bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding Combined Health and Business Risk Behaviour: Small Tourism Firm Owners Reopening Amid COVID-19 in Pingyao, China
Authors: Zhang Haizhou , Shi Zhaoyuan , Chen Jieqi , Zhang Ziang
Published: September 2022

This study explores the psychological factors affecting small tourism firm (STF) owners’ decision making about reopening businesses in the midst of COVID-19 based on protection motivation theory and the theory of planned behaviour. The data were collected from a sample of 300 STFs in the Ancient City of Pingyao when the lockdown policy was lifted in China. A symmetric approach, i.e., partial least squares structural equation modelling (PLS–SEM), and an asymmetric model, i.e., a fuzzy set/qualitative comparative analysis (fsQCA), were used to analyse the net effect of the psychological determinants and correlations between the variables leading to high and low behavioural intentions to reopen businesses. The results indicate that social norms and perceived business uncertainty were the critical factors influencing the intention to reopen. The pathway (low perceived risk of infection, low perceived business uncertainty, high reward, high response efficacy, high self-efficacy, high attitude, and high subjective norm) was only one configuration for a high intention to reopen. The study results are discussed based on dual-process theory, and practical implications are offered to guide STF recovery amid COVID-19.
AAC and Autism: Manual Signs and Pecs, a Comparison
Authors: Frolli Alessandro , Ciotola Sonia , Esposito Clara , Fraschetti Sara , Ricci Maria Carla , Cerciello Francesco , Russo Maria Grazia
Published: September 2022

Autism Spectrum Disorders (ASD) represent a heterogeneous group of disorders, with onset in developmental age, which present a clinical expressiveness that varies from subject to subject and in the same subject over time. The DSM 5 defines Autism Spectrum Disorders according to two main criteria: persistent deficits in social communication and social interaction in multiple contexts and limited and repetitive patterns of behavior, interests or activities. This disorder can manifest itself across a broad spectrum of severity levels. Indeed, ASD includes clinical conditions from low functioning (LF—Low Functioning) to high functioning (HF—High Functioning), taking cognitive and adaptive functioning as a reference. One of the main characteristics of individuals with ASD is a delay in receptive and expressive communication. These deficits have led to the identification of evidence-based practices, particularly for those with severe communication difficulties. Augmentative Alternative Communication (AAC) has been implemented to compensate for deficits in functional communication and language skills in individuals with complex communication deficits. The AAC comprises communication systems including the Manual Signs, speech and image output devices (Communicators), and Image Exchange Systems (PECS); these systems have been shown to actually improve various abilities in autism such as social skills, modify and improve dysfunctional behaviors and, above all, improve learning. Recent meta-analyses have shown how PECS and Manual Sign can have great effects on the communication skills of young people with autism. The aim of this study is to compare these two types of intervention to improve communication in terms of vocalization in subjects with ASD and try to understand which of the two lead to more significant and rapid improvements.
Does Internet Entertainment Reduce the Cognitive Ability of Children? Evidence from the China Education Panel Survey
Authors: Hu Wenxin , Mao Yufei , Huang Kevin , Sun Yanqi
Published: September 2022

Internet technology has been assimilated into children’s educational system on an in-depth level. In particular, the number of children who use the internet for entertainment has been rapidly increasing. However, there has been a debate as to whether internet entertainment can have a detrimental impact on children’s cognitive ability. This paper investigates the effect of internet entertainment on the cognitive ability of children in the Chinese context. The results show no evidence of associations between internet entertainment and children’s cognitive ability. However, the additional analysis provides preliminary evidence suggesting that internet entertainment can be beneficial to children who use it for entertainment only on weekends but detrimental for those who spend leisure time online daily. In addition, the findings are robust in a variety of sensitivity tests. We also examine whether the effects of internet entertainment on children’s cognitive ability in different family environments are heterogeneous. The findings suggest that parents’ internet habits, parents’ internet supervision, parental relationship, family education and living area play a moderating role in the relationship between internet entertainment and children’s cognitive ability. This study offers useful insights into the current global debate on the nexus between internet entertainment and children’s cognitive ability and also provides suggestions for parents, children, regulators and policymakers.
Measuring Well-Being of Migrant Gig Workers: Exampled as Hangzhou City in China
Authors: Chen Tinggui , Song Weijin , Song Junying , Ren Yixuan , Dong Yuzhu , Yang Jianjun , Zhang Shuyuan
Published: September 2022

The consistent innovations and applications of information technology drive the vigorous development of the gig economy, and generate gig workers such as food delivery workers and couriers, and make a great contribution to stabilizing employment and increasing income. Gig workers, mostly made up of migrants, and suffer from job and status difficulties. Research on the well-being of migrant gig workers can reveal the practical problems and provide suggestions for narrowing the wealth gap to promote social fairness and justice. Taking Hangzhou city in China as an example, this paper explores the well-being of food delivery workers, couriers, and online car-hailing drivers as representatives of migrant gig workers. Firstly, the relevant data are acquired through the questionnaire. Secondly, the characteristics of this group are analyzed through descriptive analysis, namely: most of them are migrant workers aged between 20 and 39 with low occupation satisfaction due to insufficient social security coverage and limited well-being, despite relatively high income. Based on the analysis of differences in demographic variables and structural equation modeling, the factors affecting the well-being of migrant gig workers are studied, which mainly are occupation satisfaction, social interaction, and social security. The results show that occupation satisfaction is positively affected by family characteristics, social interaction, and social security. In addition, family characteristics and social security positively impact social interaction, but the former has no significant effect on well-being. Finally, this paper enriches the research on the well-being of specific migrant gig workers and gives policy suggestions for enhancing the well-being of migrant gig workers in Hangzhou city from the perspective of optimizing the mechanism, pilot construction, and platform provision.
Decarbonization of the Colombian Building Sector: Social Network Analysis of Enabling Stakeholders
Authors: Salazar John , Guevara Jose , Espinosa Monica , Rivera Felipe , Franco Juan F.
Published: September 2022

Reducing greenhouse gas (GHG) emissions is one of the main challenges to stopping climate change; in particular, the building sector acts as one of the main emitters. In response, governments have been developing nationally determined contributions (NDCs) and roadmaps to establish measures to achieve net-zero emissions. One of the main barriers to implementing these measures, particularly in the building sector, underlays in stakeholder integration. Through social network analysis (SNA) concepts, this research explores the roles of the actors whose participation is required in decarbonizing the Colombian building sector. These stakeholders engage in enabling categories (e.g., policy, finance, technology, and capacity development) required to achieve net-zero emissions, according to the goals proposed by the Colombian Green Building Council (CGBC). For the network analysis, we employ the results of semi-structured interviews led by the CGBC within the framework of the Zero Carbon Building Accelerator (ZCBA) project. Findings show highly interconnected networks characterized by redundant connections among actors. Three types of actors are identified within each enabler network: prominent actors with high centrality values, in charge of coordinating most of the actions required to achieve net-zero emissions; second-level actors limited to specific roles in policy-making processes; and perimeter actors focused on a few particular actions.
Developing an Evaluation Model to Measure the Intelligence Level of Smart Industrial Parks
Authors: Wang Ailing , Yang Yixin , Sun Shaonan , Zuo Yiming , Wang Zhihui , Sun Haili
Published: September 2022

The intelligent development of smart industrial parks (SIPs) can not only promote the development of smart cities, but also promote the development of intelligent large-scale buildings. China is strengthening the construction of SIPs; however, the development of SIPs is limited. Due to different understandings of SIPs, the intelligence level of each SIP varies greatly. It is necessary to develop a SIP intelligence level assessment model to check these limitations. Most of the existing evaluations focus on the qualitative evaluation of the overall intelligence level of SIPs, ignoring the influence of each individual dimension. Therefore, this study used quantitative methods to measure the intelligence level of SIPs from the overall and dimensional levels. The evaluation method included five processes: (1) Classifying the intelligence level of SIPs through expert interviews; (2) Using the literature analysis method to identify various dimensions of the intelligence level; (3) Using literature analysis and expert interviews to determine the evaluation indicators (4) Weighting indicators based on correlation and induced ordered weighted average (IOWA) operator; (5) Using grey clustering analysis to calculate the overall intelligence performance of SIPs and each dimension. Finally, the developed model was verified by Z SIP. The analysis results show that the developed model can measure both overall and dimensional performance of SIPs, and demonstrated that enterprise information services, public information services, SIP security, and energy consumption monitoring platform construction make the greatest contributions to the improvement of the intelligence level. Our research results will help to improve the intelligence level of SIPs, and lay the foundation for the determination of the operating costs of SIPs and the formulation of national standards related to SIPs in the future.
Energy Optimization for Fenestration Design: Evidence-Based Retrofitting Solution for Office Buildings in the UAE
Authors: Abdou Yasmin , KIM YOUNG KI , Abdou Alaa , Anabtawi Rim
Published: September 2022

With the prevalent use of large glazings, particularly in office buildings, offices receive an abundance of light and are among the largest consumers of electricity. Moreover, in an extreme hot arid climate such as in the UAE, achieving comfortable daylighting levels without increasing solar heat gain is a challenge, in which the window or fenestration design plays an essential role. This research adopts a case study of a higher education (HE) office building on the United Arab Emirates University (UAEU) campus, selected to investigate an evidence-based retrofitting solution for the west façade that can be applied in existing office buildings in the UAE in order to reduce cooling energy load as well as enhance indoor environmental quality. To achieve an evidence-based retrofitting solution, the research design built upon a comprehensive exploratory investigation that included indoor environmental quality physical monitoring and occupant satisfaction surveying. Model simulation was performed by means of DesignBuilder software to perform a single- and multiparameter sensitivity analysis for three key passive window design parameters, i.e., window-to-wall ratio, glazing type, and external shading, aimed towards minimizing annual cooling load and solar heat gain, while maintaining appropriate indoor daylight illuminance levels. The results highlight the importance of the window-to-wall ratio (WWR), as it is the single most significant parameter effecting total energy consumption and daylighting levels. The results recommend 20–30% WWR as the optimum range in the west façade. However, by utilizing high performance glazing types and external shading, equal energy savings can be achieved with a larger WWR. Double Low E tinted glazing and 0.4 projection shading overhang and side fin revealed a noteworthy reduction of energy use intensity of 14%. The study concludes with final retrofitting solutions and design recommendations that aim to contribute validated knowledge towards enhancing window performance in a hot arid climate to guide architects and stakeholders to apply a range of passive parameters towards reducing energy consumption and improving occupant comfort in office buildings.
Classification of Biophilic Buildings as Sustainable Environments
Authors: Grazuleviciute-Vileniske Indre , Daugelaite Aurelija , Viliunas Gediminas
Published: September 2022

Biophilic design approach aims at creating favorable conditions for humans in various types of anthropogenic environments, while at the same time restoring broken human–nature connection. The biophilic design guidelines and principles are general and flexible and allow wide array of architectural expressions. In order to better understand the architectural expression possibilities provided by biophilic design approach, the existing classifications of biophilic architecture and biophilic design examples were analyzed with the aim to develop the classification that would reflect the links between a building’s architectural expression and biophilic qualities. Three categories of biophilic architecture were distinguished in the developed classification: mimetic, applied, and organic. The distinguished categories were illustrated with the characteristic building examples and the evaluation of biophilic qualities and human-nature collaboration potential of these example buildings was carried out using comprehensive system of criteria. The analysis has demonstrated that all three distinguished categories—mimetic, applied, organic—allow for the creation of biophilic environments and hold the potential for human–nature collaboration, although organic biophilic design would be currently considered as the least developed, although most promising category.
Numerical Investigation on Local Scour and Flow Field around the Bridge Pier under Protection of Perforated Baffle and Ring-Wing Plate
Authors: Wang Yan , Chen Jinchao , Wang Zhihang , Zhu Ziqi , Yan Junxiong
Published: September 2022

In this paper, a series of numerical experiments are carried out on the anti-scour device combined with perforated baffle and ring-wing plate. In addition, the optimal dimensions and location of the combined device are obtained: The perforated ratio of the baffle is S = 20%, the distance from the center of the bridge pier is L = 2d (d is the diameter of the bridge pier), and the ring-wing plate is located at H = 1/3h (h is the water depth). To verify the effect of the anti-scour device, the scour characteristics and flow field are further investigated. Compared with single pier and single ring-wing plate, the results revealed that the combined device with the optimal dimensions is of great anti-scour performance. Moreover, the maximum scour depth at the front and side of the pier reduced by 84.20% and 78.95%, which is better than the single ring-wing plate and other combined conditions in the orthogonal experiments. Due to the diversion of perforated baffle and ring-wing plate, the flow velocity at the pier side near the bed surface decreases by 30.7%, and the down-flow is almost eliminated on the vertical plane. Furthermore, the turbulent kinetic energy at different horizontal and vertical planes is reduced due to the reduction in horseshoe vortex and wake flow. Based on the investigation presented herein, the combined device is a promising tool for mitigating scour around the bridge pier.
Fire Safety in Museums: Simulation of Fire Scenarios for Development of Control Evacuation Schemes from the Winter Palace of the Hermitage
Authors: Kirik Ekaterina , Bogdanov Aleksey , Sushkova Olga , Gravit Marina , Shabunina Daria , Rozov Artem , Vitova Tatyana , Lazarev Yuriy
Published: September 2022

The manuscript is focused on the problems of evacuation in case of fire from the buildings of museums as places with a mass presence of people. Features specific to museums and how they affect safe evacuation conditions are discussed. Most attention is paid to evacuation management, since the vast majority of museum visitors are not familiar with the layout of the building. In this case, the actions of staff in evacuation management are decisive. The paper considers the development of evacuation schemes, taking into account the spread of fire hazards in the building and the development of instructions on their basis for the staff. Using the example of the Winter Palace of the State Hermitage Museum, the solution of the marked tasks with the use of computer simulation of evacuation during a fire is given. The analysis of the simulation results showed the vulnerabilities of the museum. In this work, the evacuation schemes for the scenarios are considered. The maximum number of visitors at a single time in the Winter Palace has been set at 4000. The principles of making evacuation schemes are formulated, including taking into account the peculiarities of space-planning solutions inherent in museums, such as enfilades and the connections of rooms.
Inhibition of Tumor Microenvironment Cytokine Signaling Sensitizes Ovarian Cancer Cells to Antiestrogen Therapy
Authors: Tan Lijun , Tondo-Steele Katelyn , Foster Caroline , McIlwain Carrie , Bolland Danielle E. , Crawford Howard C. , Sciallis Andrew , McLean Karen
Published: September 2022

Antiestrogen therapy (AET) is an alternative to cytotoxic chemotherapy for recurrent ovarian cancer, yet the often short duration of response suggests mechanisms of resistance. We previously demonstrated that tumor microenvironment interleukin-6/leukemia inhibitory factor (IL6/LIF) cytokines induce tumor cell JAK-STAT signaling to promote cancer growth. Crosstalk between estrogen signaling and cytokine signaling has been reported. Therefore, we sought to characterize the impact of IL6/LIF signaling on estrogen signaling in epithelial ovarian cancer and investigate the efficacy of combination therapy. We first assessed patient tumors for cytokine expression and compared it with response to AET to determine clinical relevance. In vitro, we determined the effect of IL6/LIF on estrogen receptor expression and signaling. Cell viability assays were used to determine the efficacy and potential synergy of cytokine blockade and AET. We then extended studies to animal models, incorporating patient-derived stromal cells. Our results demonstrated shorter progression-free interval on AET in patients with stromal IL6/LIF expression. In vitro, IL6/LIF increased tumor cell estrogen receptor expression and signaling, and combination cytokine blockade and AET resulted in synergistic inhibition of tumor cell growth. The anticancer effect was verified in a mouse model. In conclusion, due to crosstalk between IL6/LIF cytokine signaling and estrogen signaling, dual blockade is a potential new treatment approach for ovarian cancer.
Oncogenic Dysregulation of Circulating Noncoding RNAs: Novel Challenges and Opportunities in Sarcoma Diagnosis and Treatment
Authors: Chellini Lidia , Palombo Ramona , Riccioni Veronica , Paronetto Maria Paola
Published: September 2022

Sarcomas comprise a heterogeneous group of rare mesenchymal malignancies. Sarcomas can be grouped into two categories characterized by different prognosis and treatment approaches: soft tissue sarcoma and primary bone sarcoma. In the last years, research on novel diagnostic, prognostic or predictive biomarkers in sarcoma management has been focused on circulating tumor-derived molecules as valuable tools. Liquid biopsies that measure various tumor components, including circulating cell-free DNA and RNA, circulating tumor cells, tumor extracellular vesicles and exosomes, are gaining attention as methods for molecular screening and early diagnosis. Compared with traditional tissue biopsies, liquid biopsies are minimally invasive and blood samples can be collected serially over time to monitor cancer progression. This review will focus on circulating noncoding RNA molecules from liquid biopsies that are dysregulated in sarcoma malignancies and discuss advantages and current limitations of their employment as biomarkers in the management of sarcomas. It will also explore their utility in the evaluation of the clinical response to treatments and of disease relapse. Moreover, it will explore state-of-the-art techniques that allow for the early detection of these circulating biomarkers. Despite the huge potential, current reports highlight poor sensitivity, specificity, and survival benefit of these methods, that are therefore still insufficient for routine screening purposes.
Neoadjuvant Chemotherapy-Chemoradiation for Borderline-Resectable Pancreatic Adenocarcinoma: A UK Tertiary Surgical Oncology Centre Series
Authors: Gorbudhun Rachna , Patel Pranav H. , Hopping Eve , Doyle Joseph , Geropoulos Georgios , Mavroeidis Vasileios K. , Kumar Sacheen , Bhogal Ricky H.
Published: September 2022

Background: Patients with borderline-resectable pancreatic ductal adenocarcinoma (BR-PDAC) have historically poor survival, even after curative pancreatic resection and adjuvant chemotherapy. Emerging evidence suggests that neoadjuvant chemoradiation (NCR) improves R0 resection rates in BR-PDAC patients. We evaluated the R0 resection rate, disease-free survival (DFS) and overall survival (OS) in our patients who underwent NCR for BR-PDAC at our institution. Methods: All patients who underwent NCR for BR-PDAC from January 2010 to March 2020 were included in the study. The patients received a variety of NCR regimens during the study period, and in patients with radiological evidence of tumour stability or regression, pancreatic resection was performed. The primary endpoint was the OS, and the secondary endpoints included patient morbidity, the R0 resection rate, histological parameters and the DFS. Results: The study included 29 patients (16 men and 13 women), with a median age of 65 years (range 46–74 years). Of these 29 patients, 17 received FOLFIRINOX and 12 received gemcitabine (GEM)-based NCR regimens. All patients received chemoradiation at the end of chemotherapy (range 45–56 Gy). R0 resection was achieved in 75% of the patients, with a higher rate noted in the FOLFIRINOX group. The median DFS was 22 months for the whole cohort but higher in the FOLFIRINOX group (34 months). The median OS for the cohort was 29 months, with a higher median OS noted for the FOLFIRINOX cohort versus the GEM cohort (42 versus 28 months). Conclusion: NCR, particularly FOLFIRINOX-based treatment, for BR-PDAC results in higher rates of R0 resection and an increased median DFS and OS, supporting its continued use in this patient group.
Meta-Analytic Comparison of Global RNA Transcriptomes of Acute and Chronic Myeloid Leukemia Cells Reveals Novel Gene Candidates Governing Myeloid Malignancies
Authors: Jurgec Staša , Jezernik Gregor , Gorenjak Mario , Büdefeld Tomaž , Potočnik Uroš
Published: September 2022

Background: Acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) represent a group of hematological malignancies characterized by the pathogenic clonal expansion of leukemic myeloid cells. The diagnosis and clinical outcome of AML and CML are complicated by genetic heterogeneity of disease; therefore, the identification of novel molecular biomarkers and pharmacological targets is of paramount importance. Methods: RNA-seq-based transcriptome data from a total of five studies were extracted from NCBI GEO repository and subjected to an in-depth bioinformatics analysis to identify differentially expressed genes (DEGs) between AML and CML. A systemic literature survey and functional gene ontology (GO) enrichment analysis were performed for the top 100 DEGs to identify novel candidate genes and biological processes associated with AML and CML. Results: LINC01554, PTMAP12, LOC644936, RPS27AP20 and FAM133CP were identified as novel risk genes for AML and CML. GO enrichment analysis showed that DEGs were significantly associated with pre-RNA splicing, reactive oxygen species and glycoprotein metabolism, the cellular endomembrane system, neutrophil migration and antimicrobial immune response. Conclusions: Our study revealed novel biomarkers and specific biological processes associated with AML and CML. Further studies are required to evaluate their value as molecular targets for managing and treating the myeloid malignancies.
Plant-Derived Sulforaphane Suppresses Growth and Proliferation of Drug-Sensitive and Drug-Resistant Bladder Cancer Cell Lines In Vitro
Authors: Xie Hui , Rutz Jochen , Maxeiner Sebastian , Grein Timothy , Thomas Anita , Juengel Eva , Chun Felix K.-H. , Cinatl Jindrich , Haferkamp Axel , Tsaur Igor , Blaheta Roman A.
Published: September 2022

Combined cisplatin–gemcitabine (GC) application is standard for treating muscle-invasive bladder cancer. However, since rapid resistance to treatment often develops, many patients turn to supplements in the form of plant-based compounds. Sulforaphane (SFN), derived from cruciferous vegetables, is one such compound, and the present study was designed to investigate its influence on growth and proliferation in a panel of drug-sensitive bladder cancer cell lines, as well as their gemcitabine- and cisplatin-resistant counterparts. Chemo-sensitive and -resistant RT4, RT112, T24, and TCCSUP cell lines were exposed to SFN in different concentrations, and tumor growth, proliferation, and clone formation were evaluated, in addition to apoptosis and cell cycle progression. Means of action were investigated by assaying cell-cycle-regulating proteins and the mechanistic target of rapamycin (mTOR)/AKT signaling cascade. SFN significantly inhibited growth, proliferation, and clone formation in all four tumor cell lines. Cells were arrested in the G2/M and/or S phase, and alteration of the CDK–cyclin axis was closely associated with cell growth inhibition. The AKT/mTOR signaling pathway was deactivated in three of the cell lines. Acetylation of histone H3 was up-regulated. SFN, therefore, does exert tumor-suppressive properties in cisplatin- and gemcitabine-resistant bladder cancer cells and could be beneficial in optimizing bladder cancer therapy.
Risk Factors for Pancreatic Cancer in Patients with New-Onset Diabetes: A Systematic Review and Meta-Analysis
Authors: Mellenthin Claudia , Balaban Vasile Daniel , Dugic Ana , Cullati Stephane
Published: September 2022

(1) Background: Patients with new-onset diabetes (NOD) are at risk of pancreatic ductal adenocarcinoma (PDAC), but the most relevant additional risk factors and clinical characteristics are not well established. (2) Objectives: To compare the risk for PDAC in NOD patients to persons without diabetes. Identify risk factors of PDAC among NOD patients. (3) Methods: Medline, Embase, and Google Scholar were last searched in June 2022 for observational studies on NOD patients and assessing risk factors for developing PDAC. Data were extracted, and Meta-Analysis was performed. Pooled effect sizes with 95% confidence intervals (CI) were estimated with DerSimonian & Laird random effects models. (4) Findings: Twenty-two studies were included, and 576,210 patients with NOD contributed to the analysis, of which 3560 had PDAC. PDAC cases were older than controls by 6.14 years (CI 3.64–8.65, 11 studies). The highest risk of PDAC involved a family history of PDAC (3.78, CI 2.03–7.05, 4 studies), pancreatitis (5.66, CI 2.75–11.66, 9 studies), cholecystitis (2.5, CI 1.4–4.45, 4 studies), weight loss (2.49, CI 1.47–4.22, 4 studies), and high/rapidly increasing glycemia (2.33, CI 1.85–2.95, 4 studies) leading to more insulin use (4.91, CI 1.62–14.86, 5 studies). Smoking (ES 1.20, CI 1.03–1.41, 9 studies) and alcohol (ES 1.23, CI 1.09–1.38, 9 studies) have a smaller effect. (5) Conclusion: Important risk factors for PDAC among NOD patients are age, family history, and gallstones/pancreatitis. Symptoms are weight loss and rapid increase in glycemia. The identified risk factors could be used to develop a diagnostic model to screen NOD patients.
Association between Submucosal Fibrosis and Endoscopic Submucosal Dissection of Recurrent Esophageal Squamous Cell Cancers after Chemoradiotherapy
Authors: Kato Tsunetaka , Hikichi Takuto , Nakamura Jun , Hashimoto Minami , Kobashi Ryoichiro , Yanagita Takumi , Suzuki Rei , Sugimoto Mitsuru , Sato Yuki , Irie Hiroki , Takasumi Mika , Oka Yuka , Takagi Tadayuki , Hashimoto Yuko , Kobayakawa Masao , Ohira Hiromasa
Published: September 2022

Endoscopic resection is a treatment of choice for a metachronous early-stage esophageal squamous cell carcinoma (ESCC) appearing after a radical cure of esophageal cancer by chemoradiotherapy (CRT). However, non-curative resection, and procedural complications including perforation due to radiation-induced submucosal fibrosis, are a concern. This study aimed to evaluate the association between submucosal fibrosis and the usefulness and safety of endoscopic submucosal dissection (ESD) in ESCC after CRT. This study retrospectively analyzed 13 lesions in 11 patients in our institute. Submucosal fibrosis under the lesion (F score) was classified into three levels (F0: none or mild, F1: moderate, and F2: severe) based on endoscopic and histopathologic findings. All lesions were F1 or greater (F1: 8 lesions and F2: 5 lesions). En bloc and R0 resection rates were both 100%. The procedural speed was slower in F2 than in F1 (F1 vs. F2; 15.1 mm2/min vs. 7.1 mm2/min, p = 0.019), without procedure-related adverse events. At a median follow-up of 42 months (range: 14–117 months) after ESD, 7 of 11 (63.6%) patients were alive without recurrence, and without ESCC-related death. ESCC after CRT reliably and safely resected en bloc by ESD but was more difficult in lesions with strong submucosal fibrosis.
Cross-Domain Text Mining to Predict Adverse Events from Tyrosine Kinase Inhibitors for Chronic Myeloid Leukemia
Authors: Mehra Nidhi , Varmeziar Armon , Chen Xinyu , Kronick Olivia , Fisher Rachel , Kota Vamsi , Mitchell Cassie S.
Published: September 2022

Tyrosine kinase inhibitors (TKIs) are prescribed for chronic myeloid leukemia (CML) and some other cancers. The objective was to predict and rank TKI-related adverse events (AEs), including under-reported or preclinical AEs, using novel text mining. First, k-means clustering of 2575 clinical CML TKI abstracts separated TKIs by significant (p < 0.05) AE type: gastrointestinal (bosutinib); edema (imatinib); pulmonary (dasatinib); diabetes (nilotinib); cardiovascular (ponatinib). Next, we propose a novel cross-domain text mining method utilizing a knowledge graph, link prediction, and hub node network analysis to predict new relationships. Cross-domain text mining of 30+ million articles via SemNet predicted and ranked known and novel TKI AEs. Three physiology-based tiers were formed using unsupervised rank aggregation feature importance. Tier 1 ranked in the top 1%: hematology (anemia, neutropenia, thrombocytopenia, hypocellular marrow); glucose (diabetes, insulin resistance, metabolic syndrome); iron (deficiency, overload, metabolism), cardiovascular (hypertension, heart failure, vascular dilation); thyroid (hypothyroidism, hyperthyroidism, parathyroid). Tier 2 ranked in the top 5%: inflammation (chronic inflammatory disorder, autoimmune, periodontitis); kidney (glomerulonephritis, glomerulopathy, toxic nephropathy). Tier 3 ranked in the top 10%: gastrointestinal (bowel regulation, hepatitis, pancreatitis); neuromuscular (autonomia, neuropathy, muscle pain); others (secondary cancers, vitamin deficiency, edema). Results suggest proactive TKI patient AE surveillance levels: regular surveillance for tier 1, infrequent surveillance for tier 2, and symptom-based surveillance for tier 3.
Cranial MRI in Childhood Acute Leukemia during Treatment and Follow-Up Including the Impact of Intrathecal MTX—A Single-Center Study and Review of the Literature
Authors: Mergen Marvin , Scheid Sascha , Schubmehl Hannah , Backens Martin , Reith Wolfgang , Graf Norbert
Published: September 2022

Due to high survival rates, long-term sequelae, especially neurotoxicity, need to be considered in childhood acute leukemias. In this retrospective analysis of morphologic changes of the brain in children treated for acute leukemias, we included 94 patients (77 ALL, 17 AML; 51 male, 43 female; median age: 5 years) from a single center. We analyzed 170 cranial MRI scans (T2, FLAIR axial) for morphologic alterations of the brain and variations of the ventricular width (GDAH). In addition, the corresponding literature was reviewed. More than 50% of all patients showed cerebral pathomorphologies (CP). They were seen more often in children with ALL (55.8%), ≤ 6 years of age (60.8%), in relapse (58.8%) or after CNS irradiation (75.0%) and included white matter changes, brain atrophy, sinus vein thrombosis and ischemic events. GDAH significantly enlarged mainly in children up to 6 years, with relapse, high-risk leukemias or ALL patients. However, GDAH can normalize again. The number of intrathecal Methotrexate applications (≤12 vs. >12) showed no correlation to morphologic alterations besides a significant increase in GDAH (−0.3 vs. 0.9 mm) between the first and last follow-up MRI in ALL patients receiving >12 ith. MTX applications. The role of ith. MTX on CP needs to be further investigated and correlated to the neurocognitive outcome of children with acute leukemias.
Genome-Wide Association Study Identifies Candidate Loci Associated with Opioid Analgesic Requirements in the Treatment of Cancer Pain
Authors: Nishizawa Daisuke , Terui Takeshi , Ishitani Kunihiko , Kasai Shinya , Hasegawa Junko , Nakayama Kyoko , Ebata Yuko , Ikeda Kazutaka
Published: September 2022

Considerable individual differences have been widely observed in the sensitivity to opioids. We conducted a genome-wide association study (GWAS) in patients with cancer pain to identify potential candidate single-nucleotide polymorphisms (SNPs) that contribute to individual differences in opioid analgesic requirements in pain treatment by utilizing whole-genome genotyping arrays with more than 650,000 markers. The subjects in the GWAS were 428 patients who provided written informed consent and underwent treatment for pain with opioid analgesics in a palliative care unit at Higashi-Sapporo Hospital. The GWAS showed two intronic SNPs, rs1283671 and rs1283720, in the ANGPT1 gene that encodes a secreted glycoprotein that belongs to the angiopoietin family. These two SNPs were strongly associated with average daily opioid requirements for the treatment of pain in both the additive and recessive models (p < 5.0000 × 10−8). Several other SNPs were also significantly associated with the phenotype. In the gene-based analysis, the association was significant for the SLC2A14 gene in the additive model. These results indicate that these SNPs could serve as markers that predict the efficacy of opioid analgesics in cancer pain treatment. Our findings may provide valuable information for achieving satisfactory pain control and open new avenues for personalized pain treatment.
Assessment of Vocal Fold Stiffness by Means of High-Speed Videolaryngoscopy with Laryngotopography in Prediction of Early Glottic Malignancy: Preliminary Report
Authors: Kaluza Justyna , Niebudek-Bogusz Ewa , Malinowski Jakub , Strumillo Pawel , Pietruszewska Wioletta
Published: September 2022

One of the most important challenges in laryngological practice is the early diagnosis of laryngeal cancer. Detection of non-vibrating areas affected by neoplastic lesions of the vocal folds can be crucial in the recognition of early cancerogenous infiltration. Glottal pathologies associated with abnormal vibration patterns of the vocal folds can be detected and quantified using High-speed Videolaryngoscopy (HSV), also in subjects with severe voice disorders, and analyzed with the aid of computer image processing procedures. We present a method that enables the assessment of vocal fold pathologies with the use of HSV. The calculated laryngotopographic (LTG) maps of the vocal folds based on HSV allowed for a detailed characterization of vibration patterns and abnormalities in different regions of the vocal folds. We verified our methods with HSV recordings from 31 subjects with a normophonic voice and benign and malignant vocal fold lesions. We proposed the novel Stiffness Asymmetry Index (SAI) to differentiate between early glottis cancer (SAI = 0.65 ± 0.18) and benign vocal fold masses (SAI = 0.16 ± 0.13). Our results showed that these glottal pathologies might be noninvasively distinguished prior to histopathological examination. However, this needs to be confirmed by further research on larger groups of benign and malignant laryngeal lesions.
Automated Assessment of Breast Positioning Quality in Screening Mammography
Authors: Brahim Mouna , Westerkamp Kai , Hempel Louisa , Lehmann Reiner , Hempel Dirk , Philipp Patrick
Published: September 2022

Screening mammography is a widely used approach for early breast cancer detection, effectively increasing the survival rate of affected patients. According to the Food and Drug Administration’s Mammography Quality Standards Act and Program statistics, approximately 39 million mammography procedures are performed in the United States each year. Therefore, breast cancer screening is among the most common radiological tasks. Interpretation of screening mammograms by a specialist radiologist includes primarily the review of breast positioning quality, which is a key factor affecting the sensitivity of mammography and thus the diagnostic performance. Each mammogram with inadequate positioning may lead to a missed cancer or, in case of false positive signal interpretation, to follow-up activities, increased emotional burden and potential over-therapy and must be repeated, requiring the return of the patient. In this study, we have developed deep convolutional neuronal networks to differentiate mammograms with inadequate breast positioning from the adequate ones. The aim of the proposed automated positioning quality evaluation is to assist radiology technologists in detecting poorly positioned mammograms during patient visits, improve mammography performance, and decrease the recall rate. The implemented models have achieved 96.5% accuracy in cranio-caudal view classification and 93.3% accuracy in mediolateral oblique view regarding breast positioning quality. In addition to these results, we developed a software module that allows the study to be applied in practice by presenting the implemented model predictions and informing the technologist about the missing quality criteria.
Identification of Monobenzone as a Novel Potential Anti-Acute Myeloid Leukaemia Agent That Inhibits RNR and Suppresses Tumour Growth in Mouse Xenograft Model
Authors: Dong Jingwen , Zhong Tingting , Xu Zhijian , Chen Haiyi , Wang Xianjun , Yang Lili , Lou Zhiyuan , Xu Yuanling , Hou Tingjun , Xu Rongzhen , Zhu Weiliang , Shao Jimin
Published: September 2022

Acute myeloid leukaemia (AML) is one of the most common types of haematopoietic malignancy. Ribonucleotide reductase (RNR) is a key enzyme required for DNA synthesis and cell proliferation, and its small subunit RRM2 plays a key role for the enzymatic activity. We predicted monobenzone (MB) as a potential RRM2 target compound based on the crystal structure of RRM2. In vitro, MB inhibited recombinant RNR activity (IC50 = 0.25 μM). Microscale thermophoresis indicated that MB inhibited RNR activity by binding to RRM2. MB inhibited cell proliferation (MTT IC50 = 6–18 μM) and caused dose-dependent DNA synthesis inhibition, cell cycle arrest, and apoptosis in AML cells. The cell cycle arrest was reversed by the addition of deoxyribonucleoside triphosphates precursors, suggesting that RNR was the intracellular target of the compound. Moreover, MB overcame drug resistance to the common AML drugs cytarabine and doxorubicin, and treatment with the combination of MB and the Bcl-2 inhibitor ABT-737 exerted a synergistic inhibitory effect. Finally, the nude mice xenografts study indicated that MB administration produced a significant inhibitory effect on AML growth with relatively weak toxicity. Thus, we propose that MB has the potential as a novel anti-AML therapeutic agent in the future.
Breast Tumor Cell-Stimulated Bone Marrow-Derived Mesenchymal Stem Cells Promote the Sprouting Capacity of Endothelial Cells by Promoting VEGF Expression, Mediated in Part through HIF-1α Increase
Authors: Kim Wootak , Park Aran , Jang Hyun Hee , Kim Seung-Eun , Park Ki-Sook
Published: September 2022

Breast tumor cells recruit bone marrow-derived mesenchymal stem cells (BM-MSCs) and alter their cellular characteristics to establish a tumor microenvironment. BM-MSCs enhance tumor angiogenesis through various mechanisms. We investigated the mechanisms by which BM-MSCs promote angiogenesis in response to breast tumor. Conditioned media from MDA-MB-231 (MDA CM) and MCF7 (MCF7 CM) breast tumor cells were used to mimic breast tumor conditions. An in vitro spheroid sprouting assay using human umbilical vein endothelial cells (HUVECs) was conducted to assess the angiogenesis-stimulating potential of BM-MSCs in response to breast tumors. The ROS inhibitor N-acetylcysteine (NAC) and JAK inhibitor ruxolitinib attenuated increased HIF-1α in BM-MSCs in response to MDA CM and MCF7 CM. HIF-1α knockdown or HIF-1β only partially downregulated VEGF expression and, therefore, the sprouting capacity of HUVECs in response to conditioned media from BM-MSCs treated with MDA CM or MCF7 CM. Inactivation of the VEGF receptor using sorafenib completely inhibited the HUVECs’ sprouting. Our results suggest that increased HIF-1α expression under normoxia in BM-MSCs in response to breast tumor cells is mediated by ROS and JAK/Stat3, and that both HIF-1α-dependent and -independent mechanisms increase VEGF expression in BM-MSCs to promote the angiogenic sprouting capacity of endothelial cells in a VEGF-dependent manner.
Mutation Patterns in Portuguese Families with Hereditary Breast and Ovarian Cancer Syndrome
Authors: Vicente Rodrigo , Alpuim Costa Diogo , Vitorino Marina , Mendes Ana Duarte , Santos Catarina , Fontes-Sousa Mário
Published: September 2022

Germline pathogenic variants in the Breast Cancer Genes 1 (BRCA1) and 2 (BRCA2) are responsible for Hereditary Breast and Ovarian Cancer (HBOC) syndrome. Genetic susceptibility to breast cancer accounts for 5–10% of all cases, phenotypically presenting with characteristics such as an autosomal dominant inheritance pattern, earlier age of onset, bilateral tumours, male breast cancer, and ovarian tumours, among others. BRCA2 pathogenic variant is usually associated with other cancers such as melanoma, prostate, and pancreatic cancers. Many rearrangements of different mutations were found in both genes, with some ethnic groups having higher frequencies of specific mutations due to founder effects. Despite the heterogeneity of germline BRCA1/BRCA2 mutations in Portuguese breast or/and ovarian cancer families, the first described founder mutation in the BRCA2 gene (c.156_157insAlu) and two other variants in the BRCA1 gene (c.3331_3334del and c.2037delinsCC) contribute to about 50% of all pathogenic mutations. Furthermore, the families with the BRCA1 c.3331_3334del or the c.2037delinsCC mutations share a common haplotype, suggesting that these may also be founder mutations in the Portuguese population. Identifying specific and recurrent/founder mutations plays an important role in increasing the efficiency of genetic testing since it allows the use of more specific, cheaper and faster strategies to screen HBOC families. Therefore, this review aims to describe the mutational rearrangements of founder mutations and evaluate their impact on the genetic testing criteria for HBOC families of Portuguese ancestry.
Effect of Concomitant Proton Pump Inhibitors with Pazopanib on Cancer Patients: A Retrospective Analysis
Authors: Moreau-Bachelard Camille , Letailleur Valentin , Bompas Emmanuelle , Soulié Patrick , Paul Julie , Raoul Jean-Luc
Published: September 2022

The absorption of pazopanib depends on gastric pH. PPIs are frequently prescribed for cancer patients to modify gastric acidity, decreasing pazopanib absorption. The aim of our study was, retrospectively, to investigate the impact of PPIs on the clinical efficacy and safety of pazopanib in a cohort of patients treated in our health center. Of the 147 patients who were included retrospectively, 79 (54%) did not take PPIs concomitantly with pazopanib (cohort 1), while 68 (46%) patients did take PPIs concomitantly with pazopanib (cohort 2). The efficacy parameters were lower in patients taking pazopanib and PPIs: the i/tumor response was statistically different between the two cohorts (p = 0.008), in particular, with 19% vs. 3% of the objective response and 24% vs. 43% of progression in cohorts 1 and 2, respectively; ii/median overall survival was 17.6 (95% CI: 12.5–32.8) months in cohort 1 and 8.6 months (95% CI: 5.9–18.6) in cohort 2 (HR = 1.7 [95% CI: 1.2–2.5]; p < 0.006); on multivariable analysis, overall survival was associated with performance status, PPI intake, tumor location, hemoglobin, and PMN/lymphocyte ratio. In contrast, the dose reduction for toxicity and severe adverse events were (non-significantly) less frequent in cohort 1. To conclude, our study shows that combining PPIs with pazopanib has an adverse effect on overall survival. The clinical modifications that were observed are in line with a decrease in pazopanib absorption due to PPIs. This co-medication should be avoided.