bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detecting and mitigating poisoning attacks in federated learning using generative adversarial networks
Authors: Zhao Ying , Chen Junjun , Zhang Jiale , Wu Di , Blumenstein Michael , Yu Shui 
Published: June 2020

SummaryIn the age of the Internet of Things (IoT), large numbers of sensors and edge devices are deployed in various application scenarios; Therefore, collaborative learning is widely used in IoT to implement crowd intelligence by inviting multiple participants to complete a training task. As a collaborative learning framework, federated learning is designed to preserve user data privacy, where participants jointly train a global model without uploading their private training data to a third party server. Nevertheless, federated learning is under the threat of poisoning attacks, where adversaries can upload malicious model updates to contaminate the global model. To detect and mitigate poisoning attacks in federated learning, we propose a poisoning defense mechanism, which uses generative adversarial networks to generate auditing data in the training procedure and removes adversaries by auditing their model accuracy. Experiments conducted on two well‐known datasets, MNIST and Fashion‐MNIST, suggest that federated learning is vulnerable to the poisoning attack, and the proposed defense method can detect and mitigate the poisoning attack.
Quantification of In Vivo Metabolic Activity of CYP2D6 Genotypes and Alleles Through Population Pharmacokinetic Analysis of Vortioxetine
Authors: Frederiksen Trine , Areberg Johan , Schmidt Ellen , Bjerregaard Stage Tore , Brøsen Kim 
Published: June 2020

Assignment of CYP2D6 phenotype from genotype data can be challenging and despite efforts to standardize translation, there is currently no universally accepted method. To facilitate standardization, there remains a need to precisely quantify the in vivo function of different CYP2D6 genotypes. Vortioxetine is metabolized to its major metabolite, Lu AA34443, primarily via CYP2D6. The aim of this study was to quantify the in vivo CYP2D6 activity of different CYP2D6 alleles and genotypes through population pharmacokinetic (PopPK) modeling of vortioxetine and Lu AA34443. Plasma concentration data of vortioxetine and Lu AA34443 from 1,140 subjects originating from 29 clinical pharmacology studies were pooled for the analysis. A joint PopPK model described the pharmacokinetics of vortioxetine and Lu AA34443 simultaneously and provided estimates of the CYP2D6‐mediated metabolism for each subject. Subjects normally classified as CYP2D6 intermediate metabolizers (IMs) showed different levels of CYP2D6 activity with carriers of one fully functional allele and one null function allele having 77% higher CYP2D6 activity compared with carriers of two decreased function alleles (P < 0.0001). The decreased function alleles were associated with different levels of reduction of CYP2D6 activity. Fixing the activity of fully functional alleles to 1.0, the relative activities of CYP2D6*9, CYP2D6*10, CYP2D6*17, and CYP2D6*41 were 0.22, 0.37, 0.17, and 0.21, respectively. The activity of CYP2D6*10 was shown to be significantly greater than that of CYP2D6*17 (P = 0.01) and CYP2D6*41 (P = 0.02). These results warrant further discussion of current CYP2D6 genotype‐phenotype classification systems particularly regarding decreased function alleles and the IM phenotype.
Cp2TiIIICl Catalysis in a New Light
Authors: Chen Yuqing , Lin Shuangjie , Li Fusheng , Zhang Xinhai , Lin Luqing , Shi Lei 
Published: June 2020

AbstractVisible‐light‐mediated photogeneration of Cp2TiIIICl has opened new avenues for titanium catalysis. The synergistic utilization of dual photoredox and Cp2TiIIICl catalysis uses Hantzsch ester (HE) as an electron donor instead of traditional super‐stoichiometric metallic reductants. This new paradigm has found numerous applications in synthetic organic chemistry. The highly efficient photoinduced electron transfer process between light‐sensitive Cp2TiCl2 and an excited photocatalyst is the key to the success of such a photocatalytic system and ensures overall catalyst turnover. Comparisons between the metal reduction approach and photo reduction approach have been made.
Making predictive modelling ART: accurate, reliable, and transparent
Authors: Bodner Korryn , Fortin Marie‐Josée , Molnár Péter K. 
Published: June 2020

AbstractModels are increasingly being used for prediction in ecological research. The ability to generate accurate and robust predictions is necessary to help respond to ecosystem change and to further scientific research. Successful predictive models are typically accurate, reliable, and transparent regarding their assumptions and expectations, indicating high predictive capacity, robustness, and clarity in their objectives and standards. Research on improving these properties is becoming more common, but often individual research projects are focused on a single aspect of the modelling process and are typically disseminated only within the field where the research originated. The goal of this review is to synthesize research from various disciplines and topics to provide a coherent framework for developing efficient predictive models. Our framework summarizes the process of creating predictive models into three main stages: (1) Framing the Question; (2) Model‐Building and Testing; and (3) Uncertainty Evaluation with proposed strategies associated with each stage to help produce more successful predictive models. The key strategies identified within our framework form specific guidelines, providing a new perspective to help researchers make predictive modelling more accurate, reliable, and transparent.
Prolonged suppression of the anti‐oxidant/anti‐inflammatory effects of BNP post‐Takotsubo syndrome
Authors: Liu Saifei , Ngo Doan , Chirkov Yuliy , Stansborough Jeanette , Chong Cher‐Rin , Horowitz John D. 
Published: June 2020

AbstractAimsTakotsubo syndrome (TTS) episodes are primarily initiated by ‘pulse’ release of catecholamines inducing neutrophil infiltration and myocardial inflammation in susceptible individuals (largely ageing women). Evidence of myocardial inflammation and associated energetic impairment persists for ≥ 3 months post‐acute TTS episodes, suggesting the existence of additional ‘perpetuating’ mechanisms. The effects of B‐type natriuretic peptide (BNP) in suppressing superoxide (O2−) release from neutrophils are transiently impaired in acute heart failure. We also evaluated the extent and duration of BNP‐induced suppression of O2− release post‐TTS.Methods and resultsTTS patients were studied acutely (n = 34) and 3 months thereafter (n = 13) and compared with control subjects (n = 25). O2− generation from neutrophils, triggered by N‐formyl‐methionyl‐leucyl‐phenylalanine and phorbol myristate acetate, and its suppression by BNP, were measured in vitro. Determinants of variability in BNP effect were sought via univariate and multivariate analyses.Relative to control subjects, in TTS patients, BNP suppression of both phorbol myristate acetate and N‐formyl‐methionyl‐leucyl‐phenylalanine‐induced O2− release was impaired acutely (P < 0.05 for both); this did not improve over the 3‐month recovery period, despite treatment with conventional anti‐failure medication in 85% of patients. No significant correlates of BNP effect (other than TTS) were identified.Conclusions(1) While TTS is associated with marked and prolonged release of BNP, there is virtually total loss of the ability of BNP to suppress neutrophil O2− release and its impact on tissue inflammation. (2) BNP responses do not recover for at least 3 months post‐attacks, suggesting that this might contribute to perpetuation of myocardial inflammation in TTS patients.
Gateway and journey of patients with cardiac amyloidosis
Authors: Dang Daniel , Fournier Pauline , Cariou Eve , Huart Antoine , Ribes David , Cintas Pascal , Roussel Murielle , Colombat Magali , Lavie‐Badie Yoan , Carrié Didier , Galinier Michel , Lairez Olivier 
Published: June 2020

AbstractAimsAdvances have been made over the last decade in the management of cardiac amyloidosis (CA), but a delayed diagnosis is still common. The aim of this study was to describe the journey to CA diagnosis from initial clinical and to analyse time to diagnosis.Methods and resultsBetween January 2001 and May 2019, 270 consecutive patients with CA diagnosed at Toulouse University Hospital were retrospectively included in this cross‐sectional study: 111 (41%) light chain amyloidosis, 122 (45%) wild‐type transthyretin amyloidosis, and 37 (14%) hereditary transthyretin amyloidosis.CA onset occurred mostly with dyspnoea (50%) or systematic follow‐up (10%). The cardiologist was the first line specialist in 68% of patients, followed by the nephrologist (9%) and neurologist (8%). Patients encountered a median (minimum–maximum) number of two (1–7) physician specialists and performed a median (minimum–maximum) number of three (1–8) tests before diagnosis. Median delay between symptom onset and CA diagnosis was 8 [IQR 5–14], 10 [IQR 3–34], and 18 [IQR 4–49] months, respectively, in light chain amyloidosis, wild‐type transthyretin amyloidosis, and hereditary transthyretin amyloidosis subgroups (P = .060). Having performed electromyography or spirometry was associated with a longer delay in diagnosis in the overall population: odds ratio = 1.13; 95% confidence interval 1.02 to 1.24; and odds ratio = 1.13; 1.03 to 1.24, respectively, probably due to non‐specific initial symptoms.ConclusionsCA is a protean disease with various first line specialists causing a diagnostic wandering despite increasing medical community awareness. It requires a multidisciplinary specialist care networks to educate and manage symptoms and therapies.
An ultrasimple and cost‐effective µPAD by pasting hydrophilic channels to a hydrophobic basement
Authors: Zhang Daohong , Yan Lingzhi , Zhang Yongzhi , Li Tao , Wang Jianlong 
Published: June 2020

AbstractThe application of the paper‐based microfluidic device (µPAD) as a potentially significant platform for clinical diagnoses has gained a great interest during the recent years. This work presented a technically ultrasimple, low‐cost, effective, and rapid method for the µPADs fabrication by pasting a hydrophilic flower‐like paper mask to a hydrophobic PVC substrate, which was purchased with adhesive on it. The whole manufacture process could be implemented in a few seconds by untrained personnel. To demonstrate the feasibility of this method in real‐world situations, the developed paper device was employed for colorimetric assays of glucose in artificial urine and nitrite in artificial saliva. The main analysis parameters, for example, the optimum volumes of reagents, reaction time, and so forth, were seriatim optimized. Under optimal conditions, the detection limits were 0.9 mM and 19.5 µM for glucose and nitrite, respectively; the detection ranges were 0.9–30 mmol/L and 19.5–312.5 µmol/L for glucose and nitrite analyses, respectively. These results showed that this equipment‐free µPAD had great potentials for the qualitative or semiquantitative detection of glucose and nitrite in real samples.
Developing novel synbiotic low‐fat yogurt with fucoxylogalacturonan from tragacanth gum: Investigation of quality parameters and Lactobacillus casei survival
Authors: Ghaderi‐Ghahfarokhi Maryam , Yousefvand Amin , Ahmadi Gavlighi Hassan , Zarei Mehdi , Farhangnia Peyman 
Published: June 2020

AbstractTragacanth gum (TG) displayed a prebiotic activity, but its application was restricted due to high viscosity and deterioration of organoleptic and textural characteristics of food. In this study, TG was depolymerized by Pectinex Ultra Color enzyme followed by membrane separation (30 kDa) to get pectinase hydrolyzed fraction of tragacanth gum (PHFTG) with molecular weight more than 30 kDa. The average molecular weight of PHFTG was 147.7 ± 11.5 g/mol having a fucoxylogalacturonan structure. The prebiotic activity was tested using PHFTG, TG, and inulin as a carbon source. The results showed that the count of Lactobacillus casei in PHFTG‐ and inulin‐supplemented media increased significantly during the 48‐hr fermentation (p < .05). Five batches of low‐fat set yogurts were prepared by the following formulation: Control (without both L. casei and prebiotic), LC‐Cont (containing L. casei), LC‐PHFTG (containing L. casei + 0.5% PHFTG), LC‐TG (containing L. casei + 0.05% TG), and LC‐In (containing L. casei + 0.5% inulin), and L. casei population and physicochemical properties were monitored during 21‐day storage at 4°C. The number of L. casei remained highly acceptable (8.54–8.61 log CFU/g) during 7–21 days of storage in LC‐PHFTG. LC‐In and LC‐PHFTG presented significantly lower syneresis and higher sensory acceptability than LC‐Cont and Control during storage (p < .05). LC‐TG displayed weaker body and texture, lower sensory acceptability, and higher syneresis than other samples. This study provides support for expanding the utilization of PHFTG as a potential prebiotic and fat replacer in non‐ or low‐fat dairy products with satisfactory sensory quality.
Dying during Covid‐19
Authors: Moore Bryanna 
Published: June 2020

AbstractI had been on the phone with Madeleine's mother for fifteen minutes, and she had sobbed throughout. She pleaded with me, “You won't even let our family visit her together. If you really want to help my daughter, you will let us stay with her.” Madeleine, who was twenty‐four years old, was dying of end‐stage acute myeloid leukemia and was intubated in one of our intensive care units. Her intensivist had requested a clinical ethics consultation for potentially inappropriate medical treatment—in my world of clinical ethics consultation, routine stuff. Except that, in March 2020, nothing was routine anymore. The Covid‐19 pandemic calls for creative thinking about ad hoc and post hoc bereavement efforts, and it may result in efforts to revise existing accounts of what constitutes a good death in order to accommodate patients’ and families’ experiences at the end of life during a pandemic.
Cotargeting BET proteins overcomes resistance arising from PI3K/mTOR blockade‐induced protumorigenic senescence in colorectal cancer
Authors: Lee Ho‐Sung , Lee Soobeom , Cho Kwang‐Hyun 
Published: June 2020

AbstractTherapeutics targeting the phosphatidylinositol 3‐kinase/mammalian target of rapamycin (PI3K/mTOR) pathway initially produce potent antitumor effects, but resistance frequently occurs. Using a phosphoproteome analysis, we found that colorectal cancer (CRC) cells exhibit resistance against PI3K/mTOR inhibition through feedback activation of multiple receptor tyrosine kinases, and their downstream focal adhesion kinase, Src and extracellular signal‐regulated kinases signaling. Unexpectedly, PI3K/mTOR blockade causes senescence, mediated by the activation of the stress kinase p38. The senescent cancer cells induce the secretion of various cytokines and this senescence‐associated secretome increases migration and invasion capabilities of CRC cells. We found that cotargeting PI3K/mTOR and bromodomain and extra‐terminal domain can suppress activation of many oncogenic kinases involved in resistance to the PI3K/mTOR inhibition, induce cell death in vitro and tumor regression in vivo, and further prolong the survival of xenograft models. Our findings provide a rationale for a novel therapeutic strategy to overcome resistance to the PI3K/mTOR inhibitors in CRC.
Characterization of a dual BET/HDAC inhibitor for treatment of pancreatic ductal adenocarcinoma
Authors: Zhang Xin , Zegar Tim , Weiser Tim , Hamdan Feda H. , Berger Benedict‐Tilman , Lucas Romain , Balourdas Dimitrios‐IIias , Ladigan Swetlana , Cheung Phyllis F. , Liffers Sven‐Thorsten , Trajkovic‐Arsic Marija , Scheffler Bjoern , Joerger Andreas C. , Hahn Stephan A. , Johnsen Steven A. , Knapp Stefan , Siveke Jens T. 
Published: June 2020

AbstractPancreatic ductal adenocarcinoma (PDAC) is resistant to virtually all chemo‐ and targeted therapeutic approaches. Epigenetic regulators represent a novel class of drug targets. Among them, BET and HDAC proteins are central regulators of chromatin structure and transcription, and preclinical evidence suggests effectiveness of combined BET and HDAC inhibition in PDAC. Here, we describe that TW9, a newly generated adduct of the BET inhibitor (+)‐JQ1 and class I HDAC inhibitor CI994, is a potent dual inhibitor simultaneously targeting BET and HDAC proteins. TW9 has a similar affinity to BRD4 bromodomains as (+)‐JQ1 and shares a conserved binding mode, but is significantly more active in inhibiting HDAC1 compared to the parental HDAC inhibitor CI994. TW9 was more potent in inhibiting tumor cell proliferation compared to (+)‐JQ1, CI994 alone or combined treatment of both inhibitors. Sequential administration of gemcitabine and TW9 showed additional synergistic antitumor effects. Microarray analysis revealed that dysregulation of a FOSL1‐directed transcriptional program contributed to the antitumor effects of TW9. Our results demonstrate the potential of a dual chromatin‐targeting strategy in the treatment of PDAC and provide a rationale for further development of multitarget inhibitors.
Evaluating polygenic risk scores in assessing risk of nine solid and hematologic cancers in European descendants
Authors: Choi Jungyoon , Jia Guochong , Wen Wanqing , Long Jirong , Zheng Wei 
Published: June 2020

AbstractGenome‐wide association studies (GWAS) have identified many genetic risk variants for cancers. The utility of these variants in assessing risk of esophageal, gastric and endometrial cancers, as well as melanoma, glioma, diffuse large B‐cell lymphoma, follicular lymphoma, chronic lymphoid leukemia and multiple myeloma, has not been adequately investigated. We constructed a site‐specific polygenic risk score (PRS) for each of these nine cancers using their GWAS‐identified risk variants. Using data from 400 807 participants of European descent in the UK Biobank, a population‐based cohort study, we estimated the hazard ratios of each cancer associated with its PRS using Cox proportional hazard models. During a median follow‐up of 5.8 years, 3905 incident cases of these nine cancers were identified in the cohort. The area under the receiver operating characteristic curve ranged from 0.53 to 0.69 for these cancers. Except for esophageal cancer, significant dose‐response associations were observed between PRS and cancer risk. Compared to individuals in the middle quintile (40%‐60%) at an average risk, those among the highest 5% of the PRS had a twofold elevated risk of melanoma, glioma, follicular lymphoma or multiple myeloma, and a fourfold elevated risk of chronic lymphoid leukemia. Using PRS, 63.0% of the participants could be classified as having an over twofold elevated risk for at least one cancer. The PRS derived using risk variants identified to date by GWAS showed the potential in identifying individuals at a significantly elevated risk of cancer for prevention.
Composite likelihood methods for large Bayesian VARs with stochastic volatility
Authors: Chan Joshua C. C. , Eisenstat Eric , Hou Chenghan , Koop Gary 
Published: June 2020

SummaryAdding multivariate stochastic volatility of a flexible form to large vector autoregressions (VARs) involving over 100 variables has proved challenging owing to computational considerations and overparametrization concerns. The existing literature works with either homoskedastic models or smaller models with restrictive forms for the stochastic volatility. In this paper, we develop composite likelihood methods for large VARs with multivariate stochastic volatility. These involve estimating large numbers of parsimonious models and then taking a weighted average across these models. We discuss various schemes for choosing the weights. In our empirical work involving VARs of up to 196 variables, we show that composite likelihood methods forecast much better than the most popular large VAR approach, which is computationally practical in very high dimensions: the homoskedastic VAR with Minnesota prior. We also compare our methods to various popular approaches that allow for stochastic volatility using medium and small VARs involving up to 20 variables. We find our methods to forecast appreciably better than these as well.
PCL/gelatin scaffolds and beta‐boswellic acid synergistically increase the efficiency of CGR8 stem cells differentiation into dopaminergic neuron: A new paradigm of Parkinson's disease cell therapy
Authors: Kheradmand Hamed , Babaloo Hamideh , Vojgani Yasaman , Mirzakhanlouei Sasan , Bayat Neda 
Published: June 2020

AbstractParkinson's disease is a progressive degenerative disorder in the central nervous system, which is distinguished by the death of dopamine‐producing nerve cells. Levodopa, a dopamine precursor drug, is the current standard of care of symptomatic treatment for Parkinson's disease. However, the long‐term use of the drug is associated with the development of motor fluctuations and dyskinesias. Cellular therapies aim to deploy fetal dopaminergic neurons as a means to replace the missing dopamine‐producing cells. The present study aims to study the impact of beta‐boswellic acid (BBA) coupled with poly ε‐caprolactone (PCL)/gelatin scaffolds on the dopaminergic differentiation course of CGR8 embryonic stem cells (ESCs). For this purpose, CGR8 ESCs were cultured on PCL/gelatin scaffolds and a five‐step protocol was employed to be promoted the neural differentiation of CGR8 ESCs. Gene expression analysis by real‐time qPCR demonstrated that PCL/gelatin scaffolds along with BBA treatment impose synergistic effects on the derivation of dopaminergic‐like cells from CGR8 ESCs. Reverse‐phase high‐performance liquid chromatography confirmed the functionality of the derived neurons by demonstrating the efficient secretion of dopamine in response to stimuli. Our results suggested that the generation of functional dopaminergic‐like cells from CGR8 ESCs was increased and supported by PCL/gelatin scaffolds and BBA treatment can heighten the efficiency. The result of this study may open insight into Parkinson's disease cell therapy and provide future directions for tissue engineering aimed at the treatment of Parkinson's disease.
Non‐stationary climate changes in summer high‐temperature extremes in Shanghai since the late 19th century
Authors: Tu Kai , Yan Zhongwei 
Published: June 2020

AbstractLong‐term changes in daily high‐temperature extremes in the summers since the late 19th century in Shanghai and their relationships with decadal or multi‐decadal climatic oscillations have been investigated via non‐stationary statistical modelling based on parametric and nonparametric frameworks. Compared to stationary modelling with the assumption of an unchanging climate, time‐varying non‐stationary models based on the generalized extreme value (GEV) result in much more reasonable estimations of the temperature extremes for the present climate in terms of their return levels and return periods. However, nonparametric modelling with cubic spline smoothing reproduced even better multi‐decadal variability for different periods. The nonparametric method also reduces the biases of estimation, especially in the heavy tail of temperature extremes in parametric GEV models. Additionally, non‐stationary models with large‐scale climate indices indicate clear influences of the large‐scale climate indices, especially the last winter's strong signals from the tropical Pacific Ocean and Indian Ocean. The significant influences of multi‐decadal variabilities from the northern Atlantic in the parametric GEV model are probably also explained by spline terms in the nonparametric method. Further application to other areas in China indicates that the developed nonparametric model can fit their extremes correctly but notable biases also remain in the estimation of distributions and heavy tails.