Miracle-dz/UniFAR-FTUs huggingface dataset:
OnabotulinumtoxinA for the prophylactic treatment of headaches in adult patients with chronic migraine: a safety evaluation

ABSTRACT Introduction: Existing oral prophylaxis for chronic migraine (CM) are often ineffective or poorly tolerated. OnabotulinumtoxinA (onabotA) is approved for headache prophylaxis in CM and ameliorates headaches in patients refractory to multiple preventatives. Areas covered: We appraise evidence regarding action mechanisms, pharmacodynamics, and pharmacokinetics of onabotA in CM prophylaxis. We critically evaluate salient clinical and real-world studies demonstrating its efficacy in improving multiple aspects of CM. We discuss onabotA safety, tolerability, and adverse events (AEs) for CM prophylaxis from clinical trials, post-authorization studies and meta-analyses, including novel pregnancy safety data and comparisons with oral prophylactics. We explore areas of future interest, particularly onabotA safety and efficacy in the context of novel antibody-based prophylaxis. Expert opinion: Clinical and real-world evidence demonstrate onabotA safety, tolerability and efficacy for CM prophylaxis. Most AEs are mild/moderate and self-limiting, with few serious AEs and no treatment-related deaths. Common AEs include neck pain, ptosis, muscle weakness, and stiffness. Modifying existing responder-criteria enables more patients to benefit from onabotA. OnabotA shows superior safety and efficacy to oral preventatives, and appears safe in pregnancy. Future pregnancy-risk register will clarify pregnancy and lactation safety further. Future research comparing onabotA safety and efficacy with newly emergent antibody-based prophylaxis is keenly awaited.
Dietary niacin affects intestinal morphology and functions via modulating cell proliferation in weaned piglets.

Niacin deficiency leads to inflammation of mucous membranes and diarrhoea. There are few reports on the effects of niacin on the intestinal health of weaned piglets. The present study was conducted to analyse the effects of niacin in weaned piglets along with its underlying mechanism. A total of 48 25-day-old weaned piglets (24 females and 24 males) were randomly allotted into four groups, each treatment were supplemented with 22.5, 30, 45, and 75 mg kg-1 niacin for a period of 14 days, with 12 piglets per diet and 1 piglet per pen. Six piglets (3 males and 3 females) were randomly selected from each treatment group and euthanised for intestinal tissue sampling on days 7 and 14 after the weaning day (day 0), respectively. Dietary niacin did not affect the growth performance of weaned piglets but quadratically affected (P < 0.05) the diarrhoea rate from days 7 to 14. The duodenal villus height and width and crypt depth in the 30 mg kg-1 niacin group were greater than those in the 45 mg kg-1 niacin group on day 7, and the jejunal crypt depth, ileal crypt depth, villus height and villus width decreased (linear, P < 0.05) with the increase in dietary niacin. However, the dietary supplementation with niacin increased (linear, P < 0.001) the jejunal villus height, crypt depth and villus width on day 14. Dietary niacin increased (linear, P < 0.05) the alkaline phosphatase activity in the jejunal mucosa of weaned piglets on day 7 but decreased (linear, P < 0.05) its activity on day 14. The number of Ki67 positive cells per crypt was decreased (linear, P < 0.05) with the dietary niacin on day 7 but increased (linear, P < 0.05) with dietary niacin contents on day 14. Moreover, dietary niacin altered (P < 0.05) SLC5A1, SLC15A1, SLC6A19, TJP-1, occludin and claudin-1 mRNA expression in the small intestine. These results indicate that dietary niacin has different effects on intestinal morphology and functions in the first and second weeks postweaning and that the dietary supplementation with niacin may, by modulating intestinal cell proliferation, affect the intestinal health.
Negative correlation of single-cell PAX3:FOXO1 expression with tumorigenicity in rhabdomyosarcoma

Single-cell PAX3:FOXO1 expression in rhabdomyosarcoma is variable. PAX3:FOXO1 low cell states are characterized by more efficient adhesion, migration and tumor-propagating capacity. Rhabdomyosarcomas (RMS) are phenotypically and functionally heterogeneous. Both primary human RMS cultures and low-passage Myf6Cre,Pax3:Foxo1,p53 mouse RMS cell lines, which express the fusion oncoprotein Pax3:Foxo1 and lack the tumor suppressor Tp53 (Myf6Cre,Pax3:Foxo1,p53), exhibit marked heterogeneity in PAX3:FOXO1 (P3F) expression at the single cell level. In mouse RMS cells, P3F expression is directed by the Pax3 promoter and coupled to eYFP. YFPlow/P3Flow mouse RMS cells included 87% G0/G1 cells and reorganized their actin cytoskeleton to produce a cellular phenotype characterized by more efficient adhesion and migration. This translated into higher tumor-propagating cell frequencies of YFPlow/P3Flow compared with YFPhigh/P3Fhigh cells. Both YFPlow/P3Flow and YFPhigh/P3Fhigh cells gave rise to mixed clones in vitro, consistent with fluctuations in P3F expression over time. Exposure to the anti-tropomyosin compound TR100 disrupted the cytoskeleton and reversed enhanced migration and adhesion of YFPlow/P3Flow RMS cells. Heterogeneous expression of PAX3:FOXO1 at the single cell level may provide a critical advantage during tumor progression.
Loganin exerts a protective effect on ischemia–reperfusion‐induced acute kidney injury by regulating JAK2/STAT3 and Nrf2/HO‐1 signaling pathways

To investigate the role of loganin in hypoxia/reperfusion (H/R)‐induced renal tubular epithelial cells and ischemia/reperfusion‐induced acute kidney injury (AKI). Cells were received H/R treatment and cultured with different concentrations of loganin. The cell activity and apoptosis were detected. The expressions of apoptosis‐related proteins, inflammatory factors, oxidative stress related molecules, and related molecules of JAK2/STAT3 and Nrf2/HO‐1 signaling pathways were measured. AKI model of mice was established by I/R procedure, and the kidney was collected for hematoxylin and eosin (HE) staining. H/R treatment inhibited cell activity and apoptosis, but loganin attenuated the effect of H/R. Moreover, loganin inhibited H/R‐induced inflammatory response and oxidative stress in tubular epithelial cells. Loganin down‐regulated the expression of apoptosis‐related proteins, suppressed JAK2/STAT3 pathway, and activated Nrf2/HO‐1 pathway. In animal experiment, loganin reduced tubular injury in AKI mice.Loganin had anti‐apoptotic, anti‐inflammatory, and anti‐oxidative stress effects on H/R‐induced tubular epithelial cells, and could improve AKI in mice induced by I/R. This effect might be achieved by inhibiting JAK2/STAT3 and activating the Nrf2/HO‐1 signaling pathway.
Association of lung function with functional limitation in older adults: A cross-sectional study

Introduction Impaired lung function is independently associated with higher rates of disability, however, few studies have examined the association between lung function and functional limitation. This study aimed to assess this association and dose-response relationship in older adults. Methods Data from the National Health and Nutrition Examination Survey (2007–2012) was used as a cross-sectional study. Lung function was determined by Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC). Functional limitation in older adults was identified by six self-reported questions on physical function. 3070 adults aged 60 and over were enrolled in our study. Logistic regression models and restricted cubic spline models were applied to examine the association between lung function and the risk of functional limitation. Results FEV1 and FVC were inversely associated with the risk of functional limitation. In the full adjusted model, compared with the lowest tertile of FEV1, the odds ratios (95% confidence intervals) of functional limitation for tertile 2 and tertile 3 were 0.5422 (0.3848–0.7639) and 0.4403 (0.2685–0.7220), and the odds ratios (95% confidence intervals) of functional limitation for tertile 2 and tertile 3 of FVC were 0.5243 (0.3503–0.7848) and 0.3726 (0.2072–0.6698). Furthermore, an inverse association persisted after stratified analysis by gender and sensitivity analysis. Dose-response analyses showed that the odds of functional limitation declined with increase in FEV1 and FVC in a nonlinear manner. Conclusions Lung function was inversely associated with functional limitation among older adults.
Comparison of psychological states and oral health-related quality of life of patients with differing severity of Temporomandibular disorders.

OBJECTIVES This study sought to compare the psychological states and oral health-related quality of life (OHRQoL) among patients with differing Temporomandibular disorder (TMD) severity. The affiliations between TMD severity, psychological distress, and OHRQoL were also explored. METHODS Adult patients (≥18 years old) with and without (controls) TMDs were recruited from the TMD/orofacial pain centre and prosthodontics department respectively. The presence and severity of TMDs were established with the Fonseca Anamnestic Index (FAI) and TMD diagnoses were confirmed with the Diagnostic Criteria for TMDs (DC/TMD). Psychological states and OHRQoL were examined with the Depression, Anxiety, Stress Scales-21 (DASS-21) and Oral Health Impact Profile for TMDs (OHIP-TMD). Data were subjected to Chi-square, Kruskal-Wallis/Mann-Whitney U tests, and Spearman's correlation (α=0.05). RESULTS A total of 961 participants with a mean age of 32.99±13.14 years; 71.19% women) were assessed. Frequencies of the various TMD categories were: No TMD/controls (12.07%), mild TMD (24.56%), moderate TMD (40.37%), and severe TMD (23.00%). The three most common TMD-related symptoms were TMJ noises, mouth opening difficulty, and muscle pain. Participants with moderate/severe TMD presented a higher proportion of intra-articular and/or combined disorders. They reported significantly higher levels of depression, anxiety, stress, and poorer OHRQoL than their counterparts with no/mild TMD (P<0.001). Moderate to strong correlations were observed between FAI and DASS-21/OHIP-TMD scores (rs =0.42-0.72). CONCLUSIONS Patients with moderate/severe TMD had significantly higher levels of psychological disturbance and poorer OHRQoL. As OHRQoL and psychological states are correlated, psychological well-being must be considered when managing patients with moderate/severe TMDs.
ANALYSIS OF SELF-CARE STRATEGIES AMONG NURSES IN SOUTHERN POLAND – A CROSS-SECTIONAL SURVEY

Objectives: This study aimed to explore the self-care strategies undertaken by Polish nurses, and more specifically: to assess the participants’ selfcare strategies; to check self-medication patterns in the study group; and to analyze compliance with medical recommendations regarding pharmacotherapy. Material and Methods: A quantitative and cross-sectional survey was conducted to examine the phenomenon of interest. The study employed a questionnaire survey with an independently designed questionnaire as a research tool. A total of 446 registered nurses taking part in different professional training courses for nurses in January–June 2018 who agreed to participate were included in the study. Results: The findings of this study reveal generally poor self-care strategies and compliance with medical recommendations among Polish nurses. The most frequent health behaviors among the surveyed nurses were caring for personal hygiene and a healthy diet. About 31% of the nurses confirmed supplements use. The most common reasons for taking supplements concerned the prevention of vitamin and mineral deficiencies (77.5%), and boosting of the immune system (49.3%). The most popular supplements included packs of vitamins (57.2%), single vitamin D3 (33.3%) and magnesium (31.2%). The vast majority of participants (79.8%) took some kind of over-the-counter drugs (OTCs) in the last 6 months, most often painkillers and flu medications, relying most frequently on the information included on the drug leaflets. The analysis showed a statistically significant relationship between declared OTC use and age, marital status, years of professional experience and economic status. Overall, 26.9% of the study participants declared the use of both supplements and OTCs, while 16.4% of the participants used neither supplements nor OTCs. Conclusions: Self-care strategies undertaken by nurses should be seen as an essential factor in their positive therapeutic relationship with patients. The ageing nursing workforce should make all of us increasingly aware that their self-care needs will increase as well.
A nomogram incorporated lifestyle indicators for predicting nonalcoholic fatty liver disease

Abstract Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and its pathogenesis is complicated and triggered by unbalanced diet, sedentary lifestyle, and genetic background. The aim of this study was to construct and validate a nomogram incorporated lifestyle habits for predicting NAFLD incidence. The overall cohort was divided into training set and test set as using computer-generated random numbers. We constructed the nomogram by multivariate logistic regression analysis in the training set. Thereafter, we validated this model by concordance index, the area under the receiver operating characteristic curve (ROC), net reclassification index, and a calibration curve in the test set. Additionally, we also evaluated the clinical usefulness of the nomogram by decision curve analysis. There were no statistically significant differences about characteristics between training cohort (n = 748) and test cohort (n = 320). Eleven features (age, sex, body mass index, drinking tea, physical exercise, energy, monounsaturated fatty acids, polyunsaturated fatty acids, hypertension, hyperlipidemia, diabetes) were incorporated to construct the nomogram, concordance index, the area under the ROC curve, net reclassification index were 0.801, 0.801, and 0.084, respectively, indicating the nomogram have good discrimination of predicting NAFLD incidence. Also, the calibration curve showed good consistency between nomogram prediction and actual probability. Moreover, the decision curve showed that when the threshold probability of an individual is within a range from approximately 0.5 to 0.8, this model provided more net benefit to predict NAFLD incidence risk than the current strategies. This nomogram can be regarded as a user-friendly tool for assessing the risk of NAFLD incidence, and thus help to facilitate management of NAFLD including lifestyle and medical interventions.
Wide angular range dynamic projection mapping method applied to drone-based avatar robot

In this study, we propose a method for dynamic projection mapping on a target moving at high speed in a wide area around the projection equipment, using a high-speed gaze control system called Saccard Mirror 3. The prototype system successfully projected images over a wide angular range using a rotating mirror and kept projecting images on a flying drone while allowing the drone to move over a wide area. We also demonstrated an avatar robot using a drone based on the proposed system in combination with a teleconference system. This application is important for improving the quality of new normal (QoNN) in the sense that it will enable remote work for customer service in a variety of stores in the future. GRAPHICAL ABSTRACT
Protein dynamics and entropy: Implications for protein-ligand binding

The nature of macromolecular interactions has been an area of deep interest for understanding many facets of biology. While a great deal of insight has been gained from structural knowledge, the contribution of protein dynamics to macromolecular interactions is not fully appreciated. This plays out from a thermodynamic perspective as the conformational entropy. The role of conformational entropy in macromolecular interactions has been difficult to address experimentally. Recently, an empirical calibration has been developed to quantify the conformational entropy of proteins using solution NMR relaxation methods. This method has been demonstrated in two distinct protein systems. The goal of this work is to expand this calibration to assess whether conformational entropy can be effectively quantified from NMR-derived protein dynamics. First, we demonstrate that NMR dynamics do not correlate well between the solid and solution states, suggesting that the relationship between the conformational entropy of proteins is limited to solution state-derived NMR dynamics. We hypothesize that this may be partially due to the role of hydration of the protein in its dynamics. Next, we expand our empirical calibration to over 30 distinct protein systems and demonstrated that the relationship between NMR dynamics and conformational entropy is both robust and general. Furthermore, we demonstrate that conformational entropy plays a significant role in macromolecular interactions. Using our empirical calibration, we then look to address if conformational entropy could be an important contribution to drug design. The latter process is often a brute force approach, and subsequent optimization of initial drug candidates is often a guess and check process. In silico drug design was thought to offer a more efficient and rational approach, but often relies on static structures. This minimizes or completely neglects the role that conformational entropy may play in binding. Here we experimentally determine the role of conformational entropy in the drug target p38a MAPK in binding to two potent inhibitors. We demonstrate evidence that conformational entropy may represent a tunable parameter in affinity optimization of lead compounds. This has important implications for lead optimization and strongly suggests that the role of conformational entropy be considered in drug design efforts. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Biochemistry & Molecular Biophysics First Advisor A. Joshua Wand
Exploring the relationship of human–nature interaction and mindfulness: a cross-sectional study

ABSTRACT History is replete with examples where humans have sought refuge in nature for psychological restoration. In this cross-sectional study we explore the relationship of nature experience and mindfulness. Nature experience is assessed through “nature in the neighbourhood”, “frequency of visit” to nature-rich spaces, as well as one's inherent connection with nature described as “nature relatedness”. The study sample consisted of 334 Indian adults. The findings from this study show that frequency of visit to nature-rich spaces has a significant positive association with mindfulness. The hierarchical regression analysis suggests an interaction effect of “nature relatedness” in the association of the presence of nature rich spaces in the neighbourhood, frequency of visit as well as mindfulness. Interestingly, when childhood experiences were explored they had a significant association with “nature relatedness” and mindfulness. The evidence from this research suggests that nature experience may find its application as one of the mindfulness techniques prescribed for self-management of mental health problems.
Women and extra-academic social research in Sweden 1900–1950: A sociology of knowledge approach

ABSTRACT How should we understand the academization of the social sciences around the turn of the twentieth century with regard to gender? In this article I argue in favour of a contextually broadened sociology of knowledge approach which highlights the importance of women’s extra-academic social research as a parallel and interconnected form of social knowledge to the new and male-dominated academic social sciences. Theoretically, the approach combines three perspectives: field theory, social movements research and historical studies of knowledge circulation. Empirically and methodologically, the study is prosopographically centred around nine female social researchers in Sweden 1900–1950 with an analytical focus on their aggregated career patterns, the gender-coded mechanisms of academic exclusion that were at play and three types of alternative arenas that were available for extra-academic social research during the period. It is concluded that we need to take this form of extra-academic social research into account to better understand the dynamics of the field of social knowledge as a whole, including the development of academic social science.
Predicting Relationship Satisfaction in LGBQ + People Using Internalized Stigma, Outness, and Concealment

Abstract Minority stress has a range of negative and protective outcomes for lesbian, gay, bisexual, queer, and other sexual minority (LGBQ+) people. The internalization of societal stigma associated with sexual minority relationships may impact decisions related to outness and/or concealment of one’s romantic relationship, which may affect the relationship. Building on previous research, we examined whether internalized stigma and sexual orientation concealment predicted lower romantic relationship satisfaction in LGBQ + people, and whether outness about one’s sexual orientation predicted better relationship satisfaction. We also examined whether outness and concealment mediated internalized stigma's effects on relationship satisfaction. Hierarchical regression results (N = 214) demonstrated that internalized stigma was a significant negative predictor of relationship satisfaction, outness was a significant positive predictor, and concealment was not a unique predictor. Mediation analysis demonstrated that internalized stigma had a significant direct effect on relationship satisfaction, along with a significant indirect effect through lower outness. Although internalized stigma was associated with greater concealment, concealment did not mediate the relationship between it and relationship satisfaction. Kelley and Thibault’s interdependence model, alongside minority stress theory, are used to understand these variables' effects on relationship satisfaction. Counseling and research implications are discussed.
Cr K-edge X-ray absorption and FTIR spectroscopic study on the reaction mechanisms of Cr(III) and Cr(VI) with lignin

AbstractThe reaction mechanisms of lignin with Cr(III) and Cr(VI) were investigated using Cr K-edge X-ray spectroscopy (XAS) and FTIR spectroscopy. The spectroscopic results for lignin reacted with Cr(III) showed that the adsorbed Cr(III) has a coordination environment similar to that of ion, and the carbonyl groups of lignin are predominately responsible for adsorbing Cr(III). Accordingly, the reaction mechanism of Cr(III) with lignin was determined to be surface adsorption through the formation of an outer-sphere complex. In contrast, Cr(VI) reaction with lignin is not simply surface adsorption. Upon reaction with lignin, Cr(VI) was reduced to Cr(III), which was either bound to lignin or released back into solution. The corresponding FTIR spectra revealed that the carbonyl and phenolic groups are the primary sites for reducing Cr(VI) to Cr(III), leading to the formation of carboxyl groups. The carboxyl groups chelate Cr(III) to form a bidentate inner-sphere complex, deduced from the XAS and FTIR results.
Indirect accountability of political appointees

This paper explores the indirect accountability of political appointees. The appointee’s quality is uncertain, and voters hold the politician accountable for the appointee’s performance. The politician has better information about the appointee than voters do, but electoral concerns induce the politician to make inefficient retention decisions. Specifically, there is over-retention of appointees relative to the social optimum. If the quality of candidates for appointment is low, then improving the pool of candidates can help reduce distortions and, in fact, it is in the interest of the politician to do so. I also show that more public information about the appointee reduces over-retention.