Miracle-dz/UniFAR-FTUs huggingface dataset:
Advance care planning: identifying system-specific barriers and facilitators.

BACKGROUND Advance care planning (acp) is an important process in health care today. How to prospectively identify potential local barriers and facilitators to uptake of acp across a complex, multi-sector, publicly funded health care system and how to develop specific mitigating strategies have not been well characterized. METHODS We surveyed a convenience sample of clinical and administrative health care opinion leaders across the province of Alberta to characterize system-specific barriers and facilitators to uptake of acp. The survey was based on published literature about the barriers to and facilitators of acp and on the Michie Theoretical Domains Framework. RESULTS Of 88 surveys, 51 (58%) were returned. The survey identified system-specific barriers that could challenge uptake of acp. The factors were categorized into four main domains. Three examples of individual system-specific barriers were "insufficient public engagement and misunderstanding," "conflict among different provincial health service initiatives," and "lack of infrastructure. " Local system-specific barriers and facilitators were subsequently explored through a semi-structured informal discussion group involving key informants. The group identified approaches to mitigate specific barriers. CONCLUSIONS Uptake of acp is a priority for many health care systems, but bringing about change in multi-sector health care systems is complex. Identifying system-specific barriers and facilitators to the uptake of innovation are important elements of successful knowledge translation. We developed and successfully used a simple and inexpensive process to identify local system-specific barriers and enablers to uptake of acp, and to identify specific mitigating strategies.
CD133 Expression in Normal Skin and in Epithelial Cutaneous Tumors

Background. Expression of human CD133 (human prominin-1) in cancer cells has been postulated to be a marker of stemness and is considered as a putative marker of cancer stem cells (CSCs). We designed a study to describe the expression pattern of CD133 in normal skin and in epithelial cutaneous neoplasms. Methods. The CD133 immunohistochemical expression of forty-three eccrine and apocrine tumors was compared to that observed in other epithelial tumors of the skin. In addition, flow cytometry was used to detect the CD133 expression of four epithelial skin neoplasms, including one porocarcinoma. Results. CD133 immunoreactivity at the apical or at the apicolateral surface of cells forming glandular structures was observed. Cells from solid areas of benign or malignant tumors were not stained. The porocarcinoma derived culture cells showed a 22% of CD133 positive cells using flow cytometry, while squamous cell carcinoma cultures contained less than 0.1%. Conclusions. These observations indicate that CD133 is a specific marker of glandular differentiation that could be included in the diagnostic panel of cutaneous tumors with possible eccrine or apocrine differentiation. However, the use of CD133 expression as a marker of CSCs should be interpreted with caution in experiments of skin.
Effects of cytochalasin and phalloidin on actin

C YTOCHALASINS and phalloidins are two groups of small, naturally occurring organic molecules that bind to actin and alter its polymerization. They have been widely used to study the role of actin in biological processes and as models for actin-binding proteins. Functionally, cytochalasins resemble capping proteins, which block an end of actin filaments, nucleate polymerization, and shorten filaments. No known actin-binding protein stabilizes actin filaments as phalloidin does, but such proteins may have been missed. Cytochalasin and phalloidin have also helped to elucidate fundamental aspects of actin polymerization. This review briefly summarizes older studies and concentrates on recent v~rk on the mechanisms of action of cytochalasin and phalloidin.
Arabidopsis Calcium-Dependent Protein Kinase AtCPK32 Interacts with ABF4, a Transcriptional Regulator of Abscisic Acid-Responsive Gene Expression, and Modulates Its Activity1

The phytohormone abscisic acid (ABA) regulates stress-responsive gene expression during vegetative growth. The ABA regulation of many genes is mediated by a subfamily of basic leucine zipper class transcription factors referred to as ABFs (i.e. ABF1–ABF4), whose transcriptional activity is induced by ABA. Here we show that a calcium-dependent protein kinase is involved in the ABA-dependent activation process. We carried out yeast two-hybrid screens to identify regulatory components of ABF4 function and isolated AtCPK32 as an ABF4-interacting protein. AtCPK32 has autophosphorylation activity and can phosphorylate ABF4 in vitro. Mutational analysis indicated that serine-110 of ABF4, which is highly conserved among ABF family members, may be phosphorylated by AtCPK32. The serine-110 residue is essential for ABF4-AtCPK32 interaction, and transient expression assay revealed that it is also required for the normal transcriptional function of ABF4. The expression patterns and subcellular localization of AtCPK32 are similar to those of ABF4. Furthermore, its overexpression affects both ABA sensitivity and the expression of a number of ABF4-regulated genes. Together, our data demonstrate that AtCPK32 is an ABA signaling component that regulates the ABA-responsive gene expression via ABF4.
Severe Intrauterine Growth Restriction Is Associated With Higher Spontaneous Carbohydrate Intake in Young Women

Intrauterine growth restriction (IUGR) is associated with metabolic disorders in adulthood. In rats, an early adverse environment alters food preferences in adult life. We investigated whether IUGR is associated with spontaneous macronutrient preferences in humans. Two thousand sixty-three participants from a Brazilian birth cohort were evaluated at 24 y of age using a food frequency questionnaire, physical examination, anthropometric measurements, and biochemical assays (glucose, insulin, cholesterol, and triglycerides). IUGR was defined by the birth weight ratio (BWR = birth weight/mean weight for gestational age). Individuals were classified as non growth restricted (BWR ≥0.85), moderately growth restricted (0.85 > BWR ≥ 0.75), and severely growth restricted (BWR <0.75). Severe IUGR women consumed a greater carbohydrate to protein ratio, even after controlling for social variables. There was a continuous association between growth restriction and later carbohydrate to protein ratio consumption in women. Women from both IUGR groups had a larger waist to hip ratio (WHR). The prevalence of metabolic syndrome was comparable between the groups. IUGR women preferred carbohydrates to protein in their regular diet, suggesting that spontaneous food choices may precede the appearance and contribute to the risk for metabolic diseases in this group.
Modeling the Behavioral Semantics of Heterogeneous Languages and their Coordination

In the software and system modeling community, research on domain-specific modeling languages (DSMLs) is focused on providing technologies for developing languages and tools that allow domain experts to develop system solutions efficiently. Unfortunately, the current lack of support for explicitly relating concepts expressed in different DSMLs makes it very difficult for software and system engineers to reason about information spread across models describing different system aspects. As a particular challenge, we present in this paper how we dealt with relationships between heterogeneous behavioral models to support their concurrent and coordinated execution. This was achieved by providing dedicated meta-language to define the behavioral semantics of DSMLs and their coordination. The approach made explicit a formal model of the control flow (MoCC); domain-specific actions (DSA) and a well-defined protocol between them (incl., mapping, feedback and callback) reified through explicit domain-specific events (DSE). The protocol is then used to infer a relevant behavioral language interface for specifying coordination patterns to be applied on conforming executable models. As a result, heterogeneous languages and their relationships can be developed in the GEMOC studio, which provides extensive support to run and debug heterogeneous models. This is outlined in the paper on the definition of the Marked Graph language and its coordination with a scenario language.
Population pharmacokinetics of imatinib mesylate in patients with chronic-phase chronic myeloid leukaemia: results of a phase III study.

AIMS This study was designed to investigate the biochemical and physiological covariates or comedications that affect the pharmacokinetics of imatinib mesylate in patients with chronic-phase chronic myeloid leukaemia (CP CML). METHODS Pharmacokinetic data were analyzed in 371 patients receiving 400 mg imatinib once daily during a phase III trial of imatinib vs interferon-alfa plus cytarabine for the treatment of newly diagnosed CP CML. Covariates included age, weight, sex, ethnicity, haemoglobin (Hb) concentration, white blood cell (WBC) count, liver function, and creatinine concentration. Blood samples for imatinib analysis were taken on treatment days 1 and 29. Nonlinear mixed effects modelling was used for the population pharmacokinetic analysis. RESULTS Population mean estimates (95% confidence interval) at day 1 for apparent clearance (CL) and apparent volume of distribution (V) of imatinib were 14 (13-15) l h(-1) and 252 (237-267) l, respectively. Modelling suggested that CL decreased by 4 (3-5) l h(-1) from day 1 to day 29, whereas V remained unchanged. Interindividual variability in CL and V was 32% and 31%, respectively. Weight, Hb, and WBC count demonstrated small effects on CL and V. Doubling body weight or Hb or halving the WBC count was associated with a 12%, 86% and 8% increase in CL, respectively, and a 32%, 60% and 5% increase in V, respectively. Comedications showed no clear effects on imatinib CL. CONCLUSIONS Population covariates and coadministered drugs minimally affected imatinib pharmacokinetics in newly diagnosed CP CML patients.
Emergency treatment of young people following deliberate self-harm.

OBJECTIVE To examine national patterns in the emergency department assessment and treatment during visits by young people, aged 7 to 24 years, who are seen following an episode of deliberate self-harm. METHOD An analysis was conducted of a nationally representative sample of hospital emergency department visits from the 1997-2002 National Hospital Ambulatory Medical Care Survey focusing on visits by persons aged 7 to 24 years related to deliberate self-harm. National census data were used to derive population-based rates of emergency department visits for deliberate self-harm overall and stratified by sex, age, race, and ethnicity. Demographic, clinical, and treatment characteristics of the visits are presented including comparisons of visits that resulted in an inpatient admission with those that resulted in discharge to the community. RESULTS Among young people aged 7 to 24 years, the annual rate of emergency visits with self-harm was 225.3 per 100,000. A mental disorder was diagnosed in 56.0% of these visits including depressive disorders in 15.1% and substance use disorders in 7.3%. Approximately one half of the visits (56.1%) resulted in an inpatient admission. As compared with visits resulting in discharge to the community, emergency department visits that resulted in inpatient admission were significantly more likely to result in the patients receiving a mental disorder diagnosis (63.8% vs 45.7%; P = .03), especially a depressive disorder (22.5% vs 5.8%; P = .005), and receiving psychotropic medications (18.0% vs 4.7%; P = .007), intravenous fluids (39.2% vs 22.3%; P = .02), gastric lavage (24.1% vs 9.8%; P = .02), and a specific antidote for poisoning (12.2% vs 1.3%; P = .02). CONCLUSIONS Mental disorders are diagnosed in roughly one half of emergency department visits by young people following an episode of deliberate self-harm. Systematic mental health assessments in the emergency department of young people following an episode of deliberate self-harm may improve detection of mental disorders.
Locally applied nerve growth factor enhances bone consolidation in a rabbit model of mandibular distraction osteogenesis

Distraction osteogenesis is widely used in treating deformities, defects, and fractures of both long bones and craniofacial bones. Demands for acceleration of bone consolidation are increased in distraction osteogenesis. Nerve growth factor (NGF) can enhance innervation and bone regeneration in a fracture model and stimulate differentiation of osteoblastic cells. In this study, we tested the ability of locally applied NGF to enhance bone regeneration in a rabbit model of mandibular distraction osteogenesis. Twenty rabbits underwent bilateral distraction osteogenesis with a rate of 0.5 mm per 12 h. Two times 0.04 mg human NGFβ (hNGFβ) in buffer was injected into the callus after distraction. The contralateral side received placebo injections. Rabbits were euthanized at consolidation times of 14 and 28 days. Specimens were subjected to radiography, callus dimensions measurement, mechanical testing, and bone histological and histomorphometric analysis. The maximum load, bone volume/total volume, mineral apposition rate of the 1st to 11th day, and mineralized bone percentage were significantly higher in the hNGFβ side at 14 and 28 days (p < 0.05). The data indicate that locally applied hNGFβ can accelerate callus maturation and may be an option to shorten the consolidation period in distraction osteogenesis. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
Homelessness and Neuropsychological Impairment: Preliminary Analysis of Adults Entering Outpatient Psychiatric Treatment

Homelessness has been associated with neuropsychological (NP) impairment, but few studies have adequately controlled for factors known to affect NP performance. We performed brief NP testing examining learning, recall, processing speed, executive functioning, and verbal fluency in 50 ever- and 22 never-homeless persons entering outpatient psychiatric treatment. Groups were matched a priori on key demographic, substance use, psychiatric, and premorbid intelligenc quotient characteristics. Rates of NP impairment were high among both groups (46%–54%). There were no significant differences in global NP impairment. There were trends toward better levels of processing speed and executive functioning among never-homeless relative to ever-homeless. Among the ever-homeless group, NP test performance was unrelated to number of homelessness episodes (median 3). Findings confirm high prevalence of NP impairment among homeless individuals but provide little evidence for broad NP differences between ever- and never-homeless persons matched for coexisting conditions that have confounded interpretation of previous results in the literature.
Individual finger contribution in submaximal voluntary contraction of gripping

The objective of this study was to evaluate individual finger force and contribution to a gripping force, the difference between actual and expected finger forces and subjective discomfort rating at 10 different submaximal voluntary contraction (%MVC) levels (10–100% in 10 increments). Seventy-two participants randomly exerted gripping force with a multi-finger force measurement system. The individual finger force, gripping force and discomfort increased as %MVC levels increased. The middle and ring fingers exerted more force and contributed to a gripping force more than the index and little fingers due to their larger mass fractions of the digit flexor muscles. It was apparent at <50% MVC; however, the index finger increased its contribution and exerted even more force than expected at more than 50% MVC. Subjective discomfort supported the results of the objective measures. This could explain the conflicting findings between index and ring fingers in previous finger contribution studies. Statement of Relevance: Hand tool design is of special interest in ergonomics due to its association with musculoskeletal disorders in the hand. This study reveals a different contribution pattern of the fingers in submaximal voluntary contraction of gripping exertion.
Perception of Shadows in Children with Autism Spectrum Disorders

Background Cast shadows in visual scenes can have profound effects on visual perception. Much as they are informative, they also constitute noise as they are salient features of the visual scene potentially interfering with the processing of other features. Here we asked i) whether individuals with autism can exploit the information conveyed by cast shadows; ii) whether they are especially sensitive to noise aspects of shadows. Methodology/Principal Findings Twenty high-functioning children with autism and twenty typically developing children were asked to recognize familiar objects while the presence, position, and shape of the cast shadow were systematically manipulated. Analysis of vocal reaction time revealed that whereas typically developing children used information from cast shadows to improve object recognition, in autistic children the presence of cast shadows—either congruent or incongruent—interfered with object recognition. Critically, vocal reaction times were faster when the object was presented without a cast shadow. Conclusions/Significance We conclude that shadow-processing mechanisms are abnormal in autism. As a result, processing shadows becomes costly and cast shadows interfere rather than help object recognition.
A Cytolethal Distending Toxin Variant from Aggregatibacter actinomycetemcomitans with an Aberrant CdtB That Lacks the Conserved Catalytic Histidine 160

The periodontopathogen Aggregatibacter actinomycetemcomitans synthesizes several virulence factors, including cytolethal distending toxin (CDT). The active CDT holoenzyme is an AB-type tripartite genotoxin that affects eukaryotic cells. Subunits CdtA and CdtC (B-components) allow binding and intracellular translocation of the active CdtB (A-component), which elicits nuclear DNA damage. Different strains of A. actinomycetemcomitans have diverse virulence genotypes, which results in varied pathogenic potential and disease progression. Here, we identified an A. actinomycetemcomitans strain isolated from two patients with advance chronic periodontitis that has a regular cdtABC operon, which, however, codes for a unique, shorter, variant of the CdtB subunit. We describe the characteristics of this CdtBΔ116–188, which lacks the intact nuclear localisation signal and the catalytic histidine 160. We show that the A. actinomycetemcomitans DO15 isolate secretes CdtBΔ116–188, and that this subunit cannot form a holotoxin and is also not genotoxic if expressed ectopically in HeLa cells. Furthermore, the A. actinomycetemcomitans DO15 isolate is not toxic, nor does it induce cellular distention upon infection of co-cultivated HeLa cells. Biological significance of this deletion in the cdtB remains to be explained.
Analysis of Functional Responses at G Protein-Coupled Receptors: Estimation of Relative Affinity Constants for the Inactive Receptor State

We describe a modification of receptor theory that enables the estimation of relative affinity constants for the inactive state of a G protein-coupled receptor. Our approach includes the traditional parameters of observed affinity (Kobs) and efficacy (fraction of ligand-receptor complex in the active state, ε) and introduces the concept of the fraction of the ligand-receptor complex in the inactive state (intrinsic inactivity, εi). The relationship between receptor activation and the ligand concentration is known as the stimulus, and the operational model expresses the response as a logistic function of the stimulus. The latter function includes Kobs and the parameter τ, which is proportional to ε. We introduce the parameter τi, which is proportional to εi. We have previously shown that the product, Kobsτ, of one agonist, expressed relative to that of another (intrinsic relative activity, RAi), is a relative measure of the affinity constant for the active state of the receptor. In this report, we show that the product, Kobsτi, of one agonist, expressed relative to that of another (intrinsic relative inactivity, RIi), is a relative measure of the affinity constant for the inactive state of the receptor. We use computer simulation techniques to verify our analysis and apply our method to the analysis of published data on agonist activity at the M3 muscarinic receptor. Our method should have widespread application in the analysis of agonist bias in drug discovery programs and in the estimation of a more fundamental relative measure of efficacy (RAi/RIi).
Surface wind‐stress threshold for glacial Atlantic overturning

Using a coupled model of intermediate complexity the sensitivity of the last glacial maximum (LGM) Atlantic meridional overturning circulation (AMOC) to the strength of surface wind‐stress is investigated. A threshold is found below which North Atlantic deep water formation (DWF) takes place south of Greenland and the AMOC is relatively weak. Above this threshold, DWF occurs north of the Greenland‐Scotland ridge, leading to a vigorous AMOC. This nonlinear behavior is explained through enhanced salt transport by the wind‐driven gyre circulation and the overturning itself. Both pattern and magnitude of the Nordic Sea's temperature difference between strong and weak AMOC states are consistent with those reconstructed for abrupt climate changes of the last glacial period. Our results thus point to a potentially relevant role of surface winds in these phenomena.
A nano-orthogonal cutting model based on a modified molecular dynamics technique

A proposed method based on combining the concepts of shape functions of the finite element method (FEM) and a molecular dynamics (MD) technique was developed to evaluate the chip formation and strain and stress distribution in the cutting of single-crystal copper by a nano-scale mechanism. The displacement components for the atom in any temporary situation during the nano-scale cutting could be found. In this paper, the atom is regarded as a node and the lattice is regarded as an element. Using the atom displacements calculated by the MD program and combining the concepts of shape functions of FEM we calculate the equivalent strain for material deformation in the atomic-scale cutting mechanism. The equivalent stress was derived from the equivalent strain from the corresponding flow stress–strain curve, whereas the flow stress–strain curve was obtained from the regression of the stress–strain curve of a nano-copper thin film tension test simulation. In addition, the chip atoms within the diamond space were moved along the tool surface using a mathematical method. Also, this study introduced a new concept: 'a combined Morse potential function and rigid tool space restrictions criterion as the chip separation criterion' for the nano-scale cutting model.