bluuebunny/crossref_metadata_2025 huggingface dataset:
Getting Noticed by Many: On the Transformations of the Popular
Authors: Werber Niels , Stein Daniel , Döring Jörg , Albrecht-Birkner Veronika , Gerlitz Carolin , Hecken Thomas , Paßmann Johannes , Schäfer Jörgen , Schubert Cornelius , Venus Jochen
Published: February 2023

This article argues that the transformations of the popular, which began in Europe around 1800 and introduced the powerful distinction between low culture and high culture, have established a competitive distinction between the popular and the non-popular that has become dominant over the course of the 20th century. As a result, the popular is no longer either the culture of the ‘lower classes’ or the inclusion of the ‘people’ in the service of higher goals. The popular today is hardly the object of desired transgressions (Leslie Fiedler’s “cross the border, close the gap”) or an expression of felt or feared “massification” or “flattening”. Rather, being popular now means getting noticed by many. Popularity is measured as well as staged, as rankings and charts provide information on what is popular while vying for popularity themselves. These quantifying formats do not speak to the quality or originality of the popular, only to its evident success across different scales of evaluation. People do not buy good products, they buy popular ones; they do not listen to the best music, but to popular music; they do not share, like, or retweet important, but popular news. Even the ‘unpopular’ can be popular: a despised politician, a hated jingle, an unpopular measure. The popular modifies whatever it affords with attention. Its quantitatively and hierarchically comparative terms (‘bestseller,’ ‘outperformer,’ ‘high score,’ ‘viral’) generate valences that do not inhere in the objects themselves. Conversely, the non-popular, which does not find any measurable resonance in these terms, risks being dismissed as irrelevant or worthless simply because it does not appear in any rankings or ratings. This can be observed particularly with artefacts whose relevance as part of high culture may be taken for granted even when they do not achieve mass resonance. The purpose of this article is to outline a theory of the popular that does justice to these developments by identifying two decisive transformations: 1. the popularization of quantifying methods to measure attention in popular culture around 1950; 2. the popularization of the internet around 2000, whereby the question of what can and cannot become popular is partially removed from the gatekeepers of the established mass media, educational institutions, and cultural elites and is increasingly decided via social media.
Health Risks Forecast of Regional Air Pollution on Allergic Rhinitis: High-Resolution City-Scale Simulations in Changchun, China
Authors: Tong Weifang , Zhang Xuelei , He Feinan , Chen Xue , Ma Siqi , Tong Qingqing , Wen Zeyi , Teng Bo
Published: February 2023

Accurate assessments of exposure to urban air pollution with higher traffic emissions and its health risks still face several challenges, such as intensive computation of air pollution modeling and the limited availability of personal activity data. The macroscopic health effects can be transmitted to the whole population for personal prevention via air quality health index (AQHI), but the possibility risk index of the specific allergic diseases is still lacking. This interdisciplinary study aims at evaluating the forecasted results of high-resolution air quality with updated traffic emissions and accessing the potential impacts of outdoor pollution on morbidity of rhinitis for urban residents. A high-resolution modelling system (1 km × 1 km) containing the online traffic emission model (VEIN), meteorological and air quality model (WRF-CHIMERE) and the health impact module was developed. A new health index of Potential Morbidity Risk Index (PMRI) was further established using higher resolution health risk coefficients of major air pollutants on allergic rhinitis, and different methods (with/without considering population distributions) targeting different user groups (residents, hospitals and health administrations) were calculated and analyzed. Operational forecasted results of hourly PMRI can be further combined with online map services to serve as an effective tool for patients with allergic rhinitis to arrange their daily activities so as to avoid acute exacerbation. The forecasted PMRIs accessible to the public will also be beneficial for the public health administrations in planning the medical resource and improving the outpatient efficiency.
Long-Term Exposure to Ambient Fine Particles and Heart Rate in Northwestern China: Findings from 1.8 Million Adults of the Kashgar Prospective Cohort Study (KPCS)
Authors: Hao Zelin , He Chuanjiang , Li Jia-Xin , Yang Haifeng , Fan Shu-Jun , Hu Li-Xin , Liu Xiao-Xuan , Zhang Yi-Dan , Qiu Hui-Ling , Xie Yu-Ting , Zhou Gang-Long , Wang Lu , Zhong Xuemei , Li Li , Xu Ai-Min , Zhang Zhoubin , Duan Chaohui , Yang Bo-Yi , Zou Xiao-Guang
Published: February 2023

Elevated heart rate (HR) can be hypothesized to be involved in the pathways by which ambient air pollution, especially fine particulate matter (PM2.5), causes cardiovascular morbidity and mortality. However, evidence concerning long-term PM2.5 exposure and HR is still limited. Therefore, in this study, we assessed the associations of PM2.5 with HR levels and tachycardia prevalence and explored potential modifiers of the associations. We used baseline data of 1,802,207 adults from the Kashgar Prospective Cohort Study (KPCS). PM2.5 exposure was assessed based on satellite sensing data, meteorological factors, multi-resolution emission inventory, and measurements from ground-based surface monitors measurements. HR was measured using a calibrated electronic sphygmomanometer, and tachycardia was defined as resting heart rate (RHR) equal to or greater than 80 beats per minute. Linear regression and logistic regression models were employed to evaluate the associations of PM2.5 levels with RHR levels and tachycardia prevalence, respectively. Stratified analyses by sex, age, ethnicity, smoking status, alcohol use, and physical activity were also performed. The mean (standard deviation) age of the study participants was 39.4 (15.5) years old. In the adjusted models, an interquartile range (8.8 µg/m3) increase in PM2.5 levels was associated with 0.515 (95% confidence interval: 0.503–0.526) bpm increase in RHR levels and with 1.062-fold (95% confidence interval: 1.059–1.064) increase in the odds of tachycardia. The results were robust against several sensitivity analyses. In addition, we observed the above associations were stronger in participants that were men, of Uyghur ethnicity, smoking cigarettes, drinking alcohol, and having physical inactivity, compared to their counterparts. In summary, our findings indicate that long-term exposure to ambient PM2.5 may be hazardously associated with HR, and women, Uyghur people, and those with unhealthy lifestyles may be more vulnerable to the hazardous effects.
Two-Stage Decomposition Multi-Scale Nonlinear Ensemble Model with Error-Correction-Coupled Gaussian Process for Wind Speed Forecast
Authors: Wang Jujie , He Maolin , Qiu Shiyao
Published: February 2023

Wind power has great potential in the fields of electricity generation, heating, et cetera, and the precise forecasting of wind speed has become the key task in an effort to improve the efficiency of wind energy development. Nowadays, many existing studies have investigated wind speed prediction, but they often simply preprocess raw data and also ignore the nonlinear features in the residual part, which should be given special treatment for more accurate forecasting. Meanwhile, the mainstream in this field is point prediction which cannot show the potential uncertainty of predicted values. Therefore, this paper develops a two-stage decomposition ensemble interval prediction model. The original wind speed series is firstly decomposed using a complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) and the decomposed subseries with the highest approximate entropy is secondly decomposed through singular-spectrum analysis (SSA) to further reduce the complexity of the data. After two-stage decomposition, auto-encoder dimensionality reduction is employed to alleviate the accumulated error problem. Then, each reconstructed subsequence will generate an independent prediction result using an elastic neural network. Extreme gradient boosting (Xgboost) is utilized to integrate the separate predicted values and also carry out the error correction. Finally, the Gaussian process (GP) will generate the interval prediction result. The case study shows the best performance of the proposed models, not only in point prediction but also in interval prediction.
Adhering Solid Precipitation in the Current and Pseudo-Global Warming Future Climate over the Canadian Provinces of Manitoba and Saskatchewan
Authors: Stewart Ronald , Liu Zhuo , Painchaud-Niemi Dylan , Hanesiak John , Thériault Julie M.
Published: February 2023

Solid precipitation falling near 0 °C, mainly snow, can adhere to surface features and produce major impacts. This study is concerned with characterizing this precipitation over the Canadian Prairie provinces of Manitoba and Saskatchewan in the current (2000–2013) and pseudo-global warming future climate, with an average 5.9 °C temperature increase, through the use of high resolution (4 km) model simulations. On average, simulations in the current climate suggest that this precipitation occurs within 11 events per year, lasting 33.6 h in total and producing 27.5 mm melted equivalent, but there are wide spatial variations that are partly due to enhancements arising from its relatively low terrain. Within the warmer climate, average values generally increase, and spatial patterns shift somewhat. This precipitation consists of four categories covering its occurrence just below and just above a wet-bulb temperature of 0 °C, and with or without liquid precipitation. It generally peaks in March or April, as well as in October, and these peaks move towards mid-winter by approximately one month within the warmer climate. Storms producing this precipitation generally produce winds with a northerly component during or shortly after the precipitation; these winds contribute to further damage. Overall, this study has determined the features of and expected changes to adhering precipitation across this region.
Environmental Impacts of Biodiesel Production Cycle from Farm to Manufactory: An Application of Sustainable Systems Engineering
Authors: Motevali Ali , Hooshmandzadeh Niusha , Fayyazi Ebrahim , Valipour Mohammad , Yue Jun
Published: February 2023

One of the key challenges in using fossil fuels is the environmental impacts of these energy sources, and to reduce these destructive effects, the use of renewable energy sources (biofuels) is necessary. One of the important biofuels is biodiesel, which can be produced from cottonseed. To properly manage the chain dealing with biodiesel production from the cottonseed chain (from farm to manufactory), environmental hotspots must be pinpointed. In the present study, it was attempted to examine the environmental impacts of the biodiesel production cycle from cottonseed (agronomic stages, ginning, oiling, and biodiesel production). The data obtained in all three stages were analyzed by the Impact 2002+ method in the SimaPro software. The highest contribution to creating environmental indicators at the agricultural stage was related to the use of nitrogen fertilizers, direct emission from the farm and fossil fuels, the ginning and oiling stage involving the use of diesel fuel and sulfuric acid, and the production of biodiesel in the manufactory involving the use of methanol and electricity. The potential environmental impacts of a functional unit of 1 kg of biodiesel include: human health, 9.05–10−6 (DAYLY); ecosystem quality, 1.369 (PDF*m2*year); climate changes, (kg CO2 eq.) 17.247; and resources (MJ primary), 89.116. Results showed that agriculture has more significant participation in the environmental impact than other sections (ginning and oiling and biodiesel production), especially due to the application of fertilizers and fuel. Surveying the environmental indicators of the results showed that at the agricultural stage, the human health indicator is 10.43, 1.21, and 5.32 times higher than the ecosystem quality, climate change, and resource indicators, respectively; at the ginning and oiling stages, it is 2.35, 31.68, and 2.09 times higher, respectively; and at the stage of biodiesel production in the manufactory, it is 16.41, 1.96, and 0.99 times higher, respectively, in terms of the destructive effects. The overall results showed that the hotspot points in the present study can be largely modified by reducing the consumption of nitrogen fertilizers, using new equipment and machinery, ginning and oiling, and using fewer methanol ratios than oil.
Atmospheric Particle Number Concentrations and New Particle Formation over the Southern Ocean and Antarctica: A Critical Review
Authors: Wang Jiayu , Xu Guojie , Chen Liqi , Chen Kui
Published: February 2023

The Southern Ocean (SO) and Antarctica play important roles in the global climate. The new particle formation (NPF) alters the availability of cloud condensation nuclei (CCN), leading to impacts on the cloud reflectance and global radiative budget. In this review, we introduce the common instruments for measuring particle number concentration (PNC) and particle number size distribution (PNSD). Based on the observations over the Antarctic and some Antarctic research stations, we explored spatial and temporal characteristics of PNCs and PNSDs. From the SO to the interior of the Antarctic, the total PNCs show a decreasing trend, and the total PNCs present an obvious seasonal cycle, with the low concentration in winter (June–August) and the high concentration in summer (December–February). By summarizing the research progress over the SO and Antarctica, we discuss possible precursors of the NPF: sulfuric acid (H2SO4, SA), methanesulfonic acid (CH3S(O)2OH, MSA), dimethyl sulfide ((CH3)2S, DMS), iodic acid (HIO3, IA), iodous acid (HIO2), ammonia (NH3), dimethylamine ((CH3)2NH, DMA), highly oxygenated organic molecules (HOMs) and other organics with low vapor pressure. We also explore several possible nucleation mechanisms: ion-induced nucleation of H2SO4 and NH3, H2SO4-amines, H2SO4-DMA-H2O, H2SO4-MSA-DMA, IA-MSA, IA-DMA, heterogeneous IA-organics nucleation mechanisms and environmental conditions required for the NPF. NPF is one of the main sources of CCN in the remote marine boundary layer, such as the SO and Antarctica. Thus, we discuss the contribution of NPF to CCN and the indirect impacts of NPF on climate. Through this review, we could better understand the PNC and NPF over the SO and Antarctica and their impacts on the global climate.
Investigating the Coupling of Supply and Demand for Urban Blue and Green Spaces’ Cooling Effects in Shandong, China
Authors: Wang Jiayun , Meng Fei , Fu Pingjie , Jin Fengxiang
Published: February 2023

It is of great significance to determine the level of demand for thermal environment regulation and the availability of blue–green spaces for thermal environment regulation to alleviate the effects of urban heat islands. Taking Shandong Province, China, as the study area, combined multi–source remote sensing data are used in this study to construct the index system of cold island supply capacity (CIS) and the cold island demand level (CID). We use the methods of spatial regression, quadrant division, and coupling coordination degree to analyze the correlation, matching status, and the level of coordinated development between the supply capacity and demand for the cooling effect. We also explore the change law and spatial characteristics of the blue–green spaces’ cooling effects supply and demand matching. Results show that: (1) The CIS and the CID are significantly negatively correlated and spatially heterogeneous in distribution, with a significant spatial spillover effect. (2) The dominant type of supply and demand is one of low supply and high demand, which means that the supply and demand for cool islands’ cooling effect are unbalanced, with significant problems of spatial mismatch and quantitative imbalance. (3) The coupling between supply capacity and demand level is on the verge of becoming dysfunctional because the uneven distribution of urban buildings, population, and blue–green spaces reduce the coupling between supply and demand levels. This research can provide a new perspective and scientific basis for the study of the cooling effects of blue and green spaces and the mitigation of the heat island effect in densely populated urban centers.
Effect of Major Dust Events on Ambient Temperature and Solar Irradiance Components over Saudi Arabia
Authors: Labban Abdulhaleem , Farahat Ashraf
Published: February 2023

The Saudi government targets building eight solar plants across the country by 2030, which are expected to produce more than 3600 MW, enough to power more than 500,000 homes. However, the vast desert environment in Saudi Arabia increases dust and aerosol loading in the atmosphere, which affect the performance of photovoltaic systems due to scattering and absorption of the solar radiation by dust particles. In this work, ground-based data from weather stations located in six Saudi cities, Dammam, Hafar Al Batin, Riyadh, Jeddah, Najran, and Arar, along with data from the Moderate Resolution Imaging Spectroradiometer (MODIS) are used to examine the effects of dust loading on aerosol optical parameters, air temperature, and solar irradiance. The effects of three major dust storms that blew over different regions in Saudi Arabia on 20 March 2017, 23 April 2018, and 15 April 2021 have been investigated. It is found that there is a strong correlation between dust loading and aerosol optical parameters. The maximum Aerosol Optical Depth (AOD) was recorded over Jeddah on 19 March 2017 (about 2), over Riyadh on 20 March 2017 (about 2.3), over Riyadh on 24 April 2018 (about 1.5), and over Najran on 15 April 2021 (about 0.9). Strong dust events are found to reduce air temperature by a few degrees in high dust loading regions. The study found that such large dust loading decreases the direct and global solar irradiance components, while it increases the diffuse component over the cities of Jeddah, Riyadh, and Najran. This could be an indication that scattering from dust particles can play a significant role in the solar irradiance intensity.
Electrothermal Monte Carlo Simulation of a GaAs Resonant Tunneling Diode
Authors: Muscato Orazio
Published: February 2023

This paper deals with the electron transport and heat generation in a Resonant Tunneling Diode semiconductor device. A new electrothermal Monte Carlo method is introduced. The method couples a Monte Carlo solver of the Boltzmann–Wigner transport equation with a steady-state solution of the heat diffusion equation. This methodology provides an accurate microscopic description of the spatial distribution of self-heating and its effect on the detailed nonequilibrium carrier dynamics.
Characterization and Control of Oxygen Uptake in the Blanketing and Purging of Tanks with Inert Gases in the Winery
Authors: del Barrio-Galán Rubén , Nevares Ignacio , del Alamo-Sanza Maria
Published: February 2023

This work presents the study of the effectiveness of different inert gases applied during racking to prevent oxygen uptake by wine. Inert gases were used for the purging of empty tanks and hoses before the start of each racking, as well as for blanketing in the full racked tank. After analyzing these operations with the different inert gases, the required volumes of each gas were optimized. The CO2:Ar (20:80) mixture proved to be the most effective for the complete purging of the empty tank, while CO2 was the most cost-effective gas. Purging the empty tank with 25% vessel volume gas was sufficient to achieve useful inerting with all the gases studied, as well as to maintain low levels of dissolved oxygen (DO) in the wine filling the tank. Applying 0.5 of vessel volume of Ar, CO2:Ar (20:80), and CO2 gases during blanketing allowed the headspace oxygen (HSO) of the racked tank to be protected throughout. During the racking of a white wine in a commercial winery, Ar showed the highest efficiency, compared to N2, for both the inerting of empty hoses and destination tank and for maintaining low levels of DO and HSO in the tank.
Toward a Physiologically Relevant 3D Helicoidal-Oriented Cardiac Model: Simultaneous Application of Mechanical Stimulation and Surface Topography
Authors: Navaee Fatemeh , Renaud Philippe , Piacentini Niccolò , Durand Mathilde , Bayat Dara Zaman , Ledroit Diane , Heub Sarah , Boder-Pasche Stephanie , Kleger Alexander , Braschler Thomas , Weder Gilles
Published: February 2023

Myocardium consists of cardiac cells that interact with their environment through physical, biochemical, and electrical stimulations. The physiology, function, and metabolism of cardiac tissue are affected by this dynamic structure. Within the myocardium, cardiomyocytes’ orientations are parallel, creating a dominant orientation. Additionally, local alignments of fibers, along with a helical organization, become evident at the macroscopic level. For the successful development of a reliable in vitro cardiac model, evaluation of cardiac cells’ behavior in a dynamic microenvironment, as well as their spatial architecture, is mandatory. In this study, we hypothesize that complex interactions between long-term contraction boundary conditions and cyclic mechanical stimulation may provide a physiological mechanism to generate off-axis alignments in the preferred mechanical stretch direction. This off-axis alignment can be engineered in vitro and, most importantly, mirrors the helical arrangements observed in vivo. For this purpose, uniaxial mechanical stretching of dECM-fibrin hydrogels was performed on pre-aligned 3D cultures of cardiac cells. In view of the potential development of helical structures similar to those in native hearts, the possibility of generating oblique alignments ranging between 0° and 90° was explored. Indeed, our investigations of cell alignment in 3D, employing both mechanical stimulation and groove constraint, provide a reliable mechanism for the generation of helicoidal structures in the myocardium. By combining cyclic stretch and geometric alignment in grooves, an intermediate angle toward favored direction can be achieved experimentally: while cyclic stretch produces a perpendicular orientation, geometric alignment is associated with a parallel one. In our 2D and 3D culture conditions, nonlinear cellular addition of the strains and strain avoidance concept reliably predicted the preferred cellular alignment. The 3D dECM-fibrin model system in this study shows that cyclical stretching supports cell survival and development. Using mechanical stimulation of pre-aligned heart cells, maturation markers are augmented in neonatal cardiomyocytes, while the beating culture period is prolonged, indicating an improved model function. We propose a simplified theoretical model based on numerical simulation and nonlinear strain avoidance by cells to explain oblique alignment angles. Thus, this work lays a possible rational basis for understanding and engineering oblique cellular alignments, such as the helicoidal layout of the heart, using approaches that simultaneously enhance maturation and function.
The Effect of Blood Rheology and Inlet Boundary Conditions on Realistic Abdominal Aortic Aneurysms under Pulsatile Flow Conditions
Authors: Tzirakis Konstantinos , Kamarianakis Yiannis , Kontopodis Nikolaos , Ioannou Christos V.
Published: February 2023

Background: The effects of non-Newtonian rheology and boundary conditions on various pathophysiologies have been studied quite extensively in the literature. The majority of results present qualitative and/or quantitative conclusions that are not thoroughly assessed from a statistical perspective. Methods: The finite volume method was employed for the numerical simulation of seven patient-specific abdominal aortic aneurysms. For each case, five rheological models and three inlet velocity boundary conditions were considered. Outlier- and heteroscedasticity-robust ANOVA tests assessed the simultaneous effect of rheological specifications and boundary conditions on fourteen variables that capture important characteristics of vascular flows. Results: The selection of inlet velocity profiles appears as a more critical factor relative to rheological specifications, especially regarding differences in the oscillatory characteristics of computed flows. Response variables that relate to the average tangential force on the wall over the entire cycle do not differ significantly across alternative factor levels, as long as one focuses on non-Newtonian specifications. Conclusions: The two factors, namely blood rheological models and inlet velocity boundary condition, exert additive effects on variables that characterize vascular flows, with negligible interaction effects. Regarding thrombus-prone conditions, the Plug inlet profile offers an advantageous hemodynamic configuration with respect to the other two profiles.
Radiographic, Biomechanical and Histological Characterization of Femoral Fracture Healing in Aged CD-1 Mice
Authors: Menger Maximilian M. , Manuschewski Ruben , Ehnert Sabrina , Rollmann Mika F. , Maisenbacher Tanja C. , Tobias Anne L. , Menger Michael D. , Laschke Matthias W. , Histing Tina
Published: February 2023

With a gradually increasing elderly population, the treatment of geriatric patients represents a major challenge for trauma and reconstructive surgery. Although, it is well established that aging affects bone metabolism, it is still controversial if aging impairs bone healing. Accordingly, we investigated fracture healing in young adult (3–4 months) and aged (16–18 months) CD-1 mice using a stable closed femoral fracture model. Bone healing was analyzed by radiographic, biomechanical and histological analysis at 1, 2, 3, 4 and 5 weeks after fracture. Our results demonstrated an increased callus diameter to femoral diameter ratio in aged animals at later time points of fracture healing when compared to young adult mice. Moreover, our biomechanical analysis revealed a significantly decreased bending stiffness at 3 and 4 weeks after fracture in aged animals. In contrast, at 5 weeks after fracture, the analysis showed no significant difference in bending stiffness between the two study groups. Additional histological analysis showed a delayed endochondral ossification in aged animals as well as a higher amounts of fibrous tissue at early healing time points. These findings indicate a delayed process of callus remodeling in aged CD-1 mice, resulting in a delayed fracture healing when compared to young adult animals. However, the overall healing capacity of the fractured femora was not affected by aging.
Using GPT-3 to Build a Lexicon of Drugs of Abuse Synonyms for Social Media Pharmacovigilance
Authors: Carpenter Kristy A. , Altman Russ B.
Published: February 2023

Drug abuse is a serious problem in the United States, with over 90,000 drug overdose deaths nationally in 2020. A key step in combating drug abuse is detecting, monitoring, and characterizing its trends over time and location, also known as pharmacovigilance. While federal reporting systems accomplish this to a degree, they often have high latency and incomplete coverage. Social-media-based pharmacovigilance has zero latency, is easily accessible and unfiltered, and benefits from drug users being willing to share their experiences online pseudo-anonymously. However, unlike highly structured official data sources, social media text is rife with misspellings and slang, making automated analysis difficult. Generative Pretrained Transformer 3 (GPT-3) is a large autoregressive language model specialized for few-shot learning that was trained on text from the entire internet. We demonstrate that GPT-3 can be used to generate slang and common misspellings of terms for drugs of abuse. We repeatedly queried GPT-3 for synonyms of drugs of abuse and filtered the generated terms using automated Google searches and cross-references to known drug names. When generated terms for alprazolam were manually labeled, we found that our method produced 269 synonyms for alprazolam, 221 of which were new discoveries not included in an existing drug lexicon for social media. We repeated this process for 98 drugs of abuse, of which 22 are widely-discussed drugs of abuse, building a lexicon of colloquial drug synonyms that can be used for pharmacovigilance on social media.
Promiscuity, a Driver of Plant Cytochrome P450 Evolution?
Authors: Werck-Reichhart Danièle
Published: February 2023

Plant cytochrome P450 monooxygenases were long considered to be highly substrate-specific, regioselective and stereoselective enzymes, in this respect differing from their animal counterparts. The functional data that have recently accumulated clearly counter this initial dogma. Highly promiscuous P450 enzymes have now been reported, mainly in terpenoid pathways with functions in plant adaptation, but also some very versatile xenobiotic/herbicide metabolizers. An overlap and predictable interference between endogenous and herbicide metabolism are starting to emerge. Both substrate preference and permissiveness vary between plant P450 families, with high promiscuity seemingly favoring retention of gene duplicates and evolutionary blooms. Yet significant promiscuity can also be observed in the families under high negative selection and with essential functions, usually enhanced after gene duplication. The strategies so far implemented, to systematically explore P450 catalytic capacity, are described and discussed.
Selective Effects of Cold Atmospheric Plasma on Bone Sarcoma Cells and Human Osteoblasts
Authors: Nitsch Andreas , Sieb Konrad F. , Qarqash Sara , Schoon Janosch , Ekkernkamp Axel , Wassilew Georgi I. , Niethard Maya , Haralambiev Lyubomir
Published: February 2023

Background: The use of cold atmospheric plasma (CAP) in oncology has been intensively investigated over the past 15 years as it inhibits the growth of many tumor cells. It is known that reactive oxidative species (ROS) produced in CAP are responsible for this effect. However, to translate the use of CAP into medical practice, it is essential to know how CAP treatment affects non-malignant cells. Thus, the current in vitro study deals with the effect of CAP on human bone cancer cells and human osteoblasts. Here, identical CAP treatment regimens were applied to the malignant and non-malignant bone cells and their impact was compared. Methods: Two different human bone cancer cell types, U2-OS (osteosarcoma) and A673 (Ewing’s sarcoma), and non-malignant primary osteoblasts (HOB) were used. The CAP treatment was performed with the clinically approved kINPen MED. After CAP treatment, growth kinetics and a viability assay were performed. For detecting apoptosis, a caspase-3/7 assay and a TUNEL assay were used. Accumulated ROS was measured in cell culture medium and intracellular. To investigate the influence of CAP on cell motility, a scratch assay was carried out. Results: The CAP treatment showed strong inhibition of cell growth and viability in bone cancer cells. Apoptotic processes were enhanced in the malignant cells. Osteoblasts showed a higher potential for ROS resistance in comparison to malignant cells. There was no difference in cell motility between benign and malignant cells following CAP treatment. Conclusions: Osteoblasts show better tolerance to CAP treatment, indicated by less affected viability compared to CAP-treated bone cancer cells. This points toward the selective effect of CAP on sarcoma cells and represents a further step toward the clinical application of CAP.
Assessing the Effects of a Perioperative Nutritional Support and Counseling in Gastrointestinal Cancer Patients: A Retrospective Comparative Study with Historical Controls
Authors: Klassen Diana , Strauch Carmen , Alteheld Birgit , Lingohr Philipp , Matthaei Hanno , Vilz Tim , Gonzalez-Carmona Maria A. , Hausen Annekristin , Gräßler Marie , Sharma Amit , Strassburg Christian , Kalff Jörg C. , Schmidt-Wolf Ingo G. H.
Published: February 2023

The aim of this study was to investigate the effects of perioperative nutritional therapy care in gastrointestinal (esophageal, gastric, gastroesophageal) cancer patients on nutritional status and disease progression (complications, hospitalization, mortality). We considered 62 gastrointestinal cancer patients treated at the Center for Integrated Oncology (CIO), University Hospital Bonn, Germany (August 2017–July 2019). Of these, 42 patients (as intervention group: IG) received pre- and postoperative nutritional support with counseling, while 20 patients (as historical control group CG) received only postoperative nutritional therapy. Several clinical parameters, such as Body Mass Index (BMI), nutritional risk screening (NRS), phase angle, postoperative complications, length of hospital stay, and mortality, were determined. There were significantly fewer patients with gastric cancer/CDH1 gene mutation and more with esophageal cancer in IG (p = 0.001). Significantly more patients received neoadjuvant therapy in IG (p = 0.036). No significant differences were found between the groups regarding BMI, NRS, complications, length of hospital stay, and mortality. However, the comparison of post- and preoperative parameters in IG showed a tendency to lose 1.74 kg of weight (p = 0.046), a decrease in phase angle by 0.59° (p = 0.004), and an increase in NRS of 1.34 points (p < 0.001). Contrary to prior reports, we found no significant effect of perioperative nutritional therapy care in gastrointestinal cancer patients; however, the small cohort size and infrequent standardization in nutritional status may possibly account for the variance. Considering that oncological pathways and metabolic nutritional pathways are interrelated, dividing patients into subgroups to provide a personalized nutritional approach may help in improving their treatment.
Contribution of Fetal Inflammatory Response Syndrome (FIRS) with or without Maternal-Fetal Inflammation in The Placenta to Increased Risk of Respiratory and Other Complications in Preterm Neonates
Authors: Nomiyama Makoto , Nakagawa Takuya , Yamasaki Fumio , Hisamoto Nami , Yamashita Natsumi , Harai Ayane , Gondo Kanako , Ikeda Masazumi , Tsuda Satoko , Ishimatsu Masato , Oshima Yuko , Ono Takeshi , Kozuma Yutaka , Tsumura Keisuke
Published: February 2023

This study classifies fetal inflammatory response syndrome (FIRS) based on the presence or absence of maternal-fetal inflammation in the placenta and clarifies the association of FIRS with neonatal morbidities. Women (330) who delivered at gestational ages of 22w0d-33w6d were enrolled and grouped into four based on FIRS and maternal/fetal inflammatory response (MIR/FIR) statuses: Group A: without FIRS and MIR/FIR (reference group); Group B: MIR/FIR alone; Group C: FIRS and MIR/FIR; and Group D: FIRS without MIR/FIR. The associations between bronchopulmonary dysplasia (BPD), adverse neonatal outcomes, extremely low gestational age and Groups B, C, and D were investigated after adjustment for potential confounders. Among patients with FIRS, 29% were in Group D. The risk of BPD was increased in Groups C (adjusted odds ratio (aOR): 3.36; 95% confidence interval (CI): 1.14–9.89) and D (aOR: 4.17; 95% CI: 1.03–16.9), as was the risk of adverse neonatal outcomes (Group C: aOR: 7.17; 95% CI: 2.56–20.1; Group D: aOR: 6.84; 95% CI: 1.85–25.2). The risk of extremely low gestational age was increased in Group D (aOR: 3.85; 95% CI: 1.56–9.52). Therefore, FIRS without MIR/FIR is not rare and may be associated with neonatal morbidities more than FIRS and MIR/FIR.
Oral Administration of Vitamin D3 Prevents Corneal Damage in a Knock-Out Mouse Model of Sjögren’s Syndrome
Authors: Trotta Maria Consiglia , Herman Hildegard , Balta Cornel , Rosu Marcel , Ciceu Alina , Mladin Bianca , Gesualdo Carlo , Lepre Caterina Claudia , Russo Marina , Petrillo Francesco , Pieretti Gorizio , Simonelli Francesca , Rossi Settimio , D’Amico Michele , Hermenean Anca
Published: February 2023

Background: Vitamin D deficiency has been associated with dry eye development during Sjögren’s syndrome (SS). Here, we investigated whether repeated oral vitamin D3 supplementation could prevent the corneal epithelium damage in an SS mouse model. Methods: 30 female mouse knock-out for the thrombospondin 1 gene were randomized (six per group) in untreated mice euthanized at 6 weeks as negative control (C−) or at 12 weeks as the positive control for dry eye (C+). Other mice were sacrificed after 6 weeks of oral vitamin D3 supplementation in the drinking water (1000, 8000, and 20,000 IU/kg/week, respectively). Results: The C+ mice showed alterations in their corneal epithelial morphologies and thicknesses (p < 0.01 vs. C−), while the mice receiving 8000 (M) and 20,000 (H) IU/kg/week of vitamin D3 showed preservation of the corneal epithelium morphology and thickness (p < 0.01 vs. C+). Moreover, while the C+ mice exhibited high levels and activity of corneal tumor necrosis factor alpha converting enzyme (TACE), neovascularization and fibrosis markers; these were all reduced in the M and H mice. Conclusions: Oral vitamin D3 supplementation appeared to counteract the negative effect of TACE on corneal epithelium in a mouse model of SS-associated dry eye.
HIV Latency and Nanomedicine Strategies for Anti-HIV Treatment and Eradication
Authors: Andre Mickensone , Nair Madhavan , Raymond Andrea D.
Published: February 2023

Antiretrovirals (ARVs) reduce Human Immunodeficiency Virus (HIV) loads to undetectable levels in infected patients. However, HIV can persist throughout the body in cellular reservoirs partly due to the inability of some ARVs to cross anatomical barriers and the capacity of HIV-1 to establish latent infection in resting CD4+ T cells and monocytes/macrophages. A cure for HIV is not likely unless latency is addressed and delivery of ARVs to cellular reservoir sites is improved. Nanomedicine has been used in ARV formulations to improve delivery and efficacy. More specifically, researchers are exploring the benefit of using nanoparticles to improve ARVs and nanomedicine in HIV eradication strategies such as shock and kill, block and lock, and others. This review will focus on mechanisms of HIV-1 latency and nanomedicine-based approaches to treat HIV.
The Role of Autophagy in Breast Cancer Metastasis
Authors: Kim Hye Min , Koo Ja Seung
Published: February 2023

Patient morbidity and mortality is significantly increased in metastatic breast cancer. The metastasis process of breast cancer is very complicated and is delicately controlled by various factors. Autophagy is one of the important regulatory factors affecting metastasis in breast cancer by engaging in cell mobility, metabolic adaptation, tumor dormancy, and cancer stem cells. Here, we discuss the effects of autophagy on metastasis in breast cancer and assess the potential use of autophagy modulators for metastasis treatment.
Gut-on-a-Chip Models: Current and Future Perspectives for Host–Microbial Interactions Research
Authors: Morelli Moran , Kurek Dorota , Ng Chee Ping , Queiroz Karla
Published: February 2023

The intestine contains the largest microbial community in the human body, the gut microbiome. Increasing evidence suggests that it plays a crucial role in maintaining overall health. However, while many studies have found a correlation between certain diseases and changes in the microbiome, the impact of different microbial compositions on the gut and the mechanisms by which they contribute to disease are not well understood. Traditional pre-clinical models, such as cell culture or animal models, are limited in their ability to mimic the complexity of human physiology. New mechanistic models, such as organ-on-a-chip, are being developed to address this issue. These models provide a more accurate representation of human physiology and could help bridge the gap between clinical and pre-clinical studies. Gut-on-chip models allow researchers to better understand the underlying mechanisms of disease and the effect of different microbial compositions on the gut. They can help to move the field from correlation to causation and accelerate the development of new treatments for diseases associated with changes in the gut microbiome. This review will discuss current and future perspectives of gut-on-chip models to study host-microbial interactions.
The Associations between Polysomnographic Parameters and Memory Impairment among Patients with Obstructive Sleep Apnea: A 10-Year Hospital-Based Longitudinal Study
Authors: Chien Wei-Chen , Lin Chung-Wei , Liu Ching-Kuan , Chen Shiou-Lan , Chou Mei-Chuan , Hsu Chung-Yao
Published: February 2023

Obstructive sleep apnea (OSA) has been associated with cognitive decline via several mechanisms, including intermittent hypoxemia, sleep fragmentation, and neuroinflammation. The neurological consequences of OSA have evolved into a major biopsychosocial concern in the elderly, especially memory impairment. We aimed to identify the polysomnographic (PSG) parameters capable of predicting memory impairment among OSA patients at or over age 50 with OSA. We reviewed the 10-year electronic medical records of OSA patients and compared the initial PSG parameters between those presenting and not presenting self-reported memory impairment. We conducted subgroup analyses based on OSA severity and performed multivariate analysis to correlate PSG parameters with memory impairment. The result showed that 25 out of the 156 (16%) investigated patients experienced self-reported memory impairment during follow-up. As compared to OSA patients without self-reported memory impairment, those reported with self-reported memory impairment had a higher oxygen desaturation index (ODI) (23.9 ± 17.8 versus 18.2 ± 12.0, p = 0.048). Regarding the associations between apnea-hypopnea index (AHI) as well as ODI and self-reported memory impairment among OSA subgroups classified by severity, the associations were only evident in the severe OSA subgroup in both univariate (p < 0.001; p = 0.005) and multivariate analyses (p = 0.014; p = 0.018). We concluded that AHI and ODI are the most relevant PSG parameters in predicting memory impairment in severe OSA patients.
Smooth Muscle Cells of Dystrophic (mdx) Mice Are More Susceptible to Hypoxia; The Protective Effect of Reducing Ca2+ Influx
Authors: Uryash Arkady , Mijares Alfredo , Estève Eric , Adams Jose A. , Lopez Jose R.
Published: February 2023

Duchenne muscular dystrophy (DMD) is an inherited muscular disorder caused by mutations in the dystrophin gene. DMD patients have hypoxemic events due to sleep-disordered breathing. We reported an anomalous regulation of resting intracellular Ca2+ ([Ca2+]i) in vascular smooth muscle cells (VSMCs) from a mouse (mdx) model of DMD. We investigated the effect of hypoxia on [Ca2+]i in isolated and quiescent VSMCs from C57BL/10SnJ (WT) and C57BL/10ScSn-Dmd (mdx) male mice. [Ca2+]i was measured using Ca2+-selective microelectrodes under normoxic conditions (95% air, 5% CO2) and after hypoxia (glucose-free solution aerated with 95% N2-5% CO2 for 30 min). [Ca2+]i in mdx VSMCs was significantly elevated compared to WT under normoxia. Hypoxia-induced [Ca2+]i overload, which was significantly greater in mdx than in WT VSMCs. A low Ca2+ solution caused a reduction in [Ca2+]i and prevented [Ca2+]i overload secondary to hypoxia. Nifedipine (10 µM), a Ca2+ channel blocker, did not modify resting [Ca2+]i in VSMCs but partially prevented the hypoxia-induced elevation of [Ca2+]i in both genotypes. SAR7334 (1 µM), an antagonist of TRPC3 and TRPC6, reduced the basal and [Ca2+]i overload caused by hypoxia. Cell viability, assessed by tetrazolium salt (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, was significantly reduced in mdx compared to WT VSMCs. Pretreatment with SAR7341 increases cell viability in normoxic mdx (p < 0.001) and during hypoxia in WT and mdx VSMCs. These results provide evidence that the lack of dystrophin makes VSMCs more susceptible to hypoxia-induced [Ca2+]i overload, which appears to be mediated by increased Ca2+ entry through L-type Ca2+ and TRPC channels.
Recent Prospective in CAR T-Based Therapy for Solid and Hematological Malignancies
Authors: Marei Hany E. , Cenciarelli Carlo
Published: February 2023

Given that CAR-T cell therapy is effective in CD19-positive blood malignancies, it offers great hope for a variety of aggressive tumors that have thus far shown very little response to available therapies [...]
Simultaneous Quantification of Ivacaftor, Tezacaftor, and Elexacaftor in Cystic Fibrosis Patients’ Plasma by a Novel LC–MS/MS Method
Authors: Pigliasco Federica , Cafaro Alessia , Stella Manuela , Baiardi Giammarco , Barco Sebastiano , Pedemonte Nicoletta , D’Orsi Claudia , Cresta Federico , Casciaro Rosaria , Castellani Carlo , Calevo Maria Grazia , Mattioli Francesca , Cangemi Giuliana
Published: February 2023

The new breakthrough cystic fibrosis (CF) drug combination of ivacaftor (IVA), tezacaftor (TEZ), and elexacaftor (ELX), namely “caftor” drugs, directly modulates the activity and trafficking of the defective CF transmembrane conductance regulator protein (CFTR) underlying the CF disease. The role of therapeutic drug monitoring (TDM) of caftor drugs in clinical settings has recently been established. The availability of reliable and robust analytical methods for the quantification of IVA, TEZ, and ELX is essential to support dose–concentration–effect studies. We have developed and validated a new liquid chromatography–tandem mass spectrometry (LC–MS/MS) for the rapid and simultaneous quantification of IVA, TEZ, and ELX from the plasma of CF patients. The method was based on a rapid extraction protocol from 50 μL human plasma and separation on a reversed-phase C-18 HPLC column after the addition of deuterated internal standards. Accurate analyte quantification using multiple reaction monitoring (MRM) detection was then obtained using a Thermofisher Quantiva triple-quadrupole MS coupled to an Ultimate 3000 UHPLC. The method has been validated following international (EMA) guidelines for bioanalytical method validation and has been tested on plasma samples from 62 CF patients treated with the three-drug combination IVA/TEZ/ELX, marketed as Kaftrio® or Trikafta®, in steady-state condition. The assay was linear over wide concentration ranges (0.008–12 mg/L) in plasma for IVA, TEZ, and ELX, suitable for a broad range of plasma concentrations, and accurate and reproducible in the absence of matrix effects. The stability of analytes for at least 30 days at room temperature could allow for cost-effective shipment and storage. On the same day of sample collection, a sweat test was evaluated for 26 associated patients’ samples, FEV1 (%) for 58, and BMI was calculated for 62. However, Spearman correlation showed no correlation between Cthrough plasma concentrations of analytes (IVA, TEZ, ELX) and sweat test, FEV1 (%), or BMI. Our method proved to be suitable for TDM and could be helpful in assessing dose–concentration–response correlations in larger studies.