Bias Plots Research Articles

Revisiting Depression Rating Scales: Analysis of a Randomized Trial.

The Hamilton Depression Rating Scale (HDRS) and Montgomery-Åsberg Depression Rating Scale (MADRS) are both frequently employed to gauge the symptoms of major depressive disorder (MDD). Limited studies have attempted to compare these two scales. The purpose of our study was to compare the HDRS and MADRS scores of the study population as well as to calculate their bias and precision. An open-label,randomized, three-arm trialwas executedon 96 MDD patients. For 16 weeks, participants were put into three groups (in a 1:1:1 ratio)and administered vortioxetine (5-20 mg/day),escitalopram (10-20 mg/day), or vilazodone (20-40 mg/day). Vortioxetineand vilazodonewere experimentaldrugs, while escitalopram actedas a control. Follow-up visits were scheduled at four-week intervals following the first visit. The per-protocol (PP) population had their HDRS and MADRS scores recorded at each visit. We contrasted the MADRS and HDRS scores through the Bland-Altman analysis and Taffé method. The former method generated the limit of agreement (LoA) plot. Moreover, the latter provided the bias, precision, and comparison plots. We prospectively registered our trial in theClinical Trial Registry of India(CTRI) (2022/07/043808). We screened 134 individuals, and 109 (81.34%) were qualified. Ninety-six (88.07%) accomplished the 16-week study. The average age was 46.3 ± 6.2 years. The study population had baseline and final HDRS scores of 30.05 ± 1.52 and 14.29 ± 1.51, respectively. The mean MADRS scores at the first and last visits were 35.73 ± 1.47 and 18.08 ± 1.92, respectively. According to the LoA plot, the mean difference between HDRS and MADRS scores was 4.78 (95% CI: 2.61-6.95). As the bias plot indicates, MADRS scores had an estimated differential bias of 3.478 (95% CI: -2.119 to 9.074) and a proportional bias of 0.816 (95% CI: 0.649 to 0.982). The precision plot demonstrated that HDRS scores had lower standard deviation values and a narrower confidence interval than MADRS scores. This meant that the HDRS was more precise. The comparison plot showed that the regression line of the recalibrated MADRS coincided with that of HDRS. The MADRS was effectively recalibrated to remove bias. After 16 weeks of therapy, we noticed substantial drops in HDRS and MADRS scores. The HDRS was proved to be more precise than the analogous MADRS. The MADRS was recalibrated to remove differential and proportional biases.

Processing time and precision of aging structures for Bighead Carp and Silver Carp in the lower Red River catchment in the southern Great Plains

AbstractObjectivePopulation demographics of invasive species are commonly evaluated to better develop management actions that are useful for reducing their abundance or controlling the population. Bighead Carp Hypophthalmichthys nobilis and Silver Carp H. molitrix are emblematic invaders in the United States, where they continue to expand their range. There is currently no consensus about which hard structure from these species is best for age estimation. Our study objective was to compare the processing time and precision of five hard structures used for age estimation of both species.MethodsWe sampled fish in the lower Red River catchment of Oklahoma, Arkansas, and Texas during summer and autumn 2021–2022 and removed the lapillus otolith, left primary pectoral fin ray, postcleithrum, urohyal bone, and anterior‐most pterygiophore of the dorsal fin from both Bighead and Silver carp. The structures (n = 1204) were either embedded in epoxy or thin‐sectioned and mounted on slides. Two readers estimated the age of the fish by using each structure and came to a consensus. Processing time was recorded from the onset of laboratory processing to the termination of polishing the cross sections for age estimation.ResultProcessing of otoliths was comparable to or faster than processing of the other structures and resulted in the highest between‐reader agreement. The lowest coefficients of variation in age estimation were represented using lapillus otoliths for Bighead Carp and postcleithra for Silver Carp. Our age bias plots indicated that all other structures underestimated age relative to the lapillus otoliths.ConclusionOur results indicated that using lapillus otoliths for age estimation of these species would have the highest between‐reader agreement and would incur no additional laboratory processing time. However, validation is needed to assess whether lapillus otoliths correctly age these species. From a management perspective, use of this structure would facilitate improved population comparisons.

The probe of current conduction mechanisms, interface states, and the forward bias intersection point of the al/Al2O3/Ge/p-Si heterostructures depending on temperature

The current conduction mechanisms (CCMs), temperature-sensitivities (S), energy-dependent interface traps (Nss), and origin of the intersection points in the forward bias (IF−VF) plots of the Al/Al2O3/Ge/p-Si heterostructure were investigated in wide temperature range of 90–420 K. Firstly, main electrical parameters, including reverse-saturation current (Io), ideality factor (n), zero-bias barrier-height (ΦBo), and series-resistance (Rs) values, were extracted for each temperature. The lnIF-VF curves illustrate two distinct linear regimes at low and intermediate bias voltages. Despite the observed decline in n values as temperature rises, the corresponding ΦBo values exhibit an upward trend. The conventional Richardson plots deviated from linearity at low temperatures, and the Richardson-constants (A*) value obtained from its linear part is quite lower than its theoretical value. Hence, ΦBo−q/2 kT, ΦBo−n, and n(kT)/q−(kT/q) correlations were plotted to seek indications of the Gaussian distribution (GD) of barrier heights (BHs) and tunneling mechanism. Temperate sensitivity (S = dV/dT) for 0.01, 0.10, 0.50, and 1 μA was found as 2.30, 2.33, 2.34, and 2.35 mV/K, which indicated that the fabricated Al/Al₂O₃/Ge/p-Si heterostructure is highly sensitive to temperature, rendering it suitable for use in temperature sensor applications. The observed crossing point at about 2.4V was explained by an increase in the apparent BH with temperature and the presence of Rs.

Analysis of Codon Usage Bias in Chloroplast Genomes of Dryas octopetala var. asiatica (Rosaceae).

Dryas octopetala var. asiatica, a dwarf shrub belonging to the Rosaceae family and native to Asia, exhibits notable plasticity in photosynthesis in response to temperature variations. However, the codon usage patterns and factors influencing them in the chloroplast genome of this species have not yet been documented. This study sequenced and assembled the complete genome of D. octopetala var. asiatica. The annotated genes in the chloroplast genome were analyzed for codon composition through multivariate statistical methods including a neutrality plot, a parity rule 2 (PR2) bias plot, and an effective number of codons (ENC) plot using CodonW 1.4.2 software. The results indicated that the mean GC content of 53 CDSs was 38.08%, with the average GC content at the third codon base position being 27.80%, suggesting a preference for A/U(T) at the third codon position in chloroplast genes. Additionally, the chloroplast genes exhibited a weak overall codon usage bias (CUB) based on ENC values and other indicators. Correlation analysis showed a significant negative correlation between ENC value and GC2, an extremely positive correlation with GC3, but no correlation with GC1 content. These findings highlight the importance of the codon composition at the third position in influencing codon usage bias. Furthermore, our analysis indicated that the CUB of the chloroplast genome of D. octopetala var. asiatica was primarily influenced by natural selection and other factors. Finally, this study identified UCA, CCU, GCU, AAU, GAU, and GGU as the optimal codons. These results offer a foundational understanding for genetic modification and evolutionary dynamics of the chloroplast genome of D. octopetala var. asiatica.

Tight Versus Liberal Blood Glucose Control in Patients With Diabetes in the ICU: A Meta-Analysis of Randomized Controlled Trials.

Introduction: Glycemia is an important factor among critically ill patients in the intensive care unit (ICU). There is conflicting evidence on the preferred strategy of blood glucose control among patients with diabetes in the ICU. We aimed to conduct a meta-analysis comparing tight with liberal blood glucose in critically ill patients with diabetes in the ICU. Methods: We systematically searched PubMed, Embase, and Cochrane Central for randomized controlled trials (RCTs) comparing tight versus liberal blood glucose control in critically ill patients with diabetes from inception to December 2023. We pooled odds-ratios (OR) and 95% confidence intervals (CI) with a random-effects model for binary endpoints. We used the Review Manager 5.17 and R version 4.3.2 for statistical analyses. Risk of bias assessment was performed with the Cochrane tool for randomized trials (RoB2). Results: Eight RCTs with 4474 patients were included. There was no statistically significant difference in all-cause mortality (OR 1.11; 95% CI 0.95-1.28; P = .18; I² = 0%) between a tight and liberal blood glucose control. RoB2 identified all studies at low risk of bias and funnel plot suggested no evidence of publication bias. Conclusion: In patients with diabetes in the ICU, there was no statistically significant difference in all-cause mortality between a tight and liberal blood glucose control. PROSPERO registration: CRD42023485032.

Hepatic steatosis modeling and MRI signal simulations for comparison of single- and dual-R2* models and estimation of fat fraction at 1.5T and 3T

Background and objectiveMagnetic resonance imaging (MRI) has emerged as a noninvasive clinical tool for assessment of hepatic steatosis. Multi-spectral fat-water MRI models, incorporating single or dual transverse relaxation decay rate(s) (R2*) have been proposed for accurate fat fraction (FF) estimation. However, it is still unclear whether single- or dual-R2* model accurately mimics in vivo signal decay for precise FF estimation and the impact of signal-to-noise ratio (SNR) on each model performance. Hence, this study aims to construct virtual steatosis models and synthesize MRI signals with different SNRs to systematically evaluate the accuracy of single- and dual-R2* models for FF and R2* estimations at 1.5T and 3.0T. MethodsRealistic hepatic steatosis models encompassing clinical FF range (0–60 %) were created using morphological features of fat droplets (FDs) extracted from human liver biopsy samples. MRI signals were synthesized using Monte Carlo simulations for noise-free (SNRideal) and varying SNR conditions (5–100). Fat-water phantoms were scanned with different SNRs to validate simulation results. Fat water toolbox was used to calculate R2* and FF for both single- and dual-R2* models. The model accuracies in R2* and FF estimates were analyzed using linear regression, bias plot and heatmap analysis. ResultsThe virtual steatosis model closely mimicked in vivo fat morphology and Monte Carlo simulation produced realistic MRI signals. For SNRideal and moderate-high SNRs, water R2* (R2*W) by dual-R2* and common R2* (R2*com) by single-R2* model showed an excellent agreement with slope close to unity (0.95–1.01) and R2 > 0.98 at both 1.5T and 3.0T. In simulations, the R2*com-FF and R2*W-FF relationships exhibited slopes similar to in vivo calibrations, confirming the accuracy of our virtual models. For SNRideal, fat R2* (R2*F) was similar to R2*W and dual-R2* model showed slightly higher accuracy in FF estimation. However, in the presence of noise, dual-R2* produced higher FF bias with decreasing SNR, while leading to only marginal improvement for high SNRs and in regions dominated by fat and water. In contrast, single-R2* model was robust and produced accurate FF estimations in simulations and phantom scans with clinical SNRs. ConclusionOur study demonstrates the feasibility of creating virtual steatosis models and generating MRI signals that mimic in vivo morphology and signal behavior. The single-R2* model consistently produced lower FF bias for clinical SNRs across entire FF range compared to dual-R2* model, hence signifying that single-R2* model is optimal for assessing hepatic steatosis.

Prevalence of gestational diabetes mellitus in Pakistan: a systematic review and meta-analysis

BackgroundA variety of screening tools and criteria are used for the diagnosis of gestational diabetes mellitus (GDM). As a result, the prevalence rate of GDM varied from 4.41% to 57.90% among studies from Pakistan. Beside this disagreement, similar multi-centric studies, community surveys and pooled evidence were lacking from the country. Therefore, this first systematic review and meta-analysis aimed to measure the overall and subgroup pooled estimates of GDM and explore the methodological variations among studies for any inconsistency.MethodsUsing the PRISMA guidelines, seventy studies were identified from PubMed, ScienceDirect, Google Scholar and PakMediNet database. Of them, twenty-four relevant studies were considered for systematic review and nine eligible studies selected for meta-analysis. AXIS was used for measuring quality of reporting, I^2 statistics for heterogeneity among studies and subgroups, funnel plot for reporting potential publication bias and forest plot for presenting pooled estimates.ResultsThe pooled sample of nine studies was 27,034 (126 – 12,450) pregnant women, of any gestational age, from all four provinces of Pakistan. Overall pooled estimate of GDM was 16.7% (95% CI 13.1 – 21.1). The highest subgroup pooled estimate of GDM observed in studies from Balochistan (35.8%), followed by Islamabad (23.9%), Khyber Pakhtunkhwa (17.2%), Sindh (13.2%), and Punjab (11.4%). The studies that adopted 75g 2-h OGTT had a little lower pooled estimate (16.3% vs. 17.3%); and that adopted diagnostic cut-off values [≥ 92 (F), ≥ 180 (1-h) and ≥ 153 (2-h)] had a greater pooled estimate (25.4% vs. 15.8%). The studies that adopted Carpenter criteria demonstrated the highest subgroup pooled estimate of GDM (26.3%), after that IADPSG criteria (25.4%), and ADA criteria (23.9%).ConclusionsAlong with poor quality of reporting, publishing in non-indexed journals and significant disagreement between studies, the prevalence rate of GDM is high in Pakistan. Consensus building among stakeholders for recommended screening methods; and continuous medical education of the physicians are much needed for a timely detection and treatment of GDM.

Acidification is required for calcium and magnesium concentration measurements in equine urine

BackgroundAcidification of equine urine to promote dissociation of ion complexes is a common practice for urine ion concentration measurements. The objective of this study was to evaluate the effect of acidification and storage after acidification on calcium (Ca), magnesium (Mg) and phosphate (P) concentrations and on fractional excretion (FE) of these electrolytes. Thirty-two fresh equine urine samples were analysed between December 2016 and July 2020. Complete urinalysis (stick and sediment) was performed on all samples. Ca, Mg, P and creatinine concentrations were measured in supernatant of centrifuged native urine, urine directly centrifuged after acidification and urine centrifuged 1 hour after acidification. Urine was acidified with hydrochloric acid to reach a pH of 1–2. Ca, Mg, P and creatinine concentrations were also measured in blood plasma, and fractional excretion of each electrolyte was calculated. Equality of medians was tested with Friedman tests and Bland-Altman bias plots were used to show the agreement between conditions.ResultsAcidification had a statistically significant effect on Ca and Mg concentrations, FECa and FEMg. Bland-Altman plot revealed a strong positive proportional bias between Ca concentration in native and acidified urine with a mean bias of 17.6 mmol/l. For Mg concentration, the difference between native and acidified urine was small with a mean bias of 1.8 mmol/l. The increase in FECa was clinically relevant. Storage of acidified urine had no effect on any of the measured ion concentrations. All P concentrations in native urine samples were below the detection limit of the assay and statistical analysis and calculation of FEP was not possible.ConclusionsUrine acidification is essential for accurate measurement of Ca and Mg concentrations and therefore FE calculations in equine urine. Storage time of 1 hour after acidification does not significantly change Ca and Mg concentrations.

Analysis of codon usage patterns in 48 Aconitum species

BackgroundThe Aconitum genus is a crucial member of the Ranunculaceae family. There are 350 Aconitum species worldwide, with about 170 species found in China. These species are known for their various pharmacological effects and are commonly used to treat joint pain, cold abdominal pain, and other ailments. Codon usage bias (CUB) analysis contributes to evolutionary relationships and phylogeny. Based on protein-coding sequences (PCGs), we selected 48 species of Aconitum for CUB analysis.ResultsThe results revealed that Aconitum species had less than 50% GC content. Furthermore, the distribution of GC content was irregular and followed a trend of GC1 > GC2 > GC3, indicating a bias towards A/T bases. The relative synonymous codon usage (RSCU) heat map revealed the presence of conservative codons with slight variations within the genus. The effective number of codons (ENC)-Plot and the parity rule 2 (PR2)-bias plot analysis indicate that natural selection is the primary factor influencing the variation in codon usage. As a result, we screened various optimal codons and found that A/T bases were preferred as the last codon. Furthermore, our Maximum Likelihood (ML) analysis based on PCGs among 48 Aconitum species yielded results consistent with those obtained from complete chloroplast (cp.) genome data. This suggests that analyzing mutation in PCGs is an efficient method for demonstrating the phylogeny of species at the genus level.ConclusionsThe CUB analysis of 48 species of Aconitum was mainly influenced by natural selection. This study reveals the CUB pattern of Aconitum and lays the foundation for future genetic modification and phylogenetic analyses.

Adaptive evidence of mitochondrial genes in Pteromalidae and Eulophidae (Hymenoptera: Chalcidoidea).

Pteromalidae and Eulophidae are predominant and abundant taxa within Chalcidoidea (Hymenoptera: Apocrita). These taxa are found in diverse ecosystems, ranging from basin deserts (200 m) to alpine grasslands (4500 m). Mitochondria, cellular powerhouses responsible for energy production via oxidative phosphorylation, are sensitive to various environmental factors such as extreme cold, hypoxia, and intense ultraviolet radiation characteristic of alpine regions. Whether the molecular evolution of mitochondrial genes in these parasitoids corresponds to changes in the energy requirements and alpine environmental adaptations remains unknown. In this study, we performed a comparative analysis of mitochondrial protein-coding genes from 11 alpine species of Pteromalidae and Eulophidae, along with 18 lowland relatives, including 16 newly sequenced species. We further examined the codon usage preferences (RSCU, ENC-GC3s, neutrality, and PR2 bias plot) in these mitochondrial protein-coding sequences and conducted positive selection analysis based on their Bayesian phylogenetic relationships, and identified positive selection sites in the ATP6, ATP8, COX1, COX3, and CYTB genes, emphasizing the crucial role of mitochondrial gene adaptive evolution in the adaptation of Pteromalidae and Eulophidae to alpine environments. The phylogenetically independent contrast (PIC) analysis results verified the ω ratio of 13 PCGs from Pteromalidae and Eulophidae increased with elevation, and results from generalized linear model confirm that ATP6, ATP8, COX3, and ND1 are closely correlated with temperature-related environmental factors. This research not only enriched the molecular data of endemic alpine species but also underscores the significance of mitochondrial genes in facilitating the adaptation of these minor parasitoids to plateau habitats.

PENDEKATAN ALGORITMA UNTUK EVALUASI DOSIS RADIASI DENGAN TLD-900 BARC PADA PENGUKURAN RADIASI ENERGI RENDAH

Accurate radiation dose evaluation for radiation workers is crucial to determine the radiation dose received from exposure. Using passive dosimeters such as TLD-900 can assist in monitoring and controlling radiation exposure by evaluating accumulated dose readings over a specific period. Due to its utilization in diverse radiation fields, the dose evaluation method should be able to differentiate the energy range employed. Energy dependence can pose a challenge in reading the received dose, particularly in the case of low-energy X-ray usage. Therefore, this study aims to develop an algorithm for individual equivalent dose evaluation Hp(10) in low-energy (<20 KeV) usage. The data will be obtained from the Nuclear Agency of Malaysia's Secondary Standard Dosimetry Laboratory (SSDL), including various ISO narrow series X-ray sources and several radioactive sources such as Cs-137, Co-60, Sr-90, Kr-85, and Pm-147. The evaluation method will involve a trumpet curve and ANSI bias plot, enabling an assessment of the performance of the developed algorithm. Ultimately, the algorithm will be used for long-term dose evaluation intercomparisons in low-dose reviews. The low-energy energy evaluation algorithm for equivalent doses has successfully been conducted. The algorithm performs very well in distinguishing energy types using the parameter r12. In contrast, the low-energy dose evaluation algorithm encounters difficulties due to the low-energy characteristics in energy deposition, which are similar for each element D. Keywords: Algorithm,radiation dose evaluation, TLD, Low Energy.

A-375 Evaluation of the CLIA-Waived Afinion HbA1c Point-of-Care Test

Abstract Background Point-of-care (POC) HbA1c tests can be essential in evaluation/monitoring of diabetes provided that the test has acceptable analytical performance. The Abbott Afinion HbA1c is an in vitro diagnostic test for quantification of HbA1c in human capillary and venous whole blood. This study aim was to evaluate the performance of Afinion HbA1c in whole blood EDTA patient samples. Methods The Afinion utilizes the boronate affinity principle for measurement of HbA1c. Hemoglobin A1c was tested on the Abbott AfinionTM 2 analyzer. Two levels of quality control (QC) and two levels of whole blood EDTA patient samples (one low and on high) were used to assess imprecision. Within-day precision was determined by assaying the 20 times in one day and between-day precision was determined by assaying the samples in duplicates over a period of 10 days. The analytical measured range (AMR) and method comparison was performed by using whole blood EDTA patient samples. Percent bias plot and Deming regression analysis was performed by EP Evaluator. Results Within-day and between-day precision and accuracy data are summarized in table 1 below. The assay displayed good linearity over the measured AMR. Lastly, the method comparison between Afinion vs Cobas pro, had a correlation coefficient R2 of 0.994, slope (m) of 1.14 and % bias was 2.5%. Afinion vs Trinity Biotech HPLC had R2 = 0.996, m = 1.04 and % bias was −2.3%. Afinion vs DCA Vantage had R2 = 0.991, m = 1.03 and % bias 1.5. Conclusion We conclude that the Abbott Afinion POC device evaluated here is precise and yields results consistent with other Clinical Chemistry analyzers such as Cobas Pro and Trinity Biotech.

B-022 Technical Evaluation of Urine Chemistry Testing on the Beckman DxC700AU Chemistry Analyzer

Abstract Background The Singapore General Hospitals’ clinical biochemistry laboratory constantly reviews and optimizes its automated chemistry testing through workflow enhancements and advancement of technology. The laboratory had evaluated 11 urine chemistry analytes on a standalone Beckman Coulter DxC700AU in view of upgrading its existing Beckman Coulter AU680. Methods The laboratory evaluated the following urine chemistry analytes: urea, sodium, potassium, chloride, creatinine, total protein, calcium, inorganic phosphate, magnesium, amylase and uric acid. The parameters evaluated were: linearity, limit of detection (LOD), carryover, imprecision and patient comparison against the AU680. Linearity was verified by analyzing Validate-It linearity materials in triplicate, and assessed by generating linearity statistics using Analyze-It v2.03. LOD was verified by analyzing 20 replicates of a blank matrix (saline) and 20 replicates of a patient specimen with concentrations near the LOD. Carryover was verified by sequentially analyzing a low concentration sample in triplicates followed by a high concentration sample in duplicates and lastly the same low concentration sample in duplicates. Imprecision was performed in triplicates across 5 days using quality control material from Bio-Rad, and assessed against the vendor’s imprecision claims. Patient comparison was performed using 60 to 80 samples for each analyte between the DxC700AU and the AU680. Passing Bablok Regression, Spearman Correlation and Altman-Bland Bias Plots was generated using the Analyze-It program. Results All analytes were verified to be linear within their respective AMRs; all linearity material recovered within ±10% of its expected target value. LOD was assessed to be satisfactory and below the lower limit of measurement. No significant carryover was observed for any analyte. Total imprecision for all the analytes were generally <4.8%. Passing Bablok Regressions, where X is the AU680 and Y is the DxC700AU, generated slopes ranging between 0.98X and 1.04X with constants ranging between -1.13 and 31.18. The large constants were partly due to analytes with large AMR (e.g. creatinine and uric acid urine). Altman-Bland Bias Plots presented bias ranging between −3.6% to 1.7% for different analytes. All analytes had excellent correlation between the 2 analyzers with R values of 1.0. Conclusion The performance characteristics of the DxC700AU in analyzing urine chemistries was found to be acceptable and highly comparable to the AU680. The upgrade of the AU680 to DxC700AU was seamless in view of excellent comparability in assay performances. Although the DxC700AU was expected to be the technological successor to the AU680, the quality-of-life improvements of the analyzer were the highlights of the DxC700AU. Improvements included a large clear LED indicator that highlights the status of the instrument and on-the-fly loading of reagent kits. Future improvements that the laboratory is looking forward to is the removal of the need to manually load specimens onto the instrument by connecting the standalone equipment onto its total laboratory automation track.

B-314 Evaluation of Everolimus QMS Immunoassay on Roche Cobas c502 and Indiko Plus Analyzers

Abstract Background Everolimus has a narrow therapeutic window and significant intra-individual variability. Rapid turn-around-time and precise results are critical for therapeutic drug monitoring and adequate dose adjustment. The Thermo Scientific Quantitiative Microsphere System (QMS®) everolimus immunoassay is the only FDA-approved immunoassay for measuring everolimus in human blood. The analytical performance of the Thermo Scientific QMS® everolimus immunoassay on Indiko Plus and Roche c502 platforms were evaluated and compared to LC-MS/MS. Methods Whole blood EDTA-anticoagulated patient samples were pretreated with methanol and precipitation reagent (immunoassay) or zinc sulfate/methanol (LC-MS/MS) to remove proteins before analysis. Imprecision was determined by running quality control and patient samples 20 times. Fifty transplant samples were used for method comparison. Deming regression, correlation coefficient (R2), and % bias plot analysis were performed using EP Evaluator® software. Results Imprecision (%CV) for QMS everolimus assay on Roche c502 was 16.7% (mean = 4.4 ng/mL) and 9.7% (mean = 10.3 ng/mL) for patient pools, and 16.5% (mean = 4.7 ng/mL), 10.3% (mean = 7.8 ng/mL), 10.7% (mean = 14.5 ng/mL) for quality control. QMS everolimus assay imprecision on Indiko Plus platform had CV of 3.1% (mean = 4.3 ng/mL), 3.3% (mean = 9.3 ng/mL), 2.8% (mean 14.3 ng/mL) for liver transplant patients and 3.3% (mean = 4.2 ng/mL), 3.3% (mean 8.3 ng/mL), 3.1 % (mean 15.6 ng/mL) for quality control. Patient comparison studies between Roche c502 vs LC-MS/MS revealed a R2 of 0.82, slope of 1.3 and %bias of −2.7%. QMS on Indiko Plus vs LC-MS/MS revealed a R2 of 0.84, slope of 0.96 and %bias of −21.9%. Conclusions The Indiko Plus platform had a constant negative bias vs LC-MS/MS while the Roche’s platform had lower average bias but it resulted in greater scatter in the therapeutic range (3–8 ng/mL) vs LC-MS/MS. Overall, we observed increased imprecision on the c502 analyzer.

Validation of annual growth zone formation in gray triggerfish Balistes capriscus dorsal spines, vertebrae, and otoliths

Uncertainty in age estimates from dorsal spines has been a persistent issue in stock assessments of gray triggerfish, Balistes capriscus. This study sought to validate the annual deposition of growth zones on dorsal spines, vertebrae, and otoliths of gray triggerfish through chemical marking. Fish (n = 101) were collected from offshore habitats and held in an aquaculture facility. 74 adult fish were chemically marked with a 50 mg/kg body weight injection of calcein, and reared for an average of 527 days post-marking. At intervals, fish were sacrificed and first dorsal spines, vertebrae, and otoliths were extracted and sectioned. Annuli, were enumerated for spines (n = 96), vertebrae (n = 94), and otoliths (n = 48) and ranged from 0 to 11 annuli for spines and vertebrae, and 1–12 annuli for otoliths. Age bias plots showed strong agreement between spine and vertebra annuli counts for all observed ages, while counts from spines and vertebrae appeared to underage beginning at age 5 when compared to otolith annuli counts. Tests of symmetry indicated that the annuli counts between paired age structures were not biased (p > 0.05). Analysis of growth zones observed distal to calcein marks in all of the age structures confirmed that these zones were deposited annually, and the expected number of these zones, or annuli, were observed in 91% of spine, 90% of vertebrae, and 100% of otolith sections. Marginal increment analysis of ageing structures indicated that annuli form during summer months. Percentages of annuli deposited on the margins peaked in June for spines (58%) and otoliths (29%), and August for vertebrae (30%). Results from this study validate the annual deposition of growth zones but further consideration needs to be taken when ageing older than age-4.

Quantitative assessment of ligand bias from bias plots: The bias coefficient “kappa”

The current methods for quantifying ligand bias involve the construction of bias plots and the calculations of bias coefficients that can be compared using statistical methods. However, widely used bias coefficients can diverge in their abilities to identify ligand bias and can give false positives. As the empirical bias plots are considered the most reliable tools in bias identification, here we develop an analytical description of bias plot trajectories and introduce a bias coefficient, kappa, which is calculated from these trajectories. The new bias coefficient complements the tool-set in ligand bias identification in cell signaling research.

Therapeutic drug monitoring of mycophenolic acid (MPA) using volumetric absorptive microsampling (VAMS) in pediatric renal transplant recipients: ultra-high-performance liquid chromatography-tandem mass spectrometry analytical method development, cross-validation, and clinical application

BackgroundMycophenolic acid (MPA) is widely used in posttransplant pharmacotherapy for pediatric patients after renal transplantation. Volumetric absorptive microsampling (VAMS) is a recent approach for sample collection, particularly during therapeutic drug monitoring (TDM). The recommended matrix for MPA determination is plasma (PL), and conversion between capillary-blood VAMS samples and PL concentrations is required for the appropriate interpretation of the results.MethodsThis study aimed to validate and develop a UHPLC-MS/MS method for MPA quantification in whole blood (WB), PL, and VAMS samples, with cross and clinical validation based on regression calculations. Methods were validated in the 0.10–15 µg/mL range for trough MPA concentration measurement according to the European Medicines Agency (EMA) guidelines. Fifty pediatric patients treated with MPA after renal transplantation were included in this study. PL and WB samples were obtained via venipuncture, whereas VAMS samples were collected after the fingerstick. The conversion from VAMSMPA to PLMPA concentration was performed using formulas based on hematocrit values and a regression model.ResultsLC–MS/MS methods were successfully developed and validated according to EMA guidelines. The cross-correlation between the methods was evaluated using Passing-Bablok regression, Bland–Altman bias plots, and predictive performance calculations. Clinical validation of the developed method was successfully performed, and the formula based on regression was successfully validated for VAMSMPA to PLMPA concentration and confirmed on an independent group of samples.ConclusionsThis study is the first development of a triple matrix-based LC–MS/MS method for MPA determination in the pediatric population after renal transplantation. For the first time, the developed methods were cross-validated with routinely used HPLC–DAD protocol.Graphical

Network Meta-analysis of Qi-benefiting and blood-activating Chinese patent medicines against ischemic stroke

This study aimed to compare the efficacy of Qi-benefiting and blood-activating Chinese patent medicines in the treatment of ischemic stroke with network Meta-analysis. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library were searched from database inception to October 2022 for randomized controlled trial(RCT) on 11 Qi-benefiting and blood-activating Chinese patent medicines in the treatment of ischemic stroke. The risk of bias plot was made by RevMan 5.3, and network Meta-analysis and efficacy ranking were performed by Stata 17. Ninety-two RCTs were included, involving 10 608 patients. According to the network Meta-analysis, in terms of the clinical total effective rate, surface under the cumulative ranking curve(SUCRA) as followed: Qilong Capsules+conventional western medicine>Zhishe Tongluo Capsules+conventional western medicine>Longshengzhi Capsules+conventional western medicine>Naoxintong Capsules+conventional western medicine>Tongsaimai Tablets+conventional western medicine>Naoan Capsules+conventional western medicine>Naoluotong Capsules+conventional western medicine>Xiaoshuan Changrong Capsules+conventional western medicine>Dengzhan Shengmai Capsules+conventional western medicine=Tongxinluo Capsules+conventional western medicine>Naomaitai Capsules+conventional western medicine. In terms of the improvement in National Institute of Health stroke scale(NIHSS) score, SUCRA as followed: Longshengzhi Capsules+conventional western medicine>Naomaitai Capsules+conventional western medicine>Naoxintong Capsules+conventional western medicine>Dengzhan Shengmai Capsules+conventional western medicine>Xiaoshuan Changrong Capsules+conventional western medicine>Naoluotong Capsules+conventional western medi-cine>Tongxinluo Capsules+conventional western medicine>Naoan Capsules+conventional western medicine>Qilong Capsules+conventional western medicine. In terms of safety, the overall adverse reactions/events of Qi-benefiting and blood-activating Chinese patent medicines + conventional western medicine were less than those of the control group. Since Qilong Capsules+conventional western medicine and Zhishe Tongluo Capsules+conventional western medicine were preferred to improve the clinical total effective rate. In the aspect of improving NIHSS score, Longshengzhi Capsules+conventional western medicine and Naomaitai Capsules+conventional western medicine were first options. Due to the lack of direct comparisons between drugs, the overall quality of RCT was not high, so more studies are needed to verify the strength of the evidence.

PADI4 and IL-33 gene polymorphisms with susceptibility to systemic lupus erythematosus and juvenile idiopathic arthritis, a systematic review and meta-analysis.

This study evaluated the association between peptidyl arginine deiminase type IV (PADI4) and interleukin 33 (IL-33) with systemic lupus erythematosus (SLE) and juvenile idiopathic arthritis (JIA). We searched the PubMed, Web of Science, Embase and Cochrane Library databases to retrieve articles published up to January 20, 2023. Stata/SE 17.0 (College Station, TX) software was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). The cohort study, case-control study focusing on the PADI4, IL-33 polymorphism, and SLE, JIA were retrieved. The data included basic information of each study and the genotypes and allele frequencies. Studies in PADI4 rs2240340 = 2 and 3 IL-33(rs1891385 = 3, rs10975498 = 2, rs1929992 = 4) were found in 6 articles. Overall, only the IL-33 rs1891385 show significant association between SLE in all 5 models. The results were OR (95% CI) = 1.528 (1.312, 1.778), P = .000 in Allele model (C vs A), OR (95% CI) =1.473 (1.092, 1.988), P = .000 in Dominant model (CC + CA vs AA), 2.302 (1.583, 3.349), P = .000 in Recessive model (CC vs CA + AA), 2.711 (1.845, 3.983), P = .000 in Homozygote model (CC vs AA), 5.568 (3.943, 7.863), P = .000 in Heterozygote model (CA vs AA). PADI4 rs2240340, IL-33 rs10975498, IL-33 rs1929992 were not found to be association with the risk of SLE and JIA. In gene model, statistically significant association was found between IL-33 rs1891385 and SLE in sensitivity analysis. Egger's publication bias plot showed there was no publication bias (P = .165). Only in recessive model the heterogeneity test was significant (I2 = 57.9%, P ≤ .093) of IL-33 rs1891385. The current study suggests that in all 5 model, IL-33 rs1891385 polymorphism may be associated with genetic susceptibility to SLE. There was unclear association found between PADI4 rs2240340, IL-33 rs10975498, and IL-33 rs1929992 polymorphisms and SLE and JIA. Due to the limitations of included studies and the risk of heterogeneity, additional research is required to confirm our findings. CRD42023391268.

A real-time and convex model for the estimation of muscle force from surface electromyographic signals in the upper and lower limbs.

Surface electromyography (sEMG) is a signal consisting of different motor unit action potential trains and records from the surface of the muscles. One of the applications of sEMG is the estimation of muscle force. We proposed a new real-time convex and interpretable model for solving the sEMG-force estimation. We validated it on the upper limb during isometric voluntary flexions-extensions at 30%, 50%, and 70% Maximum Voluntary Contraction in five subjects, and lower limbs during standing tasks in thirty-three volunteers, without a history of neuromuscular disorders. Moreover, the performance of the proposed method was statistically compared with that of the state-of-the-art (13 methods, including linear-in-the-parameter models, Artificial Neural Networks and Supported Vector Machines, and non-linear models). The envelope of the sEMG signals was estimated, and the representative envelope of each muscle was used in our analysis. The convex form of an exponential EMG-force model was derived, and each muscle's coefficient was estimated using the Least Square method. The goodness-of-fit indices, the residual signal analysis (bias and Bland-Altman plot), and the running time analysis were provided. For the entire model, 30% of the data was used for estimation, while the remaining 20% and 50% were used for validation and testing, respectively. The average R-square (%) of the proposed method was 96.77 ± 1.67 [94.38, 98.06] for the test sets of the upper limb and 91.08 ± 6.84 [62.22, 96.62] for the lower-limb dataset (MEAN ± SD [min, max]). The proposed method was not significantly different from the recorded force signal (p-value = 0.610); that was not the case for the other tested models. The proposed method significantly outperformed the other methods (adj. p-value < 0.05). The average running time of each 250ms signal of the training and testing of the proposed method was 25.7 ± 4.0 [22.3, 40.8] and 11.0 ± 2.9 [4.7, 17.8] in microseconds for the entire dataset. The proposed convex model is thus a promising method for estimating the force from the joints of the upper and lower limbs, with applications in load sharing, robotics, rehabilitation, and prosthesis control for the upper and lower limbs.