bluuebunny/crossref_metadata_2025_split huggingface dataset:
Who Cares if Parents have Unpredictable Work Schedules?: Just-in-Time Work Schedules and Child Care Arrangements
Authors: Harknett Kristen , Schneider Daniel , Luhr Sigrid 
Published: April 2020

Abstract
Working parents must arrange some type of care for their young children when they are away at work. For parents with unstable and unpredictable work schedules, the logistics of arranging care can be complex. In this paper, we use survey data from the Shift Project, collected in 2017 and 2018 from a sample of 3,653 parents who balance work in the retail and food service sector with parenting young children from infants to nine years of age. Our results demonstrate that unstable and unpredictable work schedules have consequences for children’s care arrangements. We find that parents’ exposure to on-call work and last-minute shift changes are associated with more numerous care arrangements, with a reliance on informal care arrangements, with the use of siblings to provide care, and with young children being left alone without adult supervision. Given the well-established relationship between quality of care in the early years and child development, just-in-time scheduling practices are likely to have consequences for children’s development and safety and to contribute to the intergenerational transmission of disadvantage.
Effect of water-to-feed ratio on feed disappearance, growth rate, feed efficiency, and carcass traits in growing-finishing pigs
Authors: O’Meara Fiona M , Gardiner Gillian E , O’Doherty John V , Lawlor Peadar G 
Published: April 2020

Abstract
The optimum proportion of water for preparing liquid feed to maximize growth and optimize feed efficiency (FE) in growing-finishing pigs is not known. The aim of the current study was, using an automatic short-trough sensor liquid feeding system, to identify the water-to-feed ratio at which growth was maximized and feed was most efficiently converted to live-weight. Two experiments were conducted in which four commercially used water-to-feed ratios were fed: 2.4:1, 3.0:1, 3.5:1, and 4.1:1 on a dry matter (DM) basis (the equivalent of 2:1, 2.5:1, 3.0:1, and 3.5:1 on a fresh matter basis). Each experiment comprised 216 pigs, penned in groups of 6 same sex (entire male and female) pigs/pen with a total of 9 pen replicates per treatment. The first experiment lasted 62 days (from 40.6 to 102.2 kg at slaughter) and the second experiment was for 76 days (from 31.8 to 119.6 kg at slaughter). Overall, in Exp. 1, FE was 0.421, 0.420, 0.453, and 0.448 (s.e. 0.0081 g/g; P &lt; 0.01) for pigs fed at 2.4:1, 3.0:1, 3.5:1, and 4.1:1, respectively. Overall, in Exp. 2, average daily gain was 1,233, 1,206, 1,211, and 1,177 (s.e. 12.7 g/day; P &lt; 0.05) for pigs fed at 2.4:1, 3.0:1, 3.5:1, and 4.1:1, respectively. At slaughter, in Exp. 1, dressing percentage was 76.7, 76.6, 76.7, and 75.8 (s.e. 0.17%; P &lt; 0.01) for 2.4:1, 3.0:1, 3.5:1, and 4.1:1, respectively. There were no differences between treatment groups for DM, organic matter, nitrogen, gross energy, or ash digestibilities. These findings indicate that liquid feeding a diet prepared at a water-to-feed ratio of 3.5:1 maximizes FE of growing-finishing pigs without negatively affecting dressing percentage. Therefore, preparing liquid feed for growing-finishing pigs at a water-to-feed ratio of 3.5:1 DM is our recommendation for a short-trough liquid feeding system.
Spatial ecology of closely related taxa: the case of the little shearwater complex in the North Atlantic Ocean
Authors: Ramos Raül , Paiva Vitor H , Zajková Zuzana , Precheur Carine , Fagundes Ana Isabel , Jodice Patrick G R , Mackin William , Zino Francis , Bretagnolle Vincent , González-Solís Jacob 
Published: April 2020

Abstract
Seabirds inhabiting vast water masses provide numerous examples where opposing phenomena, such as natal and breeding philopatry vs. vagility have dug cryptic taxonomic boundaries among closely related taxa. The taxonomy of little shearwaters of the North Atlantic Ocean (Little–Audubon’s shearwater complex, Puffinus assimilis–lherminieri) still remains unclear, and complementary information on non-breeding distributions and at-sea behaviour becomes essential to unravel divergent local adaptations to specific habitats. Using miniaturized light-level geolocators from seven study areas in the North Atlantic, we evaluate the spatial and habitat segregation, estimate the timing of their key life-cycle events and describe the at-sea behaviour of three taxa of these little shearwaters year-round to distinguish ecological patterns and specializations that could ultimately unravel potential lineage divergences. We also assess morphometric data from birds that were breeding at each study area to further discuss potential adaptations to specific habitats. Our results show that, while birds from different taxa segregated in space and habitats, they share ecological plasticity, similar annual phenology and diel foraging behaviour. These ecological inconsistencies, while defining the evolutionary stressors faced by these taxa, do not suggest the existence of three Evolutionary Significant Units. However, they confirm the recent evolutionary divergence among the three little shearwaters of the North Atlantic.
Unraveling the functional role of DNA methylation using targeted DNA demethylation by steric blockage of DNA methyltransferase with CRISPR/dCas9
Authors: Sapozhnikov Daniel M. , Szyf Moshe 
Published: April 2020

AbstractAlthough associations between DNA methylation and gene expression were established four decades ago, the causal role of DNA methylation in gene expression remains unresolved. Different strategies to address this question were developed; however, all are confounded and fail to disentangle cause and effect. We developed here a highly effective new method using only deltaCas9(dCas9):gRNA site-specific targeting to physically block DNA methylation at specific targets in the absence of a confounding flexibly-tethered enzymatic activity, enabling examination of the role of DNA methylationper sein living cells. We show that the extensive induction of gene expression achieved by TET/dCas9-based targeting vectors is confounded by DNA methylation-independent activities, inflating the role of DNA methylation in the promoter region. Using our new method, we show that in several inducible promoters, the main effect of DNA methylation is silencing basal promoter activity. Thus, the effect of demethylation of the promoter region in these genes is small, while induction of gene expression by different inducers is large and DNA methylation independent. In contrast, targeting demethylation to the pathologically silenced FMR1 gene targets robust induction of gene expression. We also found that standard CRISPR/Cas9 knockout generates a broad unmethylated region around the deletion, which might confound interpretation of CRISPR/Cas9 gene depletion studies. In summary, this new method could be used to reveal the true extent, nature, and diverse contribution to gene regulation of DNA methylation at different regions.
Fully human single-domain antibodies against SARS-CoV-2
Authors: Wu Yanling , Li Cheng , Xia Shuai , Tian Xiaolong , Wang Zhi , Kong Yu , Gu Chenjian , Zhang Rong , Tu Chao , Xie Youhua , Lu Lu , Jiang Shibo , Ying Tianlei 
Published: April 2020

AbstractThe COVID-19 pandemic is spreading rapidly, highlighting the urgent need for an efficient approach to rapidly develop therapeutics and prophylactics against SARS-CoV-2. We describe here the development of a phage-displayed single-domain antibody library by grafting naïve CDRs into framework regions of an identified human germline IGHV allele. This enabled the isolation of high-affinity single-domain antibodies of fully human origin. The panning using SARS-CoV-2 RBD and S1 as antigens resulted in the identification of antibodies targeting five types of neutralizing or non-neutralizing epitopes on SARS-CoV-2 RBD. These fully human single-domain antibodies bound specifically to SARS-CoV-2 RBD with subnanomolar to low nanomolar affinities. Some of them were found to potently neutralize pseudotyped and live virus, and therefore may represent promising candidates for prophylaxis and therapy of COVID-19. This study also reports unique immunogenic profile of SARS-CoV-2 RBD compared to that of SARS-CoV and MERS-CoV, which may have important implications for the development of effective vaccines against SARS-CoV-2.
Investigating structure function relationships in the NOTCH family through large-scale somatic DNA sequencing studies
Authors: Hall Michael W J , Shorthouse David , Jones Philip H , Hall Benjamin A 
Published: April 2020

AbstractThe recent development of highly sensitive DNA sequencing techniques has detected large numbers of missense mutations of genes, includingNOTCH1and 2, in ageing normal tissues. Driver mutations persist and propagate in the tissue through a selective advantage over both wild-type cells and alternative mutations. This process of selection can be considered as a large scale, in vivo screen for mutations that increase clone fitness. It follows that the specific missense mutations that are observed in individual genes may offer us insights into the structure-function relationships. Here we show that the positively selected missense mutations inNOTCH1andNOTCH2in human oesophageal epithelium cause inactivation predominantly through protein misfolding. Once these mutations are excluded, we further find statistically significant evidence for selection at the ligand binding interface and calcium binding sites. In this, we observe stronger evidence of selection at the ligand interface on EGF12 over EGF11, suggesting that in this tissue EGF12 may play a more important role in ligand interaction. Finally, we show how a mutation hotspot in the NOTCH1 transmembrane helix arises through the intersection of both a high mutation rate and residue conservation. Together these insights offer a route to understanding the mechanism of protein function throughin vivomutant selection.
Angiotensin II Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors Usage is Associated with Improved Inflammatory Status and Clinical Outcomes in COVID-19 Patients With Hypertension
Authors: Yang Guang , Tan Zihu , Zhou Ling , Yang Min , Peng Lang , Liu Jinjin , Cai Jingling , Yang Ru , Han Junyan , Huang Yafei , He Shaobin 
Published: April 2020

AbstractWith the capability of inducing elevated expression of ACE2, the cellular receptor for SARS-CoV-2, angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors (ARBs/ACEIs) treatment may have a controversial role in both facilitating virus infection and reducing pathogenic inflammation. We aimed to evaluate the correlation of ARBs/ACEIs usage with the pathogenesis of COVID-19 in a retrospective, single-center study. 126 COVID-19 patients with preexisting hypertension at Hubei Provincial Hospital of Traditional Chinese Medicine (HPHTCM) in Wuhan from January 5 to February 22, 2020 were retrospectively allocated to ARBs/ACEIs group (n=43) and non-ARBs/ACEIs group (n=83) according to their antihypertensive medication. 125 age- and sex-matched COVID-19 patients without hypertension were randomly selected as non-hypertension controls. In addition, the medication history of 1942 hypertension patients that were admitted to HPHTCM from November 1 to December 31, 2019 before COVID-19 outbreak were also reviewed for external comparison. Epidemiological, demographic, clinical and laboratory data were collected, analyzed and compared between these groups. The frequency of ARBs/ACEIs usage in hypertension patients with or without COVID-19 were comparable. Among COVID-19 patients with hypertension, those received either ARBs/ACEIs or non-ARBs/ACEIs had comparable blood pressure. However, ARBs/ACEIs group had significantly lower concentrations of CRP (p=0.049) and procalcitonin (PCT, p=0.008). Furthermore, much lower proportion of critical patients (9.3% vs 22.9%; p=0.061), and a lower death rate (4.7% vs 13.3%; p=0.216) were observed in ARBs/ACEIs group than non-ARBs/ACEIs group, although these differences failed to reach statistical significance. Our findings thus support the use of ARBs/ACEIs in COVID-19 patients with preexisting hypertension.
Hematologist-level classification of mature B-cell neoplasm using deep learning on multiparameter flow cytometry data
Authors: Zhao Max , Mallesh Nanditha , Schabath Richard , Höllein Alexander , Haferlach Claudia , Haferlach Torsten , Elsner□ Franz , Lüling□ Hannes , Krawitz Peter , Kern Wolfgang 
Published: April 2020

AbstractThe wealth of information captured by multiparameter flow cytometry (MFC) can be analyzed by recent methods of computer vision when represented as a single image file. We therefore transformed MFC raw data into a multicolor 2D image by a self-organizing map (SOM) and classified this representation using a convolutional neural network (CNN). By this means, we built an artificial intelligence that is not only able to distinguish diseased from healthy samples, but that can also differentiate seven subtypes of mature B-cell neoplasm (B-NHL). We trained our model with 18,274 cases including chronic lymphocytic leukemia (CLL) and its precursor monoclonal B-cell lymphocytosis (MBL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), prolymphocytic leukemia (PL), follicular lymphoma (FL), hairy cell leukemia (HCL), lymphoplasmacytic lymphoma (LPL) and achieved a weighted F1 score of 0.94 on a separate test set of 2,348 cases. Furthermore, we estimated the trustworthiness of a classification and could classify 70% of all cases with a confidence of 0.95 and higher. Our performance analyses indicate that particularly for rare subtypes further improvement can be expected when even more samples are available for training.
Dissecting clinical heterogeneity of bipolar disorder using multiple polygenic risk scores
Authors: Coombes Brandon J. , Markota Matej , Mann J. John , Colby Colin , Stahl Eli , Talati Ardesheer , Pathak Jyotishman , Weissman Myrna M. , McElroy Susan L. , Frye Mark A. , Biernacka Joanna M. 
Published: April 2020

AbstractBipolar disorder (BD) has high clinical heterogeneity, frequent psychiatric comorbidities, and elevated suicide risk. To determine genetic differences between common clinical sub-phenotypes of BD, we performed a systematic PRS analysis using multiple polygenic risk scores (PRSs) from a range of psychiatric, personality, and lifestyle traits to dissect differences in BD sub-phenotypes in two BD cohorts: the Mayo Clinic BD Biobank (N = 968) and Genetic Association Information Network (N = 1001). Participants were assessed for history of psychosis, early-onset BD, rapid cycling (defined as four or more episodes in a year), and suicide attempts using questionnaires and the Structured Clinical Interview for DSM-IV. In a combined sample of 1969 bipolar cases (45.5% male), those with psychosis had higher PRS for SCZ (OR = 1.3 per S.D.; p = 3e-5) but lower PRSs for anhedonia (OR = 0.87; p = 0.003) and BMI (OR = 0.87; p = 0.003). Rapid cycling cases had higher PRS for ADHD (OR = 1.23; p = 7e-5) and MDD (OR = 1.23; p = 4e-5) and lower BD PRS (OR = 0.8; p = 0.004). Cases with a suicide attempt had higher PRS for MDD (OR = 1.26; p = 1e-6) and anhedonia (OR = 1.22; p = 2e-5) as well as lower PRS for educational attainment (OR = 0.87; p = 0.003). The observed novel PRS associations with sub-phenotypes align with clinical observations such as rapid cycling BD patients having a greater lifetime prevalence of ADHD. Our findings confirm that genetic heterogeneity underlies the clinical heterogeneity of BD and consideration of genetic contribution to psychopathologic components of psychiatric disorders may improve genetic prediction of complex psychiatric disorders.
Core-periphery structure in mutualistic networks: an epitaph for nestedness?
Authors: Martín González Ana M. , Vázquez Diego P. , Ramos-Jiliberto Rodrigo , Lee Sang Hoon , Miele Vincent 
Published: April 2020

ABSTRACTThe calculation of nestedness has become a routine analysis in the study of ecological networks, as it is commonly associated with community resilience, robustness and species persistence. While meaningful in species distributional patterns, for an interaction matrix to be nested, specialist species must interact with ordered subsets of subsequently more generalized species — not just with a lower number of species. However, after reviewing 419 papers on mutualistic networks published since nestedness was introduced for the study of species interactions in 2003, we have found that only two theoretical studies considered explicitly ordered subsets. Instead, most studies interpret nestedness as a core of densely connected generalist species, surrounded by a periphery of specialist species attached to this core — a so-called core-periphery structure. Such a topological feature is generally perceived as a core-periphery structure in network science. Here, we argue that the concept of core-periphery may be more relevant for studies on mutualistic networks than the concept of nestedness, as ecologists are usually not interested in exploring in detail the ordered subsets that characterize nestedness but instead use nestedness to describe a topology with a core of densely linked generalist species surrounded by a sparsely linked periphery of specialists. To illustrate our arguments and the quantification of core-periphery structures, we calculate core-periphery and nestedness in a large publicly available dataset of mutualistic networks. We also describe the calculation of core-periphery structures, its relationship with nestedness, and provide the code inside the R packageeconetworkfor its calculation in mutualistic networks. We hope that our review will help ecologists to move beyond nestedness towards a more explicit representation of the structure of ecological networks.
Modeling the COVID-19 outbreaks and the effectiveness of the containment measures adopted across countries
Authors: De Brouwer Edward , Raimondi Daniele , Moreau Yves 
Published: April 2020

AbstractOn March 11, 2020, the World Health Organization declared the COVID-19 outbreak, originally started in China, a global pandemic. Since then, the outbreak has indeed spread across all continents, threatening the public health of numerous countries. Although the Case Fatality Rate (CFR) of COVID-19 is relatively low when optimal level of healthcare is granted to the patients, the high percentage of severe cases developing severe pneumonia and thus requiring respiratory support is worryingly high, and could lead to a rapid saturation of Intensive Care Units (ICUs). To overcome this risk, most countries enacted COVID-19 containment measures. In this study, we use a Bayesian SEIR epidemiological model to perform a parametric regression over the COVID-19 outbreaks data in China, Italy, Belgium, and Spain, and estimate the effect of the containment measures on the basic reproduction ratioR0.We find that the effect of these measures is detectable, but tends to be gradual, and that a progressive strengthening of these measures usually reduces theR0below 1, granting a decay of the outbreak. We also discuss the biases and inconsistencies present in the publicly available data on COVID-19 cases, providing an estimate for the actual number of cases in Italy on March 12, 2020. Lastly, despite the data and model’s limitations, we argue that the idea of “flattening the curve” to reach herd immunity is likely to be unfeasible.
Lack of Adipocyte Purinergic P2Y6Receptor Greatly Improves Whole Body Glucose Homeostasis
Authors: Jain Shanu , Pydi Sai P. , Toti Kiran S. , Robaye Bernard , Idzko Marco , Gavrilova Oksana , Wess Jürgen , Jacobson Kenneth A. 
Published: April 2020

ABSTRACTUridine diphosphate (UDP)-activated purinergic receptor P2Y6(P2Y6R) plays a crucial role in controlling energy balance through central mechanisms. However, P2Y6R’s roles in peripheral tissues regulating energy and glucose homeostasis remain unexplored. Here, we report the surprising novel finding that adipocyte-specific deletion of P2Y6R protects mice from diet-induced obesity, improving glucose tolerance and insulin sensitivity with reduced systemic inflammation. These changes were associated with reduced JNK signaling, and enhanced expression and activity of PPARα affecting downstream PGC1α levels leading to beiging of white fat. In contrast, P2Y6R deletion in skeletal muscle reduced glucose uptake resulting in impaired glucose homeostasis. Interestingly, whole body P2Y6R KO mice showed metabolic improvements similar to those observed with mice lacking P2Y6R only in adipocytes. Our findings provide compelling evidence that P2Y6R antagonists may prove useful for the treatment of obesity and type 2 diabetes.
The Effect of Sudanese Smokeless Tobacco (Toombak) using on Oral Microbiota
Authors: Abakar Mudathir Abdelshafea Abdelkareem , Omer Abdalazim Abubaker Ismail , Yousif Albashir Mosab Mustafa 
Published: April 2020

ABSTRACTBackgroundToombak,saffaandsaodare the common local name of Sudanese smokeless tobacco which used by large population in different regions in Sudan. That chemical nature of Toomback includes very high levels of carcinogenic substances, strong alkaline materials and microorganisms. The used of Toombak implying application of the highly addictive product in the mouth many times per day for long times differed from users to other.ObjectivesThe objective of this study was to study the effect of Toombak on the oral microbial flora (Microbiota).Materials and Methods100 buccal swabs were collected in this study, 50 swabs from Toombak users and 50 swabs from non Toombak users as control group. All the participants were non smokers. The swabs were cultured on Chocolate agar, Blood agar and Sabouraud agar and incubated aerobically for up to 7 days. Then colonial morphology, indirect microscopy and biochemical tests were used to identify the isolated organism.ResultsToomback shows inhibitory effect on theviridanas streptococciand the baccual swabs collected from toomback users show significant increase in number of mixed growth (P value 0.000/ likelihood ratio 43.24) and colonization of oral cavity withBacillus species(P value 0.000/ likelihood ratio 57.41),Aspergillus species(P value 0.003/ likelihood ratio 10.462) andAspergillus flavus(P value 0.036/ likelihood ratio 4.45).ConclusionToombak using is affecting the quality and quantity of the oral normal flora because it has inhibitory effect onviridians streptococci, leading to rising of new colonizing species such asBacillus speciesandAspergillus specieespecially aflatoxins producingAspergillus flavus. These changes in the microenvironment may affect the immunity and health of the Toombak users and may lead to serious oral and systemic health problems.