Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of angiotensin receptor–neprilysin inhibition on vascular function in heart failure with reduced ejection fraction: A pilot study

The mechanisms for the benefits of Angiotensin Receptor Neprilysin Inhibition (ARNi) in heart failure patients with reduced ejection fraction (HFrEF) are likely beyond blood pressure reduction. Measures of vascular function such as arterial stiffness and endothelial function are strong prognostic markers of cardiovascular outcomes in HFrEF, yet the impact of ARNi on vascular health remains to be explored. We hypothesized that arterial stiffness and endothelial function would improve after 12 weeks of ARNi in HFrEF. We tested 10 stable HFrEF patients at baseline and following 12 weeks of ARNi [64 ± 9 years, Men/Women: 9/1, left ventricular ejection fraction (EF): 28 ± 6%] as well as 10 stable HFrEF patients that remained on conventional treatment (CON: 60 ± 7 years, Men/Women: 6/4, EF: 31 ± 5%; all p = NS). Arterial stiffness was assessed via carotid‐femoral pulse wave velocity (PWV) and endothelial function was assessed via brachial artery flow‐mediated dilation (FMD). PWV decreased after 12 weeks of ARNi (9.0 ± 2.1 vs. 7.1 ± 1.2 m/s; p < 0.01) but not in CON (7.0 ± 2.4 vs. 7.5 ± 2.3 m/s; p = 0.35), an effect that remained when controlling for reductions in mean arterial pressure (p < 0.01). FMD increased after 12 weeks of ARNi (2.2 ± 1.9 vs. 5.5 ± 2.1%; p < 0.001) but not in CON (4.8 ± 3.8 vs. 5.4 ± 3.4%; p = 0.34). Baseline PWV (p = 0.06) and FMD (p = 0.07) were not different between groups. These preliminary data suggest that 12 weeks of ARNi therapy may reduce arterial stiffness and improve endothelial function in HFrEF. Thus, the findings from this pilot study suggest that the benefits of ARNi are beyond blood pressure reduction and include improvements in vascular function.
Distinct brainstem to spinal cord noradrenergic pathways inversely regulate spinal neuronal activity

Abstract Brainstem to spinal cord noradrenergic pathways include a locus coeruleus origin projection and diffuse noxious inhibitory controls. While both pathways are traditionally viewed as exerting an inhibitory effect on spinal neuronal activity, the locus coeruleus was previously shown to have a facilitatory influence on thermal nocioception according to the subpopulation of coerulean neurons activated. Coupled with knowledge of its functional modular organisation and the fact that diffuse noxious inhibitory controls are not expressed in varied animal models of chronicity, we hypothesized a regulatory role for the locus coeruleus on non-coerulean, discrete noradrenergic cell group(s). We implemented locus coeruleus targeting strategies by microinjecting canine adenovirus encoding for channelrhodopsin-2 under a noradrenaline-specific promoter in the spinal cord (retrogradely labelling a coeruleospinal module) or the locus coeruleus itself (labelling the entire coerulean module). Coeruleospinal module optoactivation abolished diffuse noxious inhibitory controls (two-way ANOVA, P < 0.0001), which were still expressed following locus coeruleus neuronal ablation. We propose that the cerulean system interacts with, but does not directly govern, diffuse noxious inhibitory controls. This mechanism may underlie the role of the locus coeruleus as a ‘chronic pain generator’. Pinpointing the functionality of discrete top-down pathways is crucial for understanding sensorimotor modulation in health and disease.
Visual and refractive outcomes following secondary intraocular lens implantation

ABSTRACT Purpose To analyze the visual and refractive results after secondary IOL implantation using different surgical techniques - iris-claw aphakic IOL through a corneal incision or scleral tunnel, and 3-piece IOL into the ciliary sulcus. Patients and methods Retrospective study including patients that were submitted to secondary IOL implantation from January 2017 to December 2019 at the Department of Ophthalmology of Hospital de Braga, Portugal. We collected demographic data (age, surgical indication, comorbidities, surgical technique, IOL implanted, and intra and postoperative complications) and visual and refractive data [preoperative and 3-month, 6-month, and 12-month postoperative corrected-distance visual acuity (CDVA), spherical equivalent (SE), manifest cylinder, and intraocular pressure]. Results 128 eyes from 123 patients were included. The most frequent surgical indications were IOL subluxation/luxation (62.5%) and intraoperative posterior capsular rupture (23.4%). CDVA improved from 1.26 ± 0.51 to 0.47 ± 0.49 logMar (p < .001). CDVA was significantly better in the 3-piece into the ciliary sulcus IOL group than both other groups. The final SE was −0.68 ± 0.94 diopters. The mean manifest refractive cylinder remained stable until the 6th month after the surgery (p = .454) and improved in the last 6 months of follow-up (p = .015). In the postoperative period, the cylinder was higher in the corneal incision iris-claw aphakic IOL group and lower in the 3-piece IOL into the ciliary sulcus group (p < 0,05). The corneal incision iris-claw aphakic IOL group presented the most postoperative complications. Conclusion All techniques showed satisfying results. The 3-piece IOL into the ciliary sulcus group showed the best visual and refractive performance, followed by the scleral tunnel iris-claw IOL group and the corneal incision iris-claw IOL group.
Muscular heat shock protein response and muscle damage after semi‐professional football match

A typical football match leads to neuromuscular fatigue and physical performance impairments up to 72–96 h post‐match. While muscle damage is thought to be a major factor, damage on the ultrastructural level has never been documented. The purpose of this study was to investigate post‐match cellular muscle damage by quantifying the heat shock protein (HSP) response as a proxy for protein damage.
The Theory of Planned Behavior & Bystander Intention: Differences Based on Gender and Heavy Episodic Drinking

Research indicates that people who engage in heavy episodic drinking (HED) report less intention to intervene and intervention behavior to prevent sexual violence. Researchers have also found gender differences across bystander intention, bystander confidence, and intervention behavior. However, research in this area could benefit from use of an evidence-based health behavior theory. The theory of planned behavior (TPB) posits that personal attitudes, subjective norms, and perceived behavioral control (PBC) predict behavioral intention. Substantial evidence supports the utility of the TPB for predicting behavioral intention in a variety of health-related behaviors, yet few researchers have applied this theory when predicting bystander intention to prevent sexual violence. Undergraduate students (N = 395) from a southern university (77% female; 70% White, Non-Hispanic) completed a modified Sexual Assault Bystander Behavior Questionnaire and the Daily Drinking Questionnaire. Our findings did not reveal significant differences in attitudes, subjective norms, PBC, nor intention based on HED; however, there were significant differences based on gender, with women indicating more positive attitudes and supportive subjective norms regarding bystander intervention. Multiple regression analysis indicated that theoretical antecedents of intention positively predicted bystander intention, however, the relations were not moderated by prior engagement in HED. These findings support the utility of the TPB for predicting bystander intention to intervene; however, they do not support previous research examining how HED influences bystanders’ intention to engage in prosocial actions.
Full paper: Estimation of fraction metabolized by cytochrome P450 (CYP) enzymes using long-term co-cultured human hepatocytes

Estimation of the fraction of a drug metabolized by individual hepatic cytochrome P450 (CYP) enzymes relative to hepatic metabolism (fm,CYP) or total clearance (fCL,CYP) has been challenging for low turnover compounds due to insufficient resolution of the intrinsic clearance (CLint) measurement in vitro and difficulties in quantifying the formation of low abundance metabolites. To overcome this gap, inhibition of drug depletion or selective metabolite formation for 7 marker CYP substrates was investigated using chemical inhibitors and a micro-patterned hepatocyte co-culture system (HepatoPac®). The use of 3 µM itraconazole was successfully validated for estimation of fm,CYP3A4 by demonstration of fm values within a 2-fold of in vivo estimates for 10 out of 13 CYP3A4 substrates in a reference set of marketed drugs. Other CYP3A4 inhibitors (ketoconazole and posaconazole) were not optimal for estimation of fm,CYP3A4 for low turnover compounds due to their high CLint. The current study also demonstrated that selective inhibition sufficient for fm calculation was achieved by inhibitors of CYP1A2 (20 µM furafylline), CYP2C8 (40 µM montelukast), CYP2C9 (40 µM sulfaphenazole), CYP2C19 (3 µM (-)N-3-benzyl-phenobarbital) and CYP2D6 (5 µM quinidine). Good estimation of fm,CYP2B6 was not possible in this study due to the poor selectivity of the tested inhibitor (20 µM ticlopidine). The approach verified in this study can result in an improved fm estimation which is aligned with the regulatory agencies’ guidance and can support a victim drug-drug interaction risk assessment strategy for low clearance discovery and development drug candidates.
The effect of past defaunation on ranges, niches, and future biodiversity forecasts

Humans have reshaped the distribution of biodiversity across the globe, extirpating species from regions otherwise suitable and restricting populations to a subset of their original ranges. Here, we ask if anthropogenic range contractions since the Late Pleistocene led to an under‐representation of the realized niches for megafauna, an emblematic group of taxa often targeted for restoration actions. Using reconstructions of past geographic distributions (i.e., natural ranges) for 146 extant terrestrial large‐bodied (>44 kg) mammals, we estimate their climatic niches as if they had retained their original distributions and evaluate their observed niche dynamics. We found that range contractions led to a sizeable under‐representation of the realized niches of several species (i.e., niche unfilling). For 29 species, more than 10% of the environmental space once seen in their natural ranges has been lost due to anthropogenic activity, with at least 12 species undergoing reductions of more than 50% of their realized niches. Eighteen species may now be confined to low‐suitability locations, where fitness and abundance are likely diminished; we consider these taxa 'climatic refugees'. For those species, conservation strategies supported by current ranges risk being misguided if current, suboptimal habitats are considered baseline for future restoration actions. Because most climate‐based biodiversity forecasts rely exclusively on current occurrence records, we went on to test the effect of neglecting historical information on estimates of species’ potential distribution – as a proxy of sensitivity to climate change. We found that niche unfilling driven by past range contraction leads to an overestimation of sensitivity to future climatic change, resulting in 50% higher rates of global extinction, and underestimating the potential for megafauna conservation and restoration under future climate change. In conclusion, range contractions since the Late Pleistocene have also left imprints on megafauna realized climatic niches. Therefore, niche truncation driven by defaunation can directly affect climate and habitat‐based conservation strategies.
Decreased incremental shuttle walk test distance characterized by fibrocavitary lesions in non-tuberculous mycobacterial pulmonary disease

ABSTRACT Background Patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD) have impaired exercise capacity, but the underlying factors are unknown. We investigated the characteristics of patients with NTM-PD and impaired exercise capacity. Methods In total, 149 patients with NTM-PD participated in this study. Patients completed the incremental shuttle walk test (ISWT) to assess exercise capacity. Peripheral muscle strength and pulmonary function were also assessed. Radiological findings were classified into three phenotypes: non-cavitary nodular bronchiectatic (NC-NB) form, cavitary nodular bronchiectatic form, and fibrocavitary (FC) form. Results The median ISWT distance (ISWD) and %ISWD were 450 meters and 88%. Participants were classified into three groups according to %ISWD, with %ISWD <60% as the severely decreased group, 60%-80% as the moderately decreased group, and >80% as the normal or mildly decreased group. In a comparison of %ISWD among phenotypes, FC form had significantly lower %ISWD than those with NC-NB form. In the severely decreased group, peripheral muscle strength and pulmonary function were significantly lower than the other two groups. From a radiological standpoint, significantly more patients had FC form in the group with severely decreased %ISWD. Conclusions Decreased ISWD is characterized by a deterioration in physical function and the presence of FC lesions in NTM-PD.
Improving IMU-Based Prediction of Lower Limb Kinematics in Natural Environments Using Egocentric Optical Flow

We seek to predict knee and ankle motion using wearable sensors. These predictions could serve as target trajectories for a lower limb prosthesis. In this manuscript, we investigate the use of egocentric vision for improving performance over kinematic wearable motion capture. We present an out-of-the-lab dataset of 23 healthy subjects navigating public classrooms, a large atrium, and stairs for a total of almost 12 hours of recording. The prediction task is difficult because the movements include avoiding obstacles, other people, idiosyncratic movements such as traversing doors, and individual choices in selecting the future path. We demonstrate that using vision improves the quality of the predicted knee and ankle trajectories, especially in congested spaces and when the visual environment provides information that does not appear simply in the movements of the body. Overall, including vision results in 7.9% and 7.0% improvement in root mean squared error of knee and ankle angle predictions respectively. The improvement in Pearson Correlation Coefficient for knee and ankle predictions is 1.5% and 12.3% respectively. We discuss particular moments where vision greatly improved, or failed to improve, the prediction performance. We also find that the benefits of vision can be enhanced with more data. Lastly, we discuss challenges of continuous estimation of gait in natural, out-of-the-lab datasets.
Quasi-Experimental Design and Methods: Methodological Briefs - Impact Evaluation No. 8

Quasi-experimental research designs, like experimental designs, test causal hypotheses. Quasi-experimental designs identify a comparison group that is as similar as possible to the intervention group in terms of baseline (pre-intervention) characteristics. The comparison group captures what would have been the outcomes if the programme/policy had not been implemented (i.e., the counterfactual). The key difference between an experimental and quasi-experimental design is that the latter lacks random assignment.
Estimating and Testing Causal Mediation Effects in Single-Case Experimental Designs Using State-Space Modeling

In this article, we present single-case causal mediation analysis as the application of causal mediation analysis to data collected within a single-case experiment. This method combines the focus on the individual with the focus on mechanisms of change, rendering it a promising approach for both mediation and single-case researchers. For this purpose, we propose a new method based on time-discrete state-space modeling to estimate the direct and indirect treatment effects. We demonstrate how to estimate the model for a single-case experiment on stress and craving in a routine alcohol consumer before and after an imposed period of abstinence. Furthermore, we present a simulation study that examines the estimation and testing of the standardized indirect effect. All parameters used to generate the data were recovered with acceptable precision. We use maximum likelihood and permutation procedures to calculate p-values and standard errors of the parameters estimates. The new method is promising for testing mediated effects in single-case experimental designs. We further discuss limitations of the new method with respect to causal inference, as well as more technical concerns, such as the choice of the time lags between the measurements.
Beyond p < .05: a critical review of new Bayesian proposals for assessing the p-value

ABSTRACT This paper reviews recent contributions from a Bayesian-oriented perspective, after the ASA statement on p-values (2016). We classify proposals that (i) supplement the p-value; (ii) modify the p-value itself. In the first group, we review the Bayes factor, the False Positive risk, the rejection odds and the analysis of credibility from both Matthews’ and Held’s point of view. We also put forth and discuss a new index of credibility, about which we conduct a delimited simulation study. In the second group, we discuss Gannon’s modification of the p-value based on the Bayes factor and the second-generation p-value. The theory is illustrated with two case studies on pharmacotherapy in infectious diseases. Contemporary authors still refer to the p-value as a statistical indicator but have abandoned the perspective of evaluating p-values with fixed thresholds. Statistical societies worldwide should target new strategies to disseminate the debate on p-values in all applied fields of knowledge, as well as they may promote the use of different statistical procedures to supplement p-values.
Prevalence, levels and related factors of burnout in nurse managers: A multi‐centre cross‐sectional study

Abstract Aims The aims of this study are to analyse the prevalence and levels of burnout syndrome in nurse managers and to evaluate the relationship between burnout and related sociodemographic, occupational and psychological factors. Background Burnout syndrome, defined as an emotional response to chronic stress, is a major problem among nurse managers. Methods The study was conducted using a cross‐sectional survey design and data collected by the Maslach Burnout Inventory, the revised NEO Five Factor Inventory and the Educational‐Clinical Questionnaire for Anxiety and Depression. The sample population consisted of 86 nurse managers from different hospitals from the Public Health Service of Andalusia, Spain. Results A total of 22.4% of the participants presented high levels of emotional exhaustion, 21% experienced depersonalisation and 57.6% had little sense of personal accomplishment. Working long shifts was related to burnout. Emotional exhaustion and depersonalization were predicted by depression, while personal accomplishment was predicted by conscientiousness, agreeableness and openness. Conclusions A total of 34.1% of the participants presented high levels of burnout, manifested by feelings of low personal accomplishment. Psychological and occupational factors play an important role in the development of this syndrome. Implications for Nursing Management Nurse managers should seek to detect burnout among staff and colleagues matching the risk profile for this condition and promote interventions to prevent it.
Exercise history predicts focal differences in bone volume fraction, mineral density and microdamage in the proximal sesamoid bones of Thoroughbred racehorses

Medial proximal sesamoid bones (PSBs) from Thoroughbred racehorses that did (Case) or did not (Control) experience unilateral biaxial PSB fracture were evaluated for bone volume fraction (BVF), apparent mineral density (AMD), tissue mineral density (TMD), and microdamage in Case fractured, Case contralateral limb intact, and Control bones. A majority of Case bones had a subchondral lesion with high microdamage density, and low BVF, AMD, and TMD. Lesion microdamage and densitometric measures were associated with training history by robust linear regression. Exercise intensity was negatively related to BVF (0.07 ≤ R2 ≤ 0.12) and positively related to microcrack areal density (0.21 ≤ R2 ≤ 0.29) in the lesion; however, in an undamaged site, the relationships were opposite in direction. Regardless of location, TMD decreased with event frequency for both Case and Control, suggesting increased bone remodeling with exercise. Measures of how often animals were removed from active training (layups) predicted a decrease in TMD, AMD, BVF, and microdamage at regions away from the lesion site. A steady‐state compartment model was used to organize the differences in the correlations between variables within the data set. The overall conclusions are that at the osteopenic lesion site, repair of microdamage by remodeling was not successful (e.g., lower bone mass, increased damage, and lower mineralization) but that in regions away from the lesion remodeling successfully controlled damage (e.g., higher bone mass, less microdamage, and lower mineralization).
Would the Real Loneliness Please Stand Up? The Validity of Loneliness Scores and the Reliability of Single-Item Scores

Several measures that assess loneliness have been developed for adults. Across three studies, we investigated psychometric features of scores of different versions of the Rasch-Type Loneliness Scale, the University of California Los Angeles Loneliness Scale, and three single-item measures. In Study 1 (N = 697 self-ratings, N = 282 informant-ratings of 160 targets) and Study 2 (N = 1,216 individuals from 608 couples), we investigated convergent validity, self-informant agreement, and nomological nets of the item scores using correlates related to demographic aspects, personality, satisfaction, and network characteristics. In Study 3 (N = 411), we estimated a reliability of r x x > . 70 for scores of three single-item measures of loneliness. Overall, scores of all measures and their nomological nets were highly correlated within and across studies, indicating that the scores of the included measures are all reliable and valid. Recommendations for choosing a loneliness measure are discussed.
The craft process developing student decision making

In enterprise education, learning is problem-focused and holistic. A learning process that encourages people to learn by doing develops their problem-solving skills, participation, interaction, and decision making. Craft making includes practice, development, creativity, innovativeness, and the problem-solving process, and the craft teaching aims to promote students’ substance skills of crafts and the skills they need in everyday life. Craft skills make people more active and help them to find practical solutions. Decision making seems to be one of the connecting themes between crafts and enterprise education. In this study, we examine school students’ decision making during a craft process. The study was conducted during the spring term of 2013 and examines how the students make various decisions during the craft making process. Eight 13-year-old students were interviewed and the interview data analysed using thematic analysis. The results indicate that the quality of the students’ decision making during a craft process is dependent on their personal goals, self-confidence, and previous experiences. In addition, there is a connection between the students’ decision making and the social environment when they want to emphasize their own personality or similarity to their peers.