Miracle-dz/UniFAR-FTUs huggingface dataset:
Relationships between Dream and Previous Wake Emotions Assessed through the Italian Modified Differential Emotions Scale

Despite the increasing interest in sleep and dream-related processes of emotion regulation, their reflection into wake and dream emotional experience remains unclear. Here, we aimed to assess dream emotions and their relationships with wake emotions through the modified Differential Emotions Scale (Fredrickson, 2003), which includes a broad array of both positive and negative emotions. The scale has been first validated on 212 healthy Italian participants, in two versions: a WAKE-2wks form, assessing the frequency of 22 emotions over the past 2 weeks, and a WAKE-24hr form, assessing their intensity over the past 24 h. Fifty volunteers from the wider sample completed the WAKE-24hr mDES for several days until a dream was recalled, and dream emotions were self-reported using the same scale. A bifactorial structure was confirmed for both mDES forms, which also showed good validity and reliability. Though Positive and Negative Affect (average intensity of positive and negative items, PA, and NA, respectively) were balanced in dreams, specific negative emotions prevailed; rmANOVA showed a different pattern (prevalence of PA and positive emotions) in wake (both WAKE-2wks and WAKE-24hr), with a decrease of PA and an increase of NA in the dream compared to previous wake. No significant regression model emerged between waking and dream affect, and exploratory analyses revealed a stable proportion of PA and NA (with prevailing PA) over the 3 days preceding the dream. Our findings highlight a discontinuity between wake and dream affect and suggest that positive and negative emotions experienced during wake may undertake distinct sleep-related regulation pathways.
A content-based dataset recommendation system for researchers—a case study on Gene Expression Omnibus (GEO) repository

Abstract It is a growing trend among researchers to make their data publicly available for experimental reproducibility and data reusability. Sharing data with fellow researchers helps in increasing the visibility of the work. On the other hand, there are researchers who are inhibited by the lack of data resources. To overcome this challenge, many repositories and knowledge bases have been established to date to ease data sharing. Further, in the past two decades, there has been an exponential increase in the number of datasets added to these dataset repositories. However, most of these repositories are domain-specific, and none of them can recommend datasets to researchers/users. Naturally, it is challenging for a researcher to keep track of all the relevant repositories for potential use. Thus, a dataset recommender system that recommends datasets to a researcher based on previous publications can enhance their productivity and expedite further research. This work adopts an information retrieval (IR) paradigm for dataset recommendation. We hypothesize that two fundamental differences exist between dataset recommendation and PubMed-style biomedical IR beyond the corpus. First, instead of keywords, the query is the researcher, embodied by his or her publications. Second, to filter the relevant datasets from non-relevant ones, researchers are better represented by a set of interests, as opposed to the entire body of their research. This second approach is implemented using a non-parametric clustering technique. These clusters are used to recommend datasets for each researcher using the cosine similarity between the vector representations of publication clusters and datasets. The maximum normalized discounted cumulative gain at 10 (NDCG@10), precision at 10 (p@10) partial and p@10 strict of 0.89, 0.78 and 0.61, respectively, were obtained using the proposed method after manual evaluation by five researchers. As per the best of our knowledge, this is the first study of its kind on content-based dataset recommendation. We hope that this system will further promote data sharing, offset the researchers’ workload in identifying the right dataset and increase the reusability of biomedical datasets. Database URL: http://genestudy.org/recommends/#/
Cryo‐electron microscopy structure of human ABCB6 transporter

Human ATP‐binding cassette transporter 6 of subfamily B (ABCB6) is an ABC transporter involved in the translocation toxic metals and anti‐cancer drugs. Using cryo‐electron microscopy, we determined the molecular structure of full‐length ABCB6 in an apo state. The structure of ABCB6 unravels the architecture of a full‐length ABCB transporter that harbors two N‐terminal transmembrane domains which is indispensable for its ATPase activity in our in vitro assay. A slit‐like substrate binding pocket of ABCB6 may accommodate the planar shape of porphyrins, and the existence of a secondary cavity near the mitochondrial intermembrane space side would further facilitate substrate release. Furthermore, the ATPase activity of ABCB6 stimulated with a variety of porphyrin substrates showed different profiles in the presence of glutathione (GSH), suggesting the action of a distinct substrate translocation mechanism depending on the use of GSH as a cofactor.
An Asthma Population Health Improvement Initiative for Children With Frequent Hospitalizations

In this study, we evaluate the effects of a multidisciplinary QI initiative to reduce emergency care for frequently hospitalized children with asthma, confirming the findings by using difference in differences. OBJECTIVES: A relatively small proportion of children with asthma account for an outsized proportion of health care use. Our goal was to use quality improvement methodology to reduce repeat emergency department (ED) and inpatient care for patients with frequent asthma-related hospitalization. METHODS: Children ages 2 to 17 with ≥3 asthma-related hospitalizations in the previous year who received primary care at 3 in-network clinics were eligible to receive a bundle of 4 services including (1) a high-risk asthma screener and tailored education, (2) referral to a clinic-based asthma community health worker program, (3) facilitated discharge medication filling, and (4) expedited follow-up with an allergy or pulmonology specialist. Statistical process control charts were used to estimate the impact of the intervention on monthly 30-day revisits to the ED or hospital. We then conducted a difference-in-differences analysis to compare changes between those receiving the intervention and a contemporaneous comparison group. RESULTS: From May 1, 2016, to April 30, 2017, we enrolled 79 patients in the intervention, and 128 patients constituted the control group. Among the eligible population, the average monthly proportion of children experiencing a revisit to the ED and hospital within 30 days declined by 38%, from a historical baseline of 24% to 15%. Difference-in-differences analysis demonstrated 11.0 fewer 30-day revisits per 100 patients per month among intervention recipients relative to controls (95% confidence interval: −20.2 to −1.8; P = .02). CONCLUSIONS: A multidisciplinary quality improvement intervention reduced health care use in a high-risk asthma population, which was confirmed by using quasi-experimental methodology. In this study, we provide a framework to analyze broader interventions targeted to frequently hospitalized populations.
Neuroprotective Effects of Chronic Resveratrol Treatment and Exercise Training in the 3xTg-AD Mouse Model of Alzheimer’s Disease

To date, there is no cure or effective treatment for Alzheimer’s disease (AD), a chronic neurodegenerative condition that affects memory, language, and behavior. AD is characterized by neuroinflammation, accumulation of brain amyloid-beta (Aβ) oligomers and neurofibrillary tangles, increased neuronal apoptosis, and loss of synaptic function. Promoting regular exercise and a diet containing polyphenols are effective non-pharmacological approaches that prevent the progression of neurodegenerative diseases. In this study, we measured various conformational toxic species of Aβ and markers of inflammation, apoptosis, endolysosomal degradation, and neuroprotection after 5 months of exercise training (ET), resveratrol (Resv) treatment, or combination treatment in the 3xTg-AD mouse model of AD. Our main results indicate that Resv decreased neuroinflammation and accumulation of Aβ oligomers, increased levels of neurotrophins, synaptic markers, silent information regulator, and decreased markers of apoptosis, autophagy, endolysosomal degradation and ubiquitination in the brains of 3xTg-AD mice. ET improved some markers related to neuroprotection, but when combined with Resv treatment, the benefits achieved were as effective as Resv treatment alone. Our results show that the neuroprotective effects of Resv, ET or Resv and ET are associated with reduced toxicity of Aβ oligomers, suppression of neuronal autophagy, decreased apoptosis, and upregulation of key growth-related proteins.
Spontaneous Right Ventricular Pseudoaneurysms and Increased Arrhythmogenicity in a Mouse Model of Marfan Syndrome

Patients with Marfan syndrome (MFS), a connective tissue disorder caused by pathogenic variants in the gene encoding the extracellular matrix protein fibrillin-1, have an increased prevalence of primary cardiomyopathy, arrhythmias, and sudden cardiac death. We have performed an in-depth in vivo and ex vivo study of the cardiac phenotype of Fbn1mgR/mgR mice, an established mouse model of MFS with a severely reduced expression of fibrillin-1. Using ultrasound measurements, we confirmed the presence of aortic dilatation and observed cardiac diastolic dysfunction in male Fbn1mgR/mgR mice. Upon post-mortem examination, we discovered that the mutant mice consistently presented myocardial lesions at the level of the right ventricular free wall, which we characterized as spontaneous pseudoaneurysms. Histological investigation demonstrated a decrease in myocardial compaction in the MFS mouse model. Furthermore, continuous 24 h electrocardiographic analysis showed a decreased heart rate variability and an increased prevalence of extrasystolic arrhythmic events in Fbn1mgR/mgR mice compared to wild-type littermates. Taken together, in this paper we document a previously unreported cardiac phenotype in the Fbn1mgR/mgR MFS mouse model and provide a detailed characterization of the cardiac dysfunction and rhythm disorders which are caused by fibrillin-1 deficiency. These findings highlight the wide spectrum of cardiac manifestations of MFS, which might have implications for patient care.
Stability of Alkyl Chain-Mediated Lipid Anchoring in Liposomal Membranes

Lipid exchange among biological membranes, lipoprotein particles, micelles, and liposomes is an important yet underrated phenomenon with repercussions throughout the life sciences. The premature loss of lipid molecules from liposomal formulations severely impacts therapeutic applications of the latter and thus limits the type of lipids and lipid conjugates available for fine-tuning liposomal properties. While cholesterol derivatives, with their irregular lipophilic surface shape, are known to readily undergo lipid exchange and interconvert, e.g., with serum, the situation is unclear for lipids with regular, linear-shaped alkyl chains. This study compares the propensity of fluorescence-labeled lipid conjugates of systematically varied lengths to migrate from liposomal particles consisting mainly of egg phosphatidyl choline 3 (EPC3) and cholesterol into biomembranes. We show that dialkyl glyceryl lipids with chains of 18–20 methylene units are inherently stable in liposomal membranes. In contrast, C16 lipids show some lipid exchange, albeit significantly less than comparable cholesterol conjugates. Remarkably, the C18 chain length, which confers noticeable anchor stability, corresponds to the typical chain length in biological membranes.
Review on Structures of Pesticide Targets

Molecular targets play important roles in agrochemical discovery. Numerous pesticides target the key proteins in pathogens, insect, or plants. Investigating ligand-binding pockets and/or active sites in the proteins’ structures is usually the first step in designing new green pesticides. Thus, molecular target structures are extremely important for the discovery and development of such pesticides. In this manuscript, we present a review of the molecular target structures, including those of antiviral, fungicidal, bactericidal, insecticidal, herbicidal, and plant growth-regulator targets, currently used in agrochemical research. The data will be helpful in pesticide design and the discovery of new green pesticides.
An improved whole life cycle culture protocol for the hydrozoan genetic model Clytia hemisphaerica

ABSTRACT The jellyfish species Clytia hemisphaerica (Cnidaria, Hydrozoa) has emerged as a new experimental model animal in the last decade. Favorable characteristics include a fully transparent body suitable for microscopy, daily gamete production and a relatively short life cycle. Furthermore, whole genome sequence assembly and efficient gene editing techniques using CRISPR/Cas9 have opened new possibilities for genetic studies. The quasi-immortal vegetatively-growing polyp colony stage provides a practical means to maintain mutant strains. In the context of developing Clytia as a genetic model, we report here an improved whole life cycle culture method including an aquarium tank system designed for culture of the tiny jellyfish form. We have compared different feeding regimes using Artemia larvae as food and demonstrate that the stage-dependent feeding control is the key for rapid and reliable medusa and polyp rearing. Metamorphosis of the planula larvae into a polyp colony can be induced efficiently using a new synthetic peptide. The optimized procedures detailed here make it practical to generate genetically modified Clytia strains and to maintain their whole life cycle in the laboratory. This article has an associated First Person interview with the two first authors of the paper. Summary: We developed a reliable whole life cycle culture method for the hydrozoan jellyfish Clytia hemisphaerica, a model animal for genetics and developmental biology.
Integrated Multiparametric Radiomics and Informatics System for Characterizing Breast Tumor Characteristics with the OncotypeDX Gene Assay

Simple Summary Artificial Intelligence methods using machine learning and radiomics is an emerging area of research for radiological and oncological applications for patient management. Recent evidence from breast cancer suggests that different breast cancer subtypes may respond differently to adjuvant therapies. The use of a 21-gene array assay called OncotypeDX can predict potential recurrence of cancer in patients with estrogen positive breast cancer after treatment, however, there are potential cost disadvantages that hamper its widespread use. Multiparametric magnetic resonance imaging can simultaneously identify key functional parameters and provide unique imaging phenotypes of breast cancer, which is used in radiomic analysis. Radiomics provide quantitative information of different tissue types. We have developed a new machine learning radiomic informatics tool that integrates clinical and imaging variables, single, and multiparametric radiomics to compare with the OncotypeDX test to stratify patients into three risk groups: low, medium, and high risk of breast cancer recurrence. Abstract Optimal use of multiparametric magnetic resonance imaging (mpMRI) can identify key MRI parameters and provide unique tissue signatures defining phenotypes of breast cancer. We have developed and implemented a new machine-learning informatic system, termed Informatics Radiomics Integration System (IRIS) that integrates clinical variables, derived from imaging and electronic medical health records (EHR) with multiparametric radiomics (mpRad) for identifying potential risk of local or systemic recurrence in breast cancer patients. We tested the model in patients (n = 80) who had Estrogen Receptor positive disease and underwent OncotypeDX gene testing, radiomic analysis, and breast mpMRI. The IRIS method was trained using the mpMRI, clinical, pathologic, and radiomic descriptors for prediction of the OncotypeDX risk score. The trained mpRad IRIS model had a 95% and specificity was 83% with an Area Under the Curve (AUC) of 0.89 for classifying low risk patients from the intermediate and high-risk groups. The lesion size was larger for the high-risk group (2.9 ± 1.7 mm) and lower for both low risk (1.9 ± 1.3 mm) and intermediate risk (1.7 ± 1.4 mm) groups. The lesion apparent diffusion coefficient (ADC) map values for high- and intermediate-risk groups were significantly (p < 0.05) lower than the low-risk group (1.14 vs. 1.49 × 10−3 mm2/s). These initial studies provide deeper insight into the clinical, pathological, quantitative imaging, and radiomic features, and provide the foundation to relate these features to the assessment of treatment response for improved personalized medicine.
IMPACT OF FOLIAR FERTILIZER ON PHYSIOLOGICAL COMPOUNDS IN DIFFERENT APRICOT VARIETIES

In the last decade applying of nutritive elements by foliar spraying became a usual practice for many crops, with benefit part in balancing of plant nutrition. Also, foliar fertilization have a practical and economical importance and have a low risk for environmental pollution. Implication in physiological processes, and in general in the plant metabolism of nutritive substances adsorbed by the leaves have an important role in increasing the adaptative capacity of trees to the stress conditions and therefore for growth production. The influence of foliar fertilizer on physiological and biochemical parameters of different apricot varieties was studied during two seasons at experimental orchard of Research Station Baneasa. Results indicated the increase of photosynthetic pigments content proved by a better function of photosynthetic apparatus. It also was found that polyphenolic compounds increased, which denotes the activation of tree defence mechanism for a better stress resistance.
CAR T cells targeting tumor endothelial marker CLEC14A inhibit tumor growth

Engineering T cells to express chimeric antigen receptors (CARs) specific for antigens on hematological cancers has yielded remarkable clinical responses, but with solid tumors, benefit has been more limited. This may reflect lack of suitable target antigens, immune evasion mechanisms in malignant cells, and/or lack of T cell infiltration into tumors. An alternative approach, to circumvent these problems, is targeting the tumor vasculature rather than the malignant cells directly. CLEC14A is a glycoprotein selectively overexpressed on the vasculature of many solid human cancers and is, therefore, of considerable interest as a target antigen. Here, we generated CARs from 2 CLEC14A-specific antibodies and expressed them in T cells. In vitro studies demonstrated that, when exposed to their target antigen, these engineered T cells proliferate, release IFN-γ, and mediate cytotoxicity. Infusing CAR engineered T cells into healthy mice showed no signs of toxicity, yet these T cells targeted tumor tissue and significantly inhibited tumor growth in 3 mouse models of cancer (Rip-Tag2, mPDAC, and Lewis lung carcinoma). Reduced tumor burden also correlated with significant loss of CLEC14A expression and reduced vascular density within malignant tissues. These data suggest the tumor vasculature can be safely and effectively targeted with CLEC14A-specific CAR T cells, offering a potent and widely applicable therapy for cancer.
Dioxin Disrupts Dynamic DNA Methylation Patterns in Genes that Govern Cardiomyocyte Maturation.

Congenital heart disease (CHD), the leading birth defect worldwide, has a largely unknown etiology, likely to result from complex interactions between genetic and environmental factors during heart development, at a time when the heart adapts to diverse physiological and pathophysiological conditions. Crucial among these is the regulation of cardiomyocyte development and postnatal maturation, governed by dynamic changes in DNA methylation. Previous work from our laboratory has shown that exposure to the environmental toxicant tetrachlorodibenzo-p-dioxin (TCDD) disrupts several molecular networks responsible for heart development and function. To test the hypothesis that the disruption caused by TCDD in the heart results from changes in DNA methylation and gene expression patterns of cardiomyocytes, we established a stable mouse embryonic stem cell line expressing a puromycin resistance selectable marker under control of the cardiomyocyte-specific Nkx2-5 promoter. Differentiation of these cells in the presence of puromycin induces the expression of a large suite of cardiomyocyte specific markers. To assess the consequences of TCDD treatment on gene expression and DNA methylation in these cardiomyocytes, we subjected them to transcriptome and methylome analyses in the presence of TCDD. Unlike control cardiomyocytes maintained in vehicle, the TCDD-treated cardiomyocytes showed extensive gene expression changes, with a significant correlation between differential RNA expression and DNA methylation in 111 genes, many of which are key elements of pathways that regulate cardiovascular development and function. Our findings provide an important clue towards the elucidation of the complex interactions between genetic and epigenetic mechanisms after developmental TCDD exposure that may contribute to CHD.
Differential physiological roles for BIN1 isoforms in skeletal muscle development, function and regeneration

ABSTRACT Skeletal muscle development and regeneration are tightly regulated processes. How the intracellular organization of muscle fibers is achieved during these steps is unclear. Here, we focus on the cellular and physiological roles of amphiphysin 2 (BIN1), a membrane remodeling protein mutated in both congenital and adult centronuclear myopathies (CNM), that is ubiquitously expressed and has skeletal muscle-specific isoforms. We created and characterized constitutive muscle-specific and inducible Bin1 homozygous and heterozygous knockout mice targeting either ubiquitous or muscle-specific isoforms. Constitutive Bin1-deficient mice died at birth from lack of feeding due to a skeletal muscle defect. T-tubules and other organelles were misplaced and altered, supporting a general early role for BIN1 in intracellular organization, in addition to membrane remodeling. Although restricted deletion of Bin1 in unchallenged adult muscles had no impact, the forced switch from the muscle-specific isoforms to the ubiquitous isoforms through deletion of the in-frame muscle-specific exon delayed muscle regeneration. Thus, ubiquitous BIN1 function is necessary for muscle development and function, whereas its muscle-specific isoforms fine tune muscle regeneration in adulthood, supporting that BIN1 CNM with congenital onset are due to developmental defects, whereas later onset may be due to regeneration defects. Summary: The BIN1 gene, mutated in centronuclear myopathies, expresses ubiquitous and muscle-specific isoforms. It is shown here that ubiquitous isoforms are necessary for muscle development, whereas muscle-specific isoforms fine-tune muscle regeneration.