Miracle-dz/UniFAR-FTUs huggingface dataset:
A Large Number of Protein Expression Changes Occur Early in Life and Precede Phenotype Onset in a Mouse Model for Huntington Disease*S

Huntington disease (HD) is fatal in humans within 15–20 years of symptomatic disease. Although late stage HD has been studied extensively, protein expression changes that occur at the early stages of disease and during disease progression have not been reported. In this study, we used a large two-dimensional gel/mass spectrometry-based proteomics approach to investigate HD-induced protein expression alterations and their kinetics at very early stages and during the course of disease. The murine HD model R6/2 was investigated at 2, 4, 6, 8, and 12 weeks of age, corresponding to absence of disease and early, intermediate, and late stage HD. Unexpectedly the most HD stage-specific protein changes (71–100%) as well as a drastic alteration (almost 6% of the proteome) in protein expression occurred already as early as 2 weeks of age. Early changes included mainly the up-regulation of proteins involved in glycolysis/gluconeogenesis and the down-regulation of the actin cytoskeleton. This suggests a period of highly variable protein expression that precedes the onset of HD phenotypes. Although an up-regulation of glycolysis/gluconeogenesis-related protein alterations remained dominant during HD progression, late stage alterations at 12 weeks showed an up-regulation of proteins involved in proteasomal function. The early changes in HD coincide with a peak in protein alteration during normal mouse development at 2 weeks of age that may be responsible for these massive changes. Protein and mRNA data sets showed a large overlap on the level of affected pathways but not single proteins/mRNAs. Our observations suggest that HD is characterized by a highly dynamic disease pathology not represented by linear protein concentration alterations over the course of disease.
Challenge in Classification of Depressive Symptoms Using Actigraphy Data

Monitoring human behavior through wearable devices has potential in psychiatry. Among them, actigraphy data has been used to classify depression and detect depressive symptoms. We aim to collect a larger number of data to measure classification performance. This study evaluates the performance of classifying depressive symptoms solely on actigraphy data using both public (n=1549) and collected (n=3145) datasets. We found that there are challenges in classifying depressive symptoms from actigraphy data.
Na+/H+ exchangers and the regulation of volume

The regulation of volume is fundamental to life. There exist numerous conditions that can produce perturbations of cell volume. The cell has developed mechanisms to directly counteract these perturbations so as to maintain its physiological volume. Directed influx of the major extracellular cation, sodium, serves to counteract a decreased cell volume through the subsequent osmotically coupled movement of water to the intracellular space. This process, termed regulatory volume increase is often mediated by the ubiquitous sodium/hydrogen ion exchanger, NHE1. Similarly, the maintenance of intravascular volume is essential for the maintenance of blood pressure and consequently the proper perfusion of vital organs. Numerous mechanisms exist to counterbalance alterations in intravascular volume, not the least of which is the renal absorption of sodium filtered at the glomerulus. Two‐thirds of filtered sodium and water are absorbed in the renal proximal tubule, a mechanism that intimately involves the apical sodium/hydrogen ion exchanger, NHE3. This isoform is fundamental to the maintenance and regulation of intravascular volume and blood pressure. In this article, the effects of cell volume on the activity of these different isoforms, NHE1 and NHE3, will be described and the consequences of their activity on intracellular and intravascular volume will be explored.
Review of Cardiotoxicity in Pediatric Cancer Patients: During and after Therapy

With the improvement in survival from childhood cancer, late effects of therapy are becoming more apparent. Cardiac disease, one of these late effects, has a significant impact on the life of survivors of childhood cancers. Most survivors are followed by primary care doctors and adult subspecialists after they have graduated from pediatric centers. Since much of the cardiac toxicity of therapy occurs years off of therapy, it is important for these physicians to be aware of how to monitor survivors for the development of cardiac toxicities. In this paper we will discuss the incidence of cardiac disease during treatment and in survivors, what treatment modalities contribute to its development and modalities utilized to screen for cardiac disease. Recommendations for posttherapy monitoring will be emphasized.
Multiple choice questions: to guess or not to guess

Multiple choice question papers in which the student has a ‘don't know’ option are widely used in undergraduate and postgraduate examinations in Medicine. In the present study students’ performance in papers with a ‘don't know’ option has been compared with their performance when they are instructed to answer all the questions. By completing questions left unanswered (i.e. ‘don't know’ options) students were able to increase their score significantly and the rank order of the students in class is changed. Answers omitted may indicate complete ignorance or various degrees of knowledge. It is concluded that the ‘don't know’ option in multiple choice question papers favours the bold and test‐wise student and in consequence their validity as a measure of achievement may suffer. Papers in which the student is instructed to answer all the questions are to be preferred to those in common use where there is a ‘don't know’ option.
Bowel vaginoplasty in children

OBJECTIVES: To describe our experience with bowel vaginoplasty done in children. MATERIALS AND METHODS: This is a retrospective study of eight children aged 10 months to 8 years, who underwent bowel vaginoplasty over a period of 5 years (2000-2005). The indications of bowel vaginoplasty included anorectovestibular fistula (ARVF) associated with Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome (n=6) and cloaca (n=2). The bowel segment used for vaginoplasty included colon (n=3), ileum (n=2) and duplicated rectum (n=1). In two patients of ARVF associated with uterovaginal agenesis, the distal- most part of ARVF was transected at the level of peritoneal reflection and left as neovagina, whereas the proximal bowel was pulled through at the proposed neo-anal site. All the patients were advised daily home dilatation of the neo vaginal orifice with Hegar's dilators, for a period of six weeks. RESULTS: Bowel vaginoplasty was done in eight patients. None had any significant per-operative complication. Two patients had abdominal wound dehiscence, requiring secondary suturing. Two patients had mucosal prolapse of the neovagina, which required trimming. One patient died two months after discharge, because of meningitis. Out of the eight patients, seven are in regular follow-up. Six patients have neovagina, cosmetically acceptable to the parents; all have been radiologically proven to have adequate length. One patient had unacceptable perineal appearance with nipple-like vaginal orifice and scarred perineal wound, that merits a revision. None of the patients had vaginal stenosis and excessive mucus discharge, during follow-up visits. Although post surgical results are acceptable to the parents cosmetically, the sexual and psychological outcome is yet to be assessed. Conclusions: Bowel vaginoplasty is a safe and acceptable procedure to treat the pediatric patients of uterovaginal agenesis and cloaca.
Modelling cell motility and chemotaxis with evolving surface finite elements

We present a mathematical and a computational framework for the modelling of cell motility. The cell membrane is represented by an evolving surface, with the movement of the cell determined by the interaction of various forces that act normal to the surface. We consider external forces such as those that may arise owing to inhomogeneities in the medium and a pressure that constrains the enclosed volume, as well as internal forces that arise from the reaction of the cells' surface to stretching and bending. We also consider a protrusive force associated with a reaction–diffusion system (RDS) posed on the cell membrane, with cell polarization modelled by this surface RDS. The computational method is based on an evolving surface finite-element method. The general method can account for the large deformations that arise in cell motility and allows the simulation of cell migration in three dimensions. We illustrate applications of the proposed modelling framework and numerical method by reporting on numerical simulations of a model for eukaryotic chemotaxis and a model for the persistent movement of keratocytes in two and three space dimensions. Movies of the simulated cells can be obtained from http://homepages.warwick. ac.uk/∼maskae/CV_Warwick/Chemotaxis.html.
Treating heavy smokers in primary care with the nicotine nasal spray: randomized placebo-controlled trial.

AIMS Of six established nicotine replacement therapy (NRT) formulations, only the gum and patch have been tested without specialist clinic support in placebo-controlled trials. We aimed to broaden the evidence base by examining if the nicotine nasal spray (NNS) could be effective with only brief support in general practice. DESIGN Randomized placebo-controlled trial. SETTING Twenty-seven English general practices. PARTICIPANTS A total of 761 heavy smokers received brief support and 12 weeks of treatment with NNS (506) or placebo (255). MEASUREMENTS The primary outcome was biochemically verified complete abstinence from smoking throughout weeks 3-12. FINDINGS NNS compared with placebo more than doubled the number who successfully stopped smoking [15.4% versus 6.7%, odds ratio (OR) = 2.6, 95% confidence interval (CI) = 1.5-4.4]. Many participants reported minor irritant adverse symptoms. NNS was particularly effective among those who were more highly dependent on nicotine (OR = 6.17, 95% CI = 2.13-17.9). Of those who failed to stop during the first week (417, 54.8%), only one (0.2%) achieved later success. CONCLUSIONS NNS is effective when given in primary care. The benefit was lower than in a specialist clinic but similar to that with the nicotine patch in primary care. Unlike most other NRT formulations, bupropion or varenicline, NNS was especially helpful for more dependent smokers. Continuing treatment of those initially failing was not beneficial. An initial 1-week prescription to those more dependent on nicotine is likely to be the most cost-effective NNS treatment protocol. These results should offer support to the effectiveness of the other NRT formulations untested in this setting.
Exact Exponent in Optimal Rates for Crowdsourcing

In many machine learning applications, crowdsourcing has become the primary means for label collection. In this paper, we study the optimal error rate for aggregating labels provided by a set of non-expert workers. Under the classic Dawid-Skene model, we establish matching upper and lower bounds with an exact exponent $mI(\pi)$ in which $m$ is the number of workers and $I(\pi)$ the average Chernoff information that characterizes the workers' collective ability. Such an exact characterization of the error exponent allows us to state a precise sample size requirement $m>\frac{1}{I(\pi)}\log\frac{1}{\epsilon}$ in order to achieve an $\epsilon$ misclassification error. In addition, our results imply the optimality of various EM algorithms for crowdsourcing initialized by consistent estimators.
Upregulation of Gelatinases and Epithelial–Mesenchymal Transition in Small Airway Remodeling Associated with Chronic Exposure to Wood Smoke

Background Peribronchiolar fibrosis is an important feature of small airway remodeling (SAR) in cigarette smoke-induced COPD. The aim of this study was to investigate the role of gelatinases (MMP9, MMP2) and epithelial-mesenchymal transition (EMT) in SAR related to wood smoke (WS) exposure in a rat model. Methods Forty-eight female Sprague-Dawley rats were randomly divided into the WS group, the cigarette smoke (CS) group and the clean air control group. After 4 to 7 months of smoke exposure, lung tissues were examined with morphometric measurements, immunohistochemistry and Western blotting. Serum MMP9 and TIMP1 concentrations were detected by ELISA. In vitro, primary rat tracheal epithelial cells were stimulated with wood smoke condensate for 7 days. Results The COPD-like pathological alterations in rats exposed chronically to WS were similar to those exposed to CS; the area of collagen deposition was significantly increased in the small airway walls of those exposed to WS or CS for 7 months. The expression of gelatinases in rats induced by WS or CS exposure was markedly increased in whole lung tissue, and immunohistochemistry showed that MMP9, MMP2 and TIMP1 were primarily expressed in the airway epithelium. The serum levels of MMP9 and TIMP1 were significantly higher in rats secondary to WS or CS exposure. Few cells that double immunostained for E-cadherin and vimentin were observed in the airway subepithelium of rats exposed to WS for 7 months (only 3 of these 8 rats). In vitro, the expression of MMP9 and MMP2 proteins was upregulated in primary rat tracheal epithelial cells following exposure to wood smoke condensate for 7 days by Western blotting; positive immunofluorescent staining for vimentin and type I collagen was also observed. Conclusions These findings suggest that the upregulation of gelatinases and EMT might play a role in SAR in COPD associated with chronic exposure to wood smoke.
Cyclooxygenase‐2 expression and relationship to tumour progression in human renal cell carcinoma

Aims: Cyclooxygenase (COX), which catalyses the synthesis of prostaglandins from arachidonic acid, has two isoforms; COX‐1 and COX‐2. There is ample evidence to suggest an important role for COX‐2 in cancer. The aim of this study was to evaluate the clinical significance of COX‐2 expression and its localization in the development and progression of human renal cell carcinoma (RCC).
Real-Time Video Scaling Based On Convolution Neural Network Architecture

In recent years, video super resolution techniques becomes mandatory requirements to get high resolution videos. Many super resolution techniques researched but still video super resolution or scaling is a vital challenge. In this paper, we have presented a real-time video scaling based on convolution neural network architecture to eliminate the blurriness in the images and video frames and to provide better reconstruction quality while scaling of large datasets from lower resolution frames to high resolution frames. We compare our outcomes with multiple exiting algorithms. Our extensive results of proposed technique RemCNN (Reconstruction error minimization Convolution Neural Network) shows that our model outperforms the existing technologies such as bicubic, bilinear, MCResNet and provide better reconstructed motioning images and video frames. The experimental results shows that our average PSNR result is 47.80474 considering upscale-2, 41.70209 for upscale-3 and 36.24503 for upscale-4 for Myanmar dataset which is very high in contrast to other existing techniques. This results proves our proposed model real-time video scaling based on convolution neural network architecture’s high efficiency and better performance.
The Effects of Acute Passive Smoke Exposure on Endothelium-Dependent Brachial Artery Dilation in Healthy Individuals

Passive smoking has both short-term and long-term vascular effects. It is not clear whether impairment of endothelial function reflects the acute effects of passive smoke exposure or the chronic effects. The purpose of this study was to assess the hypothesis that short-term exposure to passive smoke impairs endothelium-dependent vasodilation in healthy nonsmokers. Eighteen healthy young never smokers (12 men, 6 women) 21 to 55 years old (mean ± SD: 34 ±9 years) underwent ultrasonography measuring baseline brachial-artery diameter and brachial-artery diameter during hyperemia and after sublingual administration of nitroglycerin, twice: in a smoke-free environment, and then in the same environment polluted by 30 to 35 ppm carbon monoxide. Each subject served as his/her control. Carboxyhemoglobin was measured in blood samples of subjects tested. Mean value of carboxyhemoglobin was 0.6 ±0.5% in a smoke-free environment and 1.4 ± 0.5% in a smoking environment (p <0.02). Mean values of flow-mediated dilation (FMD) were 12.6% ± 7.8% in a smoke-free environment versus 6.8 ± 7.8% in a smoking environment (p <0.01). On the contrary, nitroglycerin-induced vasodilation did not show any statistical difference (21 ± 9.8% versus 23 ±1.4%). Finally, the increase of carboxyhemoglobin was related statistically to the impairment of flow-mediated dilation (r = 0.51; p <0.002). Passive smoking impaired flow-mediated vasodilation in healthy never smokers in a smoking environment. The impairment was strongly related to carboxyhemoglobin level.
Wiener reconstruction of the IRAS 1.2-Jy galaxy redshift survey: cosmographical implications

We utilize the method of Wiener reconstruction with spherical harmonics and Bessel functions to recover the density and velocity fields from the IRAS 1.2-Jy redshift survey. The reconstruction relies on prior knowledge of the IRAS power spectrum and the combination of density and bias parameters beta = Omega(0.6)/b. The results are robust to changes in these prior parameters and the number of expansion coefficients. Maps of these fields are presented in a variety of projections. Many known structures are observed, including clear confirmations of the clusters N1600 and A3627. The Perseus-Pisces supercluster appears to extend out to similar to 9000 km s(-1), and the reconstruction shows 'backside infall' to the Centaurus/Great Attractor region. A qualitative comparison of the reconstructed IRAS gravity field with that from Tully-Fisher peculiar velocity measurements (Mark III) shows reasonable agreement. The Wiener reconstruction of the density field is also the optimal reconstruction (in the minimum-variance sense) of any quantity which is linear in the density contrast. We show reconstructions of three such quantities. The misalignment angle between the IRAS and cosmic microwave background Local Group dipoles is only 13 degrees out to 5000 km s(-1) but increases to 25 degrees out to 20 000 km s(-1). The reconstructed IRAS bulk flow out to 5000 km s(-1) is similar to 300 km s(-1), which agrees in amplitude with that derived from the Mark III peculiar velocities (similar to 370 km s(-1)). However, the two bulk flow vectors deviate by similar to 70 degrees. Finally, moment of inertia analysis shows that the Wiener reconstructed Supergalactic Plane is aligned within similar to 30 degrees of that defined by de Vaucouleurs.
Alternating noncross‐resistant combination chemotherapy and active nonspecific immunotherapy with BCG or MER‐BCG for advanced breast carcinoma

One hundred fifty‐six evaluable patients with metastatic breast cancer were treated with vincristine, Adriamycin and cyclophosphamide alternating at fixed intervals with 5‐FU and methotrexate. Immunotherapy with BCG or MER‐BCG was administered to all patients in two consecutive treatment programs. Overall objective response rate and complete response rate were 67% and 20%, respectively. These were not significantly different between the two immunotherapeutic groups. The median time to progression was sixteen‐and‐a‐half months from initiation of therapy. The median survival of all patients was 21 months and that of responders was 26 months. Response rates, time to progression, and survival showed no significant advantage over a recent historical control group treated with FAC‐BCG. Toxicity related to the gastrointestinal tract and bone marrow was considerably higher in this protocol than in the FAC combinations. MER at the dose, route, and schedule administered in this protocol caused excessive local and systemic toxic reactions. The alternate use of these noncross‐resistant combinations in advanced breast cancer is not superior to combination chemotherapy used in the traditional manner. Cancer 45:742‐749, 1980.
Predicting Remaining Useful Life using Time Series Embeddings based on Recurrent Neural Networks

We consider the problem of estimating the remaining useful life (RUL) of a system or a machine from sensor data. Many approaches for RUL estimation based on sensor data make assumptions about how machines degrade. Additionally, sensor data from machines is noisy and often suffers from missing values in many practical settings. We propose Embed-RUL: a novel approach for RUL estimation from sensor data that does not rely on any degradation-trend assumptions, is robust to noise, and handles missing values. Embed-RUL utilizes a sequence-to-sequence model based on Recurrent Neural Networks (RNNs) to generate embeddings for multivariate time series subsequences. The embeddings for normal and degraded machines tend to be different, and are therefore found to be useful for RUL estimation. We show that the embeddings capture the overall pattern in the time series while filtering out the noise, so that the embeddings of two machines with similar operational behavior are close to each other, even when their sensor readings have significant and varying levels of noise content. We perform experiments on publicly available turbofan engine dataset and a proprietary real-world dataset, and demonstrate that Embed-RUL outperforms the previously reported state-of-the-art (Malhotra, TV, et al., 2016) on several metrics.
Investigating the Role of Glutamate and GABA in the Modulation of Transthalamic Activity: A Combined fMRI-fMRS Study

The Excitatory-Inhibitory balance (EIB) between glutamatergic and GABAergic neurons is known to regulate the function of thalamocortical neurocircuits. The thalamus is known as an important relay for glutamatergic and GABAergic signals ascending/descending to/from the somatosensory cortex in rodents. However, new investigations attribute a larger role to thalamic nuclei as modulators of information processing within the cortex. In this study, functional Magnetic Resonance Spectroscopy (fMRS) was used to measure glutamate (Glu) and GABA associations with BOLD responses during activation of the thalamus to barrel cortex (S1BF) pathway at 9.4T. In line with previous studies in humans, resting GABA and Glu correlated negatively and positively respectively with BOLD responses in S1BF. Moreover, a significant negative correlation (R = −0.68, p = 0.0024) between BOLD responses in the thalamus and the barrel cortex was found. Rats with low Glu levels and high resting GABA levels in S1BF demonstrated lower BOLD responses in S1BF and high amplitude BOLD responses in the thalamus themselves linked to the release of high GABA levels during stimulation. In addition, early analysis of resting state functional connectivity suggested EIB controlled thalamocortical neuronal synchrony. We propose that the presented approach may be useful for further characterization of diseases affecting thalamocortical neurotransmission.