bluuebunny/crossref_metadata_2025_split huggingface dataset:
2H SOLCOR: A novel tool for reducing volume variation as a source of error in external standard quantitative NMR
Authors: Ewanicki Jason , Kim William , Wang Wei 
Published: April 2020

AbstractTube to tube volume difference presents a challenge in obtaining correct external standard quantitative NMR (esqNMR) results. Deuterium (2H) NMR is easily observable, intrinsically quantitative, present in all samples, free of interfering signals, and insensitive to probe tune/match and sample saltiness. These properties make 2H peak integral an ideal parameter in esqNMR for correcting volume differences between the reference standard and analyte. We demonstrate a novel and practical technique abbreviated as “2H SOLCOR” (2H SOLvent CORrected), where the 2H peak integral from the solvent is used as a universal internal standard to correct volume variations in NMR tubes, thereby improving accuracy and precision of esqNMR method. Herein, this simple yet effective technique is described, and practical considerations for successful implementation are presented. 2H SOLCOR can be applied anywhere esqNMR is used, including where precious samples need to be accurately quantified for qualification as an authentic analytical standard.
Gremlin 1 depletion in vivo causes severe enteropathy and bone marrow failure
Authors: Rowan Simon C , Jahns Hanne , Mthunzi Liberty , Piouceau Lucie , Cornwell Joanna , Doody Róisín , Frohlich Stephen , Callanan John J , McLoughlin Paul 
Published: April 2020

AbstractThe intestinal epithelium is perpetually renewed from a stem cell niche in the base of crypts to maintain a healthy bowel mucosa. Exit from this niche and maturation of epithelial cells requires tightly controlled gradients in BMP signalling, progressing from low BMP signalling at the crypt base to high signalling at the luminal surface. The BMP antagonist gremlin 1 (Grem1) is highly expressed by subepithelial myofibroblasts adjacent to the intestinal crypts but its role in regulating the stem cell niche and epithelial renewal in vivo has not been explored. To explore the effects of Grem1 loss in adulthood following normal growth and development, we bred mice (ROSA26CreER‐Grem1
flx/flx) in which Grem1 could be deleted by tamoxifen administration. While Grem1 remained intact, these mice were healthy, grew normally, and reproduced successfully. Following Grem1 depletion, the mice became unwell and were euthanised (at 7–13 days). Post‐mortem examination revealed extensive mucosal abnormalities throughout the small and large intestines with failure of epithelial cell replication and maturation, villous atrophy, and features of malabsorption. Bone marrow hypoplasia was also observed with associated early haematopoietic failure. These results demonstrate an essential homeostatic role for gremlin 1 in maintaining normal bowel epithelial function in adulthood, suggesting that abnormalities in gremlin 1 expression can contribute to enteropathies. We also identified a previously unsuspected requirement for gremlin 1 in normal haematopoiesis. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Dosing: The key to precision plasma oncology
Authors: Dai Xiaofeng , Zhang Zhifa , Zhang Jianying , Ostrikov Kostya (Ken) 
Published: April 2020

AbstractCold atmospheric plasma (CAP) is an emerging oncotherapeutic approach with selectivity for cancer cells. It can induce different cell survival and death programs depending on the CAP dose, and it can function as a neo or adjuvant therapy against cancer. Establishing an evaluation system for precise CAP dosing is the key to make plasma therapy act alone or in combination with other therapeutic modalities for achieving desirable treatment responses. By classifying CAP‐induced effects and associating them with the dosing of plasma‐reactive agents, we identify opportunities for CAP to contribute to precision oncotherapy and discuss challenges en route to clinical applications. We emphasize the importance of dosing in plasma medicine and encourage cross‐disciplinary collaborations to develop suitable dosing metrics.
Two fatty acid‐binding proteins expressed in the intestine interact differently with endocannabinoids
Authors: Lai May Poh , Katz Francine S. , Bernard Cédric , Storch Judith , Stark Ruth E. 
Published: April 2020

AbstractTwo different members of the fatty acid‐binding protein (FABP) family are found in enterocyte cells of the gastrointestinal system, namely liver‐type and intestinal fatty acid‐binding proteins (LFABP and IFABP, also called FABP1 and FABP2, respectively). Striking phenotypic differences have been observed in knockout mice for either protein, for example, high fat‐fed IFABP‐null mice remained lean, whereas LFABP‐null mice were obese, correlating with differences in food intake. This finding prompted us to investigate the role each protein plays in directing the specificity of binding to ligands involved in appetite regulation, such as fatty acid ethanolamides and related endocannabinoids. We determined the binding affinities for nine structurally related ligands using a fluorescence competition assay, revealing tighter binding to IFABP than LFABP for all ligands tested. We found that the head group of the ligand had more impact on binding affinity than the alkyl chain, with the strongest binding observed for the carboxyl group, followed by the amide, and then the glycerol ester. These trends were confirmed using two‐dimensional 1H–15N nuclear magnetic resonance (NMR) to monitor chemical shift perturbation of the protein backbone resonances upon titration with ligand. Interestingly, the NMR data revealed that different residues of IFABP were involved in the coordination of endocannabinoids than those implicated for fatty acids, whereas the same residues of LFABP were involved for both classes of ligand. In addition, we identified residues that are uniquely affected by binding of all types of ligand to IFABP, suggesting a rationale for its tighter binding affinity compared with LFABP.
Stand ages adjust fluctuating patterns of soil respiration and decrease temperature sensitivity after revegetation
Authors: Tong Di , Xiao Haibing , Li Zhongwu , Nie Xiaodong , Huang Jinquan 
Published: April 2020

AbstractRevegetation plays an essential role in controlling soil erosion and influencing soil respiration (Rs) by changing the vegetation coverage and soil biochemical characteristics. Soil respiration and its temperature sensitivity (Q10) have been studied comprehensively. However, the effect of stand age after revegetation on Rs and Q10 remains unclear. We selected four stands (i.e., eroded hillslopes [EBs] and 0‐ to 5‐yr, 5‐ to 10‐yr, and 10‐yr apple orchards) to investigate the changes in Rs and Q10 values. A soil CO2 flux system (Li‐8100) was used to measure Rs in situ from July 2018 to December 2018 in the Luoyugou watershed on the Chinese Loess Plateau. The average Rs rate showed decreased and increased periods with stand age. Changes in Rs were mainly induced by soil nutrient status, which accounted for 44.5% of the heavy weight in principal component analysis. The Q10 values decreased with stand age after revegetation and followed the order EB (4.96) > 0‐ to 5‐yr apple orchard (3.02) > 5‐ to 10‐yr apple orchard (2.25) > 10‐yr apple orchard (1.67). Our results suggest that Rs is substantially influenced by fungal richness and soil microbial biomass carbon (C), and the Q10 values are explained by the nonmetric multidimensional scaling ordinations of bacteria, which in turn are influenced by labile organic C. We demonstrate that converting EBs to apple orchards could be an effective way to decrease Rs and Q10 values. The fluctuating patterns of Rs with stand age should be considered when accurately evaluating the global C balance and predicting future climate change.
Safety and efficacy of intrarenal arterial autologous CD34+ cell transfusion in patients with chronic kidney disease: A randomized, open-label, controlled phase II clinical trial
Authors: Yang Chih-Chao , Sung Pei-Hsun , Cheng Ben-Chung , Li Yi-Chen , Chen Yi-Ling , Lee Mel S. , Yip Hon-Kan 
Published: April 2020

Abstract

Background
This was a randomized, open-label, controlled phase II clinical trial to investigate the safety, efficacy, and outcomes of intrarenal artery infusion of autologous peripheral-blood-derived CD34+ cells for patients with chronic kidney disease (CKD; ie, stage III or IV).

Materials and Methods
Between October 2016 and July 2018, 52 consecutive patients with CKD at stage III or IV were randomly allocated into a treatment group (TG; 2.5 × 107 cells for each intrarenal artery; n = 26) and a control group (CG; standardized pharmacotherapy only; n = 26). The primary endpoints included safety and change of creatinine level/creatinine clearance. The secondary endpoints were 12-month combined unfavorable clinical outcomes (defined as dialysis or death), improvement in proteinuria, and CD34+ cell-related adverse events.

Results
All patients were uneventfully discharged after CD34+ cell therapy. The baseline endothelial progenitor cell (EPC) populations did not differ between TG and CG (P &gt; .5). Flow cytometric analysis showed increases in circulating EPC (ie, CD34+KDR+CD45dim/ CD34+CD133+CD45dim/CD31+CD133+CD45dim/CD34+CD133+KDR+/CD133+) and hematopoietic stem cell (CD34+) populations after granulocyte-colony stimulating factor treatment (all P &lt; .001). Besides, Matrigel assay of angiogenesis was also significantly enhanced (all P &lt; .001). Renal-venous blood samplings (ie, at 0, 5, 10, and 30 minutes after CD34+ cell infusion) demonstrated significant progressive increases in EPC level (P for trend &lt;.001) among the TG patients. One-year combined unfavorable clinical outcomes were significantly lower in TG than those in CG (0% [0] vs 13.3% [4], P = .038). By 12 months after CD34+ cell therapy, circulating creatinine level, ratio of urine protein to urine creatinine, and creatinine clearance showed no difference between TG and CG (all P &gt; .1).

Conclusion
CD34+ cell therapy was safe and improved 1-year outcome.

Significance statement The results of this phase II clinical trial provide important clinical information about the impact of intrarenal artery infusion of autologous peripheral-blood-derived CD34+ cells for patients with chronic kidney disease.
Multihazard fragility assessment of steel‐concrete composite frame structures with buckling‐restrained braces subjected to combined earthquake and wind
Authors: Li Hong‐Nan , Liu Yang , Li Chao , Zheng Xiao Wei 
Published: April 2020

SummaryEngineering structures may inevitably be subjected to multiple natural hazards (such as earthquakes and winds) during their life cycles. This paper presents an efficient multihazard fragility methodology based on the structural demand models. The approach is applied to two steel‐concrete composite frame structures (SCCFSs), with and without buckling‐restrained braces (BRBs), aiming to evaluate the effect of BRBs on controlling the structural responses and fragilities under the combined earthquake and wind loads. In total, 120 earthquake records are selected, and 120 sets of wind drag force time histories are simulated by considering the spatial variation along the height of the exemplar building. The combined “earthquake–wind” events are stochastically assembled, in which the intensities of these two hazards are modeled using the Monte Carlo simulation. The OpenSees platform is employed to calculate the dynamic responses of the SCCFSs with and without BRBs under simultaneous earthquake and wind loads. The goodness of fits of the first‐, second‐, and third‐order polynomial in predicting the structural demand are evaluated, and the optimal polynomial is employed to generate the multihazard fragility surfaces at different damage states. The numerical results indicate that the structural responses and fragilities under the combined earthquake and wind are higher than those under an individual hazard, while the influencing extent varies with the relative intensities of these two hazards. The impact of multiple hazards and the control effect of BRBs on the structural responses and fragilities are systematically quantified and discussed in details.
Characterization of an HLA-restricted and human cytomegalovirus-specific antibody repertoire with therapeutic potential
Authors: Bewarder Moritz , Held Gerhard , Thurner Lorenz , Stilgenbauer Stephan , Smola Sigrun , Preuss Klaus-Dieter , Carbon Gabi , Bette Birgit , Christofyllakis Konstantinos , Bittenbring Joerg Thomas , Felbel Arne , Hasse Alexander , Murawski Niels , Kaddu-Mulindwa Dominic , Neumann Frank 
Published: April 2020

AbstractWith an infection rate of 60–90%, the human cytomegalovirus (HCMV) is very common among adults but normally causes no symptoms. When T cell-mediated immunity is compromised, HCMV reactivation can lead to increased morbidity and mortality. HCMV antigens are processed and presented as peptides on the cell surface via HLA I complexes to the T cell receptor (TCR) of T cells. The generation of antibodies against HCMV peptides presented on HLA complexes (TCR-like antibodies) has been described, but is without therapeutic applications to date due to the polygenic and polymorphic nature of HLA genes. We set out to obtain antibodies specific for HLA/HCMV-peptides, covering the majority of HLA alleles present in European populations. Using phage display technology, we selected 10 Fabs, able to bind to HCMV-peptides presented in the 6 different HLA class I alleles A*0101, A*0201, A*2402, B*0702, B*0801 and B*3501. We demonstrate specific binding of all selected Fabs to HLA-typed lymphoblastoid cell lines (EBV-transformed B cells) and lymphocytes loaded with HCMV-peptides. After infection with HCMV, 4/10 tetramerized Fabs restricted to the alleles HLA-A*0101, HLA-A*0201 and HLA-B*0702 showed binding to infected primary fibroblasts. When linked to the pseudomonas exotoxin A, these Fab antibodies induce highly specific cytotoxicity in HLA matched cell lines loaded with HCMV peptides. TCR-like antibody repertoires therefore represent a promising new treatment modality for viral infections and may also have applications in the treatment of cancers.
Prevention and control measures in radiology department for COVID-19
Authors: Ding Jinli , Fu Haihong , Liu Yaou , Gao Jianbo , Li Zhenlin , Zhao Xin , Zheng Junhui , Sun Wenge , Ni Hongyan , Ma Xinwu , Feng Ji , Wu Aiqin , Liu Jie , Wang Yun , Geng Pengfei , Chen Yong 
Published: April 2020

Abstract
Since a novel coronavirus was discovered from a cluster of patients with emerging pneumonia of unknown etiology in Wuhan, China, it has spread rapidly through droplet and contact transmission. Recently, the novel coronavirus pneumonia which was named COVID-19 by the World Health Organization (WHO) has been raised as a worldwide problem. Radiological examinations were confirmed as effective methods for the screening and diagnosis of COVID-19. It is reported that some radiologists and radiological technologists were infected when giving examinations to the patients with COVID-19. In order to reduce the infection risk of medical staff in radiology department, we summarized the experience on prevention and control measures in radiology department for COVID-19, aiming to guide the prevention and practical work for radiologists and radiological technologists.

Key Points
• The novel coronavirus spreads rapidly through droplet and contact transmission.
• Radiologists and radiological technologists were possibly infected by patients.
• Prevention and control measures in radiology department for COVID-19 are important.
The emerging role of sarcopenia as a prognostic indicator in patients undergoing abdominal wall hernia repairs: a systematic review of the literature
Authors: Clark S. T. , Malietzis G. , Grove T. N. , Jenkins J. T. , Windsor A. C. J. , Kontovounisios C. , Warren O. J. 
Published: April 2020

Abstract
Background
There is strong evidence suggesting that excessive fat distribution, for example, in the bowel mesentery or a reduction in lean body mass (sarcopenia) can influence short-, mid-, and long-term outcomes from patients undergoing various types of surgery. Body composition (BC) analysis aims to measure and quantify this into a parameter that can be used to assess patients being treated for abdominal wall hernia (AWH). This study aims to review the evidence linking quantification of BC with short- and long-term abdominal wall hernia repair outcomes.

Methods
A systematic review was performed according to the PRISMA guidelines. The literature search was performed on all studies that included BC analysis in patients undergoing treatment for AWH using Medline, Google Scholar and Cochrane databases by two independent reviewers. Outcomes of interest included short-term recovery, recurrence outcomes, and long-term data.

Results
201 studies were identified, of which 4 met the inclusion criteria. None of the studies were randomized controlled trials and all were cohort studies. There was considerable variability in the landmark axial levels and skeletal muscle(s) chosen for analysis, alongside the methods of measuring the cross-sectional area and the parameters used to define sarcopenia. Only two studies identified an increased risk of postoperative complications associated with the presence of sarcopenia. This included an increased risk of hernia recurrence, postoperative ileus and prolonged hospitalisation.

Conclusion
There is some evidence to suggest that BC techniques could be used to help predict surgical outcomes and allow early optimisation in AWH patients. However, the lack of consistency in chosen methodology, combined with the outdated definitions of sarcopenia, makes drawing any conclusions difficult. Whether body composition modification can be used to improve outcomes remains to be determined.
Does linear equating improve prediction in mapping? Crosswalking MacNew onto EQ-5D-5L value sets
Authors: Lamu Admassu N. 
Published: April 2020

Abstract
Purpose
Preference-based measures are essential for producing quality-adjusted life years (QALYs) that are widely used for economic evaluations. In the absence of such measures, mapping algorithms can be applied to estimate utilities from disease-specific measures. This paper aims to develop mapping algorithms between the MacNew Heart Disease Quality of Life Questionnaire (MacNew) instrument and the English and the US-based EQ-5D-5L value sets.

Methods
Individuals with heart disease were recruited from six countries: Australia, Canada, Germany, Norway, UK and the US in 2011/12. Both parametric and non-parametric statistical techniques were applied to estimate mapping algorithms that predict utilities for MacNew scores from EQ-5D-5L value sets. The optimal algorithm for each country-specific value set was primarily selected based on root mean square error (RMSE), mean absolute error (MAE), concordance correlation coefficient (CCC), and r-squared. Leave-one-out cross-validation was conducted to test the generalizability of each model.

Results
For both the English and the US value sets, the one-inflated beta regression model consistently performed best in terms of all criteria. Similar results were observed for the cross-validation results. The preferred model explained 59 and 60% for the English and the US value set, respectively. Linear equating provided predicted values that were equivalent to observed values.

Conclusions
The preferred mapping function enables to predict utilities for MacNew data from the EQ-5D-5L value sets recently developed in England and the US with better accuracy. This allows studies, which have included the MacNew to be used in cost-utility analyses and thus, the comparison of services with interventions across the health system.
QTL analysis of shoot elongation before winter in relation to vernalization requirement in the doubled haploid population L16 × Express617 (Brassica napus L.)
Authors: Ghanbari Mohammad , Paul Madhuri , Möllers Christian 
Published: April 2020

AbstractIn winter oilseed rape shoot elongation before winter is considered as a critical component of the complex trait winter hardiness. Genotypes with an enhanced shoot length before winter are very much prone to frost damage. However, it is not known to which extent shoot elongation before winter is related to vernalization requirement. Shoot length measured 3 months after sowing of winter oilseed rape in spring has been shown to be a good quantitative estimator for vernalization requirement. The main objective of this study was to analyze inheritance of shoot elongation before winter and in spring-sown field experiments using a doubled haploid population derived from the cross between two inbred lines. A SNP based molecular marker map was used to map QTL for shoot length and flowering time. Significant genotypic effects were detected for shoot length before winter and in the spring-sown environment, but there was no correlation between both traits. Six QTL for shoot length before winter contributed 49.2% to the phenotypic variance. For shoot length in the spring-sown environment three QTL were detected that explained 68% of the phenotypic variance. Flowering time genes CONSTANS (BnaC09g41980D), FLC (BnaC09g42060D) and FT (BnaA02g12130D) were identified within C09 and A02 QTL confidence intervals. No collocation of QTL for shoot length before winter and for shoot length in the spring-sown environment was found. Results show that selection for reduced shoot length before winter would be effective and that this trait is inherited largely independent of vernalization requirement.
Revealing cytotoxic substructures in molecules using deep learning
Authors: Webel Henry E. , Kimber Talia B. , Radetzki Silke , Neuenschwander Martin , Nazaré Marc , Volkamer Andrea 
Published: April 2020

AbstractIn drug development, late stage toxicity issues of a compound are the main cause of failure in clinical trials. In silico methods are therefore of high importance to guide the early design process to reduce time, costs and animal testing. Technical advances and the ever growing amount of available toxicity data enabled machine learning, especially neural networks, to impact the field of predictive toxicology. In this study, cytotoxicity prediction, one of the earliest handles in drug discovery, is investigated using a deep learning approach trained on a highly consistent in-house data set of over 34,000 compounds with a share of less than 5% of cytotoxic molecules. The model reached a balanced accuracy of over 70%, similar to previously reported studies using Random Forest. Albeit yielding good results, neural networks are often described as a black box lacking deeper mechanistic understanding of the underlying model. To overcome this absence of interpretability, a Deep Taylor Decomposition method is investigated to identify substructures that may be responsible for the cytotoxic effects, the so-called toxicophores. Furthermore, this study introduces cytotoxicity maps which provide a visual structural interpretation of the relevance of these substructures. Using this approach could be helpful in drug development to predict the potential toxicity of a compound as well as to generate new insights into the toxic mechanism. Moreover, it could also help to de-risk and optimize compounds.