bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differently expressed microRNA in response to the first Ig replacement therapy in common variable immunodeficiency patients
Authors: De Felice Bruna , Nigro Ersilia , Polito Rita , Rossi Francesca Wanda , Pecoraro Antonio , Spadaro Giuseppe , Daniele Aurora 
Published: December 2020

AbstractCommon variable immunodeficiency (CVID) is a complex primary immunodeficiency disorder characterized by a high clinical and genetic heterogeneity. The molecular underlying causes of CVID are not still now clear and the delays in diagnosis and treatment worsen the prognosis of the patients. MicroRNAs are non-coding, endogenous small RNAs often deregulated in human diseases, such as autoimmune and other immune-based disorders. In the present study, we aimed to evaluate miRNAs associated with the CVID and, in particular, with the response to the first Ig replacement therapy. To this aim, we compared miRNA profile obtained by serum samples of treatment-naïve CVID patients before and 24 h after the first Ig replacement therapy. For the first time, using a microarray assay followed by an integrated bioinformatics/biostatistics analysis, we identified five microRNAs (hsa-miR-6742, hsa-miR-1825, hsa-miR-4769-3p, hsa-miR-1228-3p, hsa-miR-1972) differently modulated in CVID patients by Ig infusion. All of them were down-regulated, excepted miR-6742 which was up-regulated. The latter may be of particular interest, since its functions are related to pathways involving Class I MHC mediated antigen processing and adaptive as well as innate Immune System. In conclusion, this study shows for the first time the modulation of miRNAs involved in CVID patients after the first Ig replacement therapy. Further studies are needed to assess whether such miRNAs could represent novel potential biomarkers in management and therapy of CVID patients.
Novel statistical approach for assessing the persistence of the circadian rhythms of social activity from telephone call detail records in older adults
Authors: Aubourg Timothée , Demongeot Jacques , Vuillerme Nicolas 
Published: December 2020

AbstractHow circadian rhythms of activity manifest themselves in social life of humans remains one of the most intriguing questions in chronobiology and a major issue for personalized medicine. Over the past years, substantial advances have been made in understanding the personal nature and the robustness—i.e. the persistence—of the circadian rhythms of social activity by the analysis of phone use. At this stage however, the consistency of such advances as their statistical validity remains unclear. The present paper has been specifically designed to address this issue. To this end, we propose a novel statistical procedure for the measurement of the circadian rhythms of social activity which is particularly well-suited for the existing framework of persistence analysis. Furthermore, we illustrate how this procedure works concretely by assessing the persistence of the circadian rhythms of telephone call activity from a 12-month call detail records (CDRs) dataset of adults over than 65 years. The results show the ability of our approach for assessing persistence with a statistical significance. In the field of CDRs analysis, this novel statistical approach can be used for completing the existing methods used to analyze the persistence of the circadian rhythms of a social nature. More importantly, it provides an opportunity to open up the analysis of CDRs for various domains of application in personalized medicine requiring access to statistical significance such as health care monitoring.
Loss of miR-100 and miR-125b results in cancer stem cell properties through IGF2 upregulation in hepatocellular carcinoma
Authors: Seol Hyang Sook , Akiyama Yoshimitsu , Lee San-Eun , Shimada Shu , Jang Se Jin 
Published: December 2020

AbstractStemness factors control microRNA expression in cancer stem cells. Downregulation of miR-100 and miR-125b is associated with tumor progression and prognosis of various cancers. Comparing miRNA profiling of patient-derived tumorsphere (TS) and adherent (2D) hepatocellular carcinoma cells, miR-100 and miR-125b are identified to have association with stemness. In TS cells, miR-100 and miR-125b were downregulated comparing to 2D cells. The finding was reproduced in Hep3B cells. Overexpression of stemness factors NANOG, OCT4 and SOX2 by introduction of gene constructs in Hep3B cells suppressed these two miRNA expression levels. Treatment of chromeceptin, an IGF signaling pathway inhibitor, decreased numbers of TS and inhibited the AKT/mTOR pathway. Stable cell line of miR-100 and miR-125b overexpression decreased IGF2 expression and inhibited tumor growth in the xenograft model. In conclusion, miR-100 and miR-125b have tumor suppressor role in hepatocellular carcinoma through inhibiting IGF2 expression and activation of the AKT/mTOR pathway.
Multiscale 3D phenotyping of human cerebral organoids
Authors: Albanese Alexandre , Swaney Justin M. , Yun Dae Hee , Evans Nicholas B. , Antonucci Jenna M. , Velasco Silvia , Sohn Chang Ho , Arlotta Paola , Gehrke Lee , Chung Kwanghun 
Published: December 2020

AbstractBrain organoids grown from human pluripotent stem cells self-organize into cytoarchitectures resembling the developing human brain. These three-dimensional models offer an unprecedented opportunity to study human brain development and dysfunction. Characterization currently sacrifices spatial information for single-cell or histological analysis leaving whole-tissue analysis mostly unexplored. Here, we present the SCOUT pipeline for automated multiscale comparative analysis of intact cerebral organoids. Our integrated technology platform can rapidly clear, label, and image intact organoids. Algorithmic- and convolutional neural network-based image analysis extract hundreds of features characterizing molecular, cellular, spatial, cytoarchitectural, and organoid-wide properties from fluorescence microscopy datasets. Comprehensive analysis of 46 intact organoids and ~ 100 million cells reveals quantitative multiscale “phenotypes" for organoid development, culture protocols and Zika virus infection. SCOUT provides a much-needed framework for comparative analysis of emerging 3D in vitro models using fluorescence microscopy.
Impact of the transverse direction on the many-body tunneling dynamics in a two-dimensional bosonic Josephson junction
Authors: Bhowmik Anal , Haldar Sudip Kumar , Alon Ofir E. 
Published: December 2020

AbstractTunneling in a many-body system appears as one of the novel implications of quantum physics, in which particles move in space under an otherwise classically-forbidden potential barrier. Here, we theoretically describe the quantum dynamics of the tunneling phenomenon of a few intricate bosonic clouds in a closed system of a two-dimensional symmetric double-well potential. We examine how the inclusion of the transverse direction, orthogonal to the junction of the double-well, can intervene in the tunneling dynamics of bosonic clouds. We use a well-known many-body numerical method, called the multiconfigurational time-dependent Hartree for bosons (MCTDHB) method. MCTDHB allows one to obtain accurately the time-dependent many-particle wavefunction of the bosons which in principle entails all the information of interest about the system under investigation. We analyze the tunneling dynamics by preparing the initial state of the bosonic clouds in the left well of the double-well either as the ground, longitudinally or transversely excited, or a vortex state. We unravel the detailed mechanism of the tunneling process by analyzing the evolution in time of the survival probability, depletion and fragmentation, and the many-particle position, momentum, and angular-momentum expectation values and their variances. As a general rule, all objects lose coherence while tunneling through the barrier and the states which include transverse excitations do so faster. In particular for the later states, we show that even when the transverse direction is seemingly frozen, prominent many-body dynamics in a two-dimensional bosonic Josephson junction occurs. Implications are briefly discussed.
Rapid development of strong, persistent, spatiotemporally extensive cortical synchrony and underlying oscillations following acute MCA focal ischemia
Authors: Wann Ellen G. , Wodeyar Anirudh , Srinivasan Ramesh , Frostig Ron D. 
Published: December 2020

AbstractStroke is a leading cause of death and the leading cause of long-term disability, but its electrophysiological basis is poorly understood. Characterizing acute ischemic neuronal activity dynamics is important for understanding the temporal and spatial development of ischemic pathophysiology and determining neuronal activity signatures of ischemia. Using a 32-microelectrode array spanning the depth of cortex, electrophysiological recordings generated for the first time a continuous spatiotemporal profile of local field potentials (LFP) and multi-unit activity (MUA) before (baseline) and directly after (0–5 h) distal, permanent MCA occlusion (pMCAo) in a rat model. Although evoked activity persisted for hours after pMCAo with minor differences from baseline, spatiotemporal analyses of spontaneous activity revealed that LFP became spatially and temporally synchronized regardless of cortical depth within minutes after pMCAo and extended over large parts of cortex. Such enhanced post-ischemic synchrony was found to be driven by increased bursts of low multi-frequency oscillations and continued throughout the acute ischemic period whereas synchrony measures minimally changed over the same recording period in surgical sham controls. EEG recordings of a similar frequency range have been applied to successfully predict stroke damage and recovery, suggesting clear clinical relevance for our rat model.
AnOxPePred: using deep learning for the prediction of antioxidative properties of peptides
Authors: Olsen Tobias Hegelund , Yesiltas Betül , Marin Frederikke Isa , Pertseva Margarita , García-Moreno Pedro J. , Gregersen Simon , Overgaard Michael Toft , Jacobsen Charlotte , Lund Ole , Hansen Egon Bech , Marcatili Paolo 
Published: December 2020

AbstractDietary antioxidants are an important preservative in food and have been suggested to help in disease prevention. With consumer demands for less synthetic and safer additives in food products, the food industry is searching for antioxidants that can be marketed as natural. Peptides derived from natural proteins show promise, as they are generally regarded as safe and potentially contain other beneficial bioactivities. Antioxidative peptides are usually obtained by testing various peptides derived from hydrolysis of proteins by a selection of proteases. This slow and cumbersome trial-and-error approach to identify antioxidative peptides has increased interest in developing computational approaches for prediction of antioxidant activity and thereby reduce laboratory work. A few antioxidant predictors exist, however, no tool predicting the antioxidative properties of peptides is, to the best of our knowledge, currently available as a web-server. We here present the AnOxPePred tool and web-server (http://services.bioinformatics.dtu.dk/service.php?AnOxPePred-1.0) that uses deep learning to predict the antioxidant properties of peptides. Our model was trained on a curated dataset consisting of experimentally-tested antioxidant and non-antioxidant peptides. For a variety of metrics our method displays a prediction performance better than a k-NN sequence identity-based approach. Furthermore, the developed tool will be a good benchmark for future predictors of antioxidant peptides.
Indication and benefit of upfront hematopoietic stem cell transplantation for T-cell lymphoblastic lymphoma in the era of ALL-type induction therapies
Authors: Morita-Fujita Mari , Arai Yasuyuki , Yoshioka Satoshi , Ishikawa Takayuki , Kanda Junya , Kondo Tadakazu , Akasaka Takashi , Ueda Yasunori , Imada Kazunori , Moriguchi Toshinori , Yago Kazuhiro , Kitano Toshiyuki , Yonezawa Akihito , Nohgawa Masaharu , Takaori-Kondo Akifumi ,   Kyoto Stem Cell Transplantation Group (KSCTG)
Published: December 2020

AbstractSince the introduction of leukemia-type induction therapies for T-cell lymphoblastic lymphoma (T-LBL), improvements in the long-term outcomes of T-LBL have been reported. However, indications for and the appropriate timing of hematopoietic stem cell transplantation (HSCT) have not yet been established. Therefore, we performed a multicenter retrospective cohort study of patients with T-LBL treated using leukemia-type initial therapies to compare the outcomes after HSCT at different disease stages. We enrolled 21 patients with T-LBL from a total of 11 centers, and all patients received hyper-CVAD as a leukemia-type initial regimen. HSCT was performed during the CR1/PR1 (standard disease) stage in 11 patients, while it was completed at a later or non-remission (advanced disease) stage in 10 patients. Following HSCT, the overall survival rate was significantly greater in standard disease than in advanced-disease patients (79.5% vs. 30.0% at 5 years; hazard ratio (HR) 5.97; p = 0.03), with trend to the lower incidence of relapse in the former group (27.3% vs. 60.0% at 5 years; HR 2.29; p = 0.19). A prognostic difference was not detected between cases treated with allogeneic and autologous HSCTs. Our study suggests that frontline HSCT may be a feasible treatment option for T-LBL, even in the era of leukemia-type initial therapy.
Development of a human primary gut-on-a-chip to model inflammatory processes
Authors: Beaurivage Claudia , Kanapeckaite Auste , Loomans Cindy , Erdmann Kai S. , Stallen Jan , Janssen Richard A. J. 
Published: December 2020

AbstractInflammatory bowel disease (IBD) is a complex multi-factorial disease for which physiologically relevant in vitro models are lacking. Existing models are often a compromise between biological relevance and scalability. Here, we integrated intestinal epithelial cells (IEC) derived from human intestinal organoids with monocyte-derived macrophages, in a gut-on-a-chip platform to model the human intestine and key aspects of IBD. The microfluidic culture of IEC lead to an increased polarization and differentiation state that closely resembled the expression profile of human colon in vivo. Activation of the model resulted in the polarized secretion of CXCL10, IL-8 and CCL-20 by IEC and could efficiently be prevented by TPCA-1 exposure. Importantly, upregulated gene expression by the inflammatory trigger correlated with dysregulated pathways in IBD patients. Finally, integration of activated macrophages offers a first-step towards a multi-factorial amenable IBD platform that could be scaled up to assess compound efficacy at early stages of drug development or in personalized medicine.
The vascular targeted citrus FLOWERING LOCUS T3 gene promotes non-inductive early flowering in transgenic Carrizo rootstocks and grafted juvenile scions
Authors: Soares Juliana M. , Weber Kyle C. , Qiu Wenming , Stanton Daniel , Mahmoud Lamiaa M. , Wu Hao , Huyck Patrick , Zale Janice , Al Jasim Kawther , Grosser Jude W. , Dutt Manjul 
Published: December 2020

AbstractShortening the juvenile stage in citrus and inducing early flowering has been the focus of several citrus genetic improvement programs. FLOWERING LOCUS T (FT) is a small phloem-translocated protein that regulates precocious flowering. In this study, two populations of transgenic Carrizo citrange rootstocks expressing either Citrus clementina FT1 or FT3 genes under the control of the Arabidopsis thaliana phloem specific SUCROSE SYNTHASE 2 (AtSUC2) promoter were developed. The transgenic plants were morphologically similar to the non-transgenic controls (non-transgenic Carrizo citrange), however, only AtSUC2-CcFT3 was capable of inducing precocious flowers. The transgenic lines produced flowers 16 months after transformation and flower buds appeared 30–40 days on juvenile immature scions grafted onto transgenic rootstock. Gene expression analysis revealed that the expression of SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1) and APETALA1 (AP1) were enhanced in the transgenics. Transcriptome profiling of a selected transgenic line showed the induction of genes in different groups including: genes from the flowering induction pathway, APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) family genes, and jasmonic acid (JA) pathway genes. Altogether, our results suggested that ectopic expression of CcFT3 in phloem tissues of Carrizo citrange triggered the expression of several genes to mediate early flowering.
Efficient viral delivery of Cas9 into human safe harbor
Authors: Hayashi Hideki , Kubo Yoshinao , Izumida Mai , Matsuyama Toshifumi 
Published: December 2020

AbstractGene editing using CRISPR/Cas9 is a promising method to cure many human genetic diseases. We have developed an efficient system to deliver Cas9 into the adeno-associated virus integration site 1 (AAVS1) locus, known as a safe harbor, using lentivirus and AAV viral vectors, as a step toward future in vivo transduction. First, we introduced Cas9v1 (derived from Streptococcus pyogenes) at random into the genome using a lentiviral vector. Cas9v1 activity was used when the N-terminal 1.9 kb, and C-terminal 2.3 kb fragments of another Cas9v2 (human codon-optimized) were employed sequentially with specific single-guide RNAs (sgRNAs) and homology donors carried by AAV vectors into the AAVS1 locus. Then, Cas9v1 was removed from the genome by another AAV vector containing sgRNA targeting the long terminal repeat of the lentivirus vector. The reconstituted Cas9v2 in the AAVS1 locus was functional and gene editing was efficient.
Simultaneous imaging of hard and soft biological tissues in a low-field dental MRI scanner
Authors: Algarín José M. , Díaz-Caballero Elena , Borreguero José , Galve Fernando , Grau-Ruiz Daniel , Rigla Juan P. , Bosch Rubén , González José M. , Pallás Eduardo , Corberán Miguel , Gramage Carlos , Aja-Fernández Santiago , Ríos Alfonso , Benlloch José M. , Alonso Joseba 
Published: December 2020

AbstractMagnetic Resonance Imaging (MRI) of hard biological tissues is challenging due to the fleeting lifetime and low strength of their response to resonant stimuli, especially at low magnetic fields. Consequently, the impact of MRI on some medical applications, such as dentistry, continues to be limited. Here, we present three-dimensional reconstructions of ex-vivo human teeth, as well as a rabbit head and part of a cow femur, all obtained at a field strength of 260 mT. These images are the first featuring soft and hard tissues simultaneously at sub-Tesla fields, and they have been acquired in a home-made, special-purpose, pre-medical MRI scanner designed with the goal of demonstrating dental imaging at low field settings. We encode spatial information with two pulse sequences: Pointwise-Encoding Time reduction with Radial Acquisition and a new sequence we have called Double Radial Non-Stop Spin Echo, which we find to perform better than the former. For image reconstruction we employ Algebraic Reconstruction Techniques (ART) as well as standard Fourier methods. An analysis of the resulting images shows that ART reconstructions exhibit a higher signal-to-noise ratio with a more homogeneous noise distribution.
Deep-learned time-signal intensity pattern analysis using an autoencoder captures magnetic resonance perfusion heterogeneity for brain tumor differentiation
Authors: Park Ji Eun , Kim Ho Sung , Lee Junkyu , Cheong E.-Nae , Shin Ilah , Ahn Sung Soo , Shim Woo Hyun 
Published: December 2020

AbstractCurrent image processing methods for dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) do not capture complex dynamic information of time-signal intensity curves. We investigated whether an autoencoder-based pattern analysis of DSC MRI captured representative temporal features that improves tissue characterization and tumor diagnosis in a multicenter setting. The autoencoder was applied to the time-signal intensity curves to obtain representative temporal patterns, which were subsequently learned by a convolutional neural network. This network was trained with 216 preoperative DSC MRI acquisitions and validated using external data (n = 43) collected with different DSC acquisition protocols. The autoencoder applied to time-signal intensity curves and clustering obtained nine representative clusters of temporal patterns, which accurately identified tumor and non-tumoral tissues. The dominant clusters of temporal patterns distinguished primary central nervous system lymphoma (PCNSL) from glioblastoma (AUC 0.89) and metastasis from glioblastoma (AUC 0.95). The autoencoder captured DSC time-signal intensity patterns that improved identification of tumoral tissues and differentiation of tumor type and was generalizable across centers.
Diffusion kurtosis imaging of gray matter in young adults with autism spectrum disorder
Authors: McKenna Faye , Miles Laura , Donaldson Jeffrey , Castellanos F. Xavier , Lazar Mariana 
Published: December 2020

AbstractPrior ex vivo histological postmortem studies of autism spectrum disorder (ASD) have shown gray matter microstructural abnormalities, however, in vivo examination of gray matter microstructure in ASD has remained scarce due to the relative lack of non-invasive methods to assess it. The aim of this work was to evaluate the feasibility of employing diffusional kurtosis imaging (DKI) to describe gray matter abnormalities in ASD in vivo. DKI data were examined for 16 male participants with a diagnosis of ASD and IQ>80 and 17 age- and IQ-matched male typically developing (TD) young adults 18–25 years old. Mean (MK), axial (AK), radial (RK) kurtosis and mean diffusivity (MD) metrics were calculated for lobar and sub-lobar regions of interest. Significantly decreased MK, RK, and MD were found in ASD compared to TD participants in the frontal and temporal lobes and several sub-lobar regions previously associated with ASD pathology. In ASD participants, decreased kurtosis in gray matter ROIs correlated with increased repetitive and restricted behaviors and poor social interaction symptoms. Decreased kurtosis in ASD may reflect a pathology associated with a less restrictive microstructural environment such as decreased neuronal density and size, atypically sized cortical columns, or limited dendritic arborizations.
Middle eastern genetic legacy in the paternal and maternal gene pools of Chuetas
Authors: Ferragut J. F. , Ramon C. , Castro J. A. , Amorim A. , Alvarez L. , Picornell A. 
Published: December 2020

AbstractChuetas are a group of descendants of Majorcan Crypto-Jews (Balearic Islands, Spain) who were socially stigmatized and segregated by their Majorcan neighbours until recently; generating a community that, although after the seventeenth century no longer contained Judaic religious elements, maintained strong group cohesion, Jewishness consciousness, and endogamy. Collective memory fixed 15 surnames as a most important defining element of Chueta families. Previous studies demonstrated Chuetas were a differentiated population, with a considerable proportion of their original genetic make-up. Genetic data of Y-chromosome polymorphism and mtDNA control region showed, in Chuetas’ paternal lineages, high prevalence of haplogroups J2-M172 (33%) and J1-M267 (18%). In maternal lineages, the Chuetas hallmark is the presence of a new sub-branching of the rare haplogroup R0a2m as their modal haplogroup (21%). Genetic diversity in both Y-chromosome and mtDNA indicates the Chueta community has managed to avoid the expected heterogeneity decrease in their gene pool after centuries of isolation and inbreeding. Moreover, the composition of their uniparentally transmitted lineages demonstrates a remarkable signature of Middle Eastern ancestry—despite some degree of host admixture—confirming Chuetas have retained over the centuries a considerable degree of ancestral genetic signature along with the cultural memory of their Jewish origin.