Miracle-dz/UniFAR-FTUs huggingface dataset:
Information Integration and Mesoscopic Cortical Connectivity during Propofol Anesthesia

Background: The neurophysiologic mechanisms of propofol-induced loss of consciousness have been studied in detail at the macro (scalp electroencephalogram) and micro (spiking or local field potential) scales. However, the changes in information integration and cortical connectivity during propofol anesthesia at the mesoscopic level (the cortical scale) are less clear. Methods: The authors analyzed electrocorticogram data recorded from surgical patients during propofol-induced unconsciousness (n = 9). A new information measure, genuine permutation cross mutual information, was used to analyze how electrocorticogram cross-electrode coupling changed with electrode-distances in different brain areas (within the frontal, parietal, and temporal regions, as well as between the temporal and parietal regions). The changes in cortical networks during anesthesia—at nodal and global levels—were investigated using clustering coefficient, path length, and nodal efficiency measures. Results: In all cortical regions, and in both wakeful and unconscious states (early and late), the genuine permutation cross mutual information and the percentage of genuine connections decreased with increasing distance, especially up to about 3 cm. The nodal cortical network metrics (the nodal clustering coefficients and nodal efficiency) decreased from wakefulness to unconscious state in the cortical regions we analyzed. In contrast, the global cortical network metrics slightly increased in the early unconscious state (the time span from loss of consciousness to 200 s after loss of consciousness), as compared with wakefulness (normalized average clustering coefficient: 1.05 ± 0.01 vs. 1.06 ± 0.03, P = 0.037; normalized average path length: 1.02 ± 0.01 vs. 1.04 ± 0.01, P = 0.021). Conclusions: The genuine permutation cross mutual information reflected propofol-induced coupling changes measured at a cortical scale. Loss of consciousness was associated with a redistribution of the pattern of information integration; losing efficient global information transmission capacity but increasing local functional segregation in the cortical network. Using electrocorticography in subjects anesthetized with propofol, the genuine permutation cross mutual information demonstrated that, with loss of consciousness, there was a loss of efficient global information transmission and increased local functional segregation in the cortical network. Supplemental Digital Content is available in the text.
Aldehyde dehydrogenase-2 as a therapeutic target

ABSTRACT Introduction: Aldehyde dehydrogenase-2 (ALDH2) is a main contributor of the alcohol elimination process. Functional polymorphism in the ALDH2 gene and its inactive form causes unpleasant flushing responses after alcohol consumption and prevents excessive alcohol intake. ALDH2 plays a key role in removing endogenous aldehydes like 4-hydroxy-2-nonenal (4-HNE) and malondialdehyde (MDA) produced by lipid peroxidation triggered by oxidative stress. Additionally, ALDH2 is involved in the elimination of metabolites of neurotransmitters like 3,4-dihydroxyphenylacetaldehyde (DOPAL) and 3,4-dihydroxyphenylglycoaldehyde (DOPGAL) in the central nervous system (CNS). Areas covered: We examine the role of ALDH2 polymorphism in disease, aging and alcohol addiction and discuss its pharmacological targeting. Case-control studies indicate that the deficiency of ALDH2 activity influences the risk of numerous diseases while animal models show that ALDH2 activator Alda-1, could reduce cardiac ischemic damage. Moreover, many studies have reported the protective effect of Alda-1 against the development of neurodegenerative diseases. The literature search was conducted using PubMed and Cochrane Library up to August 2019. Expert opinion: ALDH2 is a promising therapeutic target in numerous diseases. The targeting of ALDH2 has much potential but requires further investigations and analysis to explore and establish its future potential role for the clinic.
Coresets for Ordered Weighted Clustering

We design coresets for Ordered k-Median, a generalization of classical clustering problems such as k-Median and k-Center, that offers a more flexible data analysis, like easily combining multiple objectives (e.g., to increase fairness or for Pareto optimization). Its objective function is defined via the Ordered Weighted Averaging (OWA) paradigm of Yager (1988), where data points are weighted according to a predefined weight vector, but in order of their contribution to the objective (distance from the centers). A powerful data-reduction technique, called a coreset, is to summarize a point set $X$ in $\mathbb{R}^d$ into a small (weighted) point set $X'$, such that for every set of $k$ potential centers, the objective value of the coreset $X'$ approximates that of $X$ within factor $1\pm \epsilon$. When there are multiple objectives (weights), the above standard coreset might have limited usefulness, whereas in a \emph{simultaneous} coreset, which was introduced recently by Bachem and Lucic and Lattanzi (2018), the above approximation holds for all weights (in addition to all centers). Our main result is a construction of a simultaneous coreset of size $O_{\epsilon, d}(k^2 \log^2 |X|)$ for Ordered k-Median. To validate the efficacy of our coreset construction we ran experiments on a real geographical data set. We find that our algorithm produces a small coreset, which translates to a massive speedup of clustering computations, while maintaining high accuracy for a range of weights.
Proteomic Analysis of Urinary Extracellular Vesicles Reveals a Role for the Complement System in Medullary Sponge Kidney Disease

Medullary sponge kidney (MSK) disease is a rare and neglected kidney condition often associated with nephrocalcinosis/nephrolithiasis and cystic anomalies in the precalyceal ducts. Little is known about the pathogenesis of this disease, so we addressed the knowledge gap using a proteomics approach. The protein content of microvesicles/exosomes isolated from urine of 15 MSK and 15 idiopathic calcium nephrolithiasis (ICN) patients was investigated by mass spectrometry, followed by weighted gene co-expression network analysis, support vector machine (SVM) learning, and partial least squares discriminant analysis (PLS-DA) to select the most discriminative proteins. Proteomic data were verified by ELISA. We identified 2998 proteins in total, 1764 (58.9%) of which were present in both vesicle types in both diseases. Among the MSK samples, only 65 (2.2%) and 137 (4.6%) proteins were exclusively found in the microvesicles and exosomes, respectively. Similarly, among the ICN samples, only 75 (2.5%) and 94 (3.1%) proteins were exclusively found in the microvesicles and exosomes, respectively. SVM learning and PLS-DA revealed a core panel of 20 proteins that distinguished extracellular vesicles representing each clinical condition with an accuracy of 100%. Among them, three exosome proteins involved in the lectin complement pathway maximized the discrimination between MSK and ICN: Ficolin 1, Mannan-binding lectin serine protease 2, and Complement component 4-binding protein β. ELISA confirmed the proteomic results. Our data show that the complement pathway is involved in the MSK, revealing a new range of potential therapeutic targets and early diagnostic biomarkers.
Cortical GABAergic Dysfunction in Stress and Depression: New Insights for Therapeutic Interventions

Major depressive disorder (MDD) is a debilitating illness characterized by neuroanatomical and functional alterations in limbic structures, notably the prefrontal cortex (PFC), that can be precipitated by exposure to chronic stress. For decades, the monoaminergic deficit hypothesis of depression provided the conceptual framework to understand the pathophysiology of MDD. However, accumulating evidence suggests that MDD and chronic stress are associated with an imbalance of excitation–inhibition (E:I) within the PFC, generated by a deficit of inhibitory synaptic transmission onto principal glutamatergic neurons. MDD patients and chronically stressed animals show a reduction in GABA and GAD67 levels in the brain, decreased expression of GABAergic interneuron markers, and alterations in GABAA and GABAB receptor levels. Moreover, genetically modified animals with deletion of specific GABA receptors subunits or interneuron function show depressive-like behaviors. Here, we provide further evidence supporting the role of cortical GABAergic interneurons, mainly somatostatin- and parvalbumin-expressing cells, required for the optimal E:I balance in the PFC and discuss how the malfunction of these cells can result in depression-related behaviors. Finally, considering the relatively low efficacy of current available medications, we review new fast-acting pharmacological approaches that target the GABAergic system to treat MDD. We conclude that deficits in cortical inhibitory neurotransmission and interneuron function resulting from chronic stress exposure can compromise the integrity of neurocircuits and result in the development of MDD and other stress-related disorders. Drugs that can establish a new E:I balance in the PFC by targeting the glutamatergic and GABAergic systems show promising as fast-acting antidepressants and represent breakthrough strategies for the treatment of depression.
Variation in blood pressure and long-term risk of dementia: A population-based cohort study

Background Variation in blood pressure may relate to dementia risk via autonomic disturbance or hemodynamic mechanisms, but the long-term associations are unclear. We aimed to determine whether blood pressure variation over a period of years, considering both magnitude and direction, is associated with the risk of dementia. Methods and findings In a prospective cohort study ongoing since 1989 in the Netherlands, 5,273 dementia-free participants (58.1% women; mean [SD] age, 67.6 [8.0] years) were included. As of 2016, 1,059 dementia cases occurred during a median follow-up of 14.6 years. Absolute variation in systolic blood pressure (SBP) was assessed as the absolute difference in SBP divided by the mean over two sequential visits every 4.2 (median) years, with the first quantile set as the reference level. The direction was the rise or fall in SBP, with the third quantile set as the reference level. We estimated the risk of dementia in relation to SBP variation measured at different time windows (i.e., at least 0, 5, 10, and 15 years) prior to dementia diagnosis, with adjustments for age, sex, education, apolipoprotein E (APOE) genotype, vascular risk factors, and history of cardiovascular disease. We repeated the above analysis for variation in diastolic blood pressure (DBP). A large SBP variation was associated with an increased dementia risk, which became more pronounced with longer intervals between the assessment of SBP variation and the diagnosis of dementia. The hazard ratio (HR) associated with large variation (the highest quintile) increased from 1.08 (95% confidence interval [CI] 0.88–1.34, P = 0.337) for risk within 5 years of SBP variation measurement to 3.13 (95% CI 2.05–4.77; P < 0.001) for risk after at least 15 years since the measurement of SBP variation. The increased long-term risk was associated with both large rises (HR for the highest quintile, 3.31 [95% CI 2.11–5.18], P < 0.001) and large falls in SBP (HR for the lowest quintile, 2.20 [95% CI 1.33–3.63], P = 0.002), whereas the higher short-term risk was only associated with large falls in SBP (HR, 1.21 [95% CI 1.00–1.48], P = 0.017). Similar findings were observed for variation in DBP. Despite our assessment of major confounders, potential residual confounding is possible, and the findings on blood pressure variability over periods of years may not be generalizable to variability over periods of days and other shorter periods. Conclusions Results of this study showed that a large blood pressure variation over a period of years was associated with an increased long-term risk of dementia. The association between blood pressure variation and dementia appears most pronounced when this variation occurred long before the diagnosis. An elevated long-term risk of dementia was observed with both a large rise and fall in blood pressure.
The relationship between ground reaction force components and peak power according to induced fatigue during 16-km walking

The previous reviewed studies on inducement of fatigue through long-time walking were not only very confined, but also not cleared on relationship among variables of fatigue inducement active force, decay rate, and power. This study analyzed relationship between power and component of ground reaction force after fatigue being induced through 16-km walking. The fatigue of adult males and females (n=16) was induced through 16-km walking. Then power, measured for pre and post of fatigue inducement, was evaluated by maximal vertical jump on ground reaction force plate. Variables of vertical jump heights, active force, power, and decay rate showed decreased tendency after fatigue inducement, which followed significant difference (P<0.05) and also positive correlation of r=0.628 (R2=39%) of between vertical jump heights and power and r=0.589 (R2=34%) of between active force and decay rate respectively. That is, long-time walking for pursuing of exercise rehabilitation, health promotion and leisure activity has been preferred. In the view of this, this study suggested the necessity to understand the relation between fatigue and power to prevent a potential possibility of injury during long-time walking.
Prefrontal-Temporal Pathway Mediates the Cross-Modal and Cognitive Reorganization in Sensorineural Hearing Loss With or Without Tinnitus: A Multimodal MRI Study

Objective: Hearing loss, one main risk factor of tinnitus and hyperacusis, is believed to involve significant central functional abnormalities. The recruitment of the auditory cortex in non-auditory sensory and higher-order cognitive processing has been demonstrated in the hearing-deprived brain. The dorsolateral prefrontal cortex (dlPFC), which has dense anatomical connections with the auditory pathway, is known to play a crucial role in multi-sensory integration, auditory regulation, and cognitive processing. This study aimed to verify the role of the dlPFC in the cross-modal reorganization and cognitive participation of the auditory cortex in long-term sensorineural hearing loss (SNHL) by combining functional and structural measurements. Methods: Thirty five patients with long-term bilateral SNHL and 35 matched healthy controls underwent structural imaging, resting-state functional magnetic resonance imaging (rs-fMRI), diffusion tensor imaging (DTI), and neuropsychological assessments. Ten SNHL patients were with subjective tinnitus. Results: No differences in gray matter volume, spontaneous neural activity, or diffusion characteristics in the dlPFC were found between the SNHL and control groups. The functional connectivity (FC) between the dlPFC and the auditory cortex and visual areas, such as the cuneus, fusiform, lingual cortex, and calcarine sulcus was increased in patients with SNHL. ANOVA and post hoc tests revealed similar FC alterations in the SNHL patients with and without tinnitus when compared with the normal hearing controls, and SNHL patients with and without tinnitus showed no difference in the dlPFC FC. The FC in the auditory cortex was associated with the symbol digit modality test (SDMT) scores in the SNHL patients, which reflect attentional function, processing speed, and visual working memory. Hearing-related FC with the dlPFC was found in the lingual cortex. A tract-based spatial statistics (TBSS) analysis revealed decreased fractional anisotropy (FA) values, mainly in the temporal inferior fronto-occipital fasciculus (IFOF), which showed remarkable negative correlations with the mean hearing thresholds in SNHL. Conclusion: Higher functional coupling between the dlPFC and auditory and visual areas, accompanied by decreased FA along the IFOF connecting the frontal cortex and the occipito-temporal area, might mediate cross-modal plasticity via top-down regulation and facilitate the involvement of the auditory cortex in higher-order cognitive processing following long-term SNHL.
Why Algae Release Volatile Organic Compounds—The Emission and Roles

A wide spectrum of volatile organic compounds (VOCs) are released from algae in aquatic ecosystems. Environmental factors such as light, temperature, nutrition conditions and abiotic stresses affect their emission. These VOCs can enhance the resistance to abiotic stresses, transfer information between algae, play allelopathic roles, and protect against predators. For homogeneous algae, the VOCs released from algal cells under stress conditions transfer stress information to other cells, and induce the acceptors to make a preparation for the upcoming stresses. For heterogeneous algae and aquatic macrophytes, the VOCs show allelopathic effects on the heterogeneous neighbors, which benefit to the emitter growth and competing for nutrients. In cyanobacterial VOCs, some compounds such as limonene, eucalyptol, β-cyclocitral, α-ionone, β-ionone and geranylacetone have been detected as the allelopathic agents. In addition, VOCs can protect the emitters from predation by predators. It can be speculated that the emission of VOCs is critical for algae coping with the complicated and changeable aquatic ecosystems.
NormalNet: Learning based Guided Normal Filtering for Mesh Denoising

Mesh denoising is a critical technology in geometry processing, which aims to recover high-fidelity 3D mesh models of objects from noise-corrupted versions. In this work, we propose a deep learning based face normal filtering scheme for mesh denoising, called \textit{NormalNet}. Different from natural images, for mesh, it is difficult to collect enough examples to build a robust end-to-end training scheme for deep networks. To remedy this problem, we propose an iterative framework to generate enough face-normal pairs, based on which a convolutional neural networks (CNNs) based scheme is designed for guidance normal learning. Moreover, to facilitate the 3D convolution operation in CNNs, for each face in mesh, we propose a voxelization strategy to transform irregular local mesh structure into regular 4D-array form. Finally, guided normal filtering is performed to obtain filtered face normals, according to which denoised positions of vertices are derived. Compared to the state-of-the-art works, the proposed scheme can generate accurate guidance normals and remove noise effectively while preserving original features and avoiding pseudo-features.
Ketone Bodies Inhibit the Opening of Acid-Sensing Ion Channels (ASICs) in Rat Hippocampal Excitatory Neurons in vitro

Objectives: Despite the long-term efficacy of antiepileptic drug treatments, frequent attacks of drug-resistant epilepsy necessitate the development of new antiepileptic drug therapy targets. The ketogenic diet is a high-fat, low-carbohydrate diet that has been shown to be effective in treating drug-resistant epilepsy, although the mechanism is yet unclear. In the ketogenic diet, excess fat is metabolized into ketone bodies (including acetoacetic acid, β-hydroxybutyric acid, and acetone). The present study explored the effect of ketone bodies on acid-sensing ion channels and provided a theoretical basis for the study of new targets of antiepileptic drugs based on “ketone body-acid sensing ion channels. ” Methods: In this study, rat primary cultured hippocampal neurons were used. The effects of acetoacetic acid, β-hydroxybutyric acid, and acetone on the open state of acid-sensing ion channels of hippocampal neurons were investigated by the patch-clamp technique. Results: At pH 6.0, the addition of acetoacetic acid, β-hydroxybutyric acid, and acetone in the extracellular solution markedly weakened the currents of acid-sensing ion channels. The three ketone bodies significantly inhibited the opening of the acid-sensing ion channels on the surface of the hippocampal neurons, and 92, 47, and 77%, respectively. Conclusions: Ketone bodies significantly inhibit the opening of acid-sensing ion channels. However, a new target for antiepileptic drugs on acid-sensing ion channels is yet to be investigated.
The Risk of Radiogenic Second Cancer Based on Differential DVH: Central Nervous System Malignant Tumor in Children

Objectives: To quantify the risk of radiogenic second cancer in pediatric patients receiving hippocampal-sparing craniospinal irradiation either with intensity-modulated radiation therapy or tomotherapy due to the development of a solid second cancer after radiotherapy using the concept of excess absolute risk. Methods: Computed tomography images of 15 pediatric patients who received craniospinal irradiation treatment were selected for this study. For each case, intensity-modulated radiation therapy and tomotherapy plans were computed. Then, the dosimetry parameters were analyzed. Differential dose–volume histograms were generated, and the excess absolute risks were calculated for each plan of each patient. Results: The tomotherapy group was superior to the intensity-modulated radiation therapy group in target area homogeneity index (P < .001). Tomotherapy offered greater hippocampal sparing than intensity-modulated radiation therapy in terms of D 2% (15.66 vs 23.05 Gy, P < .001) and Dmean (9.79 vs 20.29 Gy, P < .001). Tomotherapy craniospinal irradiation induced a much higher risk than intensity-modulated radiation therapy craniospinal irradiation to the thyroid and lungs (excess absolute risk: thyroid 28.7 vs 26.9 per 10 000 PY, P = .010; lung 20.5 vs 18.9 per 10 000 PY, P = .003). Both techniques conferred a higher risk to the stomach, but there was little difference. In addition, the 2 plans induced less carcinogenic risk to the liver (excess absolute risk 4.2 vs 4.0 per 10 000 PY, P = .020). Conclusions: The tomotherapy plan has obvious advantages in the protection of the hippocampus for children undergoing craniospinal irradiation treatment. Tomotherapy increased the risk of radiogenic second cancer in organ at risk, and therefore, it is imperative to take the risk factor into consideration in the formulation of treatment protocols.