bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics and Pharmacodynamics of High‐Dose Zidovudine Administered as a Continuous Infusion in Patients With Cancer
Authors: Marchbanks Karen , Dudley Michael N. , Posner Marshall R. , Darnowski James 
Published: October 2023

Study Objective. To investigate the pharmacokinetics and pharmacodynamics of high‐dose intravenous zidovudine (ZDV).Design. Phase 1, dose‐escalating, unblinded study in patients with cancer.Setting. A university‐affiliated cancer treatment center.Patients. Fourteen patients (6 women) with solid tumors that were unresponsive to standard therapy received 31 courses of therapy.Interventions. Intravenous ZDV was administered in doses of 2, 3, 4, 5.5, 7, 8.5, 10, 12, 15, or 20 g/m2/day as a continuous infusion over 48 hours. Patients also received fluorouracil plus leucovorin for 24 hours before the start of and during the ZDV infusion. If no dose‐limiting toxicities were encountered, subsequent doses were escalated. Blood samples were collected at 24 and 48 hours after the start of the infusion, and hourly for 4 hours after stopping the infusion. Urine was collected in five patients during the infusion and for 24 hours after stopping it. Blood for measuring peripheral white blood cells was collected before and at the end of the infusion in seven patients to measure DNA chain breaks due to incorporation of ZDV.Measurements and Main Results. Zidovudine was measured in plasma by high‐performance liquid chromatography and in urine fluorescence polarization immunoassay. Its incorporation into DNA was measured by determining DNA strand breakage in peripheral white blood cells using fluorescence analysis. Pharmacokinetic models were fit to plasma ZDV concentrations using extended least squares regression. Short‐term high‐dose ZDV was generally well tolerated, with adverse effects related to large amounts of free water administered during the infusion. The mean (SD) ZDV pharmacokinetic values were total clearance 1.44 (1.09) L/hr/kg, volume of distribution 2.72 (2.97) L/kg, and half‐life 1.2 (0.6) hours. There was considerable interpatient variability in total drug clearance. Although ZDV exposure increased proportionately with increasing dose, two of three patients receiving the highest dose (20 g/m2/day) had markedly low total drug clearances. The relation between the percentage of abnormal DNA in peripheral white blood cells and zidovudine area under the plasma ZDV versus time curve was described by the Emax pharmacodynamic model.Conclusions. The pharmacokinetics of high‐dose ZDV administered by continuous infusion to patients with cancer are similar to those reported with lower doses in patients with infection due to the human immunodeficiency virus. Further study of potential nonlinear pharmacokinetic behavior at doses above 20 g/m2/day is necessary. The high between‐patient variability in ZDV clearance results in variable levels of exposure in vivo, and indicates the need for concentration‐ or effect‐controlled study designs in the further evaluation of the agent's antineoplastic effects.
The Effect of High‐Dose Ascorbate Supplementation on Plasma Lipoprotein(a) Levels in Patients With Premature Coronary Heart Disease
Authors: Bostom Andrew G. , Hume Anne L. , Eaton Charles B. , Laurino Joseph P. , Yanek Lisa R. , Regan Mary S. , McQuade William H. , Craig Wendy Y. , Perrone Gayle , Jacques Paul F. 
Published: October 2023

Study Objective. To determine the efficacy of high‐dose ascorbate supplementation in lowering lipoprotein(a) [Lp(a)] levels in patients with premature coronary heart disease (CHD).Design. Randomized, double‐blind, placebo‐controlled trial.Setting. Outpatient clinic.Patients. Forty‐four patients with documented premature CHD. defined as confirmed myocardial infarction and/or angiographically determined stenosis of 50% or greater in at least one major coronary artery before age 60 years.Interventions. Patients were block randomized on the basis of age, gender, and screening Lp(a) concentrations to receive ascorbate 4.5 g/day or placebo for 12 weeks.Measurements and Main Results. High‐dose ascorbate was well tolerated and produced a marked elevation in mean plasma ascorbate levels (+1.2 mg/dl; p<0.001). Multiple linear regression analysis revealed no significant effect of supplementation on postintervention Lp(a) levels (p=0.39) in a model that included treatment group assignment, and baseline Lp(a) levels.Conclusions. Our findings do not support a clinically important lowering effect of high‐dose ascorbate on plasma Lp(a) in patients with premature CHD.
Bone Structure and Turnover in Postmenopausal Women With Long‐Standing Type 1 Diabetes
Authors: Shah Viral N , Qui Shijing , Stoneback Jason , Qamar Lubna , Ferguson Virginia L , Kohrt Wendy M , Snell‐Bergeon Janet K , Rao Sudhaker D 
Published: October 2023

ABSTRACTCompromised bone structural and mechanical properties are implicated in the increased fracture risk in type 1 diabetes (T1D). We investigated bone structure and turnover by histomorphometry in postmenopausal women with T1D and controls without diabetes using tetracycline double‐labeled transiliac bone biopsy. After in vivo tetracycline double labeling, postmenopausal women with T1D of at least 10 years and without diabetes underwent transiliac bone biopsy. An expert blinded to the study group performed histomorphometry. Static and dynamic histomorphometry measurements were performed and compared between the two groups. The analysis included 9 postmenopausal women with T1D (mean age 58.4 ± 7.1 years with 37.9 ± 10.9 years of diabetes and HbA1c 7.1% ± 0.4%) and 7 postmenopausal women without diabetes (mean age 60.9 ± 3.3 years and HbA1c 5.4% ± 0.2%). There were no significant differences in serum PTH (38.6 ± 8.1 versus 51.9 ± 23.9 pg/mL), CTX (0.4 ± 0.2 versus 0.51 ± 0.34 ng/mL), or P1NP (64.5 ± 26.2 versus 87.3 ± 45.3 ng/mL). Serum 25‐hydroxyvitamin D levels were higher in T1D than in controls (53.1 ± 20.8 versus 30.9 ± 8.2 ng/mL, p < 0.05). Bone structure metrics (bone volume, trabecular thickness, trabecular number, and cortical thickness) were similar between the groups. Indices of bone formation (osteoid volume, osteoid surface, and bone formation rate) were 40% lower in T1D and associated with lower activation frequency. However, the differences in bone formation were not statistically significant. Long‐standing T1D may affect bone turnover, mainly bone formation, without significantly affecting bone structure. Further research is needed to understand bone turnover and factors affecting bone turnover in people with T1D. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.
Cell culture‐derived extracellular vesicles: Considerations for reporting cell culturing parameters
Authors: Shekari Faezeh , Alibhai Faisal J. , Baharvand Hossein , Börger Verena , Bruno Stefania , Davies Owen , Giebel Bernd , Gimona Mario , Salekdeh Ghasem Hosseini , Martin‐Jaular Lorena , Mathivanan Suresh , Nelissen Inge , Nolte‐’t Hoen Esther , O'Driscoll Lorraine , Perut Francesca , Pluchino Stefano , Pocsfalvi Gabriella , Salomon Carlos , Soekmadji Carolina , Staubach Simon , Torrecilhas Ana Claudia , Shelke Ganesh Vilas , Tertel Tobias , Zhu Dandan , Théry Clotilde , Witwer Kenneth , Nieuwland Rienk 
Published: October 2023

AbstractCell culture‐conditioned medium (CCM) is a valuable source of extracellular vesicles (EVs) for basic scientific, therapeutic and diagnostic applications. Cell culturing parameters affect the biochemical composition, release and possibly the function of CCM‐derived EVs (CCM‐EV). The CCM‐EV task force of the Rigor and Standardization Subcommittee of the International Society for Extracellular Vesicles aims to identify relevant cell culturing parameters, describe their effects based on current knowledge, recommend reporting parameters and identify outstanding questions. While some recommendations are valid for all cell types, cell‐specific recommendations may need to be established for non‐mammalian sources, such as bacteria, yeast and plant cells. Current progress towards these goals is summarized in this perspective paper, along with a checklist to facilitate transparent reporting of cell culturing parameters to improve the reproducibility of CCM‐EV research.
A novel framework for a multimodel ensemble of GCMs and its application in the analysis of projected extremes
Authors: Ganguly Titas , Arya Dhyan S. 
Published: October 2023

AbstractMethodologies for evaluating global climate models (GCMs) and generating multimodel ensembles have branched to meet the diverse needs of impact assessment studies. However, there has been limited focus on their intercomparison. In this context, a comprehensive framework comprising the major strands of GCM ranking and ensemble data generation is proposed in the current study. The framework incorporates error index‐based rankings and Bayesian method‐based weight distribution. Within the Bayesian analysis, a nonparametric (orthonormal) distribution is introduced in this study with the hypothesis that the efficiency of nonparametric distribution in modelling natural random phenomena will accentuate the efficiency of the ranking and ensemble process. Precipitation and temperature data of 21 GCMs from Coupled Model Intercomparison Project Phase 5 covering India is used to validate the proposed framework. Finally, the ensemble data generated from the framework is used for the analysis of projected extremes and their attribution. Results show that Bayesian framework‐based rankings outperform other methods in 87.5% of instances. In the case of precipitation, the orthonormal distribution‐based Bayesian ranking produces better results for 85.2% of India, while it produces the lowest error ensemble for 79% of the country. The data from the framework are compared to the widely used mathematical average of GCMs. It is found that for precipitation and maximum temperature, the weighted ensemble has closer proximity to the distributive properties of the observed data for the entire study area. Furthermore, uncertainty analysis shows that the ensemble data have minimum uncertainty for the entire area in the case of precipitation. Finally, the assessment of projected extremes shows low to medium confidence (~27%) in the attribution of precipitation extremes to anthropogenic causes under representative concentration pathway (RCP) 4.5, while under RCP 8.5, the confidence is around 80%. For temperature, it is greater than 90% in both scenarios.
Classification of oolong tea varieties based on computer vision and convolutional neural networks
Authors: Zhu Yiwen , Chen Siyuan , Yin Hanzhe , Han Xihao , Xu Menghan , Wang Wenli , Zhang Yin , Feng Xiaoxiao , Liu Yuan 
Published: October 2023

AbstractBACKGROUNDIn the contemporary food industry, accurate and rapid differentiation of oolong tea varieties holds paramount importance for traceability and quality control. However, achieving this remains a formidable challenge. This study addresses this lacuna by employing machine learning algorithms – namely support vector machines (SVMs) and convolutional neural networks (CNNs) – alongside computer vision techniques for the automated classification of oolong tea leaves based on visual attributes.RESULTSAn array of 13 distinct characteristics, encompassing color and texture, were identified from five unique oolong tea varieties. To fortify the robustness of the predictive models, data augmentation and image cropping methods were employed. A comparative analysis of SVM‐ and CNN‐based models revealed that the ResNet50 model achieved a high Top‐1 accuracy rate exceeding 93%. This robust performance substantiates the efficacy of the implemented methodology for rapid and precise oolong tea classification.CONCLUSIONThe study elucidates that the integration of computer vision with machine learning algorithms constitutes a promising, non‐invasive approach for the quick and accurate categorization of oolong tea varieties. The findings have significant ramifications for process monitoring, quality assurance, authenticity validation and adulteration detection within the tea industry. © 2023 Society of Chemical Industry.
The Impact of Fused Filament Fabrication (FFF) Printing Profiles on 17‐4 PH Green and Sintered Parts
Authors: Tosto Claudio , Miani Fabio , Cicala Gianluca 
Published: October 2023

AbstractThe aim of this research is to characterize parts from innovative hybrid printing method for obtaining dense metal components using affordable fused filament fabrication (FFF). The introduction of Desktop Metal technology in 2015 really attracts an increase in industrial interest in the FFF printing of highly metal‐filled filament. Even though FFF is a well‐known process, there are not many studies on how to optimize the printing parameters for these feedstocks.The effects of the printing setting on producing high‐quality green parts and enhancing the mechanical properties of the finished 17‐4 PH metallic parts are investigated in this work. The influence of four printing profiles provided by a BASF plugin for Ultimaker Cura slicing software, obtained by combining different printing parameters is investigated.The ASTM E8 tensile test is used to determine the mechanical characteristics of the finished metal components. To identify differences in morphology, optical and scanning electron microscopy (SEM) observations are made on both sections of green and sintered samples. The effect of printing parameters on shrinkage and density are also taken into consideration.The findings demonstrate the importance of optimizing the printing of the green parts in order to produce full metal components that are both strong and dense.
Printability of a Recycled Thermoplastic Obtained from a Chemical Recycling Process of a Fully‐Recyclable Epoxy Matrix: An Upscaling Re‐Use Strategy
Authors: Saitta L. , Montalbano G. , Corvaglia I. , Brovarone C. Vitale , Cicala G. 
Published: October 2023

AbstractThis study presents an upscaling re‐use strategy for a recycled thermoplastic which is obtained starting from a chemical recycling approach for a bio‐based fully‐recyclable epoxy resin system. The recycling approach used relies on the selective cleaving of the epoxy‐cured network under mild conditions. The re‐use strategy proposed in this work consists in the use of the recycled thermoplastic (rTP), as obtained at the end of the recycling process and without any additional treatments, as raw material for a 3D printing process falling within the material extrusion category. The used 3D printing technique relies on the use of a thermoplastic printhead equipped with a metallic cartridge, fillable with the rTP material, to which a suitable pressure value is applied in order to start the extrusion process. The recycled material is characterized through thermal and rheological analysis in order to find the correct printing conditions, such as extrusion temperature and pressure applied. Next, the printability of specimens having different type of infill is investigated and the µCT analysis is used to evaluate the quality of the 3D printed samples.
Identification of a novel heterozygous PTH1R variant in a Chinese family with incomplete penetrance
Authors: Wang Jie , Zhao Chaoyue , Zhang Xin , Yang Li , Hu Yanyan 
Published: October 2023

AbstractBackgroundMutations in PTH1R are associated with Jansen‐type metaphyseal chondrodysplasia (JMC), Blomstrand osteochondrodysplasia (BOCD), Eiken syndrome, enchondroma, and primary failure of tooth eruption (PFE). Inheritance of the PTH1R gene can be either autosomal dominant or autosomal recessive, indicating the complexity of the gene. Our objective was to identify the phenotypic differences in members of a family with a novel PTH1R mutation.MethodsThe proband was a 13‐year, 6‐month‐old girl presenting with short stature, abnormal tooth eruption, skeletal dysplasia, and midface hypoplasia. The brother and father of the proband presented with short stature and abnormal tooth eruption. High‐throughput sequencing was performed on the proband, and the variant was confirmed in the proband and other family members by Sanger sequencing. Amino acid sequence alignment was performed using ClustalX software. Three‐dimensional structures were analyzed and displayed using the I‐TASSER website and PyMOL software.ResultsHigh‐throughput genome sequencing and Sanger sequencing validation showed that the proband, her father, and her brother all carried the PTH1R (NM_000316) c.1393G>A (p.E465K) mutation. The c.1393G>A (p.E465K) mutation was novel, as it has not been reported in the literature database. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, the p.E465K variant was considered to have uncertain significance. Biological information analysis demonstrated that this identified variant was highly conserved and highly likely pathogenic.ConclusionsWe identified a novel heterozygous mutation in the PTH1R gene leading to clinical manifestations with incomplete penetrance that expands the spectrum of known PTH1R mutations.
Living with and without an intestinal stoma: Factors that promote psychological well‐being and self‐care: A cross‐sectional study
Authors: Simpson Ellen , Pourshahidi Kirsty , Davis James , Slevin Mary , Lawther Roger , O'Connor Gloria , Porrett Terri , Marley Jerome , Gill Chris 
Published: October 2023

AbstractAimsThis study compared those living with and without an intestinal stoma in relation to physical and psychological health, stress and coping, quality of life and resilience. Also, identifying factors that could be used to promote better self‐care in stoma patients in the future.DesignA cross‐sectional and comparative study design was employed.MethodsParticipants were recruited via email and social media (Facebook and Twitter) between August 2018 and March 2019, to complete an online survey. The data were analysed using analysis of variance to examine group difference and a series of hierarchical linear regression analyses determining predictors of psychological well‐being.ResultsOf 278 participants aged 18–68 years who completed the survey, 129 (46%) had a stoma and reported significantly poorer physical health. Approximately one‐fifth experienced problems with stoma management. Psychological well‐being was mediated by the duration of living with a stoma (under 3 years) and frequency of leaks (weekly and monthly).
Associations among prenatal exposure to gestational diabetes mellitus, brain structure, and child adiposity markers
Authors: Luo Shan , Hsu Eustace , Lawrence Katherine E. , Adise Shana , Pickering Trevor A. , Herting Megan M. , Buchanan Thomas , Page Kathleen A. , Thompson Paul M. 
Published: October 2023

AbstractObjectiveThe aim of this study was to investigate the mediating role of child brain structure in the relationship between prenatal gestational diabetes mellitus (GDM) exposure and child adiposity.MethodsThis was a cross‐sectional study of 9– to 10‐year‐old participants and siblings across the US. Data were obtained from the baseline assessment of the Adolescent Brain Cognitive Development (ABCD) Study®. Brain structure was evaluated by magnetic resonance imaging. GDM exposure was self‐reported, and discordance for GDM exposure within biological siblings was identified. Mixed effects and mediation models were used to examine associations among prenatal GDM exposure, brain structure, and adiposity markers with sociodemographic covariates.ResultsThe sample included 8521 children (7% GDM‐exposed), among whom there were 28 sibling pairs discordant for GDM exposure. Across the entire study sample, prenatal exposure to GDM was associated with lower global and regional cortical gray matter volume (GMV) in the bilateral rostral middle frontal gyrus and superior temporal gyrus. GDM‐exposed siblings also demonstrated lower global cortical GMV than unexposed siblings. Global cortical GMV partially mediated the associations between prenatal GDM exposure and child adiposity markers.ConclusionsThe results identify brain markers of prenatal GDM exposure and suggest that low cortical GMV may explain increased obesity risk for offspring prenatally exposed to GDM.image
A Triptycene‐Based Layered/Flower‐Like 2D Conductive Metal–Organic Framework with 3D Extension as an Electrode for Efficient Li Storage
Authors: Liu Xiaobin , Yu Mengxiao , Liu Jiaqiang , Wu Songgu , Gong Junbo 
Published: October 2023

Abstract2D metal–organic frameworks (2D MOFs) with π conjugation have attracted widespread attention in the field of lithium storage due to their unique electron transfer units and structural characteristics. However, the periodic 2D planar extension structure hides some active sites, which is not conducive to the utilization of its structural advantages. In this work, a series of triptycene‐based 2D conductive MOFs (M‐DBH, M = Ni, Mn, and Co) with 3D extension structures are constructed by coordinating 9,10‐dihydro‐9,10‐[1,2]benzenoanthracene‐2,3,6,7,14,15‐hexaol with metal ions to explore their potential applications in lithium‐ion and lithium–sulfur batteries. This is the first study in which 2D conductive MOFs with the 3D extended molecule are used as electrode materials for lithium storage. The designed material generates rich active sites through staggered stacking layers and shows excellent performance in lithium‐ion and lithium–sulfur batteries. The capacity retention rate of Ni‐DBH can reach over 70% after 500 cycles at 0.2 C in lithium‐ion batteries, while the capacity of S@Mn‐DBH exceeds 305 mAh g−1 after 480 cycles at 0.5 C in lithium–sulfur batteries. Compared with the materials with 2D planar extended structures, the M‐DBH electrodes with 3D extended structures in this work exhibit better performance in terms of cycle time and lithium storage capacity.
Introducing Design Strategies to Preserve N‐Heterocycles Throughout the On‐Surface Synthesis of Graphene Nanostructures
Authors: Tenorio Maria , Moreno Cesar , Vilas‐Varela Manuel , Castro‐Esteban Jesús , Febrer Pol , Pruneda Miguel , Peña Diego , Mugarza Aitor 
Published: October 2023

AbstractDespite the impressive advances in the synthesis of atomically precise graphene nanostructures witnessed during the last decade, advancing in compositional complexity faces major challenges. The concept of introducing the desired functional groups or dopants in the molecular precursor often fails due to their lack of stability during the reaction path. Here, a study on the stability of different pyridine and pyrimidine moieties during the on‐surface synthesis of graphene nanoribbons on Au(111) is presented. Combining bond‐resolved scanning tunneling microscopy with X‐ray photoelectron spectroscopy, the thermal evolution of the nitrogen dopants throughout the whole reaction sequence is tracked. A comparative experimental and ab initio electronic characterization confirms the presence of dopants in the final structures, revealing also that the pyridinic nitrogen leads to a significant band downshift. The results demonstrate that, by using synthetic strategies to lower the reaction temperatures, one can preserve specific N‐heterocycles throughout all the reaction steps of the synthesis of graphene nanoribbons and beyond the interibbon coupling reaction that leads to nanoporous graphene.