bluuebunny/crossref_metadata_2025 huggingface dataset:
A plant cytorhabdovirus modulates locomotor activity of insect vectors to enhance virus transmission
Authors: Gao Dong-Min , Qiao Ji-Hui , Gao Qiang , Zhang Jiawen , Zang Ying , Xie Liang , Zhang Yan , Wang Ying , Fu Jingyan , Zhang Hua , Han Chenggui , Wang Xian-Bing
Published: September 2023

Transmission of many plant viruses relies on phloem-feeding insect vectors. However, how plant viruses directly modulate insect behavior is largely unknown. Barley yellow striate mosaic virus (BYSMV) is transmitted by the small brown planthopper (SBPH, Laodelphax striatellus). Here, we show that BYSMV infects the central nervous system (CNS) of SBPHs, induces insect hyperactivity, and prolongs phloem feeding duration. The BYSMV accessory protein P6 interacts with the COP9 signalosome subunit 5 (LsCSN5) of SBPHs and suppresses LsCSN5-regulated de-neddylation from the Cullin 1 (CUL1), hereby inhibiting CUL1-based E3 ligases-mediated degradation of the circadian clock protein Timeless (TIM). Thus, virus infection or knockdown of LsCSN5 compromises TIM oscillation and induces high insect locomotor activity for transmission. Additionally, expression of BYSMV P6 in the CNS of transgenic Drosophila melanogaster disturbs circadian rhythm and induces high locomotor activity. Together, our results suggest the molecular mechanisms whereby BYSMV modulates locomotor activity of insect vectors for transmission.
Food inflation and child undernutrition in low and middle income countries
Authors: Headey Derek , Ruel Marie
Published: September 2023

The 21st Century has been marked by increased volatility in food prices, with global price spikes in 2007-08, 2010-11, and again in 2021-22. The impact of food inflation on the risk of child undernutrition is not well understood, however. This study explores the potential impacts of food inflation on wasting and stunting among 1.27 million pre-school children from 44 developing countries. On average, a 5 percent increase in the real price of food increases the risk of wasting by 9 percent and severe wasting by 14 percent. These risks apply to young infants, suggesting a prenatal pathway, as well as to older children who typically experience a deterioration in diet quality in the wake of food inflation. Male children and children from poor and rural landless households are more severely impacted. Food inflation during pregnancy and the first year after birth also increases the risk of stunting for children 2-5 years of age. This evidence provides a strong rationale for interventions to prevent food inflation and mitigate its impacts on vulnerable children and their mothers.
Genome-wide analysis of DNA-PK-bound MRN cleavage products supports a sequential model of DSB repair pathway choice
Authors: Deshpande Rajashree A. , Marin-Gonzalez Alberto , Barnes Hannah K. , Woolley Phillip R. , Ha Taekjip , Paull Tanya T.
Published: September 2023

The Mre11-Rad50-Nbs1 (MRN) complex recognizes and processes DNA double-strand breaks for homologous recombination by performing short-range removal of 5ʹ strands. Endonucleolytic processing by MRN requires a stably bound protein at the break site—a role we postulate is played by DNA-dependent protein kinase (DNA-PK) in mammals. Here we interrogate sites of MRN-dependent processing by identifying sites of CtIP association and by sequencing DNA-PK-bound DNA fragments that are products of MRN cleavage. These intermediates are generated most efficiently when DNA-PK is catalytically blocked, yielding products within 200 bp of the break site, whereas DNA-PK products in the absence of kinase inhibition show greater dispersal. Use of light-activated Cas9 to induce breaks facilitates temporal resolution of DNA-PK and Mre11 binding, showing that both complexes bind to DNA ends before release of DNA-PK-bound products. These results support a sequential model of double-strand break repair involving collaborative interactions between homologous and non-homologous repair complexes.
Theoretical design of a space bioprocessing system to produce recombinant proteins
Authors: Soundararajan Mathangi , Paddock Matthew B. , Dougherty Michael , Jones Harry W. , Hogan John A. , Donovan Frances M. , Galazka Jonathan M. , Settles A. Mark
Published: September 2023

Space-based biomanufacturing has the potential to improve the sustainability of deep space exploration. To advance biomanufacturing, bioprocessing systems need to be developed for space applications. Here, commercial technologies were assessed to design space bioprocessing systems to supply a liquid amine carbon dioxide scrubber with active carbonic anhydrase produced recombinantly. Design workflows encompassed biomass dewatering of 1 L Escherichia coli cultures through to recombinant protein purification. Non-crew time equivalent system mass (ESM) analyses had limited utility for selecting specific technologies. Instead, bioprocessing system designs focused on minimizing complexity and enabling system versatility. Three designs that differed in biomass dewatering and protein purification approaches had nearly equivalent ESM of 357–522 kg eq. Values from the system complexity metric (SCM), technology readiness level (TRL), integration readiness level (IRL), and degree of crew assistance metric identified a simpler, less costly, and easier to operate design for automated biomass dewatering, cell lysis, and protein affinity purification.
Quantum networks with neutral atom processing nodes
Authors: Covey Jacob P. , Weinfurter Harald , Bernien Hannes
Published: September 2023

Quantum networks providing shared entanglement over a mesh of quantum nodes will revolutionize the field of quantum information science by offering novel applications in quantum computation, enhanced precision in networks of sensors and clocks, and efficient quantum communication over large distances. Recent experimental progress with individual neutral atoms demonstrates a high potential for implementing the crucial components of such networks. We highlight latest developments and near-term prospects on how arrays of individually controlled neutral atoms are suited for both efficient remote entanglement generation and large-scale quantum information processing, thereby providing the necessary features for sharing high-fidelity and error-corrected multi-qubit entangled states between the nodes. We describe both the functionality requirements and several examples for advanced, large-scale quantum networks composed of neutral atom processing nodes.
Variation of wine preference amongst consumers is influenced by the composition of salivary proteins
Authors: Luo Jiaqiang , Ruan Xinwei , Ang Ching-Seng , Nolvachai Yada , Marriott Philip J. , Zhang Pangzhen , Howell Kate
Published: September 2023

The preferences of consumers for different flavours and aromas in wine are varied and may be explained by inherent factors such as cultural background, wine education and personal taste of the wine consumer. Wine flavour, as perceived in the mouth, includes aroma compounds released through the retronasal pathway, which are shaped by interactions with saliva. Saliva and wine interactions could provide an explanation as to why wine tasters express different preferences for wine. To test this hypothesis, 13 Western and 13 Chinese experienced wine tasters were recruited. Sensory evaluation was performed in formal surroundings to acquire free description-based and perceived sensory intensity data using the Pivot® Profile and continuous scale assessment, respectively. Participants’ saliva samples were collected before the sensory evaluation and spiked into a wine sample to investigate the impact on the wine’s volatile release using comprehensive two-dimensional gas chromatography–mass spectrometry (GC × GC–MS). Saliva samples were subjected to enzyme activity assays and protein composition profiling by Tandem Mass Tag (TMT) quantitative proteomics. The wine tasters showed differences in wine flavour perception, which was supported by the difference in wine volatile release resulting from the addition of saliva. The two groups of participants did not have significant differences in total salivary protein concentrations or the amounts of esterase and α-amylase. However, statistically significant variations in the concentrations of specific proteins (proline-rich proteins (PRPs) and lipocalin-1 (LCN-1); p < 0.01) were found between the two groups. Significant correlations between perceived intensities of wine attributes and concentrations of PRPs and LCN-1 were observed. These results indicate that the composition of proteins in saliva is a factor that influences wine perception and preference. Our results provide a biochemical basis for understanding preference for food based on interactions between aroma compounds and salivary proteins and could be used to suggest foods or beverages to particular cultural groups.
Whole genomes from bacteria collected at diagnostic units around the world 2020
Authors: Nag Sidsel , Larsen Gunhild , Szarvas Judit , Birkedahl Laura Elmlund Kohl , Gulyás Gábor Máté , Ciok Wojchiech Jakub , Lagermann Timmie Mikkel , Tafaj Silva , Bradbury Susan , Collignon Peter , Daley Denise , Dougnon Victorien , Fabiyi Kafayath , Coulibaly Boubacar , Dembélé René , Nikiema Georgette , Magloire Natama , Ouindgueta Isidore Juste , Hossain Zenat Zebin , Begum Anowara , Donchev Deyan , Diggle Mathew , Turnbull LeeAnn , Lévesque Simon , Berlinger Livia , Sogaard Kirstine Kobberoe , Guevara Paula Diaz , Valderrama Carolina Duarte , Maikanti Panagiota , Amlerova Jana , Drevinek Pavel , Tkadlec Jan , Dilas Milica , Kaasch Achim , Westh Henrik Torkil , Bachtarzi Mohamed Azzedine , Amhis Wahiba , Salazar Carolina Elisabeth Satán , Villacis JoséEduardo , Lúzon Mária Angeles Dominguez , Palau Dámaris Berbel , Duployez Claire , Paluche Maxime , Asante-Sefa Solomon , Moller Mie , Ip Margaret , Mareković Ivana , Pál-Sonnevend Agnes , Cocuzza Clementiza Elvezia , Dambrauskiene Asta , Macanze Alexandre , Cossa Anelsio , Mandomando Inácio , Nwajiobi-Princewill Philip , Okeke Iruka N. , Kehinde Aderemi O. , Adebiyi Ini , Akintayo Ifeoluwa , Popoola Oluwafemi , Onipede Anthony , Blomfeldt Anita , Nyquist Nora Elisabeth , Bocker Kiri , Ussher James , Ali Amjad , Ullah Nimat , Khan Habibullah , Gustafson Natalie Weiler , Jarrar Ikhlas , Al-Hamad Arif , Luvira Viravarn , Paveenkittiporn Wantana , Baran Irmak , Mwansa James C. L. , Sikakwa Linda , Yamba Kaunda , Hendriksen Rene Sjogren , Aarestrup Frank Moller
Published: September 2023

The Two Weeks in the World research project has resulted in a dataset of 3087 clinically relevant bacterial genomes with pertaining metadata, collected from 59 diagnostic units in 35 countries around the world during 2020. A relational database is available with metadata and summary data from selected bioinformatic analysis, such as species prediction and identification of acquired resistance genes.
DrugMechDB: A Curated Database of Drug Mechanisms
Authors: Gonzalez-Cavazos Adriana Carolina , Tanska Anna , Mayers Michael , Carvalho-Silva Denise , Sridharan Brindha , Rewers Patrick A. , Sankarlal Umasri , Jagannathan Lakshmanan , Su Andrew I.
Published: September 2023

Computational drug repositioning methods have emerged as an attractive and effective solution to find new candidates for existing therapies, reducing the time and cost of drug development. Repositioning methods based on biomedical knowledge graphs typically offer useful supporting biological evidence. This evidence is based on reasoning chains or subgraphs that connect a drug to a disease prediction. However, there are no databases of drug mechanisms that can be used to train and evaluate such methods. Here, we introduce the Drug Mechanism Database (DrugMechDB), a manually curated database that describes drug mechanisms as paths through a knowledge graph. DrugMechDB integrates a diverse range of authoritative free-text resources to describe 4,583 drug indications with 32,249 relationships, representing 14 major biological scales. DrugMechDB can be employed as a benchmark dataset for assessing computational drug repositioning models or as a valuable resource for training such models.
Forest growth in Europe shows diverging large regional trends
Authors: Pretzsch Hans , del Río Miren , Arcangeli Catia , Bielak Kamil , Dudzinska Malgorzata , Forrester David Ian , Klädtke Joachim , Kohnle Ulrich , Ledermann Thomas , Matthews Robert , Nagel Jürgen , Nagel Ralf , Ningre François , Nord-Larsen Thomas , Biber Peter
Published: September 2023

Forests cover about one-third of Europe’s surface and their growth is essential for climate protection through carbon sequestration and many other economic, environmental, and sociocultural ecosystem services. However, reports on how climate change affects forest growth are contradictory, even for same regions. We used 415 unique long-term experiments including 642 plots across Europe covering seven tree species and surveys from 1878 to 2016, and showed that on average forest growth strongly accelerated since the earliest surveys. Based on a subset of 189 plots in Scots pine (the most widespread tree species in Europe) and high-resolution climate data, we identified clear large-regional differences; growth is strongly increasing in Northern Europe and decreasing in the Southwest. A less pronounced increase, which is probably not mainly driven by climate, prevails on large areas of Western, Central and Eastern Europe. The identified regional growth trends suggest adaptive management on regional level for achieving climate-smart forests.
Validation of the irritation scale on a representative German sample: new normative data
Authors: Gralla Maria S. , Guendel Harald , Mueller Andreas , Braehler Elmar , Häuser Winfried , Kruse Johannes , Muschalla Beate , Rigotti Thomas , Strauss Bernhard , Balint Elisabeth M.
Published: September 2023

The irritation scale is a widely used and reliable self-report scale for measuring cognitive and emotional strain related to the work environment. It extends existing measures by providing a sensitive assessment for pre-clinical stress at work. Existing normative data are based on convenience samples and are therefore not representative. This study provides new normative data for the irritation scale based on a representative German sample (N = 1480). The new normative data indicate that the overall level of irritation in the German workforce is significantly lower compared to previously published data. Convergent and discriminant validity is confirmed by correlations with depression and anxiety (Patient Health Questionnaire-4 for Depression and Anxiety), somatic symptom scales (Bodily Distress Syndrome 25 checklist, Somatic Symptom Scale-8, Giessen Subjective Complaints List-8, comorbidity), psychological functioning (Mini-ICF rating for activity and participation disorders in mental illness), work-related stressors (overcommitment and bullying) and individual resources (self-efficacy). The results confirm the utility of the irritation scale and provide new benchmarks that avoid an underestimation of the levels of irritation in future studies.
Label-free drug response evaluation of human derived tumor spheroids using three-dimensional dynamic optical coherence tomography
Authors: Abd El-Sadek Ibrahim , Shen Larina Tzu-Wei , Mori Tomoko , Makita Shuichi , Mukherjee Pradipta , Lichtenegger Antonia , Matsusaka Satoshi , Yasuno Yoshiaki
Published: September 2023

This study aims at demonstrating label-free drug-response-patterns assessment of different tumor spheroids and drug types by dynamic optical coherence tomography (D-OCT). The study involved human breast cancer (MCF-7) and colon cancer (HT-29) spheroids. The MCF-7 and HT-29 spheroids were treated with paclitaxel (Taxol; PTX) and the active metabolite of irinotecan SN-38, respectively. The drugs were applied with 0 (control), 0.1, 1, and 10 μM concentrations and the treatment durations were 1, 3, and 6 days. A swept-source OCT microscope equipped with a repeated raster scanning protocol was used to scan the spheroids. Logarithmic intensity variance (LIV) and late OCT correlation decay speed (OCDS$$_l$$l) algorithms were used to visualize the tumor spheroid dynamics. LIV and OCDS$$_l$$limages visualized different response patterns of the two types of spheroids. In addition, spheroid morphology, LIV, and OCDS$$_l$$lquantification showed different time-courses among the spheroid and drug types. These results may indicate different action mechanisms of the drugs. The results showed the feasibility of D-OCT for the evaluation of drug response patterns of different cell spheroids and drug types and suggest that D-OCT can perform anti-cancer drug testing.
Epigenomic analysis reveals a unique DNA methylation program of metastasis-competent circulating tumor cells in colorectal cancer
Authors: Bao-Caamano Aida , Costa-Fraga Nicolás , Cayrefourcq Laure , Jácome María Amalia , Rodriguez-Casanova Aitor , Muinelo-Romay Laura , López-López Rafael , Alix-Panabières Catherine , Díaz-Lagares Angel
Published: September 2023

Circulating tumor cells (CTCs) and epigenetic alterations are involved in the development of metastasis from solid tumors, such as colorectal cancer (CRC). The aim of this study was to characterize the DNA methylation profile of metastasis-competent CTCs in CRC. The DNA methylome of the human CRC-derived cell line CTC-MCC-41 was analyzed and compared with primary (HT29, Caco2, HCT116, RKO) and metastatic (SW620 and COLO205) CRC cells. The association between methylation and the transcriptional profile of CTC-MCC-41 was also evaluated. Differentially methylated CpGs were validated with pyrosequencing and qMSP. Compared to primary and metastatic CRC cells, the methylation profile of CTC-MCC-41 was globally different and characterized by a slight predominance of hypomethylated CpGs mainly distributed in CpG-poor regions. Promoter CpG islands and shore regions of CTC-MCC-41 displayed a unique methylation profile that was associated with the transcriptional program and relevant cancer pathways, mainly Wnt signaling. The epigenetic regulation of relevant genes in CTC-MCC-41 was validated. This study provides new insights into the epigenomic landscape of metastasis-competent CTCs, revealing biological information for metastasis development, as well as new potential biomarkers and therapeutic targets for CRC patients.
Supervised machine learning to validate a novel scoring system for the prediction of disease remission of functional pituitary adenomas following transsphenoidal surgery
Authors: McKevitt Chase , Gabriel Ellie , Marenco-Hillembrand Lina , Otamendi-Lopez Andrea , Jeevaratnam Suren , Almeida Joao Paulo , Samson Susan , Chaichana Kaisorn L.
Published: September 2023

Functional pituitary adenomas (FPAs) are associated with hormonal hypersecretion resulting in systemic endocrinopathies and increased mortality. The heterogenous composition of the FPA population has made modeling predictive factors of postoperative disease remission a challenge. Here, we aim to define a novel scoring system predictive of disease remission following transsphenoidal surgery (TSS) for FPAs and validate our process using supervised machine learning (SML). 392 patients with FPAs treated at one of the three Mayo Clinic campuses were retrospectively reviewed. Variables found significant on multivariate analysis were incorporated into our novel Pit-SCHEME score. The Pit-SCHEME score with a cut-off value ≥ 6 achieved a sensitivity of 86% and positive likelihood ratio of 2.88. In SML models, without the Pit-SCHEME score, the k-nearest neighbor (KNN) model achieved the highest accuracy at 75.6%. An increase in model sensitivity was achieved with inclusion of the Pit-SCHEME score with the linear discriminant analysis (LDA) model achieving an accuracy of 86.9%, which suggests the Pit-SCHEME score is the variable of most importance for prediction of postoperative disease remission. Ultimately, these results support the potential clinical utility of the Pit-SCHEME score and its prospective future for aiding in the perioperative decision making in patients with FPAs.
Method for efficient calculating earth pressure of retaining wall considering plant transpiration
Authors: Zhang Junhui , Hu Huiren , Fu Wei , Peng Junhui , Li Feng , Ding Le
Published: September 2023

An accurate estimation of earth pressure on retaining walls is imperative to achieving its design. This paper presents an analytical method framework that considers the effect of plant transpiration relative to the traditional calculation approaches. Specifically, a closed-form solution for one-dimensional steady unsaturated flow considering plant transpiration is incorporated into a representation of effective stress to obtain the changes in matric suction, and effective stress. The representations are used to extend Hooke’s law and Rankine’s earth pressure theory to determine at-rest, active, and passive earth pressures. Subsequently, the analytical method is used in a series of analysis case studies on the influence of root architecture types, transpiration rates, and soil types on earth pressure, to reveal that it can rapidly obtain the earth pressure. Notably, the effect of plant transpiration on earth pressure is significant. Furthermore, it is found that soil types and transpiration rates have a larger influence than root architecture types. Collectively, the research not only reveals the effect of plant on earth pressure for retaining wall, but also provides a theoretical basis for further exploration of the contribution of plants to the stability of retaining wall.
Anxiety and depression from age 3 to 8 years in children with and without ADHD symptoms
Authors: Ingeborgrud Christine Baalsrud , Oerbeck Beate , Friis Svein , Zeiner Pål , Pripp Are Hugo , Aase Heidi , Biele Guido , Dalsgaard Søren , Overgaard Kristin Romvig
Published: September 2023

Childhood anxiety and depressive symptoms may be influenced by symptoms of attention deficit/hyperactivity disorder (ADHD). We investigated whether parent- and teacher-reported anxiety, depressive and ADHD symptoms at age 3 years predicted anxiety disorders and/or depression in children with and without ADHD at age 8 years. This study is part of the longitudinal, population-based Norwegian Mother, Father and Child Cohort Study. Parents of 3-year-olds were interviewed, and preschool teachers rated symptoms of anxiety disorders, depression and ADHD. At age 8 years (n = 783), Child Symptom Inventory-4 was used to identify children who fulfilled the diagnostic criteria for anxiety disorders and/or depression (hereinafter: Anx/Dep), and ADHD. Univariable and multivariable logistic regression analyses were used. In the univariable analyses, parent-reported anxiety, depressive and ADHD symptoms, and teacher-reported anxiety symptoms at age 3 years all significantly predicted subsequent Anx/Dep. In the multivariable analyses, including co-occurring symptoms at age 3 years and ADHD at 8 years, parent-reported anxiety and depressive symptoms remained significant predictors of subsequent Anx/Dep. At age 3 years, regardless of ADHD symptoms being present, asking parents about anxiety and depressive symptoms, and teachers about anxiety symptoms, may be important to identify children at risk for school-age anxiety disorders and/or depression.
A cross-cohort computational framework to trace tumor tissue-of-origin based on RNA sequencing
Authors: He Binsheng , Sun Hongmei , Bao Meihua , Li Haigang , He Jianjun , Tian Geng , Wang Bo
Published: September 2023

Carcinoma of unknown primary (CUP) is a type of metastatic cancer with tissue-of-origin (TOO) unidentifiable by traditional methods. CUP patients typically have poor prognosis but therapy targeting the original cancer tissue can significantly improve patients’ prognosis. Thus, it’s critical to develop accurate computational methods to infer cancer TOO. While qPCR or microarray-based methods are effective in inferring TOO for most cancer types, the overall prediction accuracy is yet to be improved. In this study, we propose a cross-cohort computational framework to trace TOO of 32 cancer types based on RNA sequencing (RNA-seq). Specifically, we employed logistic regression models to select 80 genes for each cancer type to create a combined 1356-gene set, based on transcriptomic data from 9911 tissue samples covering the 32 cancer types with known TOO from the Cancer Genome Atlas (TCGA). The selected genes are enriched in both tissue-specific and tissue-general functions. The cross-validation accuracy of our framework reaches 97.50% across all cancer types. Furthermore, we tested the performance of our model on the TCGA metastatic dataset and International Cancer Genome Consortium (ICGC) dataset, achieving an accuracy of 91.09% and 82.67%, respectively, despite the differences in experiment procedures and pipelines. In conclusion, we developed an accurate yet robust computational framework for identifying TOO, which holds promise for clinical applications. Our code is available at http://github.com/wangbo00129/classifybysklearn.
Usage of extruded diamond multi-injectors for improvement of fuel mixing inside the supersonic combustion chamber
Authors: Seraj Hossein , Hosseinnejad Farhad , Rostamiyan Yasser , Fallah Keivan
Published: September 2023

The main attention of this work is to investigate the usage of diamond multi extruded injectors on the fuel distribution in combustor of scramjet. This study applied the computational technique to simulate the transverse fuel jets released from extruded nozzles. The main focus is to evaluate the role of induced shock waves on the penetration and distribution of fuel jets. The effects of jet space and usage of annular nozzle for the fuel injection system are revealed. Results of this work shows that the gap of jet would be more efficient for mixing when the inner air jet is also used. Also, injection of the air from the core of annular nozzle significantly increase the fuel mixing.
Ferroptosis-related factors in the substantia nigra are associated with Parkinson’s disease
Authors: Liu Lei , Cui Yange , Chang Yan-Zhong , Yu Peng
Published: September 2023

Ferroptosis is an iron-dependent, lipid peroxidation-driven cell death pathway, while Parkinson’s disease (PD) patients exhibit iron deposition and lipid peroxidation in the brain. Thus, the features of ferroptosis highly overlap with the pathophysiological features of PD. Despite this superficial connection, the possible role(s) of ferroptosis-related (Fr) proteins in dopaminergic neurons and/or glial cells in the substantia nigra (SN) in PD have not been examined in depth. To explore the correlations between the different SN cell types and ferroptosis at the single-cell level in PD patients, and to explore genes that may affect the sensitivity of dopaminergic neurons to ferroptosis, we performed in silico analysis of a single cell RNA sequence (RNA-seq) set (GSE178265) from the Gene Expression Omnibus (GEO) database. We identified differentially expressed genes (DEGs) in the different cell types in the human SN, and proceeded to perform enrichment analysis, constructing a protein–protein interaction network from the DEGs of dopaminergic neurons with the Metascape database. We examined the intersection of Fr genes present in the FerrDb database with DEGs from the GSE178265 set to identify Fr-DEGs in the different brain cells. Further, we identified Fr-DEGs encoding secreted proteins to implicate cell–cell interactions in the potential stimulation of ferroptosis in PD. The Fr-DEGs we identified were verified using the bulk RNA-seq sets (GSE49036 and GSE20164). The number of dopaminergic neurons decreased in the SN of PD patients. Interestingly, non-dopaminergic neurons possessed the fewest DEGs. Enrichment analysis of dopaminergic neurons’ DEGs revealed changes in transmission across chemical synapses and ATP metabolic process in PD. The secreted Fr-DEGs identified were ceruloplasmin (CP), high mobility group box 1 (HMGB1) and transferrin (TF). The bulk RNA-seq set from the GEO database demonstrates that CP expression is increased in the PD brain. In conclusion, our results identify CP as a potential therapeutic target to protect dopaminergic neurons by reducing neurons’ sensitivity to ferroptosis.
Unraveling the link between PTBP1 and severe asthma through machine learning and association rule mining method
Authors: Pirmoradi Saeed , Hosseiniyan Khatibi Seyed Mahdi , Zununi Vahed Sepideh , Homaei Rad Hamed , Khamaneh Amir Mahdi , Akbarpour Zahra , Seyedrezazadeh Ensiyeh , Teshnehlab Mohammad , Chapman Kenneth R. , Ansarin Khalil
Published: September 2023

Severe asthma is a chronic inflammatory airway disease with great therapeutic challenges. Understanding the genetic and molecular mechanisms of severe asthma may help identify therapeutic strategies for this complex condition. RNA expression data were analyzed using a combination of artificial intelligence methods to identify novel genes related to severe asthma. Through the ANOVA feature selection approach, 100 candidate genes were selected among 54,715 mRNAs in blood samples of patients with severe asthmatic and healthy groups. A deep learning model was used to validate the significance of the candidate genes. The accuracy, F1-score, AUC-ROC, and precision of the 100 genes were 83%, 0.86, 0.89, and 0.9, respectively. To discover hidden associations among selected genes, association rule mining was applied. The top 20 genes including the PTBP1, RAB11FIP3, APH1A, and MYD88 were recognized as the most frequent items among severe asthma association rules. The PTBP1 was found to be the most frequent gene associated with severe asthma among those 20 genes. PTBP1 was the gene most frequently associated with severe asthma among candidate genes. Identification of master genes involved in the initiation and development of asthma can offer novel targets for its diagnosis, prognosis, and targeted-signaling therapy.
Effect of metabolic activity of lactic acid bacteria and propionibacteria on cheese protein digestibility and fatty acid profile
Authors: Ziarno Małgorzata , Bryś Joanna , Kowalska Ewa , Cichońska Patrycja
Published: September 2023

This study aimed at investigating the influence of different variants of bacterial starter cultures on the metabolism of the bacteria used, cheese protein digestibility, and fatty acid profile. The results revealed that lactic acid bacteria had a significant effect on the proportions of fatty acids in cheeses, with saturated fatty acids being predominant in in all cheese variants. Fatty acid proportions are complex and depend on the type of cheese culture and monoculture used. Additionally, the analysis of fatty acid composition showed variations in the proportion of saturated and unsaturated fatty acids, impacting the values of atherogenic and thrombogenic indices. Notably, the atherogenic index was highest in samples of mature cheeses obtained from a typical mesophilic cheese culture, whereas it was lowest in samples of fresh milk and mature cheeses obtained from a mesophilic cheese culture and monocultures of Lacticaseibacillus casei and Propionibacterium. The study also highlighted the influence of lactobacilli on the content of available free lysine, glycine, and methionine in cheese proteins. Mature cheeses obtained with Propionibacterium and L. casei starter cultures exhibited higher free lysine and glycine content compared with fresh cheeses and those obtained solely with the cheese culture. Additionally, mature cheeses obtained with starter cultures of mesophilic cheese culture, Propionibacterium, and L. casei had the highest free methionine content. Based on these findings, it is evident that the choice of cheese making cultures and monocultures can significantly affect the fatty acid composition and amino acid content of cheese and fresh milk, potentially bearing important health implications.
Interactions between C-steel and blended cement in concrete under radwaste repository conditions at 80 °C
Authors: Fabian Margit , Czompoly Otto , Tolnai Istvan , De Windt Laurent
Published: September 2023

Deep geological repository is widely considered as the preferred solution for the final disposal of high-level radioactive waste. Investigation representative of the Hungarian disposal concept was conducted using mock-up diffusion cells to study the chemical changes of S235JR carbon steel canister and CEM II/B concrete of the Public Limited Company for Radioactive Waste Management under anerobic and water saturated conditions at 80 °C. Micro-Raman, Scanning Electron Microscopy-Energy Dispersive X-ray Spectroscopy, fluid and potentiometric analysis were performed over a period of 12 months. The analysis was supported by thermodynamic and reactive transport modeling using the HYTEC code. The findings revealed that a uniform corrosion process occurred, leading to rapid passivation of the C-steel with magnetite as the primary corrosion product. Modeling demonstrated that the increase in temperature to 80 °C and the chemical evolution of the concrete did not significantly affect the corrosion passivation process. Although the formation of Fe-siliceous hydrogarnets is thermodynamically possible at 80 °C, it did not jeopardize magnetite passivation. The results show that the passivation of the containers occurred under the test conditions and this is a promising result for further investigations.
Feasibility of administration of calcitonin gene-related peptide receptor antagonist on attenuation of pain and progression in osteoarthritis
Authors: Nekomoto Akinori , Nakasa Tomoyuki , Ikuta Yasunari , Ding Chenyang , Miyaki Shigeru , Adachi Nobuo
Published: September 2023

Suppressing inflammation and abnormal subchondral bone turnover is essential for reducing osteoarthritis (OA) progression and pain relief. This study focused on calcitonin gene-related peptide (CGRP), which is involved in inflammation and bone metabolism, and investigated whether a CGRP receptor antagonist (rimegepant) could suppress OA progression and relieve pain in two OA models. C57BL/6 mice (10-week-old) underwent surgical destabilization of the medial meniscus, and Rimegepant (1.0 mg/kg/100 μL) or phosphate-buffered saline (100 μL) was administered weekly intraperitoneally after OA surgery and evaluated at 4, 8, and 12 weeks. In the senescence-accelerated mice (SAM)-prone 8 (SAMP8), rimegepant was administered weekly before and after subchondral bone sclerosis and sacrificed at 9 and 23 weeks, respectively. Behavioral assessment and immunohistochemical staining (CGRP) of the dorsal root ganglion (DRG) were conducted to assess pain. In DMM mice, synovitis, cartilage degeneration, and osteosclerosis were significantly suppressed in the rimegepant group. In SAMP8, synovitis, cartilage degeneration, and osteosclerosis were significantly suppressed by rimegepant at 9 weeks; however, not at 23 weeks. Behavioral assessment shows the traveled distance and the number of standings in the rimegepant group were significantly longer and higher. In addition, CGRP expression of the DRG was significantly lower in the rimegepant group at 8 and 12 weeks of DMM and 9 weeks of SAMP8 treatment. No adverse effects were observed in either of the mouse models. Inhibition of CGRP signaling has the potential to be a therapeutic target to prevent OA progression and suppress pain through the attenuation of subchondral bone sclerosis and synovitis.
The effect of material defect orientation on rolling contact fatigue of a ball bearing
Authors: Ghazanfari Holagh Akbar , Alizadeh Kaklar Javad
Published: September 2023

In this study, finite element method (FEM) is applied to investigate the effect of material defect orientation on subsurface crack initiation in rolling bearings. First, the history of stress intensity factors (SIFs) of a subsurface cubic material defect is calculated. SIFs calculation is conducted when it is parallel to the rolling surface of a bearing ring ($$\varphi = 0^\circ$$

φ
=

0
∘

) under a ball rolling on the ring. Then, the effect of defect orientation, varying from $$\varphi = 0^\circ$$

φ
=

0
∘

to $$\varphi \; = \;30,\; 45\; {\text{and}} \;60^\circ$$

φ

=

30
,

45

and

60
∘

, on the history of SIFs is investigated. It is deduced that changing the defect orientation results in a threefold increase in the equivalent SIF range compared to parallel orientation.
Outcomes of targeted treatment in immunocompromised patients with asymptomatic or mild COVID-19: a retrospective study
Authors: Lahouati M. , Cazanave C. , Labadie A. , Gohier P. , Guirlé L. , Desclaux A. , Gigan M. , Malvy D. , Pedeboscq S. , Xuereb F. , Duvignaud A. ,   The Bordeaux COVID-19 Treatment Group, Barthod Laure , Bellecave Pantxika , Blanc Jean-Frédéric , Blanchard Elodie , Bonnet Fabrice , Camou Fabrice , Carrer Mathilde , Cazanave Charles , Chermak Faiza , Couzi Lionel , Daste Amaury , Dauchy Frédéric-Antoine , De Ledinghen Victor , Domblides Charlotte , Duffau Pierre , Dutronc Hervé , Duvignaud Alexandre , Faure Maxime , Forcade Edouard , Issa Nahéma , Kaminski Hannah , Hiriart Jean-Baptise , Lahouati Marin , Leitao Julie , Lescure Maëlig , Lazaro Estibaliz , Maachi Isabelle , Neau Didier , Nguyen Duc , Nubret Karine , Pédeboscq Stéphane , Pistone Thierry , Pribat Frédérique , Puges Mathilde , Ruet Aurélie , Tumiotto Camille , Vandenhende Marie-Anne , Wirth Gaétane
Published: September 2023

The aim of this study was to describe the outcomes of targeted COVID-19 treatments in immunocompromised patients with asymptomatic or mild COVID-19 during the period of expansion of the different Omicron subvariants in France. A retrospective monocentric observational study was performed. All immunocompromised patients aged 18 or more, with asymptomatic SARS-CoV-2 infection or mild COVID-19, and who had received a targeted treatment with sotrovimab, tixagevimab/cilgavimab, nirmatrelvir/ritonavir or remdesivir at the Bordeaux University Hospital from 1st January 2022 to 31st December 2022 were eligible. The primary outcomes of interest was defined as a composite of either (i) progression to moderate (WHO-Clinical Progression Scale at 4 or 5) or severe COVID-19 (WHO-CPS ≥ 6), or (ii) the occurrence of COVID-19-related death. The secondary outcomes of interest were the components of the primary outcome. Outcomes were collected until day 30 after targeted treatment administration or at discharge for patients still hospitalised in relation with COVID-19 at day 30. 223 immunocompromised patients received targeted treatment for asymptomatic SARS-CoV-2 infection or mild COVID-19: 114 received sotrovimab, 50 tixagevimab/cilgavimab, 49 nirmatrelvir/ritonavir, and 10 remdesivir. Among 223 treated patients, 10 (4.5%) progressed to moderate or severe disease: three patients (1.3%) progressed to moderate COVID-19 and 7 (3.1%) patients progressed to severe disease. Among them, 4 (1.8%) died of COVID-19. More than 95% of immunocompromised patients with asymptomatic SARS-CoV-2 infection or mild COVID-19 treated by targeted therapies during the Omicron subvariants era did not progress to moderate or severe disease.
Landslide risk evaluation method of open-pit mine based on numerical simulation of large deformation of landslide
Authors: Jia Lan , Wang Jiaqi , Gao Shisong , Fang Linhao , Wang Dong
Published: September 2023

It is of great practical significance to carry out quantitative risk assessment of landslide disaster to protect people’s lives and property safety and maintain the sustainable development of social economy. The delineation of landslide disaster range is the key link of landslide risk evaluation in open-pit mine. This study took the open-pit coal mine coal mine in Block I of Thar coal field in Pakistan as the research background, and constructed a framework for landslide risk evaluation in open-pit mines. Based on the numerical simulation method of large deformation of landslide, the disaster range of landslide in open-pit mine was delineated. The stability of stope slope was analyzed based on rigid body limit equilibrium method. The probability of landslide instability was calculated based on Monte Carlo method. And the comprehensive fuzzy evaluation model was established to calculate the total risk value of landslide. The results showed that: through numerical simulation and empirical formula calculation, the landslide disaster range was accurately delineated, and the comprehensive vulnerability of the disaster bearing body was determined to be medium vulnerability; the annual probability of landslide instability under natural conditions was 0.003, which belongs to moderate risk. The annual probability of landslide instability under rainstorm conditions was 0.024, which was highly dangerous; the annual probability of landslide instability under seismic conditions was 0.018, which was highly dangerous. Under natural conditions, the total risk value of landslide was 114,686.4 rmb, and the annual mortality rate of population was 0.0255 people/year. The total risk value of landslide under rainstorm condition was 11,707,570 rmb, and the annual mortality rate of population was 0.18375 people/year. The total risk value of landslide under earthquake condition was 43,007,400 rmb, and the annual mortality rate of population was 0.135 person/year, which was an unacceptable risk. The economic loss was a small geological disaster risk under natural conditions, and it was a medium-sized geological disaster risk under both rainstorm and earthquake conditions. Therefore, landslide prevention and control and management measures such as slope deformation monitoring were proposed to ensure the safety of personnel and property in open-pit mines.
Mild sleep restriction increases endothelial oxidative stress in female persons
Authors: Shah Riddhi , Shah Vikash Kumar , Emin Memet , Gao Su , Sampogna Rosemary V. , Aggarwal Brooke , Chang Audrey , St-Onge Marie-Pierre , Malik Vikas , Wang Jianlong , Wei Ying , Jelic Sanja
Published: September 2023

Sleep restriction is associated with increased cardiovascular risk, which is more pronounced in female than male persons. We reported recently first causal evidence that mild, prolonged sleep restriction mimicking “real-life” conditions impairs endothelial function, a key step in the development and progression of cardiovascular disease, in healthy female persons. However, the underlying mechanisms are unclear. In model organisms, sleep restriction increases oxidative stress and upregulates antioxidant response via induction of the antioxidant regulator nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Here, we assessed directly endothelial cell oxidative stress and antioxidant responses in healthy female persons (n = 35) after 6 weeks of mild sleep restriction (1.5 h less than habitual sleep) using randomized crossover design. Sleep restriction markedly increased endothelial oxidative stress without upregulating antioxidant response. Using RNA-seq and a predicted protein–protein interaction database, we identified reduced expression of endothelial Defective in Cullin Neddylation-1 Domain Containing 3 (DCUN1D3), a protein that licenses Nrf2 antioxidant responses, as a mediator of impaired endothelial antioxidant response in sleep restriction. Thus, sleep restriction impairs clearance of endothelial oxidative stress that over time increases cardiovascular risk.

Trial Registration: NCT02835261
Unclear tumor border in magnetic resonance imaging as a prognostic factor of squamous cell cervical cancer
Authors: Sato Mamiko , Tamauchi Satoshi , Yoshida Kosuke , Yoshihara Masato , Ikeda Yoshiki , Yoshikawa Nobuhisa , Kajiyama Hiroaki
Published: September 2023

Magnetic resonance imaging (MRI) is used for pretreatment staging in cervical cancer. In the present study, we used pretreatment images to categorize operative cases into two groups and evaluated their prognosis. A total of 53 cervical cancer patients with squamous cell carcinoma who underwent radical hysterectomy were included in this study. Based on MRI, the patients were classified into two groups, namely clear and unclear tumor border. For each patient, the following characteristics were evaluated: overall survival; recurrence-free survival; lymph node metastasis; lymphovascular space invasion; and pathological findings, including immunohistochemical analysis of vimentin. The clear and unclear tumor border groups included 40 and 13 patients, respectively. Compared with the clear tumor border group, the unclear tumor border group was associated with higher incidence rates of recurrence (3/40 vs. 3/13, respectively), lymphovascular space invasion (24/40 vs. 13/13, respectively), lymph node metastasis (6/40 vs. 10/13, respectively), and positivity for vimentin (18/40 vs. 10/13, respectively). Despite the absence of significant difference in recurrence-free survival (p = 0.0847), the unclear tumor border group had a significantly poorer overall survival versus the clear tumor border group (p = 0.0062). According to MRI findings, an unclear tumor border in patients with squamous cell cervical cancer is linked to poorer prognosis, lymph node metastasis, and distant recurrence of metastasis.
North Atlantic subpolar gyre provides downstream ocean predictability
Authors: Fan Hongdou , Borchert Leonard F. , Brune Sebastian , Koul Vimal , Baehr Johanna
Published: September 2023

Slowly varying large-scale ocean circulation can provide climate predictability on decadal time scales. It has been hypothesized that the North Atlantic subpolar gyre (SPG) exerts substantial influence on climate predictability. However, a clear identification of the downstream impact of SPG variations is still lacking. Using the MPI-ESM-LR1.2 decadal prediction system, we show that along the Atlantic water pathway, a dynamical link to the SPG causes salinity to be considerably better predicted than temperature. By modulating the slow northward ocean propagation, the subsurface memory of SPG variations enables salinity to be skillfully predicted up to 8 years ahead. In contrast, the SPG loses influence on temperature before Atlantic water penetrates into the Nordic Seas, and in turn, limits temperature to be predicted only 2 years ahead. This study identifies the key role of SPG signals in downstream prediction and highlights how SPG signals determine prediction time scales for different quantities, opening the door for investigating potentially associated predictions in the subarctic for the earth system, marine ecosystems in particular.
First-in-human prospective trial of sonobiopsy in high-grade glioma patients using neuronavigation-guided focused ultrasound
Authors: Yuan Jinyun , Xu Lu , Chien Chih-Yen , Yang Yaoheng , Yue Yimei , Fadera Siaka , Stark Andrew H. , Schwetye Katherine E. , Nazeri Arash , Desai Rupen , Athiraman Umeshkumar , Chaudhuri Aadel A. , Chen Hong , Leuthardt Eric C.
Published: September 2023

Sonobiopsy is an emerging technology that combines focused ultrasound (FUS) with microbubbles to enrich circulating brain disease-specific biomarkers for noninvasive molecular diagnosis of brain diseases. Here, we report the first-in-human prospective trial of sonobiopsy in high-grade glioma patients to evaluate its feasibility and safety in enriching plasma circulating tumor biomarkers. A nimble FUS device integrated with a clinical neuronavigation system was used to perform sonobiopsy following an established clinical workflow for neuronavigation. Analysis of blood samples collected before and after FUS sonication showed that sonobiopsy enriched plasma circulating tumor DNA (ctDNA), including a maximum increase of 1.6-fold for the mononucleosome cell-free DNA (cfDNA) fragments (120–280 bp), 1.9-fold for the patient-specific tumor variant ctDNA level, and 5.6-fold for the TERT mutation ctDNA level. Histological analysis of surgically resected tumors confirmed the safety of the procedure. Transcriptome analysis of sonicated and nonsonicated tumor tissues found that FUS sonication modulated cell physical structure-related genes. Only 2 out of 17,982 total detected genes related to the immune pathways were upregulated. These feasibility and safety data support the continued investigation of sonobiopsy for noninvasive molecular diagnosis of brain diseases.