Miracle-dz/UniFAR-FTUs huggingface dataset:
Rapid Identification and Evaluation of Neoantigen-reactive T-Cell Receptors From Single Cells

Supplemental Digital Content is available in the text. Engineered T cells expressing tumor-specific T-cell receptors (TCRs) are emerging as a mode of personalized cancer immunotherapy that requires identification of TCRs against the products of known driver mutations and novel mutations in a timely fashion. We present a nonviral and non–next-generation sequencing platform for rapid, and efficient neoantigen-specific TCR identification and evaluation that does not require the use of recombinant cloning techniques. The platform includes an innovative method of TCRα detection using Sanger sequencing, TCR pairings and the use of TCRα/β gene fragments for putative TCR evaluation. Using patients’ samples, we validated and compared our new methods head-to-head with conventional approaches used for TCR discovery. Development of a unique demultiplexing method for identification of TCRα, adaptation of synthetic TCRs for gene transfer, and a reliable reporter system significantly shortens TCR discovery time over conventional methods and increases throughput to facilitate testing prospective personalized TCRs for adoptive cell therapy.
Lessons learned from clinical phenotypes in early psoriatic arthritis: the real-world Dutch south west Early Psoriatic ARthritis study

Objective: This paper describes the baseline demographics, clinical characteristics, and patient-reported outcomes (PROs) according to clinical phenotype of patients with early psoriatic arthritis (PsA) for the purpose of creating a decision support system for daily clinical practice. Method: Patients with newly diagnosed PsA were included in the Dutch south west Early Psoriatic ARthritis (DEPAR) study. No classification criteria were applied, to ensure collection of real-world data on demographics, medication, clinical characteristics, and PROs. An IT infrastructure facilitated data collection. Results: We described 527 patients, categorized according to the clinical phenotype stated by the rheumatologist at the time of diagnosis, namely monoarthritis (15%), oligoarthritis (40%), polyarthritis (23%), enthesitis (10%), axial disease (2%), and dactylitis (10%). Overall psoriasis severity was mild and 83 patients (16%) had no psoriasis. Short-term sick leave (> 1 day per 4 weeks) was 17% and long-term sick leave (> 4 weeks) was 4%. The group with phenotype enthesitis reported the longest duration of complaints, had the highest fatigue scores, and contained the highest percentage of patients with a Hospital Anxiety and Depression Scale (HADS) anxiety score ≥ 8 and depression score ≥ 8. Conclusion: PsA patients presenting at outpatient clinics in the Netherlands had a mild degree of psoriasis, with impairment of quality of life and work productivity. Most patients presented with phenotype oligoarthritis. Those presenting with phenotype enthesitis more often reported scores suggestive of an anxiety or depression disorder and fatigue. It is important for attending rheumatologists to be aware of these differences when assessing patients with PsA.
A Simplified and Efficient Method for Himar-1 Transposon Sequencing in Bacteria, Demonstrated by Creation and Analysis of a Saturated Transposon-Mutant Library in Mycobacterium abscessus

Transposon insertion sequencing is a powerful tool, but many researchers are discouraged by the apparent technical complexity of preparing the genomic library for deep sequencing and by the complicated computational analysis needed for insertion site identification. Our proposed method makes the preparation of the library easy and straightforward, relying on well-known molecular biology techniques. In addition, the results obtained from the deep sequencing are easily analyzed in terms of transposon insertion site identification, placing library preparation and analysis within the reach of more researchers in the microbiology community, including those with less computational and bioinformatic resources and experience. This is demonstrated by analysis of the most saturated Tn-mutant library created to date in the emerging pathogen Mycobacterium abscessus. ABSTRACT We present a technically simple, easy-to-perform method for generating the genomic libraries for Himar-1 transposon site sequencing (Tn-seq). In addition to being simpler than present methods in the technical aspect, it also allows more robust and straightforward identification of the insertion site, by generating a longer sequence surrounding the insertion TA in the genome. The method makes Tn-seq more user-friendly and accessible to laboratories with more-limited bioinformatic resources. Finally, we created a saturated transposon-mutant library in Mycobacterium abscessus and demonstrated the usefulness of the method in analysis of genes involved in colony morphology, as well as in analysis of the whole Tn-mutant library, with identification of over 8,000 unique mutants. IMPORTANCE Transposon insertion sequencing is a powerful tool, but many researchers are discouraged by the apparent technical complexity of preparing the genomic library for deep sequencing and by the complicated computational analysis needed for insertion site identification. Our proposed method makes the preparation of the library easy and straightforward, relying on well-known molecular biology techniques. In addition, the results obtained from the deep sequencing are easily analyzed in terms of transposon insertion site identification, placing library preparation and analysis within the reach of more researchers in the microbiology community, including those with less computational and bioinformatic resources and experience. This is demonstrated by analysis of the most saturated Tn-mutant library created to date in the emerging pathogen Mycobacterium abscessus.
Effect of baicalin on gestational hypertension-induced vascular endothelial cell damage

Objective Baicalin is a compound extracted from the dried root of Scutellaria baicalensis Georgi. Studies have shown that baicalin has a protective effect on vascular endothelial cells, but whether baicalin could alleviate ascular endothelial cell damage in pregnancy-induced hypertensive patients remains unknown. Materials and methods We established a hypertensive pregnant rat model to study vascular endothelial injury during pregnancy-induced hypertension. Plasma epoprostenol (PGI-2), thromboxane A2 (Txa-2), β-human chorionic gonadotropin (β-HCG), and estrogen levels in rats were detected using ELISA. Vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), and C-reactive protein (CRP) expression were detected using western blotting and quantitative PCR (q-PCR). Results Results showed that baicalin alleviated symptoms of pregnancy-induced hypertension. CRP, Txa-2, and β-HCG expression were significantly upregulated, while VEGF, eNOS, PGI-2, and estrogen expression was decreased in plasma and placental tissues of hypertensive rats. However, the levels of these injury indicators were significantly decreased after baicalin therapy, while the expression of protective indicators was significantly increased. Conclusion Baicalin reversed vascular endothelial cell injury in pregnant hypertensive rats by promoting VEGF, eNOS, PGI-2, and estrogen expression.
The WNT/β‐catenin dependent transcription: A tissue‐specific business

Abstract β‐catenin‐mediated Wnt signaling is an ancient cell‐communication pathway in which β‐catenin drives the expression of certain genes as a consequence of the trigger given by extracellular WNT molecules. The events occurring from signal to transcription are evolutionarily conserved, and their final output orchestrates countless processes during embryonic development and tissue homeostasis. Importantly, a dysfunctional Wnt/β‐catenin pathway causes developmental malformations, and its aberrant activation is the root of several types of cancer. A rich literature describes the multitude of nuclear players that cooperate with β‐catenin to generate a transcriptional program. However, a unified theory of how β‐catenin drives target gene expression is still missing. We will discuss two types of β‐catenin interactors: transcription factors that allow β‐catenin to localize at target regions on the DNA, and transcriptional co‐factors that ultimately activate gene expression. In contrast to the presumed universality of β‐catenin's action, the ensemble of available evidence suggests a view in which β‐catenin drives a complex system of responses in different cells and tissues. A malleable armamentarium of players might interact with β‐catenin in order to activate the right “canonical” targets in each tissue, developmental stage, or disease context. Discovering the mechanism by which each tissue‐specific β‐catenin response is executed will be crucial to comprehend how a seemingly universal pathway fosters a wide spectrum of processes during development and homeostasis. Perhaps more importantly, this could ultimately inform us about which are the tumor‐specific components that need to be targeted to dampen the activity of oncogenic β‐catenin. This article is categorized under: Cancer > Molecular and Cellular Physiology Cancer > Genetics/Genomics/Epigenetics Cancer > Stem Cells and Development
Regulation of Reactive Oxygen Species-Mediated Damage in the Pathogenesis of Schizophrenia

The biochemical integrity of the brain is paramount to the function of the central nervous system, and oxidative stress is a key contributor to cerebral biochemical impairment. Oxidative stress, which occurs when an imbalance arises between the production of reactive oxygen species (ROS) and the efficacy of the antioxidant defense mechanism, is believed to play a role in the pathophysiology of various brain disorders. One such disorder, schizophrenia, not only causes lifelong disability but also induces severe emotional distress; however, because of its onset in early adolescence or adulthood and its progressive development, consuming natural antioxidant products may help regulate the pathogenesis of schizophrenia. Therefore, elucidating the functions of ROS and dietary antioxidants in the pathogenesis of schizophrenia could help formulate improved therapeutic strategies for its prevention and treatment. This review focuses specifically on the roles of ROS and oxidative damage in the pathophysiology of schizophrenia, as well as the effects of nutrition, antipsychotic use, cognitive therapies, and quality of life on patients with schizophrenia. By improving our understanding of the effects of various nutrients on schizophrenia, it may become possible to develop nutritional strategies and supplements to treat the disorder, alleviate its symptoms, and facilitate long-term recovery.
The Prognostic Role of Glutathione Peroxidase 1 and Immune Infiltrates in Glioma Investigated Using Public Datasets

Background Glutathione peroxidase 1 (GPX1) is an essential component of the intracellular antioxidant enzyme system, but little is known about the role of GPX1 in the progression of malignancy in gliomas. Using public datasets, this study investigated the prognostic role of GPX1 and immune infiltrates in glioma. Material/Methods We investigated GPX1 expression levels in different cancers using the ONCOMINE and Tumor Immune Estimation Resource (TIMER) datasets. We also explored the prognostic landscape of GPX1 in gliomas based on The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) datasets. Some significant pathways were identified by function enrichment analysis. We then explored the association between GPX1 expression and levels of tumor-infiltrating immune cells based on TIMER and Gene Expression Profiling Interactive Analysis (GEPIA) datasets. Results Expression of GPX1 in brain and central nervous system cancers is at a much high level than in normal tissues, and it is higher in glioblastoma (GBM) than in lower-grade glioma (LGG). We found GPX1 expression to be positively correlated with the malignant clinicopathologic characteristics of gliomas. Univariate analysis and multivariate analysis revealed that overexpression of GPX1 was correlated with a worse prognosis in patients, and a nomogram indicated that GPX1 expression can predict clinical prognosis of glioma. Function enrichment analysis showed that some important pathways are related to glioma malignancy. Expression of GPX1 was positively associated with infiltrating levels of 6 types of immune cells and most of their gene markers in GBM and LGG. Conclusions These results indicate that GPX1 is an independent prognostic factor and a novel biomarker for predicting the progression of malignancy in gliomas, which is associated with immune infiltration.
Understanding the experience of initiating community-based group physical activity by people with serious mental illness: A systematic review using a meta-ethnographic approach

Abstract Background People living with serious mental illness (SMI) experience debilitating symptoms that worsen their physical health and quality of life. Regular physical activity (PA) may bring symptomatic improvements and enhance wellbeing. When undertaken in community-based group settings, PA may yield additional benefits such as reduced isolation. Initiating PA can be difficult for people with SMI, so PA engagement is commonly low. Designing acceptable and effective PA programs requires a better understanding of the lived experiences of PA initiation among people with SMI. Methods This systematic review of qualitative studies used the meta-ethnography approach by Noblit and Hare (1988). Electronic databases were searched from inception to November 2017. Eligible studies used qualitative methodology; involved adults (≥18 years) with schizophrenia, bipolar affective disorder, major depressive disorder, or psychosis; reported community-based group PA; and captured the experience of PA initiation, including key features of social support. Study selection and quality assessment were performed by four reviewers. Results Sixteen studies were included in the review. We identified a “journey” that depicted a long sequence of phases involved in initiating PA. The journey demonstrated the thought processes, expectations, barriers, and support needs of people with SMI. In particular, social support from a trusted source played an important role in getting people to the activity, both physically and emotionally. Discussion The journey illustrated that initiation of PA for people with SMI is a long complex transition. This complex process needs to be understood before ongoing participation in PA can be addressed. Registration—The review was registered on the International Prospective Register of Systematic Reviews (PROSPERO) on 22/03/2017 (registration number CRD42017059948).
Influence of Flood Pulse on Termite Diversity (INSECTA: ISOPTERA) in the Pantanal

This research aimed to associate termite diversity to flood pulse by Paraguay River, and with savannas and pasture areas. The study was conducted nearby the town of Caceres, in Pantanal - Mato Grosso, on six livestock farms subject to Paraguay River flood pulse. Types of land use sampled were native savanna and cultivated pasture. Flooded and dry plots were selected, both the savanna and the pasture in each sampling area. Termite richness and abundance was analysed based on the environments as an explanatory variable (FP – flooded pasture, DP – dry pasture, FS – flooded savanna, DS – dry savanna) through GLM; Tukey’s test was subsequently performed to determine whether land use and/or flood pulse can significantly affect the termite community. There were 37 termite species and 19 genera. Richness and abundance of termite species cannot be explain by flooding pulse, but were explained only by land use (pasture and savanna). The similarity analysis also identified that species composition was quite affected by flood in grazing areas, but this disturbance does not affect the savanna areas. In conclusion, flood pulse is not a determining factor for savannas or pasture termite richness, but change the composition of the termite fauna in the environment.
An Exploration of the Function of Specific Components of the Predicted Secretome of Fusarium graminearum During Wheat Infection

Fusarium graminearum is a major fungal pathogen of wheat and other small grain cereal crops globally, causing Fusarium ear blight (FEB) disease. Like many other plant pathogens, F. graminearum is predicted to produce in planta secreted effector proteins that modulate plant metabolism to suppress or re-programme plant defences. Understanding the molecular functions of Fg effectors will help to elucidate the processes underlying wheat spike colonisation and fungal pathogenicity. With the aim of identifying Fg effector proteins that can suppress host plant defences, I selected using next generation sequencing and bioinformatic analysis, a set of small secreted proteins (SSP) to express in planta using the Barley stripe mosaic virus over-expression system (BSMV-VOX). I then tested whether expression of any of these SSPs enhanced Fg fungal infection of susceptible wheat spikes. Amongst the set of Fg SSP tested, FgSSP8, which encodes a ribonuclease protein, induced strong symptoms of necrosis in N. benthamiana leaves when infiltrated via the BSMV:FgSSP8. Three other genes tested (FgSSP7, FgSSP6 and FgSSP5) enhance FEB disease formation in the majority of the experiments when overexpressed in wheat ears prior to infecting with F. graminearum. FgSSP6 and FgSSP7 belong to the cerato-platanin protein (CPP) family. In several other plant pathogenic fungi, CPPs have been implicated in a number of virulence and plant protection mechanisms, including induction of host plant cell death, binding specific polymers and/or expansin-like activity. FgSSP5 encodes a protein that possesses the pfam domain RALF (Rapid alkalinization factor; PF05498.6). RALF domain-containing proteins are predominately found in plants and play a role in plant development regulating tissue expansion and/or negatively regulating pollen tube elongation. BLAST analyses identified RALF domain containing proteins in a restricted range of different pathogen species. Based on the VOX results and biochemical tests, our hypothesis is that pre-elevated cerato-platanins (FgSSP6 and FgSSP7) levels in the apoplast/surrounding the hyphae could initially shield the hyphae from detection by the plant, but late induce an intense defence response culminating in cell death to benefit the necrotrophic phase of Fg by increasing nutrient availability. FgSSP5 may be a specific virulence factor that manipulates a key plant process, by alkalinising the plant environment during infection, and using the same plant receptor repertoire used to recognise plant proteins. Once the mechanisms are further understood, these genes/proteins could potentially be novel intervention targets either for conventional chemistries and/or for methods such as host-induced gene silencing to achieve FEB disease and/or mycotoxin control. The characterisation of single and double gene deletion F. graminearum mutants is in progress.
Agro-Morphological and Chemical Traits Diversity in Nine Maize (Zea mays L.) Genotypes

Diversity of traits is a major need of any plant breeding program that concerns the natural evolution and causes sustainable plant production under various environments. Phenotypic variations based on agro-morphological and chemical traits of nine maize genotypes were studied under field and laboratory conditions during 2015 at the experimental farm of the Faculty of Agricultural Sciences, Qlyasan in Iraq. The genotypes differed significantly for all traits studied. Fajr 260 was the tallest plant. Talar was the latest genotype for number of days to tasseling and silking while Es-Solito 635 needed the maximum number of days for harvesting. The best performances of number of kernels per row, the number of kernels per ear and kernels yield were observed by genotypes Btaris and Cantabpis. Plant height, number of kernels per row, ear weight and kernel weight per ear were the most influential characters that conferred to the genetic diversity. Data indicated a wide range of variation among maize genotypes for traits of oil and protein contents. Talar had the maximum kernel oil and ash content; whereas, Iranian genotypes exhibited the lowest values of all chemical composition traits. The results of the principal component analysis (PCA) showed that the first two components accounted for more than 62.35% of total variation. Cluster analysis based on 23 traits exhibited three distinct clusters. High similarity was observed between Cantapbis and Bataris. At the same time, ZP434xA and Talar were more differentiated from others. This information about the genetic diversity may be utilized in the future maize breeding programs.
Estimation of HRV Based on Low Frequency Data Transmission

Smart devices, including the popular smart watches, often collect information on the heart beat rhythm and transmit it to a central server for storage or further processing. A factor introducing important limitations in the amount of data collected, transmitted and finally processed is the life of the mobile device or smart watch battery. Some devices choose to transmit the mean heart rate over relatively long periods of time, to save power. Heart Rate Variability (HRV) analysis gives useful information about the human heart, by only examining the heart rate time series. Its discriminating capability is affected by the amount of available information to process. Ideally, the whole RR interval time series should be used. We investigate here how this discriminating capability is affected, when the analysis is based on mean heart rate values transmitted over relatively long time periods. We show that we still can get useful information and the discriminating power is still remarkable, even when the amount of the available data is relatively small.
The ecological relevance of chemical diversity in plants : pyrrolizidine alkaloids in Jacobaea species

The Jacobaea hybrid system has been proved to be a good tool to study the interaction between PA variation and herbivore resistance. Based on this hybrid system, we have explored how the biotic and abiotic factors influence the PA diversity. All the herbivore tests were integrated to draw the general conclusion that the selection pressures from different herbivores contribute to the diversity in PA composition and that generalist and specialist herbivores exert a divergent selection pressure on PA concentrations. The PAs showed seasonal variation within each genotype and the relative differences between genotypes remained constant over time, which was the first study to report the seasonal variation of SMs. The application of MeJA can lead to a shift in PA composition and primary metabolites. Importantly the shift in metabolite diversity induced by MeJA application can conversely affect the feeding of chewing herbivores and cell-content feeders. However, SA application did not lead to significant changes in PAs and the metabolite profile changes detected by NMR rendered J. aquatica more resistance to piercing-sucking herbivore thrips, showing that PAs did not affect thrips resistance. Several metabolites detected by NMR were found to be correlated with resistance and susceptibility to thrips F. occidentalis.