bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal Associations Between Discrimination, Neighborhood Social Cohesion, and Telomere Length: The Multi-Ethnic Study of Atherosclerosis
Authors: Hailu Elleni M , Lewis Tené T , Needham Belinda L , Lin Jue , Seeman Teresa E , Mujahid Mahasin S 
Published: July 2021

AbstractBackgroundWe aimed to examine if neighborhood social cohesion moderated longitudinal associations between baseline reports of discrimination and 10-year changes in leukocyte telomere length (LTL).MethodsData are from the Multi-Ethnic Study of Atherosclerosis (N = 1064; age range 45–84 years). Baseline discrimination was measured using the Major Experiences of Discrimination Scale (MDS; none, 1 domain, ≥2 domains) and the Experiences of Discrimination Scale (EDS; none, moderate, high). Neighborhood social cohesion at baseline was assessed via a community survey within census tract–defined neighborhoods. 10-year change in LTL was defined as regression to the mean-corrected 10-year difference in the ratio of telomeric DNA to a single-copy gene (T/S).ResultsIn linear mixed-effects models, we found that neighborhood social cohesion modified the effect of baseline reports of MDS on 10-year changes in LTL, independent of sociodemographic characteristics, health behaviors, and health conditions (p(χ 2) = .01). Among those residing in neighborhoods with low social cohesion, experiencing major discrimination in ≥2 domains was associated with faster LTL attrition over 10 years, compared to reporting no discrimination (β = −0.03; 95% confidence interval: −0.06, −0.003). We found no main associations for either discrimination measure and no interaction between EDS and neighborhood social cohesion.ConclusionsResults indicate that neighborhood social cohesion is an important dimension of the neighborhood context that may moderate the impact of major experiences of discrimination on telomere length attrition. These findings help advance our understanding of the integral role that neighborhood environments play in attenuating the effect of discrimination on accelerated cell aging.
Accelerated deciphering of the genetic architecture of agricultural economic traits in pigs using a low-coverage whole-genome sequencing strategy
Authors: Yang Ruifei , Guo Xiaoli , Zhu Di , Tan Cheng , Bian Cheng , Ren Jiangli , Huang Zhuolin , Zhao Yiqiang , Cai Gengyuan , Liu Dewu , Wu Zhenfang , Wang Yuzhe , Li Ning , Hu Xiaoxiang 
Published: July 2021

Abstract

Background
Uncovering the genetic architecture of economic traits in pigs is important for agricultural breeding. However, high-density haplotype reference panels are unavailable in most agricultural species, limiting accurate genotype imputation in large populations. Moreover, the infinitesimal model of quantitative traits implies that weak association signals tend to be spread across most of the genome, further complicating the genetic analysis. Hence, there is a need to develop new methods for sequencing large cohorts without large reference panels.

Results
We describe a Tn5-based highly accurate, cost- and time-efficient, low-coverage sequencing method to obtain 11.3 million whole-genome single-nucleotide polymorphisms in 2,869 Duroc boars at a mean depth of 0.73×. On the basis of these single-nucleotide polymorphisms, a genome-wide association study was performed, resulting in 14 quantitative trait loci (QTLs) for 7 of 21 important agricultural traits in pigs. These QTLs harbour genes, such as ABCD4 for total teat number and HMGA1 for back fat thickness, and provided a starting point for further investigation. The inheritance models of the different traits varied greatly. Most follow the minor-polygene model, but this can be attributed to different reasons, such as the shaping of genetic architecture by artificial selection for this population and sufficiently interconnected minor gene regulatory networks.

Conclusions
Genome-wide association study results for 21 important agricultural traits identified 14 QTLs/genes and showed their genetic architectures, providing guidance for genetic improvement harnessing genomic features. The Tn5-based low-coverage sequencing method can be applied to large-scale genome studies for any species without a good reference panel and can be used for agricultural breeding.
M2aia—Interactive, fast, and memory-efficient analysis of 2D and 3D multi-modal mass spectrometry imaging data
Authors: Cordes Jonas , Enzlein Thomas , Marsching Christian , Hinze Marven , Engelhardt Sandy , Hopf Carsten , Wolf Ivo 
Published: July 2021

Abstract

Background
Mass spectrometry imaging (MSI) is a label-free analysis method for resolving bio-molecules or pharmaceuticals in the spatial domain. It offers unique perspectives for the examination of entire organs or other tissue specimens. Owing to increasing capabilities of modern MSI devices, the use of 3D and multi-modal MSI becomes feasible in routine applications—resulting in hundreds of gigabytes of data. To fully leverage such MSI acquisitions, interactive tools for 3D image reconstruction, visualization, and analysis are required, which preferably should be open-source to allow scientists to develop custom extensions.

Findings
We introduce M2aia (MSI applications for interactive analysis in MITK), a software tool providing interactive and memory-efficient data access and signal processing of multiple large MSI datasets stored in imzML format. M2aia extends MITK, a popular open-source tool in medical image processing. Besides the steps of a typical signal processing workflow, M2aia offers fast visual interaction, image segmentation, deformable 3D image reconstruction, and multi-modal registration. A unique feature is that fused data with individual mass axes can be visualized in a shared coordinate system. We demonstrate features of M2aia by reanalyzing an N-glycan mouse kidney dataset and 3D reconstruction and multi-modal image registration of a lipid and peptide dataset of a mouse brain, which we make publicly available.

Conclusions
To our knowledge, M2aia is the first extensible open-source application that enables a fast, user-friendly, and interactive exploration of large datasets. M2aia is applicable to a wide range of MSI analysis tasks.
From clinical trials to clinical practice: How long are drugs tested and then used by patients?
Authors: Yuan Chi , Ryan Patrick B , Ta Casey N , Kim Jae Hyun , Li Ziran , Weng Chunhua 
Published: July 2021

Abstract

Objective
Evidence is scarce regarding the safety of long-term drug use, especially for drugs treating chronic diseases. To bridge this knowledge gap, this research investigated the differences in drug exposure between clinical trials and clinical practice.

Materials and Methods
We extracted drug follow-up times from clinical trials in ClinicalTrials.gov and compared the difference between clinical trials and real-world usage data for 914 drugs taken by 96 645 927 patients.

Results
A total of 17.5% of drugs had longer median exposure in practice than in trials, 6% of patients had extended exposure to at least 1 drug, and drugs treating nervous system disorders and cardiovascular diseases were the most common among drugs with high rates of extended exposure.

Conclusions
For most of patients, the drug use length is shorter than the tested length in clinical trials. Still, a remarkable number of patients experienced extended drug exposure, particularly for drugs treating nervous system disorders or cardiovascular disorders.
Determination of β-Galactooligosaccharides (GOS) in Infant Formula and Adult Nutritionals: Single-Laboratory Validation, First Action 2021.01
Authors: Cuany Denis , Andetsion Fikrey , Fontannaz Xavier , Bénet Thierry , Spichtig Véronique , Austin Sean 
Published: July 2021

Abstract

Background
β-Galactooligosaccharides (GOS) are typically used in infant formula and adult nutritionals as a source of nondigestible oligosaccharides, which may bring beneficial effects through modulation of the gut microbiota. However, suitable methods for the determination of GOS in products with a high background of lactose do not exist.

Objective
The aim of this work was to develop a method suitable for the determination of GOS in infant formula and adult nutritionals and demonstrate suitability through single laboratory validation.

Methods
Reducing oligosaccharides are labeled with 2-aminobenzamide (2AB), separated by hydrophilic interaction LC, and determined assuming that all oligosaccharides give an equimolar response in the detector. The same sample is analyzed a second time after treatment with β-galactosidase to remove GOS. The difference in the determined oligosaccharides between the two measurements will be the GOS content of the sample. The method was validated in a single laboratory on infant formula and adult nutritionals.

Results
Recoveries were in the range 91.5–102%, relative standards of deviation (RSDr) were in the range 0.7–5.99%, and one sample had an RSDr of 8.30%. Except for the one sample with an RSDr of 8.30%, the performance is within the requirements outlined in the Standard Method Performance Requirements, which specifies recoveries in the range 90–110% and RSDr of below 6%.

Conclusions
The method is suitable for the determination of GOS in infant formula and adult nutritionals.

Highlights
A method has been developed which is suitable for the determination of GOS in products with a high background concentration of lactose (infant fromula and adult nutritionals). The method does not require access to the GOS ingredient used for the production of the finished product. It is also possible to separately quantify the amount of GOS containing three or more monomeric units in order to support dietary fibre analysis.
Investigating pig survival in different production phases using genomic models
Authors: Leite Natália Galoro , Knol Egbert Frank , Garcia André Luiz Seccatto , Lopes Marcos Soares , Zak Louisa , Tsuruta Shogo , Silva Fabyano Fonseca e , Lourenco Daniela 
Published: July 2021

Abstract
Pig survival is an economically important trait with relevant social welfare implications, thus standing out as an important selection criterion for the current pig farming system. We aimed to estimate (co)variance components for survival in different production phases in a crossbred pig population as well as to investigate the benefit of including genomic information through single-step genomic best linear unbiased prediction (ssGBLUP) on the prediction accuracy of survival traits compared with results from traditional BLUP. Individual survival records on, at most, 64,894 crossbred piglets were evaluated under two multi-trait threshold models. The first model included farrowing, lactation, and combined postweaning survival, whereas the second model included nursery and finishing survival. Direct and maternal breeding values were estimated using BLUP and ssGBLUP methods. Furthermore, prediction accuracy, bias, and dispersion were accessed using the linear regression validation method. Direct heritability estimates for survival in all studied phases were low (from 0.02 to 0.08). Survival in preweaning phases (farrowing and lactation) was controlled by the dam and piglet additive genetic effects, although the maternal side was more important. Postweaning phases (nursery, finishing, and the combination of both) showed the same or higher direct heritabilities compared with preweaning phases. The genetic correlations between survival traits within preweaning and postweaning phases were favorable and strong, but correlations between preweaning and postweaning phases were moderate. The prediction accuracy of survival traits was low, although it increased by including genomic information through ssGBLUP compared with the prediction accuracy from BLUP. Direct and maternal breeding values were similarly accurate with BLUP, but direct breeding values benefited more from genomic information. Overall, a slight increase in bias was observed when genomic information was included, whereas dispersion of breeding values was greatly reduced. Combined postweaning survival presented higher direct heritability than in the preweaning phases and the highest prediction accuracy among all evaluated production phases, therefore standing out as a candidate trait for improving survival. Survival is a complex trait with low heritability; however, important genetic gains can still be obtained, especially under a genomic prediction framework.
Signal-Separated Quantification of γ-Hydroxybutyrate with Liquid Chromatography–Tandem Mass Spectrometry in Human Urine and Serum as an Improvement of the Analyte Adduct Ion-Based Quantification
Authors: Dziadosz Marek , Klintschar Michael , Teske Jörg 
Published: July 2021

Abstract
The aim of the work was the development and validation of a liquid chromatography–tandem mass spectrometry (LC–MS-MS) γ-hydroxybutyrate (GHB) quantification method in urine and human serum by the use of the analyte adduct ion formation strategy. A combined detection with a conventional precursor ion in the negative electrospray mode and additionally GHB adduct ions with both sodium acetate and lithium acetate was in focus. Therefore, GHB quantification was based on separated MS-MS signals. Two tandem mass spectrometers representing different MS-MS generations (Sciex API 4000 QTrap and Sciex API 5500 QTrap) were used for method validation and comparison. Shimadzu HPLC systems equipped with a Luna 5-µm C18 (2) 100 A, 150-mm × 2-mm analytical column were successfully applied for sample analyses. Infusion experiments were performed for adduct identification and analyte detection optimization. Sample preparation could be limited to a simple and fast protein precipitation/sample dilution. An effective signal-separated GHB quantification with three independent precursor ions representing separated areas of the mass spectrum was developed, validated according to forensic guidelines and applied in the routine. The developed and applied strategy resulted in a higher safety factor for the analyte quantification performed in the forensic toxicology. A relevant analytical improvement could be achieved with this alternative adduct-based GHB analysis since a good correlation of analyte concentrations calculated on the basis of separated signals was stated as useful analytical information.
‘Antisocial Behaviour, Unfriendly Relations’: Assessing the Contemporary Value of the Categories of Unfriendly Acts and Retorsion in International Law
Authors: McDonald Neil , McLeod Anna 
Published: July 2021

Abstract
This article considers the international law categories of unfriendly acts and retorsion in the modern context. To date, these categories articulating the freedoms that States enjoy below the threshold of international wrongfulness have received little attention in academic debate. But we consider both categories are of increasing relevance in the context of modern international conflict (in the broadest sense) and inter-State competition, particularly in relation to the regulation of hostile cyber activity between States. Unfriendly acts denotes State activity which, while lawful as a matter of international law, would nonetheless not be welcomed by the States it targets. Retorsion covers another sub-set of lawful but unfriendly State activity, substantively the same as unfriendly acts but done in response to prior unwelcome acts of other States. Having defined these categories, including by reference to a survey of contemporary State practice and judicial treatment, this article then considers why their utility and relevance to States are increasing. The article ends on the cautionary note that while unfriendly acts and retorsion may be increasingly necessary and desirable to States as international law tools as hostile activity occupies more of the space below forcible acts, they equally need to be properly understood and ‘handled with care’ by international lawyers, to ensure they are not bestowed with legal characteristics they do not possess, unduly constraining States in the process. The risk of misuse of these categories by States also needs to be kept in mind.
Relative Precision of the Sibship and LD Methods for Estimating Effective Population Size With Genomics-Scale Datasets
Authors: Waples Robin S 
Published: July 2021

Abstract
Computer simulations were used to compare relative precision of 2 widely used single-sample methods for estimating effective population size (Ne)—the sibship method and the linkage disequilibrium (LD) method. Emphasis is on performance when thousands of gene loci are used, which now can easily be achieved even for nonmodel species. Results show that unless Ne is very small, if at least 500–2000 diallelic loci are used, precision of the LD method is higher than the maximum possible precision for the sibship method, which occurs when all sibling relationships have been correctly identified. Results also show that when precision is high for both methods, their estimates of Ne are highly and positively correlated, which limits additional gains in precision that might be obtained by combining information from the 2 estimators.
Emerging neurotropic features of SARS-CoV-2
Authors: Zhan Wen-Rong , Huang Jing , Zeng Peng-Ming , Tian Wei-Ya , Luo Zhen-Ge 
Published: July 2021

Abstract
The prevailing coronavirus disease-19 (COVID-19) caused by a novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has presented some neurological manifestations including hyposmia, hypogeusia, headache, stroke, encephalitis, Guillain–Barre syndrome, and some neuropsychiatric disorders. Although several cell types in the brain express angiotensin-converting enzyme-2 (ACE2), the main SARS-CoV-2 receptor, and other related proteins, it remains unclear whether the observed neurological manifestations are attributed to virus invasion into the brain or just comorbidities caused by dysregulation of systemic factors. Here, we briefly review the neurological manifestations of SARS-CoV-2, summarize recent evidence for the potential neurotropism of SARS-CoV-2, and discuss the potential mechanisms of COVID-19-associated neurological diseases.
The virological impacts of SARS-CoV-2 D614G mutation
Authors: Wang Chenxi , Zheng You , Niu Zubiao , Jiang Xiaoyi , Sun Qiang 
Published: July 2021

Abstract
The coronavirus diseases 2019 (COVID-19) caused by the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 has caused more than 140 million infections worldwide by the end of April 2021. As an enveloped single-stranded positive-sense RNA virus, SARS-CoV-2 underwent constant evolution that produced novel variants carrying mutation conferring fitness advantages. The current prevalent D614G variant, with glycine substituted for aspartic acid at position 614 in the spike glycoprotein, is one of such variants that became the main circulating strain worldwide in a short period of time. Over the past year, intensive studies from all over the world had defined the epidemiological characteristics of this highly contagious variant and revealed the underlying mechanisms. This review aims at presenting an overall picture of the impacts of D614G mutation on virus transmission, elucidating the underlying mechanisms of D614G in virus pathogenicity, and providing insights into the development of effective therapeutics.
Efficacy of Brincidofovir in Pediatric Stem Cell Transplant Recipients With Adenovirus Infections
Authors: Ehlert Karoline , Schulte Johannes H , Kühl Jörn-Sven , Lang Peter , Eggert Angelika , Voigt Sebastian 
Published: July 2021

Abstract

Background
Adenovirus (AdV) infections are of particular concern in pediatric hematopoietic stem cell transplantation (HSCT) recipients as therapeutic options are limited. Brincidofovir (BCV) is the lipid-conjugated pro-drug of cidofovir (CDV) with oral bioavailability and higher intracellular concentrations of the active drug.

Methods
In this retrospective, single-center analysis, we included allogeneic pediatric HSCT recipients with refractory AdV infections because of contraindications or insufficient response to CDV. Common posttransplant viruses were monitored at least weekly by PCR in blood, stool, and urine.

Results
Each of the 8 patients received 6 to 12 doses of BCV. BCV treatment was initiated between days +5 and +77. AdV DNAemia and intestinal AdV infection disappeared completely in 6/8 patients. Early AdV DNAemia before day +21 did not result in increased mortality. One patient with a systemic, acyclovir-resistant HSV-1 infection responded rapidly to BCV. Four patients did not survive. AdV infection-related death in 2 patients was accompanied by &gt;1 × 109/mL AdV copy numbers in the blood. Two more patients died of graft-vs-host disease and acute respiratory distress syndrome, respectively, both not related to AdV.

Conclusions
AdV DNAemia and intestinal infection subsided completely in 75% of pediatric HSCT recipients treated with BCV. AdV DNAemia exceeding 1 × 109/mL and a poor lymphocyte recovery of &lt;250/µL were associated with high mortality. Early AdV DNAemia before day +21, however, did not result in a worse outcome. Although access to BCV is currently suspended, further clinical trials are needed to clarify the role of BCV in HSCT recipients with AdV infections and its potential benefit in preventing AdV DNAemia in immunocompromised patients.
Economic assessment of urban space and blue-green infrastructure in Singapore
Authors: Lim Mabel , Xenarios Stefanos 
Published: July 2021

Abstract
The urban conglomeration has accentuated the role of urban greenery as a determinant factor for sustainable living, especially in highly dense cities. The country of Singapore has consistently attempted to develop and rehabilitate urban greenery by attempting to align the green space policy with the pursuit of better life quality. In this study, we assess the benefits arising from the rehabilitated Bishan-Ang Mo Kio (AMK) Park in north Singapore and the effects on economic welfare. The Bishan-AMK Park was initially constructed in the late 70 s as a drainage area for the avoidance of flooding incidents. In 2012, a pilot project was introduced to create a blue-green infrastructure (BGI) space for the provision of drainage and flood prevention but also for recreational and environmental improvement in the area. Yet, the benefits emerging from BGI are not well explored and still underestimated. To this extent, we evaluate selected services related to recreational, socio-cultural and tourism-related values by indicating the economic benefits from the introduction of BGI in condensed urban environments like Singapore. The findings indicate that the benefits deriving from the selected services could be within the range of US$100 million to US$220 million with a mean value of US$160 million per year by substantially contributing to human well-being. The assessment of environmental services can raise the awareness of residents and local authorities on the contribution of urban greenery to livelihoods and economic development in Singapore and similar densely populated areas.