bluuebunny/crossref_metadata_2025 huggingface dataset:
The Efficacy of Music for Emotional Wellbeing During the COVID-19 Lockdown in Spain: An Analysis of Personal and Context-Related Variables
Authors: Martínez-Castilla Pastora , Gutiérrez-Blasco Isabel M. , Spitz Daniel H. , Granot Roni
Published: April 2021

The strict lockdown experienced in Spain during March–June 2020 as a consequence of the COVID-19 crisis has led to strong negative emotions. Music can contribute to enhancing wellbeing, but the extent of this effect may be modulated by both personal and context-related variables. This study aimed to analyze the impact of the two types of variables on the perceived efficacy of musical behaviors to fulfill adults’ emotional wellbeing-related goals during the lockdown established in Spain. Personal variables included age, gender, musical training, personality, resilience, and perception of music’s importance. Contextual variables referred to living in a region with a high COVID-19 impact, perception of belonging to a risk group, being alone, having caring responsibilities during confinement, and amount of time of music listening as compared to prior to the crisis. The study was conducted retrospectively during August–December 2020, when the strict lockdown was over in Spain. An online survey was disseminated among the general population and groups of musicians, and the answers of 507 adults (from 18 years on, 73.9% females, 51.3% musically trained adults) were analyzed. Only personal, but not COVID-19 context-related variables, showed an impact on music’s efficacy. The youngest age group of adults and those with musical training reported the highest efficacy of music for wellbeing enhancement, and music’s importance was found to be the main significant predictor of music’s perceived efficacy. Our findings suggest that the people who have been reported to be emotionally more vulnerable during the lockdown, due to either a strong impact on their daily lives or their lower resilience, perceive a higher benefit from musical behaviors. Being musically trained, even for a small number of years, also leads to a perception of higher efficacy of music for the achievement of emotional wellbeing goals. However, this effect is explained by the musically trained individuals’ higher perception of music’s importance. Although musical behaviors can be generally considered as important for wellbeing enhancement, our study highlights who are the potential individuals who could benefit the most from music-related activities for obtaining better levels of wellbeing, at least within the current context of the COVID-19 crisis.
Evaluation and Analysis of Mental Health Level of College Students With Financial Difficulties Under the Background of COVID-19
Authors: Feng Yongpeng , Zhang Yunting
Published: April 2021

Against the backdrop of COVID-19, the mental health of college students with financial difficulties deserves scientific attention. This paper on the relationship between mental resilience and the mental health of students with financial difficulties summarizes the research on the psychological resilience of students with financial difficulties during the COVID-19 pandemic. It also suggests ways in which to improve the mental health levels of students with financial difficulties by improving their mental resilience.
Quality of Life and Its Predictive Factors Among Healthcare Workers After the End of a Movement Lockdown: The Salient Roles of COVID-19 Stressors, Psychological Experience, and Social Support
Authors: Woon Luke Sy-Cherng , Mansor Nor Shuhada , Mohamad Mohd Afifuddin , Teoh Soon Huat , Leong Bin Abdullah Mohammad Farris Iman
Published: April 2021

Although healthcare workers play a crucial role in helping curb the hazardous health impact of coronavirus disease 2019 (COVID-19), their lives and major functioning have been greatly affected by the pandemic. This study examined the effects of the COVID-19 pandemic on the quality of life (QoL) of Malaysian healthcare workers and its predictive factors. An online sample of 389 university-based healthcare workers completed questionnaires on demographics, clinical features, COVID-19-related stressors, psychological experiences, and perceived social support after the movement lockdown was lifted. All domains of QoL were within the norms of the general population except for social relationship QoL, which was lower than the norm. Multiple linear regression analysis indicated that COVID-19-related stressors (e.g., stress due to annual leave being frozen, loss of daily routine, and frequent exposure to COVID-19 patients) and psychological sequelae (e.g., greater severity of depression, anxiety, and stress) predicted lower QoL. Conversely, greater perceived social support from friends and significant others predicted higher QoL. Clinical and demographic characteristics predicted QoL to a lesser extent: A history of pre-existing medical illness was associated only with lower physical health QoL, whereas older age and being single, divorced, or widowed were only predictive of higher environmental QoL. Efforts to enhance QoL among healthcare workers in response to the pandemic should focus on mitigating COVID-19-related stressors and psychological sequelae and facilitating social support.
The Pharmacodynamics of Antipsychotic Drugs in Women and Men
Authors: Seeman Mary V.
Published: April 2021

Background: Animal and human experiments have confirmed sex differences in the expression of hepatic enzymes that metabolize antipsychotic drugs and that may, in this way, be partly responsible for the clinical sex/gender differences observed in the efficacy and tolerability of antipsychotic treatment.

Aim: The aim of this mini review is to synthesize the literature on the pharmacodynamics of male/female differential response to antipsychotic drugs.

Method: Relevant search terms were used to search for pre-clinical and human trials and analysis of antipsychotic differential drug response and occurrence/severity of adverse effects in women and men.

Results: The search found that sex influences drug response via the amount of a given drug that enters the brain and the number of neurotransmitter receptors to which it can bind. Consequently, sex partly determines the efficacy of a specific drug and its liability to induce unwanted effects. There are other factors that can overshadow or enhance the dimorphic effect of sex, for instance, the host's age, hormonal status, diet and life style as well as the molecular structure of the drug and its dose, and the method of its administration. Most of all, the host's individual genetics affects each step of a drug's pharmacodynamics.

Conclusion: On average, women's psychotic symptoms respond to antipsychotic drugs at doses lower than men's. This means that many women may be de facto overdosed and, thus, experience unnecessary adverse effects. That being said, factors such as genetics and age probably determine drug response and tolerability to a greater degree than do biological sex or gender social roles.
Alexithymia in Patients With Substance Use Disorders and Its Relationship With Psychiatric Comorbidities and Health-Related Quality of Life
Authors: Palma-Álvarez Raul F. , Ros-Cucurull Elena , Daigre Constanza , Perea-Ortueta Marta , Serrano-Pérez Pedro , Martínez-Luna Nieves , Salas-Martínez Anna , Robles-Martínez María , Ramos-Quiroga Josep A. , Roncero Carlos , Grau-López Lara
Published: April 2021

Background: Alexithymia frequently correlates with several psychiatric disorders, including substance use disorder (SUD). However, most studies reporting the associations between alexithymia and psychiatric disorders have been performed in populations without SUD. This research, therefore, evaluates alexithymia in Spanish patients with SUD and the relationship among alexithymia, psychiatric comorbidities, psychological symptoms/traits, SUD variables, and health-related quality of life (HRQoL).

Methodology: A cross-sectional study was conducted with 126 Spanish outpatients with SUD (75.4% males; mean age 43.72 ± 14.61 years), correlating their alexithymia levels (using the Toronto Alexithymia Scale 20 [TAS-20]) to their psychiatric comorbidities, psychological symptoms/traits, SUD variables, and HRQoL.

Results: Alexithymia was significantly higher in patients who had cannabis use disorder. Higher alexithymia scores were also related to higher levels of depression, anxiety, impulsivity, and lower HRQoL. After multivariate analysis, trait anxiety, impulsivity, and the physical component summary of the HRQoL were found to be independently related to alexithymia.

Conclusions: SUD patients with higher alexithymia levels have more frequently psychiatric comorbidities, present specific psychological features, and have worse HRQoL. Hence, it is important to evaluate these factors and offer more accurate psychotherapeutic approaches for this patient population.
Risks of Adverse Neonatal Outcomes in Early Adolescent Pregnancy Using Group Prenatal Care as a Strategy for Public Health Policies: A Retrospective Cohort Study in Brazil
Authors: Honorato Danylo José Palma , Fulone Izabela , Silva Marcus Tolentino , Lopes Luciane Cruz
Published: April 2021

Background: Adolescent pregnancy is a public health concern and many studies have evaluated neonatal outcomes, but few have compared younger adolescents with older using adequate prenatal care.

Objective: To compare the risks of adverse neonatal outcomes in younger pregnant adolescents who are properly followed through group prenatal care (GPC) delivered by specialized public services.

Methods: This retrospective cohort study followed pregnant adolescents (aged 10–17 years) who received GPC from specialized public services in Brazil from 2009 to 2014. Data were obtained from medical records and through interviews with a multidisciplinary team that treated the patients. The neonatal outcomes (low birth weight, prematurity, Apgar scores with 1 and 5 min, and neonatal death) of newborns of adolescents aged 10–13 years were compared to those of adolescents aged 14–15 years and 16–17 years. Incidence was calculated with 95% confidence intervals (CIs) and compared over time using a chi-squared test to observe trends. Poisson Multivariate logistic regression was used to adjust for confounding variables. The results are presented as adjusted relative risks or adjusted mean differences.

Results: Of the 1,112 adolescents who were monitored, 758 were included in this study. The overall incidence of adverse neonatal outcomes (low birth weight and prematurity) was measured as 10.2% (95% CI: 9.7–11.5). Apgar scores collected at 1 and 5 min were found to be normal, and no instance of fetal death occurred. The incidence of low birth weight was 16.1% for the 10–13 age group, 8.7% for the 14–15 age group and 12.1% for the 16–17 age group. The incidence of preterm was measured at 12, 8.5, and 12.6% for adolescents who were 10–13, 14–15, and 16–17 years of age, respectively. Neither low birth weight nor prematurity levels significantly differed among the groups (p > 0.05). The infants born to mothers aged 10–13 years presented significantly (p < 0.05) lower Apgar scores than other age groups, but the scores were within the normal range.

Conclusions: Our findings showed lower incidence of neonatal adverse outcomes and no risk difference of neonatal outcomes in younger pregnancy adolescents. It potentially suggests that GPC model to care pregnant adolescents is more important than the age of pregnant adolescent, however further research is needed.
The Role of Community Cooperative Institutions in Building Rural–Urban Linkages Under Urbanization of Pastoral Regions in China
Authors: Gongbuzeren  , Wenjun Li , Yupei Lai
Published: April 2021

In contrast to agricultural settings, the process of urbanization in the pastoral regions of China are largely driven by long-term influences of ecological conservation and the provision of social services. Consequently, many of the herders who have migrated into nearby secondary urban centers depend on resources from pastoral regions to support their livelihoods, forming complex patterns of rural–urban linkages. While current literature has discussed the processes of herder out-migration and their implications on rural and urban livelihood development, few studies have examined the linkages between the herders living in the pastoral regions and those who have out-migrated to urban regions and their importance in rural livelihood transformation. Based on past studies, we argue that, in a changing pastoral social–ecological system, herders living in both rural and urban regions depend on each other to support their livelihoods through three types of mobility: (1) livestock mobility, (2) herder mobility, and (3) resource mobility. However, what innovative institutions in rangeland resource management and herder economic cooperation can do to help maintain these three types of mobility to sustain rural livelihood development, becomes a critical challenge. Innovative community cooperative institutions developed by pastoral communities from the Tibetan Plateau and Inner Mongolia may be able to offer new perspective and insight on how to better maintain rural–urban linkages in the processes of urbanization in pastoral regions. In this current study will present the two cases of innovative institutions and the roles they play in facilitating the three types of mobility to address livelihood challenges. While current studies recommend an increase of government subsidies, provision of vocational training, and social insurance that help herders better adapt to urban livelihood, we argue that rangeland management and community economic cooperation in innovative institutions are needed to facilitate the mobility of livestock, resources, and the herder population, and maybe only then the livelihood challenges that migrated herders are facing will be addressed effectively.
The Impact of the Introduction of Innovative REDS Scale for the Evaluation of Central Tunnelled Catheter (CTC) Exit Site on Infection Prevention in Long-Term Haemodialyzed Patients
Authors: Porazko Tomasz , Stasiak Edyta , Klinger Marian
Published: April 2021

Central tunneled catheter (CTC)-related infections are a leading cause of a catheter loss, thus being the source of significant morbidity and mortality. The study aims at evaluating the impact of the implementation of the innovative redness, edema, discharge and tenderness, symptoms (REDS) scale (devised by the authors) for the description of the tunnel condition on the frequency of infection in long-term catheter users. The same cohort of the 40 patients was observed for 4 years altogether: 2 years before and 2 years after REDS application. The results, as well as follow-up evaluation of participants, were compared. The 2-year cumulative incidence of the CTC exit site infection (ESI) dropped significantly (log-rankp< 0.001) from 0.89 episode/1,000 catheter days (53.5%, 95% CI [35.9%; 66.2%]) in the period before REDS was used—to 0.26 episode/1,000 catheter days (18.6%, 95% CI [6.1%; 29.4%]) in the time of REDS application. There were also significantly fewer episodes of ESI complicated with catheter-related blood stream infection (CRBSI) requiring the CTC removal (0.6 episode/1,000 catheter days; 18.6%, 95% CI [6.1%; 29.4%] vs. 0.3 episode/1,000 catheter days; 4.7%, 95% CI [0.0; 10.7%]; log-rankp= 0.04, in pre-REDS and REDS time, respectively). The REDS scale appears to be a simple, cost-effective tool reducing the frequency of the tunneled CTC exit site infection and associated bloodstream infections.
Transport to School and Mental Well-Being of Schoolchildren in Ireland
Authors: Költő András , Gavin Aoife , Kelly Colette , Nic Gabhainn Saoirse
Published: April 2021

Objectives: We explored whether modes of transport (cycling, walking, public transport or private vehicle) between home and school are associated with mental well-being in children aged 10–17 years, participating in the Irish Health Behaviour in School-aged Children (HBSC) study.

Methods: Scores on the World Health Organization Well-being Index and the Mental Health Inventory five-item versions, self-reported life satisfaction, happiness with self, body satisfaction, excellent self-rated health, and multiple health complaints of 9,077 schoolchildren (mean age: 13.99 ± 1.91 years, percentage girls: 52.2%) were compared across modes of transport, unadjusted and adjusted for gender, age, family affluence and area of residence.

Results: Those who reported using public transport reported poorer mental well-being than those using other means of transport, but adjusting for sociodemographic variables obscured these differences. The only exception was excellent health, where children who cycled outperformed the other three groups, even after adjustment for sociodemographic variables.

Conclusions: Cycling can improve well-being in children. However, in promotion of cycling, social and environmental determinants and inequalities which influence adolescents’ and their parents’ decisions on modes of transport, need to be considered.
Diagnostic Utility of BAP1, EZH2 and Survivin in Differentiating Pleural Epithelioid Mesothelioma and Reactive Mesothelial Hyperplasia: Immunohistochemical Study
Authors: Hakim Sarah Adel , Abou Gabal Hoda Hassan
Published: April 2021

Background: Epithelioid mesothelioma (EM) is the commonest subtype of malignant pleural mesothelioma. Its histopathological discrimination from reactive mesothelial hyperplasia (RMH) could be challenging. Thus, an immunohistochemical panel is mandatory for better discrimination. BAP1 is a newly identified diagnostic marker whose loss is specific to malignant mesothelioma. EZH2 overexpression is reported in different cancers, but its relation to BAP1 in malignant mesothelioma has not been fully understood. Survivin expression is said to be significantly higher in EM than in non-neoplastic pleural tissue, but its diagnostic utility as an immunohistochemical marker has not been thoroughly investigated in this field. To the best of our knowledge, no previous studies have been conducted to assess the diagnostic accuracy of the combined use of these three nuclear markers (BAP1, EZH2 and Survivin) in discriminating pleural EM from RMH.

Methods: This retrospective study includes two groups: 81 cases of pleural EM and 67 cases of RMH, retrieved from the archives of Pathology Department of Ain Shams University Hospitals and Ain-Shams University Specialized Hospital during the period from January 2016 to December 2019. An immunohistochemical study was performed using BAP1, EZH2 and Survivin antibodies.

Results: There were highly statistically significant relations between study groups as regards the studied markers (p = 0.001 for each). The specificity was 100% for all combinations of immunohistochemical markers. Sensitivity of any combination of the immunohistochemical markers used in this study was found to be higher than the sensitivity of any of these markers used individually. The combination of all three markers showed the highest diagnostic accuracy (95.9%) and the highest sensitivity (92.6%). However, the combination of Survivin and EZH2 yielded the same diagnostic accuracy and sensitivity.

Conclusion: Adding EZH2, Survivin and BAP1 to the diagnostic IHC panel for differentiating pleural EM and RMH could enhance diagnostic sensitivity. Moreover, Survivin is a potentially promising marker in this context, especially when combined with EZH2.
NOTCH Single Nucleotide Polymorphisms in the Predisposition of Breast and Colorectal Cancers in Saudi Patients
Authors: Alanazi Ibrahim O. , Shaik Jilani Purusottapatnam , Parine Narasimha Reddy , Al Naeem Abdulrahman , Azzam Nahla A. , Almadi Majid A. , Aljebreen Abdulrahman M. , Alharbi Othman , Alanazi Mohammad Saud , Khan Zahid
Published: April 2021

Breast cancer (BC) is a heterogeneous disease and is one of the most common malignancy affecting women worldwide while colorectal cancer (CRC) is estimated to be the third common cancer and second leading cause of cancer related death globally. Both BC and CRC involve multiple genetic and epigenetic alterations in genes belonging to various signaling pathways including NOTCH that has been implicated in the development of these cancers. We investigated four single nucleotide polymorphisms, each in genes encoding NOTCH1-4 receptors for their role in susceptibility to breast and colorectal cancers in Saudi population. In this case-control study, TaqMan genotypic analysis of rs3124591 in NOTCH1 and rs3820041 in NOTCH4 did not exhibit association with breast as well as colorectal cancers. However, a strong association of rs11249433 which is in close proximity to NOTCH2 was observed with breast cancer susceptibility especially with those having an early onset of the disease. Interestingly, the rs1043994 located in NOTCH3 showed gender preference and was found to be significantly associated with colorectal cancers in males. Validation of these findings in bigger populations of different ethnicities may prove beneficial in identifying rs11249433 and rs1043994 as genetic screening markers for early detection of breast and colorectal carcinomas, respectively.
An Improved Artificial Bee Colony for Feature Selection in QSAR
Authors: Lin Yanhong , Wang Jing , Li Xiaolin , Zhang Yuanzi , Huang Shiguo
Published: April 2021

Quantitative Structure–Activity Relationship (QSAR) aims to correlate molecular structure properties with corresponding bioactivity. Chance correlations and multicollinearity are two major problems often encountered when generating QSAR models. Feature selection can significantly improve the accuracy and interpretability of QSAR by removing redundant or irrelevant molecular descriptors. An artificial bee colony algorithm (ABC) that mimics the foraging behaviors of honey bee colony was originally proposed for continuous optimization problems. It has been applied to feature selection for classification but seldom for regression analysis and prediction. In this paper, a binary ABC algorithm is used to select features (molecular descriptors) in QSAR. Furthermore, we propose an improved ABC-based algorithm for feature selection in QSAR, namely ABC-PLS-1. Crossover and mutation operators are introduced to employed bee and onlooker bee phase to modify several dimensions of each solution, which not only saves the process of converting continuous values into discrete values, but also reduces the computational resources. In addition, a novel greedy selection strategy which selects the feature subsets with higher accuracy and fewer features helps the algorithm to converge fast. Three QSAR datasets are used for the evaluation of the proposed algorithm. Experimental results show that ABC-PLS-1 outperforms PSO-PLS, WS-PSO-PLS, and BFDE-PLS in accuracy, root mean square error, and the number of selected features. Moreover, we also study whether to implement scout bee phase when tracking regression problems and drawing such an interesting conclusion that the scout bee phase is redundant when dealing with the feature selection in low-dimensional and medium-dimensional regression problems.
Multimodal Optimization of Permutation Flow-Shop Scheduling Problems Using a Clustering-Genetic-Algorithm-Based Approach
Authors: Zou Pan , Rajora Manik , Liang Steven Y.
Published: April 2021

Though many techniques were proposed for the optimization of Permutation Flow-Shop Scheduling Problem (PFSSP), current techniques only provide a single optimal schedule. Therefore, a new algorithm is proposed, by combining the k-means clustering algorithm and Genetic Algorithm (GA), for the multimodal optimization of PFSSP. In the proposed algorithm, the k-means clustering algorithm is first utilized to cluster the individuals of every generation into different clusters, based on some machine-sequence-related features. Next, the operators of GA are applied to the individuals belonging to the same cluster to find multiple global optima. Unlike standard GA, where all individuals belong to the same cluster, in the proposed approach, these are split into multiple clusters and the crossover operator is restricted to the individuals belonging to the same cluster. Doing so, enabled the proposed algorithm to potentially find multiple global optima in each cluster. The performance of the proposed algorithm was evaluated by its application to the multimodal optimization of benchmark PFSSP. The results obtained were also compared to the results obtained when other niching techniques such as clearing method, sharing fitness, and a hybrid of the proposed approach and sharing fitness were used. The results of the case studies showed that the proposed algorithm was able to consistently converge to better optimal solutions than the other three algorithms.
Aircraft Observations of Characteristics and Growth of Ice Particles of Two Different Snowfall Clouds in Shanxi Province, China
Authors: Feng Qiujuan , Niu Shengjie , Hou Tuanjie , Yue Zhiguo , Shen Dongdong
Published: April 2021

The ice crystal habits, distributions and growth processes in two snowfall cloud cases on 29 November 2009 and 3 March 2012 in northern China were compared and analyzed with aircraft data. The results showed that ice crystal habits were affected by the height of ice clouds. Ice crystals in clouds with cloud top temperatures of −12.6 °C were predominantly needle, plate, dendrite and irregular. When the cloud top temperature was lower than −19.5 °C, plates, dendrites and irregular ice crystals were observed in addition to needles, capped-column crystals were observed in the lower and middle layers of clouds, and column crystals were observed in the upper layer of clouds. The liquid water content of the two snowfall processes was lower than 0.1 g·m−3. Ice particles grew mainly via deposition, riming and aggregation processes. On 29 November, the liquid water content of the stratospheric mixed snowfall cloud was distributed in the lower part of the cloud. The maximum values of particle concentration and ice water content detected by a cloud imaging probe were 187 L−1 and 1.05 g·m−3, which were at −8.7 °C, and the ice water content was higher. On 3 March, the liquid water content of snowfall in stratiform clouds was located in the middle layer, and the maximum ice water was low, which was only 0.052 g m−3. The ice water value on 29 November was higher, which was mainly due to the convective zone embedded in the cumulus mixed cloud containing a large number of riming and aggregated snow crystals. Using an exponential function to fit the crystal spectrum of the two snowfall processes, N0 and λ were 109−1011 m−4 and 108−1010 m−4 and 103−104 m−1 and 104 m−1, respectively. Compared with 3 March, N0 on 29 November was larger and the variation range of λ was one more order of magnitude. N0 and λ conformed to a power function distribution. By analyzing the scatter plot of the correlation coefficient and slope, it was found that the exponential function can accurately express the crystal spectrum of snow clouds.
Introduction to the Special Issue “Radiative Transfer in the Earth Atmosphere”
Authors: Sokolik Irina
Published: April 2021

This Special Issue aims at addressing the recent developments towards improving our understanding of the diverse radiative impact of different types of aerosols and clouds [...]
Tractography for Subcortical Resection of Gliomas Is Highly Accurate for Motor and Language Function: ioMRI-Based Elastic Fusion Disproves the Severity of Brain Shift
Authors: Ille Sebastian , Schwendner Maximilian , Zhang Wei , Schroeder Axel , Meyer Bernhard , Krieg Sandro M.
Published: April 2021

When using preoperative tractography intraoperatively, inaccuracies due to brain shift might occur. Intraoperative tractography is rarely performed. Elastic fusion (EF) is a tool developed to compensate for brain shift, gravity, and tissue resection based on intraoperative images. Our hypothesis was that preoperative tractography is accurate and adjustments of tractography by intraoperative magnetic resonance imaging (ioMRI)-based EF (IBEF) compensate for brain shift. Between February 2018 and June 2019, 78 patients underwent eloquent (46 motor, 32 language) glioma resection in our department using intraoperative MRI. Mean distances between the resection cavity and tractography were analyzed and correlated with clinical outcomes. The mean ± standard deviation (range) distance after the application of IBEF was 5.0 ± 2.9 mm (0–10 mm) in patients without surgery-related motor deficits compared with 1.1 ± 1.6 mm (0–5 mm) in patients who showed new permanent surgery-related motor deficits postoperatively (p < 0.001). For language, the distance was 0.7 ± 1.2 mm (0–2 mm) in patients with new permanent deficits compared with 3.1 ± 4.5 mm (0–14 mm) in patients without new permanent surgery-related language deficits (p = 0.541). Preoperative tractography corrected by IBEF for subcortical resection of gliomas is highly accurate. However, at least for such subcortical anatomy, the severity of brain shift was considerably overestimated in the past.
Analysis of Intra-Tumoral Macrophages and T Cells in Non-Small Cell Lung Cancer (NSCLC) Indicates a Role for Immune Checkpoint and CD200-CD200R Interactions
Authors: Tøndell Anders , Subbannayya Yashwanth , Wahl Sissel Gyrid Freim , Flatberg Arnar , Sørhaug Sveinung , Børset Magne , Haug Markus
Published: April 2021

Non-small cell lung carcinoma (NSCLC) is one of the most commonly diagnosed cancers and a leading cause of cancer-related deaths. Immunotherapy with immune checkpoint inhibitors shows beneficial responses, but only in a proportion of patients. To improve immunotherapy in NSCLC, we need to map the immune checkpoints that contribute immunosuppression in NSCLC-associated immune cells and to identify novel pathways that regulate immunosuppression. Here, we investigated the gene expression profiles of intra-tumoral immune cells isolated from NSCLC patients and compared them to the expression profiles of their counterparts in adjacent healthy tissue. Transcriptome analysis was performed on macrophages, CD4+ and CD8+ T cells. The data was subjected to Gene Ontology (GO) term enrichment and weighted correlation network analysis in order to identify mediators of immunosuppression in the tumor microenvironment in NSCLC. Immune cells from NSCLC revealed a consistent differential expression of genes involved in interactions between myeloid cells and lymphocytes. We further identified several immunosuppressive molecules and pathways that may be activated in tumor-associated macrophages in NSCLC. Importantly, we report novel data on immune cell expression of the newly described CD200/CD200R1 pathway, and the leukocyte immunoglobulin-like receptors (LILRs), which may represent novel innate immune checkpoints, dampening the anti-tumor T cell immune response in NSCLC. Our study substantiates the importance of tumor-associated macrophages as a mediator of immunosuppression and a promising target for immunotherapy.
Novel Benzenesulfonate Scaffolds with a High Anticancer Activity and G2/M Cell Cycle Arrest
Authors: Malarz Katarzyna , Mularski Jacek , Kuczak Michał , Mrozek-Wilczkiewicz Anna , Musiol Robert
Published: April 2021

Sulfonates, unlike their derivatives, sulphonamides, have rarely been investigated for their anticancer activity. Unlike the well-known sulphonamides, esters are mainly used as convenient intermediates in a synthesis. Here, we present the first in-depth investigation of quinazoline sulfonates. A small series of derivatives were synthesized and tested for their anticancer activity. Based on their structural similarity, these compounds resemble tyrosine kinase inhibitors and the p53 reactivator CP-31398. Their biological activity profile, however, was more related to sulphonamides because there was a strong cell cycle arrest in the G2/M phase. Further investigation revealed a multitargeted mechanism of the action that corresponded to the p53 protein status in the cell. Although the compounds expressed a high submicromolar activity against leukemia and colon cancers, pancreatic cancer and glioblastoma were also susceptible. Apoptosis and autophagy were confirmed as the cell death modes that corresponded with the inhibition of metabolic activity and the activation of the p53-dependent and p53-independent pathways. Namely, there was a strong activation of the p62 protein and GADD44. Other proteins such as cdc2 were also expressed at a higher level. Moreover, the classical caspase-dependent pathway in leukemia was observed at a lower concentration, which again confirmed a multitargeted mechanism. It can therefore be concluded that the sulfonates of quinazolines can be regarded as promising scaffolds for developing anticancer agents.
Circulating Biomarkers of Response and Toxicity of Immunotherapy in Advanced Non-Small Cell Lung Cancer (NSCLC): A Comprehensive Review
Authors: Indini Alice , Rijavec Erika , Grossi Francesco
Published: April 2021

Immune checkpoint inhibitors (ICIs) targeting the programmed cell death (PD)-1 protein and its ligand, PD-L1, and cytotoxic T-lymphocyte-associated antigen (CTLA)-4, have revolutionized the management of patients with advanced non-small cell lung cancer (NSCLC). Unfortunately, only a small portion of NSCLC patients respond to these agents. Furthermore, although immunotherapy is usually well tolerated, some patients experience severe immune-related adverse events (irAEs). Liquid biopsy is a non-invasive diagnostic procedure involving the isolation of circulating biomarkers, such as circulating tumor cells (CTC), cell-free DNA (cfDNA), and microRNAs (miRNAs). Thanks to recent advances in technologies, such as next-generation sequencing (NGS) and digital polymerase chain reaction (dPCR), liquid biopsy has become a useful tool to provide baseline information on the tumor, and to monitor response to treatments. This review highlights the potential role of liquid biomarkers in the selection of NSCLC patients who could respond to immunotherapy, and in the identification of patients who are most likely to experience irAEs, in order to guide improvements in care.
Multi-View Data Integration Methods for Radiotherapy Structure Name Standardization
Authors: Syed Khajamoinuddin , Sleeman William C. , Hagan Michael , Palta Jatinder , Kapoor Rishabh , Ghosh Preetam
Published: April 2021

Standardization of radiotherapy structure names is essential for developing data-driven personalized radiotherapy treatment plans. Different types of data are associated with radiotherapy structures, such as the physician-given text labels, geometric (image) data, and Dose-Volume Histograms (DVH). Prior work on structure name standardization used just one type of data. We present novel approaches to integrate complementary types (views) of structure data to build better-performing machine learning models. We present two methods, namely (a) intermediate integration and (b) late integration, to combine physician-given textual structure name features and geometric information of structures. The dataset consisted of 709 prostate cancer and 752 lung cancer patients across 40 radiotherapy centers administered by the U.S. Veterans Health Administration (VA) and the Department of Radiation Oncology, Virginia Commonwealth University (VCU). We used randomly selected data from 30 centers for training and ten centers for testing. We also used the VCU data for testing. We observed that the intermediate integration approach outperformed the models with a single view of the dataset, while late integration showed comparable performance with single-view results. Thus, we demonstrate that combining different views (types of data) helps build better models for structure name standardization to enable big data analytics in radiation oncology.
Tumor Microenvironment in Adrenocortical Carcinoma: Barrier to Immunotherapy Success?
Authors: Georgantzoglou Natalia , Kokkali Stefania , Tsourouflis Gerasimos , Theocharis Stamatios
Published: April 2021

Adrenocortical carcinoma is a rare malignancy with aggressive behavior, with up to 40% of patients presenting with metastases at the time of diagnosis. Both conventional chemotherapeutic regimens and novel immunotherapeutic agents, many of which are currently being tested in ongoing clinical trials, have yielded modest results so far, bringing the need for a deeper understanding of adrenal cancer behavior to the forefront. In the recent years, the tumor microenvironment has emerged as a major determinant of cancer response to immunotherapy and an increasing number of studies on other solid tumors have focused on manipulating the microenvironment in the favor of the host and discovering new potential target molecules. In the present review we aim to explore the characteristics of adrenocortical cancer’s microenvironment, highlighting the mechanisms of immune evasion responsible for the modest immunotherapeutic results, and identify novel potential strategies.
GSK-3α Inhibition in Drug-Resistant CML Cells Promotes Susceptibility to NK Cell-Mediated Lysis in an NKG2D- and NKp30-Dependent Manner
Authors: Kim Nayoung , Kim Mi Yeon , Choi Woo Seon , Yi Eunbi , Lee Hyo Jung , Kim Hun Sik
Published: April 2021

Natural killer (NK) cells are innate cytotoxic lymphocytes that provide early protection against cancer. NK cell cytotoxicity against cancer cells is triggered by multiple activating receptors that recognize specific ligands expressed on target cells. We previously demonstrated that glycogen synthase kinase (GSK)-3β, but not GSK-3α, is a negative regulator of NK cell functions via diverse activating receptors, including NKG2D and NKp30. However, the role of GSK-3 isoforms in the regulation of specific ligands on target cells is poorly understood, which remains a challenge limiting GSK-3 targeting for NK cell-based therapy. Here, we demonstrate that GSK-3α rather than GSK-3β is the primary isoform restraining the expression of NKG2D ligands, particularly ULBP2/5/6, on tumor cells, thereby regulating their susceptibility to NK cells. GSK-3α also regulated the expression of the NKp30 ligand B7-H6, but not the DNAM-1 ligands PVR or nectin-2. This regulation occurred independently of BCR-ABL1 mutation that confers tyrosine kinase inhibitor (TKI) resistance. Mechanistically, an increase in PI3K/Akt signaling in concert with c-Myc was required for ligand upregulation in response to GSK-3α inhibition. Importantly, GSK-3α inhibition improved cancer surveillance by human NK cells in vivo. Collectively, our results highlight the distinct role of GSK-3 isoforms in the regulation of NK cell reactivity against target cells and suggest that GSK-3α modulation could be used to enhance tumor cell susceptibility to NK cells in an NKG2D- and NKp30-dependent manner.
Hydrogen Evolution on Reduced Graphene Oxide-Supported PdAu Nanoparticles
Authors: Rakočević Lazar , Srejić Irina , Maksić Aleksandar , Golubović Jelena , Štrbac Svetlana
Published: April 2021

Hydrogen evolution reaction (HER) was investigated on reduced graphene oxide (rGO)-supported Au and PdAu nanoparticles in acid solution. The graphene spread over glassy carbon (rGO/GC) was used as a support for the spontaneous deposition of Au and Pd. The resulting Au/rGO and PdAu/rGO electrodes were characterized using atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS) techniques. Phase AFM images have shown that the edges of the rGO sheets were active sites for the deposition of both Au and Pd. XPS analysis revealed that the atomic percentages of both Au and PdAu nanoparticles were slightly higher than 1%. The activity of the PdAu/rGO electrode for the HER was remarkably high, with the overpotential close to zero. HER activity was stable over a 3 h testing time, with a low Tafel slope of approx. −46 mV/dec achieved after prolonged hydrogen evolution at a constant potential.
Healthcare Provider Perspectives on Adherence to Adjuvant Endocrine Therapy after Breast Cancer
Authors: Lambert Leah K. , Balneaves Lynda G. , Howard A. Fuchsia , Chia Stephen L. K. , Gotay Carolyn C.
Published: April 2021

Adherence to adjuvant endocrine therapy (AET) for breast cancer is suboptimal. The purpose of this study was to: (1) explore the experiences and perspectives of healthcare providers (HCPs) in providing care to breast cancer survivors prescribed AET, (2) identify how social and structural factors influence the provision of AET-related care, and (3) ascertain HCP recommendations for optimizing AET adherence and related care. Individual, in-depth interviews were conducted with 14 HCPs using an interpretive descriptive approach to inquiry and the theoretical lens of relational autonomy. Data was analyzed using thematic and constant comparative techniques. Healthcare providers focused on four main components of AET-related care: (1) the importance of having careful conversations about AET, (2) difficulties in navigating transitions in care, (3) symptom management as a big part of their role, and (4) dealing with AET discontinuation. Recommendations to improve AET adherence focused on developing sustainable and efficient models of delivering high-quality care to women on AET. Healthcare providers play a pivotal role educating women about AET and supporting their adherence to therapy. Sustainable healthcare system innovations and new models of care that address current system gaps are needed to enhance survivorship care, AET adherence, and ultimately, reduce cancer recurrence and mortality.
The Correlation of Transformer Oil Electrical Properties with Water Content Using a Regression Approach
Authors: Abdi Sifeddine , Harid Noureddine , Safiddine Leila , Boubakeur Ahmed , Haddad Abderrahmane (Manu)
Published: April 2021

An experimental investigation is conducted to measure and correlate the impact of the water content on the electrical characteristics of the mineral oil for transformers, particularly the breakdown voltage, the resistivity, and the dielectric dissipation factor. Regression method is carried out to compare the results obtained through laboratory experiments with those predicted using an analytical model. A treatment to reduce water content in oil involving filtration, degassing and dehydration using a SESCO mobile station was applied to the new, regenerated, and used oil samples in service. The breakdown voltage, the resistivity, and the dielectric dissipation factor of the samples were measured. Regression analysis using an exponential model was applied to examine the samples electrical properties. The results show that, after treatment, the breakdown voltage and resistivity increase as the water content decreases, unlike the dielectric dissipation factor which exhibits a decreasing trend. This trend is found to be similar for the three oil samples: new, regenerated, and used. The results of the regression analysis give close agreement with the experimental results for all the samples and all studied characteristics. The model shows strong correlation with high coefficients (>90%).
How Policies Affect the Dissemination of Electric Passenger Cars Worldwide
Authors: Siebenhofer Marina , Ajanovic Amela , Haas Reinhard
Published: April 2021

Road transportation is one of the largest emitters of greenhouse gas emissions. The EU set the target to reduce overall transport emissions by 60% by 2050 compared to 1990. Electric mobility is considered a proper means to achieve this goal. Battery electric vehicles (BEVs) are a mature technology. The high investment costs, limited driving range and a charging infrastructure that is not extensive yet are currently the main challenges. This work analyses how policies affect the dissemination of BEVs in selected countries with remarkable market shares of BEVs. The core objective is to investigate how policies affect BEV economics compared to conventional car economics. Financial policies and their effects on BEVs for the major markets of China, the USA and Europe were analysed. To do so, the total cost of ownership (TCO) was calculated for each country. The major conclusions were: (i) The investment cost of a car had the most significant impact on the TCO; (ii) Low TCO as an incentive was not enough to ensure successful BEV dissemination; (iii) Non-monetary incentives such as access to certain zones and the usage of bus lanes for BEVs combined with registration taxes, low electricity prices and high fuel prices were very favourable conditions.
Fully Coupled Large Eddy Simulation of Conjugate Heat Transfer in a Ribbed Channel with a 0.1 Blockage Ratio
Authors: Ahn Joon , Song Jeong Chul , Lee Joon Sik
Published: April 2021

Large eddy simulations are performed to analyze the conjugate heat transfer of turbulent flow in a ribbed channel with a heat-conducting solid wall. An immersed boundary method (IBM) is used to determine the effect of heat transfer in the solid region on that in the fluid region in a unitary computational domain. To satisfy the continuity of the heat flux at the solid–fluid interface, effective conductivity is introduced. By applying the IBM, it is possible to fully couple the convection on the fluid side and the conduction inside the solid and use a dynamic subgrid scale model in a Cartesian grid. The blockage ratio (e/H) is set at 0.1, which is typical for gas turbine blades. Through conjugate heat transfer analysis, it is confirmed that the heat transfer peak in front of the rib occurs because of the impinging of the reattached flow and not the influence of the thermal boundary condition. When the rib turbulator acts as a fin, its efficiency and effectiveness are predicted to be 98.9% and 8.32, respectively. When considering conjugate heat transfer, the total heat transfer rate is reduced by 3% compared with that of the isothermal wall. The typical Biot number at the internal cooling passage of a gas turbine is <0.1, and the use of the rib height as the characteristic length better represents the heat transfer of the rib.
Investigation into the Relationship between Super-Knock and Misfires in an SI GDI Engine
Authors: Gao Jian , Yao Anren , Zhang Yeyi , Qu Guofan , Yao Chunde , Zhang Shemin , Li Dongsheng
Published: April 2021

The super-knock poses new challenges for further increasing the power density of spark ignition (SI) engines. The critical factors and mechanism connecting regarding the occurrence of super-knock are still unclear. Misfire is a common phenomenon in SI engines that the mixture in cylinder is not ignited normally, which is often caused by spark plug failure. However, the effect of misfire on engine combustion has not been paid enough attention to, particularly regarding connection to super-knock. The paper presents the results of experimental investigation into the relationship between super-knock and misfires at low speed and full load conditions. In this work, a boosted gasoline direct injection (GDI) engine with an exhaust manifold integrated in the cylinder head was employed. Four piezoelectric pressure transducers were used to acquire the data of a pressure trace in cylinder. The spark plugs of four cylinders were controlled manually, of which the ignition system could be cut off as demanded. In particular, a piezoelectric pressure transducer was installed at the exhaust pipe before the turbocharger to capture the pressure traces in the exhaust pipe. The results illustrated that misfires in one cylinder would cause super-knock in the other cylinders as well as the cylinder of itself. After one cylinder misfired, the unburned mixture would burn in the exhaust pipe to produce oscillating waves. The abnormal pressure fluctuation in the exhaust pipe was strongly correlated with the occurrence of super-knock. The sharper the pressure fluctuation, the greater the intensity of knock in the power cylinder. The cylinder whose exhaust valve overlapped with the exhaust valve of the misfired cylinder was prone to super-knock.