bluuebunny/crossref_metadata_2025 huggingface dataset:
The landscape of extrachromosomal circular DNA (eccDNA) in the normal hematopoiesis and leukemia evolution
Authors: Zeng Tiansheng , Huang Wenhui , Cui Longzhen , Zhu Pei , Lin Qing , Zhang Wenjuan , Li Junyi , Deng Cong , Wu Zhihua , Huang Zeyong , Zhang Zhiyong , Qian Tingting , Xie Wei , Xiao Min , Chen Yingyu , Fu Lin
Published: September 2022

Elevated extrachromosomal circular DNA (eccDNA) has been reported to accelerate tumor pathogenesis. Although the eccDNA profiles of other tumors have been established, the landscape of the eccDNA of acute myeloid leukemia (AML) has not been revealed. Our study first depicted the eccDNA profile of normal hematopoiesis and AML evolution by exploiting the ATAC-seq and RNA-seq data from nine healthy donors and 12 AML patients, which contained a total of 137 cell samples and 96 RNA-seq samples (including 16 blood cell types of the normal hematopoietic and AML hierarchies). We found the number of eccDNAs generally increased with the evolution of normal hematopoiesis and AML. The ecDNAs and ring chromosomes were found to reappear both in normal hematopoiesis and AML cells. Furthermore, we compared the eccDNAs of AML with normal cells. There were almost 300 AML-specific genes, including the known oncogenes NRAS, MCL1, EVI1, GATA2, WT1, and PAK1. And the ecDNA (chr11: 58668376-58826008) occurred in five out of 17 AML evolution-related cells, which was associated with the high expression of the GLYATL1 gene and the high expressed GLYATL1 was a poor prognostic factor. In conclusion, the eccDNA profiles of normal hematopoiesis and AML evolution were depicted and the recurrent eccDNAs we revealed might be utilized in the treatment of AML as biomarkers.
Regional gene expression signatures are associated with sex-specific functional connectivity changes in depression
Authors: Talishinsky Aleksandr , Downar Jonathan , Vértes Petra E. , Seidlitz Jakob , Dunlop Katharine , Lynch Charles J. , Whalley Heather , McIntosh Andrew , Vila-Rodriguez Fidel , Daskalakis Zafiris J. , Blumberger Daniel M. , Liston Conor
Published: September 2022

The neural substrates of depression may differ in men and women, but the underlying mechanisms are incompletely understood. Here, we show that depression is associated with sex-specific patterns of abnormal functional connectivity in the default mode network and in five regions of interest with sexually dimorphic transcriptional effects. Regional differences in gene expression in two independent datasets explained the neuroanatomical distribution of abnormal connectivity. These gene sets varied by sex and were strongly enriched for genes implicated in depression, synapse function, immune signaling, and neurodevelopment. In an independent sample, we confirmed the prediction that individual differences in default mode network connectivity are explained by inferred brain expression levels for six depression-related genes, includingPCDH8, a brain-specific protocadherin integral membrane protein implicated in activity-related synaptic reorganization. Together, our results delineate both shared and sex-specific changes in the organization of depression-related functional networks, with implications for biomarker development and fMRI-guided therapeutic neuromodulation.
Effect of booster vaccination against Delta and Omicron SARS-CoV-2 variants in Iceland
Authors: Norddahl Gudmundur L. , Melsted Pall , Gunnarsdottir Kristbjorg , Halldorsson Gisli H. , Olafsdottir Thorunn A. , Gylfason Arnaldur , Kristjansson Mar , Magnusson Olafur T. , Sulem Patrick , Gudbjartsson Daniel F. , Thorsteinsdottir Unnur , Jonsdottir Ingileif , Stefansson Kari
Published: September 2022

By the end of July 2021, the majority of the Icelandic population had received vaccination against COVID-19. In mid-July a wave of SARS-CoV-2 infections, dominated by the Delta variant, spread through the population, followed by an Omicron wave in December. A booster vaccination campaign was initiated to curb the spread of the virus. We estimate the risk of infection for different vaccine combinations using vaccination data from 276,028 persons and 963,557 qPCR tests for 277,687 persons. We measure anti-Spike-RBD antibody levels and ACE2-Spike binding inhibitory activity in 371 persons who received one of four recommended vaccination schedules with or without an mRNA vaccine booster. Overall, we find different antibody levels and inhibitory activity in recommended vaccination schedules, reflected in the observed risk of SARS-CoV-2 infections. We observe an increased protection following mRNA boosters, against both Omicron and Delta variant infections, although BNT162b2 boosters provide greater protection against Omicron than mRNA-1273 boosters.
Multi-context genetic modeling of transcriptional regulation resolves novel disease loci
Authors: Thompson Mike , Gordon Mary Grace , Lu Andrew , Tandon Anchit , Halperin Eran , Gusev Alexander , Ye Chun Jimmie , Balliu Brunilda , Zaitlen Noah
Published: September 2022

A majority of the variants identified in genome-wide association studies fall in non-coding regions of the genome, indicating their mechanism of impact is mediated via gene expression. Leveraging this hypothesis, transcriptome-wide association studies (TWAS) have assisted in both the interpretation and discovery of additional genes associated with complex traits. However, existing methods for conducting TWAS do not take full advantage of the intra-individual correlation inherently present in multi-context expression studies and do not properly adjust for multiple testing across contexts. We introduce CONTENT—a computationally efficient method with proper cross-context false discovery correction that leverages correlation structure across contexts to improve power and generate context-specific and context-shared components of expression. We apply CONTENT to bulk multi-tissue and single-cell RNA-seq data sets and show that CONTENT leads to a 42% (bulk) and 110% (single cell) increase in the number of genetically predicted genes relative to previous approaches. We find the context-specific component of expression comprises 30% of heritability in tissue-level bulk data and 75% in single-cell data, consistent with cell-type heterogeneity in bulk tissue. In the context of TWAS, CONTENT increases the number of locus-phenotype associations discovered by over 51% relative to previous methods across 22 complex traits.
Using MARSIS signal attenuation to assess the presence of South Polar Layered Deposit subglacial brines
Authors: Lauro Sebastian E. , Pettinelli Elena , Caprarelli Graziella , Baniamerian Jamaledin , Mattei Elisabetta , Cosciotti Barbara , Stillman David E. , Primm Katherine M. , Soldovieri Francesco , Orosei Roberto
Published: September 2022

Knowledge of the physical and thermal properties of the South Polar Layer Deposits (SPLD) is key to constrain the source of bright basal reflections at Ultimi Scopuli detected by the MARSIS (Mars Advanced Radar for Subsurface and Ionosphere Sounding) radar sounder. Here we present a detailed analysis of attenuation, based on data acquired by MARSIS at 3, 4, and 5 MHz. We show that attenuation is frequency dependent, and that its behavior is consistent throughout the entire region. This suggests that the SPLD are compositionally homogeneous at Ultimi Scopuli, and our results are consistent with dust contents of 5 to 12%. Using these values as input, and plausible estimates of surface temperature and heat flux, we inferred basal temperatures around 200 K: these are consistent with perchlorate brines within liquid vein networks as the source of the reflections. Furthermore, extrapolation of the attenuation to higher frequencies explains why SHARAD (Shallow Radar) has thus far not detected basal reflections within the SPLD at Ultimi Scopuli.
Tri-explosophoric groups driven fused energetic heterocycles featuring superior energetic and safety performances outperforms HMX
Authors: Li Jie , Liu Yubing , Ma Wenqi , Fei Teng , He Chunlin , Pang Siping
Published: September 2022

The design and synthesis of novel energetic compounds with integrated properties of high density, high energy, good thermal stability and sensitivities is particularly challenging due to the inherent contradiction between energy and safety for energetic compounds. In this study, a novel structure of 4-amino-7,8-dinitropyrazolo-[5,1-d] [1,2,3,5]-tetrazine 2-oxide (BITE-101) is designed and synthesized in three steps. With the help of the complementary advantages of different explosophoric groups and diverse weak interactions, BITE-101 is superior to the benchmark explosive HMX in all respects, including higher density of 1.957 g·cm−3, highest decomposition temperature of 295 °C (onset) among CHON-based high explosives to date and superior detonation velocity and pressure (D: 9314 m·s−1, P: 39.3 GPa), impact and friction sensitivities (IS: 18 J, FS: 128 N), thereby showing great potential for practical application as replacement for HMX, the most powerful military explosive in current use.
In vivo self-assembled siRNA as a modality for combination therapy of ulcerative colitis
Authors: Zhou Xinyan , Yu Mengchao , Ma Luzhen , Fu Jinyu , Guo Jingwei , Lei Jieqiong , Fu Zheng , Fu Yong , Zhang Qipeng , Zhang Chen-Yu , Chen Xi
Published: September 2022

Given the complex nature of ulcerative colitis, combination therapy targeting multiple pathogenic genes and pathways of ulcerative colitis may be required. Unfortunately, current therapeutic strategies are usually based on independent chemical compounds or monoclonal antibodies, and the full potential of combination therapy has not yet been realized for the treatment of ulcerative colitis. Here, we develop a synthetic biology strategy that integrates the naturally existing circulating system of small extracellular vesicles with artificial genetic circuits to reprogram the liver of male mice to self-assemble multiple siRNAs into secretory small extracellular vesicles and facilitate in vivo delivery siRNAs through circulating small extracellular vesicles for the combination therapy of mouse models of ulcerative colitis. Particularly, repeated injection of the multi-targeted genetic circuit designed for simultaneous inhibition of TNF-α, B7-1 and integrin α4 rapidly relieves intestinal inflammation and exerts a synergistic therapeutic effect against ulcerative colitis through suppressing the pro-inflammatory cascade in colonic macrophages, inhibiting the costimulatory signal to T cells and blocking T cell homing to sites of inflammation. More importantly, we design an AAV-driven genetic circuit to induce substantial and lasting inhibition of TNF-α, B7-1 and integrin α4 through only a single injection. Overall, this study establishes a feasible combination therapeutic strategy for ulcerative colitis, which may offer an alternative to conventional biological therapies requiring two or more independent compounds or antibodies.
TFEB regulates sulfur amino acid and coenzyme A metabolism to support hepatic metabolic adaptation and redox homeostasis
Authors: Matye David , Gunewardena Sumedha , Chen Jianglei , Wang Huaiwen , Wang Yifeng , Hasan Mohammad Nazmul , Gu Lijie , Clayton Yung Dai , Du Yanhong , Chen Cheng , Friedman Jacob E. , Lu Shelly C. , Ding Wen-Xing , Li Tiangang
Published: September 2022

Fatty liver is a highly heterogenous condition driven by various pathogenic factors in addition to the severity of steatosis. Protein insufficiency has been causally linked to fatty liver with incompletely defined mechanisms. Here we report that fatty liver is a sulfur amino acid insufficient state that promotes metabolic inflexibility via limiting coenzyme A availability. We demonstrate that the nutrient-sensing transcriptional factor EB synergistically stimulates lysosome proteolysis and methionine adenosyltransferase to increase cysteine pool that drives the production of coenzyme A and glutathione, which support metabolic adaptation and antioxidant defense during increased lipid influx. Intriguingly, mice consuming an isocaloric protein-deficient Western diet exhibit selective hepatic cysteine, coenzyme A and glutathione deficiency and acylcarnitine accumulation, which are reversed by cystine supplementation without normalizing dietary protein intake. These findings support a pathogenic link of dysregulated sulfur amino acid metabolism to metabolic inflexibility that underlies both overnutrition and protein malnutrition-associated fatty liver development.
Anomalous Josephson coupling and high-harmonics in non-centrosymmetric superconductors with S-wave spin-triplet pairing
Authors: Fukaya Yuri , Tanaka Yukio , Gentile Paola , Yada Keiji , Cuoco Mario
Published: September 2022

We study the Josephson effects arising in junctions made of non-centrosymmetric superconductors with spin-triplet pairing having s-wave orbital-singlet symmetry. We demonstrate that the orbital dependent character of the spin-triplet order parameter determines its non-trivial texture in the momentum space due to the inversion symmetry breaking and spin-orbit interactions. The emergence of this pattern is responsible for the occurrence of an anomalous Josephson coupling and a dominance of high-harmonics in the current phase relation. Remarkably, due to the spin-orbital couplings, variations in the electronic structure across the heterostructure can generally turn the ground state of the junction from 0- to a generic value of the Josephson phase, thus realizing the so-called φ-junction. Hallmarks of the resulting Josephson behavior, apart from non-standard current-phase relation, are provided by an unconventional temperature and magnetic field dependence of the critical current. These findings indicate the path for the design of superconducting orbitronics devices and account for several observed anomalies of the supercurrent in oxide interface superconductors.
De novo metatranscriptomic exploration of gene function in the millipede holobiont
Authors: Sardar Puspendu , Šustr Vladimír , Chroňáková Alica , Lorenc František , Faktorová Lucie
Published: September 2022

Invertebrate–microbial associations are widespread in the biosphere and are often related to the function of novel genes, fitness advantages, and even speciation events. Despite ~ 13,000 species of millipedes identified across the world, millipedes and their gut microbiota are markedly understudied compared to other arthropods. Exploring the contribution of individual host-associated microbes is often challenging as many are uncultivable. In this study, we conducted metatranscriptomic profiling of different body segments of a millipede at the holobiont level. This is the first reported transcriptome assembly of a tropical millipedeTelodeinopus aoutii(Demange, 1971), as well as the first study on any Myriapoda holobiont. High-throughput RNA sequencing revealed thatTelodeinopus aoutiicontained > 90% of the core Arthropoda genes. Proteobacteria, Bacteroidetes, Firmicutes, and Euryarchaeota represented dominant and functionally active phyla in the millipede gut, among which 97% of Bacteroidetes and 98% of Firmicutes were present exclusively in the hindgut. A total of 37,831 predicted protein-coding genes of millipede holobiont belonged to six enzyme classes. Around 35% of these proteins were produced by microbiota in the hindgut and 21% by the host in the midgut. Our results indicated that although major metabolic pathways operate at the holobiont level, the involvement of some host and microbial genes are mutually exclusive and microbes predominantly contribute to essential amino acid biosynthesis, short-chain fatty acid metabolism, and fermentation.
Profiling development of abdominal organs in the pig
Authors: Gabriel George C. , Devine William A. , Redel Bethany K. , Whitworth Kristin M. , Samuel Melissa , Spate Lee D. , Cecil Raissa F. , Prather Randall S. , Wu Yijen L. , Wells Kevin D. , Lo Cecilia W.
Published: September 2022

The pig is an ideal model system for studying human development and disease due to its similarities to human anatomy, physiology, size, and genome. Further, advances in CRISPR gene editing have made genetically engineered pigs viable models for the study of human pathologies and congenital anomalies. However, a detailed atlas illustrating pig development is necessary for identifying and modeling developmental defects. Here we describe normal development of the pig abdominal system and show examples of congenital defects that can arise in CRISPR gene edited SAP130 mutant pigs. Normal pigs at different gestational ages from day 20 (D20) to term were examined and the configuration of the abdominal organs was studied using 3D histological reconstructions with episcopic confocal microscopy, magnetic resonance imaging (MRI) and necropsy. This revealed prominent mesonephros, a transient embryonic organ present only during embryogenesis, at D20, while the developing metanephros that will form the permanent kidney are noted at D26. By D64 the mesonephroi are absent and only the metanephroi remain. The formation of the liver and pancreas was observed by D20 and complete by D30 and D35 respectively. The spleen and adrenal glands are first identified at D26 and completed by D42. The developing bowel and the gonads are identified at D20. The bowel appears completely rotated by D42, and testes in the male were descended at D64. This atlas and the methods used are excellent tools for identifying developmental pathologies of the abdominal organs in the pig at different stages of development.
Predicting potential global and future distributions of the African armyworm (Spodoptera exempta) using species distribution models
Authors: Gómez-Undiano Irene , Musavi Francis , Mushobozi Wilfred L. , David Grace M. , Day Roger , Early Regan , Wilson Kenneth
Published: September 2022

Invasive species have historically been a problem derived from global trade and transport. To aid in the control and management of these species, species distribution models (SDMs) have been used to help predict possible areas of expansion. Our focal organism, the African Armyworm (AAW), has historically been known as an important pest species in Africa, occurring at high larval densities and causing outbreaks that can cause enormous economic damage to staple crops. The goal of this study is to map the AAW’s present and potential distribution in three future scenarios for the region, and the potential global distribution if the species were to invade other territories, using 40 years of data on more than 700 larval outbreak reports from Kenya and Tanzania. The present distribution in East Africa coincides with its previously known distribution, as well as other areas of grassland and cropland, which are the host plants for this species. The different future climatic scenarios show broadly similar potential distributions in East Africa to the present day. The predicted global distribution shows areas where the AAW has already been reported, but also shows many potential areas in the Americas where, if transported, environmental conditions are suitable for AAW to thrive and where it could become an invasive species.
Pseudotime analysis reveals novel regulatory factors for multigenic onset and monogenic transition of odorant receptor expression
Authors: Hussainy Mohammad , Korsching Sigrun I. , Tresch Achim
Published: September 2022

During their maturation from horizontal basal stem cells, olfactory sensory neurons (OSNs) are known to select exactly one out of hundreds of olfactory receptors (ORs) and express it on their surface, a process called monogenic selection. Monogenic expression is preceded by a multigenic phase during which several OR genes are expressed in a single OSN. Here, we perform pseudotime analysis of a single cell RNA-Seq dataset of murine olfactory epithelium to precisely align the multigenic and monogenic expression phases with the cell types occurring during OSN differentiation. In combination with motif analysis of OR gene cluster-associated enhancer regions, we identify known and novel transcription (co-)factors (Ebf1, Lhx2, Ldb1, Fos and Ssbp2) and chromatin remodelers (Kdm1a, Eed and Zmynd8) associated with OR expression. The inferred temporal order of their activity suggests novel mechanisms contributing to multigenic OR expression and monogenic selection.
Identification of a prognosis-related ceRNA network in cholangiocarcinoma and potentially therapeutic molecules using a bioinformatic approach and molecular docking
Authors: Gao Xiaoling , Zhang Wenhao , Jia Yanjuan , Xu Hui , Zhu Yuchen , Pei Xiong
Published: September 2022

Cholangiocarcinoma (CCA) is a highly malignant disease with a poor prognosis, and mechanisms of initiation and development are not well characterized. It is long noncoding RNAs (lncRNAs) acting as miRNA decoys to regulate cancer-related RNAs in competing endogenous RNA (ceRNA) networks that suggest a possible molecular mechanism in CCA. The current study aims to find potential prognosis biomarkers and small molecule therapeutic targets based on the construction of a CCA prognosis-related ceRNA network. A transcriptome dataset for CCA was downloaded from the TCGA database. Differentially expressed lncRNAs (DElncRNAs), DEmiRNAs and DEmRNAs were identified based on the differential expression and a DEceRNA network was constructed using predicted miRNA-lncRNA and miRNA-mRNA interactions. Heat maps, PCA analysis, and Pathway enrichment analysis and GO enrichment analysis were conducted. The prognostic risk model and molecular docking were constructed based on identified key ceRNA networks. A DElncRNA-miRNA-mRNAs network consisting of 434 lncRNA-miRNA pairs and 284 miRNA-mRNA pairs with 200 lncRNAs, 21 miRNAs, and 245 mRNAs was constructed. There were three lncRNAs (AC090772.1, LINC00519, and THAP7-AS1) and their downstream mRNAs (MECOM, MBNL3, RCN2) screened out as prognostic factors in CAA. Three key networks (LINC00519/ hsa-mir-22/ MECOM, THAP7-AS1/hsa-mir-155/MBNL3, and THAP7-AS1/hsa-mir-155/RCN2) were identified based on binding sites prediction and survival analysis. A prognostic risk model was established with a good predictive ability (AUC = 0.66–0.83). Four anticancer small molecules, MECOM and 17-alpha-estradiol (−7.1 kcal/mol), RCN2 and emodin (−8.3 kcal/mol), RCN2 and alpha-tocopherol (−5.6 kcal/mol), and MBNL3 and 17-beta-estradiol (−7.1 kcal/mol) were identified. Based on the DEceRNA network and Kaplan–Meier survival analysis, we identified three important ceRNA networks associated with the poor prognosis of CCA. Four anti-cancer small molecules were screened out by computer-assisted drug screening as potential small molecules for the treatment of CCA. This study provides theoretical support for the development of ceRNA network-based drugs to improve the prognosis of CCA.
Deep learning alignment of bidirectional raster scanning in high speed photoacoustic microscopy
Authors: Kim Jongbeom , Lee Dongyoon , Lim Hyokyung , Yang Hyekyeong , Kim Jaewoo , Kim Jeesu , Kim Yeonggeun , Kim Hyung Ham , Kim Chulhong
Published: September 2022

Simultaneous point-by-point raster scanning of optical and acoustic beams has been widely adapted to high-speed photoacoustic microscopy (PAM) using a water-immersible microelectromechanical system or galvanometer scanner. However, when using high-speed water-immersible scanners, the two consecutively acquired bidirectional PAM images are misaligned with each other because of unstable performance, which causes a non-uniform time interval between scanning points. Therefore, only one unidirectionally acquired image is typically used; consequently, the imaging speed is reduced by half. Here, we demonstrate a scanning framework based on a deep neural network (DNN) to correct misaligned PAM images acquired via bidirectional raster scanning. The proposed method doubles the imaging speed compared to that of conventional methods by aligning nonlinear mismatched cross-sectional B-scan photoacoustic images during bidirectional raster scanning. Our DNN-assisted raster scanning framework can further potentially be applied to other raster scanning-based biomedical imaging tools, such as optical coherence tomography, ultrasound microscopy, and confocal microscopy.
Genome-wide identification and development of miniature inverted-repeat transposable elements and intron length polymorphic markers in tea plant (Camellia sinensis)
Authors: Rohilla Megha , Mazumder Abhishek , Saha Dipnarayan , Pal Tarun , Begam Shbana , Mondal Tapan Kumar
Published: September 2022

Marker-assisted breeding and tagging of important quantitative trait loci for beneficial traits are two important strategies for the genetic improvement of plants. However, the scarcity of diverse and informative genetic markers covering the entire tea genome limits our ability to achieve such goals. In the present study, we used a comparative genomic approach to mine the tea genomes of Camellia sinensis var. assamica (CSA) and C. sinensis var. sinensis (CSS) to identify the markers to differentiate tea genotypes. In our study, 43 and 60 Camellia sinensis miniature inverted-repeat transposable element (CsMITE) families were identified in these two sequenced tea genomes, with 23,170 and 37,958 putative CsMITE sequences, respectively. In addition, we identified 4912 non-redundant, Camellia sinensis intron length polymorphic (CsILP) markers, 85.8% of which were shared by both the CSS and CSA genomes. To validate, a subset of randomly chosen 10 CsMITE markers and 15 CsILP markers were tested and found to be polymorphic among the 36 highly diverse tea genotypes. These genome-wide markers, which were identified for the first time in tea plants, will be a valuable resource for genetic diversity analysis as well as marker-assisted breeding of tea genotypes for quality improvement.
Clinical and NGS predictors of response to regorafenib in recurrent glioblastoma
Authors: Chiesa Silvia , Mangraviti Antonella , Martini Maurizio , Cenci Tonia , Mazzarella Ciro , Gaudino Simona , Bracci Serena , Martino Antonella , Della Pepa Giuseppe M. , Offi Martina , Gessi Marco , Russo Rosellina , Martucci Matia , Beghella Bartoli Francesco , Larocca Luigi M. , Lauretti Liverana , Olivi Alessandro , Pallini Roberto , Balducci Mario , D’Alessandris Quintino Giorgio
Published: September 2022

Predictive factors for response to regorafenib in recurrent glioblastoma, IDH-wildtype, are scarcely recognized. The objective of this study was to identify molecular predictive factors for response to regorafenib using a clinically available platform. We analyzed a prospective cohort of 30 patients harboring recurrent glioblastoma, IDH-wildtype, and treated with regorafenib. Next-generation sequencing (NGS) analysis was performed on DNA extracted from paraffin-embedded tissues using a clinically available platform. Moreover, MGMT methylation and EGFRvIII expression analyses were performed. Six-month progression-free survival (PFS) was 30% and median overall survival (OS) was 7.5 months, in line with literature data. NGS analysis revealed a mutation in the EGFR pathway in 18% of cases and a mutation in the mitogen-activated protein-kinase (MAPK) pathway in 18% of cases. In the remaining cases, no mutations were detected. Patients carrying MAPK pathway mutation had a poor response to regorafenib treatment, with a significantly shorter PFS and a nonsignificantly shorter OS compared to EGFR-mutated patients (for PFS, 2.5 vs 4.5 months, p = 0.0061; for OS, 7 vs 9 months, p = 0.1076). Multivariate analysis confirmed that MAPK pathway mutations independently predicted a shorter PFS after regorafenib treatment (p = 0.0188). The negative prognostic role of MAPK pathway alteration was reinforced when we combined EGFR-mutated with EGFRvIII-positive cases. Recurrent glioblastoma tumors with an alteration in MAPK pathway could belong to the mesenchymal subtype and respond poorly to regorafenib treatment, while EGFR-altered cases have a better response to regorafenib. We thus provide a molecular selection criterion easy to implement in the clinical practice.
Identification of stable housekeeping genes for induced pluripotent stem cells and -derived endothelial cells for drug testing
Authors: Ong Sheena L. M. , Baelde Hans J. , van IJzendoorn David G. P. , Bovée Judith V. M. G. , Szuhai Karoly
Published: September 2022

There are no validated housekeeping genes in induced pluripotent stem cells (iPSC) and derived endothelial iPSC (iPSC-EC). Thus a comparison of gene expression levels is less reliable, especially during drug treatments. Here, we utilized transcriptome sequencing data of iPSC and iPSC-EC with or without CRISPR-Cas9 induced translocation to identify a panel of 15 candidate housekeeping genes. For comparison, five commonly used housekeeping genes (B2M, GAPDH, GUSB, HMBS, and HPRT1) were included in the study. The panel of 20 candidate genes were investigated for their stability as reference genes. This panel was analyzed and ranked based on stability using five algorithms, delta-Ct, bestkeeper, geNorm, Normfinder, and Reffinder. Based on the comprehensive ranking of Reffinder, the stability of the top two genes—RPL36AL and TMBIM6, and the bottom two genes—UBA1 and B2M, were further studied in iPSC-EC with and without genetic manipulation, and after treatment with telatinib. Using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR), it was shown that gene expression of the top two housekeeping genes, RPL36AL and TMBIM6, remained stable during drug treatment. We identified a panel of housekeeping genes that could be utilized in various conditions using iPSC and iPSC-derived endothelial cells as well as genetically modified iPSC for drug treatment.
Developing spatio-temporal approach to predict economic dynamics based on online news
Authors: Zhang Yuzhou , Sun Hua , Gao Guang , Shou Lidan , Wu Dun
Published: September 2022

Economic forecasting is a scientific decision-making tool, and it is one of the important basis for the government to formulate economic plans, predict the implementation of the plan, and guide the implementation of the plan. Current knowledge about the use of online news in the prediction of economic patterns in China is limited, especially considering the spatio-temporal dynamics over time. This study explored the spatio-temporal patterns of economic output values in Yinzhou, Ningbo, China between 2018 and 2021, and proposed generalized linear model (GLM) and Geographically weighted regression (GWR) model to predict the dynamics using online news data. The results indicated that there were spatio-temporal variations in the economic dynamics in the study area. The online news showed a great potential to predict economic dynamics, with better performance in the GWR model. The findings suggested online news combining with spatio-temporal approach can better forecast economic dynamics, which can be seen as a pre-requisite for developing an online news-based surveillance system The advanced spatio-temporal analysis enables governments to garner insights about the patterns of economic dynamics over time, which may enhance the ability of government to formulate economic plans and to predict the implementation of the plan. The proposed model may be extended to greater geographic area to validate such approach.
Irrigation and warming drive the decreases in surface albedo over High Mountain Asia
Authors: Maina Fadji Z. , Kumar Sujay V. , Gangodagamage Chandana
Published: September 2022

Human and climate induced land surface changes resulting from irrigation, snow cover decreases, and greening impact the surface albedo over High Mountain Asia (HMA). Here we use a partial information decomposition approach and remote sensing data to quantify the effects of the changes in leaf area index, soil moisture, and snow cover on the surface albedo in HMA, home to over a billion people, from 2003 to 2020. The study establishes strong evidence of anthropogenic agricultural water use over irrigated lands (e.g., Ganges–Brahmaputra) which causes the highest surface albedo decreases (≤ 1%/year). Greening and decreased snow cover from warming also drive changes in visible and near-infrared surface albedo in different areas of HMA. The significant role of irrigation and greening in influencing albedo suggests the potential of a positive feedback cycle where albedo decreases lead to increased evaporative demand and increased stress on water resources.
Blind-noise image denoising with block-matching domain transformation filtering and improved guided filtering
Authors: Jia Hongbin , Yin Qingbo , Lu Mingyu
Published: September 2022

The adaptive block size processing method in different image areas makes block-matching and 3D-filtering (BM3D) have a very good image denoising effect. Based on these observation, in this paper, we improve BM3D in three aspects: adaptive noise variance estimation, domain transformation filtering and nonlinear filtering. First, we improve the noise-variance estimation method of principle component analysis using multilayer wavelet decomposition. Second, we propose compressive sensing based Gaussian sequence Hartley domain transform filtering to reduce noise. Finally, we perform edge-preserving smoothing on the preprocessed image using the guided filtering based on total variation. Experimental results show that the proposed denoising method can be competitive with many representative denoising methods on the evaluation criteria of PSNR. However, it is worth further research on the visual quality of denoised images.
Introduction of an adhesion factor to cube in cube models and its effect on calculated moduli of particulate composites
Authors: Rech Julian , Dorp Esther Ramakers–van , Michels Patrick , Möginger Bernhard , Hausnerova Berenika
Published: September 2022

The cube in cube approach was used by Paul and Ishai-Cohen to model and derive formulas for filler content dependent Young’s moduli of particle filled composites assuming perfect filler matrix adhesion. Their formulas were chosen because of their simplicity, and recalculated using an elementary volume approach which transforms spherical inclusions to cubic inclusions. The EV approach led to expression of the composites moduli that allows introducing an adhesion factor kadh ranging from 0 and 1 to take into account reduced filler matrix adhesion. This adhesion factor scales the edge length of the cubic inclusions, thus reducing the stress transfer area between matrix and filler. Fitting the experimental data with the modified Paul model provides reasonable kadh for PA66, PBT, PP, PE-LD and BR which are in line with their surface energies. Further analysis showed that stiffening only occurs if kadh exceeds $$\sqrt{{E}_{\mathrm{M}}/{E}_{\mathrm{F}}}$$

E
M

/

E
F

and depends on the ratio of matrix modulus and filler modulus. The modified model allows for a quick calculation of any particle filled composites for known matrix modulus EM, filler modulus EF, filler volume content vF and adhesion factor kadh. Thus, finite element analysis (FEA) simulations of any particle filled polymer parts as well as materials selection are significantly eased. FEA of cubic and hexagonal EV arrangements show that stress distributions within the EV exhibit more shear stresses if one deviates from the cubic arrangement. At high filler contents the assumption that the property of the EV is representative for the whole composite, holds only for filler volume contents up to 15 or 20% (corresponding to 30 to 40 weight %). Thus, for vast majority of commercially available particulate composites, the modified model can be applied. Furthermore, this indicates that the cube in cube approach reaches two limits: (i) the occurrence of increasing shear stresses at filler contents above 20% due to deviations of EV arrangements or spatial filler distribution from cubic arrangements (singular), and (ii) increasing interaction between particles with the formation of particle network within the matrix violating the EV assumption of their homogeneous dispersion.
The degradation of performance of a state-of-the-art skin image classifier when applied to patient-driven internet search
Authors: Han Seung Seog , Navarrete-Dechent Cristian , Liopyris Konstantinos , Kim Myoung Shin , Park Gyeong Hun , Woo Sang Seok , Park Juhyun , Shin Jung Won , Kim Bo Ri , Kim Min Jae , Donoso Francisca , Villanueva Francisco , Ramirez Cristian , Chang Sung Eun , Halpern Allan , Kim Seong Hwan , Na Jung-Im
Published: September 2022

Model Dermatology (https://modelderm.com; Build2021) is a publicly testable neural network that can classify 184 skin disorders. We aimed to investigate whether our algorithm can classify clinical images of an Internet community along with tertiary care center datasets. Consecutive images from an Internet skin cancer community (‘RD’ dataset, 1,282 images posted between 25 January 2020 to 30 July 2021; https://reddit.com/r/melanoma) were analyzed retrospectively, along with hospital datasets (Edinburgh dataset, 1,300 images; SNU dataset, 2,101 images; TeleDerm dataset, 340 consecutive images). The algorithm’s performance was equivalent to that of dermatologists in the curated clinical datasets (Edinburgh and SNU datasets). However, its performance deteriorated in the RD and TeleDerm datasets because of insufficient image quality and the presence of out-of-distribution disorders, respectively. For the RD dataset, the algorithm’s Top-1/3 accuracy (39.2%/67.2%) and AUC (0.800) were equivalent to that of general physicians (36.8%/52.9%). It was more accurate than that of the laypersons using random Internet searches (19.2%/24.4%). The Top-1/3 accuracy was affected by inadequate image quality (adequate = 43.2%/71.3% versus inadequate = 32.9%/60.8%), whereas participant performance did not deteriorate (adequate = 35.8%/52.7% vs. inadequate = 38.4%/53.3%). In this report, the algorithm performance was significantly affected by the change of the intended settings, which implies that AI algorithms at dermatologist-level, in-distribution setting, may not be able to show the same level of performance in with out-of-distribution settings.
Multiscale modeling of collective cell migration elucidates the mechanism underlying tumor–stromal interactions in different spatiotemporal scales
Authors: Heidary Zarifeh , Haghjooy Javanmard Shaghayegh , Izadi Iman , Zare Nasrin , Ghaisari Jafar
Published: September 2022

Metastasis is the pathogenic spread of cancer cells from a primary tumor to a secondary site which happens at the late stages of cancer. It is caused by a variety of biological, chemical, and physical processes, such as molecular interactions, intercellular communications, and tissue-level activities. Complex interactions of cancer cells with their microenvironment components such as cancer associated fibroblasts (CAFs) and extracellular matrix (ECM) cause them to adopt an invasive phenotype that promotes tumor growth and migration. This paper presents a multiscale model for integrating a wide range of time and space interactions at the molecular, cellular, and tissue levels in a three-dimensional domain. The modeling procedure starts with presenting nonlinear dynamics of cancer cells and CAFs using ordinary differential equations based on TGFβ, CXCL12, and LIF signaling pathways. Unknown kinetic parameters in these models are estimated using hybrid unscented Kalman filter and the models are validated using experimental data. Then, the principal role of CAFs on metastasis is revealed by spatial–temporal modeling of circulating signals throughout the TME. At this stage, the model has evolved into a coupled ODE–PDE system that is capable of determining cancer cells’ status in one of the quiescent, proliferating or migratory conditions due to certain metastasis factors and ECM characteristics. At the tissue level, we consider a force-based framework to model the cancer cell proliferation and migration as the final step towards cancer cell metastasis. The ability of the multiscale model to depict cancer cells’ behavior in different levels of modeling is confirmed by comparing its outputs with the results of RT PCR and wound scratch assay techniques. Performance evaluation of the model indicates that the proposed multiscale model can pave the way for improving the efficiency of therapeutic methods in metastasis prevention.
Developing a hybrid FRP-concrete composite beam
Authors: Garnevičius Mantas , Gribniak Viktor
Published: September 2022

Current materials engineering trends put forward the development of efficient structural solutions. The steel replacement with fiber-reinforced polymers (FRP) exemplifies the key to the corrosion problem. However, the relatively low deformation modulus of typical FRP materials raises the deformations of the structural components. Together with the self-weight reduction increasing the kinematic displacements, the latter issue makes developing hybrid structures comprising compression-resistant concrete and high-performance in tension FRP profiles important. Although such hybrid systems are applicable for bridge engineering, the uncertainty of the inter-component bonding properties complicates developing these innovative structures, including the design models. The typical solution focuses on the local bond improvement, e.g., employing FRP profile perforation and mechanical anchorage systems. However, this study introduces an alternative solution, using the stress-ribbon bridge structural system for creating the hybrid beam prototype, which combines the synthetic fiber-reinforced concrete slab and pultruded FRP profile fixed on the supports. This work exemplifies the structural development concept when the finite element (FE) modeling outcome defines the target reference of the design procedure. Thus, on the one hand, this innovative structure simplifies the corresponding numerical (FE) model, which assumes the perfect bond between the components of the hybrid beam system. On the other hand, the solution to the support problem (resulting from a low resistance of pultruded FRP profiles to transverse loads) improves the structural performance of the bridge prototype, doubling the structure’s flexural stiffness and load-bearing capacity regarding the weak concrete supports’ system. The bending tests proved the adequacy of this solution in describing the design reference for further development of the proposed structural concept.
Task-related, intrinsic oscillatory and aperiodic neural activity predict performance in naturalistic team-based training scenarios
Authors: Cross Zachariah R. , Chatburn Alex , Melberzs Lee , Temby Philip , Pomeroy Diane , Schlesewsky Matthias , Bornkessel-Schlesewsky Ina
Published: September 2022

Effective teams are essential for optimally functioning societies. However, little is known regarding the neural basis of two or more individuals engaging cooperatively in real-world tasks, such as in operational training environments. In this exploratory study, we recruited forty individuals paired as twenty dyads and recorded dual-EEG at rest and during realistic training scenarios of increasing complexity using virtual simulation systems. We estimated markers of intrinsic brain activity (i.e., individual alpha frequency and aperiodic activity), as well as task-related theta and alpha oscillations. Using nonlinear modelling and a logistic regression machine learning model, we found that resting-state EEG predicts performance and can also reliably differentiate between members within a dyad. Task-related theta and alpha activity during easy training tasks predicted later performance on complex training to a greater extent than prior behaviour. These findings complement laboratory-based research on both oscillatory and aperiodic activity in higher-order cognition and provide evidence that theta and alpha activity play a critical role in complex task performance in team environments.
The ability of trimethylamine N-oxide to resist pressure induced perturbations to water structure
Authors: Laurent Harrison , Youngs Tristan G. A. , Headen Thomas F. , Soper Alan K. , Dougan Lorna
Published: September 2022

Trimethylamine N-oxide (TMAO) protects organisms from the damaging effects of high pressure. At the molecular level both TMAO and pressure perturb water structure but it is not understood how they act in combination. Here, we use neutron scattering coupled with computational modelling to provide atomistic insight into the structure of water under pressure at 4 kbar in the presence and absence of TMAO. The data reveal that TMAO resists pressure-induced perturbation to water structure, particularly in retaining a clear second solvation shell, enhanced hydrogen bonding between water molecules and strong TMAO – water hydrogen bonds. We calculate an ‘osmolyte protection’ ratio at which pressure and TMAO-induced energy changes effectively cancel out. Remarkably this ratio translates across scales to the organism level, matching the observed concentration dependence of TMAO in the muscle tissue of organisms as a function of depth. Osmolyte protection may therefore offer a molecular mechanism for the macroscale survival of life in extreme environments.
A genetically encoded BRET-based SARS-CoV-2 Mpro protease activity sensor
Authors: Geethakumari Anupriya M. , Ahmed Wesam S. , Rasool Saad , Fatima Asma , Nasir Uddin S. M. , Aouida Mustapha , Biswas Kabir H.
Published: September 2022

The main protease, Mpro, is critical for SARS-CoV-2 replication and an appealing target for designing anti-SARS-CoV-2 agents. Therefore, there is a demand for the development of improved sensors to monitor its activity. Here, we report a pair of genetically encoded, bioluminescence resonance energy transfer (BRET)-based sensors for detecting Mpro proteolytic activity in live cells as well as in vitro. The sensors were generated by sandwiching peptides containing the Mpro N-terminal autocleavage sites, either AVLQSGFR (short) or KTSAVLQSGFRKME (long), in between the mNeonGreen and NanoLuc proteins. Co-expression of the sensors with Mpro in live cells resulted in their cleavage while mutation of the critical C145 residue (C145A) in Mpro completely abrogated their cleavage. Additionally, the sensors recapitulated the inhibition of Mpro by the well-characterized pharmacological agent GC376. Further, in vitro assays with the BRET-based Mpro sensors revealed a molecular crowding-mediated increase in the rate of Mpro activity and a decrease in the inhibitory potential of GC376. The sensors developed here will find direct utility in studies related to drug discovery targeting the SARS-CoV-2 Mpro and functional genomics application to determine the effect of sequence variation in Mpro.
Transfer hydrogenation of phenol over Co-CoOx/N-doped carbon: boosted catalyst performance enabled by synergistic catalysis between Co0 and Coδ+
Authors: Nie Yunqing , Lin Wei , Zhang Yongsheng , Chen Yi , Nie Renfeng
Published: September 2022

N-doped carbon sphere supported cobalt nanoparticles (Co-CoOx/NCS) exhibited boosted capacity for transfer hydrogenation of phenol compared to Co/NCS and Co3O4/NCS, ascribing to the synergy of Co0 and Coδ+.
Generalised predictability in the synthesis of biocarbons as clean energy materials: targeted high performance CO2 and CH4 storage
Authors: Alali Ibtisam , Mokaya Robert
Published: September 2022

Biocarbons may be predictably synthesised towards exceptional energy related gas uptake at 25 °C; 5.4 mmol g−1 CO2 @ 1 bar, and methane storage of 334 cm3 (STP) cm−3 at 100 bar with deliverable capacity of 262 cm3 (STP) cm−3 (for 100–5 bar).
Brassica rapa L. (Tibetan turnip) prevents sleep-deprivation induced cognitive deficits via the inhibition of neuroinflammation and mitochondrial depolarization
Authors: Zhu Hongkang , Wang Cheng , Cheng Yuliang , Guo Yahui , Qian He , Liu Yu
Published: September 2022

Brassica rapa L., has substantial protective effects against sleep deprivation-induced learning and memory deficits, as well as other deleterious effects (ie., neuroinflammation) via AMPK/PPAR-γ signaling pathways.
Surface charge influences protein corona, cell uptake and biological effects of carbon dots
Authors: Arezki Yasmin , Delalande François , Schaeffer-Reiss Christine , Cianférani Sarah , Rapp Mickaël , Lebeau Luc , Pons Françoise , Ronzani Carole
Published: September 2022

In this first quantitative proteomic analysis of the protein corona formed on Carbon dots (CDs), we showed that protein corona identity is influenced by CD surface charge properties, which in turn impacts CD uptake and viability loss in macrophages.