bluuebunny/crossref_metadata_2025 huggingface dataset:
TP53 Mutation as a Prognostic and Predictive Marker in Sarcoma: Pooled Analysis of MOSCATO and ProfiLER Precision Medicine Trials
Authors: Nassif Elise F. , Auclin Edouard , Bahleda Rastilav , Honoré Charles , Mir Olivier , Dumont Sarah , Mery Benoite , Hodroj Khalil , Brahmi Mehdi , Trédan Olivier , Ray-Coquard Isabelle , Blay Jean-Yves , Massard Christophe , Le Cesne Axel , Dufresne Armelle
Published: July 2021

(1) Background: locally resected high-grade sarcomas relapse in 40% of cases. There is no prognostic or predictive genomic marker for response to peri-operative chemotherapy. (2) Methods: MOSCATO and ProfiLER are pan-tumor prospective precision medicine trials for advanced tumors. Molecular analysis in both trials comprised targeted next-generation sequencing and comparative genomic hybridization array. We investigated if molecular alterations identified in these trials in sarcomas were associated with disease-free survival (DFS) and response to anthracyclines. (3) Results: this analysis included 215 sarcomas, amongst which 53 leiomyosarcomas, 27 rhabdomyosarcomas, 20 undifferentiated pleomorphic sarcomas, and 17 liposarcomas. The most frequently altered gene was TP53 (46 mutations and eight deletions). There were 149 surgically resected localized sarcomas. Median DFS in TP53 wild type (WT), deleted, and mutated sarcomas was 16, 10, and 10 months, respectively (p = 0.028; deletions: HR = 1.55; 95% CI = 0.75–3.19; mutations: HR = 1.70; 95%CI = 1.13–2.64). In multivariate analysis, TP53 mutations remained associated with shorter DFS (p = 0.027; HR = 2.30; 95%CI = 1.10–4.82). There were 161 localized and advanced sarcomas evaluable for response to anthracyclines. Objective response rates were 35% and 55% in TP53 WT and mutated sarcomas, respectively (OR = 2.24; 95%CI = 1.01–5.03; p = 0.05). In multivariate analysis, TP53 mutations remained associated with increased response (OR = 3.24; 95%CI = 1.30–8.45; p = 0.01). (4) Conclusions: TP53 mutations are associated with shorter DFS and increased response to anthracyclines. Post-validation, these findings could assist in decision-making for peri-operative treatments.
Alpha-Fetoprotein- and CD40Ligand-Expressing Dendritic Cells for Immunotherapy of Hepatocellular Carcinoma
Authors: Vogt Annabelle , Sadeghlar Farsaneh , Ayub Tiyasha H. , Schneider Carlo , Möhring Christian , Zhou Taotao , Mahn Robert , Bartels Alexandra , Praktiknjo Michael , Kornek Miroslaw T. , Toma Marieta , Schmidt-Wolf Ingo G. H. , Branchi Vittorio , Matthaei Hanno , Kalff Jörg C. , Strassburg Christian P. , Gonzalez-Carmona Maria A.
Published: July 2021

Dendritic cells (DC) as professional antigen presenting cells are able to prime T-cells against the tumor-associated antigen α-fetoprotein (AFP) for immunotherapy of hepatocellular carcinoma (HCC). However, a strong immunosuppressive tumor environment limits their efficacy in patients. The co-stimulation with CD40Ligand (CD40L) is critical in the maturation of DC and T-cell priming. In this study, the impact of intratumoral (i.t.) CD40L-expressing DC to improve vaccination with murine (m)AFP-transduced DC (Ad-mAFP-DC) was analyzed in subcutaneous (s.c.) and orthotopic murine HCC. Murine DC were adenovirally transduced with Ad-mAFP or Ad-CD40L. Hepa129-mAFP-cells were injected into the right flank or the liver of C3H-mice to induce subcutaneous (s.c.) and orthotopic HCC. For treatments, 106 Ad-mAFP-transduced DC were inoculated s.c. followed by 106 CD40L-expressing DC injected intratumorally (i.t.). S.c. inoculation with Ad-mAFP-transduced DC, as vaccine, induced a delay of tumor-growth of AFP-positive HCC compared to controls. When s.c.-inoculation of Ad-mAFP-DC was combined with i.t.-application of Ad-CD40L-DC synergistic antitumoral effects were observed and complete remissions and long-term survival in 62% of tumor-bearing animals were achieved. Analysis of the tumor environment at different time points revealed that s.c.-vaccination with Ad-mAFP-DC seems to stimulate tumor-specific effector cells, allowing an earlier recruitment of effector T-cells and a Th1 shift within the tumors. After i.t. co-stimulation with Ad-CD40L-DC, production of Th1-cytokines was strongly increased and accompanied by a robust tumor infiltration of mature DC, activated CD4+-, CD8+-T-cells as well as reduction of regulatory T-cells. Moreover, Ad-CD40L-DC induced tumor cell apoptosis. Intratumoral co-stimulation with CD40L-expressing DC significantly improves vaccination with Ad-mAFP-DC in pre-established HCC in vivo. Combined therapy caused an early and strong Th1-shift in the tumor environment as well as higher tumor apoptosis, leading to synergistic tumor regression of HCC. Thus, CD40L co-stimulation represents a promising tool for improving DC-based immunotherapy of HCC.
Meta-Analysis of Circulating Cell-Free DNA’s Role in the Prognosis of Pancreatic Cancer
Authors: Milin-Lazovic Jelena , Madzarevic Petar , Rajovic Nina , Djordjevic Vladimir , Milic Nikola , Pavlovic Sonja , Veljkovic Nevena , Milic Natasa M. , Radenkovic Dejan
Published: July 2021

Introduction: The analysis of cell-free DNA (cfDNA) for genetic abnormalities is a promising new approach for the diagnosis and prognosis of pancreatic cancer patients. Insights into the molecular characteristics of pancreatic cancer may provide valuable information, leading to its earlier detection and the development of targeted therapies. Material and Methods: We conducted a systematic review and a meta-analysis of studies that reported cfDNA in pancreatic ductal adenocarcinoma (PDAC). The studies were considered eligible if they included patients with PDAC, if they had blood tests for cfDNA/ctDNA, and if they analyzed the prognostic value of cfDNA/ctDNA for patients’ survival. The studies published before 22 October 2020 were identified through the PubMED, EMBASE, Web of Science and Cochrane Library databases. The assessed outcomes were the overall (OS) and progression-free survival (PFS), expressed as the log hazard ratio (HR) and standard error (SE). The summary of the HR effect size was estimated by pooling the individual trial results using the Review Manager, version 5.3, Cochrane Collaboration. The heterogeneity was assessed using the Cochran Q test and I2 statistic. Results: In total, 48 studies were included in the qualitative review, while 44 were assessed in the quantitative synthesis, with the total number of patients included being 3524. Overall negative impacts of cfDNA and KRAS mutations on OS and PFS in PDAC (HR = 2.42, 95% CI: 1.95–2.99 and HR = 2.46, 95% CI: 2.01–3.00, respectively) were found. The subgroup analysis of the locally advanced and metastatic disease presented similar results (HR = 2.51, 95% CI: 1.90–3.31). In the studies assessing the pre-treatment presence of KRAS, there was a moderate to high degree of heterogeneity (I2 = 87% and I2 = 48%, for OS and PFS, respectively), which was remarkably decreased in the analysis of the studies measuring post-treatment KRAS (I2 = 24% and I2 = 0%, for OS and PFS, respectively). The patients who were KRAS positive before but KRAS negative after treatment had a better prognosis than the persistently KRAS-positive patients (HR = 5.30, 95% CI: 1.02–27.63). Conclusion: The assessment of KRAS mutation by liquid biopsy can be considered as an additional tool for the estimation of the disease course and outcome in PDAC patients.
Definition of Outcome-Based Prostate-Specific Antigen (PSA) Thresholds for Advanced Prostate Cancer Risk Prediction
Authors: Ferraro Simona , Bussetti Marco , Bassani Niccolò , Rossi Roberta Simona , Incarbone Giacomo Piero , Bianchi Filippo , Maggioni Marco , Runza Letterio , Ceriotti Ferruccio , Panteghini Mauro
Published: July 2021

We defined prostate-specific antigen (PSA) thresholds from a well calibrated risk prediction model for identifying and excluding advanced prostate cancer (PCa). We retrieved 902 biopsied patients with a pre-biopsy PSA determination (Roche assay). A logistic regression model predictive for PCa including the main effects [i.e., PSA, age, histological evidence of glandular inflammation (GI)] was built after testing the accuracy by calibration plots and Hosmer-Lemeshow test for goodness of fit. PSA thresholds were derived by assuming a diagnostic sensitivity of 95% (rule-out) and 80% (rule-in) for overall and advanced/poorly differentiated PCa. In patients without GI, serum PSA concentrations ≤ 4.1 (<65 years old) and ≤3.7 μg/L (≥65 years old) excluded an advanced PCa (defined as Gleason score ≥ 7 at biopsy), with a negative predictive value of 95.1% [95% confidence interval (CI): 83.0–98.7] and 88.8% (CI: 80.2–93.9), respectively, while PSA > 5.7 (<65) and >6.1 μg/L (≥65) should address biopsy referral. In presence of GI, PSA did not provide a valid estimate for risk of advanced cancer because of its higher variability and the low pre-test probability of PCa. The proposed PSA thresholds may support biopsy decision except for patients with asymptomatic prostatitis who cannot be pre-biopsy identified.
Potentially Curative Therapeutic Activity of NEO212, a Perillyl Alcohol-Temozolomide Conjugate, in Preclinical Cytarabine-Resistant Models of Acute Myeloid Leukemia
Authors: Schönthal Axel H. , Swenson Steve , Minea Radu O. , Kim Hye Na , Cho Heeyeon , Mohseni Nazleen , Kim Yong-Mi , Chen Thomas C.
Published: July 2021

Despite progress in the treatment of acute myeloid leukemia (AML), the clinical outcome remains suboptimal and many patients are still dying from this disease. First-line treatment consists of chemotherapy, which typically includes cytarabine (AraC), either alone or in combination with anthracyclines, but drug resistance can develop and significantly worsen prognosis. Better treatments are needed. We are developing a novel anticancer compound, NEO212, that was created by covalent conjugation of two different molecules with already established anticancer activity, the alkylating agent temozolomide (TMZ) and the natural monoterpene perillyl alcohol (POH). We investigated the anticancer activity of NEO212 in several in vitro and in vivo models of AML. Human HL60 and U937 AML cell lines, as well as different AraC-resistant AML cell lines, were treated with NEO212 and effects on cell proliferation, cell cycle, and cell death were investigated. Mice with implanted AraC-sensitive or AraC-resistant AML cells were dosed with oral NEO212, and animal survival was monitored. Our in vitro experiments show that treatment of cells with NEO212 results in growth inhibition via potent G2 arrest, which is followed by apoptotic cell death. Intriguingly, NEO212 was equally potent in highly AraC-resistant cells. In vivo, NEO212 treatment strikingly extended survival of AML mice and the majority of treated mice continued to thrive and survive without any signs of illness. At the same time, we were unable to detect toxic side effects of NEO212 treatment. All in all, the absence of side effects, combined with striking therapeutic activity even in an AraC-resistant context, suggests that NEO212 should be developed further toward clinical testing.
Anosmia but Not Ageusia as a COVID-19-Related Symptom among Cancer Patients—First Results from the PAPESCO-19 Cohort Study
Authors: Zhou Ke , Blanc-Lapierre Audrey , Seegers Valérie , Boisdron-Celle Michèle , Bigot Frédéric , Bourdon Marianne , Mahammedi Hakim , Lambert Aurélien , Campone Mario , Conroy Thierry , Penault-Llorca Frédérique , Bellanger Martine M. , Raoul Jean-Luc
Published: July 2021

Background: Cancer patients may fail to distinguish COVID-19 symptoms such as anosmia, dysgeusia/ageusia, anorexia, headache, and fatigue, which are frequent after cancer treatments. We aimed to identify symptoms associated with COVID-19 and to assess the strength of their association in cancer and cancer-free populations. Methods: The multicenter cohort study PAPESCO-19 included 878 cancer patients and 940 healthcare workers (HCWs). At baseline and quarterly thereafter, they reported the presence or absence of 13 COVID-19 symptoms observed over 3 months and the results of routine screening RT-PCR, and they were systematically tested for SARS-CoV-2-specific antibodies. We identified the symptom combinations significantly associated with COVID-19. Results: Eight percent of cancer patients were COVID-19 positive, and 32% were symptomatic. Among the HCWs, these proportions were 9.5 and 52%, respectively. Anosmia, anorexia, fever, headache, and rhinorrhea together accurately discriminated (c-statistic = 0.7027) COVID-19 cases from cancer patients. Anosmia, dysgeusia/ageusia, muscle pain, intense fatigue, headache, and chest pain better discriminated (c-statistic = 0.8830) COVID-19 cases among the HCWs. Anosmia had the strongest association in both the cancer patients (OR = 7.48, 95% CI: 2.96–18.89) and HCWs (OR = 5.71, 95% CI: 2.21–14.75). Conclusions: COVID-19 symptoms and their diagnostic performance differ in the cancer patients and HCWs. Anosmia is associated with COVID-19 in cancer patients, while dysgeusia/ageusia is not. Cancer patients deserve tailored preventive measures due to their particular COVID-19 symptom pattern.
Proteomics and Drug Repurposing in CLL towards Precision Medicine
Authors: Mavridou Dimitra , Psatha Konstantina , Aivaliotis Michalis
Published: July 2021

CLL is a hematological malignancy considered as the most frequent lymphoproliferative disease in the western world. It is characterized by high molecular heterogeneity and despite the available therapeutic options, there are many patient subgroups showing the insufficient effectiveness of disease treatment. The challenge is to investigate the individual molecular characteristics and heterogeneity of these patients. Proteomics analysis is a powerful approach that monitors the constant state of flux operators of genetic information and can unravel the proteome heterogeneity and rewiring into protein pathways in CLL patients. This review essences all the available proteomics studies in CLL and suggests the way these studies can be exploited to find effective therapeutic options combined with drug repurposing approaches. Drug repurposing utilizes all the existing knowledge of the safety and efficacy of FDA-approved or investigational drugs and anticipates drug alignment to crucial CLL therapeutic targets, leading to a better disease outcome. The drug repurposing studies in CLL are also discussed in this review. The next goal involves the integration of proteomics-based drug repurposing in precision medicine, as well as the application of this procedure into clinical practice to predict the most appropriate drugs combination that could ensure therapy and the long-term survival of each CLL patient.
Current Indications of Secondary Enucleation in Retinoblastoma Management: A Position Paper on Behalf of the European Retinoblastoma Group (EURbG)
Authors: Stathopoulos Christina , Lumbroso-Le Rouic Livia , Moll Annette C. , Parulekar Manoj , Maeder Philippe , Doz François , Jenkinson Helen , Beck Popovic Maja , Chantada Guillermo , Munier Francis L.
Published: July 2021

Secondary enucleation (SE) puts an irreversible end to eye-preserving therapies, whenever their prolongation is expected to violate the presumed state of metastatic grace. At present, it must be acknowledged that clear criteria for SE are missing, leading to empiric and subjective indications commonly related to disease progression or relapse, disease persistence masking the optic nerve head or treatment-related complications obscuring the fundus view. This absence of evidence-based consensus regarding SE is explained by the continuously moving frontiers of the conservative management as a result of diagnostic and therapeutic advances, as well as by the lack of studies sufficiently powered to accurately stratify the risk of metastasis in conservatively treated patients. In this position paper of the European Retinoblastoma Group (EURbG), we give an overview of the progressive shift in the indications for SE over the past decades and propose guidelines to assist decision-making with respect to when SE becomes imperative or recommended, with corresponding absolute and relative SE indications. Further studies and validation of biologic markers correlated with the risk of metastasis are expected to set more precisely the frontiers of conservative management and thus consensual criteria for SE in the future.
The Role of miRNAs in the Regulation of Endometrial Cancer Invasiveness and Metastasis—A Systematic Review
Authors: Klicka Klaudia , Grzywa Tomasz M. , Klinke Alicja , Mielniczuk Aleksandra , Włodarski Paweł K.
Published: July 2021

Endometrial cancer (EC) is the most common genital cancer in women with increasing death rates. MiRNAs are short non-coding RNAs that regulate gene expression on the post-transcriptional levels. Multiple studies demonstrated a fundamental role of miRNAs in the regulation of carcinogenesis. This systematic review is a comprehensive overview of the role of miRNAs in the regulation of cancer cell invasiveness and metastasis in EC. The literature was searched for studies investigating the role of miRNAs in the regulation of invasiveness and metastasis in EC. We explored PubMed, Embase, and Scopus using the following keywords: miRNA, metastasis, invasiveness, endometrial cancer. Data were collected from 163 articles that described the expression and role of 106 miRNAs in the regulation of EC invasiveness and metastasis out of which 63 were tumor suppressor miRNAs, and 38 were oncomiRNAs. Five miRNAs had a discordant role in different studies. Moreover, we identified 66 miRNAs whose expression in tumor tissue or concentration in serum correlated with at least one clinical parameter. These findings suggest a crucial role of miRNAs in the regulation of EC invasiveness and metastasis and present them as potential prognostic factors for patients with EC.
Oncogenic Functions and Clinical Significance of Circular RNAs in Colorectal Cancer
Authors: Radanova Maria , Mihaylova Galya , Nazifova-Tasinova Neshe , Levkova Mariya , Tasinov Oskan , Ivanova Desislava , Mihaylova Zhasmina , Donev Ivan
Published: July 2021

Colorectal cancer (CRC) is ranked as the second most commonly diagnosed disease in females and the third in males worldwide. Therefore, the finding of new more reliable biomarkers for early diagnosis, for prediction of metastasis, and resistance to conventional therapies is an important challenge in overcoming the disease. The current review presents circular RNAs (circRNAs) with their unique features as potential prognostic and diagnostic biomarkers in CRC. The review highlights the mechanism of action and the role of circRNAs with oncogenic functions in the CRC as well as the association between their expression and clinicopathological characteristics of CRC patients. The comprehension of the role of oncogenic circRNAs in CRC pathogenesis is growing rapidly and the next step is using them as suitable new drug targets in the personalized treatment of CRC patients.
Behavioral Intention towards Dietary Diversity among Adult People Living with HIV in Public Hospitals in Southwest Ethiopia Using Theory of Planned Behavior—An Explanatory Study
Authors: Teklehaimanot Aderajew Nigusse , Belachew Tefera , Gudina Esayas Kebede , Getnet Masrie , Amdisa Demuma , Dadi Lelisa Sena
Published: July 2021

Dietary diversity is a crucial element of inclusive care for people living with HIV (PLWHIV). Particularly in resource-limited countries where undernutrition and food insecurity prevail, low intention and poor attitude towards diversified diets are the common challenges. The aim of this study was to assess the intention towards dietary diversity behavior among adult PLWHIV in Jimma Zone public hospitals, Southwest Ethiopia. A hospital-based survey study was carried out in five public institutions among 403 sampled adult PLWHIV. Data were entered into Epi-Data (The EpiData Association, Odense, Denmark) and exported to SPSS version 20 (IBM, Armonk, NY, USA) for analysis. Relationships among variables were assessed using correlation coefficients. A multivariable linear regression model was fitted to assess predictors of behavioral intention towards dietary diversity at p-value ≤ 0.05. The quantitative data were supplemented by qualitative data, which were collected through key informant interviews and analyzed thematically. The significant predictors of intention to use dietary diversity were attitude (β = 0.196, p < 0.01) and subjective norm (β = 0.390, p < 0.01) of the adult PLWHIV. The constructs of theory of planned behavior (TPB) independently explained the variance in intention towards dietary diversity by 25.7%. All the intermediate, proximal and distal components of the theory of planned behavior (TPB) explained the final model finding 32.2% of variance in the intention to use dietary diversity. The qualitative findings indicated that delivery of HIV care requires a sense of livelihood development, economical improvement and creating a sense of ownership for sustainable HIV care by creating behavioral change at the individual level. Conclusion: Dietary inadequacy was strongly correlated with being in the sociodemographic groups that are at heightened risk of adverse clinical outcomes. It is worthwhile to understand behavioral intention as a potential determinant of malnutrition and the Poor ART outcomes rather than symptomatic treatment of malnutrition with food by prescription.
Evidence to Date: Evaluating Pembrolizumab in the Treatment of Extensive-Stage Small-Cell Lung Cancer
Authors: Riano Ivy , Patel Shruti R. , Liu Stephen V. , Duma Narjust
Published: July 2021

Small-cell lung cancer (SCLC) is an aggressive subtype of lung cancer characterized by a rapid initial response and early development of resistance to systemic therapy and radiation. The management of SCLC significantly changed for the first time in decades with the introduction of immune checkpoint inhibitors. Pembrolizumab, a humanized IgG4 isotype antibody, targets the programmed cell death protein 1 (PD-1) pathway to restore anti-tumor immunity. Prospective trials of pembrolizumab in patients with previously treated SCLC showed significant durability of responses. These results led to the U.S. Food and Drug Administration (FDA) granting pembrolizumab accelerated approval as second- or third-line monotherapy for patients with extensive-stage (ES) SCLC. In a recent clinical trial that included patients with previously untreated ES-SCLC, pembrolizumab in combination with platinum/etoposide met its progression-free survival endpoint, but overall survival (OS) did not cross the threshold for superiority. With the therapeutic landscape for SCLC rapidly evolving, we review prior experience and future directions of pembrolizumab in ES-SCLC.
Oak (Acorn)–Weevil Interactions across an Extensive Latitudinal Gradient in Eastern North America
Authors: Steele Michael A. , Dalgleish Harmony J. , Marino Shealyn , Bartlow Andrew W. , Curtis Rachel , Stratford Jeffrey A.
Published: July 2021

Recent studies have explored how nut weevils (Curculio and Conotrachelus spp. (Coleoptera: Curculionidae) prey on the fruits (acorns) of oak (Quercus spp.). However, few, if any, have examined these interactions over both an extensive geographic area and over several years. Here, we observed patterns of infestation in acorns of both red oak (Quercus rubra) and white oak (Quercus alba) over an eight-year period along a latitudinal transect, extending as far as 900km, across much of the shared range of these two oak species. Although weevil prevalence did not differ significantly between the two oak species, in red oak, infestation prevalence increased significantly with latitude. In contrast, an opposite pattern was evident in white oak, with the highest infestation prevalence occurring at lower latitudes. One controlled measure of cotyledon damage was significantly lower in acorns of red oak than those of white oak, which may in part be due to larger acorn size at the lower latitudes. Future investigations in this system should focus on the distribution of weevil species (with DNA barcoding) across this range and geographic variation in chemical gradients that likely determine patterns of weevil damage in individual acorns.
Applications of Advanced Ultrasound Technology in Obstetrics
Authors: Leung Kwok-Yin
Published: July 2021

Over the years, there have been several improvements in ultrasound technologies including high-resolution ultrasonography, linear transducer, radiant flow, three-/four-dimensional (3D/4D) ultrasound, speckle tracking of the fetal heart, and artificial intelligence. The aims of this review are to evaluate the use of these advanced technologies in obstetrics in the midst of new guidelines on and new techniques of obstetric ultrasonography. In particular, whether these technologies can improve the diagnostic capability, functional analysis, workflow, and ergonomics of obstetric ultrasound examinations will be discussed.
Urban Sustainability through Innovative Open Space Design. A Novel Approach to the Regeneration of Historic Open Spaces in Some Eastern European Countries and China
Authors: Fekete Albert , Hodor Katarzyna , Dai Daixin
Published: July 2021

Looking at the urban development of the past two centuries, we can conclude that engineers and architects have been dominating the field of urban design all over Europe. Architects played the most important role, which became even more significant with the increase of urban development. Beyond the architectural approach, a greater importance had been attributed to ecological aspects of urban planning by the turn of the 20th century as, for example, the advance of the garden city movement illustrates. This article focuses on the review of crucial open-space renewal projects from two Eastern European cities and China. The case studies are used to shed light on the characteristics and historical values of contemporary open-space design, based on innovative and landscape architectural approaches and artistic solutions. The study shows that the original role of urban open spaces was significantly extended during the first decades of the 21st century. The increased needs for representation—commercial, cultural and living functions, and ecological and healthy benefits—led to a multifunctional approach in design and planning. The renewal of the historic urban open spaces is carried out under an integrated framework and a unified goal: the development-oriented heritage conservation. Based on strong economic aspects, the general tendency is clearly positive—in spite of still-existing problematic issues (for instance, the management of public transport or the status of public utilities). In the time of a growing awareness of open-space heritage, this overview tries to depict possible general principles of a long-term renewal strategy built on local identity, heritage values and social sustainability.
Relationship between Socio-Emotional Competencies and the Overlap of Bullying and Cyberbullying Behaviors in Primary School Students
Authors: Rodríguez-Álvarez Juan Manuel , Yubero Santiago , Navarro Raúl , Larrañaga Elisa
Published: July 2021

Digital life forms part of daily reality for young people. For this reason, traditional bullying in school has been reproduced in the online environment, resulting in an overlap of off- and online bullying. Research on socio-emotional competencies and bullying is revealing interesting results among students in secondary schools. However, studies involving primary school students are much scarcer. In addition, the majority of studies have been carried out based on an understanding of socio-emotional competencies as a unidimensional construct. In the present study, we examined the overlap between off- and online bullying victimization and the influence of the factors comprising socio-emotional competencies on this overlap. Participants comprised 1130 students (49.7% were boys and 50.3% were girls) from the fifth and sixth grades at 15 schools in the autonomous communities of Madrid and Castilla-La Mancha (Spain). The results indicate a high rate of overlap between off- and online bullying victimization, without significant gender differences. Poor relationship skills in boys and low self-management in girls were associated with being a victim of both traditional bullying and cyberbullying. The conclusions point to an interesting line of intervention and prevention, establishing a framework of confluence for social and emotional variables within the primary education context.
A Study of Moist Air Condensation Characteristics in a Transonic Flow System
Authors: Wang Jie , Gu Hongfang
Published: July 2021

When water vapor in moist air reaches supersaturation in a transonic flow system, non-equilibrium condensation forms a large number of droplets which may adversely affect the operation of some thermal-hydraulic equipment. For a better understanding of this non-equilibrium condensing phenomenon, a numerical model is applied to analyze moist air condensation in a transonic flow system by using the theory of nucleation and droplet growth. The Benson model is adopted to correct the liquid-plane surface tension equation for realistic results. The results show that the distributions of pressure, temperature and Mach number in moist air are significantly different from those in dry air. The dry air model exaggerates the Mach number by 19% and reduces both the pressure and the temperature by 34% at the nozzle exit as compared with the moist air model. At a Laval nozzle, for example, the nucleation rate, droplet number and condensation rate increase significantly with increasing relative humidity. The results also reveal the fact that the number of condensate droplets increases rapidly when moist air reaches 60% relative humidity. These findings provide a fundamental approach to account for the effect of condensate droplet formation on moist gas in a transonic flow system.
The Role of Regulators in Promoting the Procurement of Flexibility Services within the Electricity Distribution System: A Survey of Seven Leading Countries
Authors: Anaya Karim L. , Pollitt Michael G.
Published: July 2021

This paper identifies and explores regulatory issues that may have an impact on the use of flexibility services by distribution utilities to solve grid constraints. This can be done by flexible distributed energy resources which can be instructed, for instance, to reduce export generating capacity or increasing consumption. We want to identify how regulation can better support the development of the future distribution utility in its role as neutral market facilitator, enabling more competition in local flexibility markets and optimal use of resources. A set of questionnaires were designed to capture the insights around important aspects of the regulation of flexibility markets (utilities’ network incentives, network tariff structure, market design for flexibility markets, etc.). These were sent to distribution utilities, energy regulators, energy marketplaces, energy associations and relevant experts from seven jurisdictions. The responses suggest a collective interest in the procurement of flexibility services by distribution utilities from distributed energy resources. New regulations, the adaptation of current rules and recent consultations reflect this. However, the amount of progress with and preferences for key regulatory changes differ across jurisdictions.
Environmental Sustainability of Heat Produced by Poplar Short-Rotation Coppice (SRC) Woody Biomass
Authors: Sperandio Giulio , Suardi Alessandro , Acampora Andrea , Civitarese Vincenzo
Published: July 2021

As demonstrated for some time, the reduction of greenhouse gases in the atmosphere can also take place using agroforestry biomass. Short-rotation coppice (SRC) is one of the sources of woody biomass production. In our work, the supply of woody biomass was considered by examining four different cutting shifts (2, 3, 4 and 5 years) and, for each, the Global Warming Potential (GWP) was evaluated according to the IPCC 2007 method. Regarding the rotation cycle, four biomass collection systems characterized by different levels of mechanization were analyzed and compared. In this study, it was assumed that the biomass produced by the SRC plantations was burned in a 350 kWt biomass power plant to heat a public building. The environmental impact generated by the production of 1 GJ of thermal energy was assessed for each of the forest plants examined, considering the entire life cycle, from the field phase to the energy production. The results were compared with those obtained to produce the same amount of thermal energy from a diesel boiler. Comparing the two systems analyzed, it was shown that the production and use of wood biomass to obtain thermal energy can lead to a reduction in the Global Warming Potential of over 70% compared to the use of fossil fuel.
Quercus Conservation Genetics and Genomics: Past, Present, and Future
Authors: Backs Janet R. , Ashley Mary V.
Published: July 2021

Quercus species (oaks) have been an integral part of the landscape in the northern hemisphere for millions of years. Their ability to adapt and spread across different environments and their contributions to many ecosystem services is well documented. Human activity has placed many oak species in peril by eliminating or adversely modifying habitats through exploitative land usage and by practices that have exacerbated climate change. The goal of this review is to compile a list of oak species of conservation concern, evaluate the genetic data that is available for these species, and to highlight the gaps that exist. We compiled a list of 124 Oaks of Concern based on the Red List of Oaks 2020 and the Conservation Gap Analysis for Native U.S. Oaks and their evaluations of each species. Of these, 57% have been the subject of some genetic analysis, but for most threatened species (72%), the only genetic analysis was done as part of a phylogenetic study. While nearly half (49%) of published genetic studies involved population genetic analysis, only 16 species of concern (13%) have been the subject of these studies. This is a critical gap considering that analysis of intraspecific genetic variability and genetic structure are essential for designing conservation management strategies. We review the published population genetic studies to highlight their application to conservation. Finally, we discuss future directions in Quercus conservation genetics and genomics.
An Empirical Study on Customer Churn Behaviours Prediction Using Arabic Twitter Mining Approach
Authors: Almuqren Latifah , Alrayes Fatma S. , Cristea Alexandra I.
Published: July 2021

With the rising growth of the telecommunication industry, the customer churn problem has grown in significance as well. One of the most critical challenges in the data and voice telecommunication service industry is retaining customers, thus reducing customer churn by increasing customer satisfaction. Telecom companies have depended on historical customer data to measure customer churn. However, historical data does not reveal current customer satisfaction or future likeliness to switch between telecom companies. The related research reveals that many studies have focused on developing churner prediction models based on historical data. These models face delay issues and lack timelines for targeting customers in real-time. In addition, these models lack the ability to tap into Arabic language social media for real-time analysis. As a result, the design of a customer churn model based on real-time analytics is needed. Therefore, this study offers a new approach to using social media mining to predict customer churn in the telecommunication field. This represents the first work using Arabic Twitter mining to predict churn in Saudi Telecom companies. The newly proposed method proved its efficiency based on various standard metrics and based on a comparison with the ground-truth actual outcomes provided by a telecom company.
Overcoming Drag at the Water-Air Interface Constrains Body Size in Whirligig Beetles
Authors: Jami Ludovic , Gustafson Grey T. , Steinmann Thomas , Piñeirua Miguel , Casas Jérôme
Published: July 2021

Whirligig beetles (Coleoptera: Gyrinidae) are among the best swimmers of all aquatic insects. They live mostly at the water’s surface and their capacity to swim fast is key to their survival. We present a minimal model for the viscous and wave drags they face at the water’s surface and compare them to their thrust capacity. The swimming speed accessible is thus derived according to size. An optimal size range for swimming at the water’s surface is observed. These results are in line with the evolutionary trajectories of gyrinids which evolved into lineages whose members are a few milimeter’s long to those with larger-sized genera being tens of millimeters in length. The size of these beetles appears strongly constrained by the fluid mechanical laws ruling locomotion and adaptation to the water-air interface.
Parentage Analysis in Giant Grouper (Epinephelus lanceolatus) Using Microsatellite and SNP Markers from Genotyping-by-Sequencing Data
Authors: Weng Zhuoying , Yang Yang , Wang Xi , Wu Lina , Hua Sijie , Zhang Hanfei , Meng Zining
Published: July 2021

Pedigree information is necessary for the maintenance of diversity for wild and captive populations. Accurate pedigree is determined by molecular marker-based parentage analysis, which may be influenced by the polymorphism and number of markers, integrity of samples, relatedness of parents, or different analysis programs. Here, we described the first development of 208 single nucleotide polymorphisms (SNPs) and 11 microsatellites for giant grouper (Epinephelus lanceolatus) taking advantage of Genotyping-by-sequencing (GBS), and compared the power of SNPs and microsatellites for parentage and relatedness analysis, based on a mixed family composed of 4 candidate females, 4 candidate males and 289 offspring. CERVUS, PAPA and COLONY were used for mutually verification. We found that SNPs had a better potential for relatedness estimation, exclusion of non-parentage and individual identification than microsatellites, and > 98% accuracy of parentage assignment could be achieved by 100 polymorphic SNPs (MAF cut-off < 0.4) or 10 polymorphic microsatellites (mean Ho = 0.821, mean PIC = 0.651). This study provides a reference for the development of molecular markers for parentage analysis taking advantage of next-generation sequencing, and contributes to the molecular breeding, fishery management and population conservation.
Non-Syndromic Autosomal Dominant Hearing Loss: The First Italian Family Carrying a Mutation in the NCOA3 Gene
Authors: Tesolin Paola , Morgan Anna , Notarangelo Michela , Ortore Rocco Pio , Concas Maria Pina , Notarangelo Angelantonio , Girotto Giorgia
Published: July 2021

Hearing loss (HL) is the most frequent sensory disorder, affecting about 1–3 per 1000 live births, with more than half of the cases attributable to genetic causes. Despite the fact that many HL causative genes have already been identified, current genetic tests fail to provide a diagnosis for about 40% of the patients, suggesting that other causes still need to be discovered. Here, we describe a four-generation Italian family affected by autosomal dominant non-syndromic hearing loss (ADNSHL), in which exome sequencing revealed a likely pathogenic variant in NCOA3 (NM_181659.3, c.2909G>C, p.(Gly970Ala)), a gene recently described as a novel candidate for ADNSHL in a Brazilian family. A comparison between the two families highlighted a series of similarities: both the identified variants are missense, localized in exon 15 of the NCOA3 gene and lead to a similar clinical phenotype, with non-syndromic, sensorineural, bilateral, moderate to profound hearing loss, with a variable age of onset. Our findings (i.e., the identification of the second family reported globally with HL caused by a variant in NCOA3) further support the involvement of NCOA3 in the etiopathogenesis of ADNSHL, which should, thus, be considered as a new gene for autosomal dominant non-syndromic hearing loss.
Pica (Allotriophagy): An Underestimated Risk Factor for Severe Leptospirosis (Weil’s Diseases)? Report of a Leptospira Septic Shock Successfully Managed with ECMO
Authors: Fabiani Adam , Dal Bo Eugenia , Di Bella Stefano , Gabrielli Marco , Bologna Alessandro , Albert Umberto , Sanson Gianfranco
Published: July 2021

Leptospirosis is a zoonosis caused by infection with pathogenic strains of the bacterium Leptospira. The disease can be complicated by pulmonary hemorrhages and acute respiratory distress syndrome, with the mortality rate increasing to 51–100%. We report the case of a 37-year-old man who was admitted to the emergency department with a 6-day history of fever, weakness, vomiting and diarrhea, followed by jaundice. On admission, he presented leukocytosis, thrombocytopenia and acute liver and kidney injuries. His clinical course was critical, as it was immediately complicated by sepsis and severe respiratory failure, requiring haemodialysis, mechanical ventilation and broad-spectrum antibiotic therapy. In the following days, a veno-venous extracorporeal membrane oxygenation (VV-ECMO) was started due to a dramatic deterioration in respiratory function; 20 h later, it was switched to veno-arterial ECMO because of refractory cardiogenic shock. Hantavirus or Leptospira infection etiology was suspected, so penicillin G and methylprednisolone were initiated as an empirical therapy and subsequently confirmed after a laboratory diagnosis of leptospirosis. Although the clinical course was further complicated by hemorrhagic pneumonia, a gradual, full recovery occurred, and the patient was discharged from the hospital. After excluding other sources of contact with Leptospira-infected material, an unsuspected abnormal eating behavior was identified as the most probable cause of the patient’s Leptospira infection.
A Novel Intronic Splice—Site Mutation of the CYP11A1 Gene Linked to Adrenal Insufficiency with 46,XY Disorder of Sex Development
Authors: Matusik Pawel , Gach Agnieszka , Zajdel-Cwynar Olimpia , Pinkier Iwona , Kudela Grzegorz , Gawlik Aneta
Published: July 2021

A novel CYP11A1: c.1236 + 5G > A was identified, expanding the mutation spectrum of the congenital adrenal insufficiency with 46,XY sex reversal. In a now 17-year-old girl delivered full-term (G2P2, parents unrelated), adrenal failure was diagnosed in the first year of life based on clinical picture of acute adrenal crisis with vomiting, dehydration, weight loss, hypotension, and electrolyte disturbances. At the time, hormonal tests revealed primary adrenocortical insufficiency and steroid profiles showed lack of products of steroidogenesis, and since then the patient has been treated with substitution doses of hydrocortisone and fludrocortisone. At the age of 14, considering the absence of puberty symptoms, extended diagnostic tests revealed elevated LH levels (26.5 mIU/mL) with pre-puberty FSH levels (4.9 mIU/mL), low estradiol (28 pmol/L), testosterone (<2.5 ng/mL), and extremely high levels of ACTH (4961 pg/mL). A cytogenetic study revealed a 46 XY karyotype. A molecular examination confirmed the missense mutation and a novel splice-site mutation of CYP11A1 gene. Compound heterozygosity for the CYP11A1 gene with a known pathogenic variant in one allele and a novel splice site mutation in the second allele is most probably responsible for congenital adrenal insufficiency with 46,XY sex reversal. We discuss the necessity of cytogenetic test in the case of early onset of adrenal failure in the absence of steroidogenesis metabolites in the steroid profile.
Impact of Rowing Training on Quality of Life and Physical Activity Levels in Female Breast Cancer Survivors
Authors: Gavala-González Juan , Torres-Pérez Amanda , Fernández-García José Carlos
Published: July 2021

The aim of this longitudinal study was to determine whether a rowing training program improved the quality of life and the physical activity levels in female breast cancer survivors (n = 28) (stage 1–4.54%; stage 2–36.36%; stage 3–54.54%; and stage 4–4.54%), diagnosed 4.68 ± 3.00 years previously, who had undergone a subsequent intervention (preservation 56.53% and total mastectomy 43.47%) and had a current mean age of 52.30 ± 3.78 years. The participants (n = 28) engaged in a 12-week training program, each week comprising three sessions and each session lasting 60–90 min. The short form of the International Physical Activity Questionnaire (IPAQ-SF) and the Short Form 36 Health Survey (SF-36) were also administered. The results showed statistically significant improvements in levels of physical activity and in the dimensions of quality of life. We can conclude that a 12-week rowing training program tailored to women who have had breast cancer increases physical activity levels, leading to improved health status and quality of life.
Leaf Thermal and Chemical Properties as Natural Drivers of Plant Flammability of Native and Exotic Tree Species of the Valparaíso Region, Chile
Authors: Guerrero Fabián , Hernández Carla , Toledo Mario , Espinoza Lorena , Carrasco Yulian , Arriagada Andrés , Muñoz Ariel , Taborga Lautaro , Bergmann Jan , Carmona Camilo
Published: July 2021

Forest fires are one of the main environmental threats in Chile. Fires in this Mediterranean climate region frequently affect native forests and exotic plantations, including in several cases urban and rural settlements. Considering the scarcity of information regarding the fire response dynamics of tree species that are frequently affected by fires, this study aims to establish a flammability classification according to the evolution of the fire initiation risk presented by the most affected forest species in the Valparaíso region. Three exotic species, Eucalyptus globulus, Pinus radiata, and Acacia dealbata, and two native species, Cryptocarya alba and Quillaja saponaria, were studied. Flammability assays indicate that E. globulus, A. dealbata, and C. alba are extremely flammable, whereas P. radiata and Q. saponaria are flammable. Furthermore, E. globulus and A. dealbata have the highest heating values while Q. saponaria has the lowest values. The extreme flammability of E. globulus, A. dealbata, and C. alba indicates a high susceptibility to ignite. Furthermore, the high heat of combustion of E. globulus and A. dealbata can be associated with a high energy release, increasing the risk of fires spreading. In contrast, Q. saponaria has the lowest predisposition to ignite and capacity to release heat. Accordingly, this work shows that all studied tree species contain organic metabolites that are potentially flammable (sesquiterpenes, aliphatic hydrocarbons, alcohol esters, ketones, diterpenes, and triterpenes) and can be considered as drivers of flammability in vegetation. Finally, these preliminary results will aid in the construction of more resilient landscapes in the near future.