bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of LC–MS/MS methods for the simultaneous quantification of sofosbuvir and its major metabolite (GS‐331007) in blood plasma and cerebrospinal and seminal fluid: Application to a pilot clinical trial with a focus on Zika
Authors: Vilhena Leandro Schiavo , de Azevedo da Silva Aline Campos , dias da Silva Diego Medeiros , Pinto Douglas Pereira , Coelho Estephane Fernandes , de Araújo João Felipe Garcia Medeiros , da Silveira Gabriel Parreiras Estolano , Pereira Heliana Martins , da Silva Letícia de Sá Fernandes Vallim , Estrela Marins Rita de Cássia Elias , Bortolini Roberta Ghilosso , Souza Thiago Moreno L. , dos Santos Valdiléa Gonçalves Veloso , de Assis Nascimento Viviane , Amendoeira Fábio Coelho , da Fonseca Laís Bastos 
Published: February 2023

AbstractZika still poses a threat to global health owing to its association with serious neurological conditions and the absence of a vaccine and treatment. Sofosbuvir, an anti‐hepatitis C drug, has shown anti‐Zika effects in animal and cell models. Thus, this study aimed to develop and validate novel LC–MS/MS methods for the quantification of sofosbuvir and its major metabolite (GS‐331007) in human plasma and cerebrospinal (CSF) and seminal fluid (SF), and apply the methods to a pilot clinical trial. The samples were prepared by liquid–liquid extraction and separated using isocratic mode on Gemini C18 columns. Analytical detection was performed using a triple quadrupole mass spectrometer equipped with an electrospray ionization source. The validated ranges for sofosbuvir were 0.5–2,000 ng/mL (plasma) and 0.5–100 ng/mL (CSF and SF), while for the metabolite they were 2.0–2,000 ng/mL (plasma), 5.0–200 ng/mL (CSF) and 10–1,500 ng/mL (SF). The intra‐day and inter‐day accuracies (90.8–113.8%) and precisions (1.4–14.8%) were within the acceptance range. The developed methods fulfilled all validation parameters concerning selectivity, matrix effect, carryover, linearity, dilution integrity, precision, accuracy and stability, confirming the suitability of the method for the analysis of clinical samples.
Dose–volume constraints for head‐and‐neck cancer in carbon ion radiotherapy: A literature review
Authors: Varnava Maria , Musha Atsushi , Tashiro Mutsumi , Kubo Nobuteru , Okano Naoko , Kawamura Hidemasa , Ohno Tatsuya 
Published: February 2023

AbstractBackgroundCarbon ion radiotherapy (CIRT) has been applied in cancer treatment for over 25 years. However, guidelines for dose–volume constraints have not been established yet. The aim of this review is to summarize the dose–volume constraints in CIRT for head‐and‐neck (HN) cancer that were determined through previous clinical studies based on the Japanese models for relative biological effectiveness (RBE).MethodsA literature review was conducted to identify all constraints determined for HN cancer CIRT that are based on the Japanese RBE models.ResultsDose–volume constraints are reported for 17 organs at risk (OARs), including the brainstem, ocular structures, masticatory muscles, and skin. Various treatment planning strategies are also presented for reducing the dose delivered to OARs.ConclusionsThe reported constraints will provide assistance during treatment planning to ensure that radiation to OARs is minimized, and thus adverse effects are reduced. Although the constraints are given based on the Japanese RBE models, applying the necessary conversion factors will potentially enable their application by institutions worldwide that use the local effect model for RBE.
Electrodeposition of Ni−Rh Alloys and their Use as Cathodes for Nitrate Reduction in Alkaline Solutions
Authors: Mattarozzi Luca , Cattarin Sandro , Comisso Nicola , Musiani Marco , Vázquez‐Gómez Lourdes , Verlato Enrico 
Published: February 2023

AbstractCompact Ni−Rh alloys are electrodeposited potentiostatically on rotating disk and sheet electrodes; film compositions are adjusted by varying bath composition and deposition potential Edep. SEM images of these alloys show a compact, globular morphology for Rh contents up to 30 at%, and a smoother aspect for films with a medium‐to‐high content of Rh. XRD spectra show the formation of a single crystalline phase, with diffraction peaks in intermediate positions between those of the constituent elements. Data analysis indicates that crystal lattice parameters vary with composition according to Vegard's law. Linear voltammetries of nitrate reduction in alkali highlight a maximum of activity, in terms of reduction current, for alloys in the range of 10–30 at.% Rh. Prolonged electrolysis at appropriate potential performed with Ni85Rh15 alloy shows, in comparison with pure Ni and pure Rh: much increased activity and faster abatement of nitrate; lower production of the undesired nitrite species; higher selectivity towards production of ammonia.
Carrier‐Free Enzyme Immobilizates for Flow Chemistry
Authors: Ölçücü Gizem , Krauss Ulrich , Jaeger Karl-Erich , Pietruszka Jörg 
Published: February 2023

AbstractFor the development of efficient and green industrial processes, the combination of biocatalysis and flow chemistry holds great promises. Flow chemical utilization of biocatalysts, essentially made possible by the immobilization (or retention) of enzymes in flow reactors, has attracted increased academic attention during recent years. In the present review we present an overview of immobilization strategies suitable for flow chemistry, particularly focusing on recently developed carrier‐free immobilization methods, highlighting advances in the field and presenting future trends.
A Flexible and Wearable Strain Sensor from Polypyrrole‐Doped Elastomers with Dual Functions in Motion Monitoring and Thermotherapy†
Authors: Wei Wanyuan , Wu Mengjiao , Chen Yulan 
Published: February 2023

Comprehensive SummaryFlexible strain sensors are essential components of wearable electronic skins. Here we report a new kind of flexible strain sensor by filling conductive nanowires in elastomers featuring a concentration gradient. The fabrication method involves a fast photo‐induced copolymerization of acrylates in the presence of gradient deposited polypyrrole (PPy) nanowires, which is facile and cost‐effective in steadily doping PPy into elastomeric films. The combination of delicately selected polyacrylates as the matrix filled with entangled, nano‐sized PPy endows the sensor good stretchability, sensitive deformation‐electrical signal conversion and high fatigue resistance, which can be used repeatedly without scarifying the sensitivity of electrical signal. Besides, the lower side of the composite films exhibits high light absorption (> 98%) in a wide spectral range (250—2400 nm). Systematic characterizations of the sensors support that the excellent strain sensing and light‐heat conversion performances are essentially dependent on the gradient filling of PPy nanowires. Moreover, the applications of this flexible strain sensor for human motion monitoring and wearable thermotherapy are demonstrated, manifesting a promising option for wearable electronics and personalized healthcare.
Addressing current challenges in optimization of lipid management following an ACS event: Outcomes of the ACS EuroPath III initiative
Authors: Catapano Alberico L. , De Caterina Raffaele , Jukema J. Wouter , Klempfner Robert , Landmesser Ulf , Schiele François , Sionis Alessandro 
Published: February 2023

AbstractBackgroundLow‐density lipoprotein cholesterol (LDL‐C) lowering is key to reduce atherosclerotic disease progression and recurrent events for patients after acute coronary syndrome (ACS). However, LDL‐C management for post‐ACS patients remains challenging in clinical practice.HypothesisThe ACS EuroPath III project was designed to optimize LDL‐C management in post‐ACS patients by promoting guideline implementation and translating existing evidence into effective actions.MethodsThree surveys targeting cardiologists (n = 555), general practitioners (GPs; n = 445), and patients (n = 662) were conducted in Europe, with the aim of capturing information on patient characteristics and treatment during acute phase, discharge and follow‐up. GPs’ and patients’ opinions on key treatment aspects were also collected. Based on survey results, international experts and clinicians identified areas of improvement and generated prototype solutions. Participants voted to select the most feasible and replicable proposals for co‐development and implementation.ResultsFive key areas of improvement were identified: (1) inappropriate treatment prescribed at discharge; (2) lack of lipid guidance in the discharge letter; (3) inadequate lipid‐lowering therapy (LLT) optimization; (4) gaps in guideline knowledge and lack of referral practices for GPs; (5) patients’ concerns about lipid management. Proposed solutions for these focus areas included development of a treatment algorithm for the acute phase, a standardized GP discharge letter, an assessment tool for LLT efficacy at follow‐up, an education plan for GPs/patients and a patient engagement discharge kit. The standardized GP discharge letter and treatment algorithm have been selected as the highest priority solutions for development.ConclusionThese initiatives have the potential to improve adherence to guidelines and patient management after ACS.
Decoding post‐translational modifications of mammalian septins
Authors: Sharma Khushboo , Menon Manoj B. 
Published: February 2023

AbstractSeptins are cytoskeletal GTPases that form nonpolar filaments and higher‐ordered structures and they take part in a wide range of cellular processes. Septins are conserved from yeast to mammals but absent from higher plants. The number of septin genes vary between organisms and they usually form complex heteropolymeric networks. Most septins are known to be capable of GTP hydrolysis which may regulate septin dynamics. Knowledge on regulation of septin function by post‐translational modifications is still in its infancy. In this review article, we highlight the post‐translational modifications reported for the 13 human septins and discuss their implications on septin functions. In addition to the functionally investigated modifications, we also try to make sense of the complex septin post‐translational modification code revealed from large‐scale phospho‐proteomic datasets. Future studies may determine how these isoform‐specific and homology group specific modifications affect septin structure and function.
Biomechanical study of cornea response under orthokeratology lens therapy: A finite element analysis
Authors: Zhao Gai‐Ping , Zhai Hai‐Tao , Xiang Hua‐Zhong , Wu Li‐Ming , Chen Qi‐Ou , Chen Chi , Zhou Meng 
Published: February 2023

AbstractOrthokeratology (OK) is becoming a mainstream modality for myopia correction and control, but its underlying mechanism is not yet fully understood. In this study, the biomechanical response of cornea under the OK lens was investigated to further understand the mechanism of OK therapy. Numerical models of the cornea and OK lens with different corneal refractive powers and myopia degrees were established to analyze features and differences of the spatial displacement and stress distribution in different areas of the anterior corneal surface by finite element method. Displacement distributions on the anterior cornea surface with refractive powers of 39.5, 43, 46 D, and myopia degrees of −1.0, −3.0, −6.0 D demonstrate similar deformation trends and nearly rotationally symmetrical attributes of different corneal parameters. Displacement of mid‐peripheral cornea was significantly high compared with that of the central and peripheral cornea, peaking at ~2.4 mm off the corneal apex. The stress increased with the increase in myopia degrees and was significantly large for the myopia degrees of −6.0 D at S1; the stress at S2 and S6 was low and stable and did not differ much at S3; the stress at S4 and S5, however, was extremely high. In summary, simulation result of orthokeratology can effectively evaluate the performance of OK lens and it properly associates with the differential map of the corneal topography. The base curve of the OK lens may also play a role in mid‐peripheral corneal steepening. The design around the OK lens' alignment curve needs to be optimized.
Recent advances in agricultural disease image recognition technologies: A review
Authors: Bondre Shweta , Patil Dipti 
Published: February 2023

SummaryIn the world of intelligent agriculture, agricultural disease picture detection plays a critical role. Plant disease identification must be efficient if agricultural production is to be increased sustainably. Anomalies in plants affected by viruses, insects, nutritional deficiencies, or poor weather conditions have traditionally been diagnosed by human experts. Deep learning (DL) and transfer learning, two sophisticated machine learning techniques synonymous with the advancement of artificial intelligence technologies in recent years, have started to be used for the identification of agricultural diseases. However, a variety of significant obstacles exist in the way of widespread use of these approaches. This paper looks at DL and transfer learning in particular, and discusses recent developments in using these advanced technologies to recognize agricultural disease images. Many DL architectures have recently been adopted, along with visualization tools, which are critical for identifying signs and classifying plant diseases. The analysis and evaluation of these two approaches show that transfer learning is the better choice given existing agricultural disease data tools. The paper then looks at the key problems that need to be addressed for research in this area to advance, such as image dataset creation, the collection of big data auxiliary domains, and the optimization of the transfer learning process. The construction of technically feasible agricultural disease image recognition systems requires the creation of image datasets collected under real cultivation conditions. This survey aims to learn more about DL capabilities in plant disease detection to increase device efficiency and accuracy in future research.
Evaluating the Impact of Physiologically Relevant Oxygen Tensions on Drug Metabolism in 3D Hepatocyte Cultures in Paper Scaffolds
Authors: Sitte Zachary R. , DiProspero Thomas J. , Lockett Matthew R. 
Published: February 2023

AbstractOxygen is an essential regulator of cellular function and phenotype. Despite its importance, the incorporation of physiologically relevant oxygen tensions is often overlooked in experimental setups. Ambient oxygen tensions (pO2 ∼152 mmHg) are significantly higher than those in the alveolar‐capillary barrier of the lung, which is the most oxygen‐rich interface in the body (pO2 ∼104 mmHg). The discrepancy between standard culture practices and physiologically relevant oxygen tensions is more pronounced when considering the hepatocyte‐lined sinusoids of the liver, whose pO2 values range from 65 mm Hg in the periportal region to 30 mm Hg in the perivenous region. Our previous work highlights the need to transition from standard culture conditions to more physiologically relevant microenvironments when predicting hepatocyte responses to drug candidates or potential toxins. This protocol details an experimental pipeline for quantifying differences in transcript levels, protein levels, and activity of the cytochrome P450 1A (CYP1A) enzyme family in hepatocytes maintained in a three‐dimensional environment at ambient and physiologically relevant oxygen tensions. We quantify changes in transcript with qRT‐PCR, protein expression with western blots, and activity with the ethoxyresorufin‐O‐deethylase (EROD) assay. This approach can be adapted to any drug‐metabolizing enzyme. © 2023 Wiley Periodicals LLC.This article was corrected on 28 March 2023. See the end of the full text for details.Basic Protocol 1: Preparing tissue‐like environments to evaluate HepG2 cells in paper‐based cell culture platform at physiological oxygen levelsBasic Protocol 2: Evaluating CYP1A activity of hepatocytes grown in the paper scaffolds using the EROD assayBasic Protocol 3: Evaluating CYP1A transcript levels of hepatocytes grown in the paper scaffolds using RT‐qPCRBasic Protocol 4: Evaluating CYP1A protein levels of hepatocytes grown in the paper scaffolds using western blotting
Overview of Adductomics in Toxicology
Authors: Lockridge Oksana 
Published: February 2023

AbstractAdductomics is epidemiology at the molecular level. Untargeted adductomics compares levels of chemical adducts on albumin, hemoglobin, and DNA between healthy and exposed individuals. The goal is to determine a cause‐and‐effect relationship between chemical exposure and illness. Chemical exposures are not necessarily due to synthetic chemicals but are often due to oxidation products of naturally occurring lipids, for example, 4‐hydroxynonenal and acrolein produced by lipid peroxidation of arachidonic and linoleic acids. The preferred method used in adductomics is ultra‐high pressure liquid chromatography coupled to with nanoelectrospray tandem mass spectrometry. The mass of the adduct indicates its structure and identifies the chemical. The advantages of molecular epidemiology include information about the many toxicants to which a person is exposed over a period of weeks or months and the relative exposure levels. The disadvantage is the absence of information about the mechanism of toxicity. Untargeted adductomics examines albumin and hemoglobin adducts, which serve as biomarkers of exposure but do not identify the proteins and genes responsible for the toxicity. Targeted adductomics is used when the origin of the toxicity is known. This can be either an adducted protein, such as the butyrylcholinesterase protein modified by nerve agents, or a toxicant, such as acetaminophen. Untargeted adductomics methods have identified potential protein adduct biomarkers of breast cancer, colorectal cancer, childhood leukemia, and lung cancer. Adductomics is a new research area that offers structural insights into chemical exposures and a platform for the discovery of disease biomarkers. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.
Graphite‐Based Composite Anodes with C−O−Nb Heterointerfaces Enable Fast Lithium Storage
Authors: Liu Wenhao , Wang Xuanpeng , Liu Jinshuai , Guo Changyuan , Qiao Fan , Ding Xiaoling , Liao Xiaobin , Han Chunhua 
Published: February 2023

AbstractTo better satisfy the increasing demands for electric vehicles, it is crucial to develop fast‐charging lithium‐ion batteries (LIBs). However, the fast‐charging capability of commercial graphite anodes is limited by the sluggish Li+ insertion kinetics. Herein, we report a synergistic engineering of uniform nano‐sized T‐Nb2O5 particles on graphite (Gr@Nb2O5) with C−O−Nb heterointerfaces, which prevents the growth and aggregation of T‐Nb2O5 nanoparticles. Through detailed theoretical calculations and pair distribution function analysis, the stable existence of the heterointerfaces is proved, which can accelerate the electron/ion transport. These heterointerfaces endow Gr@Nb2O5 anodes with high ionic conductivity and excellent structural stability. Consequently, Gr@10‐Nb2O5 anode, where the mass ratio of T‐Nb2O5/graphite=10/100, exhibits excellent cyclic stability and incredible rate capabilities, with 100.5 mAh g−1 after 10000 stable cycles at an ultrahigh rate of 20 C. In addition, the synergistic Li+ storage mechanism is revealed by systematic electrochemical characterizations and in situ X‐ray diffraction. This work offers new insights to the reasonable design of fast‐charging graphite‐based anodes for the next generation of LIBs.
Loss of mitochondrial Chchd10 or Chchd2 in zebrafish leads to an ALS‐like phenotype and Complex I deficiency independent of the mitochondrial integrated stress response
Authors: Petel Légaré Virginie , Rampal Christian J. , Gurberg Tyler J. N. , Aaltonen Mari J. , Janer Alexandre , Zinman Lorne , Shoubridge Eric A. , Armstrong Gary A. B. 
Published: February 2023

AbstractMutations in CHCHD10 and CHCHD2, encoding two paralogous mitochondrial proteins, have been identified in cases of amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and Parkinson's disease. Their role in disease is unclear, though both have been linked to mitochondrial respiration and mitochondrial stress responses. Here, we investigated the biological roles of these proteins during vertebrate development using knockout (KO) models in zebrafish. We demonstrate that loss of either or both proteins leads to motor impairment, reduced survival and compromised neuromuscular junction integrity in larval zebrafish. Compensation by Chchd10 was observed in the chchd2−/− model, but not by Chchd2 in the chchd10−/− model. The assembly of mitochondrial respiratory chain Complex I was impaired in chchd10−/− and chchd2−/− zebrafish larvae, but unexpectedly not in a double chchd10−/− and chchd2−/− model, suggesting that reduced mitochondrial Complex I cannot be solely responsible for the observed phenotypes, which are generally more severe in the double KO. We observed transcriptional activation markers of the mitochondrial integrated stress response (mt‐ISR) in the double chchd10−/− and chchd2−/− KO model, suggesting that this pathway is involved in the restoration of Complex I assembly in our double KO model. The data presented here demonstrates that the Complex I assembly defect in our single KO models arises independently of the mt‐ISR. Furthermore, this study provides evidence that both proteins are required for normal vertebrate development.
A novel non‐pillar coal mining technology in longwall top coal caving: A case study
Authors: Wang Haosen , Wang Jiong , He Manchao , Ma Zimin , Tian Xichun , Liu Peng 
Published: February 2023

AbstractIn longwall top coal caving (LTCC) mining methods, problems such as large deformations, loss of coal resources, and excavation relay out of balance are often encountered with the increased production in single mining panels. To address these problems, a novel non‐pillar coal mining technology in LTCC was used based on the equilibrium mining theory. This approach could cut off the stress transmission, eliminate the coal pillar, and retain the gob‐side entry. In this technology, the entry is first excavated along the roof of the coal, and then four techniques are applied to control the surrounding rock of the retained entry. The constant resistance and large deformation anchor cable are used to maintain the roof stability. The directional roof split blasting technique is adopted to separate the roof between the entry and gob. The blocking‐gangue support system (BGSS) is used to form the gangue rib lagging the mining panel. The temporary support system is applied to prevent the roadway from being affected by the dynamic pressure and prevented the BGSS from falling. Finally, the field monitoring results indicate that the surrounding rock of retained entry is stabilized at 200 m behind the working face. The deformation of retained entry is within a reasonable range at 180–190 m behind the mining panel. The results provide an important reference for the thick coal seam non‐pillar coal mining technology, specifically using this technology in LTCC panels.