bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of early anti-SARS-CoV-2 antibody production on the length of hospitalization stay among COVID-19 patients
Authors: de Almeida Dalziza Victalina , Cezar Priscila Alves , Fernandes Thais Freitas Barreto , Schwarz Marcos Gustavo Araujo , Mendonça-Lima Leila , Giacoia-Gripp Carmem Beatriz Wagner , Côrtes Fernanda Heloise , Lindenmeyer Guimarães Monick , Pilotto Jose Henrique , de Sá Nathalia Beatriz Ramos , Cazote Andressa da Silva , Gomes Larissa Rodrigues , Quintana Marcel de Souza Borges , Ribeiro-Alves Marcelo , Coelho Lara , Geraldo Kim Mattos , Ribeiro Maria Pia Diniz , Cardoso Sandra Wagner , Grinsztejn Beatriz Gilda Jegerhom , Santos Valdiléa Gonçalves Veloso dos , Morgado Mariza Gonçalves 
Published: March 2023

AbstractCOVID-19 has challenged the scientific community in the search for biological markers and information that can contribute to the early management of the severe disease. Given the global scale of COVID-19, including reports of reinfection even in the presence of effective vaccines, we have not yet been able to eradicate the disease. This factor implies the emergence of new waves and an increasing number of hospitalizations. This study aimed to characterize the neutralizing antibody (Nab) geometric mean titers (GMTs) in hospitalized patients with COVID-19 and to evaluate the association with length of stay, comorbidities, and patient outcome. Among the 103 participants, 84 (81.5%) had some previous condition associated with worsening health, and 31 (30%) died. We found that neutralization potency varied greatly across individuals and was significantly higher in patients discharged before 14 days than in patients who stayed longer in the hospital. During the study period, 15 people living with HIV (PLWH) were hospitalized, and no significant difference in clinical characteristics or anti-SARS-CoV-2 Nabs was observed. However, PLWH with severe COVID-19 were younger (41.7, IQR=17.5) than other hospitalized COVID-19 patients (59.3, IQR=22,P<0.01). A high anti-HIV-1 antibody GMT of 583.9 (95% CI: 344-990) was detected, demonstrating maintenance of anti-HIV-1 Nab production among PLWH coinfected with SARS-CoV-2. Therefore, these results indicate that neutralizing antibodies are not the only immunological response capable of controlling disease progression. Nevertheless, these data highlight the importance of more Nab screening studies to predict shorter hospital stays.
A novel approach for estimating vaccine efficacy for infections with multiple outcomes: application to a COVID-19 vaccine trial
Authors: Williams Lucy R , Voysey Merryn , Pollard Andrew J , Grassly Nicholas C 
Published: March 2023

AbstractVaccines can provide protection against infection or limit disease progression and severity. Vaccine efficacy (VE) is typically evaluated independently for different outcomes, but this can cause biased estimates of VE. We propose a new analytical framework based on a model of disease progression for VE estimation for infections with multiple possible outcomes of infection: Joint analysis of multiple outcomes in vaccine efficacy trials (JAMOVET). JAMOVET is a Bayesian hierarchical regression model that controls for biases and can evaluate covariates for VE, the risk of infection, and the probability of progression. We applied JAMOVET to simulated data, and data from COV002 (NCT04400838), a phase 2/3 trial of ChAdOx1 nCoV-19 (AZD1222) vaccine. Simulations showed that biases are corrected by explicitly modelling disease progression and imperfect test characteristics. JAMOVET estimated ChAdOx1 nCoV-19 VE against infection (VEin) at 49% (95% CI 37-59) and progression to symptoms (VEpr) at 44% (95% CI 27-58). This implies a VE against symptomatic infection of 72% (95% CI 63-80), consistent with published trial estimates.VEindecreased with age whileVEprincreased with age. JAMOVET is a powerful tool for evaluating diseases with multiple dependent outcomes and can be used to adjust for biases and identify predictors of key outcomes.
The effect of bolus properties on muscle activation patterns and TMJ loading during unilateral chewing
Authors: Sagl Benedikt , Schmid-Schwap Martina , Piehslinger Eva , Yao Hai , Rausch-Fan Xiaohui , Stavness Ian 
Published: March 2023

AbstractMastication is a vital human function and uses an intricate coordination of muscle activation to break down food. Collection of detailed muscle activation patterns is complex and commonly only masseter and anterior temporalis muscle activation are recorded. Chewing is the orofacial task with the highest muscle forces, potentially leading to high temporomandibular joint (TMJ) loading. Increased TMJ loading is often associated with the onset and progression of temporomandibular disorders (TMD). Hence, studying TMJ mechanical stress during mastication is a central task. Current TMD self-management guidelines suggest eating small and soft pieces of food, but patient safety concerns inhibitin vivoinvestigations of TMJ biomechanics.For this purpose, we have developed a state-of-the-artin silicomodel, combining rigid body bones, finite element TMJ discs and line actuator muscles. To solve the problems regarding muscle activation measurement, we used a forward dynamics tracking approach, optimizing muscle activations driven by mandibular motion. We include a total of 256 different combinations of food bolus size, stiffness and position in our study and report kinematics, muscle activation patterns and TMJ disc von Mises stress.Computed mandibular kinematics agree well with previous measurements. The computed muscle activation pattern stayed stable over all simulations, with changes to the magnitude relative to stiffness and size of the bolus. Our results agree with the clinical guidelines regarding bolus modifications as smaller and softer food boluses lead to less TMJ loading. The results help to strengthen the confidence in TMD self-management recommendations, potentially reducing pain levels of patients.
Wireless Electrical-Molecular Quantum Signalling for Cancer Cell Induced Death
Authors: Jain Akhil , Gosling Jonathan , Liu Shaochuang , Wang Haowei , Stone Eloise M. , Pérez-García Lluïsa , Amabilino David B. , Fromhold Mark , Smith Stuart , Rahman Ruman , Long Yitao , Turyanska Lyudmila , Rawson Frankie J. 
Published: March 2023

AbstractQuantum biological tunnelling for electron transfer (QBET) is involved in controlling cellular behaviour. Control of electrical-molecular communication could revolutionise the development of disruptive technologies for understanding and modulating electrically induced molecular signalling. Current communication technology is not appropriate for interfacing with cells at a spatial/temporal level equivalent to the native biological signalling. This limits our ability to tune cell function by controlling single molecular events. Here, we merge wireless nano-electrochemical tools with cancer cells. Gold-bipolar nanoelectrodes functionalised with redox active species were developed as electric field stimulated bio-actuators, that we term bio-nanoantennae. We show that a remote electrical input regulates electron transport between the redox molecules on the bio-nanoantennae in a selective manner. The wireless modulation of electron transport results in QBET triggering apoptosis in patient-derived cancer cells, representing electrical-induced induced controlled molecular signalling. Transcriptomics data highlight the electric field-induced nanoantenna targets the cancer cells in a unique manner. The insight concerning action and functional nanomaterials opens a plethora of applications in healthcare. This approach may lead to new quantum-based medical diagnostics and treatments, as well as a fundamental understanding of biological physics.
Translation dynamics in human cells visualized at high-resolution reveal cancer drug action
Authors: Xing Huaipeng , Taniguchi Reiya , Khusainov Iskander , Kreysing Jan Philipp , Welsch Sonja , Turoňová Beata , Beck Martin 
Published: March 2023

AbstractRibosomes catalyze protein synthesis by cycling through various functional states. These states have been extensively characterized in vitro, yet their distribution in actively translating human cells remains elusive. Here, we optimized a cryo-electron tomography-based approach and resolved ribosome structures inside human cells with a local resolution of up to 2.5 angstroms. These structures revealed the distribution of functional states of the elongation cycle, a Z tRNA binding site and the dynamics of ribosome expansion segments. In addition, we visualized structures of Homoharringtonine, a drug for chronic myeloid leukemia treatment, within the active site of the ribosome and found that its binding reshaped the landscape of translation. Overall, our work demonstrates that structural dynamics and drug effects can be assessed at near-atomic detail within human cells.One-Sentence SummarySnapshots of ribosome dynamics at near-atomic resolution within native and drug-treated human cells are revealed.
Direct link between convergent evolution at sequence level and phenotypic level of septal pore cap in Agaricomycotina
Authors: Iizuka Tomoyo , Nozawa Masafumi , Ikeo Kazuho 
Published: March 2023

AbstractSeveral apparently homologous morphological characters are known to have independently evolved in different lineages multiple times. However, the genetic backgrounds of such morphological convergences are not well understood. To detect any correlated genes potentially responsible for morphological convergence at the phenotypic level, we focused on the morphology of the septal pore cap (SPC), which is involved in mycelia’s complex multicellularity in fungi. SPCs are classified into three morphological types: perforate, imperforate, and vesiculate. To understand what evolutionary events occurred at the sequence level during morphological convergence of perforate SPCs in Agaricomycotina, we examined sequence differences between species with different SPC types by comparative genomic analysis. If sequences from species with perforate SPCs formed a cluster, the associated gene might be involved in generating perforate SPCs in multiple lineages. Based on this assumption, we detected eight candidate genes, including an SPC-related gene,spc33. The results showed that some amino acid substitutions independently occurred in both lineages in which species with perforate SPCs emerged. From these results, we speculate that the amino acid substitutions inspc33were critical in the emergence of perforate SPCs in multiple lineages. We also found thatspc33evolved just before imperforate SPC emergence based on homology search ofspc33and the species phylogeny. These findings illustrate the first step to clarifying the genetic basis of SPC morphological evolution. Our study contributes to both clarifying the genetic basis of morphological convergence and pioneering our understanding of fungal evolutionary morphology.
Estimating cortical thickness trajectories in children across different scanners using transfer learning from normative models
Authors: Gaiser C. , Berthet P. , Kia S.M. , Frens M. A. , Beckmann C. F. , Muetzel R. L. , Marquand A. 
Published: March 2023

AbstractThis work illustrates the use of normative models in a longitudinal neuroimaging study of children aged 6-17 years and demonstrates how such models can be used to make meaningful comparisons in longitudinal studies, even when individuals are scanned with different scanners across successive study waves. More specifically, we first estimated a large-scale reference normative model using hierarchical Bayesian regression from N=40,435 individuals across the lifespan and from dozens of sites. We then transfer these models to a longitudinal developmental cohort (N=5,985) with three measurement waves acquired on two different scanners that were unseen during estimation of the reference models. We show that the use of normative models provides individual deviation scores that are independent of scanner effects and efficiently accommodate inter-site variations. Moreover, we provide empirical evidence to guide the optimization of sample size for the transfer of prior knowledge about the distribution of regional cortical thicknesses. We show that a transfer set containing as few as 25 samples per site can lead to good performance metrics on the test set. Finally, we demonstrate the clinical utility of this approach by showing that deviation scores obtained from the transferred normative models are able to detect and chart morphological heterogeneity in individuals born pre-term.
Reentrant condensation of a multicomponent complex system of biomolecules induced by polyphosphate
Authors: Furuki Tomohiro , Nobeyama Tomohiro , Suetaka Shunji , Matsui Ryokei , Fukuoka Tatsuhiko , Arai Munehito , Shiraki Kentaro 
Published: March 2023

AbstractReentrant condensation (RC) is a phase behavior of protein solution comprising at least two components. In RC, a protein state varies from one phase to two phases and then back to one phase as the concentration of one component monotonically increases. To understand the phase behavior of multicomponent complex solutions of biomolecules, it is worth constructing an experimental multicomponent system that exhibits RC behavior. Here, we used a cola/milk mixture to investigate RC of a multicomponent complex system and explained the RC mechanism by reducing the system to two pure components, polyphosphate (polyP) and casein. In the multicomponent complex system, RC was observed with 20–60% cola and 1% milk. In the pure system, RC occurred with 0.01–2 mM tetraphosphate and 0.5 mg/ml casein. Moreover, the phase diagram showed that the condensation of casein depended on the chain length of the polyP. The present study succeeded in experimentally inducing RC in a multicomponent system and reproducing RC even when the system was reduced to its pure components. The fact that RC can be experimentally induced using common materials will provide important insights into the understanding of phase-separation behavior of biomolecules.
A Practical Approach to Constructing a Knowledge Graph for Soil Ecological Research
Authors: Le Guillarme Nicolas , Thuiller Wilfried 
Published: March 2023

AbstractWith the rapid accumulation of biodiversity data, data integration has emerged as a hot topic in soil ecology. Data integration has indeed the potential to advance our knowledge of global patterns in soil biodiversity by facilitating large-scale meta-analytical studies of soil ecosystems. However, ecologists are still poorly equipped when it comes to integrating disparate datasets into a unified knowledge graph with well-defined semantics. This paper presents a practical approach to constructing a knowledge graph from heterogeneous and distributed (semi-)structured data sources. To illustrate our approach, we integrate several datasets on the trophic ecology of soil organisms into a trophic knowledge graph and show how information can be retrieved from the graph to support multi-trophic studies.
Molecular Adverse Outcome Pathways: towards the implementation of transcriptomics data in risk assessments
Authors: Martens Marvin , Meuleman Anna Baya , Kearns Jeroen , de Windt Chesley , Evelo Chris T. , Willighagen Egon L. 
Published: March 2023

AbstractAdverse Outcome Pathways (AOPs) are designed to provide mechanistic insights into toxicological processes after exposure to a stressor and facilitate the replacement of animal studies with in vitro testing systems. Starting with a Molecular Initiating Event (MIE) and ending with an Adverse Outcome, the sequence of Key Events (KEs) spans across biological levels, but the majority of KEs in AOP-Wiki describe molecular and cellular processes.That suggests that established transcriptome-wide studies can be used to validate or measure a multitude of KEs simultaneously and be a goldmine of useful information about cellular responses.Currently, in toxicology, omics technologies are not widely applied in risk assessments of chemicals because of their complexity and lack of consensus on aspects such as standardization, analysis and interpretation. Given their value in hypothesis generation and ability to provide a vast amount of information about a biological response, the challenge lies in the acceptance of using transcriptomics data in regulatory risk assessments.We here introduce molecular AOPs to define the connections between KEs of the AOP-Wiki and curated biological pathways in WikiPathways, thereby providing a new method for the analysis and interpretation of transcriptomics data to identify KE activation.To study this, we performed case studies on liver steatosis and mitochondrial complex I inhibition, for which molecular AOPs were developed and public transcriptomics datasets were selected. Upon extension of the molecular AOP networks in Cytoscape, we mapped and analysed transcriptomics data, and calculated an enrichment score for individual KEs. Further interpretation of the data was done through the visualisation of the data on the specific molecular pathways.Two molecular AOPs were developed and KEs were linked to the appropriate molecular pathways, allowing a detailed exploration of molecular processes with the selected transcrip-tomics datasets. This has shown us that we can verify the activation of specific MIEs and KEs, and assess progression across the AOP in the steatosis case study through variables in exposure time and dose.These case studies have shown that transcriptomics data can be used for identifying the potential activation of KEs. However, it is also clear that extensive datasets are required to fully test the capabilities of molecular AOPs, and the process of linking molecular pathways and KEs can be challenging, not always allowing one-to-one mapping. While proven valuable to analyse and understand transcriptomic data, pathways linked to KEs appear to show inconsistent levels of activation and should be looked into and refined. More case studies are required to optimize the approaches used for the development and use of molecular AOPs with transcriptomics datasets.
Genome biology and evolution of mating type loci in four cereal rust fungi
Authors: Luo Zhenyan , McTaggart Alistair , Schwessinger Benjamin 
Published: March 2023

AbstractObligate heterozygous loci such as sex- or mating-compatibility regions often display suppression of recombination and signals of genomic degeneration. In Basidiomycota, two distinct gene loci confer mating compatibility. These encode for homeodomain (HD) transcription factors and pheromone receptor (Pra)-ligand pairs. To date genome level mating type (MAT) loci analysis is lacking for obligate biotrophic basidiomycetes in the orderPucciniales, which contains many economically important plant pathogens.Here, we focus on fourPucciniacereal rust species, includingP. coronataf. sp.avenae,Puccinia graminisf. sp.tritici,P. triticinaandP. striiformisf. sp.tritici, which infect oat and wheat.MATloci are located on two separate chromosomes supporting previous hypotheses of tetrapolar mating types in thePucciniales. TheHDlocus is multiallelic in all four species while thePRlocus appears to be biallelic except forP. graminisf. sp.triticiwhich displays genetic features of more than two alleles.HDloci were largely conserved in their macrosynteny within and between species without strong signals of recombination suppression.PRloci proximate regions, however, displayed extensive signs of recombination suppression and genomic degeneration in the three species with a clear biallelicPRlocus. These observations suggest a correlation between recombination suppression, genomic degeneration and allele status ofMATloci which is consistent with recent mathematical modelling and simulations. Finally, we confirm the evolutionary conservation ofMATgene expression during the asexual infection cycle of the cereal host which we propose is related to correct nuclear pairing during spore formation. Together, our study provides insights into the evolution ofMATloci of key pathogenicPucciniaspecies. This detailed understanding is important to predict possible combinations of nuclear pairs that can arise via sexual reproduction or somatic recombination to enable the evolution of newly virulent isolates of these important plant pathogens.Author summarySex of animals and some plants is determined by sex chromosomes. In fungi, mate compatibility is determined by mating type (MAT) loci, which share some features with sex chromosomes including recombination suppression around heterozygous loci. Here, we study theMATloci in fungal pathogens from the orderPuccinialesthat can cause rust diseases on many economically important plants including wheat and oat. We show that one of theMATloci is multiallelic, while the other is biallelic. The biallelic locus shows strong signs of recombination suppression and genetic deterioration with an increase in transposable elements and gene deserts surrounding the locus. Our findings on the genome biology ofMATloci in four economically important pathogens will lead to a better understanding and prediction of evolution of novel virulent isolates that can lead to large scale pandemics in agriculture.
BRD9-SMAD2/3 orchestrates stemness and tumorigenesis in pancreatic ductal adenocarcinoma
Authors: Feng Yuliang , Cai Liuyang , Pook Martin , Liu Feng , Chang Chao-Hui , Mouti Mai Abdel , Nibhani Reshma , Wu Shihong , Deng Siwei , Militi Stefania , Dunford James , Philpott Martin , Fan Yanbo , Fan Guo-Chang , Liu Qi , Qi Jun , Sadayappan Sakthivel , Jegga Anil G. , Oppermann Udo , Wang Yigang , Huang Wei , Jiang Lei , Pauklin Siim 
Published: March 2023

AbstractThe dismal prognosis of pancreatic ductal adenocarcinoma (PDAC) is linked to the presence of pancreatic cancer stem-like cells (CSCs) that respond poorly to current chemotherapy regimens. By small molecule compound screening targeting 142 epigenetic enzymes, we identified that bromodomain-containing protein BRD9, a component of the BAF histone remodelling complex, is a key chromatin regulator to orchestrate the stemness of pancreatic CSCs via cooperating with the TGFβ/Activin-SMAD2/3 signalling pathway. Inhibition and genetic ablation of BDR9 block the self-renewal, cell cycle entry into G0 phase and invasiveness of CSCs, and improve the sensitivity of CSCs to gemcitabine treatment. In addition, pharmacological inhibition of BRD9 significantly reduced the tumorigenesis in patient-derived xenografts mouse models and eliminated CSCs in tumours from pancreatic cancer patients. Mechanistically, inhibition of BRD9 disrupts enhancer-promoter looping and transcription of stemness genes in CSCs. Collectively, the data suggest BRD9 as a novel therapeutic target for PDAC treatment via modulation of CSC stemness.