Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of Pharmacokinetics and Dose Proportionality of Diazepam After Intranasal Administration of NRL‐1 to Healthy Volunteers

NRL‐1 is a novel intranasal formulation of diazepam that is being evaluated as rescue medication in patients with epilepsy who experience bouts of increased seizure activity despite stable regimens of antiepileptic drugs. This phase 1, open‐label, randomized, crossover study in healthy adult volunteers consisted of 3 single‐dose periods (5, 10, and 20 mg) followed by a 2‐dose period (2 × 10 mg) with a minimum 28‐day washout between treatments. Blood samples were taken at prespecified time points after intranasal dosing, and bioanalytic analysis of diazepam and nordiazepam was conducted using a validated liquid chromatography–tandem mass spectrometry method. Plasma pharmacokinetic parameters were summarized using descriptive statistics, and dose proportionality (peak concentration [Cmax] and area under the plasma concentration–time curve [AUC0‐∞]) was evaluated based on a power model within a 90%CI of 0.84 to 1.16. Comparisons were also conducted between single 10‐mg dose and multidose (2 × 10 mg) treatments. NRL‐1 administration resulted in rapid diazepam absorption (median time to peak concentration 1.4‐1.5 hours). Plasma concentration‐time profiles showed similar patterns of exposure that appeared to be dose dependent, with Cmax of 85.6, 133.6, and 235.3 ng/mL for the 5‐, 10‐, and 20‐mg doses, respectively, although the lower 90%CI for Cmax and AUC0‐∞ exceeded dose proportionality criteria. The coefficient of variation ranged from 59% to 67% for Cmax and 48% to 56% for AUC parameters. Dose‐normalized AUC0–∞ values were comparable between the 2 × 10‐mg and single 10‐mg doses. Treatment‐emergent adverse events were consistent with those expected for diazepam, with transient somnolence the most frequent adverse event (94.4%). These results support NRL‐1 as a potential therapy for managing seizure emergencies.
Fake news, fast and slow: Deliberation reduces belief in false (but not true) news headlines.

What role does deliberation play in susceptibility to political misinformation and "fake news"? The Motivated System 2 Reasoning (MS2R) account posits that deliberation causes people to fall for fake news, because reasoning facilitates identity-protective cognition and is therefore used to rationalize content that is consistent with one's political ideology. The classical account of reasoning instead posits that people ineffectively discern between true and false news headlines when they fail to deliberate (and instead rely on intuition). To distinguish between these competing accounts, we investigated the causal effect of reasoning on media truth discernment using a 2-response paradigm. Participants (N = 1,635 Mechanical Turkers) were presented with a series of headlines. For each, they were first asked to give an initial, intuitive response under time pressure and concurrent working memory load. They were then given an opportunity to rethink their response with no constraints, thereby permitting more deliberation. We also compared these responses to a (deliberative) 1-response baseline condition where participants made a single choice with no constraints. Consistent with the classical account, we found that deliberation corrected intuitive mistakes: Participants believed false headlines (but not true headlines) more in initial responses than in either final responses or the unconstrained 1-response baseline. In contrast-and inconsistent with the Motivated System 2 Reasoning account-we found that political polarization was equivalent across responses. Our data suggest that, in the context of fake news, deliberation facilitates accurate belief formation and not partisan bias. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
Contribution of Habitual Activity to Cruciate Ligament Rupture in Labrador Retrievers

Abstract Objective The aim of this study was to describe the contribution of signalment and habitual activity in the development of cruciate ligament rupture (CR) in Labrador Retrievers. Study Design Four hundred and twelve client-owned purebred Labrador Retrievers were recruited. Dogs were assigned either as affected with CR or as controls based on signalment, physical examination and radiographic evidence of disease. Clients were asked to complete a questionnaire related to signalment, concurrent disease and a questionnaire pertaining to their dog's activity before development of CR or general activity during the dog's most active years. Results Habitual activity was not significantly different between dogs affected with CR and controls. There was no significant difference in neuter status or body weight between CR affected dogs and controls. Labrador Retrievers with a yellow coat, and Labradors that did not maintain an optimal body weight in the opinion of their veterinarian were at increased risk of developing CR. Conclusions Habitual activity level is not a risk factor for development of CR in Labrador Retrievers. Our study did not show neuter status, sex or body weight to be risk factors for CR. However, coat colour and not sustaining optimal body condition are significant risk factors for CR.
Needs Analysis for Mountain Search and Rescue

ABSTRACT INDIVIDUALS BELONGING TO MOUNTAIN SEARCH AND RESCUE TEAMS ARE REQUIRED TO DEMONSTRATE PROFICIENCY IN TECHNICAL ROCK RESCUE, WILDERNESS SEARCH, AND SNOW/ICE OPERATIONS TO SAVE LIVES FROM INCIDENTS IN THE BACKCOUNTRY. IN MOST CASES, A HIGH LEVEL OF FITNESS IS REQUIRED TO SUCCESSFULLY PERFORM THESE TASKS. THE PURPOSE OF THIS ARTICLE IS TO PROVIDE THE READER WITH INFORMATION REGARDING THE ESSENTIAL JOB TASKS, AS WELL AS THE FITNESS AND PERFORMANCE NEEDS FOR THIS GROUP OF OCCUPATIONAL ATHLETES.
Changes in smoker characteristics in England between 2008 and 2017

Abstract Aims At a time of declining smoking prevalence in England, it is useful to document any changes in the characteristics of smokers. This has implications for targeting tobacco control policies and interventions. This study compared the characteristics of smokers from 2008 to 2017 to assess changes in smoking and quitting patterns and socio‐demographic profile. Design and setting Analysis of annual trends in results from repeated cross‐sectional surveys of representative samples of the population in England from 2008 to 2017. Participants The study included 208 813 adults aged 16+. Measurements Information was gathered on age, sex, social grade and region, cigarette consumption, cigarette dependence as measured by time to first cigarette of the day, daily smoking, smoking roll‐your‐own cigarettes, attempts to cut down, use of an e‐cigarette or nicotine replacement therapy, attempts to cut down or quit, use of support in quit attempts and whether the quit attempt was abrupt. Findings During the period, mean daily cigarette consumption [B = –0.30, 95% confidence interval (CI) = –0.33 to −0.27] and the time to first cigarette score decreased (B = –0.03, 95% CI = –0.03 to −0.02). The proportion of smokers attempting to cut down or quit decreased (odds ratio (OR) range = 0.96–0.97, 95% CI range = 0.95–0.97). Use of behavioural support [odds ratio (OR) = 0.89, 95% CI = 0.86–0.92] or no support decreased (OR = 0.98, 95% CI = 0.96–0.99), while use of pharmacological support, including e‐cigarettes, increased (OR = 1.04, 95% CI = 1.02–1.05). There was no significant change in the difference in social grade between smokers and non‐smokers comparing 2008 with 2017. Changes in smoking and quitting behaviour were independent of changes in socio‐demographic characteristics. Conclusions Between 2008 and 2017 in England, smokers appear to have become less dependent on cigarettes but less likely to try to quit or cut down. Of those who tried to quit, fewer used behavioural support and more used pharmacological support. The proportion from more disadvantaged backgrounds did not change significantly.
Clinicopathologic features and prognostic analysis of Waldeyer ring B-cell lymphoma

Abstract This retrospective study is to explore the clinicopathologic, immunophenotypic, and molecular genetic features of Waldeyer ring B-cell lymphoma (WR-BCL). Tissue arrays from 65 WR-BCL cases were subjected to pathologic and immunophenotypic detections. Expression of Epstein–Barr virus-encoded small RNA (EBER) was detected by in situ hybridization. Interferon regulatory factor 4 (IRF4), BCL-2, BCL-6, and C-myelocytomatosis viral oncogeneav (MYC) gene abnormalities were investigated using interphase fluorescence in situ hybridization. Among the 65 patients, there were 12 nasopharynx cases, 49 tonsil cases, and 4 tongue root cases. Moreover, there were 49 cases of diffuse large BCL (DLBCL) and 16 cases of follicular lymphoma (FL). More than 60% of the patients had Ann Arbor stage III/IV disease, with infiltrated neighboring organs, invaded spleens, and increased lactate dehydrogenase (LDH) levels. Tumor cells were positive for multiple myeloma antigen 1 (MUM1), BCL-2, BCL-6, and C-MYC. EBER expression was detected in lymphoma cells of 2 cases. Alteration frequencies of IRF4, BCL-2, BCL-6, and C-MYC were 24.6%, 32.3%, 27.7%, and 30.7%, respectively. Approximately 67.69% cases had stages 0 to II disease, while 32.31% cases had stage III disease. Five-year overall survival rate was 65.12%. Eastern Cooperative Oncology Group performance status (ECOG) score ≥2 was the only adverse factor for overall survival. IRF4/MUM1, C-MYC, and CD10 expressions were related to poor disease prognosis. WR-BCLs were largely dependent on ECOG, LDH, and bone marrow involvement. WR-DLBCL was associated with poor survival outcomes compared with WR-FL. The WR-DLBCLs have distinct clinicopathologic features, with correlations between the IRF4/MUM1, C-MYC and CD10 expressions, ECOG, LDH, bone marrow involvement, and the disease prognosis.
Evaluating emotional distress and health-related quality of life in patients with heart failure and their family caregivers: Testing dyadic dynamics using the Actor-Partner Interdependence Model

Purpose 1) To compare levels of emotional symptoms and health-related quality of life between patients with heart failure and their family caregivers; and 2) to examine whether patients’ and caregivers’ emotional symptoms were associated with their own, as well as their partner’s health-related quality of life. Method In this cross-sectional study, 41 patients-caregiver dyads (78% male patients, aged 68.6 years; and 83% female caregivers, aged 65.8 years) completed all nine dimensions of the Brief Symptom Inventory and the Minnesota Living with Heart failure Questionnaire. Dyadic data were analysed for 6 sub-scales of the Brief Symptom Inventory, using the Actor–Partner Interdependence Model. Results There were no statistically significant differences in emotional symptoms and health-related quality of life between patients with heart failure and their caregivers. Patients’ and caregivers’ emotional symptoms were associated with their own health-related quality of life. Caregivers’ anxiety, phobic anxiety, obsession-compulsion, depression and hostility negatively influenced their partner’s (i.e. the patient’s) health-related quality of life. There were no partner effects of patients’ emotional symptoms on the health-related quality of life of caregivers. Conclusions The results of this study suggest that patients may be particularly vulnerable to the emotional distress, i.e. thoughts, impulses and actions of their caregivers. It may be possible to improve patients’ health-related quality of life by targeting specific detrimental emotional symptoms of caregivers.
Improving the assessment of measurement invariance: Using regularization to select anchor items and identify differential item functioning.

A common challenge in the behavioral sciences is evaluating measurement invariance, or whether the measurement properties of a scale are consistent for individuals from different groups. Measurement invariance fails when differential item functioning (DIF) exists, that is, when item responses relate to the latent variable differently across groups. To identify DIF in a scale, many data-driven procedures iteratively test for DIF one item at a time while assuming other items have no DIF. The DIF-free items are used to anchor the scale of the latent variable across groups, identifying the model. A major drawback to these iterative testing procedures is that they can fail to select the correct anchor items and identify true DIF, particularly when DIF is present in many items. We propose an alternative method for selecting anchors and identifying DIF. Namely, we use regularization, a machine learning technique that imposes a penalty function during estimation to remove parameters that have little impact on the fit of the model. We focus specifically here on a lasso penalty for group differences in the item parameters within the two-parameter logistic item response theory model. We compare lasso regularization with the more commonly used likelihood ratio test method in a 2-group DIF analysis. Simulation and empirical results show that when large amounts of DIF are present and sample sizes are large, lasso regularization has far better control of Type I error than the likelihood ratio test method with little decrement in power. This provides strong evidence that lasso regularization is a promising alternative for testing DIF and selecting anchors. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
Relationship between serum 25-hydroxyvitamin D and inflammatory cytokines in Nigerian children with asthma

Abstract Background: Childhood asthma involves a network of mutually interacting inflammatory mediators and cytokines. The influence of serum vitamin D (an immunomodulatory agent) on these cytokines is poorly understood. This study sets out to determine the relationship between serum T-helper cells type 1 cytokines (Interleukins ILs-1β, 2, 6, 8 and 10), type 2 cytokines (ILs 3, 4,5,9,13), ILs-12, 17 and 25-hydroxyvitamin D (25-OHD) in Nigerian children with asthma. Methods: Children with physician-diagnosed asthma and non-asthmatics aged 2-15 years were consecutively recruited at a tertiary center in Nigeria. Serum 25-OHD and cytokines were assayed using chromatography method and association between these parameters determined. Results: A total of 180 children (90 for each group; mean age 7.5 ± 3.9 years; M:F 1.9:1) were recruited. Fifty-six (76.7%) asthmatics had mild intermittent form and symptoms were sub-optimally controlled in 16 (21.9%). The mean (SD) serum Vitamin D was lower in children with asthma (38.8 ± 17.0 ng/ml vs. 45.5 ± 16.6 ng/ml vs. p = 0.023). Also more proportion of children with asthma had suboptimal serum vitamin D level (26.0% vs. 8.8%; p = 0.022). Deficient vitamin D state was associated with higher serum Th1 and Th2 cytokines compared to insufficient state, but the highest cytokine levels were observed in normal vitamin D state. There was significant positive correlation between serum vitamin D and Th1 cytokines IL-2 and IL-8 as well as Th2 cytokines (ILs-3, 4, 5 and 9), but negative correlation with IL-13 Conclusions: Serum Vitamin D and cytokines were lower in a sample of Nigerian children with asthma than controls. Vitamin D status was not related to asthma severity and control. Serum 25-OHD seems to have a non-linear relationship with Th1 and Th2 cytokines in Nigerian asthmatics.
Expanding Point-of-Care Ultrasound Training in a Low- and Middle-Income Country: Experiences From a Collaborative Short-Training Workshop in Kenya.

BACKGROUND AND OBJECTIVES In Kenya, little data exists on point-of-care ultrasound (POCUS) training and use for family medicine physicians. In 2017, a 3-day POCUS workshop assembled most of the family medicine physicians in Kenya. Through surveys, we assessed how this workshop could affect the level of POCUS use, skill, and confidence in family medicine practitioners in the long term. METHODS Structured surveys, distributed before, after, and 10 months postworkshop assessed demographics, POCUS use, barriers, comfort, and skills based on attendee self-assessment. We compared data from the preworkshop surveys to postsurveys and post-postsurveys to assess immediate and long-term differences. Wilcoxon signed-rank test was used to evaluate continuous data, and significance was based on a P value of <. 05. RESULTS The proportion of participants who self-reported using POCUS increased significantly between presurvey and post-postsurvey (29.7% to 63.2%, P=.0161). Mean confidence scores increased significantly from presurvey to postsurvey and post-postsurvey. For all body systems, self-reported mean skill scores increased significantly from presurvey to postsurvey and post-postsurvey. Lack of access to machines and mentorship are substantial barriers to increasing POCUS use. CONCLUSIONS This study highlights the utility of one-time POCUS training in increasing long-term POCUS uptake by participants. While encouraging, our findings also show barriers to increasing POCUS use. These barriers must be addressed, potentially through intradepartmental and interorganizational exchanges of resources to ensure that future POCUS workshops are successful in supporting POCUS use in Kenya.
Impact of biparametric prebiopsy prostate magnetic resonance imaging on the diagnostics of clinically significant prostate cancer in biopsy naïve men

Abstract Background: The objective of this study was to compare the prevalence of clinically significant prostate cancer (CSPCa) in men with biparametric prebiopsy prostate magnetic resonance imaging (MRI) and lesion-targeted biopsies (TBs) to the group of men without prebiopsy MRI in an initial biopsy session. Methods: The MRI group consists of men enrolled into four prospective clinical trials investigating a biparametric MRI (bpMRI) and TB while the non-MRI group was a retrospective cohort of men collected from an era prior to a clinical use of a prostate MRI. All men had standard biopsies (SBs). In the MRI group, men had additional TBs from potential cancer-suspicious lesions. CSPCa was defined as Gleason score ≥3 + 4 in any biopsy core taken. All the patients were prostate biopsy naïve. Results: The MRI group consists of 507 while the non-MRI group 379 men. Mean age and prostate specific antigen (PSA) level differed significantly (p < 0.05) between the groups: In the MRI group, 64 years and 7.6 ng/ml, respectively, and in the non-MRI group 68 years and 8.2 ng/ml, respectively. Significantly (p < 0.05) more CSPCa was diagnosed with initial biopsies in the MRI group (48%) compared to non-MRI group (34%). In men with no CSPCa diagnosed during the initial biopsies, significantly fewer (p < 0.05) men had upgrading re-biopsies in the MRI group (5%) than in the non-MRI group (19%) during the follow up. Conclusions: Prebiopsy bpMRI with TBs combined with SBs could lead to earlier diagnoses of CSPCa compared with men without prebiopsy prostate MRI used in initial PCa diagnostics.
Early childhood anaemia more than doubles the risk of developmental vulnerability at school‐age among Aboriginal and Torres Strait Islander children of remote Far North Queensland: Findings of a retrospective cohort study

Abstract Aims Early childhood anaemia, usually attributed to iron deficiency, is associated with persistent detrimental effects on child development. This study investigates the association of anaemia between age six and 23 months with indicators of childhood development at school‐age among children of remote Aboriginal and Torres Strait Islander communities of Far North Queensland. Methods The triennial Australian Early Development Census (AEDC) encompasses five domains of early childhood development—physical health and wellbeing, social competence, emotional maturity, language and cognitive skills (school‐based), communication skills and general knowledge. AEDC 2012 and 2015 assessments were linked with health information for children and their mothers from remote Aboriginal and Torres Strait Islander communities of Far North Queensland. Results AEDC assessments were available for 250 children who had measurements of haemoglobin recorded at age 6 to 23 months. More children who had had early childhood anaemia (n = 66/143, 46.2%, [37.9%, 54.4%]) were developmentally vulnerable on two or more domains compared to those who had not been anaemic (n = 25/107, 23.4% [15.2%, 31.5%], P < .001). Multivariable analysis confirmed that early childhood anaemia more than doubled the risk of developmental vulnerability (OR 2.2 [1.1, 4.3] P = .020) at school age. Conclusions Early childhood anaemia is a risk factor for developmental vulnerability at school‐age in this setting. Interventions combining nutrition promotion and multi‐micronutrient food fortification, are effective in prevention of early childhood anaemia. Such interventions could also improve early childhood development and subsequent educational achievement.
Effect of Self-Efficacy on Quality of Life in People With Mild Cognitive Impairment and Mild Dementia: The Mediating Roles of Depression and Anxiety

Objectives: To examine the mediating effects of depression and anxiety in the relationship between self-efficacy and quality of life among people with mild cognitive impairment (MCI) or mild dementia. Method: A total of 196 patients diagnosed with MCI or dementia due to Alzheimer disease completed structured measures of self-efficacy, quality of life, and depressive and anxiety symptoms. We examined direct and mediated effects by fitting structural equation models to data. Results: Our analyses supported that the effects of self-efficacy on quality of life may be partially mediated by depression and anxiety. Both anxiety and depression had significant mediating effects, with depression showing a stronger effect. Conclusion: These results suggest that increased self-efficacy may have a positive effect on quality of life in people with MCI or dementia—partly by reducing depression and anxiety. These findings may have important practical implications for tailoring therapeutic interventions.