bluuebunny/crossref_metadata_2025 huggingface dataset:
The Association between the Regular Use of ICT Based Mobility Services and the Bicycle Mode Choice in Tehran and Cairo
Authors: Mostofi Hamid , Masoumi Houshmand , Dienel Hans-Liudger
Published: November 2020

Regarding the sharp growth rate of ICT (information and communication technology)—based mobility services like ridesourcing, it is essential to investigate the impact of these new mobility services on the transport mode choices, particularly on active mobility modes like cycling. This impact is more important in the MENA context (the Middle East and North Africa), where cycling does not constitute the main mobility mode in the modal split of most MENA cities. This paper studies the relationship between the regular use of ICT-based mobility services like ridesourcing and the tendency to cycle to near destinations. This paper contains the analysis of 4431 interviews in two large cities of the MENA region (Cairo and Tehran). This research uses logistic regression to analyze and compare the odds of cycling among regular and non-regular users of ridesourcing by considering the socio-economic, land use, and perception variables. The findings indicate that the odds of cycling among the regular users of ridesourcing are 2.30 and 1.94 times greater than these odds among non-regular ridesourcing users in Tehran and Cairo, respectively. Therefore, the regular users of ridesourcing are more likely to cycle to their near destinations than non-regular ridesourcing users in these cities.
Recovery-Oriented Intersectoral Care in Mental Health: As Perceived by Healthcare Professionals and Users
Authors: Jørgensen Kim , Rasmussen Tonie , Hansen Morten , Andreasson Kate , Karlsson Bengt
Published: November 2020

This study aimed to explore how mental health professionals and users perceive recovery-oriented intersectoral care when comparing mental health hospitals and community mental healthcare. Methodological design: Five audio-recorded focus group interviews of nurses, other health professionals and users were explored using manifest and latent content analysis. Ethical issues and approval: The study was designed in accordance with the ethical principles of the Helsinki Declaration and Danish law. Each study participant in the two intersectoral sectors gave their informed consent after verbal and written information was provided. Findings: From the health professionals’ perspective, the main theme informed by subthemes and categories was formulated: ‘Recovery-oriented intersectoral care requires more coordination and desire for collaboration’. Two subthemes were subsequently formulated: ‘The users´ perspective of the centre’ and ‘Need for a common agenda and understanding of recovery-oriented intersectoral care’. From the users´ perspective, the main theme was formulated as: ‘Recovery-oriented intersectoral care in tension between medical- and holistically oriented care’. This theme was informed by two subthemes: ‘The users´ perspective is not in focus’ and ‘A trusting relationship and a holistic approach brings coherence’. Conclusions: This study reveals that health professionals want to work in a recovery-oriented manner in intersectoral care, but several challenges appear which make achieving this aim difficult. A common understanding of recovery and how it should be carried out in intersectoral care does not exist. Care decisions are primarily made paternalistically, where the users’ and relatives’ voices are ignored. In an attempt to create coherence across sectors, intersectoral network meetings have been established with health professionals from both sectors. However, the meetings are characterised by a lack of a clear purpose regarding the meeting structure and content, and users are only minimally involved. Our results can contribute to dealing with the challenges of incorporating recovery-oriented intersectoral care as an ideology in all psychiatric and municipal contexts and is, therefore, important for health professionals and users.
Gastroenterology Procedures Generate Aerosols: An Air Quality Turnover Solution to Mitigate COVID-19’s Propagation Risk
Authors: Garbey Marc , Joerger Guillaume , Furr Shannon
Published: November 2020

The growing fear of virus transmission during the 2019 coronavirus disease (COVID-19) pandemic has called for many scientists to look into the various vehicles of infection, including the potential to travel through aerosols. Few have looked into the issue that gastrointestinal (GI) procedures may produce an abundance of aerosols. The current process of risk management for clinics is to follow a clinic-specific HVAC formula, which is typically calculated once a year and assumes perfect mixing of the air within the space, to determine how many minutes each procedural room refreshes 99% of its air between procedures when doors are closed. This formula is not designed to fit the complex dynamic of small airborne particle transport and deposition that can potentially carry the virus in clinical conditions. It results in reduced procedure throughput as well as an excess of idle time in clinics that process a large number of short procedures such as outpatient GI centers. We present and tested a new cyber-physical system that continuously monitors airborne particle counts in procedural rooms and also at the same time automatically monitors the procedural rooms’ state and flexible endoscope status without interfering with the clinic’s workflow. We use our data gathered from over 1500 GI cases in one clinical suite to understand the correlation between air quality and standard procedure types as well as identify the risks involved with any HVAC system in a clinical suite environment. Thanks to this system, we demonstrate that standard GI procedures generate large quantities of aerosols, which can potentially promote viral airborne transmission among patients and healthcare staff. We provide a solution for the clinic to improve procedure turnover times and throughput, as well as to mitigate the risk of airborne transmission of the virus.
Evaluation of Reablement Home Care: Effects on Care Attendants, Care Recipients, and Family Caregivers
Authors: Chiang Yu-Hsien , Hsu Hui-Chuan , Chen Chiung-Ling , Chen Chen-Fen , Chang-Lee Shu-Nu , Chen Ya-Mei , Hsu Shang-Wei
Published: November 2020

Background: The traditional home care model entails caring “for” people with disabilities, not “with” them. Reablement care has been applied to long-term care, but the evidence for care attendants, home care recipients, and family caregivers simultaneously is limited. Methods: First, a survey was conducted to explore the needs of home care recipients and family caregivers to achieve independence at home to develop the reablement home care model for home care. Then, an intervention with two groups was implemented. The experimental group included a total of 86 people who participated in the reablement home care model. The control group included 100 people and received usual home care. The self-reliance concept, job satisfaction, and sense of achievement for care attendants; quality of life for home care users; and caregiving burden for family caregivers were assessed. Results: The reablement home care model improved the job satisfaction and achievement of home care attendants, improved mutual support and independence in the self-reliance concept and quality of life among the users, and reduced the stress of the users and family caregivers. Conclusion: The reablement home care model improved the outcomes for providers, care recipients, and family caregivers. Reablement home care is suggested in long-term care policies.
The Incidence and Nature of Malpractice Claims against Dentists for Orthodontic Treatment with Periodontal Damage in Israel during the Years 2005–2018—A Descriptive Study
Authors: Laviv Amir , Barnea Eitan , Tagger Green Nirit , Kadry Rana , Nassar Dima , Laviv Meytal , Kolerman Roni
Published: November 2020

In recent years, dental malpractice claims have increased dramatically worldwide. The purpose of the present study is to analyze claims related to orthodontic treatment involving periodontal problems that resulted in legal decisions in Israel. This study analyzed legal claims registered by Medical Consultants International (MCI) between 2005 and 2018. Only closed cases of orthodontic claims involving periodontal problems in which a decision was made were included. The parameters studied included patients’ demographic data, the main reasons of the claim, and complications. Statistical significance was found for aesthetic damage, which was more common in claims of females (p = 0.035) and in older claims (p = 0.004); tooth damage was more common in claims of older patients (p = 0.032); violation of autonomy was higher in private practice (p = 0.047) and in more recent claims (p = 0.001). As orthodontic treatment is becoming more popular in older patients, and as lawsuit claims become more common in recent years, the orthodontists should always analyze and document the periodontal status of their patients before and during treatment in order to maintain professional practice and avoid future claims.
Evaluation of Severity Levels of the Athens Insomnia Scale Based on the Criterion of Insomnia Severity Index
Authors: Okajima Isa , Miyamoto Towa , Ubara Ayaka , Omichi Chie , Matsuda Arichika , Sumi Yukiyoshi , Matsuo Masahiro , Ito Kazuki , Kadotani Hiroshi
Published: November 2020

The Athens Insomnia Scale (AIS) can be regarded as a highly useful instrument in both clinical and research settings, except for when assessing the severity level. This study aims to determine the severity criteria for AIS by using the Insomnia Severity Index (ISI). A total of 1666 government employees aged 20 years or older were evaluated using the AIS and ISI, the Patient Health Questionnaire for depressive symptoms, the Epworth Sleepiness Scale for daytime sleepiness, and the Short Form Health Survey of the Medical Outcomes Study for health-related quality of life (QoL). A significant positive correlation (r) was found between the AIS and the ISI (r = 0.80, p < 0.001). As a result of describing receiver–operator curves, the severity criteria of the AIS are capable of categorizing insomnia severity as follows: absence of insomnia (0–5), mild insomnia (6–9), moderate insomnia (10–15), and severe insomnia (16–24). In addition, compared to all scales across groups categorized by AIS or ISI, it was revealed that similar results could be obtained (all p < 0.05). Therefore, the identification of the severity of AIS in this study is important in linking the findings of epidemiological studies with those of clinical studies.
Financial Attributes, Environmental Performance, and Environmental Disclosure in China
Authors: Wu Die , Zhu Shuzhen , Memon Aftab Ahmed , Memon Hafeezullah
Published: November 2020

Contest between the international or national enterprises stimulates the formation of innovative or improved products or of well-organized processes. Nevertheless, reliance on carbon-based materials and energy emission sources has been highlighted as a primary problem of the 21st century. The current study examines the influence of carbon disclosure information (CDI), media reporting and financial influence on state-owned enterprises (SOEs) and non-state-owned enterprises (NSOEs) by using Shenzhen and Shanghai’s heavy polluting listed industries’ dataset from 2014 to 2019. By applying different data approaches, the estimated results demonstrate that the CDI level is significantly negative related to SOE compared to NSOE. The estimated results explain that media’s positive reporting offsets the additional benefits to stakeholders. While media’s negative reporting negatively influences a firm’s competitive position, it mitigates the stock price and its social value. Our results suggest that external factors are encouraging for the financial values of stakeholders, along with those of enterprises.
Applying GIS and Text Mining Methods to Twitter Data to Explore the Spatiotemporal Patterns of Topics of Interest in Kuwait
Authors: G. Almatar Muhammad , Alazmi Huda S. , Li Liuqing , Fox Edward A.
Published: November 2020

Researchers have developed various approaches for exploring the spatial information, temporal patterns, and Twitter content in topics of interest in order to generate a better understanding of human behavior; however, few investigations have integrated these three dimensions simultaneously. This study analyzes the content of tweets in order to conduct a spatiotemporal exploration of the main topics of interest in Kuwait in order to provide a deeper understanding of the topics people think about, when they think about them, and where they tweet about them. To this end, we collect, process, and analyze tweets from nearly 120 areas in Kuwait over a 10-month period. The study’s results indicate that religion, emotions, education, and public policy are the most popular topics of interest in Kuwait. Regarding the spatiotemporal analysis, people post more tweets regarding religion on Fridays, a holy day for Muslims in Kuwait. Moreover, people are more likely to tweet about policy and education on weekdays rather than weekends. In contrast, people tweet about emotional expressions more often on weekends. From the spatial perspectives, spatial clustering in topics occurs across the days of the week. The findings are applicable to further topic analysis and similar research in other countries.
A Fuzzy Spatial Region Extraction Model for Object’s Vague Location Description from Observer Perspective
Authors: Xu Jun , Pan Xin
Published: November 2020

Descriptions of the spatial locations of disappeared objects are often recorded in eyewitness records, travel notes, and historical documents. However, in geographic information system (GIS), the observer-centered and vague nature of the descriptions causes difficulties in representing the spatial characters of these objects. To address this problem, this paper proposes a Fuzzy Spatial Region Extraction Model for Object’s Vague Location Description from Observer Perspective (FSREM-OP). In this model, the spatial relationship between the observer and the object are represented in spatial knowledge. It is composed of “phrase” and “region”. Based on the spatial knowledge, three components of spatial inference are constructed: Spatial Entities (SEs), Fuzzy Spatial Regions (FSRs), and Spatial Actions (SAs). Through spatial knowledge and the components of FSREM-OP, an object’s location can be inferred from an observer’s describing text, transforming the vagueness and subjectivity of location description into fuzzy spatial regions in the GIS. The FSREM-OP was tested by constructing a group of observers, object position relationships and vague descriptions. The results show that it is capable of extracting the spatial information and presenting location descriptions in the GIS, despite the vagueness and subjective spatial relation expressions in the descriptions.
Spatial Determinants of Land Conversion for Various Urban Use: A Case Study of Beijing
Authors: Huang Daquan , Chu Erxuan , Liu Tao
Published: November 2020

Studying the factors that influence the expansion of different types of construction land is instrumental in formulating targeted policies and regulations, and can reduce or prevent the negative impacts of unreasonable land use changes. Using land use survey data of Beijing (2001 and 2010), an autologistic model quantitatively analyzed the leading driving forces and differences in four types of construction land expansion (industrial, residential, public service, and commercial land types), focusing on the impact of spatial autocorrelation. The results showed that the influencing factors vary greatly for different types of construction land expansion; the same factor may have a different impact on different construction land, and both planning factors and spatial autocorrelation variables have a significant positive effect on the four types. Accordingly, the municipal government should consider the differences in the expansion mechanisms and driving forces of different construction land and formulate suitable planning schemes, observe the impact of spatial autocorrelation on construction land expansion, and guide spatial agglomeration through policies while appropriately controlling the scale of expansion. The methods and policy recommendations of this research are significant for urban land expansion research and policy formulations in other transition economies and developing countries.
Photoswitchable Azo- and Diazocine-Functionalized Derivatives of the VEGFR-2 Inhibitor Axitinib
Authors: Heintze Linda , Schmidt Dorian , Rodat Theo , Witt Lydia , Ewert Julia , Kriegs Malte , Herges Rainer , Peifer Christian
Published: November 2020

In this study, we aimed at the application of the concept of photopharmacology to the approved vascular endothelial growth factor receptor (VEGFR)-2 kinase inhibitor axitinib. In a previous study, we found out that the photoisomerization of axitinib’s stilbene-like double bond is unidirectional in aqueous solution due to a competing irreversible [2+2]-cycloaddition. Therefore, we next set out to azologize axitinib by means of incorporating azobenzenes as well as diazocine moieties as photoresponsive elements. Conceptually, diazocines (bridged azobenzenes) show favorable photoswitching properties compared to standard azobenzenes because the thermodynamically stable Z-isomer usually is bioinactive, and back isomerization from the bioactive E-isomer occurs thermally. Here, we report on the development of different sulfur–diazocines and carbon–diazocines attached to the axitinib pharmacophore that allow switching the VEGFR-2 activity reversibly. For the best sulfur–diazocine, we could verify in a VEGFR-2 kinase assay that the Z-isomer is biologically inactive (IC50 >> 10,000 nM), while significant VEGFR-2 inhibition can be observed after irradiation with blue light (405 nm), resulting in an IC50 value of 214 nM. In summary, we could successfully develop reversibly photoswitchable kinase inhibitors that exhibit more than 40-fold differences in biological activities upon irradiation. Moreover, we demonstrate the potential advantage of diazocine photoswitches over standard azobenzenes.
Role of microRNA and Oxidative Stress in Influenza A Virus Pathogenesis
Authors: Haque Md Mamunul , Murale Dhiraj P. , Lee Jun-Seok
Published: November 2020

MicroRNAs (miRNAs) are non-coding RNAs that regulate diverse cellular pathways by controlling gene expression. Increasing evidence has revealed their critical involvement in influenza A virus (IAV) pathogenesis. Host–IAV interactions induce different levels of oxidative stress (OS) by disrupting the balance between reactive oxygen species (ROS) and antioxidant factors. It is thought that miRNA may regulate the expression of ROS; conversely, ROS can induce or suppress miRNA expression during IAV infection. Thus, miRNA and OS are the two key factors of IAV infection and pathogenesis. Accordingly, interactions between OS and miRNA during IAV infection might be a critical area for further research. In this review, we discuss the crosstalk between miRNAs and OS during IAV infection. Additionally, we highlight the potential of miRNAs as diagnostic markers and therapeutic targets for IAV infections. This knowledge will help us to study host–virus interactions with novel intervention strategies.
Urinary Metabolomic Profiling in Streptozotocin-Induced Diabetic Mice after Treatment with Losartan
Authors: Hyeon Jin Seong , Jung Youngae , Lee Gayoung , Ha Hunjoo , Hwang Geum-Sook
Published: November 2020

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease and end-stage kidney disease. Renin–angiotensin system inhibitors such as losartan are the predominant therapeutic options in clinical practice to treat DKD. Therefore, it is necessary to identify DKD-related metabolic profiles that are affected by losartan. To investigate the change in metabolism associated with the development of DKD, we performed global and targeted metabolic profiling using 800 MHz nuclear magnetic resonance spectroscopy of urine samples from streptozotocin-induced diabetic mice (DM) with or without losartan administration. A principal component analysis plot showed that the metabolic pattern in the losartan-treated diabetic mice returned from that in the DM group toward that in the control mice (CM). We found that 33 urinary metabolites were significantly changed in DM compared with CM, and the levels of 16 metabolites among them, namely, glucose, mannose, myo-inositol, pyruvate, fumarate, 2-hydroxyglutarate, isobutyrate, glycine, threonine, dimethylglycine, methyldantoin, isoleucine, leucine, acetylcarnitine, 3-hydroxy-3-methylglutarate, and taurine, shifted closer to the control level in response to losartan treatment. Pathway analysis revealed that these metabolites were associated with branched-chain amino acid degradation; taurine and hypotaurine metabolism; glycine, serine, and threonine metabolism; the tricarboxylic acid cycle; and galactose metabolism. Our results demonstrate that metabolomic analysis is a useful tool for identifying the metabolic pathways related to the development of DKD affected by losartan administration and may contribute to the discovery of new therapeutic agents for DKD.
Sitagliptin Modulates the Response of Ovarian Cancer Cells to Chemotherapeutic Agents
Authors: Kosowska Agnieszka , Garczorz Wojciech , Kłych-Ratuszny Agnieszka , Aghdam Mohammad Reza F. , Kimsa-Furdzik Małgorzata , Simka-Lampa Klaudia , Francuz Tomasz
Published: November 2020

The strong association between diabetes mellitus type 2 and cancer is observed. The incidence of both diseases is increasing globally due to the interaction between them. Recent studies suggest that there is also an association between cancer incidence and anti-diabetic medications. An inhibitor of dipeptidyl-peptidase 4 (DPP-4), sitagliptin, is used in diabetes treatment. We examined the influence of sitagliptin alone or in combination with a cytostatic drug (paclitaxel) on the development of epithelial ovarian cancer cells and the process of metastasis. We examined migration, invasiveness, apoptosis, and metalloproteinases (MMPs) and their inhibitors’ (TIMPs) production in two human ovarian cancer cell lines. Sitagliptin induced apoptosis by caspase 3/7 activation in paclitaxel-treated SKOV-3 and OVCAR-3 cells. Sitagliptin maintained paclitaxel influence on ERK and Akt signaling pathways. Sitagliptin additionally reduced migration and invasiveness of SKOV-3 cells. There were distinct differences of metalloproteinases production in sitagliptin-stimulated ovarian cancer cells in both cell lines, despite their identical histological classification. Only the SKOV-3 cell line expressed MMPs and TIMPs. SKOV-3 cells co-treated with sitagliptin and paclitaxel decreased concentrations of MMP-1, MMP-2, MMP-7, MMP-10, TIMP-1, TIMP-2. The obtained data showed that sitagliptin used with paclitaxel may be considered as a possibility of pharmacological modulation of intracellular transmission pathways to improve the response to chemotherapy.
Plant Single-Cell Metabolomics—Challenges and Perspectives
Authors: de Souza Leonardo Perez , Borghi Monica , Fernie Alisdair
Published: November 2020

Omics approaches for investigating biological systems were introduced in the mid-1990s and quickly consolidated to become a fundamental pillar of modern biology. The idea of measuring the whole complement of genes, transcripts, proteins, and metabolites has since become widespread and routinely adopted in the pursuit of an infinity of scientific questions. Incremental improvements over technical aspects such as sampling, sensitivity, cost, and throughput pushed even further the boundaries of what these techniques can achieve. In this context, single-cell genomics and transcriptomics quickly became a well-established tool to answer fundamental questions challenging to assess at a whole tissue level. Following a similar trend as the original development of these techniques, proteomics alternatives for single-cell exploration have become more accessible and reliable, whilst metabolomics lag behind the rest. This review summarizes state-of-the-art technologies for spatially resolved metabolomics analysis, as well as the challenges hindering the achievement of sensu stricto metabolome coverage at the single-cell level. Furthermore, we discuss several essential contributions to understanding plant single-cell metabolism, finishing with our opinion on near-future developments and relevant scientific questions that will hopefully be tackled by incorporating these new exciting technologies.
Treatment Strategies and Metabolic Pathway Regulation in Urothelial Cell Carcinoma: A Comprehensive Review
Authors: Yang Huang-Yu , Wu Chao-Yi , Chen Jia-Jin , Lee Tao-Han
Published: November 2020

For a long time, cisplatin-based chemotherapy had been viewed as first-line chemotherapy for advanced and metastatic urothelial carcinoma (UC). However, many patients with UC had been classified as cisplatin-ineligible who can only receive alternative chemotherapy with poor treatment response, and the vast majority of the cisplatin-eligible patients eventually progressed, even those with objective response with cisplatin-based chemotherapy initially. By understanding tumor immunology in UC, immune checkpoint inhibitors, targeting on programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) pathways, had been proven as first-line treatment for cisplatin-ineligible metastatic UC and as second-line treatment for patients with platinum-refractory metastatic UC by the U.S Food and Drug Administration (FDA). In 2020, JAVEIN bladder 100 further reported that PD-L1 inhibitors showed benefits on prolonged survival and progression-free survival as maintenance therapy. Besides targeting on immune checkpoint, manipulation of the tumor microenvironment by metabolic pathways intervention, including inhibition on tumor glycolysis, lactate accumulation and exogenous glutamine uptake, had been investigated in the past few years. In this comprehensive review, we start by introducing traditional chemotherapy of UC, and then we summarize current evidences supporting the use of immune checkpoint inhibitors and highlight ongoing clinical trials. Lastly, we reviewed the tumor metabolic characteristic and the anti-tumor treatments targeting on metabolic pathways.
An Attempt to Identify Meaningful Descriptors of Handgrip Strength Using a Novel Prototype: Preliminary Study
Authors: Urbano Diana , Restivo Maria Teresa , Amaral Teresa F. , Abreu Paulo , Chousal Maria de Fátima
Published: November 2020

Handgrip strength (HGS) is an indicator of muscle condition and general health wellbeing. Usually, instruments measuring handgrip strength only identify its maximum value. This preliminary study is focused on identifying force vs. time parameters which could contribute to better describe individual strength. They were obtained during a Handgrip strength test of 15 s in a sample group of 94 university students. The tests were conducted with a smart multifunction novel prototype dynamometer, named BodyGrip. Mean values of quantities related to the ability to develop and to maintain strength in percentage of maximum handgrip strength, were extracted from the force vs time profile. Contrary to maximum HGS, such quantities were found to be independent of the participant’s anthropometric characteristics. Individual comparisons based on those quantities are therefore not affected by the anthropometric characteristics. It was possible to identify individuals, differing on the development of HGS. Results suggest that the functionality of the BodyGrip tool enables a more thorough characterization of the time profile of the Handgrip strength that might influence the knowledge of the muscle functions, such as power development and endurance.
Application of Shear Wave Sonoelastography in the Differential Diagnosis of Extra- and Intra-Thyroidal Ectopic Thymic Tissue
Authors: Stasiak Magdalena , Adamczewski Zbigniew , Stawerska Renata , Stasiak Bartłomiej , Lewiński Andrzej
Published: November 2020

The ultrasound (US) pattern of intrathyroidal ectopic thymus (IET) can resemble papillary thyroid carcinoma (PTC) while the extrathyroidal ectopic thymus (EET) can mimic pathological lymph nodes. Recently, the usefulness of strain elastography (SE) was demonstrated in the differential diagnosis, however this method has several limitations. The aim of the current study was to assess the usefulness of shear wave elastography (SWE) in this field. The US, SE, and SWE were performed in 31 children with 53 ectopic thymuses (ETs) and quantitative values of SWE parameters were calculated, so as to generate potential normative values of ET elasticity and of the shear wave ratio (SWR). The mean SWRIET was 0.89 ± 0.21 and the mean shear wave stiffness (SWS) was 7.47 ± 1.93 kPa. The mean SWREET was 0.84 ± 0.15 and the mean SWSEET was 11.28 ± 2.58 kPa. The results have proven that the stiffness of ETs is lower or equal to the thyroid’s. SWE was demonstrated to be a useful diagnostic method for ET evaluation. Therefore, the application of SWE in ET diagnosis allows more accurate evaluation of ET-like lesions and, in many cases, allows one to avoid invasive procedures, simultaneously providing a precise monitoring method based on combined US and SWE evaluation.
Risk Factors, Pathogenesis, and Strategies for Hepatocellular Carcinoma Prevention: Emphasis on Secondary Prevention and Its Translational Challenges
Authors: Li Shen , Saviano Antonio , Erstad Derek J. , Hoshida Yujin , Fuchs Bryan C. , Baumert Thomas , Tanabe Kenneth K.
Published: November 2020

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated mortality globally. Given the limited therapeutic efficacy in advanced HCC, prevention of HCC carcinogenesis could serve as an effective strategy. Patients with chronic fibrosis due to viral or metabolic etiologies are at a high risk of developing HCC. Primary prevention seeks to eliminate cancer predisposing risk factors while tertiary prevention aims to prevent HCC recurrence. Secondary prevention targets patients with baseline chronic liver disease. Various epidemiological and experimental studies have identified candidates for secondary prevention—both etiology-specific and generic prevention strategies—including statins, aspirin, and anti-diabetic drugs. The introduction of multi-cell based omics analysis along with better characterization of the hepatic microenvironment will further facilitate the identification of targets for prevention. In this review, we will summarize HCC risk factors, pathogenesis, and discuss strategies of HCC prevention. We will focus on secondary prevention and also discuss current challenges in translating experimental work into clinical practice.
Mechanical and Electrical Properties of Injection-Molded MWCNT-Reinforced Polyamide 66 Hybrid Composites
Authors: Zameroski Ross , Kypta Chadwick J. , Young Brian A. , Sanei Seyed Hamid Reza , Hollinger Adam S.
Published: November 2020

The addition of fillers or reinforcements has a direct influence on the mechanical and electrical properties of polymers. Such properties are a function of the morphology and the distribution of fillers in the polymer base. Each feature may have contrasting effects on mechanical and electrical properties. In this study, chopped carbon fiber of different lengths and multiwalled carbon nanotubes (MWCNTs) were added to nylon 6,6. Specimens were manufactured by injection molding of a polyamide/MWCNT masterbatch with the addition of loose chopped carbon fiber. Tensile testing of dogbone specimens was conducted to obtain Young’s modulus, ultimate tensile strength, and elongation. Electrical conductivity testing was conducted on the same specimens prior to mechanical testing. To evaluate the morphology of fillers, scanning electron micrographs were evaluated. Micrographs show the presence of a skin layer close to the surface of the specimens. For this reason, core and surface conductivities were compared. The results show that while promising electrical properties can be achieved by the addition of fillers, the improvement in mechanical properties is minimal.
A Cyp51B Mutation Contributes to Azole Resistance in Aspergillus fumigatus
Authors: Gonzalez-Jimenez Irene , Lucio Jose , Amich Jorge , Cuesta Isabel , Sanchez Arroyo Rafael , Alcazar-Fuoli Laura , Mellado Emilia
Published: November 2020

The emergence and spread of Aspergillus fumigatus azole resistance has been acknowledged worldwide. The main problem of azole resistance is the limited therapeutic options for patients suffering aspergillosis. Azole resistance mechanisms have been mostly linked to the enzyme Cyp51A, a target of azole drugs, with a wide variety of modifications responsible for the different resistance mechanisms described to date. However, there are increasing reports of A. fumigatus strains showing azole resistance without Cyp51A modifications, and thus, novel resistance mechanisms are being explored. Here, we characterized two isogenic A. fumigatus clinical strains isolated two years apart from the same patient. Both strains were resistant to clinical azoles but showed different azole resistance mechanisms. One strain (CM8940) harbored a previously described G54A mutation in Cyp51A while the other strain (CM9640) had a novel G457S mutation in Cyp51B, the other target of azoles. In addition, this second strain had a F390L mutation in Hmg1. CM9640 showed higher levels of gene expression of cyp51A, cyp51B and hmg1 than the CM8940 strain. The role of the novel mutation found in Cyp51B together with the contribution of a mutation in Hmg1 in azole resistance is discussed.
Helpful Criteria When Implementing NGS Panels in Childhood Lymphoblastic Leukemia
Authors: Vega-Garcia Nerea , Benito Rocío , Esperanza-Cebollada Elena , Llop Marta , Robledo Cristina , Vicente-Garcés Clara , Alonso Javier , Barragán Eva , Fernández Guerau , Hernández-Sánchez Jesús , Martín-Izquierdo Marta , Maynou Joan , Minguela Alfredo , Montaño Adrián , Ortega Margarita , Torrebadell Montserrat , Cervera José , Sánchez Joaquín , Jiménez-Velasco Antonio , Riesco Susana , Hernández-Rivas Jesús , Lassaletta Álvaro , Fernández José , Rives Susana , Dapena José , Ramírez Manuel , Camós Mireia ,   on behalf of the Group of Leukemia of the Spanish Society of Pediatric Hematology and Oncology (SEHOP)
Published: November 2020

The development of Next-Generation Sequencing (NGS) has provided useful diagnostic, prognostic, and therapeutic strategies for individualized management of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients. Consequently, NGS is rapidly being established in clinical practice. However, the technology’s complexity, bioinformatics analysis, and the different available options difficult a broad consensus between different laboratories in its daily routine introduction. This collaborative study among Spanish centers was aimed to assess the feasibility, pros, and cons of our customized panel and other commercial alternatives of NGS-targeted approaches. The custom panel was tested in three different sequencing centers. We used the same samples to assess other commercial panels (OncomineTM Childhood Cancer Research Assay; Archer®FusionPlex® ALL, and Human Comprehensive Cancer Panel GeneRead Panel v2®). Overall, the panels showed a good performance in different centers and platforms, but each NGS approach presented some issues, as well as pros and cons. Moreover, a previous consensus on the analysis and reporting following international guidelines would be preferable to improve the concordance in results among centers. Our study shows the challenges posed by NGS methodology and the need to consider several aspects of the chosen NGS-targeted approach and reach a consensus before implementing it in daily practice.
An Overview of the Application of Systems Biology in an Understanding of Chronic Rhinosinusitis (CRS) Development
Authors: Michalik Michał , Samet Alfred , Dmowska-Koroblewska Agnieszka , Podbielska-Kubera Adrianna , Waszczuk-Jankowska Małgorzata , Struck-Lewicka Wiktoria , Markuszewski Michał J.
Published: November 2020

Chronic rhinosinusitis (CRS) is an inflammatory disease of the paranasal sinuses. It is defined as the presence of a minimum of two out of four main symptoms such as hyposmia, facial pain, nasal blockage, and discharge, which last for 8–12 weeks. CRS significantly impairs a patient’s quality of life. It needs special treatment mainly focusing on preventing local infection/inflammation with corticosteroid sprays or improving sinus drainage using nasal saline irrigation. When other treatments fail, endoscopic sinus surgery is considered an effective option. According to the state-of-the-art knowledge of CRS, there is more evidence suggesting that it is more of an inflammatory disease than an infectious one. This condition is also treated as a multifactorial inflammatory disorder as it may be triggered by various factors, such as bacterial or fungal infections, airborne irritants, defects in innate immunity, or the presence of concomitant diseases. Due to the incomplete understanding of the pathological processes of CRS, there is a continuous search for new indicators that are directly related to the pathogenesis of this disease—e.g., in the field of systems biology. The studies adopting systems biology search for possible factors responsible for the disease at genetic, transcriptomic, proteomic, and metabolomic levels. The analyses of the changes in the genome, transcriptome, proteome, and metabolome may reveal the dysfunctional pathways of inflammatory regulation and provide a clear insight into the pathogenesis of this disease. Therefore, in the present paper, we have summarized the state-of-the-art knowledge of the application of systems biology in the pathology and development of CRS.
Sex Differences in Time-Series Changes in Pseudo-R2 Values Regarding Hyperuricemia in Relation to the Kidney Prognosis
Authors: Kataoka Hiroshi , Ohara Mamiko , Mochizuki Toshio , Iwadoh Kazuhiro , Ushio Yusuke , Kawachi Keiko , Watanabe Kentaro , Watanabe Saki , Akihisa Taro , Makabe Shiho , Manabe Shun , Sato Masayo , Iwasa Naomi , Yoshida Rie , Sawara Yukako , Hanafusa Norio , Tsuchiya Ken , Nitta Kosaku
Published: November 2020

Studies on sex differences in time-series changes in pseudo-R2 values regarding hyperuricemia (HU) in relation to the kidney prognosis among patients with chronic kidney disease (CKD) are scant. The kidney prognosis was evaluated in 200 patients with CKD (median follow-up, 12.3 years). Survival analyses and logistic regression analyses were conducted, generating time-series pseudo-R2 values. We used four definitions of HU according to serum uric acid (SUA) levels (HU6, SUA ≥ 6.0 mg/dL; HU7, SUA ≥ 7.0 mg/dL; HU8, SUA ≥ 8.0 mg/dL) and antihyperuricemic agent use to calculate the mean and percentage of the change in pseudo-R2 values from the 6th year until the end of the study (6Y–End Mean and 6Y–End Change, respectively). The multivariable Cox regression analysis showed that HU7 was significantly associated with kidney outcomes. When stratified by sex, the 6Y–End Mean was clearly higher in women than in men for all HU definitions, with the highest value (0.1755) obtained for HU7 in women. The pseudo-R2 values for HU6 in women showed an increasing pattern, with a 6Y–End Change of 11.4%/year. Thus, it may be clinically meaningful to consider sex differences in the time-series pseudo-R2 values regarding HU and kidney outcomes.
Correlation between the Expression of Angiogenic Factors and Stem Cell Markers in Human Uveal Melanoma
Authors: Fodor Klára , Sipos Éva , Dobos Nikoletta , Nagy János , Steiber Zita , Méhes Gábor , Dull Kata , Székvölgyi Lóránt , Schally Andrew V. , Halmos Gábor
Published: November 2020

Uveal melanoma (UM) is the most common malignant tumor of the eye with extremely high metastatic potential. UM tumor cells can disseminate only hematogenously, thus, angiogenic signals have a particular role in the prognosis of the disease. Although the presence of cancer stem cells (CSCs) in densely vascularized UMs has been reported previously, their role in the process of hematogenous spread of UM has not been studied. In this study, we investigated the regulation of angiogenesis in UM in correlation with the presence of CSCs. Seventy UM samples were collected to analyze the expression of CSC markers and angiogenic factors. The expression of CSC markers was studied by RT-PCR, Western blotting techniques and IHC-TMA technique. RT-PCR showed high expression of CSC markers, particularly nestin, FZD6 and SOX10 and somewhat lower expression of NGFR. The protein expression of FZD6, HIF-1α and VEGFA was further evaluated in 52 UM samples by the IHC-TMA technique. We report here for the first time a significant correlation between FZD6 and VEGFA expression in UM samples. The observed correlation between FZD6 and VEGFA suggests the presence of CSCs in UM that are associated with the vascularization process.
Influence of Heat Treatment on Cyclic Response of Nickel-Based Superalloy Inconel 718 up to Very-High Cycle Regime
Authors: Zhao Mengxiong , Zhao Zhenhua , Liu Lulu , Luo Gang , Chen Wei
Published: November 2020

Cyclic response and fatigue behavior are sensitive to the microstructure of material induced by heat treatment. In this paper, three sets of high-temperature superalloy Inconel 718 with different heat treatment, namely annealed, aged, and directly aged high quality (DAHQ), are compared. Difference in grain size distribution, phase, and precipitate, etc., were investigated using an optical camera and scanning electron microscopy. Yield and ultimate strength were found to increase obviously after aging heat treatment. Self-heating phenomenon at 20 kHz was attenuated as grain size decreased. There was a transition from cyclic hardening to softening. Very-high cycle fatigue (VHCF) behavior of Inconel 718 was tested using an ultrasonic fatigue device. Crack initiation duration occupied greater than 99% of the total fatigue life. It concluded that average grain size influences VHCF strength and crack initiation mechanism, and that self-heating phenomenon is not a decisive factor on VHCF strength for Inconel 718.
Effect of Hydrophobic Treatments on Improving the Salt Frost Resistance of Concrete
Authors: Li Guo , Fan Chunhua , Lv Yajun , Fan Fujun
Published: November 2020

Hydrophobic treatment is an important method to improve the waterproof properties of concrete. To evaluate the effectiveness of hydrophobic treatments on improving the salt frost resistance of concrete, two representative commercial ordinary water repellent agents of silane and organosilicone emulsion were selected, and concrete specimens with three water/cement ratios were fabricated. After the application of repellent agents on concrete surfaces, accelerated saline (5% MgCl2) freeze-thaw cycles were conducted on the specimens. The mass losses and relative dynamic modulus of elasticity (RDME) of concrete were tested periodically. The contact angles and water absorption ratios of concrete with and without hydrophobic treatments were also tested. Results showed that the repellent agents could substantially enhance the hydrophobicity of concrete and greatly reduce its water absorption. Different repellent agents exerted diverse improvements on concrete hydrophobicity. Meanwhile, the repellent agents could improve concrete resistance against salt scaling and RDME losses to a certain degree, and concrete with strong hydrophobicity showed relatively high salt frost resistance. However, the ordinary water repellent agents cannot achieve the same enhancement on salt frost resistance of concrete as that on the water hydrophobicity of concrete. With saline freezing and thawing cycles, the hydrophobic layer formed by the repellent agents on superficial concrete was destroyed gradually. As a result, the salt frost resistance of concrete from the hydrophobic treatments was ultimately lost.
Transportation Optimization Models for Intermodal Networks with Fuzzy Node Capacity, Detour Factor, and Vehicle Utilization Constraints
Authors: Wang Chia-Nan , Dang Thanh-Tuan , Le Tran Quynh , Kewcharoenwong Panitan
Published: November 2020

This paper develops a mathematical model for intermodal freight transportation. It focuses on determining the flow of goods, the number of vehicles, and the transferred volume of goods transported from origin points to destination points. The model of this article is to minimize the total cost, which consists of fixed costs, transportation costs, intermodal transfer costs, and CO2 emission costs. It presents a mixed integer linear programming (MILP) model that minimizes total costs, and a fuzzy mixed integer linear programming (FMILP) model that minimizes imprecise total costs under conditions of uncertain data. In the models, node capacity, detour, and vehicle utilization are incorporated to estimate the performance impact. Additionally, a computational experiment is carried out to evaluate the impact of each constraint and to analyze the characteristics of the models under different scenarios. Developed models are tested using real data from a case study in Southern Vietnam in order to demonstrate their effectiveness. The results indicate that, although the objective function (total cost) increased by 20%, the problem became more realistic to address when the model was utilized to solve the constraints of node capacity, detour, and vehicle utilization. In addition, on the basis of the FMILP model, fuzziness is considered in order to investigate the impact of uncertainty in important model parameters. The optimal robust solution shows that the total cost of the FMILP model is enhanced by 4% compared with the total cost of the deterministic model. Another key measurement related to the achievement of global sustainable development goals is considered, reducing the additional intermodal transfer cost and the cost of CO2 emissions in the objective function.
Improving Convergence in Therapy Scheduling Optimization: A Simulation Study
Authors: Chimal-Eguia Juan C. , Rangel-Reyes Julio C. , Paez-Hernandez Ricardo T.
Published: November 2020

The infusion times and drug quantities are two primary variables to optimize when designing a therapeutic schedule. In this work, we test and analyze several extensions to the gradient descent equations in an optimal control algorithm conceived for therapy scheduling optimization. The goal is to provide insights into the best strategies to follow in terms of convergence speed when implementing our method in models for dendritic cell immunotherapy. The method gives a pulsed-like control that models a series of bolus injections and aims to minimize a cost a function, which minimizes tumor size and to keep the tumor under a threshold. Additionally, we introduce a stochastic iteration step in the algorithm, which serves to reduce the number of gradient computations, similar to a stochastic gradient descent scheme in machine learning. Finally, we employ the algorithm to two therapy schedule optimization problems in dendritic cell immunotherapy and contrast our method’s stochastic and non-stochastic optimizations.