bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leveraging ToxCast data and protein sequence conservation to complement aquatic life criteria derivation
Authors: Schaupp Christopher M. , LaLone Carlie A. , Blackwell Brett R. , Ankley Gerald T. , Villeneuve Daniel L. 
Published: April 2022

Abstract
The USEPA's 1985 guidelines for the derivation of aquatic life criteria (ALC) are robust but data-intensive. For many chemicals, the extensive in vivo data sets required for ALC derivation are not available. Thus, alternative analyses and processes that can provide provisional values to guide states, tribes, and other stakeholders while data accumulate and more rigorous criteria are derived would be beneficial. The overarching purpose of this study was to assess the feasibility of using data from new approach methodologies (NAMs) like ToxCast to derive first-pass, provisional values to guide chemical prioritization and resource management as a complement to traditional ALC derivation. To address this goal, the study objectives were to (1) estimate chemical potency using data from NAMs for nine compounds with available aquatic benchmarks, (2) evaluate the utility of using NAM data to elucidate potential mechanisms of toxicity to guide problem formulation, and (3) determine the species relevance of toxicity pathways for compounds with clearly defined mechanisms of action as a means to evaluate whether minimum data requirements could potentially be waived when deriving a more formal ALC. Points of departure were derived from ToxCast data based on the fifth percentile of the distribution of activity concentration above cutoff values falling below the cytotoxic burst. Mechanistic inferences were made based on active target hits in ToxCast and, where applicable, assessed for taxonomic conservation using SeqAPASS. ToxCast-based point-of-departure aligned relatively closely (six of nine test chemicals within a factor of 10; eight of nine within a factor of 100) with aquatic benchmarks from the USEPA and US Department of Energy (DOE). Moreover, pathways of toxicity gleaned from NAM data were reflective of in vivo-based findings from the literature. These results, while preliminary, and based on a limited number of substances, support the potential application of NAM data to complement traditional ALC derivation approaches and prioritization. Integr Environ Assess Manag 2023;19:224–238. © 2022 Society of Environmental Toxicology & Chemistry (SETAC). This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
Localization of vasoactive intestinal peptide and toll‐like receptor 2 immunoreactive cells in endostyle of urochordate Styela plicata (Lesueur, 1823)
Authors: Alesci Alessio , Pergolizzi Simona , Lo Cascio Patrizia , Capillo Gioele , Lauriano Eugenia Rita 
Published: April 2022

AbstractThe endostyle is the first component of the ascidian digestive tract, it is shaped like a through and is located in the pharynx's ventral wall. This organ is divided longitudinally into nine zones that are parallel to each other. Each zone's cells are physically and functionally distinct. Support elements are found in zones 1, 3, and 5, while mucoproteins secreting elements related to the filtering function are found in zones 2, 4, and 6. Zones 7, 8, and 9, which are located in the lateral dorsal section of the endostyle, include cells with high iodine and peroxidase concentrations. Immunohistochemical technique using the following antibodies, Toll‐like receptor 2 (TLR‐2) and vasoactive intestinal peptide (VIP), and lectin histochemistry (WGA—wheat‐germagglutinin), were used in this investigation to define immune cells in the endostyle of Styela plicata (Lesueur, 1823). Our results demonstrate the presence of immune cells in the endostyle of S. plicata, highlighting that innate immune mechanisms are highly conserved in the phylogeny of the chordates.Research highlights
Immune cells positive to TLR‐2 and VIP in the endostyle of Styela plicata.
Expression of WGA in several zones of endostyle.
Use of comparative biology to improve the knowledge about immunology in ascidians.
Preliminary Study on Quantitative Assessment of the Fetal Brain Using MOLLI T1 Mapping Sequence
Authors: Jia Fenglin , Liao Yi , Li Xuesheng , Ye Zhijun , Li Pei , Zhou Xiaoyue , Li Qing , Wang Shaoyu , Ning Gang , Qu Haibo 
Published: April 2022

BackgroundPrenatal quantitative evaluation of myelin is important. However, few techniques are suitable for the quantitative evaluation of fetal myelination.PurposeTo optimize a modified Look–Locker inversion recovery (MOLLI) T1 mapping sequence for fetal brain development study.Study TypeProspective observational preliminary cohort study.PopulationA total of 71 women with normal fetuses divided into mid‐pregnancy (gestational age 24–28 weeks, N = 25) and late pregnancy (gestational age > 28 weeks, N = 46) groups.Field Strength/SequenceA 3 T/MOLLI sequence.AssessmentT1 values were measured in pedunculus cerebri, basal ganglia, thalamus, posterior limb of the internal capsule, temporal white matter, occipital white matter, frontal white matter, and parietal white matter by two radiologists (11 and 16 years of experience, respectively).Statistical TestsThe Kruskal–Wallis test was used for reginal comparison. For each region of interest (ROI), differences in T1 values between the mid and late pregnancy groups were assessed by the Mann Whitney U test. Pearson correlation coefficients (r) were used to evaluate the correlations between T1 values and gestational age for each ROI. Intraobserver and interobserver agreement was determined by the intraclass correlation coefficient (ICC). A P value <0.05 was considered statistically significant.ResultsInterobserver and intraobserver agreements of T1 were good for all ROIs (all ICCs > 0.700). There were significant differences in T1 values between lobal white matter and deep regions, respectively. Significant T1 values differences were found between middle and late pregnancy groups in pedunculus cerebri, basal ganglion, thalamus, posterior limb of the internal capsule, temporal, and occipital white matter. The T1 values showed significantly negative correlations with gestational weeks in pedunculus cerebri (r = −0.80), basal ganglion (r = −0.60), thalamus (r = −0.68), and posterior limb of the internal capsule (r = −0.77).Data ConclusionThe T1 values of fetal brain may be assessed using the MOLLI sequence and may reflect the myelination.Evidence Level3Technical EfficacyStage 2
Caging Cationic Polymer Brush‐Coated Plasmonic Nanostructures for Traceable Selective Antimicrobial Activities
Authors: Ma Jielin , Hou Shuai , Lu Derong , Zhang Bo , Xiong Qirong , Chan‐Park Mary B. , Duan Hongwei 
Published: April 2022

AbstractCationic polymers are under intense research to achieve prominent antimicrobial activity. However, the cellular and in vivo toxicity caused by nonspecific electrostatic interaction has become a major challenge for their practical applications. Here, the development of a “caging” strategy based on the use of a block copolymer consisting of a stealth block and an anionic block that undergoes degradation in presence of enzymes secreted by selective bacterial pathogens of interest is reported. The results have shown that antimicrobial cationic polymer brushes‐coated gold nanorods (AuNRs) can be caged by the block polymer of poly(ethylene glycol) and anionic, lipase‐degradable block of ε‐caprolactone and methacrylic acid copolymer to afford neutrally charged surfaces. The caged AuNRs are activated by lipase released by bacteria of interest to endow an excellent bactericidal effect but show minimal binding and toxicity against mammalian cells and nonspecific bacteria that do not produce lipase. In this design, AuNRs play multifunctional roles as the scaffolds for polymer brushes, photothermal transducers, and imaging probes for traceable delivery of the activation and delivery of bactericidal cationic polymer brushes. The caging strategy opens new opportunities for the safe delivery of antimicrobial materials for the treatment of bacterial infections.
Role of hemoglobin alpha and hemoglobin beta in non‐small‐cell lung cancer based on bioinformatics analysis
Authors: Kang Ning , Qiu Wen‐Jia , Wang Bin , Tang Dong‐fang , Shen Xiao‐Yong 
Published: April 2022

AbstractThe differentially expressed genes (DEGs) were identified and screened differentially in non‐small‐cell lung cancer (NSCLC) using information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases, and the correlation of DEGs in protein interaction, function, and pathway enrichment were analyzed to search for new biomarkers and potential therapeutic targets for NSCLC. Protein–protein interaction network (PPI) analysis showed that CDK1 and GNGT1 were the most significantly upregulated hub nodes, while FPR2 was the most significantly downregulated. Gene Ontology enrichment analysis showed that upregulated DEGs were significantly enriched in protein heterodimerization activity and other functions, while downregulated DEGs were enriched in functions such as heparin‐binding. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that upregulation of DEGs were significantly associated with neuroactive ligand‐receptor interaction pathways, while downregulation of DEGs were significantly associated with malaria pathways. According to the analysis results, we identified hemoglobin alpha (HBA) and hemoglobin beta (HBB) as the genes of interest for further study. Through tissue level and cell level experiments, we found that the expressions of HBA and HBB in NSCLC tissues were significantly lower than those in paracancerous tissues, and downregulation of HBA and HBB could significantly affect the proliferation ability of NSCLC cells. In addition, we also found that changes in HBA and HBB may affect NSCLC cells through the p38/MAPK pathway and JNK pathway, and ultimately affect the occurrence and development of NSCLC.
Dynamics of chip formation during the cutting process using imaging techniques: A review
Authors: Nie Guangchao , Yang Zhengyan , Zhang Dong , Zhang Xiaoming , Outeiro José , Ding Han 
Published: April 2022

AbstractImaging techniques have been widely implemented to study the dynamics of chip formation. They can offer a direct method and a full field measurement of the cutting process, providing kinematic information of the chip formation process. In this article, the state of the art of the imaging techniques reported in the literature has been summarized and analyzed. The imaging techniques have been applied to study the chip formation mechanism, friction behavior, strain/strain rate, and stress fields. Furthermore, the study of surface integrity has been advanced by deriving the thermo‐mechanical loading, subsurface deformation, and material constitutive model from the imaging technique. Finally, achievements in the area of imaging techniques have been summarized, followed by future directions for their application in the study of surface integrity.
Applications ofhydrogel‐baseddelivery systems in wound care and treatment: Anup‐to‐datereview
Authors: Divyashri Gangaraju , Badhe Ravindra V. , Sadanandan Bindu , Vijayalakshmi Vaniyamparambath , Kumari Mamta , Ashrit Priya , Bijukumar Divya , Mathew Mathew T. , Shetty Kalidas , Raghu Anjanapura V. 
Published: April 2022

AbstractNatural wound healing is a highly complex and regulated process. Disruption and barriers to cellular and tissue repair processes contributes to impaired wound healing, including sustained infections. Superficial wound healing requires many factors to work in concrete at the wound site, and thus many treatment options and wound dressings have evolved to address the barriers to wound healing. Biomaterials are proven to encourage the wound healing process by stimulating repair and regeneration of injured tissues and preventing wound infections. A wide range of natural and synthetic hydrophilic and porous formulations such as foams, films, fibers, and hydrogels have been examined for these applications. Among these formulations, polymeric hydrogels have gained considerable interest in the medical applications. They effectively absorb wound exudates and provide a moist environment for aiding the wound healing process. However, chronic wounds that are sustained longer might need supplementary healing features as addendums such as antimicrobials, stem cells, growth factors, peptides, vitamins, and natural compounds. Therefore, when combined with hydrogels healing supporting addendums promote rapid and effective wound healing. Although there have been several advancements in biopolymer‐based hydrogel systems, only limited reviews on various management strategies in wound healing are available in medical research and applications. Therefore, in this review, we have compiled and integrated various hydrogel‐based approaches with the potential to improve chronic wound healing and advance important outcomes. In addition, in‐situ injectable hydrogel preparation that have the advantage of packing patient wounds of different sizes and using 3D printing based tailor‐made hydrogels, and bio‐inks for wound closure applications are also highlighted.
Non‐immune hydrops fetalis caused by PIEZO1 compound heterozygous deletions detected only by exome sequencing
Authors: Reytan Sivan , Zunz Henig Noa , Yinon Yoav , Avnet Hagai , Kurolap Alina , Yaron Yuval , Baris Feldman Hagit 
Published: April 2022

Key pointsWhat's already known about this topic?

Genetic lymphatic disorders are a common cause of non‐immune hydrops fetalis, with PIEZO1 being one of the more recently established disease‐causing genes.

What does this study add?

Disease‐causing PIEZO1 variants have mostly been reported as single nucleotide variants or small indels. We report on a fetus with compound heterozygous deletions within and including PIEZO1. The deletions were not detected by chromosomal microarray (CMA).

This case highlights the value of exome sequencing in detecting copy number variants that are below CMA resolution.
Parental mosaicism for apparent de novo genetic variants: Scope, detection, and counseling challenges
Authors: Zemet Roni , Van den Veyver Ignatia B. , Stankiewicz Paweł 
Published: April 2022

AbstractThe disease burden of de novo mutations (DNMs) has been evidenced only recently when the common application of next‐generation sequencing technologies enabled their reliable and affordable detection through family‐based clinical exome or genome sequencing. Implementation of exome sequencing into prenatal diagnostics revealed that up to 63% of pathogenic or likely pathogenic variants associated with fetal structural anomalies are apparently de novo, primarily for autosomal dominant disorders. Apparent DNMs have been considered to primarily occur as germline or zygotic events, with consequently negligible recurrence risks. However, there is now evidence that a considerable proportion of them are in fact inherited from a parent mosaic for the variant. Here, we review the burden of DNMs in prenatal diagnostics and the influence of parental mosaicism on the interpretation of apparent DNMs and discuss the challenges with detecting and quantifying parental mosaicism and its effect on recurrence risk. We also describe new bioinformatic and technological tools developed to assess mosaicism and discuss how they improve the accuracy of reproductive risk counseling when parental mosaicism is detected.
Non‐psychotropic Cannabis sativa L. phytocomplex modulates microglial inflammatory response through CB2 receptors‐, endocannabinoids‐, and NF‐κB‐mediated signaling
Authors: Borgonetti Vittoria , Benatti Cristina , Governa Paolo , Isoldi Giovanni , Pellati Federica , Alboni Silvia , Tascedda Fabio , Montopoli Monica , Galeotti Nicoletta , Manetti Fabrizio , Miraldi Elisabetta , Biagi Marco , Rigillo Giovanna 
Published: April 2022

AbstractCannabis sativa L. is increasingly emerging for its protective role in modulating neuroinflammation, a complex process orchestrated among others by microglia, the resident immune cells of the central nervous system. Phytocannabinoids, especially cannabidiol (CBD), terpenes, and other constituents trigger several upstream and downstream microglial intracellular pathways. Here, we investigated the molecular mechanisms of a CBD‐ and terpenes‐enriched C. sativa extract (CSE) in an in vitro model of neuroinflammation. We evaluated the effect of CSE on the inflammatory response induced by exposure to lipopolysaccharide (LPS) in BV‐2 microglial cells, compared with CBD and β‐caryophyllene (CAR), CB2 receptors (CB2r) inverse and full agonist, respectively. The LPS‐induced upregulation of the pro‐inflammatory cytokines IL‐1β, IL‐6, and TNF‐α was significantly attenuated by CSE and only partially by CBD, whereas CAR was ineffective. In BV‐2 cells, these anti‐inflammatory effects exerted by CSE phytocomplex were only partially dependent on CB2r modulation and they were mediated by the regulation of enzymes responsible for the endocannabinoids metabolism, by the inhibition of reactive oxygen species release and the modulation of JNK/p38 cascade with consequent NF‐κB p65 nuclear translocation suppression. Our data suggest that C. sativa phytocomplex and its multitarget mechanism could represent a novel therapeutic strategy for neuroinflammatory‐related diseases.
A critical evaluation of risk to reward ratio of quercetin supplementation for COVID‐19 and associated comorbid conditions
Authors: Pawar Anil , Russo Maria , Rani Isha , Goswami Kalyan , Russo Gian Luigi , Pal Amit 
Published: April 2022

AbstractThe interim results of the large, multinational trials on coronavirus disease 2019 (COVID‐19) using a combination of antiviral drugs appear to have little to no effect on the 28‐day mortality or the in‐hospital course. Therefore, there is a still vivid interest in finding alternate re‐purposed drugs and nutrition supplements, which can halt or slow the disease severity. We review here the multiple preclinical studies, partially supported by clinical evidence showing the quercetin's possible therapeutic/prophylaxis efficacy against severe acute respiratory syndrome coronavirus (SARS‐CoV) as well as comorbidities like chronic obstructive pulmonary disease (COPD), diabetes mellitus, obesity, coagulopathy, and hypertension. Currently, 14 interventional clinical trials are underway assessing the efficacy of quercetin along with other antiviral drugs/nutritional supplements as prophylaxis/treatment option against COVID‐19. The present review is tempting to suggest that, based on circumstantial scientific evidence and preliminary clinical data, the flavonoid quercetin can ameliorate COVID‐19 infection and symptoms acting in concert on two parallel and independent paths: inhibiting key factors responsible for SARS‐CoV‐2 infections and mitigating the clinical manifestations of the disease in patients with comorbid conditions. Despite the broad therapeutic properties of quercetin, further high power randomized clinical trials are needed to firmly establish its clinical efficacy against COVID‐19.
Influence of grid resolution of large‐eddy simulations on foehn‐cold pool interaction
Authors: Umek L. , Gohm A. , Haid M. , Ward H. C. , Rotach M. W. 
Published: April 2022

AbstractNumerical simulations are performed to assess the influence of horizontal and vertical model resolution on the turbulent erosion of a cold‐air pool (CAP) by foehn winds in an Alpine valley near Innsbruck, Austria. Strong wind shear in the transition zone from the CAP to the overlying foehn generates turbulence by shear‐flow instability and contributes to the CAP erosion. The sensitivity of this process to grid resolution in the “grey zone” of turbulence is studied with the Weather Research and Forecasting model in large‐eddy simulation (LES) mode with a horizontal grid spacing of 200, 40, and 13.33 m and in mesoscale mode with a grid spacing of 1 km. Moreover, two different vertical resolutions are tested. The mesoscale simulation exhibits deficiencies in the CAP development and is neither able to resolve nor parametrize the effect of Kelvin–Helmholtz (K–H) instability. In contrast, the LES with the coarsest horizontal grid spacing begins to explicitly permit K–H instability, albeit individual K–H waves are not completely resolved, and thereby greatly improves the stability and wind profile of the foehn. Refining the LES grid spacing leads to a more explicit and realistic representation of turbulence, but surprisingly has little impact on mean quantities. An increase in the vertical resolution shows the greatest benefit in the turbulent upper part of the foehn jet, whereas an increase in the horizontal resolution improves the turbulence characteristics, especially at the foehn–CAP interface. However, spectral analysis indicates that even a horizontal grid spacing of 40 m does not fully capture the energy cascade in the inertial subrange. Eddies remain too large and foehn–CAP interaction is too vigorous compared with the simulation with 13.33 m grid spacing. Nevertheless, results illustrate the potential benefit of an (100 m) model resolution for improving numerical weather predictions in complex terrain.
An initial step toward a quantum annealing approach to the discrete logarithm problem
Authors: Mahasinghe Anuradha , Jayasinghe Youvin 
Published: April 2022

AbstractThe discrete logarithm problem over a multiplicative group of integer modulo n is the key ingredient in the ElGamal encryption system. This problem has been proven to be tractable in polynomial time on a quantum computer by Shor's algorithm. This algorithm makes use of basic quantum gates, circuits, measurements and it has been experimented in the circuit‐gate framework of quantum computing. On the other hand, the adiabatic framework of quantum computing with the quantum annealers such as the D‐Wave machine that simulates the adiabatic process has become very popular, showing its potential for making a practical pathway to achieve quantum speedup. Furthermore, much progress has been reported recently on the tractability of the integer factoring problem, which is the other widely‐used encryption method, on quantum annealers. In this context, it is important to explore the tractability of the discrete logarithm problem too using quantum annealers. In this work we present a first step made in this direction, by converting the discrete logarithm problem over a multiplicative group into the problem of minimizing a binary quadratic form, a standard problem format acceptable to a quantum annealer. Our formulation was tested for small‐scale problem instances using the quantum‐classical hybrid platform PyQUBO and we discuss the computational challenges and propose several potential improvements to the formulation.