Miracle-dz/UniFAR-FTUs huggingface dataset:
Directly injected lentiviral vector–based T cell vaccine protects mice against acute and chronic viral infection

Lentiviral vector–based dendritic cell vaccines induce protective T cell responses against viral infection and cancer in animal models. In this study, we tested whether preventative and therapeutic vaccination could be achieved by direct injection of antigen-expressing lentiviral vector, obviating the need for ex vivo transduction of dendritic cells. Injected lentiviral vector preferentially transduced splenic dendritic cells and resulted in long-term expression. Injection of a lentiviral vector encoding an MHC class I–restricted T cell epitope of lymphocytic choriomeningitis virus (LCMV) and CD40 ligand induced an antigen-specific cytolytic CD8+ T lymphocyte response that protected the mice from infection. The injection of chronically infected mice with a lentiviral vector encoding LCMV MHC class I and II T cell epitopes and a soluble programmed cell death 1 microbody rapidly cleared the virus. Vaccination by direct injection of lentiviral vector was more effective in sterile alpha motif and HD-domain containing protein 1–knockout (SAMHD1-knockout) mice, suggesting that lentiviral vectors containing Vpx, a lentiviral protein that increases the efficiency of dendritic cell transduction by inducing the degradation of SAMHD1, would be an effective strategy for the treatment of chronic disease in humans.
Mefenoxam and pyraclostrobin: toxicity and in vitro inhibitory activity against Pythium insidiosum

The objective of this study is to verify in vitro susceptibility of Pythium insidiosum against the agricultural fungicides mefenoxam and pyraclostrobin and evaluate the toxicity of both compounds. Twenty‐one P. insidiosum isolates were tested against mefenoxam and pyraclostrobin using the broth microdilution method. Minimum inhibitory and oomicidal concentrations for both compounds were established. Additionally, scanning electron microscopy was performed on P. insidiosum hyphae treated with the sublethal concentration of each fungicide. The toxicity of the compounds was evaluated in vivo Caenorhabditis elegans model. The concentration to inhibit 100% of P. insidiosum growth ranged from 0·625 to 10 μg ml−1 for mefenoxam and from 0·019 to 5 μg ml−1 for pyraclostrobin. The SEM analysis revealed changes on the surface of the hyphae treated with the fungicides, suggesting possible damage caused by these compounds. There was no evidence of toxicity in vivo models. Mefenoxam and pyraclostrobin did not show toxicity at the doses evaluated and have inhibitory effects on the pathogenic oomycete P. insidiosum. However, further evaluations of their pharmacokinetics and toxicity in different animal species and possible pharmacological interactions are necessary to infer a possible use in the clinical management of pythiosis.
Reframing Our Health Care System for Patients With Hearing Loss

Purpose: Nearly 20% of U.S. Americans report a hearing loss, yet our current health care system is poorly designed and equipped to effectively care for these individuals. Individuals with hearing loss report communication breakdowns, inaccessible health information, reduced awareness and training by health care providers, and decreased satisfaction while struggling with inadequate health literacy. These all contribute to health inequities and increased health care expenditures and inefficiencies. It is time to reframe the health care system for these individuals using existing models of best practices and accessibility to mitigate inequities and improve quality of care. Method: A review of system-, clinic-, provider-, and patient-level barriers, along with existing and suggested efforts to improve care for individuals with hearing loss, are presented. Results: These strategies include improving screening and identification of hearing loss, adopting universal design and inclusion principles, implementing effective communication approaches, leveraging assistive technologies and training, and diversifying a team to better care for patients with hearing loss. Patients should also be encouraged to seek social support and resources from hearing loss organizations while leveraging technologies to help facilitate communication. Conclusions: The strategies described introduce actionable steps that can be made at the system, clinic, provider, and patient levels. With implementation of these steps, significant progress can be made to more proactively meet the needs of patients with hearing loss. Presentation Video: https://doi.org/10.23641/asha.21215843
(2018). Circadian oscillations of cytosolic free calcium regulate the Arabidopsis circadian clock. Nature Plants (9),

30 In the last decade, the view of circadian oscillators has expanded from transcriptional 31 feedback to incorporate post-transcriptional, post-translational, metabolic processes 32 and ionic signalling. In plants and animals, there are circadian oscillations in the 33 concentration of cytosolic-free Ca 2+ ([Ca 2+ ] cyt ), though their purpose has not been fully 34 characterised. We investigated whether circadian oscillations of [Ca 2+ ] cyt regulate the 35 circadian oscillator of Arabidopsis thaliana . We report that in Arabidopsis, [Ca 2+ ] cyt 36 circadian oscillations can regulate circadian clock function through the Ca 2+ -dependent 37 action of CALMODULIN-LIKE24 (CML24). Genetic analyses demonstrate a linkage 38 between CML24 and the circadian oscillator, through pathways involving the circadian 39 oscillator gene TIMING OF CAB2 EXPRESSION1 ( TOC1 ). 40 41 Circadian oscillators confer competitive advantage by modulating physiology and development . In circadian are comprised of feedback loops of transcriptional the genes differ between the Kingdoms 2, , We tested the hypothesis that circadian oscillations of [Ca 2+ ] cyt can feed back into the circadian oscillator. We demonstrate that [Ca 2+ ] cyt signals can regulate the expression
A prospective, multi-center, randomised controlled trial for evaluation of the effectiveness of the Blimp scoring balloon in lesions not crossable with a conventional balloon or microcatheter: the BLIMP study

Abstract Background Balloon uncrossable coronary lesions are lesions that cannot be crossed with a conventional balloon. Multiple balloons have been designed to overcome this problem. The Blimp balloon has a very low scoring profile (0.6 mm) with a very high rated burst pressure (30 atmospheres). We aimed to evaluate the efficacy of this balloon compared to customary low-profile balloons. Methods We conducted a multicenter, prospective, randomised, controlled trial in which 126 patients with an uncrossable lesion were randomly (1:1 randomization) assigned to treatment first with the Blimp balloon or low-profile balloon. The primary endpoint was the success of crossing the lesion after initial failure with a microcatheter (group A) or with a conventional balloon (group B). Results Overall, the first attempt of Blimp was successful in 29 out of 61 cases (48%) while the LP balloon immediately crossed in 30 out 67 cases (45%; p = 0.761). Using a low-profile balloon in the BLIMP group after failure of the Blimp balloon increased the success to 64% (39 out of 61 cases). Using the Blimp balloon in the low-profile first group after failure of the low-profile balloon increased the success to 60% (40 out of 67 cases). After the placement of a guide catheter extension, the overall successful lesion crossing in the BLIMP group was 80% (49 out of 61 cases) compared to 76% (51 out of 67 cases) in the LP Balloon group (p = 0.327). Conclusions The Blimp balloon catheter showed no superiority to customary low-profile balloons in uncrossable lesions. It can however be complementary in treating uncrossable lesions.
Is survivorship an endless experience?

The article by Colonna and colleagues 1 in this issue of Cancer describes two indicators of cancer cure worthy of attention among French patients with cancer. The first indicator is the time beyond which the probability of death from cancer becomes lower than that of death from other causes. The second is the number of years needed for patients who are living after a cancer diagnosis to reach a probability ≤ 1% of death from cancer. The authors introduce an additional method to measure health status and to estimate the long- term excess risk of death in patients who are living after most common cancer types. Several approaches and statistical models have been proposed to estimate the cure fraction (i.e., the proportion of patients who will die from causes unrelated to their cancer), 2,3 the time to cure (the number of years after cancer diagnosis when the excess mortality from cancer becomes negligible), 4– 8 and other parameters helpful for classifying patients according to their risk of death or cancer recurrence. All of these approaches use reliable and widely reproducible methods. Therefore, in the last decade, many epidemiologic investigations have provided consistent estimates of cancer cure in high- income countries. shared definition word meanings— standard—
Vacuum-Structure and a Relativistic Pilot Wave

We study a model for analyzing the effect of a principal violation of the Lorentzinvariance on the structure of vacuum. The model is based on the divergence theory developed by Salehi (1997). It is shown that the divergence theory can be used to model an ensemble of particles. The ensemble is characterized by the condition that its members are basically at rest in the rest frame of a preferred inertial observer in vacuum. In this way we find a direct dynamical interplay between a particle and its associated ensemble. We show that this effect can be understood in terms of the interaction of a particle with a relativistic pilot wave through an associated quantum potential.
Path to Parkinson Disease Prevention

Tremendous progress in our understanding of the pathophysiology and clinical manifestations of the prodromal phase of Parkinson disease (PD) offers a unique opportunity to start therapeutic interventions as early as possible to slow or even stop the progression to clinically manifest motor PD. A Parkinson's Prevention Conference, “Planning for Prevention of Parkinson's: A trial design symposium and workshop” was convened to discuss all issues that need to be addressed before the launch of the first PD prevention study. In this review, we summarize the major opportunities and challenges in designing prevention trials in PD, organized by the following critical trial design questions: Who (should be enrolled)? What (to test)? How (to measure prevention)? and the pivotal question, When during the prodromal disease (should we start these trials)? We outline the implications of these questions and their meaning for a responsible, sustainable, and fruitful further planning for prevention trials. Despite the great progress that has been made, it needs to be acknowledged that several queries remain to be carefully considered and addressed because prevention trials are being planned and become a reality.
Characterisation of NLRP3 pathway-related neuroinflammation in temporal lobe epilepsy

Objective Inflammation of brain structures, in particular the hippocampal formation, can induce neuronal degeneration and be associated with increased excitability manifesting as propensity for repetitive seizures. An increase in the abundance of individual proinflammatory molecules including interleukin 1 beta has been observed in brain tissue samples of patients with pharmacoresistant temporal lobe epilepsy (TLE) and corresponding animal models. The NLRP3-inflammasome, a cytosolic protein complex, acts as a key regulator in proinflammatory innate immune signalling. Upon activation, it leads to the release of interleukin 1 beta and inflammation-mediated neurodegeneration. Transient brain insults, like status epilepticus (SE), can render hippocampi chronically hyperexcitable and induce segmental neurodegeneration. The underlying mechanisms are referred to as epileptogenesis. Here, we have tested the hypothesis that distinct NLRP3-dependent transcript and protein signalling dynamics are induced by SE and whether they differ between two classical SE models. We further correlated the association of NLRP3-related transcript abundance with convulsive activity in human TLE hippocampi of patients with and without associated neurodegenerative damage. Methods Hippocampal mRNA- and protein-expression of NLRP3 and associated signalling molecules were analysed longitudinally in pilocarpine- and kainic acid-induced SE TLE mouse models. Complementarily, we studied NLRP3 inflammasome-associated transcript patterns in epileptogenic hippocampi with different damage patterns of pharmacoresistant TLE patients that had undergone epilepsy surgery for seizure relief. Results Pilocarpine- and kainic acid-induced SE elicit distinct hippocampal Nlrp3-associated molecular signalling. Transcriptional activation of NLRP3 pathway elements is associated with seizure activity but independent of the particular neuronal damage phenotype in KA-induced and in human TLE hippocampi. Significance These data suggest highly dynamic inflammasome signalling in SE-induced TLE and highlight a vicious cycle associated with seizure activity. Our results provide promising perspectives for the inflammasome signalling pathway as a target for anti-epileptogenic and -convulsive therapeutic strategies. The latter may even applicable to a particularly broad spectrum of TLE patients with currently pharmacoresistant disease.
A feasibility study comparing gel immersion endoscopic resection and underwater endoscopic mucosal resection for superficial nonampullary duodenal epithelial tumors

Background Although gel immersion endoscopic resection (GIER) is a potential alternative to underwater endoscopic mucosal resection (UEMR) for superficial nonampullary duodenal epithelial tumors (SNADETs), comparisons between the two are currently insufficient. Methods 40 consecutive procedures performed in 35 patients were retrospectively reviewed; the primary outcome was procedure time, and the secondary outcomes were en bloc and R0 resection rates, tumor and specimen size, and adverse events. Results Lesions were divided into GIER (n = 22) and UEMR groups (n = 18). The median (range) procedure time was significantly shorter in the GIER group than in the UEMR group (2.75 [1–3.5] minutes vs. 3 2 3 4 5 6 7 8 9 10 minutes; P = 0.01). The en bloc resection rate was 100 % in the GIER group, but only 83.3 % in the UEMR group. The R0 resection rate was significantly higher in the GIER group than in the UEMR group (95.5 % vs. 66.7 %; P = 0.03). The median specimen size was larger in the GIER group than in the UEMR group (14 mm vs. 7.5 mm; P < 0.001). The tumor size was not significantly different between the groups and no adverse events were observed. Conclusions GIER is efficacious and safe to treat SNADETs, although additional studies are needed.
Patient-Reported Outcomes Correlate With Microbial Community Composition Independent of Mucosal Inflammation in Pediatric Inflammatory Bowel Disease.

BACKGROUND Inflammatory bowel diseases (IBDs) involve an aberrant host response to intestinal microbiota causing mucosal inflammation and gastrointestinal symptoms. Patient-reported outcomes (PROs) are increasingly important in clinical care and research. Our aim was to examine associations between PROs and fecal microbiota in patients 0 to 22 years of age with IBD. METHODS A longitudinal, prospective, single-center study tested for associations between microbial community composition via shotgun metagenomics and PROs including stool frequency and rectal bleeding in ulcerative colitis (UC) and abdominal pain and stool frequency in Crohn's disease (CD). Mucosal inflammation was assessed with fecal calprotectin. A negative binomial mixed-effects model including clinical characteristics and fecal calprotectin tested for differentially abundant species and metabolic pathways by PROs. RESULTS In 70 CD patients with 244 stool samples, abdominal pain correlated with increased relative abundance of Haemophilus and reduced Clostridium spp. There were no differences relative to calprotectin level. In 23 UC patients with 76 samples, both rectal bleeding and increased stool frequency correlated with increased Klebsiella and reduced Bacteroides spp. Conversely, UC patients with lower calprotectin had reduced Klebsiella. Both UC and CD patients with active symptoms exhibited less longitudinal microbial community stability. No differences in metabolic pathways were observed in CD. Increased sulfoglycolysis and ornithine biosynthesis correlated with symptomatic UC. CONCLUSIONS Microbial community composition correlated with PROs in both CD and UC. Metabolic pathways differed relative to PROs in UC, but not CD. Data suggest that microbiota may contribute to patient symptoms in IBD, in addition to effects of mucosal inflammation.
Analysis of Aspergillus versicolor exudate composition

Aspergillus versicolor, a widely distributed fungus, is associated with pollution and carcinogenic hazards. This study aimed to examine the functions of the A. versicolor exudate and laid a scientific foundation for improving our understanding, utilization, and control of A. versicolor. The A. versicolor exudate proteome, ion content, and amino acid components were determined using label‐free quantitation, atomic absorption spectrophotometry, and high‐performance liquid chromatography, respectively. In total, 502 proteins were identified in the A. versicolor exudate. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and cluster of orthologous group analyses were used to annotate the functional classification and pathways of the aligned proteins. Proteins identified in the exudate were mainly enriched in carbohydrate metabolic process, translation, oxidoreductase activity, oxidoreductase activity, hydrolase activity, cell wall‐related processes, catalytic activity, and unknown functions. The exudate comprised Na, K, Ca, Fe, and Mg cations. Among the 17 types of amino acids detected in the exudate, 7 were essential and 10 were nonessential. The exudate may be involved in the vital processes of A. versicolor. Additionally, the exudate may play an important role in the growth, development, reproduction, homeostasis, nutrient supply for regrowth, and virulence of A. versicolor.
The Chromatin Remodeler BRAHMA Recruits HISTONE DEACETYLASE6 to Regulate Root Growth Inhibition in Response to Phosphate Starvation in Arabidopsis.

Plasticity in root system architecture (RSA) allows plants to adapt to changing nutritional status in the soil. Phosphorus availability is a major determinant of crop yield, and RSA remodeling is critical to increasing the efficiency of phosphorus acquisition. Although substantial progress has been made in understanding the signaling mechanism driving phosphate starvation responses in plants, whether and how epigenetic regulatory mechanisms contribute is poorly understood. Here, we report that the Switch defective/sucrose non-fermentable (SWI/SNF) ATPase BRAHMA (BRM) is involved in the local response to phosphate (Pi) starvation. The loss of BRM function induces iron (Fe) accumulation through increased LOW PHOSPHATE ROOT1 (LPR1) and LPR2 expression, reducing primary root length under Pi deficiency. We also demonstrate that BRM recruits the histone deacetylase (HDA) complex HDA6-HDC1 to facilitate histone H3 deacetylation at LPR loci, thereby negatively regulating local Pi deficiency responses. BRM is degraded under Pi deficiency conditions through the 26S proteasome pathway, leading to increased histone H3 acetylation at the LPR loci. Collectively, our data suggest that the chromatin remodeler BRM, in concert with HDA6, negatively regulates Fe-dependent local Pi starvation responses by transcriptionally repressing the RSA-related genes LPR1 and LPR2 in Arabidopsis thaliana. This article is protected by copyright. All rights reserved.
Demystifying non-coding GWAS variants: an overview of computational tools and methods

Abstract Genome-wide association studies (GWAS) have found the majority of disease-associated variants to be non-coding. Major efforts into the charting of the non-coding regulatory landscapes have allowed for the development of tools and methods which aim to aid in the identification of causal variants and their mechanism of action. In this review, we give an overview of current tools and methods for the analysis of non-coding GWAS variants in disease. We provide a workflow that allows for the accumulation of in silico evidence to generate novel hypotheses on mechanisms underlying disease and prioritize targets for follow-up study using non-coding GWAS variants. Lastly, we discuss the need for comprehensive benchmarks and novel tools for the analysis of non-coding variants.
Reliable Design of PMaSynRM

Electric vehicles require highly reliable and resilient electric motors, due to the harsh operating conditions they must withstand. To this end, there is a current trend to design rareearth-free machines. Traction electric motors must be optimized in terms of efficiency, torque density, power factor, constant power speed ratio, and cost. Although different technologies are available, permanent magnet assisted synchronous reluctance motors (PMa-SynRM) are promising candidates for such applications. Nowadays, the optimal design process of electrical motors is based on finite element method (FEM) simulations. However, it is very time consumingwith a heavy computational burden process, so in order to speed up the optimization process, it is very appealing to have an accurate pre-design of the machine. In this chapter, the electromagnetic pre-design of a PMaSynRM is developed. In the proposed electromagnetic pre-design process, the geometry of the machine is calculated based on analytical equations that take into account the thermal, electrical, magnetic, and mechanical behavior of the machine to ensure a suitable and reliable design.
Evaluating the efficacy of Mazao Tickoff (Metarhizium anisopliae ICIPE 7) in controlling natural tick infestations on cattle in coastal Kenya: Study protocol for a randomized controlled trial

Ticks and tick-borne diseases cause substantial economic losses to the livestock industry in sub-Saharan Africa. Mazao Tickoff is a novel bioacaricide developed for tick control and is based on the entomopathogenic fungus Metarhizium anisopliae sensu lato (s.l.) isolate ICIPE 7. To date, no randomized controlled study has been undertaken to demonstrate the efficacy of this bioacaricide in reducing natural tick infestation on cattle. To this end, this field trial is designed to evaluate the anti-tick efficacy of Mazao Tickoff on cattle in coastal Kenya compared to a standard chemical tick control protocol. In this prospective, multi-center randomized controlled trial, eligible herds will be randomized by the herd size to the intervention arm in a 1:1:1 ratio to either Triatix® (active ingredient: amitraz); Mazao Tickoff (active ingredient: M. anisopliae ICIPE 7); or placebo (excipients of the Mazao Tickoff), with a total enrollment target of 1,077 cattle. Treatments will be dispensed on Day 0 (defined individually as the day each animal receives the first treatment) and thereafter every two weeks until Day 182. Ticks will be counted on every animal in each herd (herds to be included have at least one animal bearing at least one tick on Day 0), and thereafter on bi-weekly intervals until Day 182. The primary efficacy assessments of Mazao Tickoff will be based on the mean percentage reduction in tick counts at each post-treatment follow-up visit compared to the placebo group and the Triatix® arm. Further, the effect of Mazao Tickoff on the prevalence of common cattle pathogens, Anaplasma marginale and Theileria parva, will be determined by assessing incidence and seroprevalence at four different time points. This protocol describes the first rigorous evaluation of the efficacy of Mazao Tickoff and its potential as a viable alternative non-chemical acaricide tool for tick control in Kenya and elsewhere.