Mogrol-mediated enhancement of radiotherapy sensitivity in non-small cell lung cancer: a mechanistic study.

This study investigated mogrol's impact on non-small cell lung cancer (NSCLC) radiosensitivity and underlying mechanisms, using various methods including assays, bioinformatics, and xenograft models. CCK-8, clonogenic, flow cytometry, TUNEL, and Western blot assays evaluated mogrol and radiation effects on NSCLC viability and apoptosis. Ubiquitin-specific protease 22 (USP22) expression in NSCLC patient tissues was determined by RT-qPCR and Western blot. A xenograft model validated mogrol's effects on tumor growth. Bioinformatics identified four ubiquitin-specific proteases, including USP22, in NSCLC. Kaplan-Meier analysis confirmed USP22's value in lung cancer survival. Human Protein Atlas (HPA) database analysis indicated higher USP22 expression in lung cancer tissues. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis implicated ERK1/2 in NSCLC progression, and molecular docking showed stability between mogrol and ERK1/2. Further in vivo and in vitro experiments have demonstrated that mogrol enhances the inhibitory effect of radiation on NSCLC cell viability and clonogenic capacity. Cell viability and clonogenic capacity are reduced by >50%, and an increase in cellular apoptosis is observed, with apoptotic levels reaching 10%. USP22 expression was significantly elevated in NSCLC tissues, particularly in radiotherapy-resistant patients. Mogrol downregulated USP22 expression by inhibiting the ERK/CREB pathway, lowering COX2 expression. Mogrol also enhanced radiation's inhibition of tumor growth in mice. Mogrol enhances NSCLC radiosensitivity by downregulating USP22 via the ERK/CREB pathway, leading to reduced COX2 expression.NEW & NOTEWORTHY Mogrol enhances non-small cell lung cancer (NSCLC) cell sensitivity to radiotherapy by downregulating USP22 through the ERK/CREB pathway, reducing COX2 expression. These findings highlight mogrol's potential as an adjunct to improve NSCLC radiotherapy and open avenues for further research and clinical applications.

Platelet-derived microvesicles regulate vascular smooth muscle cell energy metabolism via PRKAA after intimal injury.

Vascular intimal injury initiates various cardiovascular disease processes. Exposure to subendothelial collagen can cause platelet activation, leading to collagen-activated platelet-derived microvesicles (aPMVs) secretion. In addition, vascular smooth muscle cells (VSMCs) exposed to large amounts of aPMVs undergo abnormal energy metabolism; they proliferate excessively and migrate after the loss of endothelium, eventually contributing to neointimal hyperplasia. However, the roles of aPMVs in VSMC energy metabolism are still unknown. Our carotid artery intimal injury model indicated that platelets adhered to injured blood vessels. In vitro, phosphorylated Pka (cAMP-dependent protein kinase) content was increased in aPMVs. We also found that aPMVs significantly reduced VSMC glycolysis and increased oxidative phosphorylation, and promoted VSMC migration and proliferation by upregulating phosphorylated PRKAA (α catalytic subunit of AMP-activated protein kinase) and phosphorylated FoxO1. Compound C, an inhibitor of PRKAA, effectively reversed the enhancement of cellular function and energy metabolism triggered by aPMVs in vitro and neointimal formation in vivo. We show that aPMVs can affect VSMC energy metabolism through the Pka-PRKAA-FoxO1 signaling pathway and this ultimately affects VSMC function, indicating that the shift in VSMC metabolic phenotype by aPMVs can be considered a potential target for the inhibition of hyperplasia. This provides a new perspective for regulating the abnormal activity of VSMCs after injury.

Coronary angiography-derived index for assessing microcirculatory resistance in patients with non-obstructed vessels: The FLASH IMR study.

BACKGROUND: Assessing index of microcirculatory resistance (IMR) is customarily performed using intracoronary wires fitted with sensors by at least 3 intracoronary injections of 3 to 4 mL of room-temperature saline during sustained hyperemia, which is time- and cost-consuming. METHODS: The FLASH IMR study is a prospective, multicenter, randomized study to assess the diagnostic performance of coronary angiography-derived IMR (caIMR) in patients with suspected myocardial ischemia with nonobstructive coronary arteries using wire-based IMR as a reference. The caIMR was calculated by an optimized computational fluid dynamics model simulating hemodynamics during diastole based on coronary angiograms. TIMI frame count and aortic pressure were included in computation. caIMR was determined onsite in real time and compared blind to wire-based IMR by an independent core laboratory, using wire-based IMR ≥25 units as indicative of abnormal coronary microcirculatory resistance. The primary endpoint was the diagnostic accuracy of caIMR, using wire-based IMR as a reference, with a pre-specified performance goal of 82%. RESULTS: A total of 113 patients underwent paired caIMR and wire-based IMR measurements. Order of performance of tests was based on randomization. Diagnostic accuracy, sensitivity, specificity, positive and negative predictive values of caIMR were 93.8% (95% CI: 87.7%-97.5%), 95.1% (95% CI: 83.5%- 99.4%), 93.1% (95% CI: 84.5%-97.7%), 88.6% (95% CI: 75.4%-96.2%) and 97.1% (95% CI: 89.9%-99.7%). The receiver-operating curve for caIMR to diagnose abnormal coronary microcirculatory resistance had area under the curve of 0.963 (95% CI: 0.928-0.999). CONCLUSIONS: Angiography-based caIMR has a good diagnostic yield with wire-based IMR. GOV IDENTIFIER: NCT05009667.

Coronary angiography-derived contrast fractional flow reserve.

BACKGROUND: Based on coronary angiography and mean aortic pressure, a specially designed computational flow dynamics (CFD) method is proposed to determine contrast fractional flow reserve (cFFR) without using invasive pressure wire. This substudy assessed diagnostic performance of coronary angiography-derived cFFR in catheterization laboratory, based on a previous multicenter trial for online assessment of coronary angiography-derived FFR (caFFR). METHODS: Patients with diagnosis of stable angina pectoris or unstable angina pectoris were enrolled in six centers. Wire-based FFR was measured in coronary arteries with 30-90% diameter stenosis. Offline angiography-derived cFFR was computed in blinded fashion against the wire-based FFR and caFFR at an independent core laboratory. RESULTS: A total of 330 patients were enrolled to fulfill inclusion/exclusion criteria from June 26 to December 18, 2018. Offline angiography-derived cFFR and wire-based FFR results were compared in 328 interrogated vessels. The statistical analysis showed the highest diagnostic accuracy of 89.0 and 86.6% for angiography-derived cFFR with a cutoff value of 0.94 and 0.93 against the wire-based FFR with a cutoff value of 0.80 and 0.75, respectively. The corresponding sensitivity and specificity were 92.2 and 87.3% for the cutoff value of 0.94 and 80.0 and 88.4% for the cutoff value of 0.93, which are similar to those against the caFFR. The receiver-operating curve has area under the curve of 0.951 and 0.972 for the wire-based FFR with the cutoff value of 0.80 and 0.75, respectively. CONCLUSIONS: Coronary angiography-derived cFFR showed higher accuracy, sensitivity, and specificity against wired-based FFR and caFFR. Hence, angiography-derived cFFR could enhance the hemodynamic assessment of coronary lesions.

PINK1 Phosphorylates Drp1S616 to Improve Mitochondrial Fission and Inhibit the Progression of Hypertension-Induced HFpEF.

(1) Background: Heart failure with preserved ejection fraction (HFpEF) is a major subtype of HF with no effective treatments. Mitochondrial dysfunctions relevant to the imbalance of fusion and fission occur in HFpEF. Drp1 is a key protein regulating mitochondrial fission, and PINK1 is the upstream activator of Drp1, but their relationship with HF has not been clarified. The aim of the study is to investigate molecular mechanisms of mitochondrial dysfunctions in animals with hypertension-induced HFpEF. (2) Methods and Results: The hypertension-induced HFpEF model was established by feeding Dahl/SS rats with high salt, showing risk factors such as hypertension, mitochondrial dysfunctions, and so on. Physiological and biological measurements showed a decrease in the expression of mitochondrial function-related genes, ATP production, and mitochondrial fission index. PINK1 knockout in H9C2 cardiomyocytes showed similar effects. Moreover, PINK1 myocardium-specific overexpression activated Drp1S616 phosphorylation and enhanced mitochondrial fission to slow the progression of hypertension-induced HFpEF. (3) Conclusions: PINK1 could phosphorylate Drp1S616 to improve mitochondrial fission and relieve mitochondrial dysfunctions, which highlights potential treatments of HFpEF.

Sickle Cell Anemia Mediates Carotid Artery Expansive Remodeling That Can Be Prevented by Inhibition of JNK (c-Jun N-Terminal Kinase).

OBJECTIVE: Sickle cell anemia (SCA) causes chronic inflammation and multiorgan damage. Less understood are the arterial complications, most evident by increased strokes among children. Proteolytic mechanisms, biomechanical consequences, and pharmaceutical inhibitory strategies were studied in a mouse model to provide a platform for mechanistic and intervention studies of large artery damage due to sickle cell disease. Approach and Results: Townes humanized transgenic mouse model of SCA was used to test the hypothesis that elastic lamina and structural damage in carotid arteries increased with age and was accelerated in mice homozygous for SCA (sickle cell anemia homozygous genotype [SS]) due to inflammatory signaling pathways activating proteolytic enzymes. Elastic lamina fragmentation observed by 1 month in SS mice compared with heterozygous littermate controls (sickle cell trait heterozygous genotype [AS]). Positive immunostaining for cathepsin K, a powerful collagenase and elastase, confirmed accelerated proteolytic activity in SS carotids. Larger cross-sectional areas were quantified by magnetic resonance angiography and increased arterial compliance in SS carotids were also measured. Inhibiting JNK (c-jun N-terminal kinase) signaling with SP600125 significantly reduced cathepsin K expression, elastin fragmentation, and carotid artery perimeters in SS mice. By 5 months of age, continued medial thinning and collagen degradation was mitigated by treatment of SS mice with JNK inhibitor. CONCLUSIONS: Arterial remodeling due to SCA is mediated by JNK signaling, cathepsin proteolytic upregulation, and degradation of elastin and collagen. Demonstration in Townes mice establishes their utility for mechanistic studies of arterial vasculopathy, related complications, and therapeutic interventions for large artery damage due to SCA.

Age-dependent characterization of carotid and cerebral artery geometries in a transgenic mouse model of sickle cell anemia using ultrasound and microcomputed tomography.

To define morphological changes in carotid and cerebral arteries in sickle cell transgenic mice (SS) as they age, a combination of ultrasound and microcomputed tomography of plastinated arteries was used to quantify arterial dimensions and changes in mice 4, 12, and 24 weeks of age. 12-week SS mice had significantly larger common carotid artery diameters than AS mice, which continued through to the extracranial and intracranial portions of the internal carotid artery (ICA). There were also side specific differences in diameters between the left and right vessels. Significant ICA tapering along its length occurred by 12- and 24-weeks in SS mice, decreasing by as much as 70%. Significant narrowing along the length was also measured in SS anterior cerebral arteries at 12- and 24-weeks, but not AS. Collectively, these findings indicate that sickle cell anemia induces arterial remodeling in 12- and 24-weeks old mice. Catalog of measurements are also provided for the common carotid, internal carotid, anterior cerebral, and middle cerebral arteries for AS and SS genotypes, as a reference for other investigators using mathematical and computational models of age-dependent arterial complications caused by sickle cell anemia.

Morphometric, Hemodynamic, and Multi-Omics Analyses in Heart Failure Rats with Preserved Ejection Fraction.

(1) Background: There are no successive treatments for heart failure with preserved ejection fraction (HFpEF) because of complex interactions between environmental, histological, and genetic risk factors. The objective of the study is to investigate changes in cardiomyocytes and molecular networks associated with HFpEF. (2) Methods: Dahl salt-sensitive (DSS) rats developed HFpEF when fed with a high-salt (HS) diet for 7 weeks, which was confirmed by in vivo and ex vivo measurements. Shotgun proteomics, microarray, Western blot, and quantitative RT-PCR analyses were further carried out to investigate cellular and molecular mechanisms. (3) Results: Rats with HFpEF showed diastolic dysfunction, impaired systolic function, and prolonged repolarization of myocytes, owing to an increase in cell size and apoptosis of myocytes. Heatmap of multi-omics further showed significant differences between rats with HFpEF and controls. Gene Set Enrichment Analysis (GSEA) of multi-omics revealed genetic risk factors involved in cardiac muscle contraction, proteasome, B cell receptor signaling, and p53 signaling pathway. Gene Ontology (GO) analysis of multi-omics showed the inflammatory response and mitochondrial fission as top biological processes that may deteriorate myocyte stiffening. GO analysis of protein-to-protein network indicated cytoskeleton protein, cell fraction, enzyme binding, and ATP binding as the top enriched molecular functions. Western blot validated upregulated Mff and Itga9 and downregulated Map1lc3a in the HS group, which likely contributed to accumulation of aberrant mitochondria to increase ROS and elevation of myocyte stiffness, and subsequent contractile dysfunction and myocardial apoptosis. (4) Conclusions: Multi-omics analysis revealed multiple pathways associated with HFpEF. This study shows insight into molecular mechanisms for the development of HFpEF and may provide potential targets for the treatment of HFpEF.

[Experimental measurement and modeling analysis of active and passive mechanical properties of arterial vessel wall].

Coronary artery diseases (CAD) have always been serious threats to human health. The measurement, constitutive modeling, and analysis of mechanical properties of the blood vessel wall can provide a tool for disease diagnosis, stent implantation, and artificial artery design. The vessel wall has both active and passive mechanical properties. The passive mechanical properties are mainly determined by elastic and collagen fibers, and the active mechanical properties are determined by the contraction of vascular smooth muscle cells (VSMC). Substantial studies have shown that, the two-layer model of the vessel wall can feature the mechanical properties well, and the circumferential, axial and radial strain and stress are of great significance in arterial wall mechanics. This study reviewed recent investigations of mechanical properties of the vessel wall. Challenges and opportunities in this area are discussed relevant to the clinical treatment of coronary artery diseases.

Nitrate decreases ruminal methane production with slight changes to ruminal methanogen composition of nitrate-adapted steers.

BACKGROUND: This study was conducted to examine effects of nitrate on ruminal methane production, methanogen abundance, and composition. Six rumen-fistulated Limousin×Jinnan steers were fed diets supplemented with either 0% (0NR), 1% (1NR), or 2% (2NR) nitrate (dry matter basis) regimens in succession. Rumen fluid was taken after two-week adaptation for evaluation of in vitro methane production, methanogen abundance, and composition measurements. RESULTS: Results showed that nitrate significantly decreased in vitro ruminal methane production at 6 h, 12 h, and 24 h (P < 0.01; P < 0.01; P = 0.01). The 1NR and 2NR regimens numerically reduced the methanogen population by 4.47% and 25.82% respectively. However, there was no significant difference observed between treatments. The alpha and beta diversity of the methanogen community was not significantly changed by nitrate either. However, the relative abundance of the methanogen genera was greatly changed. Methanosphaera (PL = 0.0033) and Methanimicrococcus (PL = 0.0113) abundance increased linearly commensurate with increasing nitration levels, while Methanoplanus abundance was significantly decreased (PL = 0.0013). The population of Methanoculleus, the least frequently identified genus in this study, exhibited quadratic growth from 0% to 2% when nitrate was added (PQ = 0.0140). CONCLUSIONS: Correlation analysis found that methane reduction was significantly related to Methanobrevibacter and Methanoplanus abundance, and negatively correlated with Methanosphaera and Methanimicrococcus abundance.

Association between antidepressant medication use and epithelial ovarian cancer risk: a systematic review and meta-analysis of observational studies.

AIM: The aim of this paper is to clarify the inconsistent findings in the association between antidepressant use and the risk of epithelial ovarian cancer (EOC). METHODS: This study is a meta-analysis of observational studies retrieved from the PubMed, EMBASE, and Web of Science databases prior to August 15, 2017. Two researchers independently screened studies and extracted study characteristics and risk estimates. The odds ratios (OR) and 95% confidence intervals (CI) of EOC risk were summarized using an inverse variance weighted random-effects model. Heterogeneity between studies was assessed with the I2 statistic. RESULTS: Eight case-control studies involving 7878 EOC cases and 73 913 controls were identified. Compared with non-use, use of antidepressants was not significantly associated with EOC risk (summarized OR = 1.10, 95% CI: 0.91-1.32, I2  = 74.4%). Similar null results were also observed in the use of selective serotonin reuptake inhibitors (OR = 1.04, 95% CI = 0.80-1.35), tricyclic antidepressants (OR = 1.01, 95% CI = 0.79-1.30), and other antidepressant drugs (OR = 0.91, 95% CI = 0.74-1.12). Subgroup analyses of study characteristics, stratified by the type of control subjects, geographic location, exposure assessment, number of cases, and adjustment for potential confounders, showed that the ORs were broadly consistent across strata. The OR per 1 year-increment of duration was 0.99 (95% CI = 0.94-1.05, I2  = 40.0%, P = 0.154). Additionally, the OR for the greatest intensity of antidepressant use compared with never use was 0.82 (95% CI = 0.70-0.98, I2  = 0%, P = 0.489). Furthermore, no evidence of publication bias was detected through Funnel plots as well as Egger's and Begg's tests. CONCLUSIONS: There is no association between antidepressant use and EOC risk. Further prospective studies are warranted to confirm these findings.

Intraspecific scaling laws are preserved in ventricular hypertrophy but not in heart failure.

It is scientifically and clinically important to understand the structure-function scaling of coronary arterial trees in compensatory (e.g., left and right ventricular hypertrophy, LVH and RVH) and decompensatory vascular remodeling (e.g., congestive heart failure, CHF). This study hypothesizes that intraspecific scaling power laws of vascular trees are preserved in hypertrophic hearts but not in CHF swine hearts. To test the hypothesis, we carried out the scaling analysis based on morphometry and hemodynamics of coronary arterial trees in moderate LVH, severe RVH, and CHF compared with age-matched respective control hearts. The scaling exponents of volume-diameter, length-volume, and flow-diameter power laws in control hearts were consistent with the theoretical predictions (i.e., 3, 7/9, and 7/3, respectively), which remained unchanged in LVH and RVH hearts. The scaling exponents were also preserved with an increase of body weight during normal growth of control animals. In contrast, CHF increased the exponents of volume-diameter and flow-diameter scaling laws to 4.25 ± 1.50 and 3.15 ± 1.49, respectively, in the epicardial arterial trees. This study validates the predictive utility of the scaling laws to diagnose vascular structure and function in CHF hearts to identify the borderline between compensatory and decompensatory remodeling.

Morphometric and hemodynamic analysis of atherosclerotic progression in human carotid artery bifurcations.

Although atherosclerosis has been widely investigated at carotid artery bifurcation, there is a lack of morphometric and hemodynamic data at different stages of the disease. The purpose of this study was to determine the lesion difference in patients with carotid artery disease compared with healthy control subjects. The three-dimensional (3D) geometry of carotid artery bifurcation was reconstructed from computed tomography angiography (CTA) images of Chinese control subjects (n = 30) and patients with carotid artery disease (n = 30). We defined two novel vector angles (i.e., angles 1 and 2) that were tangential to the reconstructed contour of the 3D vessel. The best-fit diameter was computed along the internal carotid artery (ICA) center line. Hemodynamic analysis was performed at various bifurcations. Patients with stenotic vessels have larger angles 1 and 2 (151 ± 11° and 42 ± 20°) and smaller diameters of the external carotid artery (ECA) (4.6 ± 0.85 mm) compared with control subjects (144 ± 13° and 36 ± 16°, 5.2 ± 0.57 mm) although there is no significant difference in the common carotid artery (CCA) (7.1 ± 1.2 vs. 7.5 ± 1.0 mm, P = 0.18). In particular, all patients with carotid artery disease have a stenosis at the proximal ICA (including both sinus and carina regions), while 20% of patients have stenosis at the middle ICA and 20% have stenosis expansion to the entire cervical ICA. Morphometric and hemodynamic analyses suggest that atherosclerotic plaques initiate at both sinus and carina regions of ICA and progress downstream.

Effects of Nitrate Addition on Rumen Fermentation, Bacterial Biodiversity and Abundance.

This study examined changes of rumen fermentation, ruminal bacteria biodiversity and abundance caused by nitrate addition with Ion Torrent sequencing and real-time polymerase chain reaction. Three rumen-fistulated steers were fed diets supplemented with 0%, 1%, and 2% nitrate (dry matter %) in succession. Nitrate supplementation linearly increased total volatile fatty acids and acetate concentration obviously (p = 0.02; p = 0.02; p<0.01), butyrate and isovalerate concentration numerically (p = 0.07). The alpha (p>0.05) and beta biodiversity of ruminal bacteria were not affected by nitrate. Nitrate increased typical efficient cellulolytic bacteria species (Ruminococcus flavefaciens, Ruminococcus ablus, and Fibrobacter succinogenes) (p<0.01; p = 0.06; p = 0.02). Ruminobactr, Sphaerochaeta, CF231, and BF311 genus were increased by 1% nitrate. Campylobacter fetus, Selenomonas ruminantium, and Mannheimia succiniciproducens were core nitrate reducing bacteria in steers and their abundance increased linearly along with nitrate addition level (p<0.01; p = 0.02; p = 0.04). Potential nitrate reducers in the rumen, Campylobacter genus and Cyanobacteria phyla were significantly increased by nitrate (p<0.01; p = 0.01). To the best of our knowledge, this was the first detailed view of changes in ruminal microbiota by nitrate. This finding would provide useful information on nitrate utilization and nitrate reducer exploration in the rumen.

An analysis of the influencing factors of false negative autoantibodies in patients with non-small cell lung cancer.

Objectives: To analyze the clinical significance of seven autoantibodies (P53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGE, and CAGE) in patients with non-small cell lung cancer (NSCLC) and the factors that influence false-negative results. Methods: Seven autoantibodies were measured in the serum of 502 patients with non-small cell lung cancer (NSCLC) using ELISA, and their correlations with age, sex, smoking history, pathological type, clinical stage, and PD-L1 gene expression were analyzed. The clinicopathological data of the false-negative and positive groups for the seven autoantibodies were compared to determine the influencing factors. Results: P53 antibody expression level was correlated with lobulation sign, PGP9.5 antibody expression level with sex and vascular convergence; SOX2 antibody expression level with pathological type, clinical stage, and enlarged lymph nodes; and MAGE antibody expression level with the pathological type (P<0.05). False-negative autoantibodies are prone to occur in lung cancer patients with ground-glass nodules, no enlarged lymph nodes, no vascular convergence, and PD-L1 gene expression <1% (P <0.05). Conclusion: Detection of seven autoantibodies was clinically significant in patients with NSCLC. However, poor sensitivity should be considered in clinical diagnoses to prevent missed diagnoses.

Occurrence, accumulation, ecological risk, and source identification of potentially toxic elements in multimedia in a subtropical bay, Southeast China.

Potentially toxic elements (PTEs) in seawater and sediments may be amplified along the aquatic food chain, posing a health threat to humans. This study comprehensively analyzed the concentrations, distribution, potential sources, and health risk of 7 PTEs in multimedia (seawater, sediment and organism) in typical subtropical bays in southern China. The results indicated that Zn was the most abundant element in seawater, and the average concentration of Cd in sediment was 3.93 times higher than the background value. Except for As, the seasonal differences in surface seawater were not significant. The content of Zn in fishes, crustacea, and shellfish was the highest, while the contents of Hg and Cd were relatively low. Bioaccumulation factor indicated that Zn was a strongly bioaccumulated element in seawater, while Cd was more highly enriched by aquatic organisms in sediment. According to principal component analysis (PCA), and positive matrix factorization (PMF), the main sources of PTEs in Quanzhou Bay were of natural derivation, industrial sewage discharge, and agricultural inputs, each contributing 40.4 %, 24.2 %, and 35.4 %, respectively. This study provides fundamental and significant information for the prevention of PTEs contamination in subtropical bays, the promotion of ecological safety, and the assessment of human health risk from PTEs in seafood.

Predicting left ventricular remodeling post-MI through coronary physiological measurements based on computational fluid dynamics.

Early detection of left ventricular remodeling (LVR) is crucial. While cardiac magnetic resonance (CMR) provides valuable information, it has limitations. Coronary angiography-derived fractional flow reserve (caFFR) and index of microcirculatory resistance (caIMR) offer viable alternatives. 157 patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention were prospectively included. 23.6% of patients showed LVR. Machine learning algorithms constructed three LVR prediction models: Model 1 incorporated clinical and procedural parameters, Model 2 added CMR parameters, and Model 3 included echocardiographic and functional parameters (caFFR and caIMR) with Model 1. The random forest algorithm showed robust performance, achieving AUC of 0.77, 0.84, and 0.85 for Models 1, 2, and 3. SHAP analysis identified top features in Model 2 (infarct size, microvascular obstruction, admission hemoglobin) and Model 3 (current smoking, caFFR, admission hemoglobin). Findings indicate coronary physiology and echocardiographic parameters effectively predict LVR in patients with STEMI, suggesting their potential to replace CMR.

CT-based diagnosis of diffuse coronary artery disease on the basis of scaling power laws.

PURPOSE: To provide proof of concept for a diagnostic method to assess diffuse coronary artery disease (CAD) on the basis of coronary computed tomography (CT) angiography. MATERIALS AND METHODS: The study was approved by the Cleveland Clinic Institutional Review Board, and all subjects gave informed consent. Morphometric data from the epicardial coronary artery tree, determined with CT angiography in 120 subjects (89 patients with metabolic syndrome and 31 age- and sex-matched control subjects) were analyzed on the basis of the scaling power law. Results obtained in patients with metabolic syndrome and control subjects were compared statistically. RESULTS: The mean lumen cross-sectional area (ie, lumen cross-sectional area averaged over each vessel of an epicardial coronary artery tree) and sum of intravascular volume in patients with metabolic syndrome (0.039 cm(2) ± 0.015 [standard deviation] and 2.71 cm(3) ± 1.75, respectively) were significantly less than those in control subjects (0.054 cm(2)± 0.015 and 3.29 cm(3)± 1.77, respectively; P < .05). The length-volume power law showed coefficients of 27.0 cm(-4/3) ± 9.0 (R(2) = 0.91 ± 0.08) for patients with metabolic syndrome and 19.9 cm(-4/3) ± 4.3 (R(2) = 0.92 ± 0.07) for control subjects (P < .05). The probability frequency shows that more than 65% of patients with metabolic syndrome had a coefficient of 23 or more for the length-volume scaling power law, whereas approximately 90% of the control subjects had a coefficient of less than 23. CONCLUSION: The retrospective scaling analysis provides a quantitative rationale for diagnosis of diffuse CAD.

[Performance of computer-assisted imaging system in detection of squamous intraepithelial lesion of uterine cervix].

OBJECTIVE: To evaluate the performance of computer-assisted imaging system in the detection of cervical squamous intraepithelial lesion and quality-assurance. METHODS: Manual PAP screening (n = 140 580) and image-assisted screening (n = 32 885) were compared for the detection rates of squamous cell abnormalities, the atypical squamous cells (ASC) to squamous intraepithelial lesion (SIL) ratio, the positive rates of high risk human papillomavirus (HR-HPV) test in the case of atypical squamous cells of undetermined significance (ASC-US), and the correlation between cytopathology and histopathology. RESULTS: Compared with manual screening, computer-assisted imaging system showed increased overall positive detection by 0.32%, decreased detection of ASC by 0.21%, increased detection of low-grade squamous intraepithelial lesion (LSIL) by 0.22%, increased detection of high-grade squamous intraepithelial lesion or worse (HSIL) by 0.31%, and decreased ASC to SIL ratio from 2.59 to 1.60. Computer-assisted imaging system did not change the HR-HPV positive rate of the patients who were ASC-US, or the coincidence rate between cytopathology and histopathology. Moreover, the productivity of the laboratory operation increased 58.33%. CONCLUSION: Computer-assisted imaging system significantly increases the overall positive detection rate of cervical SIL, improves accuracy and work efficiency of screening, decreases the ASC/SIL rate, and strengths the quality-assurance of laboratory testing.

Myocardial infarction impaired wall mechanics and hemodynamics in peripheral arteries.

Myocardial infarction (MI) impaired both cardiac functions and peripheral arteries. The changes in normal and shear stresses in the peripheral artery wall are of importance for understanding the progression of MI-induced heart failure (HF). The aim of the study is to investigate the corresponding changes of normal and shear stresses. The coronary artery ligation was used to induce the MI in Wistar rats. The analysis of wall mechanics and hemodynamics was performed based on in vivo and in vitro measurements. Myocardial infarction increased wall stiffness in elastic carotid and muscular femoral arteries significantly albeit different changes occurred between the two vessels from 3 to 6 weeks postoperatively. Moreover, the hemodynamic analysis showed the gradually deteriorated wall shear stress, oscillatory shear index and relative residence time in the two arteries. This study probably shed light on understanding the interaction between abnormal systemic circulation and peripheral mechanics and hemodynamics during the development of MI-induced HF.