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Hu antigen R (HuR) plays a key role in regulating genes critical to the pathogenesis of diabetic nephropathy (DN). This study investigates the therapeutic potential of niclosamide (NCS) as an HuR inhibitor in DN. Uninephrectomized mice were assigned to four groups: normal control; untreated db/db mice terminated at 14 and 22 weeks, respectively; and db/db mice treated with NCS (20 mg/kg daily via i.p.) from weeks 18 to 22. Increased HuR expression was observed in diabetic kidneys from db/db mice, which was mitigated by NCS treatment. Untreated db/db mice exhibited obesity, progressive hyperglycemia, albuminuria, kidney hypertrophy and glomerular mesangial matrix expansion, increased renal production of fibronectin and a-smooth muscle actin, and decreased glomerular WT-1+-podocytes and nephrin expression. NCS treatment did not affect mouse body weight, but reduced blood glucose and HbA1c levels and halted the DN progression observed in untreated db/db mice. Renal production of inflammatory and oxidative stress markers (NF-κBp65, TNF-a, MCP-1) and urine MDA levels increased during disease progression in db/db mice but were halted by NCS treatment. Additionally, the Wnt1-signaling-pathway downstream factor, Wisp1, was identified as a key downstream mediator of HuR-dependent action and found to be markedly increased in db/db mouse kidneys, which was normalized by NCS treatment. These findings suggest that inhibition of HuR with NCS is therapeutic for DN by improving hyperglycemia, renal inflammation, and oxidative stress. The reduction in renal Wisp1 expression also contributes to its renoprotective effects. This study supports the potential of repurposing HuR inhibitors as a novel therapy for DN. [ABSTRACT FROM AUTHOR]

Rubble-pile asteroids may be the type of near-Earth object most likely to threaten Earth in a future collision event. Small-scale impact experiments and numerical simulations for large-scale impacts were conducted to clarify the size ratio of the boulder/projectile diameter effects on ejecta size–velocity distribution. A series of small-scale impact cratering experiments were performed on porous gypsum–basalt targets at velocities of 2.3 to 5.5 km·s−1. Three successive ejection processes were observed by high-speed and ultra-high-speed cameras. The momentum transfer coefficient and cratering size were measured. A three-dimensional numerical model reflecting the random distribution of the interior boulders of the rubble-pile structure asteroid is established. The size ratio (length to diameter) of the boulder size inside the asteroid to the projectile diameter changed from 0.25 to 1.7. We conducted a smoothed particle hydrodynamics numerical simulation in the AUTODYN software to study the boulder size effect on the ejecta size–velocity distribution. Simulation results suggest that the microscopic porosity on regolith affects the propagation of shock waves and reduces the velocity of ejecta. Experiments and numerical simulation results suggest that both excavation flow and spalling ejection mechanism can eject boulders (0.12–0.72 m) out of the rubble-pile asteroid. These experiments and simulation results help us select the potential impact site in a planetary defense scenario and reduce deflection risk. are comprised primarily of boulders of a range of sizes. [ABSTRACT FROM AUTHOR]

Background: Microsatellite instability-high (MSI-H) is a unique genomic status in many cancers. However, its role in the genomic features and immunotherapy in cholangiocarcinoma (CCA) is unclear. This study aimed to systematically investigate the genomic characterization and immunotherapy efficacy of MSI-H patients with CCA. Methods: We enrolled 887 patients with CCA in this study. Tumor samples were collected for next-generation sequencing. Differences in genomic alterations between the MSI-H and microsatellite stability (MSS) groups were analyzed. We also investigated the survival of PD-1 inhibitor-based immunotherapy between two groups of 139 patients with advanced CCA. Results: Differential genetic alterations between the MSI-H and MSS groups included mutations in ARID1A, ACVR2A, TGFBR2, KMT2D, RNF43, and PBRM1 which were enriched in MSI-H groups. Patients with an MSI-H status have a significantly higher tumor mutation burden (TMB) (median 41.7 vs. 3.1 muts/Mb, P < 0.001) and more positive programmed death ligand 1 (PD-L1) expression (37.5% vs. 11.9%, P < 0.001) than those with an MSS status. Among patients receiving PD-1 inhibitor-based therapy, those with MSI-H had a longer median overall survival (OS, hazard ratio (HR) = 0.17, P = 0.001) and progression-free survival (PFS, HR = 0.14, P < 0.001) than patients with MSS. Integrating MSI-H and PD-L1 expression status (combined positive score ≥ 5) could distinguish the efficacy of immunotherapy. Conclusions: MSI-H status was associated with a higher TMB value and more positive PD-L1 expression in CCA tumors. Moreover, in patients with advanced CCA who received PD-1 inhibitor-based immunotherapy, MSI-H and positive PD-L1 expression were associated with improved both OS and PFS. Trial registration: This study was registered on ClinicalTrials.gov on 07/01/2017 (NCT03892577). [ABSTRACT FROM AUTHOR]

Lake-level changes can significantly affect paleoenvironmental evolution, resource occurrence, terrestrial carbon budget, and biodiversity in continental basins. Climate is one of the most critical factors controlling lake-level changes. Paleoclimate of the Early Jurassic has been evidenced by oscillating icehouses to (super) greenhouses with interrupted intermittent extreme climatic events (hyperthermal and cooling), e.g., the Toarcian oceanic anoxic event (~183 Ma) and the late Pliensbachian cooling event (~185 Ma). Lake-level evolution and hydrologic cycling on Earth's surface during the Early Jurassic icehouses-to-(super)greenhouses are thus far poorly understood due to a lack of continuous high-resolution nonmarine evidence. Here we present a super-long nonmarine lake level record for this pivotal interval from the early Pliensbachian to Toarcian by sedimentary noise modeling, and construct a 16.7-Myr-long astronomical time scale (174.2 Ma to 190.9 Ma) based on cyclostratigraphy analysis of rock color datasets (CIE b*) of the Qaidam Basin. Our results document lake-level oscillations on a 5-to 10-million-year (Myr) scale which shows a pronounced correlation with long-term climate variation and extreme climatic events, and 1- to 2.5-Myr-scale lake-level changes that are prominently paced by the 2.4-Myr long-eccentricity forcing and the 1.2-Myr obliquity forcing. At the Pliensbachian Stage, the 1.2-Myr-scale lake-level changes are in phase with the coeval sea-level variations. Orbitally forced growth and decay of the ephemeral or permanent ice sheets in polar regions are interpreted to control the synchronous ups-and-downs of continental lake level and global sea level. However, during the Toarcian ice-free greenhouses to (super)greenhouses, the 1.2-Myr-scale lake-level variations show an anti-phase relationship with global sea level, indicating a 'seesaw' interaction between continental reservoirs (lakes and groundwater) and global oceans. The 2.4-Myr long-eccentricity cycles mainly regulate variations of lake level and sea level by controlling the growth and decay of small-scale continental ice sheets, which is especially notable during the Pliensbachian Stage. These findings indicate a remarkable transition of hydrological cycling pattern during the Pliensbachian-Toarcian icehouses to (super)greenhouses, which provides new perspectives and evidence for investigating the hypothesis of global sea-level changes (e.g., glacio-eustasy and aquifer-eustasy) and long-period astronomical forcing in nonmarine stratigraphy. [ABSTRACT FROM AUTHOR]

Effective vehicle detection plays a crucial role in various applications in cities, including traffic management, urban planning, vehicle transport, and surveillance systems. However, existing vehicle detection methods suffer from low recognition accuracy, high computational costs, and excessive parameters. To address these challenges, this paper proposed a high-precision and lightweight detector along with a new dataset for construction-related vehicles. The dataset comprises 8425 images across 13 different categories of vehicles. The detector was based on a modified version of the You Only Look Once (YOLOv4) algorithm. DenseNet was utilized as the backbone to optimize feature transmission and reuse, thereby improving detection accuracy and reducing computational costs. Additionally, the detector employed depth-wise separable convolutions to optimize the model structure, specifically focusing on the lightweight neck and head components. Furthermore, H-swish was used to enhance non-linear feature extraction. The experimental results demonstrated that the proposed detector achieves a mean average precision (mAP) of 96.95% on the provided dataset, signifying a 4.03% improvement over the original YOLOv4. The computational cost and parameter count of the detector were 26.09GFLops and 16.08 MB, respectively. The proposed detector not only achieves lower computational costs but also provides higher detection when compared to YOLOv4 and other state-of-the-art detectors. [ABSTRACT FROM AUTHOR]

Ge2Sb2Te5 (GST) alloy has the ability to quickly transform between the amorphous phase and the crystalline phase; therefore, it can be used in non-volatile phase change storage. First-principles molecular dynamics was used to simulate the reversible phase change process of GST alloy, namely, amorphization and crystallization. The amorphous state was obtained by melting (∼3000 K) and cooling, and the amorphization process was characterized by the pair correlation function and bond angle distribution. The bond angles of amorphous GST were mainly distributed around 60°, 90°, and 110°, indicating the existence of octahedral and tetrahedral bonding configurations. The crystalline state was obtained by annealing at a temperature of 600 K, and the crystallization process was characterized by the pair correlation function, component disordered number, bond angle distribution, and dynamic atomic structure change. The results show that the bond angle of GST in crystallization is mainly distributed around 90°, and the structure mainly contains four-membered rings formed by Ge–Te and Sb–Te. By analyzing the optical properties, with the growth of crystallization time, the absorption coefficient, reflectivity, and conductivity of GST were significantly improved. [ABSTRACT FROM AUTHOR]

Illegal construction poses a safety hazard to both cities and people and affects the social stability and long-term stability of the country. Therefore, it is important to detect illegal buildings as early as possible. However, current illegal building detection methods generally suffer from either detection cycles or low detection accuracies. To solve these challenges, this study adopts an unusual method that detects illegal building objects to prevent illegal building behavior. A detection model, CRMNet, which is based on the anchor-free detection model CenterNet, and dataset for illegal building objects are proposed. ResNet50 is selected as the backbone for extracting futures after weighing the computational cost and detection accuracy. Furthermore, Mish, a new activation function, is used to improve the identification accuracy of illegal building objects. Experimental results show that the mean average precision (mAP) of the proposed detector on the illegal building object dataset reached 88.16%, which is higher than that of other popular object detection methods. Additionally, in contrast to mainstream target detection methods, the proposed detection method has fewer parameters and a higher detection accuracy, which can be better applied to mobile devices and smart devices. [ABSTRACT FROM AUTHOR]

An access-transistor-free (0T1R) structure has been reported to have great advantages in reducing the area of the phase-change memory cell, but leakage current has limited its application in large-scale arrays. In this study, a GeTe/InP heterostructure is proposed as the integration of a selector and phase-change cell in a 0T1R structure. The effect of establishing a GeTe/InP heterostructure is explored based on first-principles study, and the performance is further optimized by doping. The results show that, compared with GeTe, the band gap value of the GeTe/InP heterostructure decreases, and the space charge region forms at the interface, which effectively suppresses the leakage current of the 0T1R structure. In addition, to further improve the performance of GeTe/InP, group III-V elements are used as substitutional dopants at the P site. We find that when N and B dopants are used, the electrical conductivity of GeTe/InP and the charge transfer between interfaces are enhanced. The current–voltage characteristic curves show that the establishment of the GeTe/InP heterostructure and doping significantly improved the nonlinear coefficient of the phase-change memory cell, which can better suppress the leakage current in the 0T1R structure. [ABSTRACT FROM AUTHOR]

In order to reduce the volatilization of Bi2O3 in the sintering process due to low melting point, and improve the microstructure uniformity of samples obtained by ball milling, ZnO–Bi2O3 varistor ceramics were prepared by two-step sintering method with sintering temperature lower than 1000 °C. This two-step method was contrary to most previous research, which owed lower turning point temperature T1. The samples were first heated up to T1(T1 = 750 °C, 800 °C and 850 °C, respectively) before sintering at T2(T2 = 950 °C), while T1 was selected based on the sintering characteristics. Samples prepared by traditional one-step sintering were used as reference. Microstructure and electrical properties of ceramics were investigated to discuss the enhanced effect of two-step sintering regimes. Results showed that the two-step sintered samples had higher breakdown voltage, higher relative density and uniform microstructure. The best performance was obtained when T1 was 800 °C and T2 was 950 °C, the breakdown voltage was 883 V/mm, the nonlinear coefficient was 10.1, the leakage current was below 0.1 μA. This special two-step sintering method also contributed to avoiding high-temperature and obtain better composite performance. The work may supply useful reference for the exploration and application of low-temperature silver co-fired multilayer chip device. [ABSTRACT FROM AUTHOR]

Extending the benefits of tumor molecular profiling for all cancer patients requires a comprehensive analysis of tumor genomes across distinct patient populations worldwide. In this study, we perform deep next-generation DNA sequencing (NGS) from tumor tissues and matched blood specimens from over 10,000 patients in China by using a 450-gene comprehensive assay, developed and implemented under international clinical regulations. We perform a comprehensive comparison of somatically altered genes, the distribution of tumor mutational burden (TMB), gene fusion patterns, and the spectrum of various somatic alterations between Chinese and American patient populations. Here, we show 64% of cancers from Chinese patients in this study have clinically actionable genomic alterations, which may affect clinical decisions related to targeted therapy or immunotherapy. These findings describe the similarities and differences between tumors from Chinese and American patients, providing valuable information for personalized medicine. Understanding the mutation landscape of cancer may enable the development of more targeted therapies. Here, the authors sequence a panel of genes in a large Asian cohort and compare to American cohorts and find 64% of the Asian patients have actionable mutations. [ABSTRACT FROM AUTHOR]

Ignorance is commonly assumed to be a lack of knowledge in Plato's Socratic dialogues. I challenge that assumption. In the Protagoras , ignorance is conceived to be a substantive, structural psychic flaw—the soul's domination by inferior elements that are by nature fit to be ruled. Ignorant people are characterized by both false beliefs about evaluative matters in specific situations and an enduring deception about their own psychic conditions. On my interpretation, akrasia, moral vices, and epistemic vices are products or forms of ignorance, and a person who lacks knowledge is not necessarily ignorant. [ABSTRACT FROM AUTHOR]

The two-dimensional guided filter is a linear time-varying filter that can filter the noise and retain the detailed information of the image better. It is widely used in image denoising. However, in its application process, it is necessary to calculate the parameters required by filtering in real time according to the data. The operation process involves complex floating point multiplication and division operations, which leads to the high complexity of hardware implementation and excessive resource overhead. It is also difficult to improve the comprehensive speed of the system, which is not good for real-time signal processing. Aiming at the above problems, based on the theory of guided filtering and taking full advantage of the parallelism of FPGA, we proposed a two-dimensional guided filter hardware optimization system based on FPGA. In the system, first, the original image data are cached in real time to reduce the occupation of other hardware resources. Then, the complex mean and variance operations are split into simple sum operations, which reduces the computational complexity. Finally, the system is designed by using serial and parallel flow operation methods, which effectively improve the operation speed of the system. The results show that the operating frequency of the optimized hardware system is up to 146.953 MHz, which is 28.322 MHz higher than that of the original guided filtering algorithm. [ABSTRACT FROM AUTHOR]

Although chlorobromoisocyanuric acid has been widely used in agriculture, its deleterious toxicity on aquatic organisms remains rare. In this study, zebrafish were exposed to chlorobromoisocyanuric acid (0, 30, 40, and 50 mg/L) from 10 to 96 h post‐fertilization (hpf). We found a significant reduction in immune cell numbers (neutrophils and macrophages) and the area of thymus at 96 hpf. The expression of immune‐related genes and pro‐inflammatory cytokines genes were upregulated. Besides, chlorobromoisocyanuric acid triggered neutrophils cell apoptosis. The mRNA and protein levels of pro‐apoptotic p53 pathway and the Bax/Bcl‐2 ratio further indicated the underlying mechanism. Furthermore, the oxidative stress was observed that the accumulation of reactive oxygen species and malondialdehyde significantly increased. Subsequently, the antioxidant agent astaxanthin significantly attenuated the level of oxidative stress and the dysregulation of inflammatory response. In summary, our results showed that chlorobromoisocyanuric acid induced developmental defects and immunotoxicity of zebrafish, partly owing to oxidative stress and cell apoptosis. [ABSTRACT FROM AUTHOR]

When the traditional dark channel prior (DCP) algorithm is used for image defogging, it faces some problems such as unsatisfactory restoration of the target edge details, distortion in large‐scale and high‐brightness sky regions. To solve these problems, this paper proposes an improved dark channel defogging algorithm based on the HSI colour space, named the IDCP algorithm. First, an asymmetric mean filter window is used to obtain the modified dark channel image to improve the grey value mutation in the traditional dark channel image. Based on this work, an improved global atmospheric transmittance calculation method is proposed, which effectively improves the inapplicability of the dark channel prior in large‐scale and high‐brightness sky regions. Finally, the Laplacian operator is used to sharpen the image to enhance the target edge information. Simulation results show that the proposed algorithm can effectively solve the distortion phenomenon caused by the traditional DCP algorithm when handling large‐scale and high‐brightness sky regions, improve the target edge details, and restore the true colour of the image scene. [ABSTRACT FROM AUTHOR]

Purpose: Dietary sodium and potassium intake are associated with stroke, but the potential mechanisms are unclear. We aimed to study the association between sodium and potassium intake and subclinical cerebrovascular health in hypertensive older males using multimodal magnetic resonance imaging. Methods: A total of 189 hypertensive male subjects without previous cardiovascular or cerebrovascular disease were included. Daily urinary sodium and potassium excretion were estimated from a fasting spot urine sample using a formula approach. A dedicated cerebrovascular health imaging protocol including vessel wall imaging, angiography, arterial spin labeling imaging and T2-weighted fluid-attenuated inversion recovery imaging was performed to study intracranial atherosclerosis, vascular rarefaction (defined as fewer discernible vessels on angiography), brain perfusion and small vessel disease, respectively. Results: The mean age was 64.9 (± 7.2) years. The average daily urinary and potassium excretion was 4.7 (± 1.4) g/L and 2.1 (± 0.5) g/L, respectively. Increased urinary sodium excretion was associated with decreased cerebral blood flow and elevated urinary potassium excretion was associated with reduced prevalence of intracranial plaque. The associations remained significant after adjusting for covariates, even including blood pressure control. Quadratic regression analysis indicated a marginally significant U-shaped association between urinary sodium intake and white matter hyperintensity, which lost significance in fully adjusted models. No significant association of urinary sodium and potassium excretion with other cerebrovascular health measures was noted. Conclusion: We concluded that in hypertensive older males without overt cardiovascular disease, increased sodium intake and reduced potassium intake are associated with impaired subclinical cerebrovascular health. [ABSTRACT FROM AUTHOR]

Growth differentiation factor 15(GDF15) is a distant member of the superfamily of the transforming growth factor beta (TGF-β). It has been established that increased GDF15 levels are associated with an increased risk of cardiovascular disease. However, the detail effect of GDF15 on cardiovascular system in patients with chronic kidney disease (CKD) needs detail analysis. Patients with CKD who did not need dialysis were enrolled in the study. Blood pressure (BP), endothelial function, pulse wave velocity (PWV) and heart rate variability (HRV) were taken in all subjects. Plasma GDF15 concentration was measured by an enzyme-linked immunosorbent assay. Among the 355 participants, the mean age was 57.4 (±14.2) years old and the mean estimated glomerular filtration rate (eGFR) was 50.1 (±33.2) mL/min/1.73m2. The average plasma GDF15 level was 1394.7 (±610.1) pg/mL. Higher GDF15 concentrations were significantly associated with decreased eGFR and increased urine protein-to-creatinine ratio (uPCR). In multivariable models, after adjusting for potential confounders, plasma GDF15 has negative concerning with HRV parameters including the standard deviation of the normal-to-normal (NN) interval (SDNN), the square root of the mean of the sum of the squares of differences between adjacent NN intervals (RMSSD) and Triangular Index. We observed there was a link between increased plasma of GDF15 and decreased HRV. The mechanisms and prediction of GDF15 in the cardiovascular disease with CKD needs further discussion and study. [ABSTRACT FROM AUTHOR]

To investigate the seismic performance of buckling-restrained braces under the earthquake action, the shaking table test with a two-story 1/4 scale model is carried out for the ordinary pure steel frame and the buckling-restrained bracing steel frame with low-yield-point steel as the core plate. The failure modes, dynamic characteristics, acceleration response, interstory drift ratio, strain, shear force, and other mechanical properties of those two comparative structures subjected to different levels of seismic waves are mainly evaluated by the experiment. The test results show that under the action of seismic waves with different intensities, the apparent observations of damage occur in the pure frame structure, while no obvious or serious damage in the steel members of BRB structure is observed. With the increase in loading peak acceleration for the earthquake waves, the natural frequency of both structures gradually decreases and the damping ratio gradually increases. At the end of the test, the stiffness degradation rate of the pure frame structure is 11.2%, while that of the buckling-restrained bracing steel frame structure is only 5.4%. The acceleration response of the buckling-restrained bracing steel frame is smaller than that of the pure steel frame, and the acceleration amplification factor at the second story is larger than that at the first story for both structures. The average interstory drift ratios are, respectively, 1/847 and 1/238 for the pure steel frame under the frequent earthquake and rare earthquake and are 1/3000 and 1/314 for the buckling-restrained bracing steel frame, which reveals that the reduction rate of lateral displacement reaches a maximum of 71.71% after the installation of buckling-restrained brace in the pure steel frame. The strain values at each measuring point of the structural beam and column gradually increase with the increase of the peak seismic acceleration, but the strain values of the pure steel frame are significantly larger than those of the buckling-restrained bracing steel frame, which indicates that the buckling-restrained brace as the first seismic line of defense in the structure can dramatically protect the significant structural members. The maximum shear force at each floor of the structure decreases with the increase in height, and the shear response of the pure frame is apparently higher than that of the buckling-restrained bracing structure. [ABSTRACT FROM AUTHOR]

Introduction: C-X-C motif chemokine ligand 16 (CXCL16) is an inflammatory marker that has been found to be predictive of outcomes in patients with cardiovascular disease. Our previous work has also demonstrated its relation to cardiac injury in dialysis patients. However, it is yet unclear whether there is an association between CXCL16 and adverse outcomes in dialysis patients. We aimed to evaluate its prognostic value along with several traditional inflammatory markers in the current study. Methods: This is a multicenter longitudinal study of prevalent dialysis patients. Circulating inflammatory markers including CXCL16, C-reactive protein (CRP), tumor necrosis factor-α, and interleukin-6 (IL-6) were measured using a multiplex assay. The primary outcomes were all-cause mortality and a composite of major adverse cardiovascular events (MACEs). The associations between biomarkers and outcomes were analyzed using Cox proportional hazards regression models. Results: Of the 366 participants with available plasma samples, the average age was 52.5 (±12.1) years, and there were 160 (43.7%) female participants. For all-cause mortality, logarithmically transformed CXCL16, IL-6, and CRP were independent predictors after adjustment for covariates. When the 3 markers were included in the same model, CXCL16 was the only one remaining its significance. For MACEs, logarithmically transformed CXCL16 and IL-6 were significant predictors when analyzed separately and CXCL16 was an independent predictor even after adjustment for IL-6. When the biomarkers were analyzed as categorical variables, only CXCL16 was associated with both outcomes. Adding CXCL16 to established risk factors improved risk prediction as revealed by Net Reclassification Index (NRI). Conclusion: Using a multimarker approach, we determined that CXCL16 is a potent predictor of all-cause mortality and cardiovascular events in dialysis patients. Our data suggest CXCL16 may improve risk stratification and could be a potential interventional target. [ABSTRACT FROM AUTHOR]

3D printing technology is widely used in the manufacturing of fine ceramic fields due to its simple operation, rapid molding, and applications in preparation of complex structures. In this paper, the characteristics of different 3D printing technologies in ceramic preparation were reviewed based on the material morphology of 3D printing ceramics. The application and mechanism of binder and dispersant applied in direct ink writing, stereolithography and inkjet printing 3D printing technology of ceramics were introduced, and these additive components of water based and non-water based were summarized and discussed, aiming to provide reference for the preparation of high-performance ceramic samples via 3D printing technology. [ABSTRACT FROM AUTHOR]

Vascular dysfunctions, including arterial stiffness and endothelial dysfunction, are prevalent in hypertensive subjects. We aimed to study their relations to subclinical intracranial vascular health in this study. A total of 200 older hypertensive males without overt cardiovascular or cerebrovascular diseases were recruited. Arterial elasticity was measured as carotid-femoral pulse wave velocity (cfPWV) and endothelial function was measured as digital reactive hyperemia index (RHI). Cerebrovascular health was evaluated using MRI in four aspects: intracranial atherosclerosis, brain perfusion as cerebral blood flow (CBF), vascular rarefaction analyzed as visible arterial branches on angiography using a custom-developed analysis technique and small vessel disease measured as white matter hyperintensity (WMH). There was a significant negative association between cfPWV and CBF, suggesting a link between arterial stiffness and CBF decline. Higher cfPWV was also associated with presence of intracranial stenotic plaque and greater WMH volume. RHI was positively related to CBF, indicating that endothelial dysfunction was associated with reduced CBF. All the associations remained significant after adjustment for confounding variables. Arterial stiffness and endothelial dysfunction are associated with reduced brain perfusion in older hypertensive males. Arterial stiffness is also associated with global cerebral vascular injury, affecting both small and medium-to-large arteries. [ABSTRACT FROM AUTHOR]

Objectives: The study aimed to analyze the association between hypertension control and subclinical cerebrovascular health using a comprehensive multimodal imaging approach. Methods: The study included 200 hypertensive older males without previous cardiovascular diseases. Clinic blood pressure (BP) was measured using a standard approach. Cerebrovascular health was evaluated using magnetic resonance imaging in the following four aspects: Intracranial atherosclerosis as determined by vessel wall imaging; Vascular rarefaction (defined as less discernible vessels on angiography) was evaluated using a custom-developed technique. Cerebral blood flow (CBF) and white matter hyperintensity (WMH) were assessed using arterial spin-labeling imaging and fluid-attenuated inversion recovery imaging, respectively. Results: A total of 189 subjects had MRI scans. The mean age was 64.9 (± 7.2) years. For intracranial atherosclerosis, there was a significant association between uncontrolled hypertension and presence of intracranial plaque. When systolic and diastolic BP were analyzed separately, the association remained significant for both. For vascular rarefaction, uncontrolled hypertension was associated with less discernible vessel branches or shorter vessel length on angiography. Further analysis revealed that this is due to uncontrolled diastolic BP, but not uncontrolled systolic BP. There was an association between uncontrolled hypertension and reduced CBF, which was also mainly driven by uncontrolled diastolic BP. We also found that uncontrolled diastolic BP, but not uncontrolled systolic BP, was associated with increased WMH volume. Conclusions: Uncontrolled hypertension was associated with subclinical cerebrovascular injury globally, with both small and medium-to-large arteries being affected. Key Points: • In this study, we leveraged the advantage of a series of cutting-edge MR imaging and analysis techniques and found uncontrolled hypertension is associated with subclinical globally compromised cerebrovascular health. • The detrimental consequences of uncontrolled BP affect not only the small vessels but also the medium-to-large arteries, and uncontrolled systolic and diastolic BP are both independently associated with certain types of cerebrovascular injury. • Our data suggest that cerebrovascular health is impaired globally in uncontrolled hypertension before the onset of stroke. [ABSTRACT FROM AUTHOR]

Introduction: The current study aimed to depict intrinsic structural changes and the spontaneous brain activity patterns in voxel level in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD) by using diffusion-tensor imaging and resting-state functional magnetic resonance (MR) imaging with an amplitude of low-frequency fluctuations (ALFF) algorithm and their clinical relevance. Materials and Methods: In the study, the diffusion-tensor imaging and resting-state functional MR imaging were performed in forty-two hemodialysis patients with ESRD and 42 healthy control subjects. Neuropsychological and laboratory tests were performed in all subjects. ALFF, fraction anisotropy (FA), and mean diffusivity (MD) values were compared between the two groups. Correlations between ALFF, FA or MD values, and clinical markers were analyzed. Results: We found that ESRD patients exhibited significantly lower ALFF values in multiple areas, including medial frontal gyrus, limbic lobe, superior frontal gyrus, bilateral lingual gyri, occipital lobe, parahippocampal gyrus, precuneus, while increased ALFF values in medial frontal gyrus than healthy controls. FA values were decreased in medial frontal gyrus, parietal lobe, and left precuneus regions in the ESRD group compared with controls. Importantly, FA for the frontal and parietal lobes was negatively associated with the dialysis duration of ESRD patients, ALFF z-scores for the medial prefrontal cortex (MPFC) were positively correlated with the dialysis duration of ESRD patients and Serum calcium of ESRD patients negatively correlated with FA values in the frontal and parietal lobes (p< 0.05). Conclusion: Our study revealed that both impaired brain structure and function in ESRD patients with routine hemodialysis distributed mainly in the parietal, temporal, and frontal lobes. ESRD patients have cognitive impairment and declined memory ability. Serum calcium and dialysis duration might be associated with the impairment of brain structure and function in patients with ESRD. [ABSTRACT FROM AUTHOR]

Wood-based sandwich composite with a paper honeycomb core, especially for thick boards, has the advantage of high strength-to-weight ratio for the use in lightweight furniture products, interior walls etc. Employing both theoretical and experimental methods, this study investigated the influencing factors of various failure modes and its transition to obtain optimized structural parameters after a quasi-static load was applied. The results reveal that the skins of MDF are too strong for the paper honeycomb core. Both failure modes are caused by weak core properties. If the thickness or strength of the skins could be reduced or the core strength could be reinforced, then optimal failure mode of simultaneous core and skin failure could be reached. The intersection point of three transition lines is the best combination of structural parameters, meaning highest strength-to-weight ratio. At this point, failure of core shear, indentation and face fracture occurs simultaneously. The distance from a structural parameter to intersection is an effective index to express the degree of optimization for the strength-to-weight ratio of composites. Specimens close to the intersection point have optimal structural parameters and high strength-to-weight ratio. On application level, the optimum strength-to-weight ratio could be obtained easily by adjusting the surface or core thickness, if the materials were fixed first. [ABSTRACT FROM AUTHOR]

Purpose: To develop a fully automated vessel wall (VW) analysis workflow (fully automated and robust analysis technique for popliteal artery evaluation, FRAPPE) on the popliteal artery in standardized knee MR images. Methods: Popliteal artery locations were detected from each MR slice by a deep neural network model and connected into a 3D artery centerline. Vessel wall regions around the centerline were then segmented using another neural network model for segmentation in polar coordinate system. Contours from vessel wall segmentations were used for vascular feature calculation, such as mean wall thickness and wall area. A transfer learning and active learning framework was applied in training the localization and segmentation neural network models to maintain accuracy while reducing manual annotations. This new popliteal artery analysis technique (FRAPPE) was validated against manual segmentation qualitatively and quantitatively in a series of 225 cases from the Osteoarthritis Initiative (OAI) dataset. Results: FRAPPE demonstrated high accuracy and robustness in locating popliteal arteries, segmenting artery walls, and quantifying arterial features. Qualitative evaluations showed 1.2% of slices had noticeable major errors, including segmenting the wrong target and irregular vessel wall contours. The mean Dice similarity coefficient with manual segmentation was 0.79, which is comparable to inter‐rater variations. Repeatability evaluations show most of the vascular features have good to excellent repeatability from repeated scans of same subjects, with intra‐class coefficient ranging from 0.80 to 0.98. Conclusion: This technique can be used in large population‐based studies, such as OAI, to efficiently assess the burden of atherosclerosis from routine MR knee scans. [ABSTRACT FROM AUTHOR]

Featured Application: the research content of this article may provide a reference for military defense engineering as well as shielding design for aerospace applications. Impact cratering experiments were performed on semi-infinite concrete targets with 7 mm-diameter 40CrNiMo steel long-rod projectiles at impact velocities ranging from 2117 m/s to 3086 m/s by using a two-stage combustion light-gas gun. After the impact experiments, the crater diameter and depth as well as the crater volume were carefully measured. The concrete fragments were collected from the target chamber and the fragment mass was measured. The size of the crater (including the volume, diameter, and depth) and the fragment mass increased with increasing impact velocities, while the fragment distributions at different impact velocities were almost the same. Scaling laws for the crater volume impacted by the rod-shaped projectile were discussed and an empirical formula of crater volume was determined by the experimental data from the literature. Through the verification of the present experimental results, the predictive ability of the empirical formula proved to be reliable. Scaling laws for the size distribution of concrete fragments were also discussed. The normalized fragment mass distribution was proportional to the impact velocity raised to the power 1.5. [ABSTRACT FROM AUTHOR]

China's stock market crash in 2015 aroused scholarly attention on financial systemic risk in China. Using data on China's stock market from January 5, 2007 to September 28, 2018, this study calculated three different measures of systemic risk, i.e., temporal fluctuation of financial institutions' contribution to systemic risk (CoVaR), sensitivity of financial institutions to systemic risk (MES) and long-run expected capital shortfall (SRISK), to assess the formation, occurrence, and consequences of systemic risk in China. The results show that Δ CoVaR and MES exhibited an abnormal rise during the outbreak of the 2008 global financial crisis and the 2015 domestic stock market crash, whereas SRISK showed a steady increase throughout the observation window, indicating China's ever-growing SRISK despite the CoVaR and MES. More importantly, regardless of temporal fluctuation, (1) the vast majority of systemic risk comes from banks, followed by insurance firms, which is shown by the institutions' ranking in terms of Δ CoVaR; (2) securities firms followed by insurance firms are exposed to more systemic risk as indicated by short-run expected equity loss (i.e., MES); and (3) banks accumulate more SRISK than any other financial institution. The findings suggest that, in the event of a severe Chinese financial crisis, likely banks will endure the greatest amount of capital shortfall, whereas securities firms will suffer more short-run loss proportionally and thus risk a higher probability of bankruptcy. We conclude with a comparison of systemic risk in financial systems between China and the USA and policy implications. [ABSTRACT FROM AUTHOR]

The application of fluorescent method to metal ions detection features high sensitivity, simple operation and real‐time monitoring. A 2,7‐dihydroxynaphthalene‐functionalized dimethyl glycoluril (called clip 1) was synthesized, using a relatively simple method. And it is fully characterized by 1H NMR, 13C NMR, HR‐MS and single crystal X‐ray diffraction. The recognition properties of molecular clip 1 were analyzed systematically toward several metal ions using fluorescence spectroscopy, and it was found that molecular clip 1 is selective and sensitive to Fe3+. At the same time, the clip 1 shows good anti‐interference ability when other metal ions existed. The limit detection of Fe3+ is 3×10−7M. The fluorescence of clip 1 was quenched apparently by Fe3+, which was speculated to be caused by ligand–metal charge transfer mechanism (LMCT). As a new fluorescence probe for Fe3+ ion, it may expanded the application of glycoluril molecular clips. [ABSTRACT FROM AUTHOR]

We report the synthesis of a new acyclic CB[n]-type host (1) that features a central glycoluril trimer capped by triptycene sidewalls. Host 1 has good solubility in water (≈ 3 mM) and does not undergo strong self-association (Ks = 480 M−1). We probed the geometry of the complexes by analyzing the complexation induced changes in the 1H NMR spectra and measured the complexation thermodynamics by isothermal titration calorimetry. The conformation of 1 and its packing in the solid state was revealed by single crystal X-ray diffraction measurements. [ABSTRACT FROM AUTHOR]

Background: Incorporation of next‐generation sequencing (NGS) technology into clinical utility in targeted and immunotherapies requires stringent validation, including the assessment of tumor mutational burden (TMB) and microsatellite instability (MSI) status by NGS as important biomarkers for response to immune checkpoint inhibitors. Materials and Methods: We designed an NGS assay, Cancer Sequencing YS panel (CSYS), and applied algorithms to detect five classes of genomic alterations and two genomic features of TMB and MSI. Results: By stringent validation, CSYS exhibited high sensitivity and predictive positive value of 99.7% and 99.9%, respectively, for single nucleotide variation; 100% and 99.9%, respectively, for short insertion and deletion (indel); and 95.5% and 100%, respectively, for copy number alteration (CNA). Moreover, CSYS achieved 100% specificity for both long indel (50–3,000 bp insertion and deletion) and gene rearrangement. Overall, we used 33 cell lines and 208 clinical samples to validate CSYS's NGS performance, and genomic alterations in clinical samples were also confirmed by fluorescence in situ hybridization, immunohistochemistry, and polymerase chain reaction (PCR). Importantly, the landscape of TMB across different cancers of Chinese patients (n = 3,309) was studied. TMB by CSYS exhibited a high correlation (Pearson correlation coefficient r = 0.98) with TMB by whole exome sequencing (WES). MSI measurement showed 98% accuracy and was confirmed by PCR. Application of CSYS in a clinical setting showed an unexpectedly high occurrence of long indel (6.3%) in a cohort of tumors from Chinese patients with cancer (n = 3,309), including TP53, RB1, FLT3, BRCA2, and other cancer driver genes with clinical impact. Conclusion: CSYS proves to be clinically applicable and useful in disclosing genomic alterations relevant to cancer target therapies and revealing biomarkers for immune checkpoint inhibitors. Implications for Practice: The study describes a specially designed sequencing panel assay to detect genomic alterations and features of 450 cancer genes, including its overall workflow and rigorous clinical and analytical validations. The distribution of pan‐cancer tumor mutational burden, microsatellite instability, gene rearrangement, and long insertion and deletion mutations was assessed for the first time by this assay in a broad array of Chinese patients with cancer. The Cancer Sequencing YS panel and its validation study could serve as a blueprint for developing next‐generation sequencing‐based assays, particularly for the purpose of clinical application. Incorporating next‐generation sequencing technology for use in targeted therapies and immunotherapies requires precise validation. This article describes a reliable next‐generation sequencing‐based panel assay, Cancer Sequencing YS panel (CSYS), for detecting genomic alterations. [ABSTRACT FROM AUTHOR]

The binding ability of acyclic CB[n]-type receptors M1, M2 and macrocyclic CB[7] toward explosive materials was investigated. Acyclic M2 demonstrates an overall better binding and solubilizing ability, and lower fluorescence in the presence of aromatic explosive compounds, suggesting its future application for the detection of harmful explosive materials. [ABSTRACT FROM AUTHOR]

Impaired orthostatic blood pressure (BP) stabilization is prevalent in patients with chronic kidney disease (CKD) and is associated with adverse outcomes. We aimed to test the hypothesis that reduced hemoglobin is an important contributor to orthostatic intolerance in CKD in the present study. This study included 262 patients with non-dialysis-dependent CKD. Seated and standing BP was measured, and orthostatic BP reduction was calculated for both systolic BP (∆ SBP) and diastolic BP (∆ DBP). The association between orthostatic BP reduction and hemoglobin was determined by multiple linear regression models. We also performed mediation analysis to test to what extent the effect of renal dysfunction on impaired orthostatic BP stabilization can be explained by reduced hemoglobin. The mean age of the patients was 57.7 (±14.5) years, and 61.5% were male. Both ∆ SBP and ∆ DBP correlated negatively with estimated glomerular filtration rate (eGFR). With adjustment for age and sex, hemoglobin level was negatively associated with ∆ SBP (β = -1.4, SE = 0.4, P < .001) and ∆ DBP (β = -0.6, SE = 0.2, P = .009). The associations remained significant with further adjustment for additional covariates. When eGFR was introduced as a covariate, it did not eliminate the significance (both P < .05). The associations remained essentially unchanged in a sensitivity analysis excluding those with concurrent erythropoietin use. Mediation analysis demonstrated that reduced hemoglobin accounted for 35.4% (P = .004) of the effect of eGFR on ∆ SBP and 47.7% (P = .032) on ∆ DBP. Our study suggests that reduced hemoglobin is a potentially important contributor to the development of orthostatic hypotension in CKD. [ABSTRACT FROM AUTHOR]

Proper treatment of large amounts of produced water in offshore oil & gas development necessitates the development of advanced water treatment technology. The Compact Flotation Unit (CFU) is a promising technique for removing oil and suspended solids from produced water due to many attractive features such as high separation efficiency, short hydraulic residence time (HRT), and small footprint. In this article, the Machine Learning method (GA-BP neural network model) is used to learn, train, feedback, and predict the correlation between structural parameters and separation characteristics, thus realizing the structural optimization and performance improvement of the device. Mean squared error of GA-BP neural network model is 0.009, and the maximum squared error is 0.028. Separation efficiency of the CFU after optimization can reach up to 92.82%, that is, an improvement of 13.6%. The effects of inlet flow rate, split ratio, and inlet oil content on separation performance of CFU have been predicted. It is showed that when the inlet flow rate increases from 2 m3/h to 6 m3/h, the separation efficiency of CFU decreases greatly. As the split ratio rises from 1% to 8%, the separation efficiency has increased from 89.2% to 95.0%. The rise of split ratio means the increases of hydraulic loading rate in the water clarification zone, which is beneficial to the floating up of oil droplets, thus leading to the improvement of separation efficiency. Increase of inlet oil content is advantageous to promote the collision and coalescence of oil droplets and leads to the improvement of oil–water separation efficiency. Generally speaking, this method can quickly and accurately obtain the influence of structure parameters on separation characteristics, which is helpful to optimize the flow field distribution and improve the performance of related environmental protection equipment, as well as minimize the R&D costs and shorten the R&D cycle. [ABSTRACT FROM AUTHOR]

A new glycoluril derivative‐1H, 4H, 5H, 8H‐2, 3a, 4a, 6, 7a, 8a‐hexaazacyclopenta[def]fluorene‐4, 8‐dione, hexahydro‐2, 6‐bis(phenylmethyl) (3) is strategically designed and synthesized through the reaction between glycoluril, formaldehyde and benzylamine with the optimized molar ratio of 1:6:2. Compound 3 is fully characterized by 1H NMR, 13C NMR, IR, MS and X‐ray single crystal diffraction. Reduction of compound 3 delivers a potential precursor‐imidazo[4, 5‐d]imidazole, octahydro‐hexahydro‐2, 6‐bis(phenylmethyl) (4) for the synthesis of novel nitramine explosives (i.e. bicyclo‐HMX and bi‐RDX). The nitration and hydrolysis of compound 4 are investigated in detail and three ring‐opened molecules N, 2, 4‐trinitro‐benzenemethanamine (8a), N, 2‐dinitro‐benzenemethanamine (8b) and N‐methylene‐benzenemethanamine (9) are obtained. The synthesis, X‐ray crystal structure, hydrolysis, nitrolysis of two potential precursors for the preparation of nitramine explosives (bicycle‐HMX and bi‐RDX) are reported. [ABSTRACT FROM AUTHOR]

Dysfunction of microRNAs (miRs) has been implicated in the development and progression of various human cancers. Our previous study demonstrated that miR-101 inhibited bladder cancer cell proliferation and invasion through inhibition of c-FOS expression. As an miR generally has many targets, other targets of miR-101 may also serve important roles in bladder cancer progression. Reverse transcription-quantitative polymerase chain reaction and western blot analyses were used to examine mRNA and protein expression, respectively. Wound healing and Transwell assays were conducted to study cell migration and invasion, respectively. The luciferase reporter gene assay was performed to verify one of the targets of miR-101. The data in the present study indicate that the expression of miR-101 is significantly reduced in bladder cancer tissues compared with that in adjacent non-tumour tissues. In addition, miR-101 expression is also downregulated in bladder cancer cell lines compared with that in normal bladder epithelial cells. Furthermore, low expression of miR-101 was significantly associated with tumour metastasis, advanced clinical stage, and poor prognosis in bladder cancer. Frizzled class receptor 4 (FZD4) was identified as a novel target of miR-101 in bladder cancer cells. The expression of FZD4 was significantly upregulated in bladder cancer tissues and cell lines. Both miR-101 overexpression and FZD4 inhibition caused a significant reduction of the migration and invasion of bladder cancer cells, whereas overexpression of FZD4 reversed the suppressive effects of miR-101 on bladder cancer cell migration and invasion. In conclusion, it was demonstrated that miR-101 downregulation is associated with bladder cancer progression and that miR-101 can inhibit bladder cancer cell migration and invasion via directly targeting FZD4. The present study expands the understanding of the molecular mechanisms underlying bladder cancer progression. [ABSTRACT FROM AUTHOR]

Abstract: We designed and synthesized a “hybrid” molecular container 1, which is structurally related to both cucurbit[n]uril (CB[n]) and pillar[n]arene type receptors. Receptor 1 was fully characterized by 1H NMR, 13C NMR, IR, MS and X‐ray single crystal diffraction. The self‐association behavior, host–guest recognition properties of 1, and the [salt] dependence of Ka were investigated in detail by 1H NMR and isothermal titration calorimetry (ITC). Optical transmittance and TEM measurements provide strong evidence that receptor 1 undergoes co‐assemble with amphiphilic guest C10 in water to form supramolecular bilayer vesicles (diameter 25.6±2.7 nm, wall thickness ≈3.5 nm) that can encapsulate the hydrophilic anticancer drug doxorubicin (DOX) and the hydrophobic dye Nile red (NR). The release of encapsulated DOX or NR from the vesicles can be triggered by hexamethonium (8 c) or spermine (10) which leads to the disruption of the supramolecular vesicles. [ABSTRACT FROM AUTHOR]

Mechanisms underlying elevated blood pressure in dialysis patients are complex as a variety of non-traditional factors are involved. We sought to explore the association of circulating betaine, a compound widely distributed in food, with blood pressure in dialysis patients. We used baseline data of an ongoing cohort study involving patients on hemodialysis. Plasma betaine was measured by high performance liquid chromatography in 327 subjects. Blood pressure level was determined by intradialytic ambulatory blood pressure monitoring. The mean age of the patients was 52.6 ± 11.9 years, and 58.4% were male. Average interdialytic ambulatory systolic and diastolic blood pressure were 138.4 ± 22.7 mm Hg and 84.4 ± 12.5 mm Hg, respectively. Mean plasma betaine level was 37.6 μmol/L. Multiple linear regression analysis revealed significant associations of betaine with both systolic blood pressure (β = -3.66, P = .003) and diastolic blood pressure (β = -2.00, P = .004). The associations persisted even after extensive adjustment for cardiovascular covariates. Subgroup analysis revealed that the association between betaine and blood pressure was mainly limited to female patients. Our data suggest that alteration of circulating betaine possibly contributes to blood pressure regulation in these patients. [ABSTRACT FROM AUTHOR]

We address the multiframe superresolution problem using the variational Bayesian method in this paper. In the variational Bayesian framework, the prior is crucial in transferring the ill-posed reconstruction problem to a well-posed one. We propose a prior combination method based on filter bank and l1 norm. Multiple filters are used in our prior model, and the corresponding combination coefficient vector can be estimated by the characteristics of the filtered image and noise. Furthermore, the local adaptive coefficients of every filter are more effective in removing noise and preserving image edges. Extensive experiments demonstrate the advantages of the proposed method. [ABSTRACT FROM AUTHOR]

Illegal construction should be detected as early as possible as it can damage the environment and economy. However, the existing methods for detecting illegal construction can be improved in terms of their detection cycles, accuracy, and speed. Moreover, there are relatively few valuable real-world image datasets for detecting illegal construction. To address these issues, a high-precision real-time detection model named YEMNet and a new large-scale dataset for detection of illegal construction objects (ICOS) are proposed herein. Our YEMNet is based on the You Only Look Once v3 object detection model; this model adopts a lightweight convolutional neural network called "EfficientNet" as the backbone for feature extraction. Then, YEMNet employs a new activation function Mish outside the backbone to achieve efficient optimization and strong generalization, thereby improving the recognition accuracy for ICOS in complicated scenes. Our proposed dataset comprises 15 categories and 13,701 photographs of ICOS captured under different conditions concerning weather, lighting, and natural scenes. Extensive experiments on the proposed dataset show that YEMNet achieves a mean average precision of 91.41% with fewer parameters, thereby outperforming state-of-the-art object detectors. Our dataset and code are available at https://github.com/king-king-king/ICOS-Dataset. [ABSTRACT FROM AUTHOR]

Background: Recent data suggest that there is a pathogenic role for CXC ligand 16 (CXCL16) in cardiovascular diseases. Little is known about circulating CXCL16 in patients with kidney dysfunction. We explored the relationships of plasma CXCL16 with cardiac injury markers in a group of dialysis patients.Methods: Plasma CXCL16 and C-reactive protein (CRP) were measured in 366 patients who were on maintenance hemodialysis. Cardiac injury was evaluated via measurements of the circulating B-type natriuretic peptide (BNP), N-terminal prohormone of brain natriuretic peptide (NT proBNP), Troponin I (TnI), and Troponin T (TnT). Sixty healthy subjects who were frequency matched with the patients on the basis of age and gender were recruited as healthy controls.Results: The mean age of the patients was 52.5 ± 12.1 years and 56.3% were male. Circulating CXCL16 was significantly higher in the patients than in the controls (patients vs.Controls: 477.3 (367.0-647.1) pg/mL vs. 229.5 (203.8-254.5) pg/mL; p < 0.001). The log-transformed (log-) CXCL16 level was correlated with all 4 cardiac markers (log-BNP, log-NTproBNP, log-TnI, and log-TnT) with high levels of significance (all p < 0.001), even after extensive controls for the covariates. In contrast, CRP was correlated only with BNP (marginally) and NT proBNP and was not correlated with troponins.Conclusion: We showed, for the first time, highly significant relationships of circulating CXCL16 level with cardiac injury markers in dialysis patients. Our data suggest that circulating CXCL16 is possibly involved in the pathological process of cardiovascular damage in dialysis patients and may serve as a therapeutic target for cardiac protection in these patients. [ABSTRACT FROM AUTHOR]