bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multimodal deep learning models for early detection of Alzheimer’s disease stage
Authors: Venugopalan Janani , Tong Li , Hassanzadeh Hamid Reza , Wang May D. 
Published: February 2021

AbstractMost current Alzheimer’s disease (AD) and mild cognitive disorders (MCI) studies use single data modality to make predictions such as AD stages. The fusion of multiple data modalities can provide a holistic view of AD staging analysis. Thus, we use deep learning (DL) to integrally analyze imaging (magnetic resonance imaging (MRI)), genetic (single nucleotide polymorphisms (SNPs)), and clinical test data to classify patients into AD, MCI, and controls (CN). We use stacked denoising auto-encoders to extract features from clinical and genetic data, and use 3D-convolutional neural networks (CNNs) for imaging data. We also develop a novel data interpretation method to identify top-performing features learned by the deep-models with clustering and perturbation analysis. Using Alzheimer’s disease neuroimaging initiative (ADNI) dataset, we demonstrate that deep models outperform shallow models, including support vector machines, decision trees, random forests, and k-nearest neighbors. In addition, we demonstrate that integrating multi-modality data outperforms single modality models in terms of accuracy, precision, recall, and meanF1 scores. Our models have identified hippocampus, amygdala brain areas, and the Rey Auditory Verbal Learning Test (RAVLT) as top distinguished features, which are consistent with the known AD literature.
Heterostructural transformation of mesoporous silica–titania hybrids
Authors: Paengjun Navarut , Vibulyaseak Kasimanat , Ogawa Makoto 
Published: February 2021

AbstractMesoporous silica (SBA-15 with the BJH pore size of 8 nm) containing anatase nanoparticles in the pore with two different titania contents (28 and 65 mass%), which were prepared by the infiltration of the amorphous precursor derived from tetraisopropyl orthotitanate into the pore, were heat treated in air to investigate the structural changes (both mesostructure of the SBA-15 and the phase and size of the anatase in the pore). The mesostructure of the mesoporous silica and the particle size of anatase unchanged by the heat treatment up to 800 °C. The heat treatment at the temperature higher than 1000 °C resulted in the collapse of the mesostructure and the growth of anatase nanoparticles as well as the transformation to rutile, while the transformation of anatase to rutile was suppressed especially for the sample with the lower titania content (28 mass%). The resulting mesoporous silica-anatase hybrids exhibited higher benzene adsorption capacity (adsorption from water) over those heated at lower temperature, probably due to the dehydroxylation of the silanol group on the pore surface. The photocatalytic decomposition of benzene in water by the present hybrid heated at 1100 °C was efficient as that by P25, a benchmark photocatalyst.
An in silico deep learning approach to multi-epitope vaccine design: a SARS-CoV-2 case study
Authors: Yang Zikun , Bogdan Paul , Nazarian Shahin 
Published: February 2021

AbstractThe rampant spread of COVID-19, an infectious disease caused by SARS-CoV-2, all over the world has led to over millions of deaths, and devastated the social, financial and political entities around the world. Without an existing effective medical therapy, vaccines are urgently needed to avoid the spread of this disease. In this study, we propose an in silico deep learning approach for prediction and design of a multi-epitope vaccine (DeepVacPred). By combining the in silico immunoinformatics and deep neural network strategies, the DeepVacPred computational framework directly predicts 26 potential vaccine subunits from the available SARS-CoV-2 spike protein sequence. We further use in silico methods to investigate the linear B-cell epitopes, Cytotoxic T Lymphocytes (CTL) epitopes, Helper T Lymphocytes (HTL) epitopes in the 26 subunit candidates and identify the best 11 of them to construct a multi-epitope vaccine for SARS-CoV-2 virus. The human population coverage, antigenicity, allergenicity, toxicity, physicochemical properties and secondary structure of the designed vaccine are evaluated via state-of-the-art bioinformatic approaches, showing good quality of the designed vaccine. The 3D structure of the designed vaccine is predicted, refined and validated by in silico tools. Finally, we optimize and insert the codon sequence into a plasmid to ensure the cloning and expression efficiency. In conclusion, this proposed artificial intelligence (AI) based vaccine discovery framework accelerates the vaccine design process and constructs a 694aa multi-epitope vaccine containing 16 B-cell epitopes, 82 CTL epitopes and 89 HTL epitopes, which is promising to fight the SARS-CoV-2 viral infection and can be further evaluated in clinical studies. Moreover, we trace the RNA mutations of the SARS-CoV-2 and ensure that the designed vaccine can tackle the recent RNA mutations of the virus.
The Drosophila Forkhead/Fox transcription factor Jumeau mediates specific cardiac progenitor cell divisions by regulating expression of the kinesin Nebbish
Authors: Kump Andrew J. , Panta Manoj , Schwab Kristopher R. , Inlow Mark H. , Ahmad Shaad M. 
Published: February 2021

AbstractForkhead (Fkh/Fox) domain transcription factors (TFs) mediate multiple cardiogenic processes in both mammals and Drosophila. We showed previously that the Drosophila Fox gene jumeau (jumu) controls three categories of cardiac progenitor cell division—asymmetric, symmetric, and cell division at an earlier stage—by regulating Polo kinase activity, and mediates the latter two categories in concert with the TF Myb. Those observations raised the question of whether other jumu-regulated genes also mediate all three categories of cardiac progenitor cell division or a subset thereof. By comparing microarray-based expression profiles of wild-type and jumu loss-of-function mesodermal cells, we identified nebbish (neb), a kinesin-encoding gene activated by jumu. Phenotypic analysis shows that neb is required for only two categories of jumu-regulated cardiac progenitor cell division: symmetric and cell division at an earlier stage. Synergistic genetic interactions between neb, jumu, Myb, and polo and the rescue of jumu mutations by ectopic cardiac mesoderm-specific expression of neb demonstrate that neb is an integral component of a jumu-regulated subnetwork mediating cardiac progenitor cell divisions. Our results emphasize the central role of Fox TFs in cardiogenesis and illustrate how a single TF can utilize different combinations of other regulators and downstream effectors to control distinct developmental processes.
Lipid tethering of breast tumor cells reduces cell aggregation during mammosphere formation
Authors: Bhandary Lekhana , Bailey Patrick C. , Chang Katarina T. , Underwood Karen F. , Lee Cornell J. , Whipple Rebecca A. , Jewell Christopher M. , Ory Eleanor , Thompson Keyata N. , Ju Julia A. , Mathias Trevor M. , Pratt Stephen J. P. , Vitolo Michele I. , Martin Stuart S. 
Published: February 2021

AbstractMammosphere assays are widely used in vitro to identify prospective cancer-initiating stem cells that can propagate clonally to form spheres in free-floating conditions. However, the traditional mammosphere assay inevitably introduces cell aggregation that interferes with the measurement of true mammosphere forming efficiency. We developed a method to reduce tumor cell aggregation and increase the probability that the observed mammospheres formed are clonal in origin. Tethering individual tumor cells to lipid anchors prevents cell drift while maintaining free-floating characteristics. This enables real-time monitoring of single tumor cells as they divide to form mammospheres. Monitoring tethered breast cancer cells provided detailed size information that correlates directly to previously published single cell tracking data. We observed that 71% of the Day 7 spheres in lipid-coated wells were between 50 and 150 μm compared to only 37% in traditional low attachment plates. When an equal mixture of MCF7-GFP and MCF7-mCherry cells were seeded, 65% of the mammospheres in lipid-coated wells demonstrated single color expression whereas only 32% were single-colored in low attachment wells. These results indicate that using lipid tethering for mammosphere growth assays can reduce the confounding factor of cell aggregation and increase the formation of clonal mammospheres.
Human, animal, water source interactions and leptospirosis in Thailand
Authors: Narkkul Udomsak , Thaipadungpanit Janjira , Srisawat Nattachai , Rudge James W. , Thongdee Metawee , Pawarana Rungrawee , Pan-ngum Wirichada 
Published: February 2021

AbstractIn Thailand, leptospirosis is primarily associated with those who work in agricultural occupations. Leptospirosis control is hampered by a poor understanding of the complex interactions between humans, animal reservoirs, Leptospira, and the variable spatial environment in which these factors coexist. We aimed to address key knowledge gaps concerning leptospirosis disease dynamics and the human–animal–water-source interface in two high-risk areas in Thailand. We conducted a cross-sectional survey among 746 study participants in two high-risk areas for leptospirosis in Thailand: Sisaket (SSK) and Nakhon Si Thammarat (NST). Interactions among humans, animals and water sources were quantified and analyzed. The presence of different animal species and thus contact patterns were different in NST and SSK. The consumption of water from the shared sources between the two areas was different. Those whose occupations were related to animals or environmental water and those who consumed water from more than two sources were more likely to have been infected with leptospirosis, with adjusted odds ratios 4.31 (95% CI 1.17–15.83) and 10.74 (95% CI 2.28–50.53), respectively. Understanding specific water-source sharing networks and human–animal contact patterns is useful when designing national and area-specific control programmes to prevent and control leptospirosis outbreaks.
Differentiation of physical and chemical cross-linking in gelatin methacryloyl hydrogels
Authors: Rebers Lisa , Reichsöllner Raffael , Regett Sophia , Tovar Günter E. M. , Borchers Kirsten , Baudis Stefan , Southan Alexander 
Published: February 2021

AbstractGelatin methacryloyl (GM) hydrogels have been investigated for almost 20 years, especially for biomedical applications. Recently, strengthening effects of a sequential cross-linking procedure, whereby GM hydrogel precursor solutions are cooled before chemical cross-linking, were reported. It was hypothesized that physical and enhanced chemical cross-linking of the GM hydrogels contribute to the observed strengthening effects. However, a detailed investigation is missing so far. In this contribution, we aimed to reveal the impact of physical and chemical cross-linking on strengthening of sequentially cross-linked GM and gelatin methacryloyl acetyl (GMA) hydrogels. We investigated physical and chemical cross-linking of three different GM(A) derivatives (GM10, GM2A8 and GM2), which provided systematically varied ratios of side-group modifications. GM10 contained the highest methacryloylation degree (DM), reducing its ability to cross-link physically. GM2 had the lowest DM and showed physical cross-linking. The total modification degree, determining the physical cross-linking ability, of GM2A8 was comparable to that of GM10, but the chemical cross-linking ability was comparable to GM2. At first, we measured the double bond conversion (DBC) kinetics during chemical GM(A) cross-linking quantitatively in real-time via near infrared spectroscopy-photorheology and showed that the DBC decreased due to sequential cross-linking. Furthermore, results of circular dichroism spectroscopy and differential scanning calorimetry indicated gelation and conformation changes, which increased storage moduli of all GM(A) hydrogels due to sequential cross-linking. The data suggested that the total cross-link density determines hydrogel stiffness, regardless of the physical or chemical nature of the cross-links.
Molecular characterization of atherosclerosis in HIV positive persons
Authors: Cornwell Adam , Palli Rohith , Singh Meera V. , Benoodt Lauren , Tyrell Alicia , Abe Jun-ichi , Schifitto Giovanni , Maggirwar Sanjay B. , Thakar Juilee 
Published: February 2021

AbstractPeople living with HIV are at higher risk of atherosclerosis (AS). The pathogenesis of this risk is not fully understood. To assess the regulatory networks involved in AS we sequenced mRNA of the peripheral blood mononuclear cells (PBMCs) and measured cytokine and chemokine levels in the plasma of 13 persons living with HIV and 12 matched HIV-negative persons with and without AS. microRNAs (miRNAs) are known to play a role in HIV infection and may modulate gene regulation to drive AS. Hence, we further assessed miRNA expression in PBMCs of a subset of 12 HIV+ people with and without atherosclerosis. We identified 12 miRNAs differentially expressed between HIV+ AS+ and HIV+ , and validated 5 of those by RT-qPCR. While a few of these miRNAs have been implicated in HIV and atherosclerosis, others are novel. Integrating miRNA measurements with mRNA, we identified 27 target genes including SLC4A7, a critical sodium and bicarbonate transporter, that are potentially dysregulated during atherosclerosis. Additionally, we uncovered that levels of plasma cytokines were associated with transcription factor activity and miRNA expression in PBMCs. For example, BACH2 activity was associated with IL-1β, IL-15, and MIP-1α. IP10 and TNFα levels were associated with miR-124-3p. Finally, integration of all data types into a single network revealed increased importance of miRNAs in network regulation of the HIV+ group in contrast with increased importance of cytokines in the HIV+ AS+ group.
Rats show direct reciprocity when interacting with multiple partners
Authors: Kettler Nina , Schweinfurth Manon K. , Taborsky Michael 
Published: February 2021

AbstractDirect reciprocity, where individuals apply the decision rule ‘help someone who has helped you’, is believed to be rare in non-human animals due to its high cognitive demands. Especially if previous encounters with several partners need to be correctly remembered, animals might either stop reciprocating favours previously received from an individual, or switch to the simpler generalized reciprocity mechanism. Here we tested the decision rules Norway rats apply when interacting with multiple partners before being able to return received help. In a sequential prisoner’s dilemma situation, focal subjects encountered four different partners that were either helpful or not, on four consecutive days. On the fifth day, the focal subject was paired with one of the previous four partners and given the opportunity to provide it with food. The focal rats returned received help by closely matching the quantity of help their partner had previously provided, independently of the time delay between received and given help, and independently of the ultimate interaction preceding the test. This shows that direct reciprocity is not limited to dyadic situations in Norway rats, suggesting that cognitive demands involved in applying the required decision rules can be met by non-human animals even when they interact with multiple partners differing in helping propensity.
N-linked glycosylation enzymes in the diatom Thalassiosira oceanica exhibit a diel cycle in transcript abundance and favor for NXT-type sites
Authors: Behnke Joerg , Cohen Alejandro M. , LaRoche Julie 
Published: February 2021

AbstractN-linked glycosylation is a posttranslational modification affecting protein folding and function. The N-linked glycosylation pathway in algae is poorly characterized, and further knowledge is needed to understand the cell biology of algae and the evolution of N-linked glycosylation. This study investigated the N-linked glycosylation pathway in Thalassiosira oceanica, an open ocean diatom adapted to survive at growth-limiting iron concentrations. Here we identified and annotated the genes coding for the essential enzymes involved in the N-linked glycosylation pathway of T. oceanica. Transcript levels for genes coding for calreticulin, oligosaccharyltransferase (OST), N-acetylglucosaminyltransferase (GnT1), and UDP-glucose glucosyltransferase (UGGT) under high- and low-iron growth conditions revealed diel transcription patterns with a significant decrease of calreticulin and OST transcripts under iron-limitation. Solid-phase extraction of N-linked glycosylated peptides (SPEG) revealed 118 N-linked glycosylated peptides from cells grown in high- and low-iron growth conditions. The identified peptides had 81% NXT-type motifs, with X being any amino acids except proline. The presence of N-linked glycosylation sites in the iron starvation-induced protein 1a (ISIP1a) confirmed its predicted topology, contributing to the biochemical characterization of ISIP1 proteins. Analysis of extensive oceanic gene databases showed a global distribution of calreticulin, OST, and UGGT, reinforcing the importance of glycosylation in microalgae.
Low-dose exposure of glyphosate-based herbicides disrupt the urine metabolome and its interaction with gut microbiota
Authors: Hu Jianzhong , Lesseur Corina , Miao Yu , Manservisi Fabiana , Panzacchi Simona , Mandrioli Daniele , Belpoggi Fiorella , Chen Jia , Petrick Lauren 
Published: February 2021

AbstractGlyphosate-based herbicides (GBHs) can disrupt the host microbiota and influence human health. In this study, we explored the potential effects of GBHs on urinary metabolites and their interactions with gut microbiome using a rodent model. Glyphosate and Roundup (equal molar for glyphosate) were administered at the USA glyphosate ADI guideline (1.75 mg/kg bw/day) to the dams and their pups. The urine metabolites were profiled using non-targeted liquid chromatography—high resolution mass spectrometry (LC-HRMS). Our results found that overall urine metabolite profiles significantly differed between dams and pups and between female and male pups. Specifically, we identified a significant increase of homocysteine, a known risk factor of cardiovascular disease in both Roundup and glyphosate exposed pups, but in males only. Correlation network analysis between gut microbiome and urine metabolome pointed to Prevotella to be negatively correlated with the level of homocysteine. Our study provides initial evidence that exposures to commonly used GBH, at a currently acceptable human exposure dose, is capable of modifying urine metabolites in both rat adults and pups. The link between Prevotella-homocysteine suggests the potential role of GBHs in modifying the susceptibility of homocysteine, which is a metabolite that has been dysregulated in related diseases like cardiovascular disease or inflammation, through commensal microbiome.
Variable selection methods for predicting clinical outcomes following allogeneic hematopoietic cell transplantation
Authors: Pasin Chloé , Moy Ryan H. , Reshef Ran , Yates Andrew J. 
Published: February 2021

AbstractAllogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative procedure for a large number of diseases. However, the greatest barriers to the success of allo-HCT are relapse and graft-versus-host-disease (GVHD). Many studies have examined the reconstitution of the immune system after allo-HCT and searched for factors associated with clinical outcome. Serum biomarkers have also been studied to predict the incidence and prognosis of GVHD. However, the use of multiparametric immunophenotyping has been less extensively explored: studies usually focus on preselected and predefined cell phenotypes and so do not fully exploit the richness of flow cytometry data. Here we aimed to identify cell phenotypes present 30 days after allo-HCT that are associated with clinical outcomes in 37 patients participating in a trial relating to the prevention of GVHD, derived from 82 flow cytometry markers and 13 clinical variables. To do this we applied variable selection methods in a competing risks modeling framework, and identified specific subsets of T, B, and NK cells associated with relapse. Our study demonstrates the value of variable selection methods for mining rich, high dimensional clinical data and identifying potentially unexplored cell subpopulations of interest.
Genome-scale phylogenetic analyses confirm Olpidium as the closest living zoosporic fungus to the non-flagellated, terrestrial fungi
Authors: Chang Ying , Rochon D’Ann , Sekimoto Satoshi , Wang Yan , Chovatia Mansi , Sandor Laura , Salamov Asaf , Grigoriev Igor V. , Stajich Jason E. , Spatafora Joseph W. 
Published: February 2021

AbstractThe zoosporic obligate endoparasites,Olpidium,hold a pivotal position to the reconstruction of the flagellum loss in fungi, one of the key morphological transitions associated with the colonization of land by the early fungi. We generated genome and transcriptome data from non-axenic zoospores ofOlpidium bornovanusand used a metagenome approach to extract phylogenetically informative fungal markers. Our phylogenetic reconstruction strongly supportedOlpidiumas the closest zoosporic relative of the non-flagellated terrestrial fungi. Super-alignment analyses resolvedOlpidiumas sister to the non-flagellated terrestrial fungi, whereas a super-tree approach recovered different placements ofOlpidium,but without strong support. Further investigations detected little conflicting signal among the sampled markers but revealed a potential polytomy in early fungal evolution associated with the branching order amongOlpidium, Zoopagomycota and Mucoromycota. The branches defining the evolutionary relationships of these lineages were characterized by short branch lengths and low phylogenetic content and received equivocal support for alternative phylogenetic hypotheses from individual markers. These nodes were marked by important morphological innovations, including the transition to hyphal growth and the loss of flagellum, which enabled early fungi to explore new niches and resulted in rapid and temporally concurrent Precambrian diversifications of the ancestors of several phyla of fungi.
Lipidomic analysis of facial skin surface lipid reveals the causes of pregnancy-related skin barrier weakness
Authors: Yang Manli , Zhou Mingyue , Li Yuan , Huang Hong , Jia Yan 
Published: February 2021

AbstractSelf-reported skin discomfort is a common problem during pregnancy, but it is not clear whether skin barrier function is altered in the process. Few studies have described the skin barrier function during pregnancy. In this work, we used highly sensitive and high-resolution ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) to distinguish skin surface lipid (SSL) combined with multivariate analysis of lipids and metabolic changes to determine the relationship between SSL changes and skin physiology during pregnancy in order to better understand the skin condition of pregnant women. The results showed a significant reduction in the total lipid content in pregnant women. A total of 2270 lipids were detected, and the relative abundances of fatty acyls and glycerolipids were significantly reduced, while glycerophospholipids (GPs), sphingolipids, and saccharolipids was significantly increased in the pregnancy group. Multivariate data analysis indicated that 23 entities constituted the most important individual species responsible for the discrimination and phosphatidylcholine was the most abundant lipid in pregnancy group. In addition, compared to SSL profile of control group, it was observed that the average chain length of ceramides and fatty acids both decreased in SSL profile of pregnancy group. The main and most commonly affected pathway was that of GP pathways. These findings indicate that skin lipids are significantly altered in mid-pregnancy compared to the control group. Changes in ostrogen during pregnancy also make the skin more susceptible to inflammatory factors and lead to more fragile and susceptible skin, weakening the skin barrier along with the lipid alterations.