Miracle-dz/UniFAR-FTUs huggingface dataset:
Biochemical and functional characterization of OsCSD3, a novel CuZn superoxide dismutase from rice.

Superoxide dismutases (SODs, EC 1.15.1.1) belong to an important group of antioxidant metalloenzymes. Multiple SODs exist for scavenging of reactive oxygen species (ROS) in different cellular compartments to maintain an intricate ROS balance. The present study deals with molecular and biochemical characterization of CuZn SOD encoded by LOC_Os03g11960 (referred to as OsCSD3), which is the least studied among the four rice isozymes. The OsCSD3 showed higher similarity to peroxisomal SODs in plants. The OsCSD3 transcript was up-regulated in response to salinity, drought, and oxidative stress. Full-length cDNA encoding OsCSD3 was cloned and expressed in Escherichia coli and analyzed for spectral characteristics. UV (ultraviolet)-visible spectroscopic analysis showed evidences of d-d transitions, while circular dichroism analysis indicated high β-sheet content in the protein. The OsCSD3 existed as homodimer (∼36 kDa) with both Cu2+ and Zn2+ metal cofactors and was substantially active over a wide pH range (7.0-10.8), with optimum pH of 9.0. The enzyme was sensitive to diethyldithiocarbamate but insensitive to sodium azide, which are the characteristics features of CuZn SODs. The enzyme also exhibited bicarbonate-dependent peroxidase activity. Unlike several other known CuZn SODs, OsCSD3 showed higher tolerance to hydrogen peroxide and thermal inactivation. Heterologous overexpression of OsCSD3 enhanced tolerance of E. coli sod double-knockout (ΔsodA ΔsodB) mutant and wild-type strain against methyl viologen-induced oxidative stress, indicating the in vivo function of this enzyme. The results show that the locus LOC_Os03g11960 of rice encodes a functional CuZn SOD with biochemical characteristics similar to the peroxisomal isozymes.
Clonal evolution in long‐term follow‐up patients with hepatocellular carcinoma

To investigate tumor clonal evolution in hepatocellular carcinoma (HCC), we collected 31 tumor samples,16 peritumor samples and matched PBMCs from 11 long‐term follow‐up patients with HCC. Whole‐exome sequencing was performed to obtain SNVs and CNVs for each sample. An average of 652.2 somatic mutations were identified in each patient and the mean percentage of nonubiquitous tumor mutations was 63.7% (range, 0.7%–100%), reflecting the variety of tumor heterogeneity. Further analysis of clonal evolution was conducted based on mutation clustering results and revealed that different clonal evolution patterns indeed existed in single and multifocal HCC while these patterns were significantly correlated to patients’ clinical course. These patterns clearly demonstrated different mechanisms of tumor recurrence. During tumor clonal evolution, potential therapeutic targets also emerged and vanished dynamically. Moreover, mutation analysis revealed that the contribution of mutational signature was correlated with clonal evolution history. Target sequencing of follow‐up plasma samples also confirmed that ctDNA level could dynamically reflect tumor clonal/subclonal burden. By investigating clonal evolution in HCC patients, our analysis revealed that different patterns indeed existed during HCC progression and proposed a novel strategy for identifying the origin of recurrent tumor as well as optimizing treatment selection.
Evaluating the Effectiveness of a Focused Debate on the Development of Ethical Reasoning Skills in Pharmacy Technician Students

Objective. To evaluate the effectiveness of debating an ethical dilemma on the development of ethical reasoning skills in pharmacy technician students. Methods. A mixture of qualitative and quantitative methods was used. This included analysis of before and after 5-minute papers, a sentiment survey, thematic analysis of student reflective writing and a qualitative questionnaire by an independent observer. Results. Twenty-five students participated in the study. The 5-minute papers showed improvement in student learning. In the sentiment survey, 83% of students agreed or strongly agreed that they had a better understanding of ethical dilemmas following the debate. The main theme identified from student blogs was the variety of different opinions expressed during the debate. Conclusion. Debating was an effective means of exploring ethics with pharmacy technician students.
The multi‐ethnic global lung initiative 2012 (GLI-2012) norms reflect contemporary adult's Algerian spirometry

Background The validation of the multi-ethnic GLI-2012 spirometric norms has been debated in several countries. However, its applicability in Algeria has not been verified. Aim To ascertain how well the GLI-2012 norms fit contemporary adult Algerian spirometric data. Methods This was a cross-sectional study of a convenience sample of 300 healthy non-smoker adults (50% men, age range: 18–85 years) recruited from the Algiers region general population. All participants underwent a clinical examination and a plethysmography measurement. Z-scores for some spirometric data [FEV1, FVC, FEV1/FVC and forced expiratory flow at 25–75% of FVC (FEF25-75%)] were calculated. If the average Z-score deviated by “< ± 0.5” from the overall mean, the GLI-2012 norms would be considered as reflective of contemporary Algerian spirometry. Results The means±SDs of age, height, weight, FVC, FEV1, FEV1/FVC and FEF25-75% of the participants were, respectively, 48±17 years, 1.65±0.10 m, 73±14 kg, 4.04±1.04 L, 3.18±0.82 L, 0.79±0.05 and 4.09±1.09 L/s. Almost the quarter of participants were obese. The total sample means±SDs Z-scores were 0.22±0.87 for FVC, 0.04±0.88 for FEV1, -0.34±0.67 for FEV1/FVC and 0.93±0.79 for FEF25-75%. For men and women, only the means±SDs of the FEF25-75% Z-scores exceeded the threshold of “± 0.5”, respectively, 1.13±0.77 and 0.73±0.76. Conclusion Results of the present study, performed in an Algerian population of healthy non-smoking adults, supported the applicability of the GLI-2012 norms to interpret FEV1, FVC and FEV1/FVC but not the FEF25-75%.
The DH31/CGRP enteroendocrine peptide triggers intestinal contractions favoring the elimination of opportunistic bacteria

The digestive tract is the first organ affected by the ingestion of foodborne bacteria. While commensal bacteria become resident, opportunistic or virulent bacteria are eliminated from the gut by the local innate immune system. Here we characterize a new mechanism of defense, independent of the immune system, in Drosophila melanogaster. We observed strong contractions of longitudinal visceral muscle fibers for the first 2 hours following bacterial ingestion. We showed that these visceral muscle contractions are induced by immune reactive oxygen species (ROS) that accumulate in the lumen and depend on the ROS-sensing TRPA1 receptor. We then demonstrate that both ROS and TRPA1 are required in a subset of anterior enteroendocrine cells for the release of the DH31 neuropeptide which activates its receptor in the neighboring visceral muscles. The resulting contractions of the visceral muscles favors quick expulsion of the bacteria, limiting their presence in the gut. Our results unveil a precocious mechanism of defense against ingested opportunistic bacteria, whether they are Gram-positive like Bacillus thuringiensis or Gram-negative like Erwinia carotovora carotovora. Finally, we found that the human homolog of DH31, CGRP, has a conserved function in Drosophila.
Automated Instruction Stream Throughput Prediction for Intel and AMD Microarchitectures

An accurate prediction of scheduling and execution of instruction streams is a necessary prerequisite for predicting the in-core performance behavior of throughput-bound loop kernels on out-of-order processor architectures. Such predictions are an indispensable component of analytical performance models, such as the Roofline and the Execution-Cache-Memory (ECM) model, and allow a deep understanding of the performance-relevant interactions between hardware architecture and loop code. We present the Open Source Architecture Code Analyzer (OSACA), a static analysis tool for predicting the execution time of sequential loops comprising x86 instructions under the assumption of an infinite first-level cache and perfect out-of-order scheduling. We show the process of building a machine model from available documentation and semi-automatic benchmarking, and carry it out for the latest Intel Skylake and AMD Zen micro-architectures. To validate the constructed models, we apply them to several assembly kernels and compare runtime predictions with actual measurements. Finally we give an outlook on how the method may be generalized to new architectures.
Emergence of Communication in an Interactive World with Consistent Speakers

Training agents to communicate with one another given task-based supervision only has attracted considerable attention recently, due to the growing interest in developing models for human-agent interaction. Prior work on the topic focused on simple environments, where training using policy gradient was feasible despite the non-stationarity of the agents during training. In this paper, we present a more challenging environment for testing the emergence of communication from raw pixels, where training using policy gradient fails. We propose a new model and training algorithm, that utilizes the structure of a learned representation space to produce more consistent speakers at the initial phases of training, which stabilizes learning. We empirically show that our algorithm substantially improves performance compared to policy gradient. We also propose a new alignment-based metric for measuring context-independence in emerged communication and find our method increases context-independence compared to policy gradient and other competitive baselines.
A Novel Scoring System for Rupture Risk Stratification of Intracranial Aneurysms: A Hemodynamic and Morphological Study

Objective: The aim of the present study is to investigate the potential morphological and hemodynamic risk factors related to intracranial aneurysms (IAs) rupture and establish a system to stratify the risk of IAs rupture to help the clinical decision-making. Methods: Patients admitted to our hospital for single-IAs were selected from January 2012 and January 2018. A propensity score matching was conducted to match patients. The morphological parameters were obtained from high solution CTA images, and the hemodynamic parameters were obtained in accordance with the outcomes of computational fluid dynamics (CFDs) simulation. Differences in the morphologic and hemodynamic parameters were compared. The significant parameters were selected to establish a novel scoring system (Intracranial Aneurysm Rupture Score, IARS). The comparison was drawn between the discriminating accuracy of IARS and the Rupture Resemblance Score (RRS) system to verify the value of IARS. Then, a group of patients with unruptured IAs was stratified into the high risk and low risk groups by IARS and RRS system separately and was followed up for 18–27 months to verify the value of IARS. The outcome of different stratifications was compared. Results: The matching process yielded 167 patients in each group. Differences of statistical significance were found in aneurysm length (p = 0.001), perpendicular height (H) (p < 0.001), aspect ratio (AR) (p < 0.001), size ratio (SR) (p < 0.001), deviated angle (DA) (p < 0.001), normalized average wall shear stress (NWSSa) (p < 0.001), wall shear stress gradient (WSSG) (p < 0.001), low shear area ratio (LSAR) (p = 0.01), and oscillatory shear index (OSI) (p = 0.01). Logistic regression analysis further demonstrated that SR, DA, NWSSa, LSAR, and OSI were the independent risk factors of IAs rupture. SR, DA, LSAR, and OSI were finally selected to establish the IARS. Our present IARS showed a higher discriminating value (AUC 0.81 vs. 0.77) in comparison with the RRS (SR, NWSSa, and OSI). After follow-up, seven patients were subject to IAs rupture. 5/26 in high risk group stratified by IARS, yet 7/57 in high risk group stratified by RRS. The accuracy of IARS was further verified (19.2% vs. 12.3%, AUC for the IARS and the RRS was 0.723 and 0.673, respectively). Conclusion: SR, DA, NWSSa, LSAR, and OSI were considered the independent risk factors of IAs rupture. Our novel IARS showed higher accuracy in discriminating IA rupture in comparison with RRS.
Managing limb pain using virtual reality: a systematic review of clinical and experimental studies

Abstract Purpose: The aim of this systematic review was to assess the effect of virtual representation of body parts on pain perception in patients with pain and in pain-free participants exposed to experimentally induced pain. Methods: Databases searched: Medline, PsycInfo, CINAHL, and Web of Science. Studies investigating participants with clinical pain or those who were pain free and exposed to experimentally induced pain were analysed separately. Results: Eighteen clinical studies and seven experimental studies were included. Randomised controlled clinical trials showed no significant difference between intervention and control groups for pain intensity. Clinical studies with a single group pretest–posttest design showed a reduction in pain after intervention. In the studies including a sample of pain free participants exposed to experimentally induced pain there was an increase in pain threshold when the virtual arm was collocated with the real arm, when it moved in synchrony with the real arm, and when the colour of the stimulated part of the virtual arm became blue. Observing a virtual arm covered with iron armour reduced pain. Conclusions: The use of virtual representations of body parts to reduce pain is promising. However, due to the poor methodological quality and limitations of primary studies, we could not find conclusive evidence. Implications for rehabilitation Virtual reality has been increasingly used in the rehabilitation of painful and dysfunctional limbs. Virtual reality can be used to distract attention away from acute pain and may also provide corrective psychological and physiological environments. Virtual representation of body parts has been used to provide a corrective re-embodiment of painful dysmorphic body parts, and primary research shows promising results.
In vivo effects of allogeneic mesenchymal stem cells in a rat model of acute ischemic kidney injury

Objective(s): Renal ischemia-reperfusion injury (IRI) as a severe condition of acute kidney injury (AKI) is the most common clinical problem with high mortality rates of 35-60% deaths in hospital. Mesenchymal stem cells (MSC) due to unique regenerative characteristics are ideal candidates for the treatment of the ischemic injuries. This work is focused on the administration of MSC to IRI-induced AKI Wistar rats and evaluating their significance in AKI treatment. Material and Methods: Animals underwent surgical procedure and AKI was induced by 40 min bilateral renal pedicle clamping. Immediately after reperfusion, 2×106 rat bone marrow derived MSCs were injected via intra-parenchymal or intra-aortic route. Results: Animals subjected to AKI after days 1 and 3 showed significant increase in the serum creatinine and blood urea nitrogen (BUN) concentration along with a declined glomerular filtration rate (GFR) when compared with non-ischemic animals. On the other hand, treated animals showed a significant enhanced regeneration as compared to ischemic animals in both administration route groups. Conclusion: According to the results concluded from the renoprotective effects of MSC in IRI/AKI, MSCs could be considered as promising therapeutic approach for AKI in clinical applications.
Learning Low Precision Deep Neural Networks through Regularization

We consider the quantization of deep neural networks (DNNs) to produce low-precision models for efficient inference of fixed-point operations. Compared to previous approaches to training quantized DNNs directly under the constraints of low-precision weights and activations, we learn the quantization of DNNs with minimal quantization loss through regularization. In particular, we introduce the learnable regularization coefficient to find accurate low-precision models efficiently in training. In our experiments, the proposed scheme yields the state-of-the-art low-precision models of AlexNet and ResNet-18, which have better accuracy than their previously available low-precision models. We also examine our quantization method to produce low-precision DNNs for image super resolution. We observe only $0.5$~dB peak signal-to-noise ratio (PSNR) loss when using binary weights and 8-bit activations. The proposed scheme can be used to train low-precision models from scratch or to fine-tune a well-trained high-precision model to converge to a low-precision model. Finally, we discuss how a similar regularization method can be adopted in DNN weight pruning and compression, and show that $401\times$ compression is achieved for LeNet-5.
Unsupervised Deep Single‐Image Intrinsic Decomposition using Illumination‐Varying Image Sequences

Machine learning based Single Image Intrinsic Decomposition (SIID) methods decompose a captured scene into its albedo and shading images by using the knowledge of a large set of known and realistic ground truth decompositions. Collecting and annotating such a dataset is an approach that cannot scale to sufficient variety and realism. We free ourselves from this limitation by training on unannotated images.
Variable Lipoprotein Hemagglutinin A Gene (vlhA) Expression in Variant Mycoplasma gallisepticum Strains In Vivo

Mycoplasma gallisepticum, the primary etiologic agent of chronic respiratory disease, is a significant poultry pathogen, causing severe inflammation and leading to economic losses worldwide. Immunodominant proteins encoded by the variable lipoprotein and hemagglutinin (vlhA) gene family are thought to be important for M. gallisepticum-host interaction, pathogenesis, and immune evasion, but their exact role remains unknown. ABSTRACT Mycoplasma gallisepticum, the primary etiologic agent of chronic respiratory disease, is a significant poultry pathogen, causing severe inflammation and leading to economic losses worldwide. Immunodominant proteins encoded by the variable lipoprotein and hemagglutinin (vlhA) gene family are thought to be important for M. gallisepticum-host interaction, pathogenesis, and immune evasion, but their exact role remains unknown. Previous work has demonstrated that vlhA phase variation is dynamic throughout the earliest stages of infection, with vlhA 3.03 being the predominant vlhA expressed during the initial infection, and that the pattern of dominant vlhA expression may be nonrandom and regulated by previously unrecognized mechanisms. To further investigate this gene family, we assessed the vlhA profile of two well-characterized vaccine strains, GT5 and Mg7, a vlhA 3.03 mutant strain, and an M. gallisepticum population expressing an alternative immunodominant vlhA. Here, we report that two M. gallisepticum vaccine strains show different vlhA profiles over the first 2 days of infection compared to that of wild-type Rlow, while the population expressing an alternative immunodominant vlhA gene reverted to a profile indistinguishable from that of wild-type Rlow. Additionally, we observed a slight shift in the vlhA gene expression profile but no reduction in virulence in a vlhA 3.03 mutant. Taken together, these data further support the hypothesis that M. gallisepticum vlhA genes change in a nonstochastic temporal progression of expression and that vlhA 3.03, while preferred, is not required for virulence. Collectively, these data may be important in elucidating mechanisms of colonization and overall pathogenesis of M. gallisepticum.
Detection of East/Central/South African genotype Chikungunya virus during an outbreak in a southeastern state of Brazil

Abstract Chikungunya virus (CHIKV) is an arbovirus transmitted by Aedes mosquitoes that was first identified in Brazil in 2014. It causes a febrile illness characterised by severe arthralgia and rash. Our group investigated a suspected CHIKV outbreak in Governador Valadares, state of Minas Gerais, Brazil and from 25 acute-phase patients, 10 had qRT-PCR positive sera samples and had E1 partial sequence amplified and Sanger sequenced. Samples were identified as East/Central/South African (ECSA) genotype by phylogenetic analysis and clustered with CHIKV sequences isolated in the neighbour state of Bahia. Our findings confirm previous predictions that ECSA genotype would spread through northeast and southeast of Brazil.
Genome‐wide DNA methylation profiling of primary colorectal laterally spreading tumors identifies disease‐specific epimutations on common pathways

Colorectal laterally spreading tumors (LSTs) grow to extremely large size while rarely invade deeply. Also, there is a low tendency to become cancerous. We used the Illumina Human Methylation 450K array to query the main epigenetic difference of LSTs. We built a discovery cohort with 10 matched cases, and a validation cohort with 9 additional matched cases. Our results suggest that LST displays significant decrease in DNA methylation, highlighted by the discovery of 1,018 hypomethylated intergenic regions (IGRs). Comparing to classic differentially methylated probes and regions that overlap transcription starting site and CpG island, IGR‐regions were associated more closely with genes involved in functional biological processes and correlated with specific histone modifications. Hypomethylated IGR regions were often annotated as tissue‐specific regulatory elements for noncolon tissues and were typically epigenetically silenced in normal colon mucosa. By integration of public data, we defined the commonality and specific epigenetic signatures for adenomas, LSTs and colon adenocarcinomas. Only 435 hypermethylated differentially methylated probes (DMPs) and differentially methylated regions (DMRs) and 517 hypomethylated DMPs and DMRs were shared by the three diseases. However, our pathway‐level analysis discovered that genes in four pathways were common target of epimutations in LSTs, adenomas and CRCs. More interestingly, different diseases seem to employ distinct epigenetic insult to disturb specific pathways. Between LST and adenoma, we found eight pathways including Ras signaling and Rap1 signaling pathway were commonly targeted but the epimutation patterns were opposite. Comparison between precancerous conditions and invasive states revealed the key pathways governing the progression to malignancy, including PI3K‐Akt pathways.
Comparison of in vivo remodeling of urinary bladder matrix and acellular dermal matrix in an ovine model.

AIM Biologically derived surgical graft materials come from a variety of sources with varying mechanical properties. This study aimed to evaluate the host response and mechanical performance of two extracellular matrix devices in a large animal preclinical model. MATERIALS & METHODS Bilateral defects were created in the fascia lata of sheep and repaired with either an acellular dermal matrix (ADM) or urinary bladder matrix (UBM). After 1 or 3 months, the repair site was explanted for histological and mechanical analysis. RESULTS & CONCLUSION Despite pre-implantation mechanical differences, both UBM and ADM demonstrated similar mechanical performance at 3 months. However, UBM was completely remodeled into site-appropriate tissue by 3 months, while ADM showed limited tissue incorporation.