bluuebunny/crossref_metadata_2025 huggingface dataset:
Fractality and Variability in Canonical and Non-Canonical English Fiction and in Non-Fictional Texts
Authors: Mohseni Mahdi , Gast Volker , Redies Christoph
Published: April 2021

This study investigates global properties of three categories of English text: canonical fiction, non-canonical fiction, and non-fictional texts. The central hypothesis of the study is that there are systematic differences with respect to structural design features between canonical and non-canonical fiction, and between fictional and non-fictional texts. To investigate these differences, we compiled a corpus containing texts of the three categories of interest, the Jena Corpus of Expository and Fictional Prose (JEFP Corpus). Two aspects of global structure are investigated, variability and self-similar (fractal) patterns, which reflect long-range correlations along texts. We use four types of basic observations, (i) the frequency of POS-tags per sentence, (ii) sentence length, (iii) lexical diversity, and (iv) the distribution of topic probabilities in segments of texts. These basic observations are grouped into two more general categories, (a) the lower-level properties (i) and (ii), which are observed at the level of the sentence (reflecting linguistic decoding), and (b) the higher-level properties (iii) and (iv), which are observed at the textual level (reflecting comprehension/integration). The observations for each property are transformed into series, which are analyzed in terms of variance and subjected to Multi-Fractal Detrended Fluctuation Analysis (MFDFA), giving rise to three statistics: (i) the degree of fractality () of the fractal spectrum. The statistics thus obtained are compared individually across text categories and jointly fed into a classification model (Support Vector Machine). Our results show that there are in fact differences between the three text categories of interest. In general, lower-level text properties are better discriminators than higher-level text properties. Canonical fictional texts differ from non-canonical ones primarily in terms of variability in lower-level text properties. Fractality seems to be a universal feature of text, slightly more pronounced in non-fictional than in fictional texts. On the basis of our results obtained on the basis of corpus data we point out some avenues for future research leading toward a more comprehensive analysis of textual aesthetics, e.g., using experimental methodologies.
Informing About the Nocebo Effect Affects Patients’ Need for Information About Antidepressants—An Experimental Online Study
Authors: Nestoriuc Yvonne , Pan Yiqi , Kinitz Timm , Weik Ella , Shedden-Mora Meike C.
Published: April 2021

Relevance: Understanding patients’ informational needs and adapting drug-related information are the prerequisites for a contextualized informed consent. Current information practices might rather harm by inducing nocebo effects.

Objective: To investigate whether informing about the nocebo effect using a short information sheet affects patients’ need for information about antidepressants.

Methods: A total of 97 patients taking recently prescribed antidepressants (≤4 months intake) were recruited over the internet and randomized to receiving either a one-page written information about the nocebo effect or a control text about the history of antidepressants. After experimental manipulation, informational needs about the side effects and mechanisms of antidepressants were assessed with 3 and 7 items on categorical and 5-point Likert scales. Group differences in informational needs were calculated with Chi-square tests and ANOVAs.

Results: Patients received antidepressants for depression (84.5%) and/or anxiety disorders (42.3%). Three participants (6.0%) of the nocebo group reported previous knowledge of the nocebo effect. After the experimental manipulation, participants in the nocebo group reported a reduced desire for receiving full side effect information [X(4,97)2 = 12.714, Cramer’s V = 0.362, p = 0.013] and agreed more frequently to the usefulness of withholding information about possible side effects [X(4,97)2 = 14.878, Cramer’s V = 0.392, p = 0.005]. Furthermore, they desired more information about the mechanisms of antidepressants (F = 6.373, p = 0.013, partial η2 = 0.063) and, specifically, non-pharmacological mechanisms, such as the role of positive expectations (F = 16.857, p < 0.001, partial η2 = 0.151).

Conclusions: Learning about the nocebo effect can alter patients’ informational needs toward desiring less information about the potential side effects of antidepressants and more information about general mechanisms, such as expectations. The beneficial effects of including nocebo information into contextualized informed consent should be studied clinically concerning more functional information-seeking behavior, which may ultimately lead to improved treatment outcomes, such as better adherence and reduced side effect burden.
Personality to Prescription Drug Misuse in Adolescents: Testing Affect Regulation, Psychological Dysregulation, and Deviance Proneness Pathways
Authors: Stewart Sherry H. , Chinneck Annie , Thompson Kara , Afzali Mohammad H. , Nogueira-Arjona Raquel , Mahu Ioan T. , Conrod Patricia J.
Published: April 2021

Background: Fifteen to 25-year-olds are the age group most likely to misuse prescription drugs. Few studies have tested theory-driven models of adolescent risk for prescription drug misuse. Moreover, rarely are distinct pathways to different forms of prescription drug misuse considered.

Methods: We tested mediational paths from personality to mental health symptoms to prescription drug misuse, informed by etiological models of addiction. We specified pathways from particular personality traits to unique forms of prescription drug misuse via specific mental health symptoms. We used semi-longitudinal data collected across two waves of the Co-Venture Trial. Our sample included students from 31 Canadian high schools tested in Grade 9 (n = 3,024) and again in Grade 10 (n = 2,869; 95% retention). Personality (hopelessness, anxiety sensitivity, impulsivity, sensation seeking) was assessed in Grade 9. Mental health symptoms (depression, anxiety, ADHD, conduct disorder) and prescription drug misuse (opioids, sedatives/tranquilizers, stimulants) were assessed at both time points.

Results: Consistent with the negative affect regulation model, hopelessness was specifically associated with opioid misuse via depressive symptoms, and anxiety sensitivity was specifically associated with sedative/tranquilizer misuse via anxiety symptoms. Consistent with positive affect regulation, sensation seeking was directly associated with stimulant misuse. Consistent with the psychological dysregulation model, impulsivity was associated with stimulant misuse via ADHD symptoms. And consistent with the deviance proneness model, impulsivity was also associated with unconstrained (i.e., all three forms of) prescription drug misuse via conduct disorder symptoms.

Conclusions: Screening for adolescents high in hopelessness, anxiety sensitivity, sensation seeking, or impulsivity and providing them with personality-matched cognitive-behavioral interventions may be helpful in preventing or mitigating prescription drug misuse. Our results point to the specific mental health symptoms that are important to target in each of these personality-matched interventions.
The Institutional Building of Science and Innovation Diplomacy in Latin America: Toward a Comprehensive Analytical Typology
Authors: da Silva Renan Gonçalves Leonel , Ferreira Gabriela Gomes Coelho , Onuki Janina , Oliveira Amâncio Jorge Nunes de
Published: April 2021

Science and Innovation Diplomacy (S&ID) has emerged in recent years as a relevant scholarly movement and interdisciplinary research agenda internationally. This field is promoting a significant impact on the understanding of the cultural and political dynamics of Science, Technology and Innovation (ST&I), implementing initiatives from local to global level. Notwithstanding, S&ID is growing asymmetrically around the world, setting up over a particular configuration in the so-called Global South (GS) societies. In Latin America (LA), although S&ID is a recent, unequal and intra-nationally fragmented process, there are important achievements that have been able to create a favorable mix of approaches, agendas, and practices in this field. Addressing the scope of the special issue “Science Diplomacy and Sustainable Development: Perspectives from Latin America,” this article aims to present a comprehensive analytical typology to the study of the emerging experiences of S&ID in LA, catching the diversity of this research agenda. This is a qualitative merged method-based study, sustained by a literature review, documentary research, online data analysis, and typology building. We understand S&ID in LA as a tentative re-organization of different states and subnational actors around the study and institutionalization of the governance of contemporary transformations on the systems of ST&I.
Switching Genes On and Off: How It Can Shape Us
Authors: Meijer Mandy , Mostert Jeanette , Franke Barbara , Klein Marieke
Published: April 2021

The human body consists of more than 200 different types of cells, but all cells contain the same DNA code. How is it possible that the same code tells the various types of cells to be different? The information for life is not only coded in the DNA, but also on the DNA. Chemical attachments, which are called DNA methylation, can “turn off” parts of the DNA code that are not needed in a specific cell. DNA methylation can also be influenced by our surroundings. Sometimes, changes in DNA methylation might lead to diseases. Understanding how our surroundings can influence DNA methylation might also help us to better understand the mechanisms causing some diseases and hopefully get better at curing and preventing them. This article describes ADHD as one example.
Recent Advances in Models of Immune-Mediated Drug-Induced Liver Injury
Authors: Tasnim Farah , Huang Xiaozhong , Lee Christopher Zhe Wei , Ginhoux Florent , Yu Hanry
Published: April 2021

Hepatic inflammation is a key feature of a variety of liver diseases including drug-induced liver injury (DILI), orchestrated by the innate immune response (Kupffer cells, monocytes, neutrophils, dendritic cells) and the adaptive immune system (T cells and natural killer T cells). In contrast to acute DILI, prediction of immune-mediated DILI (im-DILI) has been more challenging due to complex disease pathogenesis, lack of reliable models and limited knowledge of underlying mechanisms. This review summarizes in vivo and in vitro systems that have been used to model im-DILI. In particular, the review focuses on state-of-the-art in vitro human-based multicellular models which have been developed to supplement the use of in vivo models due to interspecies variation and increasing ethical concerns regarding animal use. Advantages of the co-cultures in maintaining hepatocyte functions and importantly, introducing heterotypic cell-cell interactions to mimic inflammatory hepatic microenvironment are discussed. Challenges regarding cell source and incorporation of different cells with physical cell-cell contact are outlined and potential solutions are proposed. It is likely that better understanding of the interplay of immune cells in liver models will allow for the development of more accurate systems to better predict hepatotoxicity and stratification of drugs that can cause immune-mediated effects.
Diagnosing Schizophrenia Using Effective Connectivity of Resting-State EEG Data
Authors: Ciprian Claudio , Masychev Kirill , Ravan Maryam , Manimaran Akshaya , Deshmukh AnkitaAmol
Published: April 2021

Schizophrenia is a serious mental illness associated with neurobiological deficits. Even though the brain activities during tasks (i.e., P300 activities) are considered as biomarkers to diagnose schizophrenia, brain activities at rest have the potential to show an inherent dysfunctionality in schizophrenia and can be used to understand the cognitive deficits in these patients. In this study, we developed a machine learning algorithm (MLA) based on eyes closed resting-state electroencephalogram (EEG) datasets, which record the neural activity in the absence of any tasks or external stimuli given to the subjects, aiming to distinguish schizophrenic patients (SCZs) from healthy controls (HCs). The MLA has two steps. In the first step, symbolic transfer entropy (STE), which is a measure of effective connectivity, is applied to resting-state EEG data. In the second step, the MLA uses the STE matrix to find a set of features that can successfully discriminate SCZ from HC. From the results, we found that the MLA could achieve a total accuracy of 96.92%, with a sensitivity of 95%, a specificity of 98.57%, precision of 98.33%, F1-score of 0.97, and Matthews correlation coefficient (MCC) of 0.94 using only 10 out of 1900 STE features, which implies that the STE matrix extracted from resting-state EEG data may be a promising tool for the clinical diagnosis of schizophrenia.
Tinkering under the Hood: Metabolic Optimisation of CAR-T Cell Therapy
Authors: Jenkins Yasmin , Zabkiewicz Joanna , Ottmann Oliver , Jones Nicholas
Published: April 2021

Chimeric antigen receptor (CAR)-T cells are one of the most exciting areas of immunotherapy to date. Clinically available CAR-T cells are used to treat advanced haematological B-cell malignancies with complete remission achieved at around 30–40%. Unfortunately, CAR-T cell success rates are even less impressive when considering a solid tumour. Reasons for this include the paucity of tumour specific targets and greater degree of co-expression on normal tissues. However, there is accumulating evidence that considerable competition for nutrients such as carbohydrates and amino acids within the tumour microenvironment (TME) coupled with immunosuppression result in mitochondrial dysfunction, exhaustion, and subsequent CAR-T cell depletion. In this review, we will examine research avenues being pursued to dissect the various mechanisms contributing to the immunosuppressive TME and outline in vitro strategies currently under investigation that focus on boosting the metabolic program of CAR-T cells as a mechanism to overcome the immunosuppressive TME. Various in vitro and in vivo techniques boost oxidative phosphorylation and mitochondrial fitness in CAR-T cells, resulting in an enhanced central memory T cell compartment and increased anti-tumoural immunity. These include intracellular metabolic enhancers and extracellular in vitro culture optimisation pre-infusion. It is likely that the next generation of CAR-T products will incorporate these elements of metabolic manipulation in CAR-T cell design and manufacture. Given the importance of immunometabolism and T cell function, it is critical that we identify ways to metabolically armour CAR-T cells to overcome the hostile TME and increase clinical efficacy.
Determination and Similarity Analysis of PM2.5 Emission Source Profiles Based on Organic Markers for Monterrey, Mexico
Authors: Mancilla Yasmany , Medina Gerardo , González Lucy T. , Herckes Pierre , Fraser Matthew P. , Mendoza Alberto
Published: April 2021

Source attribution of airborne particulate matter (PM) relies on a host of different chemical species. Organic molecular markers are a set of particularly useful marker compounds for estimating source contributions to the fine PM fraction (i.e., PM2.5). Although there are many source apportionment studies based on organic markers, these studies heavily rely on the few studies that report region-specific emission profiles. Source attribution efforts, particularly those conducted in countries with emerging economies, benefit from ad hoc information to conduct the corresponding analyses. In this study, we report organic molecular marker source profiles for PM2.5 emitted from 12 major sources types from five general source categories (meat cooking operations, vehicle exhausts, industries, biomass and trash burning, and urban background) for the Monterrey Metropolitan Area (Mexico). Source emission samples were obtained from a ground-based source-dominated sampling approach. Filter-based instruments were utilized, and the loaded filters were chemically characterized for organic markers by GC-MS. Levoglucosan and cholesterol dominate charbroiled-cooking operation sources while methoxyphenols, PAHs and hopanes dominate open-waste burning, vehicle exhaust and industrial emissions, respectively. A statistical analysis showed values of the Pearson distance < 0.4 and the similarity identity distance > 0.8 in all cases, indicating dissimilar source profiles. This was supported by the coefficient of divergence average values that ranged from 0.62 to 0.72. These profiles could further be utilized in receptor models to conduct source apportionment in regions with similar characteristics and can also be used to develop air pollution abatement strategies.
A Study on the Mechanisms Accounting for the Generation of a Southwest Vortex That Caused a Series of Severe Disasters during the 2020 Abnormal Meiyu Season
Authors: Ma Hui , Ma Xiaolei , Jing Yanwei , Wu Guiping
Published: April 2021

The abnormal 2020 Meiyu season caused the worst disasters over the Yangtze River Valley in recent decades. Of these, the Sichuan Basin (SCB) and its surrounding regions were one of the most severely affected areas. Disastrous weather frequently occurs in these regions, with a large proportion of it closely related to the southwest vortices (SWVs). In order to further the understanding of SWV generation, this study investigated the formation mechanisms of a quasi-stationary SWV (by using two sets of vorticity budgets), which caused torrential rainfall (resulting in flash floods in Sichuan and Chongqing), lightning activities (causing tripping incidents of transmission lines in Sichuan) and strong winds (leading to shutting down of wind turbines in Hubei). Results showed that the SWV was generated in a favorable background environment, during which an upper-tropospheric divergence and a middle-tropospheric warm advection appeared over the SCB. Trajectory analyses and vorticity budget showed that the air particles that came from the lower troposphere of the regions south of the Tibetan Plateau dominated the SWV formation. These air particles experienced notable ascending during which an increase in their cyclonic vorticity occurred mainly due to convergence-related stretching, whereas, tilting mainly decelerated this increase. The air particles sourced from the areas within the key region of the SWV and areas northeast of the key region were the second dominant factor for the vortex formation. Overall, for the air particles that formed the SWV, their most rapid changes of vorticity and divergence appeared in the period 24 h before SWV formation, implying that this was the critical period for the SWV generation.
Temperature of Paved Streets in Urban Mockups and Its Implication of Reflective Cool Pavements
Authors: Zhang Yi , Wei Peiyuan , Wang Lei , Qin Yinghong
Published: April 2021

In summer, urban heat islands increase building cooling demands, aggravate air pollution, and cause heat-related illnesses. As a mitigation strategy, reflective cool pavements have been deemed an effective measure to decrease the temperature in urban areas. However, the reflection of paved streets in an urban area will be different from that in an open area. It remains unknown which fraction of paved streets needs to be cooled upmost, and if increasing the albedo of paved streets can effectively reduce their temperature. This study measured the skin temperature of two urban mockups, of which one contained white streets and the other, gray streets. The streets were orientated at different strikes. It was found that in summer the East-West street was hotter than both the cross street and the South-North street. At nighttime, the heat released from building blocks kept the paved street about 0.2 °C hotter than paved areas in open spaces. It was also found that street orientation controlled the skin temperature of an urban street while the sky view factor (or building height and street width) acted in a secondary role only. Increasing the albedo of the paved street in an urban canyon effectively reduced the skin temperature of the street. Reflective pavements should be built preferentially on East-West streets and the cross streets.
Predictors of Mental Health after the First Wave of the COVID-19 Pandemic in Poland
Authors: Długosz Piotr
Published: April 2021

The aim of the article is to determine the predictors of mental health among Polish society. Research was conducted after the first wave of the pandemic. Due to such an approach, it was possible to determine whether the secondary effects of the pandemic have impacted on mental health, in addition to socio-demographic and psychological factors. In order to gather the research material, the CAWI on-line survey method was applied and carried out within the framework of the Ariadna Research Panel on a sample of 1079 Poles, aged 15 and over. The FCV-19S scale, which is used to measure the fear of COVID-19 was applied in the measurement. It is a verified diagnostic instrument used to measure mental health across a range of countries. The results of a hierarchical regression analysis have shown that the factors which increase the level of fear of COVID-19 are demographic, social and psychological features, as well as attitudes towards the pandemic. The results of research indicate the significance of social context in the analysis, and contribute to the explanation of the effects of disasters and cataclysms.
A Ten-Year Review of Primary School Flexible Learning Environments: Interior Design and IEQ Performance
Authors: Vijapur Diksha , Candido Christhina , Göçer Özgür , Wyver Shirley
Published: April 2021

Flexible Learning Environments (FLEs) arose as enablers for implementation of student-centric pedagogical approaches. Interior design is the key to the success of FLEs, providing the physical infrastructure needed for students to engage on several learning activities, from individual to group work, which take place in a variety of zones ranging from low to high energy. Therefore, a harmonious synergy between the interior design and subsequent Indoor Environmental Quality (IEQ) performance of FLEs’ physical configuration and learning activities is needed. The objective of this paper is to systematically review (in accordance with the PRISMA method) existing literature related to FLEs within primary school settings, typically catering to children aged 5–12 years old, to understand the body of work investigating the design and performance of FLEs over the last decade (2010–2020). Key findings suggest that the proximity and acoustic and visual permeability of zones found in FLEs may give rise to inadequate IEQ conditions delivered to students. In addition, it could be inferred from the results of the literature review that interior design and IEQ have not been sufficiently investigated in an integrated manner.
Activated Carbon from Biomass Sustainable Sources
Authors: Gan Yong X.
Published: April 2021

Biomass wastes are abundant around us. They are renewable and inexpensive. Product manufacturing from renewable resources has caught increasing interest recently. Activated carbon preparation from biomass resources, including various trees, leaves, plant roots, fruit peels, and grasses, is a good example. In this paper, an overview of activated carbon production from biomass resources will be given. The first part will be on the processing technologies. The second part will focus on the carbon activation methods. The third part will introduce the biomass resources. The fourth part will be on surface modification of activated carbon through the addition of various components. Finally, the development of product applications will be discussed with an emphasis on adsorption, filtration, water purification, energy conversions, and energy storage.
Estrogens in Hepatocellular Carcinoma: Friends or Foes?
Authors: Carruba Giuseppe
Published: April 2021

Estrogens are recognized as key players in physiological regulation of various, classical and non-classical, target organs, and tissues, including liver development, homeostasis, and function. On the other hand, multiple, though dispersed, experimental evidence is highly suggestive for the implication of estrogen in development and progression of hepatocellular carcinoma. In this paper, data from our own studies and the current literature are reviewed to help understanding this apparent discrepancy.
Clinical Effectiveness of Oncological Treatment in Metastatic Colorectal Cancer Is Independent of Comorbidities and Age
Authors: Niedersüß-Beke Dora , Orlinger Manuel , Falch David , Heiler Cordula , Piringer Gudrun , Thaler Josef , Hilbe Wolfgang , Petzer Andreas , Rumpold Holger
Published: April 2021

We aimed to investigate the effectiveness of oncological treatments in metastatic CRC related to comorbidities and age. This retrospective study included 1105 patients from three oncological centers. aaCCI and CCI was available from 577 patients. An aaCCI > 3 was of the highest predictive value compared to other aaCCI-levels, CCI or age (p < 0.001 for all). Treatment (best supportive care (BSC), systemic treatment only (STO) and resection of metastases (ROM)) significantly prolonged survival in patients with aaCCI > 3 (STO: HR 0.39, CI 0.29–0.51; ROM: HR 0.16, CI 0.10–0.24) and patients older than 70 years (STO: HR 0.56, CI 0.47–0.66; ROM: HR 0.23, 0.18–0.30). Median overall survival was shorter in patients with aaCCI or age > 70 years and interaction for treatment type not significant for aaCCI, but significant for age older or younger than 70 years (STO: p = 0.01; ROM p = 0.02). BSC is more often considered as optimal care for patients with an aaCCI > 3 (37.6% vs. 12.4%; p < 0.001) or age > 70 years (35.7% vs. 11.2%; p < 0.001). Older patients or patients with comorbidities benefit from cancer-specific therapy independently of their age and comorbidities.
Immune Monitoring during Therapy Reveals Activitory and Regulatory Immune Responses in High-Risk Neuroblastoma
Authors: Szanto Celina L. , Cornel Annelisa M. , Tamminga Sara M. , Delemarre Eveline M. , de Koning Coco C. H. , van den Beemt Denise A. M. H. , Dunnebach Ester , Tas Michelle L. , Dierselhuis Miranda P. , Tytgat Lieve G. A. M. , van Noesel Max M. , Kraal Kathelijne C. J. M. , Boelens Jaap-Jan , Huitema Alwin D. R. , Nierkens Stefan
Published: April 2021

Despite intensive treatment, including consolidation immunotherapy (IT), prognosis of high-risk neuroblastoma (HR-NBL) is poor. Immune status of patients over the course of treatment, and thus immunological features potentially explaining therapy efficacy, are largely unknown. In this study, the dynamics of immune cell subsets and their function were explored in 25 HR-NBL patients at diagnosis, during induction chemotherapy, before high-dose chemotherapy, and during IT. The dynamics of immune cells varied largely between patients. IL-2- and GM-CSF-containing IT cycles resulted in significant expansion of effector cells (NK-cells in IL-2 cycles, neutrophils and monocytes in GM-CSF cycles). Nonetheless, the cytotoxic phenotype of NK-cells was majorly disturbed at the start of IT, and both IL-2 and GM-CSF IT cycles induced preferential expansion of suppressive regulatory T-cells. Interestingly, proliferative capacity of purified patient T-cells was impaired at diagnosis as well as during therapy. This study indicates the presence of both immune-enhancing as well as regulatory responses in HR-NBL patients during (immuno)therapy. Especially the double-edged effects observed in IL-2-containing IT cycles are interesting, as this potentially explains the absence of clinical benefit of IL-2 addition to IT cycles. This suggests that there is a need to combine anti-GD2 with more specific immune-enhancing strategies to improve IT outcome in HR-NBL.
Clinical, Pathological and Prognostic Features of Rare BRAF Mutations in Metastatic Colorectal Cancer (mCRC): A Bi-Institutional Retrospective Analysis (REBUS Study)
Authors: Calegari Maria Alessandra , Salvatore Lisa , Di Stefano Brunella , Basso Michele , Orlandi Armando , Boccaccino Alessandra , Lombardo Fiorella , Auriemma Alessandra , Zurlo Ina Valeria , Bensi Maria , Camarda Floriana , Ribelli Marta , Vivolo Raffaella , Cocomazzi Alessandra , Pozzo Carmelo , Milella Michele , Martini Maurizio , Bria Emilio , Tortora Giampaolo
Published: April 2021

Recently, retrospective analysis began to shed light on metastatic colorectal cancers (mCRCs) harboring rare BRAF non-V600 mutations, documenting a distinct phenotype and a favorable prognosis. This study aimed to confirm features and prognosis of rare BRAF non-V600 mCRCs compared to BRAF V600E and BRAF wild-type mCRCs treated at two Italian Institutions. Overall, 537 cases were retrospectively evaluated: 221 RAS/BRAF wild-type, 261 RAS mutated, 46 BRAF V600E and 9 BRAF non-V600. Compared to BRAF V600E mCRC, BRAF non-V600 mCRC were more frequently left-sided, had a lower tumor burden and displayed a lower grade and an MMR proficient/MSS status. In addition, non-V600 mCRC patients underwent more frequently to resection of metastases with radical intent. Median overall survival (mOS) was significantly longer in the non-V600 compared to the V600E group. At multivariate analysis, only age < 65 years and ECOG PS 0 were identified as independent predictors of better OS. BRAF V600E mCRCs showed a statistically significant worse mOS when compared to BRAF wild-type mCRCs, whereas no significant difference was observed between BRAF non-V600 and BRAF wild-type mCRCs. Our study corroborates available evidence concerning incidence, clinicopathologic characteristics and prognosis of BRAF-mutated mCRCs.
Integration of Urinary EN2 Protein & Cell-Free RNA Data in the Development of a Multivariable Risk Model for the Detection of Prostate Cancer Prior to Biopsy
Authors: Connell Shea , Mills Robert , Pandha Hardev , Morgan Richard , Cooper Colin , Clark Jeremy , Brewer Daniel ,   The Movember GAP1 Urine Biomarker Consortium
Published: April 2021

The objective is to develop a multivariable risk model for the non-invasive detection of prostate cancer prior to biopsy by integrating information from clinically available parameters, Engrailed-2 (EN2) whole-urine protein levels and data from urinary cell-free RNA. Post-digital-rectal examination urine samples collected as part of the Movember Global Action Plan 1 study which has been analysed for both cell-free-RNA and EN2 protein levels were chosen to be integrated with clinical parameters (n = 207). A previously described robust feature selection framework incorporating bootstrap resampling and permutation was applied to the data to generate an optimal feature set for use in Random Forest models for prediction. The fully integrated model was named ExoGrail, and the out-of-bag predictions were used to evaluate the diagnostic potential of the risk model. ExoGrail risk (range 0–1) was able to determine the outcome of an initial trans-rectal ultrasound guided (TRUS) biopsy more accurately than clinical standards of care, predicting the presence of any cancer with an area under the receiver operator curve (AUC) = 0.89 (95% confidence interval(CI): 0.85–0.94), and discriminating more aggressive Gleason ≥ 3 + 4 disease returning an AUC = 0.84 (95% CI: 0.78–0.89). The likelihood of more aggressive disease being detected significantly increased as ExoGrail risk score increased (Odds Ratio (OR) = 2.21 per 0.1 ExoGrail increase, 95% CI: 1.91–2.59). Decision curve analysis of the net benefit of ExoGrail showed the potential to reduce the numbers of unnecessary biopsies by 35% when compared to current standards of care. Integration of information from multiple, non-invasive biomarker sources has the potential to greatly improve how patients with a clinical suspicion of prostate cancer are risk-assessed prior to an invasive biopsy.
Disparities in Early-Onset Colorectal Cancer
Authors: Muller Charles , Ihionkhan Ehizokha , Stoffel Elena M. , Kupfer Sonia S.
Published: April 2021

The incidence and mortality of early-onset colorectal cancer (CRC) are increasing in the United States (US) and worldwide. In the US, there are notable disparities in early-onset CRC burden by race/ethnicity and geography. African Americans, Hispanic/Latinos, and populations residing in specific regions of the Southern U.S. are disproportionately affected with CRC diagnosed at younger ages, while less is known about disparities in other countries. Reasons for these disparities are likely multi-factorial and potentially implicate differences in health determinants including biology/genetics, diet/environment, individual health behaviors, and access to high-quality health services, as well as social and policy factors. This review summarizes current understanding of early-onset CRC disparities and identifies specific research areas that will inform evidence-based interventions at individual, practice, and policy levels to reduce the global burden of this disease.
Early Reassessment of Total Metabolic Tumor Volume on FDG-PET/CT in Advanced Melanoma Patients Treated with Pembrolizumab Predicts Long-Term Outcome
Authors: Vermeulen Sim , Awada Gil , Keyaerts Marleen , Neyns Bart , Everaert Hendrik
Published: April 2021

PD-1 Immune checkpoint inhibitors, such as Pembrolizumab, can have a durable beneficial therapeutic effect in patients with advanced melanoma. However, not all patients will benefit equally from these therapies, and (potentially life-threatening) immune-related adverse events may occur. In this study, we investigate the value of early response assessment by FDG-PET/CT as a biomarker for predicting survival. We identified all patients with advanced melanoma who were treated with Pembrolizumab in our medical center and underwent a baseline and at least one follow-up FDG-PET/CT. The total metabolic tumor volume (TMTV) was calculated, and the evolution was compared to survival parameters. A total of 77 patients underwent a baseline and at least one follow-up FDG-PET/CT, 36 patients had follow-up imaging within 2–4 months, and 21 patients an FDG-PET/CT 5–6 months after baseline. When the TMTV evolution was categorized into two subgroups (stable/decrease versus increase), an association was found between stability or decrease in TMTV and better PFS and OS. A similar trend, however non-significant, was observed at 5–6 months. The evolution in TMTV as assessed by FDG-PET/CT 2–4 months after treatment initiation is associated with long-term outcomes in patients with advanced melanoma treated with Pembrolizumab.
Fuzzy Entropy-Based Spatial Hotspot Reliability
Authors: Di Martino Ferdinando , Sessa Salvatore
Published: April 2021

Cluster techniques are used in hotspot spatial analysis to detect hotspots as areas on the map; an extension of the Fuzzy C-means that the clustering algorithm has been applied to locate hotspots on the map as circular areas; it represents a good trade-off between the accuracy in the detection of the hotspot shape and the computational complexity. However, this method does not measure the reliability of the detected hotspots and therefore does not allow us to evaluate how reliable the identification of a hotspot of a circular area corresponding to the detected cluster is; a measure of the reliability of hotspots is crucial for the decision maker to assess the need for action on the area circumscribed by the hotspots. We propose a method based on the use of De Luca and Termini’s Fuzzy Entropy that uses this extension of the Fuzzy C-means algorithm and measures the reliability of detected hotspots. We test our method in a disease analysis problem in which hotspots corresponding to areas where most oto-laryngo-pharyngeal patients reside, within a geographical area constituted by the province of Naples, Italy, are detected as circular areas. The results show a dependency between the reliability and fluctuation of the values of the degrees of belonging to the hotspots.
Experimental Study of Thermal Management Characteristics of Mass via Arrays
Authors: Smarra Devin A. , Chodavarapu Vamsy P.
Published: April 2021

Mass via arrays (MVAs) are intersubstrate thermal management structures that utilize thermal meta-material design principles to target localized hot spots and extreme variation in the temperature profile of electronic systems. MVAs have shown promise for integration into electronic systems as passive thermal management techniques. Theoretical analysis has shown that, when properly designed, MVAs and MVA-like structures provide control over how the heat is transferred in an electronic substrate. While the theoretical confirmation of this behavior is promising, experimental results are important to prove and strengthen MVA design principles. In this work, MVAs are implemented using an industry-standard printed circuit board (PCB) fabrication technique with Rogers 4350B (RO4350) material. The design structures are first theoretically modeled using a multilayer RO4350 stack-up in which equivalent thermal properties are studied for a variety of MVA designs. Uncertainty metrics are integrated into this model, and an iterative, Monte Carlo process is used to simulate variability in MVA performance. Next, these theoretical structures are implemented in conventional PCBs. Sample devices are chosen at random, and the heat spreading characteristics of the devices are measured using a thermal imaging camera. The results of these measurements confirm the theoretical baseline that an MVA structure provides improved thermal management characteristics relative to conventional thermal via array (TVA) structures.
Importance of Agriculture in Creating Energy Security—A Case Study of Poland
Authors: Bielski Stanisław , Marks-Bielska Renata , Zielińska-Chmielewska Anna , Romaneckas Kęstutis , Šarauskis Egidijus
Published: April 2021

Analyses of statistical data were made and their results discussed in this article to identify the level of Poland’s energy security and to determine the role of agriculture in ensuring it. It has been demonstrated that coal continues to be the staple resource for the generation of energy in Poland. The current demands and requirements concerning the reduced consumption of non-renewable resources and Poland’s obligations towards the European Union regarding the production of energy from renewable resources—all these considerations contribute to the promotion of a skillful development of energy crop farming, which, in Poland, is likely to be very successful. Agriculture plays an important role in ensuring Poland’s energy security, and this branch of farming can grow dynamically provided adequate legal regulations and promotion are in place. The chief resource for renewable energy generation is biomass. Straw and biogas production in agricultural biogas plants are two solutions whose full energy production potential still awaits to be tapped.
Ice Load Characteristics on Floating Photovoltaic Platform
Authors: Kolerski Tomasz , Radan Parisa , Gąsiorowski Dariusz
Published: April 2021

Nowadays, based upon human needs and preferring perpetual types of energy, photovoltaic system (PV) is a suitable alternative and more frequently used in northern countries, which are recently more attracted by solar power. The new floating type of the structure is installed in the water bodies instead of land. One of the main elements in floating photovoltaic structures is the forces imposed on the panels. In the northern regions, the dominant load is considered to be ice interaction with the structure. This study aims at identifying the loads imposed on a floating PV structure located in the Łapino Reservoir on the Radunia River, which are produced by the wind action on the ice cover. The wind velocity varying between 10 and 26 m/s is implemented, and also the reduction of the pool level was studied. Wind direction plays an important role in the inclination and expansion of ice accumulation. Moreover, the magnitude of wind velocity is a determinative factor in the maximum thickness emerged in various spot of the area. Changes in pool level reduction is not able to cause noticeable changes in ice cover expansion and maximum ice thickness. Additionally, the shoving mechanism is able to originate abrupt changes in ice thickness by means of rising wind velocity.
Ab initio Study of Hydrogen Adsorption on Metal-Decorated Borophene-Graphene Bilayer
Authors: Grishakov Konstantin S. , Katin Konstantin P. , Kochaev Alexey I. , Kaya Savas , Gimaldinova Margarita A. , Maslov Mikhail M.
Published: April 2021

We studied the hydrogen adsorption on the surface of a covalently bonded bilayer borophene-graphene heterostructure decorated with Pt, Ni, Ag, and Cu atoms. Due to its structure, the borophene-graphene bilayer combines borophene activity with the mechanical stability of graphene. Based on the density functional theory calculations, we determined the energies and preferred adsorption sites of these metal atoms on the heterostructure’s borophene surface. Since boron atoms in different positions can have different reactivities with respect to metal atoms, we considered seven possible adsorption positions. According to our calculations, all three metals adsorb in the top position above the boron atom and demonstrate catalytic activity. Among the metals considered, copper had the best characteristics. Copper-decorated heterostructure possesses a feasible near-zero overpotential for hydrogen evolution reaction. However, the borophene-graphene bilayer decorated with copper is unstable with respect to compression. Small deformations lead to irreversible structural changes in the system. Thus, compression cannot be used as an effective mechanism for additional potential reduction.
Sustainability Evaluation of Rural Electrification in Cuba: From Fossil Fuels to Modular Photovoltaic Systems: Case Studies from Sancti Spiritus Province
Authors: López-González Alejandro , Domenech Bruno , Ferrer-Martí Laia
Published: April 2021

In the last ten years, there has been a progressive improvement in rural electrification indexes in developing countries, and renewable energies are progressively being integrated into electrification programs. In Cuba, the government has set a target of 700 MW in solar photovoltaic energy by 2030, including rural electrification and off-grid systems. Within this framework, 10,000 modular systems of 300 Wp are being installed in isolated communities. Nowadays, previously diesel-electrified settlements are migrating into renewable energy technologies projects in rural Cuba. The objective of this research is to evaluate the sustainability of these changes in order to identify the implications for other developing countries, taking four different dimensions into account: environmental, technical, socioeconomic, and institutional. For this purpose, the rural communities of Yaguá (diesel-based) and Río Abajo (solar-based) in the province of Sancti Spiritus are visited and studied. Results show that the institutional dimension of sustainability is positive thanks to improvements in energy security and promotion of the Cuban national plan goals. Moreover, results confirm that the energy transition from diesel-based to solar PV is environmentally sustainable in Cuba, but improvements are still necessary in the power capacity of solar modules to strengthen the socioeconomic and technical dimensions.
Current Status and Future Trends in the Operation and Maintenance of Offshore Wind Turbines: A Review
Authors: Rinaldi Giovanni , Thies Philipp R. , Johanning Lars
Published: April 2021

Operation and maintenance constitute a substantial share of the lifecycle expenditures of an offshore renewable energy farm. A noteworthy number of methods and techniques have been developed to provide decision-making support in strategic planning and asset management. Condition monitoring instrumentation is commonly used, especially in offshore wind farms, due to the benefits it provides in terms of fault identification and performance evaluation and improvement. Incorporating technology advancements, a shift towards automation and digitalisation is taking place in the offshore maintenance sector. This paper reviews the existing literature and novel approaches in the operation and maintenance planning and the condition monitoring of offshore renewable energy farms, with an emphasis on the offshore wind sector, discussing their benefits and limitations. The state-of-the-art in industrial condition-based maintenance is reviewed, together with deterioration models and fault diagnosis and prognosis techniques. Future scenarios in robotics, artificial intelligence and data processing are investigated. The application challenges of these strategies and Industry 4.0 concepts in the offshore renewables sector are scrutinised, together with the potential implications of early-stage project integration. The identified technologies are ranked against a series of indicators, providing a reference for a range of industry stakeholders.
Attempt to Identify Sex Hormones in the Bodies of Selected Norway Spruce Bark Beetles
Authors: Kacprzyk Magdalena , Bednarz Bartłomiej , Choczyński Maciej
Published: April 2021

A gas chromatography technique was applied to the adults of Ips typograhus (L.) and Pityogenes chalcographus (L.) collected from pheromone traps placed in Norway spruce stands in southern Poland in distinguished population swarming periods for the qualitative and quantitative determination of steroid compound differences between insect sexes. Ten not yet identified for bark beetle compounds from the group of sterols, including cholestenone, 4,6-cholestadiene-3-one, choles-4-en-3,6-dione and 17β-Hydroxyandrosta-1,4-dien-3-one benzoate, which can potentially act as gender hormones were detected. The presence of ecdysone and 20-hydroxyecdysone in the bodies of the studied bark beetles was confirmed. However, slight differences in the content of ecdysteroids in the bodies of males and females may be only the remains of the insect’s metamorphosis. Due to the small differences in the extracted compounds between the females and males, their variability in concentrations during the swarming period seems to be useless as a basis for sex determination.
Vertical Distribution of Mercury in Forest Soils and Its Transfer to Edible Mushrooms in Relation to Tree Species
Authors: Pecina Václav , Valtera Martin , Trávníčková Gabriela , Komendová Renata , Novotný Radek , Brtnický Martin , Juřička David
Published: April 2021

Soil pollution by mercury (Hg) is a global problem that poses risks to natural ecosystems and to human health. Forests represent an important recipient of Hg deposition, however, so far, very little is known about the tree species identity effects on the distribution of Hg in forest soils and its accumulation in edible mushrooms. To clarify the effect on the two main Central-European commercial forest tree species, soil samples were collected from organic F+H horizons and from mineral soil depths of 0–2, 2–10, 10–20, and 20–30 cm in mature Norway spruce (Picea abies (L.) H. Karst.) and European beech (Fagus sylvatica L.) dominated stands. Mushroom samples of the Boletaceae family were also collected at each sampling site. The highest Hg contents were found in the F+H layer and were significantly higher in spruce- (mean 0.46 ± 0.03 mg/kg) than in beech- (mean 0.29 ± 0.10 mg/kg) dominated stands. The variation in Hg contents in F+H was best predicted by pH, the overall lower soil pH in strongly acidic spruce stands might induce Hg immobilization in the F+H layer to cause a decrease in the bioavailability of Hg for Xerocomellus chrysenteron (Bull.) Šutara. In mineral soil, the Hg contents did not differ significantly between the spruce- and beech-dominated stands. The Hg content strongly correlated with the S, N, and C contents only in mineral soil; at the depths of 2–10, 10–20, and 20–30 cm, significantly also with the silt vs. sand, Alo, and Feo contents. Studied mushroom species were not Hg-contaminated and, therefore, their consumption does not pose serious health risks regardless of the forest type. The results suggest that species-related soil chemistry and mineral associations, rather than different atmospheric Hg interception by spruce vs. beech, drive the vertical distribution and accumulation of Hg in forest soils.