bluuebunny/crossref_metadata_2025 huggingface dataset:
Physical Cues in the Microenvironment Regulate Stemness-Dependent Homing of Breast Cancer Cells
Authors: Chu Hsueh-Yao , Chen Yin-Ju , Hsu Chun-Jieh , Liu Yang-Wei , Chiou Jeng-Fong , Lu Long-Sheng , Tseng Fan-Gang
Published: August 2020

Tissue-specific microenvironmental factors contribute to the targeting preferences of metastatic cancers. However, the physical attributes of the premetastatic microenvironment are not yet fully characterized. In this research, we develop a transwell-based alginate hydrogel (TAH) model to study how permeability, stiffness, and roughness of a hanging alginate hydrogel regulate breast cancer cell homing. In this model, a layer of physically characterized alginate hydrogel is formed at the bottom of a transwell insert, which is placed into a matching culture well with an adherent monolayer of breast cancer cells. We found that breast cancer cells dissociate from the monolayer and home to the TAH for continual growth. The process is facilitated by the presence of rich serum in the upper chamber, the increased stiffness of the gel, as well as its surface roughness. This model is able to support the homing ability of MCF-7 and MDA-MB-231 cells drifting across the vertical distance in the culture medium. Cells homing to the TAH display stemness phenotype morphologically and biochemically. Taken together, these findings suggest that permeability, stiffness, and roughness are important physical factors to regulate breast cancer homing to a premetastatic microenvironment.
The Biology of Exosomes in Breast Cancer Progression: Dissemination, Immune Evasion and Metastatic Colonization
Authors: Giordano Cinzia , La Camera Giusi , Gelsomino Luca , Barone Ines , Bonofiglio Daniela , Andò Sebastiano , Catalano Stefania
Published: August 2020

In recent decades, the study of exosome biology has gained growing interest, representing an active area of cancer research with many potential clinical applications. Exosomes are small lipid bilayer particles released by cells with pleiotropic functions that have been reported to regulate the complex intracellular pathway involved in all steps of breast cancer development—from initiation to progression toward a metastatic dissemination. Particularly, the role of these microvesicles has been explored in metastasis, which represents the leading cause of breast cancer morbidity and mortality worldwide. Reports highlight that the plasticity of breast cancer cells, fundamental for the establishment of distant metastasis, may be in part attributed to exosome-carried signals shared between adjacent cells and long-distance cells in the body. In the present review, we will discuss the functions of exosomes in the metastatic breast cancer process and secondary site outgrowth. The possibility to decode the exosome functions in advanced diseases may offer new opportunities for early detection, molecular targeted therapies and exosome-based therapeutics in breast cancer.
Characteristics of PSA Bounce after Radiotherapy for Prostate Cancer: A Meta-Analysis
Authors: Darwis Narisa Dewi Maulany , Oike Takahiro , Kubo Nobuteru , Gondhowiardjo Soehartati A , Ohno Tatsuya
Published: August 2020

The rate and characteristics of prostate-specific antigen (PSA) bounce post-radiotherapy remain unclear. To address this issue, we performed a meta-analysis. Reports of PSA bounce post-radiotherapy with a cutoff of 0.2 ng/mL were searched by using Medline and Web of Science. The primary endpoint was the occurrence rate, and the secondary endpoints were bounce characteristics such as amplitude, time to occurrence, nadir value, and time to nadir. Radiotherapy modality, age, risk classification, androgen deprivation therapy, and the follow-up period were extracted as clinical variables. Meta-analysis and univariate meta-regression were performed with random-effect modeling. Among 290 search-positive studies, 50 reports including 26,258 patients were identified. The rate of bounce was 31%; amplitude was 1.3 ng/mL; time to occurrence was 18 months; nadir value was 0.5 ng/mL; time to nadir was 33 months. Univariate meta-regression analysis showed that radiotherapy modality (29.7%), age (20.2%), and risk classification (12.2%) were the major causes of heterogeneity in the rate of bounce. This is the first meta-analysis of PSA bounce post-radiotherapy. The results are useful for post-radiotherapy surveillance of prostate cancer patients.
SARS-CoV-2 Infection and Lung Cancer: Potential Therapeutic Modalities
Authors: Gupta Ishita , Rizeq Balsam , Elkord Eyad , Vranic Semir , Al Moustafa Ala-Eddin
Published: August 2020

Human coronaviruses, especially SARS-CoV-2, are emerging pandemic infectious diseases with high morbidity and mortality in certain group of patients. In general, SARS-CoV-2 causes symptoms ranging from the common cold to severe conditions accompanied by lung injury, acute respiratory distress syndrome in addition to other organs’ destruction. The main impact upon SARS-CoV-2 infection is damage to alveolar and acute respiratory failure. Thus, lung cancer patients are identified as a particularly high-risk group for SARS-CoV-2 infection and its complications. On the other hand, it has been reported that SARS-CoV-2 spike (S) protein binds to angiotensin-converting enzyme 2 (ACE-2), that promotes cellular entry of this virus in concert with host proteases, principally transmembrane serine protease 2 (TMPRSS2). Today, there are no vaccines and/or effective drugs against the SARS-CoV-2 coronavirus. Thus, manipulation of key entry genes of this virus especially in lung cancer patients could be one of the best approaches to manage SARS-CoV-2 infection in this group of patients. We herein provide a comprehensive and up-to-date overview of the role of ACE-2 and TMPRSS2 genes, as key entry elements as well as therapeutic targets for SARS-CoV-2 infection, which can help to better understand the applications and capacities of various remedial approaches for infected individuals, especially those with lung cancer.
Phenotypic and Functional Characterization of NK Cells in αβT-Cell and B-Cell Depleted Haplo-HSCT to Cure Pediatric Patients with Acute Leukemia
Authors: Meazza Raffaella , Falco Michela , Loiacono Fabrizio , Canevali Paolo , Della Chiesa Mariella , Bertaina Alice , Pagliara Daria , Merli Pietro , Indio Valentina , Galaverna Federica , Algeri Mattia , Moretta Francesca , Colomar-Carando Natalia , Muccio Letizia , Sivori Simona , Pession Andrea , Mingari Maria Cristina , Moretta Lorenzo , Moretta Alessandro , Locatelli Franco , Pende Daniela
Published: August 2020

NK cells can exert remarkable graft-versus-leukemia (GvL) effect in HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Here, we dissected the NK-cell repertoire of 80 pediatric acute leukemia patients previously reported to have an excellent clinical outcome after αβT/B-depleted haplo-HSCT. This graft manipulation strategy allows the co-infusion of mature immune cells, mainly NK and γδT cells, and hematopoietic stem cells (HSCs). To promote NK-cell based antileukemia activity, 36/80 patients were transplanted with an NK alloreactive donor, defined according to the KIR/KIR-Ligand mismatch in the graft-versus-host direction. The analysis of the reconstituted NK-cell repertoire in these patients showed relatively high proportions of mature and functional KIR+NKG2A−CD57+ NK cells, including the alloreactive NK cell subset, one month after HSCT. Thus, the NK cells adoptively transfused with the graft persist as a mature source of effector cells while new NK cells differentiate from the donor HSCs. Notably, the alloreactive NK cell subset was endowed with the highest anti-leukemia activity and its size in the reconstituted repertoire could be influenced by human cytomegalovirus (HCMV) reactivation. While the phenotypic pattern of donor NK cells did not impact on post-transplant HCMV reactivation, in the recipients, HCMV infection/reactivation fostered a more differentiated NK-cell phenotype. In this cohort, no significant correlation between differentiated NK cells and relapse-free survival was observed.
Expression and Characterization of a GH16 Family β-Agarase Derived from the Marine Bacterium Microbulbifer sp. BN3 and Its Efficient Hydrolysis of Agar Using Raw Agar-Producing Red Seaweeds Gracilaria sjoestedtii and Gelidium amansii as Substrates
Authors: Li Ren Kuan , Ying Xi Juan , Chen Zhi Lin , Ng Tzi Bun , Zhou Zhi Min , Ye Xiu Yun
Published: August 2020

Agarases catalyze the hydrolysis of agarose to oligosaccharides which display an array of biological and physiological functions with important industrial applications in health-related fields. In this study, the gene encoding agarase (Aga-ms-R) was cloned from Microbulbifer sp. BN3 strain. Sequence alignment indicated that Aga-ms-R belongs to the GH16 family and contains one active domain and two carbohydrate binding module (CBM) domains. The mature Aga-ms-R was expressed successfully by employing the Brevibacillus system. Purified rAga-ms-R was obtained with a specific activity of 100.75 U/mg. rAga-ms-R showed optimal activity at 50 °C and pH 7.0, and the enzyme activity was stable at 50 °C and also over the pH range of 5.0–9.0. After exposure of rAga-ms-R to 70 °C for 30 min, only partial enzyme activity remained. Thin layer chromatographic analysis of the enzymatic hydrolysate of agar obtained using rAga-ms-R disclosed that the hydrolysate comprised, in a long intermediate-stage of the hydrolysis reaction, mainly neoagarotetraose (NA4) and neoagarohexaose (NA6) but ultimately, predominantly neoagarotetraose and trace amounts of neoagarobiose (NA2). Hydrolysates of the raw red seaweeds Gracilaria sjoestedtii and Gelidium amansii, produced by incubation with rAga-ms-R, were mainly composed of neoagarotetraose. The results demonstrate the high efficiency of rAga-ms-R in producing neoagaraoligosaccharide under low-cost conditions.
Enhancement of Photocatalytic Activities with Nanosized Polystyrene Spheres Patterned Titanium Dioxide Films for Water Purification
Authors: Seo Hyeon Jin , Lee Ji Won , Na Young Hoon , Boo Jin-Hyo
Published: August 2020

For environmental applications, such as water and air purification utilizing photocatalysts, we synthesized patterned titanium dioxide (TiO2) thin films using polystyrene (PS) spheres. This was primarily done to enhance the surface area and photocatalytic activities. TiO2 thin films were deposited on silicon wafers attached to variously sized PS spheres via the spin coating method and were annealed at 600 °C. The processing step involved patterning and coating a TiO2 sol–gel. The photocatalytic performance was analyzed using an UV–visible spectrophotometer. Within 20 min, a high catalytic efficiency (98% removal) with a 20-time faster decomposition rate of the malachite green (MG) solution than that of the nonpatterned TiO2 was obtained from the patterned TiO2 with 400 nm sized PS due to the large surface area. In addition, the phenol in the water removed as much as 50% within 2 h with the same photocatalyst, which was expected to be one of the strong candidates to be applied to the next generation of photocatalysts for water purification.
Epigenomic Dysregulation in Schizophrenia: In Search of Disease Etiology and Biomarkers
Authors: Khavari Behnaz , Cairns Murray J.
Published: August 2020

Schizophrenia is a severe psychiatric disorder with a complex array of signs and symptoms that causes very significant disability in young people. While schizophrenia has a strong genetic component, with heritability around 80%, there is also a very significant range of environmental exposures and stressors that have been implicated in disease development and neuropathology, such as maternal immune infection, obstetric complications, childhood trauma and cannabis exposure. It is postulated that epigenetic factors, as well as regulatory non-coding RNAs, mediate the effects of these environmental stressors. In this review, we explore the most well-known epigenetic marks, including DNA methylation and histone modification, along with emerging RNA mediators of epigenomic state, including miRNAs and lncRNAs, and discuss their collective potential for involvement in the pathophysiology of schizophrenia implicated through the postmortem analysis of brain tissue. Given that peripheral tissues, such as blood, saliva, and olfactory epithelium have the same genetic composition and are exposed to many of the same environmental exposures, we also examine some studies supporting the application of peripheral tissues for epigenomic biomarker discovery in schizophrenia. Finally, we provide some perspective on how these biomarkers may be utilized to capture a signature of past events that informs future treatment.
Evaluating and Enhancing the Preparation of Patients and Families before Pediatric Surgery
Authors: Newell Christopher , Leduc-Pessah Heather , Bell-Graham Lisa , Rasic Nivez , Carter Kerryn
Published: August 2020

Surgery can be a difficult and unfamiliar experience for children and their families. We examined the ability of existing information to help families feel better prepared for surgery at the Alberta Children’s Hospital (ACH) and evaluated the best way to enhance its content and accessibility. We developed an online survey for families who have had surgery at ACH. Participants were recruited through pre-existing patient networks and from the ACH Short Stay Unit (SSU) between October 2018 and October 2019. The survey asked participants to evaluate the information available to prepare them for surgery and requested suggestions for improvement. Our survey results show that those who completed the in-person Surgery 101 program felt significantly more prepared for surgery. Of those who did not attend; 40% would have been interested in participating but were unaware that the program existed; and 17% planned to attend but were unable to; due to work or travel distance. Participants felt additional resources via online content or paper handouts would be most valuable. We used this information to prepare an online accessible summary of the Surgery 101 program and tour in the form of a video to reach more Albertan families preparing for surgery for their children
The Effect of Various Surface Treatments of Ti6Al4V on the Growth and Osteogenic Differentiation of Adipose Tissue-Derived Stem Cells
Authors: Stepanovska Jana , Matejka Roman , Otahal Martin , Rosina Jozef , Bacakova Lucie
Published: August 2020

The physical and chemical properties of the material surface, especially its roughness and wettability, have a crucial effect on the adhesion, proliferation, and differentiation of cells. The aim of this study is to select the most appropriate surface modifications of Ti6Al4V implants for pre-colonization of the implants with adipose tissue-derived stem cells (ASCs) in order to improve their osseointegration. We compared the adhesion, growth, and osteogenic differentiation of rat ASCs on Ti6Al4V samples modified by methods commonly used for preparing clinically used titanium-based implants, namely polishing (PL), coating with diamond-like carbon (DLC), brushing (BR), anodizing (AND), and blasting (BL). The material surface roughness, measured by the Ra and Rq parameters, increased in the following order: PL < DLC ˂ BR ˂ AND ˂ BL. The water drop contact angle was in the range of 60–74°, with the exception of the DLC-coated samples, where it was only 38°. The cell number, morphology, mitochondrial activity, relative fluorescence intensity of osteogenic markers RUNX2, type 1 collagen, and osteopontin, the calcium consumption by the cells and the alkaline phosphatase activity depended on the surface roughness rather than on the surface wettability of the materials. Materials with a surface roughness of several tens of nanometers (Ra 60–70 nm), i.e., the BR and AND samples, supported a satisfactory level of cell proliferation. At the same time, they achieved the highest level of osteogenic cell differentiation. These surface modifications therefore seem to be most suitable for pre-colonization of Ti6Al4V implants with stem cells pre-differentiated toward osteoblasts, and then for implanting them into the bone tissue.
Architecture and Steel. Reflection and Analysis on the Use of Steel Structures (in Sight) as a Concept in the History of Architecture
Authors: Campos Inês D. D. , Bernardo Luís F. A.
Published: August 2020

This is the first of two companion articles which aim to address the research on Architecture and Steel. In this article, some architectural projects are analyzed to show the potentiality to conjugate architectural conception and steel structures, as well as to show the contribution and influence from architectural history. This article also aims to contribute to the reflection of the knowledge and legacy left to us by several architects throughout the history of architecture in using aesthetic, visual and structurally safe profiled steel structures in architectural conception. The presented analysis and reflection are based on the characteristics and influences of the Industrial Revolution and, mainly, the Modern Movement, where the first housing projects came up with this constructive system, combined with the “simplistic” ways of living in architecture, highlighting the relationship with the place, cultural, spatial and typological references, the structural systems and associated materiality. In view of the diversity of alternatives allowed by the use of steel “Skeletons”, modular and standardized, combined with a huge variety of existing materials and constructive complexity, well combined and interconnected, it is possible to obtain a final product whose characteristics seduce by their beauty and elegance. Moreover, the practical and functional comfort which allows the safeguarding of the architectural integration of such product, with the necessary serenity in space and nature, in full environmental integration, is also emphasized.
Recent and Current Advances in FDG-PET Imaging within the Field of Clinical Oncology in NSCLC: A Review of the Literature
Authors: Kaseda Kaoru
Published: August 2020

Lung cancer is the leading cause of cancer-related deaths around the world, the most common type of which is non-small-cell lung cancer (NSCLC). Computed tomography (CT) is required for patients with NSCLC, but often involves diagnostic issues and large intra- and interobserver variability. The anatomic data obtained using CT can be supplemented by the metabolic data obtained using fluorodeoxyglucose F 18 (FDG) positron emission tomography (PET); therefore, the use of FDG-PET/CT for staging NSCLC is recommended, as it provides more accuracy than either modality alone. Furthermore, FDG-PET/magnetic resonance imaging (MRI) provides useful information on metabolic activity and tumor cellularity, and has become increasingly popular. A number of studies have described FDG-PET/MRI as having a high diagnostic performance in NSCLC staging. Therefore, multidimensional functional imaging using FDG-PET/MRI is promising for evaluating the activity of the intratumoral environment. Radiomics is the quantitative extraction of imaging features from medical scans. The chief advantages of FDG-PET/CT radiomics are the ability to capture information beyond the capabilities of the human eye, non-invasiveness, the (virtually) real-time response, and full-field analysis of the lesion. This review summarizes the recent advances in FDG-PET imaging within the field of clinical oncology in NSCLC, with a focus on surgery and prognostication, and investigates the site-specific strengths and limitations of FDG-PET/CT. Overall, the goal of treatment for NSCLC is to provide the best opportunity for long-term survival; therefore, FDG-PET/CT is expected to play an increasingly important role in deciding the appropriate treatment for such patients.
Economic Performance of Genetically Improved Reforestation Material in Joint Production of Timber and Carbon Sequestration: A Case Study from Finland
Authors: Ahtikoski Anssi , Ahtikoski Roope , Haapanen Matti , Hynynen Jari , Kärkkäinen Katri
Published: August 2020

Genetically improved material has been proven to financially outperform unimproved material in timber production according to various studies. Genetic improvements in carbon sequestration are also promising, implying a possibility for further financial gains. Research Highlights: Including carbon pricing (i.e., timber production combined with carbon sequestration) with genetically improved material improves financial performance compared to pure timber production. Furthermore, the proportion of carbon benefit (%) of absolute bare land value fluctuates between 27% and 42%, indicating a substantial role of carbon sequestration to financial performance. Background and Objectives: Until now, economic analyses of the impact of tree improvement have mainly dealt with growth performance: volume yield or height growth. Yet planted forests can have a significant contribution to carbon sequestration, which will play a major role in carbon markets. This study focuses on comparing the financial performance between genetically improved and unimproved reforestation material when stand management is optimized according to timber production or to joint production (timber and carbon sequestration together). Another goal is to reveal possible differences in financial performance related to climatic conditions along the south–north gradient. Materials and Methods: The stand projections are based on simulations with and without genetic gains for joint production (timber + carbon) and merely timber production in eight locations in Finland. Stand-level optimization is applied for financial analyses. Results: Genetically improved reforestation material considerably enhanced financial performance when the joint production of timber and carbon was applied, regardless of the climatic region. Conclusions: If carbon pricing became a reality, there would be a distinctive shift in bare land values, which is further boosted by a genetic gain.
Diversity and Pathogenicity of Phytophthora Species Associated with Declining Alder Trees in Italy and Description of Phytophthora alpina sp. nov
Authors: Bregant Carlo , Sanna Gian Paolo , Bottos Adriano , Maddau Lucia , Montecchio Lucio , Linaldeddu Benedetto T.
Published: August 2020

Extensive decline and mortality events of alder trees have recently been observed in several riparian ecosystems in Italy. Since there is little information about the aetiology of this disease and given the high ecological relevance of riparian ecosystems, an in-depth study was conducted in three sites spanning from the Mediterranean to Alpine regions. From spring 2019 to spring 2020, 261 samples of bleeding cankers, rhizosphere soil and leaves used as baits along waterways were collected and used for Phytophthora isolation. Based on morphology, colony appearance and DNA sequence data, 10 species belonging to 6 clades were identified. These included P. plurivora (84 isolates), P. pseudocryptogea (50), P. hydropathica (18), P. gonapodyides (14), P. bilorbang (13), P. pseudosyringae (12), P. lacustris (11), P. acerina (7), P. cactorum (1) and one isolate of the hybrid Phytophthora ×serendipita. In addition, two new Phytophthora species, one of which is described here as Phytophthora alpina sp. nov., were isolated. The pathogenicity of P. alpina and other species obtained from samples collected in the green alder stand was assessed on 3-year-old seedlings. All species proved to be pathogenic on green alder causing symptoms congruent with field observations. Results obtained have allowed us to expand knowledge about alder decline aetiology. The diversity of pathogenicity of Phytophthora species associated with symptomatic alder trees suggested that no single agent is responsible for the disease, but that it is the result of multiple infections of different Phytophthora species, variable in assemblages among sites.
Modelling Organic Gel Growth in Three Dimensions: Textural and Fractal Properties of Resorcinol–Formaldehyde Gels
Authors: Martin Elisha , Prostredny Martin , Fletcher Ashleigh , Mulheran Paul
Published: August 2020

Tailoring the properties of porous organic materials, such as resorcinol–formaldehyde gels, for use in various applications has been a central focus for many studies in recent years. In order to achieve effective optimisation for each application, this work aims to assess the impact of the various synthesis parameters on the final textural properties of the gel. Here, the formation of porous organic gels is modelled using a three-dimensional lattice-based Monte Carlo simulation. We model growth from monomer species into the interconnected primary clusters of a gel, and account for varying catalyst concentration and solids content, two parameters proven to control gel properties in experimental work. In addition to analysing the textural properties of the simulated materials, we also explore their fractal properties through correlation dimension and Hurst exponent calculations. The correlation dimension shows that while fractal properties are not typically observed in scattering experiments, they are possible to achieve with sufficiently low solids content and catalyst concentration. Furthermore, fractal properties are also apparent from the analysis of the diffusion path of guest species through the gel’s porous network. This model, therefore, provides insight into how porous organic gels can be manufactured with their textural and fractal properties computationally tailored according to the intended application.
Color Intensity of the Red-Fleshed Berry Phenotype of Vitis vinifera Teinturier Grapes Varies Due to a 408 bp Duplication in the Promoter of VvmybA1
Authors: Röckel Franco , Moock Carina , Braun Ulrike , Schwander Florian , Cousins Peter , Maul Erika , Töpfer Reinhard , Hausmann Ludger
Published: August 2020

Grapevine (Vitis vinifera) teinturier cultivars are characterized by their typical reddish leaves and red-fleshed berries due to ectopic anthocyanin formation. Wines of these varieties have economic importance as they can be used for blending to enhance the color of red wines. The unique and heritable mutation has been known for a long time but the underlying genetic mechanism still is not yet understood. Here we describe the association of the red-fleshed berry phenotype with a 408 bp repetitive DNA element in the promoter of the VvmybA1 gene (grapevine color enhancer, GCE). Three different clones of ‘Teinturier’ were discovered with two, three and five allelic GCE repeats (MybA1t2, MybA1t3 and MybA1t5). All three clones are periclinal chimeras; these clones share the same L1 layer, but have distinct L2 layers with different quantities of GCE repeats. Quantitative real time PCR and HPLC analysis of leaf and berry samples showed that the GCE repeat number strongly correlates with an increase of the expression of VvmybA1 itself and the VvUFGT gene regulated by it and the anthocyanin content. A model is proposed based on autoregulation of VvmybA1t to explain the red phenotype which is similar to that of red-fleshed apples. This study presents results about the generation and modes of action of three MybA1t alleles responsible for the red-fleshed berry phenotype of teinturier grapevines.
Combining Random Forests and a Signal Detection Method Leads to the Robust Detection of Genotype-Phenotype Associations
Authors: Ramzan Faisal , Gültas Mehmet , Bertram Hendrik , Cavero David , Schmitt Armin Otto
Published: August 2020

Genome wide association studies (GWAS) are a well established methodology to identify genomic variants and genes that are responsible for traits of interest in all branches of the life sciences. Despite the long time this methodology has had to mature the reliable detection of genotype–phenotype associations is still a challenge for many quantitative traits mainly because of the large number of genomic loci with weak individual effects on the trait under investigation. Thus, it can be hypothesized that many genomic variants that have a small, however real, effect remain unnoticed in many GWAS approaches. Here, we propose a two-step procedure to address this problem. In a first step, cubic splines are fitted to the test statistic values and genomic regions with spline-peaks that are higher than expected by chance are considered as quantitative trait loci (QTL). Then the SNPs in these QTLs are prioritized with respect to the strength of their association with the phenotype using a Random Forests approach. As a case study, we apply our procedure to real data sets and find trustworthy numbers of, partially novel, genomic variants and genes involved in various egg quality traits.
High-Density SNP-Based Association Mapping of Seed Traits in Fenugreek Reveals Homology with Clover
Authors: Abd El-Wahab Mustafa M. H. , Aljabri Maha , Sarhan Mohamed S. , Osman Gamal , Wang Shichen , Mabrouk Mahmoud , El-Shabrawi Hattem M. , Gabr Ahmed M. M. , Abd El-Haliem Ahmed M. , O'Sullivan Donal M. , El-Soda Mohamed
Published: August 2020

Fenugreek as a self-pollinated plant is ideal for genome-wide association mapping where traits can be marked by their association with natural mutations. However, fenugreek is poorly investigated at the genomic level due to the lack of information regarding its genome. To fill this gap, we genotyped a collection of 112 genotypes with 153,881 SNPs using double digest restriction site-associated DNA sequencing. We used 38,142 polymorphic SNPs to prove the suitability of the population for association mapping. One significant SNP was associated with both seed length and seed width, and another SNP was associated with seed color. Due to the lack of a comprehensive genetic map, it is neither possible to align the newly developed markers to chromosomes nor to predict the underlying genes. Therefore, systematic targeting of those markers to homologous genomes of other legumes can overcome those problems. A BLAST search using the genomic fenugreek sequence flanking the identified SNPs showed high homology with several members of the Trifolieae tribe indicating the potential of translational approaches to improving our understanding of the fenugreek genome. Using such a comprehensively-genotyped fenugreek population is the first step towards identifying genes underlying complex traits and to underpin fenugreek marker-assisted breeding programs.
Pathological Consequences of Hepatic mTORC1 Dysregulation
Authors: Cho Chun-Seok , Kowalsky Allison Ho , Lee Jun Hee
Published: August 2020

The mammalian target of rapamycin complex 1 (mTORC1) is a central regulator of metabolism that integrates environmental inputs, including nutrients, growth factors, and stress signals. mTORC1 activation upregulates anabolism of diverse macromolecules, such as proteins, lipids, and nucleic acids, while downregulating autolysosomal catabolism. mTORC1 dysregulation is often found in various diseases, including cancer, cardiovascular and neurodegenerative diseases, as well as metabolic syndromes involving obesity and type II diabetes. As an essential metabolic organ, the liver requires proper regulation of mTORC1 for maintaining homeostasis and preventing pathologies. For instance, aberrant hyper- or hypoactivation of mTORC1 disrupts hepatocellular homeostasis and damages the structural and functional integrity of the tissue, leading to prominent liver injury and the development of hepatocellular carcinogenesis. Proper regulation of mTORC1 during liver diseases may be beneficial for restoring liver function and ameliorating the detrimental consequences of liver failure.
Influential Factors Associated with Consecutive Crash Severity: A Two-Level Logistic Modeling Approach
Authors: Meng Fanyu , Xu Pengpeng , Song Cancan , Gao Kun , Zhou Zichu , Yang Lili
Published: August 2020

A consecutive crash series is composed by a primary crash and one or more subsequent secondary crashes that occur immediately within a certain distance. The crash mechanism of a consecutive crash series is distinctive, as it is different from common primary and secondary crashes mainly caused by queuing effects and chain-reaction crashes that involve multiple collisions in one crash. It commonly affects a large area of road space and possibly causes congestions and significant delays in evacuation and clearance. This study identified the influential factors determining the severity of primary and secondary crashes in a consecutive crash series. Basic, random-effects, random-parameters, and two-level binary logistic regression models were established based on crash data collected on the freeway network of Guizhou Province, China in 2018, of which 349 were identified as consecutive crashes. According to the model performance metrics, the two-level logistic model outperformed the other three models. On the crash level, double-vehicle primary crash had a negative association with the severity of secondary consecutive crashes, and the involvement of trucks in the secondary consecutive crash had a positive contribution to its crash severity. On a road segment level, speed limit, traffic volume, tunnel, and extreme weather conditions such as rainy and cloudy days had positive effects on consecutive crash severity, while the number of lanes was negatively associated with consecutive crash severity. Policy suggestions are made to alleviate the severity of consecutive crashes by reminding the drivers with real-time potential hazards of severe consecutive crashes and providing educative programs to specific groups of drivers.
Factors Influencing Patient Adherence to Tuberculosis Treatment in Ethiopia: A Literature Review
Authors: Nezenega Zekariyas Sahile , Perimal-Lewis Lua , Maeder Anthony John
Published: August 2020

Background: Tuberculosis (TB) is a major global public health problem and one of the leading causes of death among infectious diseases. Although TB can be cured with first-line antibiotics treatment of 6 months regimen, non-adherence to the treatment remains the main challenge for TB prevention and control. Interventions to promote adherence need to address multiple underlying factors linked to non-adherence, which requires a synthesis of studies to understand these factors in the local context. Our review accordingly examines these factors for TB treatment in Ethiopia. Methods: Articles were searched from PubMed and ScienceDirect databases, as well as manual searches through Google and Google Scholar search engines. Both quantitative and qualitative studies that showed factors associated with or reasons for non-adherence, default or loss to follow up from TB treatment were included. A total of 276 articles were screened, and 29 articles were ultimately included in the review. Findings: The extracted factors were synthesized thematically into seven dimensions of patient-centred, social, economic, health system, therapy, lifestyle, and geographic access factors. More than 20 distinct factors were identified under these headings. Some of these factors may also apply quite widely in other settings, with greater or lesser influence, but some are particularly applicable to the Ethiopian setting. Conclusion: Helping patients to achieve full adherence to TB medication is a complex problem as it is influenced by interplay between many factors. Healthcare managers, providers, and researchers need to consider and address multiple underlying factors when designing adherence interventions. This work provides a reference set of such factors for Ethiopian interventions.
To Work at Clinics or at Hospitals? Analysis of Family Physician Recruitment Advertising in Taiwan
Authors: Cheng Yi-Shin , Tan Ann Charis , Hsu Ya-Chuan , Chen Tzeng-Ji
Published: August 2020

Family physicians act as gatekeepers of the healthcare system and have an indispensable role in providing holistic care in the primary care system. While previous studies had focused on the geographic maldistribution of family physicians, the current study investigated the distribution of job opportunities for family physicians by analyzing recruitment advertisements posted in medical association journals, as an indirect way to observe the marketplace demand for physicians. We collected all the recruitment advertisements for family physicians in the twelve issues of the Taiwan Medical Journal, the official organ of the Taiwan Medical Association, in 2018. In contrast to 124 new trainees annually, 739 advertisements for family physicians were posted within the entire year. After eliminating repeated advertisements, there were 302 distinct advertisements, of which hospitals accounted for 18.9% (n = 57). The job opportunities at hospitals were offered mainly by regional hospitals (n = 26) and community hospitals (n = 29), but only two by medical centers. Family physicians in Taiwan were in great demand not only by primary care clinics but also by hospitals. The role of family physicians in hospitals is worth further study.
Quantitative Analysis of Effects of a Single 60Co Gamma Ray Point Exposure on Time-Dependent Change in Locomotor Activity in Rats
Authors: Otani Keiko , Ohtaki Megu , Fujimoto Nariaki , Saimova Aisulu , Chaizhunusova Nailya , Rakhypbekov Tolebay , Sato Hitoshi , Kawano Noriyuki , Hoshi Masaharu
Published: August 2020

Investigating initial behavioral changes caused by irradiation of animals might provide important information to aid understanding of early health effects of radiation exposure and clinical features of radiation injury. Although previous studies in rodents suggested that radiation exposure leads to reduced activity, detailed properties of the effects were unrevealed due to a lack of proper statistical analysis, which is needed to better elucidate details of changes in locomotor activity. Ten-week-old male Wistar rats were subjected to single point external whole-body irradiation with 60Co gamma rays at 0, 2.0, 3.5, and 5.0 Gy (four rats per group). Infrared sensors were used to continuously record the locomotor activity of each rat. The cumulative number of movements during the night was defined as “activity” for each day. A non-linear mixed effects model accounting for individual differences and daily fluctuation of activity was applied to analyze the rats’ longitudinal locomotor data. Our statistical method revealed characteristics of the changes in locomotor activity after radiation exposure, showing that (1) reduction in activity occurred immediately—and in a dose-dependent manner—after irradiation and (2) recovery to pre-irradiation levels required almost one week, with the same recovery rate in each dose group.
Dispensing Practices of Fixed Dose Combination Controller Therapy for Asthma in Australian Children and Adolescents
Authors: Homaira Nusrat , Daniels Benjamin , Pearson Sallie , Jaffe Adam
Published: August 2020

The Australian Asthma Handbook does not recommend use of fixed dose combination (FDC) controller medicines for asthma in children aged ≤5 years. FDCs are only recommended in children and adolescents (aged 6–18 years) not responding to initial inhaled corticosteroid (ICS) therapy. Using Pharmaceutical Benefits Scheme dispensing claims from 2013–2018, we examined the annual incident FDC dispensing and the incident FDC dispensing without prior ICS up to 365 days. We also determined cost of FDCs to government and patients. During 2013–2018, there were 35,635 FDC initiations and 31,368 (88%) did not have a preceding ICS dispensing. The annual incidence of FDC dispensing declined from 14.7 to 7.2/1000 children. Incidence of FDC dispensing/1000 children without a preceding ICS declined from 2.1 to 0.5 in children aged 1–2 years, 7.2 to 1.7 in 3–5 years, 14.8 to 5.1 in 6–11 years, and 18.6 to 11.9 in ≥12years. The cost of FDCs was 7.8 million Australian dollars (AUD); of which 4.4 million AUD was to government and 3.3 million AUD was to patient. Despite inappropriate dispensing of FDCs in children aged ≤5 years, incidence of FDC dispensing and more importantly incidence without a preceding ICS is declining in Australia.
The Coupling and Coordinated Development from Urban Land Using Benefits and Urbanization Level: Case Study from Fujian Province (China)
Authors: Wang Kun , Tang Yingkai , Chen Yaozhi , Shang Longwen , Ji Xuanming , Yao Mengchao , Wang Ping
Published: August 2020

In recent years, urbanization has been developing rapidly. However, it is also accompanied by land management problems, such as low land use efficiency. In this research, we manage to explore the temporal and spatial evolution laws as well as characteristics of the coupling and coordinated development between urbanization and land use benefits. Through this, it is possible for us to provide policy recommendations for the sustainable development of the urbanization in Fujian Province. In this study, we take prefecture-level municipal districts and county-level cities in Fujian as the research subject. We construct an index system, based on data in 2002, 2005, 2010, 2015, and 2017, to evaluate the urban land use benefits and urbanization. Besides, we leverage the Gini coefficient weighting method to give weight to each index and calculate the value of its benefits. Moreover, it is the relative development degree and the coupling coordination degree model that we comprehensively leverage to study the spatiotemporal evolution law of the coupling coordination degree (CCD). The results show that: (1) Urban land use benefits and urbanization level are positively correlated with the regional administrative level and economic development status; (2) The CCD of urban land use benefits and urbanization level in various regions of Fujian is still low. However, the overall development direction is good; (3) From the perspective of spatial distribution, the CCD owns a “center-periphery” pattern that is based on the law of diminishing CCD power from three central cities of Fuzhou, Xiamen, and Sanming. Consequently, it requires governments to take action. Firstly, they should promote the intensive land use in the urbanization process. Meanwhile, they should also pay attention to ecological environment protection. Besides, it is recommendable to give full play to the radiating and leading effect of central cities on surrounding ones. Finally, they are required to provide appropriate policies and resource support to peripheral cities.
Absolute Accelerometer-Based Intensity Prescription Compared to Physiological Variables in Pregnant and Nonpregnant Women
Authors: Birnbaumer Philipp , Dietz Pavel , Watson Estelle Dorothy , Mukoma Gudani , Müller Alexander , Sattler Matteo Christian , Jaunig Johannes , van Poppel Mireille Nicoline Maria , Hofmann Peter
Published: August 2020

Estimation of the intensity of physical activity (PA) based on absolute accelerometer cut points (Cp) likely over- or underestimates intensity for a specific individual. The purpose of this study was to investigate the relationship between absolute moderate intensity Cp and the first ventilatory threshold (VT1). A group of 24 pregnant and 15 nonpregnant women who performed a submaximal incremental walking test with measures of ventilatory parameters and accelerations from three different accelerometers on the wrist (ActiGraph wGT3X-BT, GENEActiv, Axivity AX3) and one on the hip (Actigraph wGT3X-BT) were analyzed. Cp were determined corresponding to 3 metabolic equivalents of task (MET), using the conventional MET definition (Cp3.5) (3.5 mL/kg×min) and individual resting metabolic rate (Cpind). The ventilatory equivalent (VE/VO2) was used to determine VT1. Accelerations at VT1 were significantly higher (p < 0.01) compared to Cp3.5 and Cpind in both groups. Cp3.5 and Cpind were significantly different in nonpregnant (p < 0.01) but not in pregnant women. Walking speed at VT1 (5.7 ± 0.5/6.2 ± 0.8 km/h) was significantly lower (p < 0.01) in pregnant compared to nonpregnant women and correspondent to 3.8 ± 0.7/4.9 ± 1.4 conventional METs. Intensity at absolute Cp was lower compared to the intensity at VT1 independent of the device or placement in pregnant and nonpregnant women. Therefore, we recommend individually tailored cut points such as the VT1 to better assess the effect of the intensity of PA.
I Want to Become a Registered Nurse as a Non-Traditional, Returning, Evening, and Adult Student in a Community College: A Study of Career-Changing Nursing Students
Authors: Dos Santos Luis Miguel
Published: August 2020

The current significant human resource and workforce shortages of registered nurses (RNs) are impacting urban, suburban, and rural hospitals and healthcare facilities all over the globe, regardless of the entities’ economic and financial backgrounds. The purpose of this research study is to understand why non-traditional, returning, evening, and adult (NTREA) students decided to enrol at the Associate Degree in Nursing programme during their mid-adulthood? 40 s-career nursing students who are pursuing their nursing programme were invited to individual interview sessions and focus group activities on sharing and expressing the motivations in the New England region in the United States. Based on the theoretical framework of Social Cognitive Career Theory, the researcher concluded that family consideration and higher social status were two of the major themes. The study provided a blueprint for human resource professionals, health and social caring leaders, government agencies, policymakers, and researchers to reform their current nursing curriculum and health workforce policy to attract potential second-career nursing joining the nursing profession.
Psychodynamic Based Equine—Assisted Psychotherapy in Adults with Intertwined Personality Problems and Traumatization: A Systematic Review
Authors: Kovács Géza , van Dijke Annemiek , Enders-Slegers Marie-Jose
Published: August 2020

The growing field of equine-assisted psychotherapy (EAP), a subfield of animal-assisted psychotherapy (AAP), needs theoretically-based clinical studies. This systematic review examines the existing clinical studies in adult populations on psychodynamic psychotherapy combined with equine-assisted psychotherapy. An electronic database search was divided in two studies to identify publications on 1) EAP combined with psychodynamic psychotherapy and 2) EAP combined to personality problems and traumatization in order to compile studies by population, intervention, outcome and therapeutic assets. Study 1 revealed no relevant clinical studies on EAP with a psychodynamic background with an adult population. Study 2 revealed 12 publications to review predominantly addressing veterans with PTSD. The methodological limitations of most of the studies restrain the overall findings on outcome. However, overall positive effects for EAP, specifically on its experiential features and on finding interpersonal trust for patients, can be discerned. There is an apparent need for clinical studies meeting methodological standards on psychodynamic underpinned EAP methodologies in adults with intertwined personality problems and traumatization.