bluuebunny/crossref_metadata_2025_split huggingface dataset:
Left atrial strain in multisystem inflammatory syndrome in children (MIS-C) and associations with systemic inflammation and cardiac injury
Authors: Jepson Bryan M. , Beaver Matthew , Colquitt John L. , Truong Dongngan T. , Crandall Hillary , McFarland Carol , Williams Richard , Ou Zhining , Jensen Devri , Minich L. LuAnn , Binka Edem 
Published: May 2023

AbstractBackgroundMultisystem inflammatory syndrome in children (MIS-C) commonly involves cardiac injury with both systolic and diastolic dysfunction. Left atrial strain (LAS) detects subclinical diastolic dysfunction in adults but is infrequently used in children. We evaluated LAS in MIS-C and the associations with systemic inflammation and cardiac injury.MethodsIn this retrospective cohort study, conventional parameters and LAS (reservoir [LAS-r], conduit [LAS-cd], and contractile [LAS-ct]) obtained from admission echocardiograms of MIS-C patients were compared to healthy controls and between MIS-C patients with and without cardiac injury (BNP >500 pg/ml or troponin-I >0.04 ng/ml). Correlation and logistic regression analyses were performed to assess LAS associations with admission inflammatory and cardiac biomarkers. Reliability testing was performed.ResultsMedian LAS components were reduced in MIS-C patients (n=118) compared to controls (n=20) (LAS-r: 31.8 vs. 43.1%, p<0.001; LAS-cd: -28.8 vs. -34.5%, p=0.006; LAS-ct: -5.2 vs. -9.3%, p<0.001) and reduced in MIS-C patients with cardiac injury (n=59) compared to no injury (n=59) (LAS-r: 29.6 vs. 35.8%, p=0.001; LAS-cd: -26.5 vs. -30.4%, p=0.036; LAS-ct: -4.6 vs. -9.3%, p=0.008). An LAS-ct peak was absent in 65 (55%) MIS-C patients but present in all controls (p<0.001). Procalcitonin had strong correlation with averaged E/e’ (r=0.55, p=0.001); ESR had moderate correlation with LAS-ct (r=-0.41, p=0.007); BNP had moderate correlation with LAS-r (r=-0.39, p<0.001) and LAS-ct (r=0.31, p=0.023), and troponin-I had only weak correlations. No strain indices were independently associated with cardiac injury on regression analysis. Intra-rater reliability was good for all LAS components; and inter-rater reliability was good to excellent for LAS-r, and fair for LAS-cd and LAS-ct.ConclusionsLAS analysis, particularly the absence of a LAS-ct peak, was reproducible and may be superior to conventional echocardiographic parameters for detecting diastolic dysfunction in MIS-C. No strain parameters on admission were independently associated with cardiac injury.
Neural assemblies coordinated by cortical waves are associated with waking and hallucinatory brain states
Authors: Aggarwal Adeeti , Luo Jennifer , Chung Helen , Contreras Diego , Kelz Max B. , Proekt Alex 
Published: May 2023

AbstractThe relationship between sensory stimuli and perceptions is brain-state dependent: in wakefulness stimuli evoke perceptions; under anesthesia perceptions are abolished; during dreaming and in dissociated states, percepts are internally generated. Here, we exploit this state dependence to identify brain activity associated with internally generated or stimulus-evoked perception. In awake mice, visual stimuli phase reset spontaneous cortical waves to elicit 3-6 Hz feedback traveling waves. These stimulus-evoked waves traverse the cortex and entrain visual and parietal neurons. Under anesthesia and during ketamine-induced dissociation, visual stimuli do not disrupt spontaneous waves. Uniquely in the dissociated state, spontaneous waves traverse the cortex caudally and entrain visual and parietal neurons, akin to stimulus-evoked waves in wakefulness. Thus, coordinated neuronal assemblies orchestrated by traveling cortical waves emerge in states in which perception can manifest. The awake state is privileged in that this coordination is elicited by specifically by external visual stimuli.
A variational autoencoder trained with priors from canonical pathways increases the interpretability of transcriptome data
Authors: Liu Bin , Rosenhahn Bodo , Illig Thomas , DeLuca David S. 
Published: May 2023

AbstractInterpreting transcriptome data is an important yet challenging aspect of bioinformatic analysis. While gene set enrichment analysis is a standard tool for interpreting regulatory changes, we utilize deep learning techniques, specifically autoencoder architectures, to learn latent variables that drive transcriptome signals. We investigate whether simple, variational autoencoder (VAE), and beta-weighted VAE are capable of learning reduced representations of transcriptomes that retain critical biological information. We propose a novel VAE which utilizes priors from biological data to direct the network to learn a representation of the transcriptome that is based on understandable biological concepts.After training five different autoencoder architectures on 22310 transcriptomes, we benchmarked their performance on organ and disease classification tasks on separate selection of 5577 test samples. Every tested architecture succeeded in reducing the transcriptomes to 50 latent dimensions, which captured enough variation for accurate reconstruction. The simple, fully connected autoencoder, performs best across the benchmarks, but lacks the characteristic of having directly interpretable latent dimensions. The beta-weighted, prior-informed VAE implementation is able to solve the benchmarking tasks, and provide semantically accurate latent features equating to biological pathways.This study opens a new direction for differential pathway analysis in transcriptomics with increased transparency and interpretability.Author summaryThe ability to measure the human transcriptome has been a critical tool to studying health and disease. However, transcriptomes data sets are too large and complex for direct human interpretation. Deep learning techniques such as autoencoders are capable of distilling high-level features from complex data. However, even if deep learning models find patterns, these patterns are not necessarily represented in a way that humans can easily understand. By bringing in the prior knowledge of biological pathways, we have trained the model to “speak the language” of the biologist, and represent complex transcrtomes, in simpler concepts that are already familiar to biologists. We can then apply the tool to compare for example samples from lung cancer cells to healthy cells, and show which biological processes are perturbed.
Identification of immune-related genes for the diagnosis of ischaemic heart failure based on bioinformatics and three machine learning models
Authors: Yu Yi-ding , Xue Yi-tao , Li Yan 
Published: May 2023

BackgroundThe role of immune cells in the pathogenesis of ischaemic heart failure (IHF) is well-established. However, identifying key diagnostic candidate genes in patients with IHF remains a challenge. Therefore, this study aimed to use bioinformatics and machine learning algorithms to identify potential diagnostic genes for IHF.MethodsTwo IHF datasets were obtained from the GEO database, and key genes for IHF were identified using Limma and WGCNA. Functional enrichment analysis was performed to explore the potential mechanisms of IHF. Next, we used three machine learning algorithms, namely LASSO, RF, and SVM-REF, to identify immune-related diagnostic genes for IHF. ssGSEA enrichment analysis was also completed. To assess the diagnostic value of the identified genes, we developed nomogram and validated them on additional GEO datasets. Finally, an immune infiltration analysis was conducted using the CIBERSORT algorithm to explore immune cell dysregulation in IHF.ResultsOur analysis yielded a total of 92 key genes associated with IHF. Enrichment analysis revealed that the mechanisms underlying IHF are mostly associated with immunity and inflammation. Using the machine learning algorithms, we identified four IHF diagnostic genes, namely RNASE2, MFAP4, CHRDL1, and KCNN3. We constructed nomogram and validated the diagnostic value of these genes on additional GEO datasets. The results showed that these four genes had high diagnostic value (AUC value of 0.961). Furthermore, our immune infiltration analysis revealed the presence of three dysregulated immune cells in IHF, namely Macrophages M2, Monocytes, and T cells gamma delta.ConclusionIn summary, our study identified four potential diagnostic candidate genes for IHF by using bioinformatics and machine learning algorithms. We also explored the potential molecular mechanisms of IHF and the immune cell infiltration environment of the failing myocardium. These findings provide new insights into the pathogenesis, diagnosis, and treatment of IHF.
Neo-functionalization and co-option of Pif genes facilitate the evolution of a novel shell microstructure in oysters
Authors: Bai Yitian , Liu Shikai , Hu Yiming , Yu Hong , Kong Lingfeng , Xu Chengxun , Li Qi 
Published: May 2023

AbstractMolluscan shell, composed of a diverse range of architectures and microstructures, is a classic model system to study the relationships between molecular evolution and biomineralized structure formation. The shells of oysters differ from those of other molluscs by possessing a novel microstructure, chalky calcite, which facilitates adaptation to the sessile lifestyle. However, the genetic basis and evolutionary origin of this adaptive innovation remain largely unknown. Here, we present the first chromosome-level genome and shell proteomes of the Iwagaki oysterCrassostrea nippona. Multi-omic integrative analyses revealed that independently evolved and co-opted genes as well as lineage-specific domains are involved in the formation of chalky layer in the oysters. Rapid mineralization involving chalky calcite are essential for reconstruction of the shell. Importantly, von Willebrand factor type A and chitin-binding domains are identified as basic members of molluscan biomineralization toolkit. We show that the well-known Pif shared a common origin in the last common ancestor of Bilateria. Furthermore, Pif and LamG3 genes acquire new genetic function for shell mineralization in bivalves and the chalky layer formation in oysters through a combination of gene duplication and domain reorganization. Our findings highlight neo-functionalization as a crucial mechanism for shell diversity, which may be applied more widely for studies on the evolution of metazoan biomineralization. This study also has potential implications for material science and biomimetic research.
Formation of a stable RNase Y-RicT (YaaT) complex requires RicA (YmcA) and RicF (YlbF)
Authors: Dubnau Eugenie , DeSantis Micaela , Dubnau David 
Published: May 2023

ABSTRACTInBacillus subtilis, the RicT (YaaT), RicA (YmcA) and RicF (YlbF) proteins, which form a stable ternary complex, are needed together with RNase Y (Rny), to cleave and thereby stabilize several key transcripts encoding enzymes of intermediary metabolism. We show here that RicT, but not RicA or RicF, forms a stable complex with Rny, and that this association requires the presence of RicA and RicF. We propose that RicT is handed off from the ternary complex to Rny. We show further that the two iron-sulfur clusters carried by the ternary Ric complex are required for the formation of the stable RicT-Rny complex. We demonstrate that proteins of the degradosome-like network ofB. subtilis, which also interact with Rny, are dispensable for processing of thegapAoperon. Thus, Rny participates in distinct RNA-related processes, determined by its binding partners, and a RicT-Rny complex is likely the functional entity forgapAmRNA maturation.IMPORTANCEThe action of nucleases on RNA is universal and essential for all forms of life and includes processing steps that lead to the mature and functional forms of certain transcripts. InB. subtilisit has been shown that key transcripts for energy producing steps of glycolysis, for nitrogen assimilation and for oxidative phosphorylation, all of them crucial processes of intermediary metabolism, are cleaved at specific locations, resulting in mRNA stabilization. The proteins required for these cleavages inB. subtilis(Rny (RNase Y), RicA (YmcA), RicF (YlbF) and RicT (YaaT)) are broadly conserved among the firmicutes, including in several important pathogens, hinting that regulatory mechanisms they control may also be conserved. Several aspects of these regulatory events have been explored: phenotypes associated with the absence of these proteins have been described, the impact of these absences on the transcriptome has been documented, and there has been significant exploration of the biochemistry and structural biology of Rny and the Ric proteins. The present study further advances our understanding of the association of Ric proteins and Rny and shows that a complex of Rny with RicT is probably the entity that carries out mRNA maturation.
Effects of focused ultrasound in a “clean” mouse model of ultrasonic neuromodulation
Authors: Guo Hongsun , Salahshoor Hossein , Wu Di , Yoo Sangjin , Sato Tomokazu , Tsao Doris Y. , Shapiro Mikhail G. 
Published: May 2023

ABSTRACTRecent studies on ultrasonic neuromodulation (UNM) in rodents have shown that focused ultrasound (FUS) can activate peripheral auditory pathways, leading to off-target and brain-wide excitation, which obscures the direct activation of the target area by FUS. To address this issue, we developed a new mouse model, the double transgenic Pou4f3+/DTR × Thy1-GCaMP6s, which allows for inducible deafening using diphtheria toxin and minimizes off-target effects of UNM while allowing effects on neural activity to be visualized with fluorescent calcium imaging. Using this model, we found that the auditory confounds caused by FUS can be significantly reduced or eliminated within a certain pressure range. At higher pressures, FUS can result in focal fluorescence dips at the target, elicit non-auditory sensory confounds, and damage tissue, leading to spreading depolarization. Under the acoustic conditions we tested, we did not observe direct calcium responses in the mouse cortex. Our findings provide a cleaner animal model for UNM and sonogenetics research, establish a parameter range within which off-target effects are confidently avoided, and reveal the non-auditory side effects of higher-pressure stimulation.
Spatiotemporal modulation of a fixed set of muscle synergies during unpredictable and predictable gait perturbations in older adults
Authors: Brüll Leon , Santuz Alessandro , Mersmann Falk , Bohm Sebastian , Schwenk Michael , Arampatzis Adamantios 
Published: May 2023

AbstractMuscle synergies as functional low-dimensional building blocks of the neuromotor system regulate the activation patterns of muscle groups in a modular structure during locomotion. The purpose of the current study was to explore how older adults organize locomotor muscle synergies to counteract unpredictable and predictable gait perturbations during the perturbed and the recovery steps. Sixty-three healthy older adults (71.2 ± 5.2 years) participated in the study. Mediolateral and anteroposterior unpredictable and predictable perturbations during walking were introduced using a treadmill. Muscle synergies were extracted from the electromyographic activity of 13 lower limb muscles using Gaussian non-negative matrix factorization. The four basic synergies responsible for unperturbed walking (weight acceptance, propulsion, early swing and late swing) were preserved in all applied gait perturbations, yet their temporal recruitment and muscle contribution in each synergy were modified (p<0.05). These modifications were observed up to four recovery steps and were more pronounced (p<0.05) following unpredictable perturbations. The recruitment of the four basic walking synergies in the perturbed and recovery gait cycles indicates a robust neuromotor control of locomotion by using activation patterns of a few and well-known muscle synergies with specific adjustments within the synergies. The selection of pre-existing muscle synergies while adjusting the time of their recruitment during challenging locomotor conditions may facilitate the effectiveness to deal with perturbations and promote the transfer of adaptation between different kinds of perturbations.Summary statementThe flexible recruitment of the four and well-known muscle synergies responsible for unperturbed walking during unpredictable and predictable gait perturbations indicates an effective way to counteract locomotor perturbations, where fast reactive responses are necessary to maintain postural stability.
PHOSPHORYLATION OF RyR2 SIMULTANEOUSLY EXPANDS THE DYAD AND REARRANGES THE TETRAMERS
Authors: Asghari Parisa , Scriven David R.L. , Shahrasebi Saba , Valdivia Hector H. , Wehrens Xander H.T. , Moore Edwin D.W. 
Published: May 2023

AbstractWe have previously demonstrated that type II ryanodine receptors (RyR2) tetramers can be rapidly rearranged in response to a phosphorylation cocktail. The cocktail modified downstream targets indiscriminately making it impossible to determine whether phosphorylation of RyR2 was an essential element of the response. We therefore used the β-agonist isoproterenol and mice with one of the homozygous mutations, S2030A+/+, S2808A+/+, S2814A+/+, or S2814D+/+, to address this question and to elucidate the role of these clinically relevant mutations. We measured the length of the dyad using transmission electron microscopy (TEM) and directly visualized RyR2 distribution using dual-tilt electron tomography. We found that: 1) The S2814D mutation, by itself, significantly expanded the dyad and reorganized the tetramers suggesting a direct link between the phosphorylation state of the tetramer and the microarchitecture. 2) All of the wild-type, as well as the S2808A and S2814A mice, had significant expansions of their dyads in response to ISO, while S2030A did not. 3) In agreement with functional data from the same mutants, S2030 and S2808 were necessary for a complete β-adrenergic response, whereas S2814 was not. 4) All the mutated residues had unique effects on the organization of their tetramer arrays. 5) The correlation of structure with function suggests that tetramer-tetramer contacts play an important functional role. We conclude that both the size of the dyad and the arrangement of the tetramers are linked to the state of the channel tetramer and can be dynamically altered by a β-adrenergic receptor agonist.SummaryAnalysis of RyR2 mutants suggests a direct link between the phosphorylation state of the channel tetramer and the microarchitecture of the dyad. All phosphorylation site mutations produced significant and unique effects on the structure of the dyad and its response to isoproterenol.
Guild-level response of the gut microbiota to isocaloric time-restricted feeding in high-fat diet-fed mice
Authors: Ghosh Shreya , Li Yue , Yang Xin , Wu Guojun , Zhang Chenhong , Zhao Liping 
Published: May 2023

AbstractTime-restricted feeding (TRF) during the active phase protects against high-fat diet (HFD)-induced obesity, and its impact on gut microbiota has been previously investigated using bacterial taxa as functional units. However, in the gut ecosystem, bacteria from different taxonomic backgrounds form coherent functional groups called guilds, whose members exhibit co-abundant behavior. Thirty-five co-abundance groups (CAGs), clustered from 297 prevalent amplicon sequence variants (ASVs), showed greater concordance with beta-diversity plots based on all 1131 ASVs than the 130 classifiable genera, leading to a significantly improved preservation of community-level information. TRF-enriched CAGs positively correlated with metabolic improvement, while TRF-reduced CAGs negatively correlated. TRF restored the diurnal rhythm of most of these key CAGs. Novel ASVs, unclassifiable at the genus level, were identified in these key CAGs. Overall, this suggests that the key bacterial guilds may mediate the beneficial metabolic effects of TRF through the restoration of diurnal oscillation.
Employing Deep Learning Model to Evaluate Speech Information in Vocoder Simulations of Auditory Implants
Authors: Sinha Rahul , Azadpour Mahan 
Published: May 2023

AbstractVocoder simulations have played a crucial role in the development of sound coding and speech processing techniques for auditory implant devices. Vocoders have been extensively used to model the effects of implant signal processing as well as individual anatomy and physiology on speech perception of implant users. Traditionally, such simulations have been conducted on human subjects, which can be time-consuming and costly. In addition, perception of vocoded speech varies significantly across individual subjects, and can be significantly affected by small amounts of familiarization or exposure to vocoded sounds. In this study, we propose a novel method that differs from traditional vocoder studies. Rather than using actual human participants, we use a speech recognition model to examine the influence of vocoder-simulated cochlear implant processing on speech perception. We used the OpenAI Whisper, a recently developed advanced open-source deep learning speech recognition model. The Whisper model’s performance was evaluated on vocoded words and sentences in both quiet and noisy conditions with respect to several vocoder parameters such as number of spectral bands, input frequency range, envelope cut-off frequency, envelope dynamic range, and number of discriminable envelope steps. Our results indicate that the Whisper model exhibited human-like robustness to vocoder simulations, with performance closely mirroring that of human subjects in response to modifications in vocoder parameters. Furthermore, this proposed method has the advantage of being far less expensive and quicker than traditional human studies, while also being free from inter-individual variability in learning abilities, cognitive factors, and attentional states. Our study demonstrates the potential of employing advanced deep learning models of speech recognition in auditory prosthesis research.