Linear Correlation Research Articles

Upgrading Electrolyte Antioxidant Chemistry by Constructing Potential Scaling Relationship.

Rational design of advanced electrolytes to improve the high-voltage capability has been attracting wide attention as one critical solution to enable next-generation high-energy-density batteries. However, the limited understanding of electrolyte antioxidant chemistry as well as the lack of valid quantization approaches have resulted in knowledge gap, which hinders the formulation of new electrolytes. Herein, we construct a standard curve based on representative solvation structures to quantify the oxidation stability of ether-based electrolytes, which reveals the linear correlation between the oxidation potential and the atomic charge of the least oxidation-resistant solvent. Dictating by the regularity between solvation composition and oxidation potential, a (Trifluoromethyl)cyclohexane-based localized high-concentration electrolyte dominated by anion-less solvation structures was designed to optimize the cycling performance of 4.5 V 30-μm-Li||3.8-mAh cm-2-LiCoO2 batteries, which maintained 80% capacity retention even after 440 cycles. The consistency of experimental and computational results validates the proposed principles, offering a fundamental guideline to evaluate and design aggressive electrochemical systems.

Active drug-coated flow diverter in a preclinical model of intracranial stenting

BackgroundFlow diverters carry the risk of thromboembolic complications (TEC). We tested a coating with covalently bound heparin that activates antithrombin to address TEC by locally downregulating the coagulation cascade. We...

Sequence-developability mapping of affibody and fibronectin paratopes via library-scale variant characterization.

Protein developability is requisite for use in therapeutic, diagnostic, or industrial applications. Many developability assays are low throughput, which limits their utility to the later stages of protein discovery and evolution. Recent approaches enable experimental or computational assessment of many more variants, yet the breadth of applicability across protein families and developability metrics is uncertain. Here, three library-scale assays-on-yeast protease, split green fluorescent protein (GFP), and non-specific binding-were evaluated for their ability to predict two key developability outcomes (thermal stability and recombinant expression) for the small protein scaffolds affibody and fibronectin. The assays' predictive capabilities were assessed via both linear correlation and machine learning models trained on the library-scale assay data. The on-yeast protease assay is highly predictive of thermal stability for both scaffolds, and the split-GFP assay is informative of affibody thermal stability and expression. The library-scale data was used to map sequence-developability landscapes for affibody and fibronectin binding paratopes, which guides future design of variants and libraries.

Visceral fat area is more strongly associated with arterial stiffness than abdominal subcutaneous fat area in Chinese patients with type 2 diabetes

BackgroundFew studies have compared the correlation between visceral fat area (VFA) and abdominal subcutaneous fat area (SFA) with arterial stiffness (AS) in patients with type 2 diabetes (T2D). In addition, there is currently controversy regarding the correlation between VFA and SFA with AS. We aimed to investigate the relationship between VFA and SFA with AS in patients with T2D.MethodsIn this cross-sectional study, 1475 Chinese T2D patients with an average age of 52.32 ± 10.96 years were included. VFA and SFA were determined by a dual bioelectrical impedance analyzer, and AS was determined by measurement of brachial-ankle pulse wave conduction velocity (baPWV). Atherosclerosis was deemed present in study participants with baPWV values higher than 75th percentile (1781 cm/s). Independent correlations of logVFA and logSFA with AS were assessed using multiple linear regression and multivariate logistic regression.ResultsThe baPWV was linked with VFA, waist circumference, and women’s SFA in a general linear correlation study (P < 0.05), but not with body mass index (P = 0.3783) or men’s SFA (P = 0.1899). In both men and women, VFA and SFA were positively correlated with AS, according to the generalized additive model (GAM). After fully adjusting for confounders, multiple linear regression analyses showed that for every 1-unit increase in logVFA, the beta coefficient of baPWV increased by 63.1 cm/s (95% CI: 18.4, 107.8) (P < 0.05). logSFA did not correlate significantly with baPWV (P = 0.125). In the multiple logistic regression analysis, the odds ratio (OR) of elevated baPWV was 1.8 (95% CI: 1.1, 3.1) (P = 0.019) per 1-unit increase in logVFA. logSFA did not correlate significantly with AS (P = 0.091). In the subgroup analysis, the correlation between logVFA and baPWV did not interact across subgroups (P-interaction > 0.05).ConclusionsCompared with SFA, VFA had a stronger independent positive correlation with AS in Chinese T2D patients. Patients with T2D should pay more attention to monitoring VFA and lowering it to minimize cardiovascular events.

Label-free colorimetric analysis strategies based on adsorption-responsive surface-enhanced photochromic phenomena of tungsten(VI) oxide nanoparticles for amino acids.

Herein, we present a colorimetric detection method based on the surface-enhanced photochromic phenomenon of tungsten (VI) oxide (WO3) nanocolloid particles for α-amino acid (AA) molecules, including L-aspartic acid (Asp), L-glutamic acid (Glu), L-histidine (His), L-isoleucine (Ile), L-leucine (Leu), L-lysine (Lys), L-phenylalanine (Phe), and L-valine (Val). The UV-induced photochromic phenomena in the AA/WO3 binary aqueous systems were investigated using UV-Vis absorption spectrometry. The adsorption properties of the AA molecules on the surface of the WO3 nanocolloid particles have been identified using a combination of adsorption isotherm analysis and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. A good linear correlation between the concentration of the AAs adsorbed on the surface of the WO3 nanocolloid particles and the initial photochromic coloration rate in the corresponding UV-irradiated WO3 colloidal aqueous solution was obtained with over three orders of magnitude, indicating that the surface-enhanced photochromic phenomenon of the WO3 nanocolloid particle can be used to detect the AA molecules. In addition, based on the results of the UV-Vis absorption, ATR-FTIR, and adsorption isotherm analyses, we have experimentally demonstrated that the AA/WO3 binary aqueous system with inner-sphere adsorbed Ile, Leu, Lys, or Val molecules on the surface of the WO3 nanocolloid particles exhibits a more significant surface-enhanced photochromic phenomenon than the system with outer-sphere adsorbed Asp, Glu, His, or Phe molecules. The strong inner-sphere adsorption of the AA molecules successfully improved the limit of detection. This study provides valuable insights into a "label-free" colorimetric assay system based on the surface-enhanced photochromic phenomenon of the WO3 nanocolloid probe.

Comparing the performance of machine learning models for predicting the compressive strength of concrete

This work aimed to investigate and compare the performance of different machine learning models in predicting the compressive strength of concrete using a data set of 1234 compressive strength values. The predictive variables were selected based on their relevance using the SelectKBest method, resulting in an analysis of eight and six predictive variables. The evaluation was conducted through linear correlation studies via simple linear regression and non-linear correlation studies using support vector regression (SVR), random forest (RF), gradient boosting (GB), and artificial neural networks (ANN). The results showed a coefficient of determination (R2) = 0.897 and a root mean square error (RMSE) = 6.535 MPa for SVR, R2 = 0.885 and RMSE = 5.437 MPa for GB, R2 = 0.868 and RMSE = 5.859 MPa for GB and R2 = 0.894 and RMSE = 5.192 MPa for ANN, all for test set and eight predictor variables. The comparison between the machine learning methods revealed significant differences. For instance, ANN stood out with a higher R2 value, demonstrating its remarkable ability to explain the variability in the data. ANN also showed the lowest RMSE value, indicating notable accuracy in the predictions. Although ANN has demonstrated higher performance, GB shows a closer performance, which no differences from a practical application. The choice between these approaches depends on considerations regarding the balance between explainability and accuracy. While GB provides a more in-depth understanding of the relationship between variables, ANN stands out for the accuracy of its predictions.

Lipocalin-2 as a marker of inflammation, bone density, and triglyceride-glucose index for new-onset arthritis patients in Mosul, Iraq.

Lipocalin-2 is an acute phase-associated adipokine that can serve as an inflammatory and biomarker indicator of cartilage deterioration in osteoarthritis. However, its role in the musculoskeletal system remains not fully understood. Hence, this study aimed to evaluate lipocalin-2 and its relationship with markers of inflammation (Interferon-gamma, ESR, and CRP), bone density (vitamin D3 and calcium), and the triglyceride-glucose index in new-onset arthritis patients in Mosul, Iraq. This study included 125 participants aged 20 to 65, divided into two groups. The Arthritis Patient Group comprised 70 participants (37 females and 33 males) attending the Bone Diseases Consultation Unit at the Ibn Sina Teaching Hospital in Mosul, Iraq. The Control Group comprised 31 females and 24 males. Ethical approval was obtained from the Iraqi Ministry of Health - Nineveh Health (No. 2022095). Commercial ELISA kits were used to measure serum lipocalin-2, Interferon-gamma, ESR, and CRP as inflammation markers, vitamin D3, and calcium as bone density markers. Moreover, the Triglyceride Glucose (TYG) Index was evaluated. The findings revealed a significant increase in lipocalin-2 levels in males compared to females, with LCN-2 increasing with age. Arthritis patients showed a significant increase (72%) in lipocalin-2 levels. Inflammatory indicators (erythrocyte sedimentation rate, C-reactive protein, interferon-gamma) displayed significant increases (46%, 1200%, and 581%, respectively). Glucose (23%), triglycerides (71%), and TYG index (21%) also exhibited significant increases. Meanwhile, bone density indicators (vitamin D3 and calcium) found a significant decrease (53% and 20%, respectively) in arthritis patients. Linear correlation coefficient (R) analysis revealed a significant positive relationship between lipocalin-2 and indicators of inflammation, glucose, TG, and TYG index. This study's findings suggest that LCN-2 serum levels were higher in patients with new-onset arthritis than in controls in Mosul, and LCN-2 serum increased in males compared with females and getting older serum LCN-2 increased for the patients and control groups. Furthermore, a significant correlation was found between the Triglyceride Glucose Index, which measures metabolic disorders, and serum LCN-2 levels and inflammatory indicators in new-onset arthritis patients in Mosul, Iraq.

Pollen- and Weather-Based Machine Learning Models for Estimating Regional Olive Production

The olive tree is one of the most common type of cultivation in the Mediterranean area, having high economic and social importance. The Alentejo region, Portugal, is an area with a high presence of olive groves, which in 2022 accounted for 201,474 hectares. The aim of this study was to assess the relationship between olive pollen, weather data, and olive tree production, between the years 2002 and 2022. Pollen data were obtained from an urban station located in Évora, in the Alentejo region, and were used to calculate several metrics, such as the Pollen Season Duration (PSD), Seasonal Pollen Index (SPIn), peak value, and weekly pollen accumulation values. Monthly minimum, maximum, and mean temperature and precipitation sums were obtained from the E-OBS observational dataset. Considering the relationship between pollen/weather and olive production, mutual information and correlation analyses were conducted. Subsequently, several machine learning algorithms were trained using pollen and weather datasets, and we obtained suitable forecast models for olive tree production after cross-validation. The results showed high variability in pollen concentrations in Évora over the years. Complex associations were found, with certain weeks of pollen accumulation showing significant mutual information with olive production, particularly during June. The analyzed linear correlation coefficients remained generally low, underscoring the challenge of predicting olive production based on linear relationships. Among the machine learning algorithms employed to predict olive production, Decision Trees, Extreme Gradient Boosting, and Gradient Boosting Regressor were the most robust performers (r2 &gt; 0.70), while linear models displayed a subpar performance (r2 &lt; 0.5), emphasizing the complexity of this approach. These models highlight the roles of maximum and minimum temperatures during March and May and pollen accumulation during the second half of June. The developed models may be used as decision-support tools by growers and stakeholders to further enhance the sustainability of the thriving olive sector in southern Portugal.

Experimental and theoretical studies on deformation characteristics of Geosynthetic-Reinforced Soil (GRS) abutments induced by vertical loads

This study conducted five centrifuge model tests to investigate the deformation characteristics of the Geosynthetics Reinforced Soil (GRS) abutments under vertical loads, considering the setback distance ab and beam seat width B as two major influencing factors. Test results show that a linear correlation existed between the maximum lateral facing displacements DL and the maximum settlements at the top of the GRS abutments Dv. The ab and the B had different effects on the deformation characteristics of the GRS abutments as well as the relationship between the DL and the Dv. The total volumetric strains of the GRS abutments were smaller than 0.3% for all the cases investigated in this study, indicating that it was reasonable to use the assumption of zero-volume change for the deformation calculation of the GRS abutments. This study proposed an improved semi-empirical method to describe the relationship between the DL and the Dv. Centrifuge test results and data collected from the literature were used to validate the improved method. It was concluded that the improved method had the advantage of considering the effects of the ab and the B separately and therefore significantly improved the prediction accuracy of the deformations of the GRS abutments.

Plastic zone characteristics and rapid stability evaluation indexes of circular tunnels subjected to non-hydrostatic stress: A novel complex variable solution incorporating 3D rock mass strength

The morphological characteristics and distribution range of the plastic zone around tunnels, influenced by the true three-dimensional high geostress environment in deep engineering, constitute fundamental reference data for both tunnel design and the control of surrounding rock stability. Based on the GZZ three-dimensional rock mass strength criteria and the complex variable method, a novel semi-analytical method for solving the plastic zone of a circular tunnel subjected to non-hydrostatic stress is presented. The conformal mapping is employed to intricately transform the complex boundaries of plastic zones characterized by diverse shapes onto the unit circle boundary within the image plane. This framework proves invaluable for the precise analytical process of the complex plastic zone morphology and the plastic influence range within the surrounding rock under complex stress conditions. In contrast to traditional analytical methods, the efficacy and versatility of our proposed approach are substantiated. Notably, it demonstrates unique advantages, particularly in the context of non-hydrostatic stress fields and varied rock mass parameters, with respect to predicting both surrounding rock stability and plastic zone morphology. Through the analysis of numerous cases, the study reveals the systematic patterns of influence that in-situ stress and surrounding rock characteristic parameters have on the shape and maximum depth of the plastic zone. The results indicate that (1) there are notable disparities in the morphology and extent of the plastic zone between the GZZ and GHB criteria; (2) the transition of the plastic zone in surrounding rock from U-shaped to V-shaped is significantly influenced by the geostress-to-strength ratio Kσ; (3) there is a notable linear correlation observed between the maximum plastic zone thickness rmax and both Kσ and the stress concentration factor KSCF, importantly, this correlation is independent of far-field stress and the brittleness characteristics of the surrounding rock. These findings provide a novel discriminative method for the rapid analysis of surrounding rock stability in deep circular tunnels.

Experience of rigorous practice of antimicrobial stewardship program and its impact on antibiotic consumption

Objectives: Antimicrobial resistance (AMR) is the next pandemic with a huge global economic burden. A customized antimicrobial stewardship program (AMSP) is a well-recognized tool for containment of AMR. The current study was undertaken to identify the impact of AMSP measures on the trends of antibiotic consumption rates, e.g., defined daily dose (DDD) and days of therapy (DOT) per 100 patient days in pre-identified areas of the hospital. Materials and Methods: The present study was a case-record-based extended cross-sectional study carried out in a tertiary care institute in central India from January 2021 to September 2021. Time-bound feasible sampling was undertaken, and all cases were included without any exclusion criteria. The study was approved by the Ethics Committee of the Institute and funded by the Indian Council of Medical Research (ICMR). Statistical Analysis: The data was entered into a spreadsheet. The calculation of DDD and DOT was performed individually for each antibiotic as per WHO tool per 100 patient days. Results: In high-priority areas such as intensive care unit and high dependency unit, the top three DDD/100 days were meropenem (77.9), colistin (41.4), and piperacillin-tazobactam (13.5) versus the top 3 DOT/100 patient days were meropenem (40.5), colistin (20.9), and piperacillin-tazobactam (15.7). In low-priority areas such as general wards, the top 3 DDD/100 patient days were meropenem (45.4), piperacillin-tazobactam (22.6), and cefoperazone (5.0) versus the top three DOT/100 patient days were meropenem (45.4), cefoperazone (44.9), and piperacillintazobactam (22.6). There was a downward trend of consumption of almost all these antibiotics when measured at baseline and the next two quarters. DDD and DOT per 100 patient days had a positive linear correlation during the study period. Conclusions: The present study demonstrates about 50% reduction in consumption of ICMR priority antibiotics with a yearlong AMSP. DDD and DOT per 100 patient days can be calculated with minimal effort, even in extremely busy hospitals. DOT tools are less labor-intensive and, hence, should be the pivotal tool for antibiotic exposure measurement.

HIFAST: An HI Data Calibration and Imaging Pipeline for FAST II. Flux Density Calibration

Abstract Accurate flux density calibration is essential for precise analysis and interpretation of observations across different observation modes and instruments. In this research, we introduce the flux calibration model incorporated in HIFAST pipeline, designed for processing HI 21-cm spectra. Furthermore, we investigate different calibration techniques and assess the dependence of the gain parameter on the time and environmental factors. A comparison is carried out in various observation modes (e.g. tracking and scanning modes) to determine the flux density gain (G), revealing insignificant discrepancies in G among different methods. Long-term monitoring data shows a linear correlation between G and atmospheric temperature. After subtracting the G - Temperature dependence, the dispersion of G is reduced to &lt;3% over a one-year time scale. The stability of the receiver response of FAST is considered sufficient to facilitate HI observations that can accommodate a moderate error in flux calibration (e.g., &gt;~5%) when utilizing a constant G for calibration purposes. Our study will serve as a useful addition to the results provided by Jiang et al (2020). Detailed measurements of G for the 19 beams of FAST, covering the frequency range 1000 MHz - 1500 MHz can be found on the HIFAST homepage: https://hifast.readthedocs.io/fluxgain

The Influence of Microstructural Arrangement on the Failure Characteristics of 3D-Printed Polymers: Exploring Damage Behaviour in Acrylonitrile Butadiene Styrene.

This study investigated how printing conditions influence the fracture behaviour of 3D-printed acrylonitrile butadiene styrene (ABS) under tensile loading. Dog-bone-shaped ABS specimens were produced using the fusion filament fabrication technique, with varying printing angles. Tensile tests were conducted on pre-notched specimens with consistent pre-notch lengths but different orientations. Optical and scanning electron microscopies were employed to analyse crack propagation in the pre-notched specimens. In order to support experimental evidence, finite element computation was implemented to study the damage induced by the microstructural rearrangement of the filaments when subject to tensile loading. The findings revealed the simple linear correlation between the failure properties including elongation at break and maximum stress in relation to the printing angle for different pre-notch lengths. A more progressive damage was found to support the ultimate performance of the studied material. This experiment evidence was used to build a damage model of 3D-printed ABS that accounts for the onset, growth, and damage saturation. This damage modelling is able to capture the failure properties as a function of the printing angle using a sigmoid-like damage function and a modulation of the stiffness within the raster. The numerical results demonstrated that damage pattern develops as a result of the filament arrangement and weak adhesion between adjacent filaments and explains the diffuse damage kinetics observed experimentally. This study concludes with a topological law relating the notch size and orientation to the rupture properties of 3D-printed ABS. This study supports the idea of tailoring the microstructural arrangement to control and mitigate the mechanical instabilities that lead to the failure of 3D-printed polymers.

Combined interaction of fungicides binary mixtures: experimental study and machine learning-driven QSAR modeling

Fungicide mixtures are an effective strategy in delaying the development of fungicide resistance. In this research, a fixed ratio ray design method was used to generate fifty binary mixtures of five fungicides with diverse modes of action. The interaction of these mixtures was then analyzed using CA and IA models. QSAR modeling was conducted to assess their fungicidal activity through multiple linear regression (MLR), support vector machine (SVM), and artificial neural network (ANN). Most mixtures exhibited additive interaction, with the CA model proving more accurate than the IA model in predicting fungicidal activity. The MLR model showed a good linear correlation between selected theoretical descriptors by the genetic algorithm and fungicidal activity. However, both ML-based models demonstrated better predictive performance than the MLR model. The ANN model showed slightly better predictability than the SVM model, with R2 and R2cv at 0.91 and 0.81, respectively. For external validation, the R2test value was 0.845. In contrast, the SVM model had values of 0.91, 0.78, and 0.77 for the same metrics. In conclusion, the proposed ML-based model can be a valuable tool for developing potent fungicidal mixtures to delay fungicidal resistance emergence.

Ratiometric two-photon fluorescent probe for imaging hydrogen peroxide during stroke-induced ferroptosis

Ischemic stroke (IS) initiates a programmed cell death through apoptosis, autophagy, and ferroptosis, which results in neuronal damage and brain injury. However, existing methods for in situ detection of ferroptosis are currently insufficient. Therefore, we constructed a series of hydrogen peroxide (H2O2—one of the major ROS) probes (QH2O2, MQH2O2, and BQH2O2) with quinoline derivatives as two-photon fluorophores and boronate as the recognition domain. Experimental results indicated that the linear response range of the probe MQH2O2 to H2O2 increased from < 10–300 μM as compared with the probe QH2O2. Moreover, the linear correlation coefficient also increased from 0.9012 to 0.999, indicating that the ratiometric fluorescent probe has built-in corrections for environmental interference, which allows a more accurate fluorescence analysis. Modification of the probe by connecting triethylene glycol monomethyl ether (BQH2O2) increased the lipophilic index of the probe to 2.01, which enhanced its ability to cross the blood–brain barrier. Therefore, the developed probe is useful for analyzing the H2O2 production during an ischemic stroke and its fluctuation with ferroptosis.

Surging Liver Transplantation for Nonalcoholic Steatohepatitis from 2000-2022: A National Database Study.

Our aim was to provide an up-to-date, large-scale overview of the trends and clinicodemographics for NASH LTs performed in the United States compared with all other LT indications between 2000 and 2022. We also examined the demographic factors that will predict future demand for NASH LT. Our analysis of NASH LT from the Organ Procurement & Transplantation Network database spanning 2000-2022 consisted primarily of descriptive statistics and hypothesis testing with corrections for multiple testing when necessary. Trend lines and linear correlations were also explored. NASH LTs have experienced a remarkable surge, escalating from 0.12% of all LTs in 2000 to a substantial 14.7% in 2022, marking a 100-fold increase. Examining demographic trends, a significant proportion of NASH LTs recipients fall within the 50- to 64-year-old age group. Moreover, 52% of these recipients concurrently exhibit type 2 diabetes mellitus, a notably higher percentage than the 19% observed in all LT recipients. Type 2 diabetes mellitus emerges as a prominent risk factor for NASH progressing to end-stage liver disease. The phenomenon of repeat transplantation is noteworthy; although 6% of all LTs necessitate repeat procedures, this figure dramatically drops to 0.6% for NASH LTs. Ethnic disparities are apparent, with African Americans representing a mere 2% of NASH LT recipients, significantly lower than their representation in the overall population. Regionally, the East Coast has a higher proportion of NASH LT recipients compared with waitlist additions. This trend holds true across demographics. Our findings underscore the need for increased resources, particularly for minority, uninsured, or noncitizen individuals requiring LT for NASH. This analysis provides valuable insights into the dynamic landscape of LTs in the context of NASH, shaping the trajectory of medical interventions in the 21st century.

Three-dimensional changes of condylar position after bimaxillary surgery to correct skeletal III malocclusion: CBCT voxel-based superimposition analysis

BackgroundThe stability of the condylar position within the first three months after orthognathic surgery in patients with skeletal Class III malocclusion is crucial for subsequent orthodontic treatment. PurposeThe purpose was to compare condylar positional changes three months after bimaxillary surgery to correct skeletal Class III deformities, utilizing the conventional two-dimensional (2D) combined with the cone beam computed tomography (CBCT) voxel-based superimposition analysis. Study design, setting, sampleThis retrospective cohort study included skeletal Class III patients undergoing bimaxillary orthognathic surgery at Khon Kaen University, Thailand in 2020. Exclusion criteria were patients with temporomandibular disorder (TMD) symptoms, facial asymmetry prior to the surgery, or surgical complications. Exposure variableThe exposure variable was the timing, both preoperatively and 3 months postoperatively. This 3-month postoperative time point was chosen because complete healing of the bimaxillary surgery is expected by then, without any potential influence of condylar changes resulting from subsequent orthodontic treatment. Main outcome variablesThe outcome variable is condylar position measurement, joint space (mm) and axial condylar angle (degrees). CovariatesDemographics (age, sex), and surgical details (direction and amount of movement) were collected as covariates. AnalysesStatistical analysis of condylar positional changes and correlations was performed using paired t-test and linear correlation (P-value < 0.05), respectively. ResultsThe sample included 11 subjects (22 condyles), with a mean age of 24±5.24 years. Both 2D measurements and voxel-based 3D superimposition showed significant changes in condylar position three months after bimaxillary surgery: inferior (0.45±0.26 mm, P < 0.001), posterior (0.46±0.39 mm, P = 0.003), lateral (0.38±0.42 mm, P = 0.01) displacement, and inward rotation (5.21±2.54°, P < 0.001). No significant correlation was found between jaw movement distance and condylar changes. Conclusions and relevanceTo our knowledge, this is the first study to report measures of condylar changes at 3 months, when complete healing of the osteotomies would be expected, using Le Fort I osteotomy for maxillary advancement combined with bilateral sagittal split ramus osteotomy (BSSRO) for mandibular setback. These changes are small in magnitude and may be of little relevance to patient care.

Correlation of Noninvasive Cardiac MRI Measures of Left Ventricular Myocardial Function and Invasive Pressure-Volume Parameters in a Porcine Ischemia-Reperfusion Model.

Purpose To assess the correlation between noninvasive cardiac MRI-derived parameters with pressure-volume (PV) loop data and evaluate changes in left ventricular function after myocardial infarction (MI). Materials and Methods Sixteen adult female swine were induced with MI, with six swine used as controls and 10 receiving platelet-derived growth factor-AB (PDGF-AB). Load-independent measures of cardiac function, including slopes of end-systolic pressure-volume relationship (ESPVR) and preload recruitable stroke work (PRSW), were obtained on day 28 after MI. Cardiac MRI was performed on day 2 and day 28 after infarct. Global longitudinal strain (GLS) and global circumferential strain (GCS) were measured. Ventriculo-arterial coupling (VAC) was derived from PV loop and cardiac MRI data. Pearson correlation analysis was performed. Results GCS (r = 0.60, P = .01), left ventricular ejection fraction (LVEF) (r = 0.60, P = .01), and cardiac MRI-derived VAC (r = 0.61, P = .01) had a significant linear relationship with ESPVR. GCS (r = 0.75, P < .001) had the strongest significant linear relationship with PRSW, followed by LVEF (r = 0.67, P = .005) and cardiac MRI-derived VAC (r = 0.60, P = .01). GLS was not significantly correlated with ESPVR or PRSW. There was a linear correlation (r = 0.82, P < .001) between VAC derived from cardiac MRI and from PV loop data. GCS (-3.5% ± 2.3 vs 0.5% ± 1.4, P = .007) and cardiac MRI-derived VAC (-0.6 ± 0.6 vs 0.3 ± 0.3, P = .001) significantly improved in the animals treated with PDGF-AB 28 days after MI compared with controls. Conclusion Cardiac MRI-derived parameters of MI correlated with invasive PV measures, with GCS showing the strongest correlation. Cardiac MRI-derived measures also demonstrated utility in assessing therapeutic benefit using PDGF-AB. Keywords: Cardiac MRI, Myocardial Infarction, Pressure Volume Loop, Strain Imaging, Ventriculo-arterial Coupling Supplemental material is available for this article. © RSNA, 2024.

A first-in-human, phase I, dose-escalation study to evaluate pharmacokinetics, safety, and tolerability of KD6001, a novel anti-CTLA-4 monoclonal antibody (mAb) in patients with advanced solid tumors.

e14501 Background: KD6001, a novel fully human anti-CTLA4 IgG1 monoclonal antibody, exhibits immunomodulatory effects, enhances T-cell-mediated antitumor immune response and shows promising activity in preclinical models of solid tumors. Here we present the pharmacokinetics, safety and tolerability data from the phase 1 study of KD6001 (NCT05230290) in patients with advanced solid tumors. Methods: patients were enrolled in a 3+3 dose escalation phase 1 study with the following pre-defined KD6001 cohorts: 0.2mg/kg, 1mg/kg, 3mg/kg or 6mg/kg, every 2 weeks via intravenous infusion for 4 cycles. The primary objective was to evaluate the safety and tolerability of KD6001 and determine the MTD/RP2D. The secondary objectives were to measure antitumor activity, immunogenicity and pharmacokinetics (PK). All AEs are graded using NCI CTCAE v5.0. Efficacy assessments are per RECIST 1.1. Blood samples are obtained for pharmacokinetics (PK) and for immunogenicity assessments, measured by the development of anti-drug antibodies. Results: The study had been completed. Thirteen pts with melanoma had been enrolled and treated at 0.2 mg/kg (n = 1), 1mg/kg (n = 3), 3 mg/kg (n = 6) and 6mg/kg (n = 3) at Beijing Cancer Hospital. The average age was 57.2 years (range 34-68). Baseline ECOG scores were 0 (n = 5), 1(n = 8) with all pts. Seven pts (53.85%) received ≥ 2 lines of previous systemic therapies and 12 pts (92.31%) received previous PD-1/PD-L1 treatment. KD6001 was well-tolerated with no dose-limiting toxicities (DLTs) observed, nor was the MTD reached at the highest doses administered. All the thirteen pts had at least one adverse event during treatment, and eleven of them (84.62%) had Treatment Related Adverse Events (TRAEs), most of which were Grades 1-2. There were no permanent drug discontinuation or deaths due to adverse events. Pharmacokinetic analysis indicated a linear correlate between the drug exposure (Cmax, AUC0-t and AUC0-inf) and study drug dosages evaluated. The geometric mean T1/2 was 10 days (CV%: 31%). The peak concentration and exposure level increased proportionally to dose from 0.2mg/kg to 6 mg/kg. No anti-drug antibodies were detected in any of the patient’s serum samples. Clinical efficacy was observed in 12 evaluable pts: 3 patients at 3mg/kg had a stable disease (SD) and 1 patient at 3mg/kg had a confirmed partial response (PR). The ORR of the 3mg/kg dose group was 16.7% (1/6), the DCR was 66.67% (4/6). The median PFS was 109 days and the median OS was not reached. Conclusions: KD6001 showed promising antitumor activity and a tolerable safety profile in patients with advanced solid tumors. Hence, 3mg/kg was selected as the RP2D. Clinical trial information: NCT05230290 .

Effects of dietary glycerol monolaurate on growth and digestive performance, lipid metabolism, immune defense and gut microbiota of shrimp (Penaeus vannamei)

The advancement of the Penaeus vannamei industry in a sustainable manner necessitates the creation of eco-friendly and exceptionally effective feed additives. To achieve this, 720 similarly-sized juvenile shrimp (0.88 ± 0.02 g) were randomly divided into four groups in this study, with each group consisting of three replicates, each tank (400 L) containing 60 shrimp. Four experimental diets were formulated by adding 0, 500, 1000, and 1500 mg kg−1 glycerol monolaurate (GML) to the basal diet, and the feeding trial lasted for 42 days. Subsequently, a 72-h White Spot Syndrome Virus (WSSV) challenge test was conducted. Polynomial orthogonal contrasts analysis revealed that with the increase in the concentration of GML, those indicators related to growth, metabolism and immunity, exhibit linear or quadratic correlations (P < 0.05). The results indicate that the GML groups exhibited a significant improvement in the shrimp weight gain rate, specific growth rate, and a reduction in the feed conversion ratio (P < 0.05). Furthermore, the GML groups promoted the lipase activity and reduced lipid content of the shrimp, augmented the expression of triglyceride and fatty acid decomposition-related genes and lowered the levels of plasma triglycerides (P < 0.05). GML can also enhanced the humoral immunity of the shrimp by activating the Toll-like receptor and Immune deficiency immune pathways, improved the phagocytic capacity and antibacterial ability of shrimp hemocytes. The challenge test revealed that GML significantly reduced the mortality of the shrimp compared to control group. The 16S rRNA sequencing indicates that the GML group can increases the abundance of beneficial bacteria. However, 1500 mg kg−1 GML adversely affected the stability of the intestinal microbiota, significantly upregulating intestinal antimicrobial peptide-related genes and tumor necrosis factor-alpha levels (P < 0.05). In summary, 1000 mg kg−1 GML was proven to enhance the growth performance, lipid absorption and metabolism, humoral immune response, and gut microbiota condition of P. vannamei, with no negative physiological effects.