bluuebunny/crossref_metadata_2025_split huggingface dataset:
DESTINATION: a phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the long-term safety and tolerability of tezepelumab in adults and adolescents with severe, uncontrolled asthma
Authors: Menzies-Gow Andrew , Ponnarambil Sandhia , Downie John , Bowen Karin , Hellqvist Åsa , Colice Gene 
Published: October 2020

Abstract
Background
Tezepelumab is a human monoclonal antibody that blocks the activity of the epithelial cytokine thymic stromal lymphopoietin. The efficacy, safety and oral corticosteroid-sparing potential of tezepelumab are being investigated in two ongoing, phase 3, randomized, double-blind, placebo-controlled studies (NAVIGATOR [NCT03347279] and SOURCE [NCT03406078]). DESTINATION (NCT03706079) is a long-term extension (LTE) of these studies.

Methods
DESTINATION is a randomized, double-blind, placebo-controlled LTE study in adults (18–80 years old) and adolescents (12–17 years old) with severe, uncontrolled asthma who are receiving treatment with medium- or high-dose inhaled corticosteroids plus at least one additional controller medication with or without oral corticosteroids. The study population will comprise patients who complete the 52- and 48-week NAVIGATOR and SOURCE studies, respectively. Patients who were randomized to receive tezepelumab 210 mg every 4 weeks (Q4W) in either predecessor study will continue to receive this regimen for 1 year; those who were previously randomized to receive placebo will be re-randomized (1:1) to receive either tezepelumab 210 mg Q4W or placebo for 1 year. Patients will receive their prescribed controller medications throughout DESTINATION and study physicians will have the opportunity to down- or up-titrate dosage of these medications, if appropriate. The primary objective is to evaluate the long-term safety and tolerability of tezepelumab over 104 weeks (inclusive of the treatment period of either predecessor study). The secondary objective is to assess the long-term effect of tezepelumab on asthma exacerbations. Patients recruited from SOURCE will be followed up post-treatment for 12 weeks. Patients recruited from NAVIGATOR who complete 100 weeks of tezepelumab treatment will be eligible for either 12 weeks of follow-up or a 36-week extended follow-up during which the clinical benefit of tezepelumab after treatment cessation will be investigated.

Discussion
DESTINATION will evaluate the long-term safety, tolerability and efficacy of tezepelumab versus placebo with continued dosing for up to 2 years. DESTINATION will also evaluate the clinical effect of tezepelumab after treatment cessation. This LTE study aims to elucidate the long-term safety implications of receiving tezepelumab and to assess its potential long-term treatment benefits in patients with severe, uncontrolled asthma.

Trial registration
NCT03706079 (ClinicalTrials.gov). Registered 15 October 2018.
Persisting alterations of iron homeostasis in COVID-19 are associated with non-resolving lung pathologies and poor patients’ performance: a prospective observational cohort study
Authors: Sonnweber Thomas , Boehm Anna , Sahanic Sabina , Pizzini Alex , Aichner Magdalena , Sonnweber Bettina , Kurz Katharina , Koppelstätter Sabine , Haschka David , Petzer Verena , Hilbe Richard , Theurl Markus , Lehner Daniela , Nairz Manfred , Puchner Bernhard , Luger Anna , Schwabl Christoph , Bellmann-Weiler Rosa , Wöll Ewald , Widmann Gerlig , Tancevski Ivan , Judith-Löffler-Ragg  , Weiss Günter 
Published: October 2020

Abstract
Background
Severe coronavirus disease 2019 (COVID-19) is frequently associated with hyperinflammation and hyperferritinemia. The latter is related to increased mortality in COVID-19. Still, it is not clear if iron dysmetabolism is mechanistically linked to COVID-19 pathobiology.

Methods
We herein present data from the ongoing prospective, multicentre, observational CovILD cohort study (ClinicalTrials.gov number, NCT04416100), which systematically follows up patients after COVID-19. 109 participants were evaluated 60 days after onset of first COVID-19 symptoms including clinical examination, chest computed tomography and laboratory testing.

Results
We investigated subjects with mild to critical COVID-19, of which the majority received hospital treatment. 60 days after disease onset, 30% of subjects still presented with iron deficiency and 9% had anemia, mostly categorized as anemia of inflammation. Anemic patients had increased levels of inflammation markers such as interleukin-6 and C-reactive protein and survived a more severe course of COVID-19. Hyperferritinemia was still present in 38% of all individuals and was more frequent in subjects with preceding severe or critical COVID-19. Analysis of the mRNA expression of peripheral blood mononuclear cells demonstrated a correlation of increased ferritin and cytokine mRNA expression in these patients. Finally, persisting hyperferritinemia was significantly associated with severe lung pathologies in computed tomography scans and a decreased performance status as compared to patients without hyperferritinemia.

Discussion
Alterations of iron homeostasis can persist for at least two months after the onset of COVID-19 and are closely associated with non-resolving lung pathologies and impaired physical performance. Determination of serum iron parameters may thus be a easy to access measure to monitor the resolution of COVID-19.

Trial registration
ClinicalTrials.gov number: NCT04416100.
Distinct genomic subclasses of high-grade/progressive meningiomas: NF2-associated, NF2-exclusive, and NF2-agnostic
Authors: Williams Erik A. , Santagata Sandro , Wakimoto Hiroaki , Shankar Ganesh M. , Barker Fred G. , Sharaf Radwa , Reddy Abhinav , Spear Phoebe , Alexander Brian M. , Ross Jeffrey S. , Brastianos Priscilla K. , Cahill Daniel P. , Ramkissoon Shakti H. , Juratli Tareq A. 
Published: October 2020

Abstract
Background
Genomic studies of high-grade/progressive meningiomas have reported a heterogeneous mutation spectrum, identifying few recurrently mutated genes. Most studies have been underpowered to detect genomic subclasses of aggressive meningiomas due to relatively small number of available samples. Here, we present a genomic survey of one of the largest multi-institutional cohorts of high-grade/progressive meningiomas to date.

Methods
850 high-grade/progressive meningiomas, including 441 WHO grade 2 and 176 WHO grade 3 meningiomas and 220 progressive WHO grade 1 meningiomas, were tested as part of a clinical testing program by hybridization capture of 406 cancer-related genes to detect base substitutions, indels, amplifications, deletions, and rearrangements. Information from pathology reports, histopathology review, and patient clinical data was assessed.

Results
Genomic analyses converged to identify at least three distinct patterns of biologically-aggressive meningiomas. The first and most common contained NF2-mutant tumors (n = 426, 50%), was associated with male sex (64.4% %, p = 0.0001) and often harbored additional mutations in CDKN2A/B (24%), and the chromatin regulators ARID1A (9%), and KDM6A (6%). A second group (NF2-agnostic) featured TERT promoter (TERTp; n = 56) or TP53 mutations (n = 25) and were either NF2-mutant or wild-type, and displayed no association with either sex (p = 0.39). The remaining group generally lacked NF2 mutations, and accounted for 40% of the cases—with three subgroups. One consistent primarily of grade 3 lesions harboring alterations in chromatin regulators BAP1 (n = 22) or PBRM1 (n = 16). A second subgroup contained AKT1 (n = 26), PIK3CA (n = 14) and SMO (n = 7) mutant skull-based meningiomas, and a third mixed subgroup included 237 meningiomas with a heterogeneous spectrum of low frequency and non-recurrent alterations.

Conclusions
Our findings indicate that the patterns of genomic alterations in high-grade/progressive meningiomas commonly group into three different categories. The most common NF2-associated canonical group frequently harbored CDKN2A/B alterations, which is potentially amenable to targeted therapies. An NF2-agnostic group harbored frequent TERTp and TP53 mutations. The final subclass, distinct from the canonical NF2 mutant associated pathway, was partly characterized by BAP1/PBRM1 alterations (rhabdoid/papillary histology) or skull-base disease. Overall, these data increase our understanding of the pathobiology of high-grade/progressive meningiomas and can guide the design of clinical trials.

IRB approval status
Reviewed and approved by Western IRB; Protocol No. 20152817.
Altered interoception in patients with borderline personality disorder: a study using heartbeat-evoked potentials
Authors: Flasbeck Vera , Popkirov Stoyan , Ebert Andreas , Brüne Martin 
Published: October 2020

Abstract
Background
Patients with borderline personality disorder (BPD) experience difficulties in emotional awareness (alexithymia), and often develop dissociative symptoms, which may reflect broader deficits in interoceptive awareness. Whether this is associated with alterations in cortical processing of interoception is currently unknown.

Methods
We utilized an electrophysiological marker of interoception, i.e. heartbeat-evoked potentials (HEP), and examined its relationship with electrocardiographic correlates of autonomic nervous system (ANS) functioning (heart rate variability), and with self-report measures of alexithymia, dissociation and borderline symptom severity in patients with BPD.

Results
Individuals with BPD had higher HEP amplitudes over frontal electrodes compared to healthy controls. Sympathetic ANS activity was greater in BPD patients than in controls. Across groups, HEP amplitudes were associated with parasympathetic activity over central electrodes and correlated with alexithymia over frontal electrodes.

Conclusions
These findings support the idea that difficulties in emotional awareness in BPD are reflected in altered frontal electrophysiological markers of interception. Therefore, emotional awareness can be understood as failures of modulation between interoceptive and exteroceptive attention. Future research may aim to investigate whether altered interoception and its electrophysiological correlates are malleable by therapeutic intervention.
Characterization of polyvinyl alcohol-borax/agarose (PVA-B/AG) double network hydrogel utilized for the cleaning of works of art
Authors: Al-Emam Ehab , Soenen Hilde , Caen Joost , Janssens Koen 
Published: October 2020

Abstract
Since cleaning of artworks may cause undesirable physicochemical alterations and is a nonreversible procedure, it is mandatory to adopt the proper cleaning procedure. Such a procedure should remove undesired materials whilst preserving the original surface. In this regard, numerous gels have been developed and exploited for the cleaning of various artwork surfaces. Lately, agarose (AG) and polyvinyl alcohol-borax (PVA-B) hydrogels have been widely employed as cleaning tools by conservators. Both hydrogels show some limitations in specific cleaning practices. In this work, we investigated the influence of including increased levels of agarose into PVA-B systems. For this reason, we performed a detailed characterization on the double network (DN) hydrogel including the chemical structure, the liquid phase retention, the rheological behavior, and the self-healing behavior of various PVA-B/AG double network hydrogels. These new hydrogels revealed better properties than PVA-B hydrogels and obviated their limitations. The inclusion of AG into PVA-B systems enhanced the liquid retention capacity, shape-stability, and mechanical strength of the blend. Furthermore, AG minimized the expelling/syneresis issue that occurs when loading PVA-B systems with low polarity solvents or chelating agents. The resultant double network hydrogel exhibits relevant self-healing properties. The PVA-B/AG double network is a new and useful cleaning tool that can be added to the conservators’ tool-kit. It is ideal for cleaning procedures dealing with porous and complex structured surfaces, vertical surfaces and for long time applications.
Association of meal timing with dietary quality in a Serbian population sample
Authors: Djuric Zora , Nikolic Marina , Zekovic Milica , Plegue Melissa , Glibetic Marija 
Published: October 2020

AbstractBackgroundThe world-wide adoption of Western lifestyles and eating patterns is associated with adverse effects on nutrient intakes. Here we evaluated the relationships between timing of meals and diet quality in Serbia, a Balkan country with a traditional eating pattern that includes the largest meal of the day as a late lunch.MethodsA dietary survey was done in the Republic of Serbia using a nationally-representative sample of 74 children and 260 non-pregnant adults. Nutrient intakes were calculated from two 24-h recalls. A Dietary Quality Score (DQS) enumerated how many European Union (EU) Science Hub recommendations were met for fruit and vegetables, fiber, saturated fat, sodium, and sugar. We evaluated whether the timing of dietary intakes is associated with DQS and body mass index.ResultsThe dietary intakes of children ages 10–17 and adults were similar and were high in total fat intake, with an average of 40% of energy from fat. Mean fruit and vegetable intakes of 473 g/day in adults exceeded the minimal EU recommendation. The most worrisome aspects of the Serbian diet were high intakes of saturated fat, sugar and sodium. Lunch was the meal with the highest mean content of energy, followed by breakfast and dinner, and the average time for lunch was 15:15. Consumption of a higher percentage of calories before 16:00 in adults was associated with higher fruit and vegetable intakes and with higher DQS. The subgroup of adults consuming their largest meal after 20:00 had a lower mean age, more men, and a larger percentage was employed outside of the home. There were no associations of meal timing with BMI, but the prevalence of obesity in this population sample was only 13%.ConclusionsThese results indicate that an earlier meal pattern, and especially consuming the largest meal of the day earlier in the day, was associated with better quality diets. Public health efforts are needed to preserve nutrient intakes as the population shifts away from the traditional Serbian eating pattern. Long-term, deterioration of nutrient intakes could contribute to the increasing rates of obesity that have been observed in Serbia and world-wide.
Long-term follow-up of therapeutic efficacy of everolimus-eluting bioresorbable vascular scaffold in comparison to everolimus-eluting stent in treatment of chronic total occlusion guided by intracoronary imaging
Authors: Eltahlawi Mohammad Abdallah , Abdel-Aziz Abdel-Aziz Fouad , Sherif Abdel-Salam , Shokry Khalid Abdel-Azeem , Shehata Islam Elsayed 
Published: October 2020

Abstract
Background
We hypothesized that 1st generation everolimus-eluting bioresorbable vascular scaffold (BVS) stent associated with less complication and less restenosis rate than everolimus-eluting stent (EES) in chronic total occlusion (CTO) recanalization guided by intracoronary imaging. Therefore, we aimed to assess the safety and performance of BVS stent in CTO revascularization in comparison to EES guided by intracoronary imaging.
Our prospective comparative cross-sectional study was conducted on 60 CTO patients divided into two groups according to type of stent revascularization: group I (EES group): 40 (66.7%) patients and group II (BVS group): 20 (33.3%) patients. All patients were subjected to history taking, electrocardiogram (ECG), echocardiography, laboratory investigation, stress thallium study to assess viability before revascularization. Revascularization of viable CTO lesion guided by intracoronary imaging using optical coherence tomography (OCT). Then, long-term follow-up over 1 year clinically and by multi-slice CT coronary angiography (MSCT). Our clinical and angiographic endpoints were to detect any clinical or angiographic complications during the follow-up period.

Results
At 6 months angiographic follow-up, BVS group had not inferior angiographic parameters but without statistically significant difference (p = 0.566). At 12 months follow-up, there was no difference at end points between the two groups (p = 0.476).
No differences were found at angiographic or clinical follow-up between BVS and EES.

Conclusion
This study shows that 1st generation everolimus-eluting BVS is non-inferior to EES for CTO revascularization. Further studies are needed to clearly state which new smaller footprint BVS, faster reabsorption, magnesium-based less thrombogenicity, and advanced mechanical properties is under development. We cannot dismiss the efficacy and safety of new BVS technology.

Trial registration
ZU-IRB#2498/3-12-2016 Registered 3 December 2016, email: IRB_123@medicine.zu.edu.eg
Mental health and well-being during the COVID-19 pandemic: longitudinal analyses of adults in the UK COVID-19 Mental Health & Wellbeing study
Authors: O'Connor Rory C. , Wetherall Karen , Cleare Seonaid , McClelland Heather , Melson Ambrose J. , Niedzwiedz Claire L. , O'Carroll Ronan E. , O'Connor Daryl B. , Platt Steve , Scowcroft Elizabeth , Watson Billy , Zortea Tiago , Ferguson Eamonn , Robb Kathryn A. 
Published: October 2020

BackgroundThe effects of coronavirus disease 2019 (COVID-19) on the population's mental health and well-being are likely to be profound and long lasting.AimsTo investigate the trajectory of mental health and well-being during the first 6 weeks of lockdown in adults in the UK.MethodA quota survey design and a sampling frame that permitted recruitment of a national sample was employed. Findings for waves 1 (31 March to 9 April 2020), 2 (10 April to 27 April 2020) and 3 (28 April to 11 May 2020) are reported here. A range of mental health factors was assessed: pre-existing mental health problems, suicide attempts and self-harm, suicidal ideation, depression, anxiety, defeat, entrapment, mental well-being and loneliness.ResultsA total of 3077 adults in the UK completed the survey at wave 1. Suicidal ideation increased over time. Symptoms of anxiety, and levels of defeat and entrapment decreased across waves whereas levels of depressive symptoms did not change significantly. Positive well-being also increased. Levels of loneliness did not change significantly over waves. Subgroup analyses showed that women, young people (18–29 years), those from more socially disadvantaged backgrounds and those with pre-existing mental health problems have worse mental health outcomes during the pandemic across most factors.ConclusionsThe mental health and well-being of the UK adult population appears to have been affected in the initial phase of the COVID-19 pandemic. The increasing rates of suicidal thoughts across waves, especially among young adults, are concerning.
Longitudinal assessment of cardiac function in infants with Down’s syndrome using novel echocardiography techniques – project protocol
Authors: Smith Aisling , Molloy Eleanor , Miletin Jan , Curley Anna , Balfe Joanne , Franklin Orla , EL-Khuffash Afif 
Published: October 2020

Background: Down’s syndrome (DS) is the most common chromosomal abnormality globally. Ireland has one of the highest rates of DS in the western world with an incidence of 1:444 live births. Congenital heart disease (CHD) and pulmonary hypertension (PH) are the commonest morbidities affecting the cardiovascular system in DS. PH is associated with significant morbidity and an increase risk of mortality. The impact of the diagnosis of DS, the presence of CHD and the associated PH on myocardial function during transition and over the first 2 years of age in this population is not well defined and warrants further study. In particular, serial measurements of pulmonary pressures in this population over the first week of age are lacking. This study aims to characterise myocardial function and pulmonary haemodynamics in infants with Down syndrome during the transitional period (over the first week of age) and throughout the first two years of age. Methods: A prospective, observational study utilising novel echocardiography techniques to assess myocardial function and pulmonary haemodynamics over the first two years of age in infants with Down Syndrome. A population of healthy infants without CHD or a diagnosis of DS will be recruited as controls. This study will be conducted across the three Dublin maternity units. Discussion: In total, 70 babies with DS have been enrolled into this study with 292 echocardiograms performed to date. Further evaluation of cardiac performance in DS infants with and without CHD may yield more insight into the pathophysiology of cardiac dysfunction and pulmonary hypertension that are recognised features in these patients. This could aid in our ability to monitor and treat patients, as well as improve our ability to predict outcomes.
Machine-Building Industry of Tyumen Region Economy: Analysis of the Current State and Development Trends
Authors: Lysenko I. 
Published: October 2020

The machine-building industry of the Tyumen region is one of the key areas of specialization in the entire regional production complex. The Tyumen industry is in urgent need of products from the local machine-building complex in the conditions of sectoral restrictions and macroeconomic instability, which cause the unavailability of imported machinery and equipment. The state and strategic development of mechanical engineering in the region will also determine the development trends of the industrial sector. In turn, the pace and scale of development of regional production have an impact on the direction and priorities of development of Tyumen engineering.
The article reviews the dynamics of statistical indicators that characterize the current state of the machine-building industry in the Tyumen region. Trends in innovation and investment activity of machine-building enterprises are revealed. The foreign economic activity of the sector is studied. The place of the industry in the structure of the regional economy is analyzed.