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Journal of the American Medical... Jun 2024ABO blood types have widespread clinical use and robust associations with disease. The purpose of this study is to evaluate the portability and suitability of tag...
OBJECTIVES
ABO blood types have widespread clinical use and robust associations with disease. The purpose of this study is to evaluate the portability and suitability of tag single-nucleotide polymorphisms (tSNPs) used to determine ABO alleles and blood types across diverse populations in published literature.
MATERIALS AND METHODS
Bibliographic databases were searched for studies using tSNPs to determine ABO alleles. We calculated linkage between tSNPs and functional variants across inferred continental ancestry groups from 1000 Genomes. We compared r2 across ancestry and assessed real-world consequences by comparing tSNP-derived blood types to serology in a diverse population from the All of Us Research Program.
RESULTS
Linkage between functional variants and O allele tSNPs was significantly lower in African (median r2 = 0.443) compared to East Asian (r2 = 0.946, P = 1.1 × 10-5) and European (r2 = 0.869, P = .023) populations. In All of Us, discordance between tSNP-derived blood types and serology was high across all SNPs in African ancestry individuals and linkage was strongly correlated with discordance across all ancestries (ρ = -0.90, P = 3.08 × 10-23).
DISCUSSION
Many studies determine ABO blood types using tSNPs. However, tSNPs with low linkage disequilibrium promote misinference of ABO blood types, particularly in diverse populations. We observe common use of inappropriate tSNPs to determine ABO blood type, particularly for O alleles and with some tSNPs mistyping up to 58% of individuals.
CONCLUSION
Our results highlight the lack of transferability of tSNPs across ancestries and potential exacerbation of disparities in genomic research for underrepresented populations. This is especially relevant as more diverse cohorts are made publicly available.
PubMed: 38917427
DOI: 10.1093/jamia/ocae161 -
Journal of AOAC International Jun 2024The Mettler-Toledo 7000RMS analyzer is a Bio-Fluorescent Particle Counter (BFPC) used to monitor real-time bioburden results from Purified Water (PW).
BACKGROUND
The Mettler-Toledo 7000RMS analyzer is a Bio-Fluorescent Particle Counter (BFPC) used to monitor real-time bioburden results from Purified Water (PW).
OBJECTIVE
Validation of the analyzer using 13 microorganisms and a low-intensity, fluorescent, polystyrene bead.
METHODS
During the execution of the validation, a laboratory water system that met Purified Water (PW) quality standards was connected to the 7000RMS, and a syringe pump was used to introduce various concentrations of microorganisms and fluorescent polystyrene beads to the analyzer. Samples were collected and tested via the traditional Membrane Filtration (MF) method and the Colony Forming Unit (CFU) plate count results were compared to the Auto-Fluorescent Unit (AFU) of the 7000RMS analyzer. The validation study was designed to follow the guidance in United States Pharmacopeia (USP) Chapter <1223 > (1), European Pharmacopeia (EP) Chapter 5.1.6 (2), PDA Technical Report 33 (3). Concepts and strategies were adapted from EP Chapter 2.6.12 Microbiological Examination of Non-sterile Products: Microbial Enumeration Tests, EP 10.2 (4), European Pharmacopeia Chapter 2.6.1 Sterility, EP 10.2 (5), USP Chapter <61> Microbiological Examination of Non-sterile Products: Microbial Enumeration Tests (6), USP Chapter <71> Sterility Tests (7), Japanese Pharmacopoeia (JP) General Information Chapter G8 Water: Quality Control of Water for Pharmaceutical Use (8).
RESULTS AND CONCLUSION
All pre-determined validation acceptance criteria for Accuracy, Specificity, Precision, Limit of Detection (LOD), Limit of Quantitation (LOQ), Linearity, and Range were met. Further, the 7000RMS demonstrated Performance Equivalence to the MF method per USP <1223> but characteristically lacked correlation to the CFU.
HIGHLIGHTS
This validation approach highlights the superior capabilities of the 7000RMS when compared against the traditional compendial MF testing method for PW.
PubMed: 38917406
DOI: 10.1093/jaoacint/qsae050 -
Therapeutic Drug Monitoring Jun 2024In neonatal and pediatric intensive care units, Gram-positive infections are a significant cause of morbidity and mortality. The increase in infections caused by...
Development and Validation of a High-Performance Liquid Chromatography With Ultraviolet Detection Method to Facilitate Therapeutic Monitoring of Teicoplanin Using Dried Blood Spots.
BACKGROUND
In neonatal and pediatric intensive care units, Gram-positive infections are a significant cause of morbidity and mortality. The increase in infections caused by methicillin-resistant Staphylococcus aureus and methicillin-resistant coagulase-negative Staphylococci have led to the increased use of glycopeptides, which treat invasive infections caused by Gram-positive organisms, particularly those resistant to beta-lactam antibiotics. Teicoplanin has bacteriostatic activity against Gram-positive bacteria, but its pharmacokinetics in children is highly variable, with most children failing to reach target levels at the recommended dose. This study aimed to develop a cost-effective method for determining concentrations using dried blood spot (DBS).
METHODS
A method to determine the concentrations of teicoplanin in 20 µL blood or plasma using the Whatman 903 Protein Saver filter was evaluated. High-performance liquid chromatography with ultraviolet detection high-performance liquid chromatography with ultraviolet/vis was used, with internal standard ketoconazole. In addition, a method to quantify teicoplanin using 50 µL of liquid plasma was established to compare the results with the values obtained by DBS and dried plasma methods.
RESULTS
The method was successfully developed and validated for 20 µL DBS. Furthermore, 50 µL of plasma was used to quantify teicoplanin with a lower limit of quantification of 10 mg/L. Precision and accuracy ranged from 2.3% to 10.7% and 95%-114.2%, respectively. A consistent factor (1.15) was used to calculate teicoplanin plasma concentrations from whole blood, indicating the reliability of the DBS method for therapeutic drug monitoring of teicoplanin.
CONCLUSIONS
A simple, reliable, and cost-effective method using high-performance liquid chromatography with ultraviolet/vis was established to determine pediatric teicoplanin concentrations in both small plasma sample volumes and whole blood using DBS, and an accurate correlation factor for estimating teicoplanin plasma concentrations from DBS was identified. This method is suitable for the use in pediatrics.
PubMed: 38917389
DOI: 10.1097/FTD.0000000000001202 -
JCO Clinical Cancer Informatics Jun 2024The estimation of prognosis and life expectancy is critical in the care of patients with advanced cancer. To aid clinical decision making, we build a prognostic strategy...
PURPOSE
The estimation of prognosis and life expectancy is critical in the care of patients with advanced cancer. To aid clinical decision making, we build a prognostic strategy combining a machine learning (ML) model with explainable artificial intelligence to predict 1-year survival after palliative radiotherapy (RT) for bone metastasis.
MATERIALS AND METHODS
Data collected in the multicentric PRAIS trial were extracted for 574 eligible adults diagnosed with metastatic cancer. The primary end point was the overall survival (OS) at 1 year (1-year OS) after the start of RT. Candidate covariate predictors consisted of 13 clinical and tumor-related pre-RT patient characteristics, seven dosimetric and treatment-related variables, and 45 pre-RT laboratory variables. ML models were developed and internally validated using the Python package. The effectiveness of each model was evaluated in terms of discrimination. A Shapley Additive Explanations (SHAP) explainability analysis to infer the global and local feature importance and to understand the reasons for correct and misclassified predictions was performed.
RESULTS
The best-performing model for the classification of 1-year OS was the extreme gradient boosting algorithm, with AUC and F1-score values equal to 0.805 and 0.802, respectively. The SHAP technique revealed that higher chance of 1-year survival is associated with low values of interleukin-8, higher values of hemoglobin and lymphocyte count, and the nonuse of steroids.
CONCLUSION
An explainable ML approach can provide a reliable prediction of 1-year survival after RT in patients with advanced cancer. The implementation of SHAP analysis provides an intelligible explanation of individualized risk prediction, enabling oncologists to identify the best strategy for patient stratification and treatment selection.
Topics: Humans; Machine Learning; Bone Neoplasms; Palliative Care; Male; Female; Prognosis; Aged; Middle Aged; Algorithms
PubMed: 38917384
DOI: 10.1200/CCI.24.00027 -
Therapeutic Drug Monitoring Jun 2024To establish a method for determining the bictegravir (BIC) concentration in human plasma using high-performance liquid chromatography coupled with ultraviolet detection.
BACKGROUND
To establish a method for determining the bictegravir (BIC) concentration in human plasma using high-performance liquid chromatography coupled with ultraviolet detection.
METHODS
The analysis was performed on a CLC-octadecylsilane column (150 × 6.0 mm, 5 μm) using a mixture of phosphate buffer and acetonitrile (62:38, v/v) as the mobile phase at the flow rate of 1.4 mL/min. The column temperature was maintained at 40°C. Using triamcinolone acetonide as the internal standard, 100 μL of plasma sample was extracted by methyl tert-butyl ether, followed by evaporating under nitrogen stream, redissolving with 100 μL mobile phase, and injection of 20-40 μL of supernatant into the chromatographic system. Ultraviolet detection was performed at 260 nm, and the total run time for each sample was 14 minutes.
RESULTS
The method exhibited good linearity within the range from 0.10 to 10.0 mcg/mL (r = 0.9995, n = 5). The intraday and interday relative standard deviations for low-, medium-, and high-concentration quality control samples (0.20, 4.00, 8.00 mcg/mL) and the lower limit of quantification (0.10 mcg/mL) were 1.31%-6.20% (n = 10) and 1.18%-2.87% (n = 5), respectively. The intraday and interday accuracies were 100.53%-102.32% and 97.96%-103.84%, respectively. The extraction recovery rates ranged from 80.00% to 88.09% (n = 3). The stability tests showed that the BIC concentration changed by <15%.
CONCLUSIONS
This study successfully established a high-performance liquid chromatography coupled with ultraviolet detection method for determining plasma BIC concentrations. This method is simple, selective, sensitive, and accurate, making it suitable for clinical monitoring and pharmacokinetic studies of BIC.
PubMed: 38917376
DOI: 10.1097/FTD.0000000000001235 -
Traffic Injury Prevention Jun 2024Collisions are a significant cause of injury and fatality among young novice drivers. Using real crash data, this study further explores the multifaceted and complex...
OBJECTIVE
Collisions are a significant cause of injury and fatality among young novice drivers. Using real crash data, this study further explores the multifaceted and complex nature of young novice drivers' crash injury risk by synthesizing different driver attributes and crash scenarios in order to update and validate previous research findings and provide more feasible recommendations for preventive measures.
METHODS
Detailed data on traffic crash of young novice drivers were extracted from the National Automobile Accident In-Depth Investigation System (NAIS) in China, and a mixed research methodology using a Random Forest and multinomial logit modeling framework was used in order to explore and study the important influences on traffic crash injuries of young novice drivers in Songjiang District, Shanghai, during the period from 2018 to 2022.
RESULTS
The results of the study showed that human, vehicle, road and environmental characteristics contributed 36.83%, 22.65%, 17.07% and 23.45% respectively to the prediction of crash injury level of novice drivers. Among the various single factors, driver negligence was the most important factor affecting the crash injury level of novice drivers. Age of the vehicle, crash location, road signal condition and time of crash all had a significant effect on the crash injury level of young novice drivers (95% of the confidence level).
CONCLUSIONS
The study comprehensively analyzed young novice driver crash data to reveal the crash injury risk and its severity faced by young novice drivers in different contexts, and suggested targeted safety improvements. There are similarities and differences with the results of previous studies, in which there are new contributions to understanding the driving risks of young novice drivers in daytime and nighttime.
PubMed: 38917367
DOI: 10.1080/15389588.2024.2367504 -
Operative Neurosurgery (Hagerstown, Md.) Jun 2024The combined petrosal intertentorial approach (CPIA) has been proposed as an alternative to standard combined petrosal approach (SCPA). CPIA has been designed to...
BACKGROUND AND OBJECTIVES
The combined petrosal intertentorial approach (CPIA) has been proposed as an alternative to standard combined petrosal approach (SCPA). CPIA has been designed to maintain integrity of the temporal dura with a view to reduce temporal lobe morbidity and venous complications. This study has been designed to perform a quantitative comparison between these approaches.
METHODS
Five human specimens were used for this study. CPIA was performed on one side and SCPA on the opposite side. The area of exposure (petroclival and brainstem), surgical freedom, and angles of attack to a predefined target were measured and compared.
RESULTS
SCPA provided a significantly larger petroclival area of exposure (6.81 ± 0.60 cm2) over the CPIA (5.59 ± 0.59 cm2), P = .012. The area of brainstem exposed with SCPA was greater than with CPIA (7.17 ± 0.84 vs 5.63 ± 0.72, P = .014). The area of surgical freedom was greater in SCPA rather than in CPIA (8.59 ± 0.55 and 7.13 ± 0.96 cm2, respectively, P = .019). There was no significative difference between CPIA and SCPA in the vertical angles of attack for the Meckel cave, Dorello canal, and root entry zone of cranial nerve VII. Conversely, the horizontal angles of attack permitted by the CPIA were significantly smaller for the Meckel cave (52.36° ± 5.01° vs 64.4° ± 5.3°, P = .006) and root entry zone of cranial nerve VII (30.7° ± 4.4° vs 40.1° ± 6.2°, P = .025).
CONCLUSION
CPIA is associated with a reduction in terms of the area of surgical freedom (22%), skull base (18%), brainstem exposure (17%), and horizontal angles of attack (18%-23%) when compared with SCPA. This loss in terms of exposure is counterbalanced by the advantage of keeping the temporal lobe covered by an extra layer of meningeal tissue, thus possibly reducing the risk of temporal lobe injury and venous infarction. These results need to be validated with adequate clinical experience.
PubMed: 38917345
DOI: 10.1227/ons.0000000000001244 -
Analytical Chemistry Jun 2024Here, we report an electrochemiluminescence (ECL)-based approach for imaging of local photoelectrochemical processes on hematite in a spatially and temporally controlled...
Here, we report an electrochemiluminescence (ECL)-based approach for imaging of local photoelectrochemical processes on hematite in a spatially and temporally controlled manner. The local processes were guided by flexible and dynamic light illumination, not requiring any prepatterned conductive features or photomasks, with a digital micromirror device (DMD). The imaging approach was based on light-addressable electrochemical reactions on hematite, resulting in photoinduced ECL emission for spatiotemporally resolved imaging of photoelectrochemical processes selectively guided by light illumination. After clarifying the capability of hematite as a photosensitive electrode, we validated that the illuminated hematite exhibited stable light-guided ECL emission in correspondence with the illuminated area, with a spatial resolution of 0.8 μm and a temporal resolution of 1 μs, even over a long period of 6 h. More importantly, this study exemplified the simple yet effective ECL-based approach for electrochemical visualization of local photoelectrochemical processes guided by flexible and dynamic adjustment of light illumination in a spatiotemporally controlled way.
PubMed: 38917341
DOI: 10.1021/acs.analchem.3c05097 -
Langmuir : the ACS Journal of Surfaces... Jun 2024Polymer-based functional surface coatings are extensively used in advanced technologies, including optics, energy, and environmental applications. Surface thermodynamic...
Polymer-based functional surface coatings are extensively used in advanced technologies, including optics, energy, and environmental applications. Surface thermodynamic properties profoundly impact the molecular interactions that control interfacial behaviors, such as adhesion and wettability, which in turn dictate coating processes and performance. Conventionally, contact angle measurements are used to assess the surface energy of polymer films and coatings, where the wettability of a surface is assessed using probe fluids (liquid drops). However, contact angle measurement oftentimes can be nontrivial due to the roughness or chemical heterogeneity of the solid surface, as well as the potential for the liquid drop to swell or even dissolve the material being measured. Alternatively, inverse gas chromatography (iGC) is a versatile technique to measure surface thermodynamics and Lewis acid-base properties while also providing environmental control such as temperature and humidity. Despite these benefits, the application of iGC has been limited to powders or fibers, while the direct measurement of supported thin films or coatings is still a nascent area of research. This creates a challenge when using iGC as a comprehensive platform for measuring the physicochemical properties of solid surfaces. Here, we demonstrate how to effectively use iGC to characterize the surface energy of supported polymer thin films by using a two-dimensional (2D) film holder and modifying operational controls, such as the concentration range of the injected gas probe molecules. This enables the precise control of surface coverage required for analyzing samples having minimal surface area, such as thin films. Poly(methyl methacrylate) (PMMA) was employed as a benchmark to determine suitable iGC parameters and to validate our approach on polymer thin films. The seminal work presented here expands the capability of state-of-the-art iGC to embrace supported thin films (2D iGC) that could either be smooth or display texture/roughness (patterned films) as well as coatings with heterogeneous chemical/structural composition.
PubMed: 38917337
DOI: 10.1021/acs.langmuir.4c01400 -
Biomacromolecules Jun 2024Wound dressings made from natural-derived polymers are highly valued for their biocompatibility, biodegradability, and biofunctionality. However, natural polymer-based...
Wound dressings made from natural-derived polymers are highly valued for their biocompatibility, biodegradability, and biofunctionality. However, natural polymer-based hydrogels can come with their own set of limitations, such as low mechanical strength, limited cell affinity, and the potential cytotoxicity of cross-linkers, which delineate the boundaries of their usage and hamper their practical application. To overcome the limitation of natural-derived polymers, this study utilized a mixture of oxidized alginate and gelatin with 5 mg/mL polycaprolactone (PCL):gelatin nanofiber fragments at a ratio of 7:3 (OGN-7) to develop a hydrogel composite wound dressing that can be injected and has the ability to be remended. The in situ formation of the remendable hydrogel is facilitated by dual cross-linking of oxidized alginate chains with gelatin and PCL/gelatin nanofibers through Schiff-base mechanisms, supported by the physical integration of nanofibers, thereby obviating the need for additional cross-linking agents. Furthermore, OGN-7 exhibits increased stiffness (γ = 79.4-316.3%), reduced gelation time (543 ± 5 to 475 ± 5 s), improved remendability of the hydrogel, and excellent biocompatibility. Notably, OGN-7 achieves full fusion within 1 h of incubation and maintains structural integrity under external stress, effectively overcoming the inherent mechanical weaknesses of natural polymer-based dressings and enhancing biofunctionality. The therapeutic efficacy of OGN-7 was validated through a full-thickness wound healing analysis, which demonstrated that OGN-7 significantly accelerates wound closure compared to alginate-based dressings and control groups. Histological analysis further revealed that re-epithelialization and collagen deposition were markedly enhanced in the regenerating skin of the OGN-7 group, confirming the superior therapeutic performance of OGN-7. In summary, OGN-7 optimized the synergistic effects of natural polymers, which enhances their collective functionality as a wound dressing and expands their utility across diverse biomedical applications.
PubMed: 38917335
DOI: 10.1021/acs.biomac.4c00406