Miracle-dz/UniFAR-FTUs huggingface dataset:
Amyotrophic lateral sclerosis-related mutant superoxide dismutase 1 aggregates inhibit 14-3-3-mediated cell survival by sequestration into the JUNQ compartment

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by motor neuron loss in the spinal cord and brain. Mutations in the superoxide dismutase 1 (SOD1) gene have been linked to familial ALS. To elucidate the role of SOD1 mutations in ALS, we investigated 14-3-3, a crucial regulator of cell death that was identified in patients with familial ALS. In a transgenic mouse model (SOD1-G93A) of ALS, 14-3-3 co-localized with mutant SOD1 aggregates and was more insoluble in the spinal cords of mutant SOD1 transgenic mice than in those of wild-type mice. Immunofluorescence and co-immunoprecipitation experiments showed that the 14-3-3ɛ and θ isoforms interact with mutant SOD1 aggregates in the juxtanuclear quality control compartment of N2a neuroblastoma cells. Fluorescence loss in photobleaching experiments revealed that movement of the isoforms of 14-3-3 was markedly reduced in SOD1 aggregates. Bax translocation into and cytochrome c release from the mitochondria were promoted by the sequestration of 14-3-3 into mutant SOD1 aggregates, increasing cell death. Mutant SOD1 aggregates were dissolved by the Hsp104 chaperone, which increased the interaction of 14-3-3 with Bax, reducing cell death. Our study demonstrates that mutant SOD1 inhibits 14-3-3-mediated cell survival. This information may contribute to the identification of a novel therapeutic target for ALS.
Grape seed proanthocyanidins and metformin combination attenuate hepatic endoplasmic reticulum stress in rats subjected to nutrition excess

Abstract Context: Endoplasmic reticulum (ER) stress in the liver is a pathological outcome of nutrient excess and is suggested to be one of the hits for progressive liver injury. Objective: This study investigated whether grape seed proanthocyanidins (GSP) and metformin (MET) alone or in combination can relieve hepatic ER stress induced in rats subjected to calorie excess. Material and methods: Male albino Wistar rats were given high calorie diet (HCD) for 45 days, while GSP (100 mg/kg body weight) and MET (50 mg/kg body weight) were administered either alone or in combination for last 15 days. Results: GSP, MET or both had reduced the levels of ER stress markers and chaperons, and suppressed the activation of lipogenic and inflammatory mediators in rat liver. Discussion: Though GSP and MET had reduced ER stress and inflammation individually, combination treatment with GSP + MET was more effective. Conclusion: We suggest intervention with GSP and MET intake has to be considered for the management of liver disorders.
Systemic interferon type I and type II signatures in primary Sjögren’s syndrome reveal differences in biological disease activity

Objective To assess the relationships between systemic IFN type I (IFN-I) and II (IFN-II) activity and disease manifestations in primary SS (pSS). Methods RT-PCR of multiple IFN-induced genes followed by principal component analysis of whole blood RNA of 50 pSS patients was used to identify indicator genes of systemic IFN-I and IFN-II activities. Systemic IFN activation levels were analysed in two independent European cohorts (n = 86 and 55, respectively) and their relationships with clinical features were analysed. Results Three groups could be stratified according to systemic IFN activity: IFN inactive (19-47%), IFN-I (53-81%) and IFN-I + II (35-55%). No patient had isolated IFN-II activation. IgG levels were highest in patients with IFN-I + II, followed by IFN-I and IFN inactive patients. The prevalence of anti-SSA and anti-SSB was higher among those with IFN activation. There was no difference in total-EULAR SS Disease Activity Index (ESSDAI) or ClinESSDAI between the three subject groups. For individual ESSDAI domains, only the biological domain scores differed between the three groups (higher among the IFN active groups). For patient reported outcomes, there were no differences in EULAR Sjögren's syndrome patient reported index (ESSPRI), fatigue or dryness between groups, but pain scores were lower in the IFN active groups. Systemic IFN-I but not IFN-I + II activity appeared to be relatively stable over time. Conclusions Systemic IFN activation is associated with higher activity only in the ESSDAI biological domain but not in other domains or the total score. Our data raise the possibility that the ESSDAI biological domain score may be a more sensitive endpoint for trials targeting either IFN pathway.
Accelerating drug development for neuroblastoma - New Drug Development Strategy: an Innovative Therapies for Children with Cancer, European Network for Cancer Research in Children and Adolescents and International Society of Paediatric Oncology Europe Neuroblastoma project

ABSTRACT Introduction: Neuroblastoma, the commonest paediatric extra-cranial tumour, remains a leading cause of death from cancer in children. There is an urgent need to develop new drugs to improve cure rates and reduce long-term toxicity and to incorporate molecularly targeted therapies into treatment. Many potential drugs are becoming available, but have to be prioritised for clinical trials due to the relatively small numbers of patients. Areas covered: The current drug development model has been slow, associated with significant attrition, and few new drugs have been developed for neuroblastoma. The Neuroblastoma New Drug Development Strategy (NDDS) has: 1) established a group with expertise in drug development; 2) prioritised targets and drugs according to tumour biology (target expression, dependency, pre-clinical data; potential combinations; biomarkers), identifying as priority targets ALK, MEK, CDK4/6, MDM2, MYCN (druggable by BET bromodomain, aurora kinase, mTORC1/2) BIRC5 and checkpoint kinase 1; 3) promoted clinical trials with target-prioritised drugs. Drugs showing activity can be rapidly transitioned via parallel randomised trials into front-line studies. Expert opinion: The Neuroblastoma NDDS is based on the premise that optimal drug development is reliant on knowledge of tumour biology and prioritisation. This approach will accelerate neuroblastoma drug development and other poor prognosis childhood malignancies.
Occupational and genetic risk factors for osteoarthritis: a review.

BACKGROUND Osteoarthritis (OA) is a multifactorial disease with strong genetic and occupational components. Although published studies have described several risk factors for OA, very few studies have investigated the occupational and genetic factors that contribute to this debilitating condition. OBJECTIVE To describe occupational and genetic factors that may contribute to the risk of developing (OA). METHODS A literature search was conducted in PubMed using the search terms osteoarthritis, occupation, work, and genetics. RESULTS Heavy physical work load was the most common occupational risk factor for OA in several anatomical locations. Other factors include kneeling and regular stair climbing, crawling, bending and whole body vibration, and repetitive movements. Numerous studies have also shown the influence of genetic variability in the pathogenesis of OA. Genetic variants of several groups of genes e.g., cartilage extracellular matrix structural genes and the genes related to bone density have been implicated in disease pathogenesis. CONCLUSION This review shows that occupational factors were extensively studied in knee OA unlike OA of other anatomical regions. Although genetic association studies performed to date identified a number of risk variants, some of these associations have not been consistently replicated across different studies and populations. Therefore, more research is needed.
Comprehensive replication of the relationship between myopia-related genes and refractive errors in a large Japanese cohort.

PURPOSE We investigated the association between refractive error in a Japanese population and myopia-related genes identified in two recent large-scale genome-wide association studies. METHODS Single-nucleotide polymorphisms (SNPs) in 51 genes that were reported by the Consortium for Refractive Error and Myopia and/or the 23andMe database were genotyped in 3712 healthy Japanese volunteers from the Nagahama Study using HumanHap610K Quad, HumanOmni2.5M, and/or HumanExome Arrays. To evaluate the association between refractive error and recently identified myopia-related genes, we used three approaches to perform quantitative trait locus analyses of mean refractive error in both eyes of the participants: per-SNP, gene-based top-SNP, and gene-based all-SNP analyses. Association plots of successfully replicated genes also were investigated. RESULTS In our per-SNP analysis, eight myopia gene associations were replicated successfully: GJD2, RASGRF1, BICC1, KCNQ5, CD55, CYP26A1, LRRC4C, and B4GALNT2.Seven additional gene associations were replicated in our gene-based analyses: GRIA4, BMP2, QKI, BMP4, SFRP1, SH3GL2, and EHBP1L1. The signal strength of the reported SNPs and their tagging SNPs increased after considering different linkage disequilibrium patterns across ethnicities. Although two previous studies suggested strong associations between PRSS56, LAMA2, TOX, and RDH5 and myopia, we could not replicate these results. CONCLUSIONS Our results confirmed the significance of the myopia-related genes reported previously and suggested that gene-based replication analyses are more effective than per-SNP analyses. Our comparison with two previous studies suggested that BMP3 SNPs cause myopia primarily in Caucasian populations, while they may exhibit protective effects in Asian populations.
Disclosure of cancer information among Saudi cancer patients.

BACKGROUND Cancer has been perceived as an incurable disease, and therefore, disclosure of cancer could harm patients. Therefore, the aim of this study was to explore Saudi cancer patients' views regarding disclosure of cancer information and the impact of gender, regions, and level of education on their desire to be disclosed of the diagnosis and prognosis. MATERIALS AND METHODS A face-to-face interview was conducted during patient's evaluation at our hospital prior to their knowledge of being diagnosed with cancer. RESULTS Of 420 patients, 97.62% wanted to know all information about cancer and more than 96% wished to know the benefits and side effects of chemotherapy. None of the patients wanted to be treated without knowing their diagnosis, and almost all of them (94.76%) wanted to know about the prognosis. Patients from eastern region and male patients wanted to know their diagnosis more frequently than those from other regions and female patients (98.2% vs. 74.47%, P = 0.001; 97.90% vs. 92.17%, P = 0.008, respectively). Patients from Eastern Province, male patients, and educated patients wished to know their prognosis more frequently than those from other regions, female patients, and illiterate patients (94.98% vs. 68.79%, P = 0.001; 94.74% vs. 86.09%, P = 0.003; and 94.23% vs. 98.58%, P = 0.016, respectively). CONCLUSION This study indicates that almost all the Saudi cancer patients wanted to know about their cancer diagnosis, prognosis, benefits and side effects of chemotherapy. Regions, gender, and level of education may affect patient's desire for cancer information.
Public Debt and Economic Growth in Emerging Market Economies

This paper empirically studies the relationship between public debt and economic growth for selected emerging market economies by performing panel data estimations. The results reveal a statistically significant positive correlation between public debt and the subsequent growth rate of per capita gross domestic product (GDP). Population and investment are also positively correlated with per capita growth, whereas the initial level of real GDP per capita exerts a negative influence on growth, implying conditional convergence. Other variables such as the inflation rate, the trade balance or the exchange rate do not yield a statistically significant effect with respect to economic growth.
Long-Term Efficacy of Photorefractive Keratectomy In Hyperopia Patients

Hyperopia is a common refractive error that is usually corrected with eyeglasses or contact lenses. Following the fast advancement in refractive surgery and technology, eyeglasses or contact lenses were no longer the single treatment option in refractive errors. Today, extraction of transparent lens and intraocular lens implantation, phacic intraocular lens applications and corneal surgeries are performed for correction and treatment of refractive errors. Excimer Laser is the most widely used method in refractive surgery methods. In this method, cornea is reshaped using 193 nm argon-flourine laser and cornea is corrected according to patient’s refractive error. Different techniques can be chosen for patients with differences in cornea structure, refraction errors and patient expectations. The most frequently used methods are PRK (Photorefractive keratectomy), LASIK (Laser in situ keratomileusis) and LASEK (Laser subepithelial keratomileusis) [1, 2]. PRK is the first widely used excimer laser method. In this method, cornea epithelium is mechanically peeled and then excimer laser is applied. PRK is used as a safe, efficient and predictable method in correction of myopia and astigmatism as well as treatment of hyperopia. However, post-operative pain, corneal haze formation, high regression rate and late stabilization of visual acuity in patients with high grade hyperopia (>+6.00) are the disadvantages of this method [3, 4].
Pharmacist-Led Group Medical Appointment Model in Type 2 Diabetes

Purpose The purpose of this study was to assess whether the VA-MEDIC (Veterans Affairs Multi-disciplinary Education and Diabetes Intervention for Cardiac risk reduction), a pharmacist-led group medical visit program, could improve achievement of target goals in hypertension, hyperglycemia, hyperlipidemia, and tobacco use in patients with type 2 diabetes compared to usual care. Methods This was a randomized controlled trial of VA-MEDIC intervention in addition to usual care versus usual care alone in diabetic patients to reduce cardiac risk factors. VA-MEDIC consisted of a 40- to 60-minute educational component by nurse, nutritionist, physical therapist, or pharmacist followed by pharmacist-led behavioral and pharmacological interventions over 4 weekly sessions. Measures The attainment of target goals in hemoglobin A1C (A1C), blood pressure, fasting lipids, and tobacco use recommended by the American Diabetes Association. Results Of 118 participants, 109 completed the study. VA-MEDIC (n = 58) participants were younger and had greater tobacco use at baseline than usual care but were similar in other cardiovascular risk factors. After 4 months, a greater proportion of VA-MEDIC participants versus controls achieved an A1C of less than 7% and a systolic blood pressure less than 130 mm Hg. No significant change was found in lipid control or tobacco use between the 2 study arms. Conclusion Pharmacist-led group medical visits are feasible and efficacious for improving cardiac risk factors.
Detecting Traversable Area and Water Hazards for the Visually Impaired with a pRGB-D Sensor

The use of RGB-Depth (RGB-D) sensors for assisting visually impaired people (VIP) has been widely reported as they offer portability, function-diversity and cost-effectiveness. However, polarization cues to assist traversability awareness without precautions against stepping into water areas are weak. In this paper, a polarized RGB-Depth (pRGB-D) framework is proposed to detect traversable area and water hazards simultaneously with polarization-color-depth-attitude information to enhance safety during navigation. The approach has been tested on a pRGB-D dataset, which is built for tuning parameters and evaluating the performance. Moreover, the approach has been integrated into a wearable prototype which generates a stereo sound feedback to guide visually impaired people (VIP) follow the prioritized direction to avoid obstacles and water hazards. Furthermore, a preliminary study with ten blindfolded participants suggests its effectivity and reliability.
A Three-Year Longitudinal Study of Reading and Spelling Difficulty in Chinese Developmental Dyslexia: The Matter of Morphological Awareness.

In the present study, we used a three-time point longitudinal design to investigate the associations of morphological awareness to word reading and spelling in a small group of those with and without dyslexia taken from a larger sample of 164 Hong Kong Chinese children who remained in a longitudinal study across ages 6, 7 and 8. Among those 164 children, 15 had been diagnosed as having dyslexia by professional psychologists, and 15 other children manifested average reading ability and had been randomly selected from the sample for comparison. All children were administered a battery of tasks including Chinese character recognition, word dictation, morphological awareness, phonological awareness and rapid automatized naming. Multivariate analysis of variance and predictive discriminate analysis were performed to examine whether the dyslexic children showed differences in the cognitive-linguistic tasks in comparison with controls. Results suggested that the dyslexic groups had poorer performance in morphological awareness and RAN across all 3 years. However, phonological awareness was not stable in distinguishing the groups. Findings suggest that morphological awareness is a relatively strong correlate of spelling difficulties in Chinese, but phonological awareness is not. Copyright © 2017 John Wiley & Sons, Ltd.
Understanding explicit arithmetic word problems and explicit plane geometry problems using syntax-semantics models

This paper presents two algorithms for understanding explicit arithmetic word problems (EAWPs) and explicit plane geometry problems (EPGPs) following the sharing approach, respectively. This approach proposed in this paper models understanding math problems as a problem of relation extraction, instead of as the problem of understanding the semantics of natural language. Then it further proposes a syntax-semantics (S2) model method to extract math relations. The S2 model method is very effective in that only 116 models can extract most of relations in EAWPs and that only 48 models can extract most of relations in EPGP texts. The experimental results show that the proposed algorithms can understand EAWPs and EPGPs very well.
High Order Recurrent Neural Networks for Acoustic Modelling

Vanishing long-term gradients are a major issue in training standard recurrent neural networks (RNNs), which can be alleviated by long short-term memory (LSTM) models with memory cells. However, the extra parameters associated with the memory cells mean an LSTM layer has four times as many parameters as an RNN with the same hidden vector size. This paper addresses the vanishing gradient problem using a high order RNN (HORNN) which has additional connections from multiple previous time steps. Speech recognition experiments using British English multi-genre broadcast (MGB3) data showed that the proposed HORNN architectures for rectified linear unit and sigmoid activation functions reduced word error rates (WER) by 4.2% and 6.3% over the corresponding RNNs, and gave similar WERs to a (projected) LSTM while using only 20%-50% of the recurrent layer parameters and computation.
Exact fast smoothing in switching models with application to stochastic volatility

We consider the problem of statistical smoothing in nonlinear non-Gaussian systems. Our novel method relies on a Markov-switching model to operate recursively on series of noisy input data to produce an estimate of the underlying system state. We show through a set of experiments that our technique is efficient within the framework of the stochastic volatility model.
Evaluation of a mindfulness intervention for Paralympic leaders prior to the Paralympic Games

This article presents an evaluation of the effectiveness of an applied mindfulness intervention for stress reduction delivered to Paralympic leaders prior to the Paralympic Games. The intervention group of Swedish Paralympic leaders (n = 10) received a mindfulness intervention of eight web-based seminars, while a Norwegian reference group (n = 6) received no intervention. Three assessments were performed for both samples: at baseline, post-intervention and six weeks post-intervention. The evaluation indicated intervention effects of higher psychological flexibility (p = .03), less rumination (p = .02) and lower perceived stress (p = .001), and offers initial support for the applied usefulness of a web-based mindfulness training program as a supplement in stress-reduction programs for elite sport leaders. General challenges from an applied sport psychology perspective related to the implementation of mindfulness interventions in samples with experienced high levels of stress and perceived time-constraints are discussed.
Multiclass Common Spatial Pattern for EEG based Brain Computer Interface with Adaptive Learning Classifier

In Brain Computer Interface (BCI), data generated from Electroencephalogram (EEG) is non-stationary with low signal to noise ratio and contaminated with artifacts. Common Spatial Pattern (CSP) algorithm has been proved to be effective in BCI for extracting features in motor imagery tasks, but it is prone to overfitting. Many algorithms have been devised to regularize CSP for two class problem, however they have not been effective when applied to multiclass CSP. Outliers present in data affect extracted CSP features and reduces performance of the system. In addition to this non-stationarity present in the features extracted from the CSP present a challenge in classification. We propose a method to identify and remove artifact present in the data during pre-processing stage, this helps in calculating eigenvectors which in turn generates better CSP features. To handle the non-stationarity, Self-Regulated Interval Type-2 Neuro-Fuzzy Inference System (SRIT2NFIS) was proposed in the literature for two class EEG classification problem. This paper extends the SRIT2NFIS to multiclass using Joint Approximate Diagonalization (JAD). The results on standard data set from BCI competition IV shows significant increase in the accuracies from the current state of the art methods for multiclass classification.
Zero-Shot Visual Recognition Using Semantics-Preserving Adversarial Embedding Networks

We propose a novel framework called Semantics-Preserving Adversarial Embedding Network (SP-AEN) for zero-shot visual recognition (ZSL), where test images and their classes are both unseen during training. SP-AEN aims to tackle the inherent problem - semantic loss - in the prevailing family of embedding-based ZSL, where some semantics would be discarded during training if they are non-discriminative for training classes, but could become critical for recognizing test classes. Specifically, SP-AEN prevents the semantic loss by introducing an independent visual-to-semantic space embedder which disentangles the semantic space into two subspaces for the two arguably conflicting objectives: classification and reconstruction. Through adversarial learning of the two subspaces, SP-AEN can transfer the semantics from the reconstructive subspace to the discriminative one, accomplishing the improved zero-shot recognition of unseen classes. Comparing