bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prioritizing antiviral drugs against SARS-CoV-2 by integrating viral complete genome sequences and drug chemical structures
Authors: Peng Lihong , Shen Ling , Xu Junlin , Tian Xiongfei , Liu Fuxing , Wang Juanjuan , Tian Geng , Yang Jialiang , Zhou Liqian 
Published: March 2021

AbstractThe outbreak of a novel febrile respiratory disease called COVID-19, caused by a newfound coronavirus SARS-CoV-2, has brought a worldwide attention. Prioritizing approved drugs is critical for quick clinical trials against COVID-19. In this study, we first manually curated three Virus-Drug Association (VDA) datasets. By incorporating VDAs with the similarity between drugs and that between viruses, we constructed a heterogeneous Virus-Drug network. A novel Random Walk with Restart method (VDA-RWR) was then developed to identify possible VDAs related to SARS-CoV-2. We compared VDA-RWR with three state-of-the-art association prediction models based on fivefold cross-validations (CVs) on viruses, drugs and virus-drug associations on three datasets. VDA-RWR obtained the best AUCs for the three fivefold CVs, significantly outperforming other methods. We found two small molecules coming together on the three datasets, that is, remdesivir and ribavirin. These two chemical agents have higher molecular binding energies of − 7.0 kcal/mol and − 6.59 kcal/mol with the domain bound structure of the human receptor angiotensin converting enzyme 2 (ACE2) and the SARS-CoV-2 spike protein, respectively. Interestingly, for the first time, experimental results suggested that navitoclax could be potentially applied to stop SARS-CoV-2 and remains to further validation.
Sparsely methylated mitochondrial cell free DNA released from cardiomyocytes contributes to systemic inflammatory response accompanied by atrial fibrillation
Authors: Yamazoe Masahiro , Sasano Tetsuo , Ihara Kensuke , Takahashi Kentaro , Nakamura Wakana , Takahashi Naomi , Komuro Hiroaki , Hamada Satomi , Furukawa Tetsushi 
Published: March 2021

AbstractSystemic inflammation is assumed to be the consequence and the cause of atrial fibrillation (AF); however, the underlying mechanism remains unclear. We aimed to evaluate the level of cell-free DNA (cfDNA) in patients with AF and AF mimicking models, and to illuminate its impact on inflammation. Peripheral blood was obtained from 54 patients with AF and 104 non-AF controls, and cfDNA was extracted. We extracted total cfDNA from conditioned medium after rapid pacing to HL-1 cells. Nuclear and mitochondrial DNA were separately extracted and fragmented to simulate nuclear-cfDNA (n-cfDNA) and mitochondrial-cfDNA (mt-cfDNA). The AF group showed higher cfDNA concentration than the non-AF group (12.6 [9.0–17.1] vs. 8.1 [5.3–10.8] [ng/mL], p < 0.001). The copy numbers of n-cfDNA and mt-cfDNA were higher in AF groups than in non-AF groups; the difference of mt-cfDNA was particularly apparent (p = 0.011 and p < 0.001, respectively). Administration of total cfDNA and mt-cfDNA to macrophages significantly promoted IL-1β and IL-6 expression through TLR9, whereas n-cfDNA did not. Induction of cytokine expression by methylated mt-cfDNA was lower than that by unmethylated mt-cfDNA. Collectively, AF was associated with an increased cfDNA level, especially mt-cfDNA. Sparsely methylated mt-cfDNA released from cardiomyocytes may be involved in sterile systemic inflammation accompanied by AF.
Computational evidence for nitro derivatives of quinoline and quinoline N-oxide as low-cost alternative for the treatment of SARS-CoV-2 infection
Authors: Assis Letícia C. , de Castro Alexandre A. , de Jesus João P. A. , Nepovimova Eugenie , Kuca Kamil , Ramalho Teodorico C. , La Porta Felipe A. 
Published: March 2021

AbstractA new and more aggressive strain of coronavirus, known as SARS-CoV-2, which is highly contagious, has rapidly spread across the planet within a short period of time. Due to its high transmission rate and the significant time–space between infection and manifestation of symptoms, the WHO recently declared this a pandemic. Because of the exponentially growing number of new cases of both infections and deaths, development of new therapeutic options to help fight this pandemic is urgently needed. The target molecules of this study were the nitro derivatives of quinoline and quinoline N-oxide. Computational design at the DFT level, docking studies, and molecular dynamics methods as a well-reasoned strategy will aid in elucidating the fundamental physicochemical properties and molecular functions of a diversity of compounds, directly accelerating the process of discovering new drugs. In this study, we discovered isomers based on the nitro derivatives of quinoline and quinoline N-oxide, which are biologically active compounds and may be low-cost alternatives for the treatment of infections induced by SARS-CoV-2.
Integrated multi-omics analysis of ovarian cancer using variational autoencoders
Authors: Hira Muta Tah , Razzaque M. A. , Angione Claudio , Scrivens James , Sawan Saladin , Sarker Mosharraf 
Published: March 2021

AbstractCancer is a complex disease that deregulates cellular functions at various molecular levels (e.g., DNA, RNA, and proteins). Integrated multi-omics analysis of data from these levels is necessary to understand the aberrant cellular functions accountable for cancer and its development. In recent years, Deep Learning (DL) approaches have become a useful tool in integrated multi-omics analysis of cancer data. However, high dimensional multi-omics data are generally imbalanced with too many molecular features and relatively few patient samples. This imbalance makes a DL based integrated multi-omics analysis difficult. DL-based dimensionality reduction technique, including variational autoencoder (VAE), is a potential solution to balance high dimensional multi-omics data. However, there are few VAE-based integrated multi-omics analyses, and they are limited to pancancer. In this work, we did an integrated multi-omics analysis of ovarian cancer using the compressed features learned through VAE and an improved version of VAE, namely Maximum Mean Discrepancy VAE (MMD-VAE). First, we designed and developed a DL architecture for VAE and MMD-VAE. Then we used the architecture for mono-omics, integrated di-omics and tri-omics data analysis of ovarian cancer through cancer samples identification, molecular subtypes clustering and classification, and survival analysis. The results show that MMD-VAE and VAE-based compressed features can respectively classify the transcriptional subtypes of the TCGA datasets with an accuracy in the range of 93.2-95.5% and 87.1-95.7%. Also, survival analysis results show that VAE and MMD-VAE based compressed representation of omics data can be used in cancer prognosis. Based on the results, we can conclude that (i) VAE and MMD-VAE outperform existing dimensionality reduction techniques, (ii) integrated multi-omics analyses perform better or similar compared to their mono-omics counterparts, and (iii) MMD-VAE performs better than VAE in most omics dataset.
Acetic-acid-induced jasmonate signaling in root enhances drought avoidance in rice
Authors: Ogawa Daisuke , Suzuki Yuya , Yokoo Takayuki , Katoh Etsuko , Teruya Miyu , Muramatsu Masayuki , Ma Jian Feng , Yoshida Yuri , Isaji Shunsaku , Ogo Yuko , Miyao Mitsue , Kim Jong-Myong , Kojima Mikiko , Takebayashi Yumiko , Sakakibara Hitoshi , Takeda Shin , Okada Kazunori , Mori Naoki , Seki Motoaki , Habu Yoshiki 
Published: March 2021

AbstractConferring drought resistant traits to crops is one of the major aims of current breeding programs in response to global climate changes. We previously showed that exogenous application of acetic acid to roots of various plants could induce increased survivability under subsequent drought stress conditions, but details of the metabolism of exogenously applied acetic acid, and the nature of signals induced by its application, have not been unveiled. In this study, we show that rice rapidly induces jasmonate signaling upon application of acetic acid, resulting in physiological changes similar to those seen under drought. The major metabolite of the exogenously applied acetic acid in xylem sap was determined as glutamine—a common and abundant component of xylem sap—indicating that acetic acid is not the direct agent inducing the observed physiological responses in shoots. Expression of drought-responsive genes in shoot under subsequent drought conditions was attenuated by acetic acid treatment. These data suggest that acetic acid activates root-to-shoot jasmonate signals that partially overlap with those induced by drought, thereby conferring an acclimated state on shoots prior to subsequent drought.
Controlling metal–insulator transitions in reactively sputtered vanadium sesquioxide thin films through structure and stoichiometry
Authors: Thorsteinsson Einar B. , Shayestehaminzadeh Seyedmohammad , Ingason Arni S. , Magnus Fridrik , Arnalds Unnar B. 
Published: March 2021

AbstractWe present a study of $$\hbox {V}_{2}\hbox {O}_{3}$$

V
2

O
3

thin films grown on c-plane $$\hbox {Al}_{2}\hbox {O}_{3}$$

Al
2

O
3

substrates by reactive dc-magnetron sputtering. Our results reveal three distinct types of films displaying different metal–insulator transitions dependent on the growth conditions. We observe a clear temperature window, spanning 200 $$^{\circ }$$

∘

C, where highly epitaxial films of $$\hbox {V}_{2}\hbox {O}_{3}$$

V
2

O
3

can be obtained wherein the transition can be tuned by controlling the amount of interstitial oxygen in the films through the deposition conditions. Although small structural variations are observed within this window, large differences are observed in the electrical properties of the films with strong differences in the magnitude and temperature of the metal–insulator transition which we attribute to small changes in the stoichiometry and local strain in the films. Altering the sputtering power we are able to tune the characteristics of the metal–insulator transition suppressing and shifting the transition to lower temperatures as the power is reduced. Combined results for all the films fabricated for the study show a preferential increase in the a lattice parameter and reduction in the c lattice parameter with reduced deposition temperature with the film deviating from a constant volume unit cell to a higher volume.
Suppressing the impact of the COVID-19 pandemic using controlled testing and isolation
Authors: Cohen Kobi , Leshem Amir 
Published: March 2021

AbstractThe Corona virus disease has significantly affected lives of people around the world. Existing quarantine policies led to large-scale lock-downs because of the slow tracking of the infection paths, and indeed we see new waves of the disease. This can be solved by contact tracing combined with efficient testing policies. Since the number of daily tests is limited, it is crucial to exploit them efficiently to improve the outcome of contact tracing (technological or human-based epidemiological investigations). We develop a controlled testing framework to achieve this goal. The key is to test individuals with high probability of being infected to identify them before symptoms appear. These probabilities are updated based on contact tracing and test results. We demonstrate that the proposed method could reduce the quarantine and morbidity rates compared to existing methods by up to a 50%. The results clearly demonstrate the necessity of accelerating the epidemiological investigations by using technological contact tracing. Furthermore, proper use of the testing capacity using the proposed controlled testing methodology leads to significantly improved results under both small and large testing capacities. We also show that for small new outbreaks controlled testing can prevent the large spread of new waves. Author contributions statement: The authors contributed equally to this work, including conceptualization, analysis, methodology, software, and drafting the work.
Global network analysis in Schizosaccharomyces pombe reveals three distinct consequences of the common 1-kb deletion causing juvenile CLN3 disease
Authors: Minnis Christopher J. , Townsend StJohn , Petschnigg Julia , Tinelli Elisa , Bähler Jürg , Russell Claire , Mole Sara E. 
Published: March 2021

AbstractJuvenile CLN3 disease is a recessively inherited paediatric neurodegenerative disorder, with most patients homozygous for a 1-kb intragenic deletion in CLN3. The btn1 gene is the Schizosaccharomyces pombe orthologue of CLN3. Here, we have extended the use of synthetic genetic array (SGA) analyses to delineate functional signatures for two different disease-causing mutations in addition to complete deletion of btn1. We show that genetic-interaction signatures can differ for mutations in the same gene, which helps to dissect their distinct functional effects. The mutation equivalent to the minor transcript arising from the 1-kb deletion (btn1102–208del) shows a distinct interaction pattern. Taken together, our results imply that the minor 1-kb deletion transcript has three consequences for CLN3: to both lose and retain some inherent functions and to acquire abnormal characteristics. This has particular implications for the therapeutic development of juvenile CLN3 disease. In addition, this proof of concept could be applied to conserved genes for other mendelian disorders or any gene of interest, aiding in the dissection of their functional domains, unpacking the global consequences of disease pathogenesis, and clarifying genotype–phenotype correlations. In doing so, this detail will enhance the goals of personalised medicine to improve treatment outcomes and reduce adverse events.
4-methylumbelliferone-mediated polarization of M1 macrophages correlate with decreased hepatocellular carcinoma aggressiveness in mice
Authors: Rodríguez Marcelo M. , Onorato Agostina , Cantero María José , Domínguez Luciana , Bayo Juan , Fiore Esteban , García Mariana , Atorrasagasti Catalina , Canbay Ali , Malvicini Mariana , Mazzolini Guillermo D. 
Published: March 2021

AbstractHepatocellular carcinoma (HCC) arises in the setting of advanced liver fibrosis, a dynamic and complex inflammatory disease. The tumor microenvironment (TME) is a mixture of cellular components including cancer cells, cancer stem cells (CSCs), tumor-associated macrophages (TAM), and dendritic cells (DCs), which might drive to tumor progression and resistance to therapies. In this work, we study the effects of 4-methylumbelliferone (4Mu) on TME and how this change could be exploited to promote a potent immune response against HCC. First, we observed that 4Mu therapy induced a switch of hepatic macrophages (Mϕ) towards an M1 type profile, and HCC cells (Hepa129 cells) exposed to conditioned medium (CM) derived from Mϕ treated with 4Mu showed reduced expression of several CSCs markers and aggressiveness. HCC cells incubated with CM derived from Mϕ treated with 4Mu grew in immunosuppressed mice while presented delayed tumor progression in immunocompetent mice. HCC cells treated with 4Mu were more susceptible to phagocytosis by DCs, and when DCs were pulsed with HCC cells previously treated with 4Mu displayed a potent antitumoral effect in therapeutic vaccination protocols. In conclusion, 4Mu has the ability to modulate TME into a less hostile milieu and to potentiate immunotherapeutic strategies against HCC.
Quantification of Phytophthora infestans population densities and their changes in potato field soil using real-time PCR
Authors: Osawa Hisashi , Suzuki Nobuyuki , Akino Seishi , Araki Hiromichi , Asano Kenji , Akai Kotaro , Kondo Norio 
Published: March 2021

AbstractTuber infection of Phytophthora infestans often occurs at harvest. However, it is difficult to accurately estimate the population densities of P. infestans in soil, especially Japanese soil. In the present study, P. infestans DNA was extracted from soil samples using a modified CTAB-bead method and quantified using real-time PCR to accurately, rapidly and easily estimate the P. infestans population densities in upland soils in Japan. P. infestans was well quantified in eleven types of soil samples, including nine types of upland soils in Japan, that were artificially inoculated with a zoosporangia suspension. The amounts of P. infestans DNA estimated by the real-time PCR were proportional to the inoculum densities. In the non-controlled experimental potato field, P. infestans population densities in soil corresponded to the development of symptoms and were correlated with the number of lesions on the potato foliage. These results imply that the proposed real-time PCR assay is suitable for the estimation or monitoring of P. infestans population densities in upland soils in Japan. The population densities at the ridge bottoms were larger than those at any other location in commercial potato fields. These results were similar to those of a previous report using a bioassay. Moreover, a correlation between DNA quantity and inoculum potential was observed. In conclusion, the real-time PCR assay developed in this study is suitable for indirect estimation of the inoculum potential of P. infestans.
Exploring dementia and neuronal ceroid lipofuscinosis genes in 100 FTD-like patients from 6 towns and rural villages on the Adriatic Sea cost of Apulia
Authors: Sassi Celeste , Capozzo Rosa , Hammer Monia , Zecca Chiara , Federoff Monica , Blauwendraat Cornelis , Bernstein Nick , Ding Jinhui , Gibbs J. Raphael , Price Timothy , Singleton Andrew , Logroscino Giancarlo 
Published: March 2021

AbstractFrontotemporal dementia (FTD) refers to a complex spectrum of clinically and genetically heterogeneous disorders. Although fully penetrant mutations in several genes have been identified and can explain the pathogenic mechanisms underlying a great portion of the Mendelian forms of the disease, still a significant number of families and sporadic cases remains genetically unsolved. We performed whole exome sequencing in 100 patients with a late-onset and heterogeneous FTD-like clinical phenotype from Apulia and screened mendelian dementia and neuronal ceroid lipofuscinosis genes. We identified a nonsense mutation inSORL1VPS domain (p.R744X), in 2 siblings displaying AD with severe language problems and primary progressive aphasia and a near splice-site mutation inCLCN6(p.S116P) segregating with an heterogeneous phenotype, ranging from behavioural FTD to FTD with memory onset and to the logopenic variant of primary progressive aphasia in one family. Moreover 2 sporadic cases with behavioural FTD carried heterozygous mutations in theCSF1RTyrosin kinase flanking regions (p.E573K and p.R549H). By contrast, only a minority of patients carried pathogenicC9orf72repeat expansions (1%) and likely moderately pathogenic variants inGRN(p.C105Y, p.C389fs and p.C139R) (3%). In concert with recent studies, our findings support a common pathogenic mechanisms between FTD and neuronal ceroid lipofuscinosis and suggests that neuronal ceroid lipofuscinosis genes should be investigated also in dementia patients with predominant frontal symptoms and language impairments.
Adipose most abundant 2 protein is a predictive marker for cisplatin sensitivity in cancers
Authors: Kamimura Kenya , Suda Takeshi , Fukuhara Yasuo , Okuda Shujiro , Watanabe Yu , Yokoo Takeshi , Osaki Akihiko , Waguri Nobuo , Ishikawa Toru , Sato Toshihiro , Aoyagi Yutaka , Takamura Masaaki , Wakai Toshifumi , Terai Shuji 
Published: March 2021

AbstractCisplatin (CDDP) is one of the chemotherapeutic drugs being used to treat various cancers. Although effective in many cases, as high doses of CDDP cause cytotoxic effects that may worsen patients’ condition, therefore, a marker of sensitivity to CDDP is necessary to enhance the safety and efficiency of CDDP administration. This study focused on adipose most abundant 2 (APM2) to examine its potential as a marker of CDDP sensitivity. The relationship of APM2 expression with the mechanisms of CDDP resistance was examined in vitro and in vivo using hepatocellular carcinoma (HCC) cells, tissues and serum of HCC patients (n = 71) treated initially with intrahepatic arterial infusion of CDDP followed by surgical resection. The predictability of serum APM2 for CDDP sensitivity was assessed in additional 54 HCC patients and 14 gastric cancer (GC) patients. APM2 expression in CDDP-resistant HCC was significantly higher both in serum and the tissue. Bioinformatic analyses and histological analyses demonstrated upregulation of ERCC6L (DNA excision repair protein ERCC6-like) by APM2, which accounts for the degree of APM2 expression. The serum APM2 level and chemosensitivity for CDDP were assessed and cut-off value of serum APM2 for predicting the sensitivity to CDDP was determined to be 18.7 µg/mL. The value was assessed in HCC (n = 54) and GC (n = 14) patients for its predictability of CDDP sensitivity, resulted in predictive value of 77.3% and 100%, respectively. Our study demonstrated that APM2 expression is related to CDDP sensitivity and serum APM2 can be an effective biomarker of HCC and GC for determining the sensitivity to CDDP.Trial registration: This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000028487).
The undetected loss of aged carbon from boreal mineral soils
Authors: Hensgens Geert , Laudon Hjalmar , Johnson Mark S. , Berggren Martin 
Published: March 2021

AbstractThe boreal forest is among the largest terrestrial biomes on earth, storing more carbon (C) than the atmosphere. Due to rapid climatic warming and enhanced human development, the boreal region may have begun transitioning from a net C sink to a net source. This raises serious concern that old biogenic soil C can be re-introduced into the modern C cycle in near future. Combining bio-decay experiments, mixing models and the Keeling plot method, we discovered a distinct old pre-bomb organic carbon fraction with high biodegradation rate. In total, 34 ± 12% of water-extractable organic carbon (WEOC) in podzols, one of the dominating boreal soil types, consisted of aged (~ 1000 year) labile C. The omission of this aged (i.e., Δ14C depleted) WEOC fraction in earlier studies is due to the co-occurrence with Δ14C enriched modern C formed following 1950s nuclear bomb testing masking its existence. High lability of aged soil WEOC and masking effects of modern Δ14C enriched C suggests that the risk for mobilization and re-introduction of this ancient C pool into the modern C cycle has gone undetected. Our findings have important implications for earth systems models in terms of climate-carbon feedbacks and the future C balance of the boreal forest.