bluuebunny/crossref_metadata_2025_split huggingface dataset:
Small extrachromosomal circular DNAs as biomarkers for multi‐cancer diagnosis and monitoring
Authors: Luo Xuanmei , Zhang Lili , Cui Jian , An Qi , Li Hexin , Zhang Zaifeng , Sun Gaoyuan , Huang Wei , Li Yifei , Li Chang , Jia Wenzhuo , Zou Lihui , Zhao Gang , Xiao Fei 
Published: August 2023

AbstractBackgroundSmall extrachromosomal circular DNAs (eccDNAs) have the potential to be cancer biomarkers. However, the formation mechanisms and functions of small eccDNAs selected in carcinogenesis are not clear, and whether the small eccDNA profile in the plasma of cancer patients represents that in cancer tissues remains to be elucidated.MethodsA novel sequencing workflow based on the nanopore sequencing platform was used to sequence naturally existing full‐length small eccDNAs in tissues and plasma collected from 25 cancer patients (including prostate cancer, hepatocellular carcinoma and colorectal cancer), and from an independent validation cohort (including 7 cancer plasma and 14 healthy plasma).ResultsCompared with those in non‐cancer tissues, small eccDNAs detected in cancer tissues had a significantly larger number and size (P = 0.040 and 2.2e‐16, respectively), along with more even distribution and different formation mechanisms. Although small eccDNAs had different general characteristics and genomic annotation between cancer tissues and the paired plasma, they had similar formation mechanisms and cancer‐related functions. Small eccDNAs originated from some specific genes had great multi‐cancer diagnostic value in tissues (AUC ≥ 0.8) and plasma (AUC > 0.9), especially increasing the accuracy of multi‐cancer prediction of CEA/CA19‐9 levels. The high multi‐cancer diagnostic value of small eccDNAs originated from ALK&ETV6 could be extrapolated from tissues (AUC = 0.804) to plasma and showed high positive predictive value (100%) and negative predictive value (82.35%) in a validation cohort.ConclusionsAs independent and stable circular DNA molecules, small eccDNAs in both tissues and plasma can be used as ideal biomarkers for cost‐effective multi‐cancer diagnosis and monitoring.
SMAD4: A critical regulator of cardiac neural crest cell fate and vascular smooth muscle development
Authors: Alexander Brianna E. , Zhao Huaning , Astrof Sophie 
Published: August 2023

AbstractBackgroundDuring embryogenesis, cardiac neural crest‐derived cells (NCs) migrate into the pharyngeal arches and give rise to the vascular smooth muscle cells (vSMCs) of the pharyngeal arch arteries (PAAs). vSMCs are critical for the remodeling of the PAAs into their final adult configuration, giving rise to the aortic arch and its arteries (AAAs).ResultsWe investigated the role of SMAD4 in NC‐to‐vSMC differentiation using lineage‐specific inducible mouse strains. We found that the expression of SMAD4 in the NC is indelible for regulating the survival of cardiac NCs. Although the ablation of SMAD4 at E9.5 in the NC lineage led to a near‐complete absence of NCs in the pharyngeal arches, PAAs became invested with vSMCs derived from a compensatory source. Analysis of AAA development at E16.5 showed that the alternative vSMC source compensated for the lack of NC‐derived vSMCs and rescued AAA morphogenesis.ConclusionsOur studies uncovered the requisite role of SMAD4 in the contribution of the NC to the pharyngeal arch mesenchyme. We found that in the absence of SMAD4+ NCs, vSMCs around the PAAs arose from a different progenitor source, rescuing AAA morphogenesis. These findings shed light on the remarkable plasticity of developmental mechanisms governing AAA development.
Correlation between E‐cadherin/β‐catenin, Vimentin expression, clinicopathologic features and drug resistance prediction in naïve prostate cancer: A molecular and clinical study
Authors: Said Rahma , Hernández‐Losa Javier , Derouiche Amine , Moline Teresa , de Haro Rosa Somoza Lopez , Zouari Skander , Blel Ahlem , Rammeh Soumaya , Ouerhani Slah 
Published: August 2023

SummaryAlthough epithelial–mesenchymal markers play an important role in prostate cancer (PC), further research is needed to better understand their utility in diagnosis, cancer progression prevention, and treatment resistance prediction. Our study included 111 PC patients who underwent transurethral resection, as well as 16 healthy controls. Reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) was used to examine the expression of E‐cadherin, β‐catenin, and Vimentin. We found that E‐cadherin and β‐catenin were underexpressed in primary PC tissues. E‐cadherin expression was found to be inversely associated with prostate‐specific antigen progression (PSA‐P; serum marker of progression; p = 0.01; |r| = 0.262). Furthermore, the underexpression of two markers, E‐cadherin and β‐catenin, was found to be associated with advanced tumor stage and grade (p < 0.05). On the other hand, Vimentin was overexpressed in PC patients with a fold change of 2.141, and it was associated with the diagnosis, prognosis, and prediction of treatment resistance to androgen deprivation therapy (p = 0.002), abiraterone‐acid (p = 0.001), and taxanes (p = 0.029). Moreover, the current study highlighted that poor survival could be significantly found in patients who progressed after primary surgery, did not use drugs, and expressed these genes aberrantly. In Cox regression multivariate analysis (p < 0.05), a positive correlation between the Vimentin marker and coronary heart disease in PC patients was identified (p = 0.034). In summary, the present study highlights the diagnostic (p < 0.001), prognostic (p < 0.001), and therapeutic potential of Vimentin in primary PC (p < 0.05), as well as its implications for cardiovascular disease. Furthermore, we confirm the potential prognostic value of E‐cadherin and β‐catenin.
Avian species functional diversity and habitat use: The role of forest structural attributes and tree diversity in the Midlands Mistbelt Forests of KwaZulu‐Natal, South Africa
Authors: Bitani Nasiphi , Cordier Craig P. , Ehlers Smith David A. , Ehlers Smith Yvette C. , Downs Colleen T. 
Published: August 2023

AbstractForest transformation has major impacts on biodiversity and ecosystem functioning. Identifying the influence of forest habitat structure and composition on avian functional communities is important for conserving and managing forest systems. This study investigated the effect of forest structure and composition characteristics on bird species community structure, habitat use and functional diversity in 14 Mistbelt Forest patches of the Midlands of KwaZulu‐Natal in South Africa. We surveyed bird communities using point counts. We quantified bird functional diversity for each forest patch using three diversity indices: functional richness, functional evenness and functional divergence. We further assessed species‐specific responses by focussing on three avian forest specialists, orange ground‐thrush Geokichla gurneyi, forest canary Crithagra scotops and Cape parrot Poicephalus robustus. We found that bird community and forest‐specialist species responses to forest structure and tree species diversity differed. Also, forest structural complexity, canopy cover and tree species richness were the main forest characteristics better at explaining microhabitat influence on bird functional diversity. Forest patches with relatively high structural complexity and tree species richness had higher functional richness. Different structural characteristics influenced habitat use by the three forest specialists. Tree species diversity influenced C. scotops and G. gurneyi positively, while P. robustus responded negatively to forest patches with high tree species richness. Our study showed that site‐scale forest structure and composition characteristics are important for bird species richness and functional richness. Forest patches with high tree species diversity and structural complexity should be maintained to conserve forest specialists, bird species richness and functional richness.
What drives seed dispersal effectiveness?
Authors: Nevo Omer , Filla Caitlynn , Valenta Kim , Schupp Eugene W. 
Published: August 2023

AbstractSeed dispersal is a critical phase in plant reproduction and forest regeneration. In many systems, the vast majority of woody species rely on seed dispersal by fruit‐eating animals. Animals differ in their size, movement patterns, seed handling, gut physiology, and many other factors that affect the number of seeds they disperse, the quality of treatment each individual seed receives, and consequently their relative contribution to plant fitness. The seed dispersal effectiveness framework (SDE) was developed to allow systematic and standardized quantification of these processes, offering a potential for understanding the large‐scale dynamics of animal–plant interactions and the ecological and evolutionary consequences of animal behavior for plant reproductive success. Yet, despite its wide acceptance, the SDE framework has primarily been employed descriptively, almost always in the context of local systems. As such, the drivers of variation in SDE across systems and the relationship between its components remain unknown. We systematically searched studies that quantified endozoochorous SDE for multiple animal species dispersing one or more plant species in a given system and offered an integrative examination of the factors driving variation in SDE. Specifically, we addressed three main questions: (a) Is there a tradeoff between high dispersal quality and quantity? (b) Does animal body mass affect SDE or its main components? and (c) What drives more variation in SDE, seed dispersal quality, or quantity? We found that: (a) the relationship between quality and quantity is mediated by body size; (b) this is the result of differential relationships between body mass and the two components, while total SDE is unaffected by body mass; (c)neither quality nor quantity explain more variance in SDE globally. Our results also highlight the need for more standardized data to assess large‐scale patterns in SDE.
Comparison of metabolic rate between two genetically distinct populations of lake sturgeon
Authors: Yoon Gwangseok R. , Thorstensen Matt J. , Bugg William S. , Bouyoucos Ian A. , Deslauriers David , Anderson W. Gary 
Published: August 2023

AbstractEnvironmental temperatures differ across latitudes in the temperate zone, with relatively lower summer and fall temperatures in the north leading to a shorter growing season prior to winter. As an adaptive response, during early life stages, fish in northern latitudes may grow faster than their conspecifics in southern latitudes, which potentially manifests as different allometric relationships between body mass and metabolic rate. In the present study, we examined if population or year class had an effect on the variation of metabolic rate and metabolic scaling of age‐0 lake sturgeon (Acipenser fulvescens) by examining these traits in both a northern (Nelson River) and a southern (Winnipeg River) population. We compiled 6 years of data that used intermittent flow respirometry to measure metabolic rate within the first year of life for developing sturgeon that were raised in the same environment at 16°C. We then used a Bayesian modeling approach to examine the impacts of population and year class on metabolic rate and mass‐scaling of metabolic rate. Despite previous reports of genetic differences between populations, our results showed that there were no significant differences in standard metabolic rate, routine metabolic rate, maximum metabolic rate, and metabolic scaling between the two geographically separated populations at a temperature of 16°C. Our analysis implied that the lack of metabolic differences between populations could be due to family effects/parental contribution, or the rearing temperature used in the study. The present research provided insights for conservation and reintroduction strategies for these populations of lake sturgeon, which are endangered or threatened across most of their natural range.
Genomic analysis reveals complex population structure within the smooth newt, Lissotriton vulgaris, in Central Europe
Authors: Herczeg Dávid , Palomar Gemma , Zieliński Piotr , van Riemsdijk Isolde , Babik Wiesław , Dankovics Róbert , Halpern Bálint , Cvijanović Milena , Vörös Judit 
Published: August 2023

AbstractSpecies with wide‐range distributions usually display high genetic variation. This variation can be partly explained by historical lineages that were temporally isolated from each other and are back into secondary reproductive contact, and partly by local adaptations. The smooth newt (Lissotriton vulgaris) is one of the most widely distributed amphibians species across Eurasia and forms a species complex with a partially overlapping distribution and morphology. In the present study, we explored the population genomic structure of smooth newt lineages in the Carpathian Basin (CB) relying on single‐nucleotide polymorphisms. Our dataset included new and previously published data to study the secondary contact zone between lineages in the CB and also tested for the barrier effect of rivers to gene flow between these lineages. We confirmed the presence of the South L. v. vulgaris Lineage distributed in Transdanubia and we provided new distribution records of L. v. ampelensis inhabiting the eastern territories of the CB. High genetic diversity of smooth newts was observed, especially in the North Hungarian Mountains and at the interfluves of the main rivers in the South with four distinct lineages of L. v. vulgaris and one lineage of L. v. ampelensis showing a low level of admixture with the spatially closest L. v. vulgaris lineage. Moreover, admixture detected at the interfluve of the main rivers (i.e. Danube and Tisza) suggested a secondary contact zone in the area. Finally, we found that the river Danube has a very weak effect on population divergence, while the river Tisza is a geographical barrier limiting gene flow between smooth newt lineages. As the range boundaries of L. v. vulgaris and L. v. ampelensis in the CB coincide with the river Tisza, our study underpins the influence of rivers in lineage diversification.
Lagging behind the Western countries: the knowledge gaps of gender differences in heart failure in Asia
Authors: Qiu Weida , Cai Anping , Li Liwen , Feng Yingqing 
Published: August 2023

AbstractGender differences in heart failure (HF), ranging from epidemiological and pathophysiological factors to therapeutic response and prognosis, have been well documented in Western countries, especially in Europe and North America. The above gender differences in HF found in Westerners are rarely investigated in Asians. In this review, we explore the worrying knowledge gap on the gender differences in HF that existed in Asia in contrast with Western populations based on the following four aspects: epidemiology, risk factors, therapy, and prognosis. Finally, we conclude that investigations of gender differences in HF in Asia lag behind those in Europe and North America. Future work is required to establish and better use the high‐level, population‐based cohorts and develop our own high‐quality, convincing clinical trials to deliver robust gender‐specific conclusions in Asia.
Synthesis of Deuterated and Protiated Triacylglycerides by Using 1,1’‐Carbonyldiimidazole Activated Fatty Acids
Authors: Schwärzer Kuno , Heiden‐Hecht Theresia , Chen Yao , Holderer Olaf , Frielinghaus Henrich , Li Peixun , Allgaier Jürgen 
Published: August 2023

AbstractSynthetic model triacylglyceride oils are important compounds for applications in pharmaceutical and food chemistry. Herein, a practical and highly efficient methodology for the synthesis of saturated and unsaturated triacylglycerides utilizing saturated and unsaturated fatty acids activated by 1,1’‐carbonyldiimidazole (CDI) has been developed and applied in the synthesis of deuterated medium chain triglyceride (MCT) oil for studies of plant‐based and diary food emulsions. The deuterium labelled compounds were used to gain new insight into the mechanism of the reaction, which was confirmed by density‐functional theory (DFT) calculations.
System verification via Model‐Checking: A case study of an autonomous multi‐differential drive robot
Authors: Phillips Ibukun , Kenley C. Robert 
Published: August 2023

AbstractModel‐Based Systems Engineering (MBSE) has been utilized in practice to design and behavioral modeling cyber‐physical systems. The Vee model helps frame MBSE's lifecycle approach, with system verification a vital aspect of the qualification process. However, popular modeling language tools in MBSE, such as Systems Modeling Language (SysML), are incapable of formally verifying these systems. Model checking allows for the development of formal system models similar in abstraction to SysML models for automatically checking if these formal models satisfy formal specifications. We propose an approach to translate behavioral diagrams in SysML, such as state‐machine diagrams, to the popular symbolic model checker NuSMV for formal verification. As a case study, we apply this process to autonomous multi‐differential drive robots (DDR). Subsequently, the NuSMV model is verified against some formal operational specifications obtained from the requirements diagram of the DDR. This system verification approach can help System Engineers identify design flaws or incorrect modeling or specifications that could be missed during the design phase through the results of the model checking process.
ASPICE compliance development of Cyber‐Physical Systems by using Model‐Based Systems Engineering
Authors: Fanmuy Gauthier , Hassan Bassem 
Published: August 2023

AbstractCurrent automotive Industry is facing numerous challenges. Business model is transitioning from ownership to shared mobility. Mobility of the future is becoming smarter, safer, more secured and connected. Distributed interconnected automotive systems will deliver added‐value mobility services. In the meantime, industrial standards require description of systems engineering practices as well as the practices justification. Automotive SPICE (ASPICE), a standard of software development best practices for automotive industry, for example, was one of the first to support the development of system and software now include hardware and cybersecurity. Traditional systems engineering development approaches are not any more appropriate. The current automotive system complexity requires new approaches like Model‐Based Systems Engineering (MBSE), using modeling and simulation. To address compliance to industry standards, traditional quality approaches consisting of or defining a quality system with a set of processes (e.g. Requirement elicitation process, documentation process…) are no more sufficient. Addressing these challenges require a digital transformation with two pillars. The first pillar is an MBSE methodology such as Cyber MagicGrid (Dassault Systèmes MBSE method) to define a set of best practices to develop a system. The second pillar is a quality management system that relies on the MBSE methodology rather than on a set of enterprise processes to address compliance with standards. Benefits of this approach is in acceleration of the digital enterprise transformation which is achieved by capitalizing the know‐how and considering the industry standards constraints.
Model‐based Framework for Data and Knowledge‐Driven Systems Architecting Demonstrated on a Hydrogen‐Powered Concept Aircraft
Authors: Kuelper Nils , Bielsky Thimo , Broehan Jasmin , Thielecke Frank 
Published: August 2023

AbstractAircraft development is a protracted process over many years. Novel concept aircraft with new energy sources and disruptive systems technologies are investigated during the aircraft conceptual design phase with the goal to achieve sustainable aviation. Current development cycles need to be accelerated to reduce time to market and development costs of novel aircraft, while still handling complexity and uncertainty of systems technologies. Therefore, a holistic framework for knowledge‐based systems architecting using a model‐based systems engineering approach is presented. This framework has the purpose to conserve and provide knowledge, i.e., information, data, and experiences about existing systems architectures, to the engineer. The developed framework consists of a database concept, a method for model‐based systems architecting, and an interface to the overall systems design software toolGeneSys. Based on evaluating different modeling languages and tools,MathWorks System Composeris selected as most suitable tool for knowledge‐based systems architecting. The developed framework is then demonstrated by conserving and reusing formalized knowledge for the design of a novel hydrogen‐powered concept aircraft. On‐board systems architecture models are saved in a database and automatically recreated reducing development time. The complete graphical representation could not yet be stored in a formalized manner partly reducing the advantage of a clear representation of model‐based systems architecting. However, this did not reduce automatic recreation and evaluation capabilities.
Exertional Heat Strain Detection: Application of the Human Performance Model Based Systems Engineering System Architecture (MBSE‐SA)
Authors: Sarathi Tara , Morris Heather , Collins Paula , Shatz Michael 
Published: August 2023

AbstractExertional Heat Illness is a significant health concern for the US military, with over 12,300 incidents having occurred during the last five years. In order to help implement preventative measures, wearable devices can be used to provide military leaders with real‐time physiological status monitoring of warfighters. While there are a large number of commercial‐off‐the‐shelf (COTS) wearable devices that could be used for this purpose, not every wearable device is suitable for every military use case. To expedite the process of recommending which wearable systems are suitable for a variety of military use cases, we utilized the Wearables Model Based Systems Engineering System Architecture (MBSE‐SA) developed in our previous work. In addition, we developed a cost‐benefit simulation within the MBSE‐SA to allow users to visualize the cost impact of a chosen system on heat‐related medical costs.
Using model‐based systems engineering to design system‐based digital twins
Authors: Pereira Pessoa Marcus Vinicius , Lopes Schuch Ana Paula , Bezerra Juliana Melo 
Published: August 2023

AbstractAlthough the application of model‐based systems engineering (MBSE) is an alternative for designing digital twins (DTs), MBSE possesses a steep learning curve, and quite often companies struggle to translate its theoretical benefits into their reality. Furthermore, the challenge of determining the DT model's fidelity, which brings balance between simulation accuracy and development costs, increases the modelling task difficulty. This paper presents the initial results from the research into facilitating the design of a system‐based DT, where various models are combined to obtain the desired representation of reality. The main contribution of this paper is towards MBSE practice, where a simplified eight‐step MBSE modelling approach for system‐based DTs is proposed. The modelling approach begins with the existing physical product and the need for a DT and results in a simulation model that constitutes the core of an actionable virtual twin. To shorten the MBSE learning curve, a set of guidelines is proposed to delimitate the Systems Modelling Language (SysML) use in Eclipse Papyrus, and a Python parser was built to convert the SysML models' information into the simulation model. The approach, guidelines and parser are analysed via an application example. In this example, the model's creation, validation and use are illustrated. The initial results indicate that the approach and modelling guidelines provide the necessary scaffolding for simplifying and facilitating MBSE application and SysML use in the design of system‐based DTs.