bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic risk score has added value over initial clinical grading stage in predicting disease progression in age-related macular degeneration
Authors: Heesterbeek Thomas J. , de Jong Eiko K. , Acar Ilhan E. , Groenewoud Joannes M. M. , Liefers Bart , Sánchez Clara I. , Peto Tunde , Hoyng Carel B. , Pauleikhoff Daniel , Hense Hans W. , den Hollander Anneke I. 
Published: April 2019

AbstractSeveral prediction models for progression of age-related macular degeneration (AMD) have been developed, but the added value of using genetic information in those models in addition to clinical characteristics is ambiguous. In this prospective cohort study, we explored the added value of genetics using a genetic risk score (GRS) based on 52 AMD-associated variants, in addition to the clinical severity grading at baseline as quantified by validated drusen detection software, to predict disease progression in 177 AMD patients after 6.5 years follow-up. The GRS was strongly associated with the drusen coverage at baseline (P < 0.001) and both the GRS and drusen coverage were associated with disease progression. When the GRS was added as predictor in addition to the drusen coverage, R2 increased from 0.46 to 0.56. This improvement by the GRS was predominantly seen in patients with a drusen coverage <15%. In patients with a larger drusen coverage, the GRS had less added value to predict progression. Thus, genetic information has added value over clinical characteristics in predicting disease progression in AMD, but only in patients with a less severe disease stage. Patients with a high GRS should be made aware of their risk and could be selected for clinical trials for arresting progression.
Collective Motion as an Ultimate Effect in Crowded Selfish Herds
Authors: Yang Wen-Chi , Schmickl Thomas 
Published: April 2019

AbstractThe selfish herd hypothesis explains how social prey can assemble cohesive groups for maximising individual fitness. However, previous models often abstracted away the physical manifestation of the focal animals such that the influence of getting stuck in a crowded herd on individual adaptation was less intensively investigated. Here, we propose an evolutionary model to simulate the adaptation of egoistic social prey to predation given that individual mobility is strictly restrained by the presence of other conspecifics. In our simulated evolutionary races, agents were set to either be confined by neighbours or move to empty cells on the lattice, and the behavioural traits of those less exposed were selected and inherited. Our analyses show that under this crowded environment, cohesive and steady herds were consistently replaced by morphing and moving aggregates via the attempt of border agents to share predation risk with the inner members. This kind of collective motion emerges purely from the competition among selfish individuals regardless of any group benefit. Our findings reveal that including the crowding effect with the selfish herd scenario permits additional diversity in the predicted outcomes and imply that a wider set of collective animal behaviours are explainable purely by individual-level selection.
Bruch’s Membrane Thickness and Retinal Pigment Epithelium Cell Density in Experimental Axial Elongation
Authors: Dong Li , Shi Xu Han , Kang Yi Kun , Wei Wen Bin , Wang Ya Xing , Xu Xiao Lin , Gao Fei , Jonas Jost B. 
Published: April 2019

AbstractTo assess anatomical changes in eyes with progressive myopia, we morphometrically examined the eyes of guinea pigs with lens-induced axial elongation. Starting at an age of 3–4 weeks, guinea pigs in the experimental group (n = 20 animals) developed unilateral lens-induced axial elongation by wearing goggles for 5 weeks compared to a control group of 20 animals without intervention (axial length:8.91 ± 0.08 mm versus 8.74 ± 0.07 mm; P < 0.001). Five weeks after baseline, the animals were sacrificed, and the eyes enucleated. As measured histomorphometrically, Bruch’s membrane thickness was not significantly correlated with axial length in either group at the ora serrata (P = 0.41), equator (P = 0.41), midpoint between equator and posterior pole (MBEPP) (P = 0.13) or posterior pole (P = 0.89). Retinal pigment epithelium (RPE) cell density decreased with longer axial length at the MBEPP (P = 0.04; regression coefficient beta = −0.33) and posterior pole (P = 0.01; beta = −0.40). Additionally, the thickness of the retina and sclera decreased with longer axial length at the MBEPP (P = 0.01; beta = −0.42 and P < 0.001; beta = −0.64, respectively) and posterior pole (P < 0.001; beta = −0.51 and P < 0.001; beta = −0.45, respectively). Choroidal thickness decreased at the posterior pole (P < 0.001; beta = −0.51). Experimental axial elongation was associated with a thinning of the retina, choroid and sclera and a decrease in RPE cell density, most markedly at the posterior pole. Bruch’s membrane thickness was not related to axial elongation.
Identification and functional prediction of cold-related long non-coding RNA (lncRNA) in grapevine
Authors: Wang Pengfei , Dai Lingmin , Ai Jun , Wang Yongmei , Ren Fengshan 
Published: April 2019

AbstractPlant long non-coding RNA (lncRNA) undergoes dynamic regulation and acts in developmental and stress regulation. In this study, we surveyed the expression dynamics of lncRNAs in grapevine (Vitis vinifera L.) under cold stress using high-throughput sequencing. Two-hundred and three known lncRNAs were significantly up-regulated and 144 known lncRNAs were significantly down-regulated in cold-treated grapevine. In addition, 2 088 novel lncRNA transcripts were identified in this study, with 284 novel lncRNAs significantly up-regulated and 182 novel lncRNAs significantly down-regulated in cold-treated grapevine. Two-hundred and forty-two differentially expressed grapevine lncRNAs were predicted to target 326 protein-coding genes in a cis-regulatory relationship. Many differentially expressed grapevine lncRNAs targeted stress response-related genes, such as CBF4 transcription factor genes, late embryogenesis abundant protein genes, peroxisome biogenesis protein genes, and WRKY transcription factor genes. Sixty-two differentially expressed grapevine lncRNAs were predicted to target 100 protein-coding genes in a trans-regulatory relationship. The expression of overall target genes in both cis and trans-regulatory relationships were positively related to the expression of lncRNAs in grapevines under cold stress. We identified 31 known lncRNAs as 34 grapevine micro RNA (miRNA) precursors and some miRNAs may be derived from multiple lncRNAs. We found 212 lncRNAs acting as targets of miRNAs in grapevines, involving 150 miRNAs; additionally, 120 grapevine genes were predicted as targets of grapevine miRNAs and lncRNAs. We found one gene cluster that was up-regulated and showed the same expression trend. In this cluster, many genes may be involved in abiotic stress response such as WRKY, Hsf, and NAC transcription factor genes.
Eomes transcription factor is required for the development and differentiation of invariant NKT cells
Authors: Shimizu Kanako , Sato Yusuke , Kawamura Masami , Nakazato Hiroshi , Watanabe Takashi , Ohara Osamu , Fujii Shin-ichiro 
Published: April 2019

AbstractEomes regulates the differentiation of CD8+ T cells into effector and memory phases. However, its role in invariant (i)NKT cells remains unknown. Here, we show the impact of Eomes on iNKT cells in the thymus and peripheral tissue using conditional knockout (Eomes-cKO) mice. In the thymus, CD1d-tetramer+CD24+CD44−NK1.1−CD69+stage 0 iNKT cells express higher levels of Eomes than the other iNKT stages. We also found that Eomes regulates NKT1 cell differentiation predominantly. Interestingly, the expression of Eomes in the steady state is low, but can be upregulated after TCR stimulation. We also showed epigenetic changes in the Eomes locus after activation. In addition, vaccination of C57BL/6, but not Eomes-cKO mice with iNKT ligand-loaded dendritic cells generated KLRG1+iNKT cells in lung, characterized as effector memory phenotype by transcriptome profiling. Thus, Eomes regulates not only the differentiation of NKT1 cells in the thymus, but also their differentiation into memory-like KLRG1+iNKT cells in the periphery.
Calibration of the Dermal Advanced REACH Tool (dART) Mechanistic Model
Authors: McNally Kevin , Gorce Jean-Philippe , Goede Henk A , Schinkel Jody , Warren Nick 
Published: April 2019

Abstract
The dermal Advanced REACH Tool (dART) is a Tier 2 exposure modelling tool currently in development for estimating dermal exposure to the hands (mg min−1) for non-volatile liquid and solids-in-liquid products. The dART builds upon the existing ART framework and describes three mass transport processes [deposition (Dhands), direct emission and direct contact (Ehands), and contact transfer (Thands)] that may each contribute to dermal exposure. The mechanistic model that underpins the dART and its applicability domain has already been described in previous work. This paper describes the process of calibrating the mechanistic model such that the dimensionless score that results from encoding contextual information about a task into the determinants of the dART can be converted into a prediction of exposure (mg min−1). Furthermore, as a consequence of calibration, the uncertainty in a dART prediction may be quantified via a confidence interval. Thirty-six experimental studies were identified that satisfied the conditions of: (i) high-quality contextual information that was sufficient to confidently code the dART mechanistic model determinants; (ii) reliable exposure measurement data sets were available. From these studies, 40 exposure scenarios were subsequently developed. A non-linear log-normal mixed-effect model was fitted to the data set of Dhands, Ehands, and Thands scores and corresponding measurement data. The dART model was shown to be consistent with activities covering a broad range of tasks [spray applications, activities involving open liquid surfaces (e.g. dipping, mixing), handling of contaminated objects, spreading of liquid products, and transfer of products (e.g. pouring of liquid)]. Exposures resulting from a particular task were each dominated by one or two of the identified mass transport processes. As a consequence of calibration, an estimate of the uncertainty associated with a mechanistic model estimate is available. A 90% multiplicative interval is approximately a factor of six. This represents poorer overall precision than the (inhalation) ART model for dusts and vapours, although better than the ART model for mists. Considering the complexity of the conceptual model compared with the ART, the wide variety of exposure scenarios considered with differing dominant routes, and the particular challenges that result from the consideration of measurement data both above and beneath a protective glove, the precision of the calibrated dART mechanistic model is reasonable for well-documented exposure scenarios coded by experts. However, as the inputs to the model are based upon user judgement, in practical use, the reliability of predictions will be dependent upon both the competence of users and the quality of contextual information available on an exposure scenario.
Delayed onset Takotsubo syndrome following exercise ECG: a case report
Authors: Ghose Aruni , Banerjee Suvro 
Published: April 2019

Abstract

Background
Takotsubo syndrome usually occurs immediately following a physical or emotional trigger. In some cases, a triggering stress may not be evident. A delayed manifestation of the syndrome may account for such cases.

Case summary
An asymptomatic 69-year-old woman presented for a routine cardiac check-up, which revealed normal electrocardiogram (ECG), echocardiography, and exercise ECG. She did not complain of any chest pain during or immediately after the tests. After about 24 h, she developed chest pain for which she was admitted with the provisional diagnosis of acute coronary syndrome. ECG showed dynamic T-wave changes with QTc prolongation. Cardiac biomarkers were mildly elevated. Characteristic reversible left ventricular dysfunction in absence of coronary stenosis ultimately led to the diagnosis of Takotsubo syndrome.

Discussion
Our case represents a delayed occurrence of Takotsubo syndrome triggered by a treadmill exercise stress test, which manifested about 24 h following the stressor. Such delayed manifestation may account for those cases of Takotsubo syndrome where no immediate triggering stressor is evident.
Addressing the Diversity–Validity Dilemma Using Situational Judgment Tests
Authors: Juster Fern R. , Baum Robin Camhi , Zou Christopher , Risucci Don , Ly Anhphan , Reiter Harold , Miller D. Douglas , Dore Kelly L. 
Published: April 2019

Purpose
To examine the magnitudes of score differences across different demographic groups for three academic (grade point average [GPA], old Medical College Admission Test [MCAT], and MCAT 2015) and one nonacademic (situational judgment test [SJT]) screening measures and one nonacademic (multiple mini-interview [MMI]) interview measure (analysis 1), and the demographic implications of including an SJT in the screening stage for the pool of applicants who are invited to interview (analysis 2).

Method
The authors ran the analyses using data from New York Medical College School of Medicine applicants from the 2015–2016 admissions cycle. For analysis 1, effect sizes (Cohen d) were calculated for GPA, old MCAT, MCAT 2015, CASPer (an online SJT), and MMI. Comparisons were made across gender, race, ethnicity (African American, Hispanic/Latino), and socioeconomic status (SES). For analysis 2, a series of simulations were conducted to estimate the number of underrepresented in medicine (UIM) applicants who would have been invited to interview with different weightings of GPA, MCAT, and CASPer scores.

Results
A total of 9,096 applicants were included in analysis 1. Group differences were significantly smaller or reversed for CASPer and MMI compared with the academic assessments (MCAT, GPA) across nearly all demographic variables/indicators. The simulations suggested that a higher weighting of CASPer may help increase gender, racial, and ethnic diversity in the interview pool; results for low-SES applicants were mixed.

Conclusions
The inclusion of an SJT in the admissions process has the potential to widen access to medical education for a number of UIM groups.
Preanalytical Stability of Piperacillin, Tazobactam, Meropenem, and Ceftazidime in Plasma and Whole Blood Using Liquid Chromatography–Tandem Mass Spectrometry
Authors: Mortensen Janni S. , Jensen Berit P. , Zhang Mei , Doogue Matthew 
Published: April 2019

Background:
Therapeutic drug monitoring (TDM) is increasingly used to optimize the dosing of beta-lactam antibiotics in critically ill patients. However, beta-lactams are inherently unstable and degrade over time. Hence, patient samples need to be appropriately handled and stored before analysis to generate valid results for TDM. The appropriate handling and storage conditions are not established, with few and conflicting studies on the stability of beta-lactam antibiotics in clinical samples. The aim of this study was to assess the preanalytical stability of piperacillin, tazobactam, meropenem, and ceftazidime in human plasma and whole blood using a liquid chromatography–tandem mass spectrometry method for simultaneous quantification.

Methods:
A reverse phase liquid chromatography–tandem mass spectrometry method for the quantification of piperacillin, tazobactam, meropenem, and ceftazidime in plasma after protein precipitation was developed and validated. The preanalytical stability of these beta-lactams was assessed in EDTA- and citrate-anticoagulated plasma at 24, 4, and −20°C. The whole blood stability of the analytes in EDTA-anticoagulated tubes was assessed at 24°C. Stability was determined by nonlinear regression analysis defined by the lower limit of the 95th confidence interval of the time to 15% of degradation.

Results:
Based on the lower limit of the 95th confidence interval of the time to 15% of degradation, piperacillin, tazobactam, meropenem, and ceftazidime were stable in EDTA-anticoagulated plasma for at least 6 hours at 24°C, 3 days at 4°C, and 4 days at −20°C. Stability in EDTA- and citrate-anticoagulated plasma was similar. Stability in whole blood was similar to plasma at 24°C.

Conclusions:
Plasma samples for the TDM of piperacillin, tazobactam, meropenem, and ceftazidime should be processed within 6 hours if kept at room temperature and within 3 days if kept at 4°C. All long-term storage of samples should be at −80°C.
Modulation of DNA polymerase IV activity by UmuD and RecA* observed by single-molecule time-lapse microscopy
Authors: Henrikus Sarah S. , McGrath Amy E. , Jergic Slobodan , Ritger Matthew L. , Pham Phuong T. , Wood Elizabeth A. , Goodman Myron F. , Cox Michael M. , van Oijen Antoine M. , Ghodke Harshad , Robinson Andrew 
Published: April 2019

AbstractDNA polymerase IV (pol IV) is expressed at increased levels inEscherichia colicells suffering high levels of DNA damage. In a recent single-molecule imaging study, we demonstrated that elevating the pol IV concentration is not sufficient to provide access to binding sites on the nucleoid, suggesting that other factors may recruit pol IV to its substrates once the DNA becomes damaged. Here we extend this work, investigating the proteins UmuD and RecA as potential modulators of pol IV activity. UmuD promotes long-lived association of pol IV with the nucleoid, whereas its cleaved form, UmuD’, which accumulates in DNA-damaged cells, inhibits binding. In agreement with proposed roles for pol IV in homologous recombination, up to 40% of pol IV foci colocalise with a probe for RecA* nucleoprotein filaments in ciprofloxacin-treated cells. A hyperactive RecA mutant,recA(E38K), allows pol IV to bind the nucleoid even in the absence of exogenous DNA damage.In vitro,RecA(E38K) forms RecA*-like structures that can recruit pol IV, even on double-stranded DNA, consistent with a physical interaction between RecA and pol IV. Together, the results indicate that UmuD and RecA modulate the binding of pol IV to its DNA substrates, which frequently coincide with RecA* structures.
Temporal Effects on Radiation Responses in Nonhuman Primates: Identification of Biofluid Small Molecule Signatures by Gas Chromatography – Mass Spectrometry Metabolomics
Authors: Pannkuk Evan L. , Laiakis Evagelia C. , Girgis Michael , Dowd Sarah E. , Dhungana Suraj , Nishita Denise , Bujold Kim , Bakke James , Gahagen Janet , Authier Simon , Chang Polly , Fornace Albert J. 
Published: April 2019

AbstractWhole body exposure to ionizing radiation (IR) (> 0.7 Gy) damages tissues leading to a range of physical symptoms contributing to acute radiation syndrome (ARS). Radiation biodosimetry aims to determine characteristic early biomarkers indicative of radiation exposure (generally at doses > 2 Gy) and is a necessity for effective triage in the event of an unanticipated radiological incident and emergency preparedness. Radiation metabolomics can address this aim by assessing metabolic perturbations following various emergency scenarios (e.g., elapsed time to medical care, absorbed dose, combined injury). Gas chromatography – mass spectrometry (GC-MS) is a standardized platform ideal for chromatographic separation, identification, and quantification of metabolites to discriminate molecular signatures that can be utilized in assessing radiation injury. We performed GC time-of-flight (TOF) MS for global profiling of nonhuman primate (NHP) urine and serum samples up to 60 d after a single 4 Gy γ-ray total body exposure. Multivariate statistical analysis showed a higher separation of groups from urine signatures vs. serum signatures. We identified biofluid markers involved in amino acid, lipid, purine, and serotonin metabolism, some of which may indicate host microbiome dysbiosis. Sex differences were observed amino acid fold changes in serum samples. Additionally, we explored mitochondrial dysfunction by analysis of tricarboxylic acid (TCA) intermediates with a GC tandem quadrupole (TQ) MS platform in samples collected in a time course during the first week (1, 3, 5, and 7 d) after exposure. By adding this temporal component to our previous work exploring dose effects at a single time point of 7 d, we observed the highest fold changes occurring at 3 d, returning closer to basal levels by 7 d. These results emphasize the utility of both MS-based metabolomics for biodosimetry and complementary analytical platforms for increased metabolome coverage.
The First Report on Cryptococcus Profiles of Isolates from Patients Attending Dr George Mukhari Academic Hospital, South Africa
Authors: Jiyane Elliot Zwelibanzi , Nemarude Mis Leah , Nchabeleng Maphoshane 
Published: April 2019

ABSTRACTIntroductionCryptococcosis is a fungal opportunistic infection that is vastly diagnosed among immune-compromised patients. Reduced susceptibility on commonly used antifungals is of concern. In the communities served by Dr. George Mukhari Tertiary (DGMT-Laboratory) Laboratory is not available.MethodologyE-test method was used to determine if isolates with reduced susceptibility to antifungals fluconazole, voriconazole and amphotericin-B had emerged. A multiplex Polymerase Chain Reaction (PCR) method was used to further identify serotypes that are circulating at Dr. George Mukhari Tertiary (DGMT-Hospital) Hospital.ResultsE-test strips were interpreted as resistance, intermediate or susceptible in relation to each serotype identified. Of the 50 incident isolates tested, 100% were inhibited by both voriconazole and amphotericin-B. Fluconazole was resistance to 50% of incident isolates.ConclusionC. neoformansserotype A is the predominant serotype in the area served by DGMT-Laboratory, accounting for 96% of the isolates. It is important for public health to continuously monitor resistance emergence.
Microbial Similarity Between Students in a Common Dormitory Environment Reveals the Forensic Potential of Individual Microbial Signatures
Authors: Richardson Miles , Gottel Neil , Gilbert Jack A , Lax Simon 
Published: April 2019

AbstractThe microbiota of the built environment is an amalgamation of both human and environmental sources. While human sources have been examined within single-family households or in public environments, it is unclear what effect a large number of cohabitating people have on the microbial communities of their shared environment. We sampled the public and private spaces of a college dormitory, disentangling individual microbial signatures and their impact on the microbiota of common spaces. We compared multiple methods for marker gene sequence clustering, and found that Minimum Entropy Decomposition (MED) was best able to distinguish between the microbial signatures of different individuals, and was able to uncover more discriminative taxa across all taxonomic groups. Further, weighted UniFrac- and random forest-based graph analyses uncovered two distinct spheres of hand or shoe associated samples. For hand-associated samples, connection between cliques was enriched for hands, implicating them as a primary means of transmission. By contrast, shoe-associated samples were found to be freely interacting, with individual shoes more connected to each other than to the floors they interact with. Individual interactions were highly dynamic, with groups of samples originating from individuals clustering freely with other individuals, while all floor and shoe samples consistently clustered together.ImportanceHumans leave behind a microbial trail, regardless of intention. This may allow for the identification of individuals based on the ‘microbial signatures’ they shed in built environments. In a shared living environment, these trails intersect, and through interaction with common surfaces may become homogenized, potentially confounding our ability to link individuals to their associated microbiota. We sought to understand the factors that influence the mixing of individual signatures, and how best to process sequencing data to best tease apart these signatures.