bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Electric Bus Charging on Distribution Substation and Local Grid in Warsaw
Authors: Zagrajek Krzysztof , Paska Józef , Kłos Mariusz , Pawlak Karol , Marchel Piotr , Bartecka Magdalena , Michalski Łukasz , Terlikowski Paweł
Published: March 2020

Electric buses are increasingly appearing on the streets of cities around the world. Thus, it is necessary to consider the impact of their charging on the distribution system operation, especially near the charging point. This article presents the problems that may arise while new charging points are connected. Research was carried out on the existing charging point at Spartańska Street in Warsaw, which allowed to obtain daily bus charging profiles and voltage curves. The authors then proposed an exemplary model of a bus terminus with the designed infrastructure for charging buses, based on the assumptions of the public transport operator in Warsaw. The comparison of these two solutions was made and based on it, a methodology of calculating daily demand for any terminus was prepared. In addition, no problems with the power quality were found during the research. This allows us to state that the introduction of electric buses into the fleet of passenger carriers will have a minor impact on the operation of the power system in Warsaw.
The Influence of Insulating Layers on the Acoustic Performance of Lightweight Frame Floors Intended for Use in Residential Buildings
Authors: Nowotny Łukasz , Nurzyński Jacek
Published: March 2020

The acoustic performance of floors plays a primary role in the total quality rating of a residential building. The sound insulation of lightweight frame floors, which are increasingly being used in housing, depends on a number of factors and technical details. In effect, the sound transmission scheme is distinctly more complicated than in the case of homogeneous massive partitions. The aim of the study was to develop effective insulating layers of lightweight floors intended for use in residential buildings. The floor system should satisfy legal requirements in terms of airborne and impact sound insulation. The research was based on laboratory measurements taken in a standard test facility. Ten different models of wood and metal floors were considered. The acoustic performance of their basic structure was insufficient; however, the application of effective floating floors and suspended ceilings improved it greatly and succeeded in potential meeting requirements and satisfying most inhabitants’ expectations. The results demonstrate how different lightweight floor components influence the acoustic performance of the floor and how the insulating layers cooperate when applied together. The findings will be useful in working on a new floor design and optimizing its structure in terms of acoustics.
A Reliability-Based Network Reconfiguration Model in Distribution System with DGs and ESSs Using Mixed-Integer Programming
Authors: Guo Shanghua , Lin Jian , Zhao Yuming , Wang Longjun , Wang Gang , Liu Guowei
Published: March 2020

Widely used distribution generations (DGs) and energy storage systems (ESSs) enable a distribution system to have a more flexible fault reconfiguration capability. In order to enhance the service reliability and the benefit of distribution networks with DGs and ESSs, this paper proposes a novel distribution system reconfiguration (DSR) model including DGs and ESSs. Meanwhile, the impact of sectionalizing switches and tie switches on reliability is considered. The concept of “boundary switch” is introduced for quantifying the customer interruption duration. The DSR model is presented to minimize the sum of the customer interruption cost, the operation cost of switches, and the depreciation cost of DGs and ESSs. Furthermore, the proposed model is converted into a mixed-integer linear programming, which can be efficiently solved by commercial solvers. Finally, the validity and efficiency of the proposed DSR model are verified by a modified IEEE 33-bus system and a modified PG&E69-bus network. The obtained results indicate the advantages of DGs and ESSs in reducing outage time, and suggest that the types and locations of SSs have great effects on the resulting benefit of DGs and ESSs.
Genome-Wide Analysis of the Lateral Organ Boundaries Domain Gene Family in Brassica Napus
Authors: Xie Tao , Zeng Lei , Chen Xin , Rong Hao , Wu Jingjing , Batley Jacqueline , Jiang Jinjin , Wang Youping
Published: March 2020

The plant specific LATERAL ORGAN BOUNDARIES (LOB)-domain (LBD) proteins belong to a family of transcription factors that play important roles in plant growth and development, as well as in responses to various stresses. However, a comprehensive study of LBDs in Brassica napus has not yet been reported. In the present study, 126 BnLBD genes were identified in B. napus genome using bioinformatics analyses. The 126 BnLBDs were phylogenetically classified into two groups and nine subgroups. Evolutionary analysis indicated that whole genome duplication (WGD) and segmental duplication played important roles in the expansion of the BnLBD gene family. On the basis of the RNA-seq analyses, we identified BnLBD genes with tissue or developmental specific expression patterns. Through cis-acting element analysis and hormone treatment, we identified 19 BnLBD genes with putative functions in plant response to abscisic acid (ABA) treatment. This study provides a comprehensive understanding on the origin and evolutionary history of LBDs in B. napus, and will be helpful in further functional characterisation of BnLBDs.
Entropy’s Enemies: Postmodern Fission and Transhuman Fusion in the Post-War Era
Authors: Burr Jordan
Published: March 2020

In the early to mid-twentieth century, thermodynamic entropy—the inevitable diffusion of usable energy in the Universe—became a ubiquitous metaphor for the dissolution of Western values and cultural energy. Many Golden Age science fiction writers portrayed twentieth century technological progress as anti-entropic, a sign of Universal progress and unity which might postpone or negate both cultural and thermodynamic forms of entropy. Following the evolutionary metaphysics of Georg Hegel and Pierre Teilhard de Chardin, Golden Age science fiction writers like Arthur C. Clarke and Isaac Asimov imagined the creation of powerful collective beings whose unitary existence signified the defeat of entropy. In contrast, later literary postmodernists like Thomas Pynchon and Pamela Zoline often accepted and even exalted in the chaotic, liberating potential of entropy. In postmodern fiction, the disorder of entropy was often compared favorably to the stifling hegemony of cultural universalism. More broadly, these two responses might be understood to represent two societal stages of grief-- denial and acceptance—to the new trauma introduced to the world by the parallel concepts of cultural entropy and a Universal “heat death.”
Promising Results from the Use of a Korean Drama to Address Knowledge, Attitudes, and Behaviors on School Bullying and Mental Health among Asian American College-Aged Students
Authors: Ta Park Van My , Suen Diwata Joyce , Win Nolee , Ton Vy , Nam Bora , Rajabally Waleed , Jones Vanya C.
Published: March 2020

The limited research on bullying, mental health (MH), and help-seeking for Asian American (ASA) college students is concerning due to the public health importance. Korean drama (K-Drama) television shows may be an innovative approach to improve knowledge, attitudes, and behaviors (KAB) on bullying. This study examined whether the KAB about school bullying improved after watching a K-Drama and asked participants about their perspectives of using a K-Drama as an intervention. A convenience sample of college students (n = 118) watched a K-Drama portraying school bullying and MH issues. Pre-/post-tests on KAB on bullying were conducted. Interviews (n = 16) were used to understand their experiences with K-Dramas. The mean age was 22.1 years (1.6 SD), 83.9% were female, and 77.1% were ASAs. Many reported experiences with anxiety (67.8%), depression (38.1%), and school bullying victim experience (40.8%). Post-test scores revealed significant differences in knowledge by most school bullying variables (e.g., victim; witness) and MH issues. There were varying significant findings in post-test scores in attitudes and behaviors by these variables. Participants reported that they “love” the drama, felt an emotional connection, and thought that K-Dramas can be an educational tool for ASAs. K-Dramas may be an effective population-level tool to improve health outcomes among ASAs.
Cigarette Smoking and Its Associations with Substance Use and HIV-Related Sexual Risks among Chinese Men Who Have Sex with Men
Authors: Xu Wenjian , Tang Wanjie , Zhang Jing , Shi Xin , Zheng Yong , Kaufman Michelle R.
Published: March 2020

China has the largest population of male smokers globally. Men who have sex with men (MSM) are at greater risk of cigarette smoking compared to the general population. Limited data are available regarding cigarette smoking and its associations with other health issues among Chinese MSM. Eligible MSM (n = 1100) were recruited from mainland China using an online national cross-sectional survey conducted in 2014–2015. Socio-demographic characteristics, smoking behavior, substance use, homosexual stigma and outness, HIV-related risk behavior, and HIV status were obtained. Logistic regression analyses were performed to evaluate predictors of current cigarette smoking frequency and the co-occurrence of smoking and drug use. Nearly 41% (n = 446) of participants had ever smoked cigarettes; 25% (n = 278) were current frequent smokers; and 13% (n = 138) were current infrequent smokers. Factors associated with a history of smoking included age, employment status, and monthly salary. Risk factors associated with current frequent smoking included self-identification as gay, having female sexual partners, binge drinking, drug use, higher levels of homosexual stigma, and being partially or fully “out” as gay. Adjusted multinomial analysis showed that human immunodeficiency virus (HIV) related risks, including risky sexual behaviors, lack of condom use, and a reported history of sexually transmitted infections (STIs), were associated with co-occurrence of current smoking and drug use. Cigarette smoking rates remain high among MSM in China. Cigarette smoking is associated with binge drinking, drug use, and HIV-related risks in this community. There is a clear opportunity for smoking cessation interventions to be linked with HIV and substance use prevention interventions, thereby addressing multiple health issues simultaneously for the MSM community in China.
Does Better Health-Related Knowledge Predict Favorable Health Behavior in Adolescents?
Authors: Nagy-Pénzes Gabriella , Vincze Ferenc , Sándor János , Bíró Éva
Published: March 2020

The importance of puberty on later health status and behavior is indisputable, which also means that it is worth making intervention efforts during this period of life. However, whether better health-related knowledge is correlated with favorable health behavior in adolescents is an important, still unanswered question. Our objective was to examine this relationship. The participants were ninth-grade secondary school students. Data were collected using anonymous, self-administered questionnaires. The knowledge-related questions were compiled by the authors, while the questions concerning eating habits, physical activity, demographic and socioeconomic data were taken from the Health Behavior in School-Aged Children survey. The relationship between knowledge and behavior was investigated with structural equation modeling adjusted for gender, age, and socioeconomic status. The results demonstrated a good fit to the data, but better knowledge was not related to behavior in our sample. This finding suggests that adolescents’ health behavior is highly influenced by the living context; therefore, appropriate knowledge is necessary but not sufficient to improve adolescents’ behavior. Hence, comprehensive health promotion programs could provide solutions for encouraging healthy behavior.
The Effect of Ultraviolet B Irradiation Compared with Oral Vitamin D Supplementation on the Well-being of Nursing Home Residents with Dementia: A Randomized Controlled Trial
Authors: Veleva Bistra I. , Caljouw Monique A. A. , van der Steen Jenny T. , Mertens Bart J. A. , Chel Victor G. M. , Numans Mattijs E.
Published: March 2020

There are indications that ultraviolet B (UVB) exposure has beneficial effects on well-being through mechanisms other than vitamin D synthesis alone. We conducted a randomized controlled multicenter trial to compare the effects of UVB light and vitamin D supplementation (VD) in terms of the well-being of nursing home residents with dementia. Participants were randomly assigned to the intervention group (UVB group, n = 41; half-body UVB irradiation, twice weekly over 6 months, with 1 standard erythema dose (SED)) or to the control group (VD group, n = 37; 5600 International units (IU) cholecalciferol supplementation once a week). The main outcome was well-being, measured by the Cohen-Mansfield Agitation Inventory (CMAI) and the Cornell scale for depression in dementia at 0, 3, and 6 months. Secondary outcomes were QUALIDEM quality of life domains and biochemical parameters of bone homeostasis. Intention-to-treat analysis with linear mixed modeling showed no significant between-group differences on agitation (p = 0.431) or depressive symptoms (p = 0.982). At six months, the UVB group showed less restless/tense behavior compared to the VD group (mean difference of the mean change scores 2.2, 95% CI 0.8 to 3.6; p = 0.003 for group x time interaction) and lower serum 25(OH)D3 concentration (estimated mean difference - 21.9, 95% CI −32.6 to −11.2; p = 0.003 for group difference). The exposure of nursing home residents with dementia to UVB light showed no positive benefits in terms of wellbeing. UVB treatment may have a positive effect on the restless/tense behavior characteristic of advanced dementia but more research is needed to confirm this finding.
Periodontal Condition Is Correlated with Deep and Subcortical White Matter Hyperintensity Lesions in Japanese Adults
Authors: Hada Minako , Azuma Tetsuji , Irie Koichiro , Yonenaga Takatoshi , Watanabe Kazutoshi , Deguchi Fumiko , Obora Akihiro , Kojima Takao , Tomofuji Takaaki
Published: March 2020

Deep and subcortical white matter hyperintensity (DSWMH) lesions are a small-vessel disease of the brain. The aim of this cross-sectional study was to investigate the relationship between DSWMH lesions and periodontal status in Japanese adults who participated in a health check. We enrolled 444 consecutive participants (mean age, 54.5 years) who received both brain and oral health evaluation services at the Asahi University Hospital. Magnetic resonance imaging was used to detect DSWMH lesions. Periodontal status was assessed using the community periodontal index. Of the study participants, 215 (48.4%) had DSWMH lesions. Multivariate logistic regression showed that the presence of DSWMH lesions was significantly related to age ≥ 65 years (vs. < 65 years, odds ratio [OR] = 2.984, 95% confidence interval [CI] = 1.696–5.232), systolic blood pressure ≥ 140 mmHg (vs. < 140 mmHg, OR = 2.579, 95% CI = 1.252–5.314), the presence of ≥ 28 teeth (vs. < 28 teeth, OR = 0.635, 95% CI = 0.420–0.961), and probing pocket depth (PPD) ≥ 6 mm (vs. PPD < 6 mm, OR = 1.948, 95% CI = 1.132–3.354) after adjustment for confounding factors. Having PPD ≥ 6 mm may be a risk factor for DSWMH lesions in Japanese adults.
Building Interdisciplinary Partnerships for Community-Engaged Environmental Health Research in Appalachian Virginia
Authors: Satterwhite Emily , Bell Shannon Elizabeth , Marr Linsey C. , Thompson Christopher K. , Prussin Aaron J. , Buttling Lauren , Pan Jin , Gohlke Julia M.
Published: March 2020

This article describes a collaboration among a group of university faculty, undergraduate students, local governments, local residents, and U.S. Army staff to address long-standing concerns about the environmental health effects of an Army ammunition plant. The authors describe community-responsive scientific pilot studies that examined potential environmental contamination and a related undergraduate research course that documented residents’ concerns, contextualized those concerns, and developed recommendations. We make a case for the value of resource-intensive university–community partnerships that promote the production of knowledge through collaborations across disciplinary paradigms (natural/physical sciences, social sciences, health sciences, and humanities) in response to questions raised by local residents. Our experience also suggests that enacting this type of research through a university class may help promote researchers’ adoption of “epistemological pluralism”, and thereby facilitate the movement of a study from being “multidisciplinary” to “transdisciplinary”.
Progress towards Health for All: Time to End Discrimination and Marginalization
Authors: Gilmour Stuart , Mai Phuong Le , Nguyen Phuong , Dhungel Bibha , Tomizawa Maki , Nguyen Huy
Published: March 2020

Although it has been more than 40 years since “health for all” was presented as a focus in the Alma Ata declaration [...]
Participation and Performance Trends in the Oldest 100-km Ultramarathon in the World
Authors: Knechtle Beat , Scheer Volker , Nikolaidis Pantelis Theodoros , Sousa Caio Victor
Published: March 2020

Participation and performance trends in ultramarathon running have been investigated for large datasets and long period of times with an increase in participants and an improvement in performance. However, the analysis of ultramarathons across many decades is missing. We analyzed these trends for 96,036 athletes (88,286 men and 7750 women) from 67 countries competing between 1956 and 2019 in ‘100 km Lauf Biel’ in Switzerland, the oldest 100-km ultramarathon in the world. More men than women participated in all years. The number of male participants reached a peak at around 1985 and a decline in participation occurred thereafter. Women started competing in 1962. Men were always faster than women and both women and men reduced their race times over years. After about 1985, both overall women and men and both female and male winners were not able to improve race times. For men, athletes from all age groups below the age of 49 years old reached a peak of participation in the 1980s, and showed a decrease since then. Regarding age groups, the decrease first started in age group 20–29 years, followed by 30–39, 40–49, 50–59, and 60–69 years. For athletes in age groups 70–79 and 80–89 years, no decrease occurred. For women, age group athletes in age groups 40–49, 50–59, and 60–69 years increased their participation, whereas age groups 20–29 and 30–39 peaked in the late 1980s and started to decrease or stabilize, respectively. Switzerland, Germany, and France were the countries with the highest numbers of participants throughout the history of the race. In men, race times increased after about 1990 for most nationalities; only runners from Germany seemed to stabilize their performance. In women, runners from Italy, France, and Austria improved their performance over the years. In summary, the analysis of the oldest 100-km ultramarathon in the world showed a decrease in participation and an impairment in performance in the last 60 years. These changes were due to a decrease in the number of male ultramarathoners in around the 1980s, where mainly the number of age group runners younger than 70 years decreased.
In Utero Exposure to Aluminium and Other Neurotoxic Elements in Urban Coastal South African Women at Delivery: An Emerging Concern
Authors: Röllin Halina B. , Channa Kalavati , Olutola Bukola , Nogueira Claudina , Odland Jon Ø.
Published: March 2020

Aluminium (Al) is a non-essential neurotoxicant and there is limited information regarding exposure to Al in utero. This study sought to evaluate the in utero exposure to Al in urban South African women, its effects on birth outcomes and possible synergistic effects between Al, essential and neurotoxic elements such as lead (Pb), mercury (Hg) and arsenic (As), as well as a a potential sex-dependent response to these elements in neonates. This study has found elevated levels of Al in urban women at delivery. The Spearman’s rank correlation coefficients (p-value) of the association between maternal serum Al and birth outcomes (gestational age and parity), and between maternal serum Al and Cu, Zn and Se, were statistically significant. However, in the general and the stratified models, no association was found between any of the birth outcomes and maternal serum Al. The association between maternal serum Al and neurotoxic elements at delivery showed a significant positive correlation for Pb only (rho = 0.361; p < 0.001) which was found to be sex-dependent in neonates (males, rho = 0.285; p < 0.004 and females, rho = 0.444, p < 0.001). Our preliminary findings indicate that in utero exposure to Al is an emerging concern requiring further research and directives from public health authorities.
Low Burden Strategies Are Needed to Reduce Smoking in Rural Healthcare Settings: A Lesson from Cancer Clinics
Authors: Ramsey Alex T. , Baker Timothy B. , Pham Giang , Stoneking Faith , Smock Nina , Colditz Graham A. , James Aimee S. , Liu Jingxia , Bierut Laura J. , Chen Li-Shiun
Published: March 2020

Rural populations face significant smoking-related health disparities, such as a higher prevalence of lung cancer and cancer mortality, higher prevalence of smoking, and lower likelihood of receiving cessation treatment than urban counterparts. A significant proportion of health disparities in rural populations could be eliminated with low-barrier, easy-access treatment delivery methods for smoking cessation. In this study, we assessed treatment engagement among patients in rural and urban settings. Then, we examined the effect of an electronic health record-based smoking cessation module on patient receipt of evidence-based cessation care. As part of a quality improvement project, we retrospectively observed 479,798 unique patients accounting for 1,426,089 outpatient clinical encounters from June 2018–March 2019 across 766 clinics in the greater St. Louis, southern Illinois, and mid-Missouri regions. Smoking prevalence was higher in rural versus urban clinics (20.7% vs. 13.9%, 6.7% [6.3, 7.1], odds ratio = 1.6 [1.6, 1.6], p < 0.0001), and yet rural smokers were nearly three times less likely than their urban counterparts to receive any smoking cessation treatment after adjusting for patients clustering within clinics (9.6% vs. 25.8%, −16.2% [−16.9, −15.5], odds ratio = 0.304 [0.28, 0.33], p < 0.0001). Although not yet scaled up in the rural setting, we examined the effects of a low-burden, point-of-care smoking module currently implemented in cancer clinics. After adjusting for patient clustering within clinics, patients were more likely to receive smoking treatment in clinics that implemented the module versus clinics that did not implement the module (31.2% vs. 17.5%, 13.7% [10.8, 16.6], odds ratio = 2.1 [1.8, 2.6], p < 0.0001). The point-of-care treatment approach offers a promising solution for rural settings, both in and outside the context of cancer care.
Kindergarten Teachers’ Perspectives on Young Children’s Bullying Roles in Relation to Dominance and Peer Relationships: A Short-Term Longitudinal Approach in South Korea
Authors: Lee Seung-ha
Published: March 2020

There are several studies on young children’s bullying roles in relation to dominance or peer relationships. Although those are closely related, few studies examined this from longitudinal view and the influence of bullying role change on dominance and peer relationships. This study aimed to examine (1) the relationship between bullying roles and dominance, (2) the relationship between bullying roles and peer relationships, (3) the percentage of bullying role change over time, and (4) the changes in bullying roles in relation to changes in dominance and peer relationships. Sixty-three South Korean kindergarten teachers completed questionnaires regarding bullying roles, dominance, and peer relationships about 1312 children aged 3–5. The data were collected in mid-October 2017 and January 2018. The results showed that bullies had the highest dominance. No-role children had the most positive peer relationships, followed by bullies. About 10% of all sampled children remained involved in bullying over time. Their role changes related to changes in dominance rather than to changes in peer relationships. The findings imply that dominance should be considered to prevent young children’s bullying, in which peer relationships are interrelated. Intervention should be implemented as soon as possible to stop repeated victimization or bullying in early childhood.
State-Dependent Stock Liquidity Premium: The Case of the Warsaw Stock Exchange
Authors: Stereńczak Szymon
Published: March 2020

The effect of stock liquidity on stock returns is well documented in the developed capital markets, while similar studies on emerging markets are still scarce and their results ambiguous. This paper aims to analyze the state-dependent variance of liquidity premium in the Polish stock market. The Polish capital market may serve as a benchmark for other emerging markets in the region of Central and Eastern Europe, hence the results of this research should be of great interest for investors and policy makers in Poland and other post-communist European countries. In the empirical, study a unique empirical methodology has been applied, which guarantees the uniqueness of the results obtained. The results obtained suggest that on the Polish stock market exists stock liquidity premium, which is statistically significant, but constitutes only a small fraction of returns. It also does not increase during periods of bearish market, what results from the lengthening of average holding period when market liquidity decreases.
Aberrant Expression of RAD52, Its Prognostic Impact in Rectal Cancer and Association with Poor Survival of Patients
Authors: Ho Vincent , Chung Liping , Singh Amandeep , Lea Vivienne , Abubakar Askar , Lim Stephanie H. , Chua Wei , Ng Weng , Lee Mark , Roberts Tara L. , de Souza Paul , Lee Cheok Soon
Published: March 2020

The DNA damage response enables cells to survive and maintain genome integrity. RAD52 is a DNA-binding protein involved in the homologous recombination in DNA repair, and is important for the maintenance of tumour genome integrity. We investigated possible correlations between RAD52 expression and cancer survival and response to preoperative radiotherapy. RAD52 expression was examined in tumour samples from 179 patients who underwent surgery for rectal cancer, including a sub-cohort of 40 patients who were treated with neoadjuvant therapy. A high score for RAD52 expression in the tumour centre was significantly associated with worse disease-free survival (DFS; p = 0.045). In contrast, reduced RAD52 expression in tumour centre samples from patients treated with neoadjuvant therapy (n = 40) significantly correlated with poor DFS (p = 0.025) and overall survival (OS; p = 0.048). Our results suggested that RAD52 may have clinical value as a prognostic marker of tumour response to neoadjuvant radiation and both disease-free status and overall survival in patients with rectal cancer.
EPA is More Effective than DHA to Improve Depression-Like Behavior, Glia Cell Dysfunction and Hippcampal Apoptosis Signaling in a Chronic Stress-Induced Rat Model of Depression
Authors: Peng Zhilan , Zhang Cai , Yan Ling , Zhang Yongping , Yang Zhiyou , Wang Jiajia , Song Cai
Published: March 2020

Clinical evidence indicated that eicosapentaenoic acid (EPA) was more effective than docosahexaenoic acid (DHA) in depression treatment. However, possible mechanisms remain unclear. Here, a chronic unpredictable mild stress (CUMS)-induced model of depression was used to compare EPA and DHA anti-depressant effects. After EPA or DHA feeding, depression-like behavior, brain n-3/n-6 PUFAs profile, serum corticosterone and cholesterol concentration, hippocampal neurotransmitters, microglial and astrocyte related function, as well as neuronal apoptosis and survival signaling pathways were studied. EPA was more effective than DHA to ameliorate CUMS-induced body weight loss, and depression-like behaviors, such as increasing sucrose preference, shortening immobility time and increasing locomotor activity. CUMS-induced corticosterone elevation was reversed by bother fatty acids, while increased cholesterol was only reduced by EPA supplement. Lower hippocampal noradrenaline and 5-hydroxytryptamine concentrations in CUMS rats were also reversed by both EPA and DHA supplement. However, even though CUMS-induced microglial activation and associated increased IL-1β were inhibited by both EPA and DHA supplement, increased IL-6 and TNF-α levels were only reduced by EPA. Compared to DHA, EPA could improve CUMS-induced suppressive astrocyte biomarkers and associated BDNF-TrkB signaling. Moreover, EPA was more effective than DHA to attenuate CUMS-induced higher hippocampal NGF, GDNF, NF-κB, p38, p75, and bax expressions, but reversed bcl-2 reduction. This study for the first time revealed the mechanisms by which EPA was more powerful than DHA in anti-inflammation, normalizing astrocyte and neurotrophin function and regulating NF-κB, p38 and apoptosis signaling. These findings reveal the different mechanisms of EPA and DHA in clinical depression treatment.
Insulin: The Friend and the Foe in the Development of Type 2 Diabetes Mellitus
Authors: Rachdaoui Nadia
Published: March 2020

Insulin, a hormone produced by pancreatic β-cells, has a primary function of maintaining glucose homeostasis. Deficiencies in β-cell insulin secretion result in the development of type 1 and type 2 diabetes, metabolic disorders characterized by high levels of blood glucose. Type 2 diabetes mellitus (T2DM) is characterized by the presence of peripheral insulin resistance in tissues such as skeletal muscle, adipose tissue and liver and develops when β-cells fail to compensate for the peripheral insulin resistance. Insulin resistance triggers a rise in insulin demand and leads to β-cell compensation by increasing both β-cell mass and insulin secretion and leads to the development of hyperinsulinemia. In a vicious cycle, hyperinsulinemia exacerbates the metabolic dysregulations that lead to β-cell failure and the development of T2DM. Insulin and IGF-1 signaling pathways play critical roles in maintaining the differentiated phenotype of β-cells. The autocrine actions of secreted insulin on β-cells is still controversial; work by us and others has shown positive and negative actions by insulin on β-cells. We discuss findings that support the concept of an autocrine action of secreted insulin on β-cells. The hypothesis of whether, during the development of T2DM, secreted insulin initially acts as a friend and contributes to β-cell compensation and then, at a later stage, becomes a foe and contributes to β-cell decompensation will be discussed.
Synthetic HDL Nanoparticles Delivering Docetaxel and CpG for Chemoimmunotherapy of Colon Adenocarcinoma
Authors: Scheetz Lindsay M. , Yu Minzhi , Li Dan , Castro María G. , Moon James J. , Schwendeman Anna
Published: March 2020

Colon carcinomas comprise over two-thirds of all colorectal cancers with an overall 5-year survival rate of 64%, which rapidly decreases to 14% when the cancer becomes metastatic. Depending on the stage of colon carcinoma at diagnosis, patients can undergo surgery to attempt complete tumor resection or move directly to chemotherapy with one or a combination of drugs. As with most cancers, colon carcinomas do not always respond to chemotherapies, so targeted therapies and immunotherapies have been developed to aid chemotherapy. We report the development of a local combination therapy for colon carcinoma whereby chemo- and immunotherapeutic entities are delivered intratumorally to maximize efficacy and minimize off-target side effects. A hydrophobic chemotherapeutic agent, docetaxel (DTX), and cholesterol-modified Toll-like receptor 9 (TLR9) agonist CpG (cho-CpG) oligonucleotide are co-loaded in synthetic HDL (sHDL) nanodiscs. In vivo survival analysis of MC-38 tumor-bearing mice treated intratumorally with DTX-sHDL/CpG (median survival; MS = 43 days) showed significant improvement in overall survival compared to mice treated with single agents, free DTX (MS = 23 days, p < 0.0001) or DTX-sHDL (MS = 28 days, p < 0.0001). Two of seven mice treated with DTX-sHDL/CpG experienced complete tumor regression. None of the mice experienced any systemic toxicity as indicated by body weight maintenance and normal serum enzyme and protein levels. In summary, we have demonstrated that chemo- and immunotherapies can be co-loaded into sHDLs, delivered locally to the tumor, and can be used to improve survival outcomes significantly compared to chemotherapy alone.
Upregulation of CD20 Positive B-Cells and B-Cell Aggregates in the Tumor Infiltration Zone is Associated with Better Survival of Patients with Pancreatic Ductal Adenocarcinoma
Authors: Brunner Maximilian , Maier Katharina , Rümmele Petra , Jacobsen Anne , Merkel Susanne , Benard Alan , Krautz Christian , Kersting Stephan , Grützmann Robert , Weber Georg F.
Published: March 2020

Patients with pancreatic ductal adenocarcinoma (PDAC) normally have a poor long-term prognosis. However, some rare cases of long-term survivors have been reported. The tumor microenvironment, consisting of cellular and stromal components, possibly plays an important role and might influence prognosis. In this context, the role of tumor-infiltrating B-cells and its impact on the survival in patients with PDAC remains controversial. We therefore aimed to assess the prognostic value of CD20-positive B-cells and CD20-positive B-cell aggregates as well as CD138, IgM, Pax5, and Ki67 on the survival of patients with PDAC using immunohistochemistry of FFPE pancreatectomy tissue sections from patients that underwent primary surgery for pT3- and R0-pancreatic adenocarcinoma between 1995 and 2016. Patients with PDAC were matched and grouped in 16 long-term-survivors (LTS, median overall survival (OS): 96 months [range: 61–177 months]) and 16 short-term-survivors (STS, median OS: 16 months [range: 7–32 months]). CD20-positive B-cells and B-cell aggregates in the tumor infiltration zone were significantly upregulated in the LTS-group compared to the STS-group (p = 0.0499 respectively p = 0.0432). Regarding the entire patient cohort (n = 32) CD20 positive B-cell aggregates in the tumor infiltration zone were an independent prognostic marker for overall survival in multivariate analysis (HR 9.2, CI 1.6–51.4, p = 0.012). These results underline the importance of tumor-associated B-cells for prognosis of patients with PDAC. The detailed role of B cells in the pathomechanism of PDAC should be further investigated for predicting outcome, identifying appropriate treatment regimens, and developing novel therapeutic options.
Oxylipin Profiles as Functional Characteristics of Acute Inflammatory Responses in Astrocytes Pre-Treated with IL-4, IL-10, or LPS
Authors: Chistyakov Dmitry V. , Gavrish Gleb E. , Goriainov Sergei V. , Chistyakov Viktor V. , Astakhova Alina A. , Azbukina Nadezda V. , Sergeeva Marina G.
Published: March 2020

Functional phenotypes, which cells can acquire depending on the microenvironment, are currently the focus of investigations into new anti-inflammatory therapeutic approaches. Glial cells, microglia, and astrocytes are major participants in neuroinflammation, but their roles differ, as microglia are cells of mesodermal origin, while astrocytes are cells of ectodermal origin. The inflammatory phenotype of cells can be modulated by ω-6- and ω-3-polyunsaturated fatty acid-derived oxylipins, although data on changes in oxylipin profiles in different cell adaptations to pro- and anti-inflammatory stimuli are scarce. Our study aimed to compare UPLC-MS/MS-measured oxylipin profiles in various rat astrocyte adaptation states. We used cells treated for 24 h with lipopolysaccharide (LPS) for classical pro-inflammatory adaptation and with interleukin 4 (IL-4) or 10 (IL-10) for alternative anti-inflammatory adaptation, with the resulting phenotypes characterized by quantitative real-time PCR (RT-PCR). We also tested long-term, low-concentration LPS treatment (endotoxin treatment) as a model of astrocyte adaptations. The functional response of astrocytes was estimated by acute (4 h) LPS-induced cell reactivity, measured by gene expression markers and oxylipin synthesis. We discovered that, as well as gene markers, oxylipin profiles can serve as markers of pro- (A1-like) or anti-inflammatory (A2-like) adaptations. We observed predominant involvement of ω-6 polyunsaturated fatty acid (PUFA) and the cyclooxygenase branch for classical (LPS) pro-inflammatory adaptations and ω-3 PUFA and the lipoxygenase branch for alternative (IL-4) anti-inflammatory adaptations. Treatment with IL-4, but not IL-10, primes the ability of astrocytes to activate the innate immunity signaling pathways in response to LPS. Endotoxin-treated astrocytes provide an alternative anti-inflammatory adaptation, which makes cells less sensitive to acute LPS stimulation than the IL-4 induced adaptation. Taken together, the data reveal that oxylipin profiles associate with different states of polarization to generate a pro-inflammatory or anti-inflammatory phenotype. This association manifests itself both in native cells and in their responses to a pro-inflammatory stimulus.
Systems Biology Analysis Reveals Eight SLC22 Transporter Subgroups, Including OATs, OCTs, and OCTNs
Authors: Engelhart Darcy C. , Granados Jeffry C. , Shi Da , Saier Jr. Milton H. , Baker Michael E. , Abagyan Ruben , Nigam Sanjay K.
Published: March 2020

The SLC22 family of OATs, OCTs, and OCTNs is emerging as a central hub of endogenous physiology. Despite often being referred to as “drug” transporters, they facilitate the movement of metabolites and key signaling molecules. An in-depth reanalysis supports a reassignment of these proteins into eight functional subgroups, with four new subgroups arising from the previously defined OAT subclade: OATS1 (SLC22A6, SLC22A8, and SLC22A20), OATS2 (SLC22A7), OATS3 (SLC22A11, SLC22A12, and Slc22a22), and OATS4 (SLC22A9, SLC22A10, SLC22A24, and SLC22A25). We propose merging the OCTN (SLC22A4, SLC22A5, and Slc22a21) and OCT-related (SLC22A15 and SLC22A16) subclades into the OCTN/OCTN-related subgroup. Using data from GWAS, in vivo models, and in vitro assays, we developed an SLC22 transporter-metabolite network and similar subgroup networks, which suggest how multiple SLC22 transporters with mono-, oligo-, and multi-specific substrate specificity interact to regulate metabolites. Subgroup associations include: OATS1 with signaling molecules, uremic toxins, and odorants, OATS2 with cyclic nucleotides, OATS3 with uric acid, OATS4 with conjugated sex hormones, particularly etiocholanolone glucuronide, OCT with neurotransmitters, and OCTN/OCTN-related with ergothioneine and carnitine derivatives. Our data suggest that the SLC22 family can work among itself, as well as with other ADME genes, to optimize levels of numerous metabolites and signaling molecules, involved in organ crosstalk and inter-organismal communication, as proposed by the remote sensing and signaling theory.
Arginine Derivatives in Cerebrovascular Diseases: Mechanisms and Clinical Implications
Authors: Grosse Gerrit M. , Schwedhelm Edzard , Worthmann Hans , Choe Chi-un
Published: March 2020

The amino acid L-arginine serves as substrate for the nitric oxide synthase which is crucial in vascular function and disease. Derivatives of arginine, such as asymmetric (ADMA) and symmetric dimethylarginine (SDMA), are regarded as markers of endothelial dysfunction and have been implicated in vascular disorders. While there is a variety of studies consolidating ADMA as biomarker of cerebrovascular risk, morbidity and mortality, SDMA is currently emerging as an interesting metabolite with distinct characteristics in ischemic stroke. In contrast to dimethylarginines, homoarginine is inversely associated with adverse events and mortality in cerebrovascular diseases and might constitute a modifiable protective risk factor. This review aims to provide an overview of the current evidence for the pathophysiological role of arginine derivatives in cerebrovascular ischemic diseases. We discuss the complex mechanisms of arginine metabolism in health and disease and its potential clinical implications in diverse aspects of ischemic stroke.
Cell Fusion-Mediated Tissue Regeneration as an Inducer of Polyploidy and Aneuploidy
Authors: Dörnen Jessica , Sieler Mareike , Weiler Julian , Keil Silvia , Dittmar Thomas
Published: March 2020

The biological phenomenon of cell fusion plays a crucial role in several physiological processes, including wound healing and tissue regeneration. Here, it is assumed that bone marrow-derived stem cells (BMSCs) could adopt the specific properties of a different organ by cell fusion, thereby restoring organ function. Cell fusion first results in the production of bi- or multinucleated hybrid cells, which either remain as heterokaryons or undergo ploidy reduction/heterokaryon-to-synkaryon transition (HST), thereby giving rise to mononucleated daughter cells. This process is characterized by a merging of the chromosomes from the previously discrete nuclei and their subsequent random segregation into daughter cells. Due to extra centrosomes concomitant with multipolar spindles, the ploidy reduction/HST could also be associated with chromosome missegregation and, hence, induction of aneuploidy, genomic instability, and even putative chromothripsis. However, while the majority of such hybrids die or become senescent, aneuploidy and genomic instability appear to be tolerated in hepatocytes, possibly for stress-related adaption processes. Likewise, cell fusion-induced aneuploidy and genomic instability could also lead to a malignant conversion of hybrid cells. This can occur during tissue regeneration mediated by BMSC fusion in chronically inflamed tissue, which is a cell fusion-friendly environment, but is also enriched for mutagenic reactive oxygen and nitrogen species.
Combined Use of CFTR Correctors in LGMD2D Myotubes Improves Sarcoglycan Complex Recovery
Authors: Carotti Marcello , Scano Martina , Fancello Irene , Richard Isabelle , Risato Giovanni , Bensalah Mona , Soardi Michela , Sandonà Dorianna
Published: March 2020

Sarcoglycanopathies are rare limb girdle muscular dystrophies, still incurable, even though symptomatic treatments may slow down the disease progression. Most of the disease-causing defects are missense mutations leading to a folding defective protein, promptly removed by the cell’s quality control, even if possibly functional. Recently, we repurposed small molecules screened for cystic fibrosis as potential therapeutics in sarcoglycanopathy. Indeed, cystic fibrosis transmembrane regulator (CFTR) correctors successfully recovered the defective sarcoglycan-complex in vitro. Our aim was to test the combined administration of some CFTR correctors with C17, the most effective on sarcoglycans identified so far, and evaluate the stability of the rescued sarcoglycan-complex. We treated differentiated myogenic cells from both sarcoglycanopathy and healthy donors, evaluating the global rescue and the sarcolemma localization of the mutated protein, by biotinylation assays and western blot analyses. We observed the additive/synergistic action of some compounds, gathering the first ideas on possible mechanism/s of action. Our data also suggest that a defective α-sarcoglycan is competent for assembly into the complex that, if helped in cell traffic, can successfully reach the sarcolemma. In conclusion, our results strengthen the idea that CFTR correctors, acting probably as proteostasis modulators, have the potential to progress as therapeutics for sarcoglycanopathies caused by missense mutations.
Characterization and Cytotoxicity Assessment of the Lipophilic Fractions of Different Morphological Parts of Acacia dealbata
Authors: Oliveira Cátia S. D. , Moreira Patrícia , Resende Judite , Cruz Maria T. , Pereira Cláudia M. F. , Silva Artur M. S. , Santos Sónia A. O. , Silvestre Armando J. D.
Published: March 2020

Acacia dealbata biomass, either from forest exploitation or from the management of invasive species, can be a strategic topic, namely as a source of high-value compounds. In this sense, the present study aimed at the detailed characterization of the lipophilic components of different morphological parts of A. dealbata and the evaluation of their cytotoxicity in cells representative of different mammals’ tissues. The chemical composition of lipophilic extracts from A. dealbata bark, wood and leaves was evaluated using gas chromatography-mass spectrometry (GC–MS). Terpenic compounds (representing 50.2%–68.4% of the total bark and leaves extracts, respectively) and sterols (60.5% of the total wood extract) were the main components of these extracts. Other constituents, such as fatty acids, long-chain aliphatic alcohols, monoglycerides, and aromatic compounds were also detected in the studied extracts. All the extracts showed low or no cytotoxicity in the different cells tested, demonstrating their safety profile and highlighting their potential to be used in nutraceutical or pharmaceutical applications. This study is therefore an important contribution to the valorization of A. dealbata, demonstrating the potential of this species as a source of high value lipophilic compounds.
Structural Characterization of an Archaeal Lipid Bilayer as a Function of Hydration and Temperature
Authors: Salvador-Castell Marta , Demé Bruno , Oger Philippe , Peters Judith
Published: March 2020

Archaea, the most extremophilic domain of life, contain ether and branched lipids which provide extraordinary bilayer properties. We determined the structural characteristics of diether archaeal-like phospholipids as functions of hydration and temperature by neutron diffraction. Hydration and temperature are both crucial parameters for the self-assembly and physicochemical properties of lipid bilayers. In this study, we detected non-lamellar phases of archaeal-like lipids at low hydration levels, and lamellar phases at levels of 90% relative humidity or more exclusively. Moreover, at 90% relative humidity, a phase transition between two lamellar phases was discernible. At full hydration, lamellar phases were present up to 70 °C and no phase transition was observed within the temperature range studied (from 25 °C to 70 °C). In addition, we determined the neutron scattering length density and the bilayer’s structural parameters from different hydration and temperature conditions. At the highest levels of hydration, the system exhibited rearrangements on its corresponding hydrophobic region. Furthermore, the water uptake of the lipids examined was remarkably high. We discuss the effect of ether linkages and branched lipids on the exceptional characteristics of archaeal phospholipids.