bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of NF‐κB is required for oleanolic acid to downregulate PD‐L1 by promoting DNA demethylation in gastric cancer cells
Authors: Lu Xirong , Li Yuyi , Yang Wei , Tao Minghao , Dai Yanmiao , Xu Jinkang , Xu Qianfei 
Published: September 2020

AbstractGastric cancer is one of the most common causes of cancer‐related death worldwide. Immunotherapy via programmed cell death protein 1 (PD‐1)/programmed cell death‐ligand 1 (PD‐L1) blockade has shown benefits for gastric cancer. Epigenetic DNA methylation critically regulates cancer immune checkpoints. We investigated how the natural compound oleanolic acid (OA) affected PD‐L1 expression in gastric cancer cells. Interleukin‐1β (IL‐1β) at 20 ng/mL was used to stimulate human gastric cancer MKN‐45 cells. IL‐1β significantly increased PD‐L1 expression, which was abolished by OA. Next, OA‐treated MKN‐45 cells were co‐cultured with activated and PD‐1‐overexpressing Jurkat T cells. OA restored IL‐2 levels in the co‐culture system and increased T cell killing toward MKN‐45 cells. Overexpression of PD‐L1 eliminated OA‐enhanced T cell killing capacity; however, PD‐1 blocking antibody abrogated the cytotoxicity of T cells. Moreover, OA abolished IL‐1β‐increased DNA demethylase activity in MKN‐45 cells. DNA methyltransferase inhibitor 5‐azacytidine rescued OA‐reduced PD‐L1 expression; whereas DNA demethylation inhibitor gemcitabine inhibited PD‐L1 expression, and, in combination with OA, provided more potent inhibitory effects. Furthermore, OA selectively reduced the expression of DNA demethylase TET3 in IL‐1β‐treated MKN‐45 cells, and overexpression of TET3 restored OA‐reduced PD‐L1 expression. Finally, OA disrupted nuclear factor κB (NF‐κB) signaling IL‐1β‐treated MKN‐45 cells, and overexpression of NF‐κB restored OA downregulation of TET3 and PD‐L1. The cytotoxicity of T cells toward MKN‐45 cells was also weakened by NF‐κB overexpression. Altogether, OA blocked the IL‐1β/NF‐κB/TET3 axis in gastric cancer cells, leading to DNA hypomethylation and downregulation of PD‐L1. Our discoveries suggested OA as an epigenetic modulator for immunotherapy or an adjuvant therapy against gastric cancer.
Privacy is a Concern: An Introduction to the Dialogue on Privacy
Authors: Krishna Aradhna 
Published: September 2020

This article is part of a Research Dialogue:Acquisti et al. (2020): https://doi.org/10.1002/jcpy.1191Oyserman & Schwarz (2020): https://doi.org/10.1002/jcpy.1189Mulligan et al. (2020): https://doi.org/10.1002/jcpy.1190Jagadish (2020): https://doi.org/10.1002/jcpy.1188Acquisti et al. (2020): https://doi.org/10.1002/jcpy.1187
Single‐cell Raman spectrum extraction from clinic biosamples
Authors: Han Xinxin , Wu Yihui , Chi Mingbo , Gao Sujun , Wang Quan 
Published: September 2020

AbstractRaman spectra of clinical samples are often affected by both the substrate and background fluorescence. The overlay of the substrate spectrum, biological Raman spectrum, and the fluorescence spectrum significantly affects the identification of biometrics. In this paper, we propose a specific‐scale analysis algorithm and a zero‐order Savitzky–Golay filtering algorithm combining local minima to separate the substrate and background fluorescent, respectively. The specific‐scale analysis algorithm based on wavelet transform can realize the linear separation of the substrate spectrum through multiresolution analysis. The zero‐order Savitzky–Golay filter algorithm combining local minima is an empirical algorithm. It estimates the background fluorescence by building a smooth curve that passes through local minima. We tested our algorithms with simulated spectra and with the Raman spectra of clinical biosamples recorded on glass. The analysis results of three gastric cancer cell lines indicated that the classification error of the processed spectrum decreased significantly.
Development of duplex real‐time polymerase chain reaction for simultaneous detection of oilfish‑ and escolar‐derived components
Authors: Yao Lin , Xin Hongmei , Qu Meng , Jiang Yanhua , Guo Yingying , Li Fengling , Li Na , Tan Zhijun , Wang Lianzhu 
Published: September 2020

AbstractBACKGROUNDOilfish (Ruvettus pretiosus) and escolar (Lepidocybium flavobrunneum) are often used to adulterate high‐value aquatic products, causing serious economic losses to consumers, and even keriorrhea in severe cases. It was difficult to identify them by morphological features for these two fish were processed into steak or fillet. The purpose of this study, therefore, is to develop an accurate and efficient method for detecting the oilfish‑ and escolar‐derived components.RESULTSBy comparing the mitochondrial 16S ribosomal RNA gene sequences of oilfish, escolar, and 16 varieties susceptible to adulteration, specific primers/probes were designed, and a duplex real‐time polymerase chain reaction (PCR) method was established to detect oilfish‑ and escolar‐derived components. The specificity and sensitivity of the method were analyzed, and the method was used to analyze 70 commercial samples to evalutate its applicability to actual samples in the market. The method developed was highly specific, without any cross‐reaction on the other 16 species, with a limit of detection (LOD) for DNA of 0.0002 ng μL−1 for R. pretiosus and 0.002 ng μL−1 for L. flavobrunneum. In addition, the LOD for mixed muscle tissues was 0.1 g kg−1. Oilfish‑ and escolar‐derived components were detected in 12 of the 70 commercial samples, a result that is consistent with the classic DNA barcoding test results.CONCLUSIONThe duplex real‐time PCR method developed can be used to detect oilfish and escolar specifically, sensitively and accurately; it provides a good technical support for the identification of authentic aquatic products. © 2020 Society of Chemical Industry
Global analysis of FSH‐regulated gene expression and histone modification in mouse granulosa cells
Authors: Madogwe Ejimedo , Tanwar Deepak K. , Taibi Milena , Schuermann Yasmin , St‐Yves Audrey , Duggavathi Raj 
Published: September 2020

AbstractFollicle‐stimulating hormone (FSH) regulates ovarian follicular development through a specific gene expression program. We analyzed FSH‐regulated transcriptome and histone modification in granulosa cells during follicular development. We used super‐stimulated immature mice and collected granulosa cells before and 48 h after stimulation with equine chorionic gonadotropin (eCG). We profiled the transcriptome using RNA‐sequencing (N = 3/time‐point) and genome‐wide trimethylation of lysine 4 of histone H3 (H3K4me3; an active transcription marker) using chromatin immunoprecipitation and sequencing (ChIP‐Seq; N = 2/time‐point). Across the mouse genome, 14,583 genes had an associated H3K4me3 peak and 63–66% of these peaks were observed within ≤1 kb promoter region. There were 72 genes with differential H3K4me3 modification at 48 h eCG (absolute log fold change > 1; false discovery rate [FDR] < 0.05) relative to 0 h eCG. Transcriptome data analysis showed 1463 differentially expressed genes at 48 h eCG (absolute log fold change > 1; FDR < 0.05). Among the 20 genes with differential expression and altered H3K4me3 modification, Lhcgr had higher H3K4me3 abundance and expression, while Nrip2 had lower H3K4me3 abundance and expression. Using ChIP‐qPCR, we showed that FSH‐regulated expression of Lhcgr, Cyp19a1, Nppc, and Nrip2 through regulation of H3K4me3 at their respective promoters. Transcript isoform analysis using Kallisto‐Sleuth tool revealed 875 differentially expressed transcripts at 48 h eCG (b > 1; FDR < 0.05). Pathway analysis of RNA‐seq data demonstrated that TGF‐β signaling and steroidogenic pathways were regulated at 48 h eCG. Thus, FSH regulates gene expression in granulosa cells through multiple mechanisms namely altered H3K4me3 modification and inducing specific transcripts. These data form the basis for further studies investigating how these specific mechanisms regulate granulosa cell functions.
Development and validation of 3D MP‐SSFP to enable MRI in inhomogeneous magnetic fields
Authors: Kobayashi Naoharu , Parkinson Ben , Idiyatullin Djaudat , Adriany Gregor , Theilenberg Sebastian , Juchem Christoph , Garwood Michael 
Published: September 2020

PurposeWe demonstrate the feasibility of MRI with missing‐pulse steady‐state free precession (MP‐SSFP) in a 4T magnet with artificially degraded homogeneity.MethodsT1, T2, and diffusion contrast of MP‐SSFP was simulated with constant and alternate radiofrequency (RF) phase using an extended phase graph. To validate MP‐SSFP performance in human brain imaging, MP‐SSFP was tested with two types of artificially introduced inhomogeneous magnetic fields: (1) a pure linear gradient field, and (2) a pseudo‐linear gradient field introduced by mounting a head‐gradient set at 36 cm from the magnet isocenter. Image distortion induced by the nonlinear inhomogeneous field was corrected using B0 mapping measured with MP‐SSFP.ResultsThe maximum flip angle in MP‐SSFP was limited to ≤10° because of the large range of resonance frequencies in the inhomogeneous magnetic fields tested in this study. Under this flip‐angle limitation, MP‐SSFP with constant RF phase provided advantages of higher signal‐to‐noise ratio and insensitivity to B1+ field inhomogeneity as compared with an alternate RF phase. In diffusion simulation, the steady‐state magnetization in constant RF phase MP‐SSFP increased with an increase of static field gradient up to 8 to 21 mT/m depending on simulation parameters. Experimental results at 4T validated these findings. In human brain imaging, MP‐SSFP preserved sufficient signal intensities, but images showed severe image distortion from the pseudo‐linear inhomogeneous field. However, following distortion correction, good‐quality brain images were achieved.ConclusionMP‐SSFP appears to be a feasible MRI technique for brain imaging in an inhomogeneous magnetic field.
Whitefly‐induced tomato volatiles mediate host habitat location of the parasitic wasp Encarsia formosa, and enhance its efficacy as a bio‐control agent
Authors: Chen Chan‐Shan , Zhao Chan , Wu Zhi‐Yi , Liu Guang‐Fu , Yu Xiao‐Ping , Zhang Peng‐Jun 
Published: September 2020

AbstractBACKGROUNDWhitefly Bemisia tabaci is a phloem‐feeding insect and causes extensive agricultural damage around the world. Although the parasitic wasp Encarsia formosa is widely used to control B. tabaci on glasshouse tomatoes, low efficiency and discontinuity are frequently recorded. It has been well‐documented that herbivore‐induced plant volatiles (HIPVs) are important cues in the foraging behavior of the natural enemies of herbivores. However, the volatiles emitted from tomatoes infested by different developmental stages of B. tabaci (nymphs versus adults) have not been compared in terms of their effects on E. formosa attraction.RESULTSOlfactometer assays with four tomato cultivars revealed that the E. formosa wasps showed a significant attraction to the volatiles from adult‐infested plants (except for cv. Castlemart), but not to those from nymph‐infested plants. In a close‐range habitat, however, the wasps appeared to use visual or tactile cues derived from nymphs for host location. Volatile analyses and behavioral assays showed that wasp attraction was correlated with enhanced β‐myrcene and β‐caryophyllene emissions from adult‐infested plants. Furthermore, the use of B. tabaci adult‐induced plant cues under glasshouse conditions resulted in a higher parasitism rate by this parasitoid.CONCLUSIONOur findings confirm that E. formosa uses the HIPVs resulting from feeding of B. tabaci adults to locate host habitat. Release of β‐myrcene and β‐caryophyllene from dispensers may enhance the efficacy of E. formosa as a biological control agent against B. tabaci in glasshouse production systems.
Teaching Simulation Literacy with Evacuations
Authors: Greubel Andre , Siller Hans-Stefan , Hennecke Martin 
Published: September 2020

AbstractAs significant policies are based on their expected outcome in computer simulations, literacy of such simulations is necessary for political participation. In this paper, we propose ways to increase such simulation literacy. We discuss simulation literacy from a theoretical perspective and argue for simulating evacuations as a simple and potent topic to increase simulation literacy. Additionally, we present , a novel educational tool to simulate the evacuating of buildings (not only) for classrooms. Lastly, we show different teaching scenarios and exercises for the usage of in an exemplary way. and further teaching material is available online at www.evadid.it.
Mirror neutrons as dark matter in the Mirror Twin Two Higgs Doublet Model
Authors: Beauchesne Hugues 
Published: September 2020

Abstract
In addition to being a solution to the little hierarchy problem, the Mirror Twin Higgs provides a natural setting for Asymmetric Dark Matter. In its incarnation with only one Higgs doublet and its mirror copy, dark matter would however almost certainly consist mostly of mirror atoms, which is severely ruled out by constraints on dark matter self-interactions. By adding a second Higgs doublet and its mirror, the vevs of the different Higgses can be arranged such that dark matter consists mostly of mirror neutrons, which is cosmologically viable. In this paper, it is shown that current constraints from colliders, flavour and cosmology can accommodate such a vev structure with little increase in the necessary tuning.
Childhood maltreatment and poor functional outcomes at the transition to adulthood: a comparison of prospective informant- and retrospective self-reports of maltreatment
Authors: Latham Rachel M. , Quilter Emma , Arseneault Louise , Danese Andrea , Moffitt Terrie E. , Newbury Joanne B. , Fisher Helen L. 
Published: September 2020

AbstractPurposeGrowing evidence suggests that prospective informant-reports and retrospective self-reports of childhood maltreatment may be differentially associated with adult psychopathology. However, it remains unknown how associations for these two maltreatment reporting types compare when considering functional outcomes. The present study compared associations between childhood maltreatment and functional outcomes at age 18 years using these two methods.MethodsWe used data from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative birth cohort of 2232 children born in England and Wales in 1994–1995. Maltreatment prior to age 12 years was assessed prospectively (during multiple home visits between birth and age of 12 years based on interviews with caregivers, researcher observations, and information from practitioners where child protection referrals were made) and retrospectively (at age 18 via self-report on the Childhood Trauma Questionnaire). Nine functional outcomes were measured at age 18, forming two variables capturing: (i) psychosocial and (ii) vocational disadvantage.ResultsAmong the 2054 participants with available data, childhood maltreatment was associated with poorer functional outcomes regardless of whether this was reported only prospectively, only retrospectively, or both. Stronger associations with psychosocial disadvantage arose in the context of retrospective recall by participants (OR = 8.25, 95% CI 4.93–13.82) than prospective reports by informants (OR = 2.03, 95% CI 1.36–3.04) of maltreatment. Conversely, associations with vocational disadvantage were comparable for both prospective informant-reports (OR = 2.19, 95% CI 1.42–3.38) and retrospective self-reports (OR = 1.93, 95% CI 1.33–2.81) of maltreatment.ConclusionResults highlight the importance of considering the maltreatment report type used when interpreting the functional consequences of childhood maltreatment.
On the Asymptotic Nature of First Order Mean Field Games
Authors: Fischer Markus , Silva Francisco J. 
Published: September 2020

AbstractFor a class of finite horizon first order mean field games and associated N-player games, we give a simple proof of convergence of symmetric N-player Nash equilibria in distributed open-loop strategies to solutions of the mean field game in Lagrangian form. Lagrangian solutions are then connected with those determined by the usual mean field game system of two coupled first order PDEs, and convergence of Nash equilibria in distributed Markov strategies is established.
Backtracking Gradient Descent Method and Some Applications in Large Scale Optimisation. Part 2: Algorithms and Experiments
Authors: Truong Tuyen Trung , Nguyen Hang-Tuan 
Published: September 2020

AbstractIn this paper, we provide new results and algorithms (including backtracking versions of Nesterov accelerated gradient and Momentum) which are more applicable to large scale optimisation as in Deep Neural Networks. We also demonstrate that Backtracking Gradient Descent (Backtracking GD) can obtain good upper bound estimates for local Lipschitz constants for the gradient, and that the convergence rate of Backtracking GD is similar to that in classical work of Armijo. Experiments with datasets CIFAR10 and CIFAR100 on various popular architectures verify a heuristic argument that Backtracking GD stabilises to a finite union of sequences constructed from Standard GD for the mini-batch practice, and show that our new algorithms (while automatically fine tuning learning rates) perform better than current state-of-the-art methods such as Adam, Adagrad, Adadelta, RMSProp, Momentum and Nesterov accelerated gradient. To help readers avoiding the confusion between heuristics and more rigorously justified algorithms, we also provide a review of the current state of convergence results for gradient descent methods. Accompanying source codes are available on GitHub.
Population pharmacokinetic analysis of nanoparticle-bound and free camptothecin after administration of NLG207 in adults with advanced solid tumors
Authors: Schmidt Keith T. , Huitema Alwin D. R. , Dorlo Thomas P. C. , Peer Cody J. , Cordes Lisa M. , Sciuto Linda , Wroblewski Susan , Pommier Yves , Madan Ravi A. , Thomas Anish , Figg William D. 
Published: September 2020

Abstract
Purpose
NLG207 (formerly CRLX101) is a nanoparticle–drug conjugate (NDC) of the potent topoisomerase I inhibitor, camptothecin (CPT). The present study sought to characterize the complex pharmacokinetics (PK) of NLG207 and better describe CPT release from nanoparticles using a population PK (popPK) model.

Methods
From 27 patients enrolled on two phase II clinical trials (NCT02769962 and NCT03531827), dense sampling was performed up to 48 h post-administration of NLG207 during cycle one and six of treatment; samples were also collected at ~ 360 h post-dose. Conjugated and free CPT concentrations were quantified from each sample, resulting in 477 observations to build a popPK model using non-linear mixed-effects modeling.

Results
The PK of NLG207 was characterized by combining two linear two-compartment models with first-order kinetics each to describe nanoparticle-bound (conjugated) and free CPT. Allometric scaling based on body weight provided the best body-size descriptor for all PK parameters. The typical volumes of distribution of the conjugated CPT central and free CPT central compartments were 3.16 L (BSV CV%; 18.1%) and 21.1 L (CV%; 79.8%), respectively. CPT release from the nanoparticle formulation was characterized via an initial rapid clearance of 5.71 L/h (CV%; 62.6%), which decreased via first-order decay (estimated half-life of 0.307 h) to the steady-state value of 0.0988 L/h (CV%; 33.5%) by ~ 4 h after end of infusion. Renal clearance of free CPT was 0.874 L/h (CV%; 42.2%).

Conclusion
The popPK model confirmed nanoparticle behavior of conjugated CPT and mechanistically characterized CPT release from NLG207. The current analysis provides a strong foundation for future study as a potential predictive tool in ongoing NLG207 clinical trials.
A modified Ising model of Barabási–Albert network with gene-type spins
Authors: Krishnan Jeyashree , Torabi Reza , Schuppert Andreas , Napoli Edoardo Di 
Published: September 2020

AbstractThe central question of systems biology is to understand how individual components of a biological system such as genes or proteins cooperate in emerging phenotypes resulting in the evolution of diseases. As living cells are open systems in quasi-steady state type equilibrium in continuous exchange with their environment, computational techniques that have been successfully applied in statistical thermodynamics to describe phase transitions may provide new insights to the emerging behavior of biological systems. Here we systematically evaluate the translation of computational techniques from solid-state physics to network models that closely resemble biological networks and develop specific translational rules to tackle problems unique to living systems. We focus on logic models exhibiting only two states in each network node. Motivated by the apparent asymmetry between biological states where an entity exhibits boolean states i.e. is active or inactive, we present an adaptation of symmetric Ising model towards an asymmetric one fitting to living systems here referred to as the modified Ising model with gene-type spins. We analyze phase transitions by Monte Carlo simulations and propose a mean-field solution of a modified Ising model of a network type that closely resembles a real-world network, the Barabási–Albert model of scale-free networks. We show that asymmetric Ising models show similarities to symmetric Ising models with the external field and undergoes a discontinuous phase transition of the first-order and exhibits hysteresis. The simulation setup presented herein can be directly used for any biological network connectivity dataset and is also applicable for other networks that exhibit similar states of activity. The method proposed here is a general statistical method to deal with non-linear large scale models arising in the context of biological systems and is scalable to any network size.
Missed diagnoses and misdiagnoses of adults with autism spectrum disorder
Authors: Fusar-Poli Laura , Brondino Natascia , Politi Pierluigi , Aguglia Eugenio 
Published: September 2020

AbstractAutism spectrum disorder (ASD) is a group of life-long neurodevelopmental disorders affecting 1.5% of the general population. The present study aimed to evaluate the psychiatric history of a group of adults who received the first diagnosis of ASD in two Italian university centers. Diagnoses of ASD were confirmed by a team of psychiatrists with wide expertise in the field, after the administration of standardized tools (i.e., ADOS-2, ADI-R). The sample comprised 161 participants, of which 114 (79.5%) were males. The median age of diagnosis was 23 years (range 18–55), with a median IQ of 100 (range 30–145). The first evaluation by a mental health professional was performed at a median age of 13 years, with a gap of 11 years between the first evaluation and the diagnosis of ASD. 33.5% of participants had never received a psychiatric diagnosis, while the rest of the sample had received one or more diagnoses different from ASD. The most common past diagnoses were intellectual disability, psychoses, personality disorders, and depression. Sex differences were detected in the age of diagnosis and ADOS-2 scores. Our results provide important information for both child and adult psychiatrists. Given the prevalence of autism and the high rates of co-occurrent psychiatric conditions, it is important for clinicians to consider ASD in the differential diagnostic process.