bluuebunny/crossref_metadata_2025 huggingface dataset:
Holocene Environmental and Anthropogenic Changes of Soils and Vegetation in the Central Russian Upland: The Case Study in the “Belogorie” Natural Reserve
Authors: Chendev Yury , Khokhlova Olga , Ponomarenko Elena , Ershova Ekaterina , Alexandrovskiy Alexander , Myakshina Tatyana
Published: December 2018

Several episodes of past afforestation were reconstructed in a grassland area of the Yamskaya Steppe site within the “Belgorie” natural reserve on the Central-Russian Upland. The pedological, palinological, pedoanthracological, and phytolith analyses were applied for studying paleosols buried under artificial and natural mounds, colluvial fan deposits in gullies, and closed depressions on watersheds. The watershed area was covered by the forest vegetation until 6000 years BP, as indicated by palinological spectra in the paleosol of this age. The Bk horizon of the Chernozemic paleosol buried under a burial mound of the Bronze Age (4630 ± 180 years BP) contained Fe-lamellae indicative of the preceded forest phase of soil formation. Micro-depressions within the local watershed contained charcoal-cored iron-manganese concretions with the radiocarbon age varying from 6055 ± 20 to 6155 ± 20 years BP. This age marked a deforestation of the area after large-scale fires. From that time on, the watershed was dominated by the grassland vegetation. The next phase of afforestation was recorded in the beginning of the Subboreal period of Holocene (4600 BP), but the forest appeared to be limited to gullies. Starting with the Subboreal period, the anthropogenic impact on the landscape became apparent.
Modeling and Imaging of Multiscale Geological Media: Exploding Reflection Revisited
Authors: Landa Evgeny , Reshetova Galina , Tcheverda Vladimir
Published: December 2018

Computation of Common Middle Point seismic sections and their subsequent time migration and diffraction imaging provides very important knowledge about the internal structure of 3D heterogeneous geological media and are key elements for successive geological interpretation. Full-scale numerical simulation, that computes all single shot seismograms, provides a full understanding of how the features of the image reflect the properties of the subsurface prototype. Unfortunately, this kind of simulations of 3D seismic surveys for realistic geological media needs huge computer resources, especially for simulation of seismic waves’ propagation through multiscale media like cavernous fractured reservoirs. Really, we need to combine smooth overburden with microstructure of reservoirs, which forces us to use locally refined grids. However, to resolve realistic statements with huge multi-shot/multi-offset acquisitions it is still not enough to provide reasonable needs of computing resources. Therefore, we propose to model 3D Common Middle Point seismic cubes directly, rather than shot-by-shot simulation with subsequent stacking. To do that we modify the well-known "exploding reflectors principle" for 3D heterogeneous multiscale media by use of the finite-difference technique on the base of grids locally refined in time and space. We develop scalable parallel software, which needs reasonable computational costs to simulate realistic models and acquisition. Numerical results for simulation of Common Middle Points sections and their time migration are presented and discussed.
Guidelines for the Treatment of PTSD Using Clinical EFT (Emotional Freedom Techniques)
Authors: Church Dawson , Stapleton Peta , Mollon Phil , Feinstein David , Boath Elizabeth , Mackay David , Sims Rebecca
Published: December 2018

Clinical EFT (Emotional Freedom Techniques) is an evidence-based method that combines acupressure with elements drawn from cognitive and exposure therapies. The approach has been validated in more than 100 clinical trials. Its efficacy for post-traumatic stress disorder (PTSD) has been investigated in a variety of demographic groups including war veterans, victims of sexual violence, the spouses of PTSD sufferers, motor accident survivors, prisoners, hospital patients, adolescents, and survivors of natural and human-caused disasters. Meta-analyses of EFT for anxiety, depression, and PTSD indicate treatment effects that exceed those of both psychopharmacology and conventional psychotherapy. Studies of EFT in the treatment of PTSD show that (a) time frames for successful treatment generally range from four to 10 sessions; (b) group therapy sessions are effective; (c) comorbid conditions such as anxiety and depression improve simultaneously; (d) the risk of adverse events is low; (e) treatment produces physiological as well as psychological improvements; (f) patient gains persist over time; (g) the approach is cost-effective; (h) biomarkers such as stress hormones and genes are regulated; and (i) the method can be adapted to online and telemedicine applications. This paper recommends guidelines for the use of EFT in treating PTSD derived from the literature and a detailed practitioner survey. It has been reviewed by the major institutions providing training or supporting research in the method. The guidelines recommend a stepped-care model, with five treatment sessions for subclinical PTSD, 10 sessions for PTSD, and escalation to intensive psychotherapy or psychopharmacology or both for nonresponsive patients and those with developmental trauma. Group therapy, social support, apps, and online and telemedicine methods also contribute to a successful treatment plan.
Prevalence and Factors Associated with Inconsistent Condom Use among Men Who Have Sex with Men (MSM) Who Use Mobile Geo-Social Networking Applications in Greater Tokyo
Authors: Hill Adam O , Bavinton Benjamin R , Armstrong Gregory
Published: December 2018

This study examined the prevalence and factors associated with inconsistent condom use among men who have sex with men (MSM) who use gay mobile geo-social networking applications (gay mobile apps) in Greater Tokyo. Among a sample of 1657 MSM recruited through advertisements on gay mobile apps, inconsistent condom use was reported by over one-third (37%) of participants with regular male partners, 18% with casual male partners, and 20% with female partners. In multiple regression analysis, inconsistent condom use with both regular and casual male partners was more commonly reported among participants without a university education, and among participants reporting lower self-efficacy for safer sex. Inconsistent condom use with casual male partners was more commonly reported among participants living in the central 23 wards of Tokyo. Inconsistent condom use with regular male partners was more commonly reported among participants who identified as a member of the gay community, and who only had male partners. These results indicate that a substantial proportion of Greater Tokyo gay mobile app users use condoms inconsistently, particularly with regular partners, and may be at risk for HIV. This paper provides useful information to help design tailored strategies to reduce inconsistent condom use.
Enablers Supporting the Implementation of Knowledge Management in the Healthcare of Pakistan
Authors: Karamat Jawad , Shurong Tong , Ahmad Naveed , Waheed Abdul , Mahmood Kashif
Published: December 2018

Knowledge is considered to be an important resource; it is the source of competitive advantage. However, if knowledge is managed well with Knowledge Management (KM), then it becomes a source for sustainable competitive advantage for organizations. If KM is implemented in an organization, it would improve the organizational competitiveness, performance, and productivity, and facilitate the efficient use of resources. Due to intense competition in the global market, many organizations are moving towards the adoption of KM. The healthcare sectors of many developed countries have moved towards the implementation of KM because it can improve the procuring of knowledge from ongoing activities by the effective use of data repositories. Developing countries have now realized the potential and benefits of KM adoption. Pakistan is one of the developing countries that have recently shown an inclination towards the adoption of KM in its healthcare sector to improve performance of its healthcare. This study was composed of two main research phases. Firstly, the enablers of KM were reviewed from earlier studies. Secondly, interpretive structural modeling (ISM) and MICMAC (Cross-Impact Matrix Multiplication Applied to Classification) techniques were used to show the interrelationships between KM enablers and driving and dependence power of each enabler. The application of ISM and MICMAC technique shows that policy incentive, long-term strategic planning, Information Technology (IT), and alignment of KM efforts with business strategy are the main enablers of KM adoption in the healthcare of Pakistan. Focusing on the identified enablers will help in the implementation of KM. Policy incentives can work as a catalyst to promote KM adoption in the healthcare of Pakistan.
Socio-Economic Status and Health: Evaluation of Human Biomonitored Chemical Exposure to Per- and Polyfluorinated Substances across Status
Authors: Buekers Jurgen , Colles Ann , Cornelis Christa , Morrens Bert , Govarts Eva , Schoeters Greet
Published: December 2018

Research on the environment, health, and well-being nexus (EHWB) is shifting from a silo toward a systemic approach that includes the socio-economic context. To disentangle further the complex interplay between the socio-exposome and internal chemical exposure, we performed a meta-analysis of human biomonitoring (HBM) studies with internal exposure data on per-and polyfluoroalkyl substances (PFASs) and detailed information on risk factors, including descriptors of socio-economic status (SES) of the study population. PFASs are persistent in nature, and some have endocrine-disrupting properties. Individual studies have shown that HBM biomarker concentrations of PFASs generally increase with SES indicators, e.g., for income. Based on a meta-analysis (five studies) of the associations between PFASs and SES indicators, the magnitude of the association could be estimated. For the SES indicator income, changes in income were expressed by a factor change, which was corrected by the Gini coefficient to take into account the differences in income categories between studies, and the income range between countries. For the SES indicator education, we had to conclude that descriptors (<college, x years of study, etc.) differed too widely between studies to perform a meta-analysis. Therefore, the use of the uniform ISCED (International Standard Classification of Education) is recommended in future studies. The meta-analysis showed that a higher income is associated with a higher internal exposure to PFASs (PFOS or perfluorooctanesulfonic acid, PFOA or perfluorooctanoic acid, PFNA or perfluorononanoic acid, PFHxS or perfluorohexane sulfonate). This is opposite to the environmental justice hypothesis, referring to an inequitable distribution of detrimental environmental effects toward poor and minority communities by a practice or policy. With a doubling of the income, internal exposure increased on average by 10%–14%. Possible explanations for this difference are given, e.g., underlying differences in diet. However, other sources can also contribute, and the exact causes of SES-related differences in PFAS concentrations remain unclear. Studies are needed that include social descriptors together with lifestyle and dietary information as explanatory variables for internal chemical exposure levels. This will help clarify the underlying factors that link SES with inequity to environmental exposures, and will raise awareness and knowledge to strengthen the capacities of people and communities to advocate chemical exposure reduction in order to reduce this health inequity.
STI Health Disparities: A Systematic Review and Meta-Analysis of the Effectiveness of Preventive Interventions in Educational Settings
Authors: Mon Kyaw Soe Nway , Bird Yelena , Schwandt Michael , Moraros John
Published: December 2018

The purpose of this systematic review and meta-analysis was to address disparities related to sexual health among students by examining the effectiveness of sexually transmitted infection (STI) preventive interventions in educational settings. PubMed, Medline, Cochrane Library, Public Health Database, and EMBASE databases were used to conduct searches. Information relating to studies, programs, participants, and quantitative outcome variables were extracted. Risk of bias was assessed and meta-analysis was conducted. This systematic review included 16 articles. The outcomes were classified into behavioral and psychosocial categories. The behavioral category included sexual partners, sexual activity, condom use, STI/HIV testing, and alcohol/drug use before sex. The psychosocial category consisted of knowledge, motivational factors, and skills. Interventions had a significantly positive impact on both behavioral (OR, 1.28; 95% CI, 1.17–1.39) and psychosocial (OR, 1.92; 95% CI, 1.36–2.72) outcomes. Among the psychosocial outcomes, the interventions were most effective at promoting knowledge (OR, 3.17; 95% CI, 2.13–4.72), followed by enhancing motivational factors (OR, 1.69; 95% CI, 1.04–2.75) and increasing behavioral skills (OR, 1.43; 95% CI, 1.13–1.81). The results of this systematic review provide empirical evidence for public health professionals and policy makers regarding planning, implementation, evaluation, and modification of STI preventive intervention programs in educational settings.
A Comparison of Stress Perception in International and Local First Semester Medical Students Using Psychometric, Psychophysiological, and Humoral Methods
Authors: Huhn Daniel , Schmid Carolin , Erschens Rebecca , Junne Florian , Herrmann-Werner Anne , Möltner Andreas , Herzog Wolfgang , Nikendei Christoph
Published: December 2018

(1) Medical doctors and medical students show increased psychological stress levels. International medical students seem to be particularly vulnerable. (2) We compared different methods of assessing stress levels in international and local first year medical students. First, study participants completed questionnaires related to stress, depression, empathy, and self-efficacy (MBI, PSQ, PHQ-9, JSPE-S, and GSE) at three separate points in time (T1 to T3). Second, their heart rate variabilities (HRVs) were recorded in an oral examination, a seminar, and in a relaxing situation. Third, hair samples were collected at the beginning and at the end of the semester to assess the cortisol concentration. (3) Included were 20 international and 20 local first semester medical students. At T1, we found considerable differences between international and local students in the JSPE-S; at T2 in the MBI factor “professional efficacy”, the PHQ-9, and in the JSPE-S; and at T3 in the MBI factors “cynicism” and “professional efficacy”, the PHQ-9, and in the JSPE-S. International and local students also differed concerning their HRVs during relaxation. Over the course of the semester, international students showed changes in the MBI factors “emotional exhaustion” and “professional efficacy”, the PHQ-9, and the GSE. Local students showed changes in the GSE. No effects were found for students’ hair cortisol concentrations. (4) All participants showed low levels of stress. However, while international students experienced their stress levels to decrease over the course of the semester, local students found their stress levels to increase.
Outbreak of Acute Gastroenteritis Caused by Norovirus Genogroup II Attributed to Contaminated Cold Dishes on a Cruise Ship in Chongqing, China, 2017
Authors: Qi Li , Xiang Xinzhi , Xiong Ying , Ling Hua , Shen Huangcheng , Deng Wenwen , Tang Wenge , Shen Tao , Li Qin
Published: December 2018

In April 2017, several travelers with acute gastroenteritis on a cruise ship were reported. We conducted an investigation to identify the pathogen, mode of transmission, and risk factors. We searched and classified case-patient according to structured case definition, and collect date of the onset, clinical manifestations, and demographic information of cases. A case-control study was implemented to compare foods consumption between cases and asymptomatic travelers. Samples such as feces, rectal swab, vomitus, and environment swab were collected for testing. The attack rate was 18.2% (101/555), four cold dishes served on 11th, April were independently associated with an increased risk of disease: cold potherb (odds ratio (OR): 14.4; 95% confidence interval (CI): 2.2–93.3) and cold garlic sprout (OR: 26.1; 95% CI: 4.9–138.0) served at lunch, cold broad bean (OR: 5.8; 95% CI: 1.3–26.2), and cold cucumber (OR: 13.9; 95% CI: 2.3–84.2) served at dinner. A total of 15 samples were positive for norovirus genogroup II (GII) by using reverse transcription polymerase chain reaction (RT-PCR). This outbreak that occurred on the cruise ship was caused by norovirus GII. The evidence indicated that norovirus was mainly transmitted through consumption of cold dishes on 11th, April, which might be contaminated by asymptomatic cold dish cook.
Non-Uniformity of the Indoor Radon Concentration under a Convective Mixing Mechanism
Authors: Spotar Sergey , Ibrayev Nurlan , Uyzbayeva Aigerim , Atabayev Jamil
Published: December 2018

This paper focuses on the results of computational fluid dynamics (CFD) modeling of radon concentration distribution in living areas within residences. The COMSOL Multiphysics® 5.3 software package has been employed for solving coupled momentum and species transport problems together with pseudo-reaction term modeling of the radon radioactive decay process. The reliability and verification of the simulation model was tested by comparing with available experimental data. The obtained results show the existence of stagnant zones where the concentration of radon is substantially higher than the average values. The impact of factors such as wind velocity, air tightness, and incoming radon flux were taken into consideration.
The Relationship between Infectious Diseases and Housing Maintenance in Indigenous Australian Households
Authors: Ali Shahmir H. , Foster Tim , Hall Nina Lansbury
Published: December 2018

This research aimed to identify systemic housing-level contributions to infectious disease transmission for Indigenous Australians, in response to the Government program to ‘close the gap’ of health and other inequalities. A narrative literature review was performed in accordance to PRISMA guidelines. The findings revealed a lack of housing maintenance was associated with gastrointestinal infections, and skin-related diseases were associated with crowding. Diarrhoea was associated with the state of food preparation and storage areas, and viral conditions such as influenza were associated with crowding. Gastrointestinal, skin, ear, eye, and respiratory illnesses are related in various ways to health hardware functionality, removal and treatment of sewage, crowding, presence of pests and vermin, and the growth of mould and mildew. The research concluded that infectious disease transmission can be reduced by improving housing conditions, including adequate and timely housing repair and maintenance, and the enabling environment to perform healthy behaviours.
Experience and Future Perceived Risk of Floods and Diarrheal Disease in Urban Poor Communities in Accra, Ghana
Authors: Abu Mumuni , Codjoe Samuel Nii Ardey
Published: December 2018

Diarrheal disease is a critical health condition in urban areas of developing countries due to increasing urbanization and its associated problems of sanitation and poor access to good drinking water. Increasing floods in cities have been linked to the risk of diarrheal disease. There are few studies that specifically link flooding with diarrhea diseases. This may be due to the fact that secondary data mainly hospital recorded cases, and not individual cases at the household level are used. Furthermore, of the few papers that consider the flood-diarrheal diseases nexus, none have considered risk perceptions in general, and more specifically, whether households that have experienced floods which resulted in a reported case of diarrhea, have higher perceived risks of future occurrences of the two phenomena compared to households that had different experiences. Yet, this is critical for the development of interventions that seek to increase protective behaviors and reduce the risk of contracting diarrhea. We surveyed 401 households in some selected urban poor communities in Accra, the capital of Ghana. Results show that households that experienced floods which resulted in a reported case of diarrhea, have higher perceived risk of future occurrence of the two phenomena compared to other households. We recommend public education that reduces the risk of exposure to flood and diarrhea through flood mitigation measures, including the construction of drains in communities and educating communities on good sanitation.
An Animal Model for Assessing the Effects of Hydroxyurea Exposure Suggests That the Administration of This Agent to Pregnant Women and Young Infants May Not Be as Safe as We Thought
Authors: Rodríguez-Vázquez Lucía , Martí Joaquín
Published: December 2018

The cytostatic agent hydroxyurea (HU) has proven to be beneficial for a variety of conditions in the disciplines of oncology, hematology, infectious disease and dermatology. It disrupts the S phase of the cell cycle by inhibiting the ribonucleotide reductase enzyme, thus blocking the transformation of ribonucleotides into deoxyribonucleotides, a rate limiting step in DNA synthesis. HU is listed as an essential medicine by the World Health Organization. Several studies have indicated that HU is well tolerated and safe in pregnant women and very young pediatric patients. To our knowledge, only a few controlled studies on the adverse effects of HU therapy have been done in humans. Despite this, the prevalence of central nervous system abnormalities, including ischemic lesions and stenosis have been reported. This review will summarize and present the effects of HU exposure on the prenatal and perinatal development of the rat cerebellar cortex and deep cerebellar nuclei neurons. Our results call for the necessity to better understand HU effects and define the administration of this drug to gestating women and young pediatric patients.
Nutrition and Cardiovascular Health
Authors: Casas Rosa , Castro-Barquero Sara , Estruch Ramon , Sacanella Emilio
Published: December 2018

Cardiovascular disease (CVD) is the leading cause of death in Western countries, representing almost 30% of all deaths worldwide. Evidence shows the effectiveness of healthy dietary patterns and lifestyles for the prevention of CVD. Furthermore, the rising incidence of CVD over the last 25 years has become a public health priority, especially the prevention of CVD (or cardiovascular events) through lifestyle interventions. Current scientific evidence shows that Western dietary patterns compared to healthier dietary patterns, such as the ‘Mediterranean diet’ (MeDiet), leads to an excessive production of proinflammatory cytokines associated with a reduced synthesis of anti-inflammatory cytokines. In fact, dietary intervention allows better combination of multiple foods and nutrients. Therefore, a healthy dietary pattern shows a greater magnitude of beneficial effects than the potential effects of a single nutrient supplementation. This review aims to identify potential targets (food patterns, single foods, or individual nutrients) for preventing CVD and quantifies the magnitude of the beneficial effects observed. On the other hand, we analyze the possible mechanisms implicated in this cardioprotective effect.
Proteomics Analysis Reveals That Caspase-Like and Metacaspase-Like Activities Are Dispensable for Activation of Proteases Involved in Early Response to Biotic Stress in Triticum aestivum L.
Authors: Balakireva Anastasia V. , Deviatkin Andrei A. , Zgoda Victor G. , Kartashov Maxim I. , Zhemchuzhina Natalia S. , Dzhavakhiya Vitaly G. , Golovin Andrey V. , Zamyatnin Andrey A.
Published: December 2018

Plants, including Triticum aestivum L., are constantly attacked by various pathogens which induce immune responses. Immune processes in plants are tightly regulated by proteases from different families within their degradome. In this study, a wheat degradome was characterized. Using profile hidden Markov model (HMMer) algorithm and Pfam database, comprehensive analysis of the T. aestivum genome revealed a large number of proteases (1544 in total) belonging to the five major protease families: serine, cysteine, threonine, aspartic, and metallo-proteases. Mass-spectrometry analysis revealed a 30% difference between degradomes of distinct wheat cultivars (Khakasskaya and Darya), and infection by biotrophic (Puccinia recondita Rob. ex Desm f. sp. tritici) or necrotrophic (Stagonospora nodorum) pathogens induced drastic changes in the presence of proteolytic enzymes. This study shows that an early immune response to biotic stress is associated with the same core of proteases from the C1, C48, C65, M24, M41, S10, S9, S8, and A1 families. Further liquid chromatography-mass spectrometry (LC-MS) analysis of the detected protease-derived peptides revealed that infection by both pathogens enhances overall proteolytic activity in wheat cells and leads to activation of proteolytic cascades. Moreover, sites of proteolysis were identified within the proteases, which probably represent targets of autocatalytic activation, or hydrolysis by another protease within the proteolytic cascades. Although predicted substrates of metacaspase-like and caspase-like proteases were similar in biotrophic and necrotrophic infections, proteolytic activation of proteases was not found to be associated with metacaspase-like and caspase-like activities. These findings indicate that the response of T. aestivum to biotic stress is regulated by unique mechanisms.
Melanogenesis Inhibitors from the Rhizoma of Ligusticum Sinense in B16-F10 Melanoma Cells In Vitro and Zebrafish In Vivo
Authors: Cheng Min-Chi , Lee Tzong-Huei , Chu Yi-Tzu , Syu Li-Ling , Hsu Su-Jung , Cheng Chia-Hsiung , Wu Jender , Lee Ching-Kuo
Published: December 2018

The rhizoma of Ligusticum sinense, a Chinese medicinal plant, has long been used as a cosmetic for the whitening and hydrating of the skin in ancient China. In order to investigate the antimelanogenic components of the rhizoma of L. sinense, we performed an antimelanogenesis assay-guided purification using semi-preparative HPLC accompanied with spectroscopic analysis to determine the active components. Based on the bioassay-guided method, 24 compounds were isolated and identified from the ethyl acetate layer of methanolic extracts of L. sinense, and among these, 5-[3-(4-hydroxy-3-methoxyphenyl)allyl]ferulic acid (1) and cis-4-pentylcyclohex-3-ene-1,2-diol (2) were new compounds. All the pure isolates were subjected to antimelanogenesis assay using murine melanoma B16-F10 cells. Compound 1 and (3S,3aR)-neocnidilide (8) exhibited antimelanogenesis activities with IC50 values of 78.9 and 31.1 μM, respectively, without obvious cytotoxicity. Further investigation showed that compound 8 demonstrated significant anti-pigmentation activity on zebrafish embryos (10‒20 μM) compared to arbutin (20 μM), and without any cytotoxicity against normal human epidermal keratinocytes. These findings suggest that (3S,3aR)-neocnidilide (8) is a potent antimelanogenic and non-cytotoxic natural compound and may be developed potentially as a skin-whitening agent for cosmetic uses.
iTRAQ-Based Quantitative Proteomic Analysis of Embryogenic and Non-embryogenic Calli Derived from a Maize (Zea mays L.) Inbred Line Y423
Authors: Liu Beibei , Shan Xiaohui , Wu Ying , Su Shengzhong , Li Shipeng , Liu Hongkui , Han Junyou , Yuan Yaping
Published: December 2018

Somatic embryos (SE) have potential to rapidly form a whole plant. Generally, SE is thought to be derived from embryogenic calli (EC). However, in maize, not only embryogenic calli (EC, can generate SE) but also nonembryogenic calli (NEC, can’t generate SE) can be induced from immature embryos. In order to understand the differences between EC and NEC and the mechanism of EC, which can easily form SE in maize, differential abundance protein species (DAPS) of EC and NEC from the maize inbred line Y423 were identified by using the isobaric tags for relative and absolute quantification (iTRAQ) proteomic technology. We identified 632 DAPS in EC compared with NEC. The results of bioinformatics analysis showed that EC development might be related to accumulation of pyruvate caused by the DAPS detected in some pathways, such as starch and sucrose metabolism, glycolysis/gluconeogenesis, tricarboxylic acid (TCA) cycle, fatty acid metabolism and phenylpropanoid biosynthesis. Based on the differentially accumulated proteins in EC and NEC, a series of DAPS related with pyruvate biosynthesis and suppression of acetyl-CoA might be responsible for the differences between EC and NEC cells. Furthermore, we speculate that the decreased abundance of enzymes/proteins involved in phenylpropanoid biosynthesis pathway in the EC cells results in reducing of lignin substances, which might affect the maize callus morphology.
Synonymous Codon Usages as an Evolutionary Dynamic for Chlamydiaceae
Authors: Li Zhaocai , Hu Wen , Cao Xiaoan , Liu Ping , Shang Youjun , Zhou Jizhang
Published: December 2018

The family of Chlamydiaceae contains a group of obligate intracellular bacteria that can infect a wide range of hosts. The evolutionary trend of members in this family is a hot topic, which benefits our understanding of the cross-infection of these pathogens. In this study, 14 whole genomes of 12 Chlamydia species were used to investigate the nucleotide, codon, and amino acid usage bias by synonymous codon usage value and information entropy method. The results showed that all the studied Chlamydia spp. had A/T rich genes with over-represented A or T at the third positions and G or C under-represented at these positions, suggesting that nucleotide usages influenced synonymous codon usages. The overall codon usage trend from synonymous codon usage variations divides the Chlamydia spp. into four separate clusters, while amino acid usage divides the Chlamydia spp. into two clusters with some exceptions, which reflected the genetic diversity of the Chlamydiaceae family members. The overall codon usage pattern represented by the effective number of codons (ENC) was significantly positively correlated to gene GC3 content. A negative correlation exists between ENC and the codon adaptation index for some Chlamydia species. These results suggested that mutation pressure caused by nucleotide composition constraint played an important role in shaping synonymous codon usage patterns. Furthermore, codon usage of T3ss and Pmps gene families adapted to that of the corresponding genome. Taken together, analyses help our understanding of evolutionary interactions between nucleotide, synonymous codon, and amino acid usages in genes of Chlamydiaceae family members.
Interaction of the GTPase Elongation Factor Like-1 with the Shwachman-Diamond Syndrome Protein and Its Missense Mutations
Authors: Gijsbers Abril , Montagut Diana Carolina , Méndez-Godoy Alfonso , Altamura Davide , Saviano Michele , Siliqi Dritan , Sánchez-Puig Nuria
Published: December 2018

The Shwachman-Diamond Syndrome (SDS) is a disorder arising from mutations in the genes encoding for the Shwachman-Bodian-Diamond Syndrome (SBDS) protein and the GTPase known as Elongation Factor Like-1 (EFL1). Together, these proteins remove the anti-association factor eIF6 from the surface of the pre-60S ribosomal subunit to promote the formation of mature ribosomes. SBDS missense mutations can either destabilize the protein fold or affect surface epitopes. The molecular alterations resulting from the latter remain largely unknown, although some evidence suggest that binding to EFL1 may be affected. We further explored the effect of these SBDS mutations on the interaction with EFL1, and showed that all tested mutations disrupted the binding to EFL1. Binding was either severely weakened or almost abolished, depending on the assessed mutation. In higher eukaryotes, SBDS is essential for development, and lack of the protein results in early lethality. The existence of patients whose only source of SBDS consists of that with surface missense mutations highlights the importance of the interaction with EFL1 for their function. Additionally, we studied the interaction mechanism of the proteins in solution and demonstrated that binding consists of two independent and cooperative events, with domains 2–3 of SBDS directing the initial interaction with EFL1, followed by docking of domain 1. In solution, both proteins exhibited large flexibility and consisted of an ensemble of conformations, as demonstrated by Small Angle X-ray Scattering (SAXS) experiments.
The Protective Effects of 2,3,5,4′-Tetrahydroxystilbene-2-O-β-d-Glucoside in the OVA-Induced Asthma Mice Model
Authors: Hwang Yun-Ho , Kim Su-Jin , Kim Hangun , Yee Sung-Tae
Published: December 2018

Asthma is an inflammatory disease caused by an imbalance of Th1 and Th2 cells. In general, asthma is characterized by a stronger Th2 response. Most conventional asthma treatment focuses on improving airway flow or suppression of airway inflammation. To reduce the side effects of currently used asthma medicines, we have conducted studies on natural products that have no side effects. 2,3,5,4′-tetrahydroxystilbene-2-O-β-d-glucoside (TSG), the main compound of Polygonum multiflorum (PM), has various biological activities, including anti-inflammation and anti-oxidation activities. However, the effect of TSG on asthma has not been studied yet. We examined the effects of TSG on Th2 immune responses using an OVA-induced asthma animal model. OVA-sensitized mice were treated with TSG. 24 h after the last intranasal challenge, airway hyperresponsiveness (AHR) was measured or serum and bronchoalveolar lavage fluid (BALF) were harvested. We measured typical Th1 and Th2 cytokines in serum and BALF. As a result, TSG suppressed Th2 responses, as shown by the lower levels of IL-4, IL-5, total IgE, OVA-specific IgE, and OVA-specific IgG1. On the other hand, TSG increased Th1 responses, as shown by the levels of IFN-gamma. Collectively, these results confirm the potential of TSG for asthma treatment through modulation of inflammatory responses. Considering that the cytotoxic effect of PM extract is due to the cis isomer of TSG, if the effect of TSG on asthma treatment is found to be non-toxic in clinical trials, it would be more effective to use it as a purified component than PM extract as an asthma treatment agent.
A Diabetes Management Information System with Glucose Prediction
Authors: Lélis Cláudio Augusto Silveira , Motta Goulart Renan
Published: December 2018

Diabetes has become a serious health concern. The use and popularization of blood glucose measurement devices have led to a tremendous increase on health for diabetics. Tracking and maintaining traceability between glucose measurements, insulin doses and carbohydrate intake can provide useful information to physicians, health professionals, and patients. This paper presents an information system, called GLUMIS (GLUcose Management Information System), aimed to support diabetes management activities. It is made of two modules, one for glucose prediction and one for data visualization and a reasoner to aid users in their treatment. Through integration with glucose measurement devices, it is possible to collect historical data on the treatment. In addition, the integration with a tool called the REALI System allows GLUMIS to also process data on insulin doses and eating habits. Quantitative and qualitative data were collected through an experimental case study involving 10 participants. It was able to demonstrate that the GLUMIS system is feasible. It was able to discover rules for predicting future values of blood glucose by processing the past history of measurements. Then, it presented reports that can help diabetics choose the amount of insulin they should take and the amount of carbohydrate they should consume during the day. Rules found by using one patient’s measurements were analyzed by a specialist that found three of them to be useful for improving the patient’s treatment. One such rule was “if glucose before breakfast ∈ [ 47 , 89 ] , then glucose at afternoon break in [ 160 , 306 ]”. The results obtained through the experimental study and other verifications associated with the algorithm created had a double objective. It was possible to show that participants, through a questionnaire, viewed the visualizations as easy, or very easy, to understand. The secondary objective showed that the innovative algorithm applied in the GLUMIS system allows the decision maker to have much more precision and less loss of information than in algorithms that require the data to be discretized.
Anti-Proliferative and Anti-Migration Activity of Arene–Ruthenium(II) Complexes with Azole Therapeutic Agents
Authors: Colina-Vegas Legna , Oliveira Katia M. , Cunha Beatriz N. , Cominetti Marcia Regina , Navarro Maribel , Azevedo Batista Alzir
Published: December 2018

The efficacy of organoruthenium complexes containing ergosterol biosynthesis inhibitors (CTZ: clotrimazole, KTZ: ketoconazole and FCZ: fluconazole) against tumor cells, and their interaction with important macro-biomolecules such as human serum albumin and DNA have been investigated here. Our experimental results indicated that these ruthenium(II) complexes present spontaneous electrostatic interactions with albumin, and act as minor groove binders with the DNA. The ability of these Ru(II)–azole complexes to inhibit the proliferation of selected human tumor and non-tumor cell lines was determined by MTT assay. Complexes [RuCl(CTZ)(η6-p-cymene)(PPh3)]PF6 (3) and [RuCl(KTZ)(η6-p-cymene)(PPh3)]PF6 (4) were shown to be between 3- and 40-fold more cytotoxic than the free ligands and the positive control cisplatin. Complex 3 was selected to continue studies on the triple negative breast tumor cell line MDA-MB-231, inducing morphological changes, loss of adhesion, inhibition of colony formation, and migration through Boyden chambers, cell cycle arrest in the sub-G1 phase, and a mechanism of cell death by apoptosis. All these interesting results show the potential of this class of organometallic Ru(II) complexes as an antiproliferative agent.
Zinc(II) as a Versatile Template for Efficient Dipolar and Octupolar Second-Order Nonlinear Optical Molecular Materials §
Authors: Di Bella Santo , Colombo Alessia , Dragonetti Claudia , Righetto Stefania , Roberto Dominique
Published: December 2018

This short review outlines the main results obtained in the field of molecular materials based on zinc coordination compounds for second-order nonlinear optics. It presents an overview of the main classes of second-order nonlinear optical (NLO) active complexes bearing monodentate, bidentate, tridentate, or tetradentate π-delocalized ligands such as substituted stilbazoles, bipyridines, phenanthrolines, terpyridines, and Schiff bases. Macrocyclic ligands such as porphyrins and phthalocyanines are not covered. This paper shows how coordination to the Zn(II) center of π-delocalized nitrogen donor ligands produces a significant enhancement of their quadratic hyperpolarizability. Dipolar complexes are mainly presented, but octupolar zinc complexes are also presented. The coverage is mainly focused on NLO properties that are measured at the molecular level, working in solution, by means of the electric field-induced second harmonic generation (EFISH) or the hyper-Rayleigh scattering (HRS) techniques.
Endothelial Contributions to Zebrafish Heart Regeneration
Authors: Fernandez Cristina E. , Bakovic Melanie , Karra Ravi
Published: December 2018

Studies over the past two decades have shown heart regeneration in zebrafish to be a dynamic process, choreographed by multiple cell types. In particular, recent work has identified revascularization of the wound to be a sentinel event during heart regeneration. The cardiac endothelium has emerged as a key orchestrator of heart regeneration, influencing cardiomyocyte hyperplasia and tissue morphogenesis. Here, we review how the coronary vasculature regenerates after injury, how signaling pathways link the cardiac endothelium to heart regeneration, and how understanding these signaling dynamics can lead to targeted therapies for heart regeneration.
Global Expression Profiling Identifies a Novel Hyaluronan Synthases 2 Gene in the Pathogenesis of Lower Extremity Varicose Veins
Authors: Hsieh Chia-Shan , Tsai Chia-Ti , Chen Yau-Hung , Chang Sheng-Nan , Hwang Juey-Jen , Chuang Eric Y. , Wu I-Hui
Published: December 2018

Lower extremities varicose veins (VV) are among the most easily recognized venous abnormalities. The genetic mechanism of VV is largely unknown. In this study, we sought to explore the global expressional change of VV and identify novel genes that might play a role in VV. We used next-generation ribonucleic acid (RNA) sequence (RNA seq) technology to study the global messenger RNA expressional change in the venous samples of five diseased and five control patients. We identified several differentially expressed genes, which were further confirmed by conventional reverse transcription polymerase chain reaction (RT-PCR). Using these significant genes we performed in silico pathway analyses and found distinct transcriptional networks, such as angiogenesis, cell adhesion, vascular injury, and carbohydrate metabolisms that might be involved in the mechanism of VV. Among these significant genes, we also found hyaluronan synthases 2 gene (HAS2) played a pivotal role and governed all these pathways. We further confirmed that HAS2 expression was decreased in the venous samples of patients with VV. Finally, we used a zebrafish model with fluorescence emitting vasculature and red blood cells to see the morphological changes of the venous system and blood flow. We found that HAS2 knockdown in zebrafish resulted in dilated venous structural with static venous flow. HAS2 may modulate the transcriptional networks of angiogenesis, cell adhesion, vascular injury, and carbohydrate metabolisms in venous tissues and downregulation of HAS2 may underlie the mechanism of VV.
Effect of Gender on the Outcome of Patients Receiving Immune Checkpoint Inhibitors for Advanced Cancer: A Systematic Review and Meta-Analysis of Phase III Randomized Clinical Trials
Authors: Grassadonia Antonino , Sperduti Isabella , Vici Patrizia , Iezzi Laura , Brocco Davide , Gamucci Teresa , Pizzuti Laura , Maugeri-Saccà Marcello , Marchetti Paolo , Cognetti Gaetana , De Tursi Michele , Natoli Clara , Barba Maddalena , Tinari Nicola
Published: December 2018

Evidence has recently emerged on the influence of gender on the immune system. In this systematic review and meta-analysis of phase III randomized clinical trials (RCTs), we explored the impact of gender on survival in patients with advanced cancer treated with immune checkpoint inhibitors (ICIs). We performed a comprehensive search of the literature updated to April 2018, including the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE. We extracted data on study characteristics and risk of bias in duplicate. Of 423 unique citations, 21 RCTs were included, inherently to 12,635 patients. Both males and females showed reduced risk of death associated with ICIs use (HR 0.73, p < 0.001 and HR 0.77, p < 0.001, respectively). Subgroup analyses by specific ICI showed similar OS in both genders for anti-PD-1/PDL-1. Anti-CTLA-4 use was associated with longer OS in men only (HR 0.77, p < 0.012), with the exception of melanoma (in women, HR 0.80, p = 0.006). PFS was longer in men than in women (HR 0.67, p < 0.001 and HR 0.77, p = 0.100, respectively). Conclusively, ICIs use was associated with more favorable outcomes in men, particularly for anti-CTLA-4 agents. In melanoma, not gender-related factors may influence the anti-tumor immune response evoked by ICIs.
A Three-Dimensional Dense Collagen Hydrogel to Model Cancer Cell/Osteoblast Interactions
Authors: James-Bhasin Mark , Siegel Peter M. , Nazhat Showan N.
Published: December 2018

No curative treatment options exist once breast cancer metastasizes to bone. This is due, in part, to an incomplete understanding of how osteolytic cancers interact with bone. Presented here is a novel approach to study the interactions between triple negative breast cancer cells and osteoblasts within a 3D collagenous environment. More specifically, a dense collagen hydrogel was employed to model interactions between MDA-MB-231 breast cancer cells and MC3T3-E1 pre-osteoblasts. Co-cultures with these two cell types, or MDA-MB-231-derived conditioned medium applied to MC3T3-E1 cells, were established in the context of plastically compressed dense collagen gel matrices. Importantly, breast cancer-derived conditioned medium or the establishment of breast cancer/osteoblast co-cultures did not negatively influence MC3T3-E1 cell viability. The inclusion of either conditioned medium or the presence of MDA-MB-231 cells resulted in impaired MC3T3-E1 differentiation into osteoblasts, which coincided with reduced osteoblast-mediated mineralization. The results presented here demonstrate that dense collagen gels provide a model environment to examine the effect of osteolytic breast cancer cells on osteoblast differentiation and subsequent mineralization of the collagen scaffold.
Coastal Climate Adaptation Literatures of the Southeast and Northeast U.S.: Regional Comparisons among States and Document Sources
Authors: Lindeman Kenyon C. , Giannoulis Christos , Beard Bryce R.
Published: December 2018

Challenges remain in optimizing the use of increasingly large inflows of climate adaptation articles and guidance documents to improve coastal science and engineering practices. In addition to four major academic databases, the large grey literature was quantified by analyzing web sources of hundreds of government, nonprofit and university reports not previously included in reviews. Three spatial scales were examined for differences in amount and timing of adaptation documents: (a) between region (southeast and northeast U.S.); (b) among sub-region (Florida and Carolinas; New York/New Jersey and New England); and (c) among states (ten states total). Comparisons were also made across spatial scales for document sources (academic journals, government, non-governmental organizations (NGO), university, mixed sources), including four governance subcategories (federal, state, regional and local). Differences were identified among some spatial scales in academic vs. grey literature and among categories of grey literature. 53% of the literature was from grey sources (21% government, 10% university, 8% nonprofit and 14% mixed sources). This literature can be large and is grounded in applied, experiential knowledge, yet is unavailable in almost all academic databases. These relatively hidden documents provide insight into on-the-ground science and engineering case-histories, policy innovations, and power relationships across scales of geography and governance.