bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic Comparison of ORC and s-CO2 Combined Heat and Power Plants for Energy Harvesting in Industrial Gas Turbines
Authors: Ancona Maria Alessandra , Bianchi Michele , Branchini Lisa , De Pascale Andrea , Melino Francesco , Peretto Antonio , Torricelli Noemi
Published: June 2021

Gas turbine power plants are widely employed with constrained efficiency in the industrial field, where they often work under variable load conditions caused by variations in demand, leading to fluctuating exhaust gas temperatures. Suitable energy harvesting solutions can be identified in bottoming cycles, such as the conventional Organic Rankine Cycles (ORC) or the innovative supercritical CO2 (s-CO2) systems. This paper presents a detailed comparison of the potential of ORC and s-CO2 as bottomers of industrial gas turbines in a Combined Heat and Power (CHP) configuration. Different gas turbine models, covering the typical industrial size range, are taken into account and both full- and part-load operations are considered. Performance, component dimensions, and operating costs are investigated, considering ORC and s-CO2 systems specifics in line with the current state-of-the-art products, experience, and technological limits. Results of the study show that the s-CO2 could be more appropriate for CHP applications. Both the electric and thermal efficiency of s-CO2 bottoming cycle show higher values compared with ORC, also due to the fact that in the examined s-CO2 solution, the cycle pressure ratio is not affected by the thermal user temperature. At part-load operation, the gas turbine regulation strategy affects the energy harvesting performance in a CHP arrangement. The estimated total plant investment cost results to be higher for the s-CO2, caused by the higher size of the heat recovery heat exchanger but also by the high specific investment cost still associated to this component. This point seems to make the s-CO2 not profitable as the ORC solution for industrial gas turbine heat recovery applications. Nevertheless, a crucial parameter determining the feasibility of the investment is the prospective carbon tax application.
Evaluation of Stress and Fatigue of a Rail Vehicle Suspension Component
Authors: Opala Michał , Korzeb Jarosław , Koziak Seweryn , Melnik Rafał
Published: June 2021

The article discusses the use of pivot bearing friction liners, made of selected materials, in railway freight wagons’ spherical centre bowls. Comparative studies on the effect of suspension dynamics on the equivalent stresses in the liner material were carried out using the finite element method and multibody simulation. The results show the magnitude and location of the highest stresses in the liner with varying input loads, friction coefficients and interacting materials. The analysis is a basis for a simulation method for predicting the fatigue life of the suspension friction liner placed in the centre bowl between the bogie frame and the vehicle body.
Revisiting the Environmental Kuznets Curve Hypothesis: A Case of Central Europe
Authors: Jóźwik Bartosz , Gavryshkiv Antonina-Victoria , Kyophilavong Phouphet , Gruszecki Lech Euzebiusz
Published: June 2021

The rapid economic growth observed in Central European countries in the last thirty years has been the result of profound political changes and economic liberalization. This growth is partly connected with reducing carbon dioxide (CO2) emissions. However, the problem of CO2 emissions seems to remain unresolved. The aim of this paper is to test whether the Environmental Kuznets Curve (EKC) hypothesis holds true for Central European countries in an annual sample data that covers 1995–2016 in most countries. We examine cointegration by applying the Autoregressive Distributed Lag bound testing. This is the first study examining the relationship between CO2 emissions and economic growth in individual Central European countries from a long-run perspective, which allows the results to be compared. We confirmed the cointegration, but our estimates confirmed the EKC hypothesis only in Poland. It should also be noted that in all nine countries, energy consumption leads to increased CO2 emissions. The long-run elasticity ranges between 1.5 in Bulgaria and 2.0 in Croatia. We observed exceptionally low long-run elasticity in Estonia (0.49). Our findings suggest that to solve the environmental degradation problem in Central Europe, it is necessary to individualize the policies implemented in the European Union.
Metagenomic Analysis of Bacterial and Fungal Communities Inhabiting Shiro Dominant Soils of Two Production Regions of Tricholoma Matsutake S. Ito & S. Imai in Korea
Authors: An Gi-Hong , Cho Jae-Han , Kim Ok-Tae , Han Jae-Gu
Published: June 2021

Tricholoma matsutake is an ectomycorrhizal fungus that has obligate symbiotic relationships with Pinus densiflora. Its fruiting body has a distinctive flavor and is traded at a high price. Thus, it has been a significant source of income for rural communities in Korea. We hypothesized that biotic factors considerably influence the formation of the T. matsutake mushroom, and the soils producing T. matsutake share similar microbial characteristics. Therefore, the present study aimed to detect the specific fungal and bacterial groups in T. matsutake production soils (shiro+) and nonproduction soils (shiro−) of the Bonghwa and Yanyang regions via next-generation sequencing. In a total of 15 phyla, 36 classes, 234 genera of bacteria, six phyla, 29 classes, and 164 genera of fungi were detected from four samples at both sites. The species diversity of shiro+ soils was lower than the shiro− samples in both the fungal and bacterial groups. In addition, we did not find high similarities in the microbial communities between the shiro+ soils of the two regions. However, in the resulting differences between the fungal communities categorized by their trophic assembly, we found a distinguishable compositional pattern in the fungal communities from the shiro+ soils and the shiro− soils of the two sites. Thus, the similarity among the microbial communities in the forest soils may be due to the fact that the microbial communities in the T. matsutake dominant soils are closely associated with biotic factors and abiotic factors such as soil properties.
Different Physiological and Biochemical Responses of Bamboo to the Addition of TiO2 NPs under Heavy Metal Toxicity
Authors: Emamverdian Abolghassem , Ding Yulong , Mokhberdoran Farzad , Ramakrishnan Muthusamy , Ahmad Zishan , Xie Yinfeng
Published: June 2021

Bamboo forests cover a remarkable area of Chinese forestland. Recently, titanium dioxide nanoparticles (TiO2 NPs) have been used for plant protection against abiotic stress. In this study, an in vitro tissue culture experiment was conducted to determine the impact of titanium on plant tolerance to two different heavy metals (Cu and Pb). Bamboo plants (Arundinaria pygmaea L.) were grown using five concentrations of TiO2 NPS (0, 50, 80, 100, and 150 µM) without or with 100 µM Cu and 100 µM Pb for 30 days. The results showed that while Cu and Pb increased the generation of Reactive oxygen species (ROS) compounds in plants, TiO2 NP treatments played a positive role in reducing oxidative stress, as indicated by the decrease in ROS compounds, the extent of lipoperoxidation, and soluble proteins. On the other hand, the use of TiO2 NPs increased the total antioxidant capacity, chlorophyll content and general plant biomass. Moreover, the addition of TiO2 NPs significantly reduced Cu, and Pb accumulation in roots, stems, and shoots. We concluded that TiO2 NPs have the ability to reduce oxidative stress in plants by increasing the antioxidant capacity, improving the level of injury, and protecting cell membranes via reducing lipoperoxidation (reduction of Malondialdehyde (MDA) content). However, the results indicated that the efficiency of TiO2 NPs was related to the type and concentration of heavy metal, as TiO2 NPs were more effective for Cu than Pb. Additionally, a high concentration of TiO2 NPs resulted in the greatest enhancement in plant growth and development under heavy metal stress.
Flow Past Mound-Bearing Impact Craters: An Experimental Study
Authors: Gundersen Diego , Blois Gianluca , Christensen Kenneth T.
Published: June 2021

An experimental investigation into the flow produced by mound-bearing impact craters is reported herein. Both an idealized crater and a scaled model of a real martian crater are examined. Measurements were performed using high-resolution planar particle image velocimetry (PIV) in a refractive-index matching (RIM) flow environment. Rendering the crater models optically invisible with this RIM approach provided unimpeded access to the flow around and within each crater model. Results showed that the mean flow within the idealized crater exhibits more structural complexity compared to its moundless counterpart. Second-order statistics highlighted regions of minimal and elevated turbulent stresses, the latter of which revealed a complex interaction between shear layers that are present at the upstream and downstream parts of the rim and the central mound. Periodic vortex shedding of quasi-spanwise vortices from the upstream rim was revealed by POD-filtered instantaneous flow fields. Vertical flapping of this shear layer resulted in vortices occasionally impinging on the inner wall of the downstream rim. Further, conditional averaging analysis suggested periodic lateral oscillations of wall-normal vortices within the crater rim region reminiscent of those observed for flow inside spherical dimples. These results have implications for intra- to extra-crater mass and momentum exchange, and for sediment transport processes. Lastly, experiments with the Gale Crater model showed both similarities with and differences from the primary flow features found for the idealized model.
Improvement of Foaming Characteristics and Stability of Sterilized Liquid Egg with Egg White Hydrolysate (EWH)
Authors: Ho Hen-Yo , Ciou Jhih-Ying , Qiu Yi-Ting , Hsieh Shu-Ling , Shih Ming-Kuei , Chen Min-Hung , Tu Chao-Wen , Hsieh Chang-Wei , Hou Chih-Yao
Published: June 2021

A pasteurized liquid egg leads to protein denaturation and degradation of processing properties, whereas non-pasteurized eggs may have food safety risks. If the negative impact of the pasteurization process on liquid eggs can be reduced, for example, the loss of stability and foamability, companies will be willing to purchase pasteurized eggs, thereby reducing food safety risks. Therefore, in this study, specific hydrolyzation conditions were used to produce egg white hydrolysate (EWH) with a lower molecular mass of amino acid and peptide fragments, and the effects of various concentration of EWH refilling on pasteurized liquid egg properties were investigated. The results showed that up to 30.1% of EWH was hydrolyzed by protease A and papain. Adding 1% (w/w) EWH can improve the negative charge potential value, surface tension, viscosity, and weight loss analysis of the sample. In addition, the cake structure and the appearance was acceptable to consumers. Therefore, to ensure its efficient use in the baking industry and considering the cost and stability, 1% (w/w) EWH was chosen as the best concentration.
Coffee Brews: Are They a Source of Macroelements in Human Nutrition?
Authors: Olechno Ewa , Puścion-Jakubik Anna , Socha Katarzyna , Zujko Małgorzata Elżbieta
Published: June 2021

Coffee brews, made by pouring water on coffee grounds or brewing in an espresso machine, are among the most popular beverages. The aim of this study was to summarize data on the content of macroelements (sodium, potassium, calcium, magnesium, and phosphorus) in coffee brews prepared with different methods, as well as to review the factors influencing the content of the elements. Studies from 2000 to 2020, published in the PubMed and Google Scholar databases, were reviewed. Taking into account the results presented by the authors, we calculated that one portion of coffee brew can cover 7.5% or 6.4% (for women and men) and 6.6% of the daily requirement for magnesium and potassium, respectively. Coffee provides slightly lower amounts of phosphorus (up to 2.2%), sodium (up to 2.2%), and calcium (up to 0.7% of the daily requirement for women and 0.6% for men). If coffee is drunk in the quantity of three to four cups, it can be an important source of magnesium, considering the risk of magnesium deficiency in modern societies.
Typical Fluorescent Sensors Exploiting Molecularly Imprinted Hydrogels for Environmentally and Medicinally Important Analytes Detection
Authors: Zou Lihua , Ding Rong , Li Xiaolei , Miao Haohan , Xu Jingjing , Pan Guoqing
Published: June 2021

In this work, two typical fluorescent sensors were generated by exploiting molecularly imprinted polymeric hydrogels (MIPGs) for zearalenone (ZON) and glucuronic acid (GA) detection, via the analyte’s self-fluorescence property and receptor’s fluorescence effect, respectively. Though significant advances have been achieved on MIPG-fluorescent sensors endowed with superior stability over natural receptor-sensors, there is an increasing demand for developing sensing devices with cost-effective, easy-to-use, portable advantages in terms of commercialization. Zooming in on the commercial potential of MIPG-fluorescent sensors, the MIPG_ZON is synthesized using zearalanone (an analogue of ZON) as template, which exhibits good detection performance even in corn samples with a limit of detection of 1.6 μM. In parallel, fluorescein-incorporated MIPG_GA is obtained and directly used for cancer cell imaging, with significant specificity and selectivity. Last but not least, our consolidated application results unfold new opportunities for MIPG-fluorescent sensors for environmentally and medicinally important analytes detection.
PPARG Hypermethylation as the First Epigenetic Modification in Newly Onset Insulin Resistance in Human Adipocytes
Authors: Małodobra-Mazur Małgorzata , Cierzniak Aneta , Kaliszewski Krzysztof , Dobosz Tadeusz
Published: June 2021

Insulin acts by binding with a specific receptor called an insulin receptor (INSR), ending up with glucose transporter activation and glucose uptake. Insulin resistance (IR) is a state when the physiological amount of insulin is not sufficient to evoke proper action, i.e., glucose uptake. Epigenetic modifications associated with obesity and IR are some of the main mechanisms leading to IR pathogenesis. The mesenchymal stem cells of adipose tissue (subcutaneous (SAT) and visceral (VAT)) were collected during abdominal surgery. IR was induced ex vivo by palmitic acid. DNA methylation was determined at a global and site-specific level. We found higher global DNA methylation in IR adipocytes after 72 h following IR induction. Furthermore, numerous genes regulating insulin action (PPARG, SLC2A4, ADIPOQ) were hypermethylated in IR adipocytes; the earliest changes in site-specific DNA methylation have been detected for PPARG. Epigenetic changes appear to be mediated through DNMT1. DNA methylation is an important component of IR pathogenesis; the PPARG and its epigenetic modification appear to be the very first epigenetic modification in newly onset IR and are probably of the greatest importance.
Health-Related Quality of Life and Mental Health after Surgical Treatment of Hepatocellular Carcinoma in the Era of Minimal-Invasive Surgery: Resection versus Transplantation
Authors: Feldbrügge Linda , Langenscheidt Alexander , Krenzien Felix , Schulz Mareike , Krezdorn Nicco , Kamali Kaan , Hinz Andreas , Bartels Michael , Fikatas Panagiotis , Schmelzle Moritz , Pratschke Johann , Benzing Christian
Published: June 2021

Laparoscopic liver resection (LLR) is an increasingly relevant treatment option for patients with resectable hepatocellular carcinoma (HCC). Orthotopic liver transplantation (OLT) has been considered optimal treatment for HCC in cirrhosis, but is challenged by rising organ scarcity. While health-related quality of life (HRQoL) and mental health are well-documented after OLT, little is known about HRQoL in HCC patients after LLR. We identified all HCC patients who underwent LLR at our hospital between 2014 and 2018. HRQoL and mental health were assessed using the Short Form 36 and the Hospital Anxiety and Depression Scale, respectively. Outcomes were compared to a historic cohort of HCC patients after OLT. Ninety-eight patients received LLR for HCC. Postoperative morbidity was 25% with 17% minor complications. LLR patients showed similar overall HRQoL and mental health to OLT recipients, except for lower General Health (p = 0.029) and higher anxiety scores (p = 0.010). We conclude that LLR can be safely performed in patients with HCC, with or without liver cirrhosis. The postoperative HRQoL and mental health are comparable to that of OLT recipients in most aspects. LLR should thus always be considered an alternative to OLT, especially in times of organ shortage.
Propensity Score Analysis Assessing the Burden of Non-Communicable Diseases among the Transgender Population in the United States Using the Behavioral Risk Factor Surveillance System (2017–2019)
Authors: Pharr Jennifer R. , Batra Kavita
Published: June 2021

Research to assess the burden of non-communicable diseases (NCDs) among the transgender population needs to be prioritized given the high prevalence of chronic conditions and associated risk factors in this group. Previous cross-sectional studies utilized unmatched samples with a significant covariate imbalance resulting in a selection bias. Therefore, this cross-sectional study attempts to assess and compare the burden of NCDs among propensity score-matched transgender and cisgender population groups. This study analyzed Behavioral Risk Factor Surveillance System data (2017–2019) using complex weighting procedures to generate nationally representative samples. Logistic regression was fit to estimate propensity scores. Transgender and cisgender groups were matched by sociodemographic variables using a 1:1 nearest neighbor matching algorithm. McNemar, univariate, and multivariate logistic regression analyses were conducted among matched cohorts using R and SPSS version 26 software. Compared with the cisgender group, the transgender group was significantly more likely to have hypertension (31.3% vs. 27.6%), hypercholesteremia (30.8% vs. 23.7%), prediabetes (17.3% vs. 10.3%), and were heavy drinkers (6.7% vs. 6.0%) and smokers (22.4% vs. 20.0%). Moreover, the transgender group was more than twice as likely to have depression (aOR: 2.70, 95% CI 2.62–2.72), stroke (aOR: 2.52 95% CI 2.50–2.55), coronary heart disease (aOR: 2.77, 95% CI 2.74–2.81), and heart attack (aOR: 2.90, 95% CI 2.87–2.94). Additionally, the transgender group was 1.2–1.7 times more likely to have metabolic and malignant disorders. Differences were also found between transgender subgroups compared with the cisgender group. This study provides a clear picture of the NCD burden among the transgender population. These findings offer an evidence base to build health equity models to reduce disparities among transgender groups.
Pediatricians’ Compliance to the Clinical Management Guidelines for Community-Acquired Pneumonia in Infants and Young Children in Pakistan
Authors: Shakeel Sadia , Iffat Wajiha , Qamar Ambreen , Ghuman Faiza , Yamin Rabia , Ahmad Nausheen , Ishaq Saqib Muhammad , Gajdács Márió , Patel Isha , Jamshed Shazia
Published: June 2021

Community-acquired pneumonia (CAP) is among the most commonly prevailing acute infections in children that may require hospitalization. Inconsistencies among suggested care and actual management practices are usually observed, which raises the need to assess local clinical practices. The current study was conducted to evaluate pediatricians’ compliance with the standard clinical practice guidelines and their antibiotic-prescribing behavior for the management of CAP in children. Methods: A descriptive cross-sectional study was conducted using a self-administered questionnaire; which was provided to pediatricians by the researchers. Statistical analysis was performed with SPSS 25 Statistics; χ2 tests (or Fisher-exact tests) with the p-value set at < 0.05 as the threshold for statistical significance. Results: The overall response rate was 59.2%. Male respondents were (n = 101; 42.6%), and the respondents (n = 163; 68.7%) were under 30 years of age. Amoxicillin (n = 122; 51.5%) was considered as the most commonly used first-line treatment for non-severe pneumonia, whereas a smaller proportion (n = 81; 34.2%) of respondents selected amoxicillin–clavulanate. Likewise, amoxicillin (n = 100; 42.2%) was the most popular choice for non-severe pneumonia in hospitalized children; however, if children had used antibiotics earlier to admission, respondents showed an inclination to prescribe a macrolide (n = 95; 40.0%) or second-generation cephalosporin (n = 90; 37.9%). More than 90% responded that children <6 months old with suspected bacterial CAP will probably receive better therapeutic care by hospitalization. Restricting exposure to the antibiotic as much as possible (n = 71; 29.9%), improving antibiotic prescribing (n = 59; 24.8%), and using the appropriate dose of antimicrobials (n = 29; 12.2%) were considered the major factors by the respondents to reduce antimicrobials resistance. Conclusions: The selection of antibiotics and diagnostic approach was as per the recommendations, but indication, duration of treatment, and hospitalization still can be further improved.
Linking DPSIR Model and Water Quality Indices to Achieve Sustainable Development Goals in Groundwater Resources
Authors: Alexakis Dimitrios E.
Published: June 2021

The achievement of sustainable development goals in groundwater resources related to water quality issues is a critical question in many regions. This study aims to combine powerful tools for helping stakeholders and policymakers achieve sustainable development goals in groundwater resources of agricultural areas. The DPSIR (Driver–Pressure–State–Impact–Response) model in combination with the Canadian Council of Ministers of Environment Water Quality Index and Groundwater Directive 2006/118/European Community—Threshold Values was applied using a hydrogeochemical dataset derived from the analysis of groundwater samples collected from 31 monitoring sites in an unconfined alluvial aquifer. Elevated Cl− (up to 423.2 mg L−1), NO3− (up to 180.1 mg L−1) concentration and electrical conductivity (up to 2037 μS cm−1) value are observed for groundwater samples of the study area. The outcome of the “One Out-All Out” procedure revealed that the groundwater in 42% of the monitored sites is unsuitable for drinking according to the health-based guideline values established by Directive 98/83/European Community. A difficulty to achieve targets under Sustainable Development Goals 3 and 6 in the study area is revealed. The proposed response actions are reported.
A New Data-Enabled Intelligence Framework for Evaluating Urban Space Perception
Authors: Ji Haohao , Qing Linbo , Han Longmei , Wang Zhengyong , Cheng Yongqiang , Peng Yonghong
Published: June 2021

The urban environment has a great impact on the wellbeing of citizens and it is of great significance to understand how citizens perceive and evaluate places in a large scale urban region and to provide scientific evidence to support human-centered urban planning with a better urban environment. Existing studies for assessing urban perception have primarily relied on low efficiency methods, which also result in low evaluation accuracy. Furthermore, there lacks a sophisticated understanding on how to correlate the urban perception with the built environment and other socio-economic data, which limits their applications in supporting urban planning. In this study, a new data-enabled intelligence framework for evaluating human perceptions of urban space is proposed. Specifically, a novel classification-then-regression strategy based on a deep convolutional neural network and a random-forest algorithm is proposed. The proposed approach has been applied to evaluate the perceptions of Beijing and Chengdu against six perceptual criteria. Meanwhile, multi-source data were employed to investigate the associations between human perceptions and the indicators for the built environment and socio-economic data including visual elements, facility attributes and socio-economic indicators. Experimental results show that the proposed framework can effectively evaluate urban perceptions. The associations between urban perceptions and the visual elements, facility attributes and a socio-economic dimension have also been identified, which can provide substantial inputs to guide the urban planning for a better urban space.
4-1BBL as a Mediator of Cross-Talk between Innate, Adaptive, and Regulatory Immunity against Cancer
Authors: Martinez-Perez Alejandra G. , Perez-Trujillo Jose J. , Garza-Morales Rodolfo , Loera-Arias Maria J. , Saucedo-Cardenas Odila , Garcia-Garcia Aracely , Rodriguez-Rocha Humberto , Montes-de-Oca-Luna Roberto
Published: June 2021

The ability of tumor cells to evade the immune system is one of the main challenges we confront in the fight against cancer. Multiple strategies have been developed to counteract this situation, including the use of immunostimulant molecules that play a key role in the anti-tumor immune response. Such a response needs to be tumor-specific to cause as little damage as possible to healthy cells and also to track and eliminate disseminated tumor cells. Therefore, the combination of immunostimulant molecules and tumor-associated antigens has been implemented as an anti-tumor therapy strategy to eliminate the main obstacles confronted in conventional therapies. The immunostimulant 4-1BBL belongs to the tumor necrosis factor (TNF) family and it has been widely reported as the most effective member for activating lymphocytes. Hence, we will review the molecular, pre-clinical, and clinical applications in conjunction with tumor-associated antigens in antitumor immunotherapy, as well as the main molecular pathways involved in this association.
Small-Molecule Inhibitors Targeting Proteasome-Associated Deubiquitinases
Authors: Moon Seonghyeon , Muniyappan Srinivasan , Lee Sung-Bae , Lee Byung-Hoon
Published: June 2021

The 26S proteasome is the principal protease for regulated intracellular proteolysis. This multi-subunit complex is also pivotal for clearance of harmful proteins that are produced throughout the lifetime of eukaryotes. Recent structural and kinetic studies have revealed a multitude of conformational states of the proteasome in substrate-free and substrate-engaged forms. These conformational transitions demonstrate that proteasome is a highly dynamic machinery during substrate processing that can be also controlled by a number of proteasome-associated factors. Essentially, three distinct family of deubiquitinases–USP14, RPN11, and UCH37–are associated with the 19S regulatory particle of human proteasome. USP14 and UCH37 are capable of editing ubiquitin conjugates during the process of their dynamic engagement into the proteasome prior to the catalytic commitment. In contrast, RPN11-mediated deubiquitination is directly coupled to substrate degradation by sensing the proteasome’s conformational switch into the commitment steps. Therefore, proteasome-bound deubiquitinases are likely to tailor the degradation events in accordance with substrate processing steps and for dynamic proteolysis outcomes. Recent chemical screening efforts have yielded highly selective small-molecule inhibitors for targeting proteasomal deubiquitinases, such as USP14 and RPN11. USP14 inhibitors, IU1 and its progeny, were found to promote the degradation of a subset of substrates probably by overriding USP14-imposed checkpoint on the proteasome. On the other hand, capzimin, a RPN11 inhibitor, stabilized the proteasome substrates and showed the anti-proliferative effects on cancer cells. It is highly conceivable that these specific inhibitors will aid to dissect the role of each deubiquitinase on the proteasome. Moreover, customized targeting of proteasome-associated deubiquitinases may also provide versatile therapeutic strategies for induced or repressed protein degradation depending on proteolytic demand and cellular context.
Altered Expression of ESR1, ESR2, PELP1 and c-SRC Genes Is Associated with Ovarian Cancer Manifestation
Authors: Englert-Golon Monika , Andrusiewicz Mirosław , Żbikowska Aleksandra , Chmielewska Małgorzata , Sajdak Stefan , Kotwicka Małgorzata
Published: June 2021

Ovarian cancer remains the leading cause of death due to gynecologic malignancy. Estrogen-related pathways genes, such as estrogen receptors (ESR1 and ESR2) and their coregulators, proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), and proto-oncogene tyrosine-protein kinase c-Src (SRC) are involved in ovarian cancer induction and development, still they require in-depth study. In our study, tissue samples were obtained from 52 females of Caucasian descent (control group without cancerous evidence (n = 27), including noncancerous benign changes (n = 15), and the ovarian carcinoma (n = 25)). Using quantitative analyses, we investigated ESRs, PELP1, and SRC mRNA expression association with ovarian tumorigenesis. Proteins’ presence and their location were determined by Western blot and immunohistochemistry. Results showed that PELP1 and SRC expression levels were found to differ in tissues of different sample types. The expression patterns were complex and differed in the case of ovarian cancer patients compared to controls. The most robust protein immunoreactivity was observed for PELP1 and the weakest for ESR1. The expression patterns of analyzed genes represent a potentially interesting target in ovarian cancer biology, especially PELP1. This study suggests that specific estrogen-mediated functions in the ovary and ovary-derived cancer might result from different local interactions of estrogen with their receptors and coregulators.
Towards a New, Endophenotype-Based Strategy for Pathogenicity Prediction in BRCA1 and BRCA2: In Silico Modeling of the Outcome of HDR/SGE Assays for Missense Variants
Authors: Özkan Selen , Padilla Natàlia , de la Cruz Xavier
Published: June 2021

The present limitations in the pathogenicity prediction of BRCA1 and BRCA2 (BRCA1/2) missense variants constitute an important problem with negative consequences for the diagnosis of hereditary breast and ovarian cancer. However, it has been proposed that the use of endophenotype predictions, i.e., computational estimates of the outcomes of functional assays, can be a good option to address this bottleneck. The application of this idea to the BRCA1/2 variants in the CAGI 5-ENIGMA international challenge has shown promising results. Here, we developed this approach, exploring the predictive performances of the regression models applied to the BRCA1/2 variants for which the values of the homology-directed DNA repair and saturation genome editing assays are available. Our results first showed that we can generate endophenotype estimates using a few molecular-level properties. Second, we show that the accuracy of these estimates is enough to obtain pathogenicity predictions comparable to those of many standard tools. Third, endophenotype-based predictions are complementary to, but do not outperform, those of a Random Forest model trained using variant pathogenicity annotations instead of endophenotype values. In summary, our results confirmed the usefulness of the endophenotype approach for the pathogenicity prediction of the BRCA1/2 missense variants, suggesting different options for future improvements.
Mitochondrial Caseinolytic Protease P: A Possible Novel Prognostic Marker and Therapeutic Target in Cancer
Authors: Cormio Antonella , Sanguedolce Francesca , Pesce Vito , Musicco Clara
Published: June 2021

Caseinolytic protease P (ClpP) is a mitochondrial serine protease. In mammalian cells, the heterodimerization of ClpP and its AAA+ ClpX chaperone results in a complex called ClpXP, which has a relevant role in protein homeostasis and in maintaining mitochondrial functionality through the degradation of mitochondrial misfolded or damaged proteins. Recent studies demonstrate that ClpP is upregulated in primary and metastatic human tumors, supports tumor cell proliferation, and its overexpression desensitizes cells to cisplatin. Interestingly, small modulators of ClpP activity, both activators and inhibitors, are able to impair oxidative phosphorylation in cancer cells and to induce apoptosis. This review provides an overview of the role of ClpP in regulating mitochondrial functionality, in supporting tumor cell proliferation and cisplatin resistance; finally, we discuss whether this protease could represent a new prognostic marker and therapeutic target for the treatment of cancer.
Tumor-Derived Exosomes (TEX) and Their Role in Immuno-Oncology
Authors: Whiteside Theresa L. , Diergaarde Brenda , Hong Chang-Sook
Published: June 2021

Extracellular vesicles (EVs) play a key role in health and disease, including cancer. Tumors produce a mix of EVs differing in size, cellular origin, biogenesis and molecular content. Small EVs (sEV) or exosomes are a subset of 30–150 nm (virus–size) vesicles originating from the multivesicular bodies (MVBs) and carrying a cargo that in its content and topography approximates that of a parent cell. Tumor-derived exosomes (TEX) present in all body fluids of cancer patients, are considered promising candidates for a liquid tumor biopsy. TEX also mediate immunoregulatory activities: they maintain a crosstalk between the tumor and various non-malignant cells, including immunocytes. Effects that EVs exert on immune cells may be immunosuppressive or immunostimulatory. Here, we review the available data for TEX interactions with immunocytes, focusing on strategies that allow isolation from plasma and separation of TEX from sEV produced by non-malignant cells. Immune effects mediated by either of the subsets can now be distinguished and measured. The approach has allowed for the comparison of molecular and functional profiles of the two sEV fractions in plasma of cancer patients. While TEX carried an excess of immunosuppressive proteins and inhibited immune cell functions in vitro and in vivo, the sEV derived from non-malignant cells, including CD3(+)T cells, were variably enriched in immunostimulatory proteins and could promote functions of immunocytes. Thus, sEV in plasma of cancer patients are heterogenous, representing a complex molecular network which is not evident in healthy donors’ plasma. Importantly, TEX appear to be able to reprogram functions of non-malignant CD3(+)T cells inducing them to produce CD3(+)sEV enriched in immunosuppressive proteins. Ratios of stimulatory/inhibitory proteins carried by TEX and by CD3(+)sEV derived from reprogrammed non-malignant cells vary broadly in patients and appear to negatively correlate with disease progression. Simultaneous capture from plasma and functional/molecular profiling of TEX and the CD3(+)sEV fractions allows for defining their role as cancer biomarkers and as monitors of cancer patients’ immune competence, respectively.
The Molecular Characteristics of Non-Clear Cell Renal Cell Carcinoma: What’s the Story Morning Glory?
Authors: Marchetti Andrea , Rosellini Matteo , Mollica Veronica , Rizzo Alessandro , Tassinari Elisa , Nuvola Giacomo , Cimadamore Alessia , Santoni Matteo , Fiorentino Michelangelo , Montironi Rodolfo , Massari Francesco
Published: June 2021

Non-clear cell renal cell carcinomas are a miscellaneous group of tumors that include different histological subtypes, each one characterized by peculiarity in terms of genetic alteration, clinical behavior, prognosis, and treatment response. Because of their low incidence and poor enrollment in clinical trials, alongside their heterogeneity, additional efforts are required to better unveil the pathogenetic mechanisms and, consequently, to improve the treatment algorithm. Nowadays, tyrosine kinase inhibitors, mTOR and MET inhibitors, and even cisplatin-based chemotherapy and immunotherapy are potential weapons that are still under evaluation in this setting. Various biomarkers have been evaluated for detecting progression and monitoring renal cell carcinoma, but more studies are necessary to improve this field. In this review, we provide an overview on the molecular characteristics of this group of tumors and the recently published trials, giving an insight into what might become the future therapeutic standard in this complex world of non-clear cell kidney cancers.
Optimal Conditions for Diapause Survival of Aprostocetus fukutai, an Egg Parasitoid for Biological Control of Anoplophora chinensis
Authors: Wang Xingeng , Ramualde Nathalie , Aparicio Ellen M. , Maspero Matteo , Duan Jian J. , Smith Lincoln
Published: June 2021

Aprostocetus fukutai is a specialist egg parasitoid of the citrus longhorned beetle Anoplophora chinensis, a high-risk invasive pest of hardwood trees. The parasitoid overwinters as diapausing mature larvae within the host egg and emerges in early summer in synchrony with the egg-laying peak of A. chinensis. This study investigated the parasitoid’s diapause survival in parasitized host eggs that either remained in potted trees under semi-natural conditions in southern France or were removed from the wood and held at four different humidities (44, 75, 85–93 and 100% RH) at 11 °C or four different temperature regimes (2, 5, 10 and 12.5 °C) at 100% RH in the laboratory. The temperature regimes reflect overwintering temperatures across the parasitoid’s geographical distribution in its native range. Results show that the parasitoid resumed its development to the adult stage at normal rearing conditions (22 °C, 100% RH, 14L:10D) after 6- or 7-months cold chilling at both the semi-natural and laboratory conditions. It had a low survival rate (36.7%) on potted plants due to desiccation or tree wound defense response. No parasitoids survived at 44% RH, but survival rate increased with humidity, reaching the highest (93.7%) at 100% RH. Survival rate also increased from 21.0% at 2 °C to 82.8% at 12.5 °C. Post-diapause developmental time decreased with increased humidity or temperature. There was no difference in the lifetime fecundity of emerged females from 2 and 12.5 °C. These results suggest that 100% RH and 12.5 °C are the most suitable diapause conditions for laboratory rearing of this parasitoid.
Outcomes of Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome in COVID-19 Patients: A Propensity-Matched Analysis
Authors: Autschbach Teresa , Hatam Nima , Durak Koray , Grottke Oliver , Dreher Michael , Nubbemeyer Katharina , Rossaint Rolf , Marx Gernot , Marx Nikolaus , Spillner Jan , Zayat Rashad , Kalverkamp Sebastian , Kersten Alex
Published: June 2021

It remains unclear to what extent the outcomes and complications of extracorporeal membrane oxygenation (ECMO) therapy in COVID-19 patients with acute respiratory distress syndrome (ARDS) differ from non-COVID-19 ARDS patients. In an observational, propensity-matched study, outcomes after ECMO support were compared between 19 COVID-19 patients suffering from ARDS (COVID group) and 34 matched non-COVID-19 ARDS patients (NCOVID group) from our historical cohort. A 1:2 propensity matching was performed based on respiratory ECMO survival prediction (RESP) score, age, gender, bilirubin, and creatinine levels. Patients’ characteristics, laboratory parameters, adverse events, and 90-day survival were analyzed. Patients’ characteristics in COVID and NCOVID groups were similar. Before ECMO initiation, fibrinogen levels were significantly higher in the COVID group (median: 493 vs. 364 mg/dL, p < 0.001). Median ECMO support duration was similar (16 vs. 13 days, p = 0.714, respectively). During ECMO therapy, patients in the COVID group developed significantly more thromboembolic events (TEE) than did those in the NCOVID group (42% vs. 12%, p = 0.031), which were mainly pulmonary artery embolism (PAE) (26% vs. 0%, p = 0.008). The rate of major bleeding events (42% vs. 62%, p = 0.263) was similar. Fibrinogen decreased significantly more in the COVID group than in the NCOVID group (p < 0.001), whereas D-dimer increased in the COVID group (p = 0.011). Additionally, 90-day mortality did not differ (47% vs. 74%; p = 0.064) between COVID and NCOVID groups. Compared with that in non-COVID-19 ARDS patients, ECMO support in COVID-19 patients was associated with comparable in-hospital mortality and similar bleeding rates but a higher incidence of TEE, especially PAE. In contrast, coagulation parameters differed between COVID and NCOVID patients.
Factors Associated with Malnutrition and Its Impact on Postoperative Outcomes in Older Patients
Authors: Venianaki Maria , Andreou Alexandros , Nikolouzakis Taxiarchis Konstantinos , Chrysos Emmanuel , Chalkiadakis George , Lasithiotakis Konstantinos
Published: June 2021

Malnutrition is associated with dismal treatment outcomes in older patients but its impact in geriatric surgery has not been studied extensively. Herein, we report the prevalence of malnutrition risk, its risk factors and its association with postoperative outcomes in older patients undergoing operations of general surgery. This is a retrospective analysis of a prospectively maintained database including patients older than 65 years who were to undergo general surgery operations between 2012 and 2017. The Malnutrition Universal Screening Tool (MUST) was used for nutritional risk. Demographics, socioeconomic data, site and magnitude of the operation, various measures of comorbidity and functional dependence as well as postoperative complications based on Clavien–Dindo classification and length of stay were recorded. There were 501 patients. A total of 28.6% of them were at intermediate malnutrition risk (MUST = 1) and 14.6% were at high malnutrition risk (MUST ≥ 2). Variables independently associated with malnutrition risk (MUST ≥ 1) were smoking (Odds Ratio, OR:1.6, p = 0.041), upper gastrointestinal (GI) tract surgery (OR:20.4, p < 0.001), hepatobiliary-pancreatic surgery (OR:3.7, p = 0.001), lower GI surgery (OR:5.2, p < 0.001) and American Society of Anesthesiologists (ASA) class III/IV (OR:2.8, p = 0.001). In the multiple regression analysis adjusted for several confounding variables, the MUST score was significantly associated with postoperative death (OR:9.1, p = 0.047 for MUST = 1 and OR:11.9, p = 0.035 for MUST score ≥ 2) and postoperative hospital stay (adjusted incidence rate ratio, 1.3, p = 0.041 for MUST = 1 and 1.7, p < 0.001 for MUST ≥ 2). Malnutrition risk was highly prevalent in this sample, particularly in patients with operations of the gastrointestinal tract, in patients with poor physical status and it was associated with postoperative mortality and length of stay.
Altered Vascular Endothelium-Dependent Responsiveness in Frail Elderly Patients Recovering from COVID-19 Pneumonia: Preliminary Evidence
Authors: Paneroni Mara , Pasini Evasio , Vitacca Michele , Scalvini Simonetta , Comini Laura , Pedrinolla Anna , Venturelli Massimo
Published: June 2021

We evaluated vascular dysfunction with the single passive leg movement test (sPLM) in 22 frail elderly patients at 84 + 31 days after hospitalization for COVID-19 pneumonia, compared to 22 age-, sex- and comorbidity-matched controls (CTRL). At rest, all COVID-19 patients were in stable clinical condition without severe comorbidities. Patients (aged 72 ± 6 years, 73% male) had moderate disability (Barthel index score 77 ± 26), hypoxemia and normocapnia at arterial blood gas analysis and mild pulmonary restriction at spirometry. Values of circulating markers of inflammation (C-reactive protein: CRP; erythrocyte sedimentation rate: ESR) and coagulation (D-dimer) were: 27.13 ± 37.52 mg/dL, 64.24 ± 32.37 mm/1 h and 1043 ± 729 ng/mL, respectively. At rest, femoral artery diameter was similar in COVID-19 and CTRL (p = 0.16). On the contrary, COVID-19 infection deeply impacted blood velocity (p = 0.001) and femoral blood flow (p < 0.0001). After sPLM, peak femoral blood flow was dramatically reduced in COVID-19 compared to CTRL (p = 0.001), as was blood flow ∆peak (p = 0.05) and the area under the curve (p < 0.0001). This altered vascular responsiveness could be one of the unknown components of long COVID-19 syndrome leading to fatigue, changes in muscle metabolism and fibers’ composition, exercise intolerance and increased cardiovascular risk. Impact of specific treatments, such as exercise training, dietary supplements or drugs, should be evaluated.
Serum Liberation of Fetal Fibronectin Variants in Patients with Pulmonary Hypertension: ED-A+ Fn as Promising Novel Biomarker of Pulmonary Vascular and Right Ventricular Myocardial Remodeling
Authors: Bäz Laura , Roßberg Michelle , Grün Katja , Kretzschmar Daniel , Berndt Alexander , Schulze P. Christian , Jung Christian , Franz Marcus
Published: June 2021

Background and Aims: Pulmonary Hypertension (PH) represents an aetiologically and clinically heterogeneous disorder accompanied by a severely impaired prognosis. Key steps of PH pathogenesis are vascular and right ventricular myocardial remodelling entailing the re-occurrence of fetal variants of the cell adhesion modulating protein fibronectin (Fn) being virtually absent in healthy adult tissues. These variants are liberated into circulation and are therefore qualified as excellent novel serum biomarkers. Moreover, these molecules might serve as promising therapeutic targets. The current study was aimed at quantifying the serum levels of two functionally important fetal Fn variants (ED-A+ and ED-B+ Fn) in patients suffering from PH due to different aetiologies compared to healthy controls. Methods: Serum levels of ED-A+ and ED-B+ Fn were quantified using novel ELISA protocols established and validated in our group in 80 PH patients and 40 controls. Results were analysed with respect to clinical, laboratory, echocardiographic and functional parameters. Results: Serum levels of ED-A+ Fn (p = 0.001) but not ED-B+ Fn (p = 0.722) were significantly increased in PH patients compared to healthy controls. Thus, the following analyses were performed only for ED-A+ Fn. When dividing PH patients into different aetiological groups according to current ESC guidelines, the increase in ED-A+ Fn in PH patients compared to controls remained significant for group 1 (p = 0.032), 2 (p = 0.007) and 3 (p = 0.001) but not for group 4 (p = 0.156). Correlation analysis revealed a significant relation between ED-A+ Fn and brain natriuretic peptide (BNP) (r = 0.310; p = 0.002), six minutes’ walk test (r = −0.275; p = 0.02) and systolic pulmonary artery pressure (PAPsys) (r = 0.364; p < 0.001). By logistic regression analysis (backward elimination WALD) including a variety of potentially relevant patients’ characteristics, only chronic kidney disease (CKD) (OR: 8.866; CI: 1.779–44.187; p = 0.008), C reactive protein (CRP) (OR: 1.194; CI: 1.011–1.410; p = 0.037) and ED-A+ Fn (OR: 1.045; CI: 1.011–1.080; p = 0.009) could be identified as independent predictors of the presence of PH. Conclusions: Against the background of our results, ED-A+ Fn could serve as a promising novel biomarker of PH with potential value for initial diagnosis and aetiological differentiation. Moreover, it might contribute to more precise risk stratification of PH patients. Beyond that, the future role of ED-A+ Fn as a therapeutic target has to be evaluated in further studies.