bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Digital Twin-Related Competences in Manufacturing
Authors: Timperi Mira , Kokkonen Kirsi , Donoghue Ilkka , Hannola Lea , Elfvengren Kalle 
Published: January 2025

Abstract
Digital transformation has enabled data-based digital technology solutions that provide value for manufacturing businesses. One example of such a solution is the digital twin (DT), a multipurpose virtual representation of a real-life product or process. In manufacturing, a DT solution can enhance production, maintenance, decision-making, training, and many other areas. However, in addition to the technological solution, companies need a wide range of competences, resources, and collaboration practices to manage and adopt the solution. Yet, companies do not always identify these prerequisites sufficiently, leading to unrealized potential and abandoned and expensive implementation pilots. This chapter aims to tackle the issue by investigating what competences are needed to utilize DTs in the manufacturing industry. The research method was qualitative; it consisted of semi-structured thematic interviews and focus group research among manufacturing professionals. Based on a literature review and empirical data analysis, a four-field framework with technological, cognitive, soft, and managerial competences was formed. The framework and its interdependent competence classes provide manufacturing professionals with a tool to estimate their situation and identify development areas when planning or adopting a DT solution. In addition, the results highlight the importance of sufficient resources, clear ownership, and comprehensive management of the planned solution.
Navigating the Innovation Process: Challenges Faced by Deep-Tech Startups
Authors: Kask Johan , Linton Gabriel 
Published: January 2025

Abstract
This study examines the challenges faced by deep technology (deep tech) startups in the innovation process, with a focus on the financing of their long and capital-intensive development processes. Two case companies were studied—Alpha Robotics and Beta Robotics—to analyze how their different approaches to the innovation process affected their ability to secure financing and commercialize their products. Results showed that Alpha Robotics’ product had widespread market interest, but difficulty charging a high margin on the product, while Beta Robotics had a more specific market, making it more difficult to secure customers. The research further highlighted the need for an effective innovation system that provides support for deep-tech companies in terms of funding, access to human capital, and resources for industrialization processes. To better support deep-tech startups, the innovation system should invest in innovation environments that have the breadth and depth of knowledge needed to identify any deficiencies in human capital and reduce information asymmetry. Finally, close cooperation with the startup company is essential to reduce the risks associated with the financing of deep-tech projects.
Biomechanics of flail chest injuries: tidal volume and respiratory work changes in multiple segmental rib fractures
Authors: Zierke Julian N. , Duda Georg N. , Braun Karl F. , Jaecker Vera , Stöckle Ulrich , Damm Philipp , Heyland Mark , Niemann Marcel 
Published: January 2025

Abstract

Background
Flail chest (FC) injuries are segmental osseous injuries of the thorax that typically result from high-energy blunt trauma and regularly occur in multiple trauma (MT) patients. FC injuries are associated with paradoxical chest wall movements and, thus, have a high risk of respiratory insufficiency or even death. An increasing number of studies recommend an early surgical stabilization of FC injuries, but a definite trigger that would indicate surgery has, thus far, not been identified.

Methods
Based on real-world injury computed tomography (CT) data, this study aimed to establish a finite elements (FE) model of a thorax simulating spontaneous breathing. The model is based on a 0.625 mm slice thickness CT data set. In this FE model, various FC injury patterns were implemented to examine the impact of an increasingly large flail segment on tidal volume and respiratory work. The impact of the segmental defect sizes on the outcome measures mentioned above was examined using correlation analyses.

Results
The FE model in this study reliably simulated the spontaneous breathing patterns of an actively breathing patient in an uninjured setting as a reference and showed clinically realistic movements of the flail segments for various injury settings. Correlation analysis showed a significant negative correlation between the FC size and tidal volume (R2 = 0.852, p = 0.003), while absolute (R2 = 0.845, p = 0.0096) and relative loss (R2 = 0.844, p = 0.0096) of tidal volume concerning the intact model and the compensatory respiratory work required (R2 = 0.816, p = 0.0136) were positively correlated with FC size.

Conclusion
This study presents an FE model of the thorax of a patient who presented to our clinic as an MT patient with an FC injury. The FE model fulfills physiologic active breathing patterns and simulates an FC injury’s paradoxical movement, realistically depicting clinical observations. The FE model showed that the number of consecutive ribs involved in the flail segment and the length of the flail segment significantly impacted active breathing concerning tidal volumes and respiratory work. With this, we have made the first step to define a trigger for surgery.
In silico functional analysis of the human, chimpanzee, and gorilla MHC-A repertoires
Authors: Dodd Griffin Kutler , Keşmir Can 
Published: January 2025

Abstract
T cells recognize peptides displayed on the surface of cells on MHC molecules. Genetic variation in MHC genes alters their peptide-binding repertoire and thus influences the potential immune response generated against pathogens. Both gorillas and chimpanzees show reduced diversity at their MHC class I A (MHC-A) locus compared to humans, which has been suggested to be the result of a pathogen-mediated selective sweep. More specifically, gorillas lack A3 lineage alleles while chimpanzees seem to have lost the A2 lineage. While previous studies showed this using phylogenetic analysis, here, we take an in silico functional approach and use the peptide-MHC binding prediction software NetMHCpan to examine the peptide-binding repertoires of common human, chimpanzee, and gorilla MHC-A molecules. We find that both gorillas and chimpanzees lack the A02 peptide binding specificity (supertype) despite gorillas being expected to have this specificity since they kept the A2 lineage. Additionally, we show that human MHC molecules with the A02 specificity bind fewer virus-derived peptides than other MHC molecules. We also do not find differential presentation of self-peptides by the A02 supertype, making the purpose of maintaining this specificity in high frequencies in the human population unclear. Taken together, we hypothesize that poor presentation of viral peptides by A02 supertype MHC molecules could have resulted in a selective sweep in chimpanzees and/or gorillas, though we could not identify a specific virus that may have caused this sweep.
VEXAS syndrome: is it more a matter of inflammation or hematopoietic clonality? A case series approach to diagnosis, therapeutic strategies and transplant management
Authors: Costa Alessandro , Pilo Federica , Pettinau Martina , Piga Matteo , Carboni Pietro , Piras Eugenia , Targhetta Clara , Rojas Rodrigo , Deias Paola , Mulas Olga , Caocci Giovanni 
Published: January 2025

Abstract
VEXAS syndrome is a complex hemato-inflammatory disorder, driven by somatic mutations in the UBA1 gene within hematopoietic precursor cells. It is characterized by systemic inflammation, rheumatological manifestations, and frequent association with myelodysplastic syndrome (MDS). We present a series of four VEXAS cases, all of which include concomitant MDS, each displaying distinct genetic signatures and clinical features at diagnosis, with a focus on their diagnostic and therapeutic implications. Our findings underscore the importance of extending UBA1 sequencing beyond exon 3 in cases with strong clinical suspicion. Given the rarity of non-canonical variants and the limited gene annotation, germline tissue control should be considered to differentiate somatic from germline mutations. Hematological management, including considerations for transplantation, was primarily guided by the Revised International Prognostic Scoring System (IPSS-R) for MDS due to the absence of a specific risk stratification system for VEXAS or therapy guidelines. A critical point of our discussion is the role of inflammation in the peri-transplant period; in one patient, the combination of disease-modifying antirheumatic drugs (DMARDs) and high-dose corticosteroids before transplant was crucial in controlling inflammation, resulting in a successful hematopoietic stem cell transplantation (HSCT). In contrast, uncontrolled inflammation contributed to the peri-transplant death of another patient. These cases highlight the importance of effective inflammation management in optimizing HSCT outcomes. Additionally, our study emphasizes the urgent need for specific management guidelines for VEXAS syndrome, including a comprehensive risk stratification system and optimal timing for transplantation.
Self-management behaviors do not affect remission but mediate between mental health and disease outcomes in a longitudinal study of rheumatoid arthritis
Authors: Sweeney Melissa , Carpenter Lewis , de Souza Savia , Caton Emma , Galloway James , Cope Andrew , Yates Mark , Nikiphorou Elena , Norton Sam 
Published: January 2025

Abstract
Mental health has been shown to impact rheumatoid arthritis (RA) outcomes and is associated with self-management behaviors. The extent to which mental health impacts outcomes via different self-management behaviours has not been thoroughly investigated. Adult RA patients who were starting a new medication or dosage were recruited to a prospective cohort with follow-ups at 3 and 12-months covering clinical and patient-reported outcomes. The longitudinal relationships between mental health, self-management behaviors (diet, physical activity, sleep, smoking, alcohol, and medication nonadherence), disease outcome, and function were assessed. Self-management behaviors were considered mediators of mental health at baseline on outcomes at 3 and 12 months. Depression did not worsen the odds of EULAR response for the total PHQ at 3 months (OR = 0.96, p = 0.36) or 12 months (OR = 0.99, p = 0.99) nor for the categorical PHQ at 3 months (OR = 0.64, p = 0.34) or 12 months (OR = 0.67, p = 0.44). Anxiety also did not worsen the odds of EULAR response for the total GAD at 3 months (OR = 0.98, p = 0.76) or 12 months (OR1.04, 0.53) nor for the categorical GAD at 3 months (OR = 0.99, p = 0.99) or 12 months (OR = 0.94, p = 0.75). However, depression was associated with the DAS-28 at 3 months (b = 0.22, p = 0.04). Among the self-management behaviors, insomnia was found to be a significant mediator between depression and the WSAS (b = 0.08, p = 0.03) as well as anxiety and the WSAS (b = 0.07, p = 0.03). Alcohol was also a significant mediator between depression and the DAS-28 (b = 0.21, p = 0.04). Mental health was associated with worse quality of life and disease outcomes, but not EULAR response. Self-management behaviors were associated with disease outcomes and mental health.
Implementation of the 9th TNM for lung cancer: practical insights for radiologists
Authors: Argentieri Gianluca , Valsecchi Clara , Petrella Francesco , Jungblut Lisa , Frauenfelder Thomas , Del Grande Filippo , Rizzo Stefania 
Published: January 2025

Abstract
Lung cancer is the most common and deadly cancer worldwide. The 9th edition of the tumor node meta (TNM) classification system, effective from January 1, 2025, introduces significant updates. Notably, the N2 category is newly divided into N2a (single-station involvement) and N2b (multiple-station involvement), which reflects distinct prognostic implications. Additionally, the M1c category is now subcategorized into M1c1 (multiple metastases in a single organ system) and M1c2 (metastases in multiple organ systems), affecting stage classification. This reclassification allows for potential downstaging, which could expand treatment options for affected patients. Accurate imaging remains crucial for the classification of anatomical stages. As the TNM system evolves, enhanced imaging precision will play a key role in implementing these updates and ultimately improve patient outcomes.

Key Points

Question

The 9th TNM for lung cancer introduces changes in the N2 and M1c descriptors, to better align with new therapeutic options and outcome studies.

Findings

Proper knowledge of the key changes of the 9th TNM can help radiologists offer clinicians a meaningful report.

Clinical relevance

Radiologists should incorporate the 9th TNM classification into their reports and discussions in multidisciplinary meetings, thus ensuring a common language across disciplines to enable clearer communication with other specialists, supporting more precise and cohesive decision-making in patient care.
Adherence to multi-target stool DNA testing for colorectal cancer screening in the United States
Authors: Le Quang A. , Greene Mallik , Gohil Shrey , Ozbay A. Burak , Dore Michael , Fendrick A. Mark , Limburg Paul 
Published: January 2025

Abstract

Purpose
Colorectal cancer (CRC) is the second leading cause of cancer mortality in the USA and is highly preventable, with early screening vital for improving outcomes. This study aimed to evaluate adherence rates of multi-target stool DNA (mt-sDNA) testing, following updated guidelines recommending screening starting at age 45.

Methods
This retrospective cohort study used aggregated data from Exact Sciences Laboratories LLC, examining new users (first-time testers) aged 45–85 with commercial, Medicare, or Medicaid insurance who received mt-sDNA test kits (point-of-care) between January 1, 2023, and June 1, 2023. Adherence was defined as the percentage of eligible participants returning a valid non-empty test kit within 365 days of initial shipment date. Descriptive statistics and logistic regression were used to analyze adherence.

Results
Among 1,557,915 patients, the overall adherence rate to mt-sDNA testing was 71.3% (commercial insurance 72.3%, Medicare Advantage 70.2%, Medicare 69.9%, Medicaid 52.0%) (p < 0.001). Females had slightly higher adherence than males, except for commercial insurance (72.2% vs. 72.6%, p < 0.001). Adherence was highest in commercial insurance for individuals aged 76–85 (79.2%, p < 0.001), gastroenterology patients (82.5%, p < 0.001), and rural residents (73.2%, p < 0.001), along with those in Medicare Advantage earning $200 K + (78.5%, p < 0.001).

Conclusions
Adherence to mt-sDNA testing was robust, particularly among individuals with commercial insurance, older adults, gastroenterology patients, higher income groups, and rural residents. With a 71% adherence rate, the test demonstrates substantial engagement and value in colorectal cancer screening. Future research should assess its long-term impact and address disparities to optimize its benefits.
Cost–consequence analysis of early vs. delayed natalizumab use in highly active relapsing–remitting multiple sclerosis: a simulation study
Authors: Inojosa Hernan , Schriefer Dirk , Ness Nils-Henning , Dillenseger Anja , Akgün Katja , Ziemssen Tjalf 
Published: January 2025

Abstract

Background
Natalizumab (NAT) is an established disease-modifying therapy (DMT) for highly active multiple sclerosis (MS). However, its use involves complex decision-making, often leading to initial use of lower efficacy therapies. Recently, the first biosimilar NAT was approved, enabling competitive pricing. This study assessed the societal implications of initiating NAT in various scenarios through a cost–consequence analysis.

Methods
A 10-year Markov model based on the Expanded Disability Status Scale (EDSS) was employed, with 11 health states, annual cycles, and half-cycle correction. The cohort had an initial age of 36 years and 70% females. NAT was compared to common initial therapies (glatiramer acetate, teriflunomide, dimethyl fumarate, and fingolimod). Scenarios included continuous use, early (after 1 year), and delayed (5 years) switch to NAT. Baseline characteristics and probabilities for clinical and economic outcomes were derived from clinical trial data, published literature, and other available sources.

Results
Continuous NAT use resulted in the highest time spent on low EDSS levels, fewer relapses, reduced years of life lost due to disability, and a higher employment rate over a 10-year period. Switching to NAT after 1 year yielded outcomes similar to continuous NAT use. Despite higher DMT costs, disease management costs, including indirect costs and non-DMT direct medical costs, were lower in continuous use and early switch to NAT. Late switching resulted in outcomes most comparable to continuous use of the initial DMT.

Conclusion
Continuous and early switch to NAT resulted in better clinical outcomes and lower societal economic burden compared to delayed NAT initiation, indicating potential long-term cost savings.
Type-based computation of knowledge graph statistics
Authors: Savnik Iztok , Nitta Kiyoshi , Skrekovski Riste , Augsten Nikolaus 
Published: January 2025

Abstract
We propose a formal model of a knowledge graph (abbr. KG) that classifies the ground triples into sets that correspond to the triple types. The triple types are partially ordered by the sub-type relation. Consequently, the sets of ground triples that are the interpretations of triple types are partially ordered by the subsumption relation. The types of triple patterns restrict the sets of ground triples, which need to be addressed in the evaluation of triple patterns, to the interpretation of the types of triple patterns. Therefore, a schema graph of a KG should include all triple types that are likely to be determined as the types of triple patterns. The stored schema graph consists of the selected triple types that are stored in a KG and the complete schema graph includes all valid triple types of KG. We propose choosing the schema graph, which consists of the triple types from a strip around the stored schema graph, i.e., the triple types from the stored schema graph and some adjacent levels of triple types with respect to the sub-type relation. Given a selected schema graph, the statistics are updated for each ground triple t from a KG. First, we determine the set of triple types stt from the schema graph that are affected by adding a triple t to an RDF store. Finally, the statistics of triple types from the set stt are updated.
Can’t you answer while you wait?
Authors: Cruz-Filipe Luís , Gaspar Graça , Nunes Isabel 
Published: January 2025

Abstract
Many modern-day systems rely on information that is constantly arriving, and they need to make decisions based on it – a problem known as continuous query answering. In many situations, these systems can benefit from identifying possible outcomes that are consistent with the data available so far. Such scenarios are called hypothetical answers, and previous work has defined them precisely and shown how they can be updated in step with the arrival of additional input. Most existing formalisms assume that data always arrives instantaneously, which is not realistic. In this work, we relax this problem by allowing data to arrive later, and potentially out of order. By revisiting the underlying intuitions in previous work, we develop a more general framework that supports communication delays. The interaction between communication delays and negation poses some challenging problems, which we address using fixpoint theory. We show that the relevant fixpoints can be computed in finite time by a carefully designed algorithm.
LGR5: An emerging therapeutic target for cancer metastasis and chemotherapy resistance
Authors: Wang Wanqi , Lokman Noor A. , Barry Simon C. , Oehler Martin K. , Ricciardelli Carmela 
Published: January 2025

Abstract
Cancer stem cells play an important role in tumor progression and chemotherapy resistance. Leucine-rich G repeat-containing protein-coupled receptor 5 (LGR5) has been identified as a cancer stem cell marker in several cancer types. LGR5 is involved in cancer development and progression via several pathways including WNT/β-catenin signaling pathway. LGR5 plays a role in tumor progression by promoting cancer cell migration, invasion, metastasis, and angiogenesis in many cancers including colorectal, brain, gastric, and ovarian cancer. This review summarises the current knowledge on the expression and functional role of LGR5 in cancers, the molecular mechanisms regulated by LGR5, and the relationship between LGR5 and chemotherapy resistance. The review also includes highlights potential strategies to inhibit LGR5 expression and function. The majority of functional studies have shown that LGR5 plays an important role in promoting cancer progression, metastasis and chemotherapy resistance however, in some contexts LGR5 can also activate tumor-suppressive pathways and LGR5 negative cells can also promote cancer progression. The review highlights that targeting LGR5 is a promising anti-cancer treatment but the functional effect of LGR5 on tumor cells is complex may be dependent on cancer type, tumor microenvironment and cross-talk with other molecules in the LGR5 signaling pathway.
Cooperative Learning in Higher Education Physics – A Systematic Literature Review
Authors: Kilpeläinen-Pettersson Jasmin , Koskinen Pekka , Lehtinen Antti , Mäntylä Terhi 
Published: January 2025

Abstract
Due to the positive effects on students’ performance and social skills, student-centered instructional strategies such as cooperative learning are increasingly used in higher education. Although cooperative learning has been studied extensively, often these studies cannot be applied to the context of higher education physics due to differences in the nature of the disciplines and educational levels. In order to highlight research focusing explicitly on higher education physics and thus enable physics instructors to take full advantage of cooperative learning, a review of recent research is necessary. Using three databases and including peer-reviewed journal articles published after 2010 that focused on cooperative learning in physics in higher education, a total of 50 articles were analysed to examine 1) what kind of cooperative learning strategies and 2) what kind of tasks have been used recently in the context of higher education physics, and 3) how the advantages of cooperative learning is justified. The results show that the two most common strategies, i.e. Learning Together and Group Investigation, covered most of the studies reviewed. The tasks given to students highlighted the experimental and conceptual nature of physics knowledge, even though many cooperative learning strategies were developed for different disciplinary contexts. Several arguments for the advantages of cooperative learning were identified, showing that although learning is an intraindividual process, the presence of peers and the external learning setting can also influence the outcome. Based on the findings, suggestions are made for future research and application of cooperative learning in higher education physics.
On case-copying reflexives
Authors: Messick Troy , Raghotham Sreekar 
Published: January 2025

Abstract
While it is well-known that local anaphors match their antecedents in ϕ-features in many languages, it has been suggested that the form of anaphors is insensitive to the morphological case of their antecedent. We show that this is not the case for local complex reflexives (and reciprocals) in Telugu. Pieces of these elements must match in case features with their antecedents. We provide the first in-depth description and analysis of this type of reflexive. Our analysis bears on the structure of complex anaphors, the relation between anaphors and intensifiers in some languages, and the syntactic mechanisms that allow feature sharing.