bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive modeling of clinical trial terminations using feature engineering and embedding learning
Authors: Elkin Magdalyn E. , Zhu Xingquan 
Published: February 2021

AbstractIn this study, we propose to use machine learning to understand terminated clinical trials. Our goal is to answer two fundamental questions: (1) what are common factors/markers associated to terminated clinical trials? and (2) how to accurately predict whether a clinical trial may be terminated or not? The answer to the first question provides effective ways to understand characteristics of terminated trials for stakeholders to better plan their trials; and the answer to the second question can direct estimate the chance of success of a clinical trial in order to minimize costs. By using 311,260 trials to build a testbed with 68,999 samples, we use feature engineering to create 640 features, reflecting clinical trial administration, eligibility, study information, criteria etc. Using feature ranking, a handful of features, such as trial eligibility, trial inclusion/exclusion criteria, sponsor types etc., are found to be related to the clinical trial termination. By using sampling and ensemble learning, we achieve over 67% Balanced Accuracy and over 0.73 AUC (Area Under the Curve) scores to correctly predict clinical trial termination, indicating that machine learning can help achieve satisfactory prediction results for clinical trial study.
Pluripotency and immunomodulatory signatures of canine induced pluripotent stem cell-derived mesenchymal stromal cells are similar to harvested mesenchymal stromal cells
Authors: Shahsavari Arash , Weeratunga Prasanna , Ovchinnikov Dmitry A. , Whitworth Deanne J. 
Published: February 2021

AbstractWith a view towards harnessing the therapeutic potential of canine mesenchymal stromal cells (cMSCs) as modulators of inflammation and the immune response, and to avoid the issues of the variable quality and quantity of harvested cMSCs, we examined the immunomodulatory properties of cMSCs derived from canine induced pluripotent stem cells (ciMSCs), and compared them to cMSCs harvested from adipose tissue (cAT-MSC) and bone marrow (cBM-MSC). A combination of deep sequencing and quantitative RT-PCR of the ciMSC transcriptome confirmed that ciMSCs express more genes in common with cBM-MSCs and cAT-MSCs than with the ciPSCs from which they were derived. Both ciMSCs and harvested cMSCs express a range of pluripotency factors in common with the ciPSCs including NANOG, POU5F1 (OCT-4), SOX-2, KLF-4, LIN-28A, MYC, LIF, LIFR, and TERT. However, ESRRB and PRDM-14, both factors associated with naïve, rather than primed, pluripotency were expressed only in the ciPSCs. CXCR-4, which is essential for the homing of MSCs to sites of inflammation, is also detectable in ciMSCs, cAT- and cBM-MSCs, but not ciPSCs. ciMSCs constitutively express the immunomodulatory factors iNOS, GAL-9, TGF-β1, PTGER-2α and VEGF, and the pro-inflammatory mediators COX-2, IL-1β and IL-8. When stimulated with the canine pro-inflammatory cytokines tumor necrosis factor-α (cTNF-α), interferon-γ (cIFN-γ), or a combination of both, ciMSCs upregulated their expression of IDO, iNOS, GAL-9, HGF, TGF-β1, PTGER-2α, VEGF, COX-2, IL-1β and IL-8. When co-cultured with mitogen-stimulated lymphocytes, ciMSCs downregulated their expression of iNOS, HGF, TGF-β1 and PTGER-2α, while increasing their expression of COX-2, IDO and IL-1β. Taken together, these findings suggest that ciMSCs possess similar immunomodulatory capabilities as harvested cMSCs and support further investigation into their potential use for the management of canine immune-mediated and inflammatory disorders.
A non-invasive method to generate induced pluripotent stem cells from primate urine
Authors: Geuder Johanna , Wange Lucas E. , Janjic Aleksandar , Radmer Jessica , Janssen Philipp , Bagnoli Johannes W. , Müller Stefan , Kaul Artur , Ohnuki Mari , Enard Wolfgang 
Published: February 2021

AbstractComparing the molecular and cellular properties among primates is crucial to better understand human evolution and biology. However, it is difficult or ethically impossible to collect matched tissues from many primates, especially during development. An alternative is to model different cell types and their development using induced pluripotent stem cells (iPSCs). These can be generated from many tissue sources, but non-invasive sampling would decisively broaden the spectrum of non-human primates that can be investigated. Here, we report the generation of primate iPSCs from urine samples. We first validate and optimize the procedure using human urine samples and show that suspension- Sendai Virus transduction of reprogramming factors into urinary cells efficiently generates integration-free iPSCs, which maintain their pluripotency under feeder-free culture conditions. We demonstrate that this method is also applicable to gorilla and orangutan urinary cells isolated from a non-sterile zoo floor. We characterize the urinary cells, iPSCs and derived neural progenitor cells using karyotyping, immunohistochemistry, differentiation assays and RNA-sequencing. We show that the urine-derived human iPSCs are indistinguishable from well characterized PBMC-derived human iPSCs and that the gorilla and orangutan iPSCs are well comparable to the human iPSCs. In summary, this study introduces a novel and efficient approach to non-invasively generate iPSCs from primate urine. This will extend the zoo of species available for a comparative approach to molecular and cellular phenotypes.
Coherent amplification and inversion less lasing of surface plasmon polaritons in a negative index metamaterial with a resonant atomic medium
Authors: Asgarnezhad-Zorgabad Saeid 
Published: February 2021

AbstractSurface plasmon polaritons (SPPs) lasing requires population inversion, it is inefficient and possesses poor spectral properties. We develop an inversion-less concept for a quantum plasmonic waveguide that exploits unidirectional superradiant SPP (SSPP) emission of radiation to produce intense coherent surface plasmon beams. Our scheme includes a resonantly driven cold atomic medium in a lossless dielectric situated above an ultra-low loss negative index metamaterial (NIMM) layer. We propose generating unidirectional superradiant radiation of the plasmonic field within an atomic medium and a NIMM layer interface and achieve amplified SPPs by introducing phase-match between the superradiant SPP wave and coupled laser fields. We also establish a parametric resonance between the weak modulated plasmonic field and the collective oscillations of the atomic ensemble, thereby suppressing decoherence of the stably amplified directional polaritonic mode. Our method incorporates the quantum gain of the atomic medium to obtain sufficient conditions for coherent amplification of superradiant SPP waves, and we explore this method to quantum dynamics of the atomic medium being coupled with the weak polaritonic waves. Our waveguide configuration acts as a surface plasmon laser and quantum plasmonic transistor and opens prospects for designing controllable nano-scale lasers for quantum and nano-photonic applications.
A pilot study on biaxial mechanical, collagen microstructural, and morphological characterizations of a resected human intracranial aneurysm tissue
Authors: Laurence Devin W. , Homburg Hannah , Yan Feng , Tang Qinggong , Fung Kar-Ming , Bohnstedt Bradley N. , Holzapfel Gerhard A. , Lee Chung-Hao 
Published: February 2021

AbstractIntracranial aneurysms (ICAs) are focal dilatations that imply a weakening of the brain artery. Incidental rupture of an ICA is increasingly responsible for significant mortality and morbidity in the American’s aging population. Previous studies have quantified the pressure-volume characteristics, uniaxial mechanical properties, and morphological features of human aneurysms. In this pilot study, for the first time, we comprehensively quantified the mechanical, collagen fiber microstructural, and morphological properties of one resected human posterior inferior cerebellar artery aneurysm. The tissue from the dome of a right posterior inferior cerebral aneurysm was first mechanically characterized using biaxial tension and stress relaxation tests. Then, the load-dependent collagen fiber architecture of the aneurysm tissue was quantified using an in-house polarized spatial frequency domain imaging system. Finally, optical coherence tomography and histological procedures were used to quantify the tissue’s microstructural morphology. Mechanically, the tissue was shown to exhibit hysteresis, a nonlinear stress-strain response, and material anisotropy. Moreover, the unloaded collagen fiber architecture of the tissue was predominantly aligned with the testing Y-direction and rotated towards the X-direction under increasing equibiaxial loading. Furthermore, our histological analysis showed a considerable damage to the morphological integrity of the tissue, including lack of elastin, intimal thickening, and calcium deposition. This new unified characterization framework can be extended to better understand the mechanics-microstructure interrelationship of aneurysm tissues at different time points of the formation or growth. Such specimen-specific information is anticipated to provide valuable insight that may improve our current understanding of aneurysm growth and rupture potential.
Rapid seroconversion and persistent functional IgG antibodies in severe COVID-19 patients correlates with an IL-12p70 and IL-33 signature
Authors: Munitz Ariel , Edry-Botzer L. , Itan M. , Tur-Kaspa R. , Dicker D. , Marcoviciu D. , Goren M. G. , Mor M. , Lev S. , Gottesman T. , Muhsen K. , Cohen D. , Stein M. , Qimron U. , Freund N. T. , Wine Y. , Gerlic Motti 
Published: February 2021

AbstractDespite ongoing efforts to characterize the host response toward SARS-CoV-2, a major gap in our knowledge still exists regarding the magnitude and duration of the humoral response. Analysis of the antibody response in mild versus moderate/severe patients, using our new developed quantitative electrochemiluminescent assay for detecting IgM/IgA/IgG antibodies toward SARS-CoV-2 antigens, revealed a rapid onset of IgG/IgA antibodies, specifically in moderate/severe patients. IgM antibodies against the viral receptor binding domain, but not against nucleocapsid protein, were detected at early stages of the disease. Furthermore, we observed a marked reduction in IgM/IgA antibodies over-time. Adapting our assay for ACE2 binding-competition, demonstrated that the presence of potentially neutralizing antibodies is corelated with IgG/IgA. Finally, analysis of the cytokine profile in COVID-19 patients revealed unique correlation of an IL-12p70/IL33 and IgG seroconversion, which correlated with disease severity. In summary, our comprehensive analysis has major implications on the understanding and monitoring of SARS-CoV-2 infections.
The potential role of MR based radiomic biomarkers in the characterization of focal testicular lesions
Authors: Feliciani Giacomo , Mellini Lorenzo , Carnevale Aldo , Sarnelli Anna , Menghi Enrico , Piccinini Filippo , Scarpi Emanuela , Loi Emiliano , Galeotti Roberto , Giganti Melchiore , Parenti Gian Carlo 
Published: February 2021

AbstractHow to differentiate with MRI-based techniques testicular germ (TGCTs) and testicular non-germ cell tumors (TNGCTs) is still under debate and Radiomics may be the turning key. Our purpose is to investigate the performance of MRI-based Radiomics signatures for the preoperative prediction of testicular neoplasm histology. The aim is twofold: (i), differentiating TGCTs and TNGCTs status and (ii) differentiating seminomas (SGCTs) from non-seminomatous (NSGCTs). Forty-two patients with pathology-proven testicular neoplasms and referred for pre-treatment MRI, were retrospectively enrolled. Thirty-two out of 44 lesions were TGCTs. Twelve out of 44 were TNGCTs or other histologies. Two radiologists segmented the volume of interest on T2-weighted images. Approximately 500 imaging features were extracted. Least Absolute Shrinkage and Selection Operator (LASSO) was applied as method for variable selection. A linear model and a linear support vector machine (SVM) were trained with selected features to assess discrimination scores for the two endpoints. LASSO identified 3 features that were employed to build fivefold validated linear discriminant and linear SVM classifiers for the TGCT-TNGCT endpoint giving an overall accuracy of 89%. Four features were employed to build another SVM for the SGCT-SNGCT endpoint with an overall accuracy of 86%. The data obtained proved that T2-weighted-based Radiomics is a promising tool in the diagnostic workup of testicular neoplasms by discriminating germ cell from non-gem cell tumors, and seminomas from non-seminomas.
Practicable assessment of cochlear size and shape from clinical CT images
Authors: Gee Andrew H. , Zhao Yufeng , Treece Graham M. , Bance Manohar L. 
Published: February 2021

AbstractThere is considerable interpersonal variation in the size and shape of the human cochlea, with evident consequences for cochlear implantation. The ability to characterize a specific cochlea, from preoperative computed tomography (CT) images, would allow the clinician to personalize the choice of electrode, surgical approach and postoperative programming. In this study, we present a fast, practicable and freely available method for estimating cochlear size and shape from clinical CT. The approach taken is to fit a template surface to the CT data, using either a statistical shape model or a locally affine deformation (LAD). After fitting, we measure cochlear size, duct length and a novel measure of basal turn non-planarity, which we suggest might correlate with the risk of insertion trauma. Gold-standard measurements from a convenience sample of 18 micro-CT scans are compared with the same quantities estimated from low-resolution, noisy, pseudo-clinical data synthesized from the same micro-CT scans. The best results were obtained using the LAD method, with an expected error of 8–17% of the gold-standard sample range for non-planarity, cochlear size and duct length.
Respiratory syncytial virus B sequence analysis reveals a novel early genotype
Authors: Muñoz-Escalante Juan C. , Comas-García Andreu , Bernal-Silva Sofía , Noyola Daniel E. 
Published: February 2021

AbstractRespiratory syncytial virus (RSV) is a major cause of respiratory infections and is classified in two main groups, RSV-A and RSV-B, with multiple genotypes within each of them. For RSV-B, more than 30 genotypes have been described, without consensus on their definition. The lack of genotype assignation criteria has a direct impact on viral evolution understanding, development of viral detection methods as well as vaccines design. Here we analyzed the totality of complete RSV-B G gene ectodomain sequences published in GenBank until September 2018 (n = 2190) including 478 complete genome sequences using maximum likelihood and Bayesian phylogenetic analyses, as well as intergenotypic and intragenotypic distance matrices, in order to generate a systematic genotype assignation. Individual RSV-B genes were also assessed using maximum likelihood phylogenetic analyses and multiple sequence alignments were used to identify molecular markers associated to specific genotypes. Analyses of the complete G gene ectodomain region, sequences clustering patterns, and the presence of molecular markers of each individual gene indicate that the 37 previously described genotypes can be classified into fifteen distinct genotypes: BA, BA-C, BA-CC, CB1-THB, GB1-GB4, GB6, JAB1-NZB2, SAB1, SAB2, SAB4, URU2 and a novel early circulating genotype characterized in the present study and designated GB0.
Integrative analysis identifies bHLH transcription factors as contributors to Parkinson’s disease risk mechanisms
Authors: Berge-Seidl Victoria , Pihlstrøm Lasse , Toft Mathias 
Published: February 2021

AbstractGenome-wide association studies (GWAS) have identified multiple genetic risk signals for Parkinson’s disease (PD), however translation into underlying biological mechanisms remains scarce. Genomic functional annotations of neurons provide new resources that may be integrated into analyses of GWAS findings. Altered transcription factor binding plays an important role in human diseases. Insight into transcriptional networks involved in PD risk mechanisms may thus improve our understanding of pathogenesis. We analysed overlap between genome-wide association signals in PD and open chromatin in neurons across multiple brain regions, finding a significant enrichment in the superior temporal cortex. The involvement of transcriptional networks was explored in neurons of the superior temporal cortex based on the location of candidate transcription factor motifs identified by two de novo motif discovery methods. Analyses were performed in parallel, both finding that PD risk variants significantly overlap with open chromatin regions harboring motifs of basic Helix-Loop-Helix (bHLH) transcription factors. Our findings show that cortical neurons are likely mediators of genetic risk for PD. The concentration of PD risk variants at sites of open chromatin targeted by members of the bHLH transcription factor family points to an involvement of these transcriptional networks in PD risk mechanisms.
A dynamic lesion model for differentiation of malignant and benign pathologies
Authors: Cao Weiguo , Liang Zhengrong , Gao Yongfeng , Pomeroy Marc J. , Han Fangfang , Abbasi Almas , Pickhardt Perry J. 
Published: February 2021

AbstractMalignant lesions have a high tendency to invade their surrounding environment compared to benign ones. This paper proposes a dynamic lesion model and explores the 2nd order derivatives at each image voxel, which reflect the rate of change of image intensity, as a quantitative measure of the tendency. The 2nd order derivatives at each image voxel are usually represented by the Hessian matrix, but it is difficult to quantify a matrix field (or image) through the lesion space as a measure of the tendency. We conjecture that the three eigenvalues contain important information of the Hessian matrix and are chosen as the surrogate representation of the Hessian matrix. By treating the three eigenvalues as a vector, called Hessian vector, which is defined in a local coordinate formed by three orthogonal Hessian eigenvectors and further adapting the gray level occurrence computing method to extract the vector texture descriptors (or measures) from the Hessian vector, a quantitative presentation for the dynamic lesion model is completed. The vector texture descriptors were applied to differentiate malignant from benign lesions from two pathologically proven datasets: colon polyps and lung nodules. The classification results not only outperform four state-of-the-art methods but also three radiologist experts.
Retrieving the structure of probabilistic sequences of auditory stimuli from EEG data
Authors: Hernández Noslen , Duarte Aline , Ost Guilherme , Fraiman Ricardo , Galves Antonio , Vargas Claudia D. 
Published: February 2021

AbstractUsing a new probabilistic approach we model the relationship between sequences of auditory stimuli generated by stochastic chains and the electroencephalographic (EEG) data acquired while 19 participants were exposed to those stimuli. The structure of the chains generating the stimuli are characterized by rooted and labeled trees whose leaves, henceforth called contexts, represent the sequences of past stimuli governing the choice of the next stimulus. A classical conjecture claims that the brain assigns probabilistic models to samples of stimuli. If this is true, then the context tree generating the sequence of stimuli should be encoded in the brain activity. Using an innovative statistical procedure we show that this context tree can effectively be extracted from the EEG data, thus giving support to the classical conjecture.
Temporal and vertical variations of polycyclic aromatic hydrocarbon at low elevations in an industrial city of southern Taiwan
Authors: Chen Wei-Hsiang , Hsieh Ming-Tsuen , You Jie-Yu , Quadir Adnan , Lee Chon-Lin 
Published: February 2021

AbstractConsidered that human activities mostly occur below building heights, the objective of this study was to investigate the temporal variations of fine particular matter (PM2.5)-associated polycyclic aromatic hydrocarbons (PAHs) and benzo[a]pyrene-equivalent (BaPeq) concentrations at four different elevations (6.1, 12.4, 18.4, and 27.1 m) in Kaohsiung City, the largest industrial city of southern Taiwan. Temperature variation was critical for the PM2.5-associated PAH concentrations, which were dominated by benzo[g,h,i]perylene (0.27 ± 0.04 ng m−3 and 24.43% of the total concentration) and other high molecular weight (HMW) species. The PM2.5-associated BaPeq was dominated by 5-ring PAH (36.09%). The PM2.5-associated PAH and BaPeq concentrations at all elevations were significantly increased in winter. In the night, the correlations between the PM2.5-associated PAH concentrations and atmospheric temperatures became negatively stronger, notably at lower elevations (r = − 0.73 ~ − 0.86), whereas the BaPeq during daytime and nighttime were not changed significantly in most months. The PAHs analysis with different PM sizes demonstrated the importance of smaller particles such as PM2.5. The meteorological variation was more important than elevation to influence the low-elevation PM2.5-associated PAH and BaPeq concentrations in an urban area like Kaohsiung City, as the two concentrations were dominated by the PAHs with HMWs and those 5-ring species, respectively.
PHAIR: a biosensor for pH measurement in air–liquid interface cell culture
Authors: Dabaghi Mohammadhossein , Saraei Neda , Xu Gang , Chandiramohan Abiram , Yeung Jonas , Nguyen Jenny P. , Vukmirovic Milica , Selvaganapathy Ponnambalam Ravi , Hirota Jeremy A. 
Published: February 2021

AbstractIn many biological systems, pH can be used as a parameter to understand and study cell dynamics. However, measuring pH in live cell culture is limited by the sensor ion specificity, proximity to the cell surface, and scalability. Commercially available pH sensors are difficult to integrate into a small-scale cell culture system due to their size and are not cost-effective for disposable use. We made PHAIR—a new pH sensor that uses a micro-wire format to measure pH in vitro human airway cell culture. Tungsten micro-wires were used as the working electrodes, and silver micro-wires with a silver/silver chloride coating were used as a pseudo reference electrode. pH sensitivity, in a wide and narrow range, and stability of these sensors were tested in common standard buffer solutions as well as in culture media of human airway epithelial cells grown at the air–liquid interface in a 24 well cell culture plate. When measuring the pH of cells grown under basal and challenge conditions using PHAIR, cell viability and cytokine responses were not affected. Our results confirm that micro-wire-based sensors have the capacity for miniaturization and detection of diverse ions while maintaining sensitivity. This suggests the broad application of PHAIR in various biological experimental settings.