bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unsupervised and supervised learning with neural network for human transcriptome analysis and cancer diagnosis
Authors: Yuan Bo , Yang Dong , Rothberg Bonnie E. G. , Chang Hao , Xu Tian 
Published: November 2020

AbstractDeep learning analysis of images and text unfolds new horizons in medicine. However, analysis of transcriptomic data, the cause of biological and pathological changes, is hampered by structural complexity distinctive from images and text. Here we conduct unsupervised training on more than 20,000 human normal and tumor transcriptomic data and show that the resulting Deep-Autoencoder, DeepT2Vec, has successfully extracted informative features and embedded transcriptomes into 30-dimensional Transcriptomic Feature Vectors (TFVs). We demonstrate that the TFVs could recapitulate expression patterns and be used to track tissue origins. Trained on these extracted features only, a supervised classifier, DeepC, can effectively distinguish tumors from normal samples with an accuracy of 90% for Pan-Cancer and reach an average 94% for specific cancers. Training on a connected network, the accuracy is further increased to 96% for Pan-Cancer. Together, our study shows that deep learning with autoencoder is suitable for transcriptomic analysis, and DeepT2Vec could be successfully applied to distinguish cancers, normal tissues, and other potential traits with limited samples.
Chromosome-scale genome assembly for the duckweed Spirodela intermedia, integrating cytogenetic maps, PacBio and Oxford Nanopore libraries
Authors: Hoang Phuong T. N. , Fiebig Anne , Novák Petr , Macas Jiří , Cao Hieu X. , Stepanenko Anton , Chen Guimin , Borisjuk Nikolai , Scholz Uwe , Schubert Ingo 
Published: November 2020

AbstractDuckweeds are small, free-floating, morphologically highly reduced organisms belonging to the monocot order Alismatales. They display the most rapid growth among flowering plants, vary ~ 14-fold in genome size and comprise five genera. Spirodela is the phylogenetically oldest genus with only two mainly asexually propagating species: S. polyrhiza (2n = 40; 160 Mbp/1C) and S. intermedia (2n = 36; 160 Mbp/1C). This study combined comparative cytogenetics and de novo genome assembly based on PacBio, Illumina and Oxford Nanopore (ON) reads to obtain the first genome reference for S. intermedia and to compare its genomic features with those of the sister species S. polyrhiza. Both species’ genomes revealed little more than 20,000 putative protein-coding genes, very low rDNA copy numbers and a low amount of repetitive sequences, mainly Ty3/gypsy retroelements. The detection of a few new small chromosome rearrangements between both Spirodela species refined the karyotype and the chromosomal sequence assignment for S. intermedia.
Searching for target-specific and multi-targeting organics for Covid-19 in the Drugbank database with a double scoring approach
Authors: Murugan Natarajan Arul , Kumar Sanjiv , Jeyakanthan Jeyaraman , Srivastava Vaibhav 
Published: November 2020

AbstractThe current outbreak of Covid-19 infection due to SARS-CoV-2, a virus from the coronavirus family, has become a major threat to human healthcare. The virus has already infected more than 44 M people and the number of deaths reported has reached more than 1.1 M which may be attributed to lack of medicine. The traditional drug discovery approach involves many years of rigorous research and development and demands for a huge investment which cannot be adopted for the ongoing pandemic infection. Rather we need a swift and cost-effective approach to inhibit and control the viral infection. With the help of computational screening approaches and by choosing appropriate chemical space, it is possible to identify lead drug-like compounds for Covid-19. In this study, we have used the Drugbank database to screen compounds against the most important viral targets namely 3C-like protease (3CLpro), papain-like protease (PLpro), RNA-dependent RNA polymerase (RdRp) and the spike (S) protein. These targets play a major role in the replication/transcription and host cell recognition, therefore, are vital for the viral reproduction and spread of infection. As the structure based computational screening approaches are more reliable, we used the crystal structures for 3C-like main protease and spike protein. For the remaining targets, we used the structures based on homology modeling. Further, we employed two scoring methods based on binding free energies implemented in AutoDock Vina and molecular mechanics—generalized Born surface area approach. Based on these results, we propose drug cocktails active against the three viral targets namely 3CLpro, PLpro and RdRp. Interestingly, one of the identified compounds in this study i.e. Baloxavir marboxil has been under clinical trial for the treatment of Covid-19 infection. In addition, we have identified a few compounds such as Phthalocyanine, Tadalafil, Lonafarnib, Nilotinib, Dihydroergotamine, R-428 which can bind to all three targets simultaneously and can serve as multi-targeting drugs. Our study also included calculation of binding energies for various compounds currently under drug trials. Among these compounds, it is found that Remdesivir binds to targets, 3CLpro and RdRp with high binding affinity. Moreover, Baricitinib and Umifenovir were found to have superior target-specific binding while Darunavir is found to be a potential multi-targeting drug. As far as we know this is the first study where the compounds from the Drugbank database are screened against four vital targets of SARS-CoV-2 and illustrates that the computational screening using a double scoring approach can yield potential drug-like compounds against Covid-19 infection.
An individual participant data analysis of prospective cohort studies on the association between subclinical thyroid dysfunction and depressive symptoms
Authors: Wildisen Lea , Del Giovane Cinzia , Moutzouri Elisavet , Beglinger Shanthi , Syrogiannouli Lamprini , Collet Tinh-Hai , Cappola Anne R. , Åsvold Bjørn O. , Bakker Stephan J. L. , Yeap Bu B. , Almeida Osvaldo P. , Ceresini Graziano , Dullaart Robin P. F. , Ferrucci Luigi , Grabe Hans , Jukema J. Wouter , Nauck Matthias , Trompet Stella , Völzke Henry , Westendorp Rudi , Gussekloo Jacobijn , Klöppel Stefan , Aujesky Drahomir , Bauer Douglas , Peeters Robin , Feller Martin , Rodondi Nicolas 
Published: November 2020

AbstractIn subclinical hypothyroidism, the presence of depressive symptoms is often a reason for starting levothyroxine treatment. However, data are conflicting on the association between subclinical thyroid dysfunction and depressive symptoms. We aimed to examine the association between subclinical thyroid dysfunction and depressive symptoms in all prospective cohorts with relevant data available. We performed a systematic review of the literature from Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library from inception to 10th May 2019. We included prospective cohorts with data on thyroid status at baseline and depressive symptoms during follow-up. The primary outcome was depressive symptoms measured at first available follow-up, expressed on the Beck’s Depression Inventory (BDI) scale (range 0–63, higher values indicate more depressive symptoms, minimal clinically important difference: 5 points). We performed a two-stage individual participant data (IPD) analysis comparing participants with subclinical hypo- or hyperthyroidism versus euthyroidism, adjusting for depressive symptoms at baseline, age, sex, education, and income (PROSPERO CRD42018091627). Six cohorts met the inclusion criteria, with IPD on 23,038 participants. Their mean age was 60 years, 65% were female, 21,025 were euthyroid, 1342 had subclinical hypothyroidism and 671 subclinical hyperthyroidism. At first available follow-up [mean 8.2 (± 4.3) years], BDI scores did not differ between participants with subclinical hypothyroidism (mean difference = 0.29, 95% confidence interval =  − 0.17 to 0.76, I2 = 15.6) or subclinical hyperthyroidism (− 0.10, 95% confidence interval =  − 0.67 to 0.48, I2 = 3.2) compared to euthyroidism. This systematic review and IPD analysis of six prospective cohort studies found no clinically relevant association between subclinical thyroid dysfunction at baseline and depressive symptoms during follow-up. The results were robust in all sensitivity and subgroup analyses. Our results are in contrast with the traditional notion that subclinical thyroid dysfunction, and subclinical hypothyroidism in particular, is associated with depressive symptoms. Consequently, our results do not support the practice of prescribing levothyroxine in patients with subclinical hypothyroidism to reduce the risk of developing depressive symptoms.
Association between clustering of unhealthy lifestyle factors and risk of new-onset atrial fibrillation: a nationwide population-based study
Authors: Lee So-Ryoung , Choi Eue-Keun , Ahn Hyo-Jeong , Han Kyung-Do , Oh Seil , Lip Gregory Y. H. 
Published: November 2020

AbstractWe aimed to investigate the association between the combination of unhealthy lifestyle and risk of AF. Subjects aged 66 years who underwent health examination from 2009 to 2015 were included. The cohort was divided into 8 groups by the combination of unhealthy lifestyle including current smoking, heavy drinking (> 30 g/day), and lack of regular exercise, and followed up for new-onset AF till December 31, 2017. Among 1,719,401 subjects, 47,334 had incident AF (5.5 per 1000 person-years) during a 5-year mean follow-up period. Lack of regular exercise was the most powerful factor to be associated with a higher risk of AF as a single factor (adjusted hazard ratio 1.11, 95% confidence interval 1.08–1.13). Amongst combinations of two unhealthy lifestyle factors, current smoking with heavy drinking, lack of regular exercise with heavy drinking, and lack of regular exercise with current smoking were associated with a 6%, 15%, and 20% higher risks of AF, respectively. A cluster of three unhealthy lifestyle components was associated with a 22% higher risk of AF. Increased numbers of unhealthy lifestyle factors were associated with a higher risk of incident AF. These findings support the promotion of a healthy lifestyle to lower the risk of new-onset AF.
Hypoxia-inducible factor-2α is crucial for proper brain development
Authors: Kleszka Kira , Leu Tristan , Quinting Theresa , Jastrow Holger , Pechlivanis Sonali , Fandrey Joachim , Schreiber Timm 
Published: November 2020

AbstractSufficient tissue oxygenation is required for regular brain function; thus oxygen supply must be tightly regulated to avoid hypoxia and irreversible cell damage. If hypoxia occurs the transcription factor complex hypoxia-inducible factor (HIF) will accumulate and coordinate adaptation of cells to hypoxia. However, even under atmospheric O2 conditions stabilized HIF-2α protein was found in brains of adult mice. Mice with a neuro-specific knockout of Hif-2α showed a reduction of pyramidal neurons in the retrosplenial cortex (RSC), a brain region responsible for a range of cognitive functions, including memory and navigation. Accordingly, behavioral studies showed disturbed cognitive abilities in these mice. In search of the underlying mechanisms for the specific loss of pyramidal cells in the RSC, we found deficits in migration in neural stem cells from Hif-2α knockout mice due to altered expression patterns of genes highly associated with neuronal migration and positioning.
Evidence for a non-stochastic two-field hypothesis for persistent skin cancer risk
Authors: Konger Raymond L. , Ren Lu , Sahu Ravi P. , Derr-Yellin Ethel , Kim Young L. 
Published: November 2020

AbstractWith recurring carcinogen exposures, individual tumors develop in a field of genetic mutations through a stepwise process of clonal expansion and evolution. Once established, this “cancer field” persists in the absence of continued carcinogen exposures, resulting in a sustained risk for cancer development. Using a bioimaging approach, we previously demonstrated that a dermal premalignant field characterized by inflammatory angiogenesis persists following the cessation of ultraviolet light exposures and accurately predicts future overlying epidermal tumor formation. Following ultraviolet light treatments, others have observed that patches of p53 immunopositive cells persist stochastically throughout the epidermal stem cell population. However, these studies were done by random biopsies, introducing sampling bias. We now show that, rather than being randomly distributed, p53+ epidermal cells are enriched only in areas overlying this multi-focal dermal field. Moreover, we also show that the dermal field is characterized by a senescent phenotype. We propose that persistence of the overlying epithelial cancerization field in the absence of exogenous carcinogens or promoters requires a two-field composite consisting of a dermal senescent field driving the persistence of the overlying epidermal cancer field. These observations challenge current models that suggest that persistence of cancer risk in the absence of continued carcinogen exposures is simply a function of stochastically arranged, long-lived but dormant epithelial clonal stem cells mutants. The model proposed here could provide new insights into how cancer risk persists following cessation of carcinogenic exposures.
Potential involvement of Streptococcus mutans possessing collagen binding protein Cnm in infective endocarditis
Authors: Nomura Ryota , Otsugu Masatoshi , Hamada Masakazu , Matayoshi Saaya , Teramoto Noboru , Iwashita Naoki , Naka Shuhei , Matsumoto-Nakano Michiyo , Nakano Kazuhiko 
Published: November 2020

AbstractStreptococcus mutans, a significant contributor to dental caries, is occasionally isolated from the blood of patients with infective endocarditis. We previously showed that S. mutans strains expressing collagen-binding protein (Cnm) are present in the oral cavity of approximately 10–20% of humans and that they can effectively invade human umbilical vein endothelial cells (HUVECs). Here, we investigated the potential molecular mechanisms of HUVEC invasion by Cnm-positive S. mutans. The ability of Cnm-positive S. mutans to invade HUVECs was significantly increased by the presence of serum, purified type IV collagen, and fibrinogen (p < 0.001). Microarray analyses of HUVECs infected by Cnm-positive or -negative S. mutans strains identified several transcripts that were differentially upregulated during invasion, including those encoding the small G protein regulatory proteins ARHGEF38 and ARHGAP9. Upregulation of these proteins occurred during invasion only in the presence of serum. Knockdown of ARHGEF38 strongly reduced HUVEC invasion by Cnm-positive S. mutans. In a rat model of infective endocarditis, cardiac endothelial cell damage was more prominent following infection with a Cnm-positive strain compared with a Cnm-negative strain. These results suggest that the type IV collagen–Cnm–ARHGEF38 pathway may play a crucial role in the pathogenesis of infective endocarditis.
Palmitate and pyruvate carbon flux in response to choline and methionine in bovine neonatal hepatocytes
Authors: Chandler T. L. , Erb S. J. , Myers William A. , Deme Pragney , Haughey Norman J. , McFadden J. W. , White H. M. 
Published: November 2020

AbstractCholine and methionine may serve unique functions to alter hepatic energy metabolism. Our objective was to trace carbon flux through pathways of oxidation and glucose metabolism in bovine hepatocytes exposed to increasing concentrations of choline chloride (CC) and d,l-methionine (DLM). Primary hepatocytes were isolated from 4 Holstein calves and maintained for 24 h before treatment with CC (0, 10, 100, 1000 μmol/L) and DLM (0, 100, 300 μmol/L) in a factorial design. After 21 h, [1-14C]C16:0 or [2-14C]pyruvate was added to measure complete and incomplete oxidation, and cellular glycogen. Reactive oxygen species (ROS), cellular triglyceride (TG), and glucose and ß-hydroxybutyrate (BHB) export were quantified. Exported very-low density lipoprotein particles were isolated for untargeted lipidomics and to quantify TG. Interactions between CC and DLM, and contrasts for CC (0 vs. [10, 100, 1000 μmol/L] and linear and quadratic contrast 10, 100, 1000 μmol/L) and DLM (0 vs. [100, 300 μmol/L] and 100 vs. 300 μmol/L) were evaluated. Presence of CC increased complete oxidation of [1-14C]C16:0 and decreased BHB export. Glucose export was decreased, but cellular glycogen was increased by the presence of CC and increasing CC. Presence of CC decreased ROS and marginally decreased cellular TG. No interactions between CC and DLM were detected for these outcomes. These data suggest a hepato-protective role for CC to limit ROS and cellular TG accumulation, and to alter hepatic energy metabolism to support complete oxidation of FA and glycogen storage regardless of Met supply.
Graphene oxide/mussel foot protein composites for high-strength and ultra-tough thin films
Authors: Kim Eugene , Qin Xuyan , Qiao James B. , Zeng Qingqing , Fortner John D. , Zhang Fuzhong 
Published: November 2020

AbstractGraphene oxide (GO)-based composite materials have become widely popular in many applications due to the attractive properties of GO, such as high strength and high electrical conductivity at the nanoscale. Most current GO composites use organic polymer as the matrix material and thus, their synthesis suffers from the use of organic solvents or surfactants, which raise environmental and energy-consumption concerns. Inspired by mussel foot proteins (Mfp) secreted by the saltwater mussel, Mytilus galloprovincialis and by recent advances in microbial protein production, we developed an aqueous-based green synthesis strategy for preparing GO/Mfp film composites. These GO/Mfp films display high tensile strength (134–158 MPa), stretchability (~ 26% elongation), and high toughness (20–24 MJ/m3), beyond the capabilities of many existing GO composites. Renewable production of Mfp proteins and the facile fabrication process described provides a new avenue for composite material synthesis, while the unique combination of mechanical properties of GO/Mfp films will be attractive for a range of applications.
Ecological traits, genetic diversity and regional distribution of the macroalga Treptacantha elegans along the Catalan coast (NW Mediterranean Sea)
Authors: Medrano Alba , Hereu Bernat , Mariani Simone , Neiva João , Pagès-Escolà Marta , Paulino Cristina , Rovira Graciel·la , Serrão Ester A. , Linares Cristina 
Published: November 2020

AbstractThe widespread decline of canopy-forming macroalgal assemblages has been documented in many regions during the last decades. This pattern is often followed by the replacement of structurally complex algal canopies by more simplified habitats (e.g., turfs or sea urchin barren grounds). Against all odds, the fucoid Treptacantha elegans, a large Mediterranean brown macroalga, broadened its depth range to deeper and exposed environments and displayed an unexpected range expansion along the northern coast of Catalonia over the last two decades. Here, we reconstruct the spread of T. elegans in time and space and unravel ecological and demographic traits such as population dynamics and genetic patterns to provide a comprehensive and integrated view of the current status and geographical expansion for this species. Fast-growing dynamics, early fertile maturity, and high turnover rate are the main competitive advantages that allow the exposed populations of T. elegans to colonize available substrata and maintain dense and patchy populations. We also provided evidence that the deeper and exposed populations of T. elegans constitute a single group across the Catalan coast, with little genetic differentiation among populations. This seems to support the hypothesis of a unique source of spread in the last decades from the Medes Islands No-Take Zone towards both southern and northern waters.
Prediction of mitochondrial genome-wide variation through sequencing of mitochondrion-enriched extracts
Authors: Fisher Kelsey E. , Bradbury Steven P. , Coates Brad S. 
Published: November 2020

AbstractAlthough mitochondrial DNA (mtDNA) haplotype variation is often applied for estimating population dynamics and phylogenetic relationships, economical and generalized methods for entire mtDNA genome enrichment prior to high-throughput sequencing are not readily available. This study demonstrates the utility of differential centrifugation to enrich for mitochondrion within cell extracts prior to DNA extraction, short-read sequencing, and assembly using exemplars from eight maternal lineages of the insect species, Ostrinia nubilalis. Compared to controls, enriched extracts showed a significant mean increase of 48.2- and 86.1-fold in mtDNA based on quantitative PCR, and proportion of subsequent short sequence reads that aligned to the O. nubilalis reference mitochondrial genome, respectively. Compared to the reference genome, our de novo assembled O. nubilalis mitochondrial genomes contained 82 intraspecific substitution and insertion/deletion mutations, and provided evidence for correction of mis-annotated 28 C-terminal residues within the NADH dehydrogenase subunit 4. Comparison to a more recent O. nubilalis mtDNA assembly from unenriched short-read data analogously showed 77 variant sites. Twenty-eight variant positions, and a triplet ATT codon (Ile) insertion within ATP synthase subunit 8, were unique within our assemblies. This study provides a generalizable pipeline for whole mitochondrial genome sequence acquisition adaptable to applications across a range of taxa.
Hic-5 is required for activation of pancreatic stellate cells and development of pancreatic fibrosis in chronic pancreatitis
Authors: Gao Lin , Lei Xiao-Feng , Miyauchi Aya , Noguchi Masahito , Omoto Tomokatsu , Haraguchi Shogo , Miyazaki Takuro , Miyazaki Akira , Kim-Kaneyama Joo-ri 
Published: November 2020

AbstractAccumulated evidence suggests that activated pancreatic stellate cells (PSCs) serve as the main source of the extracellular matrix proteins accumulated under the pathological conditions leading to pancreatic fibrosis in chronic pancreatitis (CP). However, little is known about the mechanisms of PSC activation. PSCs have morphologic and functional similarities to hepatic stellate cells, which are activated by hydrogen peroxide-inducible clone-5 (Hic-5), a TGF-β1-induced protein. In this study, we investigated whether Hic-5 activates PSCs, which promote pancreatic fibrosis development in CP. Hic-5-knockout and wild type mice were subjected to caerulein injection to induce CP. Hic-5 expression was strongly upregulated in activated PSCs from human CP tissue and from mouse pancreatic fibrosis in caerulein-induced CP. Hic-5 deficiency significantly attenuated mouse pancreatic fibrosis and PSC activation in the experimental murine CP model. Mechanistically, Hic-5 knock down significantly inhibited the TGF-β/Smad2 signaling pathway, resulting in reduced collagen production and α-smooth muscle actin expression in the activated PSCs. Taken together, we propose Hic-5 as a potential marker of activated PSCs and a novel therapeutic target in CP treatment.