bluuebunny/crossref_metadata_2025 huggingface dataset:
Lobular Carcinoma of the Breast: A Comprehensive Review with Translational Insights
Authors: Batra Harsh , Mouabbi Jason Aboudi , Ding Qingqing , Sahin Aysegul A. , Raso Maria Gabriela
Published: November 2023

The second most common breast carcinoma, invasive lobular carcinoma, accounts for approximately 15% of tumors of breast origin. Its incidence has increased in recent times due in part to hormone replacement therapy and improvement in diagnostic modalities. Although believed to arise from the same cell type as their ductal counterpart, invasive lobular carcinomas (ILCs) are a distinct entity with different regulating genetic pathways, characteristic histologies, and different biology. The features most unique to lobular carcinomas include loss of E-Cadherin leading to discohesion and formation of a characteristic single file pattern on histology. Because most of these tumors exhibit estrogen receptor positivity and Her2 neu negativity, endocrine therapy has predominated to treat these tumors. However novel treatments like CDK4/6 inhibitors have shown importance and antibody drug conjugates may be instrumental considering newer categories of Her 2 Low breast tumors. In this narrative review, we explore multiple pathological aspects and translational features of this unique entity. In addition, due to advancement in technologies like spatial transcriptomics and other hi-plex technologies, we have tried to enlist upon the characteristics of the tumor microenvironment and the latest associated findings to better understand the new prospective therapeutic options in the current era of personalized treatment.
Robotic Distal Pancreatectomy Yields Superior Outcomes Compared to Laparoscopic Technique: A Single Surgeon Experience of 123 Consecutive Cases
Authors: Ding Hao , Kawka Michal , Gall Tamara M. H. , Wadsworth Chris , Habib Nagy , Nicol David , Cunningham David , Jiao Long R.
Published: November 2023

Technical limitations of laparoscopic distal pancreatectomy (LDP), in comparison to robotic distal pancreatectomy (RDP), may translate to high conversion rates and morbidity. LDP and RDP procedures performed between December 2008 and January 2023 in our tertiary referral hepatobiliary and pancreatic centres were analysed and compared with regard to short-term outcomes. A total of 62 consecutive LDP cases and 61 RDP cases were performed. There was more conversion to open surgeries in the laparoscopic group compared with the robotic group (21.0% vs. 1.6%, p = 0.001). The LDP group also had a higher rate of postoperative complications (43.5% vs. 23.0%, p = 0.005). However, there was no significant difference between the two groups in terms of major complication or pancreatic fistular after operations (p = 0.20 and p = 0.71, respectively). For planned spleen-preserving operations, the RDP group had a shorter mean operative time (147 min vs. 194 min, p = 0.015) and a reduced total length of hospital stay compared with the LDP group (4 days vs. 7 days, p = 0.0002). The failure rate for spleen preservation was 0% in RDP and 20% (n = 5/25) in the LDP group (p = 0.009). RDP offered a better method for splenic preservation with Kimura’s technique compared with LDP to avoid the risk of splenic infarction and gastric varices related to ligation and division of splenic pedicles. RDP should be the standard operation for the resection of pancreatic tumours at the body and tail of the pancreas without involving the celiac axis or common hepatic artery.
Exploring the Future of Cancer Impact in Alberta: Projections and Trends 2020–2040
Authors: Brenner Darren R. , Carbonell Chantelle , O’Sullivan Dylan E. , Ruan Yibing , Basmadjian Robert B. , Bu Vickey , Farah Eliya , Loewen Shaun K. , Bond Tara R. , Estey Angela , Pujadas Botey Anna , Robson Paula J.
Published: November 2023

The impact of cancer in Alberta is expected to grow considerably, largely driven by population growth and aging. The Future of Cancer Impact (FOCI) initiative offers an overview of the present state of cancer care in Alberta and highlights potential opportunities for research and innovation across the continuum. In this paper, we present a series of detailed projections and analyses regarding cancer epidemiological estimates in Alberta, Canada. Data on cancer incidence and mortality in Alberta (1998–2018) and limited-duration cancer prevalence in Alberta (2000–2019) were collected from the Alberta Cancer Registry. We used the Canproj package in the R software to project these epidemiological estimates up to the year 2040. To estimate the direct management costs, we ran a series of microsimulations using the OncoSim All Cancers Model. Our findings indicate that from 2020, the total number of annual new cancer cases and cancer-related deaths are projected to increase by 56% and 49% by 2040, respectively. From 2019, the five-year prevalence of all cancers in Alberta is projected to increase by 86% by 2040. In line with these trends, the overall direct cost of cancer management is estimated to increase by 53% in 2040. These estimates and projections are integral to future strategic planning and investment.
Long-Smoldering T-prolymphocytic Leukemia: A Case Report and a Review of the Literature
Authors: Gjelberg Hilde K. , Helgeland Lars , Liseth Knut , Micci Francesca , Sandnes Miriam , Russnes Hege G. , Reikvam Håkon
Published: November 2023

T-prolymphocytic leukemia (T-PLL) is a rare malignancy of mature T-cells with distinct clinical, cytomorphological, and molecular genetic features. The disease typically presents at an advanced stage, with marked leukocytosis, B symptoms, hepatosplenomegaly, and bone marrow failure. It usually follows an aggressive course from presentation, and the prognosis is often considered dismal; the median overall survival is less than one year with conventional chemotherapy. This case report describes a patient with T-PLL who, after an unusually protracted inactive phase, ultimately progressed to a highly invasive, organ-involving disease. After initial treatments failed, a novel treatment approach resulted in a significant response.
Sharing Experience with Anaplastic Lymphoma Kinase Tyrosine Kinase Inhibitors in Lung Cancer: An Italian Expert Panel Discussion
Authors: Gridelli Cesare , Tiseo Marcello , Cortinovis Diego Luigi , Migliorino Maria Rita , Barbieri Vito , Bironzo Paolo , Bearz Alessandra , Attili Ilaria , de Marinis Filippo
Published: November 2023

Background: ALK tyrosine kinase inhibitors (TKIs) have revolutionized the treatment and largely improved the survival outcomes of patients with NSCLC harboring ALK rearrangements. Different ALK TKI compounds have demonstrated antitumor activity in these patients and are available in clinical practice. However, clinical expertise across countries varies according to local regulatory approval of different drugs, identifying multiple treatment scenarios to comply with international guidelines and clinical practice. Methods: A virtual webinar was held on July 2023 to discuss the state of the art and future perspectives in the treatment of ALK rearrangement in advanced NSCLC in Italy. The faculty hosting the webinar was composed of eight medical oncologists from different regions of Italy with clinical expertise in treating patients with lung cancer. Live-shared notes were used to produce a report to serve as the basis of a review manuscript on the topic. Results: Alectinib and brigatinib are the preferred front-line treatment options in Italy, pending approval of the front-line medicine lorlatinib, which would be considered among the choices. Due to a local regulatory limitation of second-line lorlatinib, which is not allowed after front-line brigatinib, alectinib is commonly the preferred front-line choice to follow a sequence of alectinib, followed by lorlatinib, followed by platinum plus pemetrexed chemotherapy. Age and performance status were not considered per se as clinical features influencing treatment choice. However, treatment compliance is deemed a relevant factor in decision making with regard to the number of pills to be administered. In general, given the availability of alternative choices, the spectrum of patients’ comorbidities and polypharmacotherapy interactions should be taken into account in treatment selection according to the toxicity profile of each compound. In addition, several issues were debated with regard to improving treatment outcomes, including testing, brain metastases, and management of an oligoprogressive disease. Conclusions: The treatment scenario of ALK-positive disease is dynamically evolving. Furthermore, not all FDA- and EMA-approved compounds are approved in Italy with the same indications. This influences therapeutic opportunities and increases the need for greater clinical expertise to help and guide treatment selection.
Further Loss of Intertidal Mussel Stands on the Nova Scotia Coast (Canada) after the Passage of Cyclone Lee
Authors: Scrosati Ricardo A.
Published: November 2023

Intertidal mussel stands are common on temperate rocky seashores and host many small invertebrates, so they are important biodiversity reservoirs. Their integrity, however, is being increasingly affected by environmental extremes. An unusual cold snap in Nova Scotia (Canada) in February 2023 was followed by the mass disappearance of mussel stands at mid-to-high elevations in rocky intertidal habitats. The present article presents evidence of significant losses at middle intertidal elevations following the passage of cyclone Lee in September 2023, which created severe surf conditions. The increasing occurrence of successive environmental extremes might challenge the persistence of these important biological systems.
Analysis of Uneven Distribution of Nodes Creating a Percolation Channel in Matrices with Translational Symmetry for Direct Current
Authors: Zukowski Pawel , Okal Pawel , Kierczynski Konrad , Rogalski Przemyslaw , Bondariev Vitalii
Published: November 2023

In this study, the phenomenon of node percolation was tested using the Monte Carlo computer simulation method for square matrices with dimensions L = 55, 101 and 151. The number of samples for each matrix was 5 × 106. The spatial distributions of the coordinates of the nodes creating the percolation channel were determined, and maps of the density distribution of these nodes were created. It has been established that in matrices with finite dimensions, an edge phenomenon occurs, consisting of a decrease in the concentration of nodes creating a percolation channel as one approaches the edge of the matrix. As the matrix dimensions increase, the intensity of this phenomenon decreases. This expands the area in which values close to the maximum occur. The length distributions of the left and right clusters of non-conducting nodes were determined for the situation when the next randomly selected node connects them and thus reaches the percolation threshold. It was found that clusters whose dimensions are close to half of the matrix dimensions are most likely to occur. The research shows that both the values of the standard deviation of the percolation threshold and the intensity of the edge phenomenon are clearly related to the dimensions of the matrices and decrease as they increase.
Are Most Polluted Regions Most Active in Energy Transition Processes? A Case Study of Polish Regions Acquiring EU Funds for Local Investments in Renewable Energy Sources
Authors: Kozera Agnieszka , Standar Aldona , Genstwa Natalia
Published: November 2023

The primary aim of this study was to assess the investment activity of basic local government units in the development of renewable energy sources co-financed by EU funds depending on CO2 emissions and other socio-economic conditions in terms of regions of Poland in the years 2007–2020. Empirical studies aimed at the verification of the research hypothesis that “the greatest investment activity in local projects co-financed from EU funds related to the development of renewable energy sources is observed for local government units in regions with highest CO2 emissions”. Empirical studies were conducted based on data from the Ministry of Investment and Economic Development in Poland, the Local Data Bank, and the National Centre for Emissions Management. Thus, the conducted analyses provide both cognitive and applicatory values for the establishment of an appropriate energy transition policy in individual regions of Poland, which may be implemented by local government authorities within the current financial framework. Data concerning CO2 emissions at the regional level were estimated by applying the original disaggregation method as modified by the authors, which made it possible to fill the research gap resulting from the lack of data on emissions at the regional level. In order to show the regional diversification in investment activity of local government units in terms of renewable energy sources, its multi-faceted analysis was conducted by applying the Ward method. Clusters of regions with similar investment activity of local government units were described based on characteristics included in the typological classification (so-called active characteristics) and selected indexes showing CO2 emission levels, as well as selected socio-economic indexes (so-called passive characteristics). Based on the empirical studies, the research hypothesis presented in this paper was negatively verified. Considering both multiannual financial frameworks, the EU financial support for the development of renewable energy sources was used primarily by local government units of a predominantly agricultural character, and less advanced in terms of their development but exhibiting conditions conducive to renewable energy development.
Analysis of the Attitudes of Central European Small- and Medium-Sized Enterprises towards Adaptation to the Low-Carbon Economy and Its Implementation Barriers
Authors: Rybarova Daniela , Remenova Katarina , Kmety Bartekova Maria , Majduchova Helena
Published: November 2023

As developed regions explore avenues to enhance their industries in order to become climate-neutral, numerous studies have identified distinct factors that may hinder the shift towards a low-carbon economy. The objective of our research was to pinpoint key barriers to adaptation to a low-carbon economy among small- and medium-sized enterprises (SMEs) of Central Europe from the viewpoint of the company’s structure. The aim was to examine whether attitudes towards barriers to adaptation to a low-carbon economy represent a key factor that prevents the faster and more effective uptake of such adaptations by SMEs. Both the industrial and service sectors were considered. A quantitative data collection method, CATI, was employed. Using our methodology, we applied a non-parametric testing procedure, specifically, the Kruskal–Wallis test, to compare more than two independent samples, together with the Mann–Whitney U test. Through this analysis, it was found that companies regard the uncertainty of return on investment and its payback period as the most serious barrier to adaption to a low-carbon economy. Meanwhile, the lack of cooperation with research institutions and universities is perceived as the least important barrier. Companies are critical of existing regulations for adaptation to the low-carbon economy, which do not provide incentives for companies, though sole traders consider this an insignificant barrier. The shift towards a low-carbon economy is one of the greatest challenges of the 21st century. Understanding the initial motivational variables can significantly contribute to the process of transition towards the use of renewable energy sources by companies, regardless of their size or sector.
Practical Dead-Time Control Methodology of a Three-Phase Dual Active Bridge Converter for a DC Grid System
Authors: Choi Hyun-Jun , Ahn Jung-Hoon , Jung Jee-Hoon , Song Sung-Geun
Published: November 2023

An effective dead-time control strategy for the three-phase dual active bridge (3P-DAB) converter of a distribution system is studied to reduce the switching losses of power switches and improve the under-light-load power conversion efficiency. Because of the advantages of a dual-active bridge converter, such as an inherent zero-voltage switching (ZVS) capability without any additional resonant tank and a seamless bi-directional power transition, this is an attractive topology for bi-directional application. The 3P-DAB converter is apt for high-power applications such as aircraft due to an interleaved structure, which can reduce conduction losses. However, the design of the dead time depends on engineering experience and empirical methods. In order to overcome the conventional practicality of the dead-time design method, the effective control of dead time is proposed based on the theoretical analysis. In this paper, the overall explanation of the 3P-DAB converter is shown with operation principles. In addition, the dead-time effect of the 3P-DAB converter is examined and the practical variable dead-time control strategy is studied. Finally, experimental results validate the proposed variable dead-time control strategy using a 25 kW prototype 3P-DAB converter.
Analysis of the Implementation of Virtual Power Plants and Their Impacts on Electrical Systems
Authors: Viana Matheus Sabino , Ramos Dorel Soares , Manassero Junior Giovanni , Udaeta Miguel Edgar Morales
Published: November 2023

The increasing penetration of Distributed Energy Resources (DERs) in Distribution Systems (DSs) has motivated studies on Virtual Power Plants (VPPs). However, few studies have jointly assessed the sizing and economic attractiveness of VPPs from the entrepreneur’s perspective and the potential benefits and impacts on power systems while maintaining the scope to DSs. This study proposes a methodology for sizing VPPs and simulating their economic optimal dispatch and economic attractiveness with a focus on the entrepreneur’s viewpoint. In addition, it also evaluates VPPs’ potential benefits and impacts on a DS or Transmission System (TS) while considering the interface between the Distribution System Operator (DSO) and the Transmission System Operator (TSO). The methodology employs optimization to minimize the Net Present Cost (NPC) of the project, in relation to sizing the DERs, and to obtain the economic optimal dispatch of the BESSs that comprise the VPP. Moreover, a power flow analysis and probabilistic reliability assessment are used to evaluate the benefits and impacts on the power system. The methodology was applied to a case study involving Photovoltaic (PV) systems and Battery Energy Storage Systems (BESSs) used by aggregated medium voltage consumers, which configure Technical Virtual Power Plants (TVPPs) participating in Demand Response (DR) via incentives, with a network model of the Brazilian National Interconnected System (SIN) adapted from the 2030 Ten-Year Energy Expansion Plan (PDE) of the Energy Research Office (EPE), along with data from the Geographic Database of the Distribution Utility (BDGD). The results indicate the economic attractiveness of DERs according to the premises adopted and indicate improvements in TS reliability indexes with the possibility of TVPPs’ dispatch after transmission contingencies.
Federated Adversarial Training Strategies for Achieving Privacy and Security in Sustainable Smart City Applications
Authors: Utomo Sapdo , Rouniyar Adarsh , Hsu Hsiu-Chun , Hsiung Pao-Ann
Published: November 2023

Smart city applications that request sensitive user information necessitate a comprehensive data privacy solution. Federated learning (FL), also known as privacy by design, is a new paradigm in machine learning (ML). However, FL models are susceptible to adversarial attacks, similar to other AI models. In this paper, we propose federated adversarial training (FAT) strategies to generate robust global models that are resistant to adversarial attacks. We apply two adversarial attack methods, projected gradient descent (PGD) and the fast gradient sign method (FGSM), to our air pollution dataset to generate adversarial samples. We then evaluate the effectiveness of our FAT strategies in defending against these attacks. Our experiments show that FGSM-based adversarial attacks have a negligible impact on the accuracy of global models, while PGD-based attacks are more effective. However, we also show that our FAT strategies can make global models robust enough to withstand even PGD-based attacks. For example, the accuracy of our FAT-PGD and FL-mixed-PGD models is 81.13% and 82.60%, respectively, compared to 91.34% for the baseline FL model. This represents a reduction in accuracy of 10%, but this could be potentially mitigated by using a more complex and larger model. Our results demonstrate that FAT can enhance the security and privacy of sustainable smart city applications. We also show that it is possible to train robust global models from modest datasets per client, which challenges the conventional wisdom that adversarial training requires massive datasets.
Quantum Tapsilou—A Quantum Game Inspired by the Traditional Greek Coin Tossing Game Tapsilou
Authors: Kastampolidou Kalliopi , Andronikos Theodore
Published: November 2023

This paper introduces a new quantum game called Quantum Tapsilou that is inspired by the classical traditional Greek coin tossing game tapsilou. The new quantum game, despite its increased complexity and scope, retains the most important characteristic of the traditional game. In the classical game, both players have 14 probability to win. The quantum version retains this characteristic feature, which is that both players have the same probability to win, but only now this probability varies considerably and depends on previous moves and choices. The two most important novelties of Quantum Tapsilou can be attributed to its implementation of entanglement via the use of rotation gates instead of Hadamard gates, which generates Bell-like states with unequal probability amplitudes, and the integral use of groups. In Quantum Tapsilou both players agree on a specific cyclic rotation group of order n, for some sufficiently large n. The game is based on the chosen group, in the sense that both players will draw their moves from its elements. More specifically, both players will pick rotations from this group to realize their actions using the corresponding Ry rotation gates. In the Quantum Tapsilou game, it is equally probable for both players to win. This fact is in accordance with a previous result in the literature showing that quantum games where both players choose their actions from the same group, exhibit perfect symmetry by providing each player with the possibility to pick the move that counteracts the other player’s action.
Inferring Causalities of Environmental and Genetic Factors for Differential Somatic Cell Count and Mastitis Pathogens in Dairy Cows Using Structural Equation Modelling
Authors: Wagner Patricia , Brügemann Kerstin , Yin Tong , Engel Petra , König Sven
Published: November 2023

The aim of this study was to establish and evaluate a structural equation model to infer causal relationships among environmental and genetic factors on udder health. For this purpose, 537 Holstein Friesian cows were genotyped, and milk samples were analyzed for novel traits including differential somatic cell counts and specific mastitis pathogens. In the structural model, four latent variables (intramammary infection (IMI), production, time and genetics) were defined, which were explained using manifest measurable variables. The measurable variables included udder pathogens and somatic differential cell counts, milk composition, as well as significant SNP markers from previous genome-wide associations for major and minor pathogens. The housing system effect (i.e., compost-bedded pack barns versus cubicle barns) indicated a small influence on IMI with a path coefficient of −0.05. However, housing system significantly affected production (0.37), with ongoing causal effects on IMI (0.17). Thus, indirect associations between housing and udder health could be inferred via structural equation modeling. Furthermore, genotype by environment interactions on IMI can be represented, i.e., the detection of specific latent variables such as significant SNP markers only for specific housing systems. For the latent variable genetics, especially one SNP is of primary interest. This SNP is located in the EVA1A gene, which plays a fundamental role in the MAPK1 signaling pathway. Other identified genes (e.g., CTNNA3 and CHL1) support results from previous studies, and this gene also contributes to mechanisms of the MAPK1 signaling pathway.
Early Life Factors and Polycystic Ovary Syndrome in a Swedish Birth Cohort
Authors: Boldis Beata Vivien , Grünberger Ilona , Cederström Agneta , Björk Jonas , Nilsson Anton , Helgertz Jonas
Published: November 2023

Polycystic ovary syndrome (PCOS) is a medical condition with important consequences for women’s well-being and reproductive outcomes. Although the etiology of PCOS is not fully understood, there is increasing evidence of both genetic and environmental determinants, including development in early life. We studied a population of 977,637 singleton women born in in Sweden between 1973 and 1995, followed sometime between the age 15 and 40. The incidence of PCOS was measured using hospital register data during 2001–2012, complemented with information about the women’s, parents’ and sisters’ health and social characteristics from population and health care registers. Cox regression was used to study how PCOS is associated with intergenerational factors, and a range of early life characteristics. 11,594 women in the study sample were diagnosed with PCOS during the follow-up period. The hazard rate for PCOS was increased 3-fold (HR 2.98, 95% CI 2.43–3.64) if the index woman’s mother had been diagnosed with PCOS, and with 1.5-fold (HR 1.51, 95% CI 1.39–1.63) if their mother had diabetes mellitus. We found associations of PCOS with lower (<7) one-minute Apgar score (HR 1.19, 95% CI 1.09–1.29) and with post-term birth (HR 1.19, 95% CI 1.13–1.26). Furthermore, heavy (10+ cigarettes/day) maternal smoking (HR 1.30, 95% CI 1.18–1.44) and maternal obesity (HR 1.90, 95% CI 1.62–2.36) were strongly associated with PCOS. This study finds support for the heritability and fetal origins of PCOS. Risk of PCOS could be reduced by further emphasizing the importance of maternal and early life health.
Experiences of Remote Provision across a Voluntary Sector Organisation Providing Mental Health and Wellbeing Services for Young People
Authors: Worsley Joanne , Hassan Shaima , Nolan Lisa , Corcoran Rhiannon
Published: November 2023

The global COVID-19 pandemic presented not only challenges for services but also opportunities for reflection and change. This study aimed to understand young people, parents/carers, and professionals’ experiences of remote provision across a voluntary sector organization to inform the nature of future delivery. Reflections from professionals (n = 7), young people (n = 7), and parents/carers (n = 2) were collected through semi-structured interviews and focus groups. Data were thematically analysed. Five overarching themes were identified: ‘Accessibility’, ‘Remote therapeutic experiences’, ‘Translating to online’, ‘Spaces of comfort/discomfort’, and ‘Moving towards hybrid provision’. The COVID-19 pandemic changed service provision, notably with accelerated digitalisation. Although the service became more accessible, the digitalisation of services impacted the relational experiences for young people. Nevertheless, online provision was described as a ‘steppingstone’, allowing young people to engage in online therapy or group programmes before transferring to in-person provision. Although remote provision can lead to improvements in young people’s mental health, this format was not suitable for all. When considering future models of provision, assessing needs, preferences, and access to private space and hardware are all important considerations when deciding which format to use to achieve the best possible outcomes.
The Promotion of Mental Health and Prevention of First-Episode Psychosis: A Pilot and Feasibility Non-Randomised Clinical Trial
Authors: Santonja Ayuso Lucia , Ruiz-Hontangas Antonio , Cervantes José Javier González , Martínez Concepción Martínez , Pons Eva Gil , Pons Sonia Ciscar , Pejó Laura Andreu , Carmona-Simarro José Vicente
Published: November 2023

Background: Mental-health-related stigma prevents active help seeking and therefore early therapeutic approaches and the recovery of functionality. National and international agencies recommend the implementation of prevention and mental health promotion programs that support the elimination of stigma in the classroom, since most mental health problems usually start in the adolescent stage. In view of the evidence that teachers present stigmatizing attitudes towards mental health, it has been considered as convenient to carry out an anti-stigma program with the main objective of evaluating the impact of an intervention based on the education and promotion of mental health, aimed at teachers and counsellors of a secondary school. The specific objectives were to get to know which were the most stigmatising attitudes that prevailed in the sample before and after the intervention; to evaluate the knowledge of the teaching staff and counsellors on psychosis before the intervention; to analyse correlations between clinically relevant variables; and assess whether this programme was beneficial and feasible for alphabetising counsellors/teachers of educational centres on stigma and FEP. Methods: This was a non-randomised clinical trial in which a nursing intervention was performed. Tools: a psychosis test (pre), Stigma Attribution Questionnaire (AQ-27) (pre-post), and satisfaction survey (post) were used. The inferential analysis included the Wilcoxon and the Pearson Correlation Test. Results: In the sample (n = 22), the predominant stigmatising attitude was “Help”. The p-values obtained in the Wilcoxon Test were statistically significant, except for “Responsibility” and “Pity”. The following constructs of interest were faced: “Fear”–“Age” and “Professional experience”; and “Help”–“Psychosis test”. Conclusions: Despite the scores obtained in “Responsibility” and “Pity”, the intervention was useful for reducing stigma in the sample. Implications for the profession: There are adolescents who have suffered stigma from their teachers, and consequently have minimized their symptoms and not asked for help. For this reason, we implemented a nursing intervention based on the education and promotion of mental health, with the aim of expanding knowledge and reducing stigma. In fact, this intervention, which we carried out on high school teachers, managed to reduce the majority of stigmatizing attitudes measured on the stigma attribution scale.
Complement System and the Kidney: Its Role in Renal Diseases, Kidney Transplantation and Renal Cell Carcinoma
Authors: Lasorsa Francesco , Rutigliano Monica , Milella Martina , Ferro Matteo , Pandolfo Savio Domenico , Crocetto Felice , Simone Simona , Gesualdo Loreto , Battaglia Michele , Ditonno Pasquale , Lucarelli Giuseppe
Published: November 2023

The crosstalk among the complement system, immune cells, and mediators of inflammation provides an efficient mechanism to protect the organism against infections and support the repair of damaged tissues. Alterations in this complex machinery play a role in the pathogenesis of different diseases. Core complement proteins C3 and C5, their activation fragments, their receptors, and their regulators have been shown to be active intracellularly as the complosome. The kidney is particularly vulnerable to complement-induced damage, and emerging findings have revealed the role of complement system dysregulation in a wide range of kidney disorders, including glomerulopathies and ischemia-reperfusion injury during kidney transplantation. Different studies have shown that activation of the complement system is an important component of tumorigenesis and its elements have been proved to be present in the TME of various human malignancies. The role of the complement system in renal cell carcinoma (RCC) has been recently explored. Clear cell and papillary RCC upregulate most of the complement genes relative to normal kidney tissue. The aim of this narrative review is to provide novel insights into the role of complement in kidney disorders.
Adenoviral Gene Therapy Vectors in Clinical Use—Basic Aspects with a Special Reference to Replication-Competent Adenovirus Formation and Its Impact on Clinical Safety
Authors: Leikas Aleksi J. , Ylä-Herttuala Seppo , Hartikainen Juha E. K.
Published: November 2023

Adenoviral vectors are commonly used in clinical gene therapy. Apart from oncolytic adenoviruses, vector replication is highly undesired as it may pose a safety risk for the treated patient. Thus, careful monitoring for the formation of replication-competent adenoviruses (RCA) during vector manufacturing is required. To render adenoviruses replication deficient, their genomic E1 region is deleted. However, it has been known for a long time that during their propagation, some viruses will regain their replication capability by recombination in production cells, most commonly HEK293. Recently developed RCA assays have revealed that many clinical batches contain more RCA than previously assumed and allowed by regulatory authorities. The clinical significance of the higher RCA content has yet to be thoroughly evaluated. In this review, we summarize the biology of adenovirus vectors, their manufacturing methods, and the origins of RCA formed during HEK293-based vector production. Lastly, we share our experience using minimally RCA-positive serotype 5 adenoviral vectors based on observations from our clinical cardiovascular gene therapy studies.
Sedanolide Activates KEAP1–NRF2 Pathway and Ameliorates Hydrogen Peroxide-Induced Apoptotic Cell Death
Authors: Tabei Yosuke , Abe Hiroko , Suzuki Shingo , Takeda Nobuaki , Arai Jun-ichiro , Nakajima Yoshihiro
Published: November 2023

Sedanolide is a bioactive compound with anti-inflammatory and antitumor activities. Although it has been recently suggested that sedanolide activates the nuclear factor E2-related factor 2 (NRF2) pathway, there is little research on its effects on cellular resistance to oxidative stress. The objective of the present study was to investigate the function of sedanolide in suppressing hydrogen peroxide (H2O2)-induced oxidative damage and the underlying molecular mechanisms in human hepatoblastoma cell line HepG2 cells. We found that sedanolide activated the antioxidant response element (ARE)-dependent transcription mediated by the nuclear translocation of NRF2. Pathway enrichment analysis of RNA sequencing data revealed that sedanolide upregulated the transcription of antioxidant enzymes involved in the NRF2 pathway and glutathione metabolism. Then, we further investigated whether sedanolide exerts cytoprotective effects against H2O2-induced cell death. We showed that sedanolide significantly attenuated cytosolic and mitochondrial reactive oxygen species (ROS) generation induced by exposure to H2O2. Furthermore, we demonstrated that pretreatment with sedanolide conferred a significant cytoprotective effect against H2O2-induced cell death probably due to preventing the decrease in the mitochondrial membrane potential and the increase in caspase-3/7 activity. Our study demonstrated that sedanolide enhanced cellular resistance to oxidative damage via the activation of the Kelch-like ECH-associated protein 1 (KEAP1)–NRF2 pathway.
The Protective Effects of Reineckia carnea Ether Fraction against Alzheimer’s Disease Pathology: An Exploration in Caenorhabditis elegans Models
Authors: Fu Hai-Jun , Zhou Xing-Yue , Li Ya-Ping , Chen Xue , He Yan-Ni , Qin Da-Lian , Yu Lu , Yu Chong-Lin , Wu Jian-Ming , Wu An-Guo , Zhou Xiao-Gang
Published: November 2023

Alzheimer’s disease (AD) presents a significant challenge to global healthcare systems, with current treatments offering only modest relief and often bringing unwanted side effects, necessitating the exploration of more effective and safer drugs. In this study, we employed the Caenorhabditis elegans (C. elegans) model, specifically the AD-like CL4176 strain expressing the human Aβ(1–42) protein, to investigate the potential of Reineckia carnea extract and its fractions. Our results showed that the Reineckia carnea ether fraction (REF) notably diminished the paralysis rates of CL4176 worms. Additionally, REF also attenuated the neurotoxicity effects prompted by Tau proteins in the BR5270 worms. Moreover, REF was observed to counteract the accumulation of Aβ and pTau proteins and their induced oxidative stress in C. elegans AD-like models. Mechanistic studies revealed that REF’s benefits were associated with the induction of autophagy in worms; however, these protective effects were nullified when autophagy-related genes were suppressed using RNAi bacteria. Together, these findings highlight Reineckia carnea ether fraction as a promising candidate for AD treatment, warranting further investigation into its autophagy-inducing components and their molecular mechanisms.
Smooth Muscle Actin as a Criterion for Gravisensitivity of Stomach and Jejunum in Laboratory Rodents
Authors: Samoilenko Tatyana , Shishkina Viktoriya , Antakova Lyubov , Goryushkina Yelena , Kostin Andrey , Buchwalow Igor , Tiemann Markus , Atiakshin Dmitrii
Published: November 2023

Smooth muscle tissue (SMT) is one of the main structural components of visceral organs, acting as a key factor in the development of adaptive and pathological conditions. Despite the crucial part of SMT in the gastrointestinal tract activity, the mechanisms of its gravisensitivity are still insufficiently studied. The study evaluated the content of smooth muscle actin (α-SMA) in the membranes of the gastric fundus and jejunum in C57BL/6N mice (30-day space flight), in Mongolian gerbils Meriones unguiculatus (12-day orbital flight) and after anti-orthostatic suspension according to E.R. Morey-Holton. A morphometric analysis of α-SMA in the muscularis externa of the stomach and jejunum of mice and Mongolian gerbils from space flight groups revealed a decreased area of the immunopositive regions, a fact indicating a weakening of the SMT functional activity. Gravisensitivity of the contractile structures of the digestive system may be due to changes in the myofilament structural components of the smooth myocytes or myofibroblast actin. A simulated antiorthostatic suspension revealed no significant changes in the content of the α-SMA expression level, a fact supporting an alteration in the functional properties of the muscularis externa of the digestive hollow organs under weightless environment. The data obtained contribute to the novel mechanisms of the SMT contractile apparatus remodeling during orbital flights and can be used to improve preventive measures in space biomedicine.
Effects of Segment Length and Crosslinking via POSS on the Calorimetric and Dynamic Glass Transition of Polyurethanes with Aliphatic Hard Segments
Authors: Raftopoulos Konstantinos N. , Klonos Panagiotis A. , Tworzydło Patrycja , Ozimek Jan , Hebda Edyta , Kyritsis Apostolos , Pielichowski Krzysztof
Published: November 2023

The glass transition in polyurethanes is a complicated phenomenon governed by a multitude of factors, including the microphase separation, which in turn depends strongly on the molar mass of the hard and soft segments, as well as the presence of additives. In this work, we study the effects of the segments’ length on the microphase separation and consequently on the calorimetric and dynamic glass transition of a polyurethane with aliphatic, “flexible” hard segments. It is found that the dependence of the calorimetric glass transition follows the same principles as those in systems with aromatic hard segments. Strikingly, however, the dynamic glass transition, as studied by dielectric spectroscopy, shows a slowing down of its dynamics despite a decrease in Tg. This discrepancy is discussed in terms of the strong dielectric response of the flexible segments, especially those close to the interface between the hard domains and soft phase, as opposed to a weak thermal one. In addition, polyhedral oligomeric silsesquioxanes (POSS) are introduced in the soft phase of the three matrices as crosslinking centres. This modification has no visible effect on the calorimetric glass transition; nevertheless, it affects the microphase separation and the dielectric response in a non-monotonic manner.
An Effective Ensemble Convolutional Learning Model with Fine-Tuning for Medicinal Plant Leaf Identification
Authors: Hajam Mohd Asif , Arif Tasleem , Khanday Akib Mohi Ud Din , Neshat Mehdi
Published: November 2023

Accurate and efficient medicinal plant image classification is of utmost importance as these plants produce a wide variety of bioactive compounds that offer therapeutic benefits. With a long history of medicinal plant usage, different parts of plants, such as flowers, leaves, and roots, have been recognized for their medicinal properties and are used for plant identification. However, leaf images are extensively used due to their convenient accessibility and are a major source of information. In recent years, transfer learning and fine-tuning, which use pre-trained deep convolutional networks to extract pertinent features, have emerged as an extremely effective approach for image-identification problems. This study leveraged the power by three-component deep convolutional neural networks, namely VGG16, VGG19, and DenseNet201, to derive features from the input images of the medicinal plant dataset, containing leaf images of 30 classes. The models were compared and ensembled to make four hybrid models to enhance the predictive performance by utilizing the averaging and weighted averaging strategies. Quantitative experiments were carried out to evaluate the models on the Mendeley Medicinal Leaf Dataset. The resultant ensemble of VGG19+DensNet201 with fine-tuning showcased an enhanced capability in identifying medicinal plant images with an improvement of 7.43% and 5.8% compared with VGG19 and VGG16. Furthermore, VGG19+DensNet201 can outperform its standalone counterparts by achieving an accuracy of 99.12% on the test set. A thorough assessment with metrics such as accuracy, recall, precision, and the F1-score firmly established the effectiveness of the ensemble strategy.
Efficient Resource Utilization in IoT and Cloud Computing
Authors: Prasad Vivek Kumar , Dansana Debabrata , Bhavsar Madhuri D. , Acharya Biswaranjan , Gerogiannis Vassilis C. , Kanavos Andreas
Published: November 2023

With the proliferation of IoT devices, there has been exponential growth in data generation, placing substantial demands on both cloud computing (CC) and internet infrastructure. CC, renowned for its scalability and virtual resource provisioning, is of paramount importance in e-commerce applications. However, the dynamic nature of IoT and cloud services introduces unique challenges, notably in the establishment of service-level agreements (SLAs) and the continuous monitoring of compliance. This paper presents a versatile framework for the adaptation of e-commerce applications to IoT and CC environments. It introduces a comprehensive set of metrics designed to support SLAs by enabling periodic resource assessments, ensuring alignment with service-level objectives (SLOs). This policy-driven approach seeks to automate resource management in the era of CC, thereby reducing the dependency on extensive human intervention in e-commerce applications. This paper culminates with a case study that demonstrates the practical utilization of metrics and policies in the management of cloud resources. Furthermore, it provides valuable insights into the resource requisites for deploying e-commerce applications within the realms of the IoT and CC. This holistic approach holds the potential to streamline the monitoring and administration of CC services, ultimately enhancing their efficiency and reliability.
Impact of Long-Term Floods on Spatial Dynamics of Myrmica scabrinodis, a Host Ant of a Highly Threatened Scarce Large Blue (Phengaris teleius)
Authors: Močilar Mitja , Jerina Klemen , Verovnik Rudi
Published: November 2023

Extensively used wet meadows with high species diversity are under threat in Europe by anthropogenic pressure. The increasing frequency of prolonged flooding is emerging as an additional threat to this fragile environment. In our study, we investigated how prolonged flooding affects the spatial distribution and temporal dynamics (through mortality and recolonization process) of the host ant species Myrmica scabrinodis, which is essential for the survival of the endangered Scarce large blue (Phengaris teleius). The study was conducted in the flood-prone Ljubljansko barje plain situated on the southern edge of the species’ global range. Prolonged flooding in the study area, possibly affecting the past and current distribution of the host ant M. scabrinodis, was recorded in 2010, 2013, and 2017. In 2020, we set 160 ant traps to estimate the distribution of host ants in a system of meadows covering the entire gradient of flood history. Results indicate that M. scabrinodis survives the flooding for up to three days, starting to disappear if flooding persists longer. After the flooding recedes, ants gradually recolonize empty habitats from the surrounding upland refugia. Our spatial analyses predict that the average recolonization speed was about 29 m per year and that in a year, ants compensate for the mortality effects of 1.8 days of flooding by recolonization in a year. These results show that flooding should be considered as an additional (in some areas, a major) threat to the endangered P. teleius through its deleterious effects on the host ant species.
Research Progress on the Species and Diversity of Ants and Their Three Tropisms
Authors: Dong Hejie , Huang Xinyi , Gao Qingqing , Li Sihan , Yang Shanglin , Chen Fajun
Published: November 2023

Ants are one of the largest insect groups, with the most species and individuals in the world, and they have an important ecological function. Ants are not only an important part of the food chains but are also one of the main decomposers on the Earth; they can also improve soil fertility, etc. However, some species of ants are harmful to human beings, which leads to people’s panic or worry about coming into contact with these insects during their daily home life or in their tourism or leisure activities. The presence of ants in indoor living facilities and in outdoor green spaces, parks, gardens, and tourist attractions seriously interferes with the leisure life and entertainment activities of all people (especially children). How can we control ants in these environments? Do we kill them by spraying insecticides, or do we adopt green prevention and control technology for the ecological management of ants? This topic is related to healthy life for the public and the protection of the ecological environment. In this paper, the species and diversity of ants are introduced, and research progress regarding ant tropism is introduced according to the three aspects of phototaxis, chromotaxis, and chemotaxis (i.e., “3-tropisms”). The research on repellent substances from plants and insects and the related ant attractants are also summarized, analyzed, and discussed, in order to help the research and application of green prevention and control technology for ant diversity protection and conservation.