Miracle-dz/UniFAR-FTUs huggingface dataset:
Crocin, a natural molecule with potentially beneficial effects against skin ageing

Oxidative stress and low‐grade chronic inflammation stand out as key features of physiological skin ageing. The aim of this study was to examine in normal human epidermal keratinocytes (NHEK) and human dermal fibroblasts (HDF) grown in vitro, the antioxidant and anti‐inflammatory properties of crocin, a carotenoid glycoside responsible for the colour of saffron. Moreover, considering the newly emerging field of skin glycobiology and the presence of two gentiobiosyl moieties in crocin, the effect of crocin on NHEK glycosylation pathways was for the first time investigated.
The Flow Engine Framework: A Cognitive Model of Optimal Human Experience

Flow is a well-known concept in the fields of positive and applied psychology. Examination of a large body of flow literature suggests there is a need for a conceptual model rooted in a cognitive approach to explain how this psychological phenomenon works. In this paper, we propose the Flow Engine Framework, a theoretical model explaining dynamic interactions between rearranged flow components and fundamental cognitive processes. Using an IPO framework (Inputs – Processes – Outputs) including a feedback process, we organize flow characteristics into three logically related categories: inputs (requirements for flow), mediating and moderating cognitive processes (attentional and motivational mechanisms) and outputs (subjective and objective outcomes), describing the process of the flow. Comparing flow with an engine, inputs are depicted as flow-fuel, core processes cylinder strokes and outputs as power created to provide motion.
Utilization of Physical Therapy Services During Transition for [LINE SEPARATOR]Young People With Cerebral Palsy: A Call for Improved Care Into Adulthood

Background Many young adults with cerebral palsy (CP) face limited participation in activities, including employment and independent living. Physical therapy during the transition period can help to support participation through promotion of self-care, ambulation, and functional mobility. Thus, ensuring appropriate access to physical therapy services for young people who can benefit from them before, during, and after transition is imperative. Objective The objective of this study was to identify factors contributing to the utilization of physical therapy services for youth with CP both during and after secondary school. Design The design was a deidentified secondary analysis of the National Longitudinal Transition Study 2 (NLTS2). Methods Multivariate regression models were run to examine demographic and disability characteristics influencing utilization of physical therapy services for youth with CP both during and after secondary school. Results The total weighted population sample included 35,290 young people with CP. When all youth were in secondary school, 59.4% of the youth utilized physical therapy services; however, once all youth were out of school, only 33.7% of them were reported to have utilized physical therapy since leaving secondary school. For young people with difficulties accessing general disability support services, demographic characteristics, including sex, race, income, and parent education status, influenced use of physical therapy services in addition to disability characteristics. Limitations This population sample included only young people in special education with Individual Education Plans (IEPs) and may not generalize to young people with CP in general education settings. Conclusions Frequency of physical therapy services decreases drastically once young adults with CP leave secondary school. Future work should examine this trend in more depth to identify therapy intervention strategies to optimize participation in young adult life for persons with CP.
Prevalence of hepatitis B and hepatitis C infection from a population-based study in Southern India

Objectives This study aims to estimate the prevalence of hepatitis B (HBV) and C (HCV) in the population through field-screening camps conducted by Chennai Liver Foundation, in the southern state of Tamil Nadu, India. This is the largest population-based study from Tamil Nadu. Patients and methods A total of 75 camps were conducted across 14 districts of Tamil Nadu (2014–2017). Screening was done by rapid point-of-care assays (SD-bioline tests) and confirmed by enzyme-linked immunosorbent assay (Monolisa tests). Those tested negative were offered first dose of HBV vaccine. Positive patients with HBV count of more than 2000 IU/ml or HCV-RNA positive on quantitative analysis were treated. Results A total of 18 589 people were screened, with HBV infection detected in 303 (prevalence 1.63%) and HCV infection in 56 (prevalence 0.3%), with significant variation among districts. Males contributed to about three-fourths of detected HBV [233/303 (77%)] or HCV [41/56 (73%)] infection. Screening detected a higher overall HBV/HCV infection rate in rural [203 (2.52%) infections in 8047 people] than in urban [156 (1.47%) infections in 10 542 people] areas (P<0.0001). Slum areas had a HBV prevalence of 5%. In a dialysis unit, all patients were found to have either HBV/HCV infection. A total of 162/303 (54%) people with HBV and 27/56 (48%) with HCV infection were treated, and 7704 people received the first dose of HBV vaccine. Conclusion The prevalence of HBV was 1.63% and HCV was 0.30% in Tamil Nadu. Three-fourths of HBV/HCV infected people were males. Prevalence of HBV/HCV was higher in rural areas. Slum area and dialysis unit had high HBV and HCV prevalence.
Enhanced mRNA delivery into lymphocytes enabled by lipid-varied libraries of charge-altering releasable transporters

Significance The transfection of lymphocytes with genetic material is a significant unmet need in immunotherapy and the treatment of many diseases. Current transfection strategies primarily rely on physical methods that must be conducted ex vivo and are often inefficient. We identified mixtures of lipid-varied mRNA delivery vehicles (charge-altering releasable transporters, CARTs) that show enhanced uptake into multiple lymphocyte cell types. The top performing lipid mixtures were rapidly identified using a combinatorial strategy and the resulting information was used to design single-delivery agents incorporating both lipid domains using our two-step organocatalytic ring-opening polymerization. Hybrid-lipid CARTs show >80% mRNA transfection efficiency in vitro and >1.5% lymphocyte transfection efficiency in mice, which is higher than previously reported systems. These materials should enable new immunotherapy strategies and applications. We report a strategy for generating a combinatorial library of oligonucleotide transporters with varied lipid domains and their use in the efficient transfection of lymphocytes with mRNA in vitro and in vivo. This library is based on amphiphilic charge-altering releasable transporters (CARTs) that contain a lipophilic block functionalized with various side-chain lipids and a polycationic α-amino ester mRNA-binding block that undergoes rearrangement to neutral small molecules, resulting in mRNA release. We show that certain binary mixtures of these lipid-varied CARTs provide up to a ninefold enhancement in mRNA translation in lymphocytes in vitro relative to either a single-lipid CART component alone or the commercial reagent Lipofectamine 2000, corresponding to a striking increase in percent transfection from 9–12% to 80%. Informed by the results with binary mixtures, we further show that CARTs consisting of optimized ratios of the two lead lipids incorporated into a single hybrid-lipid transporter molecule maintain the same delivery efficacy as the noncovalent mixture of two CARTs. The lead lipid CART mixtures and hybrid-lipid CARTs show enhanced lymphocyte transfection in primary T cells and in vivo in mice. This combinatorial approach for rapidly screening mRNA delivery vectors has provided lipid-varied CART mixtures and hybrid-lipid CARTs that exhibit significant improvement in mRNA delivery to lymphocytes, a finding of potentially broad value in research and clinical applications.
Abdominal Aortic Aneurysm: Evolving Controversies and Uncertainties

Abstract Abdominal aortic aneurysm (AAA) is defined as a permanent dilatation of the abdominal aorta that exceeds 3 cm. Most AAAs arise in the portion of abdominal aorta distal to the renal arteries and are defined as infrarenal. Most AAAs are totally asymptomatic until catastrophic rupture. The strongest predictor of AAA rupture is the diameter. Surgery is indicated to prevent rupture when the risk of rupture exceeds the risk of surgery. In this review, we aim to analyze this disease comprehensively, starting from an epidemiological perspective, exploring etiology and pathophysiology, and concluding with surgical controversies. We will pursue these goals by addressing eight specific questions regarding AAA: (1) Is the incidence of AAA increasing? (2) Are ultrasound screening programs for AAA effective? (3) What causes AAA: Genes versus environment? (4) Animal models: Are they really relevant? (5) What pathophysiology leads to AAA? (6) Indications for AAA surgery: Are surgeons over-eager to operate? (7) Elective AAA repair: Open or endovascular? (8) Emergency AAA repair: Open or endovascular?
Clinical Trials of a New Drug, Ibufenac, in the Treatment of Rheumatoid Arthritis

Since its introduction in 1899, aspirin has been widely prescribed for its anti-inflammatory and analgesic properties. Appreciation of its therapeutic imperfections, however, has led to the search for a compound of equal or greater effectiveness yet free from aspirin's troublesome side-effects. The purpose of this paper is to describe one such compound (Ibufenac-4-isobutylphenyl-acetic acid), a substance possessing anti-inflammatory, analgesic and anti-pyretic properties in animal tests (Adams and Nicholson, 1961), and to report the results of the first clinical trials of this new drug. Clinical assessment of Ibufenac had been preceded by experience with two other substances which had shown promise of anti-inflammatory activity in preliminary biological tests. Of these, the first showed no suppression of the Trafuril reaction (Truelove and Duthie, 1959), whereas the second did significantly modify it in a single oral dose of 30 gr. In clinical trials of these drugs, the first proved ineffective in controlling the symptoms of patients with rheumatoid arthritis, and the second, while controlling the symptoms adequately, was associated with the appearance of a purpuric rash in a high proportion of cases. A placebo period was incorporated in the doubleblind trials of these drugs. The use of placebo, however, was associated so constantly with exacerbations of symptoms that in subsequent trials the placebo period was omitted from the design.
Distinct human circulating NKp30+FcεRIγ+CD8+ T cell population exhibiting high natural killer-like antitumor potential

Significance CD8+ T cell recognition of tumor cells is typically based on the detection of specific MHC–peptide complexes, while natural killer (NK) cell recognition relies on the detection of NK ligands by an array of NK receptors. In this study we uncovered a distinct small population of CD8+ T cells expressing NKp30, a potent activating NK receptor, on peripheral blood from healthy donors. Those innate-like CD8+ T cells, coexpressing FcεRIγ and PZLF, could be generated and differentiated from a population of peripheral blood CD8+ T cells as result of IL-15–driven acquisition of broad innate features. This unique effector population could potently control the growth of tumors in an NK-like manner, making it promising for cancer immunotherapy by its dual target-recognition potential. CD8+ T cells are considered prototypical cells of adaptive immunity. Here, we uncovered a distinct CD8+ T cell population expressing the activating natural killer (NK) receptor NKp30 in the peripheral blood of healthy individuals. We revealed that IL-15 could de novo induce NKp30 expression in a population of CD8+ T cells and drive their differentiation toward a broad innate transcriptional landscape. The adaptor FcεRIγ was concomitantly induced and was shown to be crucial to enable NKp30 cell-surface expression and function in CD8+ T cells. FcεRIγ de novo expression required promoter demethylation and was accompanied by acquisition of the signaling molecule Syk and the “innate” transcription factor PLZF. IL-15–induced NKp30+CD8+ T cells exhibited high NK-like antitumor activity in vitro and were able to synergize with T cell receptor signaling. Importantly, this population potently controlled tumor growth in a preclinical xenograft mouse model. Our study, while blurring the borders between innate and adaptive immunity, reveals a unique NKp30+FcεRIγ+CD8+ T cell population with high antitumor therapeutic potential.
Quantitative human health risk assessment along the lifecycle of nano-scale copper-based wood preservatives

Abstract The use of nano-scale copper oxide (CuO) and basic copper carbonate (Cu2(OH)2CO3) in both ionic and micronized wood preservatives has raised concerns about the potential of these substances to cause adverse humans health effects. To address these concerns, we performed quantitative (probabilistic) human health risk assessment (HHRA) along the lifecycles of these formulations used in antibacterial and antifungal wood coatings and impregnations by means of the EU FP7 SUN project’s Decision Support System (SUNDS, www.sunds.gd). The results from the risk analysis revealed inhalation risks from CuO in exposure scenarios involving workers handling dry powders and performing sanding operations as well as potential ingestion risks for children exposed to nano Cu2(OH)2CO3 in a scenario involving hand-to-mouth transfer of the substance released from impregnated wood. There are, however, substantial uncertainties in these results, so some of the identified risks may stem from the safety margin of extrapolation to fill data gaps and might be resolved by additional testing. Our stochastic approach successfully communicated the contribution of different sources of uncertainty in the risk assessment. The main source of uncertainty was the extrapolation from short to long-term exposure, which was necessary due to the lack of (sub)chronic in vivo studies with CuO and Cu2(OH)2CO3. Considerable uncertainties also stemmed from the use of default inter- and intra-species extrapolation factors.
Staying Streetwise: Accurate Judgments of Approaching Aggression in Older Age

The extant literature has generally demonstrated that young adults can detect the trait aggression of another person with limited information. However, there is little research that investigates the life course persistence of aggression detection accuracy. Here, we aimed to explore the accuracy of older adults at detecting potential aggressors. Thirty-nine older adults (M = 71.49, SD = 7.59) and eighty-seven young adults (M = 20.24, SD = 1.74) made intimidation judgments, via video recordings, for nine people (targets). ‘Aggression detection accuracy’ was shown in the relationship between the intimidation judgments made by participants and the targets’ responses to the Buss-Perry Aggression Questionnaire. Both age groups were highly accurate in their recognition of trait aggression and accuracy was maintained into older age, with no difference in accuracy between the older and young adults. There was, however, more variability in the ratings given by the older adults compared to the young adults, suggesting less consensus in judgment for the older compared to the young group. Overall, the participants in this study were highly accurate at detecting trait aggression. There was no difference in average aggression detection between older and young adults but there was in sample agreement. These results are discussed in the context of age effects on intimidation, as well as research in accurate aggression detection.
Conserved and Divergent Functions of the cAMP/PKA Signaling Pathway in Candida albicans and Candida tropicalis

Fungal species undergo many morphological transitions to adapt to changing environments, an important quality especially in fungal pathogens. For decades, Candida albicans has been one of the most prevalent human fungal pathogens, and recently, the prevalence of Candida tropicalis as a causative agent of candidiasis has increased. In C. albicans, the ability to switch between yeast and hyphal forms is thought to be a key virulence factor and is regulated by multiple signaling cascades—including the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA), calcineurin, high-osmolarity glycerol (HOG), and mitogen-activated protein kinases (MAPK) signaling pathways—upon receiving environmental cues. The cAMP/PKA signaling pathway also triggers white-opaque switching in C. albicans. However, studies on C. tropicalis morphogenesis are limited. In this minireview, we discuss the regulation of the yeast-hypha transition, virulence, and white-opaque switching through the cAMP/PKA pathway in the closely related species C. albicans and C. tropicalis.
SINGLE-CHANNEL SOURCE SEPARATION OF SPEECH AND MUSIC USING SHORT-TIME SPECTRAL KURTOSIS

In this paper, the problem of blind monaural speech/music source separation is addressed using short-time spectral kurtosis (STSK). An estimator for STSK is introduced, and a source separation algorithm is formulated that relies on the spectral kurtosis differences of distinct signal classes. The performance of the proposed algorithm is evaluated on mixtures of speech signals and various types of music signals. The results are compared to those obtained by a competing monaural source separation algorithm, which is based on a Gaussian mixture model (GMM).
The Role of Home Literacy Environment, Mentalizing, Expressive Verbal Ability, and Print Exposure in Third and Fourth Graders’ Reading Comprehension

ABSTRACT Children with a rich home literacy environment generally show better reading comprehension. For children in the higher grades of primary school, this relation is thought to be indirect. We propose a model in which this relation ran via children’s higher order language and cognitive skills (i.e., expressive verbal ability and mentalizing ability) and via print exposure. In our correlational study with 117 children ages 8–11, we found both a direct relation between children’s home literacy environment and reading comprehension and 2 indirect relations: via children’s print exposure and via mentalizing abilities. There was no significant indirect relation via expressive verbal abilities. Our findings imply that enhancing children’s mentalizing abilities and encouraging them to read books might contribute to their reading comprehension. In addition, parental involvement in children’s reading activities can contribute to their reading performance, both directly and indirectly, even in this age group.
Effect of alpha tocopherol acetate and ascorbic acid on performance, carcass traits and incidence and severity of liver abscesses in feedlot cattle.

Liver abscesses (LA) in cattle negatively affect feedlot performance by decreasing ADG, feed intake, and G:F ratio. Abscessed livers are condemned and abdominal adhesions associated with LA can result in extensive carcass trimming during harvest, further compounding adverse economic impact. Given regulatory changes pertaining to the use of in-feed antibiotics in cattle production, there is growing interest in alternatives to antibiotics for LA control. The objective of this study was to evaluate the use of antioxidants, crystalline ascorbate and alpha tocopherol acetate, for mitigation of LA in feedlot cattle. Yearling crossbred heifers (n=392; initial BW 481 ± 9.4 kg) were blocked by previous treatment and allocated randomly to 24 dirt-surfaced feedlot pens (10 m x 35 m) with 14 heifers/pen. Heifers were weighed, implanted with Component® TE-200 implants, and placed into feeding pens. Finishing diets consisted of 60% steam-flaked corn, 30% wet corn gluten feed, 8% alfalfa, and 2% supplement (DM basis) that provided 300 mg/d monensin, and either 200 IU/d alpha tocopherol acetate (CTL) or 2000 IU/d alpha tocopherol acetate plus 500 mg/d crystalline ascorbate (AOX). Heifers were fed once daily ad libitum for 94 d, then weighed and transported 450 km to a commercial abattoir for harvest. Hot carcass weight and incidence/severity of LA were determined the day of harvest, and carcass traits were evaluated following 36 h of refrigeration. Compared to CTL, feeding AOX tended to decrease DMI (10.66 vs. 10.31 kg/d; P = 0.08) and improve G:F (0.1204 vs. 0.1254; P = 0.12), but did not impact ADG, incidence of LA (25.6 vs 23.5% for CTL and AOX, respectively), HCW (828.4 vs 830.5 kg for CTL and AOX, respectively), or other carcass traits (P>0.20). In conclusion, feeding antioxidants is not a viable alternative to decrease incidence of liver abscesses in finishing cattle.
Sequence-to-Sequence Learning for Task-oriented Dialogue with Dialogue State Representation

Classic pipeline models for task-oriented dialogue system require explicit modeling the dialogue states and hand-crafted action spaces to query a domain-specific knowledge base. Conversely, sequence-to-sequence models learn to map dialogue history to the response in current turn without explicit knowledge base querying. In this work, we propose a novel framework that leverages the advantages of classic pipeline and sequence-to-sequence models. Our framework models a dialogue state as a fixed-size distributed representation and use this representation to query a knowledge base via an attention mechanism. Experiment on Stanford Multi-turn Multi-domain Task-oriented Dialogue Dataset shows that our framework significantly outperforms other sequence-to-sequence based baseline models on both automatic and human evaluation.
Virus-like particles and enterovirus antigen found in the brainstem neurons of Parkinson’s disease

Background: In a previous study on encephalitis lethargica, we identified a virus related to enterovirus in autopsy brain material. Transmission electron microscopy (TEM), immunohistochemistry (IHC) and molecular analysis were employed. Our present objective was to investigate, using a similar approach, as to whether virus-like particles (VLP) and enterovirus antigen are present in Parkinson’s disease (PD) brainstem neurons. Methods: Fixed tissue from autopsy specimens of late onset PD and control brainstem tissue were received for study. The brain tissue was processed for TEM and IHC according to previous published methods. Results: We observed VLP in the brainstem neurons of all the cases of PD that were examined. In the neurons’ cytoplasm there were many virus factories consisting of VLP and endoplasmic reticulum membranes. In some neurons, the virus factories contained incomplete VLP. Complete VLP in some neurons’ virus factories had an average diameter of 31 nm, larger than control brain ribosomes. In the nuclei, there were VLP with an average diameter of 40 nm. In cases of human poliomyelitis, there were cytoplasmic virus factories and intranuclear virus particles similar to those observed in PD. On preparing PD brain sections for IHC there was positive staining using anti-poliovirus antibody and anti-coxsackie antibody. This result was statistically significant. Conclusions: We present evidence for an enterovirus infection in PD. For future studies, virus isolation and molecular analysis are suggested.