bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantum chemical accuracy from density functional approximations via machine learning
Authors: Bogojeski Mihail , Vogt-Maranto Leslie , Tuckerman Mark E. , Müller Klaus-Robert , Burke Kieron 
Published: October 2020

AbstractKohn-Sham density functional theory (DFT) is a standard tool in most branches of chemistry, but accuracies for many molecules are limited to 2-3 kcal ⋅ mol−1 with presently-available functionals. Ab initio methods, such as coupled-cluster, routinely produce much higher accuracy, but computational costs limit their application to small molecules. In this paper, we leverage machine learning to calculate coupled-cluster energies from DFT densities, reaching quantum chemical accuracy (errors below 1 kcal ⋅ mol−1) on test data. Moreover, density-based Δ-learning (learning only the correction to a standard DFT calculation, termed Δ-DFT ) significantly reduces the amount of training data required, particularly when molecular symmetries are included. The robustness of Δ-DFT is highlighted by correcting “on the fly” DFT-based molecular dynamics (MD) simulations of resorcinol (C6H4(OH)2) to obtain MD trajectories with coupled-cluster accuracy. We conclude, therefore, that Δ-DFT facilitates running gas-phase MD simulations with quantum chemical accuracy, even for strained geometries and conformer changes where standard DFT fails.
Xenon iron oxides predicted as potential Xe hosts in Earth’s lower mantle
Authors: Peng Feng , Song Xianqi , Liu Chang , Li Quan , Miao Maosheng , Chen Changfeng , Ma Yanming 
Published: October 2020

AbstractAn enduring geological mystery concerns the missing xenon problem, referring to the abnormally low concentration of xenon compared to other noble gases in Earth’s atmosphere. Identifying mantle minerals that can capture and stabilize xenon has been a great challenge in materials physics and xenon chemistry. Here, using an advanced crystal structure search algorithm in conjunction with first-principles calculations we find reactions of xenon with recently discovered iron peroxide FeO2, forming robust xenon-iron oxides Xe2FeO2and XeFe3O6with significant Xe-O bonding in a wide range of pressure-temperature conditions corresponding to vast regions in Earth’s lower mantle. Calculated mass density and sound velocities validate Xe-Fe oxides as viable lower-mantle constituents. Meanwhile, Fe oxides do not react with Kr, Ar and Ne. It means that if Xe exists in the lower mantle at the same pressures as FeO2, xenon-iron oxides are predicted as potential Xe hosts in Earth’s lower mantle and could provide the repository for the atmosphere’s missing Xe. These findings establish robust materials basis, formation mechanism, and geological viability of these Xe-Fe oxides, which advance fundamental knowledge for understanding xenon chemistry and physics mechanisms for the possible deep-Earth Xe reservoir.
Non-invasive decision support for NSCLC treatment using PET/CT radiomics
Authors: Mu Wei , Jiang Lei , Zhang JianYuan , Shi Yu , Gray Jhanelle E. , Tunali Ilke , Gao Chao , Sun Yingying , Tian Jie , Zhao Xinming , Sun Xilin , Gillies Robert J. , Schabath Matthew B. 
Published: October 2020

AbstractTwo major treatment strategies employed in non-small cell lung cancer, NSCLC, are tyrosine kinase inhibitors, TKIs, and immune checkpoint inhibitors, ICIs. The choice of strategy is based on heterogeneous biomarkers that can dynamically change during therapy. Thus, there is a compelling need to identify comprehensive biomarkers that can be used longitudinally to help guide therapy choice. Herein, we report a 18F-FDG-PET/CT-based deep learning model, which demonstrates high accuracy in EGFR mutation status prediction across patient cohorts from different institutions. A deep learning score (EGFR-DLS) was significantly and positively associated with longer progression free survival (PFS) in patients treated with EGFR-TKIs, while EGFR-DLS is significantly and negatively associated with higher durable clinical benefit, reduced hyperprogression, and longer PFS among patients treated with ICIs. Thus, the EGFR-DLS provides a non-invasive method for precise quantification of EGFR mutation status in NSCLC patients, which is promising to identify NSCLC patients sensitive to EGFR-TKI or ICI-treatments.
Tactile to visual number priming in the left intraparietal cortex of sighted Braille readers
Authors: Rączy Katarzyna , Czarnecka Maria , Paplińska Małgorzata , Hesselmann Guido , Knops André , Szwed Marcin 
Published: October 2020

AbstractNumbers can be presented in different notations and sensory modalities. It is currently debated to what extent these formats overlap onto a single representation. We asked whether such an overlap exists between symbolic numbers represented in two sensory modalities: Arabic digits and Braille numbers. A unique group of sighted Braille readers underwent extensive Braille reading training and was tested in an fMRI repetition-suppression paradigm with tactile Braille digit primes and visual Arabic digit targets. Our results reveal cross-modal priming: compared to repetition of two different quantities (e.g., Braille “5” and Arabic “2”), repetition of the same quantity presented in two modalities (e.g., Braille “5” and Arabic “5”) led to a reduction of activation in several sub-regions of the Intraparietal Sulcus (IPS), a key cortical region for magnitude processing. Thus, in sighted Braille readers, the representations of numbers read by sight and by touch overlap to a degree sufficient to cause repetition suppression. This effect was modulated by the numerical prime-probe distance. Altogether this indicates that the left parietal cortex hosts neural assemblies that are sensitive to numerical information from different notations (number words or Arabic digits) and modalities (tactile and visual).
Impact of porcine cytomegalovirus on long-term orthotopic cardiac xenotransplant survival
Authors: Denner Joachim , Längin Matthias , Reichart Bruno , Krüger Luise , Fiebig Uwe , Mokelke Maren , Radan Julia , Mayr Tanja , Milusev Anastasia , Luther Fabian , Sorvillo Nicoletta , Rieben Robert , Brenner Paolo , Walz Christoph , Wolf Eckhard , Roshani Berit , Stahl-Hennig Christiane , Abicht Jan-Michael 
Published: October 2020

AbstractXenotransplantation using pig organs has achieved survival times up to 195 days in pig orthotopic heart transplantation into baboons. Here we demonstrate that in addition to an improved immunosuppressive regimen, non-ischaemic preservation with continuous perfusion and control of post-transplantation growth of the transplant, prevention of transmission of the porcine cytomegalovirus (PCMV) plays an important role in achieving long survival times. For the first time we demonstrate that PCMV transmission in orthotopic pig heart xenotransplantation was associated with a reduced survival time of the transplant and increased levels of IL-6 and TNFα were found in the transplanted baboon. Furthermore, high levels of tPA-PAI-1 complexes were found, suggesting a complete loss of the pro-fibrinolytic properties of the endothelial cells. These data show that PCMV has an important impact on transplant survival and call for elimination of PCMV from donor pigs.
Analytical determination of theoretic quantities for multiple potential
Authors: Onate C. A. , Onyeaju M. C. , Abolarinwa A. , Lukman A. F. 
Published: October 2020

AbstractThe approximate analytical solutions of the three-dimensional radial Schrödinger wave equation with a multiple potential function has been studied using a suitable approximation scheme to the centrifugal term in the framework of parametric Nikiforov–Uvarov method. The energy equation and the wave function were obtained. The calculated wave function was used to study Shannon entropy and variance via expectation values. The behaviour of Shannon entropy and variance respectively with the equilibrium bond length were examined in detail. A special case of the multiple potential (pseudoharmonic-like potential) was equally examined under Shannon entropy and variance. For further application of the study, some diatomic molecules were examined under variance and Shannon entropy. Finally, some variance inequalities were derived using Cramer-Rao uncertainty relation and these were justified by numerical results.
Evaluation of the antitumor effects of PP242 in a colon cancer xenograft mouse model using comprehensive metabolomics and lipidomics
Authors: Rashid Md Mamunur , Lee Hyunbeom , Jung Byung Hwa 
Published: October 2020

AbstractPP242, an inhibitor of mechanistic target of rapamycin (mTOR), displays potent anticancer effects against various cancer types. However, the underlying metabolic mechanism associated with the PP242 effects is not clearly understood. In this study, comprehensive metabolomics and lipidomics investigations were performed using ultra-high-performance chromatography-Orbitrap-mass spectrometry (UHPLC-Orbitrap-MS) in plasma and tumor tissue to reveal the metabolic mechanism of PP242 in an LS174T cell-induced colon cancer xenograft mouse model. After 3 weeks of PP242 treatment, a reduction in tumor size and weight was observed without any critical toxicities. According to results, metabolic changes due to the effects of PP242 were not significant in plasma. In contrast, metabolic changes in tumor tissues were very significant in the PP242-treated group compared to the xenograft control (XC) group, and revealed that energy and lipid metabolism were mainly altered by PP242 treatment like other cancer inhibitors. Additionally, in this study, it was discovered that not only TCA cycle but also fatty acid β-oxidation (β-FAO) for energy metabolism was inhibited and clear reduction in glycerophospholipid was observed. This study reveals new insights into the underlying anticancer mechanism of the dual mTOR inhibitor PP242, and could help further to facilitate the understanding of PP242 effects in the clinical application.
BRCA1 and BRCA2 genes mutations among high risk breast cancer patients in Jordan
Authors: Abu-Helalah Munir , Azab Belal , Mubaidin Rasmi , Ali Dema , Jafar Hanan , Alshraideh Hussam , Drou Nizar , Awidi Abdalla 
Published: October 2020

AbstractFamilial breast cancer is estimated to account for 15–20% of all cases of breast cancer. Surveillance for familial breast cancer is well-established world-wide. However, this service does not exist in Jordan, due to the scarcity of information with regard to the genetic profiling of these patients, and therefore lack of recommendations for policy-makers. As such, patients with very strong family history of breast or ovarian cancers are not screened routinely; leading to preventable delay in diagnosis. Whole coding sequencing forBCRA1/BCRA2using next-generation sequencing (NGS)/Ion PGM System was performed. Sanger sequencing were then used to confirm the pathogenic variants detected by NGS. In this study, 192 breast cancer patients (and 8 ovarian cancer cases) were included. The prevalence of recurrent pathogenic mutations was 14.5%, while the prevalence of newly detected mutations was 3.5%. Two novel pathogenic mutations were identified inBRCA2genes. The common mutations in the Ashkenazi population used for screening may not apply in the Jordanian population, as previously reported mutations were not prevalent, and other new mutations were identified. These data will aid to establish a specific screening test forBRCA 1/BRCA2in the Jordanian population.
Non-invasive vagus nerve stimulation attenuates proinflammatory cytokines and augments antioxidant levels in the brainstem and forebrain regions of Dahl salt sensitive rats
Authors: Subramanian Madhan , Edwards Laura , Melton Avery , Branen Lyndee , Herron Angela , Sivasubramanian Mahesh Kumar , Monteiro Raisa , Stansbury Samantha , Balasubramanian Priya , Morris Lynsie , Elkholey Khaled , Niewiadomska Monika , Stavrakis Stavros 
Published: October 2020

AbstractThe anti-inflammatory effects of vagus nerve stimulation are well known. It has recently been shown that low-level, transcutaneous stimulation of vagus nerve at the tragus (LLTS) reduces cardiac inflammation in a rat model of heart failure with preserved ejection fraction (HFpEF). The mechanisms by which LLTS affect the central neural circuits within the brain regions that are important for the regulation of cardiac vagal tone are not clear. Female Dahl salt-sensitive rats were initially fed with either low salt (LS) or high salt (HS) diet for a period of 6 weeks, followed by sham or active stimulation (LLTS) for 30 min daily for 4 weeks. To study the central effects of LLTS, four brainstem (SP5, NAb, NTS, and RVLM) and two forebrain sites (PVN and SFO) were examined. HS diet significantly increased the gene expression of proinflammatory cytokines in the SP5 and SFO. LLTS reversed HS diet-induced changes at both these sites. Furthermore, LLTS augmented the levels of antioxidant Nrf2 in the SP5 and SFO. Taken together, these findings suggest that LLTS has central anti-inflammatory and antioxidant properties that could mediate the neuromodulation of cardiac vagal tone in the rat model of HFpEF.
Recruitment of parvalbumin and somatostatin interneuron inputs to adult born dentate granule neurons
Authors: Remmers Christine L. , Castillon Charlotte C. M. , Armstrong John N. , Contractor Anis 
Published: October 2020

AbstractGABA is a key regulator of adult-born dentate granule cell (abDGC) maturation so mapping the functional connectivity between abDGCs and local interneurons is required to understand their development and integration into the hippocampal circuit. We recorded from birthdated abDGCs in mice and photoactivated parvalbumin (PV) and somatostatin (SST) interneurons to map the timing and strength of inputs to abDGCs during the first 4 weeks after differentiation. abDGCs received input from PV interneurons in the first week, but SST inputs were not detected until the second week. Analysis of desynchronized quantal events established that the number of GABAergic synapses onto abDGCs increased with maturation, whereas individual synaptic strength was constant. Voluntary wheel running in mice scaled the GABAergic input to abDGCs by increasing the number of synaptic contacts from both interneuron types. This demonstrates that GABAergic innervation to abDGCs develops during a prolonged post-mitotic period and running scales both SST and PV synaptic afferents.
A computer vision approach to improving cattle digestive health by the monitoring of faecal samples
Authors: Atkinson Gary A. , Smith Lyndon N. , Smith Melvyn L. , Reynolds Christopher K. , Humphries David J. , Moorby Jon M. , Leemans David K. , Kingston-Smith Alison H. 
Published: October 2020

AbstractThe digestive health of cows is one of the primary factors that determine their well-being and productivity. Under- and over-feeding are both commonplace in the beef and dairy industry; leading to welfare issues, negative environmental impacts, and economic losses. Unfortunately, digestive health is difficult for farmers to routinely monitor in large farms due to many factors including the need to transport faecal samples to a laboratory for compositional analysis. This paper describes a novel means for monitoring digestive health via a low-cost and easy to use imaging device based on computer vision. The method involves the rapid capture of multiple visible and near-infrared images of faecal samples. A novel three-dimensional analysis algorithm is then applied to objectively score the condition of the sample based on its geometrical features. While there is no universal ground truth for comparison of results, the order of scores matched a qualitative human prediction very closely. The algorithm is also able to detect the presence of undigested fibres and corn kernels using a deep learning approach. Detection rates for corn and fibre in image regions were of the order 90%. These results indicate the potential to develop this system for on-farm, real time monitoring of the digestive health of individual animals, allowing early intervention to effectively adjust feeding strategy.
Classification of aortic stenosis using conventional machine learning and deep learning methods based on multi-dimensional cardio-mechanical signals
Authors: Yang Chenxi , Ojha Banish D. , Aranoff Nicole D. , Green Philip , Tavassolian Negar 
Published: October 2020

AbstractThis paper introduces a study on the classification of aortic stenosis (AS) based on cardio-mechanical signals collected using non-invasive wearable inertial sensors. Measurements were taken from 21 AS patients and 13 non-AS subjects. A feature analysis framework utilizing Elastic Net was implemented to reduce the features generated by continuous wavelet transform (CWT). Performance comparisons were conducted among several machine learning (ML) algorithms, including decision tree, random forest, multi-layer perceptron neural network, and extreme gradient boosting. In addition, a two-dimensional convolutional neural network (2D-CNN) was developed using the CWT coefficients as images. The 2D-CNN was made with a custom-built architecture and a CNN based on Mobile Net via transfer learning. After the reduction of features by 95.47%, the results obtained report 0.87 on accuracy by decision tree, 0.96 by random forest, 0.91 by simple neural network, and 0.95 by XGBoost. Via the 2D-CNN framework, the transfer learning of Mobile Net shows an accuracy of 0.91, while the custom-constructed classifier reveals an accuracy of 0.89. Our results validate the effectiveness of the feature selection and classification framework. They also show a promising potential for the implementation of deep learning tools on the classification of AS.
Structure-based design and discovery of novel anti-tissue factor antibodies with cooperative double-point mutations, using interaction analysis
Authors: Chiba Shuntaro , Tanabe Aki , Nakakido Makoto , Okuno Yasushi , Tsumoto Kouhei , Ohta Masateru 
Published: October 2020

AbstractThe generation of a wide range of candidate antibodies is important for the successful development of drugs that simultaneously satisfy multiple requirements. To find cooperative mutations and increase the diversity of mutants, an in silico double-point mutation approach, in which 3D models of all possible double-point mutant/antigen complexes are constructed and evaluated using interaction analysis, was developed. Starting from an antibody with very high affinity, four double-point mutants were designed in silico. Two of the double-point mutants exhibited improved affinity or affinity comparable to that of the starting antibody. The successful identification of two active double-point mutants showed that a cooperative mutation could be found by utilizing information regarding the interactions. The individual single-point mutants of the two active double-point mutants showed decreased affinity or no expression. These results suggested that the two active double-point mutants cannot be obtained through the usual approach i.e. a combination of improved single-point mutants. In addition, a triple-point mutant, which combines the distantly located active double-point mutation and an active single-point mutation collaterally obtained in the process of the double-point mutation strategy, was designed. The triple-point mutant showed improved affinity. This finding suggested that the effects of distantly located mutations are independent and additive. The double-point mutation approach using the interaction analysis of 3D structures expands the design repertoire for mutants, and hopefully paves a way for the identification of cooperative multiple-point mutations.
SPARC promotes insulin secretion through down-regulation of RGS4 protein in pancreatic β cells
Authors: Hu Li , He Fengli , Huang Meifeng , Zhao Qian , Cheng Lamei , Said Neveen , Zhou Zhiguang , Liu Feng , Dai Yan-Shan 
Published: October 2020

AbstractSPARC-deficient mice have been shown to exhibit impaired glucose tolerance and insulin secretion, but the underlying mechanism remains unknown. Here, we showed that SPARC enhanced the promoting effect of Muscarinic receptor agonist oxotremorine-M on insulin secretion in cultured mouse islets. Overexpression of SPARC down-regulated RGS4, a negative regulator of β-cell M3 muscarinic receptors. Conversely, knockdown of SPARC up-regulated RGS4 in Min6 cells. RGS4 was up-regulated in islets from sparc −/− mice, which correlated with decreased glucose-stimulated insulin secretion (GSIS). Furthermore, inhibition of RGS4 restored GSIS in the islets from sparc −/− mice, and knockdown of RGS4 partially decreased the promoting effect of SPARC on oxotremorine-M-stimulated insulin secretion. Phosphoinositide 3-kinase (PI3K) inhibitor LY-294002 abolished SPARC-induced down-regulation of RGS4. Taken together, our data revealed that SPARC promoted GSIS by inhibiting RGS4 in pancreatic β cells.
Multiscale fluorescent tracking of immune cells in the liver with a highly biocompatible far-red emitting polymer probe
Authors: Daniel Malo , Dubreil Laurence , Fleurisson Romain , Judor Jean-Paul , Bresson Timothée , Brouard Sophie , Favier Arnaud , Charreyre Marie-Thérèse , Conchon Sophie 
Published: October 2020

AbstractThe development of innovative immune cell therapies relies on efficient cell tracking strategies. For this, multiscale fluorescence-based analyses of transferred cells into the host with complementary techniques, including flow cytometry for high-throughput cell analysis and two-photon microscopy for deep tissue imaging would be highly beneficial. Ideally, cells should be labelled with a single fluorescent probe combining all the properties required for these different techniques. Due to the intrinsic autofluorescence of most tissues and especially the liver, far-red emission is also an important asset. However, the development of far-red emitting probes suitable for two-photon microscopy and compatible with clearing methods to track labelled immune cells in thick samples, remains challenging. A newly-designed water-soluble far-red emitting polymer probe, 19K-6H, with a large Stokes shift, was thus evaluated for the tracking of primary immune CD8 T cells. These cells, prepared from mouse spleen, were efficiently labelled with the 19K-6H probe, which was internalized via endocytosis and was highly biocompatible at concentrations up to 20 μM. Labelled primary CD8 T cells were detectable in culture by both confocal and two-photon microscopy as well as flow cytometry, even after 3 days of active proliferation. Finally, 19K-6H-labelled primary CD8 T cells were injected to mice in a classical model of immune mediated hepatitis. The efficient tracking of the transferred cells in the liver by flow cytometry (on purified non-parenchymal cells) and by two-photon microscopy on 800 μm thick cleared sections, demonstrated the versatility of the 19K-6H probe.