bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-Contact Molecular Chemical Imaging Assessment of Tissue Congestion: A Validation Study Compared to MRI
Authors: Saltman Adam E , Ghosh Richik N , Eckman Peter M. , Chappuis Michael , Collins Jeremy D , Morley Pamela , Mazis Holly , Schweitzer Robert , Enriquez-Sarano Maurice , Tazik Shawna K , Gomer Heather , Nelson Matthew , Treado Patrick J 
Published: November 2022

AbstractBackgroundHeart failure (HF) is a healthcare problem burdening patients, care teams, and health care systems. A relentless, downward spiral of decompensation, hospital admission, and functional deterioration is challenging to break, partly because of the lack of an objective, inexpensive tool to aid the clinician’s physical examination. We studied performance of a shortwave infrared (SWIR) molecular chemical imaging (MCI) tool to measure relative tissue congestion (TC) in HF patients’ shins, compared to MRI Dixon sequence TC measurements as ground truth.MethodsForty-seven (47) subjects underwent paired SWIR MCI and MRI measurements of their lower extremities. Thirty-six (36) subjects were hospitalized with decompensated HF while 11 healthy outpatients served as controls. A partial least squares (PLS) regression model was trained to ingest the SWIR MCI spectra and produce a CardioVerification Index (CVI) that mirrored MRI measurements.ResultsThe SWIR MCI model reflected MRI TC measurements accurately for all subjects with a 0.743 linear correlation coefficient. Surprisingly, the MRI results identified a significant fraction of non-HF subjects with elevated TC levels, so a sub-analysis was performed on “Low TC” subjects with low and undetectable levels of extremity edema. This subpopulation’s linear correlation between MRI and CVI was 0.674. A logistic classifier model differentiated HF from non-HF subjects; the area under the receiver operating characteristic curves was 0.906 for the entire subject group and 0.821 for the Low TC subpopulation.ConclusionSWIR MCI techniques can be used in a TC-measuring tool that replicates MRI TC measurements. Clinicians could use such tools to help guide therapy for HF patients during in-hospital management of acute HF decompensation and for outpatient monitoring. SWIR MCI’s ability to identify elevated TC in otherwise normal subjects may also meet the unmet need for a novel, widely applicable HF screening tool.
Effect of intranasal administration of neuroEPO in the histological structure of the olfactory mucosa of rats Wistar
Authors: Borrás Ketty Suárez , Peña Gisselle Fernández , Seguí Giselle Puldón , Hernández Carlos Luis Pérez , Cruz Yamila Rodríguez 
Published: November 2022

ABSTRACTIntroductionStrokes and neurodegenerative diseases are major global health problems. Not only because they cause high mortality and disability, but to the lack of effective therapies. NeuroEPO, a variant of recombinant human erythropoietin (rHu-EPO) with a low sialic acid content, has shown encouraging results as a potential neuroprotective agent when administered intranasally.ObjectiveTo determine the effect of intranasal administration of NeuroEPO on the histological structure of the olfactory mucosa of Wistar rats.Materials and MethodsAn experimental, prospective, and longitudinal study was conducted in Wistar rats. Ten healthy animals were randomly distributed into two groups of five each. The control group received a vehicle (0.3 μl/g/day) and the treated group received NeuroEPO (300 μg/kg/day). Both treatments were administered intranasally for 28 days. The histological characteristics of the olfactory mucosa were evaluated. The medians of the study groups were compared using the Mann-Whitney U test.ResultsThere were no alterations in the histological characteristics of the olfactory epithelium. However, at the level of the lamina propria in the group treated with NeuroEPO, slight hypertrophy, and hyperplasia of the Bowman’s glands was observed.ConclusionsThe administration of the nasal formulation of NeuroEPO did not induce histological alterations of the olfactory mucosa of Wistar rats under the experimental conditions of this research.
Quartet metabolite reference materials for assessing inter-laboratory reliability and data integration of metabolomic profiling
Authors: Zhang Naixin , Zhang Peipei , Chen Qiaochu , Zhou Kejun , Liu Yaqing , Wang Haiyan , Xie Yongming , Ren Luyao , Hou Wanwan , Yang Jingcheng , Yu Ying , Zheng Yuanting , Shi Leming 
Published: November 2022

AbstractVarious laboratory-developed metabolomic methods lead to big challenges in inter-laboratory comparability and effective integration of diverse datasets. As part of the Quartet Project, we established a publicly available suite of four metabolite reference materials derived from B-lymphoblastoid cell lines from a family quartet of parents and monozygotic twin daughters. We generated comprehensive LC-MS based metabolomic data from the Quartet reference materials using targeted and untargeted strategies in different laboratories. High variabilities in the qualitative and quantitative metabolomic measurements were observed across laboratories. Moreover, the Quartet multi-sample-based quality metrics were developed for objectively assessing the reliability of metabolomic profiling in detecting intrinsic biological differences among difference groups of samples. Importantly, the ratio-based metabolomic profiling, by scaling the absolute values of a study sample relative to those of a universal reference sample, enables data integration in long-term measurements across difference laboratories or platforms. Thus, we constructed the ratio-based high-confidence reference datasets between two reference samples, providing “ground truth” for inter-laboratory proficiency test, which enables objective assessment of various metabolomic methods. Our study provided the community with rich resources and best practice for objective assessment of inter-laboratory measurements and data integration, ensuring reliable large-scale and longitudinal metabolomic profiling.
S-BEAM: A Semi-Supervised Ensemble Approach to Rank Potential Causal Variants and Their Target Genes in Microglia for Alzheimer’s Disease
Authors: Khaire Archita , Wen Jia , Yang Xiaoyu , Zhou Haibo , Shen Yin , Li Yun 
Published: November 2022

AbstractAlzheimer’s disease (AD) is the leading cause of death among individuals over 65. Despite many AD genetic variants detected by large genome-wide association studies (GWAS), a limited number of causal genes have been confirmed. Conventional machine learning techniques integrate functional annotation data and GWAS signals to assign variants functional relevance probabilities. Yet, a large proportion of genetic variation lies in the non-coding genome, where unsupervised and semi-supervised techniques have demonstrated greater advantage. Furthermore, cell-type specific approaches are needed to better understand disease etiology. Studying AD from a microglia-specific lens is more likely to reveal causal variants involved in immune pathways. Therefore, in this study, we developed S-BEAM: a semi-supervised ensemble approach using microglia-specific data to prioritize non-coding variants and their target genes that play roles in immune-related AD mechanisms. We designed a transductive positive-unlabeled and negative-unlabeled learning model that employs a bagging technique to learn from unlabeled variants, generating multiple predicted probabilities of variant risk. Using a combined homogeneous-heterogeneous ensemble framework, we aggregated the predictions. We applied our model to AD variant data, identifying 11 risk variants acting in well-known AD genes, such asTSPAN14,INPP5D, andMS4A2. These results validated our model’s performance and demonstrated a need to study these genes in the context of microglial pathways. We also proposed further experimental study for 37 potential causal variants associated with less-known genes. Our work has utility in predicting AD relevant genes and variants functioning in microglia and can be generalized for application to other complex diseases or cell types.
Integrating Network Pharmacology And Experimental Verification To Explore The Mechanism Of Qionggui Power Against Atherosclerosis
Authors: Wang Yuqing , Man Yonghong , Jiang Xu , Shui Dong , Zhao Qing , Li Shujiao , Zhuang Guo 
Published: November 2022

AbstractQionggui Power (QP), a classic prescription in Traditional Chinese Medicine (TCM), has shown potential in the treatment of atherosclerosis during the past decades. However, the mechanism that mediates these cardiovascular benefits remains to be fully elucidated. Here, we investigated the effects and mechanisms of QP against atherosclerosis with network pharmacology approaches andin vitromodel. The active ingredients and related targets of QP were collected from public databases. The hub targets and signaling pathways of QP against AS were defined by extensive application of bioinformatics approaches, including the protein-protein interaction (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG). The predicted major targets were validated in LPS-stimulated murine macrophages RAW264.7. The anti-inflammatory properties of QP were also evaluated in this model.In silicoinvestigation of QP resulted in the identification of 18 active ingredients and 49 chemical targets intersecting with AS-related genes. And KEGG pathway analysis revealed a high enrichment in the Lipid and Atherosclerosis pathway of these chemical targets. Biochemical analysis showed marked effects of QP on the expression of predicted chemical targets (PPARr, CAT, PTGS2) and LPS-induced inflammatory genes (IL1, IL6, and TNFα). And these inhibitory effects were linked to the suppression of the NF-κB signaling pathway, which was activated by the LPS stimulus. Our findings revealed the therapeutic potential of QP in the prevention and treatment of atherosclerosis.Graphical Abstract
Age-related changes in brain metabolites underlie slowing of speed-accuracy trade-off
Authors: Revie Lauren , Metzler-Baddeley Claudia 
Published: November 2022

AbstractAging leads to response slowing but the underpinning cognitive and neural mechanisms remain elusive. We studied cognitive components of response speed with a diffusion drift model to estimate nondecision, boundary-separation, and drift-rate contributions to choice reaction times of older (62-80 years) and younger (18-29 years) adults (n=25 each). We characterised age-related differences in the metabolic and microstructural profile of cortical regions and white matter (WM) pathways of visuo-perceptual and attention networks with magnetic resonance spectroscopy and multi-shell diffusion-weighted imaging. Aging was associated with increased non-decision time and boundary-separation, reduced N-acetyl aspartate (NAA) concentrations in anterior cingulate (ACC) and posterior parietal cortices, and reduced WM microstructure in the optic radiation (OR), inferior and superior longitudinal fasciculus (ILF, SLF) and fornix. NAA in ACC and diffusivities in OR and SLF predicted non-decision time, while restricted diffusivity signal fraction in the ILF and fornix, and diffusivity in OR predicted boundary-separation. These results suggest that age-related deterioration of neuronal health and WM microstructure in visuo-perceptual and attention networks contribute to response slowing in aging.
An information theoretic approach to detecting spatially varying genes
Authors: Jones Daniel C. , Danaher Patrick , Kim Youngmi , Beechem Joseph M. , Gottardo Raphael , Newell Evan W. 
Published: November 2022

AbstractIdentifying genes with spatially coherent expression patterns is a key task in spatial transcriptomics. We adopt an information theoretic perspective on this problem by equating the degree of spatial coherence with the mutual information between nearby expression measurements. To avoid the notoriously difficult problem of computing mutual information, we use modern methods of approximation, in a method we call maximization of spatial information (Maxspin). As well as being highly scalable, we demonstrate improved accuracy across several spatial transcriptomics platforms and a variety of simulations when compared to both existing specialized methods and traditional spatial statistics methods. We use the method to analyze a renal cell carcinoma sample profiled using CosMx Spatial Molecular Imaging, revealing previously undescribed gene expression patterns.
Now you see it: fixation-related electrical potentials during a free visual search task reveal the timing of visual awareness
Authors: Qiu Zeguo , Xia Hongfeng , Becker Stefanie I. , Hamblin-Frohman Zachary , Pegna Alan J. 
Published: November 2022

AbstractIt has been repeatedly claimed that emotional faces capture attention readily, and that they are processed without awareness. Yet some observations cast doubt on these assertions. Part of the problem may lie in the experimental paradigms employed. Here, we used a free viewing visual search task and simultaneously recorded electroencephalography and eye-movements. Fixation-related potentials were computed for fearful and neutral facial expressions, and the electrical response compared when participants were aware or unaware of the fixated stimulus. We showed that the P300 increased across repeated fixations on the unseen targets, culminating in a conscious report, likely reflecting evidence accumulation. Awareness of the stimulus was associated with electrical changes emerging at around 130 ms, with emotions of the stimulus being dissociated only after awareness had arisen. These results suggest that the earliest electrical correlate of awareness emerges at around 130 ms in visual search and that emotion processing requires visual awareness.
Statistical analysis and simulation allowing simultaneously positive, negative, and no crossover interference in multilocus recombination data
Authors: Sapielkin Shaul , Frenkel Zeev , Privman Eyal , Korol Abraham B. 
Published: November 2022

AbstractCrossover interference (COI) is a widespread feature of homologous meiotic recombination. It can be quantified by the classical coefficient of coincidence (CoC) `but this characteristic is highly variable and specific to the pair of chromosomal intervals considered. Several models were proposed to characterize COI on a chromosome-wise level. In the gamma model, the strength of interference is characterized by a shape parameterν, while the gamma-sprinkled two-pathway model (GS) accounts for both interference-dependent and independent crossover (CO) events by fitting a mixture of gamma distributions withv>1 andv=1, correspondingly, and mixture proportions 1-pandp. In reality, COI can vary along chromosomes resulting in low compliance of the fitted model to real data. Additional inconsistency can be caused by common neglecting of possible negative COI in the model, earlier reported for several organisms. In this work, we propose an extension of the GS-model to take possible negative COI into account. We propose a way for data simulation and parameter estimation for such situations.
The inhibitory control of traveling waves in cortical networks
Authors: Palkar Grishma , Wu Jian-young , Ermentrout Bard 
Published: November 2022

AbstractPropagating waves of activity can be evoked and can occur spontaneouslyin vivoandin vitro. We examine the properties of these waves as inhibition varies in a cortical slice and then develop several computational models. We first show that in the slice, inhibition controls the velocity of propagation as well as the magnitude of the local field potential. We introduce a spiking model of sparsely connected excitatory and inhibitory theta neurons which are distributed on a one-dimensional domain and illustrate both evoked and spontaneous waves. The excitatory neurons have an additional spike-frequency adaptation current which limits their maximal activity. We show that increased inhibition slows the waves down and limits the participation of excitatory cells in this spiking network. Decreased inhibition leads to large amplitude faster moving waves similar to those seen in seizures. To gain further insight into the mechanism that control the waves, we then systematically reduce the model to a Wilson-Cowan type network using a mean-field approach. We simulate this network directly and by using numerical continuation to follow traveling waves in a moving coordinate system as we vary the strength and spread of inhibition and the strength of adaptation. We find several types of instability (bifurcations) that lead to the loss of waves and subsequent pattern formation. We approximate the smooth nonlinearity by a step function and obtain expressions for the velocity, wave-width, and stability.Author summaryStimuli and other aspects of neuronal activity are carried across areas in the brain through the concerted activity of recurrently connected neurons. The activity is controlled through negative feedback from both inhibitory neurons and intrinsic currents in the excitatory neurons. Evoked activity often appears in the form of a traveling pulse of activity. In this paper we study the speed, magnitude, and other properteis of these waves as various aspects of the negative feedback are altered. Inhibition enables information to be readily transmitted across distances without the neural activity blowing up into a seizure-like state.
Altering stimulus timing via fast rhythmic sensory stimulation induces STDP-like recall performance in human episodic memory
Authors: Wang Danying , Shapiro Kimron L. , Hanslmayr Simon 
Published: November 2022

AbstractAnimal studies suggest that the strength of synaptic modification depends on spike timing between pre- and post-synaptic neurons on the order of tens of milliseconds, which is termed ‘spike-timing-dependent plasticity’ (STDP). However, evidence for STDP in human episodic memory is lacking. We investigated this using rhythmic sensory stimulation to drive visual and auditory cortices at 37.5 Hz with four phase offsets. Visual relative to auditory cued recall accuracy was significantly enhanced in the 90° condition since the visual stimulus led at the shortest delay (6.67 ms). This pattern was reversed in the 270° condition when the auditory stimulus led the shortest delay. Within cue modality, recall was enhanced when a stimulus of the corresponding modality led the shortest delay as compared to the longest delay (20 ms). Our findings provide novel evidence for STDP in human memory, which builds an important bridge from in-vitro studies in animals to human behaviour.
Eos promotes TH2 differentiation by propagating the IL-2/STAT5 signaling pathway
Authors: Tuazon Jasmine A. , Read Kaitlin A. , Sreekumar Bharath K. , Yaeger Michael J. , Varikuti Sanjay , Jones Devin M. , Warren Robert T. , Powell Michael D. , Rasheed Mustafa N. , Duncan Elizabeth G. , Childs Lauren M. , Gowdy Kymberly M. , Oestreich Kenneth J. 
Published: November 2022

AbstractThe Ikaros zinc finger transcription factor Eos has been commonly implicated in regulatory T cells to promote their immunosuppressive functions. Paradoxically, a new role is emerging for Eos in promoting pro-inflammatory responses of conventional CD4+T cells in the dysregulated setting of autoimmunity. Even so, the precise role of Eos in regulating the differentiation and function of healthy effector CD4+T cell subsets remains unclear. Here, we find that Eos is a positive regulator of CD4+T helper 2 (TH2) cells—effector T cells implicated in the induction of allergic asthma. Using murine in vitro TH2 cells and an in vivo house dust mite asthma model, we found that Eos-deficient T cells had reduced expression of key TH2 transcription factors, effector cytokines, and differentiation receptors. Mechanistically, among various TH2-polarizing pathways, the IL-2/STAT5 axis and its downstream TH2 gene targets emerged as one of the most significantly downregulated networks in Eos deficiency. Using in vitro TH2 cells and overexpression of Eos zinc-finger-domain mutants, we discovered that Eos forms a novel complex with and supports the tyrosine-phosphorylated signaling activity of STAT5. Overall, these data define a novel regulatory mechanism whereby Eos promotes IL-2/STAT5 activity to facilitate TH2 differentiation.
Variability by region and method in human brain sodium concentrations estimated by23Na magnetic resonance imaging: a meta-analysis
Authors: Ridley Ben , Morsillo Filomena , Zaaraoui Wafaa , Nonino Francesco 
Published: November 2022

AbstractSodium imaging (23Na-MRI) is of interest in neurological conditions given potential sensitivity to the physiological and metabolic status of tissues. Benchmarks have so far been restricted to parenchyma or grey/white matter (GM/WM). We investigate (1) the availability of evidence, (2) regional pooled estimates and (3) variability attributable to regional/methodology.MEDLINE literature search for Tissue sodium concentration (TSC) measured in specified ‘healthy’ brain regions returned 127 reports plus 278 retrieved from bibliographies. 28 studies met inclusion criteria, including 400 individuals. Reporting variability led to nested data structure, so we used multilevel meta-analysis and a random effects model to pool effect sizes.The pooled mean from 141 TSC estimates was 40.51 mM (95% CI: 37.59 - 43.44; p< 0.001, I2Total=99.4%). Tissue as a moderator was significant (F214=65.34, p-val < .01). Six sub-regional pooled means with requisite statistical power were derived. We were unable to consider most methodological and demographic factors sought because of non-reporting, but each factor included beyond tissue improved model fit. Significant residual heterogeneity remained.The current estimates provide an empirical point of departure for better understanding in23Na-MRI. Improving on current estimates supports: (1) larger, more representative data collection/sharing, including (2) regional data, and (3) agreement on full reporting standards.
Artificial Gravity During a Spaceflight Analog Alters Brain Sensory Connectivity
Authors: McGregor Heather R. , Lee Jessica K. , Mulder Edwin R. , De Dios Yiri E. , Beltran Nichole E. , Wood Scott J , Bloomberg Jacob J. , Mulavara Ajitkumar P. , Seidler Rachael D. 
Published: November 2022

ABSTRACTSpaceflight has numerous untoward effects on human physiology. Various countermeasures are under investigation including artificial gravity (AG). Here, we investigated whether AG alters resting-state brain functional connectivity changes during head-down tilt bed rest (HDBR), a spaceflight analog. Participants underwent 60 days of HDBR. Two groups received daily AG administered either continuously (cAG) or intermittently (iAG). A control group received no AG. We assessed resting-state functional connectivity before, during, and after HDBR. We also measured balance and mobility changes from pre-to post-HDBR. We examined how functional connectivity changes throughout HDBR and whether AG is associated with differential effects. We found differential connectivity changes by group between posterior parietal cortex and multiple somatosensory regions. The control group exhibited increased functional connectivity between these regions throughout HDBR whereas the cAG group showed decreased functional connectivity. This finding suggests that AG alters somatosensory reweighting during HDBR. We also observed brain-behavioral correlations that differed significantly by group. Control group participants who showed increased connectivity between the putamen and somatosensory cortex exhibited greater mobility declines post-HDBR. For the cAG group, increased connectivity between these regions was associated with little to no mobility declines post-HDBR. This suggests that when somatosensory stimulation is provided via AG, functional connectivity increases between the putamen and somatosensory cortex are compensatory in nature, resulting in reduced mobility declines. Given these findings, AG may be an effective countermeasure for the reduced somatosensory stimulation that occurs in both microgravity and HDBR.