Potential Matches Research Articles

Factors Associated with Opting Out of an Unrelated Hematopoietic Stem Cell Donor Registry: Differences and Similarities across Five Key Groups of Young Race/Ethnically Diverse Potential Donors in the United States

Young adults from underserved racial/ethnic groups are critically needed as unrelated hematopoietic stem cell (HSC) donors, yet they are more likely than other groups to opt out of donation after having matched a patient. Understanding which factors are most strongly associated with opting out among young underserved racial/ ethnic registered donors compared with their White counterparts will provide the basis for specific interventions to improve donor retention. We sought to determine the key, modifiable psychosocial, registry-related, and donation-related characteristics that are uniquely associated with opting out across 5 key racial/ethnic groups of young HSC donor registry members who had been contacted as a potential match for a patient. This study examines data from a large cross-sectional survey of young (age 18 to 30) registry members shortly after they preliminarily matched a patient (CT-stage) and continued toward or opted out of donation (CT-C and CT-NI), stratified by racial/ethnic group and sex. We assessed psychosocial, registry-related, and donation-related characteristics for all participants. We used chi-squared and F tests to assess differences between racial/ethnic groups. A separate logistic regression analysis for each racial/ethnic group was conducted to quantify adjusted associations between each variable and opting out. Then, we compared these associations across the racial/ethnic groups by evaluating the interaction effect between each variable and racial/ethnic group, with the same outcome (CT-C versus CT-NI) in question. Nine hundred thirty-five participants were surveyed, including 284 White, 165 Hispanic, 191 Black, 192 Asian/Pacific Islander, and 103 Multiracial/multiethnic participants. There were significant differences across racial/ethnic groups in values/goals, religious objections to donation, HSC-related medical mistrust, and parental involvement in donation decisions. Adjusted logistic regression subgroup analyses indicated that ambivalence was strongly associated with opting out across all racial/ethnic groups. Greater focus on intrinsic life goals (e.g., raising a family, becoming a community leader, influencing social values) was associated with opting out in the Multiracial/multiethnic, Hispanic, and Asian/Pacific Islander groups. Healthcare mistrust and insufficient registry contact was a significant factor for Hispanic participants. Protective factors against opting out included remembering joining the registry (Black participants), and parental support for donation decision (Asian/Pacific Islander participants). The performance of each logistic regression model was strong, with area-under-the curve ≥.88, CT-stage outcome classification accuracy ≥89%, and good fit between expected and observed opt-out probabilities. In the analysis across different racial/ethnic groups, the only significant interaction was race/ethnicity by whether more contact with the registry would have changed the decision at CT-stage; this variable was significant only for the Hispanic group. In the within-group analysis for Hispanic participants, the "more registry contact" variable was strongly associated with opting out (odds ratio 5.8, P = .03). Consistent with a growing body of HSC donor research, ambivalence was a key factor associated with opting-out for all racial/ethnic groups. Other key variables were differentially associated with opting-out depending on racial/ethnic group. Our study highlights key variables that registries should focus on as they develop targeted and tailored strategies to enhance commitment and reduce attrition of potential donors.

Standardizing Extracted Data Using Automated Application of Controlled Vocabularies.

Extraction of toxicological end points from primary sources is a central component of systematic reviews and human health risk assessments. To ensure optimal use of these data, consistent language should be used for end point descriptions. However, primary source language describing treatment-related end points can vary greatly, resulting in large labor efforts to manually standardize extractions before data are fit for use. To minimize these labor efforts, we applied an augmented intelligence approach and developed automated tools to support standardization of extracted information via application of preexisting controlled vocabularies. We created and applied a harmonized controlled vocabulary crosswalk, consisting of Unified Medical Language System (UMLS) codes, German Federal Institute for Risk Assessment (BfR) DevTox harmonized terms, and The Organization for Economic Co-operation and Development (OECD) end point vocabularies, to roughly 34,000 extractions from prenatal developmental toxicology studies conducted by the National Toxicology Program (NTP) and 6,400 extractions from European Chemicals Agency (ECHA) prenatal developmental toxicology studies, all recorded based on the original study report language. We automatically applied standardized controlled vocabulary terms to 75% of the NTP extracted end points and 57% of the ECHA extracted end points. Of all the standardized extracted end points, about half (51%) required manual review for potential extraneous matches or inaccuracies. Extracted end points that were not mapped to standardized terms tended to be too general or required human logic to find a good match. We estimate that this augmented intelligence approach saved hours of manual effort and yielded valuable resources including a controlled vocabulary crosswalk, organized related terms lists, code for implementing an automated mapping workflow, and a computationally accessible dataset. Augmenting manual efforts with automation tools increased the efficiency of producing a findable, accessible, interoperable, and reusable (FAIR) dataset of regulatory guideline studies. This open-source approach can be readily applied to other legacy developmental toxicology datasets, and the code design is customizable for other study types. https://doi.org/10.1289/EHP13215.

Decision support framework for IT project manager recruitment

Information technology project managers (IT PM) have a critical influence on IT project success while attracting and selecting the right IT PM is challenging. We followed a four-level research design and firstly developed a taxonomy as an input for a cluster analysis to identify patterns in IT PM job advertisements. Based hereon, we developed a decision support framework for IT PM recruitment. We evaluated our findings in an online survey. We identified multiple design elements for IT PM job advertisements within five perspectives and deduced five IT PM archetypes. The decision support framework uses five questions to assist IT PM recruitment. We expand the knowledge base and consider not only IT PM requirements but also benefits. Our decision support framework is the first to holistically support IT PM recruitment, supports recruitment managers in structuring job interviews, identifies potential matches between applicants and recruiters, and assists in the final selection.

Experimental investigation of instantaneous lift on NACA 0018 airfoil section due to a non-harmonic pitching motion

In this study, we explore the problem of an airfoil in a harmonic and arbitrary periodic pitching motion and seek to understand how theoretical estimation with first-order potential theory match experiments. We adopt Jones’ approximation for the Wagner function for lift computations in the time domain and Theodorsen’s model in the frequency domain. We experimentally investigate a two-dimensional symmetric NACA 0018 airfoil in pitching motion under attached flow with reduced frequencies up to 0.25 and Reynolds number varying from 1.5×105 to 3×105. To eliminate the influence of the laminar separation bubble, free-stream turbulence intensity was elevated above the baseline level by placing turbulence generating grid, thus, obtaining better compatibility between the flow conditions in the experiments and the theoretical assumptions. Time-resolved sectional lift is determined by simultaneous static pressure measurement with miniature pressure transducers. The transient response is captured with accuracy in the time domain by quantifying the non-circulatory contribution. Excellent agreement is achieved in the time and frequency domains due to the highly accurate measurement of the instantaneous magnitude and phase of the time-resolved surface pressures. We further explore the applicability of the theory for high-pitching amplitudes, which results in a temporary deviation of the measured lift from the theoretical predictions. As the frequency domain unsteady theory is more widely studied than its time domain counterpart, this study provides a unique opportunity to highlight the significance of time-domain analysis in estimating instantaneous lift in non-harmonic motion.

Surrounding and background shades effect on color adjustment of single-shade composites.

This study evaluated the effects of surrounding and background shades on the color adjustment potential (CAP) and visual color match of two single-shade composites, Vittra APS Unique and Charisma Diamond One. Cylinder-shaped specimens were constructed, consisting of either single-shade composites alone (simple) or composites surrounded by the Forma material at shades A1 or A3 (dual). Simple specimens using only the Forma at the specified shades were also prepared. Color measurements of simple specimens were taken against a gray background using a spectrophotometer. For dual specimens, the color of the inner composite was measured against a gray or chromatic (the same shade as the outer composite) background. Color differences (ΔE00) between the single-shade composites and the A1/A3 composite were calculated. CAP was determined by comparing data from simple and dual specimens. Four experienced dentists scored the color match (perfect to unacceptable) for each specimen using a viewing booth illuminated by an illuminant D65. Data were analyzed with repeated-measures ANOVA and the Kruskal-Wallis test. The results showed that both single-shade composites showed the lowest color discrepancies when they were compared to A1 and A3. Using a chromatic background only significantly affected the CAP when the outer composite was A3. The visual analysis showed poor color matches between the single-shade and control chromatic composites, except for Charisma Diamond One surrounded by A1. In conclusion, the CAP values of the evaluated single-shade composites were impacted by both surrounding shade and background color, and the color match of these materials tended to be poor.

Electroreductive deuteroarylation of alkenes enabled by an organo-mediator.

Electroreduction mediated by organo-mediators has emerged as a concise and effective strategy, holding significant potential in the site-specific introduction of deuterium. In this study, we present an environmentally friendly electroreduction approach for anti-Markovnikov selective deuteroarylation of alkenes and aryl iodides with D2O as the deuterium source. The key to the protocol lies in the employment of a catalytic amount of 2,2'-bipyiridine as an efficient organo-mediator, which facilitates the generation of aryl radicals by assisting in the cleavage of the C-X (X = I or Br) bonds in aryl halides. Because its reduction potential matches that of aryl iodides, the organo-mediator can control the chemoselectivity of the reaction and avoid the side reactions of competitive substrate deuteration. These phenomena are theoretically supported by CV experiments and DFT calculations. Our protocol provides a series of mono-deuterated alkylarenes with excellent deuterium incorporation through two single-electron reductions (SER), without requiring metal catalysts, external reductants, and sacrificial anodes.

Distal Radius Allograft for Glenohumeral Instability: A Novel Osteochondral Allograft Reconstruction Option in the Setting of Glenoid Bone Loss

Background: Distal tibial allograft (DTA) reconstruction for glenoid bone loss is nonanatomic, as it does not match the glenoid radius of curvature (ROC) in the anterior-posterior (AP) plane. The dorsal articular portion of the distal radius has not been previously described as an allograft reconstruction option for glenoid bone loss. Purpose: To evaluate distal radius fresh-frozen allograft (DRA) as a potential match for glenoid reconstruction. Study Design: Controlled laboratory study. Methods: Eighteen fresh-frozen human cadaveric specimens—including 6 shoulder, 6 wrist, and 6 tibia specimens—were used. The ROC and the graft length were measured in the superior-inferior (SI) plane. A 30% defect was created in all glenoid specimens, and both DTAs and DRAs were harvested to assess graft fit after fixation. Computed tomography analysis was used to assess bony ROC and bone mineral density (BMD). Results: The cadaveric specimens had a mean age of 77 years. The mean SI glenoid length was 39.7 mm compared with 36.8 mm for the DRA and 30 mm for the DTA. The ROC in the SI plane was 29 ± 5.3 mm for the glenoid, 37.8 ± 4.9 mm for the DRA, and 24 ± 3.7 mm for the DTA. In the AP plane, the ROC was 39.6 ± 6.6 mm for the glenoid, 30.4 ± 18.6 mm for the DRA, and 126.3 ± 9.5 mm for the DTA. On computed tomography analysis, the ROC in the SI plane was 30.4 ± 1.5 mm for the glenoid, 30.3 ± 5.6 mm for the DRA, and 24.5 ± 9.4 mm for the DTA. In the AP plane, the ROC was 30.8 ± 2 mm for the glenoid, 19.1 ± 2.3 mm for the DRA, and 46.7 ± 21.7 mm for the DTA. The BMD was 226.3 ± 79 Hounsfield units (HU) for the glenoid, 228.5 ± 94.7 HU for the DRA, 235 ± 96.2 HU for the coracoid process, and 235.1 ± 84.6 HU for the DTA. Conclusion: Compared with the DTA, the DRA had a greater mean graft length in the SI plane, providing utilization in cases of larger bony defects; the DRA has a more acute ROC in the AP plane (closer to that of the glenoid), providing a greater potential buttress to anterior humeral translation. Compared with currently utilized grafts, the DRA BMD was not significantly diminished. This study presents the DRA as a novel allograft reconstruction option in the setting of anterior glenoid bone loss; further biomechanical and clinical investigation is indicated.

Term-BLAST-like alignment tool for concept recognition in noisy clinical texts.

Methods for concept recognition (CR) in clinical texts have largely been tested on abstracts or articles from the medical literature. However, texts from electronic health records (EHRs) frequently contain spelling errors, abbreviations, and other nonstandard ways of representing clinical concepts. Here, we present a method inspired by the BLAST algorithm for biosequence alignment that screens texts for potential matches on the basis of matching k-mer counts and scores candidates based on conformance to typical patterns of spelling errors derived from 2.9 million clinical notes. Our method, the Term-BLAST-like alignment tool (TBLAT) leverages a gold standard corpus for typographical errors to implement a sequence alignment-inspired method for efficient entity linkage. We present a comprehensive experimental comparison of TBLAT with five widely used tools. Experimental results show an increase of 10% in recall on scientific publications and 20% increase in recall on EHR records (when compared against the next best method), hence supporting a significant enhancement of the entity linking task. The method can be used stand-alone or as a complement to existing approaches. Fenominal is a Java library that implements TBLAT for named CR of Human Phenotype Ontology terms and is available at https://github.com/monarch-initiative/fenominal under the GNU General Public License v3.0.

A search tool based on language modelling developed for The Index of Middle English Prose.

Non-standardised early vernaculars present a problem for search tools due to the high degree of variation. The challenge lies in the variation found in orthography, syntax, and lexicon between titles, incipits, and explicits in manuscript copies of the same work. Traditional search methods relying on exact string matching or regular expressions fail to address these variations comprehensively. This project presents a web-based search tool specifically designed to handle linguistic and textual variation. The software is made available as a part of the Index of Middle English Prose (IMEP). The search tool addresses the issue of variation by utilizing a database of incipits and explicits, character-based n-gram language models (LMs) built with the Stanford Research Institute Language Modelling (SRILM) toolkit, and a fuzzy search script (IMEP: FSS) written in Python. The tool optimizes for recall, retrieving multiple potential matches for a search string, without attempting to identify the 'correct' one. The search process involves looking up exact matches in the database while simultaneously using the fuzzy search script to evaluate the incipits and explicits against a model of the search string, followed by a match of the search string against models of the incipits and explicits. This two-step process shortens the processing time, which would otherwise be unreasonably long, because while using SRILM to match the search string against each incipit or explicit in the IMEP for precision could be time-consuming, running a first step where all texts are matched against a single LM built from the search string allows for faster processing. A web application, built using Django and Docker, combines the results of the direct database lookup and the fuzzy search script, presenting them as a list with exact matches followed by fuzzy matches ordered by increasing model perplexity. The tool is made available Open Access and can be adapted to other datasets.

Feasibility of institution-agnostic, EHR-integrated regional clinical trial matching.

A lack of onsite clinical trials is the largest barrier to participation of cancer patients in trials. Development of an automated process for regional trial eligibility screening first requires identification of patient electronic health record data that allows effective trial screening, and evidence that searching for trials regionally has a positive impact compared with site-specific searching. To assess a screening framework that would support an automated regional search tool, a set of patient clinical variables was analyzed for prescreening clinical trials. The variables were used to assess regional compared with site-specific screening throughout the United States. Eight core variables from patient electronic health records were identified that yielded likely matches in a prescreen process. Assessment of the screening framework was performed using these variables to search for trials locally and regionally for an 84-patient cohort. The likelihood that a trial returned in this prescreen was a provisional trial match was 45.7%. Expanding the search radius to 20 miles led to a net 91% increase in matches across cancers within the tested cohort. In a U.S. regional analysis, for sparsely populated areas, searching a 100-mile radius using the prescreening framework was needed, whereas for urban areas a 20-mile radius was sufficient. A clinical trial screening framework was assessed that uses limited patient data to efficiently and effectively identify prescreen matches for clinical trials. This framework improves trial matching rates when searching regionally compared with locally, although the applicability of this framework may vary geographically depending on oncology practice density. Clinical trials provide cancer patients the opportunity to participate in research and development of new drugs and treatment approaches. It can be difficult to find available clinical trials for which a patient is eligible. This article describes an approach to clinical trial matching using limited patient data to search for trials regionally, beyond just the patient's local care site. Feasibility testing shows that this process can lead to a net 91% increase in the number of potential clinical trial matches available within 20 miles of a patient. Based on these findings, a software tool based on this model is being developed that will automatically send limited, deidentified information from patient medical records to services that can identify possible clinical trials within a given region.

Artificial intelligence and skull imaging advancements in forensic identification

ABSTRACT Managing the massive losses associated with large-scale disasters requires significant resources. The unexpected violence of these events generally remains a matter of casualties that urgently need to be identified in a reliable and cost-effective manner. To overcome these difficulties, many researchers have attempted to develop automated methods; moreover, a few recent research have investigated the applicability of artificial intelligence (AI)-based methods using skull, dental, and maxillofacial forensic imaging. In this review, we speculate on the advancement and potential of AI in Dental and Maxillofacial imaging that can help simplify person or victim identification and speed up the process with good accuracy. Using a few prefix search phrases, an online literature search was conducted (AI, Forensic, Skull, Dental, Imaging, Radiology) to identify papers about the advancement of AI in forensic dentistry in all kinds of radiographs, including two-dimensional (2D) and three-dimensional (3D) radiographs, cone beam computed tomography (CT) and CT. Most of the studies reported that automated methods of human identification based on 2D and 3D Dental and Skull radiographs using a convolutional neural network showed to assist in the fast and accurate identification by expertise evaluating a lot of images and quickly coming up with potential matches for identification. We advocate the application of AI techniques in the identification of individuals. However, there is a need to continue research with emphasis to validate models in skull identification.

Efficient Face Recognition in Real Time for Locating Missing Person

Abstract: This paper presents a web-based application system that utilizes deep learning as the core technology of a Face Recognition System, with the primary objective of enhancing the accuracy and efficiency of locating missing individuals. Every day, a significant number of individuals go missing due to various factors such as old age, mental health issues, or conditions like Alzheimer’s. The conventional methods employed for searching for missing persons are typically slow, expensive, and involve protracted physical searches lasting weeks or even months. In contrast, deep learning-based technologies offer a promising solution by rapidly analyzing substantial volumes of data within minutes or hours. By leveraging facial recognition technology, which is an application of deep learning, our proposed system aims to compare images and videos obtained from surveillance cameras with pictures of missing persons to identify potential matches. Specifically, we employ the Resnet deep learning algorithm to examine the images of missing individuals, thereby improving the accuracy and speed of identification and making the process more reliable and efficient. To provide a comprehensive solution, we have developed a user-friendly webbased application system that facilitates the search for missing persons. The application efficiently collects and stores information about missing individuals in a centralized database. Whenever a missing person is identified in a CCTV video stream, our application actively tracks their location. Once the missing person is successfully identified within the video stream, the application promptly sends location details via email to the person’s relative

Forensic examination of the hand

AbstractUsing anatomical feature comparison to consider potential matches from hand images to identify or eliminate suspects in an investigation, commonly relating to those involved in the production of images of child sexual abuse, is an emerging forensic methodology that has become increasingly utilized by police forces within the United Kingdom. This article gives an overview of the development of a process that is based on an understanding of anatomical variation and shows how new approaches can be introduced to forensic investigations. It describes the rationale that led to the development of the investigative methodology within the United Kingdom, and how it is implemented to ensure that comparisons and the subsequent reports are both methodologically sound and admissible in any of the courts within the UK legal jurisdictions.

Paper 02: Distal Radius Allograft for Glenohumeral Instability: A Novel Osteochondral Allograft Reconstruction Option in the Setting of Glenoid Bone Loss

Objectives: Glenoid bone loss in the setting of recurrent shoulder instability remains a challenging surgical problem. The coracoid process and iliac crest currently serve as primary autograft options for glenoid reconstruction. With regards to allograft alternatives, the distal tibia, first described in 2007, has good midterm outcomes when used during an index surgery and in cases of failed prior Latarjet reconstruction. While the distal tibia performs well in reconstructing the glenoid bony defect, it is a nonanatomic reconstruction and does not match the glenoid radius of curvature (ROC) in the anterior to posterior (AP) plane. No prior work has evaluated and described the utilization of the dorsal articular portion of the distal radius as an allograft reconstruction option for recurrent instability with glenoid bony deficiency. The purpose of this study was to evaluate distal radius fresh frozen allograft as a potential match for glenoid reconstruction through assessment of graft ROC and bone mineral density (BMD). Distal tibia allograft was utilized as the primary comparison group with both cadaveric and Computerized Tomography (CT) analysis. Methods: Eighteen fresh-frozen human cadaveric specimens (6 shoulder, 6 wrist, and 6 tibia) were utilized for this study. Specimens without osteoarthritis or prior surgical procedures were included. CT scans were obtained of all specimens to confirm the absence of osteoarthritis, significant joint deformity, or evidence of prior surgical procedure. Specimens were dissected free of all soft tissues except for the glenoid labrum of the shoulder and dorsal wrist ligaments of the distal radius. The ROC for each specimen were independently measured by two fellowship trained shoulder surgeons in both the superior to inferior (SI) and AP planes. Graft length in the SI plane was also assessed. A thirty percent defect was then created in all glenoid specimens and both distal tibia and distal radius grafts were harvested to assess graft fit post-fixation [Figure 1]. CTs were also analyzed to assess bony ROC and BMD for each specimen. Results: On cadaveric analysis, the mean SI graft length of the glenoid was 39.7 mm compared to 36.8 mm for the distal radius and 30.0 mm for the distal tibia [Table 1A]. Average ROC in the SI plane was 29.0 +/- 5.3 for the glenoid, 37.8 +/- 4.9 for the distal radius and 24.0 +/- 3.7 for the distal tibia; in the AP plan average ROC was 39.6 +/- 6.6 for the glenoid, 30.4 +/- 18.6 for the distal radius and 126.3 +/- 9.5 for the distal tibia [Table 1B]. On CT analysis, average ROC in the SI plane was 30.4 +/- 1.5 for the glenoid, 30.3 +/- 5.6 for the distal radius and 24.5 +/- 9.4 for the distal tibia; in the AP plane average ROC was 30.8 +/- 2.0 for the glenoid, 19.1 +/- 2.3 for the distal radius and 46.7 +/- 21.7 for the distal tibia [Table 2A]. Mean BMD was 226.3 +/- 79.0 for the glenoid, 228.5 +/-94.7 for the distal radius, 235.0 +/- 96.2 for the coracoid process, and 235.1 +/- 84.6 for the distal tibia [Table 2B]. Conclusions: Given fresh frozen allograft supply and cost constraints, exploration of additional graft options is necessitated. This study presents distal radius allograft as a novel reconstruction option for patients with anterior glenoid bone loss in the setting of recurrent glenohumeral instability. Compared with the distal tibia allograft, the distal radius had greater graft length in the SI plane providing possible utilization in cases of larger bony defects. The distal radius also has a more acute ROC in the AP plane (closer to that of the glenoid) compared with the distal tibia allograft providing a greater potential buttress to anterior humeral translation. Furthermore, the distal radius also has potential to employ the dorsal radio-carpal ligaments to perform an anterior capsular repair following allograft fixation. Finally, compared to currently utilized grafts (coracoid process and distal tibia), the distal radius BMD was not significantly diminished on CT analysis. This study presents the distal radius as a novel allograft reconstruction option in the setting of glenoid bone loss; further biomechanical and clinical investigation is indicated. [Table: see text][Table: see text]

Harnessing data science to improve molecular structure elucidation from tandem mass spectrometry

Compound structural identification for non-targeted screening of organic molecules in complex mixtures is commonly carried out using liquid chromatography coupled to tandem mass spectrometry (UHPLC-HRMS/MS and related techniques). Instrumental developments in recent years have increased the quality and quantity of data available; however, using current data analysis methods, structures can be assigned to only a small fraction of compounds present in typical mixtures. We present a new data analysis pipeline, “MSEI”, that harnesses data science methodologies to improve structural identification capabilities from tandem mass spectrometry data. In particular, feature vectors for fingerprint calculation are found directly from tandem mass spectra, strongly reducing computational costs, and fingerprint comparison uses an optimised methodology accounting for uncertainty to improve distinction between matching and non-matching compounds. MSEI builds on the identification of a small number of compounds through current state-of-the-art data analysis on UHPLC-HRMS/MS measurements and uses targeted training and tailored molecular fingerprints to focus identification to a particular molecular space of interest. Initial compound identifications are used as training data for a set of random forests which directly predict a custom 75-digit molecular fingerprint from a vectorised MS/MS spectrum. Kendrick mass defects (KMDs) for peaks as well as “lost” fragments removed during fragmentation were found to be useful information for fingerprint prediction. Fingerprints are then compared to potential matches from the PubChem structural database using Euclidean distance, with fingerprint digit weights determined using an SVM to maximise distance between matching and non-matching compounds. Potential matches are additionally filtered for hydrophobicity based on measured retention time, using a newly developed machine learning method for retention time prediction. MSEI was able to correctly assign > 50% of structures in a test dataset and showed > 10% better performance than current state-of-the-art methods, while using an order of magnitude less computational power and a fraction of the training data.

International molecular tumour board: A transatlantic precision oncology collaboration.

e13525 Background: Genomic testing (GT) is increasingly used to guide treatment in cancer care. There is considerable international variation in provider expertise and access to molecular tumor board (MTB) and therapeutics. In Ireland high quality GT is not broadly available; only 3% of patients receive treatment on a clinical trial. Our hypothesis is that increased GT would lead to enhanced treatment options and increase access to trials. Through institutional partnership between community cancer programs in Ireland and the United States (US), we offered GT and collaborative MTB review to patients with advanced cancer and observed the effect on treatment patterns. Methods: Eligible patients with metastatic solid tumors attending a single Irish community cancer unit between 2018 and 2022 were offered GT and collaborative MTB review on the COMPASS study. Testing was completed using a Foundation Medicine test reimbursed by multiple payors. Testing was performed on tumor tissue, or if not available, on circulating tumor DNA (ctDNA). Cases were presented virtually at MTB. Treatment decisions were based on MTB discussion of actionable alterations (AAs) with at least preclinical evidence of benefit, clinical trial availability, and local drug access. The primary outcome was impact of GT on treatment decision. Secondary outcomes included rate of AAs, and potential germline mutations. An exploratory objective evaluated potential matches to US-based NCI MATCH and ASCO TAPUR trials. Results: In total, 157 patients were screened and 120 enrolled on the COMPASS study. 46 (38.3%) male and 74 (61.7%) female with 25 different primary cancers. Tissue testing was performed for 79 (65.8%) patients and 35 (29.1%) had ctDNA testing. 105 (87.5%) patients had at least one AA by MTB criteria, 49 (46.7%) patients had more. Treatment decisions are outlined. 7 patients derived clinical benefit from treatment. 26 (21.7%) patients had a potential match for MATCH or TAPUR arms. MTB suggested 35 (29.1%) patients consider germline testing. 22 previously had genetic testing and 8 more had germline testing following GTB; 1 pathogenic germline mutation was identified. Conclusions: We successfully completely a transatlantic collaboration to introduce US MTB-directed care for Irish patients. The majority of patients had novel treatment options identified but drug access and clinical trial enrolment was limited by regional availability. International collaboration on precision oncology treatment trials should be prioritized.[Table: see text]

Using key stakeholder interviews to inform implementation of a cancer center collaborative intervention to improve clinical trial accruals.

e18650 Background: Cancer clinical trial (CT) participation rates in the US are low, especially among BIPOC populations. Patient enrollment to CTs is influenced by structural characteristics of the care delivery system, and the nature of individual needs and available resources. We are developing a multi-level intervention across 3 cancer centers in New York City by creating a collaborative pool of, and a referral system for breast, prostate, and liver cancer CTs to increase overall participation, particularly among BIPOC populations. To inform implementation of this intervention, we explored key stakeholder perceptions and attitudes around CT enrollment process across 3 hospitals within one such cancer center. Methods: We conducted semi-structured interviews with 23 key stakeholders to determine the attitudinal and structural factors affecting CT accrual at 1 cancer center and its 2 community hospital affiliates. Stakeholders included oncologists, nurses, informaticists, oncology leadership and research staff, identified using a targeted and snowball sampling approach. Guided by the Behavioral Model of Health Service Use, we identified themes related to enabling, predisposing, and need factors, and coded transcripts until theme saturation in Dedoose. Results: Key approaches to improve CT participation focused on these structural enabling themes: increased availability of CTs, personnel to screen and enroll patients, well-timed and technology-assisted clinician notification of a potential CT match (within or outside home institution), along with an institutional culture encouraging stakeholder engagement, provider outreach, and care coordination. Important predisposing and enabling themes related to stakeholders’ beliefs about patients included: financial access, knowledge and perceptions about CTs, language barriers, motivation, and medical mistrust. Knowledge about open trials, and skepticism or enthusiasm about CTs were important predisposing themes related to clinicians. Need theme affecting implementation was clinician judgment about their patients’ eligibility for CT evaluated based on functional status, comorbidities, age, advanced cancer stage, progression of disease, change in therapy, and drug targets. Conclusions: We identified actionable enabling, predisposing, and need factors that serve as barriers to CT accrual and to successful implementation of our intervention. Major findings were structural and attitudinal, including lack of staffing resources for clinicians, and financial assistance and access for patients. Updated information about open CTs, implementation of e-screening tools for patient enrollment, addressing clinician skepticism for enrollment by increased recognition for their research efforts, as well as delivery of culturally sensitive patient education around CTs may improve CT enrollment.

Integrating Bioinformatics and Network Pharmacology to Explore the Therapeutic Target and Molecular Mechanisms of Schisandrin on Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease and is currently the leading cause of sudden death in adolescent athletes. Schisandrin is a quality marker of the traditional Chinese medicine Schisandra chinensis, which has an excellent therapeutic effect on HCM, but its pharmacological mechanism remains unclear. This study aimed to explore the potential and provide scientific evidence for schisandrin as a lead compound against hypertrophic cardiomyopathy. The drug-like properties of schisandrin were predicted using the SwissADME website. Then, the PharmMapper database was used to predict potential drug targets and match gene names in the Uniprot database. HCM targets were collected from NCBI, OMIM, and Genecards databases and intersected with drug targets. The intersection targets were imported into the STRING database for PPI analysis, and core targets were identified. KEGG and GO enrichment analysis was performed on the core targets through the DAVID database, and all network maps were imported into Cytoscape software for visualization optimization. HCM-related datasets were downloaded from the GEO database to analyze core targets and screen differentially expressed target genes for molecular docking. After the PPI network analysis of the intersection targets of drugs and diseases, 12 core targets were screened out. The KEGG analysis results showed that they were mainly involved in Rap1, TNF, FoxO, PI3K-Akt, and other signaling pathways. After differential analysis, PPARG, EGFR, and MMP3 targets were also screened. The molecular docking results showed that schisandrin was well bound to the protein backbone of each target. This study used network pharmacology combined with differential expression and molecular docking to predict that schisandrin may treat HCM by acting on PPARG, EGFR, and MMP3 targets, and the regulatory process may involve signaling pathways, such as Rap1, TNF, FoxO, and PI3K-Akt, which may provide a valuable reference for subsequent studies.

Intensity-dependent mass search for improving metabolite database matches in chemical isotope labeling LC-QTOF-MS-based metabolomics

Liquid chromatography mass spectrometry (LC-MS) has been increasingly used for metabolome analysis. One of the critical steps in the LC-MS metabolome analysis workflow is related to metabolite identification. Among the measured parameters, peak mass is commonly used to search against a database for potential metabolite matches. Higher accuracy mass measurement allows the use of a narrower mass tolerance window for mass search. While various types of mass analyzers can routinely measure a peak mass with an error of less than a few ppm, mass measurement accuracy is not uniform for peaks with different intensities, particularly for quadrupole time-of-flight (QTOF) MS. Herein we present a simple and convenient method to determine the relation between peak intensity and mass error in LC-QTOF-MS-based metabolome analysis, followed by intensity-dependent mass search (IDMS) of a database for metabolite matches. This method is based on running a series of sodium formate mass calibrants, as part of the standard operating procedure (SOP) in LC-MS data acquisition, and then curve-fitting the measured mass errors and peak intensities. We show that, in two different quadrupole time-of-flight (QTOF) mass analyzers, mass accuracy is generally reduced as peak intensity decreases, which is independent of m/z values in the range commonly used for metabolite detection (e.g., m/z < 1000). We demonstrate the improvement in metabolite matches using IDMS in the analyses of dansyl labeled standards and human urine samples. We have implemented the IDMS method in the freely available MCID database at www.mycompoundid.org, which is composed of 8021 known human endogenous metabolites and their predicted metabolic products (375,809 compounds from one metabolic reaction and 10,583,901 compounds from two reactions).

Clinical outcomes, complications, and survivorship for unicompartmental knee arthroplasty versus total knee arthroplasty in patients aged 80years and older with isolated medial knee osteoarthritis: a matched cohort analysis.

The primary goal of this study is to compare clinical outcomes, complication rate, and survivorship in octogenarians who underwent total knee arthroplasty (TKA) or unicompartmental knee arthroplasty (UKA) by performing a matched cohort analysis. We analyzed 75 medial UKAs performed by a single experienced surgeon. The included cases were matched with 75 TKAs performed during the same study period. Potential TKA matches used identical exclusion criteria. UKAs were age-, gender-, and body mass index (BMI)-matched at the rate of 1 UKA to 1 TKA from our departmental database. Clinical evaluation included the visual analog scale for pain, range of motion (ROM-flexion and extension), Knee Society Score (KSS), and Oxford Knee Score (OKS). Each patient was clinically evaluated on the day before the surgery (T0) and at two follow-ups at least 12months (T1) and 24months (T2) after the surgery. For the survivorship, revision was defined as failure of the implant (periprosthetic joint infection, periprosthetic fracture, or aseptic loosening), and survival was based on implant revision or patient death. Undesirable clinical developments that were not present at baseline or that increased in severity after treatment were classified as adverse events. The mean age at the time of the surgery was 82.1 ± 1.9years for UKA and 81.5 ± 1.8years for TKA (p = 0.06). The two groups differed in regard to surgical time (UKA 44.9 ± 7.2min; TKA 54.4 ± 11.3min; p < 0.001); furthermore, the UKA group showed better function (ROM; flexion and extension) than the TKA group at each follow-up time point (p < 0.05). Both groups reported a significant improvement in all clinical scores (KSS and OKS) when compared with their preoperative status (p < 0.05), while no differences were found between the groups at each follow-up (p > 0.05). The UKA group reported 7 (9.3%) failures, while TKA reported 6 failures. There were no survival differences between the groups (T1: p = 0.2; T2: p = 0.5). Overall complication rate was 6% in the UKA group versus 9.75% in TKA (p = 0.2). The UKA and TKA patients had similar clinical outcomes, post-operative range of motion, and survivorship in octogenarians with medial knee osteoarthritis, with comparable complication rate. Both the surgical procedures may be considered in this patient population, but further long-term follow-up is needed. Level III.