bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting Gene Comutation of EGFR and TP53 by Radiomics and Deep Learning in Patients With Lung Adenocarcinomas
Authors: Wang Xiao-yan , Wu Shao-hong , Ren Jiao , Zeng Yan , Guo Li-li 
Published: September 2024

Purpose:
This study was designed to construct progressive binary classification models based on radiomics and deep learning to predict the presence of epidermal growth factor receptor (EGFR) and TP53 mutations and to assess the models’ capacities to identify patients who are suitable for TKI-targeted therapy and those with poor prognoses.

Materials and Methods:
A total of 267 patients with lung adenocarcinomas who underwent genetic testing and noncontrast chest computed tomography from our hospital were retrospectively included. Clinical information and imaging characteristics were gathered, and high-throughput feature acquisition on all defined regions of interest (ROIs) was carried out. We selected features and constructed clinical models, radiomics models, deep learning models, and ensemble models to predict EGFR status with all patients and TP53 status with EGFR-positive patients, respectively. The validity and reliability of each model were expressed as the area under the curve (AUC), sensitivity, specificity, accuracy, precision, and F1 score.

Results:
We constructed 7 kinds of models for 2 different dichotomies, namely, the clinical model, the radiomics model, the DL model, the rad-clin model, the DL-clin model, the DL-rad model, and the DL-rad-clin model. For EGFR− and EGFR+, the DL-rad-clin model got the highest AUC value of 0.783 (95% CI: 0.677-0.889), followed by the rad-clin model, the DL-clin model, and the DL-rad model. In the group with an EGFR mutation, for TP53− and TP53+, the rad-clin model got the highest AUC value of 0.811 (95% CI: 0.651-0.972), followed by the DL-rad-clin model and the DL-rad model.

Conclusion:
Our progressive binary classification models based on radiomics and deep learning may provide a good reference and complement for the clinical identification of TKI responders and those with poor prognoses.
RSV healthcare burden in adults before and since the emergence of the COVID-19 pandemic in 6 European countries
Authors: Urchueguía-Fornes Arantxa , Osei-Yeboah Richard , Jollivet Ombeline , Johannesen Caroline Klint , Lehtonen Toni , van Boven Michiel , Gideonse David , Cohen Rachel A. , Orrico-Sánchez Alejandro , Kramer Rolf , Fischer Thea K. , Heikkinen Terho , Nair Harish , Campbell Harry ,   PROMISE investigators
Published: September 2024

AbstractIntroductionRespiratory Syncytial Virus (RSV) is a major cause of morbidity in older adults. With the emergence of the coronavirus disease 2019 (COVID-19) and the subsequent changes in respiratory viral circulation, it is crucial to reassess RSV-associated healthcare burden in adults. This study assessed RSV-associated healthcare burden in adults in six European countries before and during the COVID-19 pandemic.MethodsWe conducted a retrospective analysis using national hospital admissions data from Denmark, England, Finland, the Netherlands, Scotland, and regional surveillance data from the Valencia region (Spain). We included patients aged ≥18 years hospitalised for respiratory tract infections (RTIs) from 2016 to 2023. We assessed RSV-coded and laboratory-confirmed hospitalisations, intensive care unit (ICU) admissions, in-hospital length of stay (LOS), and mortality.ResultsRSV-associated hospitalisations significantly reduced during the 2020/2021 season across all countries, coinciding with strict COVID-19 preventive measures, but resurged in subsequent seasons. We observed the highest hospitalisation rates in adults aged ≥85 years. RSV-coded hospitalisations were found to underestimate the true burden when compared with laboratory-confirmed cases. Underestimation factors ranged from 1.1 to 4.3 times across countries. No significant differences were observed in LOS or ICU admission rates for RSV-associated hospitalisations compared to RTIs.DiscussionOur findings underscore the complex epidemiology of RSV in older adults. The differences between RSV-coded and laboratory-confirmed cases highlight the critical need for improved surveillance and diagnostic practices to better assess the true burden. Our findings could be vital for guiding public health strategies, particularly with the recent introduction of RSV vaccines for older adults.
A neural mechanism for compositional generalization of structure in humans
Authors: Luettgau Lennart , Chen Nan , Erdmann Tore , Veselic Sebastijan , Moran Rani , Kurth-Nelson Zeb , Dolan Raymond J. 
Published: September 2024

AbstractAn exceptional human ability to adapt to the dynamics of novel environments relies on abstracting and generalizing past experiences. While previous research has examined how humans generalize isolated sequential processes, we know little concerning the neural mechanisms that enable adaptation to the more complex dynamics that govern everyday experience. Here, we deployed a novel sequence learning task based on graph factorization, coupled with simultaneous magnetoencephalography (MEG) recordings, to ask whether reuse of experiential “building blocks” provides an abstract structural scaffolding that enables inference and generalization. We provide behavioral evidence that participants decomposed task experience into subprocesses, abstracted dynamical subprocess structures away from sensory specifics, and transferred these to a new task environment. Neurally we show this transfer is underpinned by a representational alignment of abstract subprocesses across task phases, where this included enhanced neural similarity among stimuli that adhered to the same subprocess, a temporally evolving mapping between predictive representations of subprocesses and a generalization of the precise dynamical roles that stimuli occupy within graph structures. Crucially, decoding strength for dynamical role representations predicted behavioral success in transfer of subprocess knowledge, consistent with a role in supporting behavioral adaptation in new environments. We propose a structural scaffolding mechanism enables compositional generalization of dynamical subprocesses that facilitate efficient adaptation within new contexts.
Are Electromyography data a fingerprint for patients with cerebral palsy (CP)?
Authors: Davoudi Mehrdad , Salami Firooz , Reisig Robert , Patikas Dimitrios A. , Beckmann Nicholas A. , Gather Katharina Susanne , Wolf Sebastian I. 
Published: September 2024

AbstractThis study aimed to first investigate changes in electromyography (EMG) patterns after multilevel surgical treatment in patients with cerebral palsy (CP) and then to assess the connection between the measure of EMG and motor control indices and surgery outcomes. We analyzed retrospective EMG and gait data from 167 patients with CP before and after surgery and from 117 typically developed individuals as a reference group. The patients underwent at least one soft tissue surgery on their shank and foot muscles. Using Repeated Measures ANOVA, we examined the norm-distance (ND) of the kinematics, kinetics, and EMG patterns, in addition to the Kerpape-Rennes EMG-based Gait Index (EDI), EMG Profile Score (EPS), and Walking Dynamic Motor Control Index (DMC) before and after surgery. Participants were divided into different response groups (Poor, Mild, and Good gait quality) according to their pre- and post-treatment Gait Deviation Index (GDI), using the K-means-PSO clustering algorithm. The gait and EMG indices were compared between the responders using the nonparametric Mann-Whitney test. The ND for all kinematics and kinetics parameters significantly improved (p-value < 0.05) after the surgery. Regarding EMG, a significant reduction was only observed in the ND of the rectus femoris (p-value < 0.001) and soleus (p-value = 0.006). Among the indices, DMC was not altered post-operatively (p-value = 0.88). Although EDI and EPS were consistent across responders with a similar pre-treatment gait, a higher DMC was significantly associated with a greater improvement, particularly in patients with poor gait (p-value < 0.05). These findings indicate systematic changes in the EMG of patients with CP following surgery, which can also be demonstrated through indices. DMC is a measure that can potentially serve as a partial predictor of outcomes, particularly in patients with poor pre-operative gait. Future research should investigate the effects of different surgical strategies on the improvement of these patients.
Language Modeling Screens Parkinson’s Disease with Self-reported Questionnaires
Authors: Machado Reyes Diego , Hahn Juergen , Shen Li , Yan Pingkun 
Published: September 2024

AbstractParkinson’s disease (PD) is a growing public health challenge associated with the aging population. Current diagnostic methods rely on motor symptoms and invasive procedures, making early detection difficult. This study established a transferable artificial intelligence (AI) model, Quest2Dx, to analyze health questionnaires to enable low-cost and non-invasive PD diagnosis. Quest2Dx tackles the common challenges of missing responses and required specific modeling for each questionnaire by developing a novel language modeling approach to allow the model transfer across different questionnaires and to enhance the interpretability. Evaluated on the PPMI and Fox Insight datasets, Quest2Dx achieved AUROCs of 0.977 and 0.974, respectively, significantly outperforming existing methods. Additionally, cross-questionnaire validation achieved AUROCs of 0.920 and 0.952, respectively, from PPMI to Fox Insight and vice versa. Quest2Dx also identified key predictors from the list of questions to provide further insights. The validated technology elucidates a promising path for PD screening in primary-care settings.
Indirect costs and scientific impact at NIMH
Authors: Perlis Roy H. 
Published: September 2024

AbstractThe National Institutes of Health (NIH) awards additional funds for extramural research to support research infrastructure and administration, such that the total cost of a given research project depends on where it is conducted. We sought to understand whether greater indirects were associated with a greater scientific impact of NIH-funded work. The NIH RePORTER database was queried to retrieve all R01, R21, or R03-funded research proposals for which NIMH was listed as the primary funding source for proposals funded between 2012 and 2023. We applied multiple regression to examine the association between indirect rate and measures of scientific impact, including number of publications, their citation impact in terms of H-index per grant and total citations, and the number of patents associated with each grant. Of 5,143 projects, reflecting $9.85 billion, mean indirect rate was 47.9% (SD 16.2%). Greater indirect rate was associated with modest but statistically significantly greater number of publications (+0.30 per 10% increase in indirect rate, 95% CI 0.08-0.51); H-index at 5 years (+0.25 per 10% increase in indirect rate, 95% CI 0.18-0.33; Figure 1); and total citations (+29.71 per 10% increase in indirect rate, 95% CI 17.86-41.57). Each 10% increase in indirect rate was associated with a 20% increase in odds of patent filing (aOR 1.20, 95% CI 1.05-1.37). The results suggest small incremental benefits from conduct of research at higher-cost institutions and provide data for policymakers to consider in weighing the costs against potential benefits of work at such institutions.
Covalent on-cell conjugation of biomaterials through oxidative phenolic coupling regulates stem cell fate via intracellular biophysical programming
Authors: Johnbosco Castro , Becker Malin , Willemen Niels , Meteling Marieke , Govindaraj Kannan , Kamperman Tom , Leijten Jeroen 
Published: September 2024

AbstractMechanotransduction is widely used to guide cell fate in hydrogels. Traditionally, hydrogels contain adhesive ligands that dynamically bond with cells to stimulate biochemical signalling axis such as YAP-TAZ. However, the molecular toolbox to achieve mechanotransduction has remained virtually limited to non-covalent bonds, which limits our ability to program engineered living matter. Here, we demonstrate that on-cell chemistry can be leveraged to covalently tether biomaterials directly onto cells, and reveal that mechanotransduction is enabled via intracellular biophysical programming. Specifically, droplet microfluidics produced single-cell microgels in which individual stem cells were extracellularly conjugated to either soft or stiff hydrogels via on-cell oxidative phenolic coupling, which allowed for investigation of mechanotransduction at single-cell resolution. Interestingly, this altered intracellular molecular crowding, calcium signalling, and chromatin organization by regulating cytoplasmic and nuclear volume in a stiffness-dependent yet YAP/TAZ-independent manner. Notably, addition of conventional dynamic adhesive ligands such as RGDs decreased chondrogenic commitment indicating that covalent cell-material tethering is both efficient and sufficient for programming cell fate. Encoding biomaterials with a novel form of mechanotransduction in the form of covalent on-cell chemistry, such as oxidative phenolic coupling, expands our ability to guide cellular behaviour, which can accelerate development of drug-screening models, lab-grown meat, and engineered tissues.
INSPIRE: interpretable, flexible and spatially-aware integration of multiple spatial transcriptomics datasets from diverse sources
Authors: Zhao Jia , Zhang Xiangyu , Wang Gefei , Lin Yingxin , Liu Tianyu , Chang Rui B. , Zhao Hongyu 
Published: September 2024

AbstractRecent advances in spatial transcriptomics technologies have led to a growing number of diverse datasets, offering unprecedented opportunities to explore tissue organizations and functions within spatial contexts. However, it remains a significant challenge to effectively integrate and interpret these data, often originating from different samples, technologies, and developmental stages. In this paper, we present INSPIRE, a deep learning method for integrative analyses of multiple spatial transcriptomics datasets to address this challenge. With designs of graph neural networks and an adversarial learning mechanism, INSPIRE enables spatially informed and adaptable integration of data from varying sources. By incorporating non-negative matrix factorization, INSPIRE uncovers interpretable spatial factors with corresponding gene programs, revealing tissue architectures, cell type distributions and biological processes. We demonstrate the capabilities of INSPIRE by applying it to human cortex slices from different samples, mouse brain slices with complementary views, mouse hippocampus and embryo slices generated through different technologies, and spatiotemporal organogenesis atlases containing half a million spatial spots. INSPIRE shows superior performance in identifying detailed biological signals, effectively borrowing information across distinct profiling technologies, and elucidating dynamical changes during embryonic development. Furthermore, we utilize INSPIRE to build 3D models of tissues and whole organisms from multiple slices, demonstrating its power and versatility.
Expression of a constitutively active nitrate reductase increases SARS-CoV-2 Spike protein production inNicotiana benthamianaleaves that otherwise show traits of senescence
Authors: Hamel Louis-Philippe , Paré Marie-Ève , Poirier-Gravel Francis , Tardif Rachel , Comeau Marc-André , Lavoie Pierre-Olivier , Langlois Andréane , Goulet Marie-Claire , D’Aoust Marc-André , Michaud Dominique 
Published: September 2024

SummaryThe production of coronavirus disease 2019 vaccines can be achieved by transient expression of the Spike (S) protein of Severe Acute Respiratory Syndrome Coronavirus 2 in agroinfiltrated leaves ofNicotiana benthamiana, a process promoted by the co-expression of viral silencing suppressor P19. Upon expression, the S protein enters the cell secretory pathway, before being trafficked to the plasma membrane where formation of coronavirus-like particles (CoVLPs) occurs. We recently used RNAseq and time course sampling to characterize molecular responses ofN. benthamianaleaf cells expressing P19 only, or P19 in combination with recombinant S protein. This revealed expression of the viral proteins to deeply affect the physiological status of plant cells, including through the activation of immune responses. Here, transcriptomics shows that the production of CoVLPs also induces leaf senescence, as revealed by the upregulation of senescence-associated genes, activation of senescence-related proteases, and downregulation of genes involved in basic metabolic functions like photosynthesis or nitrogen uptake and assimilation. CoVLP production also upregulated asparagine synthetase genes and led to consequent accumulation of asparagine, a nitrogen-rich amino acid is known to facilitate the reallocation of nitrogen resources from senescent to young growing organs. Hypothesizing these combined host responses to restrain foreign protein accumulation, an attempt was made to support nitrogen reduction in CoVLP-producing leaves by co-expressing a constitutively active, light-insensitive form of the nitrate reductase. We show this strategy to increase S protein accumulation in leaf tissues, thereby suggesting that boosting nitrogen metabolism of agroinfiltrated leaves improves recombinant protein yields inN. benthamiana.
Genomic signatures of coral adaptation and recovery following a mass mortality event
Authors: Fifer James , Speare Kelly E. , Leinbach Sarah E. , Hendricks Stephanie F. , Davies Sarah W. , Rose Noah H. , Burkepile Deron E. , Adam Thomas C. , Hofmann Gretchen E. , Strader Marie E. 
Published: September 2024

ABSTRACTGlobally, corals face an increased frequency of mass mortality events (MMEs) as populations experience repeated marine heatwaves which disrupt their obligate algal symbiosis. Despite greater occurrences of MMEs, the relative roles of the environment, host, and symbiont genetic variation in survival and recovery remain unresolved. We explore these roles using high-resolution temporal and spatial whole genome sequencing of corals before, after, and several years following a MME. We show that host genetics has an impact on bleaching and mortality and that selected alleles important for adaptation persist through the next generation. We also demonstrate that survival for the bleaching event was highly polygenic and that allele frequency shifts have reef habitat specificity. This study reveals how MMEs reshape the genomic landscape and the spatial and temporal distribution of genomic diversity within coral populations facing severe threats from global change.SIGNIFICANCEInvestigations of natural selection in coral genomes following bleaching events have primarily relied on indirect inference, using contemporary populations to explore signatures of past selective pressures, or failed to link these events to the subsequent generation. This has left an open question about the ability of a coral population to adapt from host standing genetic variation in the face of a bleaching event. We demonstrate rapid evolution in a Mo’orean coral population following an MME from a marine heatwave by capturing allele frequency shifts through time. However, the complex polygenic architecture of bleaching survival shows strong habitat specificity, complicating the path towards a genomic prediction of bleaching.
Pdgfab/Pdgfra-mediated chemoattraction guides the migration of sclerotome-derived fibroblast precursors in zebrafish
Authors: Méndez-Olivos Emilio E. , Kocha Katrinka M. , Liao Shan , Huang Peng 
Published: September 2024

ABSTRACTIn vertebrates, the sclerotome is a transient embryonic structure that gives rise to various tissue support cells, including fibroblasts. However, how fibroblast precursors are guided to diverse tissues remain poorly understood. Using zebrafish, our lab has previously shown that sclerotome-derived cells undergo extensive migration to generate distinct fibroblasts subtypes, including tenocytes along the myotendinous junction and fin mesenchymal cells in the fin fold. Interestingly, the pan-fibroblast gene platelet-derived growth factor receptor a (pdgfra), which has been implicated in cell migration across various contexts, is specifically expressed in the sclerotome and its descendants. Loss of functional Pdgfra in apdgfragene-trap mutant results in severe defects in the migration of sclerotome- derived cells, leading to a dose-dependent loss of tenocytes and fin mesenchymal cells. By combining live imaging and mosaic labeling with a membrane-bound dominant-negative tool, we demonstrate that Pdgfra acts cell-autonomously to regulate the migration of sclerotome- derived cells. In the absence of ligandpdgfab, which is expressed in the medial somite, sclerotome-derived cells fail to migrate medially, resulting in a loss of tenocytes, although they can migrate normally toward the fin fold and generate fin mesenchymal cells. Strikingly, localized expression of Pdgfab inpdgfabmutants can direct the migration of sclerotome- derived cells to both normal and ectopic locations, suggesting a chemoattractive role for the Pdgfab ligand. Together, our results demonstrate that Pdgfab/Pdgfra-mediated chemoattraction guides the migration of sclerotome-derived fibroblast precursors to specific locations, where they diversify into distinct fibroblast subtypes.
Under conditions of high wall shear stress, several PfEBA and PfRH ligands are important forPlasmodium falciparummalaria blood-stage growth
Authors: Kals Emma , Kals Morten , Cicuta Pietro , Rayner Julian C. 
Published: September 2024

AbstractMalaria kills over 600,000 people annually, with all the clinical symptoms being caused by the blood stage of the infection. Malaria parasites invade red blood cells (RBCs), where they grow and multiply until daughter parasites egress to invade new RBCs. This cycle happens primarily in the blood circulation, bone marrow, and spleen, where parasites and RBCs are exposed to flow-generated forces. Despite this, almost allin vitrogrowth assays are carried out in static conditions, which are a poor mimic for the conditions that malaria parasites encounter in the body. Therefore, we systematically tested the impact of dynamic conditions created by orbital shaking platforms on parasite growth and explored the link between growth and the wall shear stress forces generated by fluid motion. For several strains of the deadliest malaria species,Plasmodium falciparum, we showed that strikingly, for any given vessel, there is a critical shaking speed at which growth rates are reduced, corresponding to when the RBCs start to aggregate in the centre of the well, before growth increases again at higher shaking speeds. The force that parasites are exposed to at this critical shaking speed corresponds cloesly with previous measurements for the forces that RBCs and parasites are exposed to in the microvasculature. During invasion, the early attachment of the parasites to RBCs is dependent on two families of attachment proteins, the Erythrocyte Binding Antigen (PfEBA) family and the Reticulocyte Binding Protein Homologue (PfRH) family, which are thought to be largely redundant in function. We used a panel of PfEBA and PfRH knock-out lines to show for the first time that several of these ligands have greater importance in high wall shear stress conditions. This both adds new understanding to the function of these ligand families, and indicates that the concept of the critical shaking speed can reveal new parasite growth phenotypes.