bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-modular AI Approach to Streamline Autism Diagnosis in Young Children
Authors: Abbas Halim , Garberson Ford , Liu-Mayo Stuart , Glover Eric , Wall Dennis P. 
Published: March 2020

AbstractAutism has become a pressing healthcare challenge. The instruments used to aid diagnosis are time and labor expensive and require trained clinicians to administer, leading to long wait times for at-risk children. We present a multi-modular, machine learning-based assessment of autism comprising three complementary modules for a unified outcome of diagnostic-grade reliability: A 4-minute, parent-report questionnaire delivered via a mobile app, a list of key behaviors identified from 2-minute, semi-structured home videos of children, and a 2-minute questionnaire presented to the clinician at the time of clinical assessment. We demonstrate the assessment reliability in a blinded, multi-site clinical study on children 18-72 months of age (n = 375) in the United States. It outperforms baseline screeners administered to children by 0.35 (90% CI: 0.26 to 0.43) in AUC and 0.69 (90% CI: 0.58 to 0.81) in specificity when operating at 90% sensitivity. Compared to the baseline screeners evaluated on children less than 48 months of age, our assessment outperforms the most accurate by 0.18 (90% CI: 0.08 to 0.29 at 90%) in AUC and 0.30 (90% CI: 0.11 to 0.50) in specificity when operating at 90% sensitivity.
Longitudinal phenotype development in a minipig model of neurofibromatosis type 1
Authors: Uthoff Johanna , Larson Jared , Sato Takashi S. , Hammond Emily , Schroeder Kimberly E. , Rohret Frank , Rogers Christopher S. , Quelle Dawn E. , Darbro Benjamin W. , Khanna Rajesh , Weimer Jill M. , Meyerholz David K. , Sieren Jessica C. 
Published: March 2020

AbstractNeurofibromatosis type 1 (NF1) is a rare, autosomal dominant disease with variable clinical presentations. Large animal models are useful to help dissect molecular mechanisms, determine relevant biomarkers, and develop effective therapeutics. Here, we studied a NF1 minipig model (NF1+/ex42del) for the first 12 months of life to evaluate phenotype development, track disease progression, and provide a comparison to human subjects. Through systematic evaluation, we have shown that compared to littermate controls, the NF1 model develops phenotypic characteristics of human NF1: [1] café-au-lait macules, [2] axillary/inguinal freckling, [3] shortened stature, [4] tibial bone curvature, and [5] neurofibroma. At 4 months, full body computed tomography imaging detected significantly smaller long bones in NF1+/ex42del minipigs compared to controls, indicative of shorter stature. We found quantitative evidence of tibial bowing in a subpopulation of NF1 minipigs. By 8 months, an NF1+/ex42del boar developed a large diffuse shoulder neurofibroma, visualized on magnetic resonance imaging, which subsequently grew in size and depth as the animal aged up to 20 months. The NF1+/ex42del minipig model progressively demonstrates signature attributes that parallel clinical manifestations seen in humans and provides a viable tool for future translational NF1 research.
Collagen type VI α5 gene variations may predict the risk of lung cancer development in Chinese Han population
Authors: Duan Ying , Liu Gaowen , Sun Yao , Wu Jiamin , Xiong Zichao , Jin Tianbo , Chen Mingwei 
Published: March 2020

AbstractThe abundant expression of collagen type VI α5 (COL6A5) exists in lung tissue, and its role in lung cancer is still unknown. We performed a genetic association study with an attempt to detect the relationships between single nucleotide polymorphisms (SNPs) in COL6A5 and lung cancer predisposition in Chinese Han population. We finally selected six tag-SNPs to determine their genotypes among 510 lung cancer patients and 495 healthy controls with the MassARRAY platform. The associations of SNPs and lung cancer risk were estimated by logistic regression method with adjustment for confounding factors. Two available databases were used for gene expression and prognosis analysis. COL6A5 rs13062453, rs1497305, and rs77123808 were significantly associated with the risk of lung cancer in the whole population or stratified subgroups (p < 0.05). Among them, COL6A5 rs13062453 and rs1497305 were also linked to the susceptibility of lung adenocarcinoma. Additionally, rs1497305 was found to be strongly related to the TNM staging under five genetic models (p < 0.05). Results from databases suggested the important role of COL6A5 in lung cancer development. COL6A5 polymorphisms rs13062453, rs1497305 and rs77123808 were associated with lung cancer risk in Chinese Han population. These findings first yield new insight of COL6A5 in lung cancer.
Whole genome analysis identifies the association of TP53 genomic deletions with lower survival in Stage III colorectal cancer
Authors: Xia Li C. , Van Hummelen Paul , Kubit Matthew , Lee HoJoon , Bell John M. , Grimes Susan M. , Wood-Bouwens Christina , Greer Stephanie U. , Barker Tyler , Haslem Derrick S. , Ford James M. , Fulde Gail , Ji Hanlee P. , Nadauld Lincoln D. 
Published: March 2020

AbstractDNA copy number aberrations (CNA) are frequently observed in colorectal cancers (CRC). There is an urgent need for CNA-based biomarkers in clinics,. n For Stage III CRC, if combined with imaging or pathologic evidence, these markers promise more precise care. We conducted this Stage III specific biomarker discovery with a cohort of 134 CRCs, and with a newly developed high-efficiency CNA profiling protocol. Specifically, we developed the profiling protocol for tumor-normal matched tissue samples based on low-coverage clinical whole-genome sequencing (WGS). We demonstrated the protocol’s accuracy and robustness by a systematic benchmark with microarray, high-coverage whole-exome and -genome approaches, where the low-coverage WGS-derived CNA segments were highly accordant (PCC >0.95) with those derived from microarray, and they were substantially less variable if compared to exome-derived segments. A lasso-based model and multivariate cox regression analysis identified a chromosome 17p loss, containing the TP53 tumor suppressor gene, that was significantly associated with reduced survival (P = 0.0139, HR = 1.688, 95% CI = [1.112–2.562]), which was validated by an independent cohort of 187 Stage III CRCs. In summary, this low-coverage WGS protocol has high sensitivity, high resolution and low cost and the identified 17p-loss is an effective poor prognosis marker for Stage III patients.
Development of voice perception is dissociated across gender cues in school-age children
Authors: Nagels Leanne , Gaudrain Etienne , Vickers Deborah , Hendriks Petra , Başkent Deniz 
Published: March 2020

AbstractChildren’s ability to distinguish speakers’ voices continues to develop throughout childhood, yet it remains unclear how children’s sensitivity to voice cues, such as differences in speakers’ gender, develops over time. This so-called voice gender is primarily characterized by speakers’ mean fundamental frequency (F0), related to glottal pulse rate, and vocal-tract length (VTL), related to speakers’ size. Here we show that children’s acquisition of adult-like performance for discrimination, a lower-order perceptual task, and categorization, a higher-order cognitive task, differs across voice gender cues. Children’s discrimination was adult-like around the age of 8 for VTL but still differed from adults at the age of 12 for F0. Children’s perceptual weight attributed to F0 for gender categorization was adult-like around the age of 6 but around the age of 10 for VTL. Children’s discrimination and weighting of F0 and VTL were only correlated for 4- to 6-year-olds. Hence, children’s development of discrimination and weighting of voice gender cues are dissociated, i.e., adult-like performance for F0 and VTL is acquired at different rates and does not seem to be closely related. The different developmental patterns for auditory discrimination and categorization highlight the complexity of the relationship between perceptual and cognitive mechanisms of voice perception.
IGFBP-3 Blocks Hyaluronan-CD44 Signaling, Leading to Increased Acetylcholinesterase Levels in A549 Cell Media and Apoptosis in a p53-Dependent Manner
Authors: Price Deanna , Muterspaugh Robert , Clegg Bradley , Williams Asana , Stephens Alexis , Guthrie Jeffrey , Heyl Deborah , Evans Hedeel Guy 
Published: March 2020

AbstractInsulin-like growth factor binding protein-3 (IGFBP-3) belongs to a family of six IGF binding proteins. We previously found that IGFBP-3 exerts its cytotoxic effects on A549 (p53 wild-type) cell survival through a mechanism that depends on hyaluronan-CD44 interactions. To shed light on the mechanism employed, we used CD44-negative normal human lung cells (HFL1), A549, and H1299 (p53-null) lung cancer cells. A synthetic IGFBP-3 peptide (215-KKGFYKKKQCRPSKGRKR-232) but not the mutant (K228AR230A), was able to bind hyaluronan more efficiently than the analogous sequences from the other IGFBPs. In a manner comparable to that of the IGFBP-3 protein, the peptide blocked hyaluronan-CD44 signaling, and more effectively inhibited viability of A549 cells than viability of either H1299 or HFL1 cell lines. Treatment with the IGFBP-3 protein or its peptide resulted in increased acetylcholinesterase concentration and activity in the A549 cell media but not in the media of either HFL1 or H1299, an effect that correlated with increased apoptosis and decreased cell viability. These effects were diminished upon the same treatment of A549 cells transfected with either p53 siRNA or acetylcholinesterase siRNA. Taken together, our results show that IGFBP-3 or its peptide blocks hyaluronan-CD44 signaling via a mechanism that depends on both p53 and acetylcholinesterase.
Ag flake/silicone rubber composite with high stability and stretching speed insensitive resistance via conductive bridge formation
Authors: Yoon In Seon , Kim Sun Hong , Oh Youngsu , Ju Byeong-Kwon , Hong Jae-Min 
Published: March 2020

AbstractHigh stability, stretchable speed insensitive properties, high stretchability, and electrical conductivity are key characteristics for the realisation of wearable devices. However, conventional research is mainly focused on achieving only high stretchability and electrical conductivity. Studies on the stability and stretching speed insensitive properties generally require complex fabrication processes, which are in need of further improvement. In this study, we propose a facile formation of a conductive bridge in composites by using surface damage and the viscoelastic property of the polymer. Surface cracks due to repeated stretching cycles formed conductive bridges via stress relaxation of the viscoelastic polymer matrix. The conductive bridge resulted in the conductor having highly stable resistance values at target strains and stretching speed insensitive resistance, even at stretching speeds that were 20 times faster than the minimum.
Two-qubit quantum gate and entanglement protected by circulant symmetry
Authors: Ivanov Peter A. , Vitanov Nikolay V. 
Published: March 2020

AbstractWe propose a method for the realization of the two-qubit quantum Fourier transform (QFT) using a Hamiltonian which possesses the circulant symmetry. Importantly, the eigenvectors of the circulant matrices are the Fourier modes and do not depend on the magnitude of the Hamiltonian elements as long as the circulant symmetry is preserved. The QFT implementation relies on the adiabatic transition from each of the spin product states to the respective quantum Fourier superposition states. We show that in ion traps one can obtain a Hamiltonian with the circulant symmetry by tuning the spin-spin interaction between the trapped ions. We present numerical results which demonstrate that very high fidelity can be obtained with realistic experimental resources. We also describe how the gate can be accelerated by using a “shortcut-to-adiabaticity” field.
Effect of elevated levels of CO2 on powdery mildew development in five cucurbit species
Authors: Khan Mujeebur Rahman , Rizvi Tanveer Fatima 
Published: March 2020

AbstractThe environment is the key factor that influences the host-parasite relationship. Elevated CO2 levels resulting from various anthropogenic sources may directly affect the surroundings around pathogens and plants. It is hypothesized that plants may respond differently to pathogens in the environment containing an elevated concentration of CO2. To test the hypothesis an experiment was conducted to examine the effects of intermittent exposures of elevated levels of CO2viz., 400, 500 and 600 ppm (5 hr/day on alternate days) on the development of Sphaerotheca fuliginea causing powdery mildew disease on five cucurbits species using open-top chambers. The elevated levels of CO2 acted as a growth promoter and significantly enhanced the plant growth of all five cucurbit species. Inoculation with the fungus incited specific mildew symptoms on the leaves and decreased the plant growth and biomass production of the cucurbits tested except bitter gourd. The intermittent exposures with elevated levels of CO2 aggravated the disease development. As a result, severe mildew developed on all five cucurbits, including bitter gourd, which expressed tolerance to the pathogen. Fungus colonization in terms of the number of conidia/cm2 leaf surface was significantly greater on the plants exposed to 500 or 600 ppm CO2. The stomata and trichome density and stomatal pore width were increased in the leaves of CO2 exposed plants. The CO2 exposures also accelerated the photosynthesis rate, but transpiration, stomatal conductance, salicylic acid and total phenols were decreased; fungus inoculation caused the effects just reverse of CO2. Interaction between S. fuliginea and CO2 was found synergistic at 500 ppm, whereas with rest of the concentrations it was near to additive.
Mdm2 enhances ligase activity of parkin and facilitates mitophagy
Authors: Kook Seunghyi , Zhan Xuanzhi , Thibeault Kimberly , Ahmed Mohamed R. , Gurevich Vsevolod V. , Gurevich Eugenia V. 
Published: March 2020

AbstractLoss-of-function mutations in the E3 ubiquitin ligase parkin have been implicated in the death of dopaminergic neurons in the substantia nigra, which is the root cause of dopamine deficit in the striatum in Parkinson's disease. Parkin ubiquitinates proteins on mitochondria that lost membrane potential, promoting the elimination of damaged mitochondria. Neuroprotective activity of parkin has been linked to its critical role in the mitochondria maintenance. Here we report a novel regulatory mechanism: another E3 ubiquitin ligase Mdm2 directly binds parkin and enhances its enzymatic activity in vitro and in intact cells. Mdm2 translocates to damaged mitochondria independently of parkin, enhances parkin-dependent ubiquitination of the outer mitochondria membrane protein mitofusin1. Mdm2 facilitates and its knockdown reduces parkin-dependent mitophagy. Thus, ubiquitously expressed Mdm2 might enhance cytoprotective parkin activity. The data suggest that parkin activation by Mdm2 could be targeted to increase its neuroprotective functions, which has implications for anti-parkinsonian therapy.
Test-time augmentation for deep learning-based cell segmentation on microscopy images
Authors: Moshkov Nikita , Mathe Botond , Kertesz-Farkas Attila , Hollandi Reka , Horvath Peter 
Published: March 2020

AbstractRecent advancements in deep learning have revolutionized the way microscopy images of cells are processed. Deep learning network architectures have a large number of parameters, thus, in order to reach high accuracy, they require a massive amount of annotated data. A common way of improving accuracy builds on the artificial increase of the training set by using different augmentation techniques. A less common way relies on test-time augmentation (TTA) which yields transformed versions of the image for prediction and the results are merged. In this paper we describe how we have incorporated the test-time argumentation prediction method into two major segmentation approaches utilized in the single-cell analysis of microscopy images. These approaches are semantic segmentation based on the U-Net, and instance segmentation based on the Mask R-CNN models. Our findings show that even if only simple test-time augmentations (such as rotation or flipping and proper merging methods) are applied, TTA can significantly improve prediction accuracy. We have utilized images of tissue and cell cultures from the Data Science Bowl (DSB) 2018 nuclei segmentation competition and other sources. Additionally, boosting the highest-scoring method of the DSB with TTA, we could further improve prediction accuracy, and our method has reached an ever-best score at the DSB.
Measurement and modelling of deep sea sediment plumes and implications for deep sea mining
Authors: Spearman Jeremy , Taylor Jonathan , Crossouard Neil , Cooper Alan , Turnbull Michael , Manning Andrew , Lee Mark , Murton Bramley 
Published: March 2020

AbstractDeep sea mining concerns the extraction of poly-metallic nodules, cobalt-rich crusts and sulphide deposits from the ocean floor. The exploitation of these resources will result in adverse ecological effects arising from the direct removal of the substrate and, potentially, from the formation of sediment plumes that could result in deposition of fine sediment on sensitive species or entrainment of sediment, chemicals and nutrients into over-lying waters. Hence, identifying the behaviour of deep-sea sediment plumes is important in designing mining operations that are ecologically acceptable. Here, we present the results of novel in situ deep sea plume experiments undertaken on the Tropic seamount, 300 nautical miles SSW of the Canary Islands. These plume experiments were accompanied by hydrographic and oceanographic field surveys and supported by detailed numerical modelling and high resolution video settling velocity measurements of the in situ sediment undertaken in the laboratory. The plume experiments involved the controlled formation of benthic sediment plumes and measurement of the plume sediment concentration at a specially designed lander placed at set distances from the plume origin. The experiments were used as the basis for validation of a numerical dispersion model, which was then used to predict the dispersion of plumes generated by full-scale mining. The results highlight that the extent of dispersion of benthic sediment plumes, resulting from mining operations, is significantly reduced by the effects of flocculation, background turbidity and internal tides. These considerations must be taken into account when evaluating the impact and extent of benthic sediment plumes.
Identification of Novel Alzheimer’s Disease Loci Using Sex-Specific Family-Based Association Analysis of Whole-Genome Sequence Data
Authors: Prokopenko Dmitry , Hecker Julian , Kirchner Rory , Chapman Brad A. , Hoffman Oliver , Mullin Kristina , Hide Winston , Bertram Lars , Laird Nan , DeMeo Dawn L. , Lange Christoph , Tanzi Rudolph E. 
Published: March 2020

AbstractWith the advent of whole genome-sequencing (WGS) studies, family-based designs enable sex-specific analysis approaches that can be applied to only affected individuals; tests using family-based designs are attractive because they are completely robust against the effects of population substructure. These advantages make family-based association tests (FBATs) that use siblings as well as parents especially suited for the analysis of late-onset diseases such as Alzheimer’s Disease (AD). However, the application of FBATs to assess sex-specific effects can require additional filtering steps, as sensitivity to sequencing errors is amplified in this type of analysis. Here, we illustrate the implementation of robust analysis approaches and additional filtering steps that can minimize the chances of false positive-findings due to sex-specific sequencing errors. We apply this approach to two family-based AD datasets and identify four novel loci (GRID1,RIOK3,MCPH1,ZBTB7C) showing sex-specific association with AD risk. Following stringent quality control filtering, the strongest candidate isZBTB7C (Pinter = 1.83 × 10−7), in which the minor allele of rs1944572 confers increased risk for AD in females and protection in males.ZBTB7Cencodes the Zinc Finger and BTB Domain Containing 7C, a transcriptional repressor of membrane metalloproteases (MMP). Members of this MMP family were implicated in AD neuropathology.
Quantum valley Hall effect in wide-gap semiconductor SiC monolayer
Authors: Lee Kyu Won , Lee Cheol Eui 
Published: March 2020

AbstractWe have investigated the valley Chern number and gapless edge states in wide-gap semiconductor SiC and BN monolayers by using the density functional theory calculations. We found that while SiC monolayer has a non-quantized valley Chern number due to a partial mixing of the Berry curvature peaks pertaining to the opposite valleys, there exist topologically protected gapless edge states within the bulk gap, leading to a quantum valley Hall effect. Doping of the opposite charge carriers causes a backscattering-free valley current flowing on the opposite edge, which can be used for experimental confirmation and application at room temperature. BN monolayer, on the other hand, was found to have gapped edge states due to the too large staggered AB-sublattice potentials.
Participation of Intussusceptive Angiogenesis in the Morphogenesis of Lobular Capillary Hemangioma
Authors: Díaz-Flores Lucio , Gutiérrez Ricardo , González-Gómez Miriam , García M. A. Pino , Carrasco José Luis , Díaz-Flores Lucio , Madrid Juan F. , Álvarez-Argüelles Hugo 
Published: March 2020

AbstractIn lobular capillary hemangioma (LCH), misnamed pyogenic granuloma, only sprouting angiogenesis (SA) has been considered. We assess the occurrence of intussusceptive angiogenesis (IA) in LCH and whether IA determines the specific and other focal patterns in the lesion. For this purpose, we study specimens of 120 cases of LCH, using semithin sections (in 10), immunohistochemistry, and confocal microscopy (in 20). In addition to SA, the results in LCH showed (1) intussusceptive phenomena, including pillars/folds and associated vessel loops, which encircled interstitial tissue structures (ITSs). (2) Two types of evolved loops depending on interendothelial contacts from opposite walls: (a) numerous interendothelial contacts, alternating with capillary-sized lumens (main capillary pattern of the lesion) and (b) few interendothelial contacts, wide open lumens, and intravascular transport of pillars/folds, which were arranged linearly, forming septa (focal sinusoidal-like pattern) or were irregularly grouped (focal intravascular papillary endothelial hyperplasia, IPEH-like pattern). In conclusion, we demonstrate that IA participates in synergistic interaction with SA in LCH development and that the prevalence of specific intussusceptive phenomena determines the predominant capillary pattern and associated sinusoidal hemangioma-like and IPEH-like patterns in the lesion, which suggest a role of IA as conditioner of vessel tumour/pseudo-tumour morphology.