Miracle-dz/UniFAR-FTUs huggingface dataset:
Interactions Between Nuclear Receptor SHP and FOXA1 Maintain Oscillatory Homocysteine Homeostasis in Mice.

BACKGROUND & AIMS Hyperhomocysteinemia is often associated with liver and metabolic diseases. We studied nuclear receptors that mediate oscillatory control of homocysteine homeostasis in mice. METHODS We studied mice with disruptions in Nr0b2 (called small heterodimer partner [SHP]-null mice), betaine-homocysteine S-methyltransferase (Bhmt), or both genes (BHMT-null/SHP-null mice), along with mice with wild-type copies of these genes (controls). Hyperhomocysteinemia was induced by feeding mice alcohol (National Institute on Alcohol Abuse and Alcoholism binge model) or chow diets along with water containing 0.18% DL-homocysteine. Some mice were placed on diets containing cholic acid (1%) or cholestyramine (2%) or high-fat diets (60%). Serum and livers were collected during a 24-hour light-dark cycle and analyzed by RNA-seq, metabolomic, and quantitative polymerase chain reaction, immunoblot, and chromatin immunoprecipitation assays. RESULTS SHP-null mice had altered timing in expression of genes that regulate homocysteine metabolism compared with control mice. Oscillatory production of S-adenosylmethionine, betaine, choline, phosphocholine, glyceophosphocholine, cystathionine, cysteine, hydrogen sulfide, glutathione disulfide, and glutathione, differed between SHP-null mice and control mice. SHP inhibited transcriptional activation of Bhmt and cystathionine γ-lyase by FOXA1. Expression of Bhmt and cystathionine γ-lyase was decreased when mice were fed cholic acid but increased when they were placed on diets containing cholestyramine or high-fat content. Diets containing ethanol or homocysteine induced hyperhomocysteinemia and glucose intolerance in control, but not SHP-null, mice. In BHMT-null and BHMT-null/SHP-null mice fed a control liquid, lipid vacuoles were observed in livers. Ethanol feeding induced accumulation of macrovesicular lipid vacuoles to the greatest extent in BHMT-null and BHMT-null/SHP-null mice. CONCLUSIONS Disruption of Shp in mice alters timing of expression of genes that regulate homocysteine metabolism and the liver responses to ethanol and homocysteine. SHP inhibits the transcriptional activation of Bhmt and cystathionine γ-lyase by FOXA1.
Integrative Review of Interprofessional Simulation in Nursing Practice.

AIM The aim of this integrative review was to examine what is known about interprofessional (IP) simulation involving practicing nurses. BACKGROUND The use of simulation within health care education and practice has rapidly expanded; however, there is a gap in what is known about the benefits of nurses engaging in IP simulation. METHOD Five reviewers conducted a systematic literature search on studies of IP simulation among practicing nurses, published between January 1, 2010, and July 1, 2016. An initial sample of 1,400 articles was found and was further narrowed to 18 studies. RESULTS There is a role for IP simulation in enhancing nurses' roles and understanding of the roles of other practitioners. However, the diversity of studies and lack of rigor prevents the formation of conclusive evidence to support IP simulation in enhancing patient care quality and safety. CONCLUSION Structured simulation research designs using published guidelines for best practice implementation are needed. J Contin Educ Nurs. 2018;49(2):91-96.
A Musical Approach to Speech Melody

We present here a musical approach to speech melody, one that takes advantage of the intervallic precision made possible with musical notation. Current phonetic and phonological approaches to speech melody either assign localized pitch targets that impoverish the acoustic details of the pitch contours and/or merely highlight a few salient points of pitch change, ignoring all the rest of the syllables. We present here an alternative model using musical notation, which has the advantage of representing the pitch of all syllables in a sentence as well as permitting a specification of the intervallic excursions among syllables and the potential for group averaging of pitch use across speakers. We tested the validity of this approach by recording native speakers of Canadian English reading unfamiliar test items aloud, spanning from single words to full sentences containing multiple intonational phrases. The fundamental-frequency trajectories of the recorded items were converted from hertz into semitones, averaged across speakers, and transcribed into musical scores of relative pitch. Doing so allowed us to quantify local and global pitch-changes associated with declarative, imperative, and interrogative sentences, and to explore the melodic dynamics of these sentence types. Our basic observation is that speech is atonal. The use of a musical score ultimately has the potential to combine speech rhythm and melody into a unified representation of speech prosody, an important analytical feature that is not found in any current linguistic approach to prosody.
Bridging the Energy Efficiency Gap: Policy Insights from Economic Theory and Empirical Evidence

Despite several decades of government policies to promote energy efficiency, estimates of the costs and benefits of such policies remain controversial. At the heart of the controversy is whether there is an “energy efficiency gap,” whereby consumers and firms fail to make seemingly positive net present value energy saving investments. High implicit discount rates, undervaluation of future fuel savings, and negative cost energy efficiency measures have all been discussed as evidence of the existence of a gap. We review explanations for an energy efficiency gap including reasons why the size of the gap may be overstated, neoclassical explanations for a gap, and recent evidence from behavioral economics that has potential to help us understand why a gap could exist. Our review raises fundamental questions about traditional welfare analysis, but we find the alternatives offered in the literature to be far from ready for use in policy analysis. Nevertheless, we offer several suggestions for policymakers and for future economic research. (JEL: Q38, Q41)
Greenery in the university environment: Students’ preferences and perceived restoration likelihood

A large body of evidence shows that interaction with greenery can be beneficial for human stress reduction, emotional states, and improved cognitive function. It can, therefore, be expected that university students might benefit from greenery in the university environment. Before investing in real-life interventions in a university environment, it is necessary to first explore students’ perceptions of greenery in the university environment. This study examined (1) preference for university indoor and outdoor spaces with and without greenery (2) perceived restoration likelihood of university outdoor spaces with and without greenery and (3) if preference and perceived restoration likelihood ratings were modified by demographic characteristics or connectedness to nature in Dutch university students (N = 722). Digital photographic stimuli represented four university spaces (lecture hall, classroom, study area, university outdoor space). For each of the three indoor spaces there were four or five stimuli conditions: (1) the standard design (2) the standard design with a colorful poster (3) the standard design with a nature poster (4) the standard design with a green wall (5) the standard design with a green wall plus interior plants. The university outdoor space included: (1) the standard design (2) the standard design with seating (3) the standard design with colorful artifacts (4) the standard design with green elements (5) the standard design with extensive greenery. Multi-level analyses showed that students gave higher preference ratings to the indoor spaces with a nature poster, a green wall, or a green wall plus interior plants than to the standard designs and the designs with the colorful posters. Students also rated preference and perceived restoration likelihood of the outdoor spaces that included greenery higher than those without. Preference and perceived restoration likelihood were not modified by demographic characteristics, but students with strong connectedness to nature rated preference and perceived restoration likelihood overall higher than students with weak connectedness to nature. The findings suggest that students would appreciate the integration of greenery in the university environment.
Additively Manufactured Scaffolds for Bone Tissue Engineering and the Prediction of their Mechanical Behavior: A Review

Additive manufacturing (AM), nowadays commonly known as 3D printing, is a revolutionary materials processing technology, particularly suitable for the production of low-volume parts with high shape complexities and often with multiple functions. As such, it holds great promise for the fabrication of patient-specific implants. In recent years, remarkable progress has been made in implementing AM in the bio-fabrication field. This paper presents an overview on the state-of-the-art AM technology for bone tissue engineering (BTE) scaffolds, with a particular focus on the AM scaffolds made of metallic biomaterials. It starts with a brief description of architecture design strategies to meet the biological and mechanical property requirements of scaffolds. Then, it summarizes the working principles, advantages and limitations of each of AM methods suitable for creating porous structures and manufacturing scaffolds from powdered materials. It elaborates on the finite-element (FE) analysis applied to predict the mechanical behavior of AM scaffolds, as well as the effect of the architectural design of porous structure on its mechanical properties. The review ends up with the authors’ view on the current challenges and further research directions.
Time-of-Flight-Based Radio Tomography for Device Free Localization

Due to its ability of realizing device free localization with wireless networks, the radio tomography becomes a promising technique that draws considerable attention. Traditional radio tomography makes use of the received signal strength (RSS) of wireless links to realize location estimation. However, the RSS measurement is particularly sensitive to noise. Inspired by the fact that similar to the RSS, the time-of-flight (TOF) measurement also changes significantly when some objects shadow the wireless link, and the fact that compared with the RSS, the TOF measurement is robust to noise, a novel TOF-based radio tomography is proposed in this paper. With the TOF measurements of the shadowed links as observation information, a modified particle filter algorithm which utilizes the compressive sensing technique to produce the importance distribution of the particle set is proposed, so as to realize localization and tracking with under-sampled measurements by making full use of the space-domain sparse and time-domain gradually changed feature of the location information. The experiments with the 802.15. 4a chirp spread spectrum ranging hardware are presented to confirm the proposed scheme.
Non-Verbal Cognitive Abilities in Children and Adolescents Affected by Migraine and Tension-Type Headache: An Observational Study Using the Leiter-3

Headache is one of the most common neurological disorders in developmental age. Several studies investigated the relationship between headache and emotional/behavioral problems. We studied non-verbal cognitive abilities, including non-verbal memory and attention skills, in order to evaluate the impact of primary headache on these domains. The latest version of the cognitive battery Leiter International Performance Scale – Third Edition (Leiter-3), a non-verbal test, was administered to 35 children and adolescents affected by migraine or tension-type headache and to 23 healthy subjects. We found that frequency of attacks and headache disability (evaluated with the Pediatric Migraine Disability Assessment Score Questionnaire) significantly correlate with non-verbal memory and sustained attention skills. However, we found that headache disability has a significant impact on specific cognitive domains related to sustained attention and non-verbal memory skills. The relationship between headache and memory/attention deficits may have an explanation based on a possible common physiopathology ground, including noradrenergic and dopaminergic pathways.
Sports Mass Age Therapy on the Reduction of Delayed Onset Muscle Soreness of the Quadriceps Femoris

Purpose. Massage therapy is one of most commonly applied treatments during athletic training. The aim of this study was to assess the effectiveness of sports massage therapy on reducing post-exercise quadriceps muscle soreness. Methods. A sample of 29 women aged 24–26 years was divided into an experimental group (n = 15) receiving classic sports massage therapy and a control group (n = 14) given no treatment. An exercise session consisting of five sets of deep squat jumps was administered after which lower limb power as assessed via the vertical jump test. Muscle soreness was assessed using the visual analogue scale (VAS) and exercise intensity with the borg Rating of Perceived Exertion Scale. Subsequent measurements of lower limb power and muscle soreness were performed 24, 48, 72 and 96 h after the exercise session. Differences between the measurements were assessed by the Friedman and least significant difference tests while between-group comparisons involved the Mann–Whitney U test. Results. The largest decrease in lower limb power was observed between the first measurement after the exercise session and 24 h later (p < 0.01). The smallest decrease in power was observed in the massage group. The highest levels of muscle soreness were noted 24 h post-exercise in the massage group and 48 h post-exercise in the control group. The experimental group showed a decrease in muscle soreness in each subsequent measurement, with the results close to zero on the VAS 96 h postexercise. Conclusions. Massage therapy quickened recovery and improved muscle efficiency post-exercise and may serve as an effective treatment of muscle soreness. The analgesic effect of massage suggests it should be widely applied in sport, physical therapy and rehabilitation.
How Temperature and Loading Rate Affect the Yield Behavior in Polymer-modified Asphalt Systems

This paper reports on how temperature and loading rate affect the low-temperature yield properties of two asphalts (California Valley and Bow River sources), straight and modified with 5% by weight of four commonly used commercial polymers (styrene–butadiene diblock, triblock and radial and ethylene–vinyl acetate copolymers). The Bow River asphalt was also tested with the addition of mineral filler. Both the source of the bitumen as well as the nature of the additive and the presence of filler were found to have a significant influence on how the yield stress changes with temperature and loading time. Only one homogeneous, California Valley binder modified with SBS triblock copolymer, provided a typical Eyring plot with a constant activation energy of 42 kJ/mol and activation volume of 3.7 nm3. Other systems showed atypical behavior in that the activation parameters changed rapidly with both temperature and rate of loading.
Crosstalk between p 53 and NF-B systems : pro-and anti-apoptotic functions of NF-B

Nuclear factors p53 and NFB control many physiological processes including cell cycle arrest, DNA repair, apoptosis, death, innate and adaptive immune responses, and inammation. There are numerous pathways linking these systems and there is a bulk of evidence for cooperation as well as for antagonisms between p53 and NFB. In this theoretical study, we use our earlier models of p53 and NFB systems and construct a crosstalk model of p53 NFB network in order to explore the consequences of the two-way coupling, in which NFB upregulates transcription of p53, while in turn p53 attenuates transcription of NFB inhibitors I B and A20. We consider a number of protocols in which cells are stimulated by TNF (that activates NFB pathway) and/or gamma irradiation (that activates p53 pathway). We demonstrated that NFB may have both antiand pro-apoptotic roles. TNF stimulation, preceding DNA damaging irradiation, makes cells more resistant to irradiation-induced apoptosis, while the same TNF stimulation, when preceded by irradiation increases the apoptotic cell fraction. Our nding suggests that diverse roles of NFB in apoptosis and cancer could be related to the dynamical context of activation of p53 and NFB pathways.
2-Hydroxypropyl-β-cyclodextrins and the Blood-Brain Barrier: Considerations for Niemann-Pick Disease Type C1

The rare, chronic, autosomal-recessive lysosomal storage disease Niemann-Pick disease type C1 (NPC1) is characterized by progressively debilitating and ultimately fatal neurological manifestations. There is an urgent need for disease-modifying therapies that address NPC1 neurological pathophysiology, and passage through the blood-brain barrier represents an important consideration for novel NPC1 drugs. Animal investigations of 2-hydroxypropyl-β-cyclodextrins (HPβCD) in NPC1 in mice demonstrated that HPβCD does not cross the blood-brain barrier in significant amounts but suggested a potential for these complex oligosaccharides to moderately impact CNS manifestations when administered subcutaneously or intraperitoneally at very high doses; however, safety concerns regarding pulmonary toxicity were raised. Subsequent NPC1 investigations in cats demonstrated far greater HPβCD efficacy at much lower doses when the drug was administered directly to the CNS. Based on this, a phase 1/2a clinical trial was initiated with intrathecal administration of a specific, well-characterized mixture of HPβCD, with a tightly controlled molar substitution specification and a defined molecular “fingerprint” of the different species. The findings were very encouraging and a phase 2b/3 clinical trial has completed enrollment and is underway. In addition, phase 1 clinical studies utilizing high-dose intravenous administration of a different HPβCD are currently recruiting. Independent studies are needed for each product to satisfactorily address questions of safety, efficacy, dosing, and route of administration. The outcomes cannot be assumed to be translatable between HPβCD products and/or routes of administration.
Reduced Working Memory Mediates the Link between Early Institutional Rearing and Symptoms of ADHD at 12 Years

Children who are raised in institutions show severe delays across multiple domains of development and high levels of psychopathology, including attention deficit/hyperactivity disorder (ADHD). Low performance in executive functions (EFs) are also common in institutionally reared children and often do not remediate following improvements in the caregiving environment. ADHD symptomatology also remains elevated even after children are removed from institutional care and placed in families. We investigate whether poor EF is a mechanism explaining elevated rates of ADHD in children reared in institutional settings in the Bucharest Early Intervention Project (BEIP). In the current study, we examine the potentially mediating role of poor EF in the association between institutionalization and symptoms of ADHD at age 12 years. A total of 107 children were assessed with the Cambridge Neuropsychological Test Automated Battery (CANTAB) on working memory, set-shifting and planning. We also obtained concurrent teacher reports on their levels of ADHD symptoms (inattention and impulsivity separately). Institutionalization strongly predicted elevations in symptoms of inattention and impulsivity at age 12 years (ps < 0.01). Indices of working memory and planning were also associated with ADHD after controlling for potential confounders (ps < 0.03). Mediation analyses revealed that poor working memory performance mediated the link between exposure to early institutionalization and higher scores of both inattention and impulsivity. These results replicate and extend the findings that we reported in the BEIP sample at age 8 years. Together, they suggest that compromised working memory is a key mechanism that continues to explain the strikingly high levels of ADHD in late childhood among children institutionalized in early life. Interventions targeting working memory may help to prevent ADHD among children exposed to institutional care.
The effect of decellularized tissue engineered constructs on periodontal regeneration

AIM To evaluate the effect of decellularized tissue engineered constructs on cell differentiation in vitro and periodontal regeneration in vivo. MATERIALS AND METHODS Periodontal ligament cell (PDLC) sheets were loaded on polycaprolactone (PCL) scaffolds and then decellularized. Constructs were assessed for their effect on allogenic PDLC and mesenchymal stem cell (MSC) differentiation in vitro, as evaluated by gene expression of bone and periodontal ligament tissue markers post-seeding. Expression of MSC marker STRO-1 was assessed by immunostaining. Decellularized constructs were evaluated in a rat periodontal defect model to assess their biocompatibility and tissue integration. Microcomputed topography (μCT) and histological assessment were performed to assess the regenerative potential of the constructs at 2 and 4 weeks postoperatively. RESULTS There was upregulation of bone marker gene expression by PDLCs especially on the 14th day. MSCs lacked bone markers expression, but showed increased collagen I marker expression on day 14. STRO-1 expression by the MSCs decreased over the three timepoints when seeded on decellularized sheets. Histological assessment demonstrated the biocompatibility of the decellularized constructs in vivo. More new attachment formation was observed on the decellularized constructs compared to scaffold only controls. CONCLUSION Decellularized tissue engineered constructs are capable of inducing cell differentiation in vitro and have the potential to facilitate periodontal regeneration in vivo.
Differences in the Synthesis and Elimination of Phosphatidylethanol 16: 0/18 1 and 16 0/18 2 After Acute Doses of Alcohol

BACKGROUND The purpose of this study was to examine the synthesis and elimination of phosphatidylethanol (PEth) 16:0/18:1 and 16:0/18:2 following the consumption of alcohol among 56 light and heavy drinkers. METHODS A transdermal alcohol monitor was used to promote alcohol absence 7 days prior, and 14 days after, alcohol consumption in the laboratory. Participants consumed a 0.4 or 0.8 g/kg dose of alcohol in 15 minutes. Blood and breath samples were collected before, at various times up to 360 minutes postconsumption, and 2, 4, 7, 11, and 14 days after alcohol consumption. Initial rates of PEth synthesis, 360 minutes area under the PEth pharmacokinetic curves (AUCs), and elimination half-lives were determined. RESULTS (i) Nonzero PEth levels were observed before alcohol dosing for most participants, despite 7 days of alcohol use monitoring; (ii) 0.4 and 0.8 g/kg doses of alcohol produced proportional increases in PEth levels in all but 1 participant; (iii) the initial rate of synthesis of both PEth homologues did not differ between the 2 doses, but was greater for PEth 16:0/18:2 than PEth 16:0/18:1 at both doses; (iv) the mean AUC of both PEth homologues was higher at 0.8 g/kg than at 0.4 g/kg; (v) the mean AUC of 16:0/18:2 was greater than that of PEth 16:0/18:1 at both alcohol doses; (vi) the mean half-life of PEth 16:0/18:1 was longer than that of PEth 16:0/18:2 (7.8 ± 3.3 [SD] days and 6.4 ± 5.0 [SD] days, respectively); and (vii) there were no sex differences in PEth 16:0/18:1 or 16:0/18:2 pharmacokinetics. CONCLUSIONS The results of this study support the use of PEth 16:0/18:1 and 16:0/18:2 as biomarkers for alcohol consumption. Because of consistent pharmacokinetic differences, the levels of these 2 PEth homologues may provide more information regarding the quantity and recentness of alcohol consumption than either alone.