bluuebunny/crossref_metadata_2025 huggingface dataset:
Decreased CTRP3 Plasma Concentrations Are Associated with Sepsis and Predict Mortality in Critically Ill Patients
Authors: Yagmur Eray , Otto Simone , Koek Ger H. , Weiskirchen Ralf , Trautwein Christian , Koch Alexander , Tacke Frank
Published: June 2019

C1q/ tumor necrosis factor (TNF)-like protein 3 (CTRP3) represents a novel member of the adipokine family that exerts favorable metabolic actions in humans. However, the role of CTRP3 in critical illness and sepsis is currently unknown. Upon admission to the medical intensive care unit (ICU), we investigated CTRP3 plasma concentrations in 218 critically ill patients (145 with sepsis, 73 without sepsis). Results were compared with 66 healthy controls. CTRP3 plasma levels were significantly decreased in critically ill patients, when compared to healthy controls. In particular, low CTRP3 levels were highly associated with the presence of sepsis. CTRP3 levels were neither associated with obesity nor diabetes. In critically ill patients, CTRP3 plasma concentrations were inversely correlated with inflammatory cytokines and classical sepsis markers. Among a wide group of adipokines, CTRP3 only correlated with circulating resistin. Low CTRP3 plasma levels were associated with the overall mortality, and CTRP3 levels below 620.6 ng/mL indicated a particularly increased mortality risk in ICU patients. Our study demonstrates for the first time the role of circulating CTRP3 as a biomarker in critically ill patients that might facilitate diagnosis of sepsis as well as prognosis prediction. The association between low CTRP3 and increased inflammation warrants further pathophysiological investigations.
Application for GPON Frame Analysis
Authors: Holik Martin , Horvath Tomas , Oujezsky Vaclav
Published: June 2019

This article presents a design of a database model used to gather and analyze data frames transmitted over gigabit passive optical network (GPON) in the downstream direction. An issue with this kind of system is the difficulty in analyzing a transmission on the optical part which is caused by the difference among devices using Ethernet frames technology and passive optical network technology with usage gigabit encapsulation method. In this article, a principle of the downstream direction is described. Next, the design of the database model for the analysis of transmitted data is discussed. Based on the design and implementation of the database, a script capable of processing data gathered by a programmable network card is proposed. The script for physical layer operation, admission, and maintenance (PLOAM) messages analysis is written in the Python programming language.
A PWM Scheme for Five-Level H-Bridge T-Type Inverter with Switching Loss Reduction
Authors: Quach Thanh-Hai , Do Duc-Tri , Nguyen Minh-Khai
Published: June 2019

In this paper, a new pulse width modulation (PWM) scheme using an offset function to reduce switching loss in the five-level H-bridge T-type inverter (5L-HBT2I) is proposed. The proposed modulation technique is implemented with a third harmonic offset voltage function. A new control voltage, that is adding the offset voltage into the initial control, is shifted to the top or bottom position of the carrier, simultaneously—where the absolute value of its load current is high or medium in comparison to other phase load currents. Due to reducing the intersection between a control voltage and the carriers, the number of switch commutations of the inverter is reduced. As a result of reducing the number of commutation count with a high current at the non-switching position, the switching losses of the inverter are decreased. Analysis and comparison of switching losses on the two-level and three-level inverters, which are components of 5L-HBT2I are presented. The power loss analysis on the 5L-HBT2I is performed. The proposed technique implements the switching loss reduction strategy based on setting the operation of the two-level inverter in six-step mode. PSIM software is used to clarify the proposed technique. The simulation results show that the total switching losses of the proposed technique in 5L-HBT2I reduce in comparison to the conventional sine PWM technique. A prototype is built to validate the proposed scheme. Simulation and experimental results match the analysis.
Characterization of In-Cylinder Combustion Temperature Based on a Flame-Image Processing Technique
Authors: Chen Hanyu , Hou Yaoqi , Wang Xi , Pan Zhixiang , Xu Hongming
Published: June 2019

The analysis of in-cylinder combustion temperatures using flame image processing technology is reliable. This method can accurately, intuitively, and in real time obtain the temperature field distribution law of the combustion flame in the cylinder, so we can more deeply understand the characteristics of the combustion process of internal combustion engines. In this paper, a high-speed charge-coupled device (CCD) camera is used to record an in-cylinder combustion image, which is calculated and corrected according to the principle of three primary color temperature measurement, and the temperature field distribution of the combustion flame in the diesel engine cylinder is analyzed in detail. In addition, the temperature of the typical combustion flame images under the open-cycle and closed cycle conditions is compared by the CMS2002 measurement and MATLAB program, respectively. The results show that the accuracy of the MATLAB program is acceptable in general but not entirely acceptable in a few ways.
Physicochemical Characterization and Biological Activities of Black and White Garlic: In Vivo and In Vitro Assays
Authors: Toledano Medina María Ángeles , Merinas-Amo Tania , Fernández-Bedmar Zahira , Font Rafael , del Río-Celestino Mercedes , Pérez-Aparicio Jesús , Moreno-Ortega Alicia , Alonso-Moraga Ángeles , Moreno-Rojas Rafael
Published: June 2019

White and three types of black garlic (13, 32, and 45 days of aging, named 0C1, 1C2, and 2C1, respectively) were selected to study possible differences in their nutraceutic potential. For this purpose, garlic were physicochemically characterized (Brix, pH, aW, L, polyphenol, and antioxidant capacity), and both in vivo and in vitro assays were carried out. Black garlic samples showed higher polyphenol content and antioxidant capacity than the white ones. The biological assays showed that none of the samples (neither raw nor black garlic) produced toxic effects in the Drosophila melanogaster animal genetic model, nor exerted protective effects against H2O2, with the exception of the 0C1 black garlic. Moreover, only white garlic was genotoxic at the highest concentration. On the other hand, 0C1 black garlic was the most antigenotoxic substance. The in vivo longevity assays showed significant extension of lifespan at some concentrations of white and 0C1and 1C2 black garlic. The in vitro experiments showed that all of the garlic samples induced a decrease in leukemia cell growth. However, no type of garlic was able to induce proapoptotic internucleosomal DNA fragmentation. Taking into account the physicochemical and biological data, black garlic could be considered a potential functional food and used in the preventive treatment of age-related diseases. In addition, our findings could be relevant for black-garlic-processing agrifood companies, as the economical and timing costs can significantly be shortened from 45 to 13 days of aging.
Nutraceutic Potential of Two Allium Species and Their Distinctive Organosulfur Compounds: A Multi-Assay Evaluation
Authors: Fernández-Bedmar Zahira , Demyda-Peyrás Sebastián , Merinas-Amo Tania , del Río-Celestino Mercedes
Published: June 2019

This study aimed to evaluate the biological activities of two Allium species (garlic and onion) as well as diallyl disulphide (DADS) and dipropyl disulphide (DPDS) as their representative bioactive compounds in a multi-assay experimental design. The genotoxic, antigenotoxic, and lifespan effects of garlic, onion, DADS, and DPDS were checked in Drosophila melanogaster and their cytotoxic, pro-apoptotic, and DNA-clastogenic activities were analyzed using HL60 tumoral cells. All compounds were non-genotoxic and antigenotoxic against H2O2-induced DNA damage with a positive dose-response effect and different inhibition percentages (the highest value: 95% for DADS) at all tested concentrations. Daily intake of Allium vegetables, DADS, or DPDS had no positive effects on flies’ lifespan and health span. Garlic and DADS exerted the highest cytotoxic effects in a positive dose-dependent manner. Garlic and DADS exerted a DNA-internucleosomal fragmentation as an index of induced proapoptotic activity on HL60 cells. Allium vegetables and DADS were able to induce clastogenic strand breaks in the DNA of HL60 cells. This study showed the genomic safety of the assayed substances and their protective genetic effects against the hydrogen peroxide genotoxine. Long-term treatments during the whole life of the Drosophila genetic model were beneficial only at low-median concentrations. The chemo-preventive activity of garlic could be associated with its distinctive organosulfur DADS. We suggest that supplementary studies are needed to clarify the cell death pathway against garlic and DADS.
Immunophenotyping of a Stromal Vascular Fraction from Microfragmented Lipoaspirate Used in Osteoarthritis Cartilage Treatment and Its Lipoaspirate Counterpart
Authors: Polancec Denis , Zenic Lucija , Hudetz Damir , Boric Igor , Jelec Zeljko , Rod Eduard , Vrdoljak Trpimir , Skelin Andrea , Plecko Mihovil , Turkalj Mirjana , Nogalo Boro , Primorac Dragan
Published: June 2019

Osteoarthritis (OA) is a degenerative joint disease accompanied by pain and loss of function. Adipose tissue harbors mesenchymal stem/stromal cells (MSC), or medicinal signaling cells as suggested by Caplan (Caplan, 2017), used in autologous transplantation in many clinical settings. The aim of the study was to characterize a stromal vascular fraction from microfragmented lipoaspirate (SVF-MLA) applied for cartilage treatment in OA and compare it to that of autologous lipoaspirate (SVF-LA). Samples were first stained using a DuraClone SC prototype tube for the surface detection of CD31, CD34, CD45, CD73, CD90, CD105, CD146 and LIVE/DEAD Yellow Fixable Stain for dead cell detection, followed by DRAQ7 cell nuclear dye staining, and analyzed by flow cytometry. In SVF-LA and SVF-MLA samples, the following population phenotypes were identified within the CD45− fraction: CD31+CD34+CD73±CD90±CD105±CD146± endothelial progenitors (EP), CD31+CD34−CD73±CD90±CD105−CD146± mature endothelial cells, CD31−CD34−CD73±CD90+CD105−CD146+ pericytes, CD31−CD34+CD73±CD90+CD105−CD146+ transitional pericytes, and CD31−CD34+CD73highCD90+CD105−CD146− supra-adventitial-adipose stromal cells (SA-ASC). The immunophenotyping profile of SVF-MLA was dominated by a reduction of leukocytes and SA-ASC, and an increase in EP, evidencing a marked enrichment of this cell population in the course of adipose tissue microfragmentation. The role of EP in pericyte-primed MSC-mediated tissue healing, as well as the observed hormonal implication, is yet to be investigated.
Identification of Stress Associated microRNAs in Solanum lycopersicum by High-Throughput Sequencing
Authors: López-Galiano María José , Sentandreu Vicente , Martínez-Ramírez Amparo C. , Rausell Carolina , Real M. Dolores , Camañes Gemma , Ruiz-Rivero Omar , Crespo-Salvador Oscar , García-Robles Inmaculada
Published: June 2019

Tomato (Solanum lycopersicum) is one of the most important crops around the world and also a model plant to study response to stress. High-throughput sequencing was used to analyse the microRNA (miRNA) profile of tomato plants undergoing five biotic and abiotic stress conditions (drought, heat, P. syringae infection, B. cinerea infection, and herbivore insect attack with Leptinotarsa decemlineata larvae) and one chemical treatment with a plant defence inducer, hexanoic acid. We identified 104 conserved miRNAs belonging to 37 families and we predicted 61 novel tomato miRNAs. Among those 165 miRNAs, 41 were stress-responsive. Reverse transcription quantitative PCR (RT-qPCR) was used to validate high-throughput expression analysis data, confirming the expression profiles of 10 out of 11 randomly selected miRNAs. Most of the differentially expressed miRNAs were stress-specific, except for sly-miR167c-3p upregulated in B. cinerea and P. syringae infection, sly-newmiR26-3p upregulated in drought and Hx treatment samples, and sly-newmiR33-3p, sly-newmiR6-3p and sly-newmiR8-3p differentially expressed both in biotic and abiotic stresses. From mature miRNAs sequences of the 41 stress-responsive miRNAs 279 targets were predicted. An inverse correlation between the expression profiles of 4 selected miRNAs (sly-miR171a, sly-miR172c, sly-newmiR22-3p and sly-miR167c-3p) and their target genes (Kinesin, PPR, GRAS40, ABC transporter, GDP and RLP1) was confirmed by RT-qPCR. Altogether, our analysis of miRNAs in different biotic and abiotic stress conditions highlight the interest to understand the functional role of miRNAs in tomato stress response as well as their putative targets which could help to elucidate plants molecular and physiological adaptation to stress.
Expression and Regulation of PpEIN3b during Fruit Ripening and Senescence via Integrating SA, Glucose, and ACC Signaling in Pear (Pyrus pyrifolia Nakai. Whangkeumbae)
Authors: Shi Haiyan , Zhang Yuxing , Chen Liang
Published: June 2019

The economic value of fruit is reduced by having a short shelf life. Whangkeumbae is a type of sand pear (Pyrus pyrifolia) considered a climacteric fruit. The pear is famous for its smooth surface and good flavor. However, its shelf life is very short because of senescence and disease after harvest and a burst of ethylene (ET) production prompting the onset of fruit ripening. In plants, ETHYLENE INSENSITIVE3 (EIN3) and EIN3like (EIL), located in the nucleus, are important components of the ET signaling pathway and act as transcription factors. EIN3s and EILs belong to a small family involved in regulating the expression of ethylene response factor gene (ERF), whose encoding protein is the final component in the ET signaling pathway. The mutation of these components will cause defects in the ethylene pathway. In this study, one gene encoding an EIN3 was cloned and identified from Whangkeumbae and designated PpEIN3b. The deduced PpEIN3b contained a conserved EIN3 domain, a bipartite nuclear localization signal profile (NLS_BP), and an N-6 adenine-specific DNA methylase signature (N6_MTASE). PpEIN3b belongs to the EIN3 super-family by phylogenetic analysis. Quantitative RT-PCR (qRT-PCR) analysis revealed that PpEIN3b was preferentially expressed in fruit. Additionally, its expression was developmentally regulated during fruit ripening and senescence. Furthermore, PpEIN3b transcripts were obviously repressed by salicylic acid (SA) and glucose treatment in pear fruit and in diseased fruit, while it was significantly induced by 1-aminocyclopropane-1-carboxylic acid (ACC) treatment. Taken together, our results reveal the expression and regulation profiles of PpEIN3b and suggest that PpEIN3b might integrate SA, glucose, and ACC signaling to regulate fruit ripening and senescence in pear, which would provide a candidate gene for this regulation to obtain fruit with a long shelf life and improved economic value.
Earthquake Environmental Effects of the 1992 MS7.3 Suusamyr Earthquake, Kyrgyzstan, and Their Implications for Paleo-Earthquake Studies
Authors: Grützner Christoph , Walker Richard , Ainscoe Eleanor , Elliott Austin , Abdrakhmatov Kanatbek
Published: June 2019

Large pre-historical earthquakes leave traces in the geological and geomorphological record, such as primary and secondary surface ruptures and mass movements, which are the only means to estimate their magnitudes. These environmental earthquake effects (EEEs) can be calibrated using recent seismic events and the Environmental Seismic Intensity Scale (ESI2007). We apply the ESI2007 scale to the 1992 MS7.3 Suusamyr Earthquake in the Kyrgyz Tien Shan, because similar studies are sparse in that area and geological setting, and because this earthquake was very peculiar in its primary surface rupture pattern. We analyze literature data on primary and secondary earthquake effects and add our own observations from fieldwork. We show that the ESI2007 distribution differs somewhat from traditional intensity assessments (MSK (Medvedev-Sponheuer-Karnik) and MM (Modified Mercalli)), because of the sparse population in the epicentral area and the spatial distribution of primary and secondary EEEs. However, the ESI2007 scale captures a similar overall pattern of the intensity distribution. We then explore how uncertainties in the identification of primary surface ruptures influence the results of the ESI2007 assignment. Our results highlight the applicability of the ESI2007 scale, even in earthquakes with complex and unusual primary surface rupture patterns.
A Survey of Rural Residents’ Perception and Response to Health Risks from Hot Weather in Ethnic Minority Areas in Southwest China
Authors: Li Haipeng , Guan Jiabao , Ye Hui , Yang Haichen
Published: June 2019

Ethnic minority areas in southwestern China are facing frequent high-temperature heatwaves. The health risk perceptions and responses of the local residents need to be investigated in order to formulate public policies to mitigate the impacts of climate change on health. In this study, a household survey was conducted in Pengshui Miao and Tujia Autonomous County of Chongqing from January to February 2019. A total of 624 local residents were sampled using the multi-stage sampling method. We used multivariate logistic regression models to explore the factors affecting risk perceptions and responses with regard to hot weather. The results showed that despite a relatively high level of risk perception, the study population had a very low level of willingness to see a doctor (24.4%), especially ethnic minority residents (17.5%). In particular, 80% of residents were aware of climate warming and 79% of residents were aware of the health risks of hot weather. Almost all survey participants reported a response to hot weather, with more than half of the participants stating that they would go somewhere cooler (58.5%) and drink more water (56.3%). Compared with the Han Chinese, ethnic minority participants had a higher perception of warm temperature (p <0.001) and associated health risks (p <0.001) but a lower perception of physical discomfort (p <0.001) and aggravated diseases (p = 0.001). The logistic models indicated that ethnic minority, residence time, outdoor working hours, and health status can significantly influence perceptions and subsequently significantly affect coping behaviors. In conclusion, our findings provide significant implications for the development of policies and health education and promotion programs for ethnic minorities in southwest China to aid them in maintaining good health during future hot weather events.
Research on Measurement of Symbiosis Degree Between National Fitness and the Sports Industry from the Perspective of Collaborative Development
Authors: Lan Qing , Liu Chunxiang , Ling Shuang
Published: June 2019

Clarifying the symbiotic relationship between national fitness and the sports industry has important theoretical and practical significance for the collaborative development of the two. In order to measure and verify the symbiotic relationship between national fitness and the sports industry, we introduce a “symbiosis degree” model test method for the measurement of the symbiotic relationship during 2000–2017 between the two. Our results show that national fitness and the sports industry have symbiotic sufficient and necessary conditions, for both of which there is a symbiotic relationship, and a non-symmetric reciprocal symbiotic mode long-term. Overall, the impact of national fitness on the sports industry is greater than the impact of the sports industry on national fitness. From a structural perspective, there is a certain difference in the mutual influence of national fitness and the sports industry in the field of sports goods and sports services. In a dynamic forecast, we found that national fitness and the sports industry have the development trend of a symmetric reciprocal symbiotic state. Through theoretical studies, data measured and simulated projections, we believe that the symbiosis degree of the measurement model for the detection and prediction of the symbiotic unit of the symbiotic relationship between them to be of practical value.
Heat Stress Response to National-Committed Emission Reductions under the Paris Agreement
Authors: Wang Fang , Zhang Jintao
Published: June 2019

With the changes in global temperature and humidity, heat stress is expected to intensify in the coming decades. Under the scenario that greenhouse gas emissions keep increasing until the end of this century, there is the possibility of extensive global exposure to high heat stress. While under new mitigation efforts (as part of the Paris Agreement, signatory nations pledged to implement the Intended Nationally Determined Contributions (INDCs) for emission reductions), the regional response of heat stress to pledged emission reductions remains unclear. In this study, we analyze the heat stress response in global hotspot regions, targeting emission scenarios resulting from the INDCs pledges. Our study revealed that under the INDCs-continuous mitigation, the heat stress effect in global hotspot regions (North China, South Asia, and the Amazon) is estimated to be lower than 29 °C in the next three decades and to be from >33 °C to less than 30 °C to this century end. The heat stress effect indicates a great reduction at the continuous mitigation compared with the delayed mitigation, and the population exposed to dangerous heat stress would also decrease approximately one order of magnitude. If limiting warming to a lesser amount (1.5/2 °C targets), significantly further reduction of the population exposed to heat stress in the middle and low latitudes can be achieved, thus avoiding the adverse effects associated with heat stress. Therefore, the national intended mitigation actions under the Paris Agreement will play a crucial role in reducing the heat stress risk in these hot and humid regions. These findings will help to improve the understanding of the future risks of heat stress and are crucial for mitigation and adaptation actions in hotspot areas (approximately 1/3 of the world’s population).
Effect of Pharmacist Intervention on a Population in Taiwan with High Healthcare Utilization and Excessive Polypharmacy
Authors: Wang Tzu-Chueh , Trezise Damien , Ku Pou-Jen , Lu Hai-Lin , Hsu Kung-Chuan , Hsu Po-Cheng
Published: June 2019

Patients with high healthcare utilization are at increased risk of polypharmacy and drug interactions. This study investigated the changes in the number of medications, drug interactions and interaction severity in high frequency outpatients with polypharmacy at hospitals and clinics in Taiwan after home pharmaceutical care, to understand the effectiveness of interventions by pharmacists. This was a retrospective observational study. Cases with excessive polypharmacy (10+ drugs) were selected from the Pharmaceutical Care Practice System database of the Taiwan Pharmacist Association in 2017. After the home care intervention, the number of drug types used decreased 1.89-fold (p < 0.001), and the number of medications fell 61.6%. The incidence of drug interaction was 93.82%. In an average case, the incidence of drug interaction after the pharmacist intervention decreased 0.6-fold (p < 0.001). The drug most commonly causing interactions was aspirin, followed by diclofenac; also common were three used in diabetes, two psycholeptics and two beta blockers. Among 22 cases of severe drug interaction, seven resulted in increased risk of extrapyramidal symptoms and neuroleptic malignant syndrome. By analyzing the relationship between the side effects of individual drugs and the pharmacokinetic Tmax, a sequential thermal zone model of adverse drug reactions can be established, the value of which could prompt physicians and pharmacists to intervene in order to prevent adverse events. It is concluded that home pharmaceutical care by pharmacists can significantly reduce the number of medications and interactions in patients with excessive polypharmacy and high healthcare utilization.
Public Attitudes toward Biobanking of Human Biological Material for Research Purposes: A Literature Review
Authors: Domaradzki Jan , Pawlikowski Jakub
Published: June 2019

Background: During the past few decades there has been a growing interest on the part of many governments in the creation of biobanks. Nevertheless, this would be impossible without participation of many donors who offer samples of their biological material for scientific research. Therefore, the aim of this paper is to provide an overview of the existing research on social attitudes towards biobanking. Material and Methods: A literature search was conducted in the database of MEDLINE (PubMed). 61 papers were included in the analysis. The retrieved articles were assessed using a thematic analysis. Results: Eight main themes were identified: (1) public knowledge about biobanks, (2) public views on biobanking, (3) willingness to donate, (4) donors’ motivations, (5) perceived benefits and risks of biobanking, (6) preferred type of consent, (7) trust toward biobanks, and (8) demographic characteristics of potential donors. Conclusions: Although the public lacks knowledge about biobanking, many individuals declare willingness to donate. Their will is influenced by: their knowledge about biobanking, the type of donated tissue, research purpose, concerns over the safety of the data, preferred type of consent, and trust towards biobanks.
Vibration and Noise Transmitted by Agricultural Backpack Powered Machines Critically Examined Using the Current Standards
Authors: Calvo Angela , Preti Christian , Caria Maria , Deboli Roberto
Published: June 2019

European Directives 2002/44/EC and 2003/10/EC establish the exposure limit values for preventing operators’ risks to vibration and noise transmitted by machines. Few studies studied noise and vibration of agricultural backpack powered machines (as mist blowers and blowers), but nobody critically studied them. This work analyzed the field back vibration, hand-arm vibration (HAV), and noise transmitted to ten operators by eight blowers and mist blowers. Unweighted and weighted vibration were analyzed, using the standards ISO 2631-1 (back), and ISO 5349-1 and ISO/TR 18570 (hand-arm system). The noise was evaluated by recording the acoustic pressure level at the operators’ ears using the ISO 9612. With the ISO 2631-1, the vibration to the operators’ back was low (0.38 ms−2), but the unweighted vibration measured along y and z-axes (not used by the ISO 2631-1) were high (>11 ms−2). HAV were also low when using the ISO 5349-1 (the highest value was 2.51 ms−2 in mist blowers), but high with the ISO/TR 18570 for the onset of vibration white finger (1446 ms−1.5 in blowers). Noise levels were always high: more than 100 dB(A), excluding the blower with the exhaust inside the blower hose. This last machine had noise levels lower than 86 dB(A), but its specific feature could increase environmental pollution.
Cadmium Exposure and Risk of Breast Cancer by Histological and Tumor Receptor Subtype in White Caucasian Women: A Hospital-Based Case-Control Study
Authors: Strumylaite Loreta , Kregzdyte Rima , Bogusevicius Algirdas , Poskiene Lina , Baranauskiene Dale , Pranys Darius
Published: June 2019

As the majority of experimental studies suggest cadmium being metalloestrogen, we examined cadmium/breast cancer (BC) association by histological and tumor receptor subtype in 509 invasive BC patients and 1170 controls. Urinary cadmium was determined by atomic absorption spectrometry, and categorized using tertiles of its distribution in the controls: <0.18, 0.18–0.33, >0.33 kg × 10−9/kg × 10−3 creatinine. Relative to the lowest category of urinary cadmium adjusted odds ratio (OR) of ductal BC was 1.18 (95% confidence interval (CI): 0.89–1.58) in the intermediate and 1.53 (95% CI: 1.15–2.04) in the highest category. There was a significant association for hormone receptor-positive ductal BC: ORs per category increase were 1.34 (95% CI: 1.14–1.59) for estrogen receptor-positive (ER+), 1.33 (95% CI: 1.09–1.61) for progesterone receptor-positive (PR+) and 1.35 (95% CI: 1.11–1.65) for ER+/PR+ BC. We found a significant association between cadmium and human epidermal growth factor receptor 2-negative (HER2−) ductal BC. The strongest association with cadmium was for ER+/PR+/HER2− ductal BC. The associations between cadmium and lobular BC with hormone receptor-positive and HER2− were positive but insignificant. There was no evidence that the associations with cadmium differed for cancers with different tumor histology (p-heterogeneity > 0.05). This study provides evidence that urinary cadmium is associated with the risk of hormone receptor-positive and HER2− breast cancer independent of tumor histology.
Red Ginseng Attenuates Aβ-Induced Mitochondrial Dysfunction and Aβ-mediated Pathology in an Animal Model of Alzheimer’s Disease
Authors: Shin Soo Jung , Jeon Seong Gak , Kim Jin-il , Jeong Yu-on , Kim Sujin , Park Yong Ho , Lee Seong-Kyung , Park Hyun Ha , Hong Sang Bum , Oh Sua , Hwang Ji-young , Kim Hyeon soo , Park HyunHee , Nam Yunkwon , Lee Yong Yook , Kim Jwa-Jin , Park Sun-Hyun , Kim Jong-Seok , Moon Minho
Published: June 2019

Alzheimer’s disease (AD) is the most common neurodegenerative disease and is characterized by neurodegeneration and cognitive deficits. Amyloid beta (Aβ) peptide is known to be a major cause of AD pathogenesis. However, recent studies have clarified that mitochondrial deficiency is also a mediator or trigger for AD development. Interestingly, red ginseng (RG) has been demonstrated to have beneficial effects on AD pathology. However, there is no evidence showing whether RG extract (RGE) can inhibit the mitochondrial deficit-mediated pathology in the experimental models of AD. The effects of RGE on Aβ-mediated mitochondrial deficiency were investigated in both HT22 mouse hippocampal neuronal cells and the brains of 5XFAD Aβ-overexpressing transgenic mice. To examine whether RGE can affect mitochondria-related pathology, we used immunohistostaining to study the effects of RGE on Aβ accumulation, neuroinflammation, neurodegeneration, and impaired adult hippocampal neurogenesis in hippocampal formation of 5XFAD mice. In vitro and in vivo findings indicated that RGE significantly improves Aβ-induced mitochondrial pathology. In addition, RGE significantly ameliorated AD-related pathology, such as Aβ deposition, gliosis, and neuronal loss, and deficits in adult hippocampal neurogenesis in brains with AD. Our results suggest that RGE may be a mitochondria-targeting agent for the treatment of AD.
Transgenic RXLR Effector PITG_15718.2 Suppresses Immunity and Reduces Vegetative Growth in Potato
Authors: Wang Jiao , Gao Cungang , Li Long , Cao Weilin , Dong Ran , Ding Xinhua , Zhu Changxiang , Chu Zhaohui
Published: June 2019

Phytophthora infestans causes the severe late blight disease of potato. During its infection process, P. infestans delivers hundreds of RXLR (Arg-x-Leu-Arg, x behalf of any one amino acid) effectors to manipulate processes in its hosts, creating a suitable environment for invasion and proliferation. Several effectors interact with host proteins to suppress host immunity and inhibit plant growth. However, little is known about how P. infestans regulates the host transcriptome. Here, we identified an RXLR effector, PITG_15718.2, which is upregulated and maintains a high expression level throughout the infection. Stable transgenic potato (Solanum tuberosum) lines expressing PITG_15718.2 show enhanced leaf colonization by P. infestans and reduced vegetative growth. We further investigated the transcriptional changes between three PITG_15718.2 transgenic lines and the wild type Désirée by using RNA sequencing (RNA-Seq). Compared with Désirée, 190 differentially expressed genes (DEGs) were identified, including 158 upregulated genes and 32 downregulated genes in PITG_15718.2 transgenic lines. Eight upregulated and nine downregulated DEGs were validated by real-time RT-PCR, which showed a high correlation with the expression level identified by RNA-Seq. These DEGs will help to explore the mechanism of PITG_15718.2-mediated immunity and growth inhibition in the future.
Comparative Genomics, Infectivity and Cytopathogenicity of American Isolates of Zika Virus that Developed Persistent Infections in Human Embryonic Kidney (HEK293) Cells
Authors: Liu Hebing , Liao Hsiao-Mei , Li Bingjie , Tsai Shien , Hung Guo-Chiuan , Lo Shyh-Ching
Published: June 2019

Zika virus (ZIKV) transmission can cause serious fetal neurological abnormalities. ZIKV persistence in various human cells and tissues can serve as infectious reservoirs and post serious threats to public health. The human embryonic kidney (HEK293) cell line with known neuronal developmental properties was readily infected by ZIKV in a strain-dependent fashion. Significant cytopathic effect in HEK293 cells infected by the prototype MR 766 strain of ZIKV resulted in complete loss of cells, while small numbers of HEK293 cells infected by contemporary ZIKV isolates (PRV or FLR strain) continued to survive and regrow to confluency in the culture around two months after initial infection. Most, if not all, of the cells in the two resulting persistently ZIKV-infected HEK293 cell lines tested positive for ZIKV antigen. Compared to HEK293 control cells, the persistently ZIKV-infected HEK293 cells had slower growth rates with some cells undergoing apoptosis in culture. The “persistent ZIKVs” produced constitutively by both PRV and FLR strains ZIKV-infected HEK293 cells had significantly attenuated cell infectivity and/or cytopathogenicity. Comparative genome sequence analyses between the persistent ZIKVs and the original inoculum ZIKVs showed no clonal selection with specific gene mutations in the prolonged process of establishing persistently PRV strain ZIKV-infected HEK293 cells; while selection of ZIKV subclones with mutations in the envelope, protein pr and multiple NS genes was evident in developing persistently FLR strain ZIKV-infected HEK293 cell line. Our study provides molecular insights into the complex interplays of ZIKV and human host cells in establishing ZIKV persistence.
Oligomerization of Silicic Acids in Neutral Aqueous Solution: A First-Principles Investigation
Authors: Liu Xin , Liu Cai , Meng Changgong
Published: June 2019

Crystallite aluminosilicates are inorganic microporous materials with well-defined pore-size and pore-structures, and have important industrial applications, including gas adsorption and separation, catalysis, etc. Crystallite aluminosilicates are commonly synthesized via hydrothermal processes, where the oligomerization of silicic acids is crucial. The mechanisms for the oligomerization of poly-silicic acids in neutral aqueous solution were systematically investigated by extensive first-principles-based calculations. We showed that oligomerization of poly-silicic acid molecules proceeds through the lateral attacking and simultaneously proton transfer from the approaching molecule for the formation of a 5-coordinated Si species as the transition state, resulting in the ejection of a water molecule from the formed poly-silicic acid. The barriers for this mechanism are in general more plausible than the conventional direct attacking of poly-silicic acid with reaction barriers in the range of 150–160 kJ/mol. The formation of linear or branched poly-silicic acids by intermolecular oligomerization is only slightly more plausible than the formation of cyclic poly-silicic acids via intramolecular oligomerization according to the reaction barriers (124.2–133.0 vs. 130.6–144.9 kJ/mol). The potential contributions of oligomer structures, such as the length of the linear oligomers, ring distortions and neighboring linear branches, etc., to the oligomerization were also investigated but found negligible. According to the small differences among the reaction barriers, we proposed that kinetic selectivity of the poly-silicic acids condensation would be weak in neutral aqueous solution and the formation of zeolite-like structures would be thermodynamics driven.
Evolution Shapes the Gene Expression Response to Oxidative Stress
Authors: Siauciunaite Rima , Foulkes Nicholas S. , Calabrò Viola , Vallone Daniela
Published: June 2019

Reactive oxygen species (ROS) play a key role in cell physiology and function. ROS represents a potential source of damage for many macromolecules including DNA. It is thought that daily changes in oxidative stress levels were an important early factor driving evolution of the circadian clock which enables organisms to predict changes in ROS levels before they actually occur and thereby optimally coordinate survival strategies. It is clear that ROS, at relatively low levels, can serve as an important signaling molecule and also serves as a key regulator of gene expression. Therefore, the mechanisms that have evolved to survive or harness these effects of ROS are ancient evolutionary adaptations that are tightly interconnected with most aspects of cellular physiology. Our understanding of these mechanisms has been mainly based on studies using a relatively small group of genetic models. However, we know comparatively little about how these mechanisms are conserved or have adapted during evolution under different environmental conditions. In this review, we describe recent work that has revealed significant species-specific differences in the gene expression response to ROS by exploring diverse organisms. This evidence supports the notion that during evolution, rather than being highly conserved, there is inherent plasticity in the molecular mechanisms responding to oxidative stress.
Trimethylamine N-Oxide Does Not Impact Viability, ROS Production, and Mitochondrial Membrane Potential of Adult Rat Cardiomyocytes
Authors: Querio Giulia , Antoniotti Susanna , Levi Renzo , Gallo Maria Pia
Published: June 2019

Trimethylamine N-oxide (TMAO) is an organic compound derived from dietary choline and L-carnitine. It behaves as an osmolyte, a protein stabilizer, and an electron acceptor, showing different biological functions in different animals. Recent works point out that, in humans, high circulating levels of TMAO are related to the progression of atherosclerosis and other cardiovascular diseases. However, studies on a direct role of TMAO in cardiomyocyte parameters are still limited. The purpose of this work is to study the effects of TMAO on isolated adult rat cardiomyocytes. TMAO in both 100 µM and 10 mM concentrations, from 1 to 24 h of treatment, does not affect cell viability, sarcomere length, intracellular ROS, and mitochondrial membrane potential. Furthermore, the simultaneous treatment with TMAO and known cardiac insults, such as H2O2 or doxorubicin, does not affect the treatment’s effect. In conclusion, TMAO cannot be considered a direct cause or an exacerbating risk factor of cardiac damage at the cellular level in acute conditions.
Molecular Modelling of the Ni(II)-Responsive Synechocystis PCC 6803 Transcriptional Regulator InrS in the Metal Bound Form
Authors: Barchi Elia , Musiani Francesco
Published: June 2019

InrS (internal nickel-responsive sensor) is a transcriptional regulator found in cyanobacteria that represses the transcription of the nickel exporter NrsD in the apo form and de-represses expression of the exporter upon Ni(II) binding. Although a crystal structure of apo-InrS from Synechocystis PCC 6803 has been reported, no structure of the protein with metal ions bound is available. Here we report the results of a computational study aimed to reconstruct the metal binding site by taking advantage of recent X-ray absorption spectroscopy (XAS) data and to envisage the structural rearrangements occurring upon Ni(II) binding. The modelled Ni(II) binding site shows a square planar geometry consistent with experimental data. The structural details of the conformational changes occurring upon metal binding are also discussed in the framework of trying to rationalize the different affinity of the apo- and holo-forms of the protein for DNA.
Integrated Pest Management (IPM) for Small-Scale Farms in Developed Economies: Challenges and Opportunities
Authors: Grasswitz Tessa R.
Published: June 2019

Small-scale farms are an important component of agricultural production even in developed economies, and have an acknowledged role in providing other biological and societal benefits, including the conservation of agricultural biodiversity and enhancement of local food security. Despite this, the small-farm sector is currently underserved in relation to the development and implementation of scale-appropriate Integrated Pest Management (IPM) practices that could help increase such benefits. This review details some of the characteristics of the small farm sectors in developed economies (with an emphasis on the USA and Europe), and identifies some of the characteristics of small farms and their operators that may favor the implementation of IPM. Some of the challenges and opportunities associated with increasing the uptake of IPM in the small-farm sector are discussed. For example, while some IPM tactics are equally applicable to virtually any scale of production, there are others that may be easier (or more cost-effective) to implement on a smaller scale. Conversely, there are approaches that have not been widely applied in small-scale production, but which nevertheless have potential for use in this sector. Examples of such tactics are discussed. Knowledge gaps and opportunities for increasing IPM outreach to small-scale producers are also identified.
Clinical Approach to the Patient in Critical State Following Immunotherapy and/or Stem Cell Transplantation: Guideline for the On-Call Physician
Authors: Constantinescu Catalin , Bodolea Constantin , Pasca Sergiu , Teodorescu Patric , Dima Delia , Rus Ioana , Tat Tiberiu , Achimas-Cadariu Patriciu , Tanase Alina , Tomuleasa Ciprian , Einsele Hermann
Published: June 2019

The initial management of the hematology patient in a critical state is crucial and poses a great challenge both for the hematologist and the intensive care unit (ICU) physician. After years of clinical practice, there is still a delay in the proper recognition and treatment of critical situations, which leads to late admission to the ICU. There is a much-needed systematic ABC (Airway, Breathing, Circulation) approach for the patients being treated on the wards as well as in the high dependency units because the underlying hematological disorder, as well as disease-related complications, have an increasing frequency. Focusing on score-based decision-making on the wards (Modified Early Warning Score (MEWS), together with Quick Sofa score), active sepsis screening with inflammation markers (C-reactive protein, procalcitonin, and presepsin), and assessment of microcirculation, organ perfusion, and oxygen supply by using paraclinical parameters from the ICU setting (lactate, central venous oxygen saturation (ScVO2), and venous-to-arterial carbon dioxide difference), hematologists can manage the immediate critical patient and improve the overall outcome.
Sex Moderates the Effect of Aerobic Exercise on Some Aspects of Cognition in Cognitively Intact Younger and Middle-Age Adults
Authors: Stern Yaakov , Lee Seonjoo , Predovan David , P. Sloan Richard
Published: June 2019

We recently reported the results of a randomized, parallel-group, observer-masked, community-based clinical trial of 132 cognitively normal individuals aged 20–67 with below median aerobic capacity who were randomly assigned to one of two 6-month, four-times-weekly conditions: aerobic exercise and stretching/toning. We now assessed potential sex moderation on exercise-related changes in aerobic capacity, BMI and cognitive function. There was no sex moderation of the effect of aerobic exercise on aerobic capacity or BMI. We had previously reported an effect of aerobic exercise on executive function that was moderated by age. We found additional moderation by sex, such that in any age range men improved more than women. Processing speed showed significant sex moderation but not significant age moderation. In men, processing speed significantly improved by week 12 (b = 0.35, p = 0.0051), but the effect was diminished relative to week 12 at week 24 (b = 0.24, p = 0.0578). In women, there was no exercise effect at either time point (week 12: b = −0.06, p = 0.4156; week 24: b = −0.11, p = 0.1841). Men benefited cognitively more than women from aerobic exercise. This study highlights the importance of using sex-disaggregated analyses when assessing the impact of physical exercise intervention, and the need to ascertain the underlying mechanisms for differential cognitive benefit by sex.
Saliva and Serum Immune Responses in Apical Periodontitis
Authors: Pietiäinen Milla , Liljestrand John M. , Akhi Ramin , Buhlin Kåre , Johansson Anders , Paju Susanna , Salminen Aino , Mäntylä Päivi , Sinisalo Juha , Tjäderhane Leo , Hörkkö Sohvi , Pussinen Pirkko J.
Published: June 2019

Apical periodontitis is an inflammatory reaction at the apex of an infected tooth. Its microbiota resembles that of marginal periodontitis and may induce local and systemic antibodies binding to bacteria- and host-derived epitopes. Our aim was to investigate the features of the adaptive immune response in apical periodontitis. The present Parogene cohort (n = 453) comprises patients with cardiac symptoms. Clinical and radiographic oral examination was performed to diagnose apical and marginal periodontitis. A three-category endodontic lesion score was designed. Antibodies binding to the bacteria- and host-derived epitopes were determined from saliva and serum, and bacterial compositions were examined from saliva and subgingival samples. The significant ORs (95% CI) for the highest endodontic scores were observed for saliva IgA and IgG to bacterial antigens (2.90 (1.01–8.33) and 4.91 (2.48–9.71)/log10 unit), saliva cross-reacting IgG (2.10 (1.48–2.97)), serum IgG to bacterial antigens (4.66 (1.22–10.1)), and Gram-negative subgingival species (1.98 (1.16–3.37)). In a subgroup without marginal periodontitis, only saliva IgG against bacterial antigens associated with untreated apical periodontitis (4.77 (1.05–21.7)). Apical periodontitis associates with versatile adaptive immune responses against both bacterial- and host-derived epitopes independently of marginal periodontitis. Saliva immunoglobulins could be useful biomarkers of oral infections including apical periodontitis—a putative risk factor for systemic diseases.
Optical Quality Assessment in Patients with Macular Diseases Using Optical Quality Analysis System
Authors: Cho Joon Hee , Bae So Hyun , Kim Ha Kyoung , Shin Young Joo
Published: June 2019

Macular diseases cause vision loss, as the macula is the functional center for vision. In this study we assessed optical quality in eyes with macular diseases and evaluated the effectiveness of the Optical Quality Analysis System (OQAS) to detect macular diseases. We analyzed 88 eyes of 88 patients with macular diseases (51 men and 37 women; mean age: 65.24 ± 12.96 years) and 43 eyes of 43 control subjects (11 men and 32 women; mean age: 54.70 ± 15.03 years). The macular diseases included age-related macular disease (n = 62), diabetic macular edema (n = 19), and retinal vein occlusion (n = 7). We measured the objective scattering index (OSI), modulation transfer function (MTF), Strehl ratio, and predicted visual acuities (PVAs) at 100, 20, and 10% contrast levels in both groups using OQAS. We measured the retinal thickness in the macular disease group on optical coherence tomography. The macular disease and control groups significantly differed in OSI, MTF, Strehl ratio, and PVAs at 20 and 10% contrast levels (p < 0.05). In the macular disease group, retinal thickness correlated with OSI (r = 0.370, p < 0.001) and MTF (r = −0.264, p = 0.014). In conclusion, optical quality was worse in the patients with macular diseases compared to the control subjects, and retinal thickness affected optical quality. Therefore, the distortion of macular shape may contribute to vision disturbance in patients with macular diseases.