bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Randomized, Double-Blinded, Placebo-Controlled, Phase 2 Study of Safety, Tolerability and Efficacy of Pirfenidone in Patients with Rheumatoid Arthritis Interstitial Lung Disease
Authors: Solomon Joshua J. , Danoff Sonye , Woodhead Felix , Hurwitz Shelley , Maurer Rie , Glaspole Ian , Dellaripa Paul F. , Gooptu Bibek , Vassallo Robert , Cox P. Gerald , Flaherty Kevin R. , Adamali Huzaifa I. , Gibbons Michael A. , Troy Lauren , Forrest Ian , Lasky Joseph A. , Spencer Lisa G. , Golden Jeffrey , Scholand Mary Beth , Chaudhuri Nazia , Perella Mark A. , Lynch David , Chambers Daniel C. , Kolb Martin , Spino Cathie , Raghu Ganesh , Goldberg Hilary , Rosas Ivan O. ,   the TRAIL1 Network Investigators
Published: April 2022

ABSTRACTBackgroundInterstitial lung disease (ILD) is a known complication of rheumatoid arthritis (RA) with a lifetime risk in any individual of 7.7%. The TRAIL1 trial was a randomized, double-blinded, placebo-controlled, phase 2 study of safety, tolerability, and efficacy of pirfenidone for the treatment of patients with RA-ILD.MethodsThe TRAIL1 was a phase 2 trial intended to enroll 270 adult patients (18 to 85 years) with established RA-ILD at 33 sites in 4 countries. Patients were randomly assigned (1:1) to 2,403 mg oral pirfenidone or placebo daily. The primary endpoint was the incidence of the composite endpoint of decline from baseline in percent predicted forced vital capacity (FVC%) of 10% or greater or death during the 52-week treatment period. Key secondary endpoints included change in absolute and FVC% over 52 weeks.FindingsThe trial was stopped early due to slow recruitment and soon after the shutdown of clinical trials as a consequence of the coronavirus disease 2019 (COVID-19) pandemic. Data from 123 patients enrolled were analyzed. The primary endpoint was met by 11.1% on pirfenidone vs. 15% on placebo [OR=0.67 (0.22, 2.03), p=0.48]. Subjects receiving pirfenidone had a slower rate of decline in lung function as measured by estimated annual change in FVC(ml) (−66 vs. -146, p=0.0082) and FVC(%) (−1.02 vs. -3.21, p=0.0028). This effect on decline was also seen when analyzed within participants with baseline usual interstitial pneumonia (UIP) pattern on HRCT (FVC(ml) (−43 vs. -169, p=0.0014) and FVC% (−0.2 vs. -3.81, p=0.0002)). There was no significant difference in the rate of treatment-emergent serious adverse events.InterpretationDue to early termination of the study, results should be interpreted with caution. Despite being underpowered to evaluate the primary endpoint, pirfenidone slowed the rate of decline of FVC over time in subjects with RA-ILD. Safety in patients with RA-ILD was similar to that seen in other pirfenidone trials.FundingFunding for this investigator initiated trial was provided by Genentech, Inc. to Ivan O. Rosas, MD, on behalf of the TRAIL1 Investigators.
Long-term performance assessment of fully automatic biomedical glottis segmentation at the point of care
Authors: Groh René , Dürr Stephan , Schützenberger Anne , Semmler Marion , Kist Andreas M. 
Published: April 2022

AbstractDeep Learning has a large impact on medical image analysis and lately has been adopted for clinical use at the point of care. However, there is only a small number of reports of long-term studies that show the performance of deep neural networks (DNNs) in such a clinical environment. In this study, we measured the long-term performance of a clinically optimized DNN for laryngeal glottis segmentation. We have collected the video footage for two years from an AI-powered laryngeal high-speed videoendoscopy imaging system and found that the footage image quality is stable across time. Next, we determined the DNN segmentation performance on lossy and lossless compressed data revealing that only 9% of recordings contain segmentation artefacts. We found that lossy and lossless compression are on par for glottis segmentation, however, lossless compression provides significantly superior image quality. Lastly, we employed continual learning strategies to continuously incorporate new data to the DNN to remove aforementioned segmentation artefacts. With modest manual intervention, we were able to largely alleviate these segmentation artefacts by up to 81%. We believe that our suggested deep learning-enhanced laryngeal imaging platform consistently provides clinically sound results, and together with our proposed continual learning scheme will have a long-lasting impact in the future of laryngeal imaging.
Uptake of COVID-19 vaccines among pregnant women: a systematic review and meta-analysis
Authors: Galanis Petros , Vraka Irene , Siskou Olga , Konstantakopoulou Olympia , Katsiroumpa Aglaia , Kaitelidou Daphne 
Published: April 2022

AbstractBackgroundMass vaccination against the COVID-19 is essential to control the pandemic. COVID-19 vaccines are recommended now during pregnancy to prevent adverse outcomes.ObjectiveTo evaluate the evidence from the literature regarding the uptake of COVID-19 vaccination among pregnant women.MethodsWe conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We searched PubMed, Medline, Scopus, ProQuest, Web of Science, CINAHL, and a pre-print service (medRxiv) from inception to March 23, 2022. We included quantitative studies reporting COVID-19 vaccination uptake among pregnant women, studies that examine predictors of COVID-19 vaccination uptake and studies that examine reasons for decline of vaccination. We performed meta-analysis to estimate the overall proportion of vaccinated pregnant women against the COVID-19.ResultsWe found 11 studies including 703,004 pregnant women. The overall proportion of vaccinated pregnant women against the COVID-19 was 27.5% (95% CI: 18.8-37.0%). The pooled proportion for studies that were conducted in Israel was higher than the proportion for studies that were conducted in USA and other countries. Predictors of COVID-19 vaccination uptake were older age, ethnicity, race, trust in COVID-19 vaccines, and fear of COVID-19 during pregnancy. On the other hand, mistrust in the government, diagnosis with COVID-19 during pregnancy, and worry about the safety and the side effects of the COVID-19 vaccines were reasons for decline of vaccination.ConclusionsThe global COVID-19 vaccination prevalence in pregnant women is low. There is a large gap in the literature on the factors influencing the decision of pregnant women to be vaccinated against the COVID-19. Targeted information campaigns are essential to improve trust and build vaccine literacy among pregnant women. Given the ongoing high case rates and the known increased risks of COVID-19 in pregnant women, our findings could help policy makers to improve the acceptance rate of COVID-19 vaccines in pregnant women especially in vulnerable subgroups.
Internet and mental health during the COVID-19 pandemic: Evidence from the UK
Authors: Quintana-Domeque Climent , Zeng Jingya , Zhang Xiaohui 
Published: April 2022

AbstractWith the COVID-19 pandemic, the Internet has become a key player in the daily lives of most people. We investigate the relationship between mental health and internet use frequency and purpose six months after the first lockdown in the UK, September 2020. Using data from the UK Household Longitudinal Study on the 12-item General Health Questionnaire and the Internet use module, and controlling for sociodemographic characteristics and personality traits, we find that older individuals (aged 59 or above) have a lower internet use frequency (twice a day or less). Younger women use the Internet for social purposes more than men do, while younger men use the Internet for leisure-and-learning purposes more than women and older men do. Both high frequency internet use and use for social purposes appear to be a protective factor for social dysfunction. Interestingly, high internet use is a protective factor for social dysfunction among younger women, but a risk factor for psychological distress among younger men. Finally, while leisure-and-learning purpose is a protective factor for social dysfunction among younger women, it is a risk factor for social dysfunction among younger men.
Evidence for feasibility of mobile health and social media-based interventions for early psychosis and clinical high risk
Authors: Franco Olivia H. , Calkins Monica E. , Giorgi Salvatore , Ungar Lyle H. , Gur Raquel E. , Kohler Christian G. , Tang Sunny X. 
Published: April 2022

AbstractBackgroundDigital technology, the internet and social media are increasingly investigated as a promising means for monitoring symptoms and delivering mental health treatment. These apps and interventions have demonstrated preliminary acceptability and feasibility, but previous reports suggests that access to technology may still be limited among individuals with psychotic disorders relative to the general population.ObjectiveWe evaluated and compared access and use of technology and social media in young adults with psychotic disorders (PD), clinical risk for psychosis (CR), and psychosis-free youths (PF).MethodsParticipants were recruited through a coordinated specialty care clinic dedicated towards early psychosis as well as ongoing studies. We surveyed 21 PD, 23 CR, and 15 PF participants regarding access to technology and use of social media, specifically Facebook and Twitter. Statistical analyses were conducted in R. Categorical variables were compared among groups Fisher’s exact test, continuous variables were compared using one-way ANOVA, and multiple linear regressions were used to evaluate for covariates.ResultsAccess to technology and social media were similar among PD, CR and PF. Individuals with PD, but not CR, were less likely to post at a weekly or higher frequency compared to psychosis-free individuals. We found that decreased active social media posting was unique to psychotic disorders and did not occur with other psychiatric diagnoses or demographic variables. Additionally, variation in age, sex, Caucasian vs. non-Caucasian race did not affect posting frequency.ConclusionsFor young people with psychosis spectrum disorders, there appears to be no “technology gap” limiting the implementation of digital and mobile health interventions. Active posting to social media was reduced for individuals with psychosis, which may be related to negative symptoms or impairment in social functioning.
Long-term psychological consequences of long Covid: a propensity score matching analysis comparing trajectories of depression and anxiety symptoms before and after contracting long Covid vs short Covid
Authors: Fancourt Daisy , Steptoe Andrew , Bu Feifei 
Published: April 2022

AbstractBackgroundThere is a growing global awareness of the psychological consequences of long Covid, supported by emerging empirical evidence. However, the mergence and long-term trajectories of psychological symptoms following the infection are still unclear.AimsTo examine when psychological symptoms first emerge following the infection with SARS-CoV-2, and the long-term trajectories of psychological symptoms comparing long and short Covid groups.MethodsWe analysed longitudinal data from the UCL Covid-19 Social Study (March 2020-November 2021). We included data from adults living in England who reported contracting SARS-CoV-2 by November 2021 (N=3,115). Of these, 15.9% reported having had long Covid (N=495). They were matched to participants who had short Covid using propensity score matching on a variety of demographic, socioeconomic and health covariates (N=962, n=13,325) and data were further analysed using growth curve modelling.ResultsDepressive and anxiety symptoms increased immediately following the onset of infection in both long and short Covid groups. But the long Covid group had substantially greater initial increases in depressive symptoms and heightened levels over 22 months follow-up. Initial increases in anxiety were not significantly different between groups, but only the short Covid group experienced an improvement in anxiety over follow-up, leading to widening differences between groups.ConclusionsThe findings shed light on the psychobiological pathways involved in the development of psychological symptoms relating to long Covid. The results highlight the need for monitoring of mental health and provision of adequate support to be interwoven with diagnosis and treatment of the physical consequences of long Covid.
Use of glycolysis enhancing drugs has less risk of Parkinson’s disease than 5α-reductase inhibitors
Authors: Simmering Jacob E. , Welsh Michael J. , Schultz Jordan , Narayanan Nandakumar S. 
Published: April 2022

AbstractBackgroundTerazosin and closely related α1-adrenergic receptor antagonists (doxazosin and alfuzosin; TZ/DZ/AZ) enhance glycolysis and reduce neurodeneration in animal models. Observational evidence in humans from several databases support this finding; however, a recent study has suggested that tamsulosin, the comparator medication, increases risk of Parkinson’s disease. We consider a different comparison group of men taking 5α-reductase inhibitors as a new, independent comparison allowing us to both obtain new estimates of the association between TZ/DZ/AZ and Parkinson’s disease outcomes and validate tamsulosin as an active comparator.MethodsUsing the Truven Health Analytics Marketscan database, we identified men without Parkinson’s disease, newly started on TZ/DZ/AZ, tamsulosin, or 5α-reductase inhibitors. We followed these matched cohorts to compare the hazard of developing Parkinson’s disease.ResultsWe found that men taking TZ/DZ/AZ had a lower hazard of Parkinson’s disease than men taking tamsulosin (HR=0.72, 95% CI: 0.66-0.78, n=239,946) and lower than men taking a 5α-reductase inhibitors (HR=0.81, 95% CI: 0.72-0.92, n=129,320). The hazard for men taking tamsulosin was not statistically significantly different than for men taking 5α-reductase inhibitors (HR=1.10, 95% CI: 1.00-1.22, n=157,490).ConclusionsThese data suggest that men using TZ/DZ/AZ have a lower risk of developing Parkinson’s disease than those using tamsulosin or 5α-reductase inhibitors while users of tamsulosin and 5α-reductase inhibitors have relatively similar survival functions.
A comparative analysis of depression between pregnant and non-pregnant adolescents in a southwestern town in Nigeria
Authors: Mosanya Julianah T. , Adegbite Temilade A. , Adebayo Kazeem O. , Egbewale Bolaji E. , Ijadunola Kayode T. 
Published: April 2022

AbstractBackgroundAdolescence constitutes a risk factor for mental health problems, and this may be further complicated by pregnancy. The rate of adolescent pregnancy is still extremely high in the sub-Saharan Africa including Nigeria. Pregnancy and mental health problems during adolescence constitute double vulnerability for negative outcomes for the adolescents and their offspring.MethodologyThe study was cross-sectional in design and it compared prevalence of depression and associated factors among pregnant and non-pregnant adolescents. It was conducted in Osogbo metropolis, Osun State, Southwest, Nigeria. The study population comprised pregnant adolescents (aged 15-19 years) attending antenatal care (ANC) in selected formal and informal health facilities. Non-pregnant adolescents who were equally attending services at the facilities were recruited as the control group. Information was obtained from the adolescents with the use of a structured questionnaire and data was analysed with IBM-SPSS version 21 software.ResultsThree hundred and thirty-four respondents (167 per group) were involved in the study; the pregnant adolescents had a mean age (±SD) of 17.92 (±1.13) years while the non-pregnant adolescents had a mean age of 17.70 (±1.23) years. The prevalence of depression among the pregnant adolescents was 8.4% while that of the non-pregnant adolescents was 3.0%. The result showed a statistically significant association between pregnancy status and depression among the adolescents (p= 0.033). Living arrangement was the only socio-demographic variable that had significant relationship with depression among the pregnant adolescents while living arrangement and employment status had significant relationships with depression among the non-pregnant adolescents. History of mental illness, childhood sexual abuse and anxiety symptoms showed significant relationship with depression among pregnant adolescents, however, only anxiety symptoms showed significant relationship with depression among non-pregnant adolescents.ConclusionThe study concluded that the prevalence of depression is significantly higher among pregnant adolescents with similarities and differences in the factors associated with depression in the two groups.
Periplasmic oxidized-protein repair during copper stress in E. coli: a focus on the metallochaperone CusF
Authors: Vergnes Alexandra , Henry Camille , Grassini Gaia , Loiseau Laurent , El Hajj Sara , Denis Yann , Galinier Anne , Vertommen Didier , Aussel Laurent , Ezraty Benjamin 
Published: April 2022

ABSTRACTMethionine residues are particularly sensitive to oxidation by reactive oxygen or chlorine species (ROS/RCS), leading to the appearance of methionine sulfoxide in proteins. This post-translational oxidation can be reversed by omnipresent protein repair pathways involving methionine sulfoxide reductases (Msr). In the periplasm of Escherichia coli, the enzymatic system MsrPQ, whose expression is triggered by the RCS, controls the redox status of methionine residues. Here we report that MsrPQ synthesis is also induced by copper stress via the CusSR two-component system, and that MsrPQ plays a role in copper homeostasis by maintaining the activity of the copper efflux pump, CusCFBA. Genetic and biochemical evidence suggest the metallochaperone CusF is the substrate of MsrPQ and our study reveal that CusF methionines are redox sensitive and can be restored by MsrPQ. Thus, the evolution of a CusSR-dependent synthesis of MsrPQ allows keeping copper homeostasis under aerobic conditions by maintenance of the reduced state of Met residues in copper-trafficking proteins.AUTHOR SUMMARYOur study investigates the interconnection between the copper stress response and the methionine redox homeostasis in the Gram-negative bacterium Escherichia coli. We report that the copper-activation of the CusSR two-component system induces the expression of the periplasmic oxidized-protein repair system, MsrPQ. We demonstrate that MsrPQ is crucial for CusCFBA copper efflux pump activity under aerobic conditions as it maintains the periplasmic component CusF in its functional reduced form. Methionine emerges as a critical residue in copper trafficking proteins: however this naturally-selected advantage must be balanced by methionine’s high susceptibility to oxidation. Therefore the induction of MsrPQ by copper allows copper homeostasis under aerobic conditions, illustrating that E. coli has developed an integrated and dynamic circuit for sensing and counteracting stress caused by copper and oxidants, thus allowing bacteria to adapt to host cellular defences.
Fasciola hepatica Fatty Acid Binding Protein 1 modulates T cell polarization by promoting dendritic cell thrombospondin-1 secretion without affecting metabolic homeostasis in obese mice
Authors: Zawistowska-Deniziak Anna , Lambooij Joost M. , Kalinowska Alicja , Patente Thiago A. , Łapiński Maciej , van der Zande Hendrik J.P. , Basałaj Katarzyna , de Korne Clarize , Chayé Mathilde A.M. , Gasan Tom , Norbury Luke J. , Giera Martin , Zaldumbide Arnaud , Smits Hermelijn H. , Guigas Bruno 
Published: April 2022

AbstractBackgroundThe parasitic trematode Fasciola hepatica evades host immune defenses through secretion of various immunomodulatory molecules. Fatty Acid Binding Proteins (fhFABPs) are among the main excreted/secreted proteins and have been shown to display anti-inflammatory properties. However, little is currently known regarding their impact on dendritic cells (DCs) and their subsequent capacity to prime specific CD4+ T cell subsets.Methodology/Principal FindingsThe immunomodulatory effects of both native F. hepatica extracts and recombinant fhFABPs were assessed on monocyte-derived human DCs (moDCs) and the underlying mechanism was next investigated using various approaches, including DC-allogenic T cell co-culture and DC phenotyping through transcriptomic, proteomic and FACS analyses. We mainly showed that fhFABP1 induced a tolerogenic-like phenotype in LPS-stimulated moDCs characterized by a dose-dependent increase in the cell-surface tolerogenic marker CD103 and IL-10 secretion, while DC co-stimulatory markers were not affected. A significant decrease in secretion of the pro-inflammatory cytokines IL-12p70 and IL-6 was also observed. In addition, these effects were associated with an increase in both Th2-on-Th1 ratio and IL-10 secretion by CD4+ T cells following DC-T cell co-culture. RNA sequencing and targeted proteomic analyses identified thrombospondin-1 (TSP-1) as a non-canonical factor highly expressed and secreted by fhFABP1-primed moDCs. The effect of fhFABP1 on T cell skewing was abolished when using a TSP-1 blocking antibody during DC-T cell co-culture. Immunomodulation by helminth molecules has been linked to improved metabolic homeostasis during obesity. Although fhFABP1 injection in high-fat diet-fed obese mice induced a potent Th2 immune response in adipose tissue, it did not improved insulin sensitivity or glucose homeostasis.Conclusions/SignificanceWe show that fhFABP1 modulates T cell polarization, notably by promoting DC TSP-1 secretion in vitro, without affecting metabolic homeostasis in a mouse model of type 2 diabetes.
Physiopathological changes of ferritin mRNA density and distribution in hippocampal astrocytes in the mouse brain
Authors: Tortuyaux Romain , Oudart Marc , Mazaré Noémie , Mailly Philippe , Deschemin Jean-Christophe , Vaulont Sophie , Escartin Carole , Cohen-Salmon Martine 
Published: April 2022

AbstractAstrocytes are thought to play a crucial role in brain iron homeostasis. How they accomplish this regulation in vivo remains unclear. In a recent transcriptomic analysis, we showed that polysomal Ftl1 and Fth1 mRNAs, encoding the ferritin light (Ftl) and heavy (Fth) chains that assemble into ferritin, a critical complex for iron storage and reduction, are enriched in perisynaptic astrocytic processes as compared to astrocytic soma. These data suggested that ferritin translation plays a specific role at the perisynaptic astrocytic interface and is tighly regulated by local translation. Here, we used our recently described AstroDot 3D in situ methodology to study the density and localization of ferritin mRNAs in astrocytes in the hippocampus in three different contexts in which local or systemic iron overload has been documented: ageing, the hepcidin knock-out mouse model of hemochromatosis and the APP/PS1dE9 mouse model of Alzheimer’s disease (AD). Our results showed that in wild type mice, Fth1 mRNA density was higher than Ftl1 and that both mRNAs were mostly distributed in astrocyte fine processes. Ageing and absence of hepcidin caused an increased Fth1/Ftl1 ratio in astrocytes and in the case of ageing, led to a redistribution of Fth1 mRNAs in astrocytic fine processes. In contrast, in AD mice, we observed a lower Fth1/Ftl1 ratio and Fth1 mRNAs became more somatic. Hence, we propose that regulation of ferritin mRNA density and distribution in astrocytes regulates iron homeostasis in physiology and pathophysiology.