Validation Protocol Research Articles

Translation and validation into Brazilian Portuguese of the English version of the International Consultation on Incontinence Modular Questionnaire for Male Lower Urinary Tract Symptoms (ICIQ-MLUTS).

To translate and cross-culturally adapt the English version of the International Consultation on Incontinence Modular Questionnaire for Male Lower Urinary Tract Symptoms (ICIQ-MLUTS)into Brazilian Portuguese and evaluate its psychometric properties. Male lower urinary tract symptoms (LUTS)are frequent and commonly assessed with questionnaires. The ICIQ-MLUTSis a robust instrument that investigates the main aspects of LUTS in men and their impact on quality of life. Although highly recommended, Grade A is not as popular as the International Prostate Symptom Score (IPSS)and remained untranslated and unvalidated for Brazilian Portuguese. After authorization by the Advisory Board of the International Consultation on Incontinence (ICIQ) the translation process was conducted according to the standard guidelines and the ICIQ validation protocol. Internal consistency was assessed using Cronbach's ⍺ coefficient and values > 0.7 were considered satisfactory. To assess test-retest reliability and reproducibility, Spearman's correlation coefficient and intraclass correlation coefficient were used. For group data, a Spearman correlation coefficient or an intraclass correlation coefficient of at least 0.70 demonstrates good test-retest reliability. A p < 0.05 was considered significant. One hundred and eighty-six, aged61.41 ± 11.01 years, suffering from LUTS participated in the study between January 2021 and October 2022. Cronbach's ⍺, 0.875, demonstrated the internal consistency of the Portuguese version of ICIQ-MLUTS.The intraclass correlation coefficient of 0.912 (0.882; 0.935 - 95% CI)for the test-retest evidenced the stability and validity of the instrument. Likewise, Spearman's correlation coefficient highlighted the agreement between IPSS and ICIQ-MLUTS,0.906, <0.001. The Portuguese version of the ICIQ-MLUTSdemonstrated internal consistency, stability, and validity, in addition to agreement with the IPSS. The ICIQ-MLUTS,translated and validated into Brazilian Portuguese, is a robust and reliable instrument to assess LUTS in Brazilian men and can be used in the evaluation of treatment and research.

Technical/Algorithm, Stakeholder, and Society (TASS) barriers to the application of artificial intelligence in medicine: A systematic review

IntroductionThe use of artificial intelligence (AI), particularly machine learning and predictive analytics, has shown great promise in health care. Despite its strong potential, there has been limited use in health care settings. In this systematic review, we aim to determine the main barriers to successful implementation of AI in healthcare and discuss potential ways to overcome these challenges. MethodsWe conducted a literature search in PubMed (1/1/2001–1/1/2023). The search was restricted to publications in the English language, and human study subjects. We excluded articles that did not discuss AI, machine learning, predictive analytics, and barriers to the use of these techniques in health care. Using grounded theory methodology, we abstracted concepts to identify major barriers to AI use in medicine. ResultsWe identified a total of 2,382 articles. After reviewing the 306 included papers, we developed 19 major themes, which we categorized into three levels: the Technical/Algorithm, Stakeholder, and Social levels (TASS). These themes included: Lack of Explainability, Need for Validation Protocols, Need for Standards for Interoperability, Need for Reporting Guidelines, Need for Standardization of Performance Metrics, Lack of Plan for Updating Algorithm, Job Loss, Skills Loss, Workflow Challenges, Loss of Patient Autonomy and Consent, Disturbing the Patient-Clinician Relationship, Lack of Trust in AI, Logistical Challenges, Lack of strategic plan, Lack of Cost-effectiveness Analysis and Proof of Efficacy, Privacy, Liability, Bias and Social Justice, and Education. ConclusionWe identified 19 major barriers to the use of AI in healthcare and categorized them into three levels: the Technical/Algorithm, Stakeholder, and Social levels (TASS). Future studies should expand on barriers in pediatric care and focus on developing clearly defined protocols to overcome these barriers.

An innovative mixed reality approach for maxillofacial osteotomies and repositioning

Craniomaxillofacial surgeries are performed using custom-made physical cutting guides and resin dental splints that present several drawbacks (e.g. time and cost required for their design and production). The literature commonly provides augmented/mixed reality (AR/MR) solutions for assisting maxillofacial osteotomies and repositioning without any interactive guide. This work proposes a new MR application, useful for osteotomy and repositioning, providing interactive, fast, and intuitive feedback to the surgeon, who is then supported in performing the bone fragment resection and replacement frame by frame. The proposed application speeds up the surgery and reduces under/overshooting errors. Moreover, the idea of integrating osteotomy and repositioning assistance in the same MR application is rarely found in the literature. It is an entirely novel approach to craniomaxillofacial surgery. The MR application has been designed with a three-button menu. The “App Start” calibrates the app, the “Osteotomy Mode” visualises the holograms of the cutting lines and drilling points, and the “Repositioning Mode” visualises the step-by-step real-time feedback to precisely support the surgeon placing the osteotomised bone fragment towards the final pre-planned position. The MR app has been developed in Unity and deployed on Microsoft HoloLens V2. A laboratory test bench was realised to validate the accuracy of the proposed MR-based approach. The validation protocol consists of two tasks to test the osteotomy and repositioning modes using a 3D-printed skull phantom. For osteotomy, the accuracy is 0.89 mm (genioplasty), 1.24 mm (maxillary osteotomy), 1.33 mm (orthognathic surgery), and 2.89 mm (mandibular angle osteotomy). For repositioning, the accuracy is 0.6 mm (anteroposterior deviation), 0.7 mm (mediolateral deviation), and 0.6° (angular deviation).

3D computational fluid and particle dynamics simulations: metrics of aerosol capture by impaction filters * *Contribution of NIST; not subject to U.S. copyright. Certain commercial equipment, instruments, software, or materials are identified in this paper in order to specify the experimental procedure and virtual experimentation adequately. Such identification is not intended to imply recommendation or endorsement by NIST, nor is

Human studies provide valuable information on components or analytes recovered from exhaled breath, but there are limitations due to inter-individual and intra-individual variation. Future development and implementation of breath tests based on aerosol analysis require a clear understanding of how human factors interact with device geometry to influence particle transport and deposition. The computational fluid and particle dynamics (CFPD) algorithm combines (i) the Eulerian approach to fluid dynamics and (ii) the Lagrangian approach to single particle transport and deposition to predict how particles are carried in fluids and deposited on surfaces. In this work, we developed a 3D multiscale CFPD model to provide insight into human factors that could be important to control or measure during sampling. We designed the model to characterize the local transport, spatial distribution, and deposition of polydisperse particles in a single impaction filter of a commercial aerosol collection device. We highlight the use of decoupling numerical strategies to simultaneously quantify the influence of filter geometry, fluid flowrate, and particle size. Our numerical models showed the remarkable effect of flowrate on aerosol dynamics. Specifically, aerosol mass deposition, spatial distribution, and deposition mechanisms inside the filter. This work as well as future studies on the effect of filter geometry and human factors on aerosol collection will guide the development, standardization, and validation of breath sampling protocols for current and emerging breath tests for forensic and clinical applications.

Development of a Universal Validation Protocol and an Open-Source Database for Multi-Contextual Facial Expression Recognition.

Facial expression recognition (FER) poses a complex challenge due to diverse factors such as facial morphology variations, lighting conditions, and cultural nuances in emotion representation. To address these hurdles, specific FER algorithms leverage advanced data analysis for inferring emotional states from facial expressions. In this study, we introduce a universal validation methodology assessing any FER algorithm's performance through a web application where subjects respond to emotive images. We present the labelled data database, FeelPix, generated from facial landmark coordinates during FER algorithm validation. FeelPix is available to train and test generic FER algorithms, accurately identifying users' facial expressions. A testing algorithm classifies emotions based on FeelPix data, ensuring its reliability. Designed as a computationally lightweight solution, it finds applications in online systems. Our contribution improves facial expression recognition, enabling the identification and interpretation of emotions associated with facial expressions, offering profound insights into individuals' emotional reactions. This contribution has implications for healthcare, security, human-computer interaction, and entertainment.

Automation, live-cell imaging, and endpoint cell viability for prostate cancer drug screens.

Androgen deprivation therapy (ADT) is the standard of care for high risk and advanced prostate cancer; however, disease progression from androgen-dependent prostate cancer (ADPC) to lethal and incurable castration-resistant prostate cancer (CRPC) and (in a substantial minority of cases) neuroendocrine prostate cancer (NEPC) is common. Identifying effective targeted therapies is challenging because of acquired resistance to established treatments and the vast heterogeneity of advanced prostate cancer (PC). To streamline the identification of potentially active prostate cancer therapeutics, we have developed an adaptable semi-automated protocol which optimizes cell growth and leverages automation to enhance robustness, reproducibility, and throughput while integrating live-cell imaging and endpoint viability assays to assess drug efficacy in vitro. In this study, culture conditions for 72-hr drug screens in 96-well plates were established for a large, representative panel of human prostate cell lines including: BPH-1 and RWPE-1 (non-tumorigenic), LNCaP and VCaP (ADPC), C4-2B and 22Rv1 (CRPC), DU 145 and PC3 (androgen receptor-null CRPC), and NCI-H660 (NEPC). The cell growth and 72-hr confluence for each cell line was optimized for real-time imaging and endpoint viability assays prior to screening for novel or repurposed drugs as proof of protocol validity. We demonstrated effectiveness and reliability of this pipeline through validation of the established finding that the first-in-class BET and CBP/p300 dual inhibitor EP-31670 is an effective compound in reducing ADPC and CRPC cell growth. In addition, we found that insulin-like growth factor-1 receptor (IGF-1R) inhibitor linsitinib is a potential pharmacological agent against highly lethal and drug-resistant NEPC NCI-H660 cells. This protocol can be employed across other cancer types and represents an adaptable strategy to optimize assay-specific cell growth conditions and simultaneously assess drug efficacy across multiple cell lines.

An enhanced version of FREM (Fracture Risk Evaluation Model) using national administrative health data: analysis protocol for development and validation of a multivariable prediction model

BackgroundOsteoporosis poses a growing healthcare challenge owing to its rising prevalence and a significant treatment gap, as patients are widely underdiagnosed and consequently undertreated, leaving them at high risk of osteoporotic fracture. Several tools aim to improve case-finding in osteoporosis. One such tool is the Fracture Risk Evaluation Model (FREM), which in contrast to other tools focuses on imminent fracture risk and holds potential for automation as it relies solely on data that is routinely collected via the Danish healthcare registers. The present article is an analysis protocol for a prediction model that is to be used as a modified version of FREM, with the intention of improving the identification of subjects at high imminent risk of fracture by including pharmacological exposures and using more advanced statistical methods compared to the original FREM. Its main purposes are to document and motivate various aspects and choices of data management and statistical analyses.MethodsThe model will be developed by employing logistic regression with grouped LASSO regularization as the primary statistical approach and gradient-boosted classification trees as a secondary statistical modality. Hyperparameter choices as well as computational considerations on these two approaches are investigated by an unsupervised data review (i.e., blinded to the outcome), which also investigates and handles multicollinarity among the included exposures. Further, we present an unsupervised review of the data and testing of analysis code with respect to speed and robustness on a remote analysis environment. The data review and code tests are used to adjust the analysis plans in a blinded manner, so as not to increase the risk of overfitting in the proposed methods.DiscussionThis protocol specifies the planned tool development to ensure transparency in the modeling approach, hence improving the validity of the enhanced tool to be developed. Through an unsupervised data review, it is further documented that the planned statistical approaches are feasible and compatible with the data employed.

Spectrographic Voice Analysis Protocol (SAP): Convergent, Concurrent, and Accuracy Validity

To verify the convergent and concurrent validity of the Spectrographic Voice Analysis Protocol (SAP) and its accuracy to discriminate dysphonic from nondysphonic patients. The study used 82 vowel /Ɛ/ samples and their respective narrowband spectrograms, analyzed with SAP. Cepstral peak prominence (CPP) and cepstral peak prominence smoothed (CPPS) verified the convergent validity of the SAP total score, while the general grade of vocal deviation (GG) verified the concurrent validity of the SAP total score. The ROC (receive operator curve) curve and its accuracy, sensitivity, and specificity values, positive predictive value(PPV) and negative predictive value(NPV), and positivelikelihood ratio (LR+) and negative likelihood ratio(LR-) verified the accuracy of the SAP score to discriminate dysphonic from nondysphonic individuals. Dysphonic and nondysphonic had different SAP total scores. In the convergent validity, the SAP score had a weak and moderate negative correlation, respectively, with CPP and CPPS, as well as a moderate positive correlation with GG. SAP performed well in discriminating dysphonic from nondysphonic individuals (area under the curve=82.0%; sensitivity=91.7%; specificity=51.7%; PPV=93.7%; NPV=44.0%; LR+=6.21; LR-=0.53) based on the 8-point cutoff score. SAP has convergent validity with CPP and CPPS and concurrent validity with GG. The SAP total score performed well in discriminating dysphonic from nondysphonic individuals. However, the specificity, NPV, and LR- values justify cautiously using SAP, always in combination with other information in clinical voice assessment.

The Environmental Footprint of Bitcoin Mining Across the Globe: Call for Urgent Action

AbstractBased on a multi‐attribute assessment of the environmental impacts and challenges associated with global Bitcoin (BTC) mining activities around the globe, we call for urgent action by the scientific, policy, and advocacy communities. The worldwide BTC mining network consumed 173.42 TWh of electricity during the 2020–2021 period, bigger than the electricity consumption of most nations. The mining process emitted over 85.89 Mt of CO2eq in the same timeframe, equivalent to the emission caused by burning 84 billion pounds of coal or running 190 natural gas‐fired power plants. The environmental footprint of BTC mining is not limited to greenhouse gas emissions. In 2020–2021, the global water footprint of BTC mining was about 1.65 km3, more than the domestic water use of 300 million people in rural Sub‐Saharan Africa. The land footprint of the global BTC mining network during this period was more than 1,870 square kilometers, 1.4 times the area of Los Angeles. These striking numbers highlight the heavy reliance of the BTC network on fossil fuels and natural resource‐intensive energy sources, resulting in major but unmonitored and unregulated environmental footprints. To mitigate the environmental costs of BTC mining, immediate policy interventions, technological advancements, and scientific research are crucial. Proposed measures include enhanced transparency, economic and regulatory tools, developing energy‐efficient alternative coins, and the adoption of greener blockchain validation protocols.

Comparison of MEA Degradation through FCV Actual Driving Test and Load-Cycle Durability Test

The degradation of a membrane electrode assembly (MEA) after an actual driving test was analyzed, and its mechanism was compared with that of a load-cycle durability test in a laboratory. MEA samples were extracted from an FC stack of a Toyota MIRAI 2014th model which had been operated in actual driving of 200,000 km for approximately 6000 h. The degradation distribution across the MEA plane was found to be insignificant. The electrolyte membrane did not show significant degradation affecting its properties following the durability tests. The MEA performance degradation is primarily attributed to the deterioration of the catalyst activity and oxygen transport properties in the catalyst layer, which is mainly caused by catalyst coarsening. The degradation was well simulated by the NEDO load-cycle durability test of 30,000 cycles. The evaluation results are applicable to validation of AST protocols and model-simulation of MEA degradation.

Horizontal-to-tilt irradiance conversion for high-latitude regions: a review and meta-analysis

This review focuses on the solar irradiance model chain for horizontal-to-tilted irradiance conversion at high latitudes. The main goals of the work are 1) to assess the extent to which the literature accounts for decomposition and transposition models specifically developed for high-latitude application; 2) to evaluate existing validation studies for these particular conditions; 3) to identify research gaps in the optimal solar irradiance model chain for high-latitude application (i.e., latitude ≥60°). In total, 112 publications are reviewed according to their publication year, country, climate, method, and keywords: 78 publications deal with decomposition models and 34 deal with transposition models. Only a few models (6) have been parameterized using data from Nordic countries. Here, we compare 57 decomposition models in terms of their performance in Nordic climate zones and analyze the geographical distribution of the data used to parametrize these models. By comparing the Normalized Root Mean Square Deviation coefficients for direct normal irradiation, the decomposition models Skartveit1 and Mondol1 are most effective on one-hour scale and Yang4 on one-minute scale. Recent studies on the empirical transposition models estimating the global tilted irradiation on vertical surfaces show the best performance for Perez4 and Muneer models. In addition, innovative methods such as artificial neural networks have been identified to further enhance the model chain. This review reveals that a validated model chain for estimating global tilted irradiation at high latitudes is missing from the literature. Moreover, there is a need for a universal validation protocol to ease the comparison of different studies.

B-032 Total lab Automation Validation/Verification Protocol: First Step of Process Excellence Journey in Smart Core Lab in Kokilaben Dhirubhai Ambani Hospital &amp; Medical Research Institute, Mumbai, India

Abstract Background The total laboratory automation (TLA) involves the integration, automation, consolidation and digitalization of pre-examination, examination, and post-examination processes. It is far simpler to introduce TLA in a lean, highly standardized smart core lab setting than it is to replicate complex procedures based on manual workflows, therefore harmonization/standardization is a requirement. In this era of modern clinical laboratory, a very important step with respect to the quality of the entire process is method validation/ verification. Hence, it is fundamental to verify/validate TLA process flow, new techniques, new methods and new test parameters.During laboratory accreditation process, the most frequently cited deficiency involves inappropriate PQ (Performance Qualification) and verification protocol. The main principles to the PQ laboratory test validation or verification protocol are Accuracy, Precision, Reference Interval, Detection Limit (LOD), Analytical Measurement Range (AMR) and Clinically Reportable Range (CRR), etc. Hence a clinically appropriate turnaround time is guaranteed via validation, which also provides accurate and precise readings. Methods Around 250 parameters, of biochemical and immunoassay for samples like serum/plasma/cerebrospinal fluid/urine have been validated/verified on this automated system. Clinical Laboratory Standards Institute (CLSI) and best practise checklist as per international and national accreditation bodies served as the foundation for verification. Following are the steps for verification. Analytical Accuracy: Run samples by both methods to evaluate bias. Verify Precision: Run 5 replicates per run for 5 days, at all levels of control sera. Check Reference Intervals: Representative 20 healthy individuals are selected. Verify LOB and LOD Values: Run 20 blank (zero calibrator) or low patient samples. Pneumatic System Verification Protocol: 20 samples carried manually by health care assistants and 20 samples transported via the pneumatic system. We have done sigma metrics of 250 parameters in the lab. Results With particular reference to Thyroid Stimulating Hormone (TSH), we have obtained the following results: For the Reference interval study, out of 353 volunteers recruited, 8 volunteer data were excluded (7 outliers, 1 abnormal TPO values). We obtained the reference interval of 0.53–4.489 μIU/mL, which is within the range specified by the manufacturer's reference range. A good level of analytical accuracy is demonstrated between the two instruments with r2 = 0.9938 having a coefficient of variation of 4.32%. The coefficient of variation values of precision for inter laboratory method comparison for lower and high-level values is 1.39% and 1.76% respectively, which is comparable with the manufacturers claims values. The coefficient of repeatability is 1.3442 is higher than 0.7 and hence considered as the two instruments having a good retest reliability. We observed more than six sigma performance of TSH. Based on Operational Specification (OPSpecs) Chart and Method Decision Chart sigma values of all the parameters are evaluated and quality control strategies have been defined. Conclusion Thus, validation of all biochemistry &amp; immunoassay parameters in TLA set up of the smart core laboratory promotes an environment, emphasizing patient safety and quality patient care.

Use of mobile technology to identify behavioral mechanisms linked to mental health outcomes in Kenya: protocol for development and validation of a predictive model

ObjectiveThis study proposes to identify and validate weighted sensor stream signatures that predict near-term risk of a major depressive episode and future mood among healthcare workers in Kenya.ApproachThe study will deploy a mobile application (app) platform and use novel data science analytic approaches (Artificial Intelligence and Machine Learning) to identifying predictors of mental health disorders among 500 randomly sampled healthcare workers from five healthcare facilities in Nairobi, Kenya.ExpectationThis study will lay the basis for creating agile and scalable systems for rapid diagnostics that could inform precise interventions for mitigating depression and ensure a healthy, resilient healthcare workforce to develop sustainable economic growth in Kenya, East Africa, and ultimately neighboring countries in sub-Saharan Africa. This protocol paper provides an opportunity to share the planned study implementation methods and approaches.ConclusionA mobile technology platform that is scalable and can be used to understand and improve mental health outcomes is of critical importance.

Validation of a New Tool to Detect and Characterize Spinal Cord Injury in the Acute Trauma Patient: The Montreal Acute Classification of Spinal Cord Injury.

Retrospective validation protocol. The International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) is the most comprehensive tool for classifying spinal cord injuries (SCI), but it is not adapted for the evaluation of trauma patients. The objective is to develop and validate a streamlined tool, the Montreal Acute Classification of Spinal Cord Injury (MAC-SCI) that can be integrated in the evaluation of trauma patients to detect and characterize traumatic SCI (tSCI). The completion rate of the ISCNSCI during initial evaluation after tSCI was estimated at a Level-1 trauma center specialized in SCI care. Using a modified Delphi technique, we designed the MAC-SCI, a new tool to detect and characterize the severity grade and level of SCI in the polytrauma patient. A cohort consisting of 35 consecutive tSCI patients with complete ISNCSCI documentation was used to validate the MAC-SCI. The severity grade and neurological level of injury (NLI) were assessed using the MAC-SCI, and compared to those obtained with the ISNCSCI. Only 33% of 148 patients admitted after a tSCI had a complete ISNCSCI performed at initial presentation. The MAC-SCI retains 53 of the 134 elements from the ISNCSCI. There was a 100% concordance in severity grade between the MAC-SCI and ISNCSCI. The NLI were within 2 levels between the MAC-SCI and ISNCSI for 100% of patients. The MAC-SCI is a streamlined tool that accurately detects and characterizes tSCI in the acute trauma setting. It could be implemented in trauma protocols to guide the management of SCI patients. Level III Diagnostic criteria.

Development and feasibility of a theory-guided and evidence-based physical activity intervention in pregnant women with high risk for gestational diabetes mellitus: a pilot clinical trial

BackgroundPhysical activity has been utilized as an effective strategy to prevent gestational diabetes mellitus (GDM). However, most pregnant women with high risk for GDM did not achieve the recommended physical activity level. Furthermore, relevant physical activity protocols have varied without theory-guided and evidence-based tailored to pregnant women with high risk for GDM. This study aimed to develop and pilot test a theory-guided and evidence-based physical activity intervention protocol for pregnant women with high risk for GDM.MethodsThe study design was guided by the Medical Research Council Framework for Developing and Evaluating Complex Intervention (the MRC framework). The preliminary protocol for physical activity intervention was developed based on self-efficacy theory, research evidence identified from systematic reviews and clinic trials, stakeholder engagement, context, and economic considerations. The preliminary intervention protocol was validated through a content validity study by an expert panel of 10 experts. A single-blinded randomized controlled trial (RCT) was designed to test the feasibility and acceptability of the intervention.ResultsThe validity of the preliminary intervention protocol was excellent as consensus was achieved. The final 13 sessions of self-efficacy enhancing physical activity intervention protocol were developed, including knowledge education, exercise clinic visits and video, and group discussions with face-to-face and online blended sessions. In the feasibility study, 34 pregnant women with high risk for GDM were randomized for the intervention (n = 17) or the control group (n = 17). The recruitment and retention rates were 82.9% and 58.9%, respectively. Women in the intervention group had a lower incidence of GDM (26.7% vs. 36.5%) than the control group (P >0.05). All participants were satisfied with the intervention and agreed that the intervention was helpful.ConclusionsThe developed self-efficacy-enhancing physical activity intervention is a feasible and acceptable intervention for enhancing physical activity among pregnant women with high risk for GDM and is ready to be tested in a more extensive RCT study.Trial registrationThe study was registered on 4 February 2022 (ChiCTR2200056355) by the Chinese Clini Trial Registry (CHiCTR).

Quantitative Dynamic Allodynograph-A Standardized Measure for Testing Dynamic Mechanical Allodynia in Chronic Limb Pain.

Dynamic mechanical allodynia (DMA) is both a symptom and a central sensitization sign, yet no standardized method for quantifying the DMA area has been reported. This study aimed to establish psychometric properties for Quantitative Dynamic Allodynography (QDA), a newly developed protocol measuring the DMA area as a percentage of the body surface. Seventy-eight patients aged 18-65 diagnosed with chronic complex regional pain syndrome (CRPS) participated in this study. Test-retest reliability was conducted twice, one week apart (N = 20), and inter-rater (N = 3) reliability was conducted on 10 participants. Disease severity (CRPS Severity Score, CSS), pain intensity (VAS), and quality of life (SF-36) measures were utilized to test construct validity. High inter-rater reliability (intraclass correlation coefficient (ICC) = 0.96, p < 0.001) and test-retest reliability (r = 0.98, p < 0.001) were found. Furthermore, the QDA score was found to be correlated with the CSS (r = 0.47, p < 0.001), VAS (r = 0.37, p < 0.001), and the SF-36 physical health total (r = -0.47, p < 0.001) scores. The QDA is the first developed reliable and valid protocol for measuring DMA in a clinical setting and may be used as a diagnostic and prognostic measure in clinics and in research, advancing the pain precision medicine approach.

Abstract PO-061: Utilizing T cell receptor-based therapy to treat anaplastic thyroid cancer

Abstract Anaplastic thyroid cancer (ATC) is considered to be among the most aggressive solid tumors in thyroid tissue, with a 6-month medium overall survival. The effectiveness of conventional treatments, such as surgery, chemotherapy, and radiation therapy, in extending the survival of patients is limited. Therefore, there is an urgent need to develop novel systemic therapeutic interventions that can induce long-lasting responses. Adoptive cell therapy has revolutionized cancer immunotherapy by successfully treating B-cell malignancies through chimeric antigen receptor-based approaches. For solid tumors, there is a need to identify a broader spectrum of tumor target antigens, and the field has now shifted towards leveraging T cell receptors (TCRs) which can recognize both intracellular and extracellular antigen-derived epitopes displayed by major histocompatibility complex (MHC) molecules. Our team has established an immunogenic epitope discovery pipeline, followed by a specialized protocol for empiric validation of candidate epitopes. We characterized immunogenic epitopes by coupling tandem mass spectrometry of MHC-eluted peptides with tumor proteome and MHC-peptide binding prediction databases. By integrating multi-omics data (genomics, transcriptomics, and immunopeptidomics) from both in-house and publicly available ATC databases, we find that ATC exhibits significant upregulation of pathways associated with microtubule-based movement, chromosome segregation, kinetochore complex components, and mitotic cytokinesis. We have identified several HLA-A2- and A24-restricted immunogenic peptides representing these pathway-associated proteins that covered more than 60% of the patient population. NDC80 kinetochore complex components (NDC80) and PDZ binding kinase (PBK) have been selected as top candidates. Peptides derived from NDC80 and PBK were subsequently utilized to isolate antigen-specific T cells from peripheral blood and identify cognate TCR. These peptide-specific T lymphocytes elicit cytotoxicity toward multiple HLA-matched ATC cell lines and tumor samples in vitro and in vivo. Furthermore, understanding the role of these genes in ATC tumorigenesis may identify novel combination strategies with adoptive cell therapy to yield synergistic effects. In conclusion, our studies contribute to the development of a new treatment paradigm for treating ATC, with the prospect of improving survival and outcome in this rare cancer patient population. Citation Format: Shao-Hsi Hung, Ying Henderson, Ke Pan, Yulun Chiu, Shailbala Singh, Yunyun Chen, Stephen Lai, Cassian Yee. Utilizing T cell receptor-based therapy to treat anaplastic thyroid cancer [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-061.

Assessing cancer risk in the anterior part of the prostate using micro-ultrasound: validation of a novel distinct protocol

PurposeTo develop and validate a micro-ultrasound risk score that predicts the likelihood of significant prostate cancer in the anterior zone.MethodsPatients were enrolled from three expert institutions familiar with micro-ultrasound. The study was conducted in two phases. First, the PRI-MUS anterior score was developed by assessing selected prostate videos from patients who subsequently underwent radical prostatectomy. Second, seven urology readers with varying levels of experience in micro-ultrasound examination evaluated prostate loops according to the PRI-MUS anterior score. Each reader watched the videos and recorded the likelihood of the presence of significant cancer in the anterior part of the prostate in a three-point scale. The coherence among the readers was calculated using the Fleiss kappa and the Cronbach alpha.ResultsA total of 102 selected prostate scans were used to develop the risk assessment for anterior zone cancer in the prostate. The score comprised three categories: likely, equivocal, and unlikely. The median (IQR) sensitivity, specificity, positive predictive value, and negative predictive value for the seven readers were 72% (68–84), 68% (64–84), 75% (72–81), and 73% (71–80), respectively. The mean SD ROC AUC was 0.75 ± 2%, while the Fleiss kappa and the Cronbach alpha were 0.179 and 0.56, respectively.ConclusionMicro-ultrasound can detect cancerous lesions in the anterior part of the prostate. When combined with the PRI-MUS protocol to assess the peripheral part, it enables an assessment of the entire prostate gland. Pending external validation, the PRI-MUS anterior score developed in this study might be implemented in clinical practice.

Methods of analyzing the long head of the biceps tendon in the management of distal supraspinatus tendon ruptures. Part 2: The role and validation of an arthroscopic exploration protocol of the long head of the biceps tendon

IntroductionInter-observer arthroscopic assessments of the Long head of the Biceps tendon (LHB) injuries, in the absence of predefined instructions, are poorly reproducible. There are several types of LHB injuries, of varying severity, which can make its intraoperative analysis subjective. HypothesisThe application of a precise arthroscopic exploration protocol, particularly dynamic, associated with an equally precise analysis of the possible tendon lesions, intrinsic or extrinsic, makes it possible to obtain a reproducible analysis of the lesions of the LHB and aid decision-making around its conservation or its resection, in distal supraspinatus tendon ruptures. Material and methodsThis was a prospective, multicenter study including 371 patients with a stage 1 rupture of the supraspinatus tendon, in accordance with the Patte classification. An exploration protocol with intraoperative video recording of the articular portion of the biceps was systematically performed by the operators. It included static intra-articular and extra-articular observation of the LHB, as well as a dynamic intra-articular hook test with mobilization in internal and external rotation, and in anterior elevation. An analysis of the lesion status of the LHB was then made by the principal operator (Op), after defining the various possible lesions: intrinsic or extrinsic. This initial diagnostic assessment was then compared with the analysis made by two independent observers (Obs1, Obs2) based on a replay of the recorded videos. The reliability of agreement was then measured using Cohen's Kappa coefficient (K) and Fleiss’ kappa. ResultsTwo hundred and fifty-seven videos were analyzable. The level of agreement between the two independent observers was strong (K=0.63) for applying the diagnosis of a healthy or pathological biceps. The agreement between the independent observers and the operator was weaker (respectively K Op-Obs1=0.51 - moderate and K Op-Obs2=0.39 - poor). ConclusionThe application of a precise protocol for the exploration of the LHB, associated with a previously defined lesion classification, makes it possible to obtain a high rate of agreement for the arthroscopic diagnostic analysis of the LHB. However, arthroscopy cannot be used as the only criterion for deciding which procedure to perform on the LHB. Other clinical and para-clinical factors must be taken into consideration. Level of evidenceIII; prospective inter-observer series.

Blood Pressure Measurement Based on the Camera and Inertial Measurement Unit of a Smartphone: Instrument Validation Study.

Even though several mobile apps that can measure blood pressure have been developed, the data about the accuracy of these apps are limited. We assessed the accuracy of AlwaysBP (test) in blood pressure measurement compared with the standard, cuff-based, manual method of brachial blood pressure measurement (reference). AlwaysBP is a smartphone software that estimates systolic blood pressure (SBP) and diastolic blood pressure (DBP) based on pulse transit time (PTT). PTT was calculated with a finger photoplethysmogram and seismocardiogram using, respectively, the camera and inertial measurement unit sensor of a commercially available smartphone. After calculating PTT, SBP and DBP were estimated via the Bramwell-Hill and Moens-Korteweg equations. A calibration process was carried out 3 times for each participant to determine the input parameters of the equations. This study was conducted from March to August 2021 at Chungnam National University Sejong Hospital with 87 participants aged between 19 and 70 years who met specific conditions. The primary analysis aimed to evaluate the accuracy of the test method compared with the reference method for the entire study population. The secondary analysis was performed to confirm the stability of the test method for up to 4 weeks in 15 participants. At enrollment, gender, arm circumference, and blood pressure distribution were considered according to current guidelines. Among the 87 study participants, 45 (52%) individuals were male, and the average age was 35.6 (SD 10.4) years. Hypertension was diagnosed in 14 (16%) participants before this study. The mean test and reference SBPs were 120.0 (SD 18.8) and 118.7 (SD 20.2) mm Hg, respectively (difference: mean 1.2, SD 7.1 mm Hg). The absolute differences between the test and reference SBPs were <5, <10, and <15 mm Hg in 57.5% (150/261), 84.3% (220/261 ), and 94.6% (247/261) of measurements. The mean test and reference DBPs were 80.1 (SD 12.6) and 81.1 (SD 14.4) mm Hg, respectively (difference: mean -1.0, SD 6.0 mm Hg). The absolute differences between the test and reference DBPs were <5, <10, and <15 mm Hg in 75.5% (197/261), 93.9% (245/261), and 97.3% (254/261) of measurements, respectively. The secondary analysis showed that after 4 weeks, the differences between SBP and DBP were 0.1 (SD 8.8) and -2.4 (SD 7.6) mm Hg, respectively. AlwaysBP exhibited acceptable accuracy in SBP and DBP measurement compared with the standard measurement method, according to the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization protocol criteria. However, further validation studies with a specific validation protocol designed for cuffless blood pressure measuring devices are required to assess clinical accuracy. This technology can be easily applied in everyday life and may improve the general population's awareness of hypertension, thus helping to control it.