Miracle-dz/UniFAR-FTUs huggingface dataset:
Quality of a Supporting Mobile App for Rheumatic Patients: Patient-Based Assessment Using the User Version of the Mobile Application Scale (uMARS)

Introduction: Mobile applications promise to improve current health care. However, current mobile app quality ratings are mostly physician-based. The aim of this study was (1) to assess the quality of the self-management app Rheuma Auszeit using the validated uMARS (User Version of the Mobile App Rating Scale) app quality assessment tool and (2) to evaluate the association between uMARS scores and patients' characteristics. Materials and Methods: Consecutive patients with rheumatoid arthritis, psoriatic arthritis and spondyloarthritis were seen at the rheumatology clinic at university hospital Erlangen, Germany. They were asked to test Rheuma Auszeit, evaluate its quality using uMARS and complete a paper-based survey evaluating the individual preferences, attitudes and ehealth literacy. The association between uMARS scores and patients' characteristics was further explored. Results: Between December 2018 and January 2019, a total of 126 patients evaluated Rheuma Auszeit using uMARS and filled out the paper-based survey. The median uMARS score was 3.9, IQR 0.7. Functionality was the domain with the highest rating (median 4.8, IQR 0.8), followed by aesthetics (median 4.0, IQR 0.7), information (median 3.5, IQR 0.8), and engagement (median 3.2, IQR 1.0). Subjective quality was average (median 3.0, IQR 1.0). The lowest scoring individual item was customization with a median of 2.5/5. Lower functionality scores were reported among older female rheumatic patients (P < 0.004). Older male rheumatic patients reported a higher subjective quality score (P < 0.024). Perceived disease activity and disease duration did not significantly correlate with any uMARS subdomain scores. eHealth literacy significantly correlated with functionality uMARS subdomain ratings (Rho = 0.18; P < 0.042). Preferred time of app usage significantly correlated with engagement (Rho = 0.20; P < 0.024), functionality (Rho = 0.19; P < 0.029), total uMARS score (Rho = 0.21; P < 0.017) and subjective quality score (Rho = 0.21; P < 0.017). The vast majority of rheumatic patients would consider recommending Rheuma Auszeit to other patients (117/126; 92.9%). Conclusion: Rheuma Auszeit was well-accepted by German patients suffering from rheumatoid arthritis, psoriatic arthritis and ankylosing spondyloarthritis. Lacking customization could lead to low app compliance and should be improved. Lower functionality scores among older female rheumatic patients highlight the need for patient education. The study underlines the potential and feasibility of therapeutic complementary digital solutions in rheumatology.
Assessing the Impact of the Assimilation of SWOT Observations in a Global High-Resolution Analysis and Forecasting System Part 1: Methods

The future Surface Water Ocean Topography (SWOT) mission due to be launched in 2022 will extend the capability of existing nadir altimeters to enable two-dimensional mapping at a much higher effective resolution. A significant challenge will be to assimilate this kind of data in high-resolution models. In this context, Observing System Simulation Experiments (OSSEs) have been performed to assess the impact of SWOT on the Mercator Ocean and Copernicus Marine Environment Monitoring Service (CMEMS) global, high-resolution analysis and forecasting system. This paper focusses on the design of these OSSEs, in terms of simulated observations and assimilation systems (ocean model and data assimilation schemes). The main results are discussed in a companion paper. Two main updates of the current Mercator Ocean data assimilation scheme have been made to improve the assimilation of information from SWOT data. The first one is related to a different parametrisation of the model error covariance, and the second to the use of a four-dimensional (4D) version of the data assimilation scheme. These improvements are described in detail and their contribution is quantified. The Nature Run (NR) used to represent the “truth ocean” is validated by comparing it with altimeter observations, and is then used to simulate pseudo-observations required for the OSSEs. Finally, the design of the OSSEs is evaluated by ensuring that the differences between the assimilation system and the NR are statistically consistent with the misfits between real ocean observations and real-time operational systems.
Social Connectedness, Excessive Screen Time During COVID-19 and Mental Health: A Review of Current Evidence

With an advancement of digital technology, excessive screen time has become a grave concern. This has pushed researchers and practitioners to focus on digital well-being. Screen time during COVID-19 has further increased as a result of public health measures enforced by governments to curb the pandemic. With the global societies under lockdown, the only medium to stay socio- emotionally connected was the digital one. A lack of comprehensive empirical overviews on screen time in COVID-19 era in the present literature prompted us to conduct this review. The present review attempts to understand the virtual social connectedness, excessive use of digital technology, its consequences and suggest strategies to maintain healthy use of digital technology. Results reveal that screen time has increased drastically during COVID-19. Though there are mixed consequences of prolonged screen time use and blurred understanding between healthy and unhealthy social connectedness over digital media, the suggestions for negative implications on (physical and) mental health warrant a strict need for inculcating healthy digital habits, especially knowing that digital technology is here to stay and grow with time.
Innate Immune Response to Viral Infections at the Maternal-Fetal Interface in Human Pregnancy

The placenta, the first and largest organ to develop after conception, not only nurtures and promotes the development of the conceptus, but, it also functions as a barrier against invading pathogens. Early phases of pregnancy are associated with expansion of specific subsets of Natural Killer cells (dNK) and macrophages (dMφ) at the maternal uterine mucosa, the basal decidua. In concert with cells of fetal origin, dNK cells, and dMφ orchestrate all steps of placenta and fetus development, and provide the first line of defense to limit vertical transmission. However, some pathogens that infect the mother can overcome this protective barrier and jeopardize the fetus health. In this review, we will discuss how members of the classical TORCH family (Toxoplasma, Other, Rubella, Cytomegalovirus, and Herpes simplex virus) and some emerging viruses (Hepatitis E virus, Zika virus, and SARS-CoV2) can afford access to the placental fortress. We will also discuss how changes in the intrauterine environment as a consequence of maternal immune cell activation contribute to placental diseases and devastating pregnancy outcomes.
Potential Implications of a Type 1 Interferon Gene Signature on COVID-19 Severity and Chronic Inflammation in Sickle Cell Disease

At the onset of the corona virus disease 19 (COVID-19) pandemic, there were concerns that patients with sickle cell disease (SCD) might be especially vulnerable to severe sequelae of SARS-CoV-2 infection. While two reports support this conclusion, multiple studies have reported unexpectedly favorable outcomes in patients with SCD. However, mechanisms explaining these disparate conclusions are lacking. Here, we review recent studies indicating that the majority of patients with SCD express elevated levels of anti-viral type 1 interferons (IFNα/β) and interferon stimulated genes, independent of COVID-19, during their baseline state of health. We also present our data from the pre-COVID-19 era, illustrating elevated expression of a well-characterized interferon stimulated gene in a cohort of patients with SCD, compared to race-matched controls. These type 1 interferons and interferon stimulated genes have the potential to contribute to the variable progression of COVID-19 and other viral infections in patients with SCD. While the majority of evidence supports a protective role, the role of IFNα/β in COVID-19 severity in the general population remains an area of current investigation. We conclude that type 1 interferon responses in patients with SCD may contribute to the variable COVID-19 responses reported in prior studies. Additional studies investigating the mechanisms underlying IFNα/β production and other clinical consequences of IFNα/β-mediated inflammation in SCD disease are warranted. Graphical Abstract Hypothesis: Baseline type I interferon activity may contribute to variable COVID-19 progression in SCD. (Top) At early stages of SARS-CoV-2 infection, high baseline IFNα/β activity may contribute to the anti-viral response in patients with SCD. Recognition of damage-associated molecular patterns by pattern recognition receptors (PRRs) induces IFNα/β production. Heme released from hemolyzed sickle cells binds Toll-like receptor 4 (TLR4), which may induce IFNα/β in vascular endothelial cells. IFNα/β bind to the IFNα/β receptor (IFNAR) in neutrophils and other cells types, leading to production of MxA and other interferon-stimulated genes (ISGs). ISGs can directly inhibit viral replication and promote B cell production of neutralizing antibodies. The IFNα/β response is one of multiple responses, including production of IL-6, TNFα, and IL-1b, by innate and adaptive immune cells that have the potential to limit COVID-19 progression. (Bottom) In contrast, reduced or absent IFNα/β activity may increase susceptibility to viral infection, leading to airway epithelial cell death and COVID-19. Dashed lines indicate potentially connected pathways, while solid lines are supported by prior studies.
IRF7-Associated Immunophenotypes Have Dichotomous Responses to Virus/Allergen Coexposure and OM-85-Induced Reprogramming

High risk for virus-induced asthma exacerbations in children is associated with an IRF7lo immunophenotype, but the underlying mechanisms are unclear. Here, we applied a Systems Biology approach to an animal model comprising rat strains manifesting high (BN) versus low susceptibility (PVG) to experimental asthma, induced by virus/allergen coexposure, to elucidate the mechanism(s)-of-action of the high-risk asthma immunophenotype. We also investigated potential risk mitigation via pretreatment with the immune training agent OM-85. Virus/allergen coexposure in low-risk PVG rats resulted in rapid and transient airways inflammation alongside IRF7 gene network formation. In contrast, responses in high-risk BN rats were characterized by severe airways eosinophilia and exaggerated proinflammatory responses that failed to resolve, and complete absence of IRF7 gene networks. OM-85 had more profound effects in high-risk BN rats, inducing immune-related gene expression changes in lung at baseline and reducing exaggerated airway inflammatory responses to virus/allergen coexposure. In low-risk PVG rats, OM-85 boosted IRF7 gene networks in the lung but did not alter baseline gene expression or cellular influx. Distinct IRF7-associated asthma risk immunophenotypes have dichotomous responses to virus/allergen coexposure and respond differentially to OM-85 pretreatment. Extrapolating to humans, our findings suggest that the beneficial effects OM-85 pretreatment may preferentially target those in high-risk subgroups.
Sex Differences in Neurophysiological Changes Following Voluntary Exercise in Adolescent Rats

Background: Adolescence is a period of time characterized by the onset of puberty and is marked by cognitive and social developments and gross physical changes that can play a role in athletic performance. Sex differences are present with differences in body size, height, physiology and behavior which contribute to differences in athletic performance as well. Pre-clinical studies representing this active group are lacking. Methods: Acute and chronic effects of exercise were evaluated. Male and female adolescent rats were given voluntary access to a running wheel for 10 consecutive days. Running behavior (males and females) and estrous cycling (females only) were analyzed daily. A second group was given 10 days of voluntary access to a running wheel, then rested for 10 days to determine the long-term effects of exercise on the adolescent brain. Brain and muscle tissue were harvested at 10 and 20 day time points to understand exercise-dependent changes in mitochondrial activity and neuroplasticity. Animal cohorts were carried out at two different sites: University of California Los Angeles and Pepperdine University. Results: On average, running distance, intensity of run, and length of running bout increased for both male and female rats across the 10 days measured. Females ran significantly further and for longer intervals compared to males. Cortical and muscle expression of PGC1α showed similar levels at 10 days regardless of sex and exercise. There was a significant increase in expression at 20 days in all groups correlating with body size (p's < 0.05). Cortical and hippocampal levels of BDNF were similar across all groups, however, BDNF was significantly higher in exercised females at the acute compared to long-term time point. Discussion: Adolescent rats allowed 10 days of exercise show changes in physiologic function. There are sex differences in running behavior not impacted by sex hormones. These results are important to further our understanding of how exercise impacts the adolescent brain.
Psychotherapists’ Challenges With Online Therapy During COVID-19: Concerns About Connectedness Predict Therapists’ Negative View of Online Therapy and Its Perceived Efficacy Over Time

Therapists’ forced transition to provide psychotherapy remotely during the COVID-19 pandemic offers a unique opportunity to examine therapists’ views and challenges with online therapy. This study aimed to investigate the main challenges experienced by therapists during the transition from in-person to online therapy at the beginning of the pandemic and 3 months later, and the association between these challenges and therapists’ perception of the quality of the relationship with their online patients, and therapists’ attitudes and views about online therapy and its efficacy at these two timepoints. As part of a large-scale international longitudinal survey, we collected data from 1,257 therapists at two timepoints: at the start of COVID-19, when many therapists switched from providing in-person therapy to online therapy, as well as 3 months later, when they had had the opportunity to adjust to the online therapy format. At both timepoints, therapists reported on perceived challenges, quality of working alliance and real relationship, attitudes toward online therapy, and their views on online therapy’s efficacy compared to in-person therapy. Factor analysis of individual survey items at both timepoints identified four different types of challenges among this therapist sample: Emotional connection (feeling connected with patients, reading emotions, express or feel empathy), Distraction during sessions (therapist or patient), Patients’ privacy (private space, confidentiality), and Therapists’ boundaries (professional space, boundary setting). Older and more experienced therapists perceived fewer challenges in their online sessions. At baseline, all four types of challenges were associated with lower perceived quality of the therapeutic relationship (working alliance and real relationship), and more negative attitudes toward online therapy and its efficacy. After 3 months, perceived challenges with three domains – Emotional connection, Patients’ privacy, and Therapists’ boundaries significantly decreased – whereas challenges in the fourth domain – Distraction – increased. In our study, therapists’ concerns about being able to connect with patients online appeared to be the most impactful, in that it predicted negative attitudes toward online therapy and its perceived efficacy 3 months later, above and beyond the effect of therapists’ age and clinical experience. Clinical and training implications are discussed.
Responsiveness, Performance and Corruption: Reasons for the Decline of Political Trust

We test the importance of responsiveness, performance and corruption to explain the evolution of political trust in Spain between 1997 and 2019. To this end, the study analyses two longitudinal datasets, namely, a repeated cross-sectional dataset from the Spanish samples of Eurobarometer and an individual-level panel survey conducted during a period of economic recovery in 2015. The study finds that perceptions about political corruption and responsiveness matter greatly in shaping political trust and to a lesser extent economic performance. Although the Great Recession is likely responsible for the sharp decline in trust towards political parties and the parliament between 2008 and 2012, the analysis suggests that trust in representative institutions remains low even after the Recession because of a series of devastating corruption incidents and a perceived lack of responsiveness of the political system. On the other hand, the study finds indications that trust in the judicial system might have been mainly affected by perceptions of corruption.
Predicting Pharmacist Intention to Contribute to COVID-19 Management at the Community Level: A Cross-Sectional Survey Study

Introduction: The role of pharmacists in public health management is expected to grow into a key player in the continuing measures of managing the COVID-19 pandemic, especially in the community setting. However, their intention to provide essential public health services for combating the pandemic and the impact of their attitude and beliefs are largely unknown. This study aimed to investigate the intention-to-practice COVID-19-related responsibilities of pharmacists based on the theory of planned behavior (TPB), identify the key factors predicting their intention, and explore the usefulness of the TPB model in predicting such an intention. Methods: A cross-sectional, self-administered questionnaire was completed by pharmacists in Macao between May and August 2020. Quantitative responses regarding intention-to-practice COVID-19-related duties, and the four TPB variables [attitude (A), subjective norms (SN), perceived behavioral control (PBC), and past behavior (PB)] were measured. Cronbach's alpha and composite reliability were used to determine the reliability and validity of the tool. In addition to descriptive statistics, Pearson's correlation was used to determine the strengths of the association, and multiple linear regression was used to predict the association between the intention and the four key variables. Results: More than half of the pharmacists practicing in Macao completed the questionnaire (296/520) giving a response rate of 56.9%. Among them, 75% were 26–40 years old and 56% were female. The majority of the participants (91.9%) demonstrated a positive intention to contribute to the COVID-19 infection management (mean = 4.19 ± 0.51). The mean scores for A, SN, PBC, and PB were 4.06 ± 0.52, 3.71 ± 0.58, 3.76 ± 0.65, and 4.03 ± 0.54, respectively. A (β = 0.671), SN (β = 0.608), PBC (β = 0.563), and PB (β = 0.829) were all positively correlated with intention (all P < 0.001). It was found that 72.5% of the variance in the intention-to-practice COVID-19-related duties could be explained by the TPB model using the four key variables with A and PB being two possible predictors. Conclusion: Pharmacists showed favorable A, SN, PBC, and intention in participating in COVID-19 management in the community setting. Specific training, enhanced stakeholder communication, and improved pharmacy management are essential to increase the willingness of pharmacists to take part in the COVID-19 pandemic and other public health emergencies alike in the future.
The Role of Cytokines in Predicting the Response and Adverse Events Related to Immune Checkpoint Inhibitors

Recently, the overall survival (OS) and progression-free survival (PFS) of patients with advanced cancer has been significantly improved due to the application of immune checkpoint inhibitors (ICIs). Low response rate and high occurrence of immune-related adverse events (irAEs) make urgently need for ideal predictive biomarkers to identity efficient population and guide treatment strategies. Cytokines are small soluble proteins with a wide range of biological activity that are secreted by activated immune cells or tumor cells and act as a bridge between innate immunity, infection, inflammation and cancer. Cytokines can be detected in peripheral blood and suitable for dynamic detection. During the era of ICIs, many studies investigated the role of cytokines in prediction of the efficiency and toxicity of ICIs. Herein, we review the relevant studies on TNF-α, IFN-γ, IL-6, IL-8, TGF-β and other cytokines as biomarkers for predicting ICI-related reactions and adverse events, and explore the immunomodulatory mechanisms. Finally, the most important purpose of this review is to help identify predictors of ICI to screen patients who are most likely to benefit from immunotherapy.
Elevated Serum Levels of Soluble ST2 Are Associated With Plaque Vulnerability in Patients With Non-ST-Elevation Acute Coronary Syndrome

Background: Recent studies have suggested that soluble suppression of tumorigenicity-2 (sST2), an inflammation-related protein receptor, is associated with atherosclerotic diseases. This study aimed to investigate the potential predictive value of sST2 on plaque vulnerability by assessing whether elevated serum levels of sST2 are associated with vulnerable plaque features in patients with non-ST-elevation acute coronary syndrome (ACS). Methods: A total of 120 patients with non-ST-elevation ACS (167 lesions) were prospectively enrolled and evaluated by standard coronary computed tomography angiography (CCTA) and coronary angiography in this study. Serum sST2 levels were measured by ELISA (Presage® ST2 Assay Kit, Critical Diagnostics), and semiautomated software (QAngioCT, Medis) was used to quantify coronary plaques. Results: The included patients were divided into 4 groups by serum sST2 level quartiles. Volumetric analysis of the whole lesion revealed that patients with higher sST2 levels had a larger absolute necrotic core (NC) volume (Quartile 4 vs. Quartile 1, 86.16 ± 59.71 vs. 45.10 ± 45.80 mm3, P = 0.001; Quartile 4 vs. Quartile 2, 86.16 ± 59.71 vs. 50.22 ± 42.56 mm3, P = 0.002) and a higher NC percentage (Quartile 4 vs. Quartile 1, 35.16 ± 9.82 vs. 23.21 ± 16.18%, P < 0.001; Quartile 4 vs. Quartile 2, 35.16 ± 9.82% vs. 22.50 ± 14.03%, P < 0.001; Quartile 4 vs. Quartile 3, 35.16 ± 9.82% vs. 25.04 ± 14.48%, P < 0.001). Correlation analysis revealed that serum sST2 levels were positively correlated with the NC (r = 0.323, P < 0.001) but negatively correlated with dense calcium (r = −0.208, P = 0.007). Furthermore, among those with plaque calcification, patients with spotty calcification exhibited higher serum sST2 levels than those with large calcification (26.06 ± 16.54 vs. 17.55 ± 7.65 ng/mL, P = 0.002). No significant differences in plaque components at the level of the minimal lumen area (MLA) were found among the groups. Conclusions: Serum sST2 levels were correlated with different coronary plaque components in patients with non-ST-elevation ACS. A higher serum level of sST2 was correlated with plaque vulnerability. Clinical Trial Registration: www.ClinicalTrials. gov, identifier: NCT04797819.