bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comparison of PCA-LDA and PLS-DA Techniques for Classification of Vibrational Spectra
Authors: Lasalvia Maria , Capozzi Vito , Perna Giuseppe
Published: May 2022

Vibrational spectroscopies provide information about the biochemical and structural environment of molecular functional groups inside samples. Over the past few decades, Raman and infrared-absorption-based techniques have been extensively used to investigate biological materials under different pathological conditions. Interesting results have been obtained, so these techniques have been proposed for use in a clinical setting for diagnostic purposes, as complementary tools to conventional cytological and histological techniques. In most cases, the differences between vibrational spectra measured for healthy and diseased samples are small, even if these small differences could contain useful information to be used in the diagnostic field. Therefore, the interpretation of the results requires the use of analysis techniques able to highlight the minimal spectral variations that characterize a dataset of measurements acquired on healthy samples from a dataset of measurements relating to samples in which a pathology occurs. Multivariate analysis techniques, which can handle large datasets and explore spectral information simultaneously, are suitable for this purpose. In the present study, two multivariate statistical techniques, principal component analysis-linear discriminate analysis (PCA-LDA) and partial least square-discriminant analysis (PLS-DA) were used to analyse three different datasets of vibrational spectra, each one including spectra of two different classes: (i) a simulated dataset comprising control-like and exposed-like spectra, (ii) a dataset of Raman spectra measured for control and proton beam-exposed MCF10A breast cells and (iii) a dataset of FTIR spectra measured for malignant non-metastatic MCF7 and metastatic MDA-MB-231 breast cancer cells. Both PCA-LDA and PLS-DA techniques were first used to build a discrimination model by using calibration sets of spectra extracted from the three datasets. Then, the classification performance was established by using test sets of unknown spectra. The achieved results point out that the built classification models were able to distinguish the different spectra types with accuracy between 93% and 100%, sensitivity between 86% and 100% and specificity between 90% and 100%. The present study confirms that vibrational spectroscopy combined with multivariate analysis techniques has considerable potential for establishing reliable diagnostic models.
Hybrid Deep Neural Network Model for Multi-Step Energy Prediction of Prosumers
Authors: Antal Marcel , Toderean Liana , Cioara Tudor , Anghel Ionut
Published: May 2022

The transition toward decentralized renewable energy transforms the energy grid, with the prosumers playing an active role in the local energy management. Accurate day-ahead prediction of their energy demand is a prerequisite to ensure the stability and efficiency of the power grid by balancing the energy demand with the production, while incorporating renewable energy as much as possible. In this paper, we propose a 24-steps-ahead energy prediction model that integrates clustering and multilayer perceptron classification models used to detect the classes of energy profiles and multilayer perceptron regression models used to fine-tune the energy prediction, considering the energy data streams. We introduce new features derived from the raw energy data collected from prosumers, such as the profile peaks and valleys, concerning the energy baseline and describe a software infrastructure for integrating the real-time energy data streams with the hybrid deep learning models training and prediction. The evaluation tests consider energy datasets that are closer to the real-time energy data streams from prosumers. The results show that, even on energy data streams, the model offers a good prediction accuracy for small- and medium-scale prosumers.
Overexpression of microRNA-345 Affects the Invasive Capacity of Pancreatic Ductal Adenocarcinoma Cell Lines by Suppressing MUC1 and TJP2 Expression
Authors: Tatsumi Shigenobu , Fujii Tomomi , Sugimoto Aya , Sekita-Hatakeyama Yoko , Morita Kohei , Uchiyama Tomoko , Itami Hiroe , Takeda Maiko , Yamazaki Masaharu , Sho Masayuki , Ohbayashi Chiho
Published: May 2022

The majority of pancreatic carcinomas are pancreatic ductal adenocarcinomas (PDAC), and the presence of non-invasive pancreatic intraepithelial neoplasia or intraductal papillary mucinous neoplasm, as an associated lesion, is considered important. These microscopic hyperplastic or grossly papillomatous lesions exhibit varying degrees of morphological atypia and may develop into invasive carcinomas. In this study, we investigated whether mucin-1 (MUC1) is involved in the progression of pancreatic carcinoma and examined the mechanisms by which microRNAs regulate MUC1 expression in vitro. In PDAC cell lines, suppression of MUC1 expression reduced cell proliferation and invasion; PDAC cell lines transfected with an miR-345 precursor suppressed the expression of MUC1, and reduced cell proliferation and invasion. Tight junction protein 2 (TJP2), a putative target of miR-345, is regulated by MUC1. The suppression of TJP2 expression reduced cell proliferation by inducing apoptosis. These results suggest that MUC1 and TJP2, the putative target molecules of miR-345, are critical in maintaining the invasive potential of pancreatic carcinoma cells, and regulating their expression may prevent the progression of non-invasive pancreatic intraductal lesions to invasive carcinomas. This study provides new insights for the development of novel molecular targeted therapies for pancreatic carcinomas.
Synthesis of Gold-PVP Nanostructured Composites by Microplasma: A Test to Study Their Inhibiting Tendency of Avian Influenza Virus Activity
Authors: Zubair Muhammad , Rafique Muhammad Shahid , Khalid Afshan , Yaqub Tahir , Alomar Suliman Yousef , Gohar Huma
Published: May 2022

Gold–polymer nanostructured composites have a great potential in the biomedical and advanced materials field as an antimicrobial agent against various pathogens, especially viruses. In the present work, gold and gold-PVP colloids have been prepared by the electrochemical reduction of hydrogen tetrachlorauric acid (HAuCl4·3H2O) precursor. The atmospheric pressure microplasma technique was used as a reducing agent, while D-Fructose was used as a stabilizing agent in the synthesis process. X-ray Diffraction (XRD) confirmed the crystalline behavior of both gold nanostructured particles and gold-PVP nanocomposites. The morphology of the nanoparticles was examined by SEM. The absorption characteristic peaks at 541 nm and 542 nm in UV-Vis spectra confirmed the surface plasmon resonance in gold nanostructured particles and gold-PVP nanostructured composites, respectively. Dynamic light scattering studies with percentage intensity distribution revealed particle size distribution ranges from 8–288 nm for gold colloids and 15–297 nm for gold-PVP colloids. Gold-PVP nanostructured composites have shown an improvement in the antiviral activity against the H9N2 virus as compared to bare gold nanostructured particles.
Short-Term Effects of Apparent Temperature on Cause-Specific Mortality in the Urban Area of Thessaloniki, Greece
Authors: Parliari Daphne , Cheristanidis Stavros , Giannaros Christos , Keppas Stavros Ch. , Papadogiannaki Sofia , de’Donato Francesca , Sarras Christos , Melas Dimitrios
Published: May 2022

Although there is a growing interest in the association between ambient temperatures and mortality, little evidence is available for Thessaloniki, the second largest city of Greece. In this study, we present an assessment of the effects of temperature on daily mortality from 2006 to 2016 in the urban area of Thessaloniki, by describing the exposure-lag-response association between temperature and cause-specific mortality with the use of a distributed lag non-linear model (DLNM). A J-shaped relationship was found between temperature and mortality. The highest values of risk were evident for respiratory (RR > 10) and cardiovascular causes (RR > 3), probably due to the fact that health status of individuals with chronic respiratory and cardiovascular diseases rapidly deteriorates during hot periods. Cold effects had longer lags of up to 15 days, whereas heat effects were short-lived, up to 4 days. Percentage change in all- and cause-specific mortality per 1 °C change above and below Minimum Mortality Temperature showed a larger increase for all-cause mortality in heat (1.95%, 95% CI: 1.07–2.84), in contrast to a smaller increase in cold (0.54%, 95% CI: 0, 1.09). Overall, 3.51% of all-cause deaths were attributable to temperature, whereas deaths attributed to heat (2.34%) were more than deaths attributed to cold (1.34%). The findings of this study present important evidence for planning public-health interventions, to reduce the health impact of extreme temperatures.
Temporal and Spatial Variation of Wetland CH4 Emissions from the Qinghai–Tibet Plateau under Future Climate Change Scenarios
Authors: Zhang Xian , Wang Jieyi , Zhang Jiang , Chen Huai , Peng Changhui , Zhu Qiuan
Published: May 2022

Wetlands are an important natural source of methane (CH4), so it is important to quantify how their emissions may vary under future climate change conditions. The Qinghai–Tibet Plateau contains more than a third of China’s wetlands. Here, we simulated temporal and spatial variation in CH4 emissions from natural wetlands on the Qinghai–Tibet Plateau from 2008 to 2100 under Representative Concentration Pathways (RCP) 2.6, 4.5, and 8.5. Based on the simulation results of the TRIPLEX-GHG model forced with data from 24 CMIP5 models of global climate, we predict that, assuming no change in wetland distribution on the Plateau, CH4 emissions from natural wetlands will increase by 35%, 98% and 267%, respectively, under RCP 2.6, 4.5 and 8.5. The predicted increase in atmospheric CO2 concentration will contribute 10–28% to the increased CH4 emissions from wetlands on the Plateau by 2100. Emissions are predicted to be majorly in the range of 0 to 30.5 g C m−2·a−1 across the Plateau and higher from wetlands in the southern region of the Plateau than from wetlands in central or northern regions. Under RCP8.5, the methane emissions of natural wetlands on the Qinghai–Tibet Plateau increased much more significantly than that under RCP2.6 and RCP4.5.
Temporal Variation of NO2 and HCHO Vertical Profiles Derived from MAX-DOAS Observation in Summer at a Rural Site of the North China Plain and Ozone Production in Relation to HCHO/NO2 Ratio
Authors: Cheng Siyang , Jin Junli , Ma Jianzhong , Lv Jinguang , Liu Shuyin , Xu Xiaobin
Published: May 2022

We performed a comprehensive and intensive field experiment including ground-based multi-axis differential optical absorption spectroscopy (MAX-DOAS) measurement at Raoyang (115°44′ E, 38°14′ N; 20 m altitude) in summer (13 June–20 August) 2014. The NO2 and HCHO profiles retrieved by MAX-DOAS take on different vertical distribution shapes, with the former declining with the increasing altitude and the latter having an elevated layer. The average levels of vertical column densities (VCDs) and near-surface volume mixing ratios (VMRs) were 1.02 ± 0.51 × 1016 molec·cm−2 and 3.23 ± 2.70 ppb for NO2 and 2.32 ± 0.56 × 1016 molec·cm−2 and 5.62 ± 2.11 ppb for HCHO, respectively. The NO2 and HCHO levels are closely connected with meteorological conditions, with the larger NO2 VCDs being associated with lower temperature, higher relative humidity (RH) and lower planetary boundary layer height (PBLH). With respect to the diurnal variations of vertical distribution, the NO2 in the residual layer gradually disappeared from 1.2 km height to the surface during the period of 7:00–11:00 Beijing time (BJ), and the near-surface NO2 had larger VMRs in the early morning and evening than in the later morning and afternoon. An elevated HCHO layer was observed to occur persistently with the lifted layer height rising from ~0.5 km to ~1.0 km before 10:00 BJ; the near-surface HCHO VMRs gradually increased and peaked around 10:00 BJ. The ratios of HCHO to NO2 (RHCHO-NO2) were generally larger than two in the boundary layer from 11:00 BJ until 19:00 BJ, the time period when ozone photochemistry was most active. Thus, ozone (O3) production was mainly in the NOx-limited regime during the observation campaign, which was closely related to relatively high temperatures and low RH. The O3 production regimes also changed with the wind’s direction. These results are significant to reveal the formation mechanism of O3 pollution and develop strategies for controlling the O3 photochemical pollution over the North China Plain.
Non-Hydrostatic Regcm4 (Regcm4-NH): Evaluation of Precipitation Statistics at the Convection-Permitting Scale over Different Domains
Authors: Stocchi Paolo , Pichelli Emanuela , Torres Alavez Jose Abraham , Coppola Erika , Giuliani Graziano , Giorgi Filippo
Published: May 2022

Recent studies over different geographical regions of the world have proven that regional climate models at the convection-permitting scale (CPMs) improve the simulation of precipitation in many aspects, such as the diurnal cycle, precipitation frequency, intensity, and extremes at daily—but even more at hourly—time scales. Here, we present an evaluation of climate simulations with the newly developed RegCM4-NH model run at the convection-permitting scale (CP-RegCM4-NH) for a decade-long period, over three domains covering a large European area. The simulations use a horizontal grid spacing of ~3 km and are driven by the ERA-Interim reanalysis through an intermediate driving RegCM4-NH simulation at ~12 km grid spacing with parameterized deep convection. The km-scale simulations are evaluated against a suite of hourly observation datasets with high spatial resolutions and are compared to the coarse-resolution driving simulation in order to assess improvements in precipitation from the seasonal to hourly scale. The results show that CP-RegCM4-NH produces a more realistic representation of precipitation than the coarse-resolution simulation over all domains. The most significant improvements were found for intensity, heavy precipitation, and precipitation frequency, both on daily and hourly time scales in all seasons. In general, CP-RegCM4-NH tends to correctly produce more intense precipitation and to reduce the frequency of events compared to the coarse-resolution one. On the daily scale, improvements in CP simulations are highly region dependent, with the best results over Italy, France, and Germany, and the largest biases over Switzerland, the Carpathians, and Greece, especially during the summer seasons. At the hourly scale, the improvement in CP simulations for precipitation intensity and spatial distribution is clearer than at the daily timescale. In addition, the representation of extreme events is clearly improved by CP-RegCM4-NH, particularly at the hourly time scale, although an overestimation over some subregions can be found. Although biases between the model simulations at the km-scale and observations still exist, this first application of CP-RegCM4-NH at high spatial resolution indicates a clear benefit of convection-permitting simulations and encourages further assessments of the added value of km-scale model configurations for regional climate change projections.
Probing the Atomic Structure of Californium by Resonance Ionization Spectroscopy
Authors: Weber Felix , Düllmann Christoph Emanuel , Gadelshin Vadim , Kneip Nina , Oberstedt Stephan , Raeder Sebastian , Runke Jörg , Mokry Christoph , Thörle-Pospiech Petra , Studer Dominik , Trautmann Norbert , Wendt Klaus
Published: May 2022

The atomic structure of californium is probed by two-step resonance ionization spectroscopy. Using samples with a total amount of about 2×1010 Cf atoms (ca. 8.3 pg), ground-state transitions as well as transitions to high-lying Rydberg states and auto-ionizing states above the ionization potential are investigated and the lifetimes of various atomic levels are measured. These investigations lead to the identification of efficient ionization schemes, important for trace analysis and nuclear structure investigations. Most of the measurements are conducted on 250Cf. In addition, the isotope shift of the isotopic chain 249−252Cf is measured for one transition. The identification and analysis of Rydberg series enables the determination of the first ionization potential of californium to EIP=50,666.76(5)cm−1. This is about a factor of 20 more precise than the current literature value.
ATOM Program System and Computational Experiment
Authors: Chernysheva Larissa V. , Ivanov Vadim K.
Published: May 2022

The article is devoted to a brief description of the ATOM computer program system, designed to study the structure, transition probabilities and cross sections of various processes in multielectron atoms. The theoretical study was based on the concept of a computational experiment, the main provisions of which are discussed in the article. The main approximate methods used in the system of programs for taking many-electron correlations into account and determining their role in photoionization processes, elastic and inelastic electron scattering, the decay of vacancies, and many others are presented. The most significant results obtained with this software are listed.
Macdonald Formula, Ricci Curvature, and Concentration Locus for Classical Compact Lie Groups
Authors: Cacciatori Sergio , Ursino Pietro
Published: May 2022

We consider the phenomenon of concentration of measures, which is restricted to the case of families of compact connected Lie groups. While in the literature, powerful general results regarding the existence of concentration and its relations to extremal amenability of infinite dimensional groups have been determined, there are few explicit examples, specially regarding the determination of the region where the measure concentrates. Since they can be relevant for concrete applications, both in mathematics and in physics, in the present paper, we provide a number of such examples, using compact Lie groups as basic ingredients. In particular, our strategy is to employ the Macdonald’s formula, giving the volume of compact simple Lie groups, and Ricci curvature of the bi-invariant metric for analyzing a “concentration locus”, which is a tool to detect where a sequence of metric, Borel measurable spaces concentrates its measure.
Can Telemedicine Optimize the HCV Care Cascade in People Who Use Drugs? Features of an Innovative Decentralization Model and Comparison with Other Micro-Elimination Strategies
Authors: Nevola Riccardo , Rosato Valerio , Conturso Vincenza , Perillo Pasquale , Le Pera Teresa , Del Vecchio Ferdinando , Mastrocinque Davide , Pappalardo Annalisa , Imbriani Simona , Delle Femine Augusto , Piacevole Alessia , Claar Ernesto
Published: May 2022

People who use drugs (PWUDs) are a crucial population in the global fight against viral hepatitis. The difficulties in linkage to care, the low adherence to therapy, the frequent loss to follow-up and the high risk of re-infection make the eradication process of the hepatitis C virus (HCV) really hard in this viral reservoir. Several management and treatment models have been tested with the aim of optimizing the HCV care cascade in PWUDs. Models of decentralization of the care process and integration of services seem to provide the highest success rates. Giving this, telemedicine could favor the decentralization of diagnostic-therapeutic management, key for the implementation of linkage to care, reduction of waiting times, optimization of adherence and results and reduction of the costs. The purpose of this literature review is to examine the role and possible impact of telemedicine in optimizing the HCV care cascade, comparing the different care models that have shown to improve the linkage to care and therapeutic adherence in this special population.
The First Mitochondrial Genomes of the Family Haplodiplatyidae (Insecta: Dermaptera) Reveal Intraspecific Variation and Extensive Gene Rearrangement
Authors: Liu Hong-Ling , Chen Song , Chen Qing-Dong , Pu De-Qiang , Chen Zhi-Teng , Liu Yue-Yue , Liu Xu
Published: May 2022

Haplodiplatyidae is a recently established earwig family with over 40 species representing a single genus, Haplodiplatys Hincks, 1955. The morphology of Haplodiplatyidae has been studied in detail, but its molecular characters remain unclear. In this study, two mitogenomes of Haplodiplatys aotouensis Ma & Chen, 1991, were sequenced based on two samples from Fujian and Jiangxi provinces, respectively. These represent the first mitogenomes for the family Haplodiplatyidae. The next-generation sequencing method and subsequent automatic assembly obtained two mitogenomes. The two mitogenomes of H. aotouensis were generally identical but still exhibit a few sequence differences involving protein-coding genes (PCGs), ribosomal RNA (rRNA) genes, control regions, and intergenic spacers. The typical set of 37 mitochondrial genes was annotated, while many transfer RNA (tRNA) genes were rearranged from their ancestral locations. The calculation of nonsynonymous (Ka) and synonymous (Ks) substitution rates in PCGs indicated the fastest evolving nd4l gene in H. aotouensis. The phylogenetic analyses supported the basal position of Apachyidae but also recovered several controversial clades.
Risks of Biologic Therapy and the Importance of Multidisciplinary Approach for an Accurate Management of Patients with Moderate-Severe Psoriasis and Concomitant Diseases
Authors: Ion Ana , Dorobanțu Alexandra Maria , Popa Liliana Gabriela , Mihai Mara Mădălina , Orzan Olguța Anca
Published: May 2022

Psoriasis is a chronic multisystem inflammatory disease associated with a plethora of comorbidities including metabolic syndrome, cardiovascular disease, hypertension, diabetes, hyperlipidemia, obesity, anxiety, depression, chronic kidney disease, and malignancy. Advancement in unveiling new key elements in the pathophysiology of psoriasis led to significant progress in the development of biologic agents which target different signaling pathways and cytokines involved in the inflammatory cascade responsible for the clinical manifestations found in psoriasis. Currently available novel therapeutic options for moderate-severe psoriasis include tumor necrosis factor alpha inhibitors, inhibitors of the interleukin 17, and inhibitors of the interleukin 23. Nevertheless, concerns have been raised with respect to the possible risks associated with the use of biologic therapy requiring close collaboration between dermatologists and physicians of different specialties. Our aim was to perform an in-depth literature review and discuss the potential risks associated with biologic therapy in patients with psoriasis and concurrent diseases with a focus on the influence of novel therapeutic agents on liver function in the context of hepatopathies, particularly viral hepatitis. A multidisciplinary teamwork and periodic evaluation of psoriasis patients under biologic therapy is highly encouraged to obtain an accurate management for each case.
Sphingosine 1-Phosphate Signaling at the Skin Barrier Interface
Authors: Masuda-Kuroki Kana , Di Nardo Anna
Published: May 2022

Sphingosine 1-phosphate (S1P) is a product of membrane sphingolipid metabolism. S1P is secreted and acts via G-protein-coupled receptors, S1PR1-5, and is involved in diverse cellular functions, including cell proliferation, immune suppression, and cardiovascular functions. Recent studies have shown that the effects of S1P signaling are extended further by coupling the different S1P receptors and their respective downstream signaling pathways. Our group has recently reported that S1P inhibits cell proliferation and induces differentiation in human keratinocytes. There is a growing understanding of the connection between S1P signaling, skin barrier function, and skin diseases. For example, the activation of S1PR1 and S1PR2 during bacterial invasion regulates the synthesis of inflammatory cytokines in human keratinocytes. Moreover, S1P-S1PR2 signaling is involved in the production of inflammatory cytokines and can be triggered by epidermal mechanical stress and bacterial invasion. This review highlights how S1P affects human keratinocyte proliferation, differentiation, immunoreaction, and mast cell immune response, in addition to its effects on the skin barrier interface. Finally, studies targeting S1P-S1PR signaling involved in inflammatory skin diseases are also presented.
Low-Salt Diet Reduces Anti-CTLA4 Mediated Systemic Immune-Related Adverse Events while Retaining Therapeutic Efficacy against Breast Cancer
Authors: Khandekar Durga , Dahunsi Debolanle O. , Manzanera Esteve Isaac V. , Reid Sonya , Rathmell Jeffrey C. , Titze Jens , Tiriveedhi Venkataswarup
Published: May 2022

Immune checkpoint inhibitor (ICI) therapy has revolutionized the breast cancer treatment landscape. However, ICI-induced systemic inflammatory immune-related adverse events (irAE) remain a major clinical challenge. Previous studies in our laboratory and others have demonstrated that a high-salt (HS) diet induces inflammatory activation of CD4+T cells leading to anti-tumor responses. In our current communication, we analyzed the impact of dietary salt modification on therapeutic and systemic outcomes in breast-tumor-bearing mice following anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) monoclonal antibody (mAb) based ICI therapy. As HS diet and anti-CTLA4 mAb both exert pro-inflammatory activation of CD4+T cells, we hypothesized that a combination of these would lead to enhanced irAE response, while low-salt (LS) diet through blunting peripheral inflammatory action of CD4+T cells would reduce irAE response. We utilized an orthotopic murine breast tumor model by injecting Py230 murine breast cancer cells into syngeneic C57Bl/6 mice. In an LS diet cohort, anti-CTLA4 mAb treatment significantly reduced tumor progression (day 35, 339 ± 121 mm3), as compared to isotype mAb (639 ± 163 mm3, p < 0.05). In an HS diet cohort, treatment with anti-CTLA4 reduced the survival rate (day 80, 2/15) compared to respective normal/regular salt (NS) diet cohort (8/15, p < 0.05). Further, HS plus anti-CTLA4 mAb caused an increased expression of inflammatory cytokines (IFNγ and IL-1β) in lung infiltrating and peripheral circulating CD4+T cells. This inflammatory activation of CD4+T cells in the HS plus anti-CTLA4 cohort was associated with the upregulation of inflammasome complex activity. However, an LS diet did not induce any significant irAE response in breast-tumor-bearing mice upon treatment with anti-CTLA4 mAb, thus suggesting the role of high-salt diet in irAE response. Importantly, CD4-specific knock out of osmosensitive transcription factor NFAT5 using CD4cre/creNFAT5flox/flox transgenic mice caused a downregulation of high-salt-mediated inflammatory activation of CD4+T cells and irAE response. Taken together, our data suggest that LS diet inhibits the anti-CTLA4 mAb-induced irAE response while retaining its anti-tumor efficacy.
Myristic Acid Supplementation Aggravates High Fat Diet-Induced Adipose Inflammation and Systemic Insulin Resistance in Mice
Authors: Saraswathi Viswanathan , Kumar Narendra , Ai Weilun , Gopal Thiyagarajan , Bhatt Saumya , Harris Edward N. , Talmon Geoffrey A. , Desouza Cyrus V.
Published: May 2022

Saturated fatty acids (SFAs) are considered to be detrimental to human health. One of the SFAs, myristic acid (MA), is known to exert a hypercholesterolemic effect in mice as well as humans. However, its effects on altering adipose tissue (AT) inflammation and systemic insulin resistance (IR) in obesity are still unclear. Here, we sought to determine the effects of a high fat (HF) diet supplemented with MA on obesity-associated metabolic disorders in mice. Wild-type C57BL/6 mice were fed a HF diet in the presence or absence of 3% MA for 12 weeks. Plasma lipids, plasma adipokines, AT inflammation, systemic IR, glucose homeostasis, and hepatic steatosis were assessed. The body weight and visceral adipose tissue (VAT) mass were significantly higher in mice receiving the HF+MA diet compared to HF diet-fed controls. Plasma total cholesterol levels were marginally increased in HF+MA-fed mice compared to controls. Fasting blood glucose was comparable between HF and HF+MA-fed mice. Interestingly, the plasma insulin and HOMA-IR index, a measure of insulin resistance, were significantly higher in HF+MA-fed mice compared to HF controls. Macrophage and inflammatory markers were significantly elevated in the AT and AT-derived stromal vascular cells upon MA feeding. Moreover, the level of circulating resistin, an adipokine promoting insulin resistance, was significantly higher in HF+MA-fed mice compared with HF controls. The insulin tolerance test revealed that the IR was higher in mice receiving the MA supplementation compared to HF controls. Moreover, the glucose tolerance test showed impairment in systemic glucose homeostasis in MA-fed mice. Analyses of liver samples showed a trend towards an increase in liver TG upon MA feeding. However, markers of oxidative stress and inflammation were reduced in the liver of mice fed an MA diet compared to controls. Taken together, our data suggest that chronic administration of MA in diet exacerbates obesity-associated insulin resistance and this effect is mediated in part, via increased AT inflammation and increased secretion of resistin.
Neuromuscular Active Zone Structure and Function in Healthy and Lambert-Eaton Myasthenic Syndrome States
Authors: Ginebaugh Scott P. , Badawi Yomna , Tarr Tyler B. , Meriney Stephen D.
Published: May 2022

The mouse neuromuscular junction (NMJ) has long been used as a model synapse for the study of neurotransmission in both healthy and disease states of the NMJ. Neurotransmission from these neuromuscular nerve terminals occurs at highly organized structures called active zones (AZs). Within AZs, the relationships between the voltage-gated calcium channels and docked synaptic vesicles govern the probability of acetylcholine release during single action potentials, and the short-term plasticity characteristics during short, high frequency trains of action potentials. Understanding these relationships is important not only for healthy synapses, but also to better understand the pathophysiology of neuromuscular diseases. In particular, we are interested in Lambert-Eaton myasthenic syndrome (LEMS), an autoimmune disorder in which neurotransmitter release from the NMJ decreases, leading to severe muscle weakness. In LEMS, the reduced neurotransmission is traditionally thought to be caused by the antibody-mediated removal of presynaptic voltage-gated calcium channels. However, recent experimental data and AZ computer simulations have predicted that a disruption in the normally highly organized active zone structure, and perhaps autoantibodies to other presynaptic proteins, contribute significantly to pathological effects in the active zone and the characteristics of chemical transmitters.
Glycome Profiling of Cancer Cell Lines Cultivated in Physiological and Commercial Media
Authors: Wang Junyao , Peng Wenjing , Yu Aiying , Fokar Mohamed , Mechref Yehia
Published: May 2022

A complex physiological culture medium (Plasmax) was introduced recently, composed of nutrients and metabolites at concentrations normally found in human plasma to mimic the in vivo environment for cell line cultivation. As glycosylation has been proved to be involved in cancer development, it is necessary to investigate the glycan expression changes in media with different nutrients. In this study, a breast cancer cell line, MDA-MB-231BR, and a brain cancer cell line, CRL-1620, were cultivated in Plasmax and commercial media to reveal cell line glycosylation discrepancies prompted by nutritional environments. Glycomics analyses of cell lines were performed using LC-MS/MS. The expressions of multiple fucosylated N-glycans, such as HexNAc4Hex3DeoxyHex1 and HexNAc5Hex3DeoxyHex1, derived from both cell lines exhibited a significant increase in Plasmax. Among the O-glycans, significant differences were also observed. Both cell lines cultivated in EMEM had the lowest amounts of O-glycans expressed. The original work described the development of Plasmax, which improves colony formation, and resulted in transcriptomic and metabolomic alterations of cancer cell lines, while our results indicate that Plasmax can significantly impact protein glycosylation. This study also provides information to guide the selection of media for in vitro cancer cell glycomics studies.
Association of Metabolomic Change and Treatment Response in Patients with Non-Alcoholic Fatty Liver Disease
Authors: Lee Kwang Seob , Cho Yongin , Kim Hongkyung , Hwang Hyunkyeong , Cho Jin Won , Lee Yong-ho , Lee Sang-Guk
Published: May 2022

Non-alcoholic fatty liver disease (NAFLD) is the major cause of chronic liver disease, yet cost-effective and non-invasive diagnostic tools to monitor the severity of the disease are lacking. We aimed to investigate the metabolomic changes in NAFLD associated with therapeutic responses. It was conducted in 63 patients with NAFLD who received either ezetimibe plus rosuvastatin or rosuvastatin monotherapy. The treatment response was determined by MRI performed at baseline and week 24. The metabolites were measured at baseline and week 12. In the combination group, a relative decrease in xanthine was associated with a good response to liver fat decrease, while a relative increase in choline was associated with a good response to liver stiffness. In the monotherapy group, the relative decreases in triglyceride (TG) 20:5_36:2, TG 18:1_38:6, acetylcarnitine (C2), fatty acid (FA) 18:2, FA 18:1, and docosahexaenoic acid were associated with a decrease in liver fat, while hexosylceramide (d18:2/16:0) and hippuric acid were associated with a decrease in liver stiffness. Models using the metabolite changes showed an AUC of >0.75 in receiver operating curve analysis for predicting an improvement in liver fat and stiffness. This approach revealed the physiological impact of drugs, suggesting the mechanism underlying the development of this disease.
Immunomodulatory Properties of Human Breast Milk: MicroRNA Contents and Potential Epigenetic Effects
Authors: Hatmal Ma’mon M. , Al-Hatamleh Mohammad A. I. , Olaimat Amin N. , Alshaer Walhan , Hasan Hanan , Albakri Khaled A. , Alkhafaji Enas , Issa Nada N. , Al-Holy Murad A. , Abderrahman Salim M. , Abdallah Atiyeh M. , Mohamud Rohimah
Published: May 2022

Infants who are exclusively breastfed in the first six months of age receive adequate nutrients, achieving optimal immune protection and growth. In addition to the known nutritional components of human breast milk (HBM), i.e., water, carbohydrates, fats and proteins, it is also a rich source of microRNAs, which impact epigenetic mechanisms. This comprehensive work presents an up-to-date overview of the immunomodulatory constituents of HBM, highlighting its content of circulating microRNAs. The epigenetic effects of HBM are discussed, especially those regulated by miRNAs. HBM contains more than 1400 microRNAs. The majority of these microRNAs originate from the lactating gland and are based on the remodeling of cells in the gland during breastfeeding. These miRNAs can affect epigenetic patterns by several mechanisms, including DNA methylation, histone modifications and RNA regulation, which could ultimately result in alterations in gene expressions. Therefore, the unique microRNA profile of HBM, including exosomal microRNAs, is implicated in the regulation of the genes responsible for a variety of immunological and physiological functions, such as FTO, INS, IGF1, NRF2, GLUT1 and FOXP3 genes. Hence, studying the HBM miRNA composition is important for improving the nutritional approaches for pregnancy and infant’s early life and preventing diseases that could occur in the future. Interestingly, the composition of miRNAs in HBM is affected by multiple factors, including diet, environmental and genetic factors.
Chemical Exchange Saturation Transfer (CEST) Signal at −1.6 ppm and Its Application for Imaging a C6 Glioma Model
Authors: Wu Qi-Xuan , Liu Hong-Qing , Wang Yi-Jiun , Chen Tsai-Chen , Wei Zi-Ying , Chang Jung-Hsuan , Chen Ting-Hao , Seema Jaya , Lin Eugene C.
Published: May 2022

The chemical exchange saturation transfer (CEST) signal at −1.6 ppm is attributed to the choline methyl on phosphatidylcholines and results from the relayed nuclear Overhauser effect (rNOE), that is, rNOE(−1.6). The formation of rNOE(−1.6) involving the cholesterol hydroxyl is shown in liposome models. We aimed to confirm the correlation between cholesterol content and rNOE(−1.6) in cell cultures, tissues, and animals. C57BL/6 mice (N = 9) bearing the C6 glioma tumor were imaged in a 7 T MRI scanner, and their rNOE(−1.6) images were cross-validated through cholesterol staining with filipin. Cholesterol quantification was obtained using an 18.8-T NMR spectrometer from the lipid extracts of the brain tissues from another group of mice (N = 3). The cholesterol content in the cultured cells was manipulated using methyl-β-cyclodextrin and a complex of cholesterol and methyl-β-cyclodextrin. The rNOE(−1.6) of the cell homogenates and their cholesterol levels were measured using a 9.4-T NMR spectrometer. The rNOE(−1.6) signal is hypointense in the C6 tumors of mice, which matches the filipin staining results, suggesting that their tumor region is cholesterol deficient. The tissue extracts also indicate less cholesterol and phosphatidylcholine contents in tumors than in normal brain tissues. The amplitude of rNOE(−1.6) is positively correlated with the cholesterol concentration in the cholesterol-manipulated cell cultures. Our results indicate that the cholesterol dependence of rNOE(−1.6) occurs in cell cultures and solid tumors of C6 glioma. Furthermore, when the concentration of phosphatidylcholine is carefully considered, rNOE(−1.6) can be developed as a cholesterol-weighted imaging technique.
Preclinical Studies of Granulysin-Based Anti-MUC1-Tn Immunotoxins as a New Antitumoral Treatment
Authors: Guerrero-Ochoa Patricia , Ibáñez-Pérez Raquel , Berbegal-Pinilla Germán , Aguilar Diederich , Marzo Isabel , Corzana Francisco , Minjárez-Sáenz Martha , Macías-León Javier , Conde Blanca , Raso Javier , Hurtado-Guerrero Ramón , Anel Alberto
Published: May 2022

Two granulysin (GRNLY) based immunotoxins were generated, one containing the scFv of the SM3 mAb (SM3GRNLY) and the other the scFv of the AR20.5 mAb (AR20.5GRNLY). These mAb recognize different amino acid sequences of aberrantly O-glycosylated MUC1, also known as the Tn antigen, expressed in a variety of tumor cell types. We first demonstrated the affinity of these immunotoxins for their antigen using surface plasmon resonance for the purified antigen and flow cytometry for the antigen expressed on the surface of living tumor cells. The induction of cell death of tumor cell lines of different origin positive for Tn antigen expression was stronger in the cases of the immunotoxins than that induced by GRNLY alone. The mechanism of cell death induced by the immunotoxins was studied, showing that the apoptotic component demonstrated previously for GRNLY was also present, but that cell death induced by the immunotoxins included also necroptotic and necrotic components. Finally, we demonstrated the in vivo tumor targeting by the immunotoxins after systemic injection using a xenograft model of the human pancreatic adenocarcinoma CAPAN-2 in athymic mice. While GRNLY alone did not have a therapeutic effect, SM3GRNLY and AR20.5GRNLY reduced tumor volume by 42 and 60%, respectively, compared with untreated tumor-bearing mice, although the results were not statistically significant in the case of AR20.5GRNLY. Histological studies of tumors obtained from treated mice demonstrated reduced cellularity, nuclear morphology compatible with apoptosis induction and active caspase-3 detection by immunohistochemistry. Overall, our results exemplify that these immunotoxins are potential drugs to treat Tn-expressing cancers.
Aqueous Heat Method for the Preparation of Hybrid Lipid–Polymer Structures: From Preformulation Studies to Protein Delivery
Authors: Pippa Natassa , Lagopati Nefeli , Forys Aleksander , Chountoulesi Maria , Katifelis Hektor , Chrysostomou Varvara , Trzebicka Barbara , Gazouli Maria , Demetzos Costas , Pispas Stergios
Published: May 2022

Liposomes with adjuvant properties are utilized to carry biomolecules, such as proteins, that are often sensitive to the stressful conditions of liposomal preparation processes. The aim of the present study is to use the aqueous heat method for the preparation of polymer-grafted hybrid liposomes without any additional technique for size reduction. Towards this scope, liposomes were prepared through the combination of two different lipids with adjuvant properties, namely dimethyldioctadecylammonium (DDA) and D-(+)-trehalose 6,6′-dibehenate (TDB) and the amphiphilic block copolymer poly(2-(dimethylamino)ethyl methacrylate)-b-poly(lauryl methacrylate) (PLMA-b-PDMAEMA). For comparison purposes, PAMAM dendrimer generation 4 (PAMAM G4) was also used. Preformulation studies were carried out by differential scanning calorimetry (DSC). The physicochemical characteristics of the prepared hybrid liposomes were evaluated by light scattering and their morphology was evaluated by cryo-TEM. Subsequently, in vitro nanotoxicity studies were performed. Protein-loading studies with bovine serum albumin were carried out to evaluate their encapsulation efficiency. According to the results, PDMAEMA-b-PLMA was successfully incorporated in the lipid bilayer, providing improved physicochemical and morphological characteristics and the ability to carry higher cargos of protein, compared to pure DDA:TDB liposomes, without affecting the biocompatibility profile. In conclusion, the aqueous heat method can be applied in polymer-grafted hybrid liposomes for protein delivery without further size-reduction processes.
Trends of Myocarditis and Endocarditis Cases before, during, and after the First Complete COVID-19-Related Lockdown in 2020 in France
Authors: Pommier Thibaut , Benzenine Eric , Bernard Chloé , Mariet Anne-Sophie , Béjot Yannick , Giroud Maurice , Morgant Marie-Catherine , Steinmetz Eric , Guenancia Charles , Bouchot Olivier , Quantin Catherine
Published: May 2022

Background. The impact of the COVID-19 pandemic on hospitalization for cardiac infections is not well known. We aimed to evaluate the nationwide trends in hospital stays for myocarditis and endocarditis cases before, during and after the nationwide lockdown for the COVID-19 pandemic in France. We then aimed to describe the proportion of myocarditis and endocarditis patients with and without COVID-19 and their clinical characteristics. Methods. Hospitalized cases of cardiac infection were extracted from the French National Discharge database, which collects the medical records of all patients discharged from all public and private hospitals in France. Age, sex, and available cardiovascular risk factors were compared between stays with and without COVID-19 during the lockdown. Results. The number of myocarditis cases was 11% higher in 2020, compared to the average of the three prior years. In 2020, 439 of 3727 cases of myocarditis were associated with COVID-19. For endocarditis, there was an increase in cases by 7% in 2020 versus prior years. For endocarditis, 3% (240 of 8128 cases) of patients with endocarditis had COVID-19. For myocarditis, older age, hypertension, diabetes, obesity, and atrial fibrillation were more frequent in patients with COVID-19 than in those without. For endocarditis, only hypertension was more frequent in patients with COVID-19 than in those without. Conclusion. Our study reports an increase in hospitalizations for both myocarditis and endocarditis in 2020, possibly related to the COVID-19 pandemic. Interestingly, the trends differ according to the COVID-19 status. Knowledge of the factors associating myocarditis or endocarditis and COVID-19 may improve the quality and the type of monitoring for people with COVID-19, the identification of patients at risk of cardiac infections, and the treatment of COVID-19 patients.
Social Priming in Speech Perception: Revisiting Kangaroo/Kiwi Priming in New Zealand English
Authors: Hurring Gia , Hay Jennifer , Drager Katie , Podlubny Ryan , Manhire Laura , Ellis Alix
Published: May 2022

We investigate whether regionally-associated primes can affect speech perception in two lexical decision tasks in which New Zealand listeners were exposed to an Australian prime (a kangaroo), a New Zealand prime (a kiwi), and/or a control animal (a horse). The target stimuli involve ambiguous vowels, embedded in a frame that would result in a real word with a KIT or a DRESS vowel and a nonsense word with the alternative vowel; thus, lexical decision responses can reveal which vowel was heard. Our pre-registered design predicted that exposure to the kangaroo would elicit more KIT-consistent responses than exposure to the kiwi. Both experiments showed significant priming effects in which the kangaroo elicited more KIT-consistent responses than the kiwi. The particular locus and details of these effects differed across experiments and participants. Taken together, the experiments reinforce the finding that regionally-associated primes can affect speech perception, but also suggest that the effects are sensitive to experimental design, stimulus acoustics, and individuals’ production and past experience.
Encode a Letter and Get Its Location for Free? Assessing Incidental Binding of Verbal and Spatial Features
Authors: Delooze Molly A. , Langerock Naomi , Macy Robin , Vergauwe Evie , Morey Candice C.
Published: May 2022

Previous studies have demonstrated that when presented with a display of spatially arranged letters, participants seem to remember the letters’ locations when letters are the focus of a recognition test, but do not remember letters’ identity when locations are tested. This strong binding asymmetry suggests that encoding location may be obligatory when remembering letters, which requires explanation within theories of working memory. We report two studies in which participants focused either on remembering letters or locations for a short interval. At test, positive probes were either intact letter–location combinations or recombinations of an observed letter and another previously occupied location. Incidental binding is observed when intact probes are recognized more accurately or faster than recombined probes. Here, however, we observed no evidence of incidental binding of location to letter in either experiment, neither under conditions where participants focused on one feature exclusively for a block, nor where the to-be-remembered feature was revealed prior to encoding with a changing pre-cue, nor where the to-be-remembered feature was retro-cued and therefore unknown during encoding. Our results call into question the robustness of a strong, consistent binding asymmetry. They suggest that while incidental location-to-letter binding may sometimes occur, it is not obligatory.