Miracle-dz/UniFAR-FTUs huggingface dataset:
Neuroprotective potential of trimetazidine against tramadol-induced neurotoxicity: role of PI3K/Akt/mTOR signaling pathways

Abstract Tramadol (TRA) causes neurotoxicity whereas trimetazidine (TMZ) is neuroprotective. The potential involvement of the PI3K/Akt/mTOR signaling pathway in the neuroprotection of TMZ against TRA-induced neurotoxicity was evaluated. Seventy male Wistar rats were divided into groups. Groups 1 and 2 received saline or TRA (50 mg/kg). Groups 3, 4, and 5 received TRA (50 mg/kg) and TMZ (40, 80, or 160 mg/kg) for 14 days. Group 6 received TMZ (160 mg/kg). Hippocampal neurodegenerative, mitochondrial quadruple complex enzymes, phosphatidylinositol-3-kinases (PI3Ks)/protein kinase B levels, oxidative stress, inflammatory, apoptosis, autophagy, and histopathology were evaluated. TMZ decreased anxiety and depressive-like behavior induced by TRA. TMZ in tramadol-treated animals inhibited lipid peroxidation, GSSG, TNF-α, and IL-1β while increasing GSH, SOD, GPx, GR, and mitochondrial quadruple complex enzymes in the hippocampus. TRA inhibited Glial fibrillary acidic protein expression and increased pyruvate dehydrogenase levels. TMZ reduced these changes. TRA decreased the level of JNK and increased Beclin-1 and Bax. TMZ decreased phosphorylated Bcl-2 while increasing the unphosphorylated form in tramadol-treated rats. TMZ activated phosphorylated PI3Ks, Akt, and mTOR proteins. TMZ inhibited tramadol-induced neurotoxicity by modulating the PI3K/Akt/mTOR signaling pathways and its downstream inflammatory, apoptosis, and autophagy-related cascades.
Giant cell tumor of bone with secondary aneurysmal bone cyst does not have a higher risk of local recurrence

Fluid–fluid levels (FFLs) is found in 10%–16% of giant cell tumor of bone (GCTB), and the presence of FFLs raises the suspicion of GCTB with secondary aneurysmal bone cyst (ABC), which can lead to increased intraoperative bleeding and, blurring the operative field, be associated with a risk of local recurrence. The first objective of this study is to determine whether secondary ABC is associated with a higher risk of local recurrence after curettage in patients with GCTB of the extremities. The second objective of this study is to investigate the sensitivity, specificity, positive predictive value, and negative predictive value of the presence of FFLs detected on magnetic resonance imaging (MRI) to diagnose secondary ABC associated with GCTB.
Immunogenicity of DaxibotulinumtoxinA for Injection in Glabellar Lines

Abstract DaxibotulinumtoxinA-lanm for injection (DAXI), a novel botulinum toxin type A formulation, contains a purified 150-kD core neurotoxin (daxibotulinumtoxinA) and proprietary stabilizing peptide (RTP004), and is approved for glabellar line treatment. As with any biologic product, DAXI may potentially be immunogenic and elicit unwanted antibody formation, possibly resulting in partial or complete treatment failure. The immunogenicity of DAXI was assessed in 2 double-blind, placebo-controlled, single-dose studies and an open-label safety study of up to 3 repeat treatments. Of the 2737 evaluable patients, none developed neutralizing antibodies to daxibotulinumtoxinA and 0.8% developed treatment-related nonneutralizing anti–daxibotulinumtoxinA-binding antibodies. Of evaluable patients exposed to RTP004 with either DAXI or placebo, 1.3% developed treatment-related anti–RTP004-binding antibodies, which were mostly transient. No patient developed binding antibodies to both daxibotulinumtoxinA and RTP004. All patients with treatment-related binding antibodies to daxibotulinumtoxinA or RTP004 achieved a clinical response (none or mild glabellar line severity) at Week 4 following each DAXI treatment cycle. The duration of clinical response was not different between treatment cycles when antibodies were detected vs when they were absent. Although the analysis population was small compared to the number of patients likely to receive repeated treatment in clinical practice, these results suggest that DAXI administration at the approved glabellar lines dose has low immunogenic potential and that nonneutralizing antibodies to daxibotulinumtoxinA or RTP004 occur infrequently and often transiently, and have no impact on clinical efficacy, safety, or duration of action. Real-world data encompassing larger numbers of patients is needed to substantiate these results. Level of Evidence: 3
Introducing robotic oesophagectomy into an Australian practice: an assessment of the early procedural outcomes and learning curve

Robotic oesophagectomy (RAMIO) is a novel procedure in Australia and New Zealand. We aimed to report the early operative and clinical outcomes achieved during the introduction of RAMIO into the practice of a single Australian surgeon and benchmark these against outcomes of patients receiving conventional minimally invasive oesophagectomy (MIO) by the same surgeon.
Electrophysiology of interoception: Parietal posterior area supports social synchronization

ABSTRACT The effect of explicit interoception manipulation on electrophysiological (EEG) patterns concurrent with an interpersonal motor synchronization task with a social purpose was investigated in this study. Thirty healthy individuals executed a task involving behavioral motor synchronization with a social framing in both focus (conceived as the focus on the breath for a specific time interval) and no focus conditions. During the task, a 15 active electrodes electroencephalogram was used to record the following frequency bands (delta, theta, alpha, and beta band) from the frontal, temporo-central, and parieto-occipital regions of interest (ROIs). According to the results, for all the frequency bands significant higher mean values were found in the focus compared to no focus condition in the parieto-occipital ROI. On the whole, the current work conveys that when a motor synchronization task is executed and the person concurrently pays attention to his/her body correlates, EEG brain activity is empowered and boosted in posterior areas at the basis of attention to visceral signals, but also interpersonal action coordination. This evidence could have potentially interesting implications because it suggests the importance of modern breath-work during all conditions that require a social motor joint task, such as physiotherapy exercises or synchronized sports.
Design optimization of ship hulls via CFD techniques

Numerical shape optimization of a tanker ship hull has been carried out with the aid of computational fluid dynamics (CFD) techniques and experimentally verified. The choice of a specific bbjective function is based on the needs of the user. In the present study, total resistance and wave pattern have been used either separately or linearly combined. In the optimization process, three different algorithms have been tested, coupled together with a CFD flow solver. A perturbation surface has been used to modify the shape of the hull, allowing for a sharp reduction of the number of design variables. Accordingly, with different objective functions and geometrical constraints, several new optimized shapes of the bulb of a tanker ship have been automatically obtained. Among them, two optimized models have been built and tested, in the INSEAN towing tank, against the original design. In both cases the measured data have confirmed the success of the optimization process.
The effect of perceived global stress and altruism on prosocial driving behavior, yielding behavior, and yielding attitude

Abstract Objective Traffic accidents are mainly caused by driver-to-pedestrian collisions or driver-to-driver collisions. Prosocial driving behavior indicates that drivers exhibit altruistic behavior toward other drivers on roads. Yielding behavior demonstrates that drivers grant the right of passage to pedestrians at unsignalized crossings, while yielding attitude presents the subjective emotional and cognitive inclination to yield to pedestrians at unsignalized crossings. This study aims to explore the effect of altruism and drivers’ perceived stress on prosocial driving behavior, yielding behavior, and yielding attitude. In addition, we endeavor to explore the effect of stress on prosocial driving behavior exhibiting an inverted “U-type” curve as Yerkes-Dodson’s law suggests and test the moderating role of perceived stress on altruism and prosocial driving behavior/yielding behavior/yielding attitude. Methods Using a survey method, we asked 454 participants to complete an altruism scale from the IPIT measuring altruism, a Perceived Stress Scale-10 measuring drivers’ perceived stress, a prosocial driving scale from the PADI measuring prosocial driving behavior, and items on yielding behavior and yielding attitude. Then, a correlational matrix, a hierarchical multiple nonparametric regression analysis, and a moderating analysis of perceived stress were employed in sequence to reach our objective. Results The hierarchical multiple nonparametric regression analysis showed that altruism positively predicts yielding attitude (F = 41.56, p < 0.001), yielding behavior (z = 8.46, p < 0.001, odds ratio = 4.90) and prosocial driving behavior (F = 110.66, p < 0.001), but stress predicts only prosocial driving behavior (F = 7.63, p < 0.001), not yielding attitude (F = 0.51, p > 0.05) or yielding behavior (z = 0.12, p > 0.05), which exhibits an inverted “U-type” curve. Moderating analyses showed that stress only moderates the relationship between altruism and yielding attitude (B = −0.24, t = −2.62, p < 0.01). Conclusions Altruism is positively related to prosocial driving behavior, yielding behavior, and yielding attitude. Stress influences prosocial driving behavior only and exhibits an inverted “U-type” curve. Stress does not directly influence the yielding behavior. Instead, stress moderates the relationship between altruism and yielding attitude only and may further increase the possibility of yielding behavior.
Long term changes in aquaculture influence migration, regional abundance, and distribution of an avian species

Agricultural development has been causing changes to the environment and the abundance and distribution of avian species. Agriculture is dynamic with changes in products occurring at large scales over relatively short time periods. The catfish aquaculture industry is one such agriculture industry that has undergone dramatic changes over the last 25 years. The double-crested cormorant (Nannopterum auritum) is a piscivorous bird that has an extensive history with the aquaculture industry of Mississippi due to its depredation of cultured catfish. A large-scale monitoring program began in 1989 to estimate the abundance and location of cormorants at every known roost in the primary catfish producing region of the state, regionally known as the Delta. We used this data set to address hypotheses pertaining to cormorant ecology within the Delta over time, particularly in relation to aquaculture. We found that, although the Midwest breeding population of cormorants has been increasing, the abundance of cormorants wintering in the Delta has been decreasing, closely following the decline of aquaculture, suggesting aquaculture area is the primary reason for cormorant inhabitation of the region. We also modeled cormorant presence and abundance at all roost sites to determine what factors most influenced cormorant distribution. Aquaculture area around roosts was a significant predictor of both cormorant presence and abundance. However, the influence of aquaculture area was seasonally dependent, with greater positive influences occurring prior to migration. Lastly, we found peak cormorant abundance in the Delta is occurring 2.14 days earlier each year, which may be indicative of changes to migration phenology. Information gained using this large dataset aids in cormorant damage mitigation and to further our understanding of cormorant ecology. Data indicate changes in agriculture, and potentially climate change, can influence phenology, distribution, and abundance of avian species at large geographic scales.
Genome sequencing and multifaceted taxonomic analysis of novel strains of violacein-producing bacteria and non-violacein-producing close relatives

Violacein is a water-insoluble violet pigment produced by various Gram-negative bacteria. The compound and the bacteria that produce it have been gaining attention due to the antimicrobial and proposed antitumour properties of violacein and the possibility that strains producing it may have broad industrial uses. Bacteria that produce violacein have been isolated from diverse environments including fresh and ocean waters, glaciers, tropical soils, trees, fish and the skin of amphibians. We report here the isolation and characterization of six violacein-producing bacterial strains and three non-violacein-producing close relatives, each isolated from either an aquatic environment or moist food materials in northern California, USA. For each isolate, we characterized traditional phenotypes, generated and analysed draft genome sequences, and carried out multiple types of taxonomic, phylogenetic and phylogenomic analyses. Based on these analyses we assign putative identifications to the nine isolates, which include representatives of the genera Chromobacterium , Aquitalea , Iodobacter , Duganella , Massilia and Janthinobacterium . In addition, we discuss the utility of various metrics for taxonomic assignment in these groups including average nucleotide identity, whole genome phylogenetic analysis and extent of recent homologous recombination using the software program PopCOGenT.
Quantifying topical antimicrobial use before and during participation in an antimicrobial stewardship programme in Dutch companion animal clinics

The emergence of bacterial strains resistant to topical antimicrobials in both human and veterinary medicine has raised concerns over retaining the efficacy of these preparations. Yet, little information is available regarding the use of topical antimicrobials in either sector for planning targeted interventions. This study aims to quantify the use of topical antimicrobials in 44 Dutch companion animal clinics before and during their participation in an antimicrobial stewardship programme (ASP), to explore the effect of the intervention on topical antimicrobial use (AMU). Hence, prescription and clinic animal population data, collected from July 2012 until June 2018 were used. Specifically, the period from July 2012 until June 2015 was defined as pre-intervention period, whereas clinics started to participate in the ASP from March 2016 onwards. As quantification metric, the Defined Daily Dose for Animals (DDDA) was used and a mixed effect times series model with auto-regression was applied to monthly topical AMU data. The intervention effect was modelled using a step function with a change in (linear) time trend and clinic characteristics, as potential determinants of topical AMU, were assessed using a multivariable regression model. A seasonal pattern was identified, in the pre-intervention period, where topical AMU was highest in July-August and lowest in February-March. In addition, total topical AMU appeared to significantly decrease over time in the pre-intervention period and the proportion of dogs in the clinic was positively associated with topical AMU. The intervention effect was significant only for second line and for skin product AMU. This study demonstrates that during participation in an ASP, second line and skin product AMU decreased in Dutch companion animal clinics. Additionally, this study demonstrates the existence of a seasonal effect and a decrease in topical AMU over time already before introduction of a targeted intervention.
Cross-sectional study of the association of social relationship resources with Staphylococcus aureus colonization in naturally occurring social groups along the US/Mexico border

Asymptomatic carriage of Staphylococcus aureus is a major risk factor for subsequent clinical infection. Diminishing returns from mitigation efforts emphasize the need to better understand colonization, spread, and transmission of this opportunistic pathogen. While contact with other people presents opportunities for pathogen exposure and transmission, diversity of social connections may be protective against pathogens such as the common cold. This study examined whether social relationship resources, including the amount and diversity of social contacts, are associated with S. aureus colonization. Participants were community members (N = 443; 68% Hispanic) in naturally occurring social groups in southwestern Arizona. Four types of social relationships and loneliness were assessed, and samples from the skin, nose and throat were obtained to ascertain S. aureus colonization. Overall S. aureus prevalence was 64.8%. Neither the amount nor the diversity of social contacts were associated with S. aureus colonization. The concurrent validity of the social relationship assessments was supported by their moderate intercorrelations and by their positive association with self-rated health. The results suggest that the association of social network diversity and susceptibility to the common cold does not extend to S. aureus colonization. Conversely, colonization prevalence was not higher among those with more social contacts. The latter pattern suggests that social transmission may be relatively infrequent or that more intimate forms of social interaction may drive transmission and colonization resulting in high community prevalence of S. aureus colonization. These data inform communicable disease control efforts.
Understanding spatiotemporal coupling of gene expression using single molecule RNA imaging technologies

ABSTRACT Across all kingdoms of life, gene regulatory mechanisms underlie cellular adaptation to ever-changing environments. Regulation of gene expression adjusts protein synthesis and, in turn, cellular growth. Messenger RNAs are key molecules in the process of gene expression. Our ability to quantitatively measure mRNA expression in single cells has improved tremendously over the past decades. This revealed an unexpected coordination between the steps that control the life of an mRNA, from transcription to degradation. Here, we provide an overview of the state-of-the-art imaging approaches for measurement and quantitative understanding of gene expression, starting from the early visualizations of single genes by electron microscopy to current fluorescence-based approaches in single cells, including live-cell RNA-imaging approaches to FISH-based spatial transcriptomics across model organisms. We also highlight how these methods have shaped our current understanding of the spatiotemporal coupling between transcriptional and post-transcriptional events in prokaryotes. We conclude by discussing future challenges of this multidisciplinary field. Abbreviations: mRNA: messenger RNA; rRNA: ribosomal rDNA; tRNA: transfer RNA; sRNA: small RNA; FISH: fluorescence in situ hybridization; RNP: ribonucleoprotein; smFISH: single RNA molecule FISH; smiFISH: single molecule inexpensive FISH; HCR-FISH: Hybridization Chain-Reaction-FISH; RCA: Rolling Circle Amplification; seqFISH: Sequential FISH; MERFISH: Multiplexed error robust FISH; UTR: Untranslated region; RBP: RNA binding protein; FP: fluorescent protein; eGFP: enhanced GFP, MCP: MS2 coat protein; PCP: PP7 coat protein; MB: Molecular beacons; sgRNA: single guide RNA.
Immunogenicity and safety of single booster dose of KD-414 inactivated COVID-19 vaccine in adults: An open-label, single-center, non-randomized, controlled study in Japan

ABSTRACT Although vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) induce effective immune responses, vaccination with booster doses is necessary because of waning immunity. We conducted an open-label, non-randomized, single-arm study in adults in Japan to assess the immunogenicity and safety of a single booster dose of the KD-414 purified whole-SARS-CoV-2-virion inactivated vaccine candidate after vaccination with a primary series of BNT162b2. The primary endpoint was serum neutralizing activity at 7 days after booster injection compared with the primary series of BNT162b2. The SARS-CoV-2-structural protein-binding antibody level and T cell response against SARS-CoV-2-Spike (S) peptides were also examined as secondary endpoints, and safety profile assessments were conducted. Twenty subjects who participated in a previous study declined an injection of KD-414 (non-KD-414 group) and received a booster dose of BNT162b2 instead. The non-KD-414 group was compared to the KD-414 group as a secondary outcome. A single dose of KD-414 induced lower serum neutralizing activity against the wild-type virus within 7 days compared to after the primary series of BNT162b2 but significantly induced anti-SARS-CoV-2-S1-receptor-binding domain-binding immunoglobulin G (IgG) antibodies and SARS-CoV-2-S peptide-specific CD4+ and CD8+ T cell responses. Local or systemic symptoms were significantly lower in the participants who received KD-414 than in those who received BNT162b2 as the third COVID-19 vaccine dose. The present data indicate that a single booster dose of KD-414 induces a substantial immune response in BNT162b2-primed individuals and has a good safety profile, thereby supporting further clinical trials to identify rational targets.