Miracle-dz/UniFAR-FTUs huggingface dataset:
SOX9 predicts progression toward cirrhosis in patients while its loss protects against liver fibrosis

Fibrosis and organ failure is a common endpoint for many chronic liver diseases. Much is known about the upstream inflammatory mechanisms provoking fibrosis and downstream potential for tissue remodeling. However, less is known about the transcriptional regulation in vivo governing fibrotic matrix deposition by liver myofibroblasts. This gap in understanding has hampered molecular predictions of disease severity and clinical progression and restricted targets for antifibrotic drug development. In this study, we show the prevalence of SOX9 in biopsies from patients with chronic liver disease correlated with fibrosis severity and accurately predicted disease progression toward cirrhosis. Inactivation of Sox9 in mice protected against both parenchymal and biliary fibrosis, and improved liver function and ameliorated chronic inflammation. SOX9 was downstream of mechanosignaling factor, YAP1. These data demonstrate a role for SOX9 in liver fibrosis and open the way for the transcription factor and its dependent pathways as new diagnostic, prognostic, and therapeutic targets in patients with liver fibrosis.
Measuring ideas of persecution and social reference: the Green et al. Paranoid Thought Scales (GPTS)

Background Paranoia is increasingly being studied in clinical and non-clinical populations. However there is no multi-dimensional measure of persecutory ideas developed for use across the general population-psychopathology continuum. This paper reports the development of such a questionnaire: the ‘Green et al. Paranoid Thought Scales’. The aim was to devise a tool to assess ideas of persecution and social reference in a simple self-report format, guided by a current definition of persecutory ideation, and incorporating assessment of conviction, preoccupation and distress. Method A total of 353 individuals without a history of mental illness, and 50 individuals with current persecutory delusions completed a pool of paranoid items and additional measures to assess validity. Items were devised from a recent definition of persecutory delusions, current assessments of paranoia, the authors' clinical experience, and incorporated dimensions of conviction, preoccupation and distress. Test–retest reliability in the non-clinical group was assessed at 2 weeks follow-up, and clinical change in the deluded group at 6 months follow-up. Results Two 16-item scales were extracted, assessing ideas of social reference and persecution. Good internal consistency and validity was established for both scales and their dimensions. The scales were sensitive to clinical change. A hierarchical relationship between social reference and persecution was found. The data provide further evidence for a continuum of paranoid ideas between deluded and healthy individuals. Conclusions A reliable and valid tool for assessing paranoid thoughts is presented. It will provide an effective way for researchers to ensure consistency in research and for clinicians to assess change with treatment.
Towards Efficient Large-Scale Feature-Rich Statistical Machine Translation

We present the system we developed to provide efficient large-scale feature-rich discriminative training for machine translation. We describe how we integrate with MapReduce using Hadoop streaming to allow arbitrarily scaling the tuning set and utilizing a sparse feature set. We report our findings on German-English and RussianEnglish translation, and discuss benefits, as well as obstacles, to tuning on larger development sets drawn from the parallel training data.
Idiotype connectance in the immune system. II. A heavy chain variable region idiotope that dominates the antibody response to the p- azobenzenearsonate group is a minor idiotope in the response to trinitrophenyl group

We describe the recurrence of a cross-reactive idiotope (CRIAD8) in antibody responses to different epitopes, and explore factors leading to its dominance in some responses, but not others. Serological and genomic DNA analyses showed that CRIAD8 is a marker of the CRIa heavy chain variable region (VH) that encodes the majority of anti-p- azobenzenearsonate (anti-ABA) antibodies. The independence of CRIAD8 from any particular light chain or antigen specificity was underscored by the fact that we could isolate hybridomas that secrete antitrinitrophenyl (TNP) antibodies expressing CRIAD8, with lambda 1 light chains. CRIAD8 is dominant in anti-ABA responses, recurrent but nondominant in anti-TNP and anti-chicken gammaglobulin responses, and is virtually absent in other antihapten responses, including that to p- azobenzenephosphonate (ABP), which contains an ABA-cross-reactive component (approximately 5-40%). Dominance in the anti-TNP response could not be achieved by immunization with doubly haptenated TNP-ABA- KLH (keyhole limpet hemocyanin), where the anti-ABA response was dominated by CRIAD8. These observations suggest that, while the CRIAD8 VH region is necessary for idiotypic dominance, it is not sufficient. Apparently, an additional specificity is required. Since immunization with ABA calls up anti-ABP antibodies that express CRIAD8, but not vice versa, it is possible that the additional specificity is ABA itself. This possibility imposes a new constraint on the specificity of the putative idiotype-specific regulation that may establish dominance in the CRIa system.
Door to needle time of streptokinase and ST segment resolution assessing the efficacy of reperfusion therapy at Karachi Institute of Heart Diseases.

BACKGROUND Early start of treatment including coronary revascularisation has been recognised as crucial variable in the outcome of acute ST-segment Elevation Myocardial Infarction (STEMI). Objectives of the study were to determine the magnitude of ST-segment resolution after thrombolytic therapy predicts short- and long-term outcomes in patients with an Acute Myocardial Infarction (AMI). METHODS The duration of quasi experimental study was 3 years, from July 2006 to June 2009, conducted at Karachi Institute of Heart Diseases. Total 1,023 patients of STEMI treated with streptokinase (SK) were enrolled in the study. RESULT Of the total 1023, 689 (67.3%) patients were males and 334 (32.6%) were females. Six hundred and twenty-nine (61.5%) were successfully resolved after thrombolytic therapy while in 395 (38.5%) patients ST-segment could not resolve into 3 conventional ST-segment resolution categories at 60 minute and 90 minute after thrombolysis. Three hundred and twelve (30%) and 444 (43.4%) with complete resolution, 344 (33.62%) and 325 (31.76%) with partial resolution, 367 (35.8%) and 491 (19.29%) were with no resolution at 60 and 90 minutes respectively. CONCLUSION Shock, congestive heart failure, and recurrent angina and ischemia occurred more often in patients with partial or no ST resolution as compare to complete resolution.
Normalizer Circuits and Quantum Computation

We introduce families of quantum circuits, that are non-universal but comprise important quantum gates such as QFT or CNOT, and investigate their potential for quantum computation. We develop an efficient formalism for simulating these circuits on discrete and continuous quantum variables and apply our techniques to investigate the emergence of exponential quantum speed-ups in algorithms such as Shor's. We derive practical methods for determining when quantum effects can provide computational advantages. We give mathematical methods to understand when QFT gates do not provide computational advantages. Conversely, we use our formalism to design new algorithms that provide quantum speedups.
Parametric PSF estimation via sparseness maximization in the wavelet domain

Image degradation is a frequently encountered problem in different imaging systems, like microscopy, astronomy, digital photography, etc. The degradation is usually modeled as a convolution with a blurring kernel (or Point Spread Function, psf) followed by noise addition. Based on the combined knowledge about the image degradation and the statistical features of the original images, one is able to compensate at least partially for the degradation using so-called image restoration algorithms and thus retrieve information hidden for the observer. One problem is that often this blurring kernel is unknown, and has to be estimated before actual image restoration can be performed. In this work, we assume that the psf can be modeled by a function with a single parameter, and we estimate the value of this parameter. As an example of such a single-parametric psf, we have used a Gaussian. However, the method is generic and can be applied to account for more realistic degradations, like optical defocus, etc.
Cool Companions to Hot White Dwarfs

Low-mass companions to high-mass stars are difficult to detect, which is partly why the binary fraction for high-mass stars is still poorly constrained. Low-mass companions can be detected more easily however, once high-mass stars turn into white dwarfs. These systems are also interesting as the progenitors of a variety of intensely studied interacting binary systems, like novae, CVs, symbiotics, Ba and CH giants, Feige 24-type systems, and dwarf carbon stars. We describe a near-IR photometric search for cool red dwarf companions to hot white dwarfs (WDs). IR photometry offers a sensitive test for low-mass main-sequence (MS) companions. Our sample of EUV-detected WDs offers several advantages over previous (largely proper motion-selected) WD samples: (1) the high WD temperatures (24,000 < Teff < 70,000 K) insure excellent IR flux contrast with cool dwarfs; (2) the range of evolutionary parameter space occupied by the WDs is considerably narrowed; and (3) the random effects of the intervening ISM provide a complete but reasonably sized sample. While some composite systems have been found optically among WDs detected in recent EUV All-Sky Surveys, we develop an IR technique that probes farther down the main sequence, detecting yet more companions. We use detailed DA model atmosphere fits to optical spectra to predict K magnitudes and distances, against which we contrast our near-IR observations. Our photometric survey reveals 10 DAs with a significant excess in both J and K. Half are newly discovered and are most likely previously unrecognized binary systems. Neither the frequency of infrared excess nor the mass estimate of the red dwarf companion correlate with white dwarf mass, as might be expected if either the EUV detectability or mass of the white dwarfs were significantly affected by a companion. Infrared spectra of these systems should help to determine the mass and spectral type of the cool companions presumably causing the IR excess, leading to better estimates of the mass ratio distribution in binaries. Counting previously known binaries, and resolved pairs, we find the total binary fraction of the sample is at least a third. Since most WD progenitors had initial masses ≥2 M☉, we thus provide a photometric measure of the binary fraction of high-mass stars that would be difficult to perform in high-mass main-sequence stars. We estimate that 90% of the companions are of type K or later.
A homology model of the pore domain of a voltage-gated calcium channel is consistent with available SCAM data

In the absence of x-ray structures of calcium channels, their homology models are used to rationalize experimental data and design new experiments. The modeling relies on sequence alignments between calcium and potassium channels. Zhen et al. (2005. J. Gen. Physiol. doi:10.1085/jgp.200509292) used the substituted cysteine accessibility method (SCAM) to identify pore-lining residues in the Cav2.1 channel and concluded that their data are inconsistent with the symmetric architecture of the pore domain and published sequence alignments between calcium and potassium channels. Here, we have built Kv1.2-based models of the Cav2.1 channel with 2-(trimethylammonium)ethyl methanethiosulfonate (MTSET)-modified engineered cysteines and used Monte Carlo energy minimizations to predict their energetically optimal orientations. We found that depending on the position of an engineered cysteine in S6 and S5 helices, the ammonium group in the long flexible MTSET-modified side chain can orient into the inner pore, an interface between domains (repeats), or an interface between S5 and S6 helices. Different local environments of equivalent positions in the four repeats can lead to different SCAM results. The reported current inhibition by MTSET generally decreases with the predicted distances between the ammonium nitrogen and the pore axis. A possible explanation for outliers of this correlation is suggested. Our calculations rationalize the SCAM data, validate one of several published sequence alignments between calcium and potassium channels, and suggest similar spatial dispositions of S5 and S6 helices in voltage-gated potassium and calcium channels.
Web Application Vulnerability Prediction Using Hybrid Program Analysis and Machine Learning

Due to limited time and resources, web software engineers need support in identifying vulnerable code. A practical approach to predicting vulnerable code would enable them to prioritize security auditing efforts. In this paper, we propose using a set of hybrid (static+dynamic) code attributes that characterize input validation and input sanitization code patterns and are expected to be significant indicators of web application vulnerabilities. Because static and dynamic program analyses complement each other, both techniques are used to extract the proposed attributes in an accurate and scalable way. Current vulnerability prediction techniques rely on the availability of data labeled with vulnerability information for training. For many real world applications, past vulnerability data is often not available or at least not complete. Hence, to address both situations where labeled past data is fully available or not, we apply both supervised and semi-supervised learning when building vulnerability predictors based on hybrid code attributes. Given that semi-supervised learning is entirely unexplored in this domain, we describe how to use this learning scheme effectively for vulnerability prediction. We performed empirical case studies on seven open source projects where we built and evaluated supervised and semi-supervised models. When cross validated with fully available labeled data, the supervised models achieve an average of 77 percent recall and 5 percent probability of false alarm for predicting SQL injection, cross site scripting, remote code execution and file inclusion vulnerabilities. With a low amount of labeled data, when compared to the supervised model, the semi-supervised model showed an average improvement of 24 percent higher recall and 3 percent lower probability of false alarm, thus suggesting semi-supervised learning may be a preferable solution for many real world applications where vulnerability data is missing.
Acceptability of a telecare intervention for persistent musculoskeletal pain

Introduction Persistent musculoskeletal pain is a prevalent, disabling, and often undertreated condition. This paper examines the acceptability of a telecare intervention for this condition. Methods The Stepped Care to Optimize Pain Care Effectiveness (SCOPE) intervention couples automatic symptom monitoring (ASM) with optimized analgesic care management by a nurse-physician team. Data from participants in the telecare intervention arm (n = 124) of a randomized control trial of SCOPE were analysed to determine the acceptability of the telecare intervention as indicated by patient use and satisfaction. Results Most (93.5%) patients completed at least one ASM report, selecting equally web-based (49%) or interactive voice-recorded (51%) reporting. The median number of ASM reports and nurse contacts per patient was 15 and 12, respectively. Of 12 demographic and clinical factors examined, none predicted the number of ASM reports, whereas nurse contacts were more frequent in patients with higher pain severity or receiving opioids. Only a minority of ASM reports required an expedited nurse call, with the most frequent alerts being for a medication change, a nurse call or side effects. Most (92%) patients rated ASM as easy to use and found the ASM reporting (76%) and nurse contacts (81%) very or moderately helpful. Nearly three-fourths of patients rated their overall pain treatment as good to excellent. The most common suggestions from patient feedback were for a free-text messaging function, more frequent nurse contact and less redundancy in ASM reporting items. Discussion Participants generally found the telecare intervention a user-friendly and helpful approach for treating persistent musculoskeletal pain.
Disadvantageous decision-making on a rodent gambling task is associated with increased motor impulsivity in a population of male rats.

BACKGROUND Impulsivity is understood as a range of behaviours, but the association between these behaviours is not well understood. Although high motor impulsivity is a key symptom of disorders like pathological gambling and addiction, in which decision-making on laboratory tasks is compromised, there have been no clear demonstrations that choice and motor impulsivity are associated in the general population. We examined this association in a large population of rodents. METHODS We performed a meta-analysis on behavioural data from 211 manipulation-naive male animals that performed a rodent gambling task in our laboratory between 2008 and 2012. The task measures an aspect of both impulsive decision-making and impulsive action, making it possible to evaluate whether these 2 forms of maladaptive behaviour are related. RESULTS Our meta-analysis revealed that motor impulsivity was positively correlated with poor decision-making under risk. Highly motor impulsive rats were slower to adopt an advantageous choice strategy and quicker to make a choice on individual trials. LIMITATIONS The data analyzed were limited to that produced by our laboratory and did not include data of other researchers who have used the task. CONCLUSION This work may represent the first demonstration of a clear association between choice and motor impulsivity in a nonclinical population. This lends support to the common practice of studying impulsivity in nonclinical populations to gain insight into impulse control disorders and suggests that differences in impulsive behaviours between clinical and nonclinical populations may be ones of magnitude rather than ones of quality.
Does Laser Surgery Interfere with Optical Nerve Identification in Maxillofacial Hard and Soft Tissue?—An Experimental Ex Vivo Study

The protection of sensitive structures (e.g., nerves) from iatrogenic damage is of major importance when performing laser surgical procedures. Especially in the head and neck area both function and esthetics can be affected to a great extent. Despite its many benefits, the surgical utilization of a laser is therefore still limited to superficial tissue ablation. A remote feedback system which guides the laser in a tissue-specific way would provide a remedy. In this context, it has been shown that nerval structures can be specifically recognized by their optical diffuse reflectance spectra both before and after laser ablation. However, for a translation of these findings to the actual laser ablation process, a nerve protection within the laser pulse is of utmost significance. Thus, it was the aim of the study to evaluate, if the process of Er:YAG laser surgery—which comes with spray water cooling, angulation of the probe (60°) and optical process emissions—interferes with optical tissue differentiation. For the first time, no stable conditions but the ongoing process of laser tissue ablation was examined. Therefore, six different tissue types (nerve, skin, muscle, fat, cortical and cancellous bone) were acquired from 15 pig heads. Measurements were performed during Er:YAG laser ablation. Diffuse reflectance spectra (4500, wavelength range: 350–650 nm) where acquired. Principal component analysis (PCA) and quadratic discriminant analysis (QDA) were calculated for classification purposes. The clinical highly relevant differentiation between nerve and bone was performed correctly with an AUC of 95.3% (cortial bone) respectively 92.4% (cancellous bone). The identification of nerve tissue against the biological very similar fat tissue yielded good results with an AUC value of 83.4% (sensitivity: 72.3%, specificity: of 82.3%). This clearly demonstrates that nerve identification by diffuse reflectance spectroscopy works reliably in the ongoing process of laser ablation in spite of the laser beam, spray water cooling and the tissue alterations entailed by tissue laser ablation. This is an essential step towards a clinical utilization.
Long-Term Effect of Manure and Fertilizer on Soil Organic Carbon Pools in Dryland Farming in Northwest China

An understanding of the dynamics of soil organic carbon (SOC) as affected by farming practices is imperative for maintaining soil productivity and mitigating global warming. The objectives of this study were to investigate the effects of long-term fertilization on SOC and SOC fractions for the whole soil profile (0–100 cm) in northwest China. The study was initiated in 1979 in Gansu, China and included six treatments: unfertilized control (CK), nitrogen fertilizer (N), nitrogen and phosphorus (P) fertilizers (NP), straw plus N and P fertilizers (NP+S), farmyard manure (FYM), and farmyard manure plus N and P fertilizers (NP+FYM). Results showed that SOC concentration in the 0–20 cm soil layer increased with time except in the CK and N treatments. Long-term fertilization significantly influenced SOC concentrations and storage to 60 cm depth. Below 60 cm, SOC concentrations and storages were statistically not significant between all treatments. The concentration of SOC at different depths in 0–60 cm soil profile was higher under NP+FYM follow by under NP+S, compared to under CK. The SOC storage in 0–60 cm in NP+FYM, NP+S, FYM and NP treatments were increased by 41.3%, 32.9%, 28.1% and 17.9%, respectively, as compared to the CK treatment. Organic manure plus inorganic fertilizer application also increased labile soil organic carbon pools in 0–60 cm depth. The average concentration of particulate organic carbon (POC), dissolved organic carbon (DOC) and microbial biomass carbon (MBC) in organic manure plus inorganic fertilizer treatments (NP+S and NP+FYM) in 0–60 cm depth were increased by 64.9–91.9%, 42.5–56.9%, and 74.7–99.4%, respectively, over the CK treatment. The POC, MBC and DOC concentrations increased linearly with increasing SOC content. These results indicate that long-term additions of organic manure have the most beneficial effects in building carbon pools among the investigated types of fertilization.
Design and optimization of self-nanoemulsifying drug delivery systems for improved bioavailability of cyclovirobuxine D

Background The main purpose of this research was to design a self-nanoemulsifying drug delivery system (SNEDDS) for improving the bioavailability of cyclovirobuxine D as a poorly water-soluble drug. Materials and methods Solubility trials, emulsifying studies, and pseudo-ternary phase diagrams were used to screen the SNEDDS formulations. The optimized drug-loaded SNEDDS was prepared at a mass ratio of 3:24:38:38 for cyclovirobuxine D, oleic acid, Solutol SH15, and propylene glycol, respectively. The optimized formulation was characterized in terms of physicochemical and pharmacokinetic parameters compared with marketed cyclovirobuxine D tablets. Results The optimized cyclovirobuxine-D-loaded SNEDDS was spontaneously dispersed to form a nanoemulsion with a globule size of 64.80±3.58 nm, which exhibited significant improvement of drug solubility, rapid absorption rate, and enhanced area under the curve, together with increased permeation and decreased efflux. Fortunately, there was a nonsignificant cytotoxic effect toward Caco-2 cells. The relative bioavailability of SNEDDS was 200.22% in comparison with market tablets, in rabbits. Conclusion SNEDDS could be a potential candidate for an oral dosage form of cyclovirobuxine D with improved bioavailability.