bluuebunny/crossref_metadata_2025 huggingface dataset:
Off‐Label, but on‐Evidence? A Review of the Level of Evidence for Pediatric Pharmacotherapy
Authors: van der Zanden Tjitske M. , Smeets Nori J.L. , de Hoop‐Sommen Marika , Schwerzel Michiel F.T. , Huang Hui Jun , Barten Lieke J.C. , van der Heijden Joyce E.M. , Freriksen Jolien J.M. , Horstink Akira A.L. , Holsappel Inge H.G. , Mooij Miriam G. , de Hoog Matthijs , de Wildt Saskia N.
Published: September 2022

Many drugs are still prescribed off‐label to the pediatric population. Although off‐label drug use not supported by high level of evidence is potentially harmful, a comprehensive overview of the quality of the evidence pertaining off‐label drug use in children is lacking. The Dutch Pediatric Formulary (DPF) provides best evidence‐based dosing guidelines for drugs used in children. For each drug‐indication‐age group combination—together compiling one record—we scored the highest available level of evidence: labeled use, systematic review or meta‐analysis, randomized controlled trial (RCT), comparative research, noncomparative research, or consensus‐based expert opinions. For records based on selected guidelines, the original sources were not reviewed. These records were scored as guideline. A total of 774 drugs were analyzed comprising a total of 6,426 records. Of all off‐label records (n = 2,718), 14% were supported by high quality evidence (4% meta‐analysis or systematic reviews, 10% RCTs of high quality), 20% by comparative research, 14% by noncomparative research, 37% by consensus‐based expert opinions, and 15% by selected guidelines. Fifty‐eight percent of all records were authorized, increasing with age from 30% in preterm neonates (n = 110) up to 64% in adolescents (n = 1,630). Many have advocated that off‐label use is only justified when supported by a high level of evidence. We show that this prerequisite would seriously limit available drug treatment for children as the underlying evidence is low across ages and drug classes. Our data identify the drugs and therapeutic areas for which evidence is clearly missing and could drive the global research agenda.
A Simple Assay for the Detection of Late‐Stage Apoptosis Features in Saccharomyces cerevisiae
Authors: Bairwa Narendra K. , Shoket Heena , Pandita Monika , Sharma Meenu
Published: September 2022

Unicellular eukaryotic organisms such as yeast and protozoa serve as useful models for studying the impact of chemicals on cell physiology, cellular growth, and genome duplication. The yeast Saccharomyces cerevisiae has been widely used to assess apoptosis induced by chemicals due to its genetic tractability, ease of evaluation, and readily available impact assessment tools. Apoptosis in S. cerevisiae is characterized by many features, including increased cell death, loss of membrane integrity, release of caspases, chromatin condensation, and nuclear fragmentation, which are similar to the ones observed in mammalian cells. Current methods of apoptosis assessment typically require specialized equipment and reagents, which limits wide adoption. Here, we describe a rapid, inexpensive, and easy‐to‐perform assay in yeast for the analysis of late‐stage apoptotic features in cells treated with a chemical. We describe a protocol for assessing loss of cell survival and changes in the nucleus. We demonstrate the approach by using acetic acid and hydrogen peroxide as test chemicals. This assay for the study of late‐stage apoptotic features in S. cerevisiae can be performed reliably and rapidly by any laboratory with basic equipment and may be extended for studying apoptosis in similar single‐cell organisms after treatment with toxicological agents. © 2022 Wiley Periodicals LLC.

Basic Protocol 1: Culture of Saccharomyces cerevisiae, treatment with acetic acid or hydrogen peroxide, and semi‐quantitative growth assay

Basic Protocol 2: DAPI staining and fluorescence microscopy for the assessment of change in nucleus‐to‐cytoplasm ratio and nuclear integrity
Establishment of a Mouse Submandibular Salivary Gland Organ Culture
Authors: Sakai Manabu , Sakai Takayoshi
Published: September 2022

The salivary glands produce saliva and are important in maintaining oral health. Saliva keeps the mouth moist, cleanses the oral cavity, aids digestion, and has antibacterial properties. Saliva also helps in swallowing and speech. Investigating the development of the salivary glands is thus relevant in the context of both health and disease. Various cell culture methods have been used to study salivary gland development, including culturing cells in two dimensions (2D). Under physiological conditions, cells constantly interact with other cells and the extracellular matrix, which controls complex biological functions such as cell migration and apoptosis, and can modulate gene expression. Since many of these functions are not accurately represented or reproduced in 2D culture, the results of in vitro experiments using such culture methods are often not reflected in vivo. The use of 3D cultures, such as organ cultures, has helped address this issue and has emerged as a model that better reflects the in vivo physiological environment. Here, we describe a protocol for establishing submandibular salivary gland organ culture that is more concise and simpler than previous methods and includes the separation and dissection of the salivary glands. We also describe the use of environmental stress (hypoxic stimulation) and inhibitors (U0126, LY294002, and rapamycin) to elucidate signaling pathways involved in salivary gland development. This protocol can provide researchers with a simpler and more robust method of salivary gland organ culture, enabling analysis of organ‐based signaling pathways to advance developmental biology research. © 2022 Wiley Periodicals LLC.

Basic Protocol 1: Submandibular salivary gland organ culture

Basic Protocol 2: Analysis of salivary gland development in the presence of hypoxia and signaling pathway inhibitors

Basic Protocol 3: Western blotting using submandibular salivary gland organ culture
Corporate social responsibility and comparative capitalism frameworks: Evidence from the United States, Poland, and Italy
Authors: Boesso Giacomo , Fryzel Barbara , Ghitti Marco
Published: September 2022

Using the varieties of capitalism perspective and institutional theory as frameworks, we analyze cross‐cultural differences between firms' corporate social responsibility (CSR) approaches. We investigate three countries with different institutional settings: the United States, representing a liberal market economy; Italy, representing a coordinated market economy; and Poland, an example of a dependent market economy. We examine the differences in their CSR stances, operationalized through Porter and Kramer's concept of the four CSR categories: good citizenship, mitigating harm from the value chain, transforming value chain activities, and strategic philanthropy, based on data from 269 questionnaires administered to managers attending executive seminars at the authors' universities. Focusing on stakeholder engagement activities (SEAs) across the three economies, we show that companies in all three countries engage in the four categories of CSR activities. However, using a series of tests and rankings on means and standard deviations, followed by the subsequent analysis of variance, we argue that SEAs are emphasized more in American than in Polish and Italian companies, with the latter two countries showing more subtle differences despite some institutional similarities. Our results shed light on how different capitalistic models are associated with different CSR approaches, allowing policy‐makers and practitioners to better tackle CSR objectives in different countries.
AI‐driven network softwarization scheme for efficient message exchange in IoT environment beyond 5G
Authors: Jadav Nilesh Kumar , Nair Anuja R. , Gupta Rajesh , Tanwar Sudeep , Lakys Yahya , Sharma Ravi
Published: September 2022

Internet of things (IoT) has massively adopted the market due to the current era demanding fully intelligent and autonomous services. However, efficient network management and message exchange are challenging in a dynamic and energy‐constrained IoT environment. Hence, for efficient message passing in IoT applications, softwarization of the IoT network is essential, wherein the logical control plane is decoupled from the data plane consisting of hardware devices such as routers and switches. Using softwarization, a centralized software‐defined networking (SDN) controller is responsible for routing data packets from source to destination in a dynamic environment. However, to reduce the computational overhead of filtering malicious and nonmalicious packets, artificial intelligence (AI) classifiers prove beneficial. Moreover, such challenges have trade‐offs with network requirements such as ultralow latency, high reliability, and higher data rates. Motivated by this, we propose an AI‐enabled network softwarization scheme for efficient message exchange under the 6G network. Lastly, the performance of the proposed scheme is evaluated with different performance metrics, such as accuracy, precision, f1‐score, packet drop ratio, and latency. The empirical result revealed that the proposed scheme outperforms in terms of accuracy and controller efficiency, that is, 81.64% and 82.2%, respectively.
Cytology of malignant pleural mesothelioma: Diagnostic criteria, WHO classification updates, and immunohistochemical staining markers diagnostic value
Authors: Shaker Nada , Wu Douglas , Abid Abdul Majeed
Published: September 2022

Malignant pleural mesothelioma (MPM) is a rare but aggressive malignancy with a poor prognosis. Because of this tumor rarity and overlapping histologic features with other malignancy types, the histopathological findings and diagnostic immunohistochemical workup are essential in establishing the final diagnosis of MPMs. We aimed to review the diagnostic criteria, WHO tumor classification updates, and immunohistochemical staining markers diagnostic value to achieve an appropriate clinical diagnosis.
Family dinner: Transcriptional plasticity of five Noctuidae (Lepidoptera) feeding on three host plant species
Authors: Breeschoten Thijmen , Schranz M. Eric , Poelman Erik H. , Simon Sabrina
Published: September 2022

Polyphagous insects often show specialization in feeding on different host plants in terms of survival and growth and, therefore, can be considered minor or major pests of particular hosts. Whether polyphagous insects employ a common transcriptional response to cope with defenses from diverse host plants is under‐studied. We focused on patterns of transcriptional plasticity in polyphagous moths (Noctuidae), of which many species are notorious pests, in relation to herbivore performance on different host plants. We compared the transcriptional plasticity of five polyphagous moth species feeding and developing on three different host plant species. Using a comparative phylogenetic framework, we evaluated if successful herbivory, as measured by larval performance, is determined by a shared or lineage‐specific transcriptional response. The upregulated transcriptional activity, or gene expression pattern, of larvae feeding on the different host plants and artificial control diet was highly plastic and moth species‐specific. Specialization, defined as high herbivore success for specific host plants, was not generally linked to a lower number of induced genes. Moths that were more distantly related and showing high herbivore success for certain host plants showed shared expression of multiple homologous genes, indicating convergence. We further observed specific transcriptional responses within phylogenetic lineages. These expression patterns for specific host plant species are likely caused by shared evolutionary histories, for example, symplesiomorphic patterns, and could therefore not be associated with herbivore success alone. Multiple gene families, with roles in plant digestion and detoxification, were widely expressed in response to host plant feeding but again showed highly moth species‐specific. Consequently, high herbivore success for specific host plants is also driven by species‐specific transcriptional plasticity. Thus, potential pest moths display a complex and species‐specific transcriptional plasticity.
The relative influence of sea surface temperature anomalies on the benthic composition of an Indo‐Pacific and Caribbean coral reef over the last decade
Authors: Johnson Jack V. , Exton Dan A. , Dick Jaimie T. A. , Oakley Joseph , Jompa Jamaluddin , Pincheira‐Donoso Daniel
Published: September 2022

Rising ocean temperatures are the primary driver of coral reef declines throughout the tropics. Such declines include reductions in coral cover that facilitate the monopolization of the benthos by other taxa such as macroalgae, resulting in reduced habitat complexity and biodiversity. Long‐term monitoring projects present rare opportunities to assess how sea surface temperature anomalies (SSTAs) influence changes in the benthic composition of coral reefs across distinct locations. Here, using extensively monitored coral reef sites from Honduras (in the Caribbean Sea), and from the Wakatobi National Park located in the center of the coral triangle of Indonesia, we assess the impact of global warming on coral reef benthic compositions over the period 2012–2019. Bayesian generalized linear mixed effect models revealed increases in the sponge, and hard coral coverage through time, while rubble coverage decreased at the Indonesia location. Conversely, the effect of SSTAs did not predict any changes in benthic coverage. At the Honduras location, algae and soft coral coverage increased through time, while hard coral and rock coverage were decreasing. The effects of SSTA at the Honduras location included increased rock coverage, but reduced sponge coverage, indicating disparate responses between both systems under SSTAs. However, redundancy analyses showed intralocation site variability explained the majority of variance in benthic composition over the course of the study period. Our findings show that SSTAs have differentially influenced the benthic composition between the Honduras and the Indonesian coral reefs surveyed in this study. However, the large intralocation variance that explains the benthic composition at both locations indicates that localized processes have a predominant role in explaining benthic composition over the last decade. The sustained monitoring effort is critical for understanding how these reefs will change in their composition as global temperatures continue to rise through the Anthropocene.
Sapwood and heartwood are not isolated compartments: Consequences for isotope ecohydrology
Authors: Fabiani Ginevra , Penna Daniele , Barbeta Adrià , Klaus Julian
Published: September 2022

In most tree species, xylem consists of two different functional parts: sapwood and heartwood. While sapwood, as the flowpath for sap, has received more attention in isotope studies assessing water sources accessed by trees (e.g. soil water from different depths, groundwater, stream water or a mixture of these), much remains unknown about heartwood and the possible water exchange between the two functional parts. We investigated four tree species (Fagus sylvatica, Quercus petraea, Pseudotsuga menziesii and Picea abies) characterised by different xylem anatomy and timing of physiological activity to evaluate the degree of differentiation in isotopic composition of water between sapwood and heartwood on a biweekly time scale. We found that the sapwood and heartwood of all species displayed a concurrent variation in their isotopic composition throughout the growing season and on a day‐night scale suggesting that the two are not isolated compartments. While the two functional parts display a consistent difference in isotopic composition in conifers, they are characterised by more similar values in broadleaved species in broadleaved species, suggesting a higher degree of water exchange. Furthermore, we have also observed a progressive change in the isotopic composition in broadleaved species with sampling depth rather than functional parts of xylem. Our study highlights the value of accounting for radial isotopic variation, which might potentially lead to uncertainties concerning the origin of the extracted water for water uptake studies.
The threat of wildfire is unique to cannabis among agricultural sectors in California
Authors: Dillis Christopher , Butsic Van , Moanga Diana , Parker‐Shames Phoebe , Wartenberg Ariani , Grantham Theodore E.
Published: September 2022

At the intersection of climate change and rural development, wildfire has emerged as a threat to agriculture in the Western United States. This nexus is particularly problematic for the rapidly developing cannabis industry in California, which includes farms located outside of traditional agricultural zones and within landscapes potentially more prone to wildfire. With the goal of determining whether cannabis is uniquely vulnerable to direct wildfire impacts (in terms of crop loss to burning), we integrated fire hazard severity zone (FHSZ) data, wildfire perimeters, and future burn regime projections in relation to the location and cultivated area of cannabis farming. We then applied descriptive statistics and generalized additive models (GAMs) to compare the location of licensed cannabis farms to other agricultural types in California, including grapes, pasture, and all other general crops combined. We found cannabis farming was located more often in high and very high FHSZs and closer to wildfire perimeters than any other agricultural type. GAM estimates of likelihood of occurrence in high and very high severity zones were highest for cannabis, even after accounting for spatial clustering of farm types, although there was no reliable difference in predicted distances to wildfire. Cannabis more often occurred in projected (from 2020 to 2100) wildfire hotspots than all other agricultural types, with GAM estimates affirming a reliably higher likelihood of cannabis in future hotspots than pasture or general crops. Our findings highlight cannabis' particular vulnerability to wildfire in California and may in fact underestimate wildfire risks given the potential indirect impacts of smoke to crops and farmworkers, which were not evaluated in this study. In light of the sector's growing economic importance in the state, these vulnerabilities should be considered in future cannabis and rural development policies.
Toward pluralizing ecology: Finding common ground across sociocultural and scientific perspectives
Authors: Pickett S. T. A. , Cadenasso M. L. , Rademacher A. M.
Published: September 2022

Ecologists increasingly work with people from other fields, in which scholars, practitioners, and activists often pluralize: “ecologies.” By contrast, biophysical ecologists use the singular. Specialists beyond ecological science may avoid the singular because it evokes environmental determinism, lack of human agency, and disrespect for ways of knowing beyond science. Some social analysts consider biophysical ecology itself to be but one way of knowing, which embodies social positioning and uneven power relations. For their part, ecologists often ignore discussions featuring the term “ecologies” as unrelated to their work. The authors—one anthropologist and two biophysical ecologists—wish to facilitate social–ecological interaction by evaluating the conceptual content of the plural versus singular contrast. We suggest there are fundamental differences between ecology in the singular and plural. We examine these differences by showing that the singular and the plural within ecological science differ in specificity versus generality. In the view of social critiques, however, the conflict reflects political power differentials and social position of science. We explore whether there are productive parallels between these contrasting implications of the singular versus plural. Social criticisms of singular ecology include lack of system openness, open‐ended dynamics, contingent pathways of change, and human agency in ecological processes. We find value in these critiques and have grappled with these issues ourselves. We find that contemporary ecology often employs concepts amenable to those in social critiques. This finding demonstrates why ecologists should not be so quick to dismiss plural ecology as a meaningful phrase. We show that concerns of the social critiques embodied in the plural term parallel ecology's use of (1) multiple models to understand a topic, (2) multifaceted, scalable concepts, and (3) nested dialog between generality and specificity. We conclude that the use of the plural and singular actually share a conceptual foundation that can facilitate interdisciplinary integration and scholarship. Furthermore, the emerging awareness by ecologists of the concerns about the politics of power in science and its use may improve the ability of ecologists not only to interact with social scientists but also to better engage with social movements and environmental justice.
Metatranscriptomics reveals a shift in microbial community composition and function during summer months in a coastal marine environment
Authors: Sutherland Ben J. G. , Finke Jan F. , Saunders Robert , Warne Snehal , Schulze Angela D. , Strohm Jeff H. T. , Chan Amy M. , Suttle Curtis A. , Miller Kristina M.
Published: September 2022

Temperate coastal marine waters are often thermally stratified from spring through fall but can be dynamic and disrupted by tidal currents and wind‐driven upwelling. These mixing events introduce deeper, cooler water with a higher partial pressure of CO2 (pCO2) and its associated microbial communities to the surface. Anecdotally, these events impact shellfish hatcheries and farms, warranting improved understanding of changes in composition and activity of marine microbial communities in relation to environmental processes. To characterize both compositional and functional changes associated with abiotic factors, here, we generate a reference metatranscriptome from the Strait of Georgia over representative seasons and analyze metatranscriptomic profiles of the microorganisms present within intake water containing different pCO2 levels at a shellfish hatchery in British Columbia from June through October. Abiotic factors studied include pH, temperature, alkalinity, aragonite, calcite, and pCO2. Community composition changes were observed to occur at broad taxonomic levels and most notably to vary with temperature and pCO2. Functional gene expression profiles indicated a strong difference between early (June–July) and late summer (August–October) associated with viral activity. The taxonomic data suggest this could be due to the termination of cyanobacteria and phytoplankton blooms by viral lysis in the late season. Functional analysis indicated fewer differentially expressed transcripts associated with abiotic variables (e.g., pCO2) than with the temporal effect. Microbial composition and activity in these waters vary with both short‐term effects observed alongside abiotic variation and long‐term effects observed across seasons. The analysis of both taxonomy and functional gene expression simultaneously in the same samples by environmental RNA (eRNA metatranscriptomics) provided a more comprehensive view for monitoring water bodies than either would in isolation.
Prussian Blue Modified Amperometric Hg2+ Ion Biosensor Based on Glucose Oxidase Inhibition
Authors: Virbickas Povilas , Ziziunaite Gerda , Ramanavicius Arunas , Valiūnienė Aušra
Published: September 2022

In this research a Hg2+ ion biosensor was developed by combining Prussian blue (PB) with glucose oxidase (GOx) – an enzyme that can be inhibited by Hg2+ ions. An application of PB in the design of Hg2+ ion biosensor enabled detecting changes in hydrogen peroxide reduction current at low operational potential of 0.2 vs Ag|AgCl,KClsat. The described Hg2+ ion biosensor exhibited wide linear range from 27 μM to 247 μM of Hg2+ and higher maximal detectable concentration of Hg2+ than other GOx inhibition‐based biosensors, making it convenient for the analysis of samples with high concentration of Hg2+ ions.
Prediction model of surface roughness of selective laser melting formed parts based on back propagation neural network
Authors: Zhang Wang , Luo Chunwang , Ma Qingyuan , Lin Zhenqiang , Yang Lan , Zheng Jun , Ge Xiaohong , Zhang Wei , Liu Yuangang , Tian Jumei
Published: September 2022

In this article, selective laser melting (SLM) equipment is used to print 316L stainless steel parts under different process parameters, and the surface roughness of the parts is measured. Based on back propagation neural networks (BP neural networks, BPNN), the upper surface roughness prediction model is established. The laser power, scanning speed, and scanning interval are used as model input, and the surface roughness of the workpiece is output. This model can easily and quickly predict the surface roughness of SLM metal printing, with high prediction accuracy, and can provide a basis for the optimization of SLM process parameters.
Recent advances of non‐fullerene organic solar cells: From materials and morphology to devices and applications
Authors: Zhang Ying , Lang Yongwen , Li Gang
Published: September 2022

The innovation of non‐fullerene acceptors (NFAs) enables the rapid progress of organic solar cells (OSCs) in power conversion efficiencies to over 19%, endowing OSCs with great potential toward real‐world application. In this critical review, we outline the recent advances of NFA‐based OSCs ‐ from ITIC‐ to Y6‐family, to exemplify the structure–performance correlations, and cover from material chemistry to nanomorphology controlling. In addition, we point out the possible degradation mechanisms behind the NFA‐based devices and strategies for mitigating the stability issues. With OSC efficiencies approaching 20% benchmark, increasing attention has been built‐up toward the technology's applications. Therefore, we describe the opportunities and challenges in the promising applications, mainly on semitransparent and flexible OSCs for commercial photovoltaics. Finally, we provide a summary and perspective to point out the primary challenges the OSC technology is facing toward commercialization.

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Strong tough hydrogel solar evaporator with wood skeleton construction enabling ultra‐durable brine desalination
Authors: Li Lin , He Nan , Yang Sen , Zhang Qian , Zhang Haotian , Wang Bingsen , Dong Tongyu , Wang Haonan , Jiang Bo , Tang Dawei
Published: September 2022

Hydrogels, a highly versatile material platform, are poised to become a promising candidate for interfacial solar evaporators on account of their record‐high evaporation rates. Nevertheless, conventional hydrogels with loose crosslinking, low solid content, and isotropic network structure are plagued by fragile mechanical tolerance, impairing their application in severe seawater environments. Herein, we develop a skeleton‐construct polyelectrolyte hydrogel (SCPH) evaporator by a universal, simple strategy that maintains not only the original properties of hydrogels, but also endows a high mechanical strength. By virtue of this strategy, the SCPH increased its mechanical strength to 1 MPa, 500 times higher than the original hydrogel. Surprisingly, the strategy also endows the SCPH with some extra properties, such as a high salt rejection ratio, a high water‐pumping rate, and low thermal conductivity, which render the SCPH a perfect evaporator. Specifically, this SCPH material significantly improves the long‐term stability of evaporators, enabling the evaporator to be capable of evaporating for 30 days in 20 wt% brine at a stable evaporation rate, exceeding the longest evaporation time ever reported. In addition, it achieves an evaporation rate of up to 2.13 kg m−2 h−1, which is twice that of the currently existing polyelectrolyte hydrogel evaporators. The skeleton construction has the potential to significantly improve the efficiency, stability, and durability of evaporators, hence bringing interfacial desalination technology toward practical applications.

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The discriminatory ability of FibroScan liver stiffness measurement, controlled attenuation parameter, and FibroScan–aspartate aminotransferase to predict severity of liver disease in children
Authors: Chaidez Alexander , Pan Zhaoxing , Sundaram Shikha S. , Boster Julia , Lovell Mark , Sokol Ronald J. , Mack Cara L.
Published: September 2022

Vibration controlled transient elastography (FibroScan) is used to predict the severity of liver fibrosis and steatosis. In pediatrics, few studies have been performed directly comparing liver histologic features with FibroScan liver stiffness measurements (LSMs) and controlled attenuation parameters (CAPs). The FibroScan–aspartate aminotransferase (FAST) score, which predicts liver disease severity in adult nonalcoholic fatty liver disease (NAFLD), has not been analyzed in children. The aims of this study were to determine if LSM and CAP correlated with liver histologic fibrosis stage and steatosis grade, respectively, and to determine the predictive capacity of FAST in pediatric NAFLD. Research participants (n = 216) included those with FibroScan within 90 days of a liver biopsy. The ability of LSM, CAP, and FAST to predict severity of liver disease was analyzed by Spearman correlation, linear regression, and receiver operating characteristic and C statistic. Significant correlations were identified between LSM and Ishak fibrosis stages, with the strongest correlation occurring in the non‐NAFLD group (Spearman r = 0.47, p < 0.0001). LSM adequately predicted Ishak stages F0–2 versus F3–F6 (area under the receiver operating characteristic curve [AUROC], 0.73 for all; 0.77 for non‐NAFLD). CAP strongly predicted histologic steatosis grade (r = 0.84; p < 0.0001; AUROC, 0.98). FAST had acceptable discriminatory ability for significant liver disease (AUROC, 0.75). A FAST cutoff ≥0.67 had a sensitivity of 89% but a specificity of only 62% at determining significant liver disease. This study encompasses one of the largest pediatric cohorts describing the accuracy of FibroScan LSM and CAP to predict liver histologic fibrosis stage and steatosis grade, respectively. In order to determine specific LSM, CAP, and FAST cut‐off values for fibrosis stages, steatosis grades, and significant liver disease, respectively, a much larger cohort is necessary and will likely entail the need for multicentered studies.
Serum levels of iCAF‐derived osteoglycin predict favorable outcome in pancreatic cancer
Authors: Dings Mark P. G. , Manoukian Paul , Waasdorp Cynthia , Quik Judith S. E. , Strijker Marin , Lodestijn Sophie C. , van Neerven Sanne M. , Moreno Leandro F. , de Oliveira Rodrigo Leite , Bonsing Bert A. , Bruno Marco J. , Busch Olivier R. , Doukas Michael , van Eijck Casper H. , Mohammad Nadia Haj , de Hingh Ignace H. , Molenaar Quintus I. , Besselink Marc G. , Vermeulen Louis , Medema Jan Paul , van Laarhoven Hanneke W. M. , Bijlsma Maarten F.
Published: September 2022

Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma, the main cellular constituents of which are cancer‐associated fibroblasts (CAFs). Stroma‐targeting agents have been proposed to improve the poor outcome of current treatments. However, clinical trials using these agents showed disappointing results. Heterogeneity in the PDAC CAF population was recently delineated demonstrating that both tumor‐promoting and tumor‐suppressive activities co‐exist in the stroma. Here, we aimed to identify biomarkers for the CAF population that contribute to a favorable outcome. RNA‐sequencing reads from patient‐derived xenografts (PDXs) were mapped to the human and mouse genome to allocate the expression of genes to the tumor or stroma. Survival meta‐analysis for stromal genes was performed and applied to human protein atlas data to identify circulating biomarkers. The candidate protein was perturbed in co‐cultures and assessed in existing and novel single‐cell gene expression analysis from control, pancreatitis, pancreatitis‐recovered and PDAC mouse models. Serum levels of the candidate biomarker were measured in two independent cohorts totaling 148 PDAC patients and related them to overall survival. Osteoglycin (OGN) was identified as a candidate serum prognostic marker. Single‐cell analysis indicated that Ogn is derived from a subgroup of inflammatory CAFs. Ogn‐expressing fibroblasts are distinct from resident healthy pancreatic stellate cells and arise during pancreatitis. Serum OGN levels were prognostic for favorable overall survival in two independent PDAC cohorts (HR = 0.47, P = .042 and HR = 0.53, P = .006). Altogether, we conclude that high circulating OGN levels inform on a previously unrecognized subgroup of CAFs and predict favorable outcomes in resectable PDAC.
Fossil fuel is the common denominator between climate change and petrochemical exposures, and effects on women and childrenʼs health
Authors: Trowbridge Jessica , Goin Dana E. , Abrahamsson Dimitri , Sklar Rachel , Woodruff Tracey J.
Published: September 2022

Synopsis

Fossil fuels contribute to climate change and petrochemicals, both of which increase maternal and child disease. Reducing fossil fuels can reap a double benefit for climate change and improved health.
Enhanced neuronal differentiation by dynamic piezoelectric stimulation
Authors: Pinho Tiffany S. , Silva Deolinda , Ribeiro Jorge Cibrão , Marote Ana , Lima Rui , Batista Salete J. , Melo Rita , Ribeiro Clarisse , Cunha Cristiana B. , Moreira Irina S. , Lanceros‐Mendez Senentxu , Salgado António J.
Published: September 2022

Electroactive smart materials play an important role for tissue regenerative applications. Poly(vinylidene fluoride) (PVDF) is a specific subtype of piezoelectric electroactive material that generates electrical potential upon mechanical stimulation. This work focuses on the application of piezoelectric PVDF films for neural differentiation. Human neural precursor cells (hNPCs) are cultured on piezoelectric poled and non‐poled β‐PVDF films with or without a pre‐coating step of poly‐d‐lysine and laminin (PDL/L). Subsequently, hNPCs differentiation into the neuronal lineage is assessed (MAP2+ and DCX+) under static or dynamic (piezoelectric stimulation) culture conditions. The results demonstrate that poled and coated β‐PVDF films induce neuronal differentiation under static culture conditions which is further enhanced with mechanical stimulation. In silico calculations of the electrostatic potential of different domains of laminin, highlight the high polarity of those domains, which shows a clear preference to interact with the varying surface electric field of the piezoelectric material under mechanical stimulation. These interactions might explain the higher neuronal differentiation induced by poled β‐PVDF films pre‐coated with PDL/L under dynamic conditions. Our results suggest that electromechanical stimuli, such as the ones induced by piezoelectric β‐PVDF films, are suitable to promote neuronal differentiation and hold great promise for the development of neuroregenerative therapies.
Direct Assessment of Rabbit Cortical Bone Basic Multicellular Unit Longitudinal Erosion Rate: A 4D Synchrotron-Based Approach
Authors: Harrison Kim D , Sales Erika , Hiebert Beverly D , Panahifar Arash , Zhu Ning , Arnason Terra , Swekla Kurtis J , Pivonka Peter , Chapman L Dean , Cooper David ML
Published: September 2022

Cortical bone remodeling is carried out by basic multicellular units (BMUs), which couple resorption to formation. Although fluorochrome labeling has facilitated study of BMU formative parameters since the 1960s, some resorptive parameters, including the longitudinal erosion rate (LER), have remained beyond reach of direct measurement. Indeed, our only insights into this spatiotemporal parameter of BMU behavior come from classical studies that indirectly inferred LER. Here, we demonstrate a 4D in vivo method to directly measure LER through in-line phase contrast synchrotron imaging. The tibias of rabbits (n = 15) dosed daily with parathyroid hormone were first imaged in vivo (synchrotron micro-CT; day 15) and then ex vivo 14 days later (conventional micro-CT; day 29). Mean LER assessed by landmarking the co-registered scans was 23.69 ± 1.73 μm/d. This novel approach holds great promise for the direct study of the spatiotemporal coordination of bone remodeling, its role in diseases such as osteoporosis, as well as related treatments. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Calculation of the anharmonic effect on the main reactions referring to ethylbenzene combustion mechanism
Authors: Song Zening , Wang Shiye , Yu Hongjing , Hu Wenye , Yao Li
Published: September 2022

About 11 reactions related to ethylbenzene are studied in this paper using transition state theory. The YL method proposed by Yao and Lin is utilized to calculate the anharmonic and the harmonic rate constants in these reaction processes in the temperature range of 300–4,000 K, energy diagram and the temperature dependence of the rate coefficients are also presented. The calculations indicate that the harmonic rate constants are larger than the anharmonic rate constants in most cases. Especially, there is a temperature junction between the high and low relationship between the anharmonic and harmonic rate constants in several reactions. Furthermore, the calculated values are in good agreement with other theoretical ones within the allowable error. Finally, the kinetic parameters and the thermodynamic parameters are calculated. To sum up, it can be concluded that the anharmonic effect in these reactions is very significant and cannot be ignored.
Fetal brain biometry and cortical development in congenital heart disease: A prospective cross sectional study
Authors: Rizzo Giuseppe , Pietrolucci Maria Elena , De Vito Marika , Pavjola Maqina , Capponi Alessandra , Mappa Ilenia
Published: September 2022

Objective

To evaluate brain biometry and cortical development by neurosonography in fetuses with congenital heart defect (CHD) and evaluate differences among different type of CHD.

Methods

In a prospective cross sectional study singleton fetus with CHD were matched with controls and grouped into two categories according to the predicted severity of cerebral arterial oxygen deficit induced by the CHD: Group A mildly reduced or normal and Group B moderately to severely reduced. Neurosonography was done at 30–33 weeks to obtain measurements of corpus callosum (CC), cerebellar vermis (CV), Sylvian fissure (SF) insula, parieto‐occipital fissure (POF), and calcarine sulci fissures (CSF). All the neurosonographic parameters were adjusted by head circumference (HC).

Results

A total of 78 fetuses with CHD (group A 30; group B 48) and 80 matched controls form uncomplicated pregnancies were considered. CHD fetuses have significantly smaller CC, CV, SF, and POF and bigger insula when compared to control fetuses. These differences are more marked in group B fetuses. These differences remained significant after correction for HC values.

Conclusion

Fetuses with CHD have an impaired cortical development and these variations are more evident in those with a predicted lower oxygen delivery to the brain.
Dietary yolk supplementation decreases rates of yolk deposition in Japanese quail
Authors: Navara Kristen J. , Graden Kylie , Mendonça Mary T.
Published: September 2022

Generation of egg yolk by birds requires the synthesis and deposition of large amounts of protein and lipid, and is often accompanied by the incorporation of additional physiological mediators. While there has been much work examining the relative quantities of yolk components, as well as potential adaptive patterns of their allocation, we still do not have a full understanding of what controls yolk formation and composition. Once ovarian follicles are recruited into the preovulatory hierarchy, the yolk is deposited in concentric rings, with one ring deposited per day. Previous studies have shown that there is substantial interspecific and intraspecific variation in the number of rings in yolks, and thus the number of days it took those yolks to grow. We hypothesized that the ability to grow follicles to maturity quickly is limited by the availability of materials to make yolk precursors in the female, either in body reserves or in dietary access. To test this, we supplemented the diets of Japanese quail with hard‐boiled chicken yolk and examined the influences of treatment and female body condition on follicle growth rates. Contrary to predictions, females with higher body condition indices produced yolks that grew more slowly, and yolks from supplemented birds grew more slowly than controls. These results indicate that females can modulate the rate of yolk incorporation into developing follicles, and that an energy balance that is too high may not be optimal for the fast growth of developing ovarian follicles.
Looking guilty: Handcuffing suspects influences judgements of deception
Authors: Zloteanu Mircea , Salman Nadine L. , Krumhuber Eva G. , Richardson Daniel C.
Published: September 2022

Veracity judgements are important in legal and investigative contexts. However, people are poor judges of deception, often relying on incorrect behavioural cues when these may reflect the situation more than the sender's internal state. We investigated one such situational factor relevant to forensic contexts: handcuffing suspects. Judges—police officers (n = 23) and laypersons (n = 83)—assessed recordings of suspects, providing truthful and deceptive responses in an interrogation setting where half were handcuffed. Handcuffing was predicted to undermine efforts to judge veracity by constraining suspects' gesticulation and by priming stereotypes of criminality. It was found that both laypersons and police officers were worse at detecting deception when judging handcuffed suspects compared to non‐handcuffed suspects, while not affecting their judgement bias; police officers were also overconfident in their judgements. The findings suggest that handcuffing can negatively impact veracity judgements, highlighting the need for research on situational factors to better inform forensic practice.
A potential association between obesity and reduced effectiveness of COVID‐19 vaccine‐induced neutralizing humoral immunity
Authors: Faizo Arwa A. , Qashqari Fadi S. , El‐Kafrawy Sherif A. , Barasheed Osamah , Almashjary Majed N. , Alfelali Mohammed , Bawazir Asma A. , Albarakati Boshra M. , Khayyat Soud A. , Hassan Ahmed M. , Alandijany Thamir A. , Azhar Esam I.
Published: September 2022

Due to the adverse effects of obesity on host immunity, this study investigated the effectiveness of COVID‐19 vaccines (BNT162b2, ChAdOx‐nCov‐2019, and mRNA‐1273) in inducing anti‐SARS‐CoV‐2 Spike (S) neutralizing antibodies among individuals with various obesity classes (class I, II, III, and super obesity). Sera from vaccinated obese individuals (n = 73) and normal BMI controls (n = 46) were subjected to S‐based enzyme‐linked immunosorbent assay (ELISA) and serum‐neutralization test (SNT) to determine the prevalence and titer of anti‐SARS‐CoV‐2 neutralizing antibodies. Nucleocapsid‐ELISA was also utilized to distinguish between immunity acquired via vaccination only versus vaccination plus recovery from infection. Data were linked to participant demographics including age, gender, past COVID‐19 diagnosis, and COVID‐19 vaccination profile. S‐based ELISA demonstrated high seroprevalence rates (>97%) in the study and control groups whether samples with evidence of past infection were included or excluded. Interestingly, however, SNT demonstrated a slightly significant reduction in both the rate and titer of anti‐SARS‐CoV‐2 neutralizing antibodies among vaccinated obese individuals (60/73; 82.19%) compared to controls (45/46; 97.83%). The observed reduction in COVID‐19 vaccine‐induced neutralizing humoral immunity among obese individuals occurs independently of gender, recovery from past infection, and period from last vaccination. Our data suggest that COVID‐19 vaccines are highly effective in inducing protective humoral immunity. This effectiveness, however, is potentially reduced among obese individuals which highlight the importance of booster doses to improve their neutralizing immunity. Further investigations on larger sample size remain necessary to comprehensively conclude about the effect of obesity on COVID‐19 vaccine effectiveness on humoral immunity induction.
Formation and physical stability of hazelnut oil nanoemulsions: Comparison of a synthetic surfactant and a natural emulsifier
Authors: Sahin Selvi Secil , Akpinar Ayse Nur , Gumus‐Bonacina Cansu Ekin
Published: September 2022

Hazelnut oil is a significant edible oil with positive effects on human health. This study aimed to integrate hazelnut oil, which is known for its cardiovascular benefits, into nanoemulsion technology for the first time as an innovative conception, to maintain its stability against environmental conditions, and to benefit more by making it more bioaccessible. Polysorbate 80 and whey protein isolate (WPI) were used to stabilize the nanoemulsions. In this way, we aimed to show that WPI, a natural emulsifier, could be an alternative to the synthetic Polysorbate 80 emulsifier known for its high emulsification ability to stabilize hazelnut oil emulsions. The emulsions, formed by using a 2% (wt/wt) emulsifier and passed through a microfluidizer five times at 96.5 MPa pressure provided the small particle size (d32) as 296 ± 7.76 nm and 216 ± 1.78 nm for the WPI and Polysorbate 80‐stabilized samples, respectively. Polysorbate 80‐stabilized nanoemulsions were more physically stable under different pH, temperature, and ionic strength conditions compared with WPI‐stabilized nanoemulsions. Finally, the fates of the emulsions were investigated under a simulated in vitro digestion system. The increase in droplet sizes during the gastric phase was to a higher extent for the WPI‐stabilized nanoemulsions (d32 = 5.500 ± 0.60 μm) compared with Polysorbate 80‐stabilized emulsions (d32 = 1.069 ± 0.09 μm). Although hazelnut nanoemulsions stabilized with Polysorbate 80 showed higher physical stability, it was determined that WPI would also be successful in producing stable hazelnut oil‐in‐water emulsions, exhibiting FFA (%) values of 88%–90.5% in the small intestine.
Comparative pharmacokinetics of 11 components from the active part of Gerberae Piloselloidis Herba after oral administration in control and asthmatic mice
Authors: Liu Chunhua , You Jingrui , Zhou Kun , Gong Zipeng , Pan Jie , Sun Jia , Liu Ting , Wang Aimin , Wang Yonglin , Lu Yuan , Li Yongjun
Published: September 2022

Gerberae Piloselloidis Herba, a traditional Chinese medicine, is often employed to treat such lung‐related diseases as coughs, asthma, and pulmonary carbuncles in southwest China. Our previous study demonstrated that its active fraction, prepared from Gerberae Piloselloidis Herba, exerts an obvious beneficial effect on asthma. However, the pharmacokinetics of its major constituents remain unclear. Therefore, an ultra‐performance mass spectrometry‐electrospray ionization‐tandem mass spectrometry method was successfully established to simultaneously perform the pharmacokinetics of the main 11 components of the active fraction between normal and ovalbumin‐induced asthmatic mice. Compared to the normal group, in asthmatic mice the peak concentration of arbutin, marmesin, caffeoylquinic acids, and flavonoid glycosides clearly increased, while for luteolin it significantly declined; the area under the curve for arbutin and luteolin showed an increase, but the values of marmesin, caffeoylquinic acids, and flavonoid glycosides revealed a decline; the peak time for arbutin, caffeoylquinic acids and flavonoid glycosides decreased, while for marmesin and luteolin it significantly augmented; apart from marmesin, the half‐life for all compounds shortened significantly. It is indicated that the pathology of asthma could lead to an alteration in the pharmacokinetic profiles of the 11 components in plasma, providing a reference for further exploration of the pharmacodynamic basis of the anti‐bronchial effect of Gerberae Piloselloidis Herba.