bluuebunny/crossref_metadata_2025_split huggingface dataset:
Model-informed dose optimization of mycophenolic acid in pediatric kidney transplant patients
Authors: Heida Astrid , Jager Nynke G. L. , Aarnoutse Rob E. , de Winter Brenda C. M. , de Jong Huib , Keizer Ron J. , Cornelissen Elisabeth A. M. , ter Heine Rob 
Published: August 2024

Abstract
Purpose
We aimed to develop and evaluate a population PK model of mycophenolic acid (MPA) in pediatric kidney transplant patients to aid MPA dose optimization.

Methods
Data were collected from pediatric kidney transplant recipients from a Dutch academic hospital (Radboudumc, the Netherlands). Pharmacokinetic model-building and model-validation analyses were performed using NONMEM. Subsequently, we externally evaluated the final model using data from another academic hospital. The final model was used to develop an optimized dosing regimen.

Results
Thirty pediatric patients were included of whom 266 measured MPA plasma concentrations, including 20 full pharmacokinetic (PK) curves and 24 limited sampling curves, were available. A two-compartment model with a transition compartment for Erlang-type absorption best described the data. The final population PK parameter estimates were Ktr (1.48 h−1; 95% CI, 1.15–1.84), CL/F (16.0 L h−1; 95% CI, 10.3–20.4), Vc/F (24.9 L; 95% CI, 93.0–6.71E25), Vp/F (1590 L; 95% CI, 651–2994), and Q/F (36.2 L h−1; 95% CI, 9.63–74.7). The performance of the PK model in the external population was adequate. An optimized initial dose scheme based on bodyweight was developed. With the licensed initial dose, 35% of patients were predicted to achieve the target AUC, compared to 42% using the optimized scheme.

Conclusion
We have successfully developed a pharmacokinetic model for MPA in pediatric renal transplant patients. The optimized dosing regimen is expected to result in better target attainment early in treatment. It can be used in combination with model-informed follow-up dosing to further individualize the dose when PK samples become available.
Insights into the transglucosylation activity of α-glucosidase from Schwanniomyces occidentalis
Authors: Merdzo Zoran , Narmontaite Egle , Gonzalez-Alfonso Jose L. , Poveda Ana , Jimenez-Barbero Jesus , Plou Francisco J. , Fernández-Lobato María 
Published: August 2024

Abstract
The α-glucosidase from Schwanniomyces occidentalis (GAM1p) was expressed in Komagataella phaffii to about 70 mg/L, and its transferase activity studied in detail. Several isomaltooligosaccharides (IMOS) were formed using 200 g/L maltose. The major production of IMOS (81.3 g/L) was obtained when 98% maltose was hydrolysed, of which 34.8 g/L corresponded to isomaltose, 26.9 g/L to isomaltotriose, and 19.6 g/L to panose. The addition of glucose shifted the IMOS synthesis towards products containing exclusively α(1 → 6)-linkages, increasing the production of isomaltose and isomaltotriose about 2–4 fold, enabling the formation of isomaltotetraose, and inhibiting that of panose to about 12 times. In addition, the potential of this enzyme to glycosylate 12 possible hydroxylated acceptors, including eight sugars and four phenolic compounds, was evaluated. Among them, only sucrose, xylose, and piceid (a monoglucosylated derivative of resveratrol) were glucosylated, and the main synthesised products were purified and characterised by MS and NMR. Theanderose, α(1 → 4)-D-glucosyl-xylose, and a mixture of piceid mono- and diglucoside were obtained with sucrose, xylose, and piceid as acceptors, respectively. Maximum production of theanderose reached 81.7 g/L and that of the glucosyl-xylose 26.5 g/L, whereas 3.4 g/L and only 1 g/L were produced of the piceid mono- and diglucoside respectively.

Key points
• Overexpression of a yeast α-glucosidase producing novel molecules.
• Yeast enzyme producing the heterooligosaccharides theanderose and glucosyl-xylose.
• Glycosylation of the polyphenol piceid by a yeast α-glucosidase.
An accelerated PETALUTE MRI sequence for in vivo quantification of sodium content in human articular cartilage at 3T
Authors: Villarreal Cameron X. , Shen Xin , Alhulail Ahmad A. , Buffo Nicholas M. , Zhou Xiaopeng , Pogue Evan , Özen Ali Caglar , Chiew Mark , Sawiak Stephen , Emir Uzay , Chan Deva D. 
Published: August 2024

Abstract

Objective
In this work, we evaluate the sodium magnetic resonance imaging (MRI) capabilities of a three-dimensional (3D) dual-echo ultrashort echo time (UTE) sequence with a novel rosette petal trajectory (PETALUTE), in comparison to the 3D density-adapted (DA) radial spokes UTE sequence in human articular cartilage in the knee.

Materials and methods
We scanned five healthy subjects using a 3D dual-echo PETALUTE acquisition and two comparable implementations of 3D DA-radial spokes acquisitions, one matching the number of k-space projections (Radial – Matched Spokes) and the other matching the total number of samples (Radial – Matched Samples) acquired in k-space.

Results
The PETALUTE acquisition enabled equivalent sodium quantification in articular cartilage volumes of interest (168.8 ± 29.9 mM, mean ± standard deviation) to those derived from the 3D radial acquisitions (171.62 ± 28.7 mM and 149.8 ± 22.2 mM, respectively). We achieved a 41% shorter scan time of 2:06 for 3D PETALUTE, compared to 3:36 for 3D radial acquisitions. We also evaluated the feasibility of further acceleration of the PETALUTE sequence through retrospective compressed sensing with 2 × and 4 × acceleration of the first echo and showed structural similarity of 0.89 ± 0.03 and 0.87 ± 0.03 when compared to non-retrospectively accelerated reconstruction.

Conclusion
We demonstrate improved scan time with equivalent performance using a 3D dual-echo PETALUTE sequence compared to the 3D DA-radial sequence for sodium MRI of articular cartilage.
Effects of crop forcing and water availability on yield and biomass partitioning in Tempranillo vines
Authors: Oliver-Manera Jordi , García-Tejera Omar , Mata Mercè , Girona Joan 
Published: August 2024

AbstractMuch recent grapevine research has focused on management techniques that allow grape harvesting under cooler conditions. Crop forcing, a summer pruning technique that ‘forces’ the vine to start a new cycle, can delay the harvest date by several weeks. However, information on how crop forcing affects root biomass production is currently limited. A two-year trial was conducted using potted vines to examine how crop forcing, and water availability might influence biomass partitioning. Six irrigation treatments were applied to forced (F) vines: deficit irrigation before forcing (F-PreF); deficit irrigation from veraison to harvest (F-V); a combination of these two treatments (F-PreF-V); deficit irrigation from veraison to harvest with no irrigation after harvest (F-V-PH); deficit irrigation throughout the growing season (F-DI); and irrigation at 100% of crop evapotranspiration (F-FI). The results were compared with unforced (UF) treatments: fully irrigated (UF-FI) and deficit irrigation throughout the growing season (UF-DI). The F-FI treatment reduced water use by 34% compared to the UF-FI treatment. Although the F treatments resulted in a significant yield reduction (85%), they increased the allocation of biomass to vegetative organs, and the crop forcing technique did not negatively affect root biomass production. Both UF-DI and F-DI treatments reduced root production compared to their respective FI treatments (UF-FI and F-FI). Furthermore, new root biomass was positively correlated with vine water use and total vine photosynthetic capacity when only F treatments were analysed.
A Homolog of the Histidine Kinase RetS Controls the Synthesis of Alginates, PHB, Alkylresorcinols, and Motility in Azotobacter vinelandii
Authors: Rosales-Cruz Araceli , Reyes-Nicolau Jimena , Minto-González Eduardo , Meneses-Carbajal Alan , Mondragón-Albarrán Claudia , López-Pliego Liliana , Castañeda Miguel 
Published: August 2024

AbstractThe two-component system GacS/A and the posttranscriptional control system Rsm constitute a genetic regulation pathway in Gammaproteobacteria; in some species of Pseudomonas, this pathway is part of a multikinase network (MKN) that regulates the activity of the Rsm system. In this network, the activity of GacS is controlled by other kinases. One of the most studied MKNs is the MKN-GacS of Pseudomonas aeruginosa, where GacS is controlled by the kinases RetS and LadS; RetS decreases the kinase activity of GacS, whereas LadS stimulates the activity of the central kinase GacS. Outside of the Pseudomonas genus, the network has been studied only in Azotobacter vinelandii. In this work, we report the study of the RetS kinase of A. vinelandii; as expected, the phenotypes affected in gacS mutants, such as production of alginates, polyhydroxybutyrate, and alkylresorcinols and swimming motility, were also affected in retS mutants. Interestingly, our data indicated that RetS in A. vinelandii acts as a positive regulator of GacA activity. Consistent with this finding, mutation in retS also negatively affected the expression of small regulatory RNAs belonging to the Rsm family. We also confirmed the interaction of RetS with GacS, as well as with the phosphotransfer protein HptB.
A multi-directional redundant 3D-LPT system for ship–flight–deck wind interactions
Authors: Hysa Ilda , Tuinstra Marthijn , Sciacchitano Andrea , Scarano Fulvio , van der Meulen Mark-Jan , Rockstroh Thomas , Roosenboom Eric W. M. 
Published: August 2024

AbstractIn the past years, volumetric velocimetry measurements with helium-filled soap bubbles as tracer particles have been introduced in wind tunnel experiments and performed at large-scale, enabling the study of complex body aerodynamics. A limiting factor is identified in the field of wind engineering, where the flow around ships is frequently investigated. Considering multiple wind directions, the optical access for illumination and 3D imaging rapidly erodes the measurement regions due to shadows and incomplete triangulation. This work formalizes the concepts of volumetric losses and camera redundancy, and examines the performance of multi-directional illumination and imaging for monolithic and partitioned modes. The work is corroborated by experiments around a representative ship model. The study shows that a redundant system of cameras yields the largest measurement volume when partitioned into subsystems. The 3D measurements employing two illumination directions and seven cameras, yield the time-averaged velocity field around the ship. Regions of flow separation and recirculation are revealed, as well as sets of counter-rotating vortices in several stations from the ship bow to the flight–deck. The unsteady regime at the flight–deck is examined by proper orthogonal decomposition, indicating that the technique is suited for the analysis of large-scale unsteady flow features.
Dietary folic acid intake, 13 genetic variants and other factors with red blood cell folate concentration in pregnancy-preparing population
Authors: He Wennan , Zhang Yi , Chen Xiaotian , Dou Yalan , He Yuanchen , Yan Weili 
Published: August 2024

Abstract
Purpose
This study aims to evaluate a combined effect of dietary folic acid intake, multiple genetic polymorphisms in folate metabolism, and other environmental factors on red blood cell (RBC) folate concentration in pregnancy-preparing population.

Methods
519 pregnancy-preparing subjects (260 couples) were investigated. Dietary intake was measured by 3-day dietary recalls. 13 Single Nucleotide polymorphisms (SNPs) reported in association with one-carbon metabolism including the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C were genotyped. RBC folate concentration was measured using chemiluminescence assay. Hierarchical regression was applied for covariate selection. Factors showed significance(p < 0.0125) on RBC folate level was included for prediction model construction and R2 estimation. Validation cohort analysis was performed as post-hoc analysis if applicable.

Results
The median RBC folate was 212.8 ng/ml. Only 10% took folic acid supplementation within three months. Based on hierarchical selection, folic acid supplementation, genetic polymorphism (especially TT genotype of MTHFR C677T), serum folate level were determinants of the variance of RBC folate concentrations, with adjusted R2 of 0.178–0.242. MTHFR A1298C polymorphism, sex difference with other socio-demographic and lifestyle factors (age, BMI, alcohol drinking, smoking, education, occupation) explained little to change in RBC folate level. Validation in another sub-cohort(n = 8105) had adjusted R2 of 0.273.

Conclusion
In pregnancy-preparing subjects, folic acid supplementation, serum folate level and TT allele of MTHFR C677T polymorphism were determinants of the total variance of RBC folate level, which explained 19.8% variance in our subjects and 27.3% in the validation cohort. Food folate intake, sex and other environmental factors explained little to RBC folate level.
Wait times for scheduling appointments with hospital affiliated dermatologists in New York City
Authors: Basch Corey H. , Hillyer Grace C. , Gold Bailey , Basch Charles E. 
Published: August 2024

AbstractPatients’ experience accessing dermatologic care is understudied. The purpose of this cross-sectional study was to examine current wait times for new patients to receive dermatological care in NYC. Websites at 58 accredited private and public hospitals in the five boroughs of NYC were reviewed to identify dermatology practices. Office telephone numbers listed on each website were called to collect information pertaining to whether the physician was accepting new patients, type of insurance accepted (public, private, both, or none), and the number of days until a new patient could be seen for an appointment. Data pertaining to the time kept on hold and availability of web-based booking were also collected. Mean waiting time for an appointment was 50 days [standard deviation, SD 66] – nearly 2 months, but the distribution was considerably skewed. The median waiting time was 19.5 days [Interquartile range, IQR 4–60]. The time kept on hold to make the appointment was negligible at about 1 min (63 s, SD = 77) but could take up to ~ 7 min. Two-thirds of dermatologists accepted private, Medicare, and Medicaid insurance (n = 228, 66%); a small number accepted only private insurance (n = 12, 4%) or no insurance at all (n = 16, 5%). The median waiting time for an appointment for the 228 providers that accepted Medicaid was 30.5 days (IQR = 5.0-73.25) while for providers who did not accept Medicaid (n = 116) the median wait time for an appointment was 13.0 days (IQR = 3.0–38.0). Just over half (56%) of the dermatologists allowed for appointments to be booked on their website (n = 193). This research highlights the necessity of incorporating new strategies into routine dermatology appointments in order to increase treatment availability and decrease healthcare inequality.
Data-driven computational mechanics: comparison of model-free and model-based methods in constitutive modeling
Authors: Stöcker Julien Philipp , Heinzig Selina , Khedkar Abhinav Anil , Kaliske Michael 
Published: August 2024

AbstractIn computational homogenization approaches, data-driven methods entail advantages due to their ability to capture complex behavior without assuming a specific material model. Within this domain, constitutive model-based and model-free data-driven methods are distinguished. The former employ artificial neural networks as models to approximate a constitutive relation, whereas the latter directly incorporate stress–strain data in the analysis. Neural network-based constitutive descriptions are one of the most widely used data-driven approaches in computational mechanics. In contrast, distance-minimizing data-driven computational mechanics enables substituting the material modeling step entirely by iteratively obtaining a physically consistent solution close to the material behavior represented by the data. The maximum entropy data-driven solver is a generalization of this method, providing increased robustness concerning outliers in the underlying data set. Additionally, a tensor voting enhancement based on incorporating locally linear tangent spaces enables interpolating in regions of sparse sampling. In this contribution, a comparison of neural network-based constitutive models and data-driven computational mechanics is made. General differences between machine learning, distance minimizing, and entropy maximizing data-driven methods are explored. These include the pre-processing of data and the required computational effort for optimization as well as evaluation. Numerical examples with synthetically generated datasets obtained by numerical material tests are employed to demonstrate the capabilities of the investigated methods. An anisotropic nonlinear elastic constitutive law is chosen for the investigation. The resulting constitutive representations are then applied in structural simulations. Thereby, differences in the solution procedure as well as use-case accuracy of the methods are investigated.
Finger millet (Eleusine coracana L.): from staple to superfood—a comprehensive review on nutritional, bioactive, industrial, and climate resilience potential
Authors: Kaur Simardeep , Kumari Arti , Seem Karishma , Kaur Gurkanwal , Kumar Deepesh , Verma Surbhi , Singh Naseeb , Kumar Amit , Kumar Manish , Jaiswal Sandeep , Bhardwaj Rakesh , Singh Binay Kumar , Riar Amritbir 
Published: August 2024

Abstract
Main conclusion
This review discusses the Finger millet's rich nutritional profile, bioactive potential, and industrial applications, combined with its climate resilience, which make it a promising crop for enhancing food security and promoting sustainable agriculture. This review also highlights its significant potential to address malnutrition and mitigate climate change impacts.

Abstract
The emergence of Finger millet from “poor man’s staple food” to “a nutrient rich cereal” has encouraged the need to explore this crop at a wider scale. It is a highly significant crop due to its rich nutritional and bioactive profile, diverse biological activities, and promising industrial applications, along with the high climate resilience. This comprehensive review evaluates its nutritional composition by comparing favorably with other cereals and millets and emphasizing its potential to address malnutrition and enhance food security. Furthermore, it explores the phytochemical/bioactive potential and strategies to enhance their bioavailability followed biological activities of Finger millet by highlighting its various health-promoting properties. The review also discusses industrial potential of finger millet including its role in nutraceutical and functional food production, as well as bioenergy generation. In addition, role of Finger millet as a climate-resilient crop; specifically, the available genetic resources and identification of genes and quantitative trait loci (QTLs) associated with major stress tolerance traits have also been discussed. By providing a comprehensive synthesis of existing knowledge, this study offers valuable insights for researchers, policymakers, and stakeholders engaged in efforts to promote sustainable agriculture, enhance food and nutrition security, and mitigate the impacts of climate change.
Visual attention and processing function in relation to executive functioning in very preterm–born children aged 3 years: a prospective cohort study
Authors: Bijlsma Alja , van Gils Maud M. , Beunders Victoria A. A. , Reiss Irwin K. M. , Joosten Koen F. M. , Pel Johan J. M. , Kooiker Marlou J. G. , Vermeulen Marijn J. 
Published: August 2024

AbstractThe ability to orient attention to one’s environment is a prerequisite for developing executive functions (EF) from preschool age. Very preterm children are vulnerable for delays in visual orienting function (VOF) and EF deficits. This study aimed to investigate associations between objective VOF and subjective parent-reported EF in very preterm–born children at 3 years corrected age (CA). In a prospective cohort study (BOND) involving 90 children born < 30 weeks, VOF and EF were assessed using an eye tracking–based method and BRIEF-P questionnaire. Associations between abnormal VOF (viewing reaction times) and EF scores (BRIEF-P scores) were studied using multivariable regression. Using a modified Delphi method, a subset of eight items related to VOF and EF was explored. Abnormal VOF was observed in 31% of the children and abnormal global EF composite scores in 41%. Abnormal VOF was not associated with global or domain-level EF scores. However, children with abnormal VOF more frequently had EF problems related to attentional behavior: “easily sidetracked” (OR 4.18 (CI: 1.21–14.41), p = 0.02) and “short attention span” (OR 4.52 (CI: 1.34–15.22), p = 0.02). Conclusion: Although abnormal VOF was not associated with global, parent-reported, EF at 3 years CA, secondary analyses did show a relation to specific attention and concentration span items. Further research is needed to study the role of VOF in objectifying preschool EF assessments in very preterm born children.

What is known:• Very preterm children are vulnerable for executive function (EF) deficits and for delays in visual orienting function, as compared to term-born children• The ability to orient attention to one’s visual environment is an important prerequisite for EF early in life and is easy to measure objectively with visual orienting function (VOF) assessment

What is new:• VOF measurement at 3 years of age relates to parent-reported attention and concentration span items, important aspects of executive functions• Future work should explore the clinical additional value of early VOF measurement in children at risk for EF deficits
A mixed-order quasicontinuum approach for beam-based architected materials with application to fracture
Authors: Kraschewski Kevin , Phlipot Gregory P. , Kochmann Dennis M. 
Published: August 2024

AbstractPredicting the mechanics of large structural networks, such as beam-based architected materials, requires a multiscale computational strategy that preserves information about the discrete structure while being applicable to large assemblies of struts. Especially the fracture properties of such beam lattices necessitate a two-scale modeling strategy, since the fracture toughness depends on discrete beam failure events, while the application of remote loads requires large simulation domains. As classical homogenization techniques fail in the absence of a separation of scales at the crack tip, we present a concurrent multiscale technique: a fully-nonlocal quasicontinuum (QC) multi-lattice formulation for beam networks, based on a conforming mesh. Like the original atomistic QC formulation, we maintain discrete resolution where needed (such as around a crack tip) while efficiently coarse-graining in the remaining simulation domain. A key challenge is a suitable model in the coarse-grained domain, where classical QC uses affine interpolations. This formulation fails in bending-dominated lattices, as it overconstrains the lattice by preventing bending without stretching of beams. Therefore, we here present a beam QC formulation based on mixed-order interpolation in the coarse-grained region—combining the efficiency of linear interpolation where possible with the accuracy advantages of quadratic interpolation where needed. This results in a powerful computational framework, which, as we demonstrate through our validation and benchmark examples, overcomes the deficiencies of previous QC formulations and enables, e.g., the prediction of the fracture toughness and the diverse nature of stress distributions of stretching- and bending-dominated beam lattices in two and three dimensions.