bluuebunny/crossref_metadata_2025_split huggingface dataset:
Model‐Informed Pediatric Dose Selection for Dapagliflozin by Incorporating Developmental Changes
Authors: Jo Heeseung , Pilla Reddy Venkatesh , Parkinson Joanna , Boulton David W. , Tang Weifeng 
Published: January 2021

This analysis reports a quantitative modeling and simulation approach for oral dapagliflozin, a primarily uridine diphosphate‐glucuronosyltransferase (UGT)–metabolized human sodium‐glucose cotransporter 2 selective inhibitor. A mechanistic dapagliflozin physiologically based pharmacokinetic (PBPK) model was developed using in vitro metabolism and clinical pharmacokinetic (PK) data and verified for context of use (e.g., exposure predictions in pediatric subjects aged 1 month to 18 years). Dapagliflozin exposure is challenging to predict in pediatric populations owing to differences in UGT1A9 ontogeny maturation and paucity of clinical PK data in younger age groups. Based on the exposure–response relationship of dapagliflozin, twofold acceptance criteria were applied between model‐predicted and observed drug exposures and PK parameters (area under the curve and maximum drug concentration) in various scenarios, including monotherapy in healthy adults (single/multiple dose), monotherapy in hepatically or renally impaired patients, and drug–drug interactions with UGT1A9 modulators, such as mefenamic acid and rifampin. The PBPK model captured the observed exposure within twofold of the observed monotherapy data in adults and adolescents and in special population. As a guide to determining dosing regimens in pediatric studies, the verified PBPK model, along with UGT enzyme ontogeny maturation understanding, was used for predictions of dapagliflozin monotherapy exposures in pediatric subjects aged 1 month to 18 years that best matched exposure in adult patients with a 10‐mg single dose of dapagliflozin.
Population pharmacokinetics of letermovir following oral and intravenous administration in healthy participants and allogeneic hematopoietic cell transplantation recipients
Authors: Prohn Marita , Viberg Anders , Zhang Da , Dykstra Kevin , Davis Casey , Macha Sreeraj , Sabato Philip , de Alwis Dinesh , Iwamoto Marian , Fancourt Craig , Cho Carolyn R. 
Published: January 2021

AbstractLetermovir is indicated for prophylaxis of cytomegalovirus infection and disease in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Two‐stage population pharmacokinetic (PK) modeling of letermovir was conducted to support dose rationale and evaluate the impact of intrinsic/extrinsic factors. Data from healthy phase I study participants over a wide dose range were modeled to evaluate the effects of selected intrinsic factors, including pharmacogenomics; next, phase III HSCT‐recipient data at steady‐state following clinical doses were modeled. The model in HSCT recipients adequately described letermovir PK following both oral or i.v. administration, and was consistent with the healthy participant model at steady‐state clinical doses. Intrinsic factor effects were not clinically meaningful. These staged analyses indicate that letermovir PK in HSCT recipients and healthy participants differ only with respect to bioavailability and absorption rate. The HSCT recipient model was suitable for predicting exposure for exposure–response analysis supporting final dose selection.
Optimized workflow for unknown screening using gas chromatography high‐resolution mass spectrometry expands identification of contaminants in silicone personal passive samplers
Authors: Travis Steven C. , Kordas Katarzyna , Aga Diana S. 
Published: January 2021

RationaleSilicone wristbands have emerged as valuable passive samplers for monitoring of personal exposure to environmental contaminants in the rapidly developing field of exposomics. Once deployed, silicone wristbands collect and hold a wealth of chemical information that can be interrogated using high‐resolution mass spectrometry (HRMS) to provide a broad coverage of chemical mixtures.MethodsGas chromatography coupled to Orbitrap™ mass spectrometry (GC/Orbitrap™ MS) was used to simultaneously perform suspect screening (using in‐house database) and unknown screening (using vendor databases) of extracts from wristbands worn by volunteers. The goal of this study was to optimize a workflow that allows detection of low levels of priority pollutants, with high reliability. In this regard, a data processing workflow for GC/Orbitrap™ MS was developed using a mixture of 123 environmentally relevant standards consisting of pesticides, flame retardants, organophosphate esters, and polycyclic aromatic hydrocarbons as test compounds.ResultsThe optimized unknown screening workflow using a search index threshold of 750 resulted in positive identification of 70 analytes in validation samples, and a reduction in the number of false positives by over 50%. An average of 26 compounds with high confidence identification, 7 level 1 compounds and 19 level 2 compounds, were observed in worn wristbands. The data were further analyzed via suspect screening and retrospective suspect screening to identify an additional 36 compounds.ConclusionsThis study provides three important findings: (1) a clear evidence of the importance of sample cleanup in addressing complex sample matrices for unknown analysis, (2) a valuable workflow for the identification of unknown contaminants in silicone wristband samplers using electron ionization HRMS data, and (3) a novel application of GC/Orbitrap™ MS for the unknown analysis of organic contaminants that can be used in exposomics studies.
Surgical outcomes of conventional laparoscopic and robotic‐assisted hysterectomy
Authors: Gitas Georgios , Alkatout Ibrahim , Proppe Louisa , Werner Nele , Rody Achim , Hanker Lars , Pados George , Freytag Damaris , Sommer Soteris , Baum Sascha 
Published: January 2021

AbstractIntroductionThe aim of the present study was to compare surgical outcomes of total laparoscopic hysterectomy with those of the robotic approach using the da Vinci Xi system.MethodsPatients who underwent hysterectomy with da Vinci Xi for early endometrial cancer or benign indications from 2018 to 2019 were selected. The control group consisted of patients who underwent conventional laparoscopy.ResultsA total of 300 patients were included in the study. The mean duration of surgery differed significantly (p = 0.025) between those who underwent laparoscopy (125.01 ± 76.168) and robotic‐assisted surgery (142.96 ± 82.657 min). Blood loss, median hospital stay, intraoperative and postoperative complications were similar in both groups. No statistical difference was observed in the subgroups with a body mass index of more than 30 kg/m2 or more than 40 kg/m2 concerning the duration of surgery or the surgical outcome.ConclusionThe da Vinci Xi did not improve surgical outcomes in patients who underwent hysterectomy by trained laparoscopists and takes more time than conventional laparoscopy when performed in patients of normal weight.
Altered gut microbial metabolites could mediate the effects of risk factors in Covid‐19
Authors: Chen Jiezhong , Hall Sean , Vitetta Luis 
Published: January 2021

SummaryCoronavirus disease 2019 (Covid‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, is now pandemic. While most Covid‐19 patients will experience mild symptoms, a small proportion will develop severe disease, which could be fatal. Clinically, Covid‐19 patients manifest fever with dry cough, fatigue and dyspnoea, and in severe cases develop into acute respiratory distress syndrome (ARDS), sepsis and multi‐organ failure. These severe patients are characterized by hyperinflammation with highly increased pro‐inflammatory cytokines including IL‐6, IL‐17 and TNF‐alpha as well as C‐reactive protein, which are accompanied by decreased lymphocyte counts. Clinical evidence supports that gut microbiota dysregulation is common in Covid‐19 and plays a key role in the pathogenesis of Covid‐19. In this narrative review, we summarize the roles of intestinal dysbiosis in Covid‐19 pathogenesis and posit that the associated mechanisms are being mediated by gut bacterial metabolites. Based on this premise, we propose possible clinical implications. Various risk factors could be causal for severe Covid‐19, and these include advanced age, concomitant chronic disease, SARS‐CoV‐2 infection of enterocytes, use of antibiotics and psychological distress. Gut dysbiosis is associated with risk factors and severe Covid‐19 due to decreased commensal microbial metabolites, which cause reduced anti‐inflammatory mechanisms and chronic low‐grade inflammation. The preconditioned immune dysregulation enables SARS‐CoV‐2 infection to progress to an uncontrolled hyperinflammatory response. Thus, a pre‐existing gut microbiota that is diverse and abundant could be beneficial for the prevention of severe Covid‐19, and supplementation with commensal microbial metabolites may facilitate and augment the treatment of severe Covid‐19.
Unified tracking control under full‐state constraints imposed irregularly
Authors: Cui Qian , Wang Yujuan , Song Yongduan 
Published: January 2021

AbstractIt is nontrivial to address the control problem of nonlinear systems with irregular constraining conditions (where the constraints, possibly time‐varying, asymmetric and alternating positively and negatively, would occur or disappear in the middle of system operation). In this work, we present a control design framework for uncertain pure‐feedback systems under the aforementioned constraining conditions. By making use of auxiliary constraining boundaries, we analytically extend the originally imposed constraints over the entire time interval of system operation, with which we introduce a useful state transformation with unique features. It is such transformation that allows for the development of the control scheme capable of uniformly addressing a variety of constraints formed dynamically and imposed irregularly. It is shown that, for the scenarios where the constraints are partially or fully imposed or removed at any time instant during system operation, one only needs to reset the corresponding extended constraining boundaries in the control scheme instead of altering its structure. Both theoretical analysis and numerical simulation authenticate the effectiveness of the proposed method.
Guaranteed cost control of rigid‐body attitude systems under control saturation
Authors: Wang Hui , Yang Jianan , Liang Ye , Zhu Yanzheng , Zhang Lixian 
Published: January 2021

AbstractThis article investigates the guaranteed cost control (GCC) problem of nonlinear rigid‐body attitude systems subject to control saturation. A novel methodology is proposed, by which the nonlinearities inherent in the attitude dynamics are effectively accounted for and thereby the existence of the proposed controller is cast into linear/bilinear matrix inequality conditions without resorting to model linearization techniques. As a result, the underlying closed‐loop attitude system can be asymptotically stabilized by limited control effort and the defined cost function has an upper bound, by which four optimal GCC methods are further formed to minimize the cost index. Simulation results are provided that fully highlight the properties of the developed methodology in terms of cost guaranteeing and control effort limiting.
Solvent‐Controlled Regioselectivity in Nucleophilic Substitution Reactions of 1‐X‐2,4‐Difluorobenzenes with Morpholine Using Deep Eutectic Solvents
Authors: Valvi Arun , Tiwari Shraeddha 
Published: January 2021

AbstractRegioselectivity in aromatic nucleophilic substitution (SNAr) reactions of activated substrates is critical but challenging to control. The use of reaction media to achieve the desired regioselectivity is a promising approach, given the sensitivity of nucleophilic substitutions to solute‐solvent interactions. The present report exploits the sensitivity of SNAr reactions to medium effects by using varying compositions of deep eutectic solvents (DES) to achieve excellent regioselectivity. Substitution reactions of 2,4‐difluoroacetophenone (1), 2,4‐diflurobenzonitrile (3) and 2,4‐difluoronitrobenzene (5) with morpholine (2) were carried out in 15 DES mixtures using the “zero VOC” strategy. The regioselectivity was determined using NMR spectra and was observed to change drastically with the substrate and nature of the eutectic mixture. Substitution reaction (1+2) was the most sensitive to reaction medium. The regioselectivity for (1+2) changed from para‐selective (85 : 15 para:ortho ratio) to ortho‐selective (24 : 76 selectivity ratio) by merely changing the DES medium. The results demonstrate that eutectic mixtures could be effectively used as reaction media to control the desired stereochemical outcome.
Thermal Stability, Kinetic Degradation and Lifetime Prediction of Chitosan Schiff Bases Derived from Aromatic Aldehydes
Authors: El Hamdaoui Lahcen , El Marouani Maryam , El Bouchti Mehdi , Kifani‐Sahban Fatima , El Moussaouiti Mohammed 
Published: January 2021

AbstractThis study intends to synthesis chitosan‐aromatic aldehyde Schiff bases (ChSB) to investigate their thermal stability and kinetics degradation. All samples were characterized by FTIR, XRD and SEM techniques. Chitosan and chitosan derivatives were subjected to thermo‐gravimetric analysis, at four multiple heating rates 5, 10, 15 and 20 °C.min−1. Calculations using two isoconversional integral methods, Flynn Wall Ozawa and Kissinger were performed. The changes in Entropy, Enthalpy, Gibbs free energy, and lifetime have been estimated. Thus, chitosan modification with aromatic aldehydes would have an accelerating effect on thermal decomposition. In addition, chitosan p‐chlorobenzaldehyde were found to have the relative highest activation energy and the highest lifetime to thermally decompose amongst the other examined biopolymers. The kinetic process for the degradation of pure chitosan, chitosan‐N,N‐dimethylaminobenzaldehyde and chitosan‐p‐chlorobenzaldehyde was most probably described by an exponential function E1.While for chitosan‐p‐methoxybenzoaldehyde the function D12 corresponding to a mechanism coupling “transfer and diffusion” seems to describe the degradation.
Impedimetric Microfluidic Sensor‐in‐a‐Tube for Label‐Free Immune Cell Analysis
Authors: Egunov Aleksandr I. , Dou Zehua , Karnaushenko Dmitriy D. , Hebenstreit Franziska , Kretschmann Nicole , Akgün Katja , Ziemssen Tjalf , Karnaushenko Daniil , Medina‐Sánchez Mariana , Schmidt Oliver G. 
Published: January 2021

AbstractAnalytical platforms based on impedance spectroscopy are promising for non‐invasive and label‐free analysis of single cells as well as of their extracellular matrix, being essential to understand cell function in the presence of certain diseases. Here, an innovative rolled‐up impedimetric microfulidic sensor, called sensor‐in‐a‐tube, is introduced for the simultaneous analysis of single human monocytes CD14+ and their extracellular medium upon liposaccharides (LPS)‐mediated activation. In particular, rolled‐up platinum microelectrodes are integrated within for the static and dynamic (in‐flow) detection of cells and their surrounding medium (containing expressed cytokines) over an excitation frequency range from 102 to 5 × 106 Hz. The correspondence between cell activation stages and the electrical properties of the cell surrounding medium have been detected by electrical impedance spectroscopy in dynamic mode without employing electrode surface functionalization or labeling. The designed sensor‐in‐a‐tube platform is shown as a sensitive and reliable tool for precise single cell analysis toward immune‐deficient diseases diagnosis.
Single‐Atom Catalysts for Nanocatalytic Tumor Therapy
Authors: Lu Xiangyu , Gao Shanshan , Lin Han , Shi Jianlin 
Published: January 2021

AbstractRecently, single‐atom catalysts (SACs) have been receiving increasing attention in various catalytic fields, and meanwhile, emerging nanocatalytic medicine provides a novel tumor chemotherapy modality without using toxic chemodrugs. The distinct properties of SACs, such as well‐defined and precisely located metal centers, identical coordination environment, tailorable composition and structure, and versatile functionality, make them promising candidates for catalytic tumor therapy. Herein, the most recent advances in nanocatalytic tumor therapy by using various types of SACs, especially their remarkable achievements in several nanocatalytic tumor therapy‐based modalities, such as chemodynamic therapy by tumor microenvironment‐responsive catalytic reactions, photodynamic therapy by photocatalytic reactions, sonodynamic therapy by sonocatalytic reactions, and parallel catalytic therapy by parallel catalytic reactions, are reviewed by focusing on the catalytic nanoplatform construction and catalytic mechanism. A concise but concentrated summary and outlook are provided finally to outline the perspectives and the remaining challenges for the future design and engineering of SACs for tumor therapy.
Sustainable Synthesis of Bimetallic Single Atom Gold‐Based Catalysts with Enhanced Durability in Acetylene Hydrochlorination
Authors: Kaiser Selina K. , Clark Adam H. , Cartocci Lucrezia , Krumeich Frank , Pérez‐Ramírez Javier 
Published: January 2021

AbstractGold single‐atom catalysts (SACs) exhibit outstanding reactivity in acetylene hydrochlorination to vinyl chloride, but their practical applicability is compromised by current synthesis protocols, using aqua regia as chlorine‐based dispersing agent, and their high susceptibility to sintering on non‐functionalized carbon supports at >500 K and/or under reaction conditions. Herein, a sustainable synthesis route to carbon‐supported gold nanostructures in bimetallic catalysts is developed by employing salts as alternative chlorine source, allowing for tailored gold dispersion, ultimately reaching atomic level when using H2PtCl6. To rationalize these observations, several synthesis parameters (i.e., pH, Cl‐content) as well as the choice of metal chlorides are evaluated, hinting at the key role of platinum in promoting a chlorine‐mediated dispersion mechanism. This can be further extrapolated to redisperse large gold agglomerates (>70 nm) on carbon carriers into isolated atoms, which has important implications for catalyst regeneration. Another key role of platinum single atoms is to inhibit the sintering of their spatially isolated gold‐based analogs up to 800 K and during acetylene hydrochlorination, without compromising the intrinsic activity of Au(I)‐Cl active sites. Accordingly, exploiting cooperativity effects of a second metal is a promising strategy towards practical applicability of gold SACs, opening up exciting opportunities for multifunctional single‐atom catalysis.
Peptide‐Engineered Fluorescent Nanomaterials: Structure Design, Function Tailoring, and Biomedical Applications
Authors: Wang Yan , Xia Kai , Wang Luchen , Wu Mingxue , Sang Xiujie , Wan Keming , Zhang Xiaodong , Liu Xiaomin , Wei Gang 
Published: January 2021

AbstractFluorescent nanomaterials have exhibited promising applications in biomedical and tissue engineering fields. To improve the properties and expand bioapplications of fluorescent nanomaterials, various functionalization and biomodification strategies have been utilized to engineer the structure and function of fluorescent nanomaterials. Due to their high biocompatibility, satisfied bioactivity, unique biomimetic function, easy structural tailoring, and controlled self‐assembly ability, supramolecular peptides are widely used as versatile modification agents and nanoscale building blocks for engineering fluorescent nanomaterials. In this work, recent advance in the synthesis, structure, function, and biomedical applications of peptide‐engineered fluorescent nanomaterials is presented. Firstly, the types of different fluorescent nanomaterials are introduced. Then, potential strategies for the preparation of peptide‐engineered fluorescent nanomaterials via templated synthesis, bioinspired conjugation, and peptide assembly‐assisted synthesis are discussed. After that, the unique structure and functions through the peptide conjugation with fluorescent nanomaterials are demonstrated. Finally, the biomedical applications of peptide‐engineered fluorescent nanomaterials in bioimaging, disease diagnostics and therapy, drug delivery, tissue engineering, antimicrobial test, and biosensing are presented and discussed in detail. It is helpful for readers to understand the peptide‐based conjugation and bioinspired synthesis of fluorescent nanomaterials, and to design and synthesize novel hybrid bionanomaterials with special structures and improved functions for advanced applications.
Room‐Temperature Exciton‐Based Optoelectronic Switch
Authors: Ye Tong , Zhou Boxuan , Liu Zeyi , Li Yongzhuo , Shen Hongzhi , Ning Cun‐Zheng , Li Dehui 
Published: January 2021

AbstractExcitons, bound pairs of electrons and holes, could act as an intermediary between electronic signal processing and optical transmission, thus speeding up the interconnection of photoelectric communication. However, up to date, exciton‐based logic devices such as switches that work at room temperature are still lacking. This work presents a prototype of a room‐temperature optoelectronic switch based on excitons in WSe2 monolayer. The emission intensity of WSe2 stacked on Au and SiO2 substrates exhibits completely opposite behaviors upon applying gate voltages. Such observation can be ascribed to different doping behaviors of WSe2 caused by charge‐transfer and chemical‐doping effect at WSe2/Au and WSe2/SiO2 interfaces, respectively, together with the charge‐drift effect. These interesting features can be utilized for optoelectronic switching, confirmed by the cyclic PL switching test for a long time exceeding 4000 s. This study offers a universal and reliable approach for the fabrication of exciton‐based optoelectronic switches, which would be essential in integrated nanophotonics.
Coupling of Silk Fibroin Nanofibrils Enzymatic Membrane with Ultra‐Thin PtNPs/Graphene Film to Acquire Long and Stable On‐Skin Sweat Glucose and Lactate Sensing
Authors: Liu Xiaotian , Zhang Wenli , Lin Zaifu , Meng Zhaohui , Shi Chenyang , Xu Zhijun , Yang Likun , Liu Xiang Yang 
Published: January 2021

AbstractThe applications of enzymatic biosensors are largely limited by their relatively poor stability and short lifespan. Herein, a bio‐active porous enzymatic nanofiber (PEN) membrane composed of silk fibroin nanofibrils (SFNFs) and enzymes is developed to effectively retain the enzymes in the 3D space. The 3D functional scaffolds formed by SFNFs can immobilize enzymes and provide a large surface area for molecular/ion diffusion and biochemical reactions. The PEN membrane is subsequently attached to an ultra‐thin PtNPs/graphene (Pt‐G) nanocomposite film to facilitate the electron transport between the enzymes and electrodes, permitting highly effective glucose and lactate sensing with long and stable performance. The as‐assembled glucose and lactate sensors demonstrate high sensitivity, good cyclic reproducibility, and in particular long‐term stability of up to 25 and 23.6 h, respectively. These glucose sensors have a working life that is ≈1.25‐times longer than that of the best available sensors reported so far. Moreover, a wearable platform based on the sensors is developed for real‐time analysis of sweat during outdoor exercising to transmit signals to a mobile handset. The high sensitivity, comfort and long‐term stability of the device can benefit for long‐term in‐line surveillance of physiological conditions.