Miracle-dz/UniFAR-FTUs huggingface dataset:
New insights into the secretory functions of brown adipose tissue.

In recent years, an important secretory role of brown adipose tissue (BAT) has emerged, which is consistent, to some extent, with the earlier recognition of the important secretory role of white fat. The so-called brown adipokines or "batokines" may play an autocrine role, which may either be positive or negative in the thermogenic function of brown adipocytes. Additionally, there is a growing recognition of the signalling molecules released by brown adipocytes that target sympathetic nerve endings (such as neuregulin-4 and S100b protein), vascular cells (e.g., bone morphogenetic protein-8b), and immune cells (e.g., C-X-C motif chemokine ligand-14) to promote the tissue remodelling associated with the adaptive BAT recruitment in response to thermogenic stimuli. Moreover, existing indications of an endocrine role of BAT are being confirmed through the release of brown adipokines acting on other distant tissues and organs; a recent example is the recognition that BAT-secreted fibroblast growth factor-21 and myostatin target the heart and skeletal muscle, respectively. The application of proteomics technologies is aiding the identification of new members of the brown adipocyte secretome, such as the extracellular matrix or complement system components. In summary, BAT can no longer be considered a mere producer of heat in response to environment or dietary challenges; it is also an active secretory tissue releasing brown adipokines with a relevant local and systemic action. The identification of the major brown adipokines and their roles is highly important for the discovery of novel candidates useful in formulating intervention strategies for metabolic diseases.
Withaferin A Improves Nonalcoholic Steatohepatitis in Mice

Nonalcoholic steatohepatitis (NASH) is the progressive stage of nonalcoholic fatty liver disease that highly increases the risk of cirrhosis and liver cancer, and there are few therapeutic options available in the clinic. Withaferin A (WA), extracted from the ayurvedic medicine Withania somnifera, has a wide range of pharmacological activities; however, little is known about its effects on NASH. To explore the role of WA in treating NASH, two well defined NASH models were used, the methionine-choline-deficient diet and the 40 kcal% high-fat diet (HFD). In both NASH models, WA treatment or control vehicle was administered to evaluate its hepatoprotective effects. As assessed by biochemical and histologic analyses, WA prevented and therapeutically improved liver injury in both models, as revealed by lower serum aminotransaminases, hepatic steatosis, liver inflammation, and fibrosis. In the HFD-induced NASH model, both elevated serum ceramides and increased hepatic oxidative stress were decreased in the WA-treated group compared with the control vehicle–treated group. To further explore whether WA has an anti-NASH effect independent of its known action in leptin signaling associated with obesity, leptin signaling–deficient ob/ob mice maintained on an HFD were used to induce NASH. WA therapeutically reduced NASH in HFD-treated leptin-deficient ob/ob mice, thus demonstrating a leptin-independent hepatoprotective effect. This study revealed that WA treatment could be an option for NASH treatment.
Muscarinic Inhibition of Hypoglossal Motoneurons: Possible Implications for Upper Airway Muscle Hypotonia during REM Sleep

Proper function of pharyngeal dilator muscles, including the genioglossus muscle of the tongue, is required to maintain upper airway patency. During sleep, the activity of these muscles is suppressed, and as a result individuals with obstructive sleep apnea experience repeated episodes of upper airway closure when they are asleep, in particular during rapid-eye-movement (REM) sleep. Blocking cholinergic transmission in the hypoglossal motor nucleus (MoXII) restores REM sleep genioglossus activity, highlighting the importance of cholinergic transmission in the inhibition of hypoglossal motor neurons (HMNs) during REM sleep. Glutamatergic afferent input from neurons in the parahypoglossal (PH) region to the HMNs is critical for MoXII respiratory motor output. We hypothesized that state-dependent cholinergic regulation may be mediated by this pathway. Here we studied the effects of cholinergic transmission in HMNs in adult male and female mice using patch-clamp recordings in brain slices. Using channelrhodopsin-2-assisted circuit mapping, we first demonstrated that PH glutamatergic neurons directly and robustly activate HMNs (PHGlut → HMNs). We then show that carbachol consistently depresses this input and that this effect is presynaptic. Additionally, carbachol directly affects HMNs by a variable combination of muscarinic-mediated excitatory and inhibitory responses. Altogether, our results suggest that cholinergic signaling impairs upper airway dilator muscle activity by suppressing glutamatergic input from PH premotoneurons to HMNs and by directly inhibiting HMNs. Our findings highlight the complexity of cholinergic control of HMNs at both the presynaptic and postsynaptic levels and provide a possible mechanism for REM sleep suppression of upper airway muscle activity. SIGNIFICANCE STATEMENT Individuals with obstructive sleep apnea can breathe adequately when awake but experience repeated episodes of upper airway closure when asleep, in particular during REM sleep. Similar to skeletal postural muscles, pharyngeal dilator muscles responsible for maintaining an open upper airway become hypotonic during REM sleep. Unlike spinal motoneurons controlling postural muscles that are inhibited by glycinergic transmission during REM sleep, hypoglossal motoneurons that control the upper airway muscles are inhibited in REM sleep by the combination of monoaminergic disfacilitation and cholinergic inhibition. In this study, we demonstrated how cholinergic signaling inhibits hypoglossal motoneurons through presynaptic and postsynaptic muscarinic receptors. Our results provide a potential mechanism for upper airway hypotonia during REM sleep.
Lifestyle, appearance satisfaction and depressive symptoms in 13–16 years old Norwegian adolescents – A cross-sectional study

Abstract Purpose: To examine gender-specific associations between multiple lifestyle-related risk factors, appearance satisfaction and depressive symptoms in a sample of Norwegian adolescents (13–16 years of age), and to study the role of appearance satisfaction as a possible confounder in the associations between lifestyle and depressive symptoms. Materials and methods: Data were obtained from Ungdata, a cross-sectional national survey of adolescents in Norway. In total 4379 subjects were included in the study. We constructed a lifestyle risk index and used multiple logistic regressions to examine the associations between lifestyle-related risk factors, appearance satisfaction, and depressive symptoms. Results: High screen time and use of alcohol were significantly associated with depressive symptoms among girls, while high screen time, tobacco and cannabis use were significantly associated with depressive symptoms among boys. An additive relationship was observed between the lifestyle risk index scores and the likelihood of depressive symptoms for both genders, the relationship being strongest among boys. Low appearance satisfaction was strongly associated with depressive symptoms, especially among boys, and identified as an important confounder in the associations between lifestyle and depressive symptoms, particularly among girls. Conclusions: High screen time was the most prevalent lifestyle risk behavior independently associated with depressive symptoms. Multiple lifestyle changes and improvement of appearance satisfaction should be included in measures targeting adolescents for the prevention and treatment of depressive symptoms. Future studies should elaborate on the gender differences in other adolescent age groups. Appearance satisfaction should be acknowledged as an important confounder in future studies of lifestyle and depressive symptoms.
Product attributes important to US adult consumers’ use of electronic nicotine delivery systems: a discrete choice experiment

Objective To understand the importance of electronic nicotine delivery systems (ENDS) product attributes to adult consumers in the USA by age and gender. Design Cross-sectional survey with a discrete choice experiment (best–worst, case 2, scaling) of 19 choice tasks in which participants answered what would make them most want to use and least want to use an ENDS product. Setting and participants A national sample of adults (aged 18+ years) in the USA who had tried an ENDS product at least once. Measures We included 9 ENDS attributes with levels that varied across 19 choice tasks. We performed a multinomial logistic regression to obtain overall importance scores, attribute-level part-worth utilities and most important attribute. Results Of 660 participants, 81% were white, 51% women and 37% had at least a 4-year college degree with an average age of 42.0 years (SD ±19.4). The attributes had the following importance: harms of use 17.6%; general effects 14.1%; cessation aid 12.6%; purchase price 12.1%; monthly cost 12.0%; nicotine content 11.4%; flavour availability 8.4%; device design 7.2%; modifiability 4.6%. Harms of use was the most important attribute for all ages and genders (p<0.05); variation in other important attributes existed by age though not by gender. Conclusion This study identified the importance of nine ENDS attributes. Perceived harms of use of ENDS use appeared most important, and modifiability was least important. Variation by consumer group existed, which may allow for targeted interventions to modify ENDS use.
Clinical Information Systems and Artificial Intelligence: Recent Research Trends

Summary Objectives: This survey aims at reviewing the literature related to Clinical Information Systems (CIS), Hospital Information Systems (HIS), Electronic Health Record (EHR) systems, and how collected data can be analyzed by Artificial Intelligence (AI) techniques. Methods: We selected the major journals (11 journals) collecting papers (more than 7,000) over the last five years from the top members of the research community, and read and analyzed the papers (more than 200) covering the topics. Then, we completed the analysis using search engines to also include papers from major conferences over the same five years. Results: We defined a taxonomy of major features and research areas of CIS, HIS, EHR systems. We also defined a taxonomy for the use of Artificial Intelligence (AI) techniques on healthcare data. In the light of these taxonomies, we report on the most relevant papers from the literature. Conclusions: We highlighted some major research directions and issues which seem to be promising and to need further investigations over a medium- or long-term period.
Titanium surface modifications and their soft-tissue interface on nonkeratinized soft tissues-A systematic review (Review).

In this systematic review, the authors explored the surface aspects of various titanium (Ti) or Ti alloy medical implants, examining the interface formed between the implant and surrounding nonkeratinized soft tissues (periosteum, muscles, tendons, fat, cicatrix, or dura mater). A comprehensive search undertaken in July 2019 used strict keywords in relevant electronic databases to identify relevant studies. Based on the authors' inclusion criteria (restricted to in vivo studies), 19 of 651 publications qualified, all pertaining to animal models. The syrcle's risk of bias tool for animal studies was applied at study level. Given the broad nature of the reported results and the many different parameters measured, the articles under scrutiny were assigned to five research subgroups according to their surface modification types: mechanical surface modifications, oxidative processes (e.g., acid etching, anodization, microarc oxidation), sol-gel derived titania (TiO2) coatings, biofunctionalized surfaces, and a subgroup for other modifications. The primary outcome was a liquid space at the interface (e.g., seroma formation) that was reported in six studies. Machining Ti implants to a roughness between Ra = 0.5 and 1.0 μm was shown to induce soft-tissue adhesion. Smoother surfaces, with the exception of acid polished and anodized Ti (Ra = 0.2 μm), prevented soft-tissue adhesion. A fibroblast growth factor 2 apatite composite coating promoted soft-tissue attachment via Sharpey-like fibers. In theory, this implant-soft tissue interface could be nearly perfect.
Organophosphate Pesticide Exposure in Pregnancy in Association with Ultrasound and Delivery Measures of Fetal Growth

Background: Perturbations in fetal growth may have adverse consequences for childhood and later life health. Organophosphate pesticide (OP) exposure has been associated with reduced birth weight at delivery but results are not consistent. We investigated this question by utilizing ultrasound measures of size in utero in combination with measures from delivery. Methods: Within Generation R, a population-based prospective cohort conducted between 2002 and 2006 in Rotterdam, Netherlands, we measured dialkyl phosphates (DAPs), OP metabolites, in urine samples from early, middle, and late pregnancy and created a subject-specific average to estimate OP exposure (n=784). Ultrasound measures of head circumference, femur length, and estimated fetal weight from middle and late pregnancy and delivery measures were converted to standard deviation scores (SDS). Associations with DAP average were examined in linear mixed effects models that included an interaction term between gestational age at measurement and DAP average to investigate whether the relationship differed over time. Windows of vulnerability to exposure were assessed by modeling urinary DAPs from each visit in relation to growth measurements. Results: A 10-fold increase in average DAPs was associated with a −0.53 SDS decrease in fetal length (95% CI =−0.83, −0.23) and a −0.32 SDS decrease in estimated fetal weight (95% CI =−0.59, −0.04) at 20 weeks of gestation. These differences corresponded to 5% and 6% decreases relative to the mean. Effect estimates were greatest in magnitude for DAP concentrations measured early in pregnancy. Associations between average DAPs and growth measures at delivery were positive but not significant for head circumference and length and were null for weight. Conclusions: Maternal urinary DAPs were associated with decreased fetal weight and length measured during mid-pregnancy, but not at delivery. https://doi.org/10.1289/EHP4858
FAD2 Gene Radiation and Positive Selection Contributed to Polyacetylene Metabolism Evolution in Campanulids1[OPEN]

Evolutionary analyses of plant FAD2 suggest that lineage-specific gene radiations and positive selections facilitated the evolution of polyacetylene biosynthesis pathways in campanulids. Polyacetylenes (PAs) are bioactive, specialized plant defense compounds produced by some species in the eudicot clade campanulids. Early steps of PA biosynthesis are catalyzed by Fatty Acid Desaturase 2 (FAD2). Canonical FAD2s catalyze desaturation, but divergent forms can catalyze hydroxylation, conjugation, acetylenation, and epoxygenation. These alternate reactions give rise to valuable unusual fatty acids, including the precursors to PAs. The extreme functional diversity of FAD2 enzymes and the origin of PA biosynthesis are poorly understood from an evolutionary perspective. We focus here on the evolution of the FAD2 gene family. We uncovered a core eudicot-wide gene duplication event giving rise to two lineages: FAD2-α and FAD2-β. Independent neofunctionalizations in both lineages have resulted in functionally diverse FAD2-LIKEs involved in unusual fatty acid biosynthesis. We found significantly accelerated rates of molecular evolution in FAD2-LIKEs and use this metric to provide a list of uncharacterized candidates for further exploration of FAD2 functional diversity. FAD2-α has expanded extensively in Asterales and Apiales, two main clades of campanulids, by ancient gene duplications. Here, we detected positive selection in both Asterales and Apiales lineages, which may have enabled the evolution of PA metabolism in campanulids. Together, these findings also imply that yet uncharacterized FAD2-α copies are involved in later steps of PA biosynthesis. This work establishes a robust phylogenetic framework in which to interpret functional data and to direct future research into the origin and evolution of PA metabolism.
MHO_0730 is a surface-exposed calcium-dependent nuclease of Mycoplasma hominis promoting neutrophils extracellular traps formation and escape.

Mycoplasma lipoproteins play a relevant role in pathogenicity and directly interact with the host immune system. Among human mycoplasmas, Mycoplasma hominis is described as a commensal bacterium that can be associated with a number of genital and extra-genital conditions. Mechanisms of M. hominis pathogenicity are still largely obscure, and only a limited number of proteins have been associated to virulence. This work focuses on investigating the role of MHO_0730 as a virulence factor. We demonstrate that MHO_0730 is a surface lipoprotein, potentially expressed in vivo during natural infection both acting as nuclease with its amino acidic portion and as a potent inducer of NETosis with its N-terminal lipid moiety. Also, evidence for M. hominis NETs escape is presented. Results highlight the relevance of MHO_0730 in promoting infection and modulation and evasion of innate immunity, and provide additional knowledge to M. hominis virulence and survival in the host.
University of Dundee Measuring mental health and wellbeing outcomes for children and adolescents to inform practice and policy

There is a growing appetite for mental health and wellbeing outcome measures that can inform clinical practice at individual and service levels, including use for local and national benchmarking. Despite a varied literature on child mental health and wellbeing outcome measures that focus on psychometric properties alone, no reviews exist that appraise the availability of psychometric evidence and suitability for use in routine practice in child and adolescent mental health services (CAMHS) including key implementation issues. This paper aimed to present the findings of the first review that evaluates existing broadband measures of mental health and wellbeing outcomes in terms of these criteria. The following steps were implemented in order to select measures suitable for use in routine practice: literature database searches, consultation with stakeholders, application of inclusion and exclusion criteria, secondary searches and filtering. Subsequently, detailed reviews of the retained measures’ psychometric properties and implementation features were carried out. 11 measures were identified as having potential for use in routine practice and meeting most of the key criteria: 1) Achenbach System of Empirically Based Assessment, 2) Beck Youth Inventories, 3) Behavior Assessment System for Children, 4) Behavioral and Emotional Rating Scale, 5) Child Health Questionnaire, 6) Child Symptom Inventories, 7) Health of the National Outcome Scale for Children and Adolescents, 8) Kidscreen, 9) Pediatric Symptom Checklist, 10) Strengths and Difficulties Questionnaire, 11) Youth Outcome Questionnaire. However, all existing measures identified had limitations as well as strengths. Furthermore, none had sufficient psychometric evidence available to demonstrate that they could reliably measure both severity and change over time in key groups. The review suggests a way of rigorously evaluating the growing number of broadband self-report mental health outcome measures against standards of feasibility and psychometric credibility in relation to use for practice and policy.
Anxiety and Pro-cyclical Risk Taking with Bayesian Agents

We provide a model that can explain empirically relevant variations in confidence and risk taking by combining horizon-dependent risk aversion (? anxiety? ) and selective memory in a Bayesian intrapersonal game. In the time series, overconfidence is more prevalent when actual risk levels are high, while underconfidence occurs when risks are low. In the cross section, more anxious agents are more prone to biased confidence and their beliefs fluctuate more. This systematic variation in confidence levels can lead to objectively excessive risk taking by ? insiders? with the potential to amplify boom-bust cycles.
Degradation Studies of Crosslinked Polyethylene. 2. Aged in water

Silane crosslinking of polyethylene was carried out by grafting an organofunctional silane (vinyltrimethoxysilane) onto polyethylene and by subsequent moisture crosslinking in hot water using a tin catalyst. This study focuses on the degradation processes, which occurred in the material after water ageing in an autoclave; ageing temperatures ranged from 90 to 190°C, while ageing times ranged from 2h to 500h. Significant changes in the chemical structure of the material were observed by FTIR, as carbonyl group concentration increased and different structures formed in the region of absorbance of groups containing silicone; the structural changes affected significantly the mechanical properties as shown by the tensile data. A chemical analysis of the extracts in chloroform of water aged samples carried out by using FTIR, LIMA and GPC techniques and some optical microscopy evidence, suggested that the mechanism of degradation in water is different from the one in air, as during water ageing the antioxidants are washed away by water and hydrolytic oxidation also occurs. ECHIP experimental design software was used in order to optimise the number of experimental trials and to model the results obtained.
In Vitro and in Vivo Anthelmintic Activities of Aqueous Leaf Infusion of Azadirachta indica against Haemonchus contortus

Anthelmintic resistance of Haemonchus contortus worm has become a major problem in ruminant production. Traditional medicinal and potential tropical plants with high tannin contents have a great potency as an alternative source of bio-anthelmintic. The study was carried out to assess the in vitro egg hatches inhibiting (EHI) and adult worm motility (AWM) tests and in vivo anthelmintic activities of aqueous leaf infusion of Azadirachta indica against H. contortus. Leaf infusion at doses of 2%, 4%, and 6% were used for in vitro treatments, and albendazole at a dose of 2 mg/mL was used as a positive control and 0.9% of sodium chloride was used as a negative control. The EHI assay was conducted two times i.e., before treatment and 24 h after treatment. The AWM were monitored 15 and 30 min, and 1, 2, 3, 4, 5, 6, 7, and 8 h post treatment. Sixteen Javanese Thin Tail ewes at the ages of ±12 months that naturally positive of H. contortus with about 1.000 EPG were selected and allocated randomly to 4 groups (n= 4). They were subsequently received the ensuing treatments i.e., A. indica infusion at doses of 0% (A) as a control, 6% (B), 8% (C), and 5 mg/BW albendazole (D) at a single oral dose as a positive control. Experimental ewes in Groups B and C were given oral infusion weekly during 4 weeks of treatment. EPG’s fecal examinations were conducted weekly. The result showed that the leaf infusion of A. indica containing condensed tannin (CT) at a dose of 6% significantly inhibited egg hatching (P<0.05) with a better effect compared to doses of 0%, 2%, and 4%. In AWM test, three doses of infusion significantly difference each other, as well as both negative and positive controls (P<0.05). After treatment, both of the A. indica containing CT levels and albendazole reduced EPG count significantly (P<0.05). Meanwhile, significant difference was not detected in dose of 8% aqueous leaf infusion of A. indica and albendazole treatments on weeks 3, 4, 5, and 6 consecutively. In conclusion, the aqueous leaf infusion of A. indica is fully potential as a bio anthelmintic against H. contortus.