Miracle-dz/UniFAR-FTUs huggingface dataset:
Accelerated Molecular Dynamics Applied to the Peptaibol Folding Problem

The use of enhanced sampling molecular dynamics simulations to facilitate the folding of proteins is a relatively new approach which has quickly gained momentum in recent years. Accelerated molecular dynamics (aMD) can elucidate the dynamic path from the unfolded state to the near-native state, “flattened” by introducing a non-negative boost to the potential. Alamethicin F30/3 (Alm F30/3), chosen in this study, belongs to the class of peptaibols that are 7–20 residue long, non-ribosomally synthesized, amphipathic molecules that show interesting membrane perturbing activity. The recent studies undertaken on the Alm molecules and their transmembrane channels have been reviewed. Three consecutive simulations of ~900 ns each were carried out where N-terminal folding could be observed within the first 100 ns, while C-terminal folding could only be achieved almost after 800 ns. It took ~1 μs to attain the near-native conformation with stronger potential boost which may take several μs worth of classical MD to produce the same results. The Alm F30/3 hexamer channel was also simulated in an E. coli mimicking membrane under an external electric field that correlates with previous experiments. It can be concluded that aMD simulation techniques are suited to elucidate peptaibol structures and to understand their folding dynamics.
What Is the Clinical Evidence Supporting Trauma Team Training (TTT): A Systematic Review and Meta-Analysis

Background and Objectives: Major trauma centres manage severely injured patients using multi-disciplinary teams but the evidence-base that targeted Trauma Team Training (TTT) improves patients’ outcomes is unclear. This systematic review aimed to identify the association between the implementation of TTT programs and patient outcomes. Materials and Methods: We searched OVID Medline, PubMed and The Cochrane Library (CENTRAL) from the date of the database commencement until 10 of April 2019 for a combination of Medical Subject Headings (MeSH) terms and keywords relating to TTT and clinical outcomes. Reference lists of appraised studies were also screened for relevant articles. We extracted data on the study setting, type and details about the learners, as well as clinical outcomes of mortality and/or time to critical interventions. A meta-analysis of the association between TTT and mortality was conducted using a random effects model. Results: The search yielded 1136 unique records and abstracts, of which 18 full texts were reviewed. Nine studies met final inclusion, of which seven were included in a meta-analysis of the primary outcome. There were no randomised controlled trials. TTT was not associated with mortality (Pooled overall odds ratio (OR) 0.83; 95% Confidence Interval; 0.64–1.09). TTT was associated with improvements in time to operating theatre and time to first computerized tomography (CT) scanning. Conclusions: Despite few publications related to TTT, its introduction was associated with improvements in time to critical interventions. Whether such improvements can translate to improvements in patient outcomes remains unknown. Further research focusing on the translation of standardised trauma team reception “actions” into TTT is required to assess the association between TTT and patient outcome.
Raw Bowl Tea (Tuocha) Polyphenol Prevention of Nonalcoholic Fatty Liver Disease by Regulating Intestinal Function in Mice

A high-fat diet-induced C57BL/6N mouse model of non-alcoholic fatty liver disease (NAFLD) was established. The effect and mechanism of Raw Bowl Tea polyphenols (RBTP) on preventing NAFLD via regulating intestinal function were observed. The serum, liver, epididymis, small intestine tissues, and feces of mice were examined by biochemical and molecular biological methods, and the composition of RBTP was analyzed by HPLC assay. The results showed that RBTP could effectively reduce the body weight, liver weight, and liver index of NAFLD mice. The serum effects of RBTP were: (1) decreases in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), D-lactate (D-LA), diamine oxidase (DAO), lipopolysaccharide (LPS), and an increase of high density lipoprotein cholesterol (HDL-C) levels; (2) a decrease of inflammatory cytokines such as interleukin 1 beta (IL-1β), interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-α), and interferon gamma (INF-γ); (3) a decrease the reactive oxygen species (ROS) level in liver tissue; and (4) alleviation of pathological injuries of liver, epididymis, and small intestinal tissues caused by NAFLD and protection of body tissues. qPCR and Western blot results showed that RBTP could up-regulate the mRNA and protein expressions of LPL, PPAR-α, CYP7A1, and CPT1, and down-regulate PPAR-γ and C/EBP-α in the liver of NAFLD mice. In addition, RBTP up-regulated the expression of occludin and ZO-1, and down-regulated the expression of CD36 and TNF-α in the small intestines of NAFLD mice. Studies on mice feces showed that RBTP reduced the level of Firmicutes and increased the minimum levels of Bacteroides and Akkermansia, as well as reduced the proportion of Firmicutes/Bacteroides in the feces of NAFLD mice, which play a role in regulating intestinal microecology. Component analysis showed that RBTP contained seven polyphenolic compounds: Gallic acid, (-)-epigallocatechin, catechin, L-epicatechin, (-)-epigallocatechin gallate, (-)-gallocatechin gallate, and (-)-epicatechin gallate (ECG), and high levels of caffeine, (-)-epigallocatechin (EGC), and ECG. RBTP improved the intestinal environment of NAFLD mice with the contained active ingredients, thus playing a role in preventing NAFLD. The effect was positively correlated with the dose of 100 mg/kg, which was even better than that of the clinical drug bezafibrate.
Serine-phosphorylated STAT3 promotes tumorigenesis via modulation of RNA polymerase transcriptional activity.

Deregulated activation of the latent oncogenic transcription factor signal transducer and activator of transcription (STAT)3 in many human epithelial malignancies, including gastric cancer (GC), has invariably been associated with its canonical tyrosine phosphorylation and enhanced transcriptional activity. By contrast, serine phosphorylation (pS) of STAT3 can augment its nuclear transcriptional activity and promote essential mitochondrial functions, yet the role of pS-STAT3 among epithelial cancers is ill-defined. Here, we reveal that genetic ablation of pS-STAT3 in the gp130F/F spontaneous GC mouse model and human GC cell line xenografts abrogated tumor growth that coincided with reduced proliferative potential of the tumor epithelium. Microarray gene expression profiling demonstrated that the suppressed gastric tumorigenesis in pS-STAT3-deficient gp130F/F mice associated with reduced transcriptional activity of STAT3-regulated gene networks implicated in cell proliferation and migration, inflammation and angiogenesis, but not mitochondrial function or metabolism. Notably, the pro-tumorigenic activity of pS-STAT3 aligned with its capacity to primarily augment RNA polymerase II-mediated transcriptional elongation, but not initiation, of STAT3 target genes. Furthermore, by employing a combinatorial in vitro and in vivo proteomics approach based on the rapid immunoprecipitation mass spectrometry of endogenous protein (RIME) assay, we identified RuvB-like AAA ATPase 1 (RUVBL1/Pontin) and enhancer of rudimentary homolog (ERH) as interacting partners of pS-STAT3 that are pivotal for its transcriptional activity on STAT3 target genes. Collectively, these findings uncover a hitherto unknown transcriptional role and obligate requirement for pS-STAT3 in GC that could be extrapolated to other STAT3-driven cancers.
High-density functional diffuse optical tomography based on frequency-domain measurements improves image quality and spatial resolution

Abstract. Measurements of dynamic near-infrared (NIR) light attenuation across the human head together with model-based image reconstruction algorithms allow the recovery of three-dimensional spatial brain activation maps. Previous studies using high-density diffuse optical tomography (HD-DOT) systems have reported improved image quality over sparse arrays. These HD-DOT systems incorporated multidistance overlapping continuous wave measurements that only recover differential intensity attenuation. We investigate the potential improvement in reconstructed image quality due to the additional incorporation of phase shift measurements, which reflect the time-of-flight of the measured NIR light, within the tomographic reconstruction from high-density measurements. To evaluate image reconstruction with and without the additional phase information, we simulated point spread functions across a whole-scalp field of view in 24 subject-specific anatomical models using an experimentally derived noise model. The addition of phase information improves the image quality by reducing localization error by up to 59% and effective resolution by up to 21% as compared to using the intensity attenuation measurements alone. Furthermore, we demonstrate that the phase data enable images to be resolved at deeper brain regions where intensity data fail, which is further supported by utilizing experimental data from a single subject measurement during a retinotopic experiment.
Linear IgA dermatosis in association with angioimmunoblastic T‐cell lymphoma infiltrating the skin: A case report with literature review

Angioimmunoblastic T‐cell lymphoma (AITL) is an aggressive form of peripheral T‐cell lymphoma, characterized by systemic symptoms, diffuse lymphadenopathy, hepatosplenomegaly and immunodysregulation. Half of AITL is associated with cutaneous symptoms, but only few cases with bullous eruption have been described. Association with a linear IgA dermatosis is extremely rare. Linear IgA dermatosis can be idiopathic, or linked with drug intake or neoplastic disorders. Some cases of linear IgA dermatosis presenting as toxic epidermal necrolysis (TEN) have been described, most of them being drug induced. We here present the case of a 72‐year‐old man recently diagnosed with AITL who developed a bullous eruption, presenting as TEN. Histopathology showed deep cutaneous involvement of the lymphoma with a sub‐epidermal blistering and direct immunofluorescence revealed a heavy IgA linear deposit on the dermal‐epidermal junction. A diagnosis of linear IgA dermatosis associated with cutaneous involvement of an angioimmunoblastic T‐cell lymphoma was made. Chemotherapy and corticosteroids allowed cutaneous improvement but the patient died of his lymphoma shortly after.
Immunomodulatory Effects of Lactobacillus plantarum on Inflammatory Response Induced by Klebsiella pneumoniae

Some respiratory infections have been associated with dysbiosis of the intestinal microbiota. The underlying mechanism is incompletely understood, but cross talk between the intestinal microbiota and local immune cells could influence the immune response at distal mucosal sites. This has led to the concept of enhancing respiratory defenses by modulating the intestinal microbiota with exogenous supplementation of beneficial strains. ABSTRACT Some respiratory infections have been associated with dysbiosis of the intestinal microbiota. The underlying mechanism is incompletely understood, but cross talk between the intestinal microbiota and local immune cells could influence the immune response at distal mucosal sites. This has led to the concept of enhancing respiratory defenses by modulating the intestinal microbiota with exogenous supplementation of beneficial strains. In this study, we examined the effect of Lactobacillus plantarum CIRM653 on the inflammatory response induced by the pathogen Klebsiella pneumoniae. Oral administration of L. plantarum CIRM653 to mice subsequently infected by K. pneumoniae via the nasal route (i) reduced the pulmonary inflammation response, with decreased numbers of lung innate immune cells (macrophages and neutrophils) and cytokines (mouse keratinocyte-derived chemokine [KC], interleukin-6 [IL-6], and tumor necrosis factor alpha [TNF-α]) in the bronchoalveolar fluid, and (ii) induced an immunosuppressive Treg response in lungs. In vitro coincubation of L. plantarum CIRM653 and K. pneumoniae with human dendritic cells and peripheral blood mononuclear cells resulted in decreased Th1 (IL-12p70 and interferon gamma [IFN-γ]) and Th17 (IL-23 and IL-17) and increased Treg (IL-10) cytokine levels compared to those observed for K. pneumoniae-infected cells. Neither K. pneumoniae nor L. plantarum CIRM653 had any effect on cytokine production by intestinal epithelial cells in vitro, but the induction of the NF-κB pathway and IL-8 and IL-6 production by K. pneumoniae in airway epithelial cells was significantly reduced when the pathogen was coincubated with L. plantarum CIRM653. The remote IL-10-mediated modulation of the K. pneumoniae inflammatory response by L. plantarum CIRM653 supports the concept of immunomodulation by beneficial bacteria through the gut-lung axis.
Additional cavotricuspid isthmus block ablation may not improve the outcome of atrial fibrillation ablation

Pulmonary vein isolation (PVI) is an effective procedure for atrial fibrillation (AF). The role of additional cavotricuspid isthmus (CTI) block ablation remains controversial in AF patients without atrial flutter (AFL). Therefore, this study aimed to explore the clinical outcome of additional CTI block ablation in patients without AFL.
Distinct Mechanisms of Imagery Differentially Influence Speech Perception

Abstract Neural representation can be induced without external stimulation, such as in mental imagery. Our previous study found that imagined speaking and imagined hearing modulated perceptual neural responses in opposite directions, suggesting motor-to-sensory transformation and memory retrieval as two separate routes that induce auditory representation (Tian and Poeppel, 2013). We hypothesized that the precision of representation induced from different types of speech imagery led to different modulation effects. Specifically, we predicted that the one-to-one mapping between motor and sensory domains established during speech production would evoke a more precise auditory representation in imagined speaking than retrieving the same sounds from memory in imagined hearing. To test this hypothesis, we built the function of representational precision as the modulation of connection strength in a neural network model. The model fitted the magnetoencephalography (MEG) imagery repetition effects, and the best-fitting parameters showed sharper tuning after imagined speaking than imagined hearing, consistent with the representational precision hypothesis. Moreover, this model predicted that different types of speech imagery would affect perception differently. In an imagery-adaptation experiment, the categorization of /ba/-/da/ continuum from male and female human participants showed more positive shifts towards the preceding imagined syllable after imagined speaking than imagined hearing. These consistent simulation and behavioral results support our hypothesis that distinct mechanisms of speech imagery construct auditory representation with varying degrees of precision and differentially influence auditory perception. This study provides a mechanistic connection between neural-level activity and psychophysics that reveals the neural computation of mental imagery.
Conjugated linoleic acid producing potential of lactobacilli isolated from goat (AXB) rumen fluid samples

Objective The present investigation was aimed to explore the potential of lactobacilli for conjugated linoleic acid (CLA) production, isolated from rumen fluid samples of lactating goats. Methods A total of 64 isolates of lactobacilli were obtained using deMan-Rogosa-Sharpe (MRS) agar from rumen fluid of goats and further subjected to morphological and biochemical characterizations. Isolates found as gram-positive, catalase negative rods were presumptively identified as Lactobacillus species and further confirmed by genus specific polymerase chain reaction (PCR). The phylogenetic tree was constructed from the nucleotide sequences using MEGA6. Results Out of the 64 isolates, 23 isolates were observed positive for CLA production by linoleate isomerase gene-based amplification and quantitatively by UV-spectrophotometric assay for the conversion of linoleic acid to CLA as well as gas chromatography-based assay. In all Lactobacillus species cis9, trans11 isomer was observed as the most predominant CLA isomer. These positive isolates were identified by 16S rRNA gene-based PCR sequencing and identified to be different species of L. ingluviei (2), L.salivarius (2), L. curvatus (15), and L. sakei (4). Conclusion The findings of the present study concluded that lactic acid bacteria isolated from ruminal fluid samples of goat have the potential to produce bioactive CLA and may be applied as a direct fed microbial to enhance the nutraceutical value of animal food products.
Shrinking Lung Syndrome

To the Editor S ystemic lupus erythematosus (SLE) is a chronic autoimmune disease with a highly heterogeneous presentation, which can lead to multiorgan damage. Respiratory tract involvement is frequent in SLE, with pleuritis as the most common finding, estimated between 17% and 60% during the disease course, whereas parenchymal manifestations occur less often, with chronic interstitial pneumonitis, reported between 3% and 13%, as the main entity. Shrinking lung syndrome (SLS), first described in 1965, is a rare condition with a prevalence around 1%, but reported in up to 6% of severe SLE cases, and female predominance. Moreover, SLS has been exceptionally described in other connective tissue diseases, such as systemic sclerosis, Sjögren syndrome, and polymyositis. Phrenic nerve dysfunction, glucocorticoidinduced myopathy, and diaphragm disease, as well as pleural inflammation, adhesion, or effusion, have been hypothesized to contribute to SLS onset, but the exact pathogenesis remains incompletely understood. Shrinking lung syndrome is characterized by reduction in lung volumes and restrictive pattern at pulmonary function tests (PFTs), which commonly show decline of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), lung diffusion capacity for carbon monoxide (DLCO), and total lung capacity (TLC). Patients present with progressive exertional dyspnea as main complaint, accompanied by pleuritic chest pain in 80% of cases, and less frequently by cough. In a recent reviewof 155 SLS cases, chest x-ray and computed tomography (CT)
Gold Nanoparticle Enhanced Proton Therapy: Monte Carlo Modeling of Reactive Species’ Distributions Around a Gold Nanoparticle and the Effects of Nanoparticle Proximity and Clustering

Gold nanoparticles (GNPs) are promising radiosensitizers with the potential to enhance radiotherapy. Experiments have shown GNP enhancement of proton therapy and indicated that chemical damage by reactive species plays a major role. Simulations of the distribution and yield of reactive species from 10 ps to 1 µs produced by a single GNP, two GNPs in proximity and a GNP cluster irradiated with a proton beam were performed using the Geant4 Monte Carlo toolkit. It was found that the reactive species distribution at 1 µs extended a few hundred nm from a GNP and that the largest enhancement occurred over 50 nm from the nanoparticle. Additionally, the yield for two GNPs in proximity and a GNP cluster was reduced by up to 17% and 60% respectively from increased absorption. The extended range of action from the diffusion of the reactive species may enable simulations to model GNP enhanced proton therapy. The high levels of absorption for a large GNP cluster suggest that smaller clusters and diffuse GNP distributions maximize the total radiolysis yield within a cell. However, this must be balanced against the high local yields near a cluster particularly if the cluster is located adjacent to a biological target.
Assessing Genetic Diversity for a Pre-Breeding Program in Piaractus mesopotamicus by SNPs and SSRs

The pacu (Piaractus mesopotamicus) is a Neotropical fish with remarkable productive performance for aquaculture. Knowledge of genetic resources in Neotropical fish is essential for their applications in breeding programs. The aim of this study was to characterize the genetic diversity of seven farmed populations of pacu which will constitute the basis for a broodstock foundation for coming breeding programs in Brazil. Analysis of one wild population (Paraná River) was used as a reference to compare genetic parameters in the farmed populations. The analyses were performed using 32 single-nucleotide polymorphisms (SNP) and 8 simple sequence repeat (SSR) markers. No significant differences in genetic diversity between populations estimated through the number of alleles and allelic richness, observed heterozygosity, expected heterozygosity, and minimum allele frequency were detected (p > 0.05). Low genetic diversity was observed in all farmed stocks and the wild population. Moreover, we detected low genetic structure when comparing farmed and wild populations for SNPs (FST = 0.07; K = 3) and SSRs (FST = 0.08; K = 2). Analysis of molecular variance (AMOVA) demonstrated that genetic variation was mostly within populations. Kinship analysis showed that most fish farms included related individuals at a proportion of at least 25%. Our results suggest that the basal broodstock for pacu breeding programs should be founded with individuals from different fish farms for higher genetic diversity and to avoid inbreeding risks.
A Taxonomy of Game Elements for Gamification in Educational Contexts: Proposal and Evaluation

Gamification has been widely employed in the educational domain over the past eight years when the term became a trend. However, the literature states that gamification still lacks formal definitions to support the design of gamified strategies. This paper aims to create a taxonomy for the game elements, based on gamification experts' opinions. After a brief review from existing work, we extract first the game elements from the current state of the art, and then evaluate them via a survey with 19 gamification and education experts. The resulting taxonomy taxonomy included the description of 21 game elements and their quantitative and qualitative evaluation by the experts. Overall, the proposed taxonomy was in general well accepted by most of the experts. They also suggested expanding it with the inclusion of Narrative and Storytelling game elements. Thus, the main contribution of this paper is proposing a new, confirmed taxonomy to standardise the terminology used to define the game elements as a mean to design and deploy gamification strategies in the educational domain.
Input-to-State Stabilization of Nonlinear Systems via Event-Triggered Impulsive Control

In this work, an event-triggered impulsive control (ETIC) method is proposed to address the input-to-state stabilization (ISS) issue for a class of nonlinear systems under external disturbance. Different from many existing impulsive controllers usually with fixed impulse instants, we design a novel one which is event-triggered and multimodule constrained. Based on that, we establish some ISS criteria for the considered system with and without data dropouts. The presented event-triggered control method can save the communication resources and avoid the Zeno behaviors. Finally, an example with simulations results is provided to illustrate the validity of the method.