Miracle-dz/UniFAR-FTUs huggingface dataset:
Physical activity disparities across Europe: clustering European regions by health-related physical activity levels

Summary In the context of stagnating global levels of physical activity (PA), this study examines the geographical segmentation of PA at the regional level (196 regions) in Europe. Cluster analysis and multinomial logistic regression are applied. Cluster analysis provides a taxonomy of four differentiated groups according to the health-related PA levels of the European regions. This taxonomy shows that there are significant regional disparities among European countries in terms of the regional PA level. The cluster profiles in terms of regional socioeconomic characteristics are described for each group, emphasizing the regional characteristics associated with PA. Regional economic variables, tertiary education and social Internet use are significant variables for characterizing the types of regions. The results emphasize the relevance of a European regional approach for reducing inter-regional PA disparities and improving health through PA in Europe. Practical implications of this research are based on regional European coordination, such as collaborative models of sport infrastructure use, co-financing of inter-regional facilities, mutual physical educational scholar programs and promotion of common inter-regional sport competitions and sporting events. Finally, formal schemes for exchanging of best regional practices to promote health-enhancing PA might increase the perception and the role of PA at the regional level in the European society.
Autoimmune Encephalitis After SARS-CoV-2 Infection

Background and Objectives Autoimmune encephalitis (AE) cases after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported, but the frequency is unknown. We aimed to determine the frequency and diagnostic features of coronavirus disease 2019 (COVID-19)–related AE. Methods Residual sera from 556 consecutive Mayo Clinic Rochester patients (laboratory cohort) who underwent autoimmune encephalopathy neural immunoglobulin G (IgG) evaluation were tested for total antibodies against the SARS-CoV-2 spike glycoprotein using a Food and Drug Administration–authorized chemiluminescence assay (October 2019–December 2020). Clinical records from patients with a positive SARS-CoV-2 antibody result and available research consent were reviewed. This laboratory cohort was cross-referenced with the Department of Neurology's COVID-19–related consultative experience (encephalopathy cohort, n = 31). Results Eighteen of the laboratory cohort (3%) were SARS-CoV-2 antibody positive (April–December 2020). Diagnoses were as follows: AE, 2; postacute sequelae of SARS CoV-2 infection (PASC), 3; toxic-metabolic encephalopathy during COVID-19 pneumonia, 2; diverse non–COVID-19 relatable neurologic diagnoses, 9; unavailable, 2. Five of the encephalopathy cohort had AE (16%, including the 2 laboratory cohort cases that overlapped), representing 0.05% of 10,384 patients diagnosed and cared for with any COVID-19 illness at Mayo Clinic Rochester in 2020. The 5 patients met definite (n = 1), probable (n = 1), or possible (n = 3) AE diagnostic criteria; median symptom onset age was 61 years (range, 46–63); 3 were women. All 5 were neural IgG negative and 4 tested were SARS-CoV-2 PCR/IgG index negative in CSF. Phenotypes (and accompanying MRI and EEG findings) were diverse (delirium [n = 5], seizures [n = 2], rhombencephalitis [n = 1], aphasia [n = 1], and ataxia [n = 1]). No acute disseminated encephalomyelitis cases were encountered. The 3 patients with possible AE had spontaneously resolving syndromes. One with definite limbic encephalitis was immune therapy responsive but had residual mood and memory problems. One patient with probable autoimmune rhombencephalitis died despite immune therapy. The remaining 26 encephalopathy cohort patients had toxic-metabolic diagnoses. Discussion We encountered occasional cases of AE in our 2020 COVID-19 experience. Consistent with sporadic reports and small case series during the COVID-19 pandemic, and prior experience of postinfectious AE, our cases had diverse clinical presentations and were neural IgG and CSF viral particle negative. Application of diagnostic criteria assists in differentiation of AE from toxic-metabolic causes arising in the setting of systemic infection.
Live-imaging rate-of-kill compound profiling for Chagas disease drug discovery with a new automated high-content assay

Chagas disease, caused by the protozoan intracellular parasite Trypanosoma cruzi, is a highly neglected tropical disease, causing significant morbidity and mortality in central and south America. Current treatments are inadequate, and recent clinical trials of drugs inhibiting CYP51 have failed, exposing a lack of understanding of how to translate laboratory findings to the clinic. Following these failures many new model systems have been developed, both in vitro and in vivo, that provide improved understanding of the causes for clinical trial failures. Amongst these are in vitro rate-of-kill (RoK) assays that reveal how fast compounds kill intracellular parasites. Such assays have shown clear distinctions between the compounds that failed in clinical trials and the standard of care. However, the published RoK assays have some key drawbacks, including low time-resolution and inability to track the same cell population over time. Here, we present a new, live-imaging RoK assay for intracellular T. cruzi that overcomes these issues. We show that the assay is highly reproducible and report high time-resolution RoK data for key clinical compounds as well as new chemical entities. The data generated by this assay allow fast acting compounds to be prioritised for progression, the fate of individual parasites to be tracked, shifts of mode-of-action within series to be monitored, better PKPD modelling and selection of suitable partners for combination therapy.
Performance of the REACH, PARIS, BleeMACS, and PRECISE-DAPT scores for predicting 1-year bleeding events in patients undergoing coronary drug-eluting stent implantation

Abstract This study aimed to evaluate the predictive performance of the REACH, PARIS, BleeMACS, and PRECISE-DAPT scores in Chinese patients undergoing coronary drug-eluting stent (DES) implantation. A total of 1911 patients undergoing coronary DES implantation were consecutively recruited and followed up for 1 year. The primary endpoints were BARC type 3 or 5 bleeding and BARC type 2,3, or 5 bleeding. The BleeMACS score and the PRECISE-DAPT score were significantly associated with 1-year incidence of BARC type 3 or 5 bleeding, but not BARC type 2, 3, or 5 bleeding. The discrimination of the PRECISE-DAPT score was moderate for BARC type 3 or 5 bleeding (c-statistic = 0.633), while those of the REACH (c-statistic = 0.533), PARIS (c-statistic = 0.553), and BleeMACS scores (c-statistic = 0.613) were relatively low. However, the analysis of c-statistic, NRI, and IDI detected no significant discrimination improvement of the PRECISE-DAPT score for BARC type 3 or 5 bleeding compared to the other three scores. The calibrations of the PRECISE-DAPT and BleeMACS scores were modest (Hosmer-Lemeshow test p > .05). Decision curve analysis indicated net benefit of the PRECISE-DAPT score in bleeding risk evaluation. In conclusion, the PRECISE-DAPT score performed moderately in predicting BARC type 3 or 5 bleeding, while the discriminative capacities of the REACH, PARIS, BleeMACS scores were relatively low in patients undergoing DES implantation. But no significant discrimination improvement of the PRECISE-DAPT score compared to the other scores could be detected. Further studies are required to develop standardized bleeding risk scores for this population.
Orem's Self-Care Deficit Nursing Theory to Improve Children's Self-Care: An Integrative Review

Often school-age children are thought of as dependent on their parents and not necessarily involved in behaviors related to their own self-care. It is important to implement and advance self-care performance early in life to promote healthy lifestyles. This review examined the use of Orem's Self Care Deficit Nursing Theory in relation to children's self-care behaviors. This integrative review followed the Whittemore and Knafl guidelines. A systematic search was conducted using the nursing databases. The sixteen study articles were identified for the review, and five themes were identified. Children can develop skills and actively participate in maintaining health and wellbeing. Self-care programs based on Orem's theory are well suited to assist individuals including children to improve self-care skills that lead better self-care practices. Nurses guided by Orem's SCDNT will be well equipped to promote children's knowledge and self-care skills for maintaining health and preventing negative health outcomes.
Headache in ADHD as comorbidity and a side effect of medications: a systematic review and meta-analysis

Abstract There is mixed evidence on the association between headache and attention-deficit/hyperactivity disorder (ADHD), as well as headache and ADHD medications. This systematic review and meta-analysis investigated the co-occurrence of headache in children with ADHD, and the effects of ADHD medications on headache. Embase, Medline and PsycInfo were searched for population-based and clinical studies comparing the prevalence of headache in ADHD and controls through January 26, 2021. In addition, we updated the search of a previous systematic review and network meta-analysis of double-blind randomized controlled trials (RCTs) on ADHD medications on June 16, 2020. Trials of amphetamines, atomoxetine, bupropion, clonidine, guanfacine, methylphenidate, and modafinil with a placebo arm and reporting data on headache as an adverse event, were included. Thirteen epidemiological studies and 58 clinical trials were eligible for inclusion. In epidemiological studies, a significant association between headache and ADHD was found [odds ratio (OR) = 2.01, 95% confidence interval (CI) = 1.63–2.46], which remained significant when limited to studies reporting ORs adjusted for possible confounders. The pooled prevalence of headaches in children with ADHD was 26.6%. In RCTs, three ADHD medications were associated with increased headache during treatment periods, compared to placebo: atomoxetine (OR = 1.29, 95% CI = 1.06–1.56), guanfacine (OR = 1.43, 95% CI = 1.12–1.82), and methylphenidate (OR = 1.33, 95% CI = 1.09–1.63). The summarized evidence suggests that headache is common in children with ADHD, both as part of the clinical presentation as such and as a side effect of some standard medications. Monitoring and clinical management strategies of headache in ADHD, in general, and during pharmacological treatment are recommended.
Characterization of Anti-Angiogenic Chemo-Sensitization via Longitudinal Ultrasound Localization Microscopy in Colorectal Carcinoma Tumor Xenografts

Objective: Super-resolution ultrasound localization microscopy (ULM) has unprecedented vascular resolution at clinically relevant imaging penetration depths. This technology can potentially screen for the transient microvascular changes that are thought to be critical to the synergistic effect(s) of combined chemotherapy-antiangiogenic agent regimens for cancer. Methods: In this paper, we apply this technology to a high-throughput colorectal carcinoma xenograft model treated with either the antiangiogenic agent sorafenib, FOLFOX-6 chemotherapy, a combination of the two treatments, or vehicle control. Results: Longitudinal ULM demonstrated morphological changes in the antiangiogenic treated cohorts, and evidence of vascular disruption caused by chemotherapy. Gold-standard histological measurements revealed reduced levels of hypoxia in the sorafenib treated cohort for both of the human cell lines tested (HCT-116 and HT-29). Therapy resistance was associated with an increase in tumor vascular fractal dimension as measured by a box-counting technique on ULM images. Conclusion: These results imply that the morphological changes evident on ULM signify a functional change in the tumor microvasculature, which may be indicative of chemo-sensitivity. Significance: ULM provides additional utility for tumor therapy response evaluation by offering a myriad of morphological and functional quantitative indices for gauging treatment effect(s).
Patients’ and Nurses’ Experiences of All Single-Room Hospital Accommodation: A Scoping Review

Aim and Objective: To identify, examine, and map literature on the experiences of single-room hospital accommodation, exploring what is known about how single-room accommodation in hospitals is viewed by patients and nurses. Background: Worldwide, hospital design is changing to mainly single-room accommodation. However, there is little literature exploring patients’ and nurses’ experiences of single-room designs. Design: Scoping review following the Joanna Briggs Institute guidance on scoping reviews. Methods: We conducted the search in medical databases for scientific and gray literature. The four authors independently used a data extraction tool to include sources from the searches. The sources were discussed during the process, and in case of a disagreement between two reviewers, the third and fourth reviewer would be invited to participate in the discussion until consensus was achieved. Results: We included 22 sources published during the period 2002–2020, with a majority (n = 16) during the period 2013–2020. The sources were distributed on 10 different countries; however, England dominated with 14 publications. We found three main maps for reporting on patients’ experiences: (1) personal control, (2) dignity, and (3) by myself. For the nurses’ experiences, we found four main maps: (1) the working environment, (2) changes of nursing practice, (3) privacy and dignity, and (4) patient safety. Conclusion: We suggested that patients’ and nurses’ experiences are predominantly interdependent and that the implications of single-room accommodation is a large and complex issue which goes beyond hospital design.
Measuring the Time to Deterioration for Health-Related Quality of Life in Patients With Metastatic Breast Cancer Using a Web-Based Monitoring Application: Longitudinal Cohort Study

Background Health-related quality of life (HRQoL) is used to evaluate the treatment of metastatic breast cancer. In a long-term therapy setting, HRQoL can be used as an important benchmark for treatment success. With the help of digital apps, HRQoL monitoring can be extended to more remote areas and be administered on a more frequent basis. Objective This study aims to evaluate 3 common HRQoL questionnaires in metastasized breast cancer in terms of TTD in a digital, web-based setting. We further aim to examine the development of the HRQoL in different systemic treatment groups in each of these evaluation instruments. Methods A total of 192 patients with metastatic breast cancer were analyzed in this bicentric prospective online cohort study at two German university hospitals. Patients completed questionnaires on HRQoL (EuroQol Visual Analog Scale [EQ-VAS], EuroQol 5 Dimension 5 Level [EQ-5D-5L], European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 item [EORTC QLQ-C30]) via an online platform over a 6-month period. Treatment schedules and medical history were retrieved from medical records. Unadjusted Cox regression analysis on treatment-related factors was performed. We conducted subgroup analyses in regard to TTD events between different treatments. Results The EQ-VAS showed a higher rate of deterioration after 8 weeks (84/179, 46.9%) than the EQ-5D-5L (47/163, 28.8%) and EORTC QLQ-C30 (65/176, 36.9%). Unadjusted Cox regression revealed significant connections between known metastases in the liver (P=.03, HR 1.64, 95% CI 1.06-2.52) and pleura (P=.04, HR 0.42, 95% CI 0.18-0.96) in the EQ-VAS. Significant relations between EQ-VAS events and single EQ-5D-5L items and the EQ-5D-5L summary score were demonstrated. All treatment groups significantly differed from the CDK4/6 inhibition subgroup in the EQ-VAS. Conclusions Compared to the EQ-5D-5L and QLQ-C30, the EQ-VAS showed a higher rate of deterioration after 8 weeks. Significant connections to certain metastatic locations were only detected in the EQ-VAS. The EQ-VAS is capable of reflecting the distinctive HRQoL profiles of different systemic treatments as well as the different aspects of HRQoL presented in the EQ-5D-5L. TTD with the EQ-VAS is an adequate mean of examining longitudinal development of HRQoL among breast cancer patients.
Estimation of Excess All-cause Mortality during COVID-19 Pandemic in Korea

Background Excess all-cause mortality is helpful to assess the full extent of the health impact, including direct and indirect deaths of coronavirus disease 2019 (COVID-19). The study aimed to estimate overall and regional excess all-cause mortality during the pandemic in Korea. Methods We obtained all-cause death data and population statistics from January 2010 to December 2020. The expected mortality in 2020 was estimated using a quasi-Poisson regression model. The model included death year, seasonal variation, cold wave (January), average death counts in the previous month, and population. Excess mortality was defined as the difference between the observed mortality and the expected mortality. Regions were classified into three areas according to the numbers of COVID-19 cases. Results There was no annual excess all-cause mortality in 2020 at the national and regional level compared to the average death for the previous ten years. The observed mortality in 2020 was 582.9 per 100,000 people, and the expected mortality was 582.3 per 100,000 people (95% confidence interval, 568.3–596.7). However, we found monthly and regional variations depending on the waves of the COVID-19 pandemic in Korea. While the mortality in August, October, and November exceeded the expected range, the mortality in September was lower than the expected range. The months in which excess deaths were identified differed by region. Conclusion Our results show that the mortality in 2020 was similar to the historical trend. However, in the era of the COVID-19 pandemic, it would be necessary to regularly investigate COVID-19-related mortality and determine its direct and indirect causes.
Acute Aquatic Toxicity and Biodegradability of Fluorinated Ionic Liquids

Several novel fluorinated ionic liquids (FILs), fully miscible with water and with excellent surfactant behavior, have been studied for pharmacological applications. The use of these novel FILs as drug delivery systems can improve the bioavailability, stability and efficacy of therapeutic proteins. An initial screening of toxicity in four different human cell lines indicated that some of the FILs possess low cytotoxicity. An environmental hazard assessment of these compounds, in the context of Green Pharmacy, is necessary before a pharmaceutical application takes place. In this work, ecotoxicity tests have been performed in aquatic species with different levels of biological organization (Vibrio fischeri, Daphnia magna and Lemna minor) to evaluate intrinsic hazard that these FILs might pose after being released to the aquatic environment from the human body or from industrial processes. Additionally, the biodegradability of these compounds has been evaluated using microorganisms from wastewater treatment .
Willingness to Accept Human Papillomavirus Vaccination and its Influencing Factors Using Information–Motivation–Behavior Skills Model: A Cross-Sectional Study of Female College Freshmen in Mainland China

Background This study aimed to assess the awareness and attitudes toward human papillomavirus (HPV) vaccination among female college freshmen and explore their willingness and associated factors to receive the HPV vaccine based on the information–motivation–behavior skills (IMB) model. Methods From February 21 to April 30, 2020, a cross-sectional survey was conducted among female freshmen in seven colleges in mainland China. Socio-demographic characteristics, health-related awareness, knowledge of HPV, motivation, and behavioral skills toward HPV vaccination were assessed using questionnaires. Univariate and multivariate logistic regression analyses were performed to identify the influencing factors of willingness to receive the HPV vaccine in the next 6 months. Results Among the 3867 students invited to participate in this study, 102 (2.64%) reported having taken the HPV vaccine. Among the unvaccinated participants, 59.89% had previously heard of HPV, and 32.08% were willing to take the HPV vaccine in the next 6 months. Willingness to get the HPV vaccine was associated with sexual experience(s) (AOR = 1.96, 95% CI: 1.25–3.08), family or friends with cancer (AOR = 1.24, 95% CI: 1.04–1.48), having heard of HPV (AOR = 1.23, 95% CI: 1.03–1.47), and having actively searched for or having consulted on issues concerning HPV vaccine (AOR = 1.22, 95% CI: 1.02–1.45). In the dimensions of the IMB model, “perceived susceptibility” (AOR = 1.20, 95% CI: 1.09–1.31), “perceived severity” (AOR = 1.24, 95% CI: 1.11–1.39), “subjective norms” (AOR = 2.09, 95% CI: 1.75–2.49), and “self-efficacy” (AOR: 2.95, 95% CI: 2.44–3.58) were positively associated with HPV vaccination acceptance, while “perceived barriers” (AOR = .60, 95% CI: .52–.69) negatively affected intention to get HPV vaccination. Conclusion HPV vaccination rates and willingness to receive the HPV vaccine in the next 6 months were found to be poor among female college freshmen in mainland China. Having a positive attitude toward HPV vaccination, creating vaccine-friendly social norms, and removing related barriers are important measures to promote HPV immunization.
Exceptionally Steep Brain-Body Evolutionary Allometry Underlies the Unique Encephalization of Osteoglossiformes

Brain-body static allometry, which is the relationship between brain size and body size within species, is thought to reflect developmental and genetic constraints. Existing evidence suggests that the evolution of large brain size without accompanying changes in body size (that is, encephalization) may occur when this constraint is relaxed. Teleost fish species are generally characterized by having close-fitting brain-body static allometries, leading to strong allometric constraints and small relative brain sizes. However, one order of teleost, Osteoglossiformes, underwent extreme encephalization, and its mechanistic bases are unknown. Here, I used a dataset and phylogeny encompassing 859 teleost species to demonstrate that the encephalization of Osteoglossiformes occurred through an increase in the slope of evolutionary (among-species) brain-body allometry. The slope is virtually isometric (1.03 ± 0.09 SE), making it one of the steepest evolutionary brain-body allometric slopes reported to date, and it deviates significantly from the evolutionary brain-body allometric slopes of other clades of teleost. Examination of the relationship between static allometric parameters (intercepts and slopes) and evolutionary allometry revealed that the dramatic steepening of the evolutionary allometric slope in Osteoglossiformes was a combined result of evolution in the slopes and intercepts of static allometry. These results suggest that the evolution of static allometry, which likely has been driven by evolutionary changes in the rate and timing of brain development, has facilitated the unique encephalization of Osteoglossiformes.