Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential Amplitude of Low-Frequency Fluctuations in brain networks after BCI Training with and without tDCS in Stroke

Mapping the brain alterations post stroke and post intervention is important for rehabilitation therapy development. Previous work has shown changes in functional connectivity based on resting-state fMRI, structural connectivity derived from diffusion MRI and perfusion as a result of brain-computer interface-assisted motor imagery (MI-BCI) and transcranial direct current stimulation (tDCS) in upper-limb stroke rehabilitation. Besides functional connectivity, regional amplitude of local low-frequency fluctuations (ALFF) may provide complementary information on the underlying neural mechanism in disease. Yet, findings on spontaneous brain activity during resting-state in stroke patients after intervention are limited and inconsistent. Here, we sought to investigate the different brain alteration patterns induced by tDCS compared to MI-BCI for upper-limb rehabilitation in chronic stroke patients using resting-state fMRI-based ALFF method. Our results suggested that stroke patients have lower ALFF in the ipsilesional somatomotor network compared to controls at baseline. Increased ALFF at contralesional somatomotor network and alterations in higher-level cognitive networks such as the default mode network (DMN) and salience networks accompany motor recovery after intervention; though the MI-BCI alone group and MI-BCI combined with tDCS group exhibit differential patterns.
Integrative Proteomic and Phosphoproteomic Profiling of Testis from Wip1 Phosphatase-Knockout Mice: Insights into Mechanisms of Reduced Fertility**

Wei et al. apply multi-layer proteomic profiling and systems biology approaches to define Wip1-deficient testis proteome and phosphoproteome landscapes, and they identify cell adhesion/tight junction, sperm motility, and inflammatory response pathways. These data establish the mechanism that proinflammatory cytokines may impair the blood-testis barrier dynamics by decreasing the expression of junction-associated proteins in Wip1 null testes, leading to subfertility and spermatogenesis defects. Graphical Abstract Highlights Mice lacking Wip1 display spermatogenesis defects at the late-stage germ cell types. Proteome and phosphoproteome profiling reveals impaired dynamics of testis junction. Elevated levels of cytokines may lead to abnormal BTB structure and spermatogenesis. Mice lacking wild-type p53-induced phosphatase 1 (Wip1) display male reproductive defects including smaller testes, subfertility and spermatogenesis defects at the round- and elongating-spermatid stages. However, the molecular mechanisms underlying these abnormalities remain unclear. Here we examined the proteome and phosphoproteome of testes from Wip1-knockout mice using a quantitative proteomic approach. From a total of 6872 proteins and 4280 phosphorylation sites identified, 58 proteins and 159 phosphorylation sites were found to be differentially regulated compared with wild type mice. Pathway enrichment analyses revealed that these regulated proteins and phosphosites were mainly involved in adherens/tight junctions, apoptosis, inflammatory response, spermatogenesis, sperm motility, and cytoskeletal assembly and depolymerization. Wip1-knockout mice showed decreased expression of junction-associated proteins (occludin, ZO-1, and N-cadherin) and impaired integrity of the blood-testis barrier. In addition, Wip1 deficiency was associated with elevated levels of cytokines and germ cell apoptosis in the testis. These results suggest that proinflammatory cytokines may impair the blood-testis barrier dynamics by decreasing the expression of junction-associated proteins, which could lead to subfertility and spermatogenesis defects. Collectively, these findings help to explain the low reproductive function caused by Wip1 deletion and provide novel insights into our understanding of causes of male infertility.
The Pro-Tumoral Activity of Heparan Sulfate 3-O-Sulfotransferase 3B (HS3ST3B) in Breast Cancer MDA-MB-231 Cells Is Dependent on the Expression of Neuropilin-1

Heparan sulfate 3-O-sulfotransferases (HS3STs) catalyze the maturation step of heparan sulfate (HS) 3-O-sulfation. This modification is relatively rare. Moreover, only a few biological processes have been described to be influenced by 3-O-sulfated HS, and few ligands have been identified so far. Among them, neuropilin-1 (Nrp1) was reported to exhibit tumor-promoting properties by enhancing the action of various growth factors. We recently demonstrated that transient overexpression of HS3ST2, 3B or 4 enhanced the proliferation of breast cancer MDA-MB-231 cells and promote efficient protection against pro-apoptotic stimuli. Hence, we hypothesized that the pro-tumoral activity of these HS3STs could depend on the expression of Nrp1. To test this, MDA-MB-231 cells were stably transfected with a construct encoding HS3ST3B and the expression of Nrp1 was down-regulated by RNA interference. First, we confirmed that stable expression of HS3ST3B effectively increased cell proliferation and viability. Silencing the expression of Nrp1 markedly attenuated the promoting effects of HS3ST3B, while the same treatment had only a moderate effect on the behavior of the parental cells. Altogether, our findings support the idea that the tumor-promoting effects of HS3ST3B could be dependent on the expression of Nrp1 in cancer cells.
Application of Transfer Learning in Continuous Time Series for Anomaly Detection in Commercial Aircraft Flight Data

In recent years, transfer learning has attracted widespread attention and research. Transfer learning is a new machine learning method that uses existing knowledge to solve different but related domain problems. It relaxes two basic assumptions in traditional machine learning: (1) Training samples for learning and new test samples satisfy the conditions of independent and identical distribution; (2) There must be enough training samples available to learn a good model. Since it is costly and dangerous to repeat testing flights at extreme conditions, building an anomaly detection model for aircraft flight is also constrained by insufficient samples in limited data for different testing flight scenarios. To handle the insufficient samples, we propose a transfer-learning based approach to establishing an anomaly detection model for dangerous actions of aircraft testing flights. In our approach, we transfer the "knowledge" obtained in some testing scenarios to other scenarios containing dangerous action. Evaluation results indicate that our approach works well in terms of convincing accuracy in prediction by models in target scenarios transferred from source scenarios.
Velocity Selective Recording: A Demonstration of Effectiveness on the Vagus Nerve in Pig

Neural interfaces that can both stimulate and record from the peripheral nervous system are an important component of future bioelectronic devices. However, despite a long history of neurostimulation, there has been relatively little success in the design of a chronically implantable device for recording from peripheral nerves. This fundamental road block must be overcome if the design of advanced implantable devices is to continue. In this paper, we demonstrate the effectiveness of one method: velocity selective recording, a method that has been proposed as a tool for online neural recording that does not require training. We present results and analysis from invivo recordings made on the right vagus nerve of pig using a multiple-electrode cuff as a chronically implantable recording array.
Andrographolide mitigates IL-1β-induced human nucleus pulposus cells degeneration through the TLR4/MyD88/NF-κB signaling pathway

Intervertebral disc degeneration (IDD) is a multifactorial disease with few efficacious clinical drugs, which has been demonstrated to be associated with nucleus pulposus (NP) cells apoptosis and degeneration of the extracellular matrix (ECM). Interleukin (IL)-1β, a common proinflammatory cytokine, is considered to be one of key regulators in IDD development. Andrographolide (AG), extracted from Andrographis paniculata, has been suggested to possess marked anti-inflammatory properties. However, the effects of AG on IDD has not been well explored. The present study aimed to investigate the effects and the mechanisms of AG on IDD in human NP cells. NP cells were treated with IL-1β in the absence or presence of AG to investigate the effects on cell viability, cellular apoptosis, production of ECM and matrix metalloproteinase (MMP)-3, MMP-9 and MMP-13, and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 and ADAMTS-5. It was identified that IL-1β-induced NP cellular apoptosis was significantly inhibited by AG treatment. Furthermore, AG mitigated the IL-1β-induced degeneration of the ECM, which was paralleled by a decrease in MMPs and ADAMTS levels. In addition, AG exhibited marked inhibitory properties against the activation of Toll-like receptors (TLRs), Myeloid differentiation factor 88 (MyD88) and the nuclear translocation of Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Taken together, these results demonstrated that AG treatment mitigated IL-1β-induced NP cells degeneration through the TLR4/MyD88/NF-κB signaling pathway, and suggested that AG may be a potential agent for IDD prevention and therapy.
Shock Wave Therapy Improves Cardiac Function in a Model of Chronic Ischemic Heart Failure: Evidence for a Mechanism Involving VEGF Signaling and the Extracellular Matrix

Background Mechanical stimulation of acute ischemic myocardium by shock wave therapy (SWT) is known to improve cardiac function by induction of angiogenesis. However, SWT in chronic heart failure is poorly understood. We aimed to study whether mechanical stimulation upon SWT improves heart function in chronic ischemic heart failure by induction of angiogenesis and postnatal vasculogenesis and to dissect underlying mechanisms. Methods and Results SWT was applied in a mouse model of chronic myocardial ischemia. To study effects of SWT on postnatal vasculogenesis, wild‐type mice received bone marrow transplantation from green fluorescence protein donor mice. Underlying mechanisms were elucidated in vitro in endothelial cells and murine aortic rings. Echocardiography and pressure/volume measurements revealed improved left ventricular ejection fraction, myocardial contractility, and diastolic function and decreased myocardial fibrosis after treatment. Concomitantly, numbers of capillaries and arterioles were increased. SWT resulted in enhanced expression of the chemoattractant stromal cell–derived factor 1 in ischemic myocardium and serum. Treatment induced recruitment of bone marrow–derived endothelial cells to the site of injury. In vitro, SWT resulted in endothelial cell proliferation, enhanced survival, and capillary sprouting. The effects were vascular endothelial growth factor receptor 2 and heparan sulfate proteoglycan dependent. Conclusions SWT positively affects heart function in chronic ischemic heart failure by induction of angiogenesis and postnatal vasculogenesis. SWT upregulated pivotal angiogenic and vasculogenic factors in the myocardium in vivo and induced proliferative and anti‐apoptotic effects on endothelial cells in vitro. Mechanistically, these effects depend on vascular endothelial growth factor signaling and heparan sulfate proteoglycans. SWT is a promising treatment option for regeneration of ischemic myocardium.
Transcriptomic analysis reveals similarities in genetic activation of detoxification mechanisms resulting from imidacloprid and chlorothalonil exposure

The Colorado potato beetle, Leptinotarsa decemlineata (Say), is an agricultural pest of commercial potatoes in parts of North America, Europe, and Asia. Plant protection strategies within this geographic range employ a variety of pesticides to combat not only the insect, but also plant pathogens. Previous research has shown that field populations of Leptinotarsa decemlineata have a chronological history of resistance development to a suite of insecticides, including the Group 4A neonicotinoids. The aim of this study is to contextualize the transcriptomic response of Leptinotarsa decemlineata when exposed to the neonicotinoid insecticide imidacloprid, or the fungicides boscalid or chlorothalonil, in order to determine whether these compounds induce similar detoxification mechanisms. We found that chlorothalonil and imidacloprid induced similar patterns of transcript expression, including the up-regulation of a cytochrome p450 and a UDP-glucuronosyltransferase transcript, which are often associated with xenobiotic metabolism. Further, transcriptomic responses varied among individuals within the same treatment group, suggesting individual insects’ responses vary within a population and may cope with chemical stressors in a variety of manners. These results further our understanding of the mechanisms involved in insecticide resistance in Leptinotarsa decemlineata. Author Contribution Statement Conceived and designed the experiments: JC, CB, RLG. Performed the experiments: JC, BSS. Analyzed the data: JC, BSS. Wrote the paper: JC, BSS, RLG.
Mobile Gait Analysis using Personalised Hidden Markov Models for Hereditary Spastic Paraplegia Patients

Gait analysis provides a quantitative method to assess disease progression or intervention effect on gait disorders. While mobile gait analysis enables continuous monitoring in free living conditions, state of the art gait analysis for diseases such as hereditary spastic paraplegia (HSP) is currently limited to motion capture systems which are large and expensive. The challenge with HSP is its heterogeneous nature and rarity, leading to a wide range of ages, severity and gait patterns as well as small patient numbers. We propose a sensor-based mobile solution, based on a personalised hierarchical hidden Markov Model (hHMM) to extract spatio-temporal gait parameters. This personalised hHMM achieves a mean absolute error of 0.04 s ± 0.03 s for stride time estimation with respect to a GAITRite® reference system. We use the successful extraction of initial ground contact to explore the limits of the double integration method for such heterogeneous diseases. While our personalised model compensates for the heterogeneity of the disease, it would require a new model per patient. We observed that the general model was sufficient for some of the less severely affected patients.
Sensitivity Enhancement of Photothermoelectric Terahertz Detectors with Series Combination between Carbon Nanotubes and Metals

This paper presents highly flexible terahertz (THz) detectors based on single-walled carbon nanotube (SWNT) films. Based on detection mechanism of the photothermoelectric effect, the effective Seebeck coefficient between the SWNT film and the electrode metal is a key parameter for sensitive THz detection. We proposed and demonstrated that the effective Seebeck coefficient was increased by employing the combination with the electrode in series, and achieved raising the sensitivity of THz detection. Particularly utilizing metals (nickel, bismuth) with negative Seebeck coefficient for the series electrode led to the sensitivity enhancement by a factor of 17 times compared to conventional parallel combination.
Towards a Universal Design Evaluation for Assessing the Performance of the Built Environment

Universal Design is a recent and innovative strategy aimed at designing spaces that are as accessible and inclusive as possible. It considers the broadest range of users, and goes beyond the prescriptive approach of accessibility legislation. Theoretical research on this strategy is currently increasing, but the reliability of its principles remains limited in design practice and it struggles to guarantee performance-based knowledge to designers. Therefore, a practical evaluation method based on reliable performance criteria is required. The purpose of the research is to investigate which means, methods, and principles of Universal Design and Design for All are currently used to evaluate the accessibility and inclusion of the built environment. The paper describes a literature review aimed to select methodologies and reflect on instruments that are inherent to the thematic. The research's outcome is therefore the definition of both open issues and gaps in this field, which is based on the comparison of the studies analysed. In addition, the potential outlooks on the issue of Universal Design and Design for All evaluation are discussed. The current results provide a basis for further research on the development of evaluation and support tools for designers that are able to improve the accessibility and inclusion of the built environment, and the reliability of Universal Design performance criteria in design practice.
Transgenerational effects of maternal bisphenol: a exposure on offspring metabolic health

Abstract Exposure to the endocrine disruptor bisphenol A (BPA) is ubiquitous and associated with health abnormalities that persist in subsequent generations. However, transgenerational effects of BPA on metabolic health are not widely studied. In a maternal C57BL/6J mice (F0) exposure model using BPA doses that are relevant to human exposure levels (10 μg/kg/day, LowerB; 10 mg/kg/day, UpperB), we showed male- and dose-specific effects on pancreatic islets of the first (F1) and second generation (F2) offspring relative to controls (7% corn oil diet; control). In this study, we determined the transgenerational effects (F3) of BPA on metabolic health and pancreatic islets in our model. Adult F3 LowerB and UpperB male offspring had increased body weight relative to Controls, however glucose tolerance was similar in the three groups. F3 LowerB, but not UpperB, males had reduced β-cell mass and smaller islets which was associated with increased glucose-stimulated insulin secretion. Similar to F1 and F2 BPA male offspring, staining for markers of T-cells and macrophages (CD3 and F4/80) was increased in pancreas of F3 LowerB and UpperB male offspring, which was associated with changes in cytokine levels. In contrast to F3 BPA males, LowerB and UpperB female offspring had comparable body weight, glucose tolerance and insulin secretion as Controls. Thus, maternal BPA exposure resulted in fewer metabolic defects in F3 than F1 and F2 offspring, and these were sex- and dose-specific.
Adversarial Risk and Robustness: General Definitions and Implications for the Uniform Distribution

We study adversarial perturbations when the instances are uniformly distributed over $\{0,1\}^n$. We study both "inherent" bounds that apply to any problem and any classifier for such a problem as well as bounds that apply to specific problems and specific hypothesis classes. As the current literature contains multiple definitions of adversarial risk and robustness, we start by giving a taxonomy for these definitions based on their goals, we identify one of them as the one guaranteeing misclassification by pushing the instances to the error region. We then study some classic algorithms for learning monotone conjunctions and compare their adversarial risk and robustness under different definitions by attacking the hypotheses using instances drawn from the uniform distribution. We observe that sometimes these definitions lead to significantly different bounds. Thus, this study advocates for the use of the error-region definition, even though other definitions, in other contexts, may coincide with the error-region definition. Using the error-region definition of adversarial perturbations, we then study inherent bounds on risk and robustness of any classifier for any classification problem whose instances are uniformly distributed over $\{0,1\}^n$. Using the isoperimetric inequality for the Boolean hypercube, we show that for initial error $0.01$, there always exists an adversarial perturbation that changes $O(\sqrt{n})$ bits of the instances to increase the risk to $0.5$, making classifier's decisions meaningless. Furthermore, by also using the central limit theorem we show that when $n\to \infty$, at most $c \cdot \sqrt{n}$ bits of perturbations, for a universal constant $c< 1.17$, suffice for increasing the risk to $0.5$, and the same $c \cdot \sqrt{n} $ bits of perturbations on average suffice to increase the risk to $1$, hence bounding the robustness by $c \cdot \sqrt{n}$.
Molecular signaling mechanisms of renal gluconeogenesis in nondiabetic and diabetic conditions

The kidneys are as involved as the liver in gluconeogenesis which can significantly contribute to hyperglycemia in the diabetic condition. Substantial evidence has demonstrated the overexpression of rate‐limiting gluconeogenic enzymes, especially phosphoenolpyruvate carboxykinase and glucose 6 phosphatase, and the accelerated glucose release both in the isolated proximal tubular cells and in the kidneys of diabetic animal models and diabetic patients. The aim of this review is to provide an insight into the mechanisms that accelerate renal gluconeogenesis in the diabetic conditions and the therapeutic approaches that could affect this process in the kidney. Increase in gluconeogenic substrates, reduced insulin concentration or insulin resistance, downregulation of insulin receptors and insulin signaling, oxidative stress, and inappropriate activation of the renin–angiotensin system are likely to participate in enhancing renal gluconeogenesis in the diabetic milieu. Several studies have suggested that controlling glucose metabolism at the renal level favors effective overall glycemic control in both type 1 and type 2 diabetes. Therefore, renal gluconeogenesis may be a promising target for effective glycemic control as a therapeutic strategy in diabetes.
Estimating Mini Mental State Examination Scores using Game-Specific Performance Values: A Preliminary Study

Individuals with permanent cognitive impairment need to be evaluated and monitored. There exists a number of clinically validated cognitive assessment tools, but they often need to be administered by trained therapists in clinical settings. This serves as a major barrier for frequent, longitudinal monitoring of cognitive function. In this work, we introduce Neuro-World, a collection of innovative 3D mobile games, that allows one to self-administer the assessment of his/her cognitive function. The game performance is analyzed and converted into a clinically-accepted measure of cognitive function, specifically the Mini Mental State Examination (MMSE) score, improving the translational impact of the system in real-world clinical settings. To validate the feasibility of our approach, we collected game-specific performance data from 12 post-stroke patients, which was used to train a supervised machine learning model to estimate the corresponding MMSE score. Our experiment results showed a normalized root mean square error of 5.3% between the actual and estimated MMSE scores. This study enables new clinical and research opportunities for accurate longitudinal assessment of cognitive function via an interactive means of playing mobile games.