bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histone demethylase KDM4A overexpression improved the efficiency of corrected human tripronuclear zygote development
Authors: Zhu Hai-Ying , Kang Xiang-Jin , Jin Long , Zhang Pu-Yao , Wu Han , Tan Tao , Yu Yang , Fan Yong 
Published: February 2021

Abstract
Human zygotes are difficult to obtain for research because of limited resources and ethical debates. Corrected human tripronuclear (ch3PN) zygotes obtained by removal of the extra pronucleus from abnormally fertilized tripronuclear (3PN) zygotes are considered an alternative resource for basic scientific research. In the present study, eight-cell and blastocyst formation efficiency were significantly lower in both 3PN and ch3PN embryos than in normal fertilized (2PN) embryos, while histone H3 lysine 9 trimethylation (H3K9me3) levels were much higher. It was speculated that the aberrant H3K9me3 level detected in ch3PN embryos may be related to low developmental competence. Microinjection of 1000 ng/µl lysine-specific demethylase 4A (KDM4A) mRNA effectively reduced the H3K9me3 level and significantly increased the developmental competence of ch3PN embryos. The quality of ch3PN zygotes improved as the grading criteria, cell number and pluripotent expression significantly increased in response to KDM4A mRNA injection. Developmental genes related to zygotic genome activation (ZGA) were also upregulated. These results indicate that KDM4A activates the transcription of the ZGA program by enhancing the expression of related genes, promoting epigenetic modifications and regulating the developmental potential of ch3PN embryos. The present study will facilitate future studies of ch3PN embryos and could provide additional options for infertile couples.
Structural mechanism of DNA recognition by the p204 HIN domain
Authors: Fan Xiaojiao , Jiang Jiansheng , Zhao Dan , Chen Feng , Ma Huan , Smith Patrick , Unterholzner Leonie , Xiao Tsan Sam , Jin Tengchuan 
Published: February 2021

Abstract
The interferon gamma-inducible protein 16 (IFI16) and its murine homologous protein p204 function in non-sequence specific dsDNA sensing; however, the exact dsDNA recognition mechanisms of IFI16/p204, which harbour two HIN domains, remain unclear. In the present study, we determined crystal structures of p204 HINa and HINb domains, which are highly similar to those of other PYHIN family proteins. Moreover, we obtained the crystal structure of p204 HINab domain in complex with dsDNA and provided insights into the dsDNA binding mode. p204 HINab binds dsDNA mainly through α2 helix of HINa and HINb, and the linker between them, revealing a similar HIN:DNA binding mode. Both HINa and HINb are vital for HINab recognition of dsDNA, as confirmed by fluorescence polarization assays. Furthermore, a HINa dimerization interface was observed in structures of p204 HINa and HINab:dsDNA complex, which is involved in binding dsDNA. The linker between HINa and HINb reveals dynamic flexibility in solution and changes its direction at ∼90° angle in comparison with crystal structure of HINab:dsDNA complex. These structural information provide insights into the mechanism of DNA recognition by different HIN domains, and shed light on the unique roles of two HIN domains in activating the IFI16/p204 signaling pathway.
Workshop report. Circadian rhythm sleep–wake disorders: gaps and opportunities
Authors: Duffy Jeanne F , Abbott Sabra M , Burgess Helen J , Crowley Stephanie J , Emens Jonathan S , Epstein Lawrence J , Gamble Karen L , Hasler Brant P , Kristo David A , Malkani Roneil G , Rahman Shadab A , Thomas S Justin , Wyatt James K , Zee Phyllis C , Klerman Elizabeth B 
Published: February 2021

Abstract
This White Paper presents the results from a workshop cosponsored by the Sleep Research Society (SRS) and the Society for Research on Biological Rhythms (SRBR) whose goals were to bring together sleep clinicians and sleep and circadian rhythm researchers to identify existing gaps in diagnosis and treatment and areas of high-priority research in circadian rhythm sleep–wake disorders (CRSWD). CRSWD are a distinct class of sleep disorders caused by alterations of the circadian time-keeping system, its entrainment mechanisms, or a misalignment of the endogenous circadian rhythm and the external environment. In these disorders, the timing of the primary sleep episode is either earlier or later than desired, irregular from day-to-day, and/or sleep occurs at the wrong circadian time. While there are incomplete and insufficient prevalence data, CRSWD likely affect at least 800,000 and perhaps as many as 3 million individuals in the United States, and if Shift Work Disorder and Jet Lag are included, then many millions more are impacted. The SRS Advocacy Taskforce has identified CRSWD as a class of sleep disorders for which additional high-quality research could have a significant impact to improve patient care. Participants were selected for their expertise and were assigned to one of three working groups: Phase Disorders, Entrainment Disorders, and Other. Each working group presented a summary of the current state of the science for their specific CRSWD area, followed by discussion from all participants. The outcome of those presentations and discussions are presented here.
Evaluation of Bacillus subtilis PB6 on feedlot phase growth performance, efficiency of dietary net energy utilization, and fecal and subiliac lymph node Salmonella prevalence in spring placement yearling beef steers fed in southeastern South Dakota1,2,3
Authors: Smith Zachary K , Broadway Paul Rand , Underwood Keith R , Rusche Warren C , Walker Julie A , Burdick Sanchez Nicole C , Carroll Jeffrey A , Lafleur Doug , Hergenreder Jerilyn E 
Published: February 2021

Abstract
Yearling crossbred beef steers [N = 238; initial shrunk body weight (BW) = 402 ± 31.2 kg] were used to investigate the influence of a Bacillus subtilis probiotic on animal growth performance, efficiency of dietary net energy (NE) utilization, carcass characteristics, and fecal and subiliac lymph node Salmonella prevalence during a 140-d finishing period at the Southeast Research Farm in Beresford, SD. Steers were allotted to 1 of 24 pens (N = 9–10 steers/pen) and assigned to 1 of 2 dietary treatments (12 pens/treatment): no probiotic (CON) or 0.5 g/steer/d of a B. subtilis PB6 probiotic (CLOSTAT500, Kemin Industries, Des Moines, IA; CLO). Bunks were managed according to a slick bunk management approach. Fecal samples were collected on study days 1, 28, 56, 112, and 140 from a subsample of steers from each pen (N = 5 steers/pen) via rectal palpation and composited by pen for the determination of Salmonella prevalence using selective enrichment and culture media. Upon harvest, subiliac lymph nodes were obtained from an equal number of steers from each treatment (collected from every other steer) following evisceration and hide removal. Data were analyzed as a randomized complete block design and pen served as the experimental unit; an α of 0.05 determined significance. Live-basis final BW and average daily gain tended (P ≤ 0.06) to be reduced for CLO. No differences were detected (P ≥ 0.11) between treatments for dry matter intake or gain efficiency. Treatment neither altered the efficiency of dietary NE utilization nor calculated dietary NE content based upon observed performance (P ≥ 0.46). No differences were detected between treatments for any carcass traits (P ≥ 0.15). No Salmonella was recovered in any fecal samples collected on study days 1, 28, or 56. On day 112, steers from CLO had a numerically lower (P = 0.17; 25.0 vs. 8.3%) incidence of fecal Salmonella compared to CON. On study day 140, fecal Salmonella incidence did not differ between treatments (P = 0.34; 0.0 vs. 8.3%) for CON and CLO, respectively. Upon harvest, no Salmonella was recovered in any subiliac lymph nodes. These data indicate that B. subtilis PB6 did not influence feedlot phase growth performance or fecal Salmonella prevalence. Additionally, Salmonella was not observed in the subiliac lymph nodes of any steers upon harvest.
Complementary value of ECG and echocardiographic left ventricular hypertrophy for prediction of adverse outcomes in the general population
Authors: Du Zhi , Xing Liying , Ye Ning , Lin Min , Sun Yingxian 
Published: February 2021

Objective:
To investigate whether ECG left ventricular hypertrophy (ECG-LVH) has prognostic value independent of echocardiography LVH (Echo-LVH).

Methods:
Participants (N = 9744, mean age, 53.81 ± 10.49 years and 45.5% male) from the Northeast China Rural Cardiovascular Health Study were included. Associations between Echo-LVH (sex-specific left ventricular mass normalized to BSA) and ECG-LVH (diagnosed using the Cornell-voltage duration product) and adverse outcomes were evaluated using Cox regression. The value of ECG-LVH for predicting adverse events was evaluated by reclassification and discrimination analyses.

Results:
Median follow-up was 4.65 years; 563 participants developed incident stroke or coronary heart disease (CHD) and 402 died. Compared with participants without either condition, those with both Echo-LVH and ECG-LVH had a significantly increased risk of incident stroke or CHD (hazard ratio, 2.42; 95% confidence interval, 1.82–3.22) and mortality (2.58; 1.85–3.60). ECG-LVH remained an independent risk factors for both outcomes when ECG-LVH and Echo-LVH were included in the model as separate variables [incident stroke or CHD (1.43; 1.14–1.79); mortality (1.41; 1.08–1.84)]. Reclassification and discrimination analyses indicated ECG-LVH addition could improve the conventional model for predicting adverse outcomes within 4 years. These relationships persisted after excluding participants with cardiovascular disease history or taking antihypertension drugs or upon applying other ECG-LVH and Echo-LVH diagnostic criteria.

Conclusion:
Our study provides strong evidence that ECG-LVH is associated with adverse outcomes, independent of Echo-LVH. Clinically, ECG-LVH could be considered as a consequential factor, especially in those with Echo-LVH. These findings have potential clinical relevance for risk stratification.
Multi-level Predictors of Depression Symptoms in the Adolescent Brain Cognitive Development (ABCD) Study
Authors: Ho Tiffany C. , Shah Rutvik , Mishra Jyoti , May April C. , Tapert Susan F. 
Published: February 2021

AbstractObjectiveTo identify multi-level factors that maximize prediction of depression symptoms in a diverse sample of children in the U.S. participating in the Adolescent Brain and Cognitive Development (ABCD) study.Methods8,507 participants (49.6% female, 75.2% white, ages 9-10) from ABCD provided complete data at baseline and 7,998 of these participants provided one-year follow-up data. Depression symptoms were measured with the Child Behavior Checklist. Predictive features included child demographic, environmental, and structural and resting-state fMRI variables, parental depression symptoms and demographic characteristics, and relevant site and scanner-related covariates. We used linear (elastic net regression, EN) and non-linear (gradient boosted trees, GBT) predictive models to identify which set of features maximized prediction of depression symptoms at baseline and, separately, at one-year follow-up.ResultsBoth linear and non-linear models achieved comparable results for predicting baseline (EN: MAE=3.628; R2=0.232; GBT: MAE=3.555; R2=0.229) and one-year follow-up (EN: MAE=4.116; R2=0.143; GBT: MAE=4.141; R2=0.1400) depression. Parental depression symptoms, family support, and child sleep duration were among the top predictors of concurrent and future child depression symptoms across both models. Although resting-state fMRI features were relatively weaker predictors, connectivity of the right caudate was consistently the strongest neural feature associated with depression symptoms at both timepoints. In contrast, brain features derived from structural MRI did not significantly predict child depression symptoms.Conclusions & RelevanceParental mental health and child sleep quality are potentially modifiable risk factors for youth depression. Functional connectivity of the caudate is a relatively weaker predictor of depression symptoms but may represent a biomarker of depression risk.
During natural viewing, neural processing of visual targets continues throughout saccades
Authors: Stankov Atanas D , Touryan Jonathan , Gordon Stephen , Ries Anthony J. , Ki Jason , Parra Lucas C 
Published: February 2021

AbstractRelatively little is known about visual processing during free-viewing visual search in realistic dynamic environments. Free-viewing is characterized by frequent saccades. During saccades, visual processing is thought to be inhibited, yet we know that the pre-saccadic visual content can modulate post-saccadic processing. To better understand these processes in a realistic setting, we study here saccades and neural responses elicited by the appearance of visual targets in a realistic virtual environment. While subjects were being driven through a 3D virtual town they were asked to discriminate between targets that appear on the road. We found that the presence of a target enhances early occipital as well as late frontocentral saccade-related responses. The earlier potential, shortly after 125ms post-saccade onset, was enhanced for targets that appeared in peripheral vision as compared to central vision, suggesting that fast peripheral processing initiated before saccade onset. The later potential, at 195ms post-saccade onset, was strongly modulated by the visibility of the target with a spatial distribution reminiscent of the classic P300 response. Together these results suggest that, during natural viewing, neural processing of the pre-saccadic visual stimulus continues throughout the saccade, apparently unencumbered by saccadic inhibition.
Paths and Pathways that Generate Cell-Type Heterogeneity and Developmental Progression in Hematopoiesis
Authors: Girard Juliet R. , Goins Lauren M. , Vuu Dung M. , Sharpley Mark S. , Spratford Carrie M. , Mantri Shreya R. , Banerjee Utpal 
Published: February 2021

AbstractMechanistic studies ofDrosophilalymph gland hematopoiesis are limited by the availability of cell-type specific markers. Using a combination of bulk RNA-Seq of FACS-sorted cells, single cell RNA-Seq and genetic dissection, we identify new blood cell subpopulations along a developmental trajectory with multiple paths to mature cell types. This provides functional insights into key developmental processes and signaling pathways. We highlight metabolism as a driver of development, show that graded Pointed expression allows distinct roles in successive developmental steps, and that mature crystal cells specifically express an alternate isoform of Hypoxia-inducible factor (Hif/Sima). Mechanistically, the Musashi-regulated protein Numb facilitates Sima-dependent non-canonical, while inhibiting canonical, Notch signaling. Broadly, we find that prior to making a fate choice, a progenitor selects between alternative, biologically relevant, transitory states allowing smooth transitions reflective of combinatorial expressions rather than stepwise binary decisions. Increasingly, this view is gaining support in mammalian hematopoiesis.
Fractal dimension of EEG signal senses complexity of fractal animations
Authors: Dorosti Sarshar , Khosrowabadi Reza 
Published: February 2021

AbstractWe are surrounded with many fractal and self-similar patterns which has been area of many researches in the recent years. We can perceive self-similarities in various spatial and temporal scales; however, the underlying neural mechanism needs to be well understood. In this study, we hypothesized that complexity of visual stimuli directly influence complexity of information processing in the brain. Therefore, changes in fractal pattern of EEG signal must follow change in fractal dimension of animation. To investigate this hypothesis, we recorded EEG signal of fifteen healthy participants while they were exposed to several 2D fractal animations. Fractal dimension of each frame of the animation was estimated by box counting method. Subsequently, fractal dimensions of 32 EEG channels were estimated in a frequency specific manner. Then, association between pattern of fractal dimensions of the animations and pattern of fractal dimensions of EEG signals were calculated using the Pearson’s correlation algorithm. The results indicated that fractal animation complexity is mainly sensed by changes in fractal dimension of EEG signals at the centro-parietal and parietal regions. It may indicate that when the complexity of visual stimuli increases the mechanism of information processing in the brain also enhances its complexity to better attend and comprehend the stimuli.
Risk of Corona virus disease 2019 (COVID-19) among spectacles wearing population of Northern India
Authors: Saxena Amit Kumar 
Published: February 2021

AbstractIntroductionSevere Acute Respiratory Syndrome Corona virus-2 (SARS-CoV-2) spread mainly through respiratory droplets and contact routes. Long term use of spectacles may prevent repeated touching and rubbing of the eyes. Aim of the study is to find out the protective effectiveness of the spectacles against COVID-19, if present.ObjectivesTo know the association between infection with SARSCoV-2 and wearing of spectacles.Materials and methodsIn this study, 304 patients of Corona virus disease 2019 (COVID-19) were selected. Their spectacles wearing behaviour were assessed through a questionnaire. Spectacles wearing behaviour of general population were obtained from older studies (for comparison). Data was put in the tabulate form and Chi- Square test was used for statistical analysis.ResultsIn this study, among the 304 total patients, 58 patients showed the behavior of using spectacles continuously during day time and always on outdoor activities. While the spectacles wearing behaviour is about 40% among general Indian population. The protective effectiveness of the spectacles was found statistically significant (p-value. 00113).ConclusionThe present study showed that the occurrence of Covid-19 was less in spectacles wearing population than the population not wearing those. The nasolacrimal duct may be a route of virus transmission from conjunctival sac to the nasopharynx.
Disease-economy trade-offs under alternative pandemic control strategies
Authors: Ash Thomas , Bento Antonio M. , Kaffine Daniel , Rao Akhil , Bento Ana I. 
Published: February 2021

AbstractPublic policy and academic debates regarding pandemic control strategies note potential disease-economy trade-offs, and often prioritize one outcome over the other. Using a calibrated, coupled epi-economic model of individual behavior embedded within the broader economy during a novel epidemic, we show that targeted isolation strategies can avert up to 91% of individual economic losses relative to voluntary isolation strategies. Notably, the economic savings from targeted isolation strategies do not impose an additional disease burden, avoiding disease-economy trade-offs. In contrast, widely-used blanket lock-downs do create sharp disease-economy trade-offs and impose substantial economic costs per additional case avoided. These results highlight the benefits of targeted isolation strategies for disease control, as targeted isolation addresses the fundamental coordination failure between infectious and susceptible individuals that drives the recession. Our coupled-systems framework uses a data-driven approach to map economic activities to contacts, which facilitates developing effective control strategies for future novel pathogens. Implementation of this framework can help control disease spread and potentially avert trillions of dollars in losses.
Blood and skeletal muscle ageing determined by epigenetic clocks and their associations with physical activity and functioning
Authors: Sillanpää Elina , Heikkinen Aino , Kankaanpää Anna , Paavilainen Aini , Kujala Urho M. , Tammelin Tuija H. , Kovanen Vuokko , Sipilä Sarianna , Pietiläinen Kirsi H. , Kaprio Jaakko , Ollikainen Miina , Laakkonen Eija K. 
Published: February 2021

AbstractThe aim of this study was to investigate the correspondence of different biological ageing estimates (i.e. epigenetic age) in blood and muscle tissue and their associations with physical activity (PA), physical function and body composition.Two independent cohorts were included, whose age span covered adulthood (23–69 years). Whole blood and m. vastus lateralis samples were collected, and DNA methylation analysed. Four different DNA methylation age (DNAmAge) estimates were calculated using genome-wide methylation data and publicly available online tools. A novel muscle-specific methylation age was estimated using the R-package ‘MEAT’. PA was measured with questionnaires and accelerometers. Several tests were conducted to estimate cardiorespiratory fitness and muscle strength. Body composition was estimated by dual-energy X-ray absorptiometry.DNAmAge estimates from blood and muscle were highly correlated with chronological age, but different age acceleration estimates were weakly associated with each other. The monozygotic twin within-pair similarity of ageing pace was higher in blood (r=0.617–0.824) than in muscle (r=0.523–0.585). Associations of age acceleration estimates with PA, physical function and body composition were weak in both tissues and mostly explained by smoking and sex. The muscle-specific epigenetic clock MEAT was developed to predict chronological age, which may explain why it did not associate with functional phenotypes. The Horvath’s clock and GrimAge were weakly associated with PA and related phenotypes, suggesting that higher PA would be linked to accelerated biological ageing in muscle. This may, however, be more reflective of the low capacity of epigenetic clock algorithms to measure functional muscle ageing than of actual age acceleration.Based our results, the investigated epigenetic clocks have rather low value in estimating muscle ageing with respect to the physiological adaptations that typically occur due to ageing or PA. Thus, further development of methods is needed to gain further insight into muscle tissue-specific ageing and the underlying biological pathways.