Miracle-dz/UniFAR-FTUs huggingface dataset:
Kappa Opioid Receptors Drive a Tonic Aversive Component of Chronic Pain

Pain is a multidimensional experience and negative affect, or how much the pain is “bothersome”, significantly impacts the sufferers' quality of life. It is well established that the κ opioid system contributes to depressive and dysphoric states, but whether this system contributes to the negative affect precipitated by the occurrence of chronic pain remains tenuous. Using a model of persistent pain, we show by quantitative real-time-PCR, florescence in situ hybridization, Western blotting and GTPgS autoradiography an upregulation of expression and the function of κ opioid receptors (KORs) and its endogenous ligand dynorphin in the mesolimbic circuitry in animals with chronic pain compared with surgical controls. Using in vivo microdialysis and microinjection of drugs into the mesolimbic dopamine system, we demonstrate that inhibiting KORs reinstates evoked dopamine release and reward-related behaviors in chronic pain animals. Chronic pain enhanced KOR agonist-induced place aversion in a sex-dependent manner. Using various place preference paradigms, we show that activation of KORs drives pain aversive states in male but not female mice. However, KOR antagonist treatment was effective in alleviating anxiogenic and depressive affective-like behaviors in both sexes. Finally, ablation of KORs from dopamine neurons using AAV-TH-cre in KORloxP mice prevented pain-induced aversive states as measured by place aversion assays. Our results strongly support the use of KOR antagonists as therapeutic adjuvants to alleviate the emotional, tonic-aversive component of chronic pain, which is argued to be the most significant component of the pain experience that impacts patients' quality of life. SIGNIFICANCE STATEMENT We show that KORs are sufficient to drive the tonic-aversive component of chronic pain; the emotional component of pain that is argued to significantly impact a patient's quality of life. The impact of our study is broadly relevant to affective disorders associated with disruption of reward circuitry and thus likely contributes to many of the devastating sequelae of chronic pain, including the poor response to treatment of many patients, debilitating affective disorders (other disorders including anxiety and depression that demonstrate high comorbidity with chronic pain) and substance abuse. Indeed, coexisting psychopathology increases pain intensity, pain-related disability and effectiveness of treatments (Jamison and Edwards, 2013).
Value of Relative Myocardial Perfusion at MRI for Fractional Flow Reserve-Defined Ischemia: A Pilot Study.

OBJECTIVE Correcting the perfusion in areas distal to coronary stenosis (risk) according to that of normal (remote) areas defines the relative myocardial perfusion index, which is similar to the fractional flow reserve (FFR) concept. The aim of this study was to assess the value of relative myocardial perfusion by MRI in predicting lesion-specific inducible ischemia as defined by FFR. MATERIALS AND METHODS Forty-six patients (33 men and 13 women; mean [± SD] age, 61 ± 9 years) who underwent adenosine perfusion MRI and FFR measurement distal to 49 coronary artery stenoses during coronary angiography were retrospectively evaluated. Subendocardial time-enhancement maximal upslopes, normalized by the respective left ventricle cavity upslopes, were obtained in risk and remote subendocardium during adenosine and rest MRI perfusion and were correlated to the FFR values. RESULTS The mean FFR value was 0.84 ± 0.09 (range, 0.60-0.98) and was less than or equal to 0.80 in 31% of stenoses (n = 15). The relative subendocardial perfusion index (risk-to-remote upslopes) during hyperemia showed better correlations with the FFR value (r = 0.59) than the uncorrected risk perfusion parameters (i.e., both the upslope during hyperemia and the perfusion reserve index [stress-to-rest upslopes]; r = 0.27 and 0.29, respectively). A cutoff value of 0.84 of the relative subendocardial perfusion index had an ROC AUC of 0.88 to predict stenosis at an FFR of less than or equal to 0.80. CONCLUSION Using adenosine perfusion MRI, the relative myocardial perfusion index enabled the best prediction of FFR-defined lesion-specific myocardial ischemia. This index could be used to noninvasively determine the need for revascularization of known coronary stenoses.
The comparison of two mouse models of inflammation-related lung tumorigenesis inducedby benzo(a)pyrene and lipopolysaccharide

Inflammation-related animal model is necessary to better understanding the association of inflammation with tumorigenesis. Although mouse models of inflammation-related lung tumorigenesis on A/J mice strain have been set up in previous study, there is no report on the model on C57BL/6J mice. In this study, C57BL/6J mice were randomly divided into two groups and instilled with benzo(a)pyrene [B(a)p] plus lipopolysaccharide (LPS) with different treatments. Mice in Group I were instilled intratracheally with B(a)p (1 mg/mouse) and LPS (5 µg/mouse), once a week for 4 times, on Tuesday and Friday, respectively [the week of the last time of B(a)p treatment named Week 0]. At Week 4, mice continued to be treated with LPS, once every four weeks for 5 times. Mice in Group II were exposed to B(a)p (1 mg/mouse, once a week for 4 times) and 3 weeks later instilled intratracheally with LPS (2.5 µg/mouse) once every three weeks for 5 times. At Week 30, the incidence, number, size and histopathology of lung tumor in two models were compared. The tumor incidence (96.97%) and mean tumor count (13.0 ± 12.4) of mice in Group II were significantly increased compared with those in Group I (69.23%, 4.9 ± 5.1), respectively. In addition, smaller tumors (≤1 mm) were more abundant in Group II than Group I. Histopathological examination found the tumors induced by B(a)p plus LPS in Group II were more advanced tumors. In conclusion, a better mouse model of inflammation-related lung tumorigenesis induced by B(a)p plus LPS in C57BL/6J mice was set up successfully.
Alexithymia Predicts Cognitive Deficits In Patients With Idiopathic Parkinson's Disease.

BACKGROUND In recent years, alexithymia has gained attention of medical researchers as a prognostic factor for serious health problems. The present study aimed to assess alexithymia as a determinant of cognitive decline in patients with Parkinson's disease. AIM The aim of our study is to assess the pain relief after CPN, reduction in analgesics consumption and evaluation of patient satisfaction post procedure. METHODS Patients diagnosed with Parkinson's disease (n=60) at Bahawal Victoria Hospital, Civil Hospital Bahawalpur and Nishter Hospital Multan during May 2016 until June 2017 participated in the study. Healthy individuals (n=60) took part in the study from local community as controls. Participants completed Bermond-Vorst Alexithymia Questionnaire and Montreal Cognitive Assessment. It was a cross sectional study design. Purposive sampling technique was used and data was analysed through multivariate analysis of variance and bivariate correlation. RESULTS Patients with Parkinson's disease (177.96±8.93) showed higher attitudes of alexithymia as compared with healthy individuals (37.46±8.01), F (1,118) = 8216.52, p<0.001, ηp2=. 98. In contrast with healthy controls (28.60±0.58), patients with Parkinson's disease (2.25±.95) were cognitively impaired F (1,118) =36424.38, p<0.001, ηp2=. 99. Alexithymia was a significant predictor of cognitive performance (R2=0.99, F (2, 119) = 5698.95, p<0.001). CONCLUSIONS Alexithymia is a significant marker of cognitive decline in patients with Parkinson's disease.
Neurogaming With Motion-Onset Visual Evoked Potentials (mVEPs): Adults Versus Teenagers

Motion-onset visually evoked potentials (mVEPs) are neural potentials that are time-locked to the onset of motion of evoking stimuli. Due to their visually elegant properties, mVEP stimuli may be suited to video game control given gaming’s inherent demand on the users’ visual attention and the requirement to process rapidly changing visual information. Here, we investigate mVEPs associated with five different stimuli to control the position of a car in a visually rich 3D racing game in a group of 15 BCI naïve teenagers and compared with 19 BCI naive adults. Results from an additional 14 BCI experienced adults were compared with BCI naïve adults. Our results demonstrate that the game control accuracy is related to the number of trials used to make a decision on the users’ chosen button/stimulus (76%, 62%, and 35% for 5, 3, and 1 trials, respectively) and information transfer rate (ITR) (13.4, 13.9, and 6.6 bits per minute (BPM)), although, even though accuracy decreases when using three compared to the commonly used five trial repetitions, ITR is maintained. A Kruskal-Wallis test suggests that BCI naïve adults do not outperform BCI naïve teenagers in the 3D racing game in the first and seconds laps (p > 0.05), but do outperform in the third lap (p < 0.05). A comparison between BCI naïve and BCI experienced adults indicates BCI experienced adults do not perform better than BCI naïve adults (p > 0.05).
Quality of urological systematic reviews registered in PROSPERO

Prior studies have documented the exponential increase in the number of systematic reviews (SRs) published in the urological literature [1]. Unfortunately, not all systematic reviews are created equal, and it has been suggested that most systematic reviews are of low or modest quality, with a significant amount of overlap and redundancy [2,3]. To address this issue, journals are increasingly enforcing methodological standards, such as those of the Assessment of Multiple Systematic Reviews (AMSTAR) [4], as well as requiring a priori SR protocol registration, with the goal of enforcing basic methodological standards and reducing redundancy of SR protocols [5]. Published protocols, what have long been standard for review published in the Cochrane Library, also guard against issues related to multiple testing and selective reporting. This article is protected by copyright. All rights reserved.
Novel Phosphorylated Penta-1,4-dien-3-one Derivatives: Design, Synthesis, and Biological Activity

A series of novel phosphorylated penta-1,4-dien-3-one derivatives were designed and synthesized. The structures of all title compounds were determined by 1H-NMR, 13C-NMR, 31P-NMR, and high-resolution mass spectrometry (HRMS). Bioassay results showed that several of the title compounds exhibited remarkable antibacterial and antiviral activities. Among these, compound 3g exhibited substantial antibacterial activity against Xanthomonas oryzae pv. Oryzae (Xoo), with a 50% effective concentration (EC50) value of 8.6 μg/mL, which was significantly superior to bismerthiazol (BT) (58.8 µg/mL) and thiodiazole-copper (TC) (78.7 μg/mL). In addition, compound 3h showed remarkable protective activity against tobacco mosaic virus (TMV), with an EC50 value of 104.2 μg/mL, which was superior to that of ningnanmycin (386.2 μg/mL). Furthermore, the microscale thermophoresis and molecular docking experiments on the interaction of compounds 3h and 3j with TMV coat protein (TMV CP) were also investigated. Compounds 3h and 3j bound to TMV CP with dissociation constants of 0.028 and 0.23 μmol/L, which were better than that of ningnanmycin (0.52 μmol/L). These results suggest that novel phosphorylated penta-1,4-dien-3-one derivatives may be considered as an activator for antibacterial and antiviral agents.
Distributed Dependency Discovery

We analyze the problem of discovering dependencies from distributed big data. Existing (non-distributed) algorithms focus on minimizing computation by pruning the search space of possible dependencies. However, distributed algorithms must also optimize communication costs, especially in shared-nothing settings, leading to a more complex optimization space. To understand this space, we introduce six primitives shared by existing dependency discovery algorithms, corresponding to data processing steps separated by communication barriers. Through case studies, we show how the primitives allow us to analyze the design space and develop communication-optimized implementations. Finally, we support our analysis with an experimental evaluation on real datasets.
Privacy Preserving Image-Based Localization

Image-based localization is a core component of many augmented/mixed reality (AR/MR) and autonomous robotic systems. Current localization systems rely on the persistent storage of 3D point clouds of the scene to enable camera pose estimation, but such data reveals potentially sensitive scene information. This gives rise to significant privacy risks, especially as for many applications 3D mapping is a background process that the user might not be fully aware of. We pose the following question: How can we avoid disclosing confidential information about the captured 3D scene, and yet allow reliable camera pose estimation? This paper proposes the first solution to what we call privacy preserving image-based localization. The key idea of our approach is to lift the map representation from a 3D point cloud to a 3D line cloud. This novel representation obfuscates the underlying scene geometry while providing sufficient geometric constraints to enable robust and accurate 6-DOF camera pose estimation. Extensive experiments on several datasets and localization scenarios underline the high practical relevance of our proposed approach.
Inhibition of tyrosine kinases protects against lipopolysaccharide‐induced acute lung injury by preventing nuclear export of Nrf2

Acute Lung Injury is a common severe pathological condition that is usually caused by lipopolysaccharide (LPS) infection from bacteria. Enhanced activity of nuclear factor erythroid 2–related factor 2 (Nrf2) could attenuate LPS induced lung injury, However, it still remains unknown whether the enhanced activity of Nrf2 via suppression of Nrf2 nucleus export attenuates the LPS induced lung injury. The aim of this study is to investigate the effects of inhibitors of Fyn on the LPS‐induced acute lung injury and to explore its underlying molecular mechanisms. Nrf2 localization in the cells was observed by using confocal microscopy and its transcriptional activation was measured by Electrophoretic Mobility Shift Assay and controlled genes expression levels. The lung injury severity was examined by histopathological scoring and oxidative stress level. In this study, we showed that PP2, LMB, and Nrf2 Y568A abrogated Nrf2 nuclear export and thus enhance the Nrf2 transcriptional activity. PP2 attenuated lung injury and the reduction of cells viability induced by LPS. The current study demonstrated, for the first time, that increase of expression of Nrf2 controlled protective genes via suppression of Nrf2 nucleus export could attenuate lung injury.
Integrative System Biology Analyses Identify Seven MicroRNAs to Predict Heart Failure

Heart failure (HF) has several etiologies including myocardial infarction (MI) and left ventricular remodeling (LVR), but its progression remains difficult to predict in clinical practice. Systems biology analyses of LVR after MI provide molecular insights into this event such as modulation of microRNA (miRNA) that could be used as a signature of HF progression. To define a miRNA signature of LVR after MI, we use 2 systems biology approaches, integrating either proteomic data generated from LV of post-MI rat induced by left coronary artery ligation or multi-omics data (proteins and non-coding RNAs) generated from plasma of post-MI patients from the REVE-2 study. The first approach predicted that 13 miRNAs and 3 of these miRNAs would be validated to be associated with LVR in vivo: miR-21-5p, miR-23a-3p and miR-222-3p. The second approach predicted that 24 miRNAs among 1310 molecules and 6 of these miRNAs would be selected to be associated with LVR in silico: miR-17-5p, miR-21-5p, miR-26b-5p, miR-222-3p, miR-335-5p and miR-375. We identified a signature of 7 microRNAs associated with LVR after MI that support the interest of integrative systems biology analyses to define a miRNA signature of HF progression.
23rd ABCM International Congress of Mechanical Engineering December 6-11, 2015, Rio de Janeiro, RJ, Brazil ESTIMATION OF STRAINS IN MIDPALATAL SUTURE: A COMPUTATIONAL BIOMECHANICAL STUDY

Rapid Maxillary Expansion (RME) is a technique very frequently indicated, for the correction of transversal problems in the maxillary arch. During the active phase of this treatment the median palatine suture (MPS) is broken and then it is ossified until restitute its original structure. It is reported that the magnitude and frequency of mechanical forces influence the shape and composition of cranial sutures. The most important cyclical force acting on the skull and jaw is the force generated during mastication of food. Thus, the objective of this study is to estimate computationally the deformation in the MPS, during mastication, after the active phase of RME, and correlate them to the mechanobiological cell differentiation theories. The three-dimensional geometry used in the model was extracted from computerized tomography of a 12 year old patient. This geometry was used to construct a finite element model to estimate strains in the MPS. All tissues were considered linear elastic materials with mechanical properties reported in literature. Considering the chewing forces for children who have 6-12 years found in the literature, a force of 35 newtons was applied to the second premolar and first molar of the higher hemiarch, in the direction of the long axis of each tooth. After computations, it was obtained that in the outer region, in contact with the jawbone, the SPM showed greater strains, with magnitudes between 0.3% and 7.3%, values close to those needed to stimulate bone synthesis. In the most inner region of the suture, strains were lower, close to 0.1%, only the edges there was strains exceeding 0.5%, values close to those needed to generate cellular resorption. That indicate that the mechanical strains are more favorable for the synthesis of bone close to the previously existent surfaces of bone, and they are the locations where bone could initially appear, as is observed in experimental studies.
Anatomic Patterns Of Right Renal Vein.

BACKGROUND Preoperative surgical planning assumes a central role in avoiding catastrophic outcomes of a surgery in the field of renal transplantation, and other urological procedures. This study was aimed to study the different anatomic patterns of human renal venous system. METHODS It is a descriptive cross-sectional study including 50 adult male cadavers with well-preserved kidneys, renal vasculature and the inferior vena cava. Cadavers with deformed or congenitally anomalous kidney, evidence of surgery, solitary kidney, tumours of kidneys or injured renal vessels / inferior vena cava were excluded from the study. The kidneys, renal veins and the inferior vena cava were exposed. After securing inferior vena cava fifty ml mixture of Indian ink and gelatine was injected into renal veins via inferior vena cava and was allowed to solidify. Following this, the renal venous anatomy was studied. RESULTS Twenty-eight cadavers had their right renal vein formed by 2 tributaries (56%), 13 (26%) had 3 tributaries, 5 (10%) had 4 tributaries, 1 cadaver had a posterior tributary (2%), while 3 cadavers had other numbers of tributaries (6%). Out of total 50 cadavers 40 (80%) had normal distribution of right renal vein. Additional renal veins were found in 14 (7%) cadavers, double renal veins in 1 (2%) and proximally double renal veins in 2 cadavers (4%). CONCLUSIONS There is considerable variation in renal venous anatomy. Knowledge of common venous patterns is necessary for minimizing intraoperative damage to renal anatomy and to prevent intra- and post-operative complications.
Kinetics of Gases Emission from Surface Layers of Sand Moulds

Gas emission from casting moulds, cores and coatings applied for sand and permanent moulds is one of the fundamental reasons of casting defects occurrence. In the previous studies, gas emission was measured in two ways: normalized, in which the evolving gas volume was measured during heating of the moulding sand sample in a sealed flask, or by measuring the amount of gas from sand core (sample) which is produced during the pouring of liquid metal. After the pouring process the sand mould is heated very unequally, the most heated areas are layers adjacent to the liquid metal. The emission of gas is significantly larger from the surface layer than from the remaining ones. New, original method of measuring kinetics of gas emission from very thin layers of sand moulds heated by liquid metal developed by the authors is presented in the hereby paper. Description of this new method and the investigation results of kinetics of gas emission from moulding sand with furan and alkyd resin are shown. Liquid grey cast iron and Al-Si alloy were used as a heat source in the sand moulds. Comparison of the kinetics of gas emission of these two kinds of moulding sands filled with two different alloys was made. The momentary metal temperature in sand mould was assigned to the kinetics of gas emission, what creates a full view of the possibility of formation of casting defects of the gaseous origin. Moulding sand with alkyd resin is characterized by larger gas emission; however gases are emitted slower than in the case of moulding sands with furan resin. This new investigation method has a high repeatability and is the only one which gives a full view of phenomenon’s in the surface layer which determines quality of the casings. The obtained results are presented on several graphs and analyzed in detail. They have a great application value and can be used in the production of iron as well as light metal alloy castings.
Regional Disparities in Access to Verified Burn Center Care in the United States.

BACKGROUND Burn injuries result in 50,000 annual admissions. Despite joint referral criteria from the American College of Surgeons (ACS) and American Burn Association (ABA), many severely injured patients are not treated at verified centers with specialized care. Only one prior study explores regional variation in access to burn centers, focusing on flight or driving distance without considering the size of the population accessing that center. We hypothesize that disparities exist in access to verified centers, measured at a population level. We aim to identify a subset of non-verified centers that, if verified, would most impact access to the highest level of burn care. METHODS We collected ABA data for all verified and non-verified adult burn centers and geocoded their locations. We used county-level population data and a two-step floating catchment method to determine weighted access in terms of total beds available locally per population. We compared regions, as defined by the ABA, in terms of overall access. Low access was calculated to be less than 0.3 beds per 100,000 people using a conservative estimate. RESULTS We identified 113 centers, 59 verified and 54 non-verified. Only 2.9% of the population lives in areas with no verified center in 300 miles; however, 24.7% live in areas with low access. Significant regional disparities exist, with 37.3% of the population in the Southern Region having low access as compared to just 10.5% in the Northeastern Region. We identified 8 non-verified centers that would most impact access in areas with no or low access. CONCLUSIONS We found significant disparities in access to verified center burn care and determined non-verified centers with the greatest potential to increase access, if verified. Our future directions include identifying barriers to verification, such as lack of fellowship-trained burn surgeons or lack of hospital commitment. LEVEL OF EVIDENCE Care management study, level IV.