Design and Experiment of Capacitive Rice Online Moisture Detection Device.

To solve the problems of poor stability and low monitoring precision in the online detection of rice moisture in the drying tower, we designed an online detection device for rice moisture at the outlet of the drying tower. The structure of a tri-plate capacitor was adopted, and the electrostatic field of the tri-plate capacitor was simulated using COMSOL software. A central composite design of three factors and five levels was carried out with the thickness, spacing, and area of the plates as the influencing factors and the capacitance-specific sensitivity as the test index. This device was composed of a dynamic acquisition device and a detection system. The dynamic sampling device was found to achieve dynamic continuous sampling and static intermittent measurements of rice using a ten-shaped leaf plate structure. The hardware circuit of the inspection system with STM32F407ZGT6 as the main control chip was designed to realize stable communication between the master and slave computers. Additionally, an optimized BP neural network prediction model based on the genetic algorithm was established using the MATLAB software. Indoor static and dynamic verification tests were also carried out. The results showed that the optimal plate structure parameter combination includes a plate thickness of 1 mm, plate spacing of 100 mm, and relative area of 18,000.069 mm2 while satisfying the mechanical design and practical application needs of the device. The structure of the BP neural network was 2-90-1, the length of individual code in the genetic algorithm was 361, and the prediction model was trained 765 times to obtain a minimum MSE value of 1.9683 × 10-5, which was lower than that of the unoptimized BP neural network with an MSE of 7.1215 × 10-4. The mean relative error of the device was 1.44% under the static test and 2.103% under the dynamic test, which met the accuracy requirements for the design of the device.

IGF2BP3-NRF2 axis regulates ferroptosis in hepatocellular carcinoma.

Poor sensitivity to sorafenib has been an important constraint on the efficacy of targeted therapy in advanced hepatocellular carcinoma (HCC). Therefore, it is particularly important to explore effective therapeutic targets to improve the sensitivity of HCC cells to sorafenib. Upregulation of IGF2BP3 is strongly associated with tumor invasion, early recurrence and poor prognosis in various human cancers, including HCC, but its roles in the sorafenib treatment of HCC remain unclear. In our study, IGF2BP3 knock-down significantly promoted ferroptosis in HCC cells through the evaluation of the Reactive Oxygen Species (ROS), Fe2+ and malondialdehyde (MDA) levels after sorafenib administration. In addition, NRF2 mRNA was identified as an important target of IGF2BP3 by bioinformatics analysis, RNA binding protein immunoprecipitation (RIP) and RNA pulldown experiments. More importantly, IGF2BP3, as an m6A (N6-Methyladenosine) reader, was shown to promote the stability of NRF2 mRNA by reading its m6A modification. Similar results were obtained from in vivo experiments. In summary, our study uncovered the role of IGF2BP3-NRF2 axis on ferroptosis in HCC, providing significant evidence for new anti-cancer strategies aimed at improving the efficacy of sorafenib.

High-Sensitivity Troponin I and Incident Coronary Events, Stroke, Heart Failure Hospitalization, and Mortality in the ARIC Study.

BACKGROUND: We assessed whether plasma troponin I measured by a high-sensitivity assay (hs-TnI) is associated with incident cardiovascular disease (CVD) and mortality in a community-based sample without prior CVD. METHODS: ARIC study (Atherosclerosis Risk in Communities) participants aged 54 to 74 years without baseline CVD were included in this study (n=8121). Cox proportional hazards models were constructed to determine associations between hs-TnI and incident coronary heart disease (CHD; myocardial infarction and fatal CHD), ischemic stroke, atherosclerotic CVD (CHD and stroke), heart failure hospitalization, global CVD (atherosclerotic CVD and heart failure), and all-cause mortality. The comparative association of hs-TnI and high-sensitivity troponin T with incident CVD events was also evaluated. Risk prediction models were constructed to assess prediction improvement when hs-TnI was added to traditional risk factors used in the Pooled Cohort Equation. RESULTS: The median follow-up period was ≈15 years. Detectable hs-TnI levels were observed in 85% of the study population. In adjusted models, in comparison to low hs-TnI (lowest quintile, hs-TnI ≤1.3 ng/L), elevated hs-TnI (highest quintile, hs-TnI ≥3.8 ng/L) was associated with greater incident CHD (hazard ratio [HR], 2.20; 95% CI, 1.64-2.95), ischemic stroke (HR, 2.99; 95% CI, 2.01-4.46), atherosclerotic CVD (HR, 2.36; 95% CI, 1.86-3.00), heart failure hospitalization (HR, 4.20; 95% CI, 3.28-5.37), global CVD (HR, 3.01; 95% CI, 2.50-3.63), and all-cause mortality (HR, 1.83; 95% CI, 1.56-2.14). hs-TnI was observed to have a stronger association with incident global CVD events in white than in black individuals and a stronger association with incident CHD in women than in men. hs-TnI and high-sensitivity troponin T were only modestly correlated ( r=0.47) and were complementary in prediction of incident CVD events, with elevation of both troponins conferring the highest risk in comparison with elevation in either one alone. The addition of hs-TnI to the Pooled Cohort Equation model improved risk prediction for atherosclerotic CVD, heart failure, and global CVD. CONCLUSIONS: Elevated hs-TnI is strongly associated with increased global CVD incidence in the general population independent of traditional risk factors. hs-TnI and high-sensitivity troponin T provide complementary rather than redundant information.

Rate, not selectivity, determines neuronal population coding accuracy in auditory cortex.

The notion that neurons with higher selectivity carry more information about external sensory inputs is widely accepted in neuroscience. High-selectivity neurons respond to a narrow range of sensory inputs, and thus would be considered highly informative by rejecting a large proportion of possible inputs. In auditory cortex, neuronal responses are less selective immediately after the onset of a sound and then become highly selective in the following sustained response epoch. These 2 temporal response epochs have thus been interpreted to encode first the presence and then the content of a sound input. Contrary to predictions from that prevailing theory, however, we found that the neural population conveys similar information about sound input across the 2 epochs in spite of the neuronal selectivity differences. The amount of information encoded turns out to be almost completely dependent upon the total number of population spikes in the read-out window for this system. Moreover, inhomogeneous Poisson spiking behavior is sufficient to account for this property. These results imply a novel principle of sensory encoding that is potentially shared widely among multiple sensory systems.

Decoding sound level in the marmoset primary auditory cortex.

Neurons that respond favorably to a particular sound level have been observed throughout the central auditory system, becoming steadily more common at higher processing areas. One theory about the role of these level-tuned or nonmonotonic neurons is the level-invariant encoding of sounds. To investigate this theory, we simulated various subpopulations of neurons by drawing from real primary auditory cortex (A1) neuron responses and surveyed their performance in forming different sound level representations. Pure nonmonotonic subpopulations did not provide the best level-invariant decoding; instead, mixtures of monotonic and nonmonotonic neurons provided the most accurate decoding. For level-fidelity decoding, the inclusion of nonmonotonic neurons slightly improved or did not change decoding accuracy until they constituted a high proportion. These results indicate that nonmonotonic neurons fill an encoding role complementary to, rather than alternate to, monotonic neurons.NEW & NOTEWORTHY Neurons with nonmonotonic rate-level functions are unique to the central auditory system. These level-tuned neurons have been proposed to account for invariant sound perception across sound levels. Through systematic simulations based on real neuron responses, this study shows that neuron populations perform sound encoding optimally when containing both monotonic and nonmonotonic neurons. The results indicate that instead of working independently, nonmonotonic neurons complement the function of monotonic neurons in different sound-encoding contexts.

Prognostic Significance of High-Sensitivity Cardiac Troponin T Concentrations between the Limit of Blank and Limit of Detection in Community-Dwelling Adults: A Metaanalysis.

BACKGROUND: There is controversy regarding whether to report concentrations of high-sensitivity cardiac troponin T (hs-cTnT) to the limit of blank (LOB) (3 ng/L) or the limit of detection (LOD) (5 ng/L) of the assay in community-based cohorts. We hypothesized that hs-cTnT concentrations between the LOB and LOD would be associated with poorer cardiovascular outcomes compared to concentrations below the LOB. METHODS: hs-cTnT was analyzed in a total of 10 723 participants from the Cardiovascular Health Study (CHS), Atherosclerosis Risk in Communities (ARIC) study, and Dallas Heart Study (DHS). Participants were divided into 2 groups, those with hs-cTnT concentrations below the limit of blank (LOB) (<3 ng/L) and those with hs-cTnT between the LOB and limit of detection (LOD) (3-4.99 ng/L). Cross-sectional associations with traditional cardiovascular risk factors and cardiac structural measurements, and longitudinal associations with long-term cardiovascular outcomes of incident heart failure and cardiovascular death, were determined. RESULTS: Participants with hs-cTnT between the LOB and LOD for all 3 cohorts were older, more likely to be male, and have a higher burden of cardiovascular risk factors and structural pathology. A metaanalysis of the 3 cohorts showed participants with hs-cTnT between the LOB and LOD were at increased risk of new-onset heart failure (hazard ratio, 1.18; 95% CI, 1.02-1.38) and cardiovascular mortality (hazard ratio, 1.29; 95% CI, 1.06-1.57). CONCLUSIONS: hs-cTnT concentrations between the LOB and LOD (3-4.99 ng/L) are associated with a higher prevalence of traditional risk factors, more cardiac pathology, and worse outcomes than concentrations below the LOB (<3 ng/L).

Small dense low-density lipoprotein-cholesterol concentrations predict risk for coronary heart disease: the Atherosclerosis Risk In Communities (ARIC) study.

OBJECTIVE: To investigate the relationship between plasma levels of small dense low-density lipoprotein-cholesterol (sdLDL-C) and risk for incident coronary heart disease (CHD) in a prospective study among Atherosclerosis Risk in Communities (ARIC) study participants. APPROACH AND RESULTS: Plasma sdLDL-C was measured in 11 419 men and women of the biracial ARIC study using a newly developed homogeneous assay. A proportional hazards model was used to examine the relationship among sdLDL-C, vascular risk factors, and risk for CHD events (n=1158) for a period of ≈11 years. Plasma sdLDL-C levels were strongly correlated with an atherogenic lipid profile and were higher in patients with diabetes mellitus than non-diabetes mellitus (49.6 versus 42.3 mg/dL; P<0.0001). In a model that included established risk factors, sdLDL-C was associated with incident CHD with a hazard ratio of 1.51 (95% confidence interval, 1.21-1.88) for the highest versus the lowest quartile, respectively. Even in individuals considered to be at low cardiovascular risk based on their LDL-C levels, sdLDL-C predicted risk for incident CHD (hazard ratio, 1.61; 95% confidence interval, 1.04-2.49). Genome-wide association analyses identified genetic variants in 8 loci associated with sdLDL-C levels. These loci were in or close to genes previously associated with risk for CHD. We discovered 1 novel locus, PCSK7, for which genetic variation was significantly associated with sdLDL-C and other lipid factors. CONCLUSIONS: sdLDL-C was associated with incident CHD in ARIC study participants. The novel association of genetic variants in PCSK7 with sdLDL-C and other lipid traits may provide new insights into the role of this gene in lipid metabolism.

Design and implementation of frequency-following response recording system.

OBJECTIVE: The frequency-following response (FFR) is the compound phase-locked brainstem response to periodic components of sound stimuli, and is closely related to pitch perception. Its weak amplitude often prevents its measurement with a high signal-to-noise ratio (SNR). Recording of FFR using multichannel EEG is possible but expensive and it involves the manual screening of raw data. DESIGN: We describe a new method to extract FFR features by prescreening the raw data using automatic monitoring of sound pressure in the ear canal. Removal of stimulus artifacts, noise reduction, and data selection were systematically studied. STUDY SAMPLE: The reliability of our new method was tested by comparing FFRs tracking accuracy and pitch perception in fifteen individuals with normal hearing. RESULTS: The extracted FFRs tracking accuracy was significantly correlated with behavioral measures of pitch perception, indicating that FFR could be used to represent individual differences in pitch perception ability among a population with similar hearing characteristics. CONCLUSION: The designed system could extract FFR signals more accurately with high SNR after signal prescreen and noise reduction.

Mosquito swarm counting via attention-based multi-scale convolutional neural network.

Monitoring mosquito density to predict the risk of transmission of the virus and develop a response in advance is an important part of prevention efforts. This paper aims to estimate accurately the mosquito swarm count from a given image. To this end, we proposed an attention-based multi-scale mosquito swarm counting model that consists of the feature extraction network (FEN) and attention based multi-scale regression network (AMRN). The FEN uses VGG-16 network to extract low-level features of mosquitoes. The AMRN adopts a multi-scale convolutional neural network, and with a squeeze and excitation channel attention module in the branch with a 7 × 7 convolution kernel to extract high-level features, map the feature map to the mosquito swarm density map and estimate mosquitoes count. We collected and labelled a data set that includes 391 mosquito swarm images with 15,466 mosquitoes. Experiments show that our method performs well on the data set and achieves mean absolute error (MAE) of 1.810 and root mean square error (RMSE) of 3.467.

ZNF8-miR-552-5p Axis Modulates ACSL4-Mediated Ferroptosis in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a common malignancy that is associated with poor prognosis in humans. Despite the development of targeted drugs, overall survival remains a significant challenge, and new therapeutic strategies are urgently needed. The aim of this study was to investigate the function of miR-552-5p in ferroptosis and the underlying mechanism, as well as to explore novel strategies for HCC treatment. CCK8 assay results showed that the viability of Huh-7 and Hep3B cells decreased significantly after transfection of the miR-552-5p inhibitor. In addition, we found that glutathione levels were depleted, intracellular Fe2+ levels were elevated, and the mean fluorescence intensity of C11-BODIPY was increased after miR-552-5p transfection. Transmission electron microscopy revealed that mitochondria became smaller and mitochondrial membrane intensity was increased in the inhibitor+RSL3 group. Mechanistically, a dual-luciferase reporter assay confirmed that miR-552-5p interacted with the 3' untranslated region (3' UTR) of acyl-CoA synthetase long-chain family member 4 (ACSL4) mRNA. qPCR and Western blotting results verified that miR-552-5p negatively regulated ACSL4 expression. In addition, we found that overexpression of ZNF8, which is a transcription factor, reduced intracellular miR-552-5p levels and enhanced sensitivity to ferroptosis. miR-552-5p reduces sensitivity to ferroptosis by targeting the 3' UTR of ACSL4 in HCC. The ZNF8-miR-552-5p-ACSL4 axis is involved in regulation of ferroptosis in HCC, and these findings may provide a new therapeutic target for treatment of HCC.

The PTBP1­NCOA4 axis promotes ferroptosis in liver cancer cells.

Polypyrimidine tract­binding protein 1 (PTBP1) plays an important role in tumor immunity, cell proliferation, apoptosis, and autophagy by regulating RNA metabolism. However, the specific function and mechanism of PTBP1 in ferroptosis remain unclear. In the present study, it was investigated whether PTBP1 regulates ferroptosis and the exact mechanism. The iron, malondialdehyde (MDA), and GSH levels were detected in sorafenib (SF)­treated liver cancer cells. si­PTBP1 introduction into SF­treated liver cancer cells resulted in a significant reduction in the levels of MDA and iron. Additionally, a significant recovery of GSH levels was observed after silencing PTBP1. StarBase v2.0 database was used to predict potential transcripts that can physically interact with PTBP1 and nuclear receptor coactivator 4 (NCOA4) mRNA was identified as the most enriched binding partner in the PTBP1­RNA complex. A dual­luciferase assay then demonstrated that PTBP1 directly interacted with NCOA4. PTBP1 silencing did not affect NCOA4 stability following treatment with cycloheximide. A pull­down assay revealed that the PTBP1­binding region was in the 5'­UTR of the NCOA4 mRNA sequence. These results suggest that PTBP1 mediates ferroptosis in liver cancer cells by regulating NCOA4 translation. In vivo experiments reconfirmed the role of the PTBP1­NCOA4 axis in a xenograft transplantation model. It was observed that the mean tumor weight increased after PTBP1 knockout. In conclusion, silencing of PTBP1 decreased the sensitivity of liver cancer cells to ferroptosis after SF treatment and regulated ferritinophagy by mediating NCOA4 translation.

Strengthening Mechanism of Rotary-Forged Deformable Biodegradable Zn-0.45Li Alloys.

The use of zinc (Zn) alloys as a biodegradable metal for medical purposes has been a popular research topic. This study investigated the strengthening mechanism of Zn alloys to enhance their mechanical properties. Three Zn-0.45Li (wt.%) alloys with different deformation amounts were prepared by rotary forging deformation. Their mechanical properties and microstructures were tested. A simultaneous increase in strength and ductility was observed in the Zn-0.45Li alloys. Grain refinement occurred when the rotary forging deformation reached 75.7%. The surface average grain size reached 1.19 ± 0.31 µm, and the grain size was uniformly distributed. Meanwhile, the maximum elongation of the deformed Zn-0.45Li was 139.2 ± 18.6%, and the ultimate tensile strength reached 426.1 ± 4.7 MPa. In situ tensile tests showed that the reinforced alloys still broke from the grain boundary. Continuous and discontinuous dynamic recrystallization during severe plastic deformation produced many recrystallized grains. During deformation, the dislocation density of the alloy first increased and then decreased, and the texture strength of the (0001) direction increased with deformation. Analysis of the mechanism of alloy strengthening showed that the strength and plasticity enhancement of Zn-Li alloys after macro deformation was a combination of dislocation strengthening, weave strengthening, and grain refinement rather than only fine-grain strengthening as observed in conventional macro-deformed Zn alloys.

Effect of Mg Contents on the Microstructure, Mechanical Properties and Cytocompatibility of Degradable Zn-0.5Mn-xMg Alloy.

The effect of magnesium (Mg) content on the microstructure, mechanical properties, and cytocompatibility of degradable Zn-0.5Mn-xMg (x = 0.05 wt%, 0.2 wt%, 0.5 wt%) alloys was investigated. The microstructure, corrosion products, mechanical properties, and corrosion properties of the three alloys were then thoroughly characterized by scanning electron microscopy (SEM), electron back-scattered diffraction (EBSD), and other methods. According to the findings, the grain size of matrix was refined by the addition of Mg, while the size and quantity of Mg2Zn11 phase was increased. The Mg content could significantly improve the ultimate tensile strength (UTS) of the alloy. Compared with the Zn-0.5Mn alloy, the UTS of Zn-0.5Mn-xMg alloy was increased significantly. Zn-0.5Mn-0.5Mg exhibited the highest UTS (369.6 MPa). The strength of the alloy was influenced by the average grain size, the solid solubility of Mg, and the quantity of Mg2Zn11 phase. The increase in the quantity and size of Mg2Zn11 phase was the main reason for the transition from ductile fracture to cleavage fracture. Moreover, Zn-0.5Mn-0.2Mg alloy showed the best cytocompatibility to L-929 cells.

An Intelligent Medical Isolation Observation Management System Based on the Internet of Things.

BACKGROUND: Since COVID-19 (coronavirus disease 2019) was discovered in December 2019, it has spread worldwide. Early isolation and medical observation management of cases and their close contacts are the key to controlling the spread of the epidemic. However, traditional medical observation requires medical staff to measure body temperature and other vital signs face to face and record them manually. There is a general shortage of human and personal protective equipment and a high risk of occupational exposure, which seriously threaten the safety of medical staff. METHODS: We designed an intelligent crowd isolation medical observation management system framework based on the Internet of Things using wireless telemetry and big data cloud platform remote management technology. Through a smart wearable device with built-in sensors, vital sign data and geographical locations of medical observation subjects are collected and automatically uploaded to the big data monitoring platform on demand. According to the comprehensive analysis of the set threshold parameters, abnormal subjects are screened out, and activity tracking and health status monitoring for medical observation and management objectives are performed through monitoring and early warning management and post-event data traceability. In the trial of this system, the subjects wore the wristwatches designed in this study and real-time monitoring was conducted throughout the whole process. Additionally, for comparison, the traditional method was also used for these people. Medical staff came to measure their temperature twice a day. The subjects were 1,128 returned overseas Chinese from Europe. RESULTS: Compared with the traditional vital sign detection method, the system designed in this study has the advantages of a fast response, low error, stability, and good endurance. It can monitor the temperature, pulse, blood pressure, and heart rate of the monitored subject in real time. The system designed in this study and the traditional vital sign detection method were both used to monitor 1,128 close contacts with COVID-19. There were six cases of abnormal body temperature that were missed by traditional manual temperature measurement in the morning and evening, and these six cases (0.53%) were sent to the hospital for further diagnosis. The abnormal body temperature of these six cases was not found in time when the medical staff came to check the temperature on a twice-a-day basis. The system designed in this study, however, can detect the abnormal body temperature of all these six people. The sensitivity and specificity of our system were both 100%. CONCLUSION: The system designed in this study can monitor the body temperature, blood oxygen, blood pressure, heart rate, and geographical location of the monitoring subject in real time. It can be extended to COVID-19 medical observation isolation points, shelter hospitals, infectious disease wards, and nursing homes.

miR-29c targets TNFAIP3, inhibits cell proliferation and induces apoptosis in hepatitis B virus-related hepatocellular carcinoma.

Recent studies have revealed that microRNA-29c (miR-29c) is involved in a variety of biological processes including carcinogenesis. Here, we report that miR-29c was significantly downregulated in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) cell lines as well as in clinical tissues compared with their corresponding controls. Tumor necrosis factor alpha-induced protein 3 (TNFAIP3), a key regulator in inflammation and immunity, was found to be inversely correlated with miR-29c levels and was identified as a target of miR-29c. Overexpression of miR-29c in HepG2.2.15 cells effectively suppressed TNFAIP3 expression and HBV DNA replication as well as inhibited cell proliferation and induced apoptosis. We conclude that miR-29c may play an important role as a tumor suppressive microRNA in the development and progression of HBV-related HCC by targeting TNFAIP3. Thus miR-29c and TNFAIP3 represent key diagnostic markers and potential therapeutic targets for the prevention and treatment of HBV infection.

Ultrafine- and uniform-grained biodegradable Zn-0.5Mn alloy: Grain refinement mechanism, corrosion behavior, and biocompatibility in vivo.

An ultrafine- and uniform-grained Zn-0.5Mn alloy (D3 alloy, stands for deformation rate of 99.5%) is fabricated via multi-pass drawing. The alloy features excellent ductility and elongation properties (up to 245.0% ± 9.0% at room temperature). Zn-0.5Mn alloys are composed of two phases, namely, Zn and MnZn13. The MnZn13 phase confers multiple effects during refinement by inducing and pinning low-angle boundaries within grains. Meanwhile, the presence of these phases along grain boundaries prevents the growth of new refined grains. D3 shows uniform corrosion behaviors in c-SBF solution on account of the even distribution of the MnZn13 phase in its microstructure. Animal implantation experiments indicate that D3 has good biocompatibility; it does not cause damage to bone tissue or other organs. Taking the results together, D3 may be developed into a new type of biodegradable material with remarkable elongation and corrosion properties and satisfactory biocompatibility for medical applications.

Associations Between Carotid Artery Plaque Burden, Plaque Characteristics, and Cardiovascular Events: The ARIC Carotid Magnetic Resonance Imaging Study.

Importance: It remains unknown whether in an asymptomatic community-based cohort magnetic resonance imaging (MRI) measures of plaque characteristics are independently associated with incident cardiovascular disease (CVD) events when adjusted for carotid artery (CA) wall thickness, a measure of plaque burden. Objective: To assess associations of CA MRI plaque characteristics with incident CVD events. Design, Setting, and Participants: The Atherosclerosis Risk in Communities (ARIC) study is a prospective epidemiologic study of the incidence of CVD in 15 792 adults of which 2066 women and men were enrolled in the ARIC Carotid MRI substudy. ARIC participants were enrolled from 1987 to 1989, and the substudy was conducted between January 2004 and December 2005. Analysis began January 2017 and ended August 2020. Exposures: Incident CVD events during a median (interquartile range [IQR]) follow-up time of 10.5 (8.1-10.9) years were assessed. Main Outcomes and Measures: Proportional hazards Cox analyses were performed to ascertain associations between MRI variables of CA plaque burden and plaque characteristics. Results: Of 15 792 ARIC participants, 2066 were enrolled in the substudy, of whom 1256 (701 women [55.8%]) had complete data and were eligible for incident CVD analyses. Carotid artery plaques in participants with incident CVD events (172 [13.7%]) compared with those without (1084 [86.3%]) had a higher normalized wall index (median [IQR], 0.48 [0.36-0.62] vs 0.43 [0.34-0.55]; P = .001), maximum CA wall thickness (median [IQR], 2.22 [1.37-3.52] mm vs 1.96 [1.29-2.85] mm; P = .01), maximum CA stenosis (median [IQR], 5% [0%-22%] vs 0% [0%-13%]; P < .001), and when present, a larger lipid core volume (median [IQR], 0.05 [0.02-0.11] mL vs 0.03 [0.01-0.07] mL; P = .03), respectively. The presence of a lipid core was independently associated with incident CVD events when adjusted for traditional CVD risk factors and maximum CA wall thickness (hazard ratio, 2.48 [95% CI, 1.36-4.51]; P = .003), whereas the presence of calcification was not. The frequency of intraplaque hemorrhage presence in this population of individuals free of CVD at baseline who were not recruited for carotid stenosis was too small to draw any meaningful conclusions (intraplaque hemorrhage presence: 68 of 1256 participants [5.4%]). Carotid artery lumen area and maximum stenosis, which were overall low, were independently associated with incident CVD events when adjusted for traditional CVD risk factors, as anticipated. Conclusions and Relevance: The presence of a CA lipid core on MRI is associated with incident CVD events independent of maximum CA wall thickness in asymptomatic participants.

Association of NT-ProBNP, Blood Pressure, and Cardiovascular Events: The ARIC Study.

BACKGROUND: Although intensive blood pressure reduction has cardiovascular benefits, the absolute benefit is greater in those at higher cardiovascular disease (CVD) risk. OBJECTIVES: This study examined whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) helps identify subjects at higher risk for CVD events across systolic blood pressure (SBP), diastolic blood pressure (DBP), or pulse pressure (PP) categories. METHODS: Participants from the ARIC (Atherosclerosis Risk In Communities) study visit 4 (1996 to 98) were grouped according to SBP, DBP, or PP categories and further stratified by NT-proBNP categories. Cox regression models were used to estimate hazard ratios for incident CVD (coronary heart disease, ischemic stroke, or heart failure hospitalization) and mortality across combined NT-proBNP and/or BP categories, adjusting for CVD risk factors. RESULTS: There were 9,309 participants (age: 62.6 ± 5.6 years; 58.3% women) with 2,416 CVD events over a median follow-up of 16.7 years. Within each SBP, DBP, or PP category, a higher category of NT-proBNP (100 to <300 or 300 pg/ml, compared with NT-proBNP <100 pg/ml) was associated with a graded increased risk for CVD events and mortality. Participants with SBP 130 to 139 mm Hg but NT-proBNP ≥300 pg/ml had a hazards ratio of 3.4 for CVD (95% confidence interval: 2.44 to 4.77) compared with a NT-proBNP of <100 pg/ml and SBP of 140 to 149 mm Hg. CONCLUSIONS: Elevated NT-proBNP is independently associated with CVD and mortality across SBP, DBP, and PP categories and helps identify subjects at the highest risk. Participants with stage 1 hypertension but elevated NT-proBNP had greater cardiovascular risk compared with those with stage 2 SBP but lower NT-proBNP. Future studies are needed to evaluate use of biomarker-based strategies for CVD risk assessment to assist with initiation or intensification of BP treatment.

Genetic risk of clozapine-induced leukopenia and neutropenia: a genome-wide association study.

BACKGROUND: Clozapine is considered to be the most effective antipsychotic medication for schizophrenia. However, it is associated with several adverse effects such as leukopenia, and the underlying mechanism has not yet been fully elucidated. The authors performed a genome-wide association study (GWAS) in a Chinese population to identify genetic markers for clozapine-induced leukopenia (CIL) and clozapine-induced neutropenia (CIN). METHODS: A total of 1879 patients (225 CIL cases, including 43 CIN cases, and 1,654 controls) of Chinese descent were included. Data from common and rare single nucleotide polymorphisms (SNPs) were tested for association. The authors also performed a trans-ancestry meta-analysis with GWAS results of European individuals from the Clozapine-Induced Agranulocytosis Consortium (CIAC). RESULTS: The authors identified several novel loci reaching the threshold of genome-wide significance level (P < 5 × 10-8). Three novel loci were associated with CIL while six were associated with CIN, and two T cell related genes (TRAC and TRAT1) were implicated. The authors also observed that one locus with evidence close to genome-wide significance (P = 5.08 × 10-8) was near the HLA-B gene in the major histocompatibility complex region in the trans-ancestry meta-analysis. CONCLUSIONS: The associations provide novel and valuable understanding of the genetic and immune causes of CIL and CIN, which is useful for improving clinical management of clozapine related treatment for schizophrenia. Causal variants and related underlying molecular mechanisms need to be understood in future developments.