Miracle-dz/UniFAR-FTUs huggingface dataset:
Vagus Nerve Stimulation Paired With Upper Limb Rehabilitation After Chronic Stroke: A Blinded Randomized Pilot Study

Background and Purpose— We assessed safety, feasibility, and potential effects of vagus nerve stimulation (VNS) paired with rehabilitation for improving arm function after chronic stroke. Methods— We performed a randomized, multisite, double-blinded, sham-controlled pilot study. All participants were implanted with a VNS device and received 6-week in-clinic rehabilitation followed by a home exercise program. Randomization was to active VNS (n=8) or control VNS (n=9) paired with rehabilitation. Outcomes were assessed at days 1, 30, and 90 post-completion of in-clinic therapy. Results— All participants completed the course of therapy. There were 3 serious adverse events related to surgery. Average FMA-UE scores increased 7.6 with active VNS and 5.3 points with control at day 1 post–in-clinic therapy (difference, 2.3 points; CI, −1.8 to 6.4; P=0.20). At day 90, mean scores increased 9.5 points from baseline with active VNS, and the control scores improved by 3.8 (difference, 5.7 points; CI, −1.4 to 11.5; P=0.055). The clinically meaningful response rate of FMA-UE at day 90 was 88% with active VNS and 33% with control VNS (P<0.05). Conclusions— VNS paired with rehabilitation was acceptably safe and feasible in participants with upper limb motor deficit after chronic ischemic stroke. A pivotal study of this therapy is justified. Clinical Trial Registration— URL: https://www.clinicaltrials. gov. Unique identifier: NCT02243020.
Soluble Markers of Immune Activation Differentially Normalize and Selectively Associate with Improvement in AST, ALT, Albumin, and Transient Elastography During IFN-Free HCV Therapy

Background: During chronic hepatitis C virus (HCV) infection, Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) levels mark active liver inflammation and tissue damage, while albumin reflects synthetic liver function and nutritional status. Transient Elastography (TE) is a clinical measure of liver stiffness that facilitates evaluation of liver damage stage. While a portion of the TE score is attributable to liver fibrosis and relatively irreversible damage, another component of the TE score is attributable to liver inflammation or edema. Markers of inflammation during chronic HCV infection include soluble markers of immune activation, which are also associated with morbid outcome (including cardiovascular disease and liver-disease progression). Whether soluble markers of immune activation or changes in their level during HCV therapy relate to normalization of AST, ALT, Albumin, or TE score, is not clear. Methods: We evaluated soluble markers of immune activation (plasma sCD14, IL-6, sCD163, autotaxin [ATX], and Mac2BP) and TE score, and their relationship in 20 HCV-infected patients before, during, and after HCV-directed IFN-free direct-acting antiviral (DAA) therapy. We evaluated normalization of parameters and the relationship between each over a 6-month window. Results: Before therapy, serum AST levels positively correlated with plasma levels of sCD14, sCD163, and Mac2BP, while ALT levels positively correlated with Mac2BP. Serum albumin level negatively correlated with plasma IL-6 and ATX levels. IFN-free therapy uniformly resulted in sustained virological response at 12 and 24 weeks after therapy completion. After initiation of therapy AST and ALT normalized, while levels of ATX, Mac2BP, sCD163, and TE score partially normalized over 6 months. Additionally, change in AST level and APRI score correlated with change in sCD163, IL-6, and Mac2BP levels, and change in ALT correlated with change in IL-6 and Mac2BP levels. Improvement in TE score correlated with a decrease in the level of sCD14 at week 4, and almost statistically significant with decrease in sCD14 at weeks 20-24 after initiation of IFN-free HCV therapy. Conclusions: Soluble markers of immune activation normalize or partially normalize at different rates after initiation of curative HCV DAA therapy, and TE scores improve, with wide variability in the degree of absolute improvement in liver stiffness from patient to patient. Decline magnitude of sCD14 was associated with improvement in TE score, while magnitude of improvement in AST correlated with reduction in sCD163 levels. These data provide support for a model where monocyte/Kupffer cell activation may account for a portion of the liver inflammation and edema, which is at least partially reversible following initiation of HCV DAA therapy.
Adversarial Learning and Explainability in Structured Datasets.

We theoretically and empirically explore the explainability benefits of adversarial learning in logistic regression models on structured datasets. In particular we focus on improved explainability due to significantly higher $\textit{feature-concentration}$ in adversarially-learned models: Compared to natural training, adversarial training tends to more efficiently shrink the weights of non-predictive and weakly-predictive features, while model performance on natural test data only degrades slightly (and even sometimes improves), compared to that of a naturally trained model. We provide theoretical insight into this phenomenon via an analysis of the expectation of the logistic model weight updates by an SGD-based adversarial learning algorithm, where examples are drawn from a random binary data-generation process. We empirically demonstrate the feature-pruning effect on a synthetic dataset, some datasets from the UCI repository, and real-world large-scale advertising response-prediction data-sets from MediaMath. In several of the MediaMath datasets there are 10s of millions of data points, and on the order of 100,000 sparse categorical features, and adversarial learning often results in model-size reduction by a factor of 20 or higher, and yet the model performance on natural test data (measured by AUC) is comparable to (and sometimes even better than) that of the naturally trained model. We also show that traditional $\ell_1$ regularization does not even come close to achieving this level of feature-concentration. We measure "feature concentration" using the Integrated Gradients-based feature-attribution method of Sundararajan et. al (2017), and derive a new closed-form expression for 1-layer networks, which substantially speeds up computation of aggregate feature attributions across a large dataset.
Preclinical Ultrasound-Guided Photoacoustic Imaging of the Placenta in Normal and Pathologic Pregnancy

Placental oxygenation varies throughout pregnancy. The detection of early changes in placental oxygenation as pregnancy progresses is important for early identification of preeclampsia or other complications. This invited commentary discusses a recent preclinical study on the application of 3-dimensional photoacoustic imaging (PAI) for assessment of regional variations in placental oxygenation and longitudinal analysis of differences in placental oxygenation throughout normal pregnancy and pregnancy associated with hypertension or placental insufficiency in mice. Three-dimensional PAI more accurately reflects oxygen saturation, hemoglobin concentrations, and changes in oxygen saturation in whole placenta compared to 2-dimensional imaging. These studies suggest that PAI is a sensitive tool to detect different levels of oxygen saturation in the placental and fetal vasculature in pathologic and normal pregnancy in mice.
Polymorphism of the programmed death‐ligand 1 gene is associated with its protein expression and prognosis in gastric cancer

While the incidence and mortality of gastric cancer (GC) remains high, and prognosis of GC remains poor, molecules in programmed death‐1 (PD‐1), programmed death‐ligand 1 (PD‐L1), and programmed death‐ligand 2 (PD‐L2) pathway are promising prognostic biomarker of GC. The polymorphisms on PD‐1, PD‐L1, and PD‐L2 may be associated with their protein expressions and affect the survival of GC patient.
INAVA-ARNO complexes bridge mucosal barrier function with inflammatory signaling

Homeostasis at mucosal surfaces requires cross-talk between the environment and barrier epithelial cells. Disruption of barrier function typifies mucosal disease. Here we elucidate a bifunctional role in coordinating this cross-talk for the inflammatory bowel disease risk-gene INAVA. Both activities require INAVA’s DUF3338 domain (renamed CUPID). CUPID stably binds the cytohesin ARF-GEF ARNO to effect lateral membrane F-actin assembly underlying cell-cell junctions and barrier function. Unexpectedly, when bound to CUPID, ARNO affects F-actin dynamics in the absence of its canonical activity as a guanine nucleotide-exchange factor. Upon exposure to IL-1β, INAVA relocates to form cytosolic puncta, where CUPID amplifies TRAF6-dependent polyubiquitination and inflammatory signaling. In this case, ARNO binding to CUPID negatively-regulates polyubiquitination and the inflammatory response. INAVA and ARNO act similarly in primary human macrophages responding to IL-1β and to NOD2 agonists. Thus, INAVA-CUPID exhibits dual functions, coordinated directly by ARNO, that bridge epithelial barrier function with extracellular signals and inflammation.
Ninjinyoeito Improves Behavioral Abnormalities and Hippocampal Neurogenesis in the Corticosterone Model of Depression

Ninjinyoeito (NYT), a traditional Chinese medicine consisting of 12 herbs, is designed to improve fatigue, cold limbs, anorexia, night sweats, and anemia. Recently, NYT was reported to improve cognitive outcome and depression in patients with Alzheimer’s disease. However, little is known about how NYT alleviates depression and cognitive dysfunction. In this study, we investigated the effects and mechanisms of NYT in a corticosterone (CORT)-induced model of depression. Chronic NYT treatment ameliorated the depressive-like behaviors induced by CORT treatment in three types of behavioral tests. In addition, chronic NYT treatment also improved memory disruptions induced by CORT in both the Y-maze and novel object recognition tests, without affecting locomotor activity. Furthermore, we also showed that NYT treatment attenuated the CORT-induced reduction in cell proliferation and immature neuronal cell numbers in mouse hippocampal dentate gyrus. These results suggest that NYT has therapeutic effects on CORT-induced behavioral abnormalities and inhibition of hippocampal neurogenesis.
Mitochondria in cancer: in the aspects of tumorigenesis and targeted therapy

Mitochondria play pivotal roles in most eukaryotic cells, ranging from energy production to regulation of apoptosis. As sites of cellular respiration, mitochondria experience accumulation of reactive oxygen species (ROS) due to damage in electron transport chain carriers. Mutations in mitochondrial DNA (mtDNA) as well as nuclear DNA are reported in various cancers. Mitochondria have a dual role in cancer: the development of tumors due to mutations in mitochondrial genome and the generation of ROS. Impairment in the mitochondria-regulated apoptosis pathway accelerates tumorigenesis. Numerous strategies targeting mitochondria have been developed to induce the mitochondrial (i.e. intrinsic) apoptosis pathway in cancer cells. This review elaborates the roles of mitochondria in cancer with respect to mutations and apoptosis and discusses mitochondria-targeting strategies as cancer therapies to enhance the killing of cancer cells.
Homeostatic and neurocognitive control of energy intake in response to exercise in pediatric obesity: a psychobiological framework

While energy intake and energy expenditure have long been studied independently, the alarming progression of obesity has led to a more integrative approach to energy balance considering their potential interactions. Although the available literature concerned with the effect of chronic and acute exercise on energy intake and appetite control in adults is considerable, these questions remain less explored among children and adolescents. Based on the search of four databases (Medline, Embase, PsycINFO and Cochrane Library; articles published until May 2018), the objective of this review is to summarize and discuss the effect of acute and chronic physical exercise on energy intake and appetite control in children and adolescents with obesity, and to identify the physiological and neurocognitive signals and pathways involved. Evidence suggested that acute intensive exercise has the potential to reduce subsequent energy intake in children and adolescents with obesity but not healthy weight, through both peripheral (mainly gastro‐peptides) and neurocognitive (neural responses to food cues) pathways. The nutritional responses to chronic physical activity remain less clear and require further consideration, especially from an anti‐obesity perspective.
Fuzzy Cognitive Map-Based Modeling of Social Acceptance to Overcome Uncertainties in Establishing Waste Biorefinery Facilities

Sustainable Waste Biorefinery Facilities (WBFs) represent multifactorial systems that necessitate the organization, cooperation and the acceptance of different social stakeholders. However, these attempts have become targets of environmental, social and legal oppositions despite their obvious economic benefits. The variety of ambivalent and heterogeneous external effects of such projects result in either local support or opposition to the facility, which in turn becomes a critical factor affecting facility location decisions, and subsequent success of a WBF. Research has shown that simple surveys do not sufficiently measure social acceptance of such endeavours, and in most cases, local community factors dominate other external valuable impacts. In the current study, a novel Fuzzy Cognitive Map (FCM) modeling approach is proposed in order to analyze the socio-economic implications and to overcome multiple uncertainties occurring in sustainable WBF development and implementation. The primary investigation relates to the factors that influence the development of organic or chemical treatment of waste by the local communities and the competent authorities. The determination of concepts involved in the FCM modeling depends on a hybrid approach where both experts’ opinion and statistical results from questionnaires distributed to stakeholders participate in the concept circumscription, thus identifying the centrality of each node in the model. Several steady state and dynamic analysis scenarios show the influence of driver concepts to receiver concepts on the social aspect FCM constructed.
Low Bacterial Co-infection Invalidates the Early Use of Non-anti-Mycoplasma pneumoniae Antibiotics in Pediatric Refractory Mycoplasma pneumoniae Pneumonia Patients

Background: Childhood refractory mycoplasma pneumoniae (MP) pneumonia (RMPP) is a lung disease with elevated level of C-reactive protein and severe clinical and radiological deterioration. Whether bacterial co-infection contributes to disease of RMPP and whether inclusion of non-anti-MP antibiotics in treatment regimen would benefit RMPP patients remains elusive. Methods: We retrospectively reviewed the medical records of 675 RMPP children. Traditional bacterial culture and next generation sequencing (NGS) were used to detect bacteria in bronchoalveolar lavage fluid in all the 675 patients and 18 patients respectively. Antibiotics used and clinical outcomes were analyzed along with other clinical measurements. Results: Positive bacterial cultures were only found in 18 out of 675 cases (2.67%) and NGS analyses of another 18 cases did not revealed positive bacterial infection, which were consistent with the results of bacterial cultures. Non-anti-MP antibiotics were utilized in 630 cases (93.33%), even last-line antibiotics, such as glycopeptides or carbapenems, were frequently used. Conclusion: Bacterial co-infection in RMPP was rare and non-anti-MP antibiotics didn't show any efficacy for early treatment of RMPP patients, which may provide a rationale for restricting the use of non-anti-MP antibiotics in RMPP patients and preventing antibiotic resistance globally.
Decreased Expression of TRPV4 Channels in HEI-OC1 Cells Induced by High Glucose Is Associated with Hearing Impairment

Purpose Previous reports have shown that hyperglycemia-induced inhibition of transient receptor potential vanilloid sub type 4 (TRPV4), a transient receptor potential ion channel, affects the severity of hearing impairment (HI). In this study, we explored the role of TRPV4 in HI using HEI-OC1 cells exposed to high glucose (HG). Materials and Methods HEI-OC1 cells were cultured in a HG environment (25 mM D-glucose) for 48 hours, and qRT-PCR and Western blotting were used to analyze the expression of TRPV4 at the mRNA and protein level. TRPV4 agonist (GSK1016790A) or antagonist (HC-067047) in cultured HEI-OC1 cells was used to obtain abnormal TRPV4 expression. Functional TRPV4 activity was assessed in cultured HEI-OC1 cells using the MTT assay and a cell death detection ELISA. Results TRPV4 agonists exerted protective effects against HG-induced HI, as evidenced by increased MTT levels and inhibition of apoptosis in HEI-OC1 cells. TRPV4 overexpression significantly increased protein levels of phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK), while TRPV4 antagonists had the opposite effect. Our results indicated that TRPV4 is a hyperglycemia-related factor that can inhibit cell proliferation and promote cell apoptosis by activating the MAPK signaling pathway in HEI-OC1 cells. Conclusion Our results show that the overexpression of TRPV4 can attenuate cell death in HEI-OC1 cells exposed to HG.
Plasmon-induced photocatalytic degradation of methylene blue dye using biosynthesized silver nanoparticles as photocatalyst

ABSTRACT Bio-fabrication of silver nanoparticles, using stem extracts of Nepeta leucophylla and their photocatalytic degradation activity, has been undertaken. The synthesized silver nanoparticles are characterized using ultraviolet-visible spectroscopy, Fourier transformed infrared spectroscopy, X-ray diffractometry, Transmission Electron Microscopy, Field Emission Scanning Electron Microscopy, Energy-dispersive X-ray spectroscopy and thermal gravimetric and differential scanning calorimetry analysis. The Surface Plasmon Resonance band detected at 430 nm in the ultraviolet-visible spectrum confirms the formation of silver nanoparticles in the aqueous solution. Transmission Electron and Field Emission Scanning Electron micrographs reveal that the synthesized silver nanoparticles are spherical with an average size in the range of 15–25 nm. But, the X-ray diffraction confirms the face-centred cubic structure of silver nanoparticles with an average crystal size of the nanoparticles is about 10 nm. Furthermore, the infrared spectrogram confirms that the stem extract of Nepeta leucophylla contains phenol which causes reduction of silver salt to silver nanoparticles and protein might act as an overlaying agent which prevents the agglomeration of these nanoparticles. Moreover, the photocatalytic degradation of methylene blue dye, by using biosynthesized silver nanoparticles of optimized dose (1.8 ml) for 180 min in the presence and absence of light are 82.8% and 61.25%, respectively, specifies that the resultant photocatalyst is proved to have good photocatalytic activity for the degradation of methylene blue dye from the liquid phase. GRAPHICAL ABSTRACT
Curved planar reformatting and convolutional neural network‐based segmentation of the small bowel for visualization and quantitative assessment of pediatric Crohn's disease from MRI

Contrast‐enhanced MRI of the small bowel is an effective imaging sequence for the detection and characterization of disease burden in pediatric Crohn's disease (CD). However, visualization and quantification of disease burden requires scrolling back and forth through 3D images to follow the anatomy of the bowel, and it can be difficult to fully appreciate the extent of disease.
miR‐375‐3p/YWHAZ/β‐catenin axis regulates migration, invasion, EMT in gastric cancer cells

YWHAZ (14‐3‐3ζ) plays crucial roles in regulating proliferation, apoptosis, migration, and invasion of gastric cancer (GC) cells. However, its extensive roles and potential mechanisms in GC cells remain unknown, and need to be researched deeply. In this study, we focus on the role of miR‐375/YWHAZ axis in migration, invasion and epithelial‐to‐mesenchymal transition (EMT) of GC cells. YWHAZ level was assessed by western blot and qPCR assays in GC cells. Scratch and transwell assays were used to determine the migration and invasion of GC cells. The protein levels of correlative molecules were detected by western blot. The regulation of miR‐375 on the expression of its target gene YWHAZ was verified by dual‐luciferase report system. According to the results, knockdown of YWHAZ inhibited the migration, invasion and EMT of GC cells. Moreover, silencing of YWHAZ restrained the activation of wnt/β‐catenin signalling pathway. YWHAZ was confirmed to be a target gene of miR‐375, and its expression was regulated by miR‐375 in GC cells. Transfection of miR‐375 inhibitor promoted the migration, invasion, EMT and activation of wnt/β‐catenin pathway in GC cells, which was suppressed by inhibition of YWHAZ. Taken together, this study suggests that miR‐375/YWHAZ axis may be served as a novel therapeutic target for GC patients.
The Influence of Agile Methods on Requirements Engineering Courses

Requirements Engineering (RE) focuses on methods, concepts, and techniques to effectively capture the desired functionality and qualities of systems. RE content is typically taught as part of a Software Engineering (SE) higher education curriculum. With the rise of agile software development methods, one can argue that the use of RE practices in industry is de-emphasized and decreasing. However, many of the techniques and conceptualizations which are part of an RE curriculum can be used in an iterative, lightweight context, and remain relevant even in an agile world. Motivated by these trends, this paper examines literature on RE pedagogy and samples existing RE course material in order to understand educational trends and practices, and in particular, how this material addresses the rise of agile. In this way, we can gain an educational view on how the RE community is adapting to the rise of agile, using this view to provide guidance to current and future RE educators.
Annexin A2 and FTH1 are potential biomarkers for lupus nephritis

Lupus nephritis (LN) occurs in ~50% of patients with systemic lupus erythematosus and is a major cause of morbidity and mortality of the affected individuals. Therefore, identification of novel and predictive biomarkers for the early diagnosis and progression of LN is required. The present study included 10 patients with LN whose diagnoses were confirmed by renal biopsy and 5 healthy participants as control subjects. Sera were collected both from patients with LN and healthy controls. Subsequently, mesangial cells were treated with these sera for 24 h. Differential proteins between groups were detected by two-dimensional difference gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization time of flight mass spectrometry analysis. 2D-DIGE maps of cellar proteins were obtained for LN and normal control groups. A total of 45 proteins were characterized, and 2 low-abundance proteins were identified. Compared with the normal human sera group, expression level of Annexin A2 was elevated in patients with LN, while the expression of the ferritin heavy chain (FTH1) decreased in the LN group; the analysis was carried out by DeCyder version 7.0 automatically. The results of the present study suggest that Annexin A2 and FTH1 contributed to the progression of LN and could serve as potential biomarkers for this disease.