bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toward Digital Phenotypes of Early Childhood Mental Health via Unsupervised and Supervised Machine Learning
Authors: Loftness Bryn C. , Rizzo Donna M. , Halvorson-Phelan Julia , O’Leary Aisling , Prytherch Shania , Bradshaw Carter , Brown Anna Jane , Cheney Nick , McGinnis Ellen W. , McGinnis Ryan S. 
Published: February 2023

AbstractChildhood mental health disorders such as anxiety, depression, and ADHD are commonly-occurring and often go undetected into adolescence or adulthood. This can lead to detrimental impacts on long-term wellbeing and quality of life. Current parent-report assessments for pre-school aged children are often biased, and thus increase the need for objective mental health screening tools. Leveraging digital tools to identify the behavioral signature of childhood mental disorders may enable increased intervention at the time with the highest chance of long-term impact. We present data from 84 participants (4-8 years old, 50% diagnosed with anxiety, depression, and/or ADHD) collected during a battery of mood induction tasks using the ChAMP System. Unsupervised Kohonen Self-Organizing Maps (SOM) constructed from movement and audio features indicate that age did not tend to explain clusters as consistently as gender within task-specific and cross-task SOMs. Symptom prevalence and diagnostic status also showed some evidence of clustering. Case studies suggest that high impairment (>80th percentile symptom counts) and diagnostic subtypes (ADHD-Combined) may account for most behaviorally distinct children. Based on this same dataset, we also present results from supervised modeling for the binary classification of diagnoses. Our top performing models yield moderate but promising results (ROC AUC .6-.82, TPR .36-.71, Accuracy .62-.86) on par with our previous efforts for isolated behavioral tasks. Enhancing features, tuning model parameters, and incorporating additional wearable sensor data will continue to enable the rapid progression towards the discovery of digital phenotypes of childhood mental health.Clinical RelevanceThis work advances the use of wearables for detecting childhood mental health disorders.
Cellograph: A Semi-supervised Approach to Analyzing Multi-condition Single-cell RNA Sequencing Data Using Graph Neural Networks
Authors: Shahir Jamshaid A. , Stanley Natalie , Purvis Jeremy E. 
Published: February 2023

AbstractWith the growing number of single-cell datasets collected under more complex experimental conditions, there is an opportunity to leverage single-cell variability to reveal deeper insights into how cells respond to perturbations. Many existing approaches rely on discretizing the data into clusters for differential gene expression (DGE), effectively ironing out any information unveiled by the single-cell variability across cell-types. In addition, DGE often assumes a statistical distribution that, if erroneous, can lead to false positive differentially expressed genes. Here, we present Cellograph: a semi-supervised framework that uses graph neural networks to quantify the effects of perturbations at single-cell granularity. Cellograph not only measures how prototypical cells are of each condition but also learns a latent space that is amenable to interpretable data visualization and clustering. The learned gene weight matrix from training reveals pertinent genes driving the differences between conditions. We demonstrate the utility of our approach on publicly-available datasets including cancer drug therapy, stem cell reprogramming, and organoid differentiation. Cellograph outperforms existing methods for quantifying the effects of experimental perturbations and offers a novel framework to analyze single-cell data using deep learning.
A cataract-causing Y204X mutation of CRYßB1 promotes C-terminal degradation and higher-order oligomerization
Authors: Jing Xuping , Lu Xiaoyun , Zhu Mingwei , Shi Lingyu , Wei Ping , Zhang Bu-Yu , Xu Yi , Xiang Dao-Man , Tang Ya-Ping , Gong Peng 
Published: February 2023

AbstractCrystallin (Cry) proteins are a class of main structural proteins of vertebrate eye lens, and their solubility and stability directly determine transparency and refractive power of the lens. Mutation in genes that encode for these Cry proteins is the common cause for congenital cataract. Despite extensive studies, the pathogenic and molecular mechanisms remain unclear. In this study, we identified a novel mutation inCRYΒB1from a congenital cataract family, and demonstrated that this mutation led to an earlier termination of protein translation, resulting in a 49-residue truncation at the CRYβB1 C-terminus. This mutant is susceptible to proteolysis and allows us to determine a 1.2- Å resolution crystal structure of CRYβB1 without the entire C-terminal domain. In this crystal lattice, two N-terminal domain monomers form a dimer that structurally resembles a wild-type (WT) monomer, but with different surface characteristics. Biochemical analyses suggest that this mutant is significantly more liable to aggregate and degrade, when compared to WT CRYβB1. All our results provide an insight into the mechanism regarding how a mutant Cry contributes to the development of congenital cataract possibly through alteration of inter-protein interactions that result in the opacity of eye lens.
Zero-shot learning enables instant denoising and super-resolution in optical fluorescence microscopy
Authors: Qiao Chang , Zeng Yunmin , Meng Quan , Chen Xingye , Chen Haoyu , Jiang Tao , Wei Rongfei , Guo Jiabao , Fu Wenfeng , Lu Huaide , Li Di , Wang Yuwang , Qiao Hui , Wu Jiamin , Li Dong , Dai Qionghai 
Published: February 2023

AbstractComputational super-resolution (SR) methods, including conventional analytical algorithms and deep learning models, have substantially improved optical microscopy. Among them, supervised deep neural networks have demonstrated outstanding SR performance, however, demanding abundant high-quality training data, which are laborious and even impractical to acquire due to the high dynamics of living cells. Here, we develop zero-shot deconvolution networks (ZS-DeconvNet) that instantly enhance the resolution of microscope images by more than 1.5-fold over the diffraction limit with 10-fold lower fluorescence than ordinary SR imaging conditions in an unsupervised manner without the need for either ground truths or additional data acquisition. We demonstrate the versatile applicability of ZS-DeconvNet on multiple imaging modalities, including total internal reflection fluorescence microscopy, three-dimensional (3D) wide-field microscopy, confocal microscopy, lattice light-sheet microscopy, and multimodal structured illumination microscopy (SIM), which enables multi-color, long-term, super-resolution 2D/3D imaging of subcellular bioprocesses from mitotic single cells to multicellular embryos of mouse and C. elegans.
Excessive apoptosis of naïve T cells resulting hyperactivation as a cause of mammalian aging
Authors: Wang Lingxia , Zhang Xixi , Zhang Haiwei , Lu Kaili , Li Ming , Li Xiaoming , Ou Yangjing , Zhao Xiaoming , Wu Xiaoxia , Wu Xuanhui , Liu Jianling , Xing Mingyan , Liu Han , Zhang Yue , Tan Yongchang , Li Fang , Deng Jiangshan , Zhang Xiaojie , Li Jinbao , Zhao Yuwu , Wang Xiuzhe , Luo Yan , Zhou Ben , Zhang Haibing 
Published: February 2023

AbstractIn mammals, the most remarkable T cell variations with aging are the shrinking of naïve T cell pool and enlargement of memory T cell pool, which are partially caused by thymic involution. However, it remains an enigma whether these T-cell-related changes are consequences or causes of mammalian aging. In this study, we find that the T-cell specificRip1KO mice present similar age-related T cell changes and exhibit signs of accelerated aging, including inflammation, multiple age-related diseases and a shorter lifespan. Mechanistically, T cells lacking RIP1 displayed excessive apoptosis, leading to T cell compensatory proliferation, hyperactivation, increased inflammation, and ultimately premature death. Consistent with this, blocking apoptosis by co-deletion ofFaddinRip1deficient T cells significantly recovered the lymphopenia and imbalance between naïve and memory T cell, substantially restored ageing-related phenotypes, and prolonged life span in T-cell specificRip1KO mice. These results suggest that changes in T cells play a causal role in mammalian aging. Therefore, replenishing or blocking apoptosis of naïve T cells could offer new therapeutic approaches for aging and age-related diseases.
Biologically informed NeuralODEs for genome-wide regulatory dynamics
Authors: Hossain Intekhab , Fanfani Viola , Fischer Jonas , Quackenbush John , Burkholz Rebekka 
Published: February 2023

AbstractModeling dynamics of gene regulatory networks using ordinary differential equations (ODEs) allow a deeper understanding of disease progression and response to therapy, thus aiding in intervention optimization. Although there exist methods to infer regulatory ODEs, these are generally limited to small networks, rely on dimensional reduction, or impose non-biological parametric restrictions — all impeding scalability and explainability. PHOENIX is a neural ODE framework incorporating prior domain knowledge as soft constraints to infer sparse, biologically interpretable dynamics. Extensive experiments - on simulated and real data - demonstrate PHOENIX’s unique ability to learn key regulatory dynamics while scaling to the whole genome.
Shared inflammatory glial cell signature after brain injury, revealed by spatial, temporal and cell-type-specific profiling of the murine cerebral cortex
Authors: Koupourtidou Christina , Schwarz Veronika , Aliee Hananeh , Frerich Simon , Fischer-Sternjak Judith , Bocchi Riccardo , Simon-Ebert Tatiana , Dichgans Martin , Götz Magdalena , Theis Fabian , Ninkovic Jovica 
Published: February 2023

AbstractTraumatic brain injury leads to a highly orchestrated immune- and glial cell response partially responsible for long-lasting disability and the development of secondary neurodegenerative diseases. A holistic understanding of the mechanisms controlling the responses of specific cell types and their crosstalk is required to develop an efficient strategy for better regeneration. Here, we combined spatial and single-cell transcriptomics to chart the transcriptomic signature of the injured murine cerebral cortex, and identified specific states of astrocytes, microglia, and oligodendrocyte precursor cells contributing to this signature. Interestingly, these cellular populations share a large fraction of injury-regulated genes, including inflammatory programs downstream of the innate immune-associated pathways Cxcr3 and Tlr1/2. Systemic manipulation of these pathways decreased the reactivity state of glial cells associated with poor regeneration. The functional relevance of the newly discovered shared signature of glial cells highlights the importance of our resource enabling comprehensive analysis of early events after brain injury.
A layer cake model for plant and metazoan chromatin
Authors: Carron Léoplod , Concia Lorenzo , Grob Stefan , Barneche Fredy , Carbone Alessandra , Mozziconacci Julien 
Published: February 2023

AbstractEarly structural studies of chromosome organisation in eukaryotic nuclei led to the identification of euchromatin and heterochromatin, two main archetypes of chromatin visible through microscopy. Subsequently, the diversity of chromatin composition along the linear genome sequence was resolved using high throughput sequencing techniques to map a multitude of chromatin marks and unravel their functional organisation. Recent analyses of human chromosome conformation capture experiments tend to point to the existence of several chromosome sub-compartments that may correspond to epigenomic variations in chromatin composition. Here, we compare genome 3D organisations in representative eukaryotic species to explore the links between chromosomal sub-compartments and chromatin marks, genome replication timing, and genomic repeats in six model organisms, including vertebrates, plants and insects. We report that the 3D organisation of chromatin in organisms with different genome content and size can be described as layers characterised by distinct chromatin marks and activities. We propose a ”layer cake” model for the genome 3D organisation as a more refined view than the prevalent ”two compartments” model of chromatin organisation in multi-cellular organisms.
Detailed spectrographic analysis of rat ultrasonic vocalizations emitted during the acoustic startle response test
Authors: Bartsoen Emilie , Wöhr Markus 
Published: February 2023

AbstractRats emit ultrasonic vocalizations (USV). During aversive situations, rats emit 22-kHz USV, which are considered “alarm calls” and supposed to reflect a negative affective state of the sender. During appetitive situations, rats emit 50-kHz USV, which are believed to reflect a positive affective state. Here, we recorded USV emission in adult male rats during the acoustic startle response test. Our results indicate varied USV emission in both the 22- and 50-kHz USV ranges. Enhanced startle responses were observed in rats with a predominant 22-kHz call profile, supporting the notion that 22-kHz USV emission is associated with a negative affective state.
Dilated Virchow-Robin Spaces are a Marker for Arterial Disease in Multiple Sclerosis
Authors: Ineichen Benjamin V. , Cananau Carmen , Plattén Michael , Ouellette Russell , Moridi Thomas , Frauenknecht Katrin B. M. , Okar Serhat V. , Kulcsar Zsolt , Kockum Ingrid , Piehl Fredrik , Reich Daniel S. , Granberg Tobias 
Published: February 2023

AbstractVirchow-Robin spaces (VRS) have been associated with neurodegeneration and neuroinflammation. However, it remains uncertain to what degree non-dilated or dilated VRS reflect specific features of neuroinflammatory pathology. Thus, we aimed at investigating the clinical relevance of VRS as imaging biomarker in multiple sclerosis (MS) and to correlate VRS to their histopathologic signature. In a cohort study comprising 205 MS patients (including a validation cohort) and 30 control subjects, we assessed the association of non-dilated and dilated VRS to clinical and magnetic resonance imaging (MRI) out-comes. Brain blocks from 6 MS patients and 3 non-MS controls were histopathologically processed to correlate VRS to their tissue substrate. The count of dilated centrum semiovale VRS was associated with increased T1 and T2 lesion volumes. There was no systematic spatial colocalization of dilated VRS with MS lesions. At tissue level, VRS mostly corresponded to arteries and were not associated with MS pathological hallmarks. Interestingly, dilated VRS in MS were associated with signs of small vessel disease. Contrary to prior beliefs, these observations suggest that VRS in MS do not associate with accumulation of immune cells. But instead, these findings indicate vascular pathology as a driver and/or consequence of neuroinflammatory pathology for this imaging feature.
Cognitive reappraisal and corresponding neural basis mediate the association between childhood maltreatment and depression
Authors: Mao Yu , Li Ling , Hou Xin , Li Yuan , Duan Shukai 
Published: February 2023

AbstractBackgroundChildhood maltreatment is considered as a robust predictor of depression. However, the underlying psychological and neurological mechanisms linking childhood maltreatment and depression remain poorly understood. Sufficient evidence demonstrates emotion dysregulation in individuals who have experienced childhood maltreatment, but it is unknown whether these changes represent vulnerability for depression. Here we speculated that decreased cognitive reappraisal and its corresponding neural basis might explain the relationship between childhood maltreatment and follow-up depression.MethodsFirst, we investigated whether cognitive reappraisal can explain the relationship between childhood maltreatment and depression, with a cross-sectional (n= 657) behavioral sample. Then we recruit 38 maltreated participants and 27 controls to complete the cognitive reappraisal functional magnetic resonance imaging (fMRI) task. The between-group difference in brain activation and functional connectivity (FC) were tested using independent t-tests. Finally, we investigated the relationship between childhood maltreatment, task-based brain activity and depression.ResultsThe behavior results suggested that cognitive reappraisal mediate the association between childhood maltreatment and depression. Specifically, participants with higher level of childhood maltreatment tend to have deficit in cognitive reappraisal, which ultimately predict higher level of depression when facing stressful life event. In addition, the maltreated group exhibited lower activation of orbitofrontal cortex (OFC) and higher FC of between the dorsolateral prefrontal cortex (DLPFC), posterior cingulate cortex (PCC), OFC, and amygdala during cognitive reappraisal, compared with healthy controls. Furthermore, the FC of DLPFC-amygdala mediates the association between childhood maltreatment and depression.ConclusionIn summary, childhood maltreatment is associated with inefficient cognitive reappraisal ability, manifesting as aberrant modulation of cortical areas on amygdala. These cognitive and neural deficits might explain the relationship between childhood maltreatment and risk of depression in later life. On the other side, cognitive reappraisal might also be a potential resilient factor for the prevention of maltreatment related emotional problems.
Integration of Apocarotenoid Profile and Expression Pattern ofCarotenoid Cleavage Dioxygenasesduring Mycorrhization in Rice
Authors: Votta Cristina , Wang Jian You , Cavallini Nicola , Savorani Francesco , Liew Kit Xi , Lanfranco Luisa , Al-Babili Salim , Fiorilli Valentina 
Published: February 2023

AbstractCarotenoids are susceptible to degrading processes initiated by oxidative cleavage reactions mediated by Carotenoid Cleavage Dioxygenases that break their backbone, leading to products called apocarotenoids. These carotenoid-derived metabolites include the phytohormones abscisic acid and strigolactones, and different signaling molecules and growth regulators, which are utilized by plants to coordinate many aspects of their life. Several apocarotenoids have been recruited for the communication between plants and arbuscular mycorrhizal (AM) fungi and as regulators of the establishment of AM symbiosis. However, our knowledge on their biosynthetic pathways and the regulation of their pattern during AM symbiosis is still limited. In this study, we generated a qualitative and quantitative profile of apocarotenoids in roots and shoots of rice plants exposed to high/low phosphate concentrations, and upon AM symbiosis in a time course experiment covering different stages of growth and AM development. To get deeper insights in the biology of apocarotenoids during this plant-fungal symbiosis, we complemented the metabolic profiles by determining the expression pattern ofCCDgenes, taking advantage of chemometric tools. This analysis revealed the specific profiles ofCCDgenes and apocarotenoids across different stages of AM symbiosis and phosphate supply conditions, identifying novel markers at both local and systemic levels.HighlightOur study presents the profiles ofCCDgene expression and apocarotenoids across different stages of AM symbiosis and Pi supply conditions and reveals novel AM markers at both local and systemic levels.
A gradual migratory divide determines not only the direction of migration but also migration strategy of a social migrant bird
Authors: Piironen Antti , Laaksonen Toni 
Published: February 2023

AbstractMigratory divides separate populations of migratory animals, facilitating the evolution of intraspecific differences in migration strategies. The optimal migration theory suggests differing migration strategies for birds using different flyways (with different habitats), but the knowledge regarding the impact of the flyway to the individual migration strategies is scarce. We used satellite tracking and neckband resightings to unravel the structure of the migratory divide between two European flyway populations of greylag geeseAnser anser. We modelled satellite tracking data using Gaussian processes to study migration strategies of birds using different flyways. The mean posterior probability for an individual to migrate along the Western Flyway decreased gradually from 0.98 to 0.06 within the Baltic Sea coast, revealing a gradual migratory divide. In addition, migration strategies differed between the flyways. The birds using Western Flyway migrated earlier in autumn, performed longer annual migration and made a clear stopover during migration, whereas the birds using Central Flyway flew directly to their wintering sites. The gradual migratory divide that also divided migration strategies provides exciting insights to ecological and evolutionary factors behind migratory divides. Gaussian processes enabled modelling of detailed migration strategies, encouraging their future usage in movement ecology.
Human immune phenotyping reveals accelerated aging in type 1 diabetes
Authors: Shapiro Melanie R. , Dong Xiaoru , Perry Daniel J. , McNichols James M. , Thirawatananond Puchong , Posgai Amanda L. , Peters Leeana , Motwani Keshav , Musca Richard S. , Muir Andrew , Concannon Patrick , Jacobsen Laura M. , Mathews Clayton E. , Wasserfall Clive H. , Haller Michael J. , Schatz Desmond A. , Atkinson Mark A. , Brusko Maigan A. , Bacher Rhonda L. , Brusko Todd M. 
Published: February 2023

AbstractThe composition of immune cells in peripheral blood is dramatically remodeled throughout the human lifespan, as environmental exposures shape the proportion and phenotype of cellular subsets. These dynamic shifts complicate efforts to identify disease-associated immune signatures in type 1 diabetes (T1D), which is variable in age of onset and rate of β-cell decline. Herein, we conducted standardized flow cytometric immune profiling on peripheral blood from a cross-sectional cohort of T1D participants (n=240), their first-degree relatives (REL,n=310), those at increased risk with two or more islet autoantibodies (RSK,n=24), and autoantibody negative healthy controls (CTR,n=252). We constructed an immune-age predictive model in healthy subjects and developed an interactive data visualization portal (ImmScape;https://ufdiabetes.shinyapps.io/ImmScape/). When applied to the T1D cohort, this model revealed accelerated immune aging (p<0.001) as well as phenotypic signatures of disease after age correction. Of 192 investigated flow cytometry and complete blood count readouts, 46 were significantly associated with age only, 25 with T1D only, and 23 with both age and T1D. Phenotypes associated with T1D after age-correction were predictive of T1D status (AUROC=82.3%). Phenotypes associated with accelerated aging in T1D included increased CXCR3+and PD-1+frequencies in naïve and memory T cell subsets, despite reduced PD-1 expression levels (mean fluorescence intensity) on memory T cells. Additionally, quantitative trait locus analysis linked an increase in HLA-DR expression on monocytes with the T1D-associated HLA-DR4/DQ8 genotype, regardless of clinical group. Our findings demonstrate advanced immune aging in T1D and highlight disease-associated phenotypes for biomarker monitoring and therapeutic interventions.One Sentence SummaryPeripheral blood characterization reveals accelerated immune-age and age-adjusted proinflammatory immune phenotypes in type 1 diabetes.