTo estimate the anti‐fatigue and antioxidative effects of water and alcohol extracts from Diaphragma juglandis (DJ), H2O2‐treated HepG2 cells were used as an in vitro model to determine the total antioxidant capacities of these two extracts, and behavioral tests on mice and biochemical assay were performed via in vivo experiments.RESULTSThe results indicate that both extracts possess remarkable HepG2 protective capacities and were capable of scavenging 2,2‐diphenyl‐1‐picrylhydrazyl and 2,2'‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) similar to vitamin C. Furthermore, they could significantly prolong the bar climbing time and force swimming time, as well as decrease the serum urea nitrogen and increase the lactate dehydrogenase level and glycogen content. These extracts could also improve the activities of total antioxidant capacity, malondialdehyde, superoxide dismutase, catalase and glutathione peroxidase.CONCLUSIONIn conclusion, both water and alcohol extracts from DJ showed good performance with respect to anti‐fatigue and could be a potential antioxidant additive in the field of functional foods. © 2020 Society of Chemical Industry
Promoting Tobacco Use Among Students: The U.S. Smokeless Tobacco Company College Marketing Program
Authors: Qian Z. Jason , Hill Matthew J. , Ramamurthi Divya , Jackler Robert K. 
Published: November 2020

Objectives/HypothesisFrom the 1970s–1990s the U.S. Smokeless Tobacco Company (USST) conducted aggressive campaigns to solicit college students to buy their smokeless tobacco (ST) products. The scope, scale, methods, and impact of this youth marketing campaign have yet to be analyzed in the academic literature.Study DesignHistorical research study.MethodsInternal industry documents describing the USST campaigns were obtained via the University of California, San Francisco's repository of tobacco company records. Marketing materials were obtained from Stanford University's Research Into the Impact of Tobacco Advertising (SRITA) collection of 657 USST advertisements.ResultsUSST's College Marketing Program (1978–mid 1980s) sponsored events in some 350 campuses and hired student representatives in at least 175 colleges and universities across America. College representatives were trained to provide free samples to fellow students. Over a typical school year approximately a quarter million Happy Days, Skoal, and Skoal Bandits samples were handed out to undergraduates. USST paid their student representatives well and offered them a variety of incentives based upon sales growth. During the 1990s, USST's Skoal Music program engaged students on campuses and at “spring break” venues such as Daytona Beach.ConclusionsTargeting of college students on campus was a common tobacco industry practice between the 1940s and early 1960s. From the 1970s through 1990s USST resurrected the method and pursued it with vigor including: distribution of free samples; sponsored events and concerts, branded intramural teams; visits by sports celebrities; logo wearables and merchandise; contests and incentives; and displays and promotions in stores on and surrounding campuses. Laryngoscope, 131:E1860–E1872, 2021
How skilful are Nowcasting Satellite Applications Facility products for tropical Africa?
Authors: Hill Peter G. , Stein Thorwald H.M. , Roberts Alexander J. , Fletcher Jennifer K. , Marsham John H. , Groves James 
Published: November 2020

AbstractSatellite nowcasting potentially provides a vital opportunity to mitigate against the risks of severe weather in tropical Africa, where population growth and climate change are exposing an ever growing number of people to weather hazards. Numerical weather prediction demonstrates limited skill for much of Africa and weather radars are rare. However, geostationary satellites provide excellent spatial and temporal coverage of the often long‐lasting convective storms that deliver heavy rain, lightning and strong winds, presenting a valuable opportunity for satellite nowcasting. Here, we evaluate the skill of satellite nowcasting products for tropical Africa: these products are routinely generated, but to our best knowledge never routinely used in tropical Africa before the Global Challenges Research Fund African SWIFT (Science for Weather Information and Forecasting Techniques) project. Focusing in particular on convective rainfall rate (CRR) and rapidly developing thunderstorm convection warning (RDT‐CW) products, we demonstrate that both are useful nowcasting tools. The CRR product produces very different rainfall climatologies for day and night in tropical Africa. This is associated with greater skill of the product during daytime, particularly for heavier rain rates. The RDT‐CW product is able to identify around 60% of heavy (>5 mm·hr−1) rainfall events with the fraction detected increasing with increasing rainfall rate. For both products, extrapolation forwards in time (up to 90 and 60 min, respectively) maintains useful skill in tropical Africa, motivating work to develop longer lead‐time nowcasts. We conclude that widespread uptake of satellite nowcasting could provide new skilful weather predictions on short time‐scales in much of tropical Africa.
Can Baseline Characteristics be Used to Predict Liver Disease Outcomes in Pediatric Nonalcoholic Fatty Liver Disease?
Authors: Orkin Sarah , Yodoshi Toshifumi , Sun Qin , Fei Lin , Meryum Syeda , Arce‐Clachar Ana Catalina , Bramlage Kristin , Beck Andrew F. , Mouzaki Marialena 
Published: November 2020

ObjectiveLongitudinal studies on childhood predictors of nonalcoholic fatty liver disease (NAFLD) progression are lacking. The objective of this study was to determine whether baseline clinical or laboratory measures predict liver disease outcomes in a pediatric NAFLD cohort.MethodsA retrospective study of patients with presumed NAFLD was conducted using baseline and follow‐up clinical and laboratory measures. Disease outcomes were defined using the mean serum alanine aminotransferase (ALT) levels from 24 to 36 months after the first visit. Logistic regression assessed the relationship between ALT progression/regression and predictor variables. Multivariable regression determined the best model for predicting the ALT outcome. Markov process modeling explored the likelihood for a patient to transition between ALT states.ResultsOf a total of 816 patients identified, 144 had sufficient data. Regression was seen in 26%, whereas 30% progressed. No baseline clinical or laboratory measurements had a significant effect on disease outcomes. Markov modeling demonstrated that subjects were more likely to either remain in their baseline ALT group or worsen rather than improve.ConclusionsRoutinely obtained baseline clinical or laboratory measures cannot help risk‐stratify youth with presumed NAFLD in terms of long‐term outcomes. Close clinical, radiographic, and histologic evaluation of patients is warranted to determine those at risk of progression.
Reliability analysis for mechanical parts considering hidden cost via the modified quality loss model
Authors: Mao Kui , Liu Xintian , Li Shuangshuang , Wang Xu 
Published: November 2020

AbstractThe improvement of mechanical parts inherent reliability has an impact on the reputation and performance of the company. To estimate the inherent reliability of products more conveniently and economically, a hidden quality cost‐production cost (HQC‐PC) reliability prediction model is put forward. To estimate the hidden quality cost (HQC) of products more accurately, a quadratic exponential quality loss function model is established, which is different from Taguchi's quadratic quality loss function (QLF) and the modified QLFs. In the new quality loss model, the growth rate of quality loss on both sides of the target value is considered. Under the condition that the quality characteristic value obeys normal distribution, the general estimation formulas of HQC in the tolerance range is obtained considering sampling error and the numerical model of inherent reliability is established. The effect of different parameters on the inherent reliability of products is discussed with practical case, such as design and production parameters. Then, the appropriate process capability index (PCI) is selected according to different production processes. The relationship between the HQC‐PC reliability prediction model and PCI is derived by a numerical model of inherent reliability. A new analysis method of inherent reliability is proposed.
Anchoring Carbon Nanodots onto Nanosilica for Phosphorescence Enhancement and Delayed Fluorescence Nascence in Solid and Liquid States
Authors: He Jiangling , Chen Yonghao , He Youling , Xu Xiaokai , Lei Bingfu , Zhang Haoran , Zhuang Jianle , Hu Chaofan , Liu Yingliang 
Published: November 2020

AbstractCarbon nanodots (CDs) anchored onto inorganic supporter (amorphous nanosilica, SiO2) like a core‐satellite structure have enhanced the room‐temperature phosphorescence (RTP) intensity along with ultralong lifetime of 1.76 s. Special and quite stable structure should account for these superiorities, including hydrogen network, covalent bond, and trap‐stabilized triplet‐state excitons that are responsible for the generation of phosphorescence. These multiple effects have efficaciously protected CDs from being restrained by the external environment, providing such long‐lived emission (LLE) that can subsist not only in powdery CDs–SiO2 but also coexist in aqueous solution, pushing a big step forward in the application prospects of liquid‐state phosphorescence. Through construction of CDs–SiO2 compound, electron trap is reasoned between CDs and SiO2 by analyzing thermoluminescent glow curve. Electron trap can capture, store, and gradually release the electrons just like an electron transporter to improve the intersystem crossing (ISC) and reserved ISC, having provided the more stabilized triplet excitons, stronger and longer phosphorescence, and also triggered the formation of thermally activated delayed fluorescence (TADF), offering a new mechanism for exploiting LLE among CD‐based field. Moreover, it is more beneficial to the formation of TADF as temperature increases, thus the afterglow color can change with the temperature.
Near-BPS baby Skyrmions
Authors: Gudnason Sven Bjarke , Barsanti Marco , Bolognesi Stefano 
Published: November 2020

Abstract
We consider the baby-Skyrme model in the regime close to the so-called restricted baby-Skyrme model, which is a BPS model with area-preserving diffeomorphism invariance. The perturbation takes the form of the standard kinetic Dirichlet term with a small coefficient ϵ. Classical solutions of this model, to leading order in ϵ, are called restricted harmonic maps. In the BPS limit (ϵ → 0) of the model with the potential being the standard pion-mass term, the solution with unit topological charge is a compacton. Using analytical and numerical arguments we obtain solutions to the problem for topological sectors greater than one. We develop a perturbative scheme in ϵ with which we can calculate the corrections to the BPS mass. The leading order ($$ \mathcal{O}\left({\upepsilon}^1\right) $$
O

ϵ
1

) corrections show that the baby Skyrmion with topological charge two is energetically preferred. The binding energy requires us to go to the third order in ϵ to capture the relevant terms in perturbation theory, however, the binding energy contributes to the total energy at order ϵ2. We find that the baby Skyrmions — in the near-BPS regime — are compactons of topological charge two, that touch each other on their periphery at a single point and with orientations in the attractive channel.
Challenges and future directions in LC-MS-based multiclass method development for the quantification of food contaminants
Authors: Steiner David , Malachová Alexandra , Sulyok Michael , Krska Rudolf 
Published: November 2020

AbstractMonitoring of food contaminants and residues has undergone a significant improvement in recent years and is now performed in an intensive manner. Achievements in the area of chromatography-mass spectrometry coupling techniques enabled the development of quantitative multi-target approaches covering several hundred analytes. Although the majority of methods are focusing on the analysis of one specific group of substances, such as pesticides, mycotoxins, or veterinary drugs, current trends are going towards the simultaneous determination of multiclass compounds from several families of contaminants and residues. This work provides an overview of relevant multiclass concepts based on LC-MS/MS and LC-HRMS instruments. Merits and shortcomings will be critically discussed based on current performance characteristics of the EU legislation system. In addition, the discussion of a recently developed multiclass approach covering >1000 substances is presented as a case study to illustrate the current developments in this area.
Population-based meta-analysis of chloroquine: informing chloroquine pharmacokinetics in COVID-19 patients
Authors: Yao Xueting , Yan Xiaoyu , Wang Xiaohan , Cai Ting , Zhang Shun , Cui Cheng , Wang Xiaoxu , Hou Zhe , Liu Qi , Li Haiyan , Lin Jing , Xiong Zi , Liu Dongyang 
Published: November 2020

Abstract
Aims
Chloroquine (CQ) has been repurposed to treat coronavirus disease 2019 (COVID-19). Understanding the pharmacokinetics (PK) in COVID-19 patients is essential to study its exposure–efficacy/safety relationship and provide a basis for a possible dosing regimen optimization.

Subject and methods
In this study, we used a population-based meta-analysis approach to develop a population PK model to characterize the CQ PK in COVID-19 patients. An open-label, single-center study (ethical review approval number: PJ-NBEY-KY-2020-063-01) was conducted to assess the safety, efficacy, and pharmacokinetics of CQ in patients with COVID-19. The sparse PK data from 50 COVID-19 patients, receiving 500 mg CQ phosphate twice daily for 7 days, were combined with additional CQ PK data from 18 publications.

Results
A two-compartment model with first-order oral absorption and first-order elimination and an absorption lag best described the data. Absorption rate (ka) was estimated to be 0.559 h−1, and a lag time of absorption (ALAG) was estimated to be 0.149 h. Apparent clearance (CL/F) and apparent central volume of distribution (V2/F) was 33.3 l/h and 3630 l. Apparent distribution clearance (Q/F) and volume of distribution of peripheral compartment (Q3/F) were 58.7 l/h and 5120 l. The simulated CQ concentration under five dosing regimens of CQ phosphate were within the safety margin (400 ng/ml).

Conclusion
Model-based simulation using PK parameters from the COVID-19 patients shows that the concentrations under the currently recommended dosing regimen are below the safety margin for side-effects, which suggests that these dosing regimens are generally safe. The derived population PK model should allow for the assessment of pharmacokinetics–pharmacodynamics (PK-PD) relationships for CQ when given alone or in combination with other agents to treat COVID-19.