bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of human in vitro metabolites of the haemoglobin S polymerization inhibitor voxelotor for doping control purposes
Authors: Rzeppa Sebastian , Voss Sven C. , Thieme Detlef , Keiler Annekathrin M. 
Published: May 2023

AbstractVoxelotor (GBT440) is a haemoglobin S polymerization inhibitor used to treat anaemia in sickle cell disease. Due to an increase of arterial oxygen saturation as well as serum erythropoietin and haemoglobin, the World Anti‐Doping Agency included voxelotor in the list of prohibited substances and methods in 2023. The objective of the present study was to identify and characterize metabolites of voxelotor to detect a potential misuse by athletes. The biotransformation was studied in vitro using the human hepatocellular cell line HepG2 and pooled human liver microsomes. The metabolites were analysed using high‐performance liquid chromatography (high‐resolution) mass spectrometry. In total, three phase I metabolites and six phase II metabolites (resulting from glucuro‐conjugation and O‐methylation) were formed by the HepG2 cells in a time‐dependent manner, and two phase I metabolites were generated by the liver microsomes, among them one also found in the HepG2 incubations. A reduced metabolite and the glucuro‐conjugate of a reduced metabolite were the most abundant formed by HepG2 cells. In addition, metabolites resulting from mono‐hydroxylation, reduction and O‐methylation in different combinations were identified. Voxelotor was also found as glucuro‐conjugate with a low abundance. With the spectrometric behaviour of voxelotor and its in vitro metabolites described herein, an implementation in doping control screening and, consequently, a detection of an abuse in an athlete urine sample might be possible.
Season‐dependent impact of forage quality on stress in alpine chamois
Authors: Corlatti Luca , Palme Rupert , Valencak Teresa G. , Gomez Kimberlina Marie 
Published: May 2023

AbstractChronically heightened stress levels in wildlife species may have detrimental effects on individual life history traits, for example, through the increased likelihood of disease, parasitic infections, and overall reduced fitness. Understanding the drivers of stress may thus have great potential for informing wildlife conservation. Although the role of climate and individual status is well studied in stress ecology, the impact of related stressors such as dietary quality is of increasing interest to wildlife research and conservation. In this study, fecal cortisol metabolites (FCMs) in Alpine chamoisRupicapra r. rupicapraused as bioindicators of stress, and their relationship with forage quality—measured as the percentage of fecal crude protein (CP)—were investigated. Data collection took place in 2011 and 2012 in the Gran Paradiso National Park (Western Italian Alps), on 22 individually marked adult males. The relationship between FCMs and CPs was analyzed through linear models and separated between winter and summer months, accounting for the effect of potentially confounding exogenous and endogenous variables. After AICc‐based model selection, we found that forage quality was negatively related to FCM levels in Alpine chamois during the summer months, meaning that higher quality forage was associated with the decreased expression of stress hormones. However, during the winter months, we did not find a significant relationship, potentially as a result of forage quality being ubiquitously poor. Although the mechanisms through which dietary variations impact FCM concentrations in wildlife populations are largely unknown, the occurrence of significant relationships between forage quality and stress levels supports potentially important implications for the long‐term effect of climatic changes on the fitness of wildlife populations.
2‐Nitroimidazole Based PET Tracers: Development of a General Synthetic Approach and Fluorination Methodology
Authors: Renault Kévin , Horion Romain , Maes Xavier , Rzeigui Maha , Joyard Yoann , Maindron Nicolas , Tadino Vincent , Vincent Stéphane 
Published: May 2023

Abstract2‐Nitroimidazole based PET tracers are widely used for non‐invasive hypoxic tumor diagnosis. In this context, we report here a general method based on a central Mitsunobu reaction to easily access 2‐nitroimidazole precursors. Optimization of fluorination conditions is described and successfully applied to the radiofluorination of the 2‐nitroimidazole precursors. Moreover, the radiosynthesis of a new potential hypoxia PET tracer is also described. Finally, this article presents a SFC analytical method allowing both an easy monitoring of the fluorination reactions and the measurement of partition coefficients (logP).
Quinone reactivity: Investigation of their contribution to nonenzymatic browning
Authors: Yu Yiran , Chen Dandan , Li Wei , Mou Yao , Geng Yaqian , Chen Fang , Hu Xiaosong , Ji Junfu , Ma Lingjun 
Published: May 2023

AbstractBrowning is a severe problem in the juice industry, which is tremendously affected by quinone (Q) reactivity. Here, the formation rate, electrophilicity, and oxidizing ability of different quinones were investigated. LC/MS was applied to monitor the loss of polyphenols and quinones in model systems during storage. Mathematical modeling of collected LC/MS data was conducted to derive the rate constants of various reactions. Polyphenols containing catechol or pyrogallol groups are more susceptible to oxidation. Periodic acid and quinone mediated oxidation were faster than the autoxidation of polyphenols. Chlorogenic acid (CQA) and 4‐methylcatechol (4MC) only containing B ring can hardly contribute to browning. They must combine with A ring to form yellow polymers. Furthermore, the electrophilicity and oxidizing ability order of quinone is: CQA‐Q ≈ 4MC‐Q > catechin quinone (CAT‐Q) ≈ epicatechin quinone (EC‐Q) > gallic acid quinone (GA‐Q). It was possible that CAT‐Q and EC‐Q would undergo nucleophilic addition with their A rings and GA‐Q's extra hydroxyl group might contribute to the electrons, resulting in lower reactivity. This work innovatively evaluated the reactivity of diverse polyphenols and quinones, attempting to illustrate their contributions to nonenzymatic browning. These findings provide a new perspective to restrain the browning in the juice processing industry.
The Ohio River Ecological Research Program (ORERP): History and Accomplishments
Authors: Seegert Greg , Vondruska Joe T , King Ron , Dixon (Retired) Doug 
Published: May 2023

Abstract
The Ohio River Ecological Research Program (ORERP), sponsored by multiple power plants along the river's main stem, was in existence for 50 years. Its goals were to collect fish community data to evaluate possible impacts to Ohio River fish communities because of either power plant discharges (i.e., thermal effects) or cooling water intakes. Studies by the ORERP have shown that thermal avoidance of discharge areas often occurs during the summer, but this avoidance is temporary and reversible, and long-term disruptions of the fish communities have not been detected. Impingement studies conducted at 13 plants from 2005 to 2007 showed that impingement was highly episodic and dominated by clupeids and Freshwater Drum Aplodinotus grunniens. Impinged fish were mainly (&gt;90%) young of the year; as a result, impingement numbers strongly reflected year-class strength. Entrainment of ichthyoplankton was conducted under the ORERP at seven plants in 2015 and 2016. Annual entrainment estimates ranged from 43 million to 3.5 billion (i.e., 3.5 × 109) ichthyoplankton depending on the plant. The principal benefit of this collaborative effort was that these data allowed the sponsoring facilities and others to access an extensive database upon which fact-based regulatory, resource management, and plant operating decisions could be based. Most importantly, the ORERP is a collaborative model for private and public organizations to collect, share, and analyze data and make resource management decisions for a large, multi-use aquatic resource.
Normalization effect of dopamine replacement therapy on brain functional connectome in Parkinson's disease
Authors: Wu Chenqing , Wu Haoting , Zhou Cheng , Guan Xiaojun , Guo Tao , Cao Zhengye , Wu Jingjing , Liu Xiaocao , Chen Jingwen , Wen Jiaqi , Qin Jianmei , Tan Sijia , Duanmu Xiaojie , Zhang Baorong , Huang Peiyu , Xu Xiaojun , Zhang Minming 
Published: May 2023

AbstractDopamine replacement therapy (DRT) represents the standard treatment for Parkinson's disease (PD), however, instant and long‐term medication influence on patients' brain function have not been delineated. Here, a total of 97 drug‐naïve patients, 43 patients under long‐term DRT, and 94 normal control (NC) were, retrospectively, enrolled. Resting‐state functional magnetic resonance imaging data and motor symptom assessments were conducted before and after levodopa challenge test. Whole‐brain functional connectivity (FC) matrices were constructed. Network‐based statistics were performed to assess FC difference between drug‐naïve patients and NC, and these significant FCs were defined as disease‐related connectomes, which were used for further statistical analyses. Patients showed better motor performances after both long‐term DRT and levodopa challenge test. Two disease‐related connectomes were observed with distinct patterns. The FC of the increased connectome, which mainly consisted of the motor, visual, subcortical, and cerebellum networks, was higher in drug‐naïve patients than that in NC and was normalized after long‐term DRT (p‐value <.050). The decreased connectome was mainly composed of the motor, medial frontal, and salience networks and showed significantly lower FC in all patients than NC (p‐value <.050). The global FC of both increased and decreased connectome was significantly enhanced after levodopa challenge test (q‐value <0.050, false discovery rate‐corrected). The global FC of increased connectome in ON‐state was negatively associated with levodopa equivalency dose (r = −.496, q‐value = 0.007). Higher global FC of the decreased connectome was related to better motor performances (r = −.310, q‐value = 0.022). Our findings provided insights into brain functional alterations under dopaminergic medication and its benefit on motor symptoms.
The demand for money at the zero interest rate bound
Authors: Watanabe Tsutomu , Yabu Tomoyoshi 
Published: May 2023

SummaryThis paper undertakes both a narrow and wide replication of the estimation of a money demand function conducted by Ireland (American Economic Review, 2009). Using US data from 1980 to 2013, we show that the substantial increase in the money‐income ratio during the period of near‐zero interest rates is captured well by the log–log specification but not by the semi‐log specification, contrary to the result obtained by Ireland (2009). Our estimate of the interest elasticity of money demand over the 1980–2013 period is about one‐tenth that of Lucas's paper published in 2000, which used a log–log specification. Finally, neither specification satisfactorily fits post‐2015 US data.
AFM‐TEM correlation microscopy and its application to lipid nanoparticles
Authors: Bagrov Dmitry V. , Adlerberg Vladimir V. , Skryabin Gleb O. , Nikishin Igor I. , Galetsky Sergey A. , Tchevkina Elena M. , Kirpichnikov Mikhail P. , Shaitan Konstantin V. 
Published: May 2023

AbstractSo far, only a few articles have demonstrated the possibility of correlated AFM‐TEM imaging – sequential imaging of the same individual objects using atomic‐force microscopy (AFM) and transmission electron microscopy (TEM). The current work contributes to the development of this approach by giving a step‐by‐step procedure, which yields pairs of correlated AFM‐TEM images. We describe the application of correlation AFM‐TEM microscopy to lipid nanoparticles (small extracellular vesicles and liposomes). The sizes of individual particles measured by the two methods were in good agreement, taking the tip broadening into account. The correlated AFM‐TEM imaging can be valuable for single‐particle analysis and nanometrology.
Biallelic deleterious germline SH2B3 variants cause a novel syndrome of myeloproliferation and multi‐organ autoimmunity
Authors: Blombery Piers , Pazhakh Vahid , Albuquerque Adriana S. , Maimaris Jesmeen , Tu Lingge , Briones Miranda Brenda , Evans Florence , Thompson Ella R. , Carpenter Ben , Proctor Ian , Curtin Julie A. , Lambert Jonathan , Burns Siobhan O. , Lieschke Graham J. 
Published: May 2023

AbstractSH2B3 is a negative regulator of multiple cytokine receptor signalling pathways in haematopoietic tissue. To date, a single kindred has been described with germline biallelic loss‐of‐function SH2B3 variants characterized by early onset developmental delay, hepatosplenomegaly and autoimmune thyroiditis/hepatitis. Herein, we described two further unrelated kindreds with germline biallelic loss‐of‐function SH2B3 variants that show striking phenotypic similarity to each other as well as to the previous kindred of myeloproliferation and multi‐organ autoimmunity. One proband also suffered severe thrombotic complications. CRISPR‐Cas9 gene editing of zebrafish sh2b3 created assorted deleterious variants in F0 crispants, which manifest significantly increased number of macrophages and thrombocytes, partially replicating the human phenotype. Treatment of the sh2b3 crispant fish with ruxolitinib intercepted this myeloproliferative phenotype. Skin‐derived fibroblasts from one patient demonstrated increased phosphorylation of JAK2 and STAT5 after stimulation with IL‐3, GH, GM‐CSF and EPO compared to healthy controls. In conclusion, these additional probands and functional data in combination with the previous kindred provide sufficient evidence for biallelic homozygous deleterious variants in SH2B3 to be considered a valid gene‐disease association for a clinical syndrome of bone marrow myeloproliferation and multi‐organ autoimmune manifestations.
Postmortem diagnosis of very long chain acyl‐CoA dehydrogenase (VLCAD) deficiency in a neonate with sudden cardiac death
Authors: Singh Prapti , Amaro Deirdre , Obi Olugbemisola , Kiran FNU , Hediger Erin , Toler Tomi L. , Dickson Patricia I. , Grange Dorothy K. 
Published: May 2023

AbstractVery long chain acyl‐CoA dehydrogenase (VLCAD) deficiency is an autosomal recessive long chain fatty acid β‐oxidation disorder with a variable clinical spectrum, ranging from an acute neonatal presentation with cardiac and hepatic failure to childhood or adult onset of symptoms with hepatomegaly or rhabdomyolysis provoked by illness or exertion. Neonatal cardiac arrest or sudden unexpected death can be the presenting phenotype in some patients, emphasizing the importance of early clinical suspicion and intervention. We report a patient who had a cardiac arrest and died at one day of age. Following her death, the newborn screen reported biochemical evidence of VLCAD deficiency, which was confirmed with pathologic findings at autopsy and by molecular genetic testing.
Functional and phylogenetic interpretation of the forelimb myology of two South American carnivorans, the ring‐tailed coati (Nasua nasua) and crab‐eating raccoon (Procyon cancrivorus)
Authors: Tarquini Juliana , Mosto M. Clelia , Ercoli Marcos D. 
Published: May 2023

AbstractA comparative analysis of the forelimb myology of two neotropical procyonids (Nasua nasua and Procyon cancrivorus) was performed to assess how observed differences in their myological configuration would be related to their diverse ecological behaviors and phylogeny. Although both species are associated with the arboreal substrate, N. nasua is a more agile climber that usually digs; whereas P. cancrivorus spends most of its time on the ground foraging, climbing on the trees as shelter and is a good swimmer. Here, myological descriptions, muscle maps, phylogenetic optimizations, and muscle mass data of the forelimb of these two procyonids are presented. The main functional muscular groups are discussed in a comparative framework with other carnivorans that present a wide ecological diversity. Also, muscular characters were mapped onto a phylogeny to explore their evolution and to obtain ancestral state reconstructions. Results indicate clear myological differences among the two neotropical procyonids associated with their ecological preferences. One of the most remarkable anatomical differences is the arrangement and relative mass of the extrinsic musculature, mainly the musculus rhomboideus and the delto‐pectoral complexes. In Nasua nasua, these suggested a greater stability in their shoulder girdle for climbing and digging and probably would provide stronger neck and head movements when they use them for foraging on the ground. Conversely, P. cancrivorus has a different extrinsic muscular configuration, which would allow an increment on the stride length and faster movements of the forelimb associated with more frequent terrestrial gaits. Also, significant differences are observed in the distal musculature, associated with strong movements of forepaws when climbing and digging in N. nasua; whereas, P. cancrivorus configuration suggested precise forearm and digits movements, related to manipulation of food items when they are catching prey or feeding. Most of the codified features of P. cancrivorus would reflect retention of plesiomorphies acquired in the common ancestor of caniforms or arctoids, whereas N. nasua shows derived traits, particularly in the proximal forelimb region. The present work increases the information available on the myology of these particular taxa and extant generalized arctoid models in general. The analyses presented here will be useful both for other comparative myological studies (morpho‐functional and phylogenetic) and for muscular reconstruction in extinct procyonids, as well as other carnivorans.
Evaluation of 3D stack‐of‐spiral turbo FLASH acquisitions for pseudo‐continuous and velocity‐selective ASL–derived brain perfusion mapping
Authors: Zhu Dan , Xu Feng , Liu Dapeng , Hillis Argye Elizabeth , Lin Doris , van Zijl Peter C. M. , Qin Qin 
Published: May 2023

PurposeThe most‐used 3D acquisitions for ASL are gradient and spin echo (GRASE)– and stack‐of‐spiral (SOS)–based fast spin echo, which require multiple shots. Alternatively, turbo FLASH (TFL) allows longer echo trains, and SOS‐TFL has the potential to reduce the number of shots to even single‐shot, thus improving the temporal resolution. Here we compare the performance of 3D SOS‐TFL and 3D GRASE for ASL at 3T.MethodsThe 3D SOS‐TFL readout was optimized with respect to fat suppression and excitation flip angles for pseudo‐continuous ASL– and velocity‐selective (VS)ASL–derived cerebral blood flow (CBF) mapping as well as for VSASL‐derived cerebral blood volume (CBV) mapping. Results were compared with 3D GRASE readout on healthy volunteers in terms of perfusion quantification and temporal SNR (tSNR) efficiency. CBF and CBV mapping derived from 3D SOS‐TFL–based ASL was demonstrated on one stroke patient, and the potential for single‐shot acquisitions was exemplified.ResultsSOS‐TFL with a 15° flip angle resulted in adequate tSNR efficiency with negligible image blurring. Selective water excitation was necessary to eliminate fat‐induced artifacts. For pseudo‐continuous ASL– and VSASL‐based CBF and CBV mapping, compared to the employed four‐shot 3D GRASE with an acceleration factor of 2, the fully sampled 3D SOS‐TFL delivered comparable performance (with a similar scan time) using three shots, which could be further undersampled to achieve single‐shot acquisition with higher tSNR efficiency. SOS‐TFL had reduced CSF contamination for VSASL‐CBF.Conclusion3D SOS‐TFL acquisition was found to be a viable substitute for 3D GRASE for ASL with sufficient tSNR efficiency, minimal relaxation‐induced blurring, reduced CSF contamination, and the potential of single‐shot, especially for VSASL.
Distortion‐corrected image reconstruction with deep learning on an MRI‐Linac
Authors: Shan Shanshan , Gao Yang , Liu Paul Z. Y. , Whelan Brendan , Sun Hongfu , Dong Bin , Liu Feng , Waddington David E. J. 
Published: May 2023

PurposeMRI is increasingly utilized for image‐guided radiotherapy due to its outstanding soft‐tissue contrast and lack of ionizing radiation. However, geometric distortions caused by gradient nonlinearities (GNLs) limit anatomical accuracy, potentially compromising the quality of tumor treatments. In addition, slow MR acquisition and reconstruction limit the potential for effective image guidance. Here, we demonstrate a deep learning‐based method that rapidly reconstructs distortion‐corrected images from raw k‐space data for MR‐guided radiotherapy applications.MethodsWe leverage recent advances in interpretable unrolling networks to develop a Distortion‐Corrected Reconstruction Network (DCReconNet) that applies convolutional neural networks (CNNs) to learn effective regularizations and nonuniform fast Fourier transforms for GNL‐encoding. DCReconNet was trained on a public MR brain dataset from 11 healthy volunteers for fully sampled and accelerated techniques, including parallel imaging (PI) and compressed sensing (CS). The performance of DCReconNet was tested on phantom, brain, pelvis, and lung images acquired on a 1.0T MRI‐Linac. The DCReconNet, CS‐, PI‐and UNet‐based reconstructed image quality was measured by structural similarity (SSIM) and RMS error (RMSE) for numerical comparisons. The computation time and residual distortion for each method were also reported.ResultsImaging results demonstrated that DCReconNet better preserves image structures compared to CS‐ and PI‐based reconstruction methods. DCReconNet resulted in the highest SSIM (0.95 median value) and lowest RMSE (<0.04) on simulated brain images with four times acceleration. DCReconNet is over 10‐times faster than iterative, regularized reconstruction methods.ConclusionsDCReconNet provides fast and geometrically accurate image reconstruction and has the potential for MRI‐guided radiotherapy applications.
Joint service placement and user assignment model in multi‐access edge computing networks against base‐station failure
Authors: Taka Haruto , He Fujun , Oki Eiji 
Published: May 2023

AbstractMulti‐access edge computing (MEC) enables users to exploit the resources of cloud computing at a base station (BS) in proximity to the users where an MEC server is hosted. While we have advantage of being able to communicate with low latency and small network load in MEC networks, the resources in BSs are limited. One challenge is where to provide users with services from to make efficient use of resources. Furthermore, to enhance the reliability of MEC system, the case that a BS fails needs to be considered. This paper proposes a service placement and user assignment model with preventive start‐time optimization against a single BS failure in MEC networks. The proposed model preventively determines the service placement and user assignment in each BS failure pattern to minimize the worst‐case penalty which is the largest penalty among all failure patterns. We formulate the proposed model as an integer linear programming problem. We prove that the considered problem is NP‐hard. When the problem size becomes large, it may not be solved in a practical computation time. To solve larger size problems, we introduce two algorithms: one is the greedy algorithm with allocation upgrade and the other is with allocation upgrade and preemption. The results show that the introduced algorithms obtain solutions with smaller worst‐case penalty than the benchmark in a practical time.