bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of gene expression and mutation data points on contribution of transcription to the mutagenesis by APOBEC enzymes
Authors: Chervova Almira , Fatykhov Bulat , Koblov Alexander , Shvarov Evgeny , Preobrazhenskaya Julia , Vinogradov Dmitry , Ponomarev Gennady V , Gelfand Mikhail S , Kazanov Marat D 
Published: July 2021

Abstract
Since the discovery of the role of the APOBEC enzymes in human cancers, the mechanisms of this type of mutagenesis remain little understood. Theoretically, targeting of single-stranded DNA by the APOBEC enzymes could occur during cellular processes leading to the unwinding of DNA double-stranded structure. Some evidence points to the importance of replication in the APOBEC mutagenesis, while the role of transcription is still underexplored. Here, we analyzed gene expression and whole genome sequencing data from five types of human cancers with substantial APOBEC activity to estimate the involvement of transcription in the APOBEC mutagenesis and compare its impact with that of replication. Using the TCN motif as the mutation signature of the APOBEC enzymes, we observed a correlation of active APOBEC mutagenesis with gene expression, confirmed the increase of APOBEC-induced mutations in early-replicating regions and estimated the relative impact of transcription and replication on the APOBEC mutagenesis. We also found that the known effect of higher density of APOBEC-induced mutations on the lagging strand was highest in middle-replicating regions and observed higher APOBEC mutation density on the sense strand, the latter bias positively correlated with the gene expression level.
Differential ATAC-seq and ChIP-seq peak detection using ROTS
Authors: Faux Thomas , Rytkönen Kalle T , Mahmoudian Mehrad , Paulin Niklas , Junttila Sini , Laiho Asta , Elo Laura L 
Published: July 2021

Abstract
Changes in cellular chromatin states fine-tune transcriptional output and ultimately lead to phenotypic changes. Here we propose a novel application of our reproducibility-optimized test statistics (ROTS) to detect differential chromatin states (ATAC-seq) or differential chromatin modification states (ChIP-seq) between conditions. We compare the performance of ROTS to existing and widely used methods for ATAC-seq and ChIP-seq data using both synthetic and real datasets. Our results show that ROTS outperformed other commonly used methods when analyzing ATAC-seq data. ROTS also displayed the most accurate detection of small differences when modeling with synthetic data. We observed that two-step methods that require the use of a separate peak caller often more accurately called enrichment borders, whereas one-step methods without a separate peak calling step were more versatile in calling sub-peaks. The top ranked differential regions detected by the methods had marked correlation with transcriptional differences of the closest genes. Overall, our study provides evidence that ROTS is a useful addition to the available differential peak detection methods to study chromatin and performs especially well when applied to study differential chromatin states in ATAC-seq data.
How Women Shape Negativity in Parliamentary Speeches—A Sentiment Analysis of Debates in the Austrian Parliament
Authors: Haselmayer Martin , Dingler Sarah C , Jenny Marcelo 
Published: July 2021

Abstract
Though negativity in political debates influences citizens’ attitudes towards legislative institutions, research on how Members of Parliaments (MPs) use negative language remains scant. This study shows how the gender of speakers and the context of debates influence the level of negativity in parliamentary speeches. We argue that female MPs use less negative language than male colleagues due to gender differences in socialisation and stereotypical expectations. Applying sentiment analysis with word embeddings to 20 years of plenary speeches in the Austrian parliament, we find that speeches by women MPs are less negative on average compared to those of their male colleagues. A more balanced gender distribution within a party group decreases differences in tone by lowering the negativity of male speakers. A growing share of women in parliament can thus change the tone of debates, which might enhance the legitimacy of political institutions and the quality of democracy.
A nitrogen stress-inducible small RNA regulates CO2 fixation in Nostoc
Authors: Brenes-Álvarez Manuel , Olmedo-Verd Elvira , Vioque Agustín , Muro-Pastor Alicia M. 
Published: July 2021

Abstract
In the absence of fixed nitrogen, some filamentous cyanobacteria differentiate heterocysts, specialized cells devoted to fixing atmospheric nitrogen (N2). This differentiation process is controlled by the global nitrogen regulator NtcA and involves extensive metabolic reprogramming, including shutdown of photosynthetic CO2 fixation in heterocysts, to provide a microaerobic environment suitable for N2 fixation. Small regulatory RNAs (sRNAs) are major post-transcriptional regulators of gene expression in bacteria. In cyanobacteria, responding to nitrogen deficiency involves transcribing several nitrogen-regulated sRNAs. Here, we describe the participation of nitrogen stress-inducible RNA 4 (NsiR4) in post-transcriptionally regulating the expression of two genes involved in CO2 fixation via the Calvin cycle: glpX, which encodes bifunctional sedoheptulose-1,7-bisphosphatase/fructose-1,6-bisphosphatase (SBPase), and pgk, which encodes phosphoglycerate kinase (PGK). Using a heterologous reporter assay in Escherichia coli, we show that NsiR4 interacts with the 5′-untranslated region (5′-UTR) of glpX and pgk mRNAs. Overexpressing NsiR4 in Nostoc sp. PCC 7120 resulted in a reduced amount of SBPase protein and reduced PGK activity, as well as reduced levels of both glpX and pgk mRNAs, further supporting that NsiR4 negatively regulates these two enzymes. In addition, using a gfp fusion to the nsiR4 promoter, we show stronger expression of NsiR4 in heterocysts than in vegetative cells, which could contribute to the heterocyst-specific shutdown of Calvin cycle flux. Post-transcriptional regulation of two Calvin cycle enzymes by NsiR4, a nitrogen-regulated sRNA, represents an additional link between nitrogen control and CO2 assimilation.
Physical Activity in De Novo Parkinson Disease: Daily Step Recommendation and Effects of Treadmill Exercise on Physical Activity
Authors: Handlery Reed , Stewart Jill Campbell , Pellegrini Christine , Monroe Courtney , Hainline Garrett , Flach Alicia , Handlery Kaci , Fritz Stacy 
Published: July 2021

Abstract

Objective
People with Parkinson disease (PD) have low physical activity (PA) levels and are at risk for cardiovascular events. The 3 purposes of this study were to determine a step threshold that corresponds to meeting aerobic PA guidelines, determine effects of treadmill exercise on PA, and quantify the relationship between changes in daily steps and fitness.

Methods
This was a secondary analysis of the Study in Parkinson’s Disease of Exercise trial, which randomized participants to high-intensity treadmill exercise, moderate-intensity treadmill exercise, or usual care for 6 months. Daily steps and moderate- to vigorous-intensity PA (MVPA) were assessed at baseline and once each month using an activity monitor. Fitness was assessed via graded exercise test at baseline and at 6 months. A step threshold that corresponds to meeting PA guidelines was determined by receiver operating characteristic curves. The effect of treadmill exercise on PA was examined in those below the step threshold (ie, the least active participants). Pearson r correlations determined the relationship between daily steps and fitness.

Results
Individuals with de novo PD (n = 110) were included. Those with ≥4200 steps were 23 times more likely (95% CI = 7.72 to 68) to meet PA guidelines than those with &lt;4200 steps. For those with &lt;4200 steps at baseline (n = 33), only those in the high-intensity exercise group increased daily steps (median of differences = 1250 steps, z = −2.35) and MVPA (median of differences = 12.5 minutes, z = −2.67) at 6 months. For those with &lt;4200 steps, changes in daily steps were not associated with changes in fitness (r = .183).

Conclusion
In people with PD and &lt;4200 daily steps at baseline, high-intensity treadmill exercise increased daily steps and MVPA, but these changes were not associated with changes in fitness.

Impact
People with PD should be encouraged to take ≥4200 daily steps to meet PA guidelines through walking.
A Research Pathway Model for evaluating the implementation of practice-based research: The case of self-management health innovations
Authors: van Beest Wilke , Boon Wouter P C , Andriessen Daan , Pol Harald , van der Veen Gerrita , Moors Ellen H M 
Published: July 2021

AbstractThis study explores the evaluation of research pathways of self-management health innovations from discovery to implementation in the context of practice-based research. The aim is to understand how a new process model for evaluating practice-based research provides insights into the implementation success of innovations. Data were collected from nine research projects in the Netherlands. Through document analysis and semi-structured interviews, we analysed how the projects start, evolve, and contribute to the healthcare practice. Building on previous research evaluation approaches to monitor knowledge utilization, we developed a Research Pathway Model. The model’s process character enables us to include and evaluate the incremental work required throughout the lifespan of an innovation project and it helps to foreground that innovation continues during implementation in real-life settings. We found that in each research project, pathways are followed that include activities to explore a new solution, deliver a prototype and contribute to theory. Only three projects explored the solution in real life and included activities to create the necessary changes for the solutions to be adopted. These three projects were associated with successful implementation. The exploration of the solution in a real-life environment in which users test a prototype in their own context seems to be a necessary research activity for the successful implementation of self-management health innovations.
Racial disparities in sleep-related cardiac function in young, healthy adults: implications for cardiovascular-related health
Authors: Letzen Janelle E , Robinson Mercedes L , Saletin Jared M , Sheinberg Rosanne B , Smith Michael T , Campbell Claudia M 
Published: July 2021

Abstract

Study Objectives
Considerable evidence shows that individuals from marginalized racial/ethnic groups in the United States experience greater rates of sleep disturbance and cardiovascular complications. Because sleep is a modifiable factor that is critically involved in cardiovascular health, improved understanding of the association between sleep and cardiovascular health during early adulthood can prevent cardiovascular disparities. This study examined racial/ethnic differences in cardiovascular function during sleep using heart rate and heart-rate-variability analyses.

Methods
Participants in this laboratory-based sleep study included healthy, “good sleepers” who were in early adulthood and resided in the United States at the time of participation (14 non-Hispanic Black [NHB; age = 30.9 (6.6), 57% female], 12 Asian [Asian, age = 26.0 (5.2), 42% female], and 24 non-Hispanic white [NHW; age = 24.6 (5.8), 79% female]).

Results
After adjusting for demographic factors and an apnea–hypopnea index, we found significantly higher heart rate within NREM Stage 2 (N2) (b = −22.6, p = .04) and REM sleep (b = −25.8, p =.048) and lower heart rate variability during N2 sleep (b = −22.6, p = .04) among NHB individuals compared with NHW individuals. Furthermore, NHB and Asian participants demonstrated significantly lower percent of time in slow wave sleep (SWS) compared with NHW participants (NHB: b = −22.6, p =.04; Asian: b = −22.6, p = .04). Individuals’ percent of time in SWS significantly mediated differences in heart rate during N2 (indirect = 0.94, 95% CI [0.03, 2.68]) and REM sleep (indirect = 1.02, 95% CI [0.04, 3.04]).

Conclusions
Our results showed disparities in sleep-related cardiovascular function in early adulthood that are mediated by SWS. These data suggest targeting sleep health in early adulthood might help reduce cardiovascular disease burden on individuals from marginalized groups.
Arousal characteristics in patients with Parkinson’s disease and isolated rapid eye movement sleep behavior disorder
Authors: Brink-Kjær Andreas , Cesari Matteo , Sixel-Döring Friederike , Mollenhauer Brit , Trenkwalder Claudia , Mignot Emmanuel , Sorensen Helge B D , Jennum Poul 
Published: July 2021

AbstractStudy ObjectivesPatients diagnosed with isolated rapid eye movement (REM) sleep behavior disorder (iRBD) and Parkinson’s disease (PD) have altered sleep stability reflecting neurodegeneration in brainstem structures. We hypothesize that neurodegeneration alters the expression of cortical arousals in sleep.MethodsWe analyzed polysomnography data recorded from 88 healthy controls (HC), 22 iRBD patients, 82 de novo PD patients without RBD, and 32 with RBD (PD + RBD). These patients were also investigated at a 2-year follow-up. Arousals were analyzed using a previously validated automatic system, which used a central electroencephalography lead, electrooculography, and chin electromyography. Multiple linear regression models were fitted to compare group differences at baseline and change to follow-up for arousal index (ArI), shifts in electroencephalographic signals associated with arousals, and arousal chin muscle tone. The regression models were adjusted for known covariates affecting the nature of arousal.ResultsIn comparison to HC, patients with iRBD and PD + RBD showed increased ArI during REM sleep and their arousals showed a significantly lower shift in α-band power at arousals and a higher muscle tone during arousals. In comparison to HC, the PD patients were characterized by a decreased ArI in non-REM (NREM) sleep at baseline. ArI during NREM sleep decreased further at the 2-year follow-up, although not significantly.ConclusionsPatients with PD and iRBD present with abnormal arousal characteristics as scored by an automated method. These abnormalities are likely to be caused by neurodegeneration of the reticular activation system due to alpha-synuclein aggregation.
Neonatal Outcomes in Pregnant Women with Systemic Lupus Erythematosus: A 13-Year Experience in Southern Thailand
Authors: Pakhathirathien Pattima , Janjindamai Waricha , Dissaneevate Supaporn , Thatrimontrichai Anucha , Maneenil Gunlawadee 
Published: July 2021

Abstract

Objectives
The purpose of the study was to determine the clinical features of NLE and to compare the neonatal outcomes between newborns born to pregnant women with SLE and healthy pregnant women.

Methods
We conducted a retrospective cohort analysis between 2007 and 2019 in a tertiary referral hospital in Thailand. A total of 118 pregnant women with SLE with 132 neonates compared with 264 randomly selected healthy pregnant women.

Results
The median (interquartile range) gestational age and birth weight of 132 neonates born to women with SLE were 37 (35–38) weeks and 2687 g (2045–3160 g), respectively. The clinical features of NLE infants were hemolytic anemia (8%), thrombocytopenia (2.7%) and hyperbilirubinemia (5.3%). There was no neonate with a congenital complete heart block or skin lesion. Moreover, logistic regression analysis found that neonates born to women with SLE increased the risk of preterm birth [odd ratio (OR) 8.87, 95% confidence interval (95% CI) 4.32–18.21, p &lt; 0.001], low birth weight (OR 10.35, 95% CI 5.08–21.08, p &lt; 0.001), birth asphyxia (OR 2.91, 95% CI 1.26–6.73, p = 0.011) and NICU admission (OR 4.26, 95% CI 2.44–7.42, p &lt; 0.001). SLE disease activity and corticosteroid and azathioprine usage were associated with preterm delivery in pregnant women with SLE.

Conclusion
The major clinical features of NLE patients were hematologic and hepatobiliary abnormalities in our study. Pregnancies with SLE dramatically increased the risk of preterm delivery and neonatal complications.

Lay summary
Neonatal lupus erythematosus (NLE) is the consequence of the transplacental passage of autoantibodies to newborns during pregnancy. The clinical features of NLE infants in our study were hemolytic anemia (8%), thrombocytopenia (2.7%) and hyperbilirubinemia (5.3%). There was no neonate with a congenital complete heart block or skin lesion. We also compared the neonatal outcomes between 118 pregnant women with SLE and 264 randomly selected healthy pregnant women. Our study found that the neonates born to women with SLE increased the risk of preterm birth, low birth weight, birth asphyxia and NICU admission. Moreover, SLE disease activity and corticosteroid and azathioprine usage were associated with preterm delivery in pregnant women with SLE.
Stemphylium Leaf Blight of Welsh Onion (Allium fistulosum): An Emerging Disease in Sanxing, Taiwan
Authors: Wang Chun-Hsiang , Tsai Yi-Chen , Tsai Ichen , Chung Chia-Lin , Lin Yu-Chen , Hung Ting-Hsuan , Suwannarach Nakarin , Cheewangkoon Ratchadawan , Elgorban Abdallah M. , Ariyawansa Hiran A. 
Published: July 2021

Welsh onion (Allium fistulosum L.) is one of the main and oldest vegetable crops grown in Taiwan. A severe epidemic of leaf blight in Welsh onion caused by a Stemphylium-like pathogen was found in Sanxing, Taiwan, from 2018 to 2020. However, correct species identification, biology, and control of Stemphylium leaf blight (SLB) of Welsh onion are not well-established. Therefore, the main objective of this study was to investigate the causal agent of SLB in Sanxing and evaluate the in vitro sensitivity of Stemphylium-like pathogen to commonly used fungicides. A phylogenetic analysis based on combining the internal transcribed spacer (ITS) region and glyceraldedyhe-3-phosphate dehydrogenase (gapdh) and calmodulin (cmdA) gene sequences together with morphological features identified that S. vesicarium is associated with SLB in Sanxing. When inoculated onto Welsh onion leaves, the isolates caused symptoms identical to those observed in the field; therefore, S. vesicarium was reisolated and Koch’s postulates were confirmed. We observed a higher incidence of SLB symptoms on the oldest leaves compared with younger leaves. The maximum and minimum temperatures for in vitro mycelial growth and conidial germination (%) of S. vesicarium were 20 to 30°C and 5°C, respectively. Sixteen fungicides were tested for their effectiveness to reduce the mycelial growth and conidial germination of S. vesicarium in vitro. Boscalid plus pyraclostrobin, fluopyram, fluxapyroxad, and fluxapyroxad plus pyraclostrobin were highly effective at reducing mycelial growth and conidial germination in S. vesicarium. However, strobilurin fungicides (azoxystrobin and kresoxim-methyl) commonly used in Welsh onion production in Sanxing were ineffective. This study discusses the emergence of SLB caused by S. vesicarium in the foliar disease complex affecting Welsh onion and the management of the disease using fungicides with different modes of action in Taiwan. The research will support the sustainable management of SLB in Sanxing, Taiwan; however, further field assessments of the fungicides are warranted.
Crustacean Meal Elicits Expression of Growth and Defense-Related Genes in Roots of Lettuce and Tomato
Authors: Kandel Shyam L. , Anchieta Amy G. , Shi Ainong , Mou Beiquan , Klosterman Steven J. 
Published: July 2021

Powdered crab and lobster shells (crustacean meal) obtained from fisheries are used as soil amendments to promote plant health and defense. In this study, a commercial crustacean meal amendment used to promote the health of lettuce, tomato, and other crop plants was applied to roots of lettuce and tomato seedlings. Gene expression profiling of the treated roots was assessed by RNA sequencing (RNA-seq) at 24 h after application relative to a 0 h time point. The RNA-seq analyses revealed upregulation of different types of genes in both tomato and lettuce roots at 24 h. Gene ontology analyses revealed increased expression of genes associated with oxidoreductases/metal ion binding in tomato roots at 24 h, while there was predominantly increased expression of genes associated with cell wall organization, lyases, and hydrolases in lettuce roots at 24 h. The types of defense-related genes expressed were also markedly different. In tomato roots, the most highly induced gene (log2 fold change 13.84, P ≤ 0.001) encoded a defense-associated miraculin-like protein, but transcripts of a similar gene were not induced in lettuce roots. Interestingly, phenylpropanoid pathway genes relating to cell wall biogenesis and lignification were significantly upregulated in both lettuce and tomato roots, suggesting that strengthening of plant cell walls is a common response to crustacean meal application. This research provides insight into gene expression patterns in the roots of lettuce and tomato in response to crustacean meal, improving our understanding of how this amendment could aid in plant health. [Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 “No Rights Reserved” license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2022.
Evolution of Anti-SARS-CoV-2 IgG Antibody and IgG Avidity Post Pfizer and Moderna mRNA Vaccinations
Authors: Bliden Kevin P. , Liu Tiancheng , Sreedhar Deepika , Kost Jessica , Hsiung Jessica , Zhao Su , Shan Dingying , Usman Abira , Walia Naval , Cho Alastair , Jerjian Christophe , Tantry Udaya S. , Gurbel Paul A. , Tang Meijie , Dai Hongjie 
Published: July 2021

AbstractMessenger RNA (mRNA) based vaccines (Pfizer/BioNTech and Moderna) are highly effective at providing immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is uncertainty about the duration of immunity, evolution of IgG antibody levels and IgG avidity (an index of antibody-antigen binding strength), and differences in the immune responses between vaccines. Here we performed a prospective pilot study of 71 previously COVID-19 free subjects upon receiving both doses of either the Pfizer (n = 54) or Moderna (n = 17) mRNA vaccine. Anti-spike protein receptor binding domain (RBD) IgG antibodies were measured longitudinally using a qualitative finger stick MidaSpot™ rapid test at the point-of-care for initial screening and a quantitative dry blood spot-based pGOLD™ laboratory test over ∼ four months post-vaccination. The average anti-RBD IgG antibody levels peaked at ∼ two weeks after the second dose of the vaccine and declined thereafter, while antibody avidity increased, suggesting antibody maturation. Moderna vaccine recipients compared to Pfizer vaccine recipients exhibited higher side effect severity, higher peak anti-RBD IgG antibody levels, and higher avidity up to the 90 days period. Differences in antibody levels diminished at ∼ 120 days post-vaccination, in line with the similar efficacy observed in the two vaccines. The MidaSpot™ rapid test detected 100% anti-SARS-CoV-2 RBD positivity for fully vaccinated subjects in both Pfizer and Moderna cohorts post full vaccination but turned negative greater than 90 days post-vaccination for 5.4% of subjects in the Pfizer cohort, whose quantitative anti-IgG were near the minimum levels of the group. Immune responses were found to vary greatly among vaccinees. Personalized longitudinal monitoring of antibodies could be necessary to assess the immunity duration of vaccinated individuals.