Real-world Laboratory Research Articles

Toward High-Quality Real-World Laboratory Data in the Era of Healthcare Big Data.

With Industry 4.0, big data and artificial intelligence have become paramount in the field of medicine. Electronic health records, the primary source of medical data, are not collected for research purposes but represent real-world data; therefore, they have various constraints. Although structured, laboratory data often contain unstandardized terminology or missing information. The major challenge lies in the lack of standardization of test results in terms of metrology, which complicates comparisons across laboratories. In this review, we delve into the essential components necessary for integrating real-world laboratory data into high-quality big data, including the standardization of terminology, data formats, equations, and the harmonization and standardization of results. Moreover, we address the transference and adjustment of laboratory results, along with the certification for quality of laboratory data. By discussing these critical aspects, we seek to shed light on the challenges and opportunities inherent to utilizing real-world laboratory data within the framework of healthcare big data and artificial intelligence.

Virtual Laboratories in STEM

Virtual laboratory utilization has been trending in STEM undergraduate curricula for over twenty years. A virtual laboratory is an interactive computer simulation that mimics real-world laboratory experiences in silico. Virtual labs are cost-effective pedagogical options for academic institutions that lack adequate funding for physical infrastructure and instrumentation. Virtual labs are an excellent proxy for lab activities threatening individual safety and public health. Further, during the COVID-19 pandemic, virtual labs were the primary pedagogical strategy for laboratory instruction. STEM faculty have developed numerous techniques for incorporating virtual labs into classroom and laboratory activities. New technology like artificial intelligence will expand virtual lab usability and effectiveness. Educational research demonstrates positive student outcomes and other benefits from virtual lab engagement. Continued effective mixed-methods research and production of essential virtual lab-based evaluation materials, such as discipline-specific rubrics, are needed to advance the application of this vital technology further. Moreover, from a software development perspective, many more virtual laboratories are needed in technology, engineering, mathematics, and specialized scientific fields.

Strategic boundary management in university‐based living labs

AbstractUniversity‐based boundary organisations provide academics with an environment where they can interact with a wide variety of societal partners to produce knowledge and work on research projects, often of a transdisciplinary nature. This environment, however, implies that their researchers may be confronted with multiple and sometimes conflicting demands coming from various stakeholders. In this study, we focus on one such case, a Real‐world Laboratory (RwL), set up by the Karlsruhe Institute of Technology. This RwL focuses on urban sustainable development challenges. Drawing on boundary work literature, we analyse the boundary work strategies employed by the lab's leading researchers to manage such demands as part of a RwL research project. We observe that the managing researchers buffer several types of boundaries in order not to compromise the transdisciplinary nature of the RwL. They appear to utilise four types of boundary devices when managing boundaries: language, people, objects, and spaces. We conclude that, to reduce tensions, the managing researchers should acknowledge the presence of boundaries early on in their RwL research project, that is, during its conception phase.

Quantitative Evaluation of the Real-World Harmonization Status of Laboratory Test Items Using External Quality Assessment Data.

In recent decades, the analytical quality of clinical laboratory results has substantially increased because of collaborative efforts. To effectively utilize laboratory results in applications, such as machine learning through big data, understanding the level of harmonization for each test would be beneficial. We aimed to develop a quantitative harmonization index that reflects the harmonization status of real-world laboratory tests. We collected 2021-2022 external quality assessment (EQA) results for eight tests (HbA1c, creatinine, total cholesterol, HDL-cholesterol, triglyceride, alpha-fetoprotein [AFP], carcinoembryonic antigen [CEA], and prostate-specific antigen [PSA]). This EQA was conducted by the Korean Association of External Quality Assessment Service, using commutable materials. The total analytical error of each test was determined according to the bias% and CV% within peer groups. The values were divided by the total allowable error from biological variation (minimum, desirable, and optimal) to establish a real-world harmonization index (RWHI) at each level (minimum, desirable, and optimal). Good harmonization was arbitrarily defined as an RWHI value ≤ 1 for the three levels. Total cholesterol, triglyceride, and CEA had an optimal RWHI of ≤ 1, indicating an optimal harmonization level. Tests with a desirable harmonization level included HDL-cholesterol, AFP, and PSA. Creatinine had a minimum harmonization level, and HbA1c did not reach the minimum harmonization level. We developed a quantitative RWHI using regional EQA data. This index may help reflect the actual harmonization level of laboratory tests in the field.

Who do we mobilise? Applied transformative mobilities research in a real-world laboratory

ABSTRACT In this paper we reflect on insights concerning participation in and effects of a real-world laboratory designed to disrupt car dependency in everyday practices in an urban setting. After outlining the project and key findings, we critically reflect on design and achievements of this real-world laboratory more generally. In particular, we discuss the following questions: Who is it that we can address through transformative mobilities research in real-world laboratories? Who are the participants and what are their motives for taking part in the research? To contextualize the research findings within a real-world setting and research paradigm we extend the scope to a second set of questions: How can we conceptualise the relationship between participants and researchers and how do we account for opposing rationalities of interruption (research) and maintenance (participants) of the organisation of everyday life? How does this research enable transformative mobilities? And, finally, what can we say about the scope of our findings and reflections? In the thicket of doing transformative research encouraging and accompanying volunteers to become active in transformative mobility research becomes questions of language, educational background and time resources from the involved, but also being aware of institutionalized change actor networks, unchallenged hierarchies of superior “academic” research and being part of political struggles that require to look closely within and outside of the actual real-world-experiment especially in times of multiple crises. To design and research with those who want to contribute to change is legitimate. However, it is necessary to keep this selectivity in mind.

Soziale Logistik: Öffentlicher Nahverkehr als regionaler Verteiler von Gütern in ländlichen Regionen. Chancen für die langfristige Etablierung eines nachhaltigen regionalen Logistikkonzepts

This paper presents initial findings on the establishment of a social logistics project in a peripheral rural region in Germany. As part of a real-life laboratory, two services were developed and tested with the aim of improving rural supply: the delivery of regional goods and the return of online orders in cooperation with a regional public transport provider, regional retailers and parcel services. An evaluation team provided support to the project in identifying, monitoring, and documenting the societal impact of the services and promoted impact-oriented project management. The concept of providing services of general interest through social logistics and testing them in a real-world laboratory was based on preliminary work in the region. The results indicate that this approach can promote this type of social logistics in the long term. A social logistics approach does not focus solely on economic aspects but emphasises social and environmental benefits for the region. A real-world laboratory approach enables an environment that promotes open exchange, involvement of different stakeholders and joint problem solving in a reflective, iterative process. This methodological approach enabled the continuation and out-scaling of the service’s core offerings immediately after ending the test phase and is seen as an important prerequisite for establishing a long-term perspective.

Examining the dynamics of social cohesion: A call for a different perspective on scaling impacts of real-world laboratories

Social cohesion is an important impact category for scaling real-world laboratory experiments. This idea has been largely overlooked in the transformative research debate. Based on observations within real-world laboratories that focused on iterative, co-creative, and practice-based climate change adaptation, we identify social cohesion, first, as a prerequisite for real-world laboratory impacts. Second, social cohesion can itself be an impact, enhancing the scaling potential of real-world laboratories. Cooperation can pave the way for amplifying real-world laboratories’ activities temporally and spatially.

Putting sufficiency into practice: Transdisciplinary sufficiency research in urban development: The Hafen-Ost real-world laboratory in Flensburg, Germany

The evaluation of real-world laboratories is crucial. Since not only successes but failures and obstacles can provide information about the conditions for transformation, it is appropriate to also examine difficulties in a methodologically guided way.The port in Flensburg, Germany, has shaped the city’s identity. Globalisation and deindustrialisation have seen the northern German port on the Baltic Sea lose its economic importance. The city of Flensburg is currently planning to build a new district on a huge redevelopment site. The idea is to create a district with an infrastructure that promotes and enables lifestyles that use resources and land sustainably. The real-world laboratory on sufficiency-oriented urban development described and evaluated here aimed to better understand the process of implementing sufficiency policies and their effects, and to develop the knowledge and skills needed for sufficiency-oriented policymaking. The real-world laboratory is a collaborative project between members of the city administration and academics from the Europa-Universität Flensburg. The evaluation shows both the difficulties of putting sufficiency policies into practice and their potential for sustainability.

Impacts beyond experimentation ‐ Conceptualising emergent impacts from long-term real-world laboratory processes

Real-world laboratories are settings for joint experimentation on sustainability challenges, through the transdisciplinary collaboration of diverse actor groups. By approaching a real-world laboratory from three perspectives, this paper uncovers the emergent impacts of a long-term collaborative process.Real-world laboratories have become a recognised research format for addressing sustainability challenges. In these transdisciplinary settings, actors from civil society, local government, and academia work together using a transdisciplinary research approach to jointly experiment and learn about sustainability transformations. While these labs are considered to have potential, their impact has not yet been fully measured. Therefore, in our paper we explore the case of the Zukunfts-stadt Lüneburg 2030+ process to uncover the impacts that this long-term effort has generated over the past eight years. By examining the process and its design features from three analytical perspectives, we identify emergent impacts in three dimensions: education, governance, and the lab as an actor for sustainability. Based on our case study, we suggest that real-world labs contribute to sustainability on a local level, beyond the intentional experiments, through impacts that emerge over the course of the joint operation of the lab.

Insights into 15 years of transdisciplinary research on a small Greek island

Small islands offer unique conditions for studying human-nature relations. Our study uses the real-world laboratory concept to reflect on a long-term transdisciplinary research process that aimed to facilitate a sustainability transition for an entire island.This article introduces a long-term transdisciplinary research process on the Greek island of Samothraki, aiming at sustainability solutions that are not only scientifically sound, but also co-designed, well received and adopted by the local community. We reflect on 15 years of socioecological research by utilizing the conceptual lens of real-world laboratories (RwLs). We present the research approach pursued on the island, based on a sociometabolic understanding of society-nature interaction, by relating local natural resources (and their self-regenerating capacities) to their social utilization and the resulting environmental pressures. We reflect on the research activities by using an established evaluation framework based on the three RwL principles: the “lab context”, “experiments”, and “interventions”. We describe success and setbacks by integrating, as objects of evaluation, the research process, its outputs, outcomes, and impacts. While we can certainly showcase success in terms of research design, scientific outputs, and institutional outcomes, gauging potential impacts poses a more challenging task.

Elevated remnant cholesterol and non-HDL cholesterol concentrations from real-world laboratory results: a cross-sectional study in Southeast Asians.

Triglyceride-rich remnant lipoproteins (TRLs) are considered atherogenic due to the presence of remnant cholesterol, which is transported by apolipoprotein B. In clinical practice, the concentration of TRLs can be estimated by calculating remnant cholesterol or non-HDL cholesterol levels. This study aims to investigate the proportion of patients who have low LDL cholesterol (LDL-C) concentration but elevated remnant cholesterol concentration, stratified by the presence of hypertriglyceridaemia and ethnicity, using real-world hospital data. Our secondary aim is to investigate the proportion of patients with elevated non-HDL cholesterol levels using guideline-recommended goals. A 2-year retrospective study was conducted at a single centre, analyzing lipid blood tests of all patients, including directly measured LDL-C. Fasting for blood tests was not mandatory. The study included a total of 21,605 consecutive patients with plasma lipid profiles analyzed in our hospital laboratory. The median age was 61 years. In patients with ASCVD (n = 14,704), 23.7% had an LDL-C level of <1.8 mmol/L, 11.3% had elevated remnant cholesterol concentrations at ≥0.65 mmol/L, and 48.8% were at the non-high-density lipoprotein cholesterol (non-HDL-C) goal (<2.6 mmol/L). Among patients diagnosed with atherosclerotic cardiovascular disease (ASCVD) with LDL-C levels of <1.8 mmol/L (n = 3,484), only 11.9% had high levels of remnant cholesterol, but 96% of the ASCVD patients also achieved the recommended non-HDL-C target of <2.6 mmol/L. When the LDL-C level was <1.8 mmol/L, the mean concentration of remnant cholesterol was 0.214 mmol/L when the triglyceride level was <1.7 mmol/L (n = 3,380), vs. 0.70 mmol/L when the triglyceride level was elevated (n = 724), p < 0.001. Among patients with a triglyceride level of ≥1.7 mmol/L and an LDL-C level of <.8 mmol/L, there were 254 patients with elevated remnant cholesterol concentration and 71 patients with suboptimal non-HDL levels. Malays had a higher mean remnant cholesterol concentration compared with both Chinese and Indians across all LDL-C levels, particularly in the presence of hypertriglyceridaemia. An elevated remnant cholesterol concentration of >0.65 mmol/L was present in 11% of all patients. The current guideline-recommended non-HDL-C goal, which uses a 0.8 mmol/L estimate of remnant cholesterol concentration, was achieved in >92% of patients, suggesting that it is unlikely to be clinically useful for the majority of our patient population except where there is concomitant hypertriglyceridaemia. Further studies are needed to establish the appropriate non-HDL-C goal or calculated remnant cholesterol concentration, paired with the LDL-C goal or otherwise, in a Southeast Asian population.

Real-world experiments as a teaching and learning approach for sustainable consumption education

PurposeThis paper aims to propose and evaluate an innovative approach to education for sustainable consumption (ESC) which empowers teenagers and young adults to improve sustainable consumption competences. This approach combines pedagogical learning approaches such as real-world learning (e.g. experiential learning and research-based learning) with transformative and transdisciplinary research approaches (i.e. real-world laboratory research).Design/methodology/approachThrough a transdisciplinary research design, the authors explore if real-world experiments (RWEs) offer a suitable approach for sustainable consumption education at schools. RWEs are a research approach for knowledge production, aiming to go beyond temporary interventions, to establish semi-permanent spaces for sustainability transformation and reflexive learning. To evaluate this proposal, the authors study already existing active teaching and learning approaches developed within and for ESC and put these in perspective, to define and understand the RWEs.FindingsInsights from a transdisciplinary research project which applied RWEs as a teaching and learning approach in German schools complement conceptual considerations. As a result, advantages, such as the development of core competencies among learners, but also challenges experienced, are illustrated. Though, the challenges found are not unique to the RWE, rather they point out important potentials for ESC through suggesting systematic changes in educational institutions and teaching approaches.Originality/valueThis paper explores RWEs as an active and participatory teaching and learning approach for sustainable consumption education at schools and delivers practical insights and a definition of RWEs as an innovative teaching and learning approach.

Optimization and intra-assay validation of a multiparametric flow cytometric test for monitoring circulating TREGs.

Multiparametric flow cytometry (MFC) represents an essential tool for immune monitoring, and validation of MFC panels is a fundamental prerequisite in routine laboratory settings as well as for translational and clinical research purposes. Regulatory T cells (TREGs) constitute a subset of CD4+ effector T cells that modulate the immune response in numerous settings, including autoimmune disease, allergy, microbial infection, tumor immunity, transplantation, and more. These cells comprise a small fraction of total CD4+ T cells in human peripheral blood and mouse spleen. In oncology, TREG cells are highly relevant, as they are involved in the suppression of the anti-tumor response in many types of cancer, to the extent that the first immune checkpoint inhibitor approved for clinical use in humans was a monoclonal antibody directed against CTLA-4, a molecule functionally associated with TREGs. Due to all these factors, robust assays are mandatory to accurately determine TREG cell frequency and function. Here, we describe the validation of an 8-color flow-cytometry protocol for TREG detection and analysis in a real-world laboratory scenario. The entire process includes the workflow plan and the standard operating procedure resembling each phase, from the panel design to the staining, acquisition, and analysis steps. Validation is planned to be performed in replicates on fresh whole blood samples derived from multiple healthy subjects. The analytical validity of the TREG cell assay is ensured by testing the intra-assay accuracy. The detailed procedure for the entire process is accompanied by important troubleshooting suggestions and other useful tips.

Inquiry Based Learning in practice to enhance an Immunological Biotechnologies laboratory experience

This paper aims to describe a teaching redesign experience that took place through the introduction of the Inquiry Based Learning methodology within the course of Immunological Biotechnology included in the program of the Master's Degree in Industrial Biotechnologies at the University of Padua. The decision to introduce this approach starts from the need to maximise and support students during the learning experience, to sustain the development of specific skills related to real-world laboratory research environments, making them more aware of the design and practical steps of the laboratory itself. The new design (and its implementation) has both enhanced student learning and improved satisfaction with the teaching. The feedback from the students also allowed us to acquire important information to work further on teaching and create more authentic and effective experiences, through a teaching and learning approach based on investigation.

Exploring fruitful links between real-world laboratory and disciplinary research: Introduction of the DKN Future Earth working group LinkLab

LinkLab is a newly established working group under the umbrella of German Committee Future Earth (DKN Future Earth). It opens up a space to discuss relevant connections and interfaces between real-world lab research and various scientific disciplines, exploring fruitful connections and pathways for mutual learning for future sustainability-oriented research.

B-096 Are we truly Choosing Wisely? An Assessment of non-specific testing, time to diagnosis and costs related to the diagnosis of Rheumatoid Arthritis

Abstract Background Treatment of Rheumatoid Arthritis (RA) early in the disease course can significantly impact patient quality of life by preventing the development of joint erosion and slowing down disease progression. Timely diagnosis is a critical aspect of early treatment. Most patients initially present within a primary care (PC) setting where a variety of non-specific tests/test algorithms are used. We reviewed 8 years’ worth of RA real-world laboratory data to assess time to diagnosis (TTD) between different tests/test combinations. Methods Data extraction spanning 2014–2021 was pulled from a US laboratory, using Rheumatoid Factor (RF) and Anti-Cyclic Citrullinated Peptide (CCP) positivity as the primary inclusion criteria. Additionally, sex, age, ordering physician specialty, ICD-10 codes, test order date and test codes (ESR, CRP, ANA screen, RF isotypes) were pulled longitudinally. Results This data set includes 3024 patients with RA (RA ICD code). Of these, 45% were first suspected and evaluated within PC. TTD between patients initially tested with only CRP or ESR had a median TTD of 920 days and those tested with ANA only had a median TTD of 685 days. Those tested with RF + CCP or RF + CCP + ANA had a median TTD of 367 days and 290 days, respectively. Conclusion Our data set highlights the impact of test methods on TTD of patients with RA, with tests combinations more specific for RA significantly decreasing TTD. Further analysis will be conducted to determine the downstream implications resulting between these diagnostic delays. Standardizing and implementing initial testing algorithms could potentially decrease RA TTD, and directly impact burden of care.

Beyond Disciplinary Constraints: Designing Transdisciplinary Research and Collaboration in Real-World Laboratories

Topics related to sustainable development are at the forefront of current local and global debates, involving social, economic, and political perspectives. To address these complex and interconnected challenges, it is necessary to think and act beyond disciplinary and field-specific boundaries. Participating in project work, research, experiments, and designing social transformation processes are at the core of transdisciplinary research and methods, such as Real-World Laboratories. This means that all participants are involved in co-designing, co-producing, and co-disseminating the project from the beginning. In these participatory processes, a systematic evaluation and evidence of the transdisciplinary process is often difficult to show even though it would be important to improve scalability and the transferability of the process. Using the example of the Tiny Fop Mob, a Real-World Laboratory on wheels, we wanted to understand how to evaluate transdisciplinary research thinking within the project team and demonstrate how systematic evaluation is crucial in participatory research. Findings show that there is a need to reflect on context-specific and team-oriented strategies during the planning and the beginning of the project.

Tracking Control of Unforced and Forced Equilibrium Positions of the Pendubot System: A Nonlinear MHE and MPC Approach

This paper presents a unified control scheme of the Pendubot based on nonlinear model predictive control (NMPC) and nonlinear moving horizon estimation (NMHE) with the objective of point-to-point tracking its unstable unforced and ultimately forced equilibrium positions. In order to implement it on this fast, underactuated mechatronic system, we employ the Gauss–Newton real-time iteration scheme tailored to obtain the efficient solution of the underlying nonlinear optimization problems via sequential quadratic programming. The control performance is experimentally assessed on a real-world laboratory setup featuring an execution timing analysis and hints how to further improve the computational efficiency of the proposed nonlinear estimation control scheme. Even nowadays, the number of practical NMPC applications in the millisecond range is still rather limited, and the presented NMHE-based NMPC of the Pendubot thus also represents a unique case study for control practitioners.

Everything is varied: The surprising impact of instantial variation on ML reliability

Instantial variation (IV) refers to variation that is due not to population differences or errors, but rather to within-subject variation, that is the intrinsic and characteristic patterns of variation pertaining to a given instance or the measurement process. Although taking into account IV is critical for the proper analysis of the results, this source of uncertainty and its impact on robustness have so far been neglected in Machine Learning (ML). To fill this gap, we look at how IV affects ML performance and generalization, and how its impact can be mitigated. Specifically, we provide a methodological contribution to formalize the problem of IV in the statistical learning framework. To prove the relevance of our contribution, we focus on one of the most critical domains, healthcare, and take individual (analytical and biological) variation as a specific kind of IV; in this domain, we use one of the largest real-world laboratory medicine datasets for the task of COVID-19 detection, to show that: (1) common state-of-the-art ML models are severely impacted by the presence of IV in data; and (2) advanced learning strategies, based on data augmentation and soft computing methods (data imprecisiation), and proper study designs can be effective at improving robustness to IV. Our findings demonstrate the critical relevance of correctly accounting for IV to enable safe deployment of ML in real-world settings.

Validation of High-sensitivity Flow Cytometry for Reliable Immune Cell Analysis in Real-world Laboratory Settings.

The adoption of high-sensitivity flow cytometry (HSFC) in routine laboratory settings has been slow owing to concerns regarding the reliability and reproducibility of results. Validation is an essential prerequisite for conducting assays, and implementing the CLSI guidelines has been confusing, primarily because many aspects are not yet established. We aimed to validate an HSFC protocol for detecting follicular helper T (Tfh) cells in a real-world laboratory environment. The analytical validity of the Tfh cell panel was ensured through rigorous testing, including evaluations of precision, stability, carryover, and sensitivity, following the CLSI H62 guidelines. We found that Tfh cells, present in very small numbers in the blood, could be sufficiently detected through HSFC, and concerns about the reliability and reproducibility of the results in real-world laboratories could be solved through systematic validation. Establishing the lower limit of quantification (LLOQ) is a critical step in HSFC evaluations. By selecting an appropriate sample, for example, collecting residual cells from CD4 isolation in our experiment and using them as low-level samples, the LLOQ could be accurately established. The strategic validation of flow cytometry panels can facilitate the adoption of HSFC in clinical laboratories, even with limited resources.