bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial Genome Study Identifies Association Between Primary Open-Angle Glaucoma and Variants in MT-CYB, MT-ND4 Genes and Haplogroups
Authors: Lo Faro Valeria , Nolte Ilja M. , Ten Brink Jacoline B. , Snieder Harold , Jansonius Nomdo M. , Bergen Arthur A. , Lifelines Cohort Study  
Published: December 2021

Background and purpose: Primary open-angle glaucoma (POAG) is an optic neuropathy characterized by death of retinal ganglion cells and atrophy of the optic nerve head. The susceptibility of the optic nerve to damage has been shown to be mediated by mitochondrial dysfunction. In this study, we aimed to determine a possible association between mitochondrial SNPs or haplogroups and POAG.Methods: Mitochondrial DNA single nucleotide polymorphisms (mtSNPs) were genotyped using the Illumina Infinium Global Screening Array-24 (GSA) 700K array set. Genetic analyses were performed in a POAG case-control study involving the cohorts, Groningen Longitudinal Glaucoma Study-Lifelines Cohort Study and Amsterdam Glaucoma Study, including 721 patients and 1951 controls in total. We excluded samples not passing quality control for nuclear genotypes and samples with low call rate for mitochondrial variation. The mitochondrial variants were analyzed both as SNPs and haplogroups. These were determined with the bioinformatics software HaploGrep, and logistic regression analysis was used for the association, as well as for SNPs.Results: Meta-analysis of the results from both cohorts revealed a significant association between POAG and the allele A of rs2853496 [odds ratio (OR) = 0.64; p = 0.006] within the MT-ND4 gene, and for the T allele of rs35788393 (OR = 0.75; p = 0.041) located in the MT-CYB gene. In the mitochondrial haplogroup analysis, the most significant p-value was reached by haplogroup K (p = 1.2 × 10−05), which increases the risk of POAG with an OR of 5.8 (95% CI 2.7–13.1).Conclusion: We identified an association between POAG and polymorphisms in the mitochondrial genes MT-ND4 (rs2853496) and MT-CYB (rs35788393), and with haplogroup K. The present study provides further evidence that mitochondrial genome variations are implicated in POAG. Further genetic and functional studies are required to substantiate the association between mitochondrial gene polymorphisms and POAG and to define the pathophysiological mechanisms of mitochondrial dysfunction in glaucoma.
Real-Life Cause-Effect Relations Between Urinary IL-6 Levels and Specific and Nonspecific Symptoms in a Patient With Mild SLE Disease Activity
Authors: Schubert Christian , Seizer Lennart , Chamson Emil , König Paul , Sepp Norbert , Ocaña-Peinado Francisco M. , Schnapka-Köpf Mirjam , Fuchs Dietmar 
Published: December 2021

BackgroundLittle is known about the real-time cause-effect relations between IL-6 concentrations and SLE symptoms.MethodsA 52-year-old woman with mild SLE activity collected her entire urine for the determination of IL-6/creatinine and protein/creatinine levels (ELISA, HPLC) for a period of 56 days in 12 h intervals (total: 112 measurements). Additionally, she answered questionnaires (VAS) on oral ulceration, facial rash, joint pain, fatigue and tiredness and measured her temperature orally twice a day. Time-series analyses consisted of ARIMA modeling and cross-correlational analyses (one lag = 12 h, significance level = p &lt; 0.05).ResultsStatistical analyses showed that increased urinary IL-6 concentrations preceded increased urinary protein levels by 36–48 h (lag3: r=+.225; p=.017) and that, in the opposite direction of effect, increased urinary protein preceded urinary IL-6 decreases by 12–24 h (lag1: r=–.322; p&lt;.001). Moreover, urinary IL-6 increases co-occurred with increased oral ulceration (lag0: r=+.186; p=.049); after 48–60 h, however, IL-6 increases showed a strong tendency to precede oral ulceration decreases (lag4: r=–.170; p=.072). Increases in facial rash preceded decreases in urinary IL-6 after 84–96 h (lag7: r=–.215; p=.023). As to fatigue, increases in urinary IL-6 co-occurred with decreased fatigue (lag0: r=–.193; p=.042); after 84–96 h, however, IL-6 increases preceded fatigue increases (+lag7: r=+.189; p=.046). Finally, joint pain, tiredness and body temperature did not significantly correlate with urinary IL-6 concentrations in either direction of effect.ConclusionsThe results of this evaluation point to real-life feedback mechanisms between immune activity and SLE symptoms. Comparison with a previous evaluation of this patient suggests a counterregulatory mechanism between Th1 activity and IL-6. These findings are preliminary and require replication to draw firm conclusions about the real-time relation between IL-6 and SLE disease activity.
Anti-SARS-CoV-2 Immunoglobulin Isotypes, and Neutralization Activity Against Viral Variants, According to BNT162b2-Vaccination and Infection History
Authors: Tarkowski Maciej , de Jager Wilco , Schiuma Marco , Covizzi Alice , Lai Alessia , Gabrieli Arianna , Corbellino Mario , Bergna Annalisa , Ventura Carla Della , Galli Massimo , Riva Agostino , Antinori Spinello 
Published: December 2021

PurposeTo compare SARS-CoV-2 antigen-specific antibody production and plasma neutralizing capacity against B.1 wild-type-like strain, and Gamma/P.1 and Delta/B.1.617.2 variants-of-concern, in subjects with different Covid-19 disease and vaccination histories.MethodsAdult subjects were: 1) Unvaccinated/hospitalized for Covid-19; 2) Covid-19-recovered followed by one BNT162b2 vaccine dose; and 3) Covid-19-naïve/2-dose BNT162b2 vaccinated. Multiplex Luminex® immunoassays measured IgG, IgA, and IgM plasma levels against SARS-CoV-2 receptor-binding domain (RBD), spike-1 (S), and nucleocapsid proteins. Neutralizing activity was determined in Vero E6 cytopathic assays.ResultsMaximum anti-RBD IgG levels were similar in Covid-19‑recovered individuals 8‒10 days after single-dose vaccination and in Covid-19-naïve subjects 7 days after 2nd vaccine dosing; both groups had ≈2‑fold higher anti-RBD IgG levels than Unvaccinated/Covid-19 subjects tracked through 2 weeks post-symptom onset. Anti-S IgG expression patterns were similar to RBD within each group, but with lower signal strengths. Viral antigen-specific IgA and IgM levels were more variable than IgG patterns. Anti-nucleocapsid immunoglobulins were not detected in Covid-19-naïve subjects. Neutralizing activity against the B.1 strain, and Gamma/P.1 and Delta/B.1.617.2 variants, was highest in Covid‑19-recovered/single-dose vaccinated subjects; although neutralization against the Delta variant in this group was only 26% compared to B.1 neutralization, absolute anti-Delta titers suggested maintained protection. Neutralizing titers against the Gamma and Delta variants were 33‒77% and 26‒67%, respectively, versus neutralization against the B.1 strain (100%) in the three groups.ConclusionThese findings support SARS-CoV-2 mRNA vaccine usefulness regardless of Covid-19 history, and confirm remarkable protection provided by a single vaccine dose in people who have recovered from Covid-19.
Mobile Responsive App—A Useful Additional Tool for Data Collection in the German Pregnancy Register Rhekiss?
Authors: Richter Jutta G. , Weiß Anja , Bungartz Christina , Fischer-Betz Rebecca , Zink Angela , Schneider Matthias , Strangfeld Anja 
Published: December 2021

Background: The German pregnancy register Rhekiss is designed as a nationwide, web-based longitudinal observational cohort established in 2015. The register follows women with inflammatory rheumatic disease prospectively from child wish or early pregnancy until 2 years post-partum. Information on clinical and laboratory parameters, drug treatment, and (adverse) pregnancy outcomes are documented in pre-specified intervals. Physicians and patients report data for the same time periods via separated accounts and forms into a web-based application (app). As data entry on mobile devices might improve response rates of patients, a responsive app as a further convenient documentation option was developed.Methods: The Rhekiss-app is available for self-reported data retrieval since August 2017 from the App stores. For the current analysis, Rhekiss register data were used from the start of the register until 30 September 2020. The analyses were performed for forms containing information on devices. Outcome parameters were compared for mobile and desktop users for the quantity and quality of filled forms.Results: In total, 5,048 forms were received and submitted by 966 patients. About 57% of forms were sent from mobile devices with the highest numbers in patients with child wishes (63%). Users of mobile devices were slightly younger and often had less high-education level (62 vs. 79%) compared with desktop users. The proportion of forms submitted via mobile devices increased steadily from 48% in the fourth quarter of 2018 to 64% in the third quarter of 2020. The proportion of forms received before and after the Rhekiss-app implementation increased with the highest increase of 12% for forms filled at time point 12 months post-partum. Mobile users submitted significantly more forms than desktop users (2.9 vs. 2.1), data sent via desktops were more often complete (88 vs. 86%).Conclusion: The responsive app is a valuable additional tool for data collection and is well-accepted by patients as indicated by its increasing use in Rhekiss. Apart from desktop/browser developments, the technological adoptions within observational cohorts and registries should take smartphone requirements and developments into account, especially when patient-reported data in young, mobile patients are collected, bearing in mind that data quality could be compromised and concepts for improving data quality should be implemented.
Proteomics-Based Approach to Identify Novel Blood Biomarker Candidates for Differentiating Intracerebral Hemorrhage From Ischemic Stroke—A Pilot Study
Authors: Malicek David , Wittig Ilka , Luger Sebastian , Foerch Christian 
Published: December 2021

Background: A reliable distinction between ischemic stroke (IS) and intracerebral hemorrhage (ICH) is required for diagnosis-specific treatment and effective secondary prevention in patients with stroke. However, in resource-limited settings brain imaging, which is the current diagnostic gold standard for this purpose, is not always available in time. Hence, an easily accessible and broadly applicable blood biomarker-based diagnostic test differing stroke subtypes would be desirable. Using an explorative proteomics approach, this pilot study aimed to identify novel blood biomarker candidates for distinguishing IS from ICH.Material and Methods: Plasma samples from patients with IS and ICH were drawn during hospitalization and were analyzed by using liquid chromatography/mass spectrometry. Proteins were identified using the human reference proteome database UniProtKB, and label-free quantification (LFQ) data were further analyzed using bioinformatic tools.Results: Plasma specimens of three patients with IS and four patients with ICH with a median National Institute of Health Stroke Scale (NIHSS) of 12 [interquartile range (IQR) 10.5–18.5] as well as serum samples from two healthy volunteers were analyzed. Among 495 identified protein groups, a total of 368 protein groups exhibited enough data points to be entered into quantitative analysis. Of the remaining 22 top-listed proteins, a significant difference between IS and ICH was found for Carboxypeptidase N subunit 2 (CPN2), Coagulation factor XII (FXII), Plasminogen, Mannan-binding lectin serine protease 1, Serum amyloid P-component, Paraoxonase 1, Carbonic anhydrase 1, Fibulin-1, and Granulins.Discussion: In this exploratory proteomics-based pilot study, nine candidate biomarkers for differentiation of IS and ICH were identified. The proteins belong to the immune system, the coagulation cascade, and the apoptosis system, respectively. Further investigations in larger cohorts of patients with stroke using additional biochemical analysis methods, such as ELISA or Western Blotting are now necessary to validate these markers, and to characterize diagnostic accuracy with regard to the development of a point-of-care-system for use in resource-limited areas.
A Comparative Study of Radiomics and Deep-Learning Based Methods for Pulmonary Nodule Malignancy Prediction in Low Dose CT Images
Authors: Astaraki Mehdi , Yang Guang , Zakko Yousuf , Toma-Dasu Iuliana , Smedby Örjan , Wang Chunliang 
Published: December 2021

ObjectivesBoth radiomics and deep learning methods have shown great promise in predicting lesion malignancy in various image-based oncology studies. However, it is still unclear which method to choose for a specific clinical problem given the access to the same amount of training data. In this study, we try to compare the performance of a series of carefully selected conventional radiomics methods, end-to-end deep learning models, and deep-feature based radiomics pipelines for pulmonary nodule malignancy prediction on an open database that consists of 1297 manually delineated lung nodules.MethodsConventional radiomics analysis was conducted by extracting standard handcrafted features from target nodule images. Several end-to-end deep classifier networks, including VGG, ResNet, DenseNet, and EfficientNet were employed to identify lung nodule malignancy as well. In addition to the baseline implementations, we also investigated the importance of feature selection and class balancing, as well as separating the features learned in the nodule target region and the background/context region. By pooling the radiomics and deep features together in a hybrid feature set, we investigated the compatibility of these two sets with respect to malignancy prediction.ResultsThe best baseline conventional radiomics model, deep learning model, and deep-feature based radiomics model achieved AUROC values (mean ± standard deviations) of 0.792 ± 0.025, 0.801 ± 0.018, and 0.817 ± 0.032, respectively through 5-fold cross-validation analyses. However, after trying out several optimization techniques, such as feature selection and data balancing, as well as adding context features, the corresponding best radiomics, end-to-end deep learning, and deep-feature based models achieved AUROC values of 0.921 ± 0.010, 0.824 ± 0.021, and 0.936 ± 0.011, respectively. We achieved the best prediction accuracy from the hybrid feature set (AUROC: 0.938 ± 0.010).ConclusionThe end-to-end deep-learning model outperforms conventional radiomics out of the box without much fine-tuning. On the other hand, fine-tuning the models lead to significant improvements in the prediction performance where the conventional and deep-feature based radiomics models achieved comparable results. The hybrid radiomics method seems to be the most promising model for lung nodule malignancy prediction in this comparative study.
Factors Influencing Implementation of Blood Transfusion Recommendations in Pediatric Critical Care Units
Authors: Steffen Katherine M. , Spinella Philip C. , Holdsworth Laura M. , Ford Mackenzie A. , Lee Grace M. , Asch Steven M. , Proctor Enola K. , Doctor Allan 
Published: December 2021

Purpose:Risks of red blood cell transfusion may outweigh benefits for many patients in Pediatric Intensive Care Units (PICUs). The Transfusion and Anemia eXpertise Initiative (TAXI) recommendations seek to limit unnecessary and potentially harmful transfusions, but use has been variable. We sought to identify barriers and facilitators to using the TAXI recommendations to inform implementation efforts.Materials and Methods:The integrated Promoting Action on Research Implementation in Health Services (iPARIHS) framework guided semi-structured interviews conducted in 8 U.S. ICUs; 50 providers in multiple ICU roles completed interviews. Adapted Framework analysis, a form of content analysis, used the iPARIHS innovation, recipient, context and facilitation constructs and subconstructs to categorize data and identify patterns as well as unique informative statements.Results:Providers perceived that the TAXI recommendations would reduce transfusion rates and practice variability, but adoption faced challenges posed by attitudes around transfusion and care in busy and complex units. Development of widespread buy-in and inclusion in implementation, integration into workflow, designating committed champions, and monitoring outcomes data were expected to enhance implementation.Conclusions:Targeted activities to create buy-in, educate, and plan for use are necessary for TAXI implementation. Recognition of contextual challenges posed by the PICU environment and an approach that adjusts for barriers may optimize adoption.
Elevating Subjective Well-Being Through Physical Exercises: An Intervention Study
Authors: Iwon Katarzyna , Skibinska Julia , Jasielska Dorota , Kalwarczyk Sonia 
Published: December 2021

Background: Physical activity is associated with higher levels of subjective well-being. However, little research has been conducted in naturalistic conditions with a longitudinal design. In the current study, we aimed to examine whether regular activity initiation can impact happiness, life satisfaction, and self-esteem 4 weeks later.Methods: The sample (N = 217, 124 women) was divided into three groups based on level of physical activity (active people, beginners, and inactive people). The participants completed measures of happiness, satisfaction with life, self-esteem, and a survey on physical activity. Ninety-five of participants who completed the same set of measures sent by email after 4 weeks were included in the analyses.Results: The study showed a strong relationship between subjective well-being and physical activity. Active people showed higher levels of happiness and self-esteem compared to beginners and inactive people and a higher level of life satisfaction than inactive people. Furthermore, after 4 weeks of exercising, beginners revealed greater life satisfaction and happiness compared to the baseline.Conclusion: These findings confirm that regular physical activity leads to higher levels of well-being. It seems that even a short engagement in physical activity (4 weeks) may contribute to an increase in subjective well-being.
Pre- and Post-treatment Levels of Plasma Metabolites in Patients With Bipolar Depression
Authors: Guo Xiang-Jie , Wu Peng , Cui Xiao-Hong , Jia Jiao , Bao Shuang , Yu Fei , Ma Li-Na , Cao Xiang-Xin , Ren Yan 
Published: December 2021

Background: Bipolar disorder (BD) is a serious mental disease with complex clinical manifestations and high recurrence rate. The purpose of this study was to detect metabolites related to the diagnosis and efficacy evaluation of bipolar depression in plasma samples by metabolomics.Methods: Thirty-one bipolar depression patients were recruited and completed 8 weeks medication and a matched group of 47 healthy controls (HCs) was recruited. Nuclear magnetic resonance spectroscopy was used to profile plasma samples of bipolar depression patients at baseline and after 8 weeks medication, and HCs. Then Multivariate statistical analysis was performed to analyze differences of plasma metabolites among the three groups.Results: We detected seven specific differential metabolites in bipolar depression. Six of the metabolites were returned to the normal levels in different degrees after 8 weeks medication, only Glycine continuously decreased in the acute and significant improvement stages of bipolar depression (VIP &gt; 1 and p &lt; 0.05). These differential metabolites involved several metabolic pathways.Limitations: The small sample size was one of the most prominent limitations. Each BD patient was given an individualized medication regimen according to the clinical guidelines.Conclusion: There were metabolites changes before and after 8 weeks medication. Glycine may be a characteristic marker of bipolar depression and does not change with the improvement of bipolar depression, while other 6 differential metabolites may be biomarkers associated with the pathological development or the improvement of bipolar depression. And, these differential metabolites mainly related to energy metabolism, amino acid metabolism and gut microbiota metabolism.
Safety, Immunogenicity and Antibody Persistence of Rift Valley Fever Virus Clone 13 Vaccine in Sheep, Goats and Cattle in Tanzania
Authors: Sindato Calvin , Karimuribo Esron D. , Swai Emmanuel S. , Mboera Leonard E. G. , Rweyemamu Mark M. , Paweska Janusz T. , Salt Jeremy 
Published: December 2021

Background:Vaccination is considered to be the best approach to control Rift Valley fever (RVF) in animals and consequently in humans. This study assessed the efficacy and safety of the RVF virus (RVFV) Clone 13 vaccine under field conditions.Methodology:A vaccine trial was conducted in sheep (230), goats (230), and cattle (140) in Ngorongoro district, Tanzania. Half of each of the animal species were vaccinated and the other half received the placebo. Animals were clinically monitored and bled before vaccination and at days 15, 30, 60, 180 and 360 (+/– 10) post-vaccination to measure Immunoglobulin M (IgM) and IgG antibody responses to RVFV. Survival analysis was conducted using cox-proportional hazard regression model to measure the time until an event of interest had occurred and to compare the cumulative proportion of events over time.Results:Of 600 animals included in the study, 120 animals were lost during the study, leaving a total of 480 (243 in the vaccinated group and 237 in the control group) for complete follow-up sampling. There was no adverse reaction reported at the injection site of the vaccine/placebo in all animals. Abortions, deaths, or body temperature variations were not associated with vaccination (p &gt; 0.05). By day 15 post-inoculation, the IgG seroconversion in vaccinated goats, cattle and sheep was 27.0% (n= 115), 20.0% (n= 70) and 10.4% (n= 115), respectively. By day 30 post-inoculation, it was 75.0% (n= 113), 74.1% (n= 112) and 57.1% (n= 70) in vaccinated sheep, goats and cattle, respectively. By day 60 post-inoculation, IgG seroconversion in sheep, goats and cattle was 88.1% (n= 109), 84.3% (n= 108) and 64.60% (n= 65), respectively. By day 180, the IgG seroconversion in sheep, goats and cattle was 88.0% (n= 108), 83.8% (n= 105) and 66.1% (n= 62), respectively. By day 360, the IgG seroconversion in sheep, goats and cattle was 87.2% (n= 94), 85.6% (n= 90) and 66.1% (n= 59), respectively. Only five animals from the vaccinated group were RVFV IgM positive, which included four sheep and a goat.Conclusion:RVFV Clone 13 vaccine was well tolerated by sheep, goats, and cattle. The vaccine induced detectable, but variable levels of IgG responses, and of different duration. The vaccine is considered safe, with high immunogenicity in sheep and goats and moderate in cattle.
On Some Generalized Simpson’s and Newton’s Inequalities for (α, m)-Convex Functions in q-Calculus
Authors: Sial Ifra Bashir , Mei Sun , Ali Muhammad Aamir , Nonlaopon Kamsing 
Published: December 2021

In this paper, we first establish two right-quantum integral equalities involving a right-quantum derivative and a parameter m∈ 0,1. Then, we prove modified versions of Simpson’s and Newton’s type inequalities using established equalities for right-quantum differentiable α,m-convex functions. The newly developed inequalities are also proven to be expansions of comparable inequalities found in the literature.