bluuebunny/crossref_metadata_2025_split huggingface dataset:
Approaches to studying the genomic architecture of complex birth defects
Authors: Taiwo Toluwani E. , Cao Xuanye , Cabrera Robert M. , Lei Yunping , Finnell Richard H. 
Published: May 2020

AbstractEvery year nearly 6 percent of children worldwide are born with a serious congenital malformation, resulting in death or lifelong disability. In the United States, birth defects remain one of the leading causes of infant mortality. Among the common structural congenital defects are conditions known as neural tube defects (NTDs). These are a class of malformation of the brain and spinal cord where the neural tube fails to close during the neurulation. Although NTDs remain among the most pervasive and debilitating of all human developmental anomalies, there is insufficient understanding of their etiology. Previous studies have proposed that complex birth defects like NTDs are likely omnigenic, involving interconnected gene regulatory networks with associated signals throughout the genome. Advances in technologies have allowed researchers to more critically investigate regulatory gene networks in ever increasing detail, informing our understanding of the genetic basis of NTDs. Employing a systematic analysis of these complex birth defects using massively parallel DNA sequencing with stringent bioinformatic algorithms, it is possible to approach a greater level of understanding of the genomic architecture underlying NTDs. Herein, we present a brief overview of different approaches undertaken in our laboratory to dissect out the genetics of susceptibility to NTDs. This involves the use of mouse models to identify candidate genes, as well as large scale whole genome/whole exome (WGS/WES) studies to interrogate the genomic landscape of NTDs. The goal of this research is to elucidate the gene‐environment interactions contributing to NTDs, thus encouraging global research efforts in their prevention.
A Comprehensive Analysis of Symmetric Arginine Dimethylation in Colorectal Cancer Tissues Using Immunoaffinity Enrichment and Mass Spectrometry
Authors: Lim Yongchul , Park Yae Eun , Ha Sujin , Lee Ji Eun , Kim Hee Cheol 
Published: May 2020

AbstractProtein arginine methyltransferase 5 (PRMT5) is a major enzyme responsible for generating monomethyl and symmetric dimethyl arginine in proteins. PRMT5 is essential for cell viability and development, and its overexpression is observed in a variety of cancers. In the present study, it is found that levels of PRMT5 protein and symmetric arginine dimethylation in colorectal cancer (CRC) tissues are increased compared to those in adjacent noncancerous tissues. Using immunoaffinity enrichment of methylated peptides combined with high‐resolution mass spectrometry, a total of 147 symmetric dimethyl‐arginine (SDMA) sites in 94 proteins are identified, many of which are RNA binding proteins and enzymes. Quantitative analysis comparing CRC and normal tissues reveals significant increase in the symmetric dimethylation of 70 arginine sites in 46 proteins and a decrease in that of four arginine sites in four proteins. Among the 94 proteins identified in this study, it is confirmed that KH‐type splicing regulatory protein is a target of PRMT5 and highly expressed in CRC tissues compared to noncancerous tissues. This study is the first comprehensive analysis of symmetric arginine dimethylation using clinical samples and extends the number of known in vivo SDMA sites. The data obtained are available via ProteomeXchange with the identifier PXD015653.
Quantitative Proteomics Reveals the Effects of Resveratrol on High‐Altitude Polycythemia Treatment
Authors: Deng Bingnan , Liu Weili , Pu Lingling , Wang Xinxing , Duan Ruifeng , Wang Tianhui , Wang Zirou , Du Lianqun , Gao Zhixian , Chen Zhaoli 
Published: May 2020

AbstractHigh‐altitude polycythemia (HAPC) is a common plateau chronic disease in which red blood cells are compensatory hyperproliferative due to high altitude hypoxic environment. HAPC severely affects the physical and mental health of populations on the plateau. However, the pathogenesis and treatment of HAPC has been rarely investigated. Here, the hypoxia‐induced HAPC model of rat is established, in which hemoglobin concentration significantly increases and platelets clearly decrease. The effect of resveratrol upon hypoxia enables HAPC remission and makes hemoglobin and platelet tend to a normal level. Furthermore, quantitative proteomics is applied to investigate the plasma proteome variation and the underlying molecular regulation during HAPC occurrence and treatment with resveratrol. Hypoxia promotes erythrocyte developing and differentiating and disrupts cytoskeleton organization. Notably, the resveratrol administration reverses the proteome change pattern due to hypoxia and contributes to plateau adaption. Quantitative verification of differentially expressed proteins confirms the roles of resveratrol in HAPC. Resveratrol is expected to be useful for HAPC treatment.
Real‐Time Reconstruction of Arbitrary Slices for Quantitative and In Situ 3D Characterization of Nanoparticles
Authors: Vanrompay Hans , Buurlage Jan‐Willem , Pelt Daniël M. , Kumar Vished , Zhuo Xiaolu , Liz‐Marzán Luis M. , Bals Sara , Batenburg K. Joost 
Published: May 2020

AbstractA detailed 3D investigation of nanoparticles at a local scale is of great importance to connect their structure and composition to their properties. Electron tomography has therefore become an important tool for the 3D characterization of nanomaterials. 3D investigations typically comprise multiple steps, including acquisition, reconstruction, and analysis/quantification. Usually, the latter two steps are performed offline, at a dedicated workstation. This sequential workflow prevents on‐the‐fly control of experimental parameters to improve the quality of the 3D reconstruction, to select a relevant nanoparticle for further characterization, or to steer an in situ tomography experiment. Here, an efficient approach to overcome these limitations is presented, based on the real‐time reconstruction of arbitrary 2D reconstructed slices through a 3D object. Implementation of this method may lead to generalized implementation of electron tomography for routine nanoparticle characterization in 3D.
Fluorescence quantum yields of matrices used in ultraviolet matrix‐assisted laser desorption/ionization
Authors: Lin Hou‐Yu , Song Botao Farren , Ni Chi‐Kung 
Published: May 2020

RationaleUltraviolet matrix‐assisted laser desorption/ionization (MALDI) is among the most popular soft ionization methods in mass spectrometry. Several theoretical models have been proposed to explain the primary ion generation in MALDI. These models require knowledge of various matrix molecular parameters for simulation. One such parameter is the fluorescence quantum yield. However, the fluorescence quantum yield reported in previous studies remains controversial.MethodsIn this study, we used a commercial and a homemade integrating sphere to measure the absorption and fluorescence quantum yields of several commonly used matrices, including 2,3‐dihydroxybenzoic acid, 2,4‐dihydroxybenzoic acid (2,4‐DHB), 2,5‐dihydroxybenzoic acid (2,5‐DHB), 2,6‐dihydroxybenzoic acid, 3,4‐dihydroxybenzoic acid, 3,5‐dihydroxybenzoic acid, α‐cyano‐4‐hydroxycinnamic acid, 2,4,6‐trihydroxyacetophenone, and ferulic acid.ResultsThe fluorescence quantum yields of these matrices were determined to be low (<0.08) at low laser fluences and decreased as the laser fluence increased. The fluorescence quantum yields at the typical laser fluence for MALDI are below 0.04 (2,4‐DHB and 2,5‐DHB) and 0.01 (the other matrices). Shot‐to‐shot fluctuations of fluorescence intensity and absorption are not directly related to the fluctuation of ions. Possible mechanisms for the decrease in the fluorescence quantum yield as the laser fluence increased were discussed.ConclusionsThe fluorescence quantum yields of these commonly used matrices are much lower than those reported in previous studies. Although fluorescence quantum yield is an important parameter and it is crucial to obtain an accurate value for theoretical models in simulations, the use of fluorescence quantum yield alone is not a sufficient parameter to justify these models.
Comparison of operative time between robotic and laparoscopic myomectomy for removal of numerous myomas
Authors: Won Seyeon , Lee Nara , Kim Miseon , Kim Mi Kyoung , Kim Mi‐La , Jung Yong Wook , Yun Bo Seong , Seong Seok Ju 
Published: May 2020

AbstractBackgroundWe hypothesized that the total operative time of robot myomectomy (RM) is shorter than that of laparoscopic myomectomy (LM) in cases where numerous myomas are removed, due to the faster suturing time of the robotic system. To verify this, we compared the surgical outcomes of RM vs LM for the number of myomas removed.MethodsThe medical records of 144 women underwent LM and 121 women underwent RM by a single surgeon were reviewed.ResultsThe operative time did not statistically differ between the groups, even when the number of removed myomas was more than 12 (200.6 ± 48.2 vs 196.0 ± 48.4 minutes, P = .791). Note that in our logistic regression analysis, the operation type was excluded from the independent risk factors prolonging operative time.ConclusionRM showed a similar operative time relative to LM regardless of the number of myomas removed (numerous or not).
Tissue-specific angiogenic and invasive properties of human neonatal thymus and bone MSCs: Role of SLIT3-ROBO1
Authors: Wang Shuyun , Huang Shan , Johnson Sean , Rosin Vadim , Lee Jeffrey , Colomb Eric , Witt Russell , Jaworski Alexander , Weiss Stephen J. , Si Ming-Sing 
Published: May 2020

Abstract
Although mesenchymal stem/stromal cells (MSCs) are being explored in numerous clinical trials as proangiogenic and proregenerative agents, the influence of tissue origin on the therapeutic qualities of these cells is poorly understood. Complicating the functional comparison of different types of MSCs are the confounding effects of donor age, genetic background, and health status of the donor. Leveraging a clinical setting where MSCs can be simultaneously isolated from discarded but healthy bone and thymus tissues from the same neonatal patients, thereby controlling for these confounding factors, we performed an in vitro and in vivo paired comparison of these cells. We found that both neonatal thymus (nt)MSCs and neonatal bone (nb)MSCs expressed different pericytic surface marker profiles. Further, ntMSCs were more potent in promoting angiogenesis in vitro and in vivo and they were also more motile and efficient at invading ECM in vitro. These functional differences were in part mediated by an increased ntMSC expression of SLIT3, a factor known to activate endothelial cells. Further, we discovered that SLIT3 stimulated MSC motility and fibrin gel invasion via ROBO1 in an autocrine fashion. Consistent with our findings in human MSCs, we found that SLIT3 and ROBO1 were expressed in the perivascular cells of the neonatal murine thymus gland and that global SLIT3 or ROBO1 deficiency resulted in decreased neonatal murine thymus gland vascular density. In conclusion, ntMSCs possess increased proangiogenic and invasive behaviors, which are in part mediated by the paracrine and autocrine effects of SLIT3.

Significance statement Mesenchymal stromal cells (MSCs), due to their ubiquity, can be isolated from various tissues and are being evaluated for their therapeutic effects. Despite their advanced clinical evaluation, the tissue-specific pro-regenerative properties of MSCs are poorly understood. Using a unique clinical situation that permits simultaneous isolation of thymus- and bone-derived MSCs from the same patient, a paired comparison was performed, which allowed to control for donor age, health status, and individual variability. It was found that neonatal thymus MSCs possess more proangiogenic, motile, and invasive behavior and that this is in part due to increased signaling from the SLIT3-ROBO1 axis. In sum, human MSCs likely have important tissue-specific regenerative characteristics and MSC SLIT3 expression may be an informative biomarker for regenerative and therapeutic potency.
Programmable NIR‐II Photothermal‐Enhanced Starvation‐Primed Chemodynamic Therapy using Glucose Oxidase‐Functionalized Ancient Pigment Nanosheets
Authors: Yang Chen , Younis Muhammad Rizwan , Zhang Jing , Qu Junle , Lin Jing , Huang Peng 
Published: May 2020

AbstractChemodynamic therapy (CDT) has attracted considerable attention recently, but the poor reaction kinetics restrict its practical utility in clinic. Herein, glucose oxidase (GOx) functionalized ancient pigment nanosheets (SrCuSi4O10, SC) for programmable near‐infrared II (NIR‐II) photothermal‐enhanced starvation primed CDT is developed. The SC nanosheets (SC NSs) are readily exfoliated from SC bulk suspension in water and subsequently functionalized with GOx to form the nanocatalyst (denoted as SC@G NSs). Upon laser irradiation, the photothermal effect of SC NSs can enhance the catalytic activity of GOx for NIR‐II photothermal‐enhanced starvation therapy, which effectively eliminates intratumoral glucose and produces abundant hydrogen peroxide (H2O2). Importantly, the high photothermal‐conversion efficiency (46.3%) of SC@G NSs in second biological window permits photothermal therapy of deep‐seated tumors under the guidance of NIR‐II photoacoustic imaging. Moreover, the acidity amplification due to gluconic acid generation will in turn accelerate the degradation of SC NSs, facilitating the release of strontium (Sr) and copper (Cu) ions. Both the elevated H2O2 and the released ions will prime the Cu2+/Sr2+‐H2O2 reaction for enhanced CDT. Thus, a programmable NIR‐II photothermal‐enhanced starvation primed CDT is established to combat cancer with minimal side effects.
A Biomimetic Nanogenerator of Reactive Nitrogen Species Based on Battlefield Transfer Strategy for Enhanced Immunotherapy
Authors: Feng Qianhua , Li Yuzhen , Wang Ning , Hao Yutong , Chang Junbiao , Wang Zeying , Zhang Xueli , Zhang Zhenzhong , Wang Lei 
Published: May 2020

AbstractCurrently, cell membrane is always utilized for the construction of biomimetic nanoparticles. By contrast, mimicking the intracellular activity seems more meaningful. Inspired by the specific killing mechanism of deoxy‐hemoglobin (Hb) dependent drug (RRx‐001) in hypoxic red blood cells (RBC), this work aims to develop an inner and outer RBC‐biomimetic antitumor nanoplatform that replicates both membrane surface properties and intracellularly certain therapeutic mechanisms of RRx‐001 in hypoxic RBC. Herein, RRx‐001 and Hb are introduced into RBC membrane camouflaged TiO2 nanoparticles. Upon arrival at hypoxic tumor microenvironment (TME), the biomimetic nanoplatform (R@HTR) is activated and triggers a series of reactions to generate reactive nitrogen species (RNS). More importantly, the potent antitumor immunity and immunomodulatory function of RNS in TME are demonstrated. Such an idea would transfer the battlefield of RRx‐001 from hypoxic RBC to hypoxic TME, enhancing its combat capability. As a proof of concept, this biomimetic nanoreactor of RNS exhibits efficient tumor regression and metastasis prevention. The battlefield transfer strategy would not only present meaningful insights for immunotherapy, but also realize substantial breakthroughs in biomimetic nanotechnology.
Dispersibility and Photochemical Stability of Delaminated MXene Flakes in Water
Authors: Shen Shuyi , Ke Tao , Rajavel Krishnamoorthy , Yang Kun , Lin Daohui 
Published: May 2020

AbstractThe environmental stability of 2D MXene flakes must be systematically studied before their further application. Herein, the colloidal dispersibility and photochemical stability of delaminated Ti3C2Tx MXene flakes modified with hydrazine (HMH) and KOH and with water as the control (HMH‐Ti3C2, KOH‐Ti3C2, and H2O‐Ti3C2, respectively) are experimentally and theoretically studied. Modification greatly increases the dispersibility of Ti3C2Tx flakes. Their critical coagulation concentrations are 28.7, 106, and 49.1 mm NaCl, and their Hamaker constants are 23.7 × 10−21, 19.1 × 10−21, and 37.7 × 10−21 J, respectively; the colloidal interaction follows the classical Derjaguin–Landau–Verwey–Overbeek theory. HMH‐Ti3C2 and KOH‐Ti3C2 exhibit higher photochemical stability, as indicated by their stronger resistance to oxidation under UV and visible light irradiation. Changes in their physicochemical properties and the generation of reactive oxygen species (ROS) are assayed. Spin‐polarized density functional theory calculations and molecular dynamics simulations are used to determine the mechanisms underlying the differences in the photochemical stability of Ti3C2Tx flakes. K+ ions protect the flakes from oxidation by acting as a middle layer to reduce the coupling between Ti3+ and ROS, while HMH provides stronger protection by absorbing photoelectrons or reacting with ROS. These findings provide new insight into the environmental transformation and design of functional MXenes.
Transdermal theranostics
Authors: Than Aung , Zan Ping , Chen Peng 
Published: May 2020

AbstractSkin offers an easily accessible site for drug administration as well as for health signal monitoring, with non‐invasiveness or minimal‐invasiveness, convenience, and good patient compliance. Transdermal theranostics promises for personalized, home‐based, and long‐term management of chronic diseases, and is expected to change the landscape of healthcare profoundly. In this article, we review the recent advances in transdermal drug delivery, diagnosis based on sweat and skin interstitial fluid, and wearable devices. The advantages, limitations, and commercialization of these emerging techniques are comparatively discussed.
Multidisciplinary multi-objective design optimization of an active morphing wing section
Authors: Dexl Florian , Hauffe Andreas , Wolf Klaus 
Published: May 2020

AbstractDesign and optimization of morphing wings are of current research interest as they promise increasing efficiency and flexibility of future aircraft. A challenging task is to find structural layouts of morphing wings that enable aerodynamically optimized shape changes without defining the target shape a priori. The current paper addresses this task and presents a method that combines the optimization of the active structure of a wing section, parameterized by Lindenmayer cellular systems, with an aerodynamic evaluation. Neither the structural layout nor the target shape has to be defined a priori. This aim is achieved by a multidisciplinary optimization using evolutionary algorithms with aerodynamic and structural objectives. The developed method allows to optimize the topology of the internal structure, the placement of linear contraction, and expansion actuators as well as the setting of their actuation degree concurrently. It is shown that the present approach allows to find optimized internal layouts containing active structural elements for morphing wing sections.
Apps und ihre Anwendungsgebiete in der Rheumatologie
Authors: Krusche M. , Ruffer N. , Grahammer M. , Knitza J. 
Published: May 2020

ZusammenfassungMit der steigenden Verwendung von Smartphones einhergehend, nimmt auch die Nutzung von mobilen Applikationen (Apps) rapide zu. Im medizinischen Kontext könnten chronisch kranke Patienten von dem Einsatz dauerhaft profitieren. Verstärkt wird diese Entwicklung durch das Digitale-Versorgung-Gesetz (DVG), wonach Patienten ab Q4/2020 einen Rechtsanspruch auf bestimmte Apps, sog. digitale Gesundheitsanwendungen (DiGAs), haben, die von den gesetzlichen Krankenkassen erstattet werden. Besonders im Bereich der Rheumatologie bieten sich für das Management chronischer Erkrankungen und ihrer Komorbiditäten verschiedene Anknüpfungspunkte. Nicht nur unter rheumatologischen Patienten ist das Interesse an App-Angeboten groß, sondern auch unter deutschen Rheumatologen zeigt sich eine steigende Bereitschaft, Apps im Berufsalltag anzuwenden und Patienten zu empfehlen. Dieser Artikel will einen Überblick über die Entwicklung der App-Landschaft in der deutschsprachigen Rheumatologie vermitteln.
Using Machine Learning for Robust Target Prediction in a Basic Oxygen Furnace System
Authors: Bae Juhee , Li Yurong , Ståhl Niclas , Mathiason Gunnar , Kojola Niklas 
Published: May 2020

AbstractThe steel-making process in a Basic Oxygen Furnace (BOF) must meet a combination of target values such as the final melt temperature and upper limits of the carbon and phosphorus content of the final melt with minimum material loss. An optimal blow end time (cut-off point), where these targets are met, often relies on the experience and skill of the operators who control the process, using both collected sensor readings and an implicit understanding of how the process develops. If the precision of hitting the optimal cut-off point can be improved, this immediately increases productivity as well as material and energy efficiency, thus decreasing environmental impact and cost. We examine the usage of standard machine learning models to predict the end-point targets using a full production dataset. Various causes of prediction uncertainty are explored and isolated using a combination of raw data and engineered features. In this study, we reach robust temperature, carbon, and phosphorus prediction hit rates of 88, 92, and 89 pct, respectively, using a large production dataset.
An In Vitro Partial Lesion Model of Differentiated Human Mesencephalic Neurons: Effect of Pericyte Secretome on Phenotypic Markers
Authors: Gaceb Abderahim , Barbariga Marco , Paul Gesine 
Published: May 2020

AbstractParkinson’s disease (PD) is characterised by the progressive degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta. Post-mortem data suggests that the loss of DA markers may long precede the cell death, leaving a window to rescue the DA phenotype. Screening for potential neuroprotective or restorative therapies, however, requires that partial lesions of DA neurons can be modelled in vitro. In order to establish a partial lesion model of DA neurons in vitro, we evaluated the effects of different exposure times to 1-methyl-4-phenylpyridinium (MPP+) and 6-hydroxydopamine (6-OHDA) on the cell survival and DA marker expression using DA neurons derived from the Lund human mesencephalic (LUHMES) cell line. We show that 24-h incubation with 50 μM of MPP+ or 6-h incubation with 100 μM of 6-OHDA leads to a significant decrease in the protein expression of DA markers without affecting overall cell death, consistent with a mild DA lesion. Using conditioned medium of human brain–derived pericytes stimulated with platelet-derived growth factor BB (PDGF-BB), we demonstrate a significant upregulation of DA markers. In conclusion, we provide an experimental model of an in vitro DA neuron partial lesion suitable to study different molecules and their potential neuroprotective or neurorestorative effects on the DA phenotype. We provide evidence that the secretome of brain pericytes stimulated via PDGF-BB/PDGFRβ affects DA marker expression and may represent one possible mechanism contributing to the neurorestoration previously observed in PD by this growth factor.