bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between Organophosphate and Pyrethroid Insecticides in Blood and Their Metabolites in Urine: A Pilot Study
Authors: Simaremare Sailent Rizki Sari , Hung Chien-Che , Hsieh Chia-Jung , Yiin Lih-Ming
Published: December 2019

We conducted a pilot study to examine the relationship between organophosphate (OP) and pyrethroid (PYR) insecticides in blood and their metabolites in urine. A total of 30 pregnant women were enrolled in the study, and blood and urine was sampled from each subject during a regular clinic visit. Two OP and nine PYR insecticides were selected for blood sample analysis, while six OP and five PYR metabolites were analyzed for urine specimens. Both types of samples were processed and analyzed on gas chromatography-mass spectrometry. For OPs in blood, chlorpyrifos had a higher mean concentration (73.33 µg/L) than terbufos. For PYRs in blood, cypermethrin and imiprothrin were the most frequently detected species with the highest mean concentrations (151.25 and 141.25 µg/L). The concentrations of PYRs appeared to be higher than that of OPs, and the most frequently detected PYRs were commonly used in domestic products, suggesting that the exposure could mostly originate from use of domestic insecticides. The correlation between insecticides in blood and their metabolites in urine was significantly high (r = 0.795 for OPs and 0.882 for PYRs, p < 0.001), indicating routine exposure at a steady state. Residents should be cautious with domestic use of insecticide products to lower their exposure.
Diagnostic Accuracy of Body Mass Index in Defining Childhood Obesity: Analysis of Cross-Sectional Data from Ghanaian Children
Authors: Adom Theodosia , Kengne André Pascal , De Villiers Anniza , Boatin Rose , Puoane Thandi
Published: December 2019

Background: Screening methods for childhood obesity are based largely on the published body mass index (BMI) criteria. Nonetheless, their accuracy in African children is largely unknown. The diagnostic accuracies of the World Health Organization (WHO), the Centers for Disease Control and Prevention (CDC), and the International Obesity Taskforce (IOTF) BMI-based criteria in defining obesity using deuterium dilution as a criterion method in a sample of Ghanaian children are presented. Methods: Data on anthropometric indices and percent body fat were collected from 183 children aged 8–11 years. The sensitivity, specificity, and predictive values were calculated. The overall performance of the BMI criteria was evaluated using the receiver operating characteristics area under the curve (AUC). Results: Overall sensitivity of WHO, CDC, and IOTF were 59.4% (40.6–76.3), 53.1% (34.7–70.9), and 46.9% (29.1–65.3) respectively. The overall specificity was high, ranging from 98.7% by WHO to 100.0% by IOTF. The AUC were 0.936 (0.865–1.000), 0.924 (0.852–0.995), and 0.945 (0.879–1.000) by the WHO, CDC, and IOTF criteria respectively for the overall sample. Prevalence of obesity by the WHO, CDC, IOTF, and deuterium oxide-derived percent body fat were 11.5%, 10.4%, 8.2%, and 17.5% respectively, with significant positive correlations between the BMI z-scores and percent body fat. Conclusions: The BMI-based criteria were largely specific but with moderate sensitivity in detecting excess body fat in Ghanaian children. To improve diagnostic accuracy, direct measurement of body fat and other health risk factors should be considered in addition to BMI.
Exploring Satisfaction and Migration Intentions of Physicians in Three University Hospitals in Poland
Authors: Dubas-Jakóbczyk Katarzyna , Domagała Alicja , Kiedik Dorota , Peña-Sánchez Juan Nicolás
Published: December 2019

Introduction: University hospitals constitute a unique group of health care organizations which traditionally link three functions: (1) providing highly specialized services, (2) teaching activities, and (3) conducting research. Objectives: To assess the level of carrier satisfaction among physicians working in three university hospitals in Poland (1); to assess whether the physicians have the intention to migrate and what the main reasons for migration are (2); and to identify the actions that might be taken at the hospital level to mitigate physicians’ intentions to migrate (3). Methods: Cross-sectional study with both quantitative and qualitative components. In the quantitative part, an online questionnaire was distributed among physicians working in three university hospitals. A total number of 396 questionnaires were analyzed. In the qualitative part, in-depth interviews with six hospital managers were conducted and analyzed using thematic analysis. Results: On a scale from one “very dissatisfied” to six “very satisfied”, the mean career satisfaction of physicians was 4.0 (SD = 0.74). The item with the lowest mean concerned salary level (2.8, SD = 1.41). In the sample, 34% of physicians declared intentions to migrate from Poland. The main reasons for the intention to migrate were: Better working conditions abroad, higher earnings, the ability to maintain better work-life balance, better training opportunities abroad, and problems due to a stressful current workplace. Hospital managers considered the actions that can be taken at the hospital level to mitigate physicians’ migration to be specific to those focused on the working environment. Conclusions: Career development opportunities and features related to the working environment are the main factors influencing physicians’ satisfaction and migration intentions that can be modified at the university hospital level.
The Nature of Reality: Human Stress Recovery during Exposure to Biodiverse, Multisensory Virtual Environments
Authors: Schebella Morgan Faith , Weber Delene , Schultz Lisa , Weinstein Philip
Published: December 2019

Immersive virtual environments (IVEs) were used to test the effects of biodiversity on recovery from induced stress. Three natural environments and one urban environment were used to represent ordinal levels of biodiversity (none, low, moderate, and high). The four IVEs comprised visual, auditory, and olfactory stimuli. An additional high biodiversity IVE without auditory or olfactory stimuli was also included to study the effects of multisensory stimulation per se on recovery from stress and perceptions of biodiversity. Following stress induction via a novel IVE Trier Social Stress Test (TSST-IVE), heart rate and five self-reported well-being measures were used to assess participants’ recovery after immersion in one of the five IVEs. The results showed consistent well-being responses across both self-reported and physiological measures, suggesting biodiversity does directly affect human well-being. However, the relationship was not linear. For most measures of well-being, stress recovery was least effective in the urban IVE, consistent with past research. The low biodiversity IVE elicited the greatest improvement in all well-being measures except self-reported calmness. One could speculate that the landscape features of the least biodiverse IVE may elicit subconscious preferences toward savanna-like landscapes, as suggested by previous studies. The IVE depicting a moderate level of biodiversity was the least restorative of the natural environments. A multisensory experience was associated with better recovery in all measures of well-being than a visual-only experience, and perceptions of landscape components significantly differed between two identical nature scenes when auditory and olfactory stimuli were removed. Nuances in the data and implications of the findings are discussed. The results signal a need for caution and question the assumption that cultural ecosystem services align with positive outcomes for biodiversity conservation.
The Dynamics of Becoming a Mother during Pregnancy and After Childbirth
Authors: Zdolska-Wawrzkiewicz Anna , Bidzan Mariola , Chrzan-Dętkoś Magdalena , Pizuńska Daria
Published: December 2019

Background: The aim of this study was to explore the relationship between one’s maternal attachment style and one’s self-image as a mother, image of one’s mother as a mother, and bond with the child over a period of several months. Methods: A total of 86 women took part in the study The Adjective Check List (ACL), Postpartum Bonding Questionnaire (PBQ), Maternal–Fetal Attachment Scale (MFAS), and a modified version of the Experiences in Close Relationships (ECR) were used. Two measurements were used: during pregnancy and about six months after the birth of the child. Results: In terms of their self-image as mothers, the women had higher results the first time they took the questionnaire, regardless of their attachment style. An interaction effect was found between attachment style and the ‘need for changes’ scale. The image of one’s mother as a mother depended on the level of avoidance in attachment, regardless of the measurement. An interaction effect was found between attachment style and the scale of ‘personal adaptation’. There was a correlation between the bond with the child during pregnancy, the bond following birth, and the style of maternal attachment; the main predictor of the bond with the child after birth is the bond with the child during the pregnancy. Conclusion: Those who provide care for pregnant women and new mothers should be aware of the complex psychological processes in the transition to motherhood, have knowledge about perinatal mental health, and when necessary, refer women to specialists such as support groups for new mothers, trained midwives, psychologists, psychotherapists, or psychiatrists.
Australian Consumer Perceptions of Regionally Grown Fruits and Vegetables: Importance, Enablers, and Barriers
Authors: Godrich Stephanie , Kent Katherine , Murray Sandra , Auckland Stuart , Lo Johnny , Blekkenhorst Lauren , Penrose Beth , Devine Amanda
Published: December 2019

Fresh fruits and vegetables are a cornerstone of a balanced diet; their consumption has health, environmental, ethical, and economic implications. This pilot study aimed to: (i) measure fruit and vegetable consumption; (ii) understand consumer perceptions of the perceived importance of regionally grown fresh fruit and vegetables (RGFFV); and (iii) identify the barriers and enablers of access and consumption of RGFFV. The study took place in Tasmania (TAS) and South Western Australia (SWA). A 54-item survey included questions relating to purchasing and consumption patterns; barriers and enablers related to access and consumption of RGFFV; and sociodemographic information. Survey data were analyzed using Chi-square test and binary logistic regression. A total of n = 120 TAS and n = 123 SWA adult respondents participated. SWA respondents had higher intakes of fruit (p < 0.001) and vegetables (p < 0.001). Almost all respondents (97%) rated purchasing of RGFFV as important. Top enablers included produce freshness (97%), and to financially support local farmers (94%) and the local community (91%). Barriers included limited seasonal availability of the produce (26%), the belief that RGFFV were expensive (12%) and food budgetary constraints (10%). Recommendations include broader marketing and labelling of seasonal RGFFV; increasing ‘buy local’ campaigns; consumer information about how RGFFV benefits producers and communities; and pricing produce according to quality.
Particulate Matter Exposure and Attention-Deficit/Hyperactivity Disorder in Children: A Systematic Review of Epidemiological Studies
Authors: Donzelli Gabriele , Llopis-Gonzalez Agustin , Llopis-Morales Agustin , Cioni Lorenzo , Morales-Suárez-Varela María
Published: December 2019

Attention-deficit/hyperactivity disorder (ADHD) is the most common cognitive and behavioural disorder affecting children, with a worldwide-pooled prevalence of around 5%. Exposure to particulate matter (PM) air pollution is suspected to be associated with autism spectrum disorders and recent studies have investigated the relationship between PM exposure and ADHD. In the absence of any synthesis of the relevant literature on this topic, this systematic review of epidemiological studies aimed to investigate the relationship between the exposure of children to PM and ADHD and identify gaps in our current knowledge. In December 2018, we searched the PubMed and EMBASE databases. We only included epidemiological studies carried out on children without any age limit, measuring PM exposure and health outcomes related to ADHD. We assessed the quality of the articles and the risk of bias for each included article using the Newcastle–Ottawa Scale and the Office of Health Assessment and Translation (OHAT) approach, respectively. The keyword search yielded 774 results. Twelve studies with a total number of 181,144 children met our inclusion criteria, of which 10 were prospective cohort studies and 2 were cross-sectional studies. We subsequently classified the selected articles as high or good quality studies. A total of 9 out of the 12 studies reported a positive association between PM exposure to outdoor air pollution and behavioral problems related to attention. Despite these results, we found a significant degree of heterogeneity among the study designs. Furthermore, 11 studies were judged to be at a probably high risk of bias in the exposure assessment. In conclusion, we opine that further high quality studies are still needed in order to clarify the association between PM exposure and ADHD diagnosis
Experience in Developing an FHIR Medical Data Management Platform to Provide Clinical Decision Support
Authors: Semenov Ilia , Osenev Roman , Gerasimov Sergey , Kopanitsa Georgy , Denisov Dmitry , Andreychuk Yuriy
Published: December 2019

This paper is an extension of work originally presented to pHealth 2019—16th International Conference on Wearable, Micro and Nano Technologies for Personalized Health. To provide an efficient decision support, it is necessary to integrate clinical decision support systems (CDSSs) in information systems routinely operated by healthcare professionals, such as hospital information systems (HISs), or by patients deploying their personal health records (PHR). CDSSs should be able to use the semantics and the clinical context of the data imported from other systems and data repositories. A CDSS platform was developed as a set of separate microservices. In this context, we implemented the core components of a CDSS platform, namely its communication services and logical inference components. A fast healthcare interoperability resources (FHIR)-based CDSS platform addresses the ease of access to clinical decision support services by providing standard-based interfaces and workflows. This type of CDSS may be able to improve the quality of care for doctors who are using HIS without CDSS features. The HL7 FHIR interoperability standards provide a platform usable by all HISs that are FHIR enabled. The platform has been implemented and is now productive, with a rule-based engine processing around 50,000 transactions a day with more than 400 decision support models and a Bayes Engine processing around 2000 transactions a day with 128 Bayesian diagnostics models.
Sources and Determinants of Discretionary Food Intake in a Cohort of Australian Children Aged 12–14 Months
Authors: Coxon Claire , Devenish Gemma , Ha Diep , Do Loc , Scott Jane A.
Published: December 2019

Despite recommendations to the contrary, consumption of discretionary (energy-dense, nutrient-poor) foods begins for some children early in the weaning period, and the proportion of children consuming discretionary foods increases markedly in the second year of life. The purpose of this study was to determine intake and sources of discretionary foods in a cohort of 828 Australian toddlers (mean age: 13.1mo), and to identify determinants of discretionary food intake. At approximately 12 months of age, 3 non-consecutive days of dietary intake data were collected using a 24-h recall and 2-day food record, and the percentage total energy derived from discretionary foods was estimated. Linear regression was used to identify associations between discretionary food intake and socio-demographic determinants (mother’s age, level of education, country of birth, pre-pregnancy body mass index, socioeconomic position, parity, age of child when mother returned to work, and child’s sex) and age at which complementary foods were introduced. The average energy intake of children in this cohort was 4040 (±954.7 SD) kJ with discretionary foods contributing an average of 11.2% of total energy. Sweet biscuits, and cakes, muffins, scones and cake-type desserts contributed 10.8% and 10.2% of energy intake from discretionary foods, respectively. Other key contributors to energy intake from discretionary foods included sausages, frankfurters and saveloys (8.3%), vegetable products and dishes where frying was the main cooking technique (8.6%), butter (7.3%), and finally manufactured infant sweet or savory snack foods (9.3%). Higher intakes of discretionary food were associated with children having two or more siblings (p = 0.002), and being born to younger mothers (<25 years) (p = 0.008) and mothers born in Australia or the United Kingdom (p < 0.001). Parents, in particular young mothers and those with larger families, need practical guidance on how much of, and how often, these foods should be eaten by their children.
A Novel Infringement Detection Method for GIS Vector Data
Authors: Tang Zhi , Zhang Yun , Huang Jing , He Hao , Ding Yue
Published: December 2019

There is undoubtedly a groundswell of support for the concept of geographic data sharing with the rapid development and wide-ranging application of geographic information science. However, copyright protection and infringement detection in the process of geographic data sharing has always been an important issue that needs to be addressed urgently. In this paper, we present a novel infringement detection method for GIS vector data to compensate for the shortcomings of vector data digital watermarking technology in infringement detection. The method determines whether infringement exists by the duplication degree between the original data and the vector data to be detected in three features including feature features, included angle features and vertex features which gets by using the spatial information of vector data to perform the feature matching based on GeoJSON format data. The experimental results indicate that the proposed algorithm can effectively resist common geometric attacks, such as interpolation attack, deletion attack, similarity transformation attack, feature order scrambling attack, and feature simplification attack, on vector data, which proves that the proposed algorithm has excellent robustness and meets the requirements of practical application.
Targeting microRNAs as a Therapeutic Strategy to Reduce Oxidative Stress in Diabetes
Authors: Grieco Giuseppina Emanuela , Brusco Noemi , Licata Giada , Nigi Laura , Formichi Caterina , Dotta Francesco , Sebastiani Guido
Published: December 2019

Diabetes mellitus is a group of heterogeneous metabolic disorders characterized by chronic hyperglycaemia as a consequence of pancreatic β cell loss and/or dysfunction, also caused by oxidative stress. The molecular mechanisms involved inβ cell dysfunction and in response to oxidative stress are also regulated by microRNAs (miRNAs). miRNAs are a class of negative gene regulators, which modulate pathologic mechanisms occurring in diabetes and its complications. Although several pharmacological therapies specifically targeting miRNAs have already been developed and brought to the clinic, most previous miRNA-based drug delivery methods were unable to target a specific miRNA in a single cell type or tissue, leading to important off-target effects. In order to overcome these issues, aptamers and nanoparticles have been described as non-cytotoxic vehicles for miRNA-based drug delivery. These approaches could represent an innovative way to specifically target and modulate miRNAs involved in oxidative stress in diabetes and its complications. Therefore, the aims of this review are: (i) to report the role of miRNAs involved in oxidative stress in diabetes as promising therapeutic targets; (ii) to shed light onto the new delivery strategies developed to modulate the expression of miRNAs in diseases.
Genome-Wide Characterization and Gene Expression Analyses of GATA Transcription Factors in Moso Bamboo (Phyllostachys edulis)
Authors: Wang Taotao , Yang Yong , Lou Shuaitong , Wei Wei , Zhao Zhixin , Ren Yujun , Lin Chentao , Ma Liuyin
Published: December 2019

Moso bamboo is well-known for its rapid-growth shoots and widespread rhizomes. However, the regulatory genes of these two processes are largely unexplored. GATA transcription factors regulate many developmental processes, but their roles in moso bamboo height control and rhizome development remains unexplored. Here, thirty-one bamboo GATA factors (PeGATAs) were identified, which are evolutionarily closer to rice than Arabidopsis, and their gene expression patterns were analyzed in bamboo development and phytohormone response with bioinformatics and molecular methods. Interestingly, PeGATAs could only be classified into three groups. Phytohormone responsive cis-elements were found in PeGATA promoters and the expression profiles showed that PeGATA genes might respond to gibberellin acid and abscisic acid but not to auxin at the transcriptional level. Furthermore, PeGATA genes have a tissue-specific expression pattern in bamboo rhizomes. Interestingly, most PeGATA genes were down-regulated during the rapid-growth of bamboo shoots. In addition, over-expressing one of the PeGATA genes, PeGATA26, significantly repressed the primary root length and plant height of transgenic Arabidopsis plants, which may be achieved by promoting the gibberellin acid turnover. Overall, our results provide insight into the function of GATA transcription factors in bamboo, and into genetic resources for engineering plant height.
CaDHN4, a Salt and Cold Stress-Responsive Dehydrin Gene from Pepper Decreases Abscisic Acid Sensitivity in Arabidopsis
Authors: Zhang Hua-feng , Liu Su-ya , Ma Ji-hui , Wang Xin-ke , Haq Saeed ul , Meng Yuan-cheng , Zhang Yu-meng , Chen Ru-gang
Published: December 2019

Dehydrins play an important role in improving plant resistance to abiotic stresses. In this study, we isolated a dehydrin gene from pepper (Capsicum annuum L.) leaves, designated as CaDHN4. Sub-cellular localization of CaDHN4 was to be found in the nucleus and membrane. To authenticate the function of CaDHN4 in cold- and salt-stress responses and abscisic acid (ABA) sensitivity, we reduced the CaDHN4 expression using virus-induced gene silencing (VIGS), and overexpressed the CaDHN4 in Arabidopsis. We found that silencing of CaDHN4 reduced the growth of pepper seedlings and CaDHN4-silenced plants exhibited more serious wilting, higher electrolyte leakage, and more accumulation of ROS in the leaves compared to pTRV2:00 plants after cold stress, and lower chlorophyll contents and higher electrolyte leakage compared to pTRV2:00 plants under salt stress. However, CaDHN4-overexpressing Arabidopsis plants had higher seed germination rates and post-germination primary root growth, compared to WT plants under salt stress. In response to cold and salt stresses, the CaDHN4-overexpressed Arabidopsis exhibited lower MDA content, and lower relative electrolyte leakage compared to the WT plants. Under ABA treatments, the fresh weight and germination rates of transgenic plants were higher than WT plants. The transgenic Arabidopsis expressing a CaDHN4 promoter displayed a more intense GUS staining than the normal growth conditions under treatment with hormones including ABA, methyl jasmonate (MeJA), and salicylic acid (SA). Our results suggest that CaDHN4 can protect against cold and salt stresses and decrease ABA sensitivity in Arabidopsis.
Proteomic Analysis of Quercetin-Treated K562 Cells
Authors: Brisdelli Fabrizia , Di Francesco Laura , Giorgi Alessandra , Lizzi Anna Rita , Luzi Carla , Mignogna Giuseppina , Bozzi Argante , Schininà M. Eugenia
Published: December 2019

Among natural products under investigation for their additive potential in cancer prevention and treatment, the flavonoid quercetin has received attention for its effects on the cell cycle arrest and apoptosis. In the past, we addressed this issue in K562 cells, a cellular model of the human chronic myeloid leukemia. Here, we applied stable isotope labeling by amino acids in cell culture (SILAC) proteomics with the aim to increase knowledge on the regulative and metabolic pathways modulated by quercetin in these cells. After 24 h of quercetin treatment, we observed that apoptosis was not completely established, thus we selected this time range to capture quantitative data. As a result, we were able to achieve a robust identification of 1703 proteins, and to measure fold changes between quercetin-treated and untreated cells for 1206 proteins. Through a bioinformatics functional analysis on a subset of 112 proteins, we propose that the apoptotic phenotype of K562 cells entails a significant modulation of the translational machinery, RNA metabolism, antioxidant defense systems, and enzymes involved in lipid metabolism. Finally, we selected eight differentially expressed proteins, validated their modulated expression in quercetin-treated K562 cells, and discussed their possible role in flavonoid cytotoxicity. This quantitative profiling, performed for the first time on this type of tumor cells upon treatment with a flavonoid, will contribute to revealing the molecular basis of the multiplicity of the effects selectively exerted by quercetin on K562 cells.
Different Effects of Cisplatin and Transplatin on the Higher-Order Structure of DNA and Gene Expression
Authors: Kishimoto Toshifumi , Yoshikawa Yuko , Yoshikawa Kenichi , Komeda Seiji
Published: December 2019

Despite the effectiveness of cisplatin as an anticancer agent, its trans-isomer, transplatin, is clinically ineffective. Although both isomers target nuclear DNA, there is a large difference in the magnitude of their biological effects. Here, we compared their effects on gene expression in an in vitro luciferase assay and quantified their effects on the higher-order structure of DNA using fluorescence microscopy (FM) and atomic force microscopy (AFM). The inhibitory effect of cisplatin on gene expression was about 7 times that of transplatin. Analysis of the fluctuation autocorrelation function of the intrachain Brownian motion of individual DNA molecules showed that cisplatin increases the spring and damping constants of DNA by one order of magnitude and these visco-elastic characteristics tend to increase gradually over several hours. Transplatin had a weaker effect, which tended to decrease with time. These results agree with a stronger inhibitory effect of cisplatin on gene expression. We discussed the characteristic effects of the two compounds on the higher-order DNA structure and gene expression in terms of the differences in their binding to DNA.
International Journal of Molecular Science 2019 Best Paper Award
Authors:   International Journal of Molecular Science Editorial Office
Published: December 2019

The Editors of the International Journal of Molecular Sciences have established the Best Paper Award to recognize the most outstanding articles published in the areas of molecular biology, molecular physics, and chemistry that have been published in the International Journal of Molecular Sciences [...]
Conditioned Medium from Human Adipose-Derived Mesenchymal Stem Cell Culture Prevents UVB-Induced Skin Aging in Human Keratinocytes and Dermal Fibroblasts
Authors: Li Lu , Ngo Hien T.T. , Hwang Eunson , Wei Xuan , Liu Ying , Liu Jia , Yi Tae-Hoo
Published: December 2019

Human adipose-derived mesenchymal stem cells-conditioned medium (ADSC-CM) contains cytokines and growth factors that can facilitate the regeneration and repair of various tissues and organs. In the present study, the protective activity of ADSC-CM treatment was investigated in UVB-irradiated human keratinocyte cell line HaCaTs and normal human dermal fibroblasts (NHDFs). It was found that ADSC-CM can modulate the expression of the signaling molecules in the early UVB responsive signaling pathways, including mitogen activated protein kinases (MAPKs), activator protein 1 (AP-1), and nuclear factor kappa B (NF-κB). In addition, ADSC-CM treatment could upregulate antioxidant response element (ARE) such as phase II gene heme oxygenase-1 (HO-1) and increase the expression of collagen synthesis enhancer gene transforming growth factor-β (TGF-β). The expression of matrix metalloproteinase-1 (MMP-1) and procollagen type I synthesis inhibitors such as interleukin-6 (IL-6) was also found to be suppressed upon ADSC-CM treatment. Taken together, our study illustrates the anti-photoaging activities of ADSC-CM in cell-based models.
Hedgehog Signaling for Urogenital Organogenesis and Prostate Cancer: An Implication for the Epithelial–Mesenchyme Interaction (EMI)
Authors: Hyuga Taiju , Alcantara Mellissa , Kajioka Daiki , Haraguchi Ryuma , Suzuki Kentaro , Miyagawa Shinichi , Kojima Yoshiyuki , Hayashi Yutaro , Yamada Gen
Published: December 2019

Hedgehog (Hh) signaling is an essential growth factor signaling pathway especially in the regulation of epithelial–mesenchymal interactions (EMI) during the development of the urogenital organs such as the bladder and the external genitalia (EXG). The Hh ligands are often expressed in the epithelia, affecting the surrounding mesenchyme, and thus constituting a form of paracrine signaling. The development of the urogenital organ, therefore, provides an intriguing opportunity to study EMI and its relationship with other pathways, such as hormonal signaling. Cellular interactions of prostate cancer (PCa) with its neighboring tissue is also noteworthy. The local microenvironment, including the bone metastatic site, can release cellular signals which can affect the malignant tumors, and vice versa. Thus, it is necessary to compare possible similarities and divergences in Hh signaling functions and its interaction with other local growth factors, such as BMP (bone morphogenetic protein) between organogenesis and tumorigenesis. Additionally, this review will discuss two pertinent research aspects of Hh signaling: (1) the potential signaling crosstalk between Hh and androgen signaling; and (2) the effect of signaling between the epithelia and the mesenchyme on the status of the basement membrane with extracellular matrix structures located on the epithelial–mesenchymal interface.
In Silico and In Cell Analysis of Openable DNA Nanocages for miRNA Silencing
Authors: Raniolo Sofia , Iacovelli Federico , Unida Valeria , Desideri Alessandro , Biocca Silvia
Published: December 2019

A computational and experimental integrated approach was applied in order to study the effect of engineering four DNA hairpins into an octahedral truncated DNA nanocage, to obtain a nanostructure able to recognize and bind specific oligonucleotide sequences. Modeling and classical molecular dynamics simulations show that the new H4-DNA nanocage maintains a stable conformation with the closed hairpins and, when bound to complementary oligonucleotides produces an opened conformation that is even more stable due to the larger hydrogen bond number between the hairpins and the oligonucleotides. The internal volume of the open conformation is much larger than the closed one, switching from 370 to 650 nm3, and the predicted larger conformational change is experimentally detectable by gel electrophoresis. H4-DNA nanocages display high stability in serum, can efficiently enter the cells where they are stable and maintain the ability to bind, and sequester an intracellular-specific oligonucleotide. Moreover, H4-DNA nanocages, modified in order to recognize the oncogenic miR21, are able to seize miRNA molecules inside cells in a selective manner.
A Clinical Approach for the Use of VIP Axis in Inflammatory and Autoimmune Diseases
Authors: Martínez Carmen , Juarranz Yasmina , Gutiérrez-Cañas Irene , Carrión Mar , Pérez-García Selene , Villanueva-Romero Raúl , Castro David , Lamana Amalia , Mellado Mario , González-Álvaro Isidoro , Gomariz Rosa P.
Published: December 2019

The neuroendocrine and immune systems are coordinated to maintain the homeostasis of the organism, generating bidirectional communication through shared mediators and receptors. Vasoactive intestinal peptide (VIP) is the paradigm of an endogenous neuropeptide produced by neurons and endocrine and immune cells, involved in the control of both innate and adaptive immune responses. Exogenous administration of VIP exerts therapeutic effects in models of autoimmune/inflammatory diseases mediated by G-protein-coupled receptors (VPAC1 and VPAC2). Currently, there are no curative therapies for inflammatory and autoimmune diseases, and patients present complex diagnostic, therapeutic, and prognostic problems in daily clinical practice due to their heterogeneous nature. This review focuses on the biology of VIP and VIP receptor signaling, as well as its protective effects as an immunomodulatory factor. Recent progress in improving the stability, selectivity, and effectiveness of VIP/receptors analogues and new routes of administration are highlighted, as well as important advances in their use as biomarkers, contributing to their potential application in precision medicine. On the 50th anniversary of VIP’s discovery, this review presents a spectrum of potential clinical benefits applied to inflammatory and autoimmune diseases.
Harnessing the Effects of BTKi on T Cells for Effective Immunotherapy against CLL
Authors: Mhibik Maissa , Wiestner Adrian , Sun Clare
Published: December 2019

B-cell receptor (BCR) signaling and tumor–microenvironment crosstalk both drive chronic lymphocytic leukemia (CLL) pathogenesis. Within the microenvironment, tumor cells shape the T-cell compartment, which in turn supports tumor growth and survival. Targeting BCR signaling using Bruton tyrosine kinase inhibitors (BTKi) has become a highly successful treatment modality for CLL. Ibrutinib, the first-in-class BTKi, also inhibits Tec family kinases such as interleukin-2–inducible kinase (ITK), a proximal member of the T-cell receptor signaling cascade. It is increasingly recognized that ibrutinib modulates the T-cell compartment of patients with CLL. Understanding these T-cell changes is important for immunotherapy-based approaches aiming to increase the depth of response and to prevent or treat the emergence of resistant disease. Ibrutinib has been shown to improve T-cell function in CLL, resulting in the expansion of memory T cells, Th1 polarization, reduced expression of inhibitory receptors and improved immune synapse formation between T cells and CLL cells. Investigating the modulation of BTKi on the T-cell antitumoral function, and having a more complete understanding of changes in T cell behavior and function during treatment with BTKi therapy will inform the design of immunotherapy-based combination approaches and increase the efficacy of CLL therapy.
Screening and Identification of Novel cGAS Homologues Using a Combination of in Vitro and In Vivo Protein Synthesis
Authors: Rolf Jascha , Siedentop Regine , Lütz Stephan , Rosenthal Katrin
Published: December 2019

The cyclic GMP-AMP synthase (cGAS) catalyzes the synthesis of the multifunctional second messenger, cGAMP, in metazoans. Although numerous cGAS homologues are predicted in protein databases, the catalytic activity towards cGAMP synthesis has been proven for only four of them. Therefore, we selected five novel and yet uncharacterized cGAS homologues, which cover a broad range in the field of vertebrates. Cell-free protein synthesis (CFPS) was used for a pre-screening to investigate if the cGAS genes originating from higher organisms can be efficiently expressed in a bacterial expression system. As all tested cGAS variants were expressible, enzymes were synthesized in vivo to supply higher amounts for a subsequent in vitro activity assay. The assays were carried out with purified enzymes and revealed vast differences in the activity of the homologues. For the first time, the cGAS homologues from the Przewalski’s horse, naked mole-rat, bald eagle, and zebrafish were proven to catalyze the synthesis of cGAMP. The extension of the list of described cGAS variants enables the acquisition of further knowledge about the structural and molecular mechanism of cGAS, potentially leading to functional improvement of the enzyme.
Relay Selection Optimization for SWIPT-Enabled Cooperative Networks
Authors: Xia Hongxing , Li Yongzhao , Lu Yonglai
Published: December 2019

Simultaneous wireless information and energy transfer based on radio frequency (RF) energy harvesting can transmit power and information at the same time and can use the same wireless signal to decode the information and to charge the battery. In order to improve spectrum efficiency of energy-constrained networks, we consider combining cooperative relay with simultaneous information and energy transfer in this paper. The optimal relay power allocation and relay selection algorithms based on statistical channel state information (CSI) and perfect CSI are proposed, respectively. Specifically, the system first selects the relay nodes that can correctly decode the source information and, then among them, selects the node with the best second hop channel condition. We derive the exact analytical outage probability of the proposed algorithms by using order statistical tool. The analytical results are compared and verified by Monte Carlo simulations. It is observed that the outage probabilities of our proposed algorithms based on statistical CSI and perfect CSI are all lower than that of the corresponding traditional max–min algorithms.
Effects of Perioperative Magnesium Sulfate Administration on Postoperative Chronic Knee Pain in Patients Undergoing Total Knee Arthroplasty: A Retrospective Evaluation
Authors: Oh Tak Kyu , Chung Seung Hyun , Park Jinwoo , Shin Hyunjung , Chang Chong Bum , Kim Tae Kyun , Do Sang-Hwan
Published: December 2019

We aimed to investigate whether perioperative magnesium sulfate administration was associated with the incidence of chronic persistent postoperative pain (PPP) following total knee arthroplasty (TKA). This retrospective observational study was performed at a single tertiary academic hospital. We reviewed the medical records of adult patients who were admitted between August 2012 and July 2017. Patients who received magnesium sulfate during surgery were the magnesium group. The presence of PPP, one year after TKA, was evaluated using a binary logistic regression analysis. A total of 924 patients were included in the analysis, and 148 patients (16.0%) experienced PPP one year after TKA. In the multivariable model, the magnesium group had a 62% lower rate of PPP one year after TKA compared to the control group (odds ratio (OR): 0.38, 95% confidence interval (CI): 0.16 to 0.90; p = 0.027). This finding was similar in the sensitivity analysis using propensity score adjustment (OR: 0.38, 95% CI: 0.16 to 0.93; p = 0.036). We showed that perioperative magnesium sulfate administration was associated with a lower rate of PPP one year after TKA. Our results suggest that magnesium sulfate administered perioperatively is effective for the alleviation of acute and chronic pain after surgery.
Obstructive Sleep Apnea as a Predictor of Abnormal Heart Rate Turbulence
Authors: Urbanik Dominika , Gać Paweł , Martynowicz Helena , Poręba Małgorzata , Podgórski Maciej , Negrusz-Kawecka Marta , Mazur Grzegorz , Sobieszczańska Małgorzata , Poręba Rafał
Published: December 2019

Obstructive sleep apnea (OSA) causes dysfunction of the autonomic nervous system, but the exact mechanism has not been fully understood. The aim of this study was to analyse the relationship between the incidence and severity of OSA and heart rate turbulence (HRT). Seventy one patients with clinical suspicion of OSA were qualified to participate in the study. All participants took part in a survey and were subjected to laboratory tests, 24-hour electrocardiogram (ECG) Holter monitoring with HRT analysis and polysomnography. The group with OSA manifested significantly higher turbulence onset (TO) and lower turbulence slope (TS) as compared to the group without OSA. Older age, diabetes, hypertension and higher apnea/hypopnea index (AHI) were found to be independent risk factors for increased TO, whereas older age, higher body mass index (BMI), higher blood glucose levels, hypertension and higher AHI were independent risk factors for TS reduction. The AHI ≥65 criterion indicates abnormal HRT in patients with OSA with 94.9% sensitivity and 50.0% specificity, which gives a prediction accuracy of 85.7%. In summary, OSA should be considered as a predictor of abnormal HRT.
Relation between Heart Rate Variability and Disease Course in Multiple Sclerosis
Authors: Reynders Tatjana , Gidron Yori , De Ville Jella , Bjerke Maria , Weets Ilse , Van Remoortel Ann , Devolder Lindsay , D’haeseleer Miguel , De Keyser Jacques , Nagels Guy , D’hooghe Marie B.
Published: December 2019

Little is known about the interplay between the autonomic nervous system and disease activity in multiple sclerosis (MS). We examined the relationship between heart rate variability (HRV), a reliable measure of vagal nerve function, and disease characteristics in a prospective MS cohort. Standard deviation of each normal-to-normal inter-beat interval (SDNN) and root mean square of successive differences (RMSSD), global indices of HRV, were measured in 114 MS patients, which included four predefined subgroups, and 30 age and sex-matched healthy controls (HC). We assessed group differences at baseline, HRV reproducibility at month 3, and used logistic regression modeling to relate baseline HRV with relapse occurrence. No significant HRV differences were found between MS and HC and between MS subgroups. In MS patients, both HRV indices correlated with age (r = −0.278, p = 0.018 and r = −0.319, p < 0.001, respectively) and with month 3 assessments (r = 0.695 and r = 0.760, p < 0.001). Higher SDNN and RMSSD at baseline were associated with self-reported relapses at month 3 (OR = 1.053, 95% CI (1.013–1.095), p = 0.009 and OR = 1.065, 95% CI (1.016–1.117), p = 0.009), and SDNN at baseline with relapses at month 12 (OR = 1.034, 95% CI (1.009–1.059), p = 0.008; ROC, AUC = 0.733, p = 0.002). There were no baseline HRV differences between MS and HC or between subgroups. Post-hoc analysis showed an association with an increased relapse risk.
Drain Amylase or Lipase for the Detection of POPF—Adding Evidence to an Ongoing Discussion
Authors: Müssle Benjamin , Oehme Florian , Schade Stephanie , Sommer Marian , Bogner Andreas , Hempel Sebastian , Pochhammer Julius , Kahlert Christoph , Distler Marius , Weitz Jürgen , Welsch Thilo
Published: December 2019

Objectives: A postoperative pancreatic fistula (POPF) is defined as a threefold increase in the amylase concentration in abdominal drains on or after the third postoperative day (POD). However, additional lipase fluid analysis is widely used despite lacking evidence. In this study, drain amylase and lipase levels were compared regarding their value in detecting POPF. Methods: We conducted a retrospective study including all patients who underwent pancreatic resections at our center between 2005 and 2016. Drain fluid analysis was performed from day 2 to 5. Results: 990 patients were included in the analysis. Overall, 333 (34%) patients developed a POPF. The median amylase and lipase concentrations at POD 3 in cases with POPF were 11.55 µmol/(s·L) (≈13 ×-fold increase) and 39 µmol/(s·L) (≈39 ×-fold increase), respectively. Seven patients with subsequent POPF (2%) were missed with amylase analysis on POD 3, but detected using 3-fold lipase analysis. The false-positive rate of lipase was 51/424 = 12%. A cutoff lipase value at POD 3 of > 4.88 yielded a specificity of 94% and a sensitivity of 89% for development of a POPF. Increased body mass index turned out as risk factor for the development of POPF in a multivariable model. Conclusions: Threefold-elevated lipase concentration may be used as an indicator of a POPF. However, the additional detection of POPF using simultaneous lipase analysis is marginal. Therefore, assessment of lipase concentration does not provide added clinical value and only results in extra costs.
Histological Scores Validate the Accuracy of Hepatic Iron Load Measured by Signal Intensity Ratio and R2* Relaxometry MRI in Dialysis Patients
Authors: Rostoker Guy , Laroudie Mireille , Blanc Raphaël , Griuncelli Mireille , Loridon Christelle , Lepeytre Fanny , Rabaté Clémentine , Cohen Yves
Published: December 2019

Almost all haemodialysis patients are treated with parenteral iron to compensate for blood loss and to allow the full therapeutic effect of erythropoiesis-stimulating agents. Iron overload is an increasingly recognised clinical situation diagnosed by quantitative magnetic resonance imaging (MRI). MRI methods have not been fully validated in dialysis patients. We compared Deugnier’s and Turlin’s histological scoring of iron overload and Scheuer’s classification (with Perls’ stain) with three quantitative MRI methods for measuring liver iron concentration (LIC)—signal intensity ratio (SIR), R2* relaxometry, and R2* multi-peak spectral modelling (Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation (IDEAL-IQ®)) relaxometry—in 16 haemodialysis patients in whom a liver biopsy was formally indicated for medical follow-up. LIC MRI with these three different methods was highly correlated with Deugnier’s and Turlin’s histological scoring (SIR: r = 0.8329, p = 0.0002; R2* relaxometry: r = −0.9099, p < 0.0001; R2* relaxometry (IDEAL-IQ®): r = −0.872, p = 0.0018). Scheuer’s classification was also significantly correlated with these three MRI techniques. The positive likelihood ratio for the diagnosis of abnormal LIC by Deugnier’s histological scoring was > 62 for the three MRI methods. This study supports the accuracy of quantitative MRI methods for the non-invasive diagnosis and follow-up of iron overload in haemodialysis patients.
Influence of Alternate Hot and Cold Thermal Stimulation in Cortical Excitability in Healthy Adults: An fMRI Study
Authors: Chen Sharon Chia-Ju , Lin Jau-Hong , Hsu Jui-Sheng , Shih Chiu-Ming , Lai Jui-Jen , Hsu Miao-Ju
Published: December 2019

Stroke rehabilitation using alternate hot and cold thermal stimulation (altTS) has been reported to improve motor function in hemiplegia; however, the influence of brain excitability induced by altTS remains unclear. This study examined cortical activation induced by altTS in healthy adults, focusing on motor-related areas. This involved a repeated crossover experimental design with two temperature settings (innocuous altTS with alternate heat-pain and cold-pain thermal and noxious altTS with alternate heat and cold thermal) testing both arms (left side and right side). Thirty-one healthy, right-handed participants received four episodes of altTS on four separate days. Functional magnetic resonance imaging scans were performed both before and after each intervention to determine whether altTS intervention affects cortical excitability, while participants performed a finger-tapping task during scanning. The findings revealed greater response intensity of cortical excitability in participants who received noxious altTS in the primary motor cortex, supplementary motor cortex, and somatosensory cortex than in those who received innocuous altTS. Moreover, there was more motor-related excitability in the contra-lateral brain when heat was applied to the dominant arm, and more sensory-associated excitability in the contra-lateral brain when heat was applied to the nondominant arm. The findings highlight the effect of heat on cortical excitability and provide insights into the application of altTS in stroke rehabilitation.